The subthalamic nucleus modulates the early phase of probabilistic classification learning
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Previous models proposed that the subthalamic nucleus (STN) is critical in the early phase of skill acquisition. We hypothesized that subthalamic deep brain stimulation modulates the learning curve in early classification learning. Thirteen idiopathic Parkinson’s disease patients (iPD) with subthalamic deep brain stimulation (STN-DBS), 9 medically treated iPD, and 21 age-matched healthy controls were tested with a probabilistic classification task. STN-DBS patients were tested with stimulation OFF and ON, and medically treated patients with medication OFF and ON, respectively. Performance and reaction time were analyzed on the first 100 consecutive trials as early learning phase. Moreover, data were separated for low and high-probability patterns, and more differentiated strategy analyses were used. The major finding was a significant modulation of the learning curve in DBS patients with stimulation ON: although overall learning was similar to healthy controls, only the stimulation ON group showed a transient significant performance dip from trials ‘41–60’ that rapidly recovered. Further analysis indicated that this might be paralleled by a modulation of the learning strategy, particularly on the high-probability patterns. The reaction time was unchanged during the dip. Our study supports that the STN serves as a relay in early classification learning and directs attention toward unacquainted content. The STN might play a role in balancing the short-term success against strategy optimization for improved long-term outcome.
KeywordsLearning Subthalamic nucleus Parkinson’s disease Deep brain stimulation Weather prediction task
This work was supported by a research grant from Medtronic, Meerbusch, Germany.
Conflict of interest
Daniel Weiss is supported by a research grant of the German Research Council (DFG) WE5375/1-1 and was supported by a Research Grant of the Medical Faculty of the University of Tübingen (AKF 259-0-0). Daniel Weiss received speaker’s honoraria from Medtronic and travel grants from Medtronic, Abott Pharmaceutical, UCB, and the Movement Disorder Society. Judith Lam declares no competing financial interest. Sorin Breit declares no competing financial interest. Alireza Gharabaghi is supported by grants from Medtronic, the German Research Council [DFG GH 94/2-1, DFG EC 307], Federal Ministry for Education and Research [BFNT 01GQ0761, BMBF 16SV3783, BMBF 03160064B, BMBF V4UKF014], and European Union [ERC 227632]. Rejko Krüger serves as Editor of European Journal of Clinical Investigation, Journal of Neural Transmission and Associate Editor of BMC Neurology and has received research grants of the German Research Council (DFG; KR2219/2-3 and KR2119/8-1), the Michael J Fox Foundation, the Fritz Thyssen foundation (10.11.2.153), and the Federal Ministry for Education and Research [BMBF, NGFNplus; 01GS08134], as well as speaker’s honoraria and/or travel grants from UCB Pharma, Cephalon, Abott Pharmaceutical, Takeda Pharmaceuticals and Medtronic. Andreas Luft is supported by grants from the EU FP7 program, the SNF and the McDonnell Foundation, and the KFSP Program of the University of Zurich. A. Luft is in the scientific advisory boards of Hocoma, Boehringer Ingelheim, Pfizer, Dynamic Devices. Tobias Wächter received speaker’s honoraria and travel reimbursement for scientific meetings from Medtronic, Solvay, Abbott Pharma, Cephalon, Merz Pharmaceuticals, Ipsen Pharma, and Schwarz Pharma. He has also received financial support for research from and conducted commissioned research for Medtronic, Abbott Pharma, Merz Pharmaceuticals, Ipsen Pharma, and Pharm-Allergan and worked on advisory boards for Ipsen Pharma, Merz Pharmaceuticals, and Medtronic.
- Sage JR, Anagnostaras SG, Mitchell S, Bronstein JM, De Salles A, Masterman D, Knowlton BJ (2003) Analysis of probabilistic classification learning in patients with Parkinson’s disease before and after pallidotomy surgery. Learn Mem 10:226–236. doi: 10.1101/lm.45903 PubMedCentralPubMedCrossRefGoogle Scholar
- Wilkinson L, Beigi M, Lagnado DA, Jahanshahi M (2011) Deep brain stimulation of the subthalamic nucleus selectively improves learning of weakly associated cue combinations during probabilistic classification learning in Parkinson’s disease. Neuropsychology 25:286–294. doi: 10.1037/a0021753 PubMedCrossRefGoogle Scholar
- Winstanley CA, Baunez C, Theobald DE, Robbins TW (2005) Lesions to the subthalamic nucleus decrease impulsive choice but impair autoshaping in rats: the importance of the basal ganglia in Pavlovian conditioning and impulse control. Eur J Neurosci 21:3107–3116. doi: 10.1111/j.1460-9568.2005.04143.x PubMedCrossRefGoogle Scholar