Rule-based category learning in patients with Parkinson's disease

Abstract

Measures of explicit rule-based category learning are commonly used in neuropsychological evaluation of individuals with Parkinson's disease (PD) and the pattern of PD performance on these measures tends to be highly varied. We review the neuropsychological literature to clarify the manner in which PD affects the component processes of rule-based category learning and work to identify and resolve discrepancies within this literature. In particular, we address the manner in which PD and its common treatments affect the processes of rule generation, maintenance, shifting and selection. We then integrate the neuropsychological research with relevant neuroimaging and computational modeling evidence to clarify the neurobiological impact of PD on each process. Current evidence indicates that neurochemical changes associated with PD primarily disrupt rule shifting, and may disturb feedback-mediated learning processes that guide rule selection. Although surgical and pharmacological therapies remediate this deficit, it appears that the same treatments may contribute to impaired rule generation, maintenance and selection processes. These data emphasize the importance of distinguishing between the impact of PD and its common treatments when considering the neuropsychological profile of the disease.

Figure 1

Summary of the component processes supporting rule based category learning, specifically rule generation, maintenance, shifting and selection.

Figure 2

Neural architecture of explicit, rule-based category learning. Solid lines indicate excitatory input; dashed lines indicate inhibitory input. Generation of rules depends upon dopamine (DA) activity within the ventral cortico-striatal circuit, including nucleus accumbens (NAc), orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Active maintenance of the rule in use depends upon recurrent excitation of the fronto-thalamic loop that represents that rule. Positive feedback supports rule maintenance through a phasic DA bursts to caudate, which increases excitation of the “Go” pathway and inhibition of the “NoGo” pathway and enables disinhibition of the relevant fronto-thalamic loop. Negative feedback triggers a phasic dip in DA availability in caudate, resulting in enhanced inhibitory output from GPi. This destabilizes the relevant rule representation in WM and increases the likelihood of a shift. Release of norepinephrine from the locus ceruleus may also govern shifting activity. Selection of the new rule depends upon the relative pattern of activation within ACC, which biases the relative patterns of activation of rule representations in prefrontal cortex (PFC). Unexpected negative or positive feedback triggers a phasic dip or burst, respectively, in DA release from the ventral tegmental area. These phasic changes alter activation in NA and ACC and these error-driven changes in ACC activation regulate activation of relevant rule representations in PFC.