Biology subjects

Kelly, J. P.

Publications and source records attributed to Kelly, J. P..

5 recordsLinked to original sources

bioRxiv2025

Gyral crowns contribute to the cortical infrastructure of human face processing

Neuroanatomical features across spatial scales contribute to functional specialization and individual differences in behavior across species. Among species with gyrencephalic brains, gyral crown height, which measures a key aspect of the morphology of cortical folding, may represent an anatomical characteristic that importantly shapes neural function. Nevertheless, little is known about the relationship between functional selectivity and gyral crowns--especially in clinical populations. Here, we investigated this relationship and found that the size and gyral crown height of the middle, but not posterior, face-selective region on the fusiform gyrus (FG) was smaller in individuals with developmental prosopagnosia (DPs; N = 22, 68% female, aged 25-62) compared to neurotypical controls (NTs; N = 25, 60% females, aged 21-55), and this difference was related to face perception. Additional analyses replicated the relationship between gyral crowns and face selectivity in 1,053 NTs (55% females, aged 22-36). These results inform theoretical models of face processing while also providing a novel neuroanatomical feature contributing to the cortical infrastructure supporting face processing. Significance StatementUnderstanding how brain structure supports specialized brain functions is a central goal of neuroscience. Here, we identified a role of gyral crown height--an understudied cortical feature--in shaping the cortical infrastructure underlying face processing. By examining face-selective regions of the fusiform gyrus in both neurotypical individuals and those with developmental prosopagnosia, we demonstrate that reduced gyral crown height is associated with diminished face-selective region surface area and impaired face recognition ability. Furthermore, this structural-functional relationship extends to a large neurotypical sample of over 1,000 individuals, highlighting a generalizable link between cortical anatomy and functional specialization. These findings introduce a new neuroanatomical factor to theoretical models of face perception, which could extend to additional neurodevelopmental disorders and other cognitive tasks.

neuroscience↗

bioRxiv2025

Declarative Memory Through the Lens of Single-Trial Peaks in High-Frequency Power

Declarative memory depends on the coordination of local processing, indexed by high-frequency broadband (HFB) activity, with global network organization, indexed by theta oscillations. However, theta and HFB exhibit asynchronous timing, raising the question of how results of local processing are communicated throughout the network. Using intracranial EEG in patients performing a recognition memory task, we examined this coordination across the medial temporal lobe (MTL) and prefrontal cortex (PFC). HFB peak activity was earlier in the MTL than PFC. Anchoring analyses of theta phase clustering and connectivity to HFB peaks revealed strong phase clustering locked to HFB peaks in the PFC, as well as connectivity between the PFC and MTL that predicted individual memory performance. Graph analysis revealed specific connections amidst sparse network connectivity during memory success. This study demonstrates that transient brain states linked to internal physiological events support memory and refines our understanding of local and network-level process interactions. HighlightsO_LIMemory-linked theta activity is time-locked to internal brain events C_LIO_LINetwork connectivity changes dynamically during memory processing C_LIO_LISparse network connectivity supports successful memory C_LIO_LISpecific sequences of transient states may be critical for declarative memory C_LI

neuroscience↗

bioRxiv2023

Direct targets of MEF2C are enriched for genes associated with schizophrenia and cognitive function and are involved in neurogenesis and mitochondrial function

Myocyte Enhancer Factor 2C (MEF2C) is a transcription factor that plays a crucial role in neurogenesis and synapse development. Genetic studies have identified MEF2C as a gene that influences cognition and risk for neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia (SCZ). Here, we investigated the involvement of MEF2C in these phenotypes using human-derived neural stem cells (NSCs) and induced neurons (iNs), which represented early and late neurodevelopmental stages. For these cellular models, MEF2C function had previously been disrupted, either by direct or indirect mutation, and gene expression assayed using RNA-seq. We integrated these RNA-seq data with MEF2C ChIP-seq data to identify dysregulated direct target genes of MEF2C in the NSCs and iNs models. Several MEF2C direct target gene-sets were enriched for SNP-based heritability for intelligence, educational attainment and SCZ, as well as being enriched for genes containing rare de novo mutations reported in ASD and/or developmental disorders. These gene-sets are enriched in both excitatory and inhibitory neurons in the hippocampus and cortex and are involved in a wide range of biological processes including neurogenesis, metabolic processes, protein modifications, as well as mitochondrial function and energy production. We observed a trans expression quantitative trait locus (eQTL) effect of a single SNP at MEF2C (rs6893807, which is associated with IQ) on the expression of a target gene, BNIP3L. BNIP3L is a prioritized risk gene from the largest genome-wide association study of SCZ and has a function in mitophagy in mitochondria. Overall, our analysis reveals that either direct or indirect disruption of MEF2C dysregulates sets of genes that contain multiple alleles associated with SCZ risk and cognitive function and implicates neurogenesis and mitochondrial function in the etiology of these phenotypes. Author SummarySchizophrenia is a complex disorder caused by many genes. Current drugs for schizophrenia are only partially effective and do not treat cognitive deficits, which are key factors for explaining disability, leading to unemployment, homelessness and social isolation. Genome-wide association studies of schizophrenia and cognitive function have been effective at identifying individual SNPs and genes that contribute to these phenotypes but have struggled to immediately uncover the bigger picture of the underlying biology of the disorder. Here we take an individual gene associated with schizophrenia and cognitive function called MEF2C, which on its own is a very important regulator of brain development. We use functional genomics data from studies where MEF2C has been mutated to identify sets of other genes that are influenced by MEF2C in developing and mature neurons. We show that several of these gene-sets are enriched for common variants associated with schizophrenia and cognitive function, and for rare variants that increase risk of various neurodevelopmental disorders. These gene-sets are involved in neurogenesis and mitochondrial function, providing evidence that these biological processes may be important in the context of the molecular mechanisms that underpin schizophrenia and cognitive function.

