V. Mylius

Noninvasive cortical modulation of experimental pain.

Summary In this paper, the ability to modulate acute provoked pain by NICS techniques (rTMS and tDCS) was reviewed. The results reported in the literature provide insight on the role played by different cortical areas in the integration and control of nociceptive information. These results are also discussed in view of optimizing the treatment of chronic pain syndromes by cortical stimulation. ABSTRACT Noninvasive cortical stimulation (NICS) can produce analgesic effects by means of repetitive transcranial magnetic stimulation or transcranial direct current stimulation (tDCS). Such effects have been demonstrated on chronic ongoing pain, as in acute provoked pain. The investigation of induced changes in the perception of experimental pain by NICS could help clinicians and researchers to better understand the mechanisms of action involved with these techniques and the role played by the cortex in the integration of nociceptive information. This review presents current literature data on the modulation of experimental pain perception by cortical stimulation. The observations found that NICS analgesic effects depend on the method used to provoke pain (referring to the type of nerve fibers and neural circuits that are recruited to mediate pain) and the parameters of cortical stimulation (especially the nature of the cortical target). The motor cortex (precentral cortical area) is the most widely used target for pain modulation. However, other targets, such as the dorsolateral prefrontal cortex, could be of particular interest to modulate various components of pain. Further developments in NICS techniques, such as image‐guided navigated brain stimulation, might lead to improvement in the beneficial effects of NICS on pain. Finally, we discuss whether the results obtained in experimental pain can be transposed to the problem of chronic pain and whether they can be used to optimize cortical stimulation therapy for pain disorders.

Effects of transcranial direct current stimulation on pain perception and working memory.

Previous studies have shown that non‐invasive stimulation of the dorsolateral prefrontal cortex (DLPFC) could modulate experimentally induced pain and working memory (WM) in healthy subjects. However, the two aspects have never been assessed concomitantly. The present study was set up to investigate the effects of transcranial direct current stimulation (tDCS) of the DLPFC on thermal pain and WM in the same population of healthy volunteers. In a randomized and balanced order of different sessions separated by 1 week, 20 min of 2 mA anodal, cathodal or sham tDCS were applied to the left or right DLPFC in two separate experiments. Twelve healthy volunteers were enrolled for each stimulated hemisphere. Warm and cold detection thresholds, heat and cold pain thresholds as well as heat pain tolerance thresholds were measured before, during and following tDCS. WM was assessed by a 2‐back task applied once during cortical stimulation. Anodal tDCS of the right DLPFC led to an increase of tolerance to heat pain. The 2‐back task revealed fewer outliers during cathodal tDCS of the left DLPFC. The present data show an involvement of the DLPFC in the processing of pain and WM. There was no correlation between these findings, suggesting that the analgesic effects of cortical stimulation are not associated with cognitive processing. However, this conclusion is difficult to affirm because of some limitations of the study regarding the parameters of stimulation or a ceiling effect of the 2‐back task for instance.

Relapses in multiple sclerosis: effects of high-dose steroids on cortical excitability

High‐dose steroid administration is the usual treatment of multiple sclerosis (MS) relapse, but it remains to determine whether this treatment may act by changing the excitability of cortical circuitry.

Stroke rehabilitation using noninvasive cortical stimulation: aphasia

Poststroke aphasia results from the lesion of cortical areas involved in the motor production of speech (Broca’s aphasia) or in the semantic aspects of language comprehension (Wernicke’s aphasia). Such lesions produce an important reorganization of speech/language-specific brain networks due to an imbalance between cortical facilitation and inhibition. In fact, functional recovery is associated with changes in the excitability of the damaged neural structures and their connections. Two main mechanisms are involved in poststroke aphasia recovery: the recruitment of perilesional regions of the left hemisphere in case of small lesion and the acquisition of language processing ability in homotopic areas of the nondominant right hemisphere when left hemispheric language abilities are permanently lost. There is some evidence that noninvasive cortical stimulation, especially when combined with language therapy or other therapeutic approaches, can promote aphasia recovery. Cortical stimulation was mainly used to either increase perilesional excitability or reduce contralesional activity based on the concept of reciprocal inhibition and maladaptive plasticity. However, recent studies also showed some positive effects of the reinforcement of neural activities in the contralateral right hemisphere, based on the potential compensatory role of the nondominant hemisphere in stroke recovery.

