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Human Brain Mapping

Wiley Online Library : Human Brain Mapping

Published: 2017-10-01T00:00:00-05:00


Dynamic functional connectivity and individual differences in emotions during social stress


Exposure to acute stress induces multiple emotional responses, each with their own unique temporal dynamics. Dynamic functional connectivity (dFC) measures the temporal variability of network synchrony and captures individual differences in network neurodynamics. This study investigated the relationship between dFC and individual differences in emotions induced by an acute psychosocial stressor. Sixteen healthy adult women underwent fMRI scanning during a social evaluative threat (SET) task, and retrospectively completed questionnaires that assessed individual differences in subjectively experienced positive and negative emotions about stress and stress relief during the task. Group dFC was decomposed with parallel factor analysis (PARAFAC) into 10 components, each with a temporal signature, spatial network of functionally connected regions, and vector of participant loadings that captures individual differences in dFC. Participant loadings of two networks were positively correlated with stress-related emotions, indicating the existence of networks for positive and negative emotions. The emotion-related networks involved the ventromedial prefrontal cortex, cingulate cortex, anterior insula, and amygdala, among other distributed brain regions, and time signatures for these emotion-related networks were uncorrelated. These findings demonstrate that individual differences in stress-induced positive and negative emotions are each uniquely associated with large-scale brain networks, and suggest that dFC is a mechanism that generates individual differences in the emotional components of the stress response. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Altered white-matter integrity in unaffected siblings of probands with autism spectrum disorders


Despite the evidence of altered white-matter tract property in individuals with autism spectrum disorder (ASD), little is known about their unaffected siblings. This study aimed to investigate white-matter integrity in unaffected siblings of ASD probands. Thirty-nine unaffected siblings (mean age 15.6 ± 6.0 years; 27 males, 69.2%) and 39 typically developing controls (TDC) (14.2 ± 5.6 years; 26 males, 66.7%) were assessed with diffusion spectrum images and neuropsychological tests. Using the tract-based automatic analysis and the threshold-free cluster weighted (TFCW) scores, we searched for the segments among 76 tracts with the largest difference over the entire brain compared to TDC. Tract integrity was quantified by calculating the mean generalized fractional anisotropy (mGFA) values of the segments with the largest difference in TFCW scores. Unaffected siblings showed reduced mGFA in the bilateral frontal aslant tracts, the right superior longitudinal fasciculus 2 (SLF2), the frontostriatal tracts from the right dorsolateral and left ventrolateral prefrontal cortices, the thalamic radiations of the left ventral and the right dorsal thalamus, the callosal fibers of the splenium, and the increased mGFA of the callosal fibers of the precuneus and the left inferior longitudinal fasciculus. Among these, reduced right SLF2 mGFA was associated with social awareness deficits; impaired frontostriatal tract was associated with internalizing problems, while right frontal aslant tract integrity was associated with visual memory deficits. In conclusion, unaffected siblings showed the aberrant integrity of several white-matter tracts, which were correlated with clinical symptoms and neurocognitive dysfunction. The altered tract integrity could be further examined in the probands with ASD. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Atypical neuronal activation during a spatial working memory task in 13-year-old very preterm children


Children born very preterm (VP; <32 weeks' gestational age) are at risk for unfavorable outcomes in several cognitive domains, including spatial working memory (WM). The underlying neural basis of these cognitive impairments is poorly understood. We investigated differences in neuronal activation during spatial WM using a backward span (BS) task relative to a control (C) task in 45 VP children and 19 term-born controls aged 13 years. VP children showed significantly more activation in the bilateral superior frontal gyrus and significantly less activation in the left parahippocampal gyrus compared with controls. We further explored the distinct contributions of maintenance and manipulation processes of WM using forward span (FS)>C and BS > FS, respectively. There were no significant group differences in neuronal activation for FS > C. However, BS > FS revealed that VP children had significantly greater activation in the left middle frontal gyrus, in the left superior parietal gyrus and right cerebellar tonsil, and significantly less activation in the right precentral and postcentral gyrus and left insula compared with controls. Taken together these results suggest that VP children at 13 years of age show an atypical neuronal activation during spatial WM, specifically related to manipulation of spatial information in WM. It is unclear whether these findings reflect delayed maturation and/or recruitment of alternative neuronal networks as a result of neuroplasticity. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Decoding the neural representation of story meanings across languages


Drawing from a common lexicon of semantic units, humans fashion narratives whose meaning transcends that of their individual utterances. However, while brain regions that represent lower-level semantic units, such as words and sentences, have been identified, questions remain about the neural representation of narrative comprehension, which involves inferring cumulative meaning. To address these questions, we exposed English, Mandarin, and Farsi native speakers to native language translations of the same stories during fMRI scanning. Using a new technique in natural language processing, we calculated the distributed representations of these stories (capturing the meaning of the stories in high-dimensional semantic space), and demonstrate that using these representations we can identify the specific story a participant was reading from the neural data. Notably, this was possible even when the distributed representations were calculated using stories in a different language than the participant was reading. Our results reveal that identification relied on a collection of brain regions most prominently located in the default mode network. These results demonstrate that neuro-semantic encoding of narratives happens at levels higher than individual semantic units and that this encoding is systematic across both individuals and languages. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Gray matter volumes of early sensory regions are associated with individual differences in sensory processing


Sensory processing (i.e., the manner in which the nervous system receives, modulates, integrates, and organizes sensory stimuli) is critical when humans are deciding how to react to environmental demands. Although behavioral studies have shown that there are stable individual differences in sensory processing, the neural substrates that implement such differences remain unknown. To investigate this issue, structural magnetic resonance imaging scans were acquired from 51 healthy adults and individual differences in sensory processing were assessed using the Sensory Profile questionnaire (Brown et al.: Am J Occup Ther 55 (2001) 75–82). There were positive relationships between the Sensory Profile modality-specific subscales and gray matter volumes in the primary or secondary sensory areas for the visual, auditory, touch, and taste/smell modalities. Thus, the present results suggest that individual differences in sensory processing are implemented by the early sensory regions. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Visuomotor effects of body part movements presented in the first-person perspective on imitative behavior


Imitative stimuli presented from a first-person perspective (FPP) produce stronger visuomotor effects than those presented from a third-person perspective (TPP) due to the relatively greater response of the mirror neuron system (MNS) to FPP stimuli. Some previous studies utilizing TPP stimuli have reported no differences in MNS activity between moving and static bodies’ stimuli. However, few studies have compared visuomotor effects of such stimuli when presented in the FPP. To clarify this issue, we measured cortical activation in 17 participants during a functional magnetic resonance imaging (MRI) imitation task involving three conditions: moving (a lifting finger was presented), static (an “X” appeared on a static finger), and control (an “X” appeared on a button). All stimuli were presented from the FPP or TPP. Participants were asked to lift the finger corresponding to the imitative stimulus. In the FPP condition, moving stimuli elicited greater MNS activation than static stimuli. Furthermore, such movement effects were stronger in the MNS and insula (a region associated with body-ownership) for FPP stimuli than for TPP stimuli. Psychophysiological interaction analysis revealed increased connectivity between the MNS and insula for moving stimuli in the FPP condition. These findings suggest that bodily movements presented in the FPP elicit a greater visuomotor response than static body presented in the FPP, and that the visuomotor effects of bodily movements were greater in the FPP condition than in the TPP condition. Our analyses further indicated that such responses are processed via the neural system underlying body-ownership. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Evidence-based source modeling of nociceptive cortical responses: A direct comparison of scalp and intracranial activity in humans


Background Source modeling of EEG traditionally relies on interplay between physiological hypotheses and mathematical estimates. We propose to optimize the process by using evidence gathered from brain imaging and intracortical recordings. Methods We recorded laser-evoked potentials in 18 healthy participants, using high-density EEG. Brain sources were modeled during the first second poststimulus, constraining their initial position to regions where nociceptive-related activity has been ascertained by intracranial EEG. These comprised the two posterior operculo-insular regions, primary sensorimotor, posterior parietal, anterior cingulate/supplementary motor (ACC/SMA), bilateral frontal/anterior insular, and posterior cingulate (PCC) cortices. Results The model yielded an average goodness of fit of 91% for individual and 95.8% for grand-average data. When compared with intracranial recordings from 27 human subjects, no significant difference in peak latencies was observed between modeled and intracranial data for 5 of the 6 assessable regions. Morphological match was excellent for operculo-insular, frontal, ACC/SMA and PCC regions (cross-correlation > 0.7) and fair for sensori-motor and posterior parietal cortex (c-c ∼ 0.5). Conclusions Multiple overlapping activities evoked by nociceptive input can be disentangled from high-density scalp EEG guided by intracranial data. Modeled sources accurately described the timing and morphology of most activities recorded with intracranial electrodes, including those coinciding with the emergence of stimulus awareness. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

5-HTTLPR moderates the association between interdependence and brain responses to mortality threats


While behavioral research suggests an association between cultural worldview and decreased anxiety of death, the underlying neurobiological mechanisms remain unclear. Using functional MRI, we investigated whether and how the serotonin transporter promoter polymorphism (5-HTTLPR), which has been associated with mental disorders such as anxiety and depression, moderates the associations between a cultural trait (i.e., interdependence) and self-report of death anxiety/depression and between interdependence and brain responses to mortality threats. Long/long and short/short allele carriers of the 5-HTTLPR were scanned using fMRI while they performed a one-back task on death-related, death-unrelated negative, and neutral words. Participants' interdependence and death anxiety/depression were assessed using questionnaires after scanning. We found that participants who assessed themselves with greater interdependence reported lower death anxiety/depression and showed decreased neural response to death-related words in emotion-related brain regions including the anterior cingulate, putamen, and thalamus. However, these results were evident in long/long allele carriers of the 5-HTTLPR but not in short/short allele carriers who even showed positive associations between interdependence and neural activities in the anterior cingulate, putamen and thalamus in response to death-related words. Our findings suggest candidate mechanisms for explaining the complex relationship between genotype, cultural traits, and mental/neural responses to mortality threats. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

“Discrete peaks” of excitability and map overlap reveal task-specific organization of primary motor cortex for control of human forearm muscles


The primary motor cortex (M1) presents a somatotopic organization of body parts, but with overlap between muscle/movement representations. This distinct but overlapping M1 organization is believed to be important for individuated control and movement coordination, respectively. Discrete peaks of greater excitability observed within M1 might underpin organization of cortical motor control. This study aimed to examine interactions between M1 representations of synergist and antagonist forearm muscles, compare regions of greater excitability during different functional tasks, and compare characteristics of M1 representation recorded using surface and fine-wire (fw) electrodes. Transcranial magnetic stimulation (TMS) was applied over M1 for mapping the representation of 4 forearm muscles (extensor carpi radialis brevis [ECRB], extensor digitorum communis, flexor carpi radialis, and flexor digitorum superficialis) during three tasks: rest, grip, and wrist extension in 14 participants. There are three main findings. First, discrete areas of peak excitability within the M1 representation of ECRBfw were identified during grip and wrist extension suggesting that different M1 areas are involved in different motor functions. Second, M1 representations of synergist muscles presented with greater overlap of M1 representations than muscles with mainly antagonist actions, which suggests a role in muscle coordination. Third, as larger normalized map volume and overlap were observed using surface than fine-wire electrodes, data suggest that cross-talk from adjacent muscles compromised interpretation of recordings made with surface electrodes in response to TMS. These results provide a novel understanding of the spatial organization of M1 with evidence of “functional somatotopy.” This has important implications for cortical control of movement. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Connectivity-based parcellation of the anterior limb of the internal capsule


The anterior limb of the internal capsule (ALIC) is an important locus of frontal-subcortical fiber tracts involved in cognitive and limbic feedback loops. However, the structural organization of its component fiber tracts remains unclear. Therefore, although the ALIC is a promising target for various neurosurgical procedures for psychiatric disorders, more precise understanding of its organization is required to optimize target localization. Using diffusion tensor imaging (DTI) collected on healthy subjects by the Human Connectome Project (HCP), we generated parcellations of the ALIC by dividing it according to structural connectivity to various frontal regions. We then compared individuals’ parcellations to evaluate the ALIC's structural consistency. All 40 included subjects demonstrated a posterior–superior to anterior–inferior axis of tract organization in the ALIC. Nonetheless, subdivisions of the ALIC were found to vary substantially, as voxels in the average parcellation were accurately assigned for a mean of only 66.2% of subjects. There were, however, some loci of consistency, most notably in the region maximally connected to orbitofrontal cortex. These findings clarify the highly variable organization of the ALIC and may represent a tool for patient-specific targeting of neuromodulation. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Microstructural white matter alterations in patients with drug induced parkinsonism


Drug-induced parkinsonism (DIP) is the second most common etiology of parkinsonism. And yet, there is little information on structural imaging in DIP to elucidate the accurate underlying pathomechanisms. To investigate microstructural white matter (WM) in patients with DIP using diffusion tensor image and to determine its relationship to severity of parkinsonian motor symptoms and cognitive function. A total of 42 patients with DIP, 65 with Parkinson's disease, and 33 control subjects were recruited from a movement disorders outpatient clinic. We performed comparative analysis of fractional anisotropy (FA) and mean diffusivity (MD) values among groups using tract-based spatial statistics. Correlation analysis between WM integrity and parkinsonian motor symptoms and cognitive performance was also performed in DIP patients using voxel-wise statistical analysis. DIP patients had significantly lower FA and higher MD values over widespread WM areas than control subjects. The patients with DIP had poor cognitive performance relative to control subjects, which correlated well with WM properties. Additionally, the parkinsonian motor symptoms were negatively correlated with FA values. In contrast, exposure time to the offending drugs prior to the development of parkinsonism or duration of parkinsonism showed no significant association with FA or MD values. The present study demonstrates that disruption of the WM microstructure is extensive in patients with DIP, and it is correlated with clinical parameters of parkinsonism and cognitive performance. This suggests that DIP may be reflective of underlying abnormality of microstructural WM. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Neural correlates of interoception: Effects of interoceptive focus and relationship to dimensional measures of body awareness


Interoception has been defined as the sensing of the physiological condition of the body, with interoceptive sensibility (IS) characterizing an individual's self-reported awareness of internal sensation. IS is a multidimensional construct including not only the tendency to be aware of sensation but also how sensations are interpreted, regulated, and used to inform behavior, with different dimensions relating to different aspects of health and disease. Here we investigated neural mechanisms of interoception when healthy individuals attended to their heartbeat and skin temperature, and examined the relationship between neural activity during interoception and individual differences in self-reported IS using the Multidimensional Scale of Interoceptive Awareness (MAIA). Consistent with prior work, interoception activated a network involving insula and sensorimotor regions but also including occipital, temporal, and prefrontal cortex. Differences based on interoceptive focus (heartbeat vs skin temperature) were found in insula, sensorimotor regions, occipital cortex, and limbic areas. Factor analysis of MAIA dimensions revealed 3 dissociable components of IS in our dataset, only one of which was related to neural activity during interoception. Reduced scores on the third factor, which reflected reduced ability to control attention to body sensation and increased tendency to distract from and worry about aversive sensations, was associated with greater activation in many of the same regions as those involved in interoception, including insula, sensorimotor, anterior cingulate, and temporal cortex. These data suggest that self-rated interoceptive sensibility is related to altered activation in regions involved in monitoring body state, which has implications for disorders associated with abnormality of interoception. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Learning to name smells increases activity in heteromodal semantic areas


