Silke Lissek

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.

Immobilization Impairs Tactile Perception and Shrinks Somatosensory Cortical Maps

Use is a major factor driving plasticity of cortical processing and cortical maps. As demonstrated of blind Braille readers and musicians, long-lasting and exceptional usage of the fingers results in the development of outstanding sensorimotor skills and in expansions of the cortical finger representations. However, how periods of disuse affect cortical representations and perception in humans remains elusive. Here, we report that a few weeks of hand and arm immobilization by cast wearing significantly reduced hand use and impaired tactile acuity, associated with reduced activation of the respective finger representations in the somatosensory cortex (SI), measured by functional magnetic resonance imaging. Hemodynamic responses in the SI correlated positively with hand-use frequency and negatively with discrimination thresholds, indicating that reduced activation was most prominent in subjects with severe perceptual impairment. We found, strikingly, compensatory effects on the contralateral, healthy hand consisting of improved perceptual performance compared to healthy controls. Two to three weeks after cast removal, perceptual and cortical changes recovered, whereas tactile acuity on the healthy side remained superior to that on the formerly immobilized side. These findings suggest that brief periods of reduced use of a limb have overt consequences and thus constitute a significant driving force of brain organization equivalent to enhanced use.

Bilateral somatosensory cortex disinhibition in complex regional pain syndrome type I

Objective: In a previous study, we found bilateral disinhibition in the motor cortex of patients with complex regional pain syndrome (CRPS). This finding suggests a complex dysfunction of central motor-sensory circuits. The aim of our present study was to assess possible bilateral excitability changes in the somatosensory system of patients with CRPS. Methods: We measured paired-pulse suppression of somatosensory evoked potentials in 21 patients with unilateral CRPS I involving the hand. Eleven patients with upper limb pain of non-neuropathic origin and 21 healthy subjects served as controls. Innocuous paired-pulse stimulation of the median nerve was either performed at the affected and the unaffected hand, or at the dominant hand of healthy controls, respectively. Results: We found a significant reduction of paired-pulse suppression in both sides of patients with CRPS, compared with control patients and healthy control subjects. Conclusion: These findings resemble our findings in the motor system and strongly support the hypothesis of a bilateral complex impairment of central motor-sensory circuits in CRPS I.

Local cytokine changes in complex regional pain syndrome type I (CRPS I) resolve after 6 months.

Summary Local cytokine changes were analyzed in CRPS I patients. TNF‐&agr;, MIP‐1&bgr;, and IL‐1RA were changed bilaterally but returned to the level of non‐CRPS patients after 6 months. Abstract There is evidence that inflammatory processes are involved in at least the early phase of complex regional pain syndrome (CRPS). We compared a panel of pro‐ and antiinflammatory cytokines in skin blister fluids and serum from patients with CRPS and patients with upper‐limb pain of other origin (non‐CRPS) in the early stage (< 1 year) and after 6 months of pain treatment. Blister fluid was collected from the affected and contralateral nonaffected side. We used a multiplex‐10 bead array cytokine assay and Luminex technology to measure protein concentrations of the cytokines interleukin‐1 receptor antagonist (IL‐1RA), IL‐2, IL‐6, IL‐8, IL‐10, IL‐12p40, and tumor necrosis factor‐alpha (TNF‐&agr;) and the chemokines eotaxin, monocyte chemotactic protein‐1 (MCP‐1), and macrophage inflammatory protein‐1&bgr; (MIP‐1&bgr;). We found bilaterally increased proinflammatory TNF‐&agr; and MIP‐1&bgr; and decreased antiinflammatory IL‐1RA protein levels in CRPS patients compared to non‐CRPS patients. Neither group showed side differences. After 6 months under analgesic treatment, protein levels of all measured cytokines in CRPS patients, except for IL‐6, significantly changed bilaterally to the level of non‐CRPS patients. These changes were not related to treatment outcome. In serum, only IL‐8, TNF‐&agr;, eotaxin, MCP‐1, and MIP‐1&bgr; were detectable without intergroup differences. Blister fluid of CRPS patients showed a bilateral proinflammatory cytokine profile. This profile seems to be relevant only at the early stage of CRPS. Almost all measured cytokine levels were comparable to those of non‐CRPS patients after 6 months of analgesic treatment and were not related to treatment outcome.

