Impaired online and enhanced offline motor sequence learning in individuals with Parkinson's disease

Abstract

Whereas memory consolidation research has traditionally focused on longer temporal windows (i.e., hours to days) following an initial learning episode, recent research has also examined the functional significance of the shorter rest epochs commonly interspersed with blocks of task practice (i.e., "micro-offline" intervals on the timescale of seconds to minutes). In the motor sequence learning domain, evidence from young, healthy individuals suggests that micro-offline epochs afford a rapid consolidation process that is supported by the hippocampus. Consistent with these findings, amnesic patients with hippocampal damage were recently found to exhibit degraded micro-offline performance improvements. Interestingly, these offline losses were compensated for by larger performance gains during online practice. Given the known role of the striatum in online motor sequence learning, we hypothesized that individuals with dysfunction of the striatal system would exhibit impaired online, yet enhanced micro-offline, learning (i.e., a pattern of results opposite to those observed in patients with hippocampal lesions). We tested this hypothesis using Parkinsons disease (PD) as a model of striatal dysfunction. Forty-two drug-naive individuals (men and women) with a clinical diagnosis of unilateral PD and 30 healthy control subjects completed a motor sequence learning paradigm. Individuals with PD exhibited deficits during online task practice that were paralleled by greater improvements over micro-offline intervals. This pattern of results could not be explained by disease-related deficits in movement execution. These data suggest that striatal dysfunction disrupts online learning, yet total learning remains unchanged because of greater micro-offline performance improvements that potentially reflect hippocampal-mediated compensatory processes. Significance StatementThe short rest intervals commonly interspersed between periods of active task engagement have traditionally been employed to minimize the build-up of fatigue. There is recent evidence, however, suggesting that these rest epochs may play an active role in motor learning and memory processes and the hippocampus appears to be a critical brain region supporting this rapid "offline" learning. Here, we show that individuals with Parkinsons disease, a movement disorder characterized by dysfunction in the basal ganglia including the striatum, exhibit deficits during active task practice but greater learning over the interspersed offline intervals. Results potentially suggest that the relatively intact hippocampus may help compensate for motor sequence learning deficits linked to a disrupted striatal system in Parkinsons disease.