Electrophysiological correlates of dentate nucleus deep brain stimulation for post-stroke motor recovery

Raghavan Gopalakrishnan; David A Cunningham; Olivia Hogue; Madeleine Schroedel; Brett A Campbell; Kenneth B Baker; Andre G Machado

doi:10.1523/JNEUROSCI.2149-23.2024

Electrophysiological correlates of dentate nucleus deep brain stimulation for post-stroke motor recovery

J Neurosci. 2024 May 9:e2149232024. doi: 10.1523/JNEUROSCI.2149-23.2024. Online ahead of print.

Authors

Raghavan Gopalakrishnan^{1

2

3}, David A Cunningham^{3

4

5}, Olivia Hogue^{1

6}, Madeleine Schroedel¹, Brett A Campbell⁷, Kenneth B Baker^{1

7}, Andre G Machado^{1

7

8}

Affiliations

¹ Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, OH, 44195.
² Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
³ Cleveland FES Center, Cleveland, OH, USA.
⁴ Physical Medicine and Rehabilitation, Case Western Reserve University School of Medicine, Cleveland, OH.
⁵ Center for Rehabilitation Research, MetroHealth Systems, Cleveland, OH, USA.
⁶ Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
⁷ Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
⁸ Department of Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland OH 44195.

PMID: 38724284
DOI: 10.1523/JNEUROSCI.2149-23.2024

Abstract

While ipsilesional cortical electroencephalography has been associated with post-stroke recovery mechanisms and outcomes, the role of cerebellum and its interaction with the ipsilesional cortex is still largely unknown. We have previously shown that post-stroke motor control relies on increased cortico-cerebellar coherence (CCC) in the low beta band to maintain motor task accuracy and to compensate for decreased excitability of the ipsilesional cortex. We now extend our work to investigate corticocerebellar network changes associated with chronic stimulation of the dentato-thalamo-cortical pathway aimed at promoting post-stroke motor rehabilitation. We investigated the excitability of ipsilesional cortex, dentate (DN), and their interaction as a function of treatment outcome measures. Relative to baseline, ten human participants (two women) at the end of 4-8 months of DN deep brain stimulation (DBS) showed 1) significantly improved motor control indexed by computerized motor tasks; 2) significant increase in ipsilesional premotor cortex event-related desynchronization that correlated with improvements in motor function; and 3) significant decrease in CCC, including causal interactions between the DN and ipsilesional cortex, which also correlated with motor function improvements. Furthermore, we show that the functional state of the DN in the post-stroke state and its connectivity with ipsilesional cortex were predictive of motor outcomes associated with DN-DBS. The findings suggest that as participants recovered, the ipsilesional cortex became more involved in motor control, with less demand on the cerebellum to support task planning and execution. Our data provide unique mechanistic insights into the functional state of cortico-cerebellar-cortical network after stroke and its modulation by DN-DBS.Significance Statement The study aims to understand the brain mechanisms underlying the effects of cerebellar dentate deep brain stimulation (DN-DBS), a novel upcoming therapy for chronic stroke. We provide evidence that functional improvements as a result of DN-DBS therapy were accompanied by significant improvements in task behavior and ipsilesional cortex excitability. More importantly.