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Biomedical subjects

M M Merzenich

Publications and source records attributed to M M Merzenich.

At least 19 recordsLinked to original sources

Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys.

This study was undertaken to document plastic changes in the functional topography of primary motor cortex (M1) that are generated in motor skill learning in the normal, intact primate. Intracortical microstimulation mapping techniques were used to derive detailed maps of the representation of movements in the distal forelimb zone of M1 of squirrel monkeys, before and after behavioral training on two different tasks that differentially encouraged specific sets of forelimb movements. After training on a small-object retrieval task, which required skilled use of the digits, their evoked-movement digit representations expanded, whereas their evoked-movement wrist/forearm representational zones contracted. These changes were progressive and reversible. In a second motor skill exercise, a monkey pronated and supinated the forearm in a key (eyebolt)-turning task. In this case, the representation of the forearm expanded, whereas the digit representational zones contracted. These results show that M1 is alterable by use throughout the life of an animal. These studies also revealed that after digit training there was an areal expansion of dual-response representations, that is, cortical sectors over which stimulation produced movements about two or more joints. Movement combinations that were used more frequently after training were selectively magnified in their cortical representations. This close correspondence between changes in behavioral performance and electrophysiologically defined motor representations indicates that a neurophysiological correlate of a motor skill resides in M1 for at least several days after acquisition. The finding that cocontracting muscles in the behavior come to be represented together in the cortex argues that, as in sensory cortices, temporal correlations drive emergent changes in distributed motor cortex representations.

Animals

Temporal processing deficits of language-learning impaired children ameliorated by training.

Children with language-based learning impairments (LLIs) have major deficits in their recognition of some rapidly successive phonetic elements and nonspeech sound stimuli. In the current study, LLI children were engaged in adaptive training exercises mounted as computer "games" designed to drive improvements in their "temporal processing" skills. With 8 to 16 hours of training during a 20-day period, LLI children improved markedly in their abilities to recognize brief and fast sequences of nonspeech and speech stimuli.

Child

Language comprehension in language-learning impaired children improved with acoustically modified speech.

A speech processing algorithm was developed to create more salient versions of the rapidly changing elements in the acoustic waveform of speech that have been shown to be deficiently processed by language-learning impaired (LLI) children. LLI children received extensive daily training, over a 4-week period, with listening exercises in which all speech was translated into this synthetic form. They also received daily training with computer "games" designed to adaptively drive improvements in temporal processing thresholds. Significant improvements in speech discrimination and language comprehension abilities were demonstrated in two independent groups of LLI children.

Algorithms

Remodelling of hand representation in adult cortex determined by timing of tactile stimulation.

The primate somatosensory cortex, which processes tactile stimuli, contains a topographic representation of the signals it receives, but the way in which such maps are maintained is poorly understood. Previous studies of cortical plasticity indicated that changes in cortical representation during learning arise largely as a result of hebbian synaptic change mechanisms. Here we show, using owl monkeys trained to respond to specific stimulus sequence events, that serial application of stimuli to the fingers results in changes to the neuronal response specificity and maps of the hand surfaces in the true primary somatosensory cortical field (S1 area 3b). In this representational remodelling stimuli applied asychronously to the fingers resulted in these fingers being integrated in their representation, whereas fingers to which stimuli were applied asynchronously were segregated in their representation. Ventroposterior thalamus response maps derived in these monkeys were not equivalently reorganized. This representational plasticity appears to be cortical in origin.

Animals

Temporal information transformed into a spatial code by a neural network with realistic properties.

Neurons exhibit a wide range of properties in addition to postsynaptic potential (PSP) summation and spike generation. Although other neuronal properties such as paired-pulse facilitation (PPF) and slow PSPs are well characterized, their role in information processing remains unclear. It is possible that these properties contribute to temporal processing in the range of hundreds of milliseconds, a range relevant to most complex sensory processing. A continuous-time neural network model based on integrate-and-fire elements that incorporate PPF and slow inhibitory postsynaptic potentials (IPSPs) was developed here. The time constants of the PPF and IPSPs were estimated from empirical data and were identical and constant for all elements in the circuit. When these elements were incorporated into a circuit inspired by neocortical connectivity, the network was able to discriminate different temporal patterns. Generalization emerged spontaneously. These results demonstrate that known time-dependent neuronal properties enable a network to transform temporal information into a spatial code in a self-organizing manner--that is, with no need to assume a spectrum of time delays or to custom-design the circuit.

Electric Stimulation

EXP: a Macintosh program for automating data acquisition and analysis applied to neurophysiology.

EXP is a Macintosh program for doing quantitative neurophysiology. It supports signal design, simultaneous signal output and data collection, spike sorting, histogram production, and many other analysis features. The hierarchical structure used to design protocols provides a straightforward method for designing complex experiments. The degree of automation supported by the program makes it possible to perform large-scale experiments and to collect and analyze large quantities of data in a reasonable amount of time. It has been used successfully in a large number of experimental paradigms by several different researchers. EXP is one of several cooperative programs designed to help perform neurophysiological experiments. These programs can be used in tandem not only to collect and analyze data but to help interpret and present results as well. The programs contain mechanisms to encourage re-analysis or 'virtual experiments' on data collected previously by oneself or other researchers.

Data Collection

MAP: a Macintosh program for generating categorical maps applied to cortical mapping.

