Peter Schwenkreis

Bilateral motor cortex disinhibition in complex regional pain syndrome (CRPS) type I of the hand

Background: Complex regional pain syndrome type I (CRPS I) develops as a consequence of trauma affecting the limbs, without obvious nerve lesion. Its features include pain, edema, autonomic dysfunction, movement disorder, and trophic changes. CNS involvement is suggested by the symptoms, but the pathophysiology of CRPS I is unknown. Objective: To assess excitability changes in the motor cortex in patients with CRPS I. Methods: The authors studied 25 patients with unilateral CRPS I involving the hand by means of transcranial magnetic stimulation using a paired-pulse paradigm. Motor threshold (MT) and intracortical inhibition and facilitation were determined on the affected and the clinically unaffected side. A control group of 20 healthy subjects was studied. Results: The authors found a significant reduction of intracortical inhibition on both sides of patients with CRPS compared with control subjects, whereas intracortical facilitation and MT did not differ significantly. However, in the patients’ group, the presence of allodynia significantly decreased MT. Conclusions: The authors showed a bilateral disinhibition of the motor cortex in patients with complex regional pain syndrome.

Sensorimotor returning in complex regional pain syndrome parallels pain reduction

Patients with complex regional pain syndrome (CRPS) and intractable pain showed a shrinkage of cortical maps on primary (SI) and secondary somatosensory cortex (SII) contralateral to the affected limb. This was paralleled by an impairment of the two‐point discrimination thresholds. Behavioral treatment over 1 to 6 months consisting of graded sensorimotor retuning led to a persistent decrease in pain intensity, which was accompanied by a restoration of the impaired tactile discrimination and regaining of cortical map size in contralateral SI and SII. This suggests that the reversal of tactile impairment and cortical reorganization in CRPS is associated with a decrease in pain. Ann Neurol 2005;57:425–429

The glutamate antagonist Riluzole suppresses intracortical facilitation

SummaryThe effect of the glutamate antagonist riluzole on excitatory and inhibitory phenomena in the human motor system was studied by transcranial magnetic stimulation (TMS) and peripheral electrical nerve stimulation. The motor threshold, the intracortical inhibition and intracortical facilitation as assessed by paired TMS, the cortical and peripheral silent periods, F wave amplitudes and F wave latencies were measured.Riluzole suppressed the intracortical facilitation whereas other parameters remained unchanged, indicating that the neurotransmitter glutamate is mainly involved in facilitatory mechanisms in the motor system.

Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.

In the complex regional pain syndrome (CRPS), several theories proposed the existence of pathophysiological mechanisms of central origin. Recent studies highlighted a smaller representation of the CRPS-affected hand on the primary somatosensory cortex (SI) during non-painful stimulation of the affected side. We addressed the question whether reorganizational changes can also be found in the secondary somatosensory cortex (SII). Moreover, we investigated whether cortical changes might be accompanied by perceptual changes within associated skin territories. Seventeen patients with CRPS of one upper limb without the presence of peripheral nerve injuries (type I) were subjected to functional magnetic resonance imaging (fMRI) during electrical stimulation of both index fingers (IFs) in order to assess hemodynamic signals of the IF representation in SI and SII. As a marker of tactile perception, we tested 2-point discrimination thresholds on the tip of both IFs. Cortical signals within SI and SII were significantly reduced contralateral to the CRPS-affected IF as compared to the ipsilateral side and to the representation of age- and sex-matched healthy controls. In parallel, discrimination thresholds of the CRPS-affected IF were significantly higher, giving rise to an impairment of tactile perception within the corresponding skin territory. Mean sustained, but not current pain levels were correlated with the amount of sensory impairment and the reduction in signal strength. We conclude that patterns of cortical reorganization in SI and SII seem to parallel impaired tactile discrimination. Furthermore, the amount of reorganization and tactile impairment appeared to be linked to characteristics of CRPS pain.

Functional Imaging of Perceptual Learning in Human Primary and Secondary Somatosensory Cortex

Cellular mechanisms underlying synaptic plasticity are in line with the Hebbian concept. In contrast, data linking Hebbian learning to altered perception are rare. Combining functional magnetic resonance imaging with psychophysical tests, we studied cortical reorganization in primary and secondary somatosensory cortex (SI and SII) and the resulting changes of tactile perception before and after tactile coactivation, a simple type of Hebbian learning. Coactivation on the right index finger (IF) for 3 hr lowered its spatial discrimination threshold. In parallel, blood-oxygen level-dependent (BOLD) signals from the right IF representation in SI and SII enlarged. The individual threshold reduction was linearly correlated with the enlargement in SI, implying a close relation between altered discrimination and cortical reorganization. Controls consisting of a single-site stimulation did not affect thresholds and cortical maps. Accordingly, changes within distributed cortical networks based on Hebbian mechanisms alter the individual percept.

