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Biomedical subjects

H R Dinse

Publications and source records attributed to H R Dinse.

At least 19 recordsLinked to original sources

Treating the aging brain: cortical reorganization and behavior.

Aging comprises many physiological modifications, including structural and metabolic changes, yet little is known about how aging affects the way in which neurons process and integrate sensory information from the environments. Here the framework of "modified use" as a determinant of cortical reorganization was applied for the investigation of age-related modifications of cortical maps and processing, and of associated changes of behavior. The age-related changes of walking behavior in rats were contrasted with the parallel changes of sensorimotor processing developing at the cortical level. Based on the regional specificity of these changes attempts are made to separate age-related changes arising as a consequence of degeneration from a result of adaptable processes following reduced use at high age. Finally, findings from long-term treatment with the Ca2+-blocker nimodipine, or from housing animals under enriched environmental conditions to ameliorate aging effects were described. Combined, these results show the general treatability of age-related changes. The data imply that age-related changes can be reversed by short periods of training and stimulation schedules even if they have developed. Clearly, the development of specific measures to delay aging processes and to rehabilitate aged brains depends on future progress in understanding mechanisms and effects of aging.

Adaptation, Physiological↗

Induction of bilateral plasticity in sensory cortical maps by small unilateral cortical infarcts in rats.

Behavioural impairments caused by brain lesions show a considerable, though often incomplete, recovery. It is hypothesized that cortical and subcortical plasticity of sensory representations contribute to this recovery. In the hindpaw representation of somatosensory cortex of adult rats we investigated the effects of focal unilateral cortical lesions on remote areas. Cortical lesions with a diameter of approximately 2 mm were induced in the parietal cortex by photothrombosis with the photosensitive dye Rose Bengal. Subsequently, animals were kept in standard cages for 7 days. On day seven, animals were anaesthetized and cutaneous receptive fields in the cortical hindpaw representations ipsi- and contralateral to the lesion were constructed from extracellular recordings of neurons in layer IV using glass microelectrodes. Receptive fields in the lesioned animals were compared to receptive fields measured in nonlesioned animals serving as controls. Quantitative analysis of receptive fields revealed a significant increase in size in the lesioned animals. This doubling in receptive field size was observed equally in the hemispheres ipsi- and contralateral to the lesion. The results indicate that the functional consequences of restricted cortical lesions are not limited to the area surrounding the lesion, but affect the cortical maps on the contralateral, nonlesioned hemisphere.

Animals↗

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.

Adult↗

Tactile coactivation-induced changes in spatial discrimination performance.

We studied coactivation-based cortical plasticity at a psychophysical level in humans. For induction of plasticity, we used a protocol of simultaneous pairing of tactile stimulation to follow as closely as possible the idea of Hebbian learning. We reported previously that a few hours of tactile coactivation resulted in selective and reversible reorganization of receptive fields and cortical maps of the hindpaw representation of the somatosensory cortex of adult rats (Godde et al., 1996). In the present study, simultaneous spatial two-point discrimination was tested on the tip of the right index finger in human subjects as a marker of plastic changes. After 2 hr of coactivation we found a significant improvement in discrimination performance that was reversible within 8 hr. Reduction of the duration of the coactivation protocol revealed that 30 min was not sufficient to drive plastic changes. Repeated application of coactivation over 3 consecutive days resulted in a delayed recovery indicating stabilization of the improvement over time. Perceptual changes were highly selective because no transfer of improved performance to fingers that were not stimulated was found. The results demonstrate the potential role of sensory input statistics (i.e., their probability of occurrence and spatiotemporal relationships) in the induction of cortical plasticity without involving cognitive factors such as attention or reinforcement.

Adult↗

A repetitive intracortical microstimulation pattern induces long-lasting synaptic depression in brain slices of the rat primary somatosensory cortex.

