Effects Of Motor Cortex Stimulation Research Articles

Long-term analgesic effect of trans-spinal direct current stimulation compared to non-invasive motor cortex stimulation in complex regional pain syndrome.

The aim of the present study was to compare the analgesic effect of motor cortex stimulation using high-frequency repetitive transcranial magnetic stimulation or transcranial direct current stimulation and transcutaneous spinal direct current stimulation in patients with complex regional pain syndrome. Thirty-three patients with complex regional pain syndrome were randomized to one of the three treatment groups (repetitive transcranial magnetic stimulation, n = 11; transcranial direct current stimulation, n = 10; transcutaneous spinal direct current stimulation, n = 12) and received a series of 12 sessions of stimulation for 3 weeks (induction phase) and 11 sessions for 4 months (maintenance therapy). The primary end-point was the mean pain intensity assessed weekly with a visual numerical scale during the month prior to treatment (baseline), the 5-month stimulation period and 1 month after the treatment. The weekly visual numerical scale pain score was significantly reduced at all time points compared to baseline in the transcutaneous spinal direct current stimulation group, at the last two time points in the repetitive transcranial magnetic stimulation group (end of the 5-month stimulation period and 1 month later), but at no time point in the transcranial direct current stimulation group. A significant pain relief was observed at the end of induction phase using transcutaneous spinal direct current stimulation compared to repetitive transcranial magnetic stimulation (P = 0.008) and to transcranial direct current stimulation (P = 0.003). In this trial, transcutaneous spinal direct current stimulation was more efficient to relieve pain in patients with complex regional pain syndrome compared to motor cortex stimulation techniques (repetitive transcranial magnetic stimulation, transcranial direct current stimulation). This efficacy was found during the induction phase and was maintained thereafter. This study warrants further investigation to confirm the potentiality of transcutaneous spinal direct current stimulation as a therapeutic option in complex regional pain syndrome.

Long-term follow-up of motor cortex stimulation on central poststroke pain in thalamic and extrathalamic stroke.

To investigate the long-term effects of motor cortex stimulation (MCS) on central poststroke pain (CPSP) in patients with thalamic and extrathalamic stroke. We retrospectively analyzed 21 cases of CPSP patients who were treated with MCS. Pain intensity was evaluated using the visual analog scale (VAS) and Neuropathic Pain Symptom Inventory (NPSI) before the operation and at follow-up assessments. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). The average follow-up time was 65.43 ± 26.12 months. In the thalamus stroke group (n=11), the mean preoperative VAS score was 8.18 ± 0.75 and the final mean follow-up VAS score was 4.0 ± 2.14. The mean total NPSI score at the last follow-up (20.45 ± 12.7) was significantly reduced relative to the pre-MCS score (30.27 ± 8.97, p < 0.001). Similarly, the mean PSQI value at the last follow-up (12.63 ± 1.91) was significantly reduced compared with the pre-MCS value (16.55 ± 1.97, p < 0.001). In the extrathalamic stroke group (n=11), the mean preoperative VAS score was 8.2 ± 0.79 and the final mean follow-up VAS score was 6.6 ± 2.12. The mean total NPSI score before MCS was not statistically different from that at the last follow-up. There were no statistical differences in sleep quality before versus after surgery. Motor cortex stimulation has higher long-term efficacy in CPSP patients with stroke confined to the thalamus than in CPSP patients with stroke involving extrathalamic structures.

Is the analgesic effect of motor cortex stimulation somatotopically driven or not?

Mechanisms of analgesic efficacy related to motor cortex stimulation (MCS) remain poorly understood. Specifically, it is unclear whether pain relief is somatotopically driven or not. We present three illustrative case-reports of MCS in which unintentional stimulation setting errors occurred, leading to differential (and reversible) pain relief outcomes across the hemi-body. After successful preoperative rTMS trials, three patients suffering from post-stroke pain were selected for MCS. Stimulation was set with the aim of activating two epidural electrodes over the somatotopic representation of the lower and upper limbs. Data regarding pain relief were prospectively collected. At the first follow-up, all three patients complained of a lack of pain relief in the lower limb, contrasting with good outcome in the upper limb. In fact, for each of them we diagnosed the same stimulation setting error, to which they were "blinded", i.e., the parasagittal electrode over the somatotopic representation of the lower limb was inadvertently turned off. Subsequently, six months after having the electrode turned on (still in a "blinded" fashion), all three patients described substantial pain relief in the lower limb, with a median improvement of 50% (range: 40-70%). These incidental case reports argue in favor of a genuine and at least partly somatotopically-driven analgesic efficacy of MCS. Therefore, the parasagittal electrode seems crucial when treating lower limb pain with MCS.