Semantic description of odors is a cognitively demanding task. Learning to name smells is, however, possible with training. This study set out to examine how improvement in olfactory semantic knowledge following training reorganizes the neural representation of smells. First, 19 nonexpert volunteers were trained for 3 days; they were exposed (i) to odorants presented without verbal labels (perceptual learning) and (ii) to other odorants paired with lexicosemantic labels (associative learning). Second, the same participants were tested in a brain imaging study (fMRI) measuring hemodynamic responses to learned odors presented in both the perceptual and associative learning conditions. The lexicosemantic training enhanced the ability to describe smells semantically. Neurally, this change was associated with enhanced activity in a set of heteromodal areas—including superior frontal gyrus—and parietal areas. These findings demonstrate that odor-name associative learning induces recruitment of brain areas involved in the integration and representation of semantic attributes of sensory events. They also offer new insights into the brain plasticity underlying the acquisition of olfactory expertise in lay people. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Neural mechanisms of motion perceptual learning in noise


Practice improves our perceptual ability. However, the neural mechanisms underlying this experience-dependent plasticity in adult brain remain unclear. Here, we studied the long-term neural correlates of motion perceptual learning. Subjects' behavioral performance and BOLD signals were tracked before, immediately after, and 2 weeks after practicing a motion direction discrimination task in noise over six daily sessions. Parallel to the specificity and persistency of the behavioral learning effect, we found that training sharpened the cortical tuning in MT, and enhanced the connectivity strength from MT to the intraparietal sulcus (IPS, a motion decision-making area). In addition, the decoding accuracy for the trained motion direction was improved in IPS 2 weeks after training. The dual changes in the sensory and the high-level cortical areas suggest that learning refines the neural representation of the trained stimulus and facilitates the information transmission in the decision process. Our findings are consistent with the functional specialization in the visual cortex, and provide empirical evidence to the reweighting theory of perceptual learning at a large spatial scale. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

A pediatric structural MRI analysis of healthy brain development from newborns to young adults


Assessment of healthy brain maturation can be useful toward better understanding natural patterns of brain growth and toward the characterization of a variety of neurodevelopmental disorders as deviations from normal growth trajectories. Structural magnetic resonance imaging (MRI) provides excellent soft-tissue contrast, which allows for the assessment of gray and white matter in the developing brain. We performed a large-scale retrospective analysis of 993 pediatric structural brain MRI examinations of healthy subjects (n = 988, aged 0–32 years) imaged clinically at 3 T, and extracted a wide variety of measurements such as white matter volumes, cortical thickness, and gyral curvature localized to subregions of the brain. All extracted structural biomarkers were tested for their correlation with subject age at time of imaging, providing measurements that may assist in the assessment of neurological maturation. Additional analyses were also performed to assess gender-based differences in the brain at a variety of developmental stages, and to assess hemispheric asymmetries. Results add to the literature by analyzing a realistic distribution of healthy participants imaged clinically, a useful cohort toward the investigation and creation of diagnostic tests for a variety of pathologies as aberrations from healthy growth trajectories. The next generation of diagnostic tests will be responsible for identifying pathological conditions from populations of healthy clinically imaged individuals. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Frequency-specific neuromodulation of local and distant connectivity in aging and episodic memory function


A growing literature has focused on the brain's ability to augment processing in local regions by recruiting distant communities of neurons in response to neural decline or insult. In particular, both younger and older adult populations recruit bilateral prefrontal cortex (PFC) as a means of compensating for increasing neural effort to maintain successful cognitive function. However, it remains unclear how local changes in neural activity affect the recruitment of this adaptive mechanism. To address this problem, we combined graph theoretical measures from functional MRI with diffusion weighted imaging and repetitive transcranial magnetic stimulation (rTMS) to resolve a central hypothesis: how do aged brains flexibly adapt to local changes in cortical activity? Specifically, we applied neuromodulation to increase or decrease local activity in a cortical region supporting successful memory encoding (left dorsolateral PFC or DLPFC) using 5 or 1 Hz rTMS, respectively. We then assessed a region's local within-module degree, or the distributed between-module degree (BMD) between distant cortical communities. We predicted that (1) local stimulation-related deficits may be counteracted by boosting BMD between bilateral PFC, and that this effect should be (2) positively correlated with structural connectivity. Both predictions were confirmed; 5 Hz rTMS increased local success-related activity and local increases in PFC connectivity, while 1 Hz rTMS decreases local activity and triggered a more distributed pattern of bilateral PFC connectivity to compensate for this local inhibitory effect. These results provide an integrated, causal explanation for the network interactions associated with successful memory encoding in older adults. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Dual-echo ASL contributes to decrypting the link between functional connectivity and cerebral blow flow


Arterial spin labeling (ASL) MRI with a dual-echo readout module (DE-ASL) enables noninvasive simultaneous acquisition of cerebral blood flow (CBF)-weighted images and blood oxygenation level dependent (BOLD) contrast. Up to date, resting-state functional connectivity (FC) studies based on CBF fluctuations have been very limited, while the BOLD is still the method most frequently used. The purposes of this technical report were (i) to assess the potentiality of the DE-ASL sequence for the quantification of resting-state FC and brain organization, with respect to the conventional BOLD (cvBOLD) and (ii) to investigate the relationship between a series of complex network measures and the CBF information. Thirteen volunteers were scanned on a 3 T scanner acquiring a pseudocontinuous multislice DE-ASL sequence, from which the concomitant BOLD (ccBOLD) simultaneously to the ASL can be extracted. In the proposed comparison, the brain FC and graph-theoretical analysis were used for quantifying the connectivity strength between pairs of regions and for assessing the network model properties in all the sequences. The main finding was that the ccBOLD part of the DE-ASL sequence provided highly comparable connectivity results compared to cvBOLD. As expected, because of its different nature, ASL sequence showed different patterns of brain connectivity and graph indices compared to BOLD sequences. To conclude, the resting-state FC can be reliably detected using DE-ASL, simultaneously to CBF quantifications, whereas a single fMRI experiment precludes the quantitative measurement of BOLD signal changes. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Preferential encoding of movement amplitude and speed in the primary motor cortex and cerebellum


Voluntary movements require control of multiple kinematic parameters, a task carried out by a distributed brain architecture. However, it remains unclear whether regions along the motor system encode single, or rather a mixture of, kinematic parameters during action execution. Here, rapid event-related functional magnetic resonance imaging was used to differentiate brain activity along the motor system during the encoding of movement amplitude, duration, and speed. We present cumulative evidence supporting preferential encoding of kinematic parameters along the motor system, based on blood-oxygenation-level dependent signal recorded in a well-controlled single-joint wrist-flexion task. Whereas activity in the left primary motor cortex (M1) showed preferential encoding of movement amplitude, the anterior lobe of the right cerebellum (primarily lobule V) showed preferential encoding of movement speed. Conversely, activity in the left supplementary motor area (SMA), basal ganglia (putamen), and anterior intraparietal sulcus was not preferentially modulated by any specific parameter. We found no preference in peak activation for duration encoding in any of the tested regions. Electromyographic data was mainly modulated by movement amplitude, restricting the distinction between amplitude and muscle force encoding. Together, these results suggest that during single-joint movements, distinct kinematic parameters are controlled by largely distinct brain-regions that work together to produce and control precise movements. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Deficits in voluntary pursuit and inhibition of risk taking in sensation seeking


Sensation seeking has been associated with substance use and other risk-taking behaviors. The present functional magnetic resonance imaging (fMRI) study investigated the neural correlates underlying risk taking in sensation seeking. Twenty-eight high sensation seekers (HSS; 14 female and 14 male young adults) and 28 low sensation seekers (LSS; 14 female and 14 male young adults) performed an interactive, sequential gambling task that allowed for voluntary pursuit or inhibition of risk taking. Behaviorally, HSS versus LSS exhibited a stronger tendency toward risk taking. Comparison of the groups revealed that when taking risks, HSS relative to LSS exhibited reduced fMRI responses in brain areas involved in risk processing, such as the dorsomedial prefrontal cortex and the thalamus. Importantly, during the voluntary inhibition of risk taking, HSS relative to LSS showed greater fMRI responses in brain areas implicated in cognitive control (the bilateral anterior cingulate cortex) and negative emotion (the right anterior insula). These findings suggest that risk taking in sensation seeking may be driven by both a hypoactive neural system in the voluntary pursuit of risk taking and a hyperactive neural system in the voluntary inhibition of risk taking, thus providing implications for future prevention programs targeting sensation-seeking behaviors. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Structural connectivity-defined thalamic subregions have different functional connectivity abnormalities in multiple sclerosis patients: Implications for clinical correlations


In spite of the well-known importance of thalami in multiple sclerosis (MS), only limited data on whole and subregional thalamic functional connectivity (FC) changes are available. Using diffusion tensor imaging, we performed a structural connectivity based thalamic parcellation and investigated subregional thalamic resting-state (RS) FC alterations and their relationship with clinical/cognitive measures in MS. MRI data from a reference set of healthy controls (HC) were used to parcellate the thalami into five subregions, according to their structural connectivity. For each thalamic subregion, a seed-based RS FC analysis was performed in 187 MS patients and 94 HC. Correlations between thalamic RS FC and clinical/cognitive variables were assessed. Compared to HC, MS patients showed increased intra- and inter-thalamic RS FC for almost all thalamic subregions, and increased RS FC between all thalamic subregions and the left insula. Frontal and motor thalamic subregions also showed reduced RS FC with the caudate nucleus. For the temporal thalamic subregion, we observed reduced RS FC with the ipsilateral thalamus, anterior and middle cingulate cortex, and cerebellum. Compared to cognitively preserved, cognitively impaired MS patients had higher thalamic RS FC with several temporal areas. In MS patients, lower RS FC between thalamic subregions and the caudate and cingulate cortex correlated with worse motor performance, whereas higher RS FC with the insula correlated with better motor performance. The main thalamic subregions have different RS-FC abnormalities in MS patients. Increased thalamic RS FC with the insula may have a compensatory role, whereas increased RS FC with temporal areas, observed in patients with cognitive impairment may reflect maladaptive mechanisms. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Hypersensitivity to low intensity fearful faces in autism when fixation is constrained to the eyes


Previous studies that showed decreased brain activation in people with autism spectrum disorder (ASD) viewing expressive faces did not control that participants looked in the eyes. This is problematic because ASD is characterized by abnormal attention to the eyes. Here, we collected fMRI data from 48 participants (27 ASD) viewing pictures of neutral faces and faces expressing anger, happiness, and fear at low and high intensity, with a fixation cross between the eyes. Group differences in whole brain activity were examined for expressive faces at high and low intensity versus neutral faces. Group differences in neural activity were also investigated in regions of interest within the social brain, including the amygdala and the ventromedial prefrontal cortex (vmPFC). In response to low intensity fearful faces, ASD participants showed increased activation in the social brain regions, and decreased functional coupling between the amygdala and the vmPFC. This oversensitivity to low intensity fear coupled with a lack of emotional regulation capacity could indicate an excitatory/inhibitory imbalance in their socio-affective processing system. This may result in social disengagement and avoidance of eye-contact to handle feelings of strong emotional reaction. Our results also demonstrate the importance of careful control of gaze when investigating emotional processing in ASD. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Central and non-central networks, cognition, clinical symptoms, and polygenic risk scores in schizophrenia


Schizophrenia is a complex disorder that may be the result of aberrant connections between specific brain regions rather than focal brain abnormalities. Here, we investigate the relationships between brain structural connectivity as described by network analysis, intelligence, symptoms, and polygenic risk scores (PGRS) for schizophrenia in a group of patients with schizophrenia and a group of healthy controls. Recently, researchers have shown an interest in the role of high centrality networks in the disorder. However, the importance of non-central networks still remains unclear. Thus, we specifically examined network-averaged fractional anisotropy (mean edge weight) in central and non-central subnetworks. Connections with the highest betweenness centrality within the average network (>75% of centrality values) were selected to represent the central subnetwork. The remaining connections were assigned to the non-central subnetwork. Additionally, we calculated graph theory measures from the average network (connections that occur in at least 2/3 of participants). Density, strength, global efficiency, and clustering coefficient were significantly lower in patients compared with healthy controls for the average network (pFDR < 0.05). All metrics across networks were significantly associated with intelligence (pFDR < 0.05). There was a tendency towards significance for a correlation between intelligence and PGRS for schizophrenia (r = −0.508, p = 0.052) that was significantly mediated by central and non-central mean edge weight and every graph metric from the average network. These results are consistent with the hypothesis that intelligence deficits are associated with a genetic risk for schizophrenia, which is mediated via the disruption of distributed brain networks. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

On the integrity of functional brain networks in schizophrenia, Parkinson's disease, and advanced age: Evidence from connectivity-based single-subject classification


Previous whole-brain functional connectivity studies achieved successful classifications of patients and healthy controls but only offered limited specificity as to affected brain systems. Here, we examined whether the connectivity patterns of functional systems affected in schizophrenia (SCZ), Parkinson's disease (PD), or normal aging equally translate into high classification accuracies for these conditions. We compared classification performance between pre-defined networks for each group and, for any given network, between groups. Separate support vector machine classifications of 86 SCZ patients, 80 PD patients, and 95 older adults relative to their matched healthy/young controls, respectively, were performed on functional connectivity in 12 task-based, meta-analytically defined networks using 25 replications of a nested 10-fold cross-validation scheme. Classification performance of the various networks clearly differed between conditions, as those networks that best classified one disease were usually non-informative for the other. For SCZ, but not PD, emotion-processing, empathy, and cognitive action control networks distinguished patients most accurately from controls. For PD, but not SCZ, networks subserving autobiographical or semantic memory, motor execution, and theory-of-mind cognition yielded the best classifications. In contrast, young–old classification was excellent based on all networks and outperformed both clinical classifications. Our pattern-classification approach captured associations between clinical and developmental conditions and functional network integrity with a higher level of specificity than did previous whole-brain analyses. Taken together, our results support resting-state connectivity as a marker of functional dysregulation in specific networks known to be affected by SCZ and PD, while suggesting that aging affects network integrity in a more global way. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Predicting hemispheric dominance for language production in healthy individuals using support vector machine


We used a Support Vector Machine (SVM) classifier to assess hemispheric pattern of language dominance of 47 individuals categorized as non-typical for language from their hemispheric functional laterality index (HFLI) measured on a sentence minus word-list production fMRI-BOLD contrast map. The SVM classifier was trained at discriminating between Dominant and Non-Dominant hemispheric language production activation pattern on a group of 250 participants previously identified as Typicals (HFLI strongly leftward). Then, SVM was applied to each hemispheric language activation pattern of 47 non-typical individuals. The results showed that at least one hemisphere (left or right) was found to be Dominant in every, except 3 individuals, indicating that the “dominant” type of functional organization is the most frequent in non-typicals. Specifically, left hemisphere dominance was predicted in all non-typical right-handers (RH) and in 57.4% of non-typical left-handers (LH). When both hemisphere classifications were jointly considered, four types of brain patterns were observed. The most often predicted pattern (51%) was left-dominant (Dominant left-hemisphere and Non-Dominant right-hemisphere), followed by right-dominant (23%, Dominant right-hemisphere and Non-Dominant left-hemisphere) and co-dominant (19%, 2 Dominant hemispheres) patterns. Co-non-dominant was rare (6%, 2 Non-Dominant hemispheres), but was normal variants of hemispheric specialization. In RH, only left-dominant (72%) and co-dominant patterns were detected, while for LH, all types were found, although with different occurrences. Among the 10 LH with a strong rightward HFLI, 8 had a right-dominant brain pattern. Whole-brain analysis of the right-dominant pattern group confirmed that it exhibited a functional organization strictly mirroring that of left-dominant pattern group. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Short-term language switching training tunes the neural correlates of cognitive control in bilingual language production


