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Biomedical subjects

Hubert R Dinse

Publications and source records attributed to Hubert R Dinse.

At least 19 recordsLinked to original sources

Age-related attenuation of dominant hand superiority.

BACKGROUND: The decline of motor performance of the human hand-arm system with age is well-documented. While dominant hand performance is superior to that of the non-dominant hand in young individuals, little is known of possible age-related changes in hand dominance. We investigated age-related alterations of hand dominance in 20 to 90 year old subjects. All subjects were unambiguously right-handed according to the Edinburgh Handedness Inventory. In Experiment 1, motor performance for aiming, postural tremor, precision of arm-hand movement, speed of arm-hand movement, and wrist-finger speed tasks were tested. In Experiment 2, accelerometer-sensors were used to obtain objective records of hand use in everyday activities. PRINCIPAL FINDINGS: Our data confirm previous findings of a general task-dependent decline in motor performance with age. Analysis of the relationship between right/left-hand performances using a laterality index showed a loss of right hand dominance with advancing age. The clear right-hand advantage present at younger ages changed to a more balanced performance in advanced age. This shift was due to a more pronounced age-related decline of right hand performance. Accelerometer-sensor measurements supported these findings by demonstrating that the frequency of hand use also shifted from a clear right hand preference in young adults to a more balanced usage of both hands in old age. Despite these age-related changes in the relative level of performance in defined motor tasks and in the frequency of hand use, elderly subjects continued to rate themselves as unambiguous right-handers. CONCLUSION: The discrepancy between hand-specific practical performance in controlled motor tests as well as under everyday conditions and the results of questionnaires concerning hand use and hand dominance suggests that most elderly subjects are unaware of the changes in hand dominance that occur over their lifespan, i.e., a shift to ambidexterity.

Adult↗

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

OBJECTIVE: 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. METHODS: As an alternative approach to training, we have introduced a tactile coactivation protocol involving Hebbian synaptic plasticity to improve tactile performance on a short timescale of a few hours. RESULTS: By applying coactivation on the index finger to drive perceptual learning, we demonstrate that in the elderly, aged 65 to 89 years, the age-related impairment of tactile two-point discrimination can be mitigated substantially. In elderly adults, tactile-acuity thresholds increased to 3.5mm compared with 1.5mm found in young adults, whereas 50-year-old subjects showed intermediate performance. As a result of coactivation, discrimination thresholds of the 80-year-old adults came to match those typically found at an age of 50, demonstrating that age-related decline in tactile performance is not irreversible, but rather subject to considerable restoration by specific stimulation protocols. INTERPRETATION: Because the preservation of sufficient tactile acuity into advanced age is an important prerequisite for the maintenance of autonomous living, we believe that the concept of coactivation might turn out to be beneficial in preserving everyday sensorimotor competence in the elderly through new forms of therapeutic interventions.

Adult↗

Cortical reorganization in the aging brain.

Aging exerts major reorganization and remodeling at all levels of brain structure and function. Studies in aged animals and in human elderly individuals demonstrate that sensorimotor cortical representational maps undergo significant alterations. Because cortical reorganization is paralleled by a decline in perceptual and behavioral performance, this type of cortical remodeling differs from the plastic reorganization observed during learning processes in young individuals where map changes are associated with a gain in performance. It is now clear that brain plasticity is operational into old age; therefore, protocols for interventions such as training, exercising, practicing, and stimulation, which make use of neuroplasticity principles, are effective to ameliorate some forms of cortical and behavioral age-related changes, indicating that aging effects are not irreversible but treatable. However, old individuals cannot be rejuvenated, but restoration of function is possible through the emergence of new processing strategies. This implies that cortical reorganization in the aging brain occurs twice: during aging, and during treatment of age-related changes.

Aging↗

Spastic paresis after perinatal brain damage in rats is reduced by human cord blood mononuclear cells.

Brain damage around birth may cause lifelong neurodevelopmental deficits. We examined the therapeutic potential of human umbilical cord blood-derived mononuclear cells containing multipotent stem cells to facilitate motor recovery after cerebral hypoxic-ischemic damage in neonatal rats. Left carotid artery ligation followed by 8% O(2) inhalation for 80 min was performed on postnatal d 7, succeeded by intraperitoneal transplantation of human umbilical cord blood-derived mononuclear cells on postnatal d 8 in a sham-controlled design. Histologic and immunohistochemical analysis on postnatal d 21 revealed that neonates developed severe cerebral damage after the hypoxic-ischemic insult. These animals also suffered from contralateral spastic paresis, as evidenced by their locomotor behavior. After transplantation of human umbilical cord blood-derived mononuclear cells, spastic paresis was largely alleviated, resulting in a normal walking behavior. This "therapeutic" effect was accompanied by the fact that mononuclear cells had entered the brain and were incorporated around the lesion without obvious signs of transdifferentiation. This study demonstrates that intraperitoneal transplantation of human umbilical cord blood-derived mononuclear cells in a rat model of perinatal brain damage leads to both incorporation of these cells in the lesioned brain area and to an alleviation of the neurologic effects of cerebral palsy as assessed by footprint and walking pattern analysis.

Animals↗

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↗

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↗

Shorter latencies for motion trajectories than for flashes in population responses of cat primary visual cortex.

