White Matter Structural Connectivity Research Articles

White matter structural connectivity abnormalities in subjects with deficit schizophrenia: A diffusion tensor imaging study

Women living with HIV who use illicit drugs may be particularly vulnerable to HIV-1 RNA viral load (VL) rebound.We used longitudinal data from 2006 to 2017 to evaluate the impact of sociodemographic, behavioral, social-structural, and clinical factors on the hazard of viral rebound for women enrolled in the ACCESS study, a prospective cohort with systematic VL monitoring. Women were included if they achieved VL suppression (<50 copies/mL) following antiretroviral therapy (ART) initiation and had more than one study interview. Sociodemographic as well as substance use, social-structural, addiction treatment, and HIV clinical factors were evaluated as predictors of viral rebound (VL > 1000 copies/mL). Cox regressions using a recurrent events framework, time-varying covariates, robust standard errors, and a frailty component were used.Of the 185 women included, 62 (34%) experienced at least one viral rebound event over an 11-year period, accumulating a total of 87 viral rebound events. In adjusted analysis, stimulant use more than doubled the hazard of viral rebound (adjusted hazard ratio [AHR]: 2.35, 95% confidence interval [CI]: 1.07–5.14) while the only factor protective against viral rebound was receipt of opioid agonist treatment (OAT) in the past six months (AHR: 0.46, 95% CI: 0.26–0.81). After adjusting for ART adherence in the past six months, the effect of OAT was attenuated (AHR: 0.57, 95% CI: 0.32–1.02).Efforts to improve access to and retention within OAT programs and decrease stimulant use may improve rates of viral suppression for HIV-positive women who use illicit drugs.

Confidence of emotion expression recognition recruits brain regions outside the face perception network.

Metacognitive beliefs about emotions expressed by others are crucial to social life, yet very little studied. To what extent does our confidence in emotion expression recognition depend on perceptual or other non-perceptual information? We obtained behavioral and magnetic resonance imaging measures while participants judged either the emotion in ambiguous faces or the size of two lines flanking these faces, and then rated their confidence on decision accuracy. Distinct behavioral and neural mechanisms were identified for confidence and perceptual decision in both tasks. Participants overestimated their emotion recognition (ER) accuracy, unlike visual size judgments. Whereas expression discrimination recruited several areas in the face-processing network, confidence for ER uniquely engaged the bilateral retrosplenial/posterior cingulate complex and left parahippocampal gyrus. Further, structural white matter connectivity of the former region predicted metacognitive sensitivity. These results highlight a key role for brain mechanisms integrating perception with contextual mnemonic information in the service of confidence during ER.

The Effects of Low Frequency Repetitive Transcranial Magnetic Stimulation on White Matter Structural Connectivity in Children with Cerebral Palsy.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive treatment technique for recovery of movement disorders by altering cortical plasticity. In this research, we studied the effects of low-frequency rTMS on white matter (WM) structural connectivity and clinical parameters in children with cerebral palsy (CP).,Four spastic hemiplegic CP children were randomly divided into experimental and control groups. In the experimental group, at first, 1Hz rTMS treatment was performed 4 days/week for 3 weeks on two hemiplegia patients over a contralesional primary motor cortex (M1). Then, 1Hz rTMS treatment was performed 4 days/week for 3 weeks followed by a 30min occupational therapy (OT). In the control group, two CP children received sham rTMS for 3 weeks and then sham rTMS combined with OT for 3 weeks in the same schedule as the experimental group. Evaluations performed using diffusion tensor imaging (DTI), and clinical measurements of gait performance before and after the treatment. Graph theoretical analysis was used to characterize topological changes of structural connectivity. Our findings demonstrate the 1Hz rTMS is effective in improving motor activity in spastic hemiplegic CP children, and is more effective when combined with OT.

