Past events

The hundreds of sex differences found in the brain beg the question as to how they develop and what is their function. Factors that cause sex differences in the brain are sex chromosomal gene expression, gonadal hormones, and environmental interactions. Parsimony dictates that these factors act directly on the brain. In fact, available literature on sexual differentiation of the mammalian brain by and large considers just two organs: the gonads and the brain. This perspective, which leaves out all other body parts, misleads us in several ways. First, there is accumulating evidence that all organs are sexually differentiated, and that sex differences in peripheral organs affect the brain. For example, there are sex differences in muscles, adipose tissue, the liver, immune system, gut, kidneys, bladder, and placenta that directly affect the nervous system and behavior. Sex differences may therefore develop in part because brains reside in fundamentally different bodies. This has consequences for brain function as well. Brains may generate different output autonomously, but if they are wired up to different bodies, similar output will have different consequences. To generate similar behaviors, the nervous system may have to compensate by giving different commands. This interaction between body and brain has to be taken into account for a full understanding of the development as well as function of sex differences in the brain. Considering the consequences of this interaction also provides possible explanations for the often remarkable sex differences in neurological and behavioral disorders. These principles will be demonstrated by discussing the development and function of sex differences in vasopressin signaling in brain and body.

Neurodevelopmental disorders encompass a wide range of childhood-onset medical conditions caused by different genetic mutations and interaction with environmental factors, affect ~2% of the population, and are a leading cause of intellectual disability and autism spectrum disorder. Evidence is accumulating that either loss or gain in dosage of proteins involved in cognitive and behavioural processes can be deleterious to the nervous system by causing a failure in the ability to maintain neuronal homeostasis. My studies are focused on the MECP2 duplication syndrome, one of the most common genomic rearrangements in males, characterized by autism, intellectual disability, motor dysfunction, anxiety, epilepsy, recurrent respiratory tract infections and early death. To determine whether the phenotypes of MECP2 duplication are reversible upon normalization of MeCP2 levels, I first generated and characterized a new mouse model that over-expresses a conditional allele of Mecp2 that could be deleted in the adult animal (Nature 2015). Upon normalization of MeCP2 in adult symptomatic mice, several phenotypes were rescued at the behavioral, physiological, and molecular levels. Next, I reduced MeCP2 using an antisense oligonucleotide (ASO) strategy, which has greater translational potential. I found that ASO treatment induced a broad phenotypic rescue in adult symptomatic MECP2 duplication mice, abolished abnormal EEG discharges and behavioral seizures, and corrected abnormal gene expression in the hippocampus. I am currently characterizing a novel “humanized” mouse model of MECP2 duplication syndrome that will precisely mimic the human condition by having two copies of human MECP2 and no copies of the mouse gene. These mice will serve as the ideal model for preclinical tests as they represent the closest construct validity model for the human condition. In addition, I am generating and characterizing neurons and cortical spheroids induced from patients’ derived pluripotent stem cells (iPSCs).

Understanding the Self has fascinated artists, writers, philosophers and psychologist for generation. In the past two decades cognitive and neurocognitive tools have been applied to the study of the Self. The talk will present research on the Self and the Friend. Not surprisingly, it is consistently found that our brain prioritize the Self. For example, deciding whether a face looks to the left or right is faster on one’s own face than on a face of a friend. This prioritization transcend time, showing similar prioritization to one’s face in the past as in the present. Lesions to the fusiform gyrus hinders Self facilitation, while lesions to lateral frontal cortices amplifies it. Associating a simple geometric shape to oneself is done much more efficiently than to a stranger an effect that is mediated via the left STS, medial and lateral frontal cortices. Participants are also better at judging a perspective of an avatar if it is tagged as them than as a stranger. But in all these studies the Friend is also prioritized relative to a stranger. Why is the friend prioritized, is it because it is relevant, or because it is liked? In a simple shape-identity matching task, we manipulated orthogonally the valence and relevance of familiar identities. We found that prioritization is given based on relevance and valence in Western culture, but primarily based on valance in Asian cultures. Using spatial maps to represent the social space, we observed consistent representation of social relations as physical distances. Physical distance between identities was affected by the valence and relevance factors, though this was modulated by the participants’ culture. Finally, presenting participants with incongruent spatial maps of their social relations, resulted in increase and decrease responses in a large network of regions including the Amygdala and superior temporal structure known to play a rule in social cognition. Taken together this body of work highlight neurocognitive mechanism by which our brain prioritize information based on social rules.