Abnormal connectional fingerprint in schizophrenia: a novel network analysis of diffusion tensor imaging data

The graph theoretical analysis of structural magnetic resonance imaging (MRI) data has received a great deal of interest in recent years to characterize the organizational principles of brain networks and their alterations in psychiatric disorders, such as schizophrenia. However, the characterization of networks in clinical populations can be challenging, since the comparison of connectivity between groups is influenced by several factors, such as the overall number of connections and the structural abnormalities of the seed regions. To overcome these limitations, the current study employed the whole-brain analysis of connectional fingerprints in diffusion tensor imaging data obtained at 3 T of chronic schizophrenia patients (n = 16) and healthy, age-matched control participants (n = 17). Probabilistic tractography was performed to quantify the connectivity of 110 brain areas. The connectional fingerprint of a brain area represents the set of relative connection probabilities to all its target areas and is, hence, less affected by overall white and gray matter changes than absolute connectivity measures. After detecting brain regions with abnormal connectional fingerprints through similarity measures, we tested each of its relative connection probability between groups. We found altered connectional fingerprints in schizophrenia patients consistent with a dysconnectivity syndrome. While the medial frontal gyrus showed only reduced connectivity, the connectional fingerprints of the inferior frontal gyrus and the putamen mainly contained relatively increased connection probabilities to areas in the frontal, limbic, and subcortical areas. These findings are in line with previous studies that reported abnormalities in striatal–frontal circuits in the pathophysiology of schizophrenia, highlighting the potential utility of connectional fingerprints for the analysis of anatomical networks in the disorder

Individual topological analysis of synchronization-based brain connectivity

Functional connectivity analysis aims at assessing the strength of functional coupling between the signal responses in distinct brain areas. Usually, functional magnetic resonance imaging (fMRI) time series connections are estimated through zero-lag correlation metrics that quantify the statistical similarity between pairs of regions or spectral measures that assess synchronization at a frequency band of interest. Here, we explored the application of a new metric to assess the functional synchronization in phase space between fMRI time series in a resting state. We applied a complete topological analysis to the resulting connectivity matrix to uncover both the macro-scale organization of the brain and detect the most important nodes. The synchronization metric is also compared with Pearson's correlation coefficient and spectral coherence to highlight similarities and differences between the topologies of the three functional networks. We found that the individual topological organization of the resulting synchronization-based connectivity networks shows a finer modular organization than that identified with the other two metrics and a low overlap with the modular partitions of the other two networks suggesting that the derived topological information is not redundant and could be potentially integrated to provide a multi-scale description of functional connectivity

Picture free recall performance linked to the brain's structural connectome

Memory functions are highly variable between healthy humans. The neural correlates of this variability remain largely unknown.; Here, we investigated how differences in free recall performance are associated with DTI-based properties of the brain's structural connectome and with grey matter volumes in 664 healthy young individuals tested in the same MR scanner.; Global structural connectivity, but not overall or regional grey matter volumes, positively correlated with recall performance. Moreover, a set of 22 inter-regional connections, including some with no previously reported relation to human memory, such as the connection between the temporal pole and the nucleus accumbens, explained 7.8% of phenotypic variance.; In conclusion, this large-scale study indicates that individual memory performance is associated with the level of structural brain connectivity

Development Of Human Brain Network Architecture Underlying Executive Function

The transition from late childhood to adulthood is characterized by refinements in brain structure and function that support the dynamic control of attention and goal-directed behavior. One broad domain of cognition that undergoes particularly protracted development is executive function, which encompasses diverse cognitive processes including working memory, inhibitory control, and task switching. Delineating how white matter architecture develops to support specialized brain circuits underlying individual differences in executive function is critical for understanding sources of risk-taking behavior and mortality during adolescence. Moreover, neuropsychiatric disorders are increasingly understood as disorders of brain development, are marked by failures of executive function, and are linked to the disruption of evolving brain connectivity. Network theory provides a parsimonious framework for modeling how anatomical white matter pathways support synchronized fluctuations in neural activity. However, only sparse data exists regarding how the maturation of white matter architecture during human brain development supports coordinated fluctuations in neural activity underlying higher-order cognitive ability. To address this gap, we capitalize on multi-modal neuroimaging and cognitive phenotyping data collected as part of the Philadelphia Neurodevelopmental Cohort (PNC), a large community-based study of brain development. First, diffusion tractography methods were applied to characterize how the development of structural brain network topology supports domain-specific improvements in cognitive ability (n=882, ages 8-22 years old). Second, structural connectivity and task-based functional connectivity approaches were integrated to describe how the development of anatomical constraints on functional communication support individual differences in executive function (n=727, ages 8-23 years old). Finally, the systematic impact of head motion artifact on measures of structural connectivity were characterized (n=949, ages 8-22 years old), providing important guidelines for studying the development of structural brain network architecture. Together, this body of work expands our understanding of how developing white matter connectivity in youth supports the emergence of functionally specialized circuits underlying executive processing. As diverse types of psychopathology are increasingly linked to atypical brain maturation, these findings could collectively lead to earlier diagnosis and personalized interventions for individuals at risk for developing mental disorders

