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The effect of subthalamic deep brain stimulation on executive and memory functions in Parkinson's disease
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Abstracts / Brain Stimulation 10 (2017) 346e540
[0241] CORTICAL TREATMENT OF NEUROPATHIC WITH RTMS AND TDCS: FROM ANECDOTE TO EVIDENCE
[0244] THE EFFECT OF SUBTHALAMIC DEEP BRAIN STIMULATION ON EXECUTIVE AND MEMORY FUNCTIONS IN PARKINSON'S DISEASE
L. Garcia-Larrea*. Inserm and University Of Lyon, France
cs 1, I. Vala lik 1, M. G. Demeter*1, 2, P. Pajkossy 1, 2, A. Szollosi 1, A. Luka ny 1, 2. 1 Budapest University of Technology and Economics, Hungary; Racsma 2 Hungarian Academy of Sciences, Hungary
Following the description of epidural motor cortex stimulation for the treatment of neuropathic pain (NP), attempts to mimic its effects with non-invasive procedures were rapidly launched. rTMS was initially meant to select optimal candidates to implanted stimulation, but has now been gaining a place as a stand-alone therapy. The bulk of published evidence led a European Task Force to assign A-level of proof to rTMS of the motor cortex as a therapeutic option for chronic NP, while the value of tDCS remains under scrutiny. Both techniques continue to evolve, and new targets and procedures are continuously tested. Regarding motor rTMS, there is consensus that significant pain relief is achieved when stimulating anteroposteriorly with focal coils at high frequencies (5 Hz) whereas low-frequency stimulation (1 Hz) does not induce pain relief. Daily sessions over 5-10 days may yield benefit lasting up to two months, and single sessions repeated every two weeks might also allow long-term analgesia. The motor cortex remains the preferred rTMS target in NP, while S1, pre-motor cortex, SMA and dorsolateral prefrontal cortex have been tested with mainly negative results. Trials aiming at targeting deep regions such as the posterior insular cortex are currently in progress. The evidence appears solid that rTMS can alleviate chronic NP in a proportion of patients; trials in fibromyalgia or diffuse pains have yielded mixed results, and this option is not yet supported by high-level evidence. Whether rTMS can decrease experimental pain remains a matter of debate, and a recent prospective study suggested that rTMS may not modify acute heat pain in healthy subjects. rTMS might behave like other anti-neuropathic drugs, which act upon abnormal mechanisms of sensitization, rather than on physiological nociception. Finding solutions to perpetuate the analgesic effects is a current major challenge, and home-based neurostimulation systems are now undergoing clinical trials. Keywords: Neuropathic pain, Home-based neurostimualtion, rTMS, tDCS [0243] LOW INTENSITY RTMS DOES NOT CHANGE EXCITABILITY IN CORTICAL LAYER V AS MEASURED BY IN VIVO LOCAL FIELD POTENTIALS M. Sykes*1, 2, A. Tang 2, J. Rodger 2, J.N.J. Reynolds 1. 1 University of Otago, New Zealand; 2 University of Western Australia, Australia Repetitive transcranial magnetic stimulation is a method commonly applied to non-invasively modulate cortical excitability, using strong (~1 tesla) magnetic pulses. Outside of the targeted, focal zone, however, are broad areas exposed to a lower strength magnetic field, for many neurons below the threshold for direct depolarisation. Increasing evidence has emerged to suggest that fields 100 milliTesla or lower are able, however, to modulate cellular properties such as calcium levels and firing thresholds in vitro. In vivo, 10Hz rTMS at this strength has also been shown to increase motor evoked potential amplitude in anaesthetised rats. To better understand the effects of low-intensity rTMS within the cortex, we made electrophysiological recordings using flexible metal wire electrodes in place of traditional, inflexible glass microelectrodes. We recorded local field potentials from layer V in the motor cortex of urethane-anaesthetised rats. Electrical stimulation of the contralateral cortical layer V produced evoked responses which were subsequently analysed. The metal wire electrode was flattened against the skull, to make way for a custom 8mm rodent rTMS coil, to deliver fields up to ~120milliTesla. Rats were treated with either one or two rounds of quadripulse (QPS-50ms or sham followed by QPS-5ms) or theta burst stimulation (iTBS or sham followed by iTBS). Slopes of the evoked potentials, paired pulse ratio and input/output curves were used to measure changes in the state of the recorded neuronal population. In all cases, no changes were observed as a result of low intensity rTMS, after either one or two rounds of magnetic stimulation. These results suggest that low intensity rTMS, at levels previously shown to elicit MEPs, does not have a substantial effect on the excitability of layer V neurons, measurable under these circumstances. Keywords: low intensity TMS, local field potentials, quadripulse, theta burst
