Decreased Neuron Density and Increased Glia Density in the Ventromedial Prefrontal Cortex (Brodmann Area 25) in Williams Syndrome.

Williams Syndrome (WS) is a neurodevelopmental disorder caused by a deletion of 25⁻28 genes on chromosome 7 and characterized by a specific behavioral phenotype, which includes hypersociability and anxiety. Here, we examined the density of neurons and glia in fourteen human brains in Brodmann area 25 (BA 25), in the ventromedial prefrontal cortex (vmPFC), using a postmortem sample of five adult and two infant WS brains and seven age-, sex- and hemisphere-matched typically developing control (TD) brains. We found decreased neuron density, which reached statistical significance in the supragranular layers, and increased glia density and glia to neuron ratio, which reached statistical significance in both supra- and infragranular layers. Combined with our previous findings in the amygdala, caudate nucleus and frontal pole (BA 10), these results in the vmPFC suggest that abnormalities in frontostriatal and frontoamygdala circuitry may contribute to the anxiety and atypical social behavior observed in WS

Cellular Disturbances in the Williams Syndrome Cortex: The Impact of Glia on Social Behavior

The evolution of the human brain has involved a substantial increase in size as well as modifications to the internal, cellular organization and developmental trajectory. These changes have resulted in enhanced cognition, highly complex social behavior, and an increased susceptibility to neurological dysfunction. Comparative neuroanatomical studies of human neurodevelopmental disorders that present with altered cognition or social behavior can increase our understanding of how microstructural changes in the brain may impact uniquely human traits and behaviors. Williams Syndrome (WS) is a rare neurodevelopmental disorder, caused by a hemi-deletion of approximately 25-28 genes on chromosome band 7q11.2, characterized by altered social and emotional behavior, specifically hypersociability, lack of social inhibition, and increased anxiety. We identified microstructural changes in the ventromedial prefrontal cortex (vmPFC) and in glia density across the cortex that may contribute to the social and emotional features of WS. We found decreased neuron density and increased glia density in the vmPFC, increased astrocyte/microglia density in unimodal cortical areas, and increased oligodendrocyte density in prefrontal and unimodal cortical areas. These results suggest that alterations in glia may be a common feature across the WS cortex, potentially affecting neuron-glia interaction and neuronal function. These findings provide evidence for the role of glia in social behavior, and aid in identifying the mechanisms underlying alterations in social function. Additionally, this work contributes to our understanding of the link between microstructural variation and brain function, and the mechanisms that link genetic variation to neuroanatomical variation

Cellular Disturbances in the Williams Syndrome Cortex: The Impact of Glia on Social Behavior

The evolution of the human brain has involved a substantial increase in size as well as modifications to the internal, cellular organization and developmental trajectory. These changes have resulted in enhanced cognition, highly complex social behavior, and an increased susceptibility to neurological dysfunction. Comparative neuroanatomical studies of human neurodevelopmental disorders that present with altered cognition or social behavior can increase our understanding of how microstructural changes in the brain may impact uniquely human traits and behaviors. Williams Syndrome (WS) is a rare neurodevelopmental disorder, caused by a hemi-deletion of approximately 25-28 genes on chromosome band 7q11.2, characterized by altered social and emotional behavior, specifically hypersociability, lack of social inhibition, and increased anxiety. We identified microstructural changes in the ventromedial prefrontal cortex (vmPFC) and in glia density across the cortex that may contribute to the social and emotional features of WS. We found decreased neuron density and increased glia density in the vmPFC, increased astrocyte/microglia density in unimodal cortical areas, and increased oligodendrocyte density in prefrontal and unimodal cortical areas. These results suggest that alterations in glia may be a common feature across the WS cortex, potentially affecting neuron-glia interaction and neuronal function. These findings provide evidence for the role of glia in social behavior, and aid in identifying the mechanisms underlying alterations in social function. Additionally, this work contributes to our understanding of the link between microstructural variation and brain function, and the mechanisms that link genetic variation to neuroanatomical variation

The Human OFC, vmPFC, and ACC : Development and Evolution

The prefrontal cortex is made up of several subdivisions. I will consider three of these, the orbitofrontal cortex, the ventromedial prefrontal cortex, and the anterior cingulate cortex. These areas make up the agranular and dysgranular portion of the prefrontal cortex and have extensive connections with the neocortex as well as several subcortical structures. They play a critical role in emotional/social regulation, reward based learning, attention and error correction. Through these functions they contribute to decision making processes. Here I will discuss the anatomy, functions, development, and evolution through reviews of comparative studies of great ape