White-matter structural connectivity predicts short-term melody and rhythm learning in non-musicians

Music learning has received increasing attention in the last decades due to the variety of functions and brain plasticity effects involved during its practice. Most previous reports interpreted the differences between music experts and laymen as the result of training. However, recent investigations suggest that these differences are due to a combination of genetic predispositions with the effect of music training. Here, we tested the relationship of the dorsal auditory-motor pathway with individual behavioural differences in short-term music learning. We gathered structural neuroimaging data from 44 healthy non-musicians (28 females) before they performed a rhythm- and a melody-learning task during a single behavioural session, and manually dissected the arcuate fasciculus (AF) in both hemispheres. The macro- and microstructural organization of the AF (i.e., volume and FA) predicted the learning rate and learning speed in the musical tasks, but only in the right hemisphere. Specifically, the volume of the right anterior segment predicted the synchronization improvement during the rhythm task, the FA in the right long segment was correlated with the learning rate in the melody task, and the volume and FA of the right whole AF predicted the learning speed during the melody task. This is the first study finding a specific relation between different branches within the AF and rhythmic and melodic materials. Our results support the relevant function of the AF as the structural correlate of both auditory-motor transformations and the feedback-feedforward loop, and suggest a crucial involvement of the anterior segment in error-monitoring processes related to auditory-motor learning. These findings have implications for both the neuroscience of music field and second-language learning investigations.

Associations Between Brain Structure and Connectivity in Infants and Exposure to Selective Serotonin Reuptake Inhibitors During Pregnancy

Selective serotonin reuptake inhibitor (SSRI) use among pregnant women is increasing, yet the association between prenatal SSRI exposure and fetal neurodevelopment is poorly understood. Animal studies show that perinatal SSRI exposure alters limbic circuitry and produces anxiety and depressive-like behaviors after adolescence, but literature on prenatal SSRI exposure in humans is limited and mixed. To examine associations between prenatal SSRI exposure and brain development using structural and diffusion magnetic resonance imaging (MRI). A cohort study conducted at Columbia University Medical Center and New York State Psychiatric Institute included 98 infants: 16 with in utero SSRI exposure, 21 with in utero untreated maternal depression exposure, and 61 healthy controls. Data were collected between January 6, 2011, and October 25, 2016. Selective serotonin reuptake inhibitors and untreated maternal depression. Gray matter volume estimates using structural MRI with voxel-based morphometry and white matter structural connectivity (connectome) using diffusion MRI with probabilistic tractography. The sample included 98 mother (31 [32%] white, 26 [27%] Hispanic/Latina, 26 [27%] black/African American, 15 [15%] other) and infant (46 [47%] boys, 52 [53%] girls) dyads. Mean (SD) age of the infants at the time of the scan was 3.43 (1.50) weeks. Voxel-based morphometry showed significant gray matter volume expansion in the right amygdala (Cohen d = 0.65; 95% CI, 0.06-1.23) and right insula (Cohen d = 0.86; 95% CI, 0.26-1.14) in SSRI-exposed infants compared with both healthy controls and infants exposed to untreated maternal depression (P < .05; whole-brain correction). In connectome-level analysis of white matter structural connectivity, the SSRI group showed a significant increase in connectivity between the right amygdala and the right insula with a large effect size (Cohen d = 0.99; 95% CI, 0.40-1.57) compared with healthy controls and untreated depression (P < .05; whole connectome correction). Our findings suggest that prenatal SSRI exposure has an association with fetal brain development, particularly in brain regions critical to emotional processing. The study highlights the need for further research on the potential long-term behavioral and psychological outcomes of these neurodevelopmental changes.

Posterior limb of the internal capsule predicts poor quality of life in patients with Parkinson's disease: connectometry approach.