The present study investigated how language switching experience would modulate the neural correlates of cognitive control involved in bilingual language production. A group of unbalanced Chinese–English bilinguals undertook an 8-day cued picture naming training during which they named pictures in either of their languages based on visually presented cues. Participants' brain activation was scanned before and after the training in the same task. Behavioral results revealed a significant training effect such that switch costs were reduced after training. fMRI results showed that after training, activation of brain areas associated with cognitive control including the anterior cingulated cortex and the caudate was reduced. Besides, the activation reduction in the left dorsal anterior cingulated cortex positively correlated with the reduction in switch costs in response time and this training effect could be transferred to untrained stimuli. These findings suggest that neural correlates of cognitive control, especially that of the conflict monitoring process, in bilingual language production could be modulated by short-term language switching training. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Gray matter asymmetries in aging and neurodegeneration: A review and meta-analysis


Inter-hemispheric asymmetries are a common phenomenon of the human brain. Some evidence suggests that neurodegeneration related to aging and disease may preferentially affect the left—usually language- and motor-dominant—hemisphere. Here, we used activation likelihood estimation meta-analysis to assess gray matter (GM) loss and its lateralization in healthy aging and in neurodegeneration, namely, mild cognitive impairment (MCI), Alzheimer's dementia (AD), Parkinson's disease (PD), and Huntington's disease (HD). This meta-analysis, comprising 159 voxel-based morphometry publications (enrolling 4,469 patients and 4,307 controls), revealed that GM decline appeared to be asymmetric at trend levels but provided no evidence for increased left-hemisphere vulnerability. Regions with asymmetric GM decline were located in areas primarily affected by neurodegeneration. In HD, the left putamen showed converging evidence for more pronounced atrophy, while no consistent pattern was found in PD. In MCI, the right hippocampus was more atrophic than its left counterpart, a pattern that reversed in AD. The stability of these findings was confirmed using permutation tests. However, due to the lenient threshold used in the asymmetry analysis, further work is needed to confirm our results and to provide a better understanding of the functional role of GM asymmetries, for instance in the context of cognitive reserve and compensation. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Complexity analysis of cortical surface detects changes in future Alzheimer's disease converters


Alzheimer's disease (AD) is a neurological disorder that creates neurodegenerative changes at several structural and functional levels in human brain tissue. The fractal dimension (FD) is a quantitative parameter that characterizes the morphometric variability of the human brain. In this study, we investigate spherical harmonic-based FD (SHFD), thickness, and local gyrification index (LGI) to assess whether they identify cortical surface abnormalities toward the conversion to AD. We study 33 AD patients, 122 mild cognitive impairment (MCI) patients (50 MCI converters and 29 MCI nonconverters), and 32 healthy controls (HC). SHFD, thickness, and LGI methodology allowed us to perform not only global level but also local level assessments in each cortical surface vertex. First, we found that global SHFD decreased in AD and future MCI converters compared to HC, and in MCI converters compared to MCI nonconverters. Second, we found that local white matter SHFD was reduced in AD compared to HC and MCI mainly in medial temporal lobe. Third, local white-matter SHFD was significantly reduced in MCI converters compared to MCI nonconverters in distributed areas, including the medial frontal lobe. Thickness and LGI metrics presented a reduction in AD compared to HC. Thickness was significantly reduced in MCI converters compared to healthy controls in entorhinal cortex and lateral temporal. In summary, SHFD was the only surface measure showing differences between MCI individuals that will convert or remain stable in the next 4 years. We suggest that SHFD may be an optimal complement to thickness loss analysis in monitoring longitudinal changes in preclinical and clinical stages of AD. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Analysis of vascular homogeneity and anisotropy on high-resolution primate brain imaging


Using a systematic investigation of brain blood volume, in high-resolution synchrotron 3D images of microvascular structures within cortical regions of a primate brain, we challenge several basic questions regarding possible vascular bias in high-resolution functional neuroimaging. We present a bilateral comparison of cortical regions, where we analyze relative vascular volume in voxels from 150 to 1000 μm side lengths in the white and grey matter. We show that, if voxel size reaches a scale smaller than 300 µm, the vascular volume can no longer be considered homogeneous, either within one hemisphere or in bilateral comparison between samples. We demonstrate that voxel size influences the comparison between vessel-relative volume distributions depending on the scale considered (i.e., hemisphere, lobe, or sample). Furthermore, we also investigate how voxel anisotropy and orientation can affect the apparent vascular volume, in accordance with actual fMRI voxel sizes. These findings are discussed from the various perspectives of high-resolution brain functional imaging. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Multiple functional networks modeling for autism spectrum disorder diagnosis


Despite countless studies on autism spectrum disorder (ASD), diagnosis relies on specific behavioral criteria and neuroimaging biomarkers for the disorder are still relatively scarce and irrelevant for diagnostic workup. Many researchers have focused on functional networks of brain activities using resting-state functional magnetic resonance imaging (rsfMRI) to diagnose brain diseases, including ASD. Although some existing methods are able to reveal the abnormalities in functional networks, they are either highly dependent on prior assumptions for modeling these networks or do not focus on latent functional connectivities (FCs) by considering discriminative relations among FCs in a nonlinear way. In this article, we propose a novel framework to model multiple networks of rsfMRI with data-driven approaches. Specifically, we construct large-scale functional networks with hierarchical clustering and find discriminative connectivity patterns between ASD and normal controls (NC). We then learn features and classifiers for each cluster through discriminative restricted Boltzmann machines (DRBMs). In the testing phase, each DRBM determines whether a test sample is ASD or NC, based on which we make a final decision with a majority voting strategy. We assess the diagnostic performance of the proposed method using public datasets and describe the effectiveness of our method by comparing it to competing methods. We also rigorously analyze FCs learned by DRBMs on each cluster and discover dominant FCs that play a major role in discriminating between ASD and NC. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Dynamic causal modeling in PTSD and its dissociative subtype: Bottom–up versus top–down processing within fear and emotion regulation circuitry


Objective Posttraumatic stress disorder (PTSD) is associated with decreased top–down emotion modulation from medial prefrontal cortex (mPFC) regions, a pathophysiology accompanied by hyperarousal and hyperactivation of the amygdala. By contrast, PTSD patients with the dissociative subtype (PTSD + DS) often exhibit increased mPFC top–down modulation and decreased amygdala activation associated with emotional detachment and hypoarousal. Crucially, PTSD and PTSD + DS display distinct functional connectivity within the PFC, amygdala complexes, and the periaqueductal gray (PAG), a region related to defensive responses/emotional coping. However, differences in directed connectivity between these regions have not been established in PTSD, PTSD + DS, or controls. Methods: To examine directed (effective) connectivity among these nodes, as well as group differences, we conducted resting-state stochastic dynamic causal modeling (sDCM) pairwise analyses of coupling between the ventromedial (vm)PFC, the bilateral basolateral and centromedial (CMA) amygdala complexes, and the PAG, in 155 participants (PTSD [n = 62]; PTSD + DS [n = 41]; age-matched healthy trauma-unexposed controls [n = 52]). Results: PTSD was characterized by a pattern of predominant bottom–up connectivity from the amygdala to the vmPFC and from the PAG to the vmPFC and amygdala. Conversely, PTSD + DS exhibited predominant top–down connectivity between all node pairs (from the vmPFC to the amygdala and PAG, and from the amygdala to the PAG). Interestingly, the PTSD + DS group displayed the strongest intrinsic inhibitory connections within the vmPFC. Conclusions: These results suggest the contrasting symptom profiles of PTSD and its dissociative subtype (hyper- vs. hypo-emotionality, respectively) may be driven by complementary changes in directed connectivity corresponding to bottom–up defensive fear processing versus enhanced top–down regulation. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Taking tests in the magnet: Brain mapping standardized tests


Standardized psychometric tests are sophisticated, well-developed, and consequential instruments; test outcomes are taken as facts about people that impact their lives in important ways. As part of an initial demonstration that human brain mapping techniques can add converging neural-level evidence to understanding standardized tests, our participants completed items from standardized tests during an fMRI scan. We compared tests for diagnosing posttraumatic stress disorder (PTSD) and the correlated measures of Neuroticism, Attachment, and Centrality of Event to a general-knowledge baseline test. Twenty-three trauma-exposed participants answered 20 items for each of our five tests in each of the three runs for a total of 60 items per test. The tests engaged different neural processes; which test a participant was taking was accurately predicted from other participants' brain activity. The novelty of the application precluded specific anatomical predictions; however, the interpretation of activated regions using meta-analyses produced encouraging results. For instance, items on the Attachment test engaged regions shown to be more active for tasks involving judgments of others than judgments of the self. The results are an initial demonstration of a theoretically and practically important test-taking neuroimaging paradigm and suggest specific neural processes in answering PTSD-related tests. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Brain activity induced by implicit processing of others' pain and pleasure


Studies indicate that both explicit and implicit processing of affectively charged stimuli may be reflected in specific behavioural markers and physiological signatures. Here, we investigated whether the pleasantness ratings of a neutral target were affected by the subliminal perception of a painful (a slap) or pleasant (a caress) touch delivered to others. In particular, we combined the continuous flash suppression technique with the affective misattribution procedure to explore subliminal processing of observed pain and pleasure in others. Results show that participants rated the neutral target as more or less likeable depending on whether they were subliminally primed with the pleasant or painful facial expression, respectively. The fMRI activity associated with painful and pleasant subliminal priming was mainly present in the anterior prefrontal cortex and the primary sensorimotor cortex, respectively. Thus, our study provides behavioural and neuro-physiological evidence that: (i) emotional reactivity toward positive or negative states of others can occur at an entirely subliminal level; (ii) specific neural substrates underpin reactivity to positive- and negative-valence of social emotions. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Decoding fMRI events in sensorimotor motor network using sparse paradigm free mapping and activation likelihood estimates


Most functional MRI (fMRI) studies map task-driven brain activity using a block or event-related paradigm. Sparse paradigm free mapping (SPFM) can detect the onset and spatial distribution of BOLD events in the brain without prior timing information, but relating the detected events to brain function remains a challenge. In this study, we developed a decoding method for SPFM using a coordinate-based meta-analysis method of activation likelihood estimation (ALE). We defined meta-maps of statistically significant ALE values that correspond to types of events and calculated a summation overlap between the normalized meta-maps and SPFM maps. As a proof of concept, this framework was applied to relate SPFM-detected events in the sensorimotor network (SMN) to six motor functions (left/right fingers, left/right toes, swallowing, and eye blinks). We validated the framework using simultaneous electromyography (EMG)–fMRI experiments and motor tasks with short and long duration, and random interstimulus interval. The decoding scores were considerably lower for eye movements relative to other movement types tested. The average successful rate for short and long motor events were 77 ± 13% and 74 ± 16%, respectively, excluding eye movements. We found good agreement between the decoding results and EMG for most events and subjects, with a range in sensitivity between 55% and 100%, excluding eye movements. The proposed method was then used to classify the movement types of spontaneous single-trial events in the SMN during resting state, which produced an average successful rate of 22 ± 12%. Finally, this article discusses methodological implications and improvements to increase the decoding performance. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Calibrated imaging reveals altered grey matter metabolism related to white matter microstructure and symptom severity in multiple sclerosis


Multiple sclerosis (MS) involves damage to white matter microstructures. This damage has been related to grey matter function as measured by standard, physiologically-nonspecific neuroimaging indices (i.e., blood-oxygen-level dependent signal [BOLD]). Here, we used calibrated functional magnetic resonance imaging and diffusion tensor imaging to examine the extent to which specific, evoked grey matter physiological processes were associated with white matter diffusion in MS. Evoked changes in BOLD, cerebral blood flow (CBF), and oxygen metabolism (CMRO2) were measured in visual cortex. Individual differences in the diffusion tensor measure, radial diffusivity, within occipital tracts were strongly associated with MS patients' BOLD and CMRO2. However, these relationships were in opposite directions, complicating the interpretation of the relationship between BOLD and white matter microstructural damage in MS. CMRO2 was strongly associated with individual differences in patients' fatigue and neurological disability, suggesting that alterations to evoked oxygen metabolic processes may be taken as a marker for primary symptoms of MS. This work demonstrates the first application of calibrated and diffusion imaging together and details the first application of calibrated functional MRI in a neurological population. Results lend support for neuroenergetic hypotheses of MS pathophysiology and provide an initial demonstration of the utility of evoked oxygen metabolism signals for neurology research. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Changes to white matter microstructure in transient ischemic attack: A longitudinal diffusion tensor imaging study


Transient ischemic attack (TIA) is associated with localized ischemic changes, identifiable by diffusion-weighted imaging. Past research has not considered whether TIA is also associated with diffuse changes to white matter microstructure; further past work has not tracked changes longitudinally. Here we examine whole-brain changes in fractional anisotropy (FA) in individuals with TIA presenting with sensorimotor symptoms. Twenty individuals with a recent (within 30 days) TIA and 12 healthy older adults were recruited. Participants underwent 3.0 T diffusion MRI at baseline; scans were repeated for the TIA group 90 days post-TIA. Track-based spatial statistics (TBSS) was used to conduct a voxel-wise analysis of FA between groups. FA was significantly lower in the TIA group relative to healthy controls, primarily in anterior white matter tracts including: forceps minor, anterior thalamic radiations, cingulum, inferior fronto-occipital fasciculus, and corticospinal tract. TBSS results informed an ROI-based longitudinal examination of FA in the TIA group. There were no changes to TBSS-identified clusters, forceps minor, or the corticospinal tract over time. There was lower FA in the anterior thalamic radiations in the TIA-affected hemisphere at baseline, but no difference between hemispheres at 90 days. In summary, individuals with TIA presenting with sensorimotor symptoms have decreased FA in tracts that are also implicated in sensorimotor function, which outlast the clinical symptoms associated with TIA. This suggests a more profound type of brain damage associated with TIA than has been typically described in past work. Diffusion tensor imaging may have utility as a marker of TIA-associated changes to white matter pathways. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Audiovisual integration as conflict resolution: The conflict of the McGurk illusion