Neurochemical effects of motor cortex stimulation in the periaqueductal gray during neuropathic pain.

Motor cortex stimulation (MCS) is a neurosurgical technique used to treat patients with refractory neuropathic pain syndromes. MCS activates the periaqueductal gray (PAG) matter, which is one of the major centers of the descending pain inhibitory system. However, the neurochemical mechanisms in the PAG that underlie the analgesic effect of MCS have not yet been described. The main goal of this study was to investigate the neurochemical mechanisms involved in the analgesic effect induced by MCS in neuropathic pain. Specifically, we investigated the release of γ-aminobutyric acid (GABA), glycine, and glutamate in the PAG and performed pharmacological antagonism experiments to validate of our findings. Male Wistar rats with surgically induced chronic constriction of the sciatic nerve, along with sham-operated rats and naive rats, were implanted with both unilateral transdural electrodes in the motor cortex and a microdialysis guide cannula in the PAG and subjected to MCS. The MCS was delivered in single 15-minute sessions. Neurotransmitter release was evaluated in the PAG before, during, and after MCS. Quantification of the neurotransmitters GABA, glycine, and glutamate was performed using a high-performance liquid chromatography system. The mechanical nociceptive threshold was evaluated initially, on the 14th day following the surgery, and during the MCS. In another group of neuropathic rats, once the analgesic effect after MCS was confirmed by the mechanical nociceptive test, rats were microinjected with saline or a glycine antagonist (strychnine), a GABA antagonist (bicuculline), or a combination of glycine and GABA antagonists (strychnine+bicuculline) and reevaluated for the mechanical nociceptive threshold during MCS. MCS reversed the hyperalgesia induced by peripheral neuropathy in the rats with chronic sciatic nerve constriction and induced a significant increase in the glycine and GABA levels in the PAG in comparison with the naive and sham-treated rats. The glutamate levels remained stable under all conditions. The antagonism of glycine, GABA, and the combination of glycine and GABA reversed the MCS-induced analgesia. These results suggest that the neurotransmitters glycine and GABA released in the PAG may be involved in the analgesia induced by cortical stimulation in animals with neuropathic pain. Further investigation of the mechanisms involved in MCS-induced analgesia may contribute to clinical improvements for the treatment of persistent neuropathic pain syndromes.

Long-term effect of motor cortex stimulation in patients suffering from chronic neuropathic pain: An observational study.

BackgroundMotor cortex stimulation (MCS) was introduced as a last-resort treatment for chronic neuropathic pain. Over the years, MCS has been used for the treatment of various pain syndromes but long-term follow-up is unknown.MethodsThis paper reports the results of MCS from 2005 until 2012 with a 3-year follow-up. Patients who suffered from chronic neuropathic pain treated with MCS were studied. The analgesic effect was determined as successful by decrease in pain-intensity on the visual analog scale (VAS) of at least 40%. The modifications in drug regimens were monitored with use of the medication quantification scale (MQS). Stimulation parameters and complications were also noted. Interference of pain with quality of life (QoL), the Quality of Life Index (QLI), was determined with use of a specific subset of questions from the MPQ-DLV score.ResultsEighteen patients were included. Mean pre-operative VAS changed from 89.4 ± 11.2 to 53.1 ± 25.0 after three years of follow-up (P < 0.0001). A successful outcome was achieved in seven responders (38.9%). All patients in the responder group suffered from pain caused by a central lesion. With regard to all the patients with central pain lesions (n = 10) and peripheral lesions (n = 8), a significant difference in response to MCS was noticed (P = 0.002). MQS scores and QLI-scores diminished during the follow-up period (P = 0.210 and P = 0.007, respectively).ConclusionMCS seems a promising therapeutic option for patients with refractory pain syndromes of central origin.

Long-term Effect and Predictive Factors of Motor Cortex and Spinal Cord Stimulation for Chronic Neuropathic Pain.