Introduction: The aim of the present study was to asses the effect of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on executive and memory functions in patients with Parkinson’s disease (PD). Methods: PD patients with DBS implantation (DBS group) and PD waitlisted patients (control group) participated in the study. A neuropsychological battery was used to assess cognitive functions. Each task was administered twice: before and after surgery in the DBS group with the stimulators on and with a similar time interval between the two taskadministration points in the control group. Surgical procedure was based on planning with custom-developed Vister-3D software frameless MRI to CT image fusion and with RM and MHT stereotactic systems. Intraoperatively 3 to 5-channel microelectrode recording has been applied with registration of Neurospot (Neurostar) recording equipment. Model 3389 electrodes were implanted bilaterally in all cases and were connected to Activa PC dual channel implantable pulse generators. Results: There was no significant difference between the DBS and the control groups’ performance in tasks measuring short-term and working memory and main executive functions. The DBS group showed a significant decline on the semantic verbal fluency task after surgery compared to its own baseline level (p < .05). Additionally, the DBS group showed a decreased execution cost score at the second assessment point of the prospective memory task, compared to the control group (p < .05). Discussion: Our results provide support for the cognitive safety of the STN DBS using a wait-listed PD control group. The DBS group showed impaired performance after the surgery only on the semantic verbal fluency task which is in line with findings of previous studies. Furthermore, to the best of our knowledge, this is the first study to show that DBS of the STN boosts prospective memory, in particular intention execution functions. Keywords: Parkinson’s disease, Deep brain stimulation, executive functions, memory [0245] CHANGES IN THE LEVEL OF VOLUNTARY ACTIVATION AFTER FATIGUING FINGER TAPPING ~ a, Spain A. Madrid*, E. Medinabeitia, J. Cudeiro, P. Arias. Universidade da Corun Introduction: Finger-tapping (FT) frequency at maximal-rate decreases in few seconds after task beginning. This form of fatigue seems to take place at supraspinal levels (1), but central-fatigue (CF) induced by fast and brief FT has not been evaluated with the twitch-interpolation technique. This technique assesses the level of voluntary activation (VA), gold-standard for CF testing. Herein, we explored the changes in VA induced by maximal-rate FT. Fatigue during FT was defined as the drop in tapping rate during several brief sets of maximal-rate FT. The VA was evaluated during maximal voluntary contractions (MVC) executed before and just following FT (no gap). Our hypothesis predicted a reduction in the VA after fatiguing FT. Methods: 12 participants (18-49 yrs; 3 women) used a 3D-printed hand-fixation system to execute index-FT on a force sensor, with the thumb secured in abduction. Participants performed 12 sets of 30s, with 3min rest. We monitored index range of motion and first dorsal interosseous (FDI) EMG-activity. In some sets, ulnar nerve supramaximal stimulation (UNS) was applied at the elbow (3 stimuli at 100 Hz), in other sets transcranial magnetic stimulation (TMS) was applied on M1-FDI hot-spot, at intensity to obtain motor-evoked potential amplitudes z50% of the Compound Muscle Action Potential in the fresh muscle; another sets included TMS+UNS or UNS+TMS. Stimulation types were counterbalanced in order. Stimulation was automatically applied during MVC (pre and post FT), at the point of force-peak, when force-plateau just started. Results: FT rate significantly decreased along the 30s of finger tapping while TMS silent-periods enlarged from pre to post; set effects were absent. MVC reduced at post and also set after set. The VA was no significantly modified.