genetics↗

bioRxiv2023

Social isolation-induced transcriptomic changes in mouse hippocampus impact the synapse and show convergence with human genetic risk for neurodevelopmental phenotypes

Early life stress (ELS) can impact brain development and is a risk factor for neurodevelopmental disorders such as schizophrenia. Post-weaning social isolation (SI) is used to model ELS in animals, using isolation stress to disrupt a normal developmental trajectory. We aimed to investigate how SI affects the expression of genes in mouse hippocampus and to investigate how these changes related to the genetic basis of neurodevelopmental phenotypes. BL/6J mice were exposed to post-weaning SI (PD21-25) or treated as group-housed controls (n = 7-8 per group). RNA sequencing was performed on tissue samples from the hippocampus of adult male and female mice. Four hundred and 1,215 differentially-expressed genes (DEGs) at a false discovery rate of < 0.05 were detected between SI and control samples for males and females respectively. DEGS for both males and females were significantly overrepresented in gene ontologies related to synaptic structure and function, especially the post-synapse. DEGs were enriched for common variant (SNP) heritability in humans that contributes to risk of neuropsychiatric disorders (schizophrenia, bipolar disorder) and to cognitive function. DEGs were also enriched for genes harbouring rare de novo variants that contribute to autism spectrum disorder and other developmental disorders. Finally, cell type analysis revealed populations of hippocampal astrocytes that were enriched for DEGs, indicating effects in these cell types as well as neurons. Overall, these data suggest a convergence between genes dysregulated by the SI stressor in the mouse and genes associated with neurodevelopmental disorders and cognitive phenotypes in humans. Author SummaryEarly life stress increases risk of developing neuropsychiatric and neurodevelopmental disorders. Early life stress can be modelled in animals using social isolation (SI) where animals are separated from others after they have stopped weaning and are housed individually rather than in groups. Here, we investigated the effect of SI on gene expression in the hippocampus, a brain region that regulates stress response and emotion, and how this relates to the known genetic aetiology of neuropsychiatric disorders and traits such as cognitive function. We found that genes altered by SI play a role in how synapses form and function - these are the connection points between nerve cells in the brain. We also found these altered genes are also the genes where common changes in the DNA code can increase risk for schizophrenia, bipolar disorder and influence cognitive ability, and where rare changes in the DNA code increase risk for autism spectrum disorder and developmental disorder. Finally, these genes altered by SI are also highly expressed in astrocytes, cells that help nerve cells to function in the hippocampus. Overall, these data suggest a convergence between genes affected by SI, the environmental stressor, and the genes associated with neurodevelopmental disorders and cognition.

genomics↗

bioRxiv2023

Sulcal morphology of posteromedial cortex substantially differs between humans and chimpanzees

Recent studies identify a surprising coupling between evolutionarily new sulci and the functional organization of human posteromedial cortex (PMC). Yet, no study has compared this modern PMC sulcal patterning between humans and non-human hominoids. To fill this gap in knowledge, we first manually defined 918 sulci in 120 chimpanzee (Pan Troglodytes) hemispheres and 1619 sulci in 144 human hemispheres. We uncovered four new PMC sulci, and quantitatively identified species differences in incidence, depth, and surface area. Interestingly, some PMC sulci are more common in humans and others, in chimpanzees. Further, we found that the prominent marginal ramus of the cingulate sulcus differs significantly between species. Contrary to classic observations, the present results reveal that the surface anatomy of PMC substantially differs between humans and chimpanzees -- findings which lay a foundation for better understanding the evolution of neuroanatomical-functional and neuroanatomical-behavioral relationships in this highly expanded region of the human cerebral cortex.

neuroscience↗