The long-term effects of motor cortex stimulation (MCS) and spinal cord stimulation (SCS) remain unknown. To identify the long-term effects after MCS or SCS and determine any associated predictive factors for the outcomes. Fifty patients underwent MCS (n = 15) or SCS (n = 35) for chronic neuropathic pain. The degree of pain was assessed preoperatively, at 1, 6, and 12 months after surgery, and during the time of the last follow-up using Visual Analog Scale (VAS). Percentage of pain relief (PPR) was calculated, with “long-term effect” defined as PPR ≥ 30% and the presence of continued pain relief over 12 months. Outcomes were classified into excellent (PPR ≥ 70%) and good (PPR 30–69%) sub-categories. Long-term effects of MCS and SCS were observed in 53.3% and 57.1% of the patients, respectively. There were no predictive factors of long-term effects identified for any of the various preoperative conditions. However, the VAS at 1 month after surgery was significantly associated with the long-term effects in both MCS and SCS. All patients with an excellent outcome at 1 month after the surgery continued to exhibit these effects. In contrast, patients with the good outcome at 1 month exhibited a significant decrease in the effects at 6 months after surgery. The long-term effects of MCS and SCS were approximately 50% during the more than 8.5 and 3.5 years of follow-up, respectively. The VAS at 1 month after surgery may be a postoperative predictor of the long-term effects for both MCS and SCS.

TDCS over the motor cortex improves lexical retrieval of action words in poststroke aphasia.

One-third of stroke survivors worldwide suffer from aphasia. Speech and language therapy (SLT) is considered effective in treating aphasia, but because of time constraints, improvements are often limited. Noninvasive brain stimulation is a promising adjuvant strategy to facilitate SLT. However, stroke might render "classical" language regions ineffective as stimulation sites. Recent work showed the effectiveness of motor cortex stimulation together with intensive naming therapy to improve outcomes in aphasia (Meinzer et al. 2016). Although that study highlights the involvement of the motor cortex, the functional aspects by which it influences language remain unclear. In the present study, we focus on the role of motor cortex in language, investigating its functional involvement in access to specific lexico-semantic (object vs. action relatedness) information in poststroke aphasia. To this end, we tested effects of anodal transcranial direct current stimulation (tDCS) to the left motor cortex on lexical retrieval in 16 patients with poststroke aphasia in a sham-controlled, double-blind study design. Critical stimuli were action and object words, and pseudowords. Participants performed a lexical decision task, deciding whether stimuli were words or pseudowords. Anodal tDCS improved accuracy in lexical decision, especially for words with action-related content and for pseudowords with an "action-like" ending ( t15 = 2.65, P = 0.036), but not for words with object-related content and pseudowords with "object-like" characteristics. We show as a proof-of-principle that the motor cortex may play a specific role in access to lexico-semantic content. Thus motor-cortex stimulation may strengthen content-specific word-to-semantic concept associations during language treatment in poststroke aphasia. NEW & NOTEWORTHY The role of motor cortex (MC) in language processing has been debated in both health and disease. Recent work has suggested that MC stimulation together with speech and language therapy enhances outcomes in aphasia. We show that MC stimulation has a differential effect on object- and action-word processing in poststroke aphasia. We propose that MC stimulation may specifically strengthen word-to-semantic concept association in aphasia. Our results potentially provide a way to tailor therapies for language rehabilitation.

The Effect of Motor Cortex Stimulation on Central Poststroke Pain in a Series of 16 Patients With a Mean Follow-Up of 28 Months

To investigate the effect of motor cortex stimulation (MCS) on central poststroke pain (CPSP) and the outcome predictors associated with medium- to long-term results. This is a retrospective review of 16 CPSP patients treated with MCS with a mean follow-up of 28.2 months. The pain intensity was assessed based on the visual analogue scale (VAS) before surgery and at various follow-up visits. An effective outcome was determined to be at least 40% pain relief. The type (hemorrhage or ischemia) and location (thalamus or non-thalamus) of the stroke, the location of the electrode (epidural or subdural), and preoperative repetitive transcranial magnetic stimulation (rTMS) results were analyzed to evaluate whether they are predictive of effective outcomes. The mean VAS before surgery was 8.0 ± 0.7 compared with 3.8 ± 2.1 one month after surgery and 5.3 ± 2.4 at the last follow-up. There were no differences in the analgesic effects between the types of stroke (hemorrhage or ischemia), stroke location (thalamus or non-thalamus), or the location of the electrode (epidural or subdural). The association between preoperative rTMS and effective outcomes was significant with a positive predictive value of 0.8571 and a negative predictive value of 0.7778. Our results suggest that MCS significantly reduces the pain intensity of CPSP. The types of stroke (hemorrhage or ischemia), stroke location (thalamus or nonthalamus), and the location of the electrode (epidural or subdural) were not significant predictors of the analgesic effects of MCS. Preoperative rTMS might be helpful for screening candidates for MCS.

