Challenges for future theories of Parkinson pathophysiology

Current theories on the basal ganglia-thalamic-cortical circuitry address the phenomena of hypokinesia and hyperkinesia. In this Perspective, we question whether the current models can address the orchestration of the motor units which is the common final pathway of the motor system. We conclude that the current theories do not to address this orchestration in health and disease. One alternative approach worthy of consideration is nonmonotonic nonlinear dynamics that contrast with a fundamentally linear or monotonic nonlinear approach that are presumed by current theories of basal ganglia-thalamic-cortical system. The purpose here is to make the case that current theories do presuppose a linear or monotonic nonlinear perspective which will be demonstrated as failing to adequately explicate the complex orchestration of motor unit activities in normal movement and in movement disorders. The notion of nonlinear dynamics is not new to neurophysiology; however, it is argued that it is new to the concepts of the physiology and pathophysiology of the basal ganglia-thalamic-cortical system. Providing a wholesale reconceptualization of the basal ganglia-thalamic-cortical system is beyond the scope of this effort. Rather, the contribution of the essay is convincing that there is a need to reconceptualize theories as nonlinear dynamical systems and there are metaphors and analogies from nonlinear science that can be productive in the reconsideration.