Depression history modulates effects of subthalamic nucleus topography on neuropsychological outcomes of deep brain stimulation for Parkinson’s disease

Abstract

Patients with psychiatric symptoms, such as depression, anxiety, and visual hallucinations, may be at increased risk for adverse effects following deep brain stimulation of the subthalamic nucleus for Parkinson’s disease, but there have been relatively few studies of associations between locations of chronic stimulation and neuropsychological outcomes. We sought to determine whether psychiatric history modulates associations between stimulation location within the subthalamic nucleus and postoperative affective and cognitive changes. We retrospectively identified 42 patients with Parkinson’s disease who received bilateral subthalamic nucleus deep brain stimulation and who completed both pre- and postoperative neuropsychological testing. Active stimulation contacts were localized in MNI space using Lead-DBS software. Linear discriminant analysis identified vectors maximizing variance in postoperative neuropsychological changes, and Pearson’s correlations were used to assess for linear relationships. Stimulation location was associated with postoperative change for only 3 of the 18 neuropsychological measures. Variation along the superioinferior (z) axis was most influential. Constraining the analysis to patients with a history of depression revealed 10 measures significantly associated with active contact location, primarily related to location along the anterioposterior (y) axis and with worse outcomes associated with more anterior stimulation. Analysis of patients with a history of anxiety revealed 5 measures with location-associated changes without a predominant axis. History of visual hallucinations was not associated with significant findings. Our results suggest that a history of depression may influence the relationship between active contact location and neuropsychological outcomes following subthalamic nucleus deep brain stimulation. These patients may be more sensitive to off-target (nonmotor) stimulation.

The pathobiological basis of depression in Parkinson disease: challenges and outlooks

“…In particular, the evolution of dopaminergic and serotonergic dysfunction and abnormalities of limbic circuits across time, involving the orbitofrontal and anterior cingulate cortices, ventral striatum, amygdala, thalamus, and other important brain networks, help to delineate the variable expression and severity of depression in patients with preclinical/prodromal, early and advances stages of PD (Prange et al 2022 ). A history of depression may also be an increased risk of adverse effects following subthalamic nucleus deep brain stimulation (Kratter et al 2020 ).…”