Patrick Ragert

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

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.

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

Superior tactile performance and learning in professional pianists: evidence for meta‐plasticity in musicians

Musicians brains constitute an interesting model for neuroplasticity. Imaging studies demonstrated that sensorimotor cortical representations are altered in musicians, which was assumed to arise from the development of skilled performance. However, the perceptual consequences of the cortical changes remain elusive. Here we ask whether cortical reorganization induced by professional musical skill training is paralleled by the evolution of other, unrelated perceptual abilities. We therefore studied psychophysically tactile spatial acuity as an indirect marker of cortical changes in professional pianists and non‐musician control subjects using a simultaneous two‐point discrimination paradigm. We show that long‐lasting piano practising resulted in lower spatial discrimination thresholds in comparison to non‐musicians. In musicians, individual discrimination thresholds were linearly correlated with the daily training duration, indicating a direct link between tactile acuity and the degree of piano practising. To investigate whether the superior acuity in pianists is subject to further improvement, we used a Hebbian stimulation protocol of tactile coactivation known to improve spatial tactile acuity. Three hours of coactivation further reduced their discrimination thresholds. The coactivation‐induced gain in pianists was significantly larger in comparison to control subjects and correlated with the years of heavy daily practising (>3 h/day), but not with the total years including casual playing. Our results suggest that despite already high‐level performance in pianists, Hebbian learning was more effective in musicians than in controls. This implies stronger capacities for plastic reorganization and points to enhanced learning abilities implicating a form of meta‐plasticity in professional pianists.

Tactile coactivation resets age-related decline of human tactile discrimination.

For young subjects, it is well‐documented that training and practice improve sensorimotor performance. However, little is known about how the typically observed age‐related decline of sensorimotor abilities can be ameliorated by sensory stimulation.

Sustained increase of somatosensory cortex excitability by 5 Hz repetitive transcranial magnetic stimulation studied by paired median nerve stimulation in humans.

Repetitive transcranial magnetic stimulation (rTMS) has been shown to alter cortical processing within primary motor cortex dependent on the choice of stimulation variables. However, little is known about the effects of TMS in other cortical areas such as the primary somatosensory cortex (SI). Here we asked whether high-frequency (5 Hz) rTMS applied over the left SI evokes sustained changes in cortical excitability. To assess excitability changes, we applied a paired-pulse protocol consisting of paired electrical stimulation of the median nerve using an interstimulus interval of 30 ms and recordings of somatosensory evoked potentials. For ipsilateral SI we found that 1 h after termination of 5 Hz rTMS applied over the left SI with a figure-of-eight coil there was a sustained suppression of the normally present paired-pulse inhibition. Latencies and N20 amplitudes of the first peak remained unchanged. No changes of paired-pulse behavior were observed in the contralateral SI that was not TMS stimulated. The sustained excitability enhancement in SI is discussed in respect to previous findings regarding an improvement of tactile discrimination behavior by rTMS.

Sustained increase of somatosensory cortex excitability by tactile coactivation studied by paired median nerve stimulation in humans correlates with perceptual gain.

Cortical excitability can be reliably assessed by means of paired‐pulse stimulation techniques. Recent studies demonstrated particularly for motor and visual cortex that cortical excitability is systematically altered following the induction of learning processes or during the development of pathological symptoms. A recent tactile coactivation protocol developed by Godde and coworkers showed that improvement of tactile performance in humans can be achieved also without training through passive stimulation on a time scale of a few hours. Tactile coactivation evokes plastic changes in somatosensory cortical areas as measured by blood oxygenation level‐dependent (BOLD) activation in fMRI or SEP‐dipole localization, which correlated with the individual gain in performance. To demonstrate changes in excitability of somatosensory cortex after tactile coactivation, we combined assessment of tactile performance with recordings of paired‐pulse SEPs after electrical median nerve stimulation of both the right coactivated and left control hand at ISIs of 30 and 100 ms before, 3 h after and 24 h after tactile coactivation. Amplitudes and latencies of the first and second cortical N20/P25 response components were calculated. For the coactivated hand, we found significantly lowered discrimination thresholds and significantly reduced paired‐pulse ratios (second N20/P25 response/first N20/P25 response) at an ISI of 30 ms after tactile coactivation indicating enhanced cortical excitability. No changes in paired‐pulse behaviour were observed for ISIs of 100 ms. Both psychophysical and cortical effects recovered to baseline 24 h after tactile coactivation. The individual increase of excitability correlated with the individual gain in discrimination performance. For the left control hand we found no effects of tactile coactivation on paired‐pulse behaviour and discrimination threshold. Our results indicate that changes in cortical excitability are modified by tactile coactivation and were scaled with the degree of improvement of the individual perceptual learning. Conceivably, changes of cortical excitability seem to constitute an additional important marker and mechanism underlying plastic reorganization.

