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M M Merzenich

Publications and source records attributed to M M Merzenich.

At least 19 recordsLinked to original sources

Topographic organization of the cochlear spiral ganglion demonstrated by restricted lesions of the anteroventral cochlear nucleus.

The morphological organization of the central projections of the cat cochlear spiral ganglion into the cochlear nucleus has been investigated by creating restricted lesions in the anteroventral cochlear nucleus (AVCN) in order to ablate selectively either the lateral or the medial aspect of isofrequency projection laminae. Such lesions induced highly selective retrograde degeneration of spiral ganglion cells. Ablation of the lateral part of the AVCN resulted in degeneration of cells within the scala tympani portion of the ganglion, whereas medial lesions within the AVCN induced degeneration of the scala vestibuli portion of the ganglion. Since most, if not all, of the primary afferent axons of the cochlear nerve bifurcate into ascending and descending branches as they enter the brainstem, it is noteworthy that selective damage to the ascending branch in the AVCN was sufficient to induce retrograde degeneration of the spiral ganglion cell somata. The peripheral and central axons also degenerated, and the losses of both the radial nerve fibers in the osseous spiral lamina and the central axons passing into the modiolus displayed selective topographies that paralleled the cell loss within the spiral ganglion. The results of this study support our previous hypothesis, based upon earlier horseradish peroxidase labeling experiments, that there is a topographic organization to the projection of the spiral ganglion within the isofrequency laminae that is orthogonal to the frequency representation within the ventral cochlear nuclei (VCN). That is, in addition to the spiral frequency organization of the ganglion, represented by the dorsal-to-ventral frequency map in the VCN, there is also an orderly and sequential distribution of inputs from the vertical (scala tympani-to-scala vestibuli) dimension of the spiral ganglion across the lateral-to-medial axis of the VCN. The interaction of these two topographic representations, distributed across the three dimensions of the VCN, must partly define the selective and/or integrative neuronal response properties at this first level of central nervous system processing of auditory signals within the cochlear nuclei.

Animals

Progressive improvement in discriminative abilities in adult owl monkeys performing a tactile frequency discrimination task.

1. Adult owl monkeys were trained to detect a difference in the frequency of sequentially applied tactile stimuli presented to a constant, restricted location on the glabrous skin of a single finger. Psychophysical performance functions and thresholds were determined on daily sessions over a 3- to 20-wk-long training period. 2. Thresholds for the trained digit progressively decreased from a 6- to 8-Hz difference to a 2- to 3-Hz difference relative to a 20-Hz standard. These thresholds were similar to those described for macaques and humans determined by the use of a two-alternative forced-choice procedure. 3. Six of the seven studied monkeys showed a continuously progressive improvement in performance with training. Early in the training period, the performance improved at about the same rate for all frequencies. Later in the training period, the performance for frequencies much greater than the comparison frequency improved sooner than did the performances for frequencies more similar to the comparison frequency. This resulted in an increase of the slope of the psychometric function near threshold. In a single monkey, no clear later-component improvements were recorded. 4. Analyses of performances using the theory of signal detection revealed a progressive increase in the measure of d' for all frequencies above threshold. 5. Some improvements in performance were also recorded when stimuli were applied on an adjacent digit, which was trained for 2 or 3 sessions spaced throughout the course of training. However, thresholds on these digits were always greater than those on the trained digit. These findings suggest that there are local changes generated by this training at somatotopically restricted regions of the central somatosensory nervous system. 6. It is concluded that this training resulted in a genuine progressive improvement in temporal acuity specific to the trained skin. The initial rapid improvement was likely due to an improvement in the "strategy" or "cognitive" aspects of the task, whereas more gradual improvements in performance recorded throughout the training period were most probably due to somatotopically localized changes in the neural representations of the behaviorally relevant stimulus.

Animals

Topographic reorganization of the hand representation in cortical area 3b owl monkeys trained in a frequency-discrimination task.

