The “levodopa-overdose hypothesis” posits that dopaminergic replacement therapy (1) increases performance on tasks that depend on the nigrostriatal-pathway (e.g., motor-control circuits), yet (2) decreases performance on tasks that depend upon the mesocorticolimbic-pathway (e.g., prefrontal cortex, PFC). Previous work in Parkinson’s disease (PD) investigated this model while focusing on cognitive function. Here, we evaluated whether this model applies to gait in patients with PD and freezing of gait (FOG). Forty participants were examined in both the OFF anti-Parkinsonian medication state (hypo-dopaminergic) and ON state (hyper-dopaminergic) while walking with and without the concurrent performance of a serial subtraction task. Wireless functional near-infrared spectroscopy measured PFC activation during walking. Consistent with the “overdose-hypothesis”, performance on the subtraction task decreased (p = 0.027) after dopamine intake. Moreover, the effect of walking condition on PFC activation depended on the dopaminergic state (i.e., interaction effect p = 0.001). Gait significantly improved after levodopa administration (p < 0.001). Nonetheless, PFC activation was higher (p = 0.013) in this state than in the OFF state during usual-walking. This increase in PFC activation in the ON state suggests that dopamine treatment interfered with PFC functioning. Otherwise, PFC activation, putatively a reflection of cognitive compensation, should have decreased. Moreover, in contrast to the OFF state, in the ON state, PFC activation failed to increase (p = 0.313) during dual-tasking, perhaps due to a “ceiling effect”. These findings extend the “levodopa-overdose hypothesis” and suggest that it also applies to gait in PD patients. While dopaminergic therapy improves certain aspects of motor performance, optimal treatment should consider the "double-edged sword" of levodopa.

“左旋多巴用药过量假设”提出，多巴胺能替代疗法（1）在依赖于纹状体纹状体途径的任务（例如，运动控制电路）上提高了表现，而（2）在依赖于中皮层皮质障碍途径的任务上降低了表现。 （例如前额叶皮层，PFC）。帕金森氏病（PD）的先前研究在关注认知功能的同时研究了该模型。在这里，我们评估了该模型是否适用于PD和步态冻结（FOG）患者的步态。在有和没有同时执行连续减法任务的情况下，步行时对40名参与者进行了OFF抗帕金森病用药状态（低多巴胺能）和ON状态（高多巴胺能）的检查。无线功能近红外光谱测量了步行过程中的PFC激活。p  = 0.027）。此外，步行条件对PFC激活的影响取决于多巴胺能状态（即，交互作用p  = 0.001）。左旋多巴给药后步态明显改善（p  <0.001）。尽管如此， 在这种状态下，PFC的激活比平常行走时的OFF状态高（p = 0.013）。在开启状态下PFC激活的这种增加表明，多巴胺治疗会干扰PFC的功能。否则，PFC激活（可能是认知补偿的反映）应该减少。此外，与OFF状态相反，在ON状态下，PFC激活无法增加（p = 0.313），可能是由于“天花板效应”造成的。这些发现扩展了“左旋多巴用药过量假说”，并暗示它也适用于PD患者的步态。尽管多巴胺能疗法可改善运动表现的某些方面，但最佳治疗应考虑左旋多巴的“双刃剑”。