Animal models of action control and cognitive dysfunction in Parkinson's disease

Recent behavioral studies in both humans and rodents have found evidence that performance in decision-making tasks depends on two different learning processes; one encoding the relationship between actions and their consequences and a second involving the formation of stimulus-response associations. These learning processes are thought to govern goal-directed and habitual actions, respectively, and have been found to depend on homologous corticostriatal networks in these species. Thus, recent research using comparable behavioral tasks in both humans and rats has implicated homologous regions of cortex (medial prefrontal cortex/medial orbital cortex in humans and prelimbic cortex in rats) and of dorsal striatum (anterior caudate in humans and dorsomedial striatum in rats) in goal-directed action and in the control of habitual actions (posterior lateral putamen in humans and dorsolateral striatum in rats). These learning processes have been argued to be antagonistic or competing because their control over performance appears to be all or none. Nevertheless, evidence has started to accumulate suggesting that they may at times compete and at others cooperate in the selection and subsequent evaluation of actions necessary for normal choice performance. It appears likely that cooperation or competition between these sources of action control depends not only on local interactions in dorsal striatum but also on the cortico-basal ganglia network within which the striatum is embedded and that mediates the integration of learning with basic motivational and emotional processes. The neural basis of the integration of learning and motivation in choice and decision-making is still controversial and we review some recent hypotheses relating to this issue.

The basal ganglia are a chain of subcortical nuclei that facilitate action selection. Two striatal projection systems--so-called direct and indirect pathways--form the functional backbone of the basal ganglia circuit. Twenty years ago, investigators proposed that the striatum's ability to use dopamine (DA) rise and fall to control action selection was due to the segregation of D(1) and D(2) DA receptors in direct- and indirect-pathway spiny projection neurons. Although this hypothesis sparked a debate, the evidence that has accumulated since then clearly supports this model. Recent advances in the means of marking neural circuits with optical or molecular reporters have revealed a clear-cut dichotomy between these two cell types at the molecular, anatomical, and physiological levels. The contrast provided by these studies has provided new insights into how the striatum responds to fluctuations in DA signaling and how diseases that alter this signaling change striatal function.

Mild cognitive impairment is common in nondemented Parkinson's disease (PD) patients and may be a harbinger of dementia. In view of its importance, the Movement Disorder Society commissioned a task force to delineate diagnostic criteria for mild cognitive impairment in PD. The proposed diagnostic criteria are based on a literature review and expert consensus. This article provides guidelines to characterize the clinical syndrome and methods for its diagnosis. The criteria will require validation, and possibly refinement, as additional research improves our understanding of the epidemiology, presentation, neurobiology, assessment, and long-term course of this clinical syndrome. These diagnostic criteria will support future research efforts to identify at the earliest stage those PD patients at increased risk of progressive cognitive decline and dementia who may benefit from clinical interventions at a predementia stage. Copyright © 2012 Movement Disorder Society.