1. Adult owl monkeys were trained to detect differences in the frequency of a tactile flutter-vibration stimulus above a 20-Hz standard. All stimuli were delivered to a constant skin site restricted to a small part of a segment of one finger. The frequency-difference discrimination performance of all but one of these monkeys improved progressively with training. 2. The distributed responses of cortical neurons ("maps") of the hand surfaces were defined in detail in somatosensory cortical area 3b. Representations of trained hands were compared with those of the opposite, untrained hand, and to the area 3b representations of hands in a second set of monkeys that were stimulated tactually in the same manner while these monkeys were attending to auditory stimuli (passive stimulation controls). 3. The cortical representations of the trained hands were substantially more complex in topographic detail than the representations of unstimulated hands or of passively stimulated control hands. 4. In all well-trained monkeys the representations of the restricted skin location trained in the behavioral task were significantly (1.5 to greater than 3 times) greater in area than were the representations of equivalent skin locations on control digits. However, the overall extents of the representations of behaviorally stimulated fingers were not larger than those of control fingers in the same hemisphere, or in opposite hemisphere controls. 5. The receptive fields representing the trained skin were significantly larger than receptive fields representing control digits in all but one trained monkey. The largest receptive fields were centered in the zone of representation of the behaviorally engaged skin, but they were not limited to it. Large receptive fields were recorded in a 1- to 2-mm-wide zone in the area 3b maps of trained hands. 6. Receptive-field sizes were also statistically significantly larger on at least one adjacent, untrained digit when compared with the receptive fields recorded on the homologous digit of the opposite hand. 7. There was an increase in the percent overlaps of receptive fields in the cortical zone of representation of the trained skin. A significant number of receptive fields were centered on the behaviorally trained skin site. 8. The effects of increased topographic complexity, increased representation of the trained skin location, increased receptive-field size, and increased receptive-field overlap were not observed in the representations of the untrained hands in these same monkeys. Only modest increases in topographic complexity were recorded in the representations of passively stimulated hands, and no effects on receptive-field size or overlap were noted.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Frequency discrimination training engaging a restricted skin surface results in an emergence of a cutaneous response zone in cortical area 3a.

1. The responses of cortical neurons evoked by cutaneous stimulation were investigated in the hand representation of cortical area 3a in adult owl monkeys that had been trained in a tactile frequency discrimination task. Cortical representations of the hands in these experimental hemispheres were compared with those representing the opposite, untrained hand, as well as with those representing a passively stimulated hand in a second class of control monkeys. 2. A large cutaneous representation of the hairy and glabrous skin surfaces of the hand emerged in area 3a in each trained hemisphere. 3. With the emergence of cutaneous responses recorded for neurons at many area 3a locations, the normally recorded deep receptor inputs were no longer evident at most of these locations. 4. There was a greater territory of representation of the small area of skin that was stimulated in the behavioral task in trained monkeys, when compared with the representations of corresponding skin sites in the opposite hemisphere of the same monkeys, or to the representations of equivalent skin sites stimulated in passively stimulated control monkeys. 5. There was great variability in the receptive-field properties of neurons responsive to cutaneous inputs among trained monkeys. In most recording sites within the representations of the behaviorally engaged hands, the cutaneous receptive fields were large, extending over a significant part of the glabrous or hairy surfaces of the hand. However, in one monkey, very small, topographically ordered cutaneous receptive fields were recorded over a wide zone of area 3a. 6. The physiologically defined borders between areas 3a and 3b were in register with the cytoarchitectonically defined borders between these two cortical areas in trained and in control monkeys. 7. This study demonstrates that there is a reorganization of the cutaneous and "deep" representation of hand in cortical area 3a, with the main change being an emergence of a large cutaneous representation and the parallel disappearance of a large part of the normal deep representation in this field. These changes are discussed in light of the possible functional roles of cortical area 3a.

Animals

Changes in the distributed temporal response properties of SI cortical neurons reflect improvements in performance on a temporally based tactile discrimination task.