One technique for studying the cortex entails mapping the distribution of neuronal response properties across a cortical zone. In sensory cortex, 'receptive fields' are arranged in an orderly way such that they form a topographical representation, or 'map', of the sensory surface on the cortex. Detailed maps can be constructed by making many microelectrode penetrations across the cortex and measuring the receptive field at each site. A computer program called MAP was designed to aid in the efficient generation of these maps. MAP allows the user to mark penetration sites on digitized images of the cortical surface and to draw receptive fields on digitized images of the skin surface being studied. Penetration sites are then automatically assigned a category based on the location of the receptive field. MAP has significantly increased the speed of this experimental process. MAP contains a number of mechanisms designed to facilitate analysis. For example, it can automatically generate cortical maps based on receptive field locations. It can also show recorded neurophysiological data at each penetration site allowing the experimenter to visualize activity across the cortical zone. These features along with several others make MAP an effective tool for cortical mapping.

Brain Mapping

Alterations of the cortical representation of the rat ventrum induced by nursing behavior.

The representation of the surfaces of the trunk was mapped in detail in a series of anesthetized adult female rats to assess cortical representational changes that might be induced in the SI cortical field by a major natural source of a differentially heavy schedule of tactile inputs: the stimulation of the rat ventrum in nursing behavior. Controls included virgin rats and postpartum age-matched rats whose litters were removed on the day of birth. The SI representation of the ventral trunk skin of lactating rats was about 1.6 x larger than in matched postpartum nonlactating or virgin controls. The greatest representational change--about twofold--was for the nipple-bearing skin between the forelimbs and hindlimbs. Indeed, changes in SI representational territory for the middle third of the ventrum, a skin zone without nipples, were not significant. As a rule, the representation of the ventrum skin in lactating rats was at least as topographically ordered as was that reconstructed for nonlactating postpartum and virgin controls. Receptive fields (RFs) representing the ventrum skin in lactating females were about one-third the sizes of those recorded in matched nonlactating or virgin controls. RF size differences were again greater for the representation of the nipple-bearing skin in the anterior and posterior thirds of the ventrum than for the central third. Changes in RF sizes were roughly inversely related to changes in the cortical magnification of representation of the ventrum on the proportion of about 3:2. Interestingly, the glabrous nipple and areolar skin were only weakly represented--or not demonstrably represented--in the SI map of either lactating or control rats. These results indicate that there is a largely unstudied cortical neurology of nursing behavior. Major CNS changes are induced by this dramatic, episodic change in behaviorally important tactile inputs. In turn, input-induced changes presumably contribute to this emergent, rapidly evolving behavior.

Animals

Alterations in correlated activity parallel ICMS-induced representational plasticity.

We studied neural interactions by cross correlation analysis during representational plasticity induced by intracortical microstimulation (ICMS). Neuron pairs were simultaneously recorded in area 3b in adult New World monkeys, and in cortical field SI in adult rats. In normal animals, the degree of correlated spontaneous activity corresponded to the extent of receptive field overlap. After several hours of ICMS, the spatial extents of cortex over which correlated activity could be recorded was enlarged several-fold. Mapping experiments revealed that increased correlated activity was only recorded within that cortical sector that was representationally reorganized, indicating a close relationship between cortical reorganization and cooperative processes. Results support the hypothesis that discharge coincidence is crucial for the formation of functionally coupled neural groups, and implicate dynamically maintained groups in the genesis of postontogenetic plasticity.

Action Potentials

Cortical plasticity and memory.

The roles of extrinsically modulated, plastic Hebb-like synapses and dynamic cortical cell assemblies underlying cortical plasticity in learning and memory operations are described. From our understanding of the distributed form of representation of learned behaviors in somatosensory and auditory cortical fields, and given new findings about the nature and distribution of responses representing learned and remembered stimuli in the inferior temporal cortex, a hypothetical picture of the cortical engram representing learned behaviors and memories is posited.

Afferent Pathways

Plasticity in the frequency representation of primary auditory cortex following discrimination training in adult owl monkeys.

Previous studies have shown that the tonotopic organization of primary auditory cortex is altered subsequent to restricted cochlear lesions (Robertson and Irvine, 1989) and that the topographic reorganization of the primary somatosensory cortex is correlated with changes in the perceptual acuity of the animal (Recanzone et al., 1992a-d). Here we report an increase in the cortical area of representation of a restricted frequency range in primary auditory cortex of adult owl monkeys that is correlated with the animal's performance at a frequency discrimination task. Monkeys trained for several weeks to discriminate small differences in the frequency of sequentially presented tonal stimuli revealed a progressive improvement in performance with training. At the end of the training period, the tonotopic organization of Al was defined by recording multiple-unit responses at 70-258 cortical locations. These responses were compared to those derived from three normal monkeys and from two monkeys that received the same auditory stimuli but that were engaged in a tactile discrimination task. The cortical representation, the sharpness of tuning, and the latency of the response were greater for the behaviorally relevant frequencies of trained monkeys when compared to the same frequencies of control monkeys. The cortical area of representation was the only studied parameter that was correlated with behavioral performance. These results demonstrate that attended natural stimulation can modify the tonotopic organization of Al in the adult primate, and that this alteration is correlated with changes in perceptual acuity.

Acoustic Stimulation

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