Psychiatric symptoms and motor impairment are major contributions to the poor quality of life in patients with Parkinson's disease (PD). Here, we applied a novel diffusion-weighted imaging approach, diffusion MRI connectometry, to investigate the correlation of quality of life, evaluated by Parkinson's Disease Questionnaire (PDQ39) with the white matter structural connectivity in 27 non-demented PD patients (disease duration of 5.3±2.9years, H and Y stage=1.5±0.6, UPDRS-III=13.7±6.5, indicating unilateral and mild motor involvement). The connectometry analysis demonstrated bilateral posterior limbs of the internal capsule(PLIC) with increased connectivity related to the higher quality of life (FDR=0.027) in a multiple regression model. The present study suggestsfor the first time a neural basis of the quality of life in PD in the light of major determinants of poor quality of life in these patients: anxiety, depression, apathy and motor impairment. Results in our sample of non-demented PD patients with relatively mild motor impairment and no apparent sign of depression/anxiety also identify a unique and inexplicable association of the PLIC to the quality of life in PD patients.

Hippocampal Subfields Volume Reduction in High Schoolers with Previous Verbal Abuse Experiences.

ObjectiveReduced hippocampal volume and alterations in white matter tracts have been frequently reported in adults having the history of emotional maltreatment. We investigated whether these structural change occur in adolescents with previous verbal abuse (VA) experiences.MethodsHippocampal subfield volume and white matter structural connectivity measures were assessed in 31 first year male high school students with various degrees of exposure to parental and peer VA.ResultsThe high VA group showed significant volume reduction in the left cornu ammonis (CA) 1 and left subiculum compared to the low VA group (p<0.05). Volumes of left hippocampal subfields CA1 and subiculum were negatively correlated with previous VA experiences (p<0.05). Increased mean diffusivity (MD) of the splenium of the corpus callosum was related to high VA score across all subjects (p<0.05). There was an inverse relationship between volume of the CA1 and subiculum and MD of the splenium (p<0.05).ConclusionExposure to parental and peer VA may affect development of the left hippocampal subfields and the splenium of corpus callosum. These structural alterations can be discernible during adolescence.

Changes in structural network are associated with cortical demyelination in early multiple sclerosis.

The aim of this study was to investigate the interplay between structural connectivity and cortical demyelination in early multiple sclerosis. About 27 multiple sclerosis patients and 18 age-matched controls underwent two MRI scanning sessions. The first was done at 7T and involved acquiring quantitative T1 and T2 * high-resolution maps to estimate cortical myelination. The second was done on a Connectom scanner and consisted of acquiring high angular resolution diffusion-weighted images to compute white matter structural connectivity metrics: strength, clustering and local efficiency. To further investigate the interplay between structural connectivity and cortical demyelination, patients were divided into four groups according to disease-duration: 0-1 year, 1-2 years, 2-3 years, and >3 years. ANOVA and Spearman's correlations were used to highlight relations between metrics. ANOVA detected a significant effect between disease duration and both cortical myelin (p = 2 × 10-8 ) and connectivity metrics (p < 10-4 ). We observed significant cortical myelin loss in the shorter disease-duration cohorts (0-1 year, p = .0015), and an increase in connectivity in the longer disease-duration cohort (2-3 years, strength: p = .01, local efficiency: p = .002, clustering: p = .001). Moreover, significant covariations between myelin estimation and white matter connectivity metrics were observed: Spearman's Rho correlation coefficients of 0.52 (p = .0003), 0.55 (p = .0001), and 0.53 (p = .0001) for strength, local efficiency, and clustering, respectively. An association between cortical myelin loss and changes in white matter connectivity in early multiple sclerosis was detected. These changes in network organization might be the result of compensatory mechanisms in response to the ongoing cortical diffuse damage in the early stages of multiple sclerosis.

The lateralized arcuate fasciculus in developmental pitch disorders among mandarin amusics: left for speech and right for music.

