22 Exploring subthalamic nucleus activity during gait dysfunction and concurrent cognitive load in Parkinson’s disease

Objectives Gait freezing is a common and disabling symptom of Parkinson’s disease characterised by sudden motor arrest during walking that increases falls, nursing home placement and morbidity.¹ A potential therapeutic strategy involves development of adaptive deep brain stimulation devices capable of detecting freezing signatures and delivering real-time, symptom-specific stimulation.² There is promising evidence that periods of increased spiking activity in the subthalamic nucleus may precede the onset of freezing episodes,³ however whether similar abnormal signatures occur with cognitive load, which commonly triggers gait freezing, is unknown.^{4 5} Extending this work, we therefore sought to capture and characterise subthalamic nucleus activity in patients with Parkinson’s disease during periods of virtual reality gait dysfunction and concurrent cognitive load.

Methods Subthalamic nucleus microelectrode recordings were collected intraoperatively from eight Parkinson’s disease patients performing a validated virtual reality gait task, which required patients to respond to on-screen cognitive cues whilst maintaining their motor output.

Results Time-frequency analysis of signals during 15 trials containing freezing or significant slowing precipitated by cognitive dual tasking revealed a sustained and statistically significant reduction in subthalamic nucleus theta frequency (3–8 Hz) firing centred on the moment of cognitive cue presentation compared to 18 trials where virtual reality motor output was unaffected by cognitive load.

Conclusions These results enrich our understanding of the neurobiological basis of the interplay between cognitive factors and gait disturbances including freezing in Parkinson’s disease, informing potential novel avenues for adaptive deep brain stimulation protocols.

References

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2. Weiss D, Massano J. Approaching adaptive control in neurostimulation for Parkinson disease: Autopilot on. Neurology 2018;90(11):497–98. doi: 10.1212/WNL.0000000000005111

3. Georgiades MJ, Shine JM, Gilat M, et al. Hitting the brakes: pathological subthalamic nucleus activity in Parkinson’s disease gait freezing. Brain 2019;142(12):3906–16. doi: 10.1093/brain/awz325

4. Weiss D, Schoellmann A, Fox MD, et al. Freezing of gait: understanding the complexity of an enigmatic phenomenon. Brain 2020;143(1):14–30. doi: 10.1093/brain/awz314

5. Ehgoetz Martens KA, Shine JM, Walton CC, et al. Evidence for subtypes of freezing of gait in Parkinson’s disease. Mov Disord 2018;33(7):1174–78. doi: 10.1002/mds.27417