Biomedical subjects

Burkhard Pleger

Publications and source records attributed to Burkhard Pleger.

At least 19 recordsLinked to original sources

PubMed2006

Neural coding of tactile decisions in the human prefrontal cortex.

The neural processes underlying tactile decisions in the human brain remain elusive. We addressed this question in a functional magnetic resonance imaging study using a somatosensory discrimination task, requiring participants to compare the frequency of two successive tactile stimuli. Tactile stimuli per se engaged somatosensory, parietal, and frontal cortical regions. Using a statistical model that accounted for the relative difference in frequencies (i.e., Weber fraction) and discrimination accuracy (i.e., correct or incorrect), we show that trial-by-trial relative frequency difference is represented linearly by activity changes in the left dorsolateral prefrontal cortex (DLPFC), the dorsal anterior cingulate cortex, and bilateral anterior insular cortices. However, a circumscribed region within the left DLPFC showed a different response pattern expressed as activity changes that were monotonically related to relative stimulation difference only for correct but not for incorrect trials. Our findings suggest that activity in the left DLPFC encodes stimulus representations that underlie veridical tactile decisions in humans.

Adult↗

PubMed2006

Anterolateral prefrontal cortex mediates the analgesic effect of expected and perceived control over pain.

Perceived control attenuates pain and pain-directed anxiety, possibly because it changes the emotional appraisal of pain. We examined whether brain areas associated with voluntary reappraisal of emotional experiences also mediate the analgesic effect of perceived control over pain. Using functional magnetic resonance imaging, we compared self-controlled noxious stimuli with physically identical stimuli that were externally controlled. Self-controlled stimulation was accompanied by less pain and anxiety and higher activation in dorsal anterior cingulate (dACC), right dorsolateral, and bilateral anterolateral prefrontal (alPFC) cortices. Activation in dACC and right alPFC was negatively correlated with pain intensity ratings. For externally controlled pain, activation in right alPFC was inversely correlated with the participants' general belief to have control over their lives. Our results are consistent with a reappraisal view of control and suggest that the analgesic effect of perceived control relies on activation of right alPFC. Failure to activate right alPFC may explain the maladaptive effects of strong general control beliefs during uncontrollable pain.

Adult↗

PubMed2006

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.

Adult↗

PubMed2006

Repetitive transcranial magnetic stimulation-induced changes in sensorimotor coupling parallel improvements of somatosensation in humans.

Repetitive transcranial magnetic stimulation (rTMS) is an established technique for non-invasive stimulation of human cortex. Although studies have shown an influence of rTMS on single cortical regions and on simple behavioral response patterns, its influences on the dynamics of task-related activity in cortical networks have not been characterized. We provide such a characterization by showing that 5 Hz rTMS over primary somatosensory cortex (SI) induces a reconfiguration of activity patterns in a sensorimotor network, comprising the stimulated region and ipsilateral primary motor cortex (MI). These plastic changes endure for up to 120 min and are correlated with behavioral improvement in discrimination. Dynamic causal modeling showed that this reconfiguration could be explained by an rTMS-induced increase in SI excitability (self-connection) and an increase in the effective connectivity from SI to MI. Thus, our data demonstrate that rTMS can temporarily induce behaviorally relevant reorganization within a complex cortical network underlying human somatosensory experience.

Adult↗

PubMed2005

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.

Adult↗

PubMed2005

The NMDA antagonist memantine affects training induced motor cortex plasticity--a study using transcranial magnetic stimulation.

