Subthalamic and nigral neurons are differentially modulated during parkinsonian gait


The parkinsonian gait disorder and freezing of gait are therapeutically demanding symptoms with considerable impact on quality of life. The aim of this study was to assess the role of subthalamic and nigral neurons in the parkinsonian gait control using intraoperative microelectrode recordings of basal ganglia neurons during a supine stepping task. 12 male patients (56±7 years) suffering from moderate idiopathic Parkinson's disease (disease duration 10±3 years, Hoehn & Yahr stage 2) participated in the study. After 10 seconds resting period, stepping at self-paced speed for 35 seconds was followed by short intervals of stepping in response to random "start" and "stop" cues. Single- and multi-unit activity was analysed offline in relation to different aspects of the stepping task (attentional "start" and "stop" cues, heel strikes, stepping irregularities) in terms of firing frequency, firing pattern, and oscillatory activity. Subthalamic nucleus and the substantia nigra neurons responded to different aspects of the stepping task. 24% of the subthalamic nucleus neurons exhibited movement-related activity modulation as an increase of the firing rate, suggesting a predominant role of the subthalamic nucleus in motor aspects of the task, while 8% of subthalamic nucleus neurons showed a modulation in response to the attentional cues. In contrast, responsive substantia nigra neurons showed activity changes exclusively associated with attentional aspects of the stepping task (15%). The firing pattern of subthalamic nucleus neurons revealed gait-related firing regulation and a drop of beta oscillations during regular stepping performance. During freezing episodes instead, there was a rise of beta oscillatory activity. This study shows for the first time specific, task-related, subthalamic nucleus and substantia nigra single unit activity during gait-like movements in humans with differential roles in motor and attentional control of gait. The emergence of perturbed firing patterns in the subthalamic nucleus indicates a disturbed information transfer within the gait network, resulting in freezing of gait.

Bibliografische Daten

StatusVeröffentlicht - 03.07.2023

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© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.

PubMed 36730026