Objective: The aim of our study is to obtain a better understanding of how DA and STN-DBS modulate basal ganglia (BG) pathway functions.

Background: Patients with Parkinson’s disease (PD) show a variety of neuropsychiatric symptoms that are relevant in terms of prognosis and quality of life. Increased impulsivity has been observed under dopamine (DA) and deep brain stimulation (DBS) of the subthalamic nucleus (STN) and can lead to serious adverse events (1). Little is known though about the effects of DA and STN-DBS on global versus specific Nogo decisions which are thought to reflect the involvement of different BG pathways (2,3).

Methods: Methods: 23 medically treated PD patients (age 62.0y ± 10.5y, disease duration 5.9y ± 4.4y) and 20 with STN-DBS (age 64.1y ±7.6y, disease duration 13.6y ± 4.9y) underwent motor and cognitive examination ON and OFF DA or DBS respectively. We applied a novel Go-Nogo paradigm with four conditions: a global and specific Go condition as well as a global and specific Nogo condition and a specific Nogo condition. Mean reaction times and error rates were calculated for each condition and compared using Wilcoxon signed-rank tests.

Results: The DBS cohort showed more advanced disease than the medically treated cohort. Medically treated patients made more errors during ON as compared to OFF in the global Nogo (ON 3.8% ± 4.7% and OFF 2.3% ± 4.9%; Z=-2,166, p=0.030) but not in the other conditions. Global Nogo errors during ON correlated with daily intake of DA (Spearman’s rho=0.427, p=0.042). Reaction times of global Nogo errors were significantly faster ON medication (ON:  563s ± 178s versus OFF: 638s ± 215s; t(22)=2.214, p=0.038). Patients ON STN-DBS were significantly faster compared to OFF STN-DBS in the global Go condition (ON 711msec ± 208msec, OFF 778msec ± 243msec; Z=-3.285, p=0.001) without making more errors in any of the conditions.

Conclusions: Better insights in non-motor side effects are crucial for the appropriate selection of individual therapeutic strategies in PD. We show that DA seems to specifically worsen global inhibition, whereas in our cohort STN-DBS had no influence on neither specific nor global inhibitory processes as measured with our new paradigm. Our data suggest a differential effect of the two therapeutic strategies DA and STN-DBS on inhibitory control.

References: (1) Weintraub, D. & Burn, D. J. Parkinson’s disease: the quintessential neuropsychiatric disorder. Mov. Disord. (2011). (2) Frank, M. Dynamic Dopamine Modulation in the Basal Ganglia: A Neurocomputational Account of Cognitive Deficits in Medicated and Nonmedicated Parkinsonism. J Cognitive Neurosci (2006). (3) Schroll, H., Vitay, J. & Hamker, F. Dysfunctional and compensatory synaptic plasticity in Parkinson’s disease. Eur J Neurosci (2014).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/global-inhibitory-control-in-pd-is-impaired-on-dopaminergic-medication-but-not-on-stn-dbs/