There are two main behavioral expressions of multisensory integration (MSI) in speech; the perceptual enhancement produced by the sight of the congruent lip movements of the speaker, and the illusory sound perceived when a speech syllable is dubbed with incongruent lip movements, in the McGurk effect. These two models have been used very often to study MSI. Here, we contend that, unlike congruent audiovisually (AV) speech, the McGurk effect involves brain areas related to conflict detection and resolution. To test this hypothesis, we used fMRI to measure blood oxygen level dependent responses to AV speech syllables. We analyzed brain activity as a function of the nature of the stimuli—McGurk or non-McGurk—and the perceptual outcome regarding MSI—integrated or not integrated response—in a 2 × 2 factorial design. The results showed that, regardless of perceptual outcome, AV mismatch activated general-purpose conflict areas (e.g., anterior cingulate cortex) as well as specific AV speech conflict areas (e.g., inferior frontal gyrus), compared with AV matching stimuli. Moreover, these conflict areas showed stronger activation on trials where the McGurk illusion was perceived compared with non-illusory trials, despite the stimuli where physically identical. We conclude that the AV incongruence in McGurk stimuli triggers the activation of conflict processing areas and that the process of resolving the cross-modal conflict is critical for the McGurk illusion to arise. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Intrinsic functional connectivity variance and state-specific under-connectivity in autism


Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with altered brain connectivity. Previous neuroimaging research demonstrates inconsistent results, particularly in studies of functional connectivity in ASD. Typically, these inconsistent findings are results of studies using static measures of resting-state functional connectivity. Recent work has demonstrated that functional brain connections are dynamic, suggesting that static connectivity metrics fail to capture nuanced time-varying properties of functional connections in the brain. Here we used a dynamic functional connectivity approach to examine the differences in the strength and variance of dynamic functional connections between individuals with ASD and healthy controls (HCs). The variance of dynamic functional connections was defined as the respective standard deviations of the dynamic functional connectivity strength across time. We utilized a large multicenter dataset of 507 male subjects (209 with ASD and 298 HC, from 6 to 36 years old) from the Autism Brain Imaging Data Exchange (ABIDE) to identify six distinct whole-brain dynamic functional connectivity states. Analyses demonstrated greater variance of widespread long-range dynamic functional connections in ASD (P < 0.05, NBS method) and weaker dynamic functional connections in ASD (P < 0.05, NBS method) within specific whole-brain connectivity states. Hypervariant dynamic connections were also characterized by weaker connectivity strength in ASD compared with HC. Increased variance of dynamic functional connections was also related to ASD symptom severity (ADOS total score) (P < 0.05), and was most prominent in connections related to the medial superior frontal gyrus and temporal pole. These results demonstrate that greater intraindividual dynamic variance is a potential biomarker of ASD. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Progression of regional atrophy in the left hemisphere contributes to clinical and cognitive deterioration in multiple sclerosis: A 5-year study


In this longitudinal study, we investigated the regional patterns of focal lesions accumulation, and gray (GM) and white matter (WM) atrophy progression over a five-year follow-up (FU) in multiple sclerosis (MS) patients and their association with clinical and cognitive deterioration. Neurological, neuropsychological and brain MRI (dual-echo and 3D T1-weighted sequences) assessments were prospectively performed at baseline (T0) and after a median FU of 4.9 years from 66 MS patients (including relapse-onset and primary progressive MS) and 16 matched controls. Lesion probability maps were obtained. Longitudinal changes of GM and WM volumes and their association with clinical and cognitive deterioration were assessed using tensor-based morphometry and SPM12. At FU, 36/66 (54.5%) MS patients showed a significant disability worsening, 14/66 (21.2%) evolved to a worse clinical phenotype, and 18/63 (28.6%) developed cognitive deterioration. At T0, compared to controls, MS patients showed a widespread pattern of GM atrophy, involving cortex, deep GM and cerebellum, and atrophy of the majority of WM tracts, which further progressed at FU (P < 0.001, uncorrected). Compared to stable patients, those with clinical and cognitive worsening showed a left-lateralized pattern of GM and WM atrophy, involving deep GM, fronto-temporo-parieto-occipital regions, cerebellum, and several WM tracts (P < 0.001, uncorrected).GM and WM atrophy of relevant brain regions occur in MS after 5 years. A different vulnerability of the two brain hemispheres to irreversible structural damage may be among the factors contributing to clinical and cognitive worsening in these patients. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Combining task-related activation and connectivity analysis of fMRI data reveals complex modulation of brain networks


Task-related effects in functional magnetic resonance imaging (fMRI) data are usually analyzed with local activation approaches or integrative connectivity approaches, for example, by psychophysiological interaction (PPI) analysis. While both approaches are often applied to the same data set, a systematic combination of the results with a whole-brain (WB) perspective is rarely conducted and the relationship between task-dependent activation and connectivity effects is relatively unexplored. Here, we combined brain activation and graph theoretical analysis of WB-PPI results in an exemplary episodic memory data set of N = 136 healthy human participants and found regions with congruent as well as incongruent activation and connectivity changes between task and control conditions. A comparison with large-scale resting state networks showed that in congruent as well as incongruent regions task-positively modulated connections were mainly between-network connections, especially with the default mode network, while task-negatively modulated connections were mainly found within resting state networks. Over all regions, the strength of absolute activation effects was associated with the tendency to exhibit task-positive connectivity changes, mainly driven by a strong relationship in negatively activated regions. These results demonstrate that task demands lead to a complex modulation of brain networks and provide evidence that task-evoked activation and connectivity effects reflect separable and complementary information on the macroscale brain level assessed by fMRI. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Neural predictors of motor control and impact of visuo-proprioceptive information in youth


For successful motor control, the central nervous system is required to combine information from the environment and the current body state, which is provided by vision and proprioception respectively. We investigated the relative contribution of visual and proprioceptive information to upper limb motor control and the extent to which structural brain measures predict this performance in youth (n = 40; age range 9–18 years). Participants performed a manual tracking task, adopting in-phase and anti-phase coordination modes. Results showed that, in contrast to older participants, younger participants performed the task with lower accuracy in general and poorer performance in anti-phase than in-phase modes. However, a proprioceptive advantage was found at all ages, that is, tracking accuracy was higher when proprioceptive information was available during both in- and anti-phase modes at all ages. The microstructural organization of interhemispheric connections between homologous dorsolateral prefrontal cortices, and the cortical thickness of the primary motor cortex were associated with sensory-specific accuracy of tracking performance. Overall, the findings suggest that manual tracking performance in youth does not only rely on brain regions involved in sensorimotor processing, but also on prefrontal regions involved in attention and working memory. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

The effects of memory training on behavioral and microstructural plasticity in young and older adults


Age differences in human brain plasticity are assumed, but have not been systematically investigated. In this longitudinal study, we investigated changes in white matter (WM) microstructure in response to memory training relative to passive and active control conditions in 183 young and older adults. We hypothesized that (i) only the training group would show improved memory performance and microstructural alterations, (ii) the young adults would show larger memory improvement and a higher degree of microstructural alterations as compared to the older adults, and (iii) changes in memory performance would relate to microstructural alterations. The results showed that memory improvement was specific to the training group, and that both the young and older participants improved their performance. The young group improved their memory to a larger extent compared to the older group. In the older sample, the training group showed less age-related decline in WM microstructure compared to the control groups, in areas overlapping the corpus callosum, the cortico-spinal tract, the cingulum bundle, the superior longitudinal fasciculus, and the anterior thalamic radiation. Less microstructural decline was related to a higher degree of memory improvement. Despite individual adaptation securing sufficient task difficulty, no training-related group differences in microstructure were found in the young adults. The observed divergence of behavioral and microstructural responses to memory training with age is discussed within a supply-demand framework. The results demonstrate that plasticity is preserved into older age, and that microstructural alterations may be part of a neurobiological substrate for behavioral improvements in older adults. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Enhanced estimations of post-stroke aphasia severity using stacked multimodal predictions


The severity of post-stroke aphasia and the potential for recovery are highly variable and difficult to predict. Evidence suggests that optimal estimation of aphasia severity requires the integration of multiple neuroimaging modalities and the adoption of new methods that can detect multivariate brain-behavior relationships. We created and tested a multimodal framework that relies on three information sources (lesion maps, structural connectivity, and functional connectivity) to create an array of unimodal predictions which are then fed into a final model that creates “stacked multimodal predictions” (STAMP). Crossvalidated predictions of four aphasia scores (picture naming, sentence repetition, sentence comprehension, and overall aphasia severity) were obtained from 53 left hemispheric chronic stroke patients (age: 57.1 ± 12.3 yrs, post-stroke interval: 20 months, 25 female). Results showed accurate predictions for all four aphasia scores (correlation true vs. predicted: r = 0.79–0.88). The accuracy was slightly smaller but yet significant (r = 0.66) in a full split crossvalidation with each patient considered as new. Critically, multimodal predictions produced more accurate results that any single modality alone. Topological maps of the brain regions involved in the prediction were recovered and compared with traditional voxel-based lesion-to-symptom maps, revealing high spatial congruency. These results suggest that neuroimaging modalities carry complementary information potentially useful for the prediction of aphasia scores. More broadly, this study shows that the translation of neuroimaging findings into clinically useful tools calls for a shift in perspective from unimodal to multimodal neuroimaging, from univariate to multivariate methods, from linear to nonlinear models, and, conceptually, from inferential to predictive brain mapping. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Deep learning with convolutional neural networks for EEG decoding and visualization


Deep learning with convolutional neural networks (deep ConvNets) has revolutionized computer vision through end-to-end learning, that is, learning from the raw data. There is increasing interest in using deep ConvNets for end-to-end EEG analysis, but a better understanding of how to design and train ConvNets for end-to-end EEG decoding and how to visualize the informative EEG features the ConvNets learn is still needed. Here, we studied deep ConvNets with a range of different architectures, designed for decoding imagined or executed tasks from raw EEG. Our results show that recent advances from the machine learning field, including batch normalization and exponential linear units, together with a cropped training strategy, boosted the deep ConvNets decoding performance, reaching at least as good performance as the widely used filter bank common spatial patterns (FBCSP) algorithm (mean decoding accuracies 82.1% FBCSP, 84.0% deep ConvNets). While FBCSP is designed to use spectral power modulations, the features used by ConvNets are not fixed a priori. Our novel methods for visualizing the learned features demonstrated that ConvNets indeed learned to use spectral power modulations in the alpha, beta, and high gamma frequencies, and proved useful for spatially mapping the learned features by revealing the topography of the causal contributions of features in different frequency bands to the decoding decision. Our study thus shows how to design and train ConvNets to decode task-related information from the raw EEG without handcrafted features and highlights the potential of deep ConvNets combined with advanced visualization techniques for EEG-based brain mapping. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

The role of vascular resistance in BOLD responses to progressive hypercapnia


The ability of the cerebral vasculature to regulate vascular diameter, hence resistance and cerebral blood flow (CBF), in response to metabolic demands (neurovascular coupling), and perfusion pressure changes (autoregulation) may be assessed by measuring the CBF response to carbon dioxide (CO2). In healthy individuals, the CBF response to a ramp CO2 stimulus from hypocapnia to hypercapnia is assumed sigmoidal or linear. However, other response patterns commonly occur, especially in individuals with cerebrovascular disease, and these remain unexplained. CBF responses to CO2 in a vascular region are determined by the combined effects of the innate vascular responses to CO2 and the local perfusion pressure; the latter ensuing from pressure-flow interactions within the cerebral vascular network. We modeled this situation as two vascular beds perfused in parallel from a fixed resistance source. Our premise is that all vascular beds have a sigmoidal reduction of resistance in response to a progressive rise in CO2. Surrogate CBF data to test the model was provided by magnetic resonance imaging of blood oxygen level-dependent (BOLD) signals. The model successfully generated all the various BOLD-CO2 response patterns, providing a physiological explanation of CBF distribution as relative differences in the network of vascular bed resistance responses to CO2. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Distinguishing stimulus and response codes in theta oscillations in prefrontal areas during inhibitory control of automated responses


Response inhibition mechanisms are mediated via cortical and subcortical networks. At the cortical level, the superior frontal gyrus, including the supplementary motor area (SMA) and inferior frontal areas, is important. There is an ongoing debate about the functional roles of these structures during response inhibition as it is unclear whether these structures process different codes or contents of information during response inhibition. In the current study, we examined this question with a focus on theta frequency oscillations during response inhibition processes. We used a standard Go/Nogo task in a sample of human participants and combined different EEG signal decomposition methods with EEG beamforming approaches. The results suggest that stimulus coding during inhibitory control is attained by oscillations in the upper theta frequency band (∼7 Hz). In contrast, response selection codes during inhibitory control appear to be attained by the lower theta frequency band (∼4 Hz). Importantly, these different codes seem to be processed in distinct functional neuroanatomical structures. Although the SMA may process stimulus codes and response selection codes, the inferior frontal cortex may selectively process response selection codes during inhibitory control. Taken together, the results suggest that different entities within the functional neuroanatomical network associated with response inhibition mechanisms process different kinds of codes during inhibitory control. These codes seem to be reflected by different oscillations within the theta frequency band. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

AxTract: Toward microstructure informed tractography


Diffusion-weighted (DW) magnetic resonance imaging (MRI) tractography has become the tool of choice to probe the human brain's white matter in vivo. However, tractography algorithms produce a large number of erroneous streamlines (false positives), largely due to complex ambiguous tissue configurations. Moreover, the relationship between the resulting streamlines and the underlying white matter microstructure characteristics remains poorly understood. In this work, we introduce a new approach to simultaneously reconstruct white matter fascicles and characterize the apparent distribution of axon diameters within fascicles. To achieve this, our method, AxTract, takes full advantage of the recent development DW-MRI microstructure acquisition, modeling, and reconstruction techniques. This enables AxTract to separate parallel fascicles with different microstructure characteristics, hence reducing ambiguities in areas of complex tissue configuration. We report a decrease in the incidence of erroneous streamlines compared to the conventional deterministic tractography algorithms on simulated data. We also report an average increase in streamline density over 15 known fascicles of the 34 healthy subjects. Our results suggest that microstructure information improves tractography in crossing areas of the white matter. Moreover, AxTract provides additional microstructure information along the fascicle that can be studied alongside other streamline-based indices. Overall, AxTract provides the means to distinguish and follow white matter fascicles using their microstructure characteristics, bringing new insights into the white matter organization. This is a step forward in microstructure informed tractography, paving the way to a new generation of algorithms able to deal with intricate configurations of white matter fibers and providing quantitative brain connectivity analysis. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Neural correlates of “Theory of Mind” in very preterm born children


Very preterm (VPT) birth (<32 weeks' gestational age) has been implicated in social-cognitive deficits including Theory of Mind (ToM); the ability to attribute mental states to others and understand that those beliefs can differ from one's own or reality. The neural bases for ToM deficits in VPT born children have not been examined. We used magnetoencephalography (MEG) for its excellent spatial and temporal resolution to determine the neural underpinnings of ToM in 24 VPT and 24 full-term born (FT) children (7–13 years). VPT children performed more poorly on neuropsychological measures of ToM but not inhibition. In the MEG task, both FT children and VPT children recruited regions involved in false belief processing such as the rIFG (VPT: 275–350 ms, FT: 250–375 ms) and left inferior temporal gyrus (VPT: 375–450 ms, FT: 325–375 ms) and right fusiform gyrus (VPT: 150–200 ms, FT: 175–250 ms). The rIPL (included in the temporal-parietal junction) was recruited in FT children (475–575 ms) and the lTPJ in VPT children (500–575 ms). However, activations in all regions were reduced in the VPT compared to the FT group. We suggest that with increasing social-cognitive demands such as varying the type of scenarios in the standardized measure of ToM, reduced activations in the rIFG and TPJ in the VPT group may reflect the decreased performance. With access to both spatial and temporal information, we discuss the role of domain general and specific regions of the ToM network in both groups. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Visually stressful striped patterns alter human visual cortical functional connectivity