Combination of 5 Hz repetitive transcranial magnetic stimulation (rTMS) and tactile coactivation boosts tactile discrimination in humans

A combination of 5 Hz repetitive transcranial magnetic stimulation (rTMS) over the left primary somatosensory cortex together with tactile coactivation applied to the right index-finger representation (coac + rTMS) boosted tactile discrimination ability tested on the right index-finger. Applying coactivation alone caused a 0.25 mm lowering in tactile discrimination thresholds. In contrast, after coac + rTMS we found a significant further improvement of discrimination thresholds in comparison to the coactivation-induced perceptual changes alone. We demonstrate that the individual further improvement after coac + rTMS depended on the effectiveness of the coactivation protocol when applied alone. Subjects, who showed little gain in tactile performance after coactivation alone, showed the largest improvement after coac + rTMS implying that the combined application was selective for poor learners. The selective effects of coac + rTMS are discussed in respect to N-methyl-D-aspartate receptor activation.

Improving human haptic performance in normal and impaired human populations through unattended activation-based learning

Human haptic performance is not fixed, but subject to major alterations through learning processes. We describe a new stimulation protocol that allows to improve haptic performance in humans in a highly systemic way through unattended activation-based learning. The so-called coactivation protocol is based upon temporal constraints of Hebbian learning where simultaneity plays a key role for the induction of plastic changes. We provide an overview about the potential of coactivation by summarizing recent findings showing that coactivation alters a broad range of basic as well as cognitively demanding types of haptic performance in parallel to cortical reorganization in somatosensory cortex. For example, coactivation applied to the tip of the index finger, or to all fingers of the dominant hand improves tactile acuity, but also haptic object recognition, and speeds up multiple-choice reaction times. Because such changes persist between 24 h and 1 week without further intervention, we interpret the underlying processes as a particular form of perceptual learning. We describe results where coactivation has been utilized for therapeutical purposes in impaired human populations, we outline new developments to optimize and extend unattended activation-based learning protocols, and we sketch the next steps necessary to apply the concept of unattended activation-based learning on a regular and reliable basis as a therapeutical tool in order to selectively interfere with impaired haptic performance.

Assessment of sensorimotor cortical representation asymmetries and motor skills in violin players

As a model for use‐dependent plasticity, the brains of professional musicians have been extensively studied to examine structural and functional adaptation to unique requirements of skilled performance. Here we provide a combination of data on motor performance and hand representation in the primary motor and somatosensory cortex of professional violin players, with the aim of assessing possible behavioural consequences of sensorimotor cortical asymmetries. We studied 15 healthy right‐handed professional violin players and 35 healthy nonmusician controls. Motor and somatosensory cortex asymmetry was assessed by recording the motor output map after transcranial magnetic stimulation from a small hand muscle, and by dipole source localization of somatosensory evoked potentials after electrical stimulation of the median and ulnar nerves. Motor performance was examined using a series of standardized motor tasks covering different aspects of hand function. Violin players showed a significant right‐larger‐than‐left asymmetry of the motor and somatosensory cortex, whereas nonmusician controls showed no significant interhemispheric difference. The amount of asymmetry in the motor and somatosensory cortices of musicians was significantly correlated. At the behavioural level, motor performance did not significantly differ between musicians and nonmusicians. The results support a use‐dependent enlargement of the left hand representation in the sensorimotor cortex of violin players. However, these cortical asymmetries were not paralleled by accompanying altered asymmetries at a behavioural level, suggesting that the reorganisation might be task‐specific and does not lead to improved motor abilities in general.