Multiple sessions of deep brain stimulation using TMS-like protocols reduce cue-induced relapse to cocaine in a rat model

Abstract

s / Brain Stimulation 8 (2015) 412e427 423 University of Auckland, Clinical Neuroscience Laboratory, Department of Medicine, Auckland, New Zealand Background: External counterpulsation (ECP) enhances cerebral blood flow in patients with subacute ischemic stroke but whether it changes corticomotor excitability, which is a powerful prognostic predictor for motor recovery, remains unknown. Methods: We randomized 30 patients with subacute ischemic stroke within 4-21 days of onset (mean 6.23 days) in this sham-controlled clinical trial to either real ECP (n1⁄415) or sham ECP (n1⁄415). Treatment consisted of daily one hour sessions of ECP for ten days. Clinical measures included National Institutes of Health Stroke Scale (NIHSS); functional measures included Purdue Pegboard Test (PPT), Hand Grip (HG), Pinch Grip (PG); and cortical excitability measures included bilateral resting motor threshold (RMT) and motor evoked potential amplitude (MEP) at 130% of RMT. Measures were made at baseline, post-ECP day 1 (Post 1), and post-ECP day 30 (post 30). Results: There were no significant differences between groups at baseline. At post 30, there were significant differences between the real ECP group vs sham ECP group in normalized ipsilesional MEP amplitude (real: 2.35 vs sham: 1.08, P1⁄40.001) and ipsilesional RMT(real: 0.89 vs sham: 0.96, P1⁄40.039). The increase in HG and PPT were also significantly different between the groups at post 30 (HG: real 9.81 vs sham 4.83, P 1⁄4 0.027; PPT: real 4.73 vs sham 2.00, P 1⁄4 0.014 ), but no differences were found in the NIHSS and PG. No differences were found in the contralesional RMT or MEP amplitude. Conclusion: ECP enhances ipsilesional corticomotor excitability in subacute stroke patients. This proof-of-principle study provides a mechanism of motor recovery facilitated by ECP treatment in ischemic stroke patients. * Joint last authors 369 Multiple sessions of deep brain stimulation using TMS-like protocols reduce cue-induced relapse to cocaine in a rat model I. Goldenberg , R. Gal , S. Zibman , N. Barnea-Ygael , A. Zangen Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel A major hallmark of drug (and especially cocaine-) addiction is relapse to drug use following a period of abstinence. In humans and animal models, relapse can be reliably triggered by presenting cues previously associated with drug self-administration, a phenomenon termed cue-induced relapse (CIR). It has been suggested that changes in neuronal activity in the medial prefrontal cortex (mPFC) following repeated drug use may play a key role in CIR. Here we used a chronically-implanted bilateral linear microelectrode array (14 recording electrodes + 2 stimulating electrodes) to record local field potentials (LFPs) and induce subconvulsive electrical stimulations (SCES) in the mPFC of behaving rats. Following array implantation, rats were trained to self-administer cocaine by pressing a reinforcing lever, and each reinforcement was coupled with a light+tone cues. Thereafter, abstinence from drug-taking was induced using the ‘conflict model’. Next, mPFC-SCES (50 trains of 2.5 sec at 20 Hz every 15 sec, 0.2 ms pulse duration, 400 mAmp) was applied daily (15min/day) for two weeks, simulating a typical human TMS-based treatment. The rats then entered a 30 min CIR-test, during which the cues were non-contingently presented. Cue-induced mPFC-LFP activity was recorded throughout the experiment. Whereas 80% of the rats that did not receive SCES ’relapsed’ to lever-pressing, only 33% of the rats treated with SCES ’relapsed’. Additionally, during the CIR-tests, an increased power was observed in the alpha and beta frequency ranges in response to the cues, but this was attenuated in the ICES treated group. Finally, the electrophysiological response to stimulation was altered during treatment particularly in these bands. It therefore seems that repeated cocaine self-administration is associated with increased saliency of the drug-associated cues manifested, at least, as increased cue-induced alpha/beta mPFC activity, and that SCES treatment of the mPFC reduces relapse rates following abstinence.