Abstracts / Brain Stimulation 10 (2017) 346e540
[0241] CORTICAL TREATMENT OF NEUROPATHIC WITH RTMS AND TDCS: FROM ANECDOTE TO EVIDENCE
[0244] THE EFFECT OF SUBTHALAMIC DEEP BRAIN STIMULATION ON EXECUTIVE AND MEMORY FUNCTIONS IN PARKINSON'S DISEASE
L. Garcia-Larrea*. Inserm and University Of Lyon, France
cs 1, I. Vala lik 1, M. G. Demeter*1, 2, P. Pajkossy 1, 2, A. Szollosi 1, A. Luka ny 1, 2. 1 Budapest University of Technology and Economics, Hungary; Racsma 2 Hungarian Academy of Sciences, Hungary
Following the description of epidural motor cortex stimulation for the treatment of neuropathic pain (NP), attempts to mimic its effects with non-invasive procedures were rapidly launched. rTMS was initially meant to select optimal candidates to implanted stimulation, but has now been gaining a place as a stand-alone therapy. The bulk of published evidence led a European Task Force to assign A-level of proof to rTMS of the motor cortex as a therapeutic option for chronic NP, while the value of tDCS remains under scrutiny. Both techniques continue to evolve, and new targets and procedures are continuously tested. Regarding motor rTMS, there is consensus that significant pain relief is achieved when stimulating anteroposteriorly with focal coils at high frequencies (5 Hz) whereas low-frequency stimulation (1 Hz) does not induce pain relief. Daily sessions over 5-10 days may yield benefit lasting up to two months, and single sessions repeated every two weeks might also allow long-term analgesia. The motor cortex remains the preferred rTMS target in NP, while S1, pre-motor cortex, SMA and dorsolateral prefrontal cortex have been tested with mainly negative results. Trials aiming at targeting deep regions such as the posterior insular cortex are currently in progress. The evidence appears solid that rTMS can alleviate chronic NP in a proportion of patients; trials in fibromyalgia or diffuse pains have yielded mixed results, and this option is not yet supported by high-level evidence. Whether rTMS can decrease experimental pain remains a matter of debate, and a recent prospective study suggested that rTMS may not modify acute heat pain in healthy subjects. rTMS might behave like other anti-neuropathic drugs, which act upon abnormal mechanisms of sensitization, rather than on physiological nociception. Finding solutions to perpetuate the analgesic effects is a current major challenge, and home-based neurostimulation systems are now undergoing clinical trials. Keywords: Neuropathic pain, Home-based neurostimualtion, rTMS, tDCS [0243] LOW INTENSITY RTMS DOES NOT CHANGE EXCITABILITY IN CORTICAL LAYER V AS MEASURED BY IN VIVO LOCAL FIELD POTENTIALS M. Sykes*1, 2, A. Tang 2, J. Rodger 2, J.N.J. Reynolds 1. 1 University of Otago, New Zealand; 2 University of Western Australia, Australia Repetitive transcranial magnetic stimulation is a method commonly applied to non-invasively modulate cortical excitability, using strong (~1 tesla) magnetic pulses. Outside of the targeted, focal zone, however, are broad areas exposed to a lower strength magnetic field, for many neurons below the threshold for direct depolarisation. Increasing evidence has emerged to suggest that fields 100 milliTesla or lower are able, however, to modulate cellular properties such as calcium levels and firing thresholds in vitro. In vivo, 10Hz rTMS at this strength has also been shown to increase motor evoked potential amplitude in anaesthetised rats. To better understand the effects of low-intensity rTMS within the cortex, we made electrophysiological recordings using flexible metal wire electrodes in place of traditional, inflexible glass microelectrodes. We recorded local field potentials from layer V in the motor cortex of urethane-anaesthetised rats. Electrical stimulation of the contralateral cortical layer V produced evoked responses which were subsequently analysed. The metal wire electrode was flattened against the skull, to make way for a custom 8mm rodent rTMS coil, to deliver fields up to ~120milliTesla. Rats were treated with either one or two rounds of quadripulse (QPS-50ms or sham followed by QPS-5ms) or theta burst stimulation (iTBS or sham followed by iTBS). Slopes of the evoked potentials, paired pulse ratio and input/output curves were used to measure changes in the state of the recorded neuronal population. In all cases, no changes were observed as a result of low intensity rTMS, after either one or two rounds of magnetic stimulation. These results suggest that low intensity rTMS, at levels previously shown to elicit MEPs, does not have a substantial effect on the excitability of layer V neurons, measurable under these circumstances. Keywords: low intensity TMS, local field potentials, quadripulse, theta burst
