Post-treatment alterations in white matter integrity in PTSD: Effects on symptoms and functional connectivity a secondary analysis of an RCT.

Post-traumatic stress disorder (PTSD) has been linked to altered communication within the limbic system, including reduced structural connectivity in the uncinate fasciculus (UNC; i.e., decreased fractional anisotropy; FA) and reduced resting-state functional connectivity (RSFC) between the hippocampus and ventromedial prefrontal cortex (vmPFC). Previous research has demonstrated attenuation of PTSD symptoms and alterations in RSFC following exposure-based psychotherapy. However, the relationship between changes in structural and functional connectivity patterns and PTSD symptoms following treatment remains unclear. To investigate this, we conducted a secondary analysis of data from a randomized clinical trial of intensive exposure therapy, evaluating alterations in UNC FA, hippocampus-vmPFC RSFC, and PTSD symptoms before (pre-treatment), 7 days after (post-treatment), and 30 days after (follow-up) the completion of therapy. Our results showed that post-treatment changes in RSFC were positively correlated with post-treatment and follow-up changes in UNC FA and that post-treatment changes in UNC FA were positively correlated with post-treatment and follow-up changes in PTSD symptoms. These findings suggest that early changes in functional connectivity are associated with sustained changes in anatomical connectivity, which in turn are linked to reduced PTSD symptom severity.

Obesity is associated with alterations in anatomical connectivity of frontal-corpus callosum.

Obesity has been linked to abnormal frontal function, including the white matter fibers of anterior portion of the corpus callosum, which is crucial for information exchange within frontal cortex. However, alterations in white matter anatomical connectivity between corpus callosum and cortical regions in patients with obesity have not yet been investigated. Thus, we enrolled 72 obese and 60 age-/gender-matched normal weight participants who underwent clinical measurements and diffusion tensor imaging. Probabilistic tractography with connectivity-based classification was performed to segment the corpus callosum and quantify white matter anatomical connectivity between subregions of corpus callosum and cortical regions, and associations between corpus callosum-cortex white matter anatomical connectivity and clinical behaviors were also assessed. Relative to normal weight individuals, individuals with obesity exhibited significantly greater white matter anatomical connectivity of corpus callosum-orbitofrontal cortex, which was positively correlated with body mass index and self-reported disinhibition of eating behavior, and lower white matter anatomical connectivity of corpus callosum-prefrontal cortex, which was significantly negatively correlated with craving for high-calorie food cues. The findings show that alterations in white matter anatomical connectivity between corpus callosum and frontal regions involved in reward and executive control are associated with abnormal eating behaviors.

Anatomical connectivity in children with developmental dyscalculia: A graph theory study.

Current theories postulate that numerical processing depends upon a brain circuit formed by regions and their connections; specialized in the representation and manipulation of the numerical properties of stimuli. It has been suggested that the damage of these network may cause Developmental Dyscalculia (DD): a persistent neurodevelopmental disorder that significantly interferes with academic performance and daily life activities that require mastery of mathematical notions and operations. However, most of the studies on the brain foundations of DD have focused on regions of interest associated with numerical processing, and have not addressed numerical cognition as a complex network phenomenon. The present study explored DD using a Graph Theory network approach. We studied the association between topological measures of integration and segregation of information processing in the brain proposed by Graph Theory; and individual variability in numerical performance in a group of 11 school-aged children with DD (5 of which presented with comorbidity with Developmental Dyslexia, the specific learning disorder for reading) and 17 typically developing peers. A statistically significant correlation was found between the Weber fraction (a measure of numerical representations' precision) and the Clustering Index (a measure of segregation of information processing) in the whole sample. The DD group showed significantly lower Characteristic Path Length (average shortest path length among all pairs of regions in the brain network) compared to controls. Also, differences in critical regions for the brain network performance (hubs) were found between groups. The presence of limbic hubs characterized the DD brain network while right Temporal and Frontal hubs found in controls were absent in the DD group. Our results suggest that the DD may be associated with alterations in anatomical brain connectivity that hinder the capacity to integrate and segregate numerical information.