Psychophysical evidence in humans indicates that localization is different for stationary flashed and coherently moving objects. To address how the primary visual cortex represents object position we used a population approach that pools spiking activity of many neurones in cat area 17. In response to flashed stationary squares (0.4 deg) we obtained localized activity distributions in visual field coordinates, which we referred to as profiles across a 'population receptive field' (PRF). We here show how motion trajectories can be derived from activity across the PRF and how the representation of moving and flashed stimuli differs in position. We found that motion was represented by peaks of population activity that followed the stimulus with a speed-dependent lag. However, time-to-peak latencies were shorter by approximately 16 ms compared to the population responses to stationary flashes. In addition, motion representation showed a directional bias, as latencies were more reduced for peripheral-to-central motion compared to the opposite direction. We suggest that a moving stimulus provides 'preactivation' that allows more rapid processing than for a single flash event.

Action Potentials↗

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↗

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↗

Receptive field scatter, topography and map variability in different layers of the hindpaw representation of rat somatosensory cortex.

We recorded neurons extracellularly in layers II/III, IV, and V of the hindpaw representation of primary somatosensory cortex in anesthetized rats and studied laminar features of receptive fields (RFs) and representational maps. On average, RFs were smallest in layer IV and largest in layer V; however, for individual penetrations we found substantial deviations from this rule. Within the hindpaw representation, a distinct rostrocaudal gradient of RF size was present in all layers. While layer V RFs were generally largest independent of this gradient, layer IV RFs recorded caudally representing the proximal portions of the paw were larger than layer II/III RFs recorded rostrally representing the digits. The individual scatter of the locations of RFs across laminar groups was in the range of several millimeters, corresponding to about 25% of the average RF diameter. The cutaneous representations of the hindpaw in extragranular layers were confined to the areal extent defined by responsive sites in layer IV. Comparison between RFs determined quantitatively and by handplotting showed a reliable correspondence. Repeated measurements of RFs revealed spontaneous fluctuations of RF size of no more than 5% of the initial condition over an observation period of several hours. The topography and variability of cortical maps of the hindpaw representation were studied with a quantitative interpolation method taking into account the geometric centers of RFs and the corresponding cortical recording sites. On average, the overall topography in terms of preservation of neighborhood relations was present in all layers, although some individual maps showed severe distortions of topography. Factors contributing to map variability were overall position of the representation on the cortical surface, internal topography and spatial extent. Interindividual variability of map layout was always highest in the digit representations. Local topographic orderliness was lowest in layer V, but comparable in layers II/III and IV. Within layer IV, the lowest orderliness was observed in the digit representations. Our data emphasize a substantial variability of RF size, overlap and position across layers and within layers. At the level of representational maps, we found a similar degree of variability that often co-varied across layers, with little evidence for significant layer specificity. Laminar differences are likely to arise from the specific input-output pattern, layer-specific cell types and the connectivity between different layers. Our findings emphasizing similarities in the variability across layers support the notion of tightly coupled columnar interactions between different layers.

Action Potentials↗

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

Musician's 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.

Adult↗

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↗

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↗

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↗

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↗

Pharmacological suppression of plastic changes in human primary somatosensory cortex after motor learning.

The strict division between motor and somatosensory systems might be less distinct than previously thought. Many brain mapping studies have described changes of somatosensory cortex (S-I) after the execution of a motor task, which supports the idea of a profound interconnectedness in the sensorimotor system. Here we report experiments in which we investigated by means of somatosensory evoked potentials (SSEPs) mapping the reorganizational capacities in primary somatosensory cortex before and after a Hebbian repetitive co-contraction task of the thumb and arm. We investigated the susceptibility of S-I plasticity to the pharmacological modulation of the GABA-neurotransmitter system by application of the GABA(A) agonist lorazepam. We found that repetitive training induced stable motor learning characterized by a significant improvement of performance. The time differences between the onset of contraction of the deltoid muscle and the abductor pollicis brevis were progressively shortened. The process of motor learning was accompanied by plastic changes in the primary somatosensory cortex as indicated by a significant increase in the dipole strength and a significant shift of the median nerve dipole on the hemisphere contralateral to the exercised side. Moreover, the individual shifts of median nerve dipole location were correlated with the individual improvement in motor performance. After administration of lorazepam, motor learning was significantly suppressed. The behavioural effect was accompanied by an abolition of the N20 dipole shift and an unchanged dipole strength. The results imply that motor learning leads to a profound reorganization in S-I which is subject to pharmacological suppression with the GABA agonist lorazepam.

Adult↗

Plasticity of orientation preference maps in the visual cortex of adult cats.

In contrast to the high degree of experience-dependent plasticity usually exhibited by cortical representational maps, a number of experiments performed in visual cortex suggest that the basic layout of orientation preference maps is only barely susceptible to activity-dependent modifications. In fact, most of what we know about activity-dependent plasticity in adults comes from experiments in somatosensory, auditory, or motor cortex. Applying a stimulation protocol that has been proven highly effective in other cortical areas, we demonstrate here that enforced synchronous cortical activity induces major changes of orientation preference maps (OPMs) in adult cats. Combining optical imaging of intrinsic signals and electrophysiological single-cell recordings, we show that a few hours of intracortical microstimulation (ICMS) lead to an enlargement of the cortical representational zone at the ICMS site and an extensive restructuring of the entire OPM layout up to several millimeters away, paralleled by dramatic changes of pinwheel numbers and locations. At the single-cell level, we found that the preferred orientation was shifted toward the orientation of the ICMS site over a region of up to 4 mm. Our results show that manipulating the synchronicity of cortical activity locally without invoking training, attention, or reinforcement, OPMs undergo large-scale reorganization reminiscent of plastic changes observed for nonvisual cortical maps. However, changes were much more widespread and enduring. Such large-scale restructuring of the visual cortical networks indicates a substantial capability for activity-dependent plasticity of adult visual cortex and may provide the basis for cognitive learning processes.

Age Factors↗