Repetitive intracortical microstimulation (ICMS) applied to the rat primary somatosensory cortex (SI) in vivo was reported to induce reorganization of receptive fields and cortical maps. The present study was designed to examine the effect of such an ICMS pattern applied to layer IV of brain slices containing SI on the efficacy of synaptic input to layer II/III. Effects of ICMS on the synaptic strength was quantified for the first synaptic component (s1) of cortical field potentials (FPs) recorded from layer II/III of SI. FPs were evoked by stimulation in layer IV. The pattern of ICMS was identical to that used in vivo. However, stimulation intensity had to be raised to induce an alteration of synaptic strength. In brain slices superfused with standard ACSF, repetitive ICMS induced a short-lasting (60 min) reduction of the amplitude (-37%) and the slope (-61%) of s1 evoked from the ICMS site, while the amplitude and the slope of s1 evoked from a control stimulation site in cortical layer IV underwent a slow onset increase (13% and 50%, respectively). In brain slices superfused with ACSF containing 1.25 microM bicuculline, ICMS induced an initial strong reduction of the amplitude (-50%) and the slope (-79%) of s1 evoked from the ICMS site. These effects decayed to a sustained level of depression by -30% (amplitude) and -60% (slope). In contrast to experiments using standard ACSF, s1 evoked from the control site was not affected by ICMS. The presynaptic volley was not affected in either of the two groups of experiments. A conventional high frequency stimulation (HFS) protocol induced input-specific long-term potentiation (LTP) of the amplitude and slope of s1 (25% and 76%, respectively). Low frequency stimulation (LFS) induced input-specific long-term depression (LTD) of the amplitude and slope of s1 (24% and 30%, respectively). Application of common forms of conditioning stimulation (HFS and LFS) resulted in LTP or LTD of s1, indicating normal susceptibility of the brain slices studied to the induction of common forms of synaptic plasticity. Therefore, the effects of repetitive ICMS on synaptic FP components were considered ICMS-specific forms of short-lasting (standard ACSF) or long-lasting synaptic depression (ACSF containing bicuculline), the latter resembling neocortical LTD. Results of this study suggest that synaptic depression of excitatory mechanisms are involved in the cortical reorganization induced by repetitive ICMS in vivo. An additional contribution of an ICMS-induced modification of inhibitory mechanisms to cortical reorganization is discussed.

Animals↗

Parametric population representation of retinal location: neuronal interaction dynamics in cat primary visual cortex.

Neuronal interactions are an intricate part of cortical information processing generating internal representations of the environment beyond simple one-to-one mappings of the input parameter space. Here we examined functional ranges of interaction processes within ensembles of neurons in cat primary visual cortex. Seven "elementary" stimuli consisting of small squares of light were presented at contiguous horizontal positions. The population representation of these stimuli was compared to the representation of "composite" stimuli, consisting of two squares of light at varied separations. Based on receptive field measurements and by application of an Optimal Linear Estimator, the representation of retinal location was constructed as a distribution of population activation (DPA) in visual space. The spatiotemporal pattern of the DPA was investigated by obtaining the activity of each neuron for a sequence of time intervals. We found that the DPA of composite stimuli deviates from the superposition of its components because of distance-dependent (1) early excitation and (2) late inhibition. (3) The shape of the DPA of composite stimuli revealed a distance-dependent repulsion effect. We simulated these findings within the framework of dynamic neural fields. In the model, the feedforward response of neurons is modulated by spatial ranges of excitatory and inhibitory interactions within the population. A single set of model parameters was sufficient to describe the main experimental effects. Combined, our results indicate that the spatiotemporal processing of visual stimuli is characterized by a delicate, mutual interplay between stimulus-dependent and interaction-based strategies contributing to the formation of widespread cortical activation patterns.

Animals↗

Low-frequency oscillations of visual, auditory and somatosensory cortical neurons evoked by sensory stimulation.

Low-frequency oscillations-LFOs-below 20 Hz in the activity of cortical neurons are a commonly observed property across all sensory modalities. However, the functional significance and potential role of these intrinsic oscillations are not well understood. Here, we attempt to provide a general framework for the interpretation of this phenomenon by considering its properties across several sensory modalities. In the first part, we provide a survey and a general description of low-frequency oscillations (LFOs) at a cellular level observed following adequate [Basar, and Schürmann, 1994]. Sensory stimulation of neurons recorded in three sensory modalities of neocortices in higher mammals. The second part will address some functional aspects of low-frequency oscillations (LFOs) such as stimulus selectivity and so-called 'interference' phenomena, specifically with findings related to 'resetting' and 'gating' of sensory processing streams. Finally, a hypotheses is outlined in which the low-frequency oscillations are regarded as an organizational principle by which continuity of sensory and motor states over time could be accomplished.