The spatial extent of anatomical connections within the thalamus varies across the cortical hierarchy in humans and macaques.

Each cortical area has a distinct pattern of anatomical connections within the thalamus, a central subcortical structure composed of functionally and structurally distinct nuclei. Previous studies have suggested that certain cortical areas may have more extensive anatomical connections that target multiple thalamic nuclei, which potentially allows them to modulate distributed information flow. However, there is a lack of quantitative investigations into anatomical connectivity patterns within the thalamus. Consequently, it remains unknown if cortical areas exhibit systematic differences in the extent of their anatomical connections within the thalamus. To address this knowledge gap, we used diffusion magnetic resonance imaging (dMRI) to perform brain-wide probabilistic tractography for 828 healthy adults from the Human Connectome Project. We then developed a framework to quantify the spatial extent of each cortical area's anatomical connections within the thalamus. Additionally, we leveraged resting-state functional MRI, cortical myelin, and human neural gene expression data to test if the extent of anatomical connections within the thalamus varied along the cortical hierarchy. Our results revealed two distinct corticothalamic tractography motifs: 1) a sensorimotor cortical motif characterized by focal thalamic connections targeting posterolateral thalamus, associated with fast, feed-forward information flow; and 2) an associative cortical motif characterized by diffuse thalamic connections targeting anteromedial thalamus, associated with slow, feed-back information flow. These findings were consistent across human subjects and were also observed in macaques, indicating cross-species generalizability. Overall, our study demonstrates that sensorimotor and association cortical areas exhibit differences in the spatial extent of their anatomical connections within the thalamus, which may support functionally-distinct cortico-thalamic information flow.

Gyral and sulcal connectivity in the human cerebral cortex.

The rapid evolution of image acquisition and data analytic methods has established in vivo whole-brain tractography as a routine technology over the last 20 years. Imaging-based methods provide an additional approach to classic neuroanatomical studies focusing on biomechanical principles of anatomical organization and can in turn overcome the complexity of inter-individual variability associated with histological and tractography studies. In this work we propose a novel, reliable framework for determining brain tracts resolving the anatomical variance of brain regions. We distinguished 4 region types based on anatomical considerations: (i) gyral regions at borders between cortical communities; (ii) gyral regions within communities; (iii) sulcal regions at invariant locations across subjects; and (iv) other sulcal regions. Region types showed strikingly different anatomical and connection properties. Results allowed complementing the current understanding of the brain's communication structure with a model of its anatomical underpinnings.

Brainnetome atlas of preadolescent children based on anatomical connectivity profiles.

During the preadolescent period, when the cerebral thickness, curvature, and myelin are constantly changing, the brain's regionalization patterns underwent persistent development, contributing to the continuous improvements of various higher cognitive functions. Using a brain atlas to study the development of these functions has attracted much attention. However, the brains of children do not always have the same topological patterns as those of adults. Therefore, age-specific brain mapping is particularly important, serving as a basic and indispensable tool to study the normal development of children. In this study, we took advantage of longitudinal data to create the brain atlas specifically for preadolescent children. The resulting human Child Brainnetome Atlas, with 188 cortical and 36 subcortical subregions, provides a precise period-specific and cross-validated version of the brain atlas that is more appropriate for adoption in the preadolescent period. In addition, we compared and illustrated for regions with different topological patterns in the child and adult atlases, providing a topologically consistent reference for subsequent research studying child and adolescent development.

Stimulation-Evoked Effective Connectivity (SEEC): An in-vivo approach for defining mesoscale corticocortical connectivity.

