Subthalamic nucleus physiology is correlated with deep brain stimulation motor and non-motor outcomes

Abstract

Abstract Subthalamic nucleus (STN) deep brain stimulation (DBS) is commonly indicated for symptomatic relief of idiopathic Parkinson’s disease. Despite the known improvement in motor scores, affective, cognitive, voice and speech functions might deteriorate following this procedure. Recent studies have correlated motor outcomes with intra-operative microelectrode recordings (MER). However, there are no MER-based tools with predictive values relating to long-term outcomes of integrative motor and non-motor symptoms. We conducted a retrospective analysis of the outcomes of patients with idiopathic Parkinson’s disease who had STN-DBS at Tel Aviv Sourasky Medical Centre (Tel Aviv, Israel) during 2015-2016. Forty-eight patients (19 women, 29 men; mean age, 58±8 years) who were implanted with a STN-DBS device underwent pre- and post-surgical assessments of motor, neuropsychological, voice and speech symptoms. Significant improvements in all motor symptoms (except axial signs) and levodopa equivalent daily dose were noted in all patients. Mild improvements were observed in more posterior-related neuropsychological functions (verbal memory, visual memory and organization) while mild deterioration was observed in frontal functions (personality changes, executive functioning and verbal fluency). The concomitant decline in speech intelligibility was mild and only partial, probably in accordance with the neuropsychological verbal fluency results. Acoustic characteristics were the least affected and remained within normal values. Dimensionality reduction of motor, neuropsychological and voice scores rendered six principal components that reflect the main clinical aspects: the tremor-dominant vs the rigidity-bradykinesia-dominant motor-symptoms, frontal vs posterior neuropsychological deficits and acoustic characteristics vs speech intelligibility abnormalities. MER of STN spiking activity were analysed off-line and correlated with the original scores, and with the principal component results. Based on 198 MER trajectories we suggest an intraoperative STN-DBS score which is a simple sum of three MER properties: normalized neuronal activity, the STN width and the relative proportion of the STN dorsolateral oscillatory region. A threshold STN-DBS score >2.5 (preferentially composed of normalized root mean square >1.5, STN width >3 mm and a dorsolateral oscillatory region/STN width ratio >1/3) predicts better motor and non-motor long-term outcomes. The algorithm presented here optimizes intraoperative decision-making of DBS contact localization based on MER with the aim of improving long-term (>1 year) motor, neuropsychological and voice symptoms.