UC San Diego

Sociality in humans is unparalleled by any other animal, and serves as an essential

defining characteristic of our species. Human/non-human primate comparative neuroanatomical studies, in conjunction with evidence from the hominin fossil record, suggest that the human brain has undergone significant changes since the human-ape ancestral split, not only in size, but more significantly in microstructural reorganization and regional specialization. The prefrontal cortex, a region attributed to many of the higher-order functions involved in human cognition, and the amygdala, a subcortical structure involved in the integration of perceptual information from the cortex and the elicitation of social and emotional responses, have both undergone recent, rapid and functionally significant change in human brain evolution. Connectivity and neuroimaging studies have shown that the amygdala and the orbitofrontal cortex (OFC), a subdivision of the prefrontal cortex implicated in social/emotional cognition, share an important functional relationship within social brain circuitry. Comparative neuroanatomical studies of human neural pathologies such as Williams syndrome (WS), a rare neurodevelopmental disorder caused by a discrete hemizygous deletion of ~26 consecutive genes and characterized by hyper-affiliative social drive and atypical social cognition, further illuminate substrates of neural architecture that are critical for normative function of the human social brain, and offer new insight into the evolutionary trajectory of the social brain in humans. Utilizing standard and advanced tissue staining techniques and quantitative stereology in postmortem human brains, this dissertation offers a cellular characterization of the orbitofrontal cortex and the amygdala in WS and typically developing individuals. Our key findings of altered microstructure in WS include decreased neuron density in the infragranular layers of the orbitofrontal cortex and relative sparing of unimodal cortical areas, increased neuron number in the lateral nucleus of the amygdala, an amygdaloid subdivision that has undergone significant reorganization human brain evolution, and decreased amygdaloid serotonergic innervation in the basolateral nuclei, which underlie sociocognitive functions of the amygdala. These findings constitute evidence supporting disrupted social brain circuitry in WS, and are a critical first step towards identifying mechanisms underlying the atypical social phenotype. Additionally, these findings identify possible microstructural specializations that may contribute to uniquely human social cognition.