Introduction: The aim of the present study was to asses the effect of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on executive and memory functions in patients with Parkinson’s disease (PD). Methods: PD patients with DBS implantation (DBS group) and PD waitlisted patients (control group) participated in the study. A neuropsychological battery was used to assess cognitive functions. Each task was administered twice: before and after surgery in the DBS group with the stimulators on and with a similar time interval between the two taskadministration points in the control group. Surgical procedure was based on planning with custom-developed Vister-3D software frameless MRI to CT image fusion and with RM and MHT stereotactic systems. Intraoperatively 3 to 5-channel microelectrode recording has been applied with registration of Neurospot (Neurostar) recording equipment. Model 3389 electrodes were implanted bilaterally in all cases and were connected to Activa PC dual channel implantable pulse generators. Results: There was no significant difference between the DBS and the control groups’ performance in tasks measuring short-term and working memory and main executive functions. The DBS group showed a significant decline on the semantic verbal fluency task after surgery compared to its own baseline level (p < .05). Additionally, the DBS group showed a decreased execution cost score at the second assessment point of the prospective memory task, compared to the control group (p < .05). Discussion: Our results provide support for the cognitive safety of the STN DBS using a wait-listed PD control group. The DBS group showed impaired performance after the surgery only on the semantic verbal fluency task which is in line with findings of previous studies. Furthermore, to the best of our knowledge, this is the first study to show that DBS of the STN boosts prospective memory, in particular intention execution functions. Keywords: Parkinson’s disease, Deep brain stimulation, executive functions, memory [0245] CHANGES IN THE LEVEL OF VOLUNTARY ACTIVATION AFTER FATIGUING FINGER TAPPING ~ a, Spain A. Madrid*, E. Medinabeitia, J. Cudeiro, P. Arias. Universidade da Corun Introduction: Finger-tapping (FT) frequency at maximal-rate decreases in few seconds after task beginning. This form of fatigue seems to take place at supraspinal levels (1), but central-fatigue (CF) induced by fast and brief FT has not been evaluated with the twitch-interpolation technique. This technique assesses the level of voluntary activation (VA), gold-standard for CF testing. Herein, we explored the changes in VA induced by maximal-rate FT. Fatigue during FT was defined as the drop in tapping rate during several brief sets of maximal-rate FT. The VA was evaluated during maximal voluntary contractions (MVC) executed before and just following FT (no gap). Our hypothesis predicted a reduction in the VA after fatiguing FT. Methods: 12 participants (18-49 yrs; 3 women) used a 3D-printed hand-fixation system to execute index-FT on a force sensor, with the thumb secured in abduction. Participants performed 12 sets of 30s, with 3min rest. We monitored index range of motion and first dorsal interosseous (FDI) EMG-activity. In some sets, ulnar nerve supramaximal stimulation (UNS) was applied at the elbow (3 stimuli at 100 Hz), in other sets transcranial magnetic stimulation (TMS) was applied on M1-FDI hot-spot, at intensity to obtain motor-evoked potential amplitudes z50% of the Compound Muscle Action Potential in the fresh muscle; another sets included TMS+UNS or UNS+TMS. Stimulation types were counterbalanced in order. Stimulation was automatically applied during MVC (pre and post FT), at the point of force-peak, when force-plateau just started. Results: FT rate significantly decreased along the 30s of finger tapping while TMS silent-periods enlarged from pre to post; set effects were absent. MVC reduced at post and also set after set. The VA was no significantly modified.