Examining relationships among NODDI indices of white matter structure in prefrontal cortical-thalamic-striatal circuitry and OCD symptomatology.

Obsessive-compulsive disorder is a psychiatric disorder characterized by intrusive thoughts and repetitive behaviors. There are two prominent features: Harm Avoidance (HA) and Incompleteness (INC). Previous resting-state studies reported abnormally elevated connectivity between prefrontal cortical (PFC) and subcortical regions (thalamus, striatum) in OCD participants. Yet, little is known about the white matter (WM) structural abnormalities in these connections. Using brain parcellation and segmentation, whole brain tractography, and Neurite Orientation Dispersion and Density Imaging (NODDI), we aimed to characterize WM structural abnormalities in OCD vs. healthy controls and determine the extent to which NODDI indices of these connections were associated with subthreshold-threshold HA, INC and overall OCD symptom severity across all participants. Four PFC regions were segmented: ventral medial (vmPFC), ventrolateral (vlPFC), dorsomedial (dmPFC), and dorsolateral (dlPFC). NODDI Neurite Density (NDI) and Orientation Dispersion (ODI) indices of WM structure were extracted from connections between these PFC regions and the thalamus (42 OCD, 44 healthy controls, mean age[SD] = 23.65[4.25]y, 63.9% female) and striatum (38 OCD, 41 healthy controls, mean age[SD] = 23.59[4.27]y, 64.5% female). Multivariate analyses of covariance revealed no between-group differences in these indices. Multivariate regression models revealed that greater NDI in vmPFC-thalamus, greater NDI and ODI in vmPFC-striatum, and greater NDI in dmPFC-thalamus connections were associated with greater INC severity (Q ≤ 0.032). These findings highlight the utility of NODDI in the examination of WM structure in OCD, provide valuable insights into specific WM alterations underlying dimensional INC, and can facilitate the development of customized treatments for OCD individuals with treatment-resistant symptoms.

Musical Sophistication and Multilingualism: Effects on Arcuate Fasciculus Characteristics.

The processing of auditory stimuli which are structured in time is thought to involve the arcuate fasciculus, the white matter tract which connects the temporal cortex and the inferior frontal gyrus. Research has indicated effects of both musical and language experience on the structural characteristics of the arcuate fasciculus. Here, we investigated in a sample of n = 84 young adults whether continuous conceptualizations of musical and multilingual experience related to structural characteristics of the arcuate fasciculus, measured using diffusion tensor imaging. Probabilistic tractography was used to identify the dorsal and ventral parts of the white matter tract. Linear regressions indicated that different aspects of musical sophistication related to the arcuate fasciculus' volume (emotional engagement with music), volumetric asymmetry (musical training and music perceptual abilities), and fractional anisotropy (music perceptual abilities). Our conceptualization of multilingual experience, accounting for participants' proficiency in reading, writing, understanding, and speaking different languages, was not related to the structural characteristics of the arcuate fasciculus. We discuss our results in the context of other research on hemispheric specializations and a dual-stream model of auditory processing.

Neural circuit mechanisms underlying context-specific halting in Drosophila.

Walking is a complex motor programme involving coordinated and distributed activity across the brain and the spinal cord. Halting appropriately at the correct time is a critical component of walking control. Despite progress in identifying neurons driving halting1-6, the underlying neural circuit mechanisms responsible for overruling the competing walking state remain unclear. Here, using connectome-informed models7-9 and functional studies, we explain two fundamental mechanisms by which Drosophila implement context-appropriate halting. The first mechanism ('walk-OFF') relies on GABAergic neurons that inhibit specific descending walking commands in the brain, whereas the second mechanism ('brake') relies on excitatory cholinergic neurons in the nerve cord that lead to an active arrest of stepping movements. We show that two neurons that deploy the walk-OFF mechanism inhibit distinct populations of walking-promotion neurons, leading to differential halting of forward walking or turning. The brake neurons, by constrast, override all walking commands by simultaneously inhibiting descending walking-promotion neurons and increasing the resistance at the leg joints. We characterized two behavioural contexts in which the distinct halting mechanisms were used by the animal in a mutually exclusive manner: the walk-OFF mechanism was engaged for halting during feeding and the brake mechanism was engaged for halting and stability during grooming.

Neuronal wiring diagram of an adult brain.

