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M M Merzenich

Publications and source records attributed to M M Merzenich.

At least 55 records · Page 3Linked to original sources

Functional architecture of the mystacial vibrissae.

We investigated the transduction operation and function of the mystacial vibrissae, using a comparative morphological analysis and behavioral experiments in rats. Vibrissal architecture was documented in a series of mammals to identify evolutionary conserved features of vibrissal organization. As a result of this analysis, we distinguish between a frontal microvibrissal system and macrovibrissal system of the mystacial pad. The latter was invariably comprised of whiskers aligned in regular rows. In each row, whiskers were oriented perpendicular to the animal's rostrocaudal axis; all shared a specific dorsoventral orientation. In all species, progressing from rostral to caudal in any vibrissal row, there was a precisely exponential increase in whisker length. Each whisker appeared to act as a lever-like transducer, providing information as to whether or not--but not where--an individual vibrissa had been deflected. The rat's frontal microvibrissae system was found to have a vibrissa tip density that was about 40 times higher than that of the mystacial macrovibrissae. In behavioral studies spatial tasks and object recognition tasks were used to investigate (a) search behaviors; (b) single whisker movements; (c) object recognition ability; and (d) effects of selective macro- or microvibrissae removal on task performances. A clear distinction between the functional roles of macro- and microvibrissae was demonstrated in these studies. Mystacial macrovibrissae were critically involved in spatial tasks, but were not essential for object recognition. Microvibrissae were critically involved in object recognition tasks, but were not essential for spatial tasks. A synthesis of these morphological and behavioral data led to the following functional concept: The mystacial macrovibrissae row is a distance decoder. Its function is to derive head centered obstacle/opening contours at the various dorsoventral angles represented by vibrissal rows. This distance detector model is functionally very different from traditional concepts of whisker function, in which the mystacial whiskers were hypothesized to form a fine grain skin-like object-recognizing tactile surface.

Animals↗

A primate model for studying focal dystonia and repetitive strain injury: effects on the primary somatosensory cortex.

BACKGROUND AND PURPOSE: Job-related repetitive strain injuries (RSIs) are increasing, and current treatment strategies often fail to return injured people to work. This study documented the neural consequences of using two different movement strategies for active, repetitive hand closing and opening. METHODS: Two owl monkeys were trained for 20 weeks to repetitively close a handpiece against an 80-g force (3-400 trials per day, training at 80%-90% accuracy). One monkey used a highly articulated hand-squeezing strategy, and the other monkey used a proximal arm-pulling strategy. Changes in motor performance were analyzed, and the electrophysiological maps of the hand representation on the trained primary sensory cortex (area 3b) were compared with those of untrained control animals and the untrained sides of the trained monkeys. RESULTS: The monkey using the articulated hand-squeezing strategy showed motor deterioration and dedifferentiation of the normally sharply segregated areas of the hand representation in area 3b. Mild degradation of the hand representation was measured in the monkey using the proximal arm-pulling strategy, but there was no motor dysfunction. CONCLUSION AND DISCUSSION: Attended, highly articulated, repetitive finger squeezing degrades the hand representation and interferes with motor control. A proximal, more variable repetitive strategy minimized the sensory degradation and preserved motor control. Restoring the hand representation may be a critical part of treatment for patients with chronic RSI and focal hand dystonia.

Animals↗

Primary cortical representation of sounds by the coordination of action-potential timing.

Cortical population coding could in principle rely on either the mean rate of neuronal action potentials, or the relative timing of action potentials, or both. When a single sensory stimulus drives many neurons to fire at elevated rates, the spikes of these neurons become tightly synchronized, which could be involved in 'binding' together individual firing-rate feature representations into a unified object percept. Here we demonstrate that the relative timing of cortical action potentials can signal stimulus features themselves, a function even more basic than feature grouping. Populations of neurons in the primary auditory cortex can coordinate the relative timing of their action potentials such that spikes occur closer together in time during continuous stimuli. In this way cortical neurons can signal stimuli even when their firing rates do not change. Population coding based on relative spike timing can systemically signal stimulus features, it is topographically mapped, and it follows the stimulus time course even where mean firing rate does not.

Action Potentials↗

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↗

A transparent model of the human scala tympani cavity.

A dimensionally accurate clear model of the human scala tympani has been produced to evaluate the insertion and position of clinically applied intracochlear electrodes for electrical stimulation. Replicates of the human scala tympani were made from low melting point metal alloy (LMA) and from polymethylmeth-acrylate (PMMA) resin. The LMA metal casts were embedded in blocks of epoxy and in clear silicone rubber. After removal of the metal alloy, a cavity was produced that accurately models the human scala tympani. Investment casting molds were made from the PMMA scala tympani casts to enable production of multiple LMA casts from which identical models were fabricated. Total dimensional distortion of the LMA casting process was less than 1% in length and 2% in diameter. The models have been successfully integrated into the design process for the iterative development of advanced intracochlear electrode arrays at UCSF. These fabrication techniques are applicable to a wide range of biomedical design problems that require modelling of visually obscured cavities.