BACKGROUND: Cortical electrical stimulation is a versatile technique for examining the structure and function of cortical regions and for implementing novel therapies. While electrical stimulation has been used to examine the local spread of neural activity, it may also enable longitudinal examination of mesoscale interregional connectivity. NEW METHOD: Here, we sought to use intracortical microstimulation (ICMS) in conjunction with recordings of multi-unit action potentials to assess the mesoscale effective connectivity within sensorimotor cortex. Neural recordings were made from multielectrode arrays placed into sensory, motor, and premotor regions during surgical experiments in three squirrel monkeys. During each recording, single-pulse ICMS was repeatably delivered to a single region. Mesoscale effective connectivity was calculated from ICMS-evoked changes in multi-unit firing. RESULTS: Multi-unit action potentials were able to be detected on the order of 1 ms after each ICMS pulse. Across sensorimotor regions, short-latency (< 2.5 ms) ICMS-evoked neural activity strongly correlated with known anatomical connections. Additionally, ICMS-evoked responses remained stable across the experimental period, despite small changes in electrode locations and anesthetic state. COMPARISON WITH EXISTING METHODS: Previous imaging studies investigating cross-regional responses to stimulation are limited to utilizing indirect hemodynamic responses and thus lack the temporal specificity of ICMS-evoked responses. CONCLUSIONS: These results show that monitoring ICMS-evoked neural activity, in a technique we refer to as Stimulation-Evoked Effective Connectivity (SEEC), is a viable way to longitudinally assess effective connectivity, enabling studies comparing the time course of connectivity changes with the time course of changes in behavioral function.

Whole-Brain Wiring Diagram of Oxytocin System in Adult Mice.

Oxytocin (Oxt) neurons regulate diverse physiological responses via direct connections with different neural circuits. However, the lack of comprehensive input-output wiring diagrams of Oxt neurons and their quantitative relationship with Oxt receptor (Oxtr) expression presents challenges to understanding circuit-specific Oxt functions. Here, we establish a whole-brain distribution and anatomic connectivity map of Oxt neurons, and their relationship with Oxtr expression using high-resolution 3D mapping methods in adult male and female mice. We use a flatmap to describe Oxt neuronal expression in four hypothalamic domains including under-characterized Oxt neurons in the tuberal nucleus (TU). Oxt neurons in the paraventricular hypothalamus (PVH) broadly project to nine functional circuits that control cognition, brain state, and somatic visceral response. In contrast, Oxt neurons in the supraoptic (SO) and accessory (AN) nuclei have limited central projection to a small subset of the nine circuits. Surprisingly, quantitative comparison between Oxt output and Oxtr expression showed no significant correlation across the whole brain, suggesting abundant indirect Oxt signaling in Oxtr-expressing areas. Unlike output, Oxt neurons in both the PVH and SO receive similar monosynaptic inputs from a subset of the nine circuits mainly in the thalamic, hypothalamic, and cerebral nuclei areas. Our results suggest that PVH-Oxt neurons serve as a central modulator to integrate external and internal information via largely reciprocal connection with the nine circuits while the SO-Oxt neurons act mainly as unidirectional Oxt hormonal output. In summary, our Oxt wiring diagram provides anatomic insights about distinct behavioral functions of Oxt signaling in the brain.SIGNIFICANCE STATEMENT Oxytocin (Oxt) neurons regulate diverse physiological functions from prosocial behavior to pain sensation via central projection in the brain. Thus, understanding detailed anatomic connectivity of Oxt neurons can provide insight on circuit-specific roles of Oxt signaling in regulating different physiological functions. Here, we use high-resolution mapping methods to describe the 3D distribution, monosynaptic input and long-range output of Oxt neurons, and their relationship with Oxt receptor (Oxtr) expression across the entire mouse brain. We found Oxt connections with nine functional circuits controlling cognition, brain state, and somatic visceral response. Furthermore, we identified a quantitatively unmatched Oxt-Oxtr relationship, suggesting broad indirect Oxt signaling. Together, our comprehensive Oxt wiring diagram advances our understanding of circuit-specific roles of Oxt neurons.

Connectional asymmetry of the inferior parietal lobule shapes hemispheric specialization in humans, chimpanzees, and rhesus macaques.