Connections between neurons can be mapped by acquiring and analysing electron microscopic brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative1-6, but nevertheless inadequate for understanding brain function more globally. Here we present a neuronal wiring diagram of a whole brain containing 5 × 107 chemical synapses7 between 139,255 neurons reconstructed from an adult female Drosophila melanogaster8,9. The resource also incorporates annotations of cell classes and types, nerves, hemilineages and predictions of neurotransmitter identities10-12. Data products are available for download, programmatic access and interactive browsing and have been made interoperable with other fly data resources. We derive a projectome-a map of projections between regions-from the connectome and report on tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine and descending neurons) across both hemispheres and between the central brain and the optic lobes. Tracing from a subset of photoreceptors to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviours. The technologies and open ecosystem reported here set the stage for future large-scale connectome projects in other species.

Network statistics of the whole-brain connectome of Drosophila.

Brains comprise complex networks of neurons and connections, similar to the nodes and edges of artificial networks. Network analysis applied to the wiring diagrams of brains can offer insights into how they support computations and regulate the flow of information underlying perception and behaviour. The completion of the first whole-brain connectome of an adult fly, containing over 130,000 neurons and millions of synaptic connections1-3, offers an opportunity to analyse the statistical properties and topological features of a complete brain. Here we computed the prevalence of two- and three-node motifs, examined their strengths, related this information to both neurotransmitter composition and cell type annotations4,5, and compared these metrics with wiring diagrams of other animals. We found that the network of the fly brain displays rich-club organization, with a large population (30% of the connectome) of highly connected neurons. We identified subsets of rich-club neurons that may serve as integrators or broadcasters of signals. Finally, we examined subnetworks based on 78 anatomically defined brain regions or neuropils. These data products are shared within the FlyWire Codex ( https://codex.flywire.ai ) and should serve as a foundation for models and experiments exploring the relationship between neural activity and anatomical structure.

Bilateral connections from the amygdala to extrastriate visual cortex in the marmoset monkey.

It is known that the primate amygdala forms projections to many areas of the ipsilateral cortex, but the extent to which it forms connections with the contralateral visual cortex remains less understood. Based on retrograde tracer injections in marmoset monkeys, we report that the amygdala forms widespread projections to the ipsilateral extrastriate cortex, including V1 and areas in both the dorsal (MT, V4T, V3a, 19M, and PG/PFG) and the ventral (VLP and TEO) streams. In addition, contralateral projections were found to target each of the extrastriate areas, but not V1. In both hemispheres, the tracer-labeled neurons were exclusively located in the basolateral nuclear complex. The number of labeled neurons in the contralateral amygdala was small relative to the ipsilateral connection (1.2% to 5.8%). The percentage of contralateral connections increased progressively with hierarchical level. An injection in the corpus callosum demonstrated that at least some of the amygdalo-cortical connections cross through this fiber tract, in addition to the previously documented path through the anterior commissure. Our results expand knowledge of the amygdalofugal projections to the extrastriate cortex, while also revealing pathways through which visual stimuli conveying affective content can directly influence early stages of neural processing in the contralateral visual field.

White matter microstructure and functional connectivity in the brains of infants with Turner syndrome.

Turner syndrome, caused by complete or partial loss of an X-chromosome, is often accompanied by specific cognitive challenges. Magnetic resonance imaging studies of adults and children with Turner syndrome suggest these deficits reflect differences in anatomical and functional connectivity. However, no imaging studies have explored connectivity in infants with Turner syndrome. Consequently, it is unclear when in development connectivity differences emerge. To address this gap, we compared functional connectivity and white matter microstructure of 1-year-old infants with Turner syndrome to typically developing 1-year-old boys and girls. We examined functional connectivity between the right precentral gyrus and five regions that show reduced volume in 1-year old infants with Turner syndrome compared to controls and found no differences. However, exploratory analyses suggested infants with Turner syndrome have altered connectivity between right supramarginal gyrus and left insula and right putamen. To assess anatomical connectivity, we examined diffusivity indices along the superior longitudinal fasciculus and found no differences. However, an exploratory analysis of 46 additional white matter tracts revealed significant group differences in nine tracts. Results suggest that the first year of life is a window in which interventions might prevent connectivity differences observed at later ages, and by extension, some of the cognitive challenges associated with Turner syndrome.

Contracted functional connectivity profiles in autism.

OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental condition that is associated with atypical brain network organization, with prior work suggesting differential connectivity alterations with respect to functional connection length. Here, we tested whether functional connectopathy in ASD specifically relates to disruptions in long- relative to short-range functional connections. Our approach combined functional connectomics with geodesic distance mapping, and we studied associations to macroscale networks, microarchitectural patterns, as well as socio-demographic and clinical phenotypes. METHODS: We studied 211 males from three sites of the ABIDE-I dataset comprising 103 participants with an ASD diagnosis (mean ± SD age = 20.8 ± 8.1 years) and 108 neurotypical controls (NT, 19.2 ± 7.2 years). For each participant, we computed cortex-wide connectivity distance (CD) measures by combining geodesic distance mapping with resting-state functional connectivity profiling. We compared CD between ASD and NT participants using surface-based linear models, and studied associations with age, symptom severity, and intelligence scores. We contextualized CD alterations relative to canonical networks and explored spatial associations with functional and microstructural cortical gradients as well as cytoarchitectonic cortical types. RESULTS: Compared to NT, ASD participants presented with widespread reductions in CD, generally indicating shorter average connection length and thus suggesting reduced long-range connectivity but increased short-range connections. Peak reductions were localized in transmodal systems (i.e., heteromodal and paralimbic regions in the prefrontal, temporal, and parietal and temporo-parieto-occipital cortex), and effect sizes correlated with the sensory-transmodal gradient of brain function. ASD-related CD reductions appeared consistent across inter-individual differences in age and symptom severity, and we observed a positive correlation of CD to IQ scores. LIMITATIONS: Despite rigorous harmonization across the three different acquisition sites, heterogeneity in autism poses a potential limitation to the generalizability of our results. Additionally, we focussed male participants, warranting future studies in more balanced cohorts. CONCLUSIONS: Our study showed reductions in CD as a relatively stable imaging phenotype of ASD that preferentially impacted paralimbic and heteromodal association systems. CD reductions in ASD corroborate previous reports of ASD-related imbalance between short-range overconnectivity and long-range underconnectivity.

Structural connectivity modifications following deep brain stimulation of the subcallosal cingulate and nucleus accumbens in severe anorexia nervosa.

PURPOSE: Anorexia nervosa (AN) is a mental health disorder characterized by significant weight loss and associated medical and psychological comorbidities. Conventional treatments for severe AN have shown limited effectiveness, leading to the exploration of novel interventional strategies, including deep brain stimulation (DBS). However, the neural mechanisms driving DBS interventions, particularly in psychiatric conditions, remain uncertain. This study aims to address this knowledge gap by examining changes in structural connectivity in patients with severe AN before and after DBS. METHODS: Sixteen participants, including eight patients with AN and eight controls, underwent baseline T1-weigthed and diffusion tensor imaging (DTI) acquisitions. Patients received DBS targeting either the subcallosal cingulate (DBS-SCC, N = 4) or the nucleus accumbens (DBS-NAcc, N = 4) based on psychiatric comorbidities and AN subtype. Post-DBS neuroimaging evaluation was conducted in four patients. Data analyses were performed to compare structural connectivity between patients and controls and to assess connectivity changes after DBS intervention. RESULTS: Baseline findings revealed that structural connectivity is significantly reduced in patients with AN compared to controls, mainly regarding callosal and subcallosal white matter (WM) tracts. Furthermore, pre- vs. post-DBS analyses in AN identified a specific increase after the intervention in two WM tracts: the anterior thalamic radiation and the superior longitudinal fasciculus-parietal bundle. CONCLUSIONS: This study supports that structural connectivity is highly compromised in severe AN. Moreover, this investigation preliminarily reveals that after DBS of the SCC and NAcc in severe AN, there are WM modifications. These microstructural plasticity adaptations may signify a mechanistic underpinning of DBS in this psychiatric disorder.

A comparative study of vestibular projection connectivity and balance in healthy young adults and elderly subjects.

