Impaired Implicit Sequence Learning in Parkinson's Disease Patients With Freezing of Gait

Objective: Freezing of gait (FOG) in Parkinson's disease (PD) may involve specific impairments in acquiring automaticity under working-memory load. This study examined whether implicit sequence learning, with or without a secondary task, is impaired in patients with FOG. Method: Fourteen freezers (FRs), 14 nonfreezers (nFRs), and 14 matched healthy controls (HCs) performed a serial reaction time (SRT) task with a deterministic stimulus sequence under single-task (ST) and dual-task (DT) conditions. The increase in reaction times (RTs) for random compared with sequenced blocks was used as a measure of implicit sequence learning. Neuropsychological tests assessing global cognitive functioning and executive dysfunction were administered in order to investigate their relation to sequence learning. Results: nFRs and HCs showed significant implicit sequence learning effects (p < 0.001). FRs demonstrated a tendency to learn sequence-specific information in the SRT-ST task (p = 0.07) but not in the SRT-DT task (p = 0.69). Severity of FOG, however, correlated positively with SRT-DT task performance (r = -0.56; p < 0.05). Conclusions: The present results suggest that PD patients suffering from FOG pathology exhibit a specific impairment in the acquisition of automaticity. When working memory capacity is supplementarily loaded by adding a DT, sequence learning in FRs becomes increasingly impaired. These findings indicate that therapies should focus on extensive training in acquiring novel motor activities and reducing working memory load to improve learning in FOG.