The arcuate fasciculus (AF) is a neural fiber tract that is critical to speech and music development. Although the predominant role of the left AF in speech development is relatively clear, how the AF engages in music development is not understood. Congenital amusia is a special neurodevelopmental condition, which not only affects musical pitch but also speech tone processing. Using diffusion tensor tractography, we aimed at understanding the role of AF in music and speech processing by examining the neural connectivity characteristics of the bilateral AF among thirty Mandarin amusics. Compared to age- and intelligence quotient (IQ)-matched controls, amusics demonstrated increased connectivity as reflected by the increased fractional anisotropy in the right posterior AF but decreased connectivity as reflected by the decreased volume in the right anterior AF. Moreover, greater fractional anisotropy in the left direct AF was correlated with worse performance in speech tone perception among amusics. This study is the first to examine the neural connectivity of AF in the neurodevelopmental condition of amusia as a result of disrupted music pitch and speech tone processing. We found abnormal white matter structural connectivity in the right AF for the amusic individuals. Moreover, we demonstrated that the white matter microstructural properties of the left direct AF is modulated by lexical tone deficits among the amusic individuals. These data support the notion of distinctive pitch processing systems between music and speech.

Super-Resolution Track-Density Imaging Reveals Fine Anatomical Features in Tree Shrew Primary Visual Cortex and Hippocampus.

Diffusion-weighted magnetic resonance imaging (dMRI) is widely used to study white and gray matter (GM) micro-organization and structural connectivity in the brain. Super-resolution track-density imaging (TDI) is an image reconstruction method for dMRI data, which is capable of providing spatial resolution beyond the acquired data, as well as novel and meaningful anatomical contrast that cannot be obtained with conventional reconstruction methods. TDI has been used to reveal anatomical features in human and animal brains. In this study, we used short track TDI (stTDI), a variation of TDI with enhanced contrast for GM structures, to reconstruct direction-encoded color maps of fixed tree shrew brain. The results were compared with those obtained with the traditional diffusion tensor imaging (DTI) method. We demonstrated that fine microstructures in the tree shrew brain, such as Baillarger bands in the primary visual cortex and the longitudinal component of the mossy fibers within the hippocampal CA3 subfield, were observable with stTDI, but not with DTI reconstructions from the same dMRI data. The possible mechanisms underlying the enhanced GM contrast are discussed.

Diffusion Tensor Imaging Tractography Reveals Disrupted White Matter Structural Connectivity Network in Healthy Adults with Insomnia Symptoms.

Neuroimaging studies have revealed that insomnia is characterized by aberrant neuronal connectivity in specific brain regions, but the topological disruptions in the white matter (WM) structural connectivity networks remain largely unknown in insomnia. The current study uses diffusion tensor imaging (DTI) tractography to construct the WM structural networks and graph theory analysis to detect alterations of the brain structural networks. The study participants comprised 30 healthy subjects with insomnia symptoms (IS) and 62 healthy subjects without IS. Both the two groups showed small-world properties regarding their WM structural connectivity networks. By contrast, increased local efficiency and decreased global efficiency were identified in the IS group, indicating an insomnia-related shift in topology away from regular networks. In addition, the IS group exhibited disrupted nodal topological characteristics in regions involving the fronto-limbic and the default-mode systems. To our knowledge, this is the first study to explore the topological organization of WM structural network connectivity in insomnia. More importantly, the dysfunctions of large-scale brain systems including the fronto-limbic pathways, salience network and default-mode network in insomnia were identified, which provides new insights into the insomnia connectome. Topology-based brain network analysis thus could be a potential biomarker for IS.

White matter structural connectivity and episodic memory in early childhood

Episodic memory undergoes dramatic improvement in early childhood; the reason for this is poorly understood. In adults, episodic memory relies on a distributed neural network. Key brain regions that supporting these processes include the hippocampus, portions of the parietal cortex, and portions of prefrontal cortex, each of which shows different developmental profiles. Here we asked whether developmental differences in the axonal pathways connecting these regions may account for the robust gains in episodic memory in young children. Using diffusion weighted imaging, we examined whether white matter connectivity between brain regions implicated in episodic memory differed with age, and were associated with memory performance differences in 4- and 6-year-old children. Results revealed that white matter connecting the hippocampus to the inferior parietal lobule significantly predicted children’s performance on episodic memory tasks. In contrast, variation in the white matter connecting the hippocampus to the medial prefrontal cortex did not relate to memory performance. These findings suggest that structural connectivity between the hippocampus and lateral parietal regions is relevant to the development of episodic memory.