OBJECTIVE: Vestibular function is controlled by interactions between various neuropathways that have different effects on balance and are connected to various brain areas. However, few studies have investigated the relation between changes in VN connectivity and aging using neuroimaging. We investigated neural connectivities in the vestibular nucleus (VN) and ventralis intermedius (VIM) nucleus of the thalamus in young and old healthy adults by diffusion tensor imaging. METHODS: This study recruited twenty-three normal healthy adults with no history of a neurological or musculoskeletal disease, that is, eleven old healthy adults (6 males, 5 females; mean age 63.36 ± 4.25 years) and 12 young healthy adults (7 males, 5 females; mean age 28.42 ± 4.40 years). Connectivity was defined as the incidence of connection between the VN, VIM, and target brain regions. Incidence of connection was counted from VN and VIM to each brain region. The subjective visual vertical (SVV) and the Berg balance scale (BBS) were used to assess vestibular function and balance. RESULTS: The VN showed high connectivity with brainstem (dentate nucleus, medial longitudinal fasciculus, and VIM), but relatively low connectivity with cerebral cortex (parieto-insular vestibular cortex (PIVC) and primary somatosensory cortex) at a threshold of 30 streamlines. In particular, VN connectivity with PIVC was significantly lower in elderly adults (> 60 years old) than in young adults (20-40 years old) (p < 0.05). VIM showed high to mid connectivity with brainstems and cerebral cortexes at a threshold of 30, but no significant difference was observed between young and old adults (p > 0.05). SVV and BBS showed no significant differences between young and old adults (p > 0.05). CONCLUSION: We investigated incidences of neural connectivities of VN and VIM in young and old healthy adults. Our results provide basic data that might be clinically useful following injury of vestibular-related areas.

Activation of the mPFC-NAc Pathway Reduces Motor Impulsivity but Does Not Affect Risk-Related Decision-Making in Innately High-Impulsive Male Rats.

Attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUD) are characterized by exacerbated motor and risk-related impulsivities, which are associated with decreased cortical activity. In rodents, the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) have been separately implicated in impulsive behaviors, but studies on the specific role of the mPFC-NAc pathway in these behaviors are limited. Here, we investigated whether heightened impulsive behaviors are associated with reduced mPFC activity in rodents and determined the involvement of the mPFC-NAc pathway in motor and risk-related impulsivities. We used the Roman High- (RHA) and Low-Avoidance (RLA) rat lines, which display divergent phenotypes in impulsivity. To investigate alterations in cortical activity in relation to impulsivity, regional brain glucose metabolism was measured using positron emission tomography and [18F]-fluorodeoxyglucose ([18F]FDG). Using chemogenetics, the activity of the mPFC-NAc pathway was either selectively activated in high-impulsive RHA rats or inhibited in low-impulsive RLA rats, and the effects of these manipulations on motor and risk-related impulsivity were concurrently assessed using the rat gambling task. We showed that basal [18F]FDG uptake was lower in the mPFC and NAc of RHA compared to RLA rats. Activation of the mPFC-NAc pathway in RHA rats reduced motor impulsivity, without affecting risk-related decision-making. Conversely, inhibition of the mPFC-NAc pathway had no effect in RLA rats. Our results suggest that the mPFC-NAc pathway controls motor impulsivity, but has limited involvement in risk-related decision-making in our current model. Our findings suggest that reducing fronto-striatal activity may help attenuate motor impulsivity in patients with impulse control dysregulation.

Distinct ventral hippocampal inhibitory microcircuits regulating anxiety and fear behaviors.

In emotion research, anxiety and fear have always been interconnected, sharing overlapping brain structures and neural circuitry. Recent investigations, however, have unveiled parallel long-range projection pathways originating from the ventral hippocampus, shedding light on their distinct roles in anxiety and fear. Yet, the mechanisms governing the emergence of projection-specific activity patterns to mediate different negative emotions remain elusive. Here, we show a division of labor in local GABAergic inhibitory microcircuits of the ventral hippocampus, orchestrating the activity of subpopulations of pyramidal neurons to shape anxiety and fear behaviors in mice. These findings offer a comprehensive insight into how distinct inhibitory microcircuits are dynamically engaged to encode different emotional states.

Disrupted basolateral amygdala circuits supports negative valence bias in depressive states.

Negative bias is an essential characteristic of depressive episodes leading patients to attribute more negative valence to environmental cues. This negative bias affects all levels of information processing including emotional response, attention and memory, leading to the development and maintenance of depressive symptoms. In this context, pleasant stimuli become less attractive and unpleasant ones more aversive, yet the related neural circuits underlying this bias remain largely unknown. By studying a mice model for depression chronically receiving corticosterone (CORT), we showed a negative bias in valence attribution to olfactory stimuli that responds to antidepressant drug. This result paralleled the alterations in odor value assignment we observed in bipolar depressed patients. Given the crucial role of amygdala in valence coding and its strong link with depression, we hypothesized that basolateral amygdala (BLA) circuits alterations might support negative shift associated with depressive states. Contrary to humans, where limits in spatial resolution of imaging tools impair easy amygdala segmentation, recently unravelled specific BLA circuits implicated in negative and positive valence attribution could be studied in mice. Combining CTB and rabies-based tracing with ex vivo measurements of neuronal activity, we demonstrated that negative valence bias is supported by disrupted activity of specific BLA circuits during depressive states. Chronic CORT administration induced decreased recruitment of BLA-to-NAc neurons preferentially involved in positive valence encoding, while increasing recruitment of BLA-to-CeA neurons preferentially involved in negative valence encoding. Importantly, this dysfunction was dampened by chemogenetic hyperactivation of BLA-to-NAc neurons. Moreover, altered BLA activity correlated with durable presynaptic connectivity changes coming from the paraventricular nucleus of the thalamus, recently demonstrated as orchestrating valence assignment in the amygdala. Together, our findings suggest that specific BLA circuits alterations might support negative bias in depressive states and provide new avenues for translational research to understand the mechanisms underlying depression and treatment efficacy.