Immediate and Sustained Effects of 5-Day Transcranial Direct Current Stimulation of the Motor Cortex in Phantom Limb Pain

The study explored the analgesic effects of transcranial direct current stimulation (tDCS) over the motor cortex on postamputation phantom limb pain (PLP). Eight subjects with unilateral lower or upper limb amputation and chronic PLP were enrolled in a crossover, double-blind, sham-controlled treatment program. For 5 consecutive days, anodal (active or sham) tDCS was applied over the motor cortex for 15 minutes at an intensity of 1.5 mA. The 5-day treatment with active, but not sham, tDCS induced a sustained decrease in background PLP and in the frequency of PLP paroxysms, which lasted for 1 week after the end of treatment. Moreover, on each day of active tDCS, patients reported an immediate PLP relief, along with an increased ability to move their phantom limb. Patients' immediate responses to sham tDCS, on the contrary, were variable, marked by an increase or decrease of PLP levels from baseline. These results show that a 5-day treatment of motor cortex stimulation with tDCS can induce stable relief from PLP in amputees. Neuromodulation targeting the motor cortex appears to be a promising option for the management of this debilitating neuropathic pain condition, which is often refractory to classic pharmacologic and surgical treatments. PerspectiveThe study describes sustained and immediate effects of motor cortex stimulation by tDCS on postamputation PLP, whose analgesic action seems linked to the motor reactivation of the phantom limb. These results are helpful for the exploitation of tDCS as a therapeutic tool for the management of neuropathic pain.

The effects of transcranial direct current stimulation in patients with neuropathic pain from spinal cord injury

ObjectiveTranscranial direct current stimulation (tDCS) has demonstrated efficacy for reducing neuropathic pain, but the respective mechanisms remain largely unknown. The current study tested the hypothesis that pain reduction with tDCS is associated with an increase in the peak frequency spectrum density in the theta–alpha range. MethodsTwenty patients with spinal cord injury and bilateral neuropathic pain received single sessions of both sham and anodal tDCS (2mA) over the left primary motor area (M1) for 20min. Treatment order was randomly assigned. Pre- to post-procedure changes in pain intensity and peak frequency of electroencephalogram spectral analysis were compared between treatment conditions. ResultsThe active treatment condition (anodal tDCS over M1) but not sham treatment resulted in significant decreases in pain intensity. In addition, consistent with the study hypothesis, peak theta–alpha frequency (PTAF) assessed from an electrode placed over the site of stimulation increased more from pre- to post-session among participants in the active tDCS condition, relative to those in the sham tDCS condition. Moreover, we found a significant association between a decrease in pain intensity and an increase in PTAF at the stimulation site. ConclusionsThe findings are consistent with the possibility that anodal tDCS over the left M1 may be effective, at least in part, because it results in an increase in M1 cortical excitability, perhaps due to a pain inhibitory effect of motor cortex stimulation that may influence the descending pain modulation system. Future research is needed to determine if there is a causal association between increased left anterior activity and pain reduction. SignificanceThe results provide new findings regarding the effects of tDCS on neuropathic pain and brain oscillation changes.

Is Life Better After Motor Cortex Stimulation for Pain Control? Results at Long-Term and their Prediction by Preoperative rTMS