Shifts in cortical representations predict human discrimination improvement

We report experiments combining assessment of spatial tactile discrimination behavior and measurements of somatosensory-evoked potentials in human subjects before and after short-term plastic changes to demonstrate a causal link between the degree of altered performance and reorganization. Plastic changes were induced by a Hebbian coactivation protocol of simultaneous pairing of tactile stimuli. As a result of coactivation, spatial discrimination thresholds were lowered; however, the amount of discrimination improvement was variable across subjects. Analysis of somatosensory-evoked potentials revealed a significant, but also variable shift in the localization of the N20-dipole of the index finger that was coactivated. The Euclidean distance between the dipole pre- and post-coactivation was significantly larger on the coactivated side (mean 9.13 ± 3.4 mm) than on the control side (mean 4.90 ± 2.7 mm, P = 0.008). Changes of polar angles indicated a lateral and inferior shift on the postcentral gyrus of the left hemisphere representing the coactivated index finger. To explore how far the variability of improvement was reflected in the degree of reorganization, we correlated the perceptual changes with the N20-dipole shifts. We found that the changes in discrimination abilities could be predicted from the changes in dipole localization. Little gain in spatial discrimination was associated with small changes in dipole shifts. In contrast, subjects who showed a large cortical reorganization also had lowest thresholds. All changes were highly selective as no transfer to the index finger of the opposite, non-coactivated hand was found. Our results indicate that human spatial discrimination performance is subject to improvement on a short time scale by a Hebbian stimulation protocol without invoking training, attention, or reinforcement. Plastic processes related to the improvement were localized in primary somatosensory cortex and were scaled with the degree of the individual perceptual improvement.

Improvement of tactile discrimination performance and enlargement of cortical somatosensory maps after 5 Hz rTMS.

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used to investigate mechanisms of brain functions and plasticity, but also as a promising new therapeutic tool. The effects of rTMS depend on the intensity and frequency of stimulation and consist of changes of cortical excitability, which often persists several minutes after termination of rTMS. While these findings imply that cortical processing can be altered by applying current pulses from outside the brain, little is known about how rTMS persistently affects learning and perception. Here we demonstrate in humans, through a combination of psychophysical assessment of two-point discrimination thresholds and functional magnetic resonance imaging (fMRI), that brief periods of 5 Hz rTMS evoke lasting perceptual and cortical changes. rTMS was applied over the cortical representation of the right index finger of primary somatosensory cortex, resulting in a lowering of discrimination thresholds of the right index finger. fMRI revealed an enlargement of the right index finger representation in primary somatosensory cortex that was linearly correlated with the individual rTMS-induced perceptual improvement indicative of a close link between cortical and perceptual changes. The results demonstrate that repetitive, unattended stimulation from outside the brain, combined with a lack of behavioral information, are effective in driving persistent improvement of the perception of touch. The underlying properties and processes that allow cortical networks, after being modified through TMS pulses, to reach new organized stable states that mediate better performance remain to be clarified.

Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type I

In complex regional pain syndrome (CRPS) many clinical symptoms suggest involvement of the central nervous system. Neuropathic pain as the leading symptom is often resistant to therapy. In the present study we investigated the analgesic efficiency of repetitive transcranial magnetic simulation (rTMS) applied to the motor cortex contralateral to the CRPS-affected side. Seven out of ten patients reported decreased pain intensities. Pain relief occurred 30 s after stimulation, whereas the maximum effect was found 15 min later. Pain re-intensified increasingly 45 min after rTMS. In contrast, sham rTMS did not alter pain perception. These findings provide evidence that in CRPS I pain perception can be modulated by repetitive motor cortex stimulation.

TMS and drugs revisited 2014

The combination of pharmacology and transcranial magnetic stimulation to study the effects of drugs on TMS-evoked EMG responses (pharmaco-TMS-EMG) has considerably improved our understanding of the effects of TMS on the human brain. Ten years have elapsed since an influential review on this topic has been published in this journal (Ziemann, 2004). Since then, several major developments have taken place: TMS has been combined with EEG to measure TMS evoked responses directly from brain activity rather than by motor evoked potentials in a muscle, and pharmacological characterization of the TMS-evoked EEG potentials, although still in its infancy, has started (pharmaco-TMS-EEG). Furthermore, the knowledge from pharmaco-TMS-EMG that has been primarily obtained in healthy subjects is now applied to clinical settings, for instance, to monitor or even predict clinical drug responses in neurological or psychiatric patients. Finally, pharmaco-TMS-EMG has been applied to understand the effects of CNS active drugs on non-invasive brain stimulation induced long-term potentiation-like and long-term depression-like plasticity. This is a new field that may help to develop rationales of pharmacological treatment for enhancement of recovery and re-learning after CNS lesions. This up-dated review will highlight important knowledge and recent advances in the contribution of pharmaco-TMS-EMG and pharmaco-TMS-EEG to our understanding of normal and dysfunctional excitability, connectivity and plasticity of the human brain.

Sensorimotor retuning [corrected] in complex regional pain syndrome parallels pain reduction.

Patients with complex regional pain syndrome (CRPS) and intractable pain showed a shrinkage of cortical maps on primary (SI) and secondary somatosensory cortex (SII) contralateral to the affected limb. This was paralleled by an impairment of the two‐point discrimination thresholds. Behavioral treatment over 1 to 6 months consisting of graded sensorimotor retuning led to a persistent decrease in pain intensity, which was accompanied by a restoration of the impaired tactile discrimination and regaining of cortical map size in contralateral SI and SII. This suggests that the reversal of tactile impairment and cortical reorganization in CRPS is associated with a decrease in pain. Ann Neurol 2005;57:425–429