1. Temporal response characteristics of neurons were sampled in fine spatial grain throughout the hand representations in cortical areas 3a and 3b in adult owl monkeys. These monkeys had been trained to detect small differences in tactile stimulus frequencies in the range of 20-30 Hz. Stimuli were presented to an invariant, restricted spot on a single digit. 2. The absolute numbers of cortical locations and the cortical area over which neurons showed entrained frequency-following responses to behaviorally important stimuli were significantly greater when stimulation was applied to the trained skin, as compared with stimulation on an adjacent control digit, or at corresponding skin sites in passively stimulated control animals. 3. Representational maps defined with sinusoidal stimuli were not identical to maps defined with just-visible tapping stimuli. Receptive-field/frequency-following response site mismatches were recorded in every trained monkey. Mismatches were less frequently recorded in the representations of control skin surfaces. 4. At cortical locations with entrained responses, neither the absolute firing rates of neurons nor the degree of the entrainment of the response were correlated with behavioral discrimination performance. 5. All area 3b cortical locations with entrained responses evoked by stimulation at trained or untrained skin sites were combined to create population peristimulus time and cycle histograms. In all cases, stimulation of the trained skin resulted in 1) larger-amplitude responses, 2) peak responses earlier in the stimulus cycle, and 3) temporally sharper responses, than did stimulation applied to control skin sites. 6. The sharpening of the response of cortical area 3b neurons relative to the period of the stimulus could be accounted for by a large subpopulation of neurons that had highly coherent responses. 7. Analysis of cycle histograms for area 3b neuron responses revealed that the decreased variance in the representation of each stimulus cycle could account for behaviorally measured frequency discrimination performance. A strong correlation between these temporal response distributions and the discriminative performances for stimuli applied at all studied skin surfaces was even stronger (r = 0.98) if only the rising phases of cycle histogram were considered in the analysis. 8. The responses of neurons in area 3a could not account for measured differences in frequency discrimination performance. 9. These representational changes did not occur in monkeys that were stimulated on the same schedule but were performing an auditory discrimination task during skin stimulation. 10. It is concluded that by behaviorally training adult owl monkeys to discriminate the temporal features of a tactile stimulus, distributed spatial and temporal response properties of cortical neurons are altered.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Neurophysiological correlates of hand preference in primary motor cortex of adult squirrel monkeys.

Variability in the functional topography of area 4 was examined in adult squirrel monkeys. Conventional intracortical microstimulation techniques were used to derive detailed maps (250 microns interpenetration distances) of distal forelimb movement representations in both hemispheres of six monkeys. Spatial features of these representational maps were then compared to the hand preferred by the individual animals during a motor task requiring skilled digit use. Beyond a few broad generalizations common to all area 4 motor maps, the local mosaic-like topography of individual distal forelimb representations was highly idiosyncratic. Using statistical procedures to determine the independent contributions of individual, side, and movement category to the total variation in motor maps, the results demonstrate statistically significant variation in representational topography among individuals as well as between hemispheres of the same individuals. In the dominant hemisphere (i.e., the hemisphere opposite the preferred hand), the distal forelimb representations generally were greater in number and larger in total area, and displayed a longer total boundary length and a greater index of spatial complexity. Because of the direct relationship between interhemispheric asymmetry and behavioral asymmetry, these studies suggest that a large source of variability found in the topography of motor maps in this and other studies derives from differences in the way particular movements and/or movement combinations are performed by individual animals.

Animals

Reorganization of somatosensory area 3b representations in adult owl monkeys after digital syndactyly.