The inferior parietal lobule (IPL) is one of the most expanded cortical regions in humans relative to other primates. It is also among the most structurally and functionally asymmetric regions in the human cerebral cortex. Whether the structural and connectional asymmetries of IPL subdivisions differ across primate species and how this relates to functional asymmetries remain unclear. We identified IPL subregions that exhibited positive allometric in both hemispheres, scaling across rhesus macaque monkeys, chimpanzees, and humans. The patterns of IPL subregions asymmetry were similar in chimpanzees and humans, but no IPL asymmetries were evident in macaques. Among the comparative sample of primates, humans showed the most widespread asymmetric connections in the frontal, parietal, and temporal cortices, constituting leftward asymmetric networks that may provide an anatomical basis for language and tool use. Unique human asymmetric connectivity between the IPL and primary motor cortex might be related to handedness. These findings suggest that structural and connectional asymmetries may underlie hemispheric specialization of the human brain.

Anatomical and functional coupling between the dorsal and ventral attention networks.

Studies have indicated that the dorsal attention network (DAN) and the ventral attention network (VAN) functionally interact via several fronto-parietal connector hubs. However, the anatomical connectivity profiles of these connector hubs, and the coupling between the anatomical and functional connectivities of them, are still unknown. In the present study, we found that functional connector hubs anatomically bridged the DAN and VAN based on multimodal magnetic resonance imaging data from the Human Connectome Project (HCP) Consortium and an independent Chinese cohort. The three hubs had unique anatomical connectivity patterns with the attention sub-networks. For each connector hub, the pattern of anatomical connectivity resembled the functional one. Finally, the strength of the anatomical connectivity of these connector hubs was positively associated with the functional connectivity at the group- and individual-levels. Our findings help to better understand the anatomical mechanisms underlying the functional interactions between the DAN and the VAN.

Anatomical connectivity and efficacy of electro-therapy for seizure control: A SANTE's single-center regression analyses.

OBJECTIVE: To assess based on a single-center data from a multicenter trial (Stimulation of the Anterior Nucleus for the Thalamus for Epilepsy (SANTE)), the role of anatomical connectivity and other factors (e.g., stimulating electrode placement) on efficacy of electro-therapy of the anterior thalamic nuclei (ATN), a node in Papez network, on pharmaco-resistant seizures. DATA SOURCE: Adults with at least 6 seizures /month were enrolled in this trial. Percent seizure reduction was compared between subjects with seizures emerging inside Papez's network (IPN) to those with seizures outside it (OPN). Statistical analyses were performed on the first year of the trial. RESULTS: Data from 11 subjects were analyzed. At Year 1, median seizure reduction was 80.5% (-100% to -40.3%) in 8/11 subjects with seizures IPN, vs. 52.8% (-61.4% to -23.7%) for 3/11 subjects with seizures OPN (2-sided Wilcoxon p = 0.08). At year 7, 3/11 subjects with seizures IPN had been seizure free for several years vs. 0/11 subjects with seizures OPN. Addition of 4 subjects from a pilot trial with nearly identical protocol to SANTE's, increased to 12/15 the number of subjects with seizures IPN. A 2-sided Fisher's exact test applied to seizure frequency reduction in the 12/15 cohort compared to the 3/15 with seizures OPN, showed significant (p = 0.04) differences in efficacy at the 70% seizure reduction rate. Median quality of life (QOL) scores for subjects with seizures IPN improved by 81% vs. 53% for subjects with seizures OPN. No other factors (e.g., current intensity) had a statistically significant effect on efficacy. CONCLUSIONS: Degree of anatomical connectivity between stimulation targets and epileptogenic networks (ENs) plays an important role in therapeutic efficacy. This may be explained by the minimization of signal attenuation inherent in impulse transmission in nervous tissue partly as a function of fiber tract length, tissue anisotropy, and number of synaptic relays between stimulation target and epileptogenic networks.

Fine-Grained Topography and Modularity of the Macaque Frontal Pole Cortex Revealed by Anatomical Connectivity Profiles.

