A Human Gait Circuit Derived from Brain Lesions and Deep Brain Stimulation

Area of Science:

• Neuroscience
• Neurology
• Human Anatomy

Background:

• Gait dysfunction is a common and debilitating symptom in neurological disorders.
• The underlying neuroanatomical basis for gait impairment post-stroke and in Parkinson's disease (PD) remains incompletely understood.
• Subthalamic deep brain stimulation (DBS) is a therapeutic intervention for PD, but its precise effects on gait neurocircuitry require elucidation.

Purpose of the Study:

• To identify the specific brain circuit associated with gait impairment following stroke.
• To determine the brain circuit involved in gait changes after subthalamic DBS in Parkinson's disease patients.
• To investigate whether these two distinct neurological conditions converge on a common gait-related brain circuit.

Main Methods:

• A cross-sectional retrospective analysis of four independent datasets comprising 109 stroke patients and 125 PD patients who underwent subthalamic DBS.
• Gait impairment was quantified using the Combined Walking Index (stroke) and the Unified Parkinson Disease Rating Scale part III gait subscore (PD).
• Brain connectivity was computed using a normative connectome, linking lesion sites or DBS locations to a priori and data-driven locomotor regions.

Main Results:

• Connectivity between stroke lesion locations and specific brain regions was significantly associated with gait impairment.
• Connectivity between subthalamic DBS sites and both a priori and data-driven gait circuits correlated with post-DBS gait changes.
• The gait circuits identified from stroke lesions and DBS in PD demonstrated similar topography and converged significantly on a common neural circuit (spatial r=0.68, p=0.0063).

Conclusions:

• Lesion locations that impair gait in stroke patients and DBS sites that modulate gait in Parkinson's disease patients converge onto a shared brain circuit.
• This convergence suggests a common neuroanatomical substrate for gait control and dysfunction across different neurological conditions.
• The findings provide crucial insights into the neuroanatomy of gait disorders and potential therapeutic targets.