Neurocomputational models of motor and cognitive deficits in Parkinson's disease.
We review the contributions of biologically constrained computational models to our understanding of motor and cognitive deficits in Parkinson's disease (PD). The loss of dopaminergic neurons innervating the striatum in PD, and the well-established role of dopamine (DA) in reinforcement learning (RL), enable neural network models of the basal ganglia (BG) to derive concrete and testable predictions. We focus in this review on one simple underlying principle - the notion that reduced DA increases activity and causes long-term potentiation in the indirect pathway of the BG. We show how this theory can provide a unified account of diverse and seemingly unrelated phenomena in PD including progressive motor degeneration as well as cognitive deficits in RL, decision making and working memory. DA replacement therapy and deep brain stimulation can alleviate some aspects of these impairments, but can actually introduce negative effects such as motor dyskinesias and cognitive impulsivity. We discuss these treatment effects in terms of modulation of specific mechanisms within the computational framework. In addition, we review neurocomputational interpretations of increased impulsivity in the face of response conflict in patients with deep-brain-stimulation.
Wiecki
Thomas V
TV
Frank
Michael J
MJ
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology; D003198:Computer Simulation; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D007858:Learning / Q000502:physiology; D007980:Levodopa / Q000494:pharmacology; D008568:Memory / Q000502:physiology; D008959:Models, Neurological; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000503:physiopathology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*
D007980:Levodopa; D004298:Dopamine