The frontal pole cortex (FPC) plays key roles in various higher-order functions and is highly developed in non-human primates. An essential missing piece of information is the detailed anatomical connections for finer parcellation of the macaque FPC than provided by the previous tracer results. This is important for understanding the functional architecture of the cerebral cortex. Here, combining cross-validation and principal component analysis, we formed a tractography-based parcellation scheme that applied a machine learning algorithm to divide the macaque FPC (2 males and 6 females) into eight subareas using high-resolution diffusion magnetic resonance imaging with the 9.4T Bruker system, and then revealed their subregional connections. Furthermore, we applied improved hierarchical clustering to the obtained parcels to probe the modular structure of the subregions, and found that the dorsolateral FPC, which contains an extension to the medial FPC, was mainly connected to regions of the default-mode network. The ventral FPC was mainly involved in the social-interaction network and the dorsal FPC in the metacognitive network. These results enhance our understanding of the anatomy and circuitry of the macaque brain, and contribute to FPC-related clinical research.

Computational framework for detection of subtypes of neuropsychiatric disorders based on DTI-derived anatomical connectivity.

Many brain disorders - such as Alzheimer's disease, Parkinson's disease, schizophrenia and autism - are heterogeneous, that is, they may have several subtypes. Traditionally, clinicians have identified subtypes, such as subtypes of psychosis, using clinical criteria. Neuroimaging has the potential to detect subtypes based on objective biomarker-based criteria; however, there are no studies that evaluate the application of combining unsupervised machine learning and anatomical connectivity analysis to accomplish this goal. We propose a computational framework to detect subtypes based on anatomical connectivity computed from diffusion tensor imaging data, in a data-driven and fully automated way. The proposed method exhibits excellent performance on simulated data. We also applied this approach to a real-world dataset: the Nathan Kline Institute data set. The Nathan Kline Institute study consists of 137 normal adult subjects (mean age 41 years (standard deviation 18), male/female 85/52). We examined the association between detected subtypes and the impulsive behavior scale. We found that a subtype characterized by lower connectivity scores was associated with a higher positive urgency score; positive urgency is a vulnerability marker for drug addiction. The top-ranked connections characterizing subtypes involve several brain regions, including the anterior cingulate gyrus, median cingulate gyrus, thalamus, superior frontal gyrus (medial), middle frontal gyrus (orbital part), inferior frontal gyrus (triangular part), superior frontal gyrus, precuneus and putamen. The proposed framework is extendable, and can be used to detect subtypes from other features, including clinical and genomic biomarkers.

Motor fatigue is associated with asymmetric connectivity properties of the corticospinal tract in multiple sclerosis.

Multiple Sclerosis (MS) is characterized by demyelination and neurodegeneration of the central nervous system and causes excessive fatigue in more than 80% of the patients. The pathophysiologic mechanisms causing fatigue are still largely unknown. In 46 right-handed patients with relapsing-remitting MS and 25 right-handed controls, we performed diffusion MRI and applied streamline based probabilistic tractography to derive unilateral anatomical connectivity maps for the white matter of the right and left hemispheres. The maps provide an indication how often a streamline has passed through a given voxel. Since tractography based anatomical connectivity mapping (ACM) is sensitive to disease-induced changes in anatomical connectivity, we used ACM to test whether motor fatigue is associated with altered ipsi-hemispherical anatomical connectivity in the major motor output pathway, the corticospinal tract (CST). Patients had higher mean ACM values in the CST than healthy controls. This indicated that a higher number of streamlines, starting from voxels in the same hemisphere, travelled through the CST and may reflect an accumulated disease-induced disintegration of CST. The motor subscale of the Fatigue Scale for Motor and Cognitive functions (FSMCMOTOR) was used to define sub-groups with (n = 29, FSMCMOTOR score ≥ 27) and without motor fatigue (n = 17, FSMSMOTOR score ≤ 26). Patients without fatigue only showed higher ACM values in right CST, while mean ACM values were unaltered in left CST. The higher the mean ACM values in the left relative to the right CST, the more patients reported motor fatigue. Left-right asymmetry in anatomical connectivity outside the CST did not scale with individual motor fatigue. Our results link lateralized changes of tractography-based microstructural properties in the CST with motor fatigue in relapsing-remitting MS.