Structure-function coupling in highly sampled individual brains.

Structural connectivity (SC) between distant regions of the brain support synchronized function known as functional connectivity (FC) and give rise to the large-scale brain networks that enable cognition and behavior. Understanding how SC enables FC is important to understand how injuries to SC may alter brain function and cognition. Previous work evaluating whole-brain SC-FC relationships showed that SC explained FC well in unimodal visual and motor areas, but only weakly in association areas, suggesting a unimodal-heteromodal gradient organization of SC-FC coupling. However, this work was conducted in group-averaged SC/FC data. Thus, it could not account for inter-individual variability in the locations of cortical areas and white matter tracts. We evaluated the correspondence of SC and FC within three highly sampled healthy participants. For each participant, we collected 78 min of diffusion-weighted MRI for SC and 360 min of resting state fMRI for FC. We found that FC was best explained by SC in visual and motor systems, as well as in anterior and posterior cingulate regions. A unimodal-to-heteromodal gradient could not fully explain SC-FC coupling. We conclude that the SC-FC coupling of the anterior-posterior cingulate circuit is more similar to unimodal areas than to heteromodal areas.

Involvement of basolateral amygdala-rostral anterior cingulate cortex in mechanical allodynia and anxiety-like behaviors and potential mechanisms of electroacupuncture.

AIMS: Chronic pain is highly associated with anxiety. Electroacupuncture (EA) is effective in relieving pain and anxiety. Currently, little is known about the neural mechanisms underlying the comorbidity of chronic pain and anxiety and the EA mechanism. This study investigated a potential neural circuit underlying the comorbid and EA mechanisms. METHODS: Spared nerve injury (SNI) surgery established the chronic neuropathic pain mouse model. The neural circuit was activated or inhibited using the chemogenetic method to explore the relationship between the neural circuit and mechanical allodynia and anxiety-like behaviors. EA combined with the chemogenetic method was used to explore whether the effects of EA were related to this neural circuit. RESULTS: EA attenuated mechanical allodynia and anxiety-like behaviors in SNI mice, which may be associated with the activity of CaMKII neurons in the basolateral amygdala (BLA). Inhibition of BLACaMKII-rACC induced mechanical allodynia and anxiety-like behaviors in sham mice. Activation of the BLACaMKII-rACC alleviated neuropathic pain and anxiety-like behaviors in SNI mice. The analgesic and anxiolytic effects of 2 Hz EA were antagonized by the inhibition of the BLACaMKII-rACC. CONCLUSION: BLACaMKII-rACC mediates mechanical allodynia and anxiety-like behaviors. The analgesic and anxiolytic effects of 2 Hz EA may be associated with the BLACaMKII-rACC.

Striato-pallidal oscillatory connectivity correlates with symptom severity in dystonia patients.

Dystonia is a hyperkinetic movement disorder that has been associated with an imbalance towards the direct pathway between striatum and internal pallidum, but the neuronal underpinnings of this abnormal basal ganglia pathway activity remain unknown. Here, we report invasive recordings from ten dystonia patients via deep brain stimulation electrodes that allow for parallel recordings of several basal ganglia nuclei, namely the striatum, external and internal pallidum, that all displayed activity in the low frequency band (3-12 Hz). In addition to a correlation with low-frequency activity in the internal pallidum (R = 0.88, P = 0.001), we demonstrate that dystonic symptoms correlate specifically with low-frequency coupling between striatum and internal pallidum (R = 0.75, P = 0.009). This points towards a pathophysiological role of the direct striato-pallidal pathway in dystonia that is conveyed via coupling in the enhanced low-frequency band. Our study provides a mechanistic insight into the pathophysiology of dystonia by revealing a link between symptom severity and frequency-specific coupling of distinct basal ganglia pathways.