1. These experiments were designed to test the hypothesis that temporally correlated afferent input activity plays a lifelong role in the establishment and modification of receptive fields (RFs) and representational topographies in the primary somatosensory cortex of adult monkeys. They were based in part on the finding that adjacent digits of the hand are represented discontinuously in area 3b of the adult owl monkey. If cortical receptive fields and the details of cortical topographic representations are shaped by the weights of the temporal correlations among afferent inputs, then representational discontinuities between digits would be expected to arise because inputs from the skin surfaces of adjacent digits are largely independent in the critical time domain. 2. In the present experiments, the skin of adjacent digits 3 and 4 of the monkey hand was surgically connected to create an artificial syndactyly, or webbed-finger condition. Highly detailed microelectrode maps of the cortical representation of the syndactyl digits were obtained 3-7.5 mo later. This experimental manipulation greatly increased the amount of simultaneous or nearly simultaneous input from the normally separated, now fused, surfaces of adjacent fingers. 3. Cortical maps of the representations of finger surfaces were highly modified from the normal after a several-month-long period of digital fusion. Specifically, the normal discontinuity between the cortical representations of adjacent fingers was abolished. Within a wide cortical zone, RFs were defined that extended across the line of syndactyly onto the surgically joined skin of both fused digits. The representational topography of the fused digits was similar to any normal single digit and was characterized by a continuous progression of partially overlapping RFs. 4. Control observations revealed that these reorganizational changes cannot be accounted for by any changes in cutaneous innervation induced by the surgery. They must arise from representational changes in the central somatosensory system. 5. These findings reveal that cortical maps can be altered in detail in adult monkeys by modifying the distributed temporal structure of afferent inputs. They support the longstanding hypothesis that the temporal coincidence of inputs plays a role in the grouping of input subsets into specific cortical RFs and, consequently, in the shaping of selected effective cortical inputs and representational topographies throughout life.

Animals

Tinnitus suppression by cochlear implants.

The beneficial effects of cochlear implants on tinnitus have been noted in several studies, but few detailed appraisals of the phenomenon have been made. Six patients fitted with the UCSF/Storz cochlear implant device were studied. The effects of use of the implant device on tinnitus were monitored, and suppression of tinnitus was tracked throughout periods of stimulation and poststimulation. Tinnitus was effectively suppressed in five of six patients with the device on and with noise input, and reduction of perceived tinnitus loudness occurred in four of six with the device on but without acoustic input to the speech processor. Unilateral stimulation frequently resulted in bilateral tinnitus suppression. These studies reveal that profound tinnitus suppression is obtained by patients using their cochlear implants. Further work is required to quantify the optimal mode of stimulation, but these findings suggest that tinnitus sufferers may ultimately benefit from development of electrical stimulation tinnitus suppression devices.

Adult

Neocortical representational dynamics in adult primates: implications for neuropsychology.

Some evidence for functional reorganization of cortical somatosensory representations in adult primates is reviewed. These examples include representation remodeling in cortical area 3b following digit amputation, digit fusion, local intracortical microstimulation, restricted cortical lesions, or as a consequence of behaviorally controlled stimulation of restricted hand surfaces. We suggest that the profound changes in the cortical representations that have been observed after these and other manipulations must bear consequences for the specific behaviors that depend on the operation of this neural machinery. Furthermore, this lifelong dynamic cortical capacity for neuronal response adaptation by use almost certainly also underlies the progressive representational remodeling that we have recorded following brain lesions.

Afferent Pathways

Speech recognition in analog multichannel cochlear prostheses: initial experiments in controlling classifications.

Computer-synthesized vowels were used to examine methods for controlling and measuring the perceptions elicited during electrical stimulation of the human cochlea. In the first experiment, we measured the importance of the second formant (F2) in the identification of vowels, matched for duration, in a single subject with a multichannel cochlear implant. The subject never confused vowels having a "low" frequency F2 with those having a "high" frequency F2. In the second experiment, identification functions were generated for a series of vowels varying only in F2. When the pattern of F2 stimulation at the basilar membrane was manipulated, vowel identification functions were altered. For the categorization of vowels, the data indicate that the relative cochlear position of F2 stimulation was more important than fine-grain temporal waveform cues. The data are supportive of cochlear implant coding strategies that make use of cochlear place information. In the later experiments, we manipulated filter passbands and channel gains to explore their effect on these classifications. These preliminary studies indicate that it is possible to "fine-tune" such classifications.

Aged

Functional reorganization of primary somatosensory cortex in adult owl monkeys after behaviorally controlled tactile stimulation.