Gender Differences in White Matter Microstructure

Sexual dimorphism in human brain structure is well recognised, but little is known about gender differences in white matter microstructure. We used diffusion tensor imaging to explore differences in fractional anisotropy (FA), an index of microstructural integrity.A whole brain analysis of 135 matched subjects (90 men and 45 women) using a 1.5 T scanner. A region of interest (ROI) analysis was used to confirm those results where proximity to CSF raised the possibility of partial-volume artefact.Men had higher fractional anisotropy (FA) in cerebellar white matter and in the left superior longitudinal fasciculus; women had higher FA in the corpus callosum, confirmed by ROI.The size of the differences was substantial--of the same order as that attributed to some pathology--suggesting gender may be a potentially significant confound in unbalanced clinical studies. There are several previous reports of difference in the corpus callosum, though they disagree on the direction of difference; our findings in the cerebellum and the superior longitudinal fasciculus have not previously been noted. The higher FA in women may reflect greater efficiency of a smaller corpus callosum. The relatively increased superior longitudinal fasciculus and cerebellar FA in men may reflect their increased language lateralisation and enhanced motor development, respectively

Module hierarchy and centralisation in the anatomy and dynamics of human cortex

Systems neuroscience has recently unveiled numerous fundamental features of the macroscopic architecture of the human brain, the connectome, and we are beginning to understand how characteristics of brain dynamics emerge from the underlying anatomical connectivity. The current work utilises complex network analysis on a high-resolution structural connectivity of the human cortex to identify generic organisation principles, such as centralised, modular and hierarchical properties, as well as specific areas that are pivotal in shaping cortical dynamics and function. After confirming its small-world and modular architecture, we characterise the cortex’ multilevel modular hierarchy, which appears to be reasonably centralised towards the brain’s strong global structural core. The potential functional importance of the core and hub regions is assessed by various complex network metrics, such as integration measures, network vulnerability and motif spectrum analysis. Dynamics facilitated by the large-scale cortical topology is explored by simulating coupled oscillators on the anatomical connectivity. The results indicate that cortical connectivity appears to favour high dynamical complexity over high synchronizability. Taking the ability to entrain other brain regions as a proxy for the threat posed by a potential epileptic focus in a given region, we also show that epileptic foci in topologically more central areas should pose a higher epileptic threat than foci in more peripheral areas. To assess the influence of macroscopic brain anatomy in shaping global resting state dynamics on slower time scales, we compare empirically obtained functional connectivity data with data from simulating dynamics on the structural connectivity. Despite considerable micro-scale variability between the two functional connectivities, our simulations are able to approximate the profile of the empirical functional connectivity. Our results outline the combined characteristics a hierarchically modular and reasonably centralised macroscopic architecture of the human cerebral cortex, which, through these topological attributes, appears to facilitate highly complex dynamics and fundamentally shape brain function

Why sex hormones matter for neuroscience: A very short review on sex, sex hormones, and functional brain asymmetries

Biological sex and sex hormones are known to affect functional cerebral asymmetries (FCAs). Men are generally more lateralized than women. The effect size of this sex difference is small but robust. Some of the inconsistencies in the literature may be explained by sex-related hormonal differences. Most studies focusing on neuromodulatory properties of sex hormones on FCAs have investigated women during the menstrual cycle. Although contradictions exist, these studies have typically shown that levels of estradiol and/or progesterone correlate with the degree of FCAs, suggesting that sex differences in FCAs partially depend on hormonal state and day of testing. The results indicate that FCAs are not fixed but are hormone dependent, and as such they can dynamically change within relatively short periods throughout life. Many issues raised in this Mini-Review refer not only to FCAs but also to other aspects of functional brain organization, such as functional connectivity within and between the cerebral hemispheres. Our understanding of sex differences in brain and behavior as well as their clinical relevance will improve significantly if more studies routinely take sex and sex hormones into account

Genetic and phylogenetic uncoupling of structure and function in human transmodal cortex

Brain structure scaffolds intrinsic function, supporting cognition and ultimately behavioral flexibility. However, it remains unclear how a static, genetically controlled architecture supports flexible cognition and behavior. Here, we synthesize genetic, phylogenetic and cognitive analyses to understand how the macroscale organization of structure-function coupling across the cortex can inform its role in cognition. In humans, structure-function coupling was highest in regions of unimodal cortex and lowest in transmodal cortex, a pattern that was mirrored by a reduced alignment with heritable connectivity profiles. Structure-function uncoupling in macaques had a similar spatial distribution, but we observed an increased coupling between structure and function in association cortices relative to humans. Meta-analysis suggested regions with the least genetic control (low heritable correspondence and different across primates) are linked to social-cognition and autobiographical memory. Our findings suggest that genetic and evolutionary uncoupling of structure and function in different transmodal systems may support the emergence of complex forms of cognition