Morphometric and Connectivity White Matter Abnormalities in Obsessive Compulsive Disorder

Two psychological mechanisms seem to be associated with the obsessive-compulsive cycle: (1) an emotional mechanism characterized by intense emotional arousal associated with intrusive thoughts of impending danger; (2) a cognitive mechanism exemplified by difficulties with inhibitory control. More recently, several studies found more extensive cognitive deficits in Obsessive Compulsive Disorder (OCD) beyond problems of inhibitory control and emotional regulation, namely: visual-spatial processing and memory. Thus, there is now extensive research showing that alterations of these psychological mechanisms in OCD (i.e., inhibitory control, emotional regulation, working memory, and visual spatial processing) are associated with morphological gray matter alterations in widespread brain regions. More recently, researchers have started looking at white matter abnormalities in OCD. In this article we review the research looking at white matter morphometric and structural connectivity alterations in OCD. Altogether, while some contradictory findings are still present, there is now evidence for widespread white matter morphometric and connectivity abnormalities affecting major white matter tracts (superior longitudinal fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, cingulum bundle, semioval center, internal capsule, different regions of the corpus callosum, thalamic radiation, uncinate fasciculus and optic radiation) as well as white matter in regions adjacent to gray matter structures (superior frontal gyrus, dorsolateral prefrontal medial frontal cortex; inferior frontal gyrus, caudate, insulate cortex, parietal cortex, supramarginal and lingual gyri, and thalamus). These white matter alterations may help explaining the diversity of OCD psychological impairments in inhibitory control, emotional regulation, memory and visual spatial processing.

Structure-function relationships during segregated and integrated network states of human brain functional connectivity.

Structural white matter connections are thought to facilitate integration of neural information across functionally segregated systems. Recent studies have demonstrated that changes in the balance between segregation and integration in brain networks can be tracked by time-resolved functional connectivity derived from resting-state functional magnetic resonance imaging (rs-fMRI) data and that fluctuations between segregated and integrated network states are related to human behavior. However, how these network states relate to structural connectivity is largely unknown. To obtain a better understanding of structural substrates for these network states, we investigated how the relationship between structural connectivity, derived from diffusion tractography, and functional connectivity, as measured by rs-fMRI, changes with fluctuations between segregated and integrated states in the human brain. We found that the similarity of edge weights between structural and functional connectivity was greater in the integrated state, especially at edges connecting the default mode and the dorsal attention networks. We also demonstrated that the similarity of network partitions, evaluated between structural and functional connectivity, increased and the density of direct structural connections within modules in functional networks was elevated during the integrated state. These results suggest that, when functional connectivity exhibited an integrated network topology, structural connectivity and functional connectivity were more closely linked to each other and direct structural connections mediated a larger proportion of neural communication within functional modules. Our findings point out the possibility of significant contributions of structural connections to integrative neural processes underlying human behavior.

Fast progressive lower motor neuron disease is an ALS variant: A two-centre tract of interest-based MRI data analysis.

BackgroundThe criteria for assessing upper motor neuron pathology in pure lower motor neuron disease (LMND) still remain a major issue of debate with respect to the clinical classification as an amyotrophic lateral sclerosis (ALS) variant.ObjectiveThe study was designed to investigate white matter damage by a hypothesis-guided tract-of-interest-based approach in patients with LMND compared with healthy controls and ´classical´ ALS patients in order to identify in vivo brain structural changes according to the neuropathologically defined ALS affectation pattern. Data were pooled from two previous studies at two different study sites (Ulm, Germany and Milano, Italy).MethodsDTI-based white matter integrity mapping was performed by voxelwise statistical comparison and by a tractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 65 LMND patients (clinically differentiated in fast and slow progressors) vs. 92 matched controls and 101 ALS patients with a ‘classical’ phenotype to identify white matter structural alterations.ResultsThe analysis of white matter structural connectivity by regional FA reductions demonstrated the characteristic alteration patterns along the CST and also in frontal and prefrontal brain areas in LMND patients compared to controls and ALS. Fast progressing LMND showed substantial involvement, like in ALS, while slow progressors showed less severe alterations. In the tract-specific analysis according to the ALS-staging pattern, fast progressing LMND showed significant alterations of ALS-related tract systems as compared to slow progressors and controls.ConclusionsThis study showed an affectation pattern for corticoefferent fibers in LMND with fast disease progression as defined for ALS, that way confirming the hypothesis that fast progressing LMND is a phenotypical variant of ALS.