1. Multiple microelectrode maps of the hand representation within and across the borders of cortical area 3b were obtained before, immediately after, or several weeks after a period of behaviorally controlled hand use. Owl monkeys were conditioned in a task that produced cutaneous stimulation of a limited sector of skin on the distal phalanges of one or more fingers. 2. Analysis of microelectrode mapping experiment data revealed that 1) stimulated skin surfaces were represented over expanded cortical areas. 2) Most of the cutaneous receptive fields recorded within these expanded cortical representational zones were unusually small. 3) The internal topography of representation of the stimulated and immediately surrounding skin surfaces differed greatly from that recorded in control experiments. Representational discontinuities emerged in this map region, and "hypercolumn" distances in this map sector were grossly abnormal. 4) Borders between the representations of individual digits and digit segments commonly shifted. 5) The functionally defined rostral border of area 3b shifted farther rostralward, manifesting either an expansion of the cutaneous area 3b fingertip representation into cortical field 3a or an emergence of a cutaneous input zone in the caudal aspect of this normally predominantly deep-receptor representational field. 6) Significant lateralward translocations of the borders between the representations of the hand and face were recorded in all cases. 7) The absolute locations--and in some cases the areas or magnifications--of representations of many skin surfaces not directly involved in the trained behavior also changed significantly. However, the most striking areal, positional, and topographic changes were related to the representations of the behaviorally stimulated skin in every studied monkey. 3. These experiments demonstrate that functional cortical remodeling of the S1 koniocortical field, area 3b, results from behavioral manipulations in normal adult owl monkeys. We hypothesize that these studies manifest operation of the basic adaptive cortical process(es) underlying cortical contributions to perception and learning.

Animals

Receptive-field changes induced by peripheral nerve stimulation in SI of adult cats.

1. Receptive fields (RFs) of neurons in the primary somatosensory (SI) cortex were defined before, during, and after electrical stimulation of myelinated fibers in the dorsal cutaneous branch of the ulnar nerve in adult pentobarbital sodium-anesthetized cats. 2. This stimulation resulted in an approximately threefold increase of SI multiunit RF sizes. Substantial changes were first recorded within 1-2 h of stimulation. RFs typically enlarged continuously over a several-hour stimulation period, then stabilized. 3. RF-area increases were observed within both the forepaw and hindpaw representational zones in the SI cortex contralateral to the stimulated forepaw nerve. RF sizes did not increase in the ipsilateral SI body surface representation or in sham-stimulation control animals. 4. Preliminary studies indicate that stimulation-induced changes can be halted and often reversed by the intravenous administration of the opiate antagonist naloxone. 5. These observations suggest a global naloxone-sensitive modulatory system that operates on large-diameter afferent inputs in the cat somatosensory system. The increases in RF size occur under nerve-stimulation conditions similar to those that result in the generation of widespread analgesia (Chung et al. 1984a,b; Gamble and Milne 1986; Toda and Ichioka 1978).

Afferent Pathways

Repetitive microstimulation alters the cortical representation of movements in adult rats.

In order to examine the effects of repetitive stimulation on functional cortical organization, standard intracortical microstimulation (ICMS) techniques were used to generate maps of movement representations in motor cortex of rat. After identification of caudal and rostral forelimb fields and adjacent vibrissae and neck fields, one or more representational borders were defined in greater detail. Then a microelectrode was introduced into one of these representational fields, and ICMS current pulses were delivered at a rate of 1/sec for 1 to 3 hr. Following repetitive ICMS, significant changes in movement representations were observed using current levels that were either suprathreshold or subthreshold for evoking the site-specific movement. Electromyographic activity could be evoked at suprathreshold and near-threshold current levels, but not at the subthreshold current levels used here. Significant border shifts ranged from 210 to 670 microns. In each case in which shifts occurred, there appeared to be expansion of the movement represented at the repetitively stimulated site. The effects were progressive and reversible. These results suggest that at least under these unusual experimental circumstances, large representational changes can be generated very rapidly within motor cortex in the absence of any evident peripheral feedback.

Animals

Neuronal discharge rate is unsuitable for encoding sound intensity at the inferior-colliculus level.

Rate-intensity functions from single neurons in the central nucleus of the inferior colliculus (ICC) of the cat in response to tone bursts and continuous noise were recorded. Only 6% of 64 quantitatively studied neurons had monotonic functions in response to tone bursts, 12.5% in response to continuous noise. The other neurons had functions with a single peak which could occur at any super-threshold level tested (3-80 dB), or with multiple peaks. In 78% of the neurons the rate-intensity functions in response to tones and noise were of different shape. We interpret this stimulus dependency of the shape of rate-intensity functions of most neurons as evidence against sound-intensity coding only on the basis of the shape of rate-intensity functions at the ICC level. Rate-intensity functions averaged from neurons with similar characteristic frequencies or from all neurons of our sample indicate a constant average discharge over at least 60 dB sound intensity. This excludes sound-intensity coding by means of an average neuronal discharge rate in the ICC.