Altered thalamocortical structural connectivity in persons with schizophrenia and healthy siblings.

Schizophrenia has long been framed as a disorder of altered brain connectivity, with dysfunction in thalamocortical circuity potentially playing a key role in the development of the illness phenotype, including psychotic symptomatology and cognitive impairments. There is emerging evidence for functional and structural hypoconnectivity between thalamus and prefrontal cortex in persons with schizophrenia spectrum disorders, as well as hyperconnectivity between thalamus and sensory and motor cortices. However, it is unclear whether thalamocortical dysconnectivity is a general marker of vulnerability to schizophrenia or a specific mechanism of schizophrenia pathophysiology. This study aimed to answer this question by using diffusion-weighted imaging to examine thalamocortical structural connectivity in 22 persons with schizophrenia or schizoaffective disorder (SZ), 20 siblings of individuals with a schizophrenia spectrum disorder (SIB), and 44 healthy controls (HC) of either sex. Probabilistic tractography was used to quantify structural connectivity between thalamus and six cortical regions of interest. Thalamocortical structural connectivity was compared among the three groups using cross-thalamic and voxel-wise approaches. Thalamo-prefrontal structural connectivity was reduced in both SZ and SIB relative to HC, while SZ and SIB did not differ from each other. Thalamo-motor structural connectivity was increased in SZ relative to SIB and HC, while SIB and HC did not differ from each other. Hemispheric differences also emerged in thalamic connectivity with motor, posterior parietal, and temporal cortices across all groups. The results support the hypothesis that altered thalamo-prefrontal structural connectivity is a general marker of vulnerability to schizophrenia, whereas altered connectivity between thalamus and motor cortex is related to illness expression or illness-related secondary factors.

Anatomical Connectivity-Based Strategy for Targeting Transcranial Magnetic Stimulation as Antidepressant Therapy.

OBJECTIVES: Abnormal activity of the subgenual anterior cingulate cortex (sACC) is implicated in depression, suggesting the sACC as a potentially effective target for therapeutic modulation in cases resistant to conventional treatments (treatment-resistant depression, TRD). We hypothesized that areas in the prefrontal cortex (PFC) with direct fiber connections to the sACC may be particularly effective sites for treatment using transcranial magnetic stimulation (TMS). The aim of this study was to identify PFC sites most strongly connected to the sACC. METHODS: Two neuroimaging data sets were used to construct anatomic and functional connectivity maps using sACC as the seed region. Data set 1 included magnetic resonance (MR) images from 20 healthy controls and Data set 2 included MR images from 15 TRD patients and 15 additional healthy controls. PFC voxels with maximum values in the mean anatomic connection probability maps were identified as optimal sites for TMS. RESULTS: Both right and left PFC contained sites strongly connected to the sACC, but the coordinates (in Montreal Neurological Institute space) of peak anatomic connectivity differed slightly between hemispheres. The left PFC site connected directly to the sACC both anatomically and functionally, while the right PFC site was functionally connected to the posterior cingulate cortex (PCC). CONCLUSIONS: Both left and right PFC are functionally connected to regions implicated in depression, the sACC and PCC, respectively. These bilateral PFC sites may be effective TMS targets to treat TRD.

Hierarchy of Connectivity-Function Relationship of the Human Cortex Revealed through Predicting Activity across Functional Domains.

Many studies showed that anatomical connectivity supports both anatomical and functional hierarchies that span across the primary and association cortices in the cerebral cortex. Even though a structure-function relationship has been indicated to uncouple in the association cortex, it is still unknown whether anatomical connectivity can predict functional activations to the same degree throughout the cortex, and it remains unclear whether a hierarchy of this connectivity-function relationship (CFR) exists across the human cortex. We first addressed whether anatomical connectivity could be used to predict functional activations across different functional domains using multilinear regression models. Then, we characterized the CFR by predicting activity from anatomical connectivity throughout the cortex. We found that there is a hierarchy of CFR between sensory-motor and association cortices. Moreover, this CFR hierarchy was correlated to the functional and anatomical hierarchies, respectively, reflected in functional flexibility and the myelin map. Our results suggest a shared hierarchical mechanism in the cortex, a finding which provides important insights into the anatomical and functional organizations of the human brain.