Visually stressful striped patterns with a spatial frequency (SF) of around 3 cycles per degree (cpd) can induce perceptual illusions/distortions and visual discomfort in most people, headaches in patients with migraine, and seizures in patients with photosensitive epilepsy. Patterns with SF ∼0.3 cpd have no such effects and are not uncomfortable to look at (non-stressful). The effects of the striped patterns on visual cortical activation have been investigated, but their effects on the visual cortical network remain to be studied. A prolonged visual stimulation with stressful patterns may alter the functional connections within the visual system, and their relationship with other networks. Using resting-state fMRI, this study revealed that the functional connections within the visual system were significantly enhanced by visually stressful stimulation. The functional connectivity between V1 and other brain regions was also significantly modified. Non-stressful stimulation produced no such significant effects. More importantly, the effects outlasted the stimulation, and this applied both to those effects within and those beyond the visual cortex, suggesting that repeated prolonged visual stimulation with stressful patterns may alter functional connections of the brain and this might be utilized as a visual neuromodulation approach for treatments of visually triggered headaches in migraine patients and visually induced seizures in patients with photosensitive epilepsy. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Electrophysiological correlates of the drift diffusion model in visual word recognition


This study was designed to explore the electrophysiological correlates of the diffusion models drift rate parameter in cognitive decision making. Eighty-two participants completed a lexical decision task while their stimulus-dependent event-related potentials (ERP) and theta frequency band power were measured. A mass univariate approach was applied to examine the timeline at which correlations were evident. Individual differences in drift rate parameter and condition-wise within-subject differences in drift rates for word emotionality and item repetition were found to be related to amplitude differences in the late positive complex (LPC). No relations to theta frequency band power changes were obtained. The drift rate parameter captures information accumulation of noisy evidence, while LPC amplitudes are discussed to reflect the strength of a memory trace. While these results point to a common underlying cognitive mechanism to explain drift rates and LPC modulation, they also provide a new angle on the timeline of visual word processing following word identification. Further confirmations of the results are needed to approve the LPC as neurophysiological marker of information accumulation. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

The relationship between subcortical brain volume and striatal dopamine D2/3 receptor availability in healthy humans assessed with [11C]-raclopride and [11C]-(+)-PHNO PET


Background Abnormalities in dopamine (DA) and brain morphology are observed in several neuropsychiatric disorders. However, it is not fully understood how these abnormalities may relate to one another. For such in vivo findings to be used as biomarkers for neuropsychiatric disease, it must be understood how variability in DA relates to brain structure under healthy conditions. We explored how the availability of striatal DA D2/3 receptors (D2/3R) is related to the volume of subcortical brain structures in a sample of healthy humans. Differences in D2/3R availability measured with an antagonist radiotracer ([11C]-raclopride) versus an agonist radiotracer ([11C]-(+)-PHNO) were examined. Methods Data from 62 subjects scanned with [11C]-raclopride (mean age = 38.98 ± 14.45; 23 female) and 68 subjects scanned with [11C]-(+)-PHNO (mean age = 38.54 ± 14.59; 25 female) were used. Subcortical volumes were extracted from T1-weighted images using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm. Partial correlations were used controlling for age, gender, and total brain volume. Results For [11C]-(+)-PHNO, ventral caudate volumes were positively correlated with BPND in the dorsal caudate and globus pallidus (GP). Ventral striatum (VS) volumes were positively correlated with BPND in the VS. With [11C]-raclopride, BPND in the VS was negatively correlated with subiculum volume of the hippocampus. Moreover, BPND in the GP was negatively correlated with the volume of the lateral posterior nucleus of the thalamus. Conclusion Findings are purely exploratory and presented corrected and uncorrected for multiple comparisons. We hope they will help inform the interpretation of future PET studies where concurrent changes in D2/3R and brain morphology are observed. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Mothers with substance addictions show reduced reward responses when viewing their own infant's face


Maternal addiction constitutes a major public health problem affecting children, with high rates of abuse, neglect, and foster care placement. However, little is known about the ways in which substance addiction alters brain function related to maternal behavior. Prior studies have shown that infant face cues activate similar dopamine-associated brain reward regions to substances of abuse. Here, we report on a functional MRI study documenting that mothers with addictions demonstrate reduced activation of reward regions when shown reward-related cues of their own infants. Thirty-six mothers receiving inpatient treatment for substance addiction were scanned at 6 months postpartum, while viewing happy and sad face images of their own infant compared to those of a matched unknown infant. When viewing happy face images of their own infant, mothers with addictions showed a striking pattern of decreased activation in dopamine- and oxytocin-innervated brain regions, including the hypothalamus, ventral striatum, and ventromedial prefrontal cortex—regions in which increased activation has previously been observed in mothers without addictions. Our results are the first to demonstrate that mothers with addictions show reduced activation in key reward regions of the brain in response to their own infant's face cues. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

The impact of T1 versus EPI spatial normalization templates for fMRI data analyses


Spatial normalization of brains to a standardized space is a widely used approach for group studies in functional magnetic resonance imaging (fMRI) data. Commonly used template-based approaches are complicated by signal dropout and distortions in echo planar imaging (EPI) data. The most widely used software packages implement two common template-based strategies: (1) affine transformation of the EPI data to an EPI template followed by nonlinear registration to an EPI template (EPInorm) and (2) affine transformation of the EPI data to the anatomic image for a given subject, followed by nonlinear registration of the anatomic data to an anatomic template, which produces a transformation that is applied to the EPI data (T1norm). EPI distortion correction can be used to adjust for geometric distortion of EPI relative to the T1 images. However, in practice, this EPI distortion correction step is often skipped. We compare these template-based strategies empirically in four large datasets. We find that the EPInorm approach consistently shows reduced variability across subjects, especially in the case when distortion correction is not applied. EPInorm also shows lower estimates for coregistration distances among subjects (i.e., within-dataset similarity is higher). Finally, the EPInorm approach shows higher T values in a task-based dataset. Thus, the EPInorm approach appears to amplify the power of the sample compared to the T1norm approach when not using distortion correction (i.e., the EPInorm boosts the effective sample size by 12–25%). In sum, these results argue for the use of EPInorm over the T1norm when no distortion correction is used. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Neural substrates of context- and person-dependent altruistic punishment


Human altruistic behaviors are heterogeneous across both contexts and people, whereas the neural signatures underlying the heterogeneity remain to be elucidated. To address this issue, we examined the neural signatures underlying the context- and person-dependent altruistic punishment, conjoining event-related fMRI with both task-based and resting-state functional connectivity (RSFC). Acting as an impartial third party, participants decided how to punish norm violators either alone or in the presence of putative others. We found that the presence of others decreased altruistic punishment due to diffusion of responsibility. Those behavioral effects paralleled altered neural responses in the dorsal anterior cingulate cortex (dACC) and putamen. Further, we identified modulation of responsibility diffusion on task-based functional connectivity of dACC with the brain regions implicated in reward processing (i.e., posterior cingulate cortex and amygdala/orbital frontal cortex). Finally, the RSFC results revealed that (i) increased intrinsic connectivity strengths of the putamen with temporoparietal junction and dorsolateral PFC were associated with attenuated responsibility diffusion in altruistic punishment and (ii) increased putamen-dorsomedial PFC connectivity strengths were associated with reduced responsibility diffusion in self-reported responsibility. Taken together, our findings elucidate the context- and person-dependent altruistic behaviors as well as associated neural substrates and thus provide a potential neurocognitive mechanism of heterogeneous human altruistic behaviors. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Abnormal functional activation and maturation of ventromedial prefrontal cortex and cerebellum during temporal discounting in autism spectrum disorder


People with autism spectrum disorder (ASD) have poor decision-making and temporal foresight. This may adversely impact on their everyday life, mental health, and productivity. However, the neural substrates underlying poor choice behavior in people with ASD, or its' neurofunctional development from childhood to adulthood, are unknown. Despite evidence of atypical structural brain development in ASD, investigation of functional brain maturation in people with ASD is lacking. This cross-sectional developmental fMRI study investigated the neural substrates underlying performance on a temporal discounting (TD) task in 38 healthy (11–35 years old) male adolescents and adults with ASD and 40 age, sex, and IQ-matched typically developing healthy controls. Most importantly, we assessed group differences in the neurofunctional maturation of TD across childhood and adulthood. Males with ASD had significantly poorer task performance and significantly lower brain activation in typical regions that mediate TD for delayed choices, in predominantly right hemispheric regions of ventrolateral/dorsolateral prefrontal cortices, ventromedial prefrontal cortex, striatolimbic regions, and cerebellum. Importantly, differential activation in ventromedial frontal cortex and cerebellum was associated with abnormal functional brain maturation; controls, in contrast to people with ASD, showed progressively increasing activation with increasing age in these regions; which furthermore was associated with performance measures and clinical ASD measures (stereotyped/restricted interests). Findings provide first cross-sectional evidence that reduced activation of TD mediating brain regions in people with ASD during TD is associated with abnormal functional brain development in these regions between childhood and adulthood, and this is related to poor task performance and clinical measures of ASD. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Cortical connectivity modulation during sleep onset: A study via graph theory on EEG data


Sleep onset is characterized by a specific and orchestrated pattern of frequency and topographical EEG changes. Conventional power analyses of electroencephalographic (EEG) and computational assessments of network dynamics have described an earlier synchronization of the centrofrontal areas rhythms and a spread of synchronizing signals from associative prefrontal to posterior areas. Here, we assess how “small world” characteristics of the brain networks, as reflected in the EEG rhythms, are modified in the wakefulness–sleep transition comparing the pre- and post-sleep onset epochs. The results show that sleep onset is characterized by a less ordered brain network (as reflected by the higher value of small world) in the sigma band for the frontal lobes indicating stronger connectivity, and a more ordered brain network in the low frequency delta and theta bands indicating disconnection on the remaining brain areas. Our results depict the timing and topography of the specific mechanisms for the maintenance of functional connectivity of frontal brain regions at the sleep onset, also providing a possible explanation for the prevalence of the frontal-to-posterior information flow directionality previously observed after sleep onset. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Neural signature of inattentional deafness


Inattentional deafness is the failure to hear otherwise audible sounds (usually alarms) that may occur under high workload conditions. One potential cause for its occurrence could be an attentional bottleneck that occurs when task demands are high, resulting in lack of resources for processing of additional tasks. In this fMRI experiment, we explore the brain regions active during the occurrence of inattentional deafness using a difficult perceptual-motor task in which the participants fly through a simulated Red Bull air race course and at the same time push a button on the joystick to the presence of audio alarms. Participants were instructed to focus on the difficult piloting task and to press the button on the joystick quickly when they noticed an audio alarm. The fMRI results revealed that audio misses relative to hits had significantly greater activity in the right inferior frontal gyrus IFG and the superior medial frontal cortex. Consistent with an attentional bottleneck, activity in these regions was also present for poor flying performance (contrast of gates missed versus gates passed for the flying task). A psychophysiological interaction analysis from the IFG identified reduced effective connectivity to auditory processing regions in the right superior temporal gyrus for missed audio alarms relative to audio alarms that were heard. This study identifies a neural signature of inattentional deafness in an ecologically valid situation by directly measuring differences in brain activity and effective connectivity between audio alarms that were not heard compared to those that were heard. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Associations between self-reported sleep quality and white matter in community-dwelling older adults: A prospective cohort study


Both sleep disturbances and decline in white matter microstructure are commonly observed in ageing populations, as well as in age-related psychiatric and neurological illnesses. A relationship between sleep and white matter microstructure may underlie such relationships, but few imaging studies have directly examined this hypothesis. In a study of 448 community-dwelling members of the Whitehall II Imaging Sub-Study aged between 60 and 82 years (90 female, mean age 69.2 ± 5.1 years), we used the magnetic resonance imaging technique diffusion tensor imaging to examine the relationship between self-reported sleep quality and white matter microstructure. Poor sleep quality at the time of the diffusion tensor imaging scan was associated with reduced global fractional anisotropy and increased global axial diffusivity and radial diffusivity values, with small effect sizes. Voxel-wise analysis showed that widespread frontal-subcortical tracts, encompassing regions previously reported as altered in insomnia, were affected. Radial diffusivity findings remained significant after additional correction for demographics, general cognition, health, and lifestyle measures. No significant differences in general cognitive function, executive function, memory, or processing speed were detected between good and poor sleep quality groups. The number of times participants reported poor sleep quality over five time-points spanning a 16-year period was not associated with white matter measures. In conclusion, these data demonstrate that current sleep quality is linked to white matter microstructure. Small effect sizes may limit the extent to which poor sleep is a promising modifiable factor that may maintain, or even improve, white matter microstructure in ageing. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Dynamic coupling between fMRI local connectivity and interictal EEG in focal epilepsy: A wavelet analysis approach


Simultaneous scalp EEG-fMRI recording is a noninvasive neuroimaging technique for combining electrophysiological and hemodynamic aspects of brain function. Despite the time-varying nature of both measurements, their relationship is usually considered as time-invariant. The aim of this study was to detect direct associations between scalp-recorded EEG and regional changes of hemodynamic brain connectivity in focal epilepsy through a time-frequency paradigm. To do so, we developed a voxel-wise framework that analyses wavelet coherence between dynamic regional phase synchrony (DRePS, calculated from fMRI) and band amplitude fluctuation (BAF) of a target EEG electrode with dominant interictal epileptiform discharges (IEDs). As a proof of concept, we applied this framework to seven patients with focal epilepsy. The analysis produced patient-specific spatial maps of DRePS-BAF coupling, which highlight regions with a strong link between EEG power and local fMRI connectivity. Although we observed DRePS-BAF coupling proximate to the suspected seizure onset zone in some patients, our results suggest that DRePS-BAF is more likely to identify wider ‘epileptic networks’. We also compared DRePS-BAF with standard EEG-fMRI analysis based on general linear modelling (GLM). There was, in general, little overlap between the DRePS-BAF maps and GLM maps. However, in some subjects the spatial clusters revealed by these two analyses appeared to be adjacent, particularly in medial posterior cortices. Our findings suggest that (1) there is a strong time-varying relationship between local fMRI connectivity and interictal EEG power in focal epilepsy, and (2) that DRePS-BAF reflect different aspects of epileptic network activity than standard EEG-fMRI analysis. These two techniques, therefore, appear to be complementary. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Towards a unified analysis of brain maturation and aging across the entire lifespan: A MRI analysis


There is no consensus in literature about lifespan brain maturation and senescence, mainly because previous lifespan studies have been performed on restricted age periods and/or with a limited number of scans, making results instable and their comparison very difficult. Moreover, the use of nonharmonized tools and different volumetric measurements lead to a great discrepancy in reported results. Thanks to the new paradigm of BigData sharing in neuroimaging and the last advances in image processing enabling to process baby as well as elderly scans with the same tool, new insights on brain maturation and aging can be obtained. This study presents brain volume trajectory over the entire lifespan using the largest age range to date (from few months of life to elderly) and one of the largest number of subjects (N = 2,944). First, we found that white matter trajectory based on absolute and normalized volumes follows an inverted U-shape with a maturation peak around middle life. Second, we found that from 1 to 8–10 y there is an absolute gray matter (GM) increase related to body growth followed by a GM decrease. However, when normalized volumes were considered, GM continuously decreases all along the life. Finally, we found that this observation holds for almost all the considered subcortical structures except for amygdala which is rather stable and hippocampus which exhibits an inverted U-shape with a longer maturation period. By revealing the entire brain trajectory picture, a consensus can be drawn since most of the previously discussed discrepancies can be explained. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

Cover Image


COVER ILLUSTRATION: Locked-in Children. Children resuscitated after near-fatal drowning often incur anoxic brain injury (ABI). Locked-in syndrome — a condition defined by the co-occurrence of quadriplegia and aphonia — is a previously unreported consequence of pediatric ABI. In this issue, Ishaque and colleagues report ICA analysis of resting-state fMRI (rs-fMRI) and network-based quantitative behavioral assessments in 10 children with drowning-induced ABI, each of whom exhibit some form of lockedin syndrome. On a per-subject basis, rs-fMRI network preservation closely paralleled behavioral results (r = 0.74), suggesting that rs-fMRI has the potential to assess cognitive status when communication is compromised.