Impaired learning of a color reversal task after NMDA receptor blockade in the pigeon (Columba livia) associative forebrain (neostriatum caudolaterale).

The neostriatum caudolaterale (NCL) in the pigeon (Columba livia) forebrain is a multisensory associative area and a functional equivalent to the mammalian prefrontal cortex (PFC). To investigate the role of N-methyl-D-aspartate (NMDA) receptors in the NCL for learning flexibility, the authors trained pigeons in a color reversal task while locally blocking NMDA receptors with D,L-2-2-amino-5-phosphonovalerate (AP-5). Controls received saline injections. AP-5-treated pigeons made significantly more errors and showed significantly stronger perseveration in a learning strategy applied by both groups but were unimpaired in initial learning. Results indicate that NMDA receptors in the NCL are necessary for efficient performance in this PFC-sensitive task, and that they are involved in extinction of obsolete information rather than in acquiring new information.

Sex differences in cortical and subcortical recruitment during simple and complex motor control: An fMRI study

In this study, we compared brain activation patterns in men and women during performance of a fine motor task, in order to investigate the influence of motor task complexity upon asymmetries of hemispheric recruitment. Thirty-three right-handed participants (17 males, 16 females) performed a self-paced finger-tapping task comprising three conditions of increasing complexity with both the dominant and the non-dominant hand. Imaging results demonstrated significant sex differences in brain activation patterns. While women showed significantly larger activation of ipsi- and contralateral task-related cortical areas than men, men exhibited significantly stronger subcortical activation in striatal regions. The observed activation differences may reflect sex differences in control of voluntary motor skills related to differential emphasis upon cortical and subcortical correlates of motor sequence processing, as well as differences in hemispheric recruitment, by means of which men and women can nevertheless achieve comparable motor performance.

Sports and brain morphology – A voxel-based morphometry study with endurance athletes and martial artists

Physical exercises and motor skill learning have been shown to induce changes in regional brain morphology, this has been demonstrated for various activities and tasks. Also individuals with special skills show differences in regional brain morphology. This has been indicated for professional musicians, London taxi drivers, as well as for athletes like dancers, golfers and judokas. However little is known about whether sports with different metabolic profiles (aerobic vs. anaerobic) are associated with different patterns of altered brain morphology. In this cross-sectional study we investigated two groups of high-performance athletes, one group performing sports that are thought to be mainly aerobic, and one group performing sports known to have intermittent phases of anaerobic metabolism. Using high-resolution structural imaging and voxel-based morphometry (VBM), we investigated a group of 26 male athletes consisting of 13 martial artists and 13 endurance athletes as well as a group of non-exercising men (n=13). VBM analyses revealed higher gray matter (GM) volumes in the supplementary motor area/dorsal premotor cortex (BA 6) in both athlete groups as compared to the control group. In addition, endurance athletes showed significantly higher GM volume in the medial temporal lobe (MTL), specifically in the hippocampus and parahippocampal gyrus, which was not seen in the martial arts group. Our data suggest that high-performance sports are associated with changes in regional brain morphology in areas implicated in motor planning and motor learning. In addition high-level endurance sports seem to affect MTL structures, areas that have previously been shown to be modulated by aerobic exercise.

Altered ventral striatal activation during reward and punishment processing in premanifest Huntington's disease: a functional magnetic resonance study.