BACKGROUND: Training of a repetitive synchronised movement of two limb muscles leads to short-term plastic changes in the primary motor cortex, which can be assessed by transcranial magnetic stimulation (TMS) mapping. We used this paradigm to study the effect of memantine, a NDMA antagonist, on short-term motor cortex plasticity in 20 healthy human subjects, and we were especially interested in possible differential effects of different treatment regimens. In a randomised double-blinded cross over study design we therefore administered placebo or memantine either as a single dosage or as an ascending dosage over 8 days. Before and after one hour of motor training, which consisted of a repetitive co-contraction of the abductor pollicis brevis (APB) and the deltoid muscle, we assessed the motor output map of the APB muscle by TMS under the different conditions. RESULTS: We found a significant medial shift of the APB motor output map after training in the placebo condition, indicating training-induced short-term plastic changes in the motor cortex. A single dosage of memantine had no significant effect on this training-induced plasticity, whereas memantine administered in an ascending dosage over 8 days was able to block the cortical effect of the motor training. The memantine serum levels after 8 days were markedly higher than the serum levels after a single dosage of memantine, but there was no individual correlation between the shift of the motor output map and the memantine serum level. Besides, repeated administration of a low memantine dosage also led to an effective blockade of training-induced cortical plasticity in spite of serum levels comparable to those reached after single dose administration, suggesting that the repeated administration was more important for the blocking effect than the memantine serum levels. CONCLUSION: We conclude that the NMDA-antagonist memantine is able to block training-induced motor cortex plasticity when administered over 8 days, but not after administration of a single dose. This differential effect might be mainly due to the prolonged action of memantine at the NMDA receptor. These findings must be considered if clinical studies are designed, which aim at evaluating the potency of memantine to prevent "maladaptive" plasticity, e.g. after limb amputation.

Adult↗

PubMed2005

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.

Behavior Therapy↗

PubMed2004

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.

Adult↗

PubMed2004

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.

Adult↗

PubMed2004

Mean sustained pain levels are linked to hemispherical side-to-side differences of primary somatosensory cortex in the complex regional pain syndrome I.

Chronic back pain as well as phantom-limb pain is characterized by a close relationship between the amount of cortical reorganization and the magnitude of pain. In patients with positively assessed complex regional pain syndrome type I (CRPS I), we found a positive correlation between representational changes of primary somatosensory cortex (SI) and mean sustained pain levels. We investigated seven right-handed patients with CRPS I of one upper limb by means of somatosensory evoked potential (SSEP) mapping. Cortical representation of the CRPS-affected hand was significantly smaller than that of the contralateral healthy hand, giving rise to a substantial side difference. Subjective pain levels experienced over the last 4 weeks were estimated according to the visual analogue scale (VAS). Individual expansion of hand representation contralateral to the CRPS-affected limb was significantly correlated with mean pain intensity. Accordingly, low pain levels were linked to small representational side-to-side differences, while subjects with a distinctive hemispherical asymmetry reported the highest pain levels. Follow-up studies using functional imaging methods might be instrumental in providing a better understanding of this issue.

Adult↗

PubMed2004

Fluoxetine facilitates use-dependent excitability of human primary motor cortex.

OBJECTIVES: In poststroke patients, fluoxetine, a selective serotonin-reuptake inhibitor, as an adjunct to physical therapy provided a better functional recovery from motor deficits. The aim of this study was to investigate the effect of a single dose of 20 mg fluoxetine on motor learning and associated cortical changes in healthy right-handed subjects in order to get deeper insight into its facilitating influence on human motor cortex. METHODS: Subjects performed a motor task consisting of a simultaneous co-contraction of the abductor pollicis brevis (APB) and the deltoid muscle with and without fluoxetine in a placebo-controlled double-blinded crossover study design. Immediately before and after motor learning motor output maps of the APB muscle were assessed in order to get insight into plastic changes of the muscle representation. RESULTS: We found a significantly improved motor performance under both conditions without having substantial differences between placebo and fluoxetine. After the completion of the motor task there was a medial shift of the APB muscle motor output map. Only after the administration of fluoxetine the sum of MEP amplitudes (SOA) increased and the motor output map enlarged. CONCLUSIONS: These findings provide evidence for a use-dependent facilitating effect of fluoxetine on cortical excitability but not on motor performance. SIGNIFICANCE: Our findings are not in line with previous experiments in poststroke patients. However, long-term treatment with fluoxetine may additionally improve motor function by upregulating serotonergic receptors. Further studies investigating the influence of long-term treatment on cortical excitability and psychophysics may therefore provide deeper insight into a possible therapeutical efficiency of fluoxetine in poststroke patients.

Adult↗

PubMed2003

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.

Adult↗

PubMed2003

Reorganization in the ipsilateral motor cortex of patients with lower limb amputation.