Background: A positive effect of motor cortex stimulation (MCS) (defined as subjective estimations of pain relief ≥ 30%) has been reported in 55 – 64% of patients. Repetitive magnetic cortical stimulation (rTMS) is considered a predictor of MCS effect. These figures are, however, mostly based on subjective reports of pain intensity, and have not been confirmed in the long-term. Objectives: This study assessed long-term pain relief (2 – 9 years) after epidural motor cortex stimulation and its pre-operative prediction by rTMS, using both intensity and Quality of Life (QoL) scales. Study Design: Analysis of the long-term evolution of pain patients treated by epidural motor cortex stimulation, and predictive value of preoperative response to rTMS. Setting: University Neurological Hospital Pain Center. Methods: Patients: Twenty patients suffering chronic pharmaco-resistant neuropathic pain. Intervention: All patients received first randomized sham vs. active 20Hz-rTMS, before being submitted to MCS surgery. Measurement: Postoperative pain relief was evaluated at 6 months and then up to 9 years post-MCS (average 6.1 ± 2.6 y) using (i) pain numerical rating scores (NRS); (ii) a combined assessment (CPA) including NRS, drug intake, and subjective quality of life; and (iii) a short questionnaire (HowRu) exploring discomfort, distress, disability, and dependence. Results: Pain scores were significantly reduced by active (but not sham) rTMS and by subsequent MCS. Ten out of 20 patients kept a long-term benefit from MCS, both on raw pain scores and on CPA. The CPA results were strictly comparable when obtained by the surgeon or by a third-party on telephonic survey (r = 0.9). CPA scores following rTMS and long-term MCS were significantly associated (Fisher P = 0.02), with 90% positive predictive value and 67% negative predictive value of preoperative rTMS over long-term MCS results. On the HowRu questionnaire, long-term MCSrelated improvement concerned “discomfort” (physical pain) and “dependence” (autonomy for daily activities), whereas “disability” (work, home, and leisure activities) and “distress” (anxiety, stress, depression) did not significantly improve. Limitations: Limited cohort of patients with inhomogeneous pain etiology. Subjectivity of the reported items by the patient after a variable and long delay after surgery. Predictive evaluation based on a single rTMS session compared to chronic MCS. Conclusions: Half of the patients still retain a significant benefit after 2 – 9 years of continuous MCS, and this can be reasonably predicted by preoperative rTMS. Adding drug intake and QoL estimates to raw pain scores allows a more realistic assessment of long-term benefits and enhance the rTMS predictive value. The aims of this study and its design were approved by the local ethics committee (University Hospitals St Etienne and Lyon, France). Key words: Neuropathic pain, chronic refractory pain, repetitive transcranial magnetic stimulation, rTMS, epidural motor cortex stimulation, MCS, quality of life, predictive value

The Changes of c-Fos Expression by Motor Cortex Stimulation in the Deafferentation Pain Model

The effect of motor cortex stimulation (MCS) therapy for deafferentation pain was evaluated based on c-Fos, a known pain marker. Nineteen mature cats weighing 1.5–3.5 kg were used. Cats were divided into three groups: a deafferentation pain group in which the left trigeminal ganglion was destroyed, an MCS group in which MCS was used following destruction of the trigeminal ganglion, and a control group. Sites and levels of c-Fos expression were examined immunohistochemically. The percentage of c-Fos-positive cells in the left spinal nucleus of the trigeminus, the bilateral insula, and the bilateral operculum increased in both the deafferentation pain and the MCS groups. There were no statistically significant differences between these groups. In the cingulate gyrus, the percentage of c-Fos-positive cells increased bilaterally in the deafferentation pain group and the MCS group, but the increase was greater in the MCS group. The increase in c-Fos-positive cells in the left spinal nucleus of the trigeminus in the deafferentation group may reflect reported electrical hyperactivity. The cingulate gyrus, insula, and parietal operculum were activated after deafferentation. This change (increase in c-Fos positive cells) is related to the development of deafferentation pain. Pain relief due to MCS is not dependent on the suppression of the activated left spinal nucleus of the trigeminus or the descending analgesic mechanism of the brain stem. Activation of the cingulate gyrus appears to be a factor in the analgesic mechanism of MCS.

Brain opioid receptor density predicts motor cortex stimulation efficacy for chronic pain

The clinical effects of motor cortex stimulation (MCS) for neuropathic pain (NP) is thought to be mediated primarily by the secretion of endogenous opioids in humans and in animal models. Because opioid receptor density is itself decreased in patients with NP, we investigated whether the magnitude and distribution of the remaining opioid receptors in patients with NP could be biological predictors of the pain-relieving effects of MCS. Using 11C-diprenorphine positron emission tomography scans, opioid receptor availability was assessed in 15 patients suffering refractory NP, who subsequently received chronically implanted MCS. All patients underwent 2 preoperative baseline scans at 2-wk intervals and were clinically assessed after 7mo of chronic MCS. The levels of preoperative opioid-binding in the insula, thalamus, periaqueductal gray, anterior cingulate, and orbitofrontal cortex were significantly and positively correlated with postoperative pain relief at 7mo. Patients with receptor density values below the lower limits in age-matched controls in the thalamus, periaqueductal gray and contralateral insula were the least likely to benefit from MCS. Opioid-receptor availability as shown in preoperative positron emission tomography scans appears to be related to the efficacy of MCS in NP and may help clinicians to select the candidates most likely to benefit from this procedure.