Reappraisal of the Anatomical Landmarks of Motor and Premotor Cortical Regions for Image-Guided Brain Navigation in TMS Practice

Image‐guided navigation systems dedicated to transcranial magnetic stimulation (TMS) have been recently developed and offer the possibility to visualize directly the anatomical structure to be stimulated. Performing navigated TMS requires a perfect knowledge of cortical anatomy, which is very variable between subjects. This study aimed at providing a detailed description of sulcal and gyral anatomy of motor cortical regions with special interest to the inter‐individual variability of sulci. We attempted to identify the most stable structures, which can serve as anatomical landmarks for motor cortex mapping in navigated TMS practice. We analyzed the 3D reconstruction of 50 consecutive healthy adult brains (100 hemispheres). Different variants were identified regarding sulcal morphology, but several anatomical structures were found to be remarkably stable (four on dorsoventral axis and five on rostrocaudal axis). These landmarks were used to define a grid of 12 squares, which covered motor cortical regions. This grid was used to perform motor cortical mapping with navigated TMS in 12 healthy subjects from our cohort. The stereotactic coordinates (x‐y‐z) of the center of each of the 12 squares of the mapping grid were expressed into the standard Talairach space to determine the corresponding functional areas. We found that the regions whose stimulation produced almost constantly motor evoked potentials mainly correspond to the primary motor cortex, with rostral extension to premotor cortex and caudal extension to posterior parietal cortex. Our anatomy‐based approach should facilitate the expression and the comparison of the results obtained in motor mapping studies using navigated TMS. Hum Brain Mapp 35:2435–2447, 2014.

Clinical pain and experimental pain sensitivity in progressive supranuclear palsy

OBJECTIVE We aimed to assess spinal nociception and experimental pain sensitivity in progressive supranuclear palsy-Richardsons syndrome (PSP-R) compared to patients with Parkinsons disease (PD) and healthy controls (HC). METHODS Spinal nociception as measured by the nociceptive flexion reflex (NFR) and experimental pain sensitivity as measured by heat and electrical pain thresholds were determined in non-demented, non-depressed, probable PSP-R patients (N = 8), PD patients (N = 19) and 17 HC. RESULTS PSP-R patients exhibited lower electrical pain thresholds and a tendency for lower NFR thresholds as compared to HC. No significant differences between PSP-R and PD patients were found with respect to experimentally-induced pain. However, significantly less PSP-R than PD patients reported disease-related pain. CONCLUSIONS Degeneration of the descending inhibitory control system within the brainstem in PSP-R might lead to increased experimental pain sensitivity while frontal cortical deterioration may alter self-estimation of pain.

Analgesic effects of navigated motor cortex rTMS in patients with chronic neuropathic pain.

Repetitive transcranial magnetic stimulation (rTMS) can relieve neuropathic pain when applied at high frequency (HF: 5–20 Hz) over the primary motor cortex (M1), contralateral to pain side. In most studies, rTMS is delivered over the hand motor hot spot (hMHS), whatever pain location. Navigation systems have been developed to guide rTMS targeting, but their value to improve rTMS efficacy remains to be demonstrated.

Transkranielle Magnetstimulation und Motorkortexstimulation bei neuropathischen Schmerzen

ZusammenfassungDie nichtinvasive und invasive Motorkortexstimulation können therapierefraktäre neuropathische Schmerzen verbessern. Mit der hochfrequenten repetitiven transkraniellen Magnetstimulation (rTMS) des kontralateralen Motorkortex können kurzzeitige therapeutische Effekte erzielt und der Effekt einer epiduralen Motorkortexstimulation (MCS) vorhergesagt werden. Der vorliegende Artikel fasst die aktuellen Erkenntnisse zu Anwendung, Mechanismen und Therapieeffekten der kortikalen Stimulation bei neuropathischen Schmerzen zusammen.AbstractNon-invasive and invasive cortical stimulation allows the modulation of therapy-refractory neuropathic pain. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralateral motor cortex yields therapeutic effects at short-term and predicts the benefits of epidural motor cortex stimulation (MCS). The present article summarizes the findings on application, mechanisms and therapeutic effects of cortical stimulation in neuropathic pain.

Navigated rTMS for the Treatment of Pain

Neuropathic pain is a very common burden of society. Although treatment options are various, their success is also limited. Cortical stimulation, which started with invasive epidural approach, first showed sufficient long-term analgesia in about half of the patients with chronic neuropathic pain, resistant to medication prior to implantation. More recently, noninvasive brain stimulation also proved to be effective in the treatment of these patients via rTMS delivered to the motor cortex. In addition, nTMS and nrTMS can be used to determine patient responsiveness and the most suitable site for subsequent electrode implantation.

Transkranielle Magnetstimulation und Motorkortexstimulation bei neuropathischen Schmerzen@@@Transcranial magnetic stimulation and motor cortex stimulation in neuropathic pain

ZusammenfassungDie nichtinvasive und invasive Motorkortexstimulation können therapierefraktäre neuropathische Schmerzen verbessern. Mit der hochfrequenten repetitiven transkraniellen Magnetstimulation (rTMS) des kontralateralen Motorkortex können kurzzeitige therapeutische Effekte erzielt und der Effekt einer epiduralen Motorkortexstimulation (MCS) vorhergesagt werden. Der vorliegende Artikel fasst die aktuellen Erkenntnisse zu Anwendung, Mechanismen und Therapieeffekten der kortikalen Stimulation bei neuropathischen Schmerzen zusammen.AbstractNon-invasive and invasive cortical stimulation allows the modulation of therapy-refractory neuropathic pain. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralateral motor cortex yields therapeutic effects at short-term and predicts the benefits of epidural motor cortex stimulation (MCS). The present article summarizes the findings on application, mechanisms and therapeutic effects of cortical stimulation in neuropathic pain.