Acoustic Stimulation↗

Optical imaging of cat auditory cortex cochleotopic selectivity evoked by acute electrical stimulation of a multi-channel cochlear implant.

We measured reflectance changes by means of optical imaging of intrinsic signals to study the effects of acute electrical cochlear stimulation on the topography of the cat auditory cortex. After single-pulse electrical stimulation at selected sites of a multichannel implant device, we found topographically restricted response areas representing mainly the high-frequency range in AI. Systematic variation of the stimulation pairs and thus of the cochlear frequency sites revealed a systematic and corresponding shift of the response areas that matched the underlying frequency organization. Intensity functions were usually very steep. Increasingly higher stimulation currents evoked increasingly larger response areas, resulting in decreasing spatial, i.e. cochleotopic, selectivity; however, we observed only slight positional shifts of the focal zones of activity. Electrophysiological recordings of local field potential maps in the same individual animals revealed close correspondence of the locations of the cortical response areas. The results suggest that the method of optical imaging can be used to map response areas evoked by electrical cochlear stimulation, thereby maintaining a profound cochleotopic selectivity. Further experiments in chronically stimulated animals will shed more light on the degree of functional and reorganizational capacities of the primary cortex and could be beneficial for our understanding of the treatment of profound deafness.

Animals↗

Short-term functional plasticity of cortical and thalamic sensory representations and its implication for information processing.

We studied phenomena, constraints, rules, and implications of cortical plastic reorganization produced by input coactivation patterns in primary somatosensory cortex of adult rats. Intracortical microstimulation (ICMS) and an associative pairing of tactile stimulation (PPTS) induced plastic changes within minutes to hours that were fully reversible. Reorganization of receptive fields and topographic maps was studied with electrophysiologic recordings, mapping techniques, and optical imaging of intrinsic signals. Utilizing the specific advantages of local application of ICMS, we investigated lamina-specific properties of cortical representational plasticity, revealing a prominent role of the input layer IV during plastic reorganization. To study subcortical plasticity, we compared ICMS and intrathalamic microstimulation (ITMS), revealing robust thalamic reorganizations that were, however, much smaller than cortical changes. Using PPTS, we found significant reorganizational processes at the cortical level, including receptive fields, overlap, and cortical representational maps. The protocol was similarly effective at the perceptual level by enhancing the spatial discrimination performance in humans, suggesting that these particular fast plastic processes have perceptual consequences. The implications were discussed with respect to parallel changes of information processing strategies. We addressed the question of the possible role of RF size and size of cortical area, inhibitory mechanisms, and Hebbian and non-Hebbian learning rules. The short time scale of the effects and the aspect of reversibility support the hypothesis of fast modulations of synaptic efficiency without necessarily involving anatomic changes. Such systems of predominantly dynamically maintained cortical and adaptive processing networks may represent the neural basis for life-long adaptational sensory and perceptual capacities and for compensational reorganizations following injuries.

Animals↗

Optical imaging of cat auditory cortical organization after electrical stimulation of a multichannel cochlear implant: differential effects of acute and chronic stimulation.

OBJECTIVE: To study the effects of electrical stimulation on cortical activation patterns. MATERIALS AND METHODS: Optical imaging of auditory cortex in cats that are acutely and chronically electrically stimulated with cochlear implants. RESULTS: Chronic electrical stimulation results in expansion of cortical territory and overlap. CONCLUSION: Effects of chronic electrical stimulation are comparable to use-dependent cortical plastic reorganization.

Animals↗

Associative pairing of tactile stimulation induces somatosensory cortical reorganization in rats and humans.

We used a protocol of associative (Hebbian) pairing of tactile stimulation (APTS) to evoke cortical plastic changes. Reversible reorganization of the adult rat paw representations in somatosensory cortex (SI) induced by a few hours of APTS included selective enlargement of the areas of cortical neurones representing the stimulated skin fields and of the corresponding receptive fields (RFs). Late, presumably NMDA receptor-mediated response components were enhanced, indicating an involvement of glutamatergic synapses. A control protocol of identical stimulus pattern applied to only a single skin site revealed no changes of RFs, indicating that co-activation is crucial for induction. Using an analogous APTS protocol in humans revealed an increase of spatial discrimination performance indicating that fast plastic processes based on co-activation patterns act on a cortical and perceptual level.

Action Potentials↗

Functional characterization of cutaneous mechanoreceptor properties in aged rats.