Oscillatory Beta Activity Mediates Neuroplastic Effects of Motor Cortex Stimulation in Humans

Continuous theta burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation protocol that can inhibit human motor cortex (M1) excitability and impair movement for ≤ 1 h. While offering valuable insights into brain function and potential therapeutic benefits, these neuroplastic effects are highly variable between individuals. The source of this variability, and the electrophysiological mechanisms underlying the inhibitory after-effects, are largely unknown. In this regard, oscillatory activity at beta frequency (15-35 Hz) is of particular interest as it is elevated in motor disorders such as Parkinson's disease and modulated during the generation of movements. Here, we used a source-level magnetoencephalography approach to investigate the hypothesis that the presence of neuroplastic effects following cTBS is associated with concurrent changes in oscillatory M1 beta activity. M1 cortices were localized with a synthetic aperture magnetometry beamforming analysis of visually cued index finger movements. Virtual electrode analysis was used to reconstruct the spontaneous and movement-related oscillatory activity in bilateral M1 cortices, before and from 10 to 45 min after cTBS. We demonstrate that 40 s of cTBS applied over left M1 reduced corticospinal excitability in the right index finger of 8/16 participants. In these responder participants only, cTBS increased the power of the spontaneous beta oscillations in stimulated M1 and delayed reaction times in the contralateral index finger. No further changes were observed in the latency or power of movement-related beta oscillations. These data provide insights into the electrophysiological mechanisms underlying cTBS-mediated impairment of motor function and demonstrate the association between spontaneous oscillatory beta activity in M1 and the inhibition of motor function.

Involvement of the periaqueductal gray in the effect of motor cortexstimulation

Several clinical and animal studies of different pain models reported that motor cortex stimulation (MCS) has an antinociceptive effect. In our previous study, the response of the primary somatosensory cortex (SI) to peripheral stimuli decreased after MCS. The aim of the present study was to investigate involvement of the periaqueductal gray (PAG) in this inhibitory effect of MCS. Responses of the SI to electrical stimuli applied to both forepaws of anesthetized rats were monitored to evaluate the effect of MCS. After sensory-evoked potentials (SEPs) were stable, either saline, opioid, or dopamine receptor antagonists were locally microinjected into the PAG. After drug or saline administration, MCS was applied to the forepaw area of the right motor cortex. SEPs after MCS were compared to those before MCS. In the saline group, SEPs ipsilateral to MCS decreased, but SEPs contralateral to MCS did not. The decrease in SEPs was prevented by pretreatment of the PAG with naloxone. Application of a nonspecific dopamine receptor antagonist (α-flupenthixol) to the PAG also blocked the inhibition of SEPs after MCS. Inhibition of SEPs after MCS was blocked by local application of a D1 antagonist (SCH-23390) in the PAG, but not by a D2 antagonist (eticlopride). These results suggest that the PAG participates in the inhibitory effect of MCS, and this effect of MCS may be mediated by opioid and dopamine D1 receptors within thePAG.

Neural mechanisms underlying deafferentation pain: a hypothesis from a neuroimaging perspective

Deafferentation pain following nerve injury annoys patients, and its management is a challenge in clinical practice. Although the mechanisms underlying deafferentation pain remain poorly understood, progress in the development of multidimensional neuroimaging techniques is casting some light on these issues. Deafferentation pain likely results from reorganization of the nervous system after nerve injury via processes that interact with the substrates for pain perception (the pain matrix). Therapeutic effects of motor cortex stimulation on deafferentation pain suggest that the core mechanisms underlying deafferentation pain also interact with the motor system. Therefore, simultaneous neuroimaging and brain stimulation, an emerging neuroimaging technique, was developed to investigate complicated interactions among motor, somatosensory, and pain systems. In healthy participants, parts of the pain matrix (the anterior cingulate cortex, parietal operculum, and thalamus) show activity during both somatosensory stimulation and brain stimulation to the motor cortex. This finding indicates that motor, somatosensory, and pain systems communicate among each other via the neural network. A better understanding of the plastic mechanisms influencing such cross-talk among these systems will help develop therapeutic interventions using brain stimulation and neurofeedback.

