Title : Genetic decoupling and global regulatory failure in diseases of agency
Abstract:
Neural mechanisms for self regulation feature prominently in studies of addiction, which is characterized by the inability to resist compulsive behavior. Such mechanisms entail not just top down processes involved in the execution of decision making events, but also the neural representation of the self/agent, generally regarded as the source of decision making capacity. Impairments of this representation can be expected to weaken the ability to enlist capacities for self regulation. Several cognitive diseases exhibit self recognition dysfunctions, suggesting that their study might reveal factors leading to self- representation impairments. Genetic studies, however, have been unable to identify molecular factors contributing to the impairments. Whole genome studies of diseases like schizophrenia, for example, have thus far failed to identify gene candidates exerting more than a marginal influence on behavioral symptoms. Affected single nuclear polymorphisms (SNPs), for example, number well above 12,000 indicating likely pool sizes of risk alleles 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. The genetic findings thus suggest the existence of a process of decoupling regulation from genetic oversight to one involving a systemic and top down supracellular organization exerting regulatory control. Consistent with this interpretation, bodily informed, sensoria driven input are known to shape the synaptic architecture of the brain, thus implicating genetic decoupling and a shift to top down regulation. The inability to attribute actions to the self seen in these diseases thus also suggests a failure in how sensorial input from the body drives the formation of a global regulatory structure. Several leading proposals that link the sensorial representation of the body to the self/agent could offer a model for investigating the etiology of these diseases and will be discussed in this talk.
