Title : Genetic decoupling of brain networks and epigenetic factors in diseases of agency
Abstract:
Impaired self recognition and action execution feature prominently in schizophrenia, as well as in several other cognitive diseases. Though identified as a diseases of agency, the etiology of schizophrenia, in particular, has remained obscure. Whole genome studies have thus far failed to identify gene candidates exerting more than a marginal influence on behavioral symptoms, with affected SNPs numbering well above 12,000 and pool sizes of risk alleles potentially running into the thousands. The indiscriminate and massive number of affected alleles seen in these studies implicates a higher order, organizational and regulatory impairment, rather than one involving specific genetic factors, which affects self- recognition and the ability to execute actions. Such a substrate is likely to be embedded within the interactive properties of large cell clusters such as those comprising neural circuits or even large-scale networks of the brain, which adopt top down regulatory control over behavioral and motor actions. The process of decoupling regulation from genetic oversight to one entailing a systemic and top down supracellular organization raises questions regarding whether the decoupling process itself or the systemic organization are impaired in these diseases. Given that decoupling processes involve developmental events, a failure in epigenetic mechanisms could affect the development of top down neural control leading to excessive or incorrect regulation of plasticity, thereby affecting self recognition. Alternatively, the regulatory structure itself could be the primary impairment. Consistent with this latter possibility, impaired body representations are correlated with the inability to attribute actions to oneself. Such representations are increasingly well understood – for example, several leading proposals link the sensorial representation of the body termed the peripersonal space (PPS) to the self/agent - and could offer a model for investigating the etiology of the disease. This talk will explore current findings of developmental and plastic processes and their influence on self regulation and self identification in these diseases.