The aim of the present study was to assess reorganization in the motor cortex of patients with lower limb amputation. We studied seven patients with traumatic lower limb amputation, and six healthy controls, using transcranial magnetic stimulation mapping, with recordings from the quadriceps femoris muscle on both sides. Motor threshold, sum of amplitudes, area and the amplitude-weighted centre of gravity (COG) of the motor output map were assessed. We found a significant lateral displacement of the COG on the hemisphere contralateral to the healthy leg, whereas other parameters did not differ significantly between sides. This finding might be indicative of cortical reorganization in the hemisphere ipsilateral to the amputation. It is discussed with respect to an altered peripheral input to this hemisphere, and to transcallosal interactions from the deafferented hemisphere.

Adaptation, Physiological↗

PubMed2003

GABAergic mechanisms gate tactile discrimination learning.

In contrast to mechanisms mediating synaptic plasticity, the pharmacological basis of perceptual learning remains to be clarified. Here we report that a specific form of perceptual learning is influenced by GABAergic mechanisms. We induced perceptual learning by Hebbian co-activation of the skin of the tip of the right index fingers in human subjects. Under placebo conditions, tactile 2-point discrimination was improved on the co-activated, but not on the left, index finger. This augmentation was completely eliminated by lorazepam, a GABAA receptor agonist. No drug effects were found on the left index finger indicating that the drugs had no effect per se on performance. The results demonstrate that perceptual learning is subject to pharmacological gating by basic mechanisms known to mediate and modulate synaptic plasticity.

Adult↗

PubMed2003

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.

Adult↗

PubMed2003

Pharmacological modulation of perceptual learning and associated cortical reorganization.

The pharmacological basis of perceptual learning and associated cortical reorganizations remains elusive. We induced perceptual learning by Hebbian coactivation of the skin of the tip of the right index finger in humans. Under placebo, tactile two-point discrimination was improved on the coactivated but not on the left index finger. This augmentation was blocked by an N-methyl-D-aspartate-receptor blocker, but doubled by amphetamine. No drug effects were found on the left index finger. The individual amount of cortical reorganization as assessed by mapping of somatosensory evoked potentials was linearly correlated with the pharmacological modulation of discrimination thresholds, implying that perceptual learning and associated cortical changes are controlled by basic mechanisms known to mediate and modulate synaptic plasticity.

Adult↗

PubMed2003

Functional magnetic resonance imaging mirrors recovery of visual perception after repetitive tachistoscopic stimulation in patients with partial cortical blindness.

We investigated three patients with partial cortical blindness after brain injury by means of functional magnetic resonance imaging (fMRI) before and after the application of a daily visual stimulation-therapy over a period of 6 months. Before therapy, fMRI data showed a severely reduced blood-oxygen-level-dependent (BOLD) signal in primary visual cortex when compared to healthy volunteers. Following several months of rehabilitative therapy a neuropsychological improvement of visual functions was accompanied by an increase in BOLD signal of residual perilesional regions whereas fMRI data of the control group remained unchanged. A high capacity of functional recovery and synaptic plasticity of surviving perilesional neuronal structures of primary visual cortex followed by an increased input into post-connected visual areas can be discussed as a basis for the reoccurrence of visual functions.

Adult↗

PubMed2003

Repetitive visual stimulation: a neuropsychological approach to the treatment of cortical blindness.

Cortical visual disturbances can occur after traumatic or ischemic brain lesion. Patients mostly suffer from hemianopia. Different treatment approaches in patients with hemianopia are being debated with respect to their effectiveness. For more severely disabled patients with cortical blindness or residual rudimentary vision (RRV) no systematic therapeutic approaches have been reported. In a case study the positive effects of a recently developed repetitive photic stimulation therapy in a patient with RRV after a bioccipital ischemic infarction are presented. The application of this new therapy over several months, supported by treatment with amphetamines led to a statistically significant improvement of different visual functions and a reoccurrence of visual abilities important in daily life. The pathophysiological basis and possible neurorehabilitative consequences that arise from these results are discussed with respect to similar findings in animal experiments.

Blindness, Cortical↗