Gait initiation is a fundamental human task, requiring one or more anticipatory postural adjustments (APA) prior to stepping. Deviations in amplitude and timing of APAs exist in Parkinson's disease (PD), causing dysfunctional postural control which increases the risk of falls. The motor cortex and basal ganglia have been implicated in the regulation of postural control, however, their dynamics during gait initiation, relationship to APA metrics, and response to pharmacotherapy such as levodopa are unknown. To address these questions, we streamed electrocorticography (ECoG) potentials from the premotor and primary motor cortices, as well as local field potentials (LFPs) from the globus pallidus in five people with PD exhibiting gait and balance dysfunction during a cued gait initiation task. Amplitude and timing of APA were evaluated with force plates and synchronized to the neural data. Subjects performed gait initiation trials under ON and LOW levodopa conditions to assess effects of medication on APA metrics and underlying neural dynamics. All subjects demonstrated pallidal and cortical oscillatory changes during different phases of gait initiation. Grouped analysis revealed that from quiet standing to the first foot step, pallidal beta power showed stepwise decrease and broadband gamma power increases, whereas cortical potentials showed low frequency (theta, alpha, beta) power decrease during gait initiation, regardless of medication state. The pallidum and motor cortices also became increasingly coherent during gait initiation compared to quiet standing prior to APA onset. Using linear mixed models, we found that while pallidal gamma powers are predictive of APA scaling, pallidal-cortical coherence (theta, alpha, beta) and premotor-M1 gamma coherence are predictive of APA timing. Our study is the first detailed characterization of basal-ganglia cortical circuit dynamics during human gait initiation. We identified significant pallidal motor cortical power and coherence changes that underlie the amplitude and timing of APA which appear to be independent of medication states of the study subjects. Our results provide evidence for a model where synchronized premotor and motor cortical activities transiently couple with the globus pallidus to regulate the timing of postural responses, and local pallidal activity regulate the amplitude of postural changes during gait initiation. It suggests that abnormal pallidal outflow and synchronization between the pallidum and motor cortices may be a pathophysiological mechanism underlying disordered postural response in Parkinson's disease.

The authors declare no competing financial interests, apart from D.D.W., who has a relationship with Medtronic, Boston Scientific Corp, and Iota Biosciences, Inc. that includes consulting or advisory work.

NCT 03582891

This study was funded by the Michael J Fox Foundation Grant MNS135499A, NIH R01NS130183. All funding was acquired by D.D.W.

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