On the Origin of Individual Functional Connectivity Variability: The Role of White Matter Architecture.

Fingerprint patterns derived from functional connectivity (FC) can be used to identify subjects across groups and sessions, indicating that the topology of the brain substantially differs between individuals. However, the source of FC variability inferred from resting-state functional magnetic resonance imaging remains unclear. One possibility is that these variations are related to individual differences in white matter structural connectivity (SC). However, directly comparing FC with SC is challenging given the many potential biases associated with quantifying their respective strengths. In an attempt to circumvent this, we employed a recently proposed test-retest approach that better quantifies inter-subject variability by first correcting for intra-subject nuisance variability (i.e., head motion, physiological differences in brain state, etc.) that can artificially influence FC and SC measures. Therefore, rather than directly comparing the strength of FC with SC, we asked whether brain regions with, for example, low inter-subject FC variability also exhibited low SC variability. From this, we report two main findings: First, at the whole-brain level, SC variability was significantly lower than FC variability, indicating that an individual's structural connectome is far more similar to another relative to their functional counterpart even after correcting for noise. Second, although FC and SC variability were mutually low in some brain areas (e.g., primary somatosensory cortex) and high in others (e.g., memory and language areas), the two were not significantly correlated across all cortical and sub-cortical regions. Taken together, these results indicate that even after correcting for factors that may differently affect FC and SC, the two, nonetheless, remain largely independent of one another. Further work is needed to understand the role that direct anatomical pathways play in supporting vascular-based measures of FC and to what extent these measures are dictated by anatomical connectivity.

White matter integrity of central executive network correlates with enhanced brain reactivity to smoking cues.

The attentional bias to smoking cues contributes to smoking cue reactivity and cognitive declines underlines smoking behaviors, which were probably associated with the central executive network (CEN). However, little is known about the implication of the structural connectivity of the CEN in smoking cue reactivity and cognitive control impairments in smokers. In the present study, the white matter structural connectivity of the CEN was quantified in 35 smokers and 26 non-smokers using the diffusion tensor imaging and deterministic fiber tractography methods. Smoking cue reactivity was evaluated using cue exposure tasks, and cognitive control performance was assessed by the Stroop task. Relative to non-smokers, smokers showed increased fractional anisotropy (FA) values of the bilateral CEN fiber tracts. The FA values of left CEN positively correlated with the smoking cue-induced activation of the dorsolateral prefrontal cortex and right middle occipital cortex in smokers. Meanwhile, the FA values of left CEN positively correlated with the incongruent errors during Stroop task in smokers. Collectively, the present study highlighted the role of the structural connectivity of the CEN in smoking cue reactivity and cognitive control performance, which may underpin the attentional bias to smoking cues and cognitive deficits in smokers. The multimodal imaging method by forging links from brain structure to brain function extended the notion that structural connections can modulate the brain activity in specific projection target regions. Hum Brain Mapp 38:6239-6249, 2017. © 2017 Wiley Periodicals, Inc.

