Dynamic Properties of Dopamine Asymmetry: A Basis for Functional Lateralization

Functional asymmetries, most commonly associated in humans with population-level hand preference and lateralization in language processing, are complex, heterogeneous traits with poorly understood biological and genetic bases. Notably, functional asymmetries are also associated with familial non-right handedness suggesting that common genetic factors influence both handedness and functional lateralization. This dissertation has two aims. The first is the development of a specific biological hypothesis that may partially account for the consistent co-lateralization of hand preference and prefrontal language function. I argue that asymmetries in local neural properties that affect the excitability and signal-to-noise ratio of neural assemblies can produce a bias in the direction and, to some extent, the degree of functional lateralization for complex functions. At a high level of representation, this hypothesis is similar to long-standing theories of hemispheric differences, but differs from these by providing a single biological difference between hemispheres that influences both motor and prefrontal asymmetries. Specifically, I propose that a hemispheric asymmetry in the ratio of activity at D1 and D2 dopamine receptors can account for both forms of asymmetry. The second aim is to identify novel electrophysiological and behavioral correlates of genetic effects linked to handedness. By applying a standard genetic model to familial handedness data, I obtain an estimate of these genetic effects for individual research participants that may improve sensitivity over previous studies that have primarily used categorical classifications to study familial handedness effects. Two EEG studies of executive function provide evidence for computational changes associated with familial handedness. The first, an auditory oddball paradigm, suggests that cortical noise is increased in conjunction with estimated genetic effects associated with left handedness. In the second study, a go-nogo task, a dissociation between response inhibition and response conflict processing was found with respect to estimated genetic effects associated with left handedness. In addition to bearing on current theories of conflict processing, these results may provide indirect evidence for dopaminergic contributions to neurological and behavioral differences associated with familial sinistrality. Additional studies of resting EEG and behavioral responses to Necker cube viewing provide additional evidence for broad effects of familial sinistrality