Amygdala connectivity is associated with withdrawn/depressed behavior in a large sample of children from the Adolescent Brain Cognitive Development (ABCD) Study®.

Many psychopathologies tied to internalizing symptomatology emerge during adolescence, therefore identifying neural markers of internalizing behavior in childhood may allow for early intervention. We utilized data from the Adolescent Brain and Cognitive Development (ABCD) Study® to evaluate associations between cortico-amygdalar functional connectivity, polygenic risk for depression (PRSD), traumatic events experienced, internalizing behavior, and internalizing subscales: withdrawn/depressed behavior, somatic complaints, and anxious/depressed behaviors. Data from 6371 children (ages 9-11) were used to analyze amygdala resting-state fMRI connectivity to Gordon parcellation based whole-brain regions of interest (ROIs). Internalizing behaviors were measured using the parent-reported Child Behavior Checklist. Linear mixed-effects models were used to identify patterns of cortico-amygdalar connectivity associated with internalizing behaviors. Results indicated left amygdala connections to auditory, frontoparietal network (FPN), and dorsal attention network (DAN) ROIs were significantly associated with withdrawn/depressed symptomatology. Connections relevant for withdrawn/depressed behavior were linked to social behaviors. Specifically, amygdala connections to DAN were associated with social anxiety, social impairment, and social problems. Additionally, an amygdala connection to the FPN ROI and the auditory network ROI was associated with social anxiety and social problems, respectively. Therefore, it may be important to account for social behaviors when looking for brain correlates of depression.

A novel method for sparse dynamic functional connectivity analysis from resting-state fMRI.

BACKGROUND: There is growing interest in understanding the dynamic functional connectivity (DFC) between distributed brain regions. However, it remains challenging to reliably estimate the temporal dynamics from resting-state functional magnetic resonance imaging (rs-fMRI) due to the limitations of current methods. NEW METHODS: We propose a new model called HDP-HSMM-BPCA for sparse DFC analysis of high-dimensional rs-fMRI data, which is a temporal extension of probabilistic principal component analysis using Bayesian nonparametric hidden semi-Markov model (HSMM). Specifically, we utilize a hierarchical Dirichlet process (HDP) prior to remove the parametric assumption of the HMM framework, overcoming the limitations of the standard HMM. An attractive superiority is its ability to automatically infer the state-specific latent space dimensionality within the Bayesian formulation. RESULTS: The experiment results of synthetic data show that our model outperforms the competitive models with relatively higher estimation accuracy. In addition, the proposed framework is applied to real rs-fMRI data to explore sparse DFC patterns. The findings indicate that there is a time-varying underlying structure and sparse DFC patterns in high-dimensional rs-fMRI data. COMPARISON WITH EXISTING METHODS: Compared with the existing DFC approaches based on HMM, our method overcomes the limitations of standard HMM. The observation model of HDP-HSMM-BPCA can discover the underlying temporal structure of rs-fMRI data. Furthermore, the relevant sparse DFC construction algorithm provides a scheme for estimating sparse DFC. CONCLUSION: We describe a new computational framework for sparse DFC analysis to discover the underlying temporal structure of rs-fMRI data, which will facilitate the study of brain functional connectivity.

Provincial and connector qualities of somatosensory brain network hubs in bipolar disorder.

Brain network hubs are highly connected brain regions serving as important relay stations for information integration. Recent studies have linked mental disorders to impaired hub function. Provincial hubs mainly integrate information within their own brain network, while connector hubs share information between different brain networks. This study used a novel time-varying analysis to investigate whether hubs aberrantly follow the trajectory of other brain networks than their own. The aim was to characterize brain hub functioning in clinically remitted bipolar patients. We analyzed resting-state functional magnetic resonance imaging data from 96 euthymic individuals with bipolar disorder and 61 healthy control individuals. We characterized different hub qualities within the somatomotor network. We found that the somatomotor network comprised mainly provincial hubs in healthy controls. Conversely, in bipolar disorder patients, hubs in the primary somatosensory cortex displayed weaker provincial and stronger connector hub function. Furthermore, hubs in bipolar disorder showed weaker allegiances with their own brain network and followed the trajectories of the limbic, salience, dorsal attention, and frontoparietal network. We suggest that these hub aberrancies contribute to previously shown functional connectivity alterations in bipolar disorder and may thus constitute the neural substrate to persistently impaired sensory integration despite clinical remission.