We investigated the effects of aging on rapidly (RA) and slowly adapting (SA) cutaneous mechanoreceptors by means of single fiber recordings and evoked sensory nerve action potentials (EAPs) of the hindpaw of the N. plantaris in adult and old Wistar rats. EAPs revealed comparable shapes and amplitudes in all animals of all age groups. In old rats, conduction velocities were slightly (15%) lengthened. The mechanoreceptor composition was different from adults, resulting in a lower number of SA units. We were not able to detect significant differences in the sizes of receptive fields and in the thresholds between old and adult animals. The absence of significant age-related changes in the cutaneous periphery of the hindpaw is discussed in respect to the previously reported alterations of cortical receptive field properties in old rats.

Aging↗

A columnar model of somatosensory reorganizational plasticity based on Hebbian and non-Hebbian learning rules.

Topographical and functional aspects of neuronal plasticity were studied in the primary somatosensory cortex of adult rats in acute electrophysiological experiments. Under these experimental conditions, we observed short-term reversible reorganization induced by intracortical microstimulation or by an associative pairing of peripheral tactile stimulation. Both types of stimulation generate large-scale and reversible changes of the representational topography and of single cell functional properties. We present a model to simulate the spatial and functional reorganizational aspects of this type of short-term and reversible plasticity. The columnar structure of the network architecture is described and discussed from a biological point of view. The simulated architecture contains three main levels of information processing. The first one is a sensor array corresponding to the sensory surface of the hind paw. The second level, a pre-cortical relay cell array, represents the thalamo-cortical projection with different levels of excitatory and inhibitory relay cells and inhibitory nuclei. The array of cortical columns, the third level, represents stellate, double bouquet, basket and pyramidal cell interactions. The dynamics of the network are ruled by two integro-differential equations of the lateral-inhibition type. In order to implement neuronal plasticity, synaptic weight parameters in those equations are variables. The learning rules are motivated by the original concept of Hebb, but include a combination of both Hebbian and non-Hebbian rules, which modifies different intra- and inter-columnar interactions. We discuss the implications of neuronal plasticity from a behavioral point of view in terms of information processing and computational resources.

Animals↗

Optical imaging of rat somatosensory cortex reveals representational overlap as topographic principle.

We measured reflectance changes by means of optical imaging of intrinsic signals to study the topography of the paw representations in rat somatosensory cortex. Following circumscribed tactile stimulation of single digits or pads, we found large and partially overlapping areas of reflectance changes (delta R). The diameters of their focal zones defined at 75% maximal delta R were in the range of 150 microns and preserved all details of the underlying maps. Zones of overlap were in the range 15-25% measured at half-maximal delta R. In contrast, we found sharp boundaries with no overlap between the fore- and hindpaw representations. The data suggest that large and overlapping cortical maps constitute a normal type of neural representation supporting the idea of a distributed neural processing scheme.

Animals↗

Effects of ageing on topographic organization of somatosensory cortex.

Deficits in limb coordination and decreased motor activity have been described in old rats older than 24 months, an approved animal model in ageing research. We investigated the implications of age-related decline of sensorimotor performance by studying the functional cortical organization of aged rats. The cutaneous receptive fields of the hindpaw representations in somatosensory cortex and the cortical areas excited by tactile point-stimulation were enlarged and highly overlapping in old rats when compared with young rats. This gives rise to a complete loss of topographic detail. These functional changes were correlated with the rat's individual walking patterns, indicating that age-related deficits in sensorimotor performance are paralleled by degradation of the functional representations in the ageing nervous system.

Age Factors↗

The timing of processing along the visual pathway in the cat.

We obtained visual response latencies and response durations following visual stimulation of neurones recorded in the lateral geniculate nucleus (LGN), areas 17, 18, 19, the posteromedial lateral suprasylvian sulcus (PMLS), and area 7 of the cat. We found an increasing lengthening of the mean response latencies, consistent with the view of a progressive advance of processing from stage to stage. However, we also observed a substantial and increasing scatter in these latencies. Moreover, response durations vastly supersede this gradual increase in latencies. Taken together, these results suggest that most of the neurones within different stages of a hierarchically organized sensory pathway are simultaneously active when stimulated. Implications of a time-based processing scheme for models of information processing in highly interconnected, multi-layered systems are discussed.

Animals↗