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[Preprint]. 2023 Mar 1:2023.02.27.23286478.
doi: 10.1101/2023.02.27.23286478.

Differential cognitive effects of unilateral left and right subthalamic nucleus deep brain stimulation for Parkinson disease

Victor A Del Bene  1   2 , Roy C Martin  1   2 , Sarah A Brinkerhoff  1 , Joseph W Olson  1 , Matthew J Nelson  3 , Dario Marotta  1 , Christopher L Gonzalez  1 , Kelly A Mills  4 , Vidyulata Kamath  5 , J Nicole Bentley  3 , Barton L Guthrie  3 , Robert T Knight  6   7 , Harrison C Walker  1
Affiliations

Differential cognitive effects of unilateral left and right subthalamic nucleus deep brain stimulation for Parkinson disease

Victor A Del Bene et al. medRxiv. .

Update in

Abstract

Objective: To investigate hemispheric effects of directional versus ring subthalamic nucleus (STN) deep brain stimulation (DBS) surgery on cognitive function in patients with advanced Parkinson's disease (PD).

Methods: We examined 31 PD patients (Left STN n = 17; Right STN n = 14) who underwent unilateral subthalamic nucleus (STN) DBS as part of a NIH-sponsored randomized, cross-over, double-blind (ring vs directional) clinical trial. Outcome measures were tests of verbal fluency, auditory-verbal memory, and response inhibition. First, all participants were pooled together to study the effects of directional versus ring stimulation. Then, we stratified the groups by surgery hemisphere and studied the longitudinal changes in cognition post-unilateral STN DBS.

Results: Relative to pre-DBS cognitive baseline performances, there were no group changes in cognition following unilateral DBS for either directional or ring stimulation. However, assessment of unilateral DBS by hemisphere revealed a different pattern. The left STN DBS group had lower verbal fluency than the right STN group (t(20.66 = -2.50, p = 0.02). Over a period of eight months post-DBS, verbal fluency declined in the left STN DBS group (p = 0.013) and improved in the right STN DBS group over time (p < .001). Similarly, response inhibition improved following right STN DBS (p = 0.031). Immediate recall did not significantly differ over time, nor was it affected by implant hemisphere, but delayed recall equivalently declined over time for both left and right STN DBS groups (left STN DBS p = 0.001, right STN DBS differ from left STN DBS p = 0.794).

Conclusions: Directional and ring DBS did not differentially or adversely affect cognition over time. Regarding hemisphere effects, verbal fluency decline was observed in those who received left STN DBS, along with the left and right STN DBS declines in delayed memory. The left STN DBS verbal fluency decrement is consistent with prior bilateral DBS research, likely reflecting disruption of the basal-ganglia-thalamocortical network connecting STN and inferior frontal gyrus. Interestingly, we found an improvement in verbal fluency and response inhibition following right STN DBS. It is possible that unilateral STN DBS, particularly in the right hemisphere, may mitigate cognitive decline.

Keywords: Deep brain stimulation; Parkinson’s disease; cognition; direction stimulation; neuropsychological assessment; subthalamic nucleus.

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Figures

Figure 1.
Figure 1.. Cognitive performance by Stimulation
(A) Line segments show within-participant changes in cognitive performance over time after DBS surgery, and bold lines show sample means. On tests of verbal fluency and memory, higher scores reflect improvement, while a lower score on response inhibition reflects an improved (i.e., faster) performance. p-values indicate significance of slopes over time. (B) Unity plots contrast cognitive performance with double-blind comparison of ring versus directional stimulation. p-values indicate significance of the binomial test in improvement on either stimulation setting.
Figure 2.
Figure 2.. Baseline and longitudinal cognitive function in unilateral STN DBS patients.
(A) Boxplots of baseline multi-domain cognitive performance by implant hemisphere. p-values indicate significance between groups at baseline. (B, C) Line segments show within-participant changes in cognitive performance over time by implant hemisphere, and bold lines show group means. On raw scores of tests of verbal fluency and memory, higher scores reflect improvement, while a lower score on a test of inhibition reflects an improved (i.e., faster) performance. On percent change of all tests, a positive change reflects improvement while a negative change reflects worsening. p-values indicate significant difference between groups in slopes over time.
See this image and copyright information in PMC

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