Recent research using various neuroimaging methods revealed the crucial role of the striatum concerning the neuropathology of Huntingtons disease. Degenerative changes located in the basal ganglia are already observable in premanifest stages of Huntingtons disease (pre-HD), i.e., before the onset of manifest motor symptoms. Although the impact of the striatum on reward and punishment processing is well-established in healthy subjects, these processes have not been investigated in manifest and premanifest HD subjects using functional magnetic resonance imaging (fMRI) so far. We used the Monetary Incentive Delay Task to investigate valence discrimination in terms of rewarding and punishing cues in 30 pre-HD and 15 healthy subjects. According to the probability of disease onset within the next 5 years, pre-HD subjects were categorized as either near to motor symptom onset (pre-HD(near); 9.9 [±2.91] years to onset) or far from manifest disease onset (pre-HD(far); 23.49 [±5.99] years to onset). Compared to pre-HD(far) and healthy subjects, pre-HD(near) subjects showed a disturbed neuronal differentiation between reward and control anticipation located in the left ventral striatum. In contrast to pre-HD(far) and healthy subjects, no significant ventral striatal discrimination between punishing and control cues was detected in pre-HD(near) subjects. In the present study, we demonstrated for the first time significant differences in valence discrimination in pre-HD(near) subjects compared to pre-HD(far) subjects and healthy controls. Altered reward and punishment processing could therefore reflect a motivational deficit that may contribute to the pathogenesis of Huntingtons disease.

Hippocampal activation during extinction learning predicts occurrence of the renewal effect in extinction recall.

The renewal effect describes the reoccurrence of a previously extinguished response in situations where the context of extinction differs from that of acquisition, thus illustrating the context-dependency of extinction learning. A number of studies on contextual fear extinction have implicated hippocampus and vmPFC in processing and retrieval of context both during extinction learning and recall of extinction. In this functional magnetic resonance imaging (fMRI) study we explored the neural correlates of the renewal effect in associative learning, using a predictive learning task that required participants to learn relations between cues and outcomes presented in particular contexts. During extinction in a novel context, compared to extinction in a context identical to the acquisition context, participants who exhibited the renewal effect (REN) showed increased activation in brain regions including bilateral posterior hippocampus and left parahippocampal gyrus. This activation pattern was absent in participants that did not show the renewal effect (NOREN). In direct comparisons between the groups, the REN group exhibited higher activation in bilateral hippocampus, while the NOREN group showed higher activation in left dlPFC (BA 46) and right anterior cingulate (BA 32). During extinction recall, stimuli that had been extinguished in a different context were again presented in the context of acquisition. Here both groups exhibited predominantly prefrontal activation, with the REN groups focus upon bilateral OFC (BA 47) and bilateral vmPFC (BA 10), while the NOREN group showed generally more widespread activation, predominantly in large clusters of dlPFC (BA 8,9,45). In a direct comparison, the REN group showed higher activation than the NOREN group in left vmPFC (BA 10), while NOREN participants exhibited more activation in dlPFC (BA 9, 46). Activation in left vmPFC during extinction recall correlated with the number of renewal effect responses, while the dlPFC activation showed a negative correlation with renewal effect responses. These results highlight the differential activation patterns of processes that will eventually produce or not produce a renewal effect, indicating that during extinction learning hippocampus encodes the relation between context and cue-outcome, while in extinction recall vmPFC is active to retrieve this association.

Out of context : NMDA receptor antagonism in the avian prefrontal cortex impairs context processing in a conditional discrimination task

Processing of context information is implicated in prefrontal functions as response selection or attention. N-methyl-D-aspartate (NMDA) receptors in the mammalian prefrontal cortex (PFC) and in the nidopallium caudolaterale (NCL) of birds, the avian functional equivalent of the PFC, are involved in learning, which also requires processing of context. The authors investigated the role of NMDA receptors in the pigeon (Columba livia) NCL for context processing and response selection in a simultaneous-matching-to-sample task with 2 trial types, requiring either processing of context information, delivered by a conditional stimulus (context dependent), or only recall of a stimulus-response association (fixed response). The competitive NMDA antagonist DL-2-amino-5-phosphonovaleric acid impaired performance only in context-dependent trials. Therefore, NMDA receptors in the avian PFC participate in response selection requiring context processing rather than in response selection per se.