FV 9 Diffusion tensor imaging in pure lower motor neuron disease

Criteria for assessing upper motor neuron pathology in lower motor neuron disease (LMND) still remain a major issue in clinical diagnosis. This study was designed to investigate patients with the clinical diagnosis of adult pure LMND by use of whole-brain based diffusion tensor imaging (DTI) in order to delineate alterations of corticoefferent pathways in vivo. Comparison of fractional anisotropy (FA) maps was performed by whole brain-based spatial statistics for 37 LMND patients vs. 53 matched controls to detect white matter structural alterations. LMND patients were clinically differentiated in fast and slow progressors. Tract specific alterations were investigated by fiber tracking techniques according to the staging hypothesis for amyotrophic lateral sclerosis (ALS). The analysis of white matter structural connectivity demonstrated widespread and characteristic patterns of alterations in patients with LMND, predominantly along the corticospinal tract (CST), with multiple clusters of regional FA reductions in the motor system at p < 0.05 (corrected for multiple comparisons). Fast progressing LMND showed substantial CST involvement, while slow progressors showed less CST alterations. In the tract-specific analysis according to the ALS-staging pattern (Kassubek et al., 2014), fast progressing LMND showed significant alterations of ALS-related tract systems (Müller et al., xxxx) beyond the CST compared to slow progressors and controls. In clinically pure LMND patients, the involvement of corticoefferent tracts was demonstrated, in particular along the CST, supporting the hypothesis that LMND is a phenotypical variant of ALS. This finding suggests to treat these patients like ALS, including the opportunity to participate in clinical trials.

Structural Brain Connectivity Constrains within-a-Day Variability of Direct Functional Connectivity.

The idea that structural white matter connectivity constrains functional connectivity (interactions among brain regions) has widely been explored in studies of brain networks; studies have mostly focused on the “average” strength of functional connectivity. The question of how structural connectivity constrains the “variability” of functional connectivity remains unresolved. In this study, we investigated the variability of resting state functional connectivity that was acquired every 3 h within a single day from 12 participants (eight time sessions within a 24-h period, 165 scans per session). Three different types of functional connectivity (functional connectivity based on Pearson correlation, direct functional connectivity based on partial correlation, and the pseudo functional connectivity produced by their difference) were estimated from resting state functional magnetic resonance imaging data along with structural connectivity defined using fiber tractography of diffusion tensor imaging. Those types of functional connectivity were evaluated with regard to properties of structural connectivity (fiber streamline counts and lengths) and types of structural connectivity such as intra-/inter-hemispheric edges and topological edge types in the rich club organization. We observed that the structural connectivity constrained the variability of direct functional connectivity more than pseudo-functional connectivity and that the constraints depended strongly on structural connectivity types. The structural constraints were greater for intra-hemispheric and heterologous inter-hemispheric edges than homologous inter-hemispheric edges, and feeder and local edges than rich club edges in the rich club architecture. While each edge was highly variable, the multivariate patterns of edge involvement, especially the direct functional connectivity patterns among the rich club brain regions, showed low variability over time. This study suggests that structural connectivity not only constrains the strength of functional connectivity, but also the within-a-day variability of functional connectivity and connectivity patterns, particularly the direct functional connectivity among brain regions.

The BDNF Val66Met Polymorphism Affects the Vulnerability of the Brain Structural Network.

Val66Met, a naturally occurring polymorphism in the human brain-derived neurotrophic factor (BDNF) gene resulting in a valine (Val) to methionine (Met) substitution at codon 66, plays an important role in neuroplasticity. While the effect of the BDNF Val66Met polymorphism on local brain structures has previously been examined, its impact on the configuration of the graph-based white matter structural networks is yet to be investigated. In the current study, we assessed the effect of the BDNF polymorphism on the network properties and robustness of the graph-based white matter structural networks. Graph theory was employed to investigate the structural connectivity derived from white matter tractography in two groups, Val homozygotes (n = 18) and Met-allele carriers (n = 55). Although there were no differences in the global network measures including global efficiency, local efficiency, and modularity between the two genotype groups, we found the effect of the BDNF Val66Met polymorphism on the robustness properties of the white matter structural networks. Specifically, the white matter structural networks of the Met-allele carrier group showed higher vulnerability to targeted removal of central nodes as compared with those of the Val homozygote group. These findings suggest that the central role of the BDNF Val66Met polymorphism in regards to neuroplasticity may be associated with inherent differences in the robustness of the white matter structural network according to the genetic variants. Furthermore, greater susceptibility to brain disorders in Met-allele carriers may be understood as being due to their limited stability in white matter structural connectivity.