Air Pressure

Receptive fields in the body-surface map in adult cortex defined by temporally correlated inputs.

Receptive fields (RFs) obtained at specific cortical sites can be used to define a topographic map of the body surface in adult mammalian somatosensory cortex. This map is not static, and RFs at particular cortical sites can change in size and location throughout adult life. Conversely, the cortical loci at which a given skin surface is represented can shift hundreds of micrometres across the cortex in the koniocortical field, area 3b (refs 1-12). This plasticity suggests that RFs derive not from rigid anatomical connections, but by the selection of a subset of a large number of inputs. We have proposed that inputs are selected on the basis of temporal correlation 11-15. Here we test this idea by altering the correlation of inputs from two adjacent digits on the adult owl monkey hand by surgically connecting the skin surfaces of the two fingers (the formation of syndactyly). This manipulation increases the correlation of inputs from skin surfaces of adjacent fingers. The striking discontinuity between the zones of representation of adjacent digits on the somatosensory cortex disappeared. These results support the hypothesis that the topography of the body-surface map in the adult cortex is influenced by the temporal correlations of afferent inputs.

Animals

Comparative studies of speech processing strategies for cochlear implants.

A wide variety of speech processing strategies for multichannel auditory prostheses were compared in studies of two patients implanted with the UCSF electrode array. Each strategy was evaluated using tests of vowel and consonant confusions, with and without lipreading. Included among the strategies were the compressed analog processor of the present UCSF/Storz prosthesis and a group of interleaved pulses processors in which the amplitudes of nonsimultaneous pulses code the spectral variations of speech. For these patients, each with indications of poor nerve survival, test scores were significantly higher with the interleaved pulses processors. We believe this superior performance was a result of 1. the substantial release from channel interactions provided by nonsimultaneous stimuli and 2. a fast enough rotation among the channels to support adequate temporal and spectral resolution of perceived speech sounds.

Cochlear Implants

Somatotopically inappropriate projections from thalamocortical neurons to the SI cortex of the cat demonstrated by the use of intracortical microstimulation.

Single thalamocortical neurons with receptive fields on the toes were antidromically activated by the passage of 300-microseconds, 0.5- to 10-microA pulses through glass micropipette electrodes placed within somatotopically identified regions of the digit representation of the cat first somatosensory (SI) cortex. The somatotopy of the cortex was determined using recordings from single cortical neurons (see "Methods"), and the positions of the all tracks were marked on an enlarged photograph of the postcruciate cortex. In two of the three protocols, a very precise map of the boundary between two adjacent toes was produced prior to attempting intracortical microstimulation. Slopes of the threshold-distance curves at the sites of the lowest recorded thresholds were on the order of 0.8 microA/10 micron. This value, together with information on the anatomy of the cortical arborizations of thalamocortical neurons (Landry and Deschenes, 1981), suggested that currents of 2 and 5 microA would not activate the cortical processes of thalamocortical neurons at distances greater than 50 and 90 microns, respectively. With currents below 5 microA, thalamocortical neurons could be antidromically activated at a number of sites at depths between 340 and 930 microns (layer IV and upper layer III) and between 1,050 and 1,460 microns (layer VI). A total of 13 thalamocortical neurons could be antidromically activated using current pulses of between 0.8 and 5.0 microA, from within tracks at tangential distances of 250-830 microns from the nearest track through the somatotopically appropriate region. Within somatotopically inappropriate regions, cortical neurons frequently had receptive fields on a toe adjacent to that bearing the receptive field of the thalamic neuron(s) under study. The possible relationship of somatotopically inappropriate projections to the reorganization of cortical somatotopy following digit amputation, paw amputation, and nerve section is discussed.

Action Potentials