Editorial board - TOC


Functional integrity in children with anoxic brain injury from drowning


Drowning is a leading cause of accidental injury and death in young children. Anoxic brain injury (ABI) is a common consequence of drowning and can cause severe neurological morbidity in survivors. Assessment of functional status and prognostication in drowning victims can be extremely challenging, both acutely and chronically. Structural neuroimaging modalities (CT and MRI) have been of limited clinical value. Here, we tested the utility of resting-state functional MRI (rs-fMRI) for assessing brain functional integrity in this population. Eleven children with chronic, spastic quadriplegia due to drowning-induced ABI were investigated. All were comatose immediately after the injury and gradually regained consciousness, but with varying ability to communicate their cognitive state. Eleven neurotypical children matched for age and gender formed the control group. Resting-state fMRI and co-registered T1-weighted anatomical MRI were acquired at night during drug-aided sleep. Network integrity was quantified by independent components analysis (ICA), at both group- and per-subject levels. Functional-status assessments based on in-home observations were provided by families and caregivers. Motor ICNs were grossly compromised in ABI patients both group-wise and individually, concordant with their prominent motor deficits. Striking preservations of perceptual and cognitive ICNs were observed, and the degree of network preservation correlated (ρ = 0.74) with the per-subject functional status assessments. Collectively, our findings indicate that rs-fMRI has promise for assessing brain functional integrity in ABI and, potentially, in other disorders. Furthermore, our observations suggest that the severe motor deficits observed in this population can mask relatively intact perceptual and cognitive capabilities. Hum Brain Mapp 38:4813–4831, 2017. © 2017 Wiley Periodicals, Inc.

Functional neuroimaging after severe anoxic brain injury in children may reveal preserved, yet covert, cognitive function


A growing body of evidence has confirmed that, after severe brain injury in adults, motoric and task-dependent factors that are essential for reliable communication, frequently interfere with an accurate assessment of cognitive status. In the current study, resting state functional magnetic resonance imaging (fMRI) in children who have sustained an anoxic brain injury following a near drowning incident suggests a similar pattern; preserved cognition amidst severe motoric impairment that effectively precludes accurate clinical diagnosis at the bedside. Hum Brain Mapp 38:4832–4833, 2017. © 2017 Wiley Periodicals, Inc.

Insula-based networks in professional musicians: Evidence for increased functional connectivity during resting state fMRI


Despite considerable research on experience-dependent neuroplasticity in professional musicians, detailed understanding of an involvement of the insula is only now beginning to emerge. We investigated the effects of musical training on intrinsic insula-based connectivity in professional classical musicians relative to nonmusicians using resting-state functional MRI. Following a tripartite scheme of insula subdivisions, coactivation profiles were analyzed for the posterior, ventral anterior, and dorsal anterior insula in both hemispheres. While whole-brain connectivity across all participants confirmed previously reported patterns, between-group comparisons revealed increased insular connectivity in musicians relative to nonmusicians. Coactivated regions encompassed constituents of large-scale networks involved in salience detection (e.g., anterior and middle cingulate cortex), affective processing (e.g., orbitofrontal cortex and temporal pole), and higher order cognition (e.g., dorsolateral prefrontal cortex and the temporoparietal junction), whereas no differences were found for the reversed group contrast. Importantly, these connectivity patterns were stronger in musicians who experienced more years of musical practice, including also sensorimotor regions involved in music performance (M1 hand area, S1, A1, and SMA). We conclude that musical training triggers significant reorganization in insula-based networks, potentially facilitating high-level cognitive and affective functions associated with the fast integration of multisensory information in the context of music performance. Hum Brain Mapp 38:4834–4849, 2017. © 2017 Wiley Periodicals, Inc.

Neural correlates of atomoxetine improving inhibitory control and visual processing in Drug-naïve adults with attention-deficit/hyperactivity disorder


Atomoxetine improves inhibitory control and visual processing in healthy volunteers and adults with attention-deficit/hyperactivity disorder (ADHD). However, little is known about the neural correlates of these two functions after chronic treatment with atomoxetine. This study aimed to use the counting Stroop task with functional magnetic resonance imaging (fMRI) and the Cambridge Neuropsychological Test Automated Battery (CANTAB) to investigate the changes related to inhibitory control and visual processing in adults with ADHD. This study is an 8-week, placebo-controlled, double-blind, randomized clinical trial of atomoxetine in 24 drug-naïve adults with ADHD. We investigated the changes of treatment with atomoxetine compared to placebo-treated counterparts using the counting Stroop fMRI and two CANTAB tests: rapid visual information processing (RVP) for inhibitory control and delayed matching to sample (DMS) for visual processing. Atomoxetine decreased activations in the right inferior frontal gyrus and anterior cingulate cortex, which were correlated with the improvement in inhibitory control assessed by the RVP. Also, atomoxetine increased activation in the left precuneus, which was correlated with the improvement in the mean latency of correct responses assessed by the DMS. Moreover, anterior cingulate activation in the pre-treatment was able to predict the improvements of clinical symptoms. Treatment with atomoxetine may improve inhibitory control to suppress interference and may enhance the visual processing to process numbers. In addition, the anterior cingulate cortex might play an important role as a biological marker for the treatment effectiveness of atomoxetine. Hum Brain Mapp 38:4850–4864, 2017. © 2017 Wiley Periodicals, Inc.

Predicting the brain activation pattern associated with the propositional content of a sentence: Modeling neural representations of events and states


Even though much has recently been learned about the neural representation of individual concepts and categories, neuroimaging research is only beginning to reveal how more complex thoughts, such as event and state descriptions, are neurally represented. We present a predictive computational theory of the neural representations of individual events and states as they are described in 240 sentences. Regression models were trained to determine the mapping between 42 neurally plausible semantic features (NPSFs) and thematic roles of the concepts of a proposition and the fMRI activation patterns of various cortical regions that process different types of information. Given a semantic characterization of the content of a sentence that is new to the model, the model can reliably predict the resulting neural signature, or, given an observed neural signature of a new sentence, the model can predict its semantic content. The models were also reliably generalizable across participants. This computational model provides an account of the brain representation of a complex yet fundamental unit of thought, namely, the conceptual content of a proposition. In addition to characterizing a sentence representation at the level of the semantic and thematic features of its component concepts, factor analysis was used to develop a higher level characterization of a sentence, specifying the general type of event representation that the sentence evokes (e.g., a social interaction versus a change of physical state) and the voxel locations most strongly associated with each of the factors. Hum Brain Mapp 38:4865–4881, 2017. © 2017 Wiley Periodicals, Inc.

Pivotal role of hMT+ in long-range disambiguation of interhemispheric bistable surface motion


It remains an open question whether long-range disambiguation of ambiguous surface motion can be achieved in early visual cortex or instead in higher level regions, which concerns object/surface segmentation/integration mechanisms. We used a bistable moving stimulus that can be perceived as a pattern comprehending both visual hemi-fields moving coherently downward or as two widely segregated nonoverlapping component objects (in each visual hemi-field) moving separately inward. This paradigm requires long-range integration across the vertical meridian leading to interhemispheric binding. Our fMRI study (n = 30) revealed a close relation between activity in hMT+ and perceptual switches involving interhemispheric segregation/integration of motion signals, crucially under nonlocal conditions where components do not overlap and belong to distinct hemispheres. Higher signal changes were found in hMT+ in response to spatially segregated component (incoherent) percepts than to pattern (coherent) percepts. This did not occur in early visual cortex, unlike apparent motion, which does not entail surface segmentation. We also identified a role for top–down mechanisms in state transitions. Deconvolution analysis of switch-related changes revealed prefrontal, insula, and cingulate areas, with the right superior parietal lobule (SPL) being particularly involved. We observed that directed influences could emerge either from left or right hMT+ during bistable motion integration/segregation. SPL also exhibited significant directed functional connectivity with hMT+, during perceptual state maintenance (Granger causality analysis). Our results suggest that long-range interhemispheric binding of ambiguous motion representations mainly reflect bottom–up processes from hMT+ during perceptual state maintenance. In contrast, state transitions maybe influenced by high-level regions such as the SPL. Hum Brain Mapp 38:4882–4897, 2017. © 2017 Wiley Periodicals, Inc.

Neural correlates of heart rate variability in PTSD during sub- and supraliminal processing of trauma-related cues


Background Posttraumatic stress disorder (PTSD) is characterized by dysregulated arousal and altered cardiac autonomic response as evidenced by decreased high-frequency heart rate variability (HF-HRV), an indirect measure of parasympathetic modulation of the heart. Indeed, subtle threatening cues can cause autonomic dysregulation, even without explicit awareness of the triggering stimulus. Accordingly, examining the neural underpinnings associated with HF-HRV during both sub- and supraliminal exposure to trauma-related cues is critical to an enhanced understanding of autonomic nervous system dysfunction in PTSD. Methods We compared neural activity in brain regions associated with HF-HRV in PTSD (n = 18) and healthy controls (n = 18) during exposure to sub- and supraliminal processing of personalized trauma-related words. Results As compared to controls, PTSD exhibited decreased HF-HRV reactivity in response to sub- and supraliminal cues. Notably, during subliminal processing of trauma-related versus neutral words, as compared to controls, PTSD showed decreased neural response associated with HF-HRV within the left dorsal anterior insula. By contrast, during supraliminal processing of trauma-related versus neutral words, decreased neural activity associated with HF-HRV within the posterior insula/superior temporal cortex, and increased neural activity associated with HF-HRV within the left centromedial amygdala was observed in PTSD as compared to controls. Conclusions Impaired parasympathetic modulation of autonomic arousal in PTSD appears related to altered activation of cortical and subcortical regions involved in the central autonomic network. Interestingly, both sub- and supraliminal trauma-related cues appear to elicit dysregulated arousal and may contribute to the maintenance of hyperarousal in PTSD. Hum Brain Mapp 38:4898–4907, 2017. © 2017 Wiley Periodicals, Inc.

Accumulation of non-numerical evidence during nonsymbolic number processing in the brain: An fMRI study


Behavioral evidence has shown that when performing a nonsymbolic number comparison task (e.g., deciding which of two dot arrays contains more dots), participants' responses are sensitive to affected by both numerical (e.g., number of items) and non-numerical magnitudes (i.e., area, density, etc.). Thus far it is unclear what brain circuits support this process of accumulating non-numerical variables during nonsymbolic number processing. To investigate this, 21 adult participants were asked to engage in a dot comparison task. To measure the neural correlates of accumulating numerical and non-numerical variables, we manipulated the number of the non-numerical magnitudes that were congruent (correlated with number) or incongruent (anticorrelated with number). In a control task, participants were asked to choose the darker of two gray rectangles (brightness task). The tasks were matched in terms of their difficulty. The results of a whole brain analysis for regions sensitive to the congruity of numerical and non-numerical magnitudes revealed a region in the right inferior frontal gyrus (rIFG). Activation in this region was found to be correlated with the relative congruency of numerical and non-numerical magnitudes. In contrast, this region was not modulated by difficulty of the brightness control task. Accordingly in view of these findings, we suggest that the rIFG supports the accumulation of non-numerical magnitudes that are positively correlated with number. Therefore taken together, this study reveals a brain region whose pattern of activity is influenced by the congruency between numerical and non-numerical variables during nonsymbolic number judgments. Hum Brain Mapp 38:4908–4921, 2017. © 2017 Wiley Periodicals, Inc.

Intrinsic connectivity of hippocampal subfields in normal elderly and mild cognitive impairment patients


Hippocampal connectivity has been widely described but connectivity specificities of hippocampal subfields and their changes in early AD are poorly known. The aim of this study was to highlight hippocampal subfield networks in healthy elderly (HE) and their changes in amnestic patients with mild cognitive impairment (aMCI). Thirty-six HE and 27 aMCI patients underwent resting-state functional MRI scans. Specific intrinsic connectivity of bilateral CA1, SUB (subiculum), and CA2/3/4/DG was identified in HE (using seeds derived from manually delineation on high-resolution scans) and compared between HE and aMCI. Compared to the other subfields, CA1 was more strongly connected to the amygdala and occipital regions, CA2/3/4/DG to the left anterior cingulate cortex, temporal, and occipital regions, and SUB to the angular, precuneus, putamen, posterior cingulate, and frontal regions. aMCI patients showed reduced connectivity within the SUB network (with frontal and posterior cingulate regions). Our study highlighted for the first time three specific and distinct hippocampal subfield functional networks in HE, and their alterations in aMCI. These findings are important to understand AD specificities in both cognitive deficits and lesion topography, given the role of functional connectivity in these processes. Hum Brain Mapp 38:4922–4932, 2017. © 2017 Wiley Periodicals, Inc.

Sensory processes modulate differences in multi-component behavior and cognitive control between childhood and adulthood


Many everyday tasks require executive functions to achieve a certain goal. Quite often, this requires the integration of information derived from different sensory modalities. Children are less likely to integrate information from different modalities and, at the same time, also do not command fully developed executive functions, as compared to adults. Yet still, the role of developmental age-related effects on multisensory integration processes has not been examined within the context of multicomponent behavior until now (i.e., the concatenation of different executive subprocesses). This is problematic because differences in multisensory integration might actually explain a significant amount of the developmental effects that have traditionally been attributed to changes in executive functioning. In a system, neurophysiological approach combining electroencephaloram (EEG) recordings and source localization analyses, we therefore examined this question. The results show that differences in how children and adults accomplish multicomponent behavior do not solely depend on developmental differences in executive functioning. Instead, the observed developmental differences in response selection processes (reflected by the P3 ERP) were largely dependent on the complexity of integrating temporally separated stimuli from different modalities. This effect was related to activation differences in medial frontal and inferior parietal cortices. Primary perceptual gating or attentional selection processes (P1 and N1 ERPs) were not affected. The results show that differences in multisensory integration explain parts of transformations in cognitive processes between childhood and adulthood that have traditionally been attributed to changes in executive functioning, especially when these require the integration of multiple modalities during response selection. Hum Brain Mapp 38:4933–4945, 2017. © 2017 Wiley Periodicals, Inc.