Comparison of resting-state functional connectivity in marmosets with tracer-based cellular connectivity.

Resting-state functional MRI (RS-fMRI) is widely used to assess how strongly different brain areas are connected. However, this connection obtained by RS-fMRI, which is called functional connectivity (FC), simply refers to the correlation of blood oxygen level-dependent (BOLD) signals across time it has yet to be quantified how accurately FC reflects cellular connectivity (CC). In this study, we elucidated this relationship using RS-fMRI and quantitative tracer data in marmosets. In addition, we also elucidated the effects of distance between two brain regions on the relationship between FC and CC across seed region. To calculate FC, we used full correlation approach that is considered to reflect not only direct (monosynaptic connections) but also indirect pathways (polysynaptic connections). Our main findings are that: (1) overall FC obtained by RS-fMRI was highly correlated with tracer-based CC, but correlation coefficients varied remarkably across seed regions; (2) the strength of FC decreased with increase in the distance between two regions; (3) correlation coefficients between FC and CC after regressing out the effects of the distance between two regions still varied across seed regions, but some regions have strong correlations. These findings suggest that although FC reflects the strength of monosynaptic pathways, it is strongly affected by the distance between regions.

Methods for analysis of brain connectivity: An IFCN-sponsored review.

The goal of this paper is to examine existing methods to study the "Human Brain Connectome" with a specific focus on the neurophysiological ones. In recent years, a new approach has been developed to evaluate the anatomical and functional organization of the human brain: the aim of this promising multimodality effort is to identify and classify neuronal networks with a number of neurobiologically meaningful and easily computable measures to create its connectome. By defining anatomical and functional connections of brain regions on the same map through an integrated approach, comprising both modern neurophysiological and neuroimaging (i.e. flow/metabolic) brain-mapping techniques, network analysis becomes a powerful tool for exploring structural-functional connectivity mechanisms and for revealing etiological relationships that link connectivity abnormalities to neuropsychiatric disorders. Following a recent IFCN-endorsed meeting, a panel of international experts was selected to produce this current state-of-art document, which covers the available knowledge on anatomical and functional connectivity, including the most commonly used structural and functional MRI, EEG, MEG and non-invasive brain stimulation techniques and measures of local and global brain connectivity.

A Role for the Claustrum in Salience Processing?

The claustrum (CLA) is a subcortical structure, present only in mammals, whose function remains uncertain. Previously, using resting-state functional magnetic resonance imaging (rs-fMRI) in awake head-fixed rats, we found evidence that the CLA is part of the rodent homolog of the default mode network (DMN; Smith et al., 2017). This network emerged as strong functional connections between the medial prefrontal cortex (mPFC), mediodorsal (MD) thalamus, and CLA in the awake state, which was not present following administration of isoflurane anesthesia. In the present report, we review evidence indicating that the rodent CLA also has connections with structures identified in the rodent homolog of the salience network (SN), a circuit that directs attention towards the most relevant stimuli among a multitude of sensory inputs (Seeley et al., 2007; Menon and Uddin, 2010). In humans, this circuit consists of functional connections between the anterior cingulate cortex (ACC) and a region that encompasses both the CLA and insular cortex. We further go on to review the similarities and differences between the functional and anatomical connections of the CLA and insula in rodents using both rs-fMRI and neuroanatomical tracing, respectively. We analyze in detail the connectivity of the CLA with the cingulate cortex, which is a major node in the SN and has been shown to modulate attention. When considered with other recent behavior and physiology studies, the data reveal a role for the CLA in salience-guided orienting. More specifically, we hypothesize that limbic information from mPFC, MD thalamus, and the basolateral amygdala (BLA) are integrated by the CLA to guide modality-related regions of motor and sensory cortex in directing attention towards relevant (i.e., salient) sensory events.