Biology subjects

Bethlehem, R. A.

Publications and source records attributed to Bethlehem, R. A..

3 recordsLinked to original sources

bioRxiv2021

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 non-human primates had a similar spatial distribution, but we observed an increased coupling between structure and function in association regions in macaques 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 establish the genetic and evolutionary uncoupling of structure and function in different transmodal systems may support the emergence of complex, culturally embedded forms of cognition.

neuroscience↗

bioRxiv2019

A moment of change: shifts in myeloarchitecture characterise adolescent development of cortical gradients

The biological processes underpinning adolescent brain maturation remain elusive. Expanding on previous work showing age-related changes in cortical morphology, we studied an accelerated longitudinal cohort of adolescents and young adults (n=223, two time points) to investigate dynamic reconfigurations in myeloarchitecture. Intracortical profiles were generated using magnetization transfer (MT) data, a myelin-sensitive magnetic resonance imaging contrast. Mixed-effect models of depth specific intracortical profiles demonstrated two separate processes i) related to overall increases in MT, and ii) showing a flattening of the MT profile related to enhanced signal in mid-to-deeper layers, especially in heteromodal and unimodal association cortices. This development was independent of morphological changes, and enhanced MT in mid-to-deeper layers was found to spatially co-localise specifically with gene expression markers of oligodendrocytes. Covariance analysis between all pairs of intracortical profiles revealed that these intracortical changes contributed to a gradual and dynamic differentiation from higher-order to lower-order systems. Depth-dependent trajectories of intracortical myeloarchitectural development contribute to the maturation of structural hierarchies in the human neocortex, providing a model for adolescent development that bridges microstructural and macroscopic scales of brain organization.\n\neLife digestIntracortical myelin imposes a spatial structure on cortico-cortical connections, yet little is known about how myeloarchitecture develops throughout youth. We formulated a novel approach to study cortical myeloarchitecture in individual humans and leveraged an accelerated longitudinal design to track age-related changes from 14-27 years. We discovered two unique processes: one involving increasing mean myelin and another characterised by the preferential accumulation of myelin in mid-to-deeper cortical layers. Both processes contributed to an increasing segregation of lower-order from higher-order systems along the macroscale cortical hierarchy. These findings illustrate how layer specific microstructural changes contribute to the maturation of cortical organization and suggest adolescent fine tuning of hierarchical gradients of cortical networks.

neuroscience↗

bioRxiv2019

Salivary sex hormone levels following oxytocin administration in autistic and typical women

Oxytocin administration, which may be of therapeutic value for social disabilities, likely influences endogenous levels of other socially-relevant hormones. However, to date, the effects of oxytocin administration on endogenous hormones have only been examined in typical males. The need to consider multi-hormone interactions is particularly warranted in oxytocin trials for autism due to evidence of irregularities in both oxytocin and sex steroid systems. Here, as part of a larger trial with a double-blind cross-over design, we assessed salivary testosterone and oestradiol levels in 16 autistic and 29 typical women before and after intranasal administration of 24IU oxytocin or placebo. Distinct patterns of change in testosterone and oestradiol across time were observed between groups, with autistic women showing increases in both hormones 90 min post-administration and typical women showing small decreases (mean %change oestradiol: +12% Autism, -10% Typical, 95%CI of difference: 5.0-39.4%, p=0.01; mean %change testosterone: +8% Autism, -14% Typical, 95%CI of difference: 7.8-35.6%, p=0.002). Under the oxytocin condition, the group difference in %change testosterone was amplified (+14.4% Autism, -15.2% Typical, p=0.018). Although baseline hormone levels did not differ between groups, greater baseline oestradiol relative to testosterone was negatively correlated with autistic-like traits (r= -0.36, p=0.019) and positively correlated (r=0.35, p=0.02) with self-reported empathy in the overall sample. These results provide further evidence that oxytocin influences endogenous testosterone, with autistic women showing increases similar to previous reports in typical men. These findings may help to identify autistic people expected to benefit most from interventions involving oxytocin.

neuroscience↗