Neural correlates of formal thought disorder: An activation likelihood estimation meta-analysis


Formal thought disorder (FTD) refers to a psychopathological dimension characterized by disorganized and incoherent speech. Whether symptoms of FTD arise from aberrant processing in language-related regions or more general cognitive networks, however, remains debated. Here, we addressed this question by a quantitative meta-analysis of published functional neuroimaging studies on FTD. The revised Activation Likelihood Estimation (ALE) algorithm was used to test for convergent aberrant activation changes in 18 studies (30 experiments) investigating FTD, of which 17 studies comprised schizophrenia patients and one study healthy subjects administered to S-ketamine. Additionally, we analyzed task-dependent and task-independent (resting-state) functional connectivity (FC) of brain regions showing convergence in activation changes. Subsequent functional characterization was performed for the initial clusters and the delineated connectivity networks by reference to the BrainMap database. Consistent activation changes were found in the left superior temporal gyrus (STG) and two regions within the left posterior middle temporal gyrus (p-MTG), ventrally (vp-MTG) and dorsally (dp-MTG). Functional characterization revealed a prominent functional association of ensuing clusters from our ALE meta-analysis with language and speech processing, as well as auditory perception in STG and with social cognition in dp-MTG. FC analysis identified task-dependent and task-independent networks for all three seed regions, which were mainly related to language and speech processing, but showed additional involvement in higher order cognitive functions. Our findings suggest that FTD is mainly characterized by abnormal activation in brain regions of the left hemisphere that are associated with language and speech processing, but also extend to higher order cognitive functions. Hum Brain Mapp 38:4946–4965, 2017. © 2017 Wiley Periodicals, Inc.

fMRI capture of auditory hallucinations: Validation of the two-steps method


Our purpose was to validate a reliable method to capture brain activity concomitant with hallucinatory events, which constitute frequent and disabling experiences in schizophrenia. Capturing hallucinations using functional magnetic resonance imaging (fMRI) remains very challenging. We previously developed a method based on a two-steps strategy including (1) multivariate data-driven analysis of per-hallucinatory fMRI recording and (2) selection of the components of interest based on a post-fMRI interview. However, two tests still need to be conducted to rule out critical pitfalls of conventional fMRI capture methods before this two-steps strategy can be adopted in hallucination research: replication of these findings on an independent sample and assessment of the reliability of the hallucination-related patterns at the subject level. To do so, we recruited a sample of 45 schizophrenia patients suffering from frequent hallucinations, 20 schizophrenia patients without hallucinations and 20 matched healthy volunteers; all participants underwent four different experiments. The main findings are (1) high accuracy in reporting unexpected sensory stimuli in an MRI setting; (2) good detection concordance between hypothesis-driven and data-driven analysis methods (as used in the two-steps strategy) when controlled unexpected sensory stimuli are presented; (3) good agreement of the two-steps method with the online button-press approach to capture hallucinatory events; (4) high spatial consistency of hallucinatory-related networks detected using the two-steps method on two independent samples. By validating the two-steps method, we advance toward the possible transfer of such technology to new image-based therapies for hallucinations. Hum Brain Mapp 38:4966–4979, 2017. © 2017 Wiley Periodicals, Inc.

Diversity of functional connectivity patterns is reduced in propofol-induced unconsciousness


Introduction Recent evidence suggests that the conscious brain is characterized by a diverse repertoire of functional connectivity patterns while the anesthetized brain shows stereotyped activity. However, classical time-averaged methods of connectivity dismiss dynamic and temporal characteristics of functional configurations. Here we demonstrate a new approach which characterizes time-varying patterns of functional connectivity at the subsecond time scale. Methods We introduce phase-lag entropy (PLE), a measure of the diversity of temporal patterns in the phase relationships between two signals. The proposed measure was applied to multichannel electroencephalogram (EEG), which were recorded from two distinct experimental settings: (1) propofol was administrated at a constant infusion rate for 60 min (n = 96); (2) administration of propofol by a target effect-site concentration-controlled infusion with simultaneous assessment of the level of consciousness (n = 10). Results From the first dataset, two substantial changes of the phase relationship during anesthesia was found: (1) the dynamics of the phase relationship between frontal channels became progressively less diverse and more stereotyped during unconsciousness, quantified as a reduction in PLE; and (2) the reduction in PLE was consistent across subjects. Furthermore, PLE provided better performance in the classification of states of consciousness than did phase-lag index, a classical time-averaged connectivity method. From the second dataset, PLE showed the highest agreement with the level of consciousness, compared to existing anesthetic depth indicators. Conclusions This study suggests that a scarcity of functional configurations is closely associated with anesthetically induced unconsciousness, and shows promise as a basis for a new consciousness monitoring system during general anesthesia. Hum Brain Mapp 38:4980–4995, 2017. © 2017 Wiley Periodicals, Inc.

Neural correlates underlying the attentional spotlight in human parietal cortex independent of task difficulty


Changes in the size of the attentional focus and task difficulty often co-vary. Nevertheless, the neural processes underlying the attentional spotlight process and task difficulty are likely to differ from each other. To differentiate between the two, we parametrically varied the size of the attentional focus in a novel behavioral paradigm while keeping visual processing difficulty either constant or not. A behavioral control experiment proved that the present behavioral paradigm could indeed effectively manipulate the size of the attentional focus per se, rather than affecting purely perceptual processes or surface processing. Imaging results showed that neural activity in a dorsal frontoparietal network, including right superior parietal cortex (SPL), was positively correlated with the size of the attentional spotlight, irrespective of whether task difficulty was constant or varied across different sizes of attentional focus. In contrast, neural activity in the ventral frontoparietal network, including the right inferior parietal cortex (IPL), was positively correlated with increasing task difficulty. Data suggest that sub-regions in parietal cortex are differentially involved in the attentional spotlight process and task difficulty: while SPL was involved in the attentional spotlight process independent of task difficulty, IPL was involved in the effect of task difficulty independent of the attentional spotlight process. Hum Brain Mapp 38:4996–5018, 2017. © 2017 Wiley Periodicals, Inc.

Extraction of dynamic functional connectivity from brain grey matter and white matter for MCI classification


Brain functional connectivity (FC) extracted from resting-state fMRI (RS-fMRI) has become a popular approach for diagnosing various neurodegenerative diseases, including Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI). Current studies mainly construct the FC networks between grey matter (GM) regions of the brain based on temporal co-variations of the blood oxygenation level-dependent (BOLD) signals, which reflects the synchronized neural activities. However, it was rarely investigated whether the FC detected within the white matter (WM) could provide useful information for diagnosis. Motivated by the recently proposed functional correlation tensors (FCT) computed from RS-fMRI and used to characterize the structured pattern of local FC in the WM, we propose in this article a novel MCI classification method based on the information conveyed by both the FC between the GM regions and that within the WM regions. Specifically, in the WM, the tensor-based metrics (e.g., fractional anisotropy [FA], similar to the metric calculated based on diffusion tensor imaging [DTI]) are first calculated based on the FCT and then summarized along each of the major WM fiber tracts connecting each pair of the brain GM regions. This could capture the functional information in the WM, in a similar network structure as the FC network constructed for the GM, based only on the same RS-fMRI data. Moreover, a sliding window approach is further used to partition the voxel-wise BOLD signal into multiple short overlapping segments. Then, both the FC and FCT between each pair of the brain regions can be calculated based on the BOLD signal segments in the GM and WM, respectively. In such a way, our method can generate dynamic FC and dynamic FCT to better capture functional information in both GM and WM and further integrate them together by using our developed feature extraction, selection, and ensemble learning algorithms. The experimental results verify that the dynamic FCT can prov[...]

Mapping the order and pattern of brain structural MRI changes using change-point analysis in premanifest Huntington's disease


Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that progressively affects motor, cognitive, and emotional functions. Structural MRI studies have demonstrated brain atrophy beginning many years prior to clinical onset (“premanifest” period), but the order and pattern of brain structural changes have not been fully characterized. In this study, we investigated brain regional volumes and diffusion tensor imaging (DTI) measurements in premanifest HD, and we aim to determine (1) the extent of MRI changes in a large number of structures across the brain by atlas-based analysis, and (2) the initiation points of structural MRI changes in these brain regions. We adopted a novel multivariate linear regression model to detect the inflection points at which the MRI changes begin (namely, “change-points”), with respect to the CAG-age product (CAP, an indicator of extent of exposure to the effects of CAG repeat expansion). We used approximately 300 T1-weighted and DTI data from premanifest HD and control subjects in the PREDICT-HD study, with atlas-based whole brain segmentation and change-point analysis. The results indicated a distinct topology of structural MRI changes: the change-points of the volumetric measurements suggested a central-to-peripheral pattern of atrophy from the striatum to the deep white matter; and the change points of DTI measurements indicated the earliest changes in mean diffusivity in the deep white matter and posterior white matter. While interpretation needs to be cautious given the cross-sectional nature of the data, these findings suggest a spatial and temporal pattern of spread of structural changes within the HD brain. Hum Brain Mapp 38:5035–5050, 2017. © 2017 Wiley Periodicals, Inc.

Alterations in white matter microstructure are associated with goal-directed upper-limb movement segmentation in children born extremely preterm


Altered white matter microstructure is commonly found in children born preterm (PT), especially those born at an extremely low gestational age (GA). These children also commonly show disturbed motor function. This study explores the relation between white matter alterations and upper-limb movement segmentation in 41 children born PT (19 girls), and 41 children born at term (18 girls) at 8 years. The PT group was subdivided into extremely PT (E-PT; GA = 25–27 weeks, N = 10), very PT (V-PT; GA = 28–32 weeks, N = 13), and moderately PT (M-PT; GA = 33–35 weeks, N = 18). Arm/hand preference (preferred/non-preferred) was determined through object interactions and the brain hemispheres were designated accordingly. White matter alterations were assessed using diffusion tensor imaging in nine areas, and movement segmentation of the body-parts head, shoulder, elbow, and wrist were registered during a unimanual goal-directed task. Increased movement segmentation was demonstrated consistently on the preferred side in the E-PT group compared with the term born group. Also compared with the term born peers, the E-PT group demonstrated reduced fractional anisotropy (FA) in the cerebral peduncle (targeting the corticospinal tract) in the hemisphere on the non-preferred side and in the splenium of corpus callosum. In contrast, in the anterior internal capsule on the preferred side, the E-PT group had increased FA. Lower FA in the cerebral peduncle, but higher FA in the anterior internal capsule, was associated with increased movement segmentation across body-parts in a contralateral manner. The results suggest that impaired development of sensorimotor tracts in E-PT children could explain a sub-optimal spatiotemporal organization of upper-limb movements. Hum Brain Mapp 38:5051–5068, 2017. © 2017 Wiley Periodicals, Inc.

Overweight is associated with lower resting state functional connectivity in females after eliminating genetic effects: A twin study


Obesity is related to altered functional connectivity of resting state brain networks that are involved in reward and motivation. It is unknown to what extent these associations reflect genetic confounding and whether the obesity-related connectivity changes are associated with differences in dietary intake. In this study, resting state functional MRI was performed after an overnight fast in 16 female monozygotic twin pairs (aged 48.8 ± 9.8 years) with a mean BMI discordance of 3.96 ± 2.1 kg/m2 (range 0.7–8.2). Functional connectivity of the salience, basal ganglia, default mode and anterior cingulate–orbitofrontal cortex networks was examined by independent component analysis. Dietary intake was assessed using 3-day 24-hour recalls. Results revealed that within the basal ganglia network, heavier versus leaner co-twins have decreased functional connectivity strength in bilateral putamen (P < 0.05, FWE-corrected). There were no differences in connectivity in the other networks examined. In the overall group, lower functional connectivity strength in the left putamen was correlated with higher intake of total fat (P < 0.01). It was concluded that, after eliminating genetic effects, overweight is associated with lower resting state functional connectivity in bilateral putamen in the basal ganglia network. The association between lower putamen connectivity and higher fat intake suggests an important role of the putamen in appetitive mechanisms. The cross-sectional nature of our study cannot discriminate cause and consequence, but the findings are compatible with an effect of lower putamen connectivity on increased BMI and associated higher fat intake. Hum Brain Mapp 38:5069–5081, 2017. © 2017 Wiley Periodicals, Inc.

Impairment in predictive processes during auditory mismatch negativity in ScZ: Evidence from event-related fields


Patients with schizophrenia (ScZ) show pronounced dysfunctions in auditory perception but the underlying mechanisms as well as the localization of the deficit remain unclear. To examine these questions, the current study examined whether alterations in the neuromagnetic mismatch negativity (MMNm) in ScZ-patients could involve an impairment in sensory predictions in local sensory and higher auditory areas. Using a whole-head MEG-approach, we investigated the MMNm as well as P300m and N100m amplitudes during a hierarchical auditory novelty paradigm in 16 medicated ScZ-patients and 16 controls. In addition, responses to omitted sounds were investigated, allowing for a critical test of the predictive coding hypothesis. Source-localization was performed to identify the generators of the MMNm, omission responses as well as the P300m. Clinical symptoms were examined with the positive and negative syndrome scale. Event-related fields (ERFs) to standard sounds were intact in ScZ-patients. However, the ScZ-group showed a reduction in the amplitude of the MMNm during both local (within trials) and global (across trials) conditions as well as an absent P300m at the global level. Importantly, responses to sound omissions were reduced in ScZ-patients which overlapped both in latency and generators with the MMNm sources. Thus, our data suggest that auditory dysfunctions in ScZ involve impaired predictive processes that involve deficits in both automatic and conscious detection of auditory regularities. Hum Brain Mapp 38:5082–5093, 2017. © 2017 Wiley Periodicals, Inc.

The independent influences of age and education on functional brain networks and cognition in healthy older adults


Healthy aging is accompanied by a constellation of changes in cognitive processes and alterations in functional brain networks. The relationships between brain networks and cognition during aging in later life are moderated by demographic and environmental factors, such as prior education, in a poorly understood manner. Using multivariate analyses, we identified three latent patterns (or modes) linking resting-state functional connectivity to demographic and cognitive measures in 101 cognitively normal elders. The first mode (P = 0.00043) captures an opposing association between age and core cognitive processes such as attention and processing speed on functional connectivity patterns. The functional subnetwork expressed by this mode links bilateral sensorimotor and visual regions through key areas such as the parietal operculum. A strong, independent association between years of education and functional connectivity loads onto a second mode (P = 0.012), characterized by the involvement of key hub regions. A third mode (P = 0.041) captures weak, residual brain–behavior relations. Our findings suggest that circuits supporting lower level cognitive processes are most sensitive to the influence of age in healthy older adults. Education, and to a lesser extent, executive functions, load independently onto functional networks—suggesting that the moderating effect of education acts upon networks distinct from those vulnerable with aging. This has important implications in understanding the contribution of education to cognitive reserve during healthy aging. Hum Brain Mapp 38:5094–5114, 2017. © 2017 Wiley Periodicals, Inc.