Long-term motor cortex stimulation for amyotrophic lateral sclerosis

Motor cortex stimulation has been proposed for treatment of amyotrophic lateral sclerosis (ALS) and preliminary studies have reported a slight reduction of disease progression using both invasive and noninvasive repetitive stimulation of the motor cortex. The aim of this proof of principle study was to investigate the effects of motor cortex stimulation performed for a prolonged period (about 2 years) on ALS progression. Two patients were included in the study; the first patient was treated with monthly cycles of repetitive transcranial magnetic stimulation (rTMS) and the second one was treated with chronic epidural motor cortex stimulation. The rate of progression of the disease before and during treatment was compared. The treatments were well tolerated by the patients. Both patients deteriorated during treatment; however, the patient treated with rTMS showed a slight reduction in deterioration rate. Although we cannot be sure whether the effects observed in the patient treated with rTMS can be attributed to this form of stimulation, our study set the groundwork for possible future studies investigating the effects of rTMS, for a prolonged period, on a larger group of ALS patients.

Article 13: Effect of Motor Cortex Stimulation During Robot-Assisted Training on Intracortical Excitability in Chronic Stroke Patients

Objective: To test whether robot-assisted training either alone or combined with transcranial magnetic stimulation (TMS) applied to contralateral motor cortex (M1) increases M1 excitability in stroke patients. Design: Randomized controlled trial. Setting: Laboratory. Participants: 6 chronic stroke patients with single lesion affecting M1 and its projections. Interventions: Robot-assisted wrist extension movements (training alone), subthreshold repetitive TMS (rTMS) (0.1Hz) applied to the contralateral or ipsilateral M1 during execution of training movements in a strictly temporal relationship.

Marked differences in the thermal characteristics of figure-of-eight shaped coils used for repetitive transcranial magnetic stimulation

Objective To compare the heating behaviour of three figure-of-eight shaped coils during repetitive transcranial magnetic stimulation (rTMS). Methods A custom-made coil (referred to as test coil) with a resistance-optimized conductor geometry was compared with two commercially available eight-shaped coils. Each coil was attached to the same energy source, which generated trains of 50 biphasic magnetic pulses every 20 s. Coil temperature was continuously measured during nine rTMS protocols using various combinations of stimulus frequencies (5, 10 or 20 Hz) and intensities (40, 50 or 60% of maximum stimulator output). A heating curve relating coil temperature and the number of applied stimuli was generated for each coil and rTMS condition. In eleven healthy volunteers, we evaluated the effectiveness of motor cortex stimulation. For each coil, we determined the motor threshold (MT) in the right first dorsal interosseus muscle. Results The slope of the heating curves of the test coil was markedly flattened relative to the heating curves of the two standard coils. This allowed the application of at least twice as many stimuli until the temperature of the coil reached 40 °C. Based on these data, we showed that a one-mass model could be used to accurately describe the heating behaviour of each coil. MTs determined with the test coil were comparable to or lower than the MTs that were determined with the standard coils. Conclusions The efficacy of the test coil to stimulate the M1 was comparable to the efficacy of the two standard coils, yet thermal characteristics were markedly improved. Significance Overheating of figure-of-eight shaped coils can be markedly delayed without reducing the efficacy of rTMS.

MULTIDISCIPLINARY PAIN ABSTRACTS: 30 . Neurology (30)

The authors describe the effectiveness of motor cortex stimulation (MCS) in a patient with complex regional pain syndrome (CRPS) type II, formerly known as causalgia, with hemibody allodynia. During MCS, a subjective sensation of warm paresthesia developed in the painful hand and forearm and spread toward the trunk. Pain and allodynia in the areas associated with this sensation were alleviated significantly. The analgesic effect of stimulation proved to be long lasting and was still present at the 12‐month follow up. The authors speculate that MCS might exert its effect through the modulation of thalamic activity in this particular case of CRPS with hemisensory deficit. A central mechanism associated with functional disturbance in noxious‐event processing in the thalamus might have an important role in the pathogenesis of the condition.