PMID- 26758832 OWN - NLM STAT- MEDLINE DCOM- 20160517 LR - 20220309 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 36 IP - 2 DP - 2016 Jan 13 TI - Cortical Plasticity Induction by Pairing Subthalamic Nucleus Deep-Brain Stimulation and Primary Motor Cortical Transcranial Magnetic Stimulation in Parkinson's Disease. PG - 396-404 LID - 10.1523/JNEUROSCI.2499-15.2016 [doi] AB - Noninvasive brain stimulation studies have shown abnormal motor cortical plasticity in Parkinson's disease (PD). These studies used peripheral nerve stimulation paired with transcranial magnetic stimulation (TMS) to primary motor cortex (M1) at specific intervals to induce plasticity. Induction of cortical plasticity through stimulation of the basal ganglia (BG)-M1 connections has not been studied. In the present study, we used a novel technique of plasticity induction by repeated pairing of deep-brain stimulation (DBS) of the BG with M1 stimulation using TMS. We hypothesize that repeated pairing of subthalamic nucleus (STN)-DBS and M1-TMS at specific time intervals will lead to plasticity in the M1. Ten PD human patients with STN-DBS were studied in the on-medication state with DBS set to 3 Hz. The interstimulus intervals (ISIs) between STN-DBS and TMS that produced cortical facilitation were determined individually for each patient. Three plasticity induction conditions with repeated pairings (180 times) at specific ISIs ( approximately 3 and approximately 23 ms) that produced cortical facilitation and a control ISI of 167 ms were tested in random order. Repeated pairing of STN-DBS and M1-TMS at short ( approximately 3 ms) and medium ( approximately 23 ms) latencies increased M1 excitability that lasted for at least 45 min, whereas the control condition (fixed ISI of 167 ms) had no effect. There were no specific changes in motor thresholds, intracortical circuits, or recruitment curves. Our results indicate that paired-associative cortical plasticity can be induced by repeated STN and M1 stimulation at specific intervals. These results show that STN-DBS can modulate cortical plasticity. SIGNIFICANCE STATEMENT: We introduced a new experimental paradigm to test the hypothesis that pairing subthalamic nucleus deep-brain stimulation (STN-DBS) with motor cortical transcranial magnetic stimulation (M1-TMS) at specific times can induce cortical plasticity in patients with Parkinson's disease (PD). We found that repeated pairing of STN-DBS with TMS at short ( approximately 3 ms) and medium ( approximately 23 ms) intervals increased cortical excitability that lasted for up to 45 min, whereas the control condition (fixed latency of 167 ms) had no effects on cortical excitability. This is the first demonstration of associative plasticity in the STN-M1 circuits in PD patients using this novel technique. The potential therapeutic effects of combining DBS and noninvasive cortical stimulation should be investigated further. CI - Copyright (c) 2016 the authors 0270-6474/16/360397-09$15.00/0. FAU - Udupa, Kaviraja AU - Udupa K AD - Edmond J. Safra Program in Parkinson's Disease, Division of Neurology and. FAU - Bahl, Nina AU - Bahl N AD - Edmond J. Safra Program in Parkinson's Disease, Division of Neurology and. FAU - Ni, Zhen AU - Ni Z AD - Edmond J. Safra Program in Parkinson's Disease, Division of Neurology and. FAU - Gunraj, Carolyn AU - Gunraj C AD - Edmond J. Safra Program in Parkinson's Disease, Division of Neurology and. FAU - Mazzella, Filomena AU - Mazzella F AUID- ORCID: 0000-0002-0655-7040 AD - Edmond J. Safra Program in Parkinson's Disease, Division of Neurology and Brain and Spinal Cord Rehabilitation Program, Toronto Rehabilitation, University Health Network, University of Toronto, Toronto, Ontario M4G 3V9, Canada, and. FAU - Moro, Elena AU - Moro E AD - Edmond J. Safra Program in Parkinson's Disease, Division of Neurology and Service de Neurologie, CHU Grenoble, Joseph Fourier University, Grenoble 38041, France. FAU - Hodaie, Mojgan AU - Hodaie M AD - Division of Neurosurgery, Krembil Neuroscience Centre, Toronto Western Research Institute, Toronto, Ontario M5T 2S8, Canada. FAU - Lozano, Andres M AU - Lozano AM AD - Division of Neurosurgery, Krembil Neuroscience Centre, Toronto Western Research Institute, Toronto, Ontario M5T 2S8, Canada. FAU - Lang, Anthony E AU - Lang AE AUID- ORCID: 0000-0003-1229-3667 AD - Edmond J. Safra Program in Parkinson's Disease, Division of Neurology and. FAU - Chen, Robert AU - Chen R AUID- ORCID: 0000-0002-8371-8629 AD - Edmond J. Safra Program in Parkinson's Disease, Division of Neurology and Robert.Chen@uhn.ca. LA - eng GR - Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 SB - IM MH - Aged MH - Analysis of Variance MH - Deep Brain Stimulation/*methods MH - Electromyography MH - Evoked Potentials, Motor/physiology MH - Female MH - Humans MH - Male MH - Middle Aged MH - Motor Cortex/*physiology MH - Neuronal Plasticity/*physiology MH - Parkinson Disease/*therapy MH - Subthalamic Nucleus/*physiology MH - Time Factors MH - *Transcranial Magnetic Stimulation PMC - PMC6602027 OTO - NOTNLM OT - deep-brain stimulation OT - hyperdirect pathway OT - intracortical circuits OT - motor cortical plasticity OT - subthalamic nucleus OT - transcranial magnetic stimulation EDAT- 2016/01/14 06:00 MHDA- 2016/05/18 06:00 PMCR- 2016/07/13 CRDT- 2016/01/14 06:00 PHST- 2016/01/14 06:00 [entrez] PHST- 2016/01/14 06:00 [pubmed] PHST- 2016/05/18 06:00 [medline] PHST- 2016/07/13 00:00 [pmc-release] AID - 36/2/396 [pii] AID - 2499-15 [pii] AID - 10.1523/JNEUROSCI.2499-15.2016 [doi] PST - ppublish SO - J Neurosci. 2016 Jan 13;36(2):396-404. doi: 10.1523/JNEUROSCI.2499-15.2016.