Partial volume model for brain MRI scan using MP2RAGE


MP2RAGE is a T1 weighted MRI sequence that estimates a composite image providing much reduction of the receiver bias, has a high intensity dynamic range, and provides an estimate of T1 mapping. It is, therefore, an appealing option for brain morphometry studies. However, previous studies have reported a difference in cortical thickness computed from MP2RAGE compared with widely used Multi-Echo MPRAGE. In this article, we demonstrated that using standard segmentation and partial volume estimation techniques on MP2RAGE introduces systematic errors, and we proposed a new model to estimate partial volume of the cortical gray matter. We also included in their model a local estimate of tissue intensity to take into account the natural variation of tissue intensity across the brain. A theoretical framework is provided and validated using synthetic and physical phantoms. A repeatability experiment comparing MPRAGE and MP2RAGE confirmed that MP2RAGE using our model could be considered for structural imaging in brain morphology study, with similar cortical thickness estimate than that computed with MPRAGE. Hum Brain Mapp 38:5115–5127, 2017. © 2017 Wiley Periodicals, Inc.

Oscillations during observations: Dynamic oscillatory networks serving visuospatial attention


The dynamic allocation of neural resources to discrete features within a visual scene enables us to react quickly and accurately to salient environmental circumstances. A network of bilateral cortical regions is known to subserve such visuospatial attention functions; however the oscillatory and functional connectivity dynamics of information coding within this network are not fully understood. Particularly, the coding of information within prototypical attention-network hubs and the subsecond functional connections formed between these hubs have not been adequately characterized. Herein, we use the precise temporal resolution of magnetoencephalography (MEG) to define spectrally specific functional nodes and connections that underlie the deployment of attention in visual space. Twenty-three healthy young adults completed a visuospatial discrimination task designed to elicit multispectral activity in visual cortex during MEG, and the resulting data were preprocessed and reconstructed in the time–frequency domain. Oscillatory responses were projected to the cortical surface using a beamformer, and time series were extracted from peak voxels to examine their temporal evolution. Dynamic functional connectivity was then computed between nodes within each frequency band of interest. We find that visual attention network nodes are defined functionally by oscillatory frequency, that the allocation of attention to the visual space dynamically modulates functional connectivity between these regions on a millisecond timescale, and that these modulations significantly correlate with performance on a spatial discrimination task. We conclude that functional hubs underlying visuospatial attention are segregated not only anatomically but also by oscillatory frequency, and importantly that these oscillatory sig[...]

The anatomical scaffold underlying the functional centrality of known cortical hubs


Cortical hubs play a fundamental role in the functional architecture of brain connectivity at rest. However, the anatomical scaffold underlying their centrality is still under debate. Certainly, the brain function and anatomy are significantly entwined through synaptogenesis and pruning mechanisms that continuously reshape structural and functional connections. Thus, if hubs are expected to exhibit a large number of direct anatomical connections with the rest of the brain, such a dense wiring is extremely inefficient in energetic terms. In this work, we investigate these aspects on fMRI and DTI data from a set of know resting-state networks, starting from the hypothesis that to promote integration, functional, and anatomical connections link different areas at different scales or hierarchies. Thus, we focused on the role of functional hubs in this hierarchical organization of functional and anatomical architectures. We found that these regions, from a structural point of view, are first linked to each other and successively to the rest of the brain. Thus, functionally central nodes seem to show few strong anatomical connections. These findings suggest an efficient strategy of the investigated cortical hubs in exploiting few direct anatomical connections to link functional hubs among each other that eventually reach the rest of the considered nodes through local indirect tracts. Hum Brain Mapp 38:5141–5160, 2017. © 2017 Wiley Periodicals, Inc.

Cingulate and cerebellar beta oscillations are engaged in the acquisition of auditory-motor sequences


Singing, music performance, and speech rely on the retrieval of complex sounds, which are generated by the corresponding actions and are organized into sequences. It is crucial in these forms of behavior that the serial organization (i.e., order) of both the actions and associated sounds be monitored and learned. To investigate the neural processes involved in the monitoring of serial order during the initial learning of sensorimotor sequences, we performed magnetoencephalographic recordings while participants explicitly learned short piano sequences under the effect of occasional alterations of auditory feedback (AAF). The main result was a prominent and selective modulation of beta (13–30 Hz) oscillations in cingulate and cerebellar regions during the processing of AAF that simulated serial order errors. Furthermore, the AAF-induced modulation of beta oscillations was associated with higher error rates, reflecting compensatory changes in sequence planning. This suggests that cingulate and cerebellar beta oscillations play a role in tracking serial order during initial sensorimotor learning and in updating the mapping of the sensorimotor representations. The findings support the notion that the modulation of beta oscillations is a candidate mechanism for the integration of sequential motor and auditory information during an early stage of skill acquisition in music performance. This has potential implications for singing and speech. Hum Brain Mapp 38:5161–5179, 2017. © 2017 Wiley Periodicals, Inc.

MEG biomarker of Alzheimer's disease: Absence of a prefrontal generator during auditory sensory gating


Magnetoencephalography (MEG), a direct measure of neuronal activity, is an underexplored tool in the search for biomarkers of Alzheimer's disease (AD). In this study, we used MEG source estimates of auditory gating generators, nonlinear correlations with neuropsychological results, and multivariate analyses to examine the sensitivity and specificity of gating topology modulation to detect AD. Our results demonstrated the use of MEG localization of a medial prefrontal (mPFC) gating generator as a discrete (binary) detector of AD at the individual level and resulted in recategorizing the participant categories in: (1) controls with mPFC generator localized in response to both the standard and deviant tones; (2) a possible preclinical stage of AD participants (a lower functioning group of controls) in which mPFC activation was localized to the deviant tone only; and (3) symptomatic AD in which mPFC activation was not localized to either the deviant or standard tones. This approach showed a large effect size (0.9) and high accuracy, sensitivity, and specificity (100%) in identifying symptomatic AD patients within a limited research sample. The present results demonstrate high potential of mPFC activation as a noninvasive biomarker of AD pathology during putative preclinical and clinical stages. Hum Brain Mapp 38:5180–5194, 2017. © 2017 Wiley Periodicals, Inc.

Mental steps: Differential activation of internal pacemakers in motor imagery and in mental imitation of gait


Gait imagery and gait observation can boost the recovery of locomotion dysfunctions; yet, a neurologically justified rationale for their clinical application is lacking as much as a direct comparison of their neural correlates. Using functional magnetic resonance imaging, we measured the neural correlates of explicit motor imagery of gait during observation of in-motion videos shot in a park with a steady cam (Virtual Walking task). In a 2 × 2 factorial design, we assessed the modulatory effect of gait observation and of foot movement execution on the neural correlates of the Virtual Walking task: in half of the trials, the participants were asked to mentally imitate a human model shown while walking along the same route (mental imitation condition); moreover, for half of all the trials, the participants also performed rhythmic ankle dorsiflexion as a proxy for stepping movements. We found that, beyond the areas associated with the execution of lower limb movements (the paracentral lobule, the supplementary motor area, and the cerebellum), gait imagery also recruited dorsal premotor and posterior parietal areas known to contribute to the adaptation of walking patterns to environmental cues. When compared with mental imitation, motor imagery recruited a more extensive network, including a brainstem area compatible with the human mesencephalic locomotor region (MLR). Reduced activation of the MLR in mental imitation indicates that this more visually guided task poses less demand on subcortical structures crucial for internally generated gait patterns. This finding may explain why patients with subcortical degeneration benefit from rehabilitation protocols based on gait observation. Hum Br[...]

Localized reductions in resting-state functional connectivity in children with prenatal alcohol exposure


Fetal alcohol spectrum disorders (FASD) are characterized by impairment in cognitive function that may or may not be accompanied by craniofacial anomalies, microcephaly, and/or growth retardation. Resting-state functional MRI (rs-fMRI), which examines the low-frequency component of the blood oxygen level dependent (BOLD) signal in the absence of an explicit task, provides an efficient and powerful mechanism for studying functional brain networks even in low-functioning and young subjects. Studies using independent component analysis (ICA) have identified a set of resting-state networks (RSNs) that have been linked to distinct domains of cognitive and perceptual function, which are believed to reflect the intrinsic functional architecture of the brain. This study is the first to examine resting-state functional connectivity within these RSNs in FASD. Rs-fMRI scans were performed on 38 children with FASD (19 with either full fetal alcohol syndrome (FAS) or partial FAS (PFAS), 19 nonsyndromal heavily exposed (HE)), and 19 controls, mean age 11.3 ± 0.9 years, from the Cape Town Longitudinal Cohort. Nine resting-state networks were generated by ICA. Voxelwise group comparison between a combined FAS/PFAS group and controls revealed localized dose-dependent functional connectivity reductions in five regions in separate networks: anterior default mode, salience, ventral and dorsal attention, and R executive control. The former three also showed lower connectivity in the HE group. Gray matter connectivity deficits in four of the five networks appear to be related to deficits in white matter tracts that provide intra-RSN connections. Hum Brain Mapp 38:5217–5233, 201[...]

Effect of abacus training on executive function development and underlying neural correlates in Chinese children


Executive function (EF) refers to a set of cognitive abilities involved in self-regulated behavior. Given the critical role of EF in cognition, strategies for improving EF have attracted intensive attention in recent years. Previous studies have explored the effects of abacus-based mental calculation (AMC) training on several cognitive abilities. However, it remains unclear whether AMC training affects EF and its neural correlates. In this study, participants were randomly assigned to AMC or control groups upon starting primary school. The AMC group received 2 h AMC training every week, while the control group did not have any abacus experience. Neural activity during an EF task was examined using functional MRI for both groups in their 4th and 6th grades. Our results showed that the AMC group performed better and faster than the control group in both grades. They also had lower activation in the frontoparietal reigons than the control group in the 6th grade. From the 4th to the 6th grade, the AMC group showed activation decreases in the frontoparietal regions, while the control group exhibited an opposite pattern. Furthermore, voxel-wise regression analyses revealed that better performance was associated with lower task-relevant brain activity in the AMC group but associated with greater task-relevant brain activity in the control group. These results suggest that long-term AMC training, with calculation ability as its original target, may improve EF and enhance neural efficiency of the frontoparietal regions during development. Hum Brain Mapp 38:5234–5249, 2017. © 2017 Wiley Periodicals, Inc.

Integration of white matter network is associated with interindividual differences in psychologically mediated placebo response in migraine patients


Individual differences of brain changes of neural communication and integration in the modular architecture of the human brain network exist for the repeated migraine attack and physical or psychological stressors. However, whether the interindividual variability in the migraine brain connectome predicts placebo response to placebo treatment is still unclear. Using DTI and graph theory approaches, we systematically investigated the topological organization of white matter networks in 71 patients with migraine without aura (MO) and 50 matched healthy controls at three levels: global network measure, nodal efficiency, and nodal intramodule/intermodule efficiency. All patients participated in an 8-week sham acupuncture treatment to induce analgesia. In our results, 30% (n = 21) of patients had 50% change in migraine days from baseline after placebo treatment. At baseline, abnormal increased network integration was found in MO patients as compared with the HC group, and the increased global efficiency before starting clinical treatment was associated with their following placebo response. For nodal efficiency, significantly increased within-subnetwork nodal efficiency and intersubnetwork connectivity of the hippocampus and middle frontal gyrus in patients' white matter network were correlated with the responses of follow-up placebo treatment. Our findings suggested that the trait-like individual differences in pain-related maladaptive stress interfered with and diminished the capacity of chronic pain modulation differently, and the placebo response for treatment could be predicted from a prior white matter ne[...]

Comparison of PASL, PCASL, and background-suppressed 3D PCASL in mild cognitive impairment


We compared three implementations of single-shot arterial spin labeled (ASL) perfusion magnetic resonance imaging: two-dimensional (2D) pulsed ASL (PASL), 2D pseudocontinuous ASL (PCASL), and background-suppressed (BS) 3D PCASL obtained in a cohort of patients with mild cognitive impairment (MCI) and elderly controls. Study subjects also underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). While BS 3D PCASL showed the lowest (P [...]

Validation of brain-derived signals in near-infrared spectroscopy through multivoxel analysis of concurrent functional magnetic resonance imaging


Near-infrared spectroscopy (NIRS) is a convenient and safe brain-mapping tool. However, its inevitable confounding with hemodynamic responses outside the brain, especially in the frontotemporal head, has questioned its validity. Some researchers attempted to validate NIRS signals through concurrent measurements with functional magnetic resonance imaging (fMRI), but, counterintuitively, NIRS signals rarely correlate with local fMRI signals in NIRS channels, although both mapping techniques should measure the same hemoglobin concentration. Here, we tested a novel hypothesis that different voxels within the scalp and the brain tissues might have substantially different hemoglobin absorption rates of near-infrared light, which might differentially contribute to NIRS signals across channels. Therefore, we newly applied a multivariate approach, a partial least squares regression, to explain NIRS signals with multivoxel information from fMRI within the brain and soft tissues in the head. We concurrently obtained fMRI and NIRS signals in 9 healthy human subjects engaging in an n-back task. The multivariate fMRI model was quite successfully able to predict the NIRS signals by cross-validation (interclass correlation coefficient = ∼0.85). This result confirmed that fMRI and NIRS surely measure the same hemoglobin concentration. Additional application of Monte-Carlo permutation tests confirmed that the model surely reflects temporal and spatial hemodynamic information, not random noise. After this thorough validation, we calculated the ratios of the contributi[...]

Analysis of structure–function network decoupling in the brain systems of spastic diplegic cerebral palsy


Manifestation of the functionalities from the structural brain network is becoming increasingly important to understand a brain disease. With the aim of investigating the differential structure–function couplings according to network systems, we investigated the structural and functional brain networks of patients with spastic diplegic cerebral palsy with periventricular leukomalacia compared to healthy controls. The structural and functional networks of the whole brain and motor system, constructed using deterministic and probabilistic tractography of diffusion tensor magnetic resonance images and Pearson and partial correlation analyses of resting-state functional magnetic resonance images, showed differential embedding of functional networks in the structural networks in patients. In the whole-brain network of patients, significantly reduced global network efficiency compared to healthy controls were found in the structural networks but not in the functional networks, resulting in reduced structural–functional coupling. On the contrary, the motor network of patients had a significantly lower functional network efficiency over the intact structural network and a lower structure–function coupling than the control group. This reduced coupling but reverse directionality in the whole-brain and motor networks of patients was prominent particularly between the probabilistic structural and partial correlation-based functional networks. Intact (or less deficient) functional network over impaired structural networks of the whole [...]

Neurodevelopmental maturation as a function of irritable temperament


Few studies have investigated the neural systems involved in decreasing behavioral reactivity to emotional stimuli as children age. It has been suggested that this process may interact with temperament-linked variations in neurodevelopment to better explain individual differences in the maturation of emotion regulation. In this investigation, children ages 4 to 12 (n = 30, mean age = 7.62 years, SD = 1.71 years) and adults (n = 21, mean age = 26.67 years) watched clips from popular children's films containing positive, negative, or neutral emotional content during functional magnetic resonance imaging. Compared to adults, children demonstrated greater activation in subcortical and visual regions (hippocampus, thalamus, visual cortex, fusiform) during negative clips and greater activation of subcortical and prefrontal regions during positive clips (hippocampus, thalamus, caudate, ACC, OFC, superior frontal cortex). In children only, we found an age by temperament interaction in frontal and subcortical regions indicating that activation increased as a function of age in the most irritable children, but decreased as a function of age in the least irritable children. Findings were not present in the temperament domain of fear. Findings replicate and extend the existing irritability literature, indicating that healthy children highest in irritability may develop comparatively greater activation of the lateral prefrontal cortex in order to support adaptive regulation during emotional chal[...]