Alloys↗

Experience-induced plasticity of cutaneous maps in the primary somatosensory cortex of adult monkeys and rats.

In a first study, the representations of skin surfaces of the hand in the primary somatosensory cortex, area 3b, were reconstructed in owl monkeys and squirrel monkeys trained to pick up food pellets from small, shallow wells, a task which required skilled use of the digits. Training sessions included limited manual exercise over a total period of a few hours of practice. From an early clumsy performance in which many retrieval attempts were required for each successful pellet retrieval, the monkeys exhibited a gradual improvement. Typically, the animals used various combinations of digits before developing a successful retrieval strategy. As the behavior came to be stereotyped, monkeys consistently engaged surfaces of the distal phalanges of one or two digits in the palpation and capture of food pellets from the smallest wells. Microelectrode mapping of the hand surfaces revealed that the glabrous skin of the fingertips predominantly involved in the dexterity task was represented over topographically expanded cortical sectors. Furthermore, cutaneous receptive fields which covered the most frequently stimulated digital tip surfaces were less than half as large as were those representing the corresponding surfaces of control digits. In a second series of experiments, Long-Evans rats were assigned to environments promoting differential tactile experience (standard, enriched, and impoverished) for 80 to 115 days from the time of weaning. A fourth group of young adult rat experienced a severe restriction of forepaw exploratory movement for either 7 or 15 days. Cortical maps derived in the primary somatosensory cortex showed that environmental enrichment induced a substantial enlargement of the cutaneous forepaw representation, and improved its spatial resolution (smaller glabrous receptive fields). In contrast, tactile impoverishment resulted in a degradation of the forepaw representation that was characterized by larger cutaneous receptive fields and the emergence of non-cutaneous responses. Cortical maps derived in the hemispheres contralateral to the immobilized forelimb exhibited a severe decrease of about 50% in the overall areal extent of the cutaneous representation of the forepaw, which resulted from the invasion of topographically organized cortical zones of non-cutaneous responses, and numerous discontinuities in the representation of contiguous skin territories. The size and the spatial arrangement of the cutaneous receptive fields were not significantly modified by the immobilization of the contralateral forelimb. Similar results were obtained regardless of whether the forelimb restriction lasted 7 or 15 days. These two studies corroborate the view that representational constructs are permanently reshaped by novel experiences through dynamic competitive processes. These studies also support the notion that subject-environment interactions play a crucial role in the maintenance of basic organizational features of somatosensory representations.

Animals↗

Associative synaptic plasticity in hippocampal CA1 neurons is not sensitive to unpaired presynaptic activity.

1. Hebbian or associative synaptic plasticity has been proposed to play an important role in learning and memory. Whereas many behaviorally relevant stimuli are time-varying, most experimental and theoretical work on synaptic plasticity has focused on stimuli or induction protocols without temporal structure. Recent theoretical studies have suggested that associative plasticity sensitive to only the conjunction of pre- and postsynaptic activity is not an effective learning rule for networks required to learn time-varying stimuli. Our goal in the current experiment was to determine whether associative long-term potentiation (LTP) is sensitive to temporal structure. We examined whether the presentation of unpaired presynaptic pulses in addition to paired pre- and postsynaptic activity altered the induction of associative LTP. 2. By using intracellular recordings from CA1 pyramidal cells, associative long-term potentiation (LTP) was induced in a control pathway by pairing a single presynaptic pulse with postsynaptic depolarization every 5 s (50-70 x). The experimental pathway received the same training, with additional unpaired presynaptic pulses delivered in close temporal proximity, either after or before associative pairing. Five separate sets of experiments were performed with intervals of -200, -50, +50, +200, or +800 ms. Negative intervals indicate that the unpaired presynaptic pulse was presented before the depolarizing pulse. Our results showed that the presence of unpaired presynaptic pulses, occurring either before or after pairing, did not significantly alter the magnitude of LTP. 3. The experimental design permitted an analysis of whether changes in paired-pulse facilitation (PPF) occur as a result of associative LTP. The average degree of PPF was the same before and after LTP. However, there was a significant inverse correlation between the initial degree of PPF and the degree of PPF after LTP. There was no relationship between the change in PPF, and whether the first or second pulse had been paired with depolarization. 4. These results indicate that the presence of unpaired presynaptic pulses does not alter the induction of synaptic plasticity, suggesting that plasticity of the Schaffer collateral-CA1 synapse is primarily conjunctive rather than correlative.

Animals↗

A primate genesis model of focal dystonia and repetitive strain injury: I. Learning-induced dedifferentiation of the representation of the hand in the primary somatosensory cortex in adult monkeys.

In this study we tested a neuroplasticity/learning origins hypothesis for repetitive strain injuries (RSIs), including occupationally induced focal dystonia. Repetitive movements produced in a specific form and in an appropriate behavioral context cause a degradation of the sensory feedback information controlling fine motor movements, resulting in the "learned" genesis of RSIs. Two adult New World owl monkeys were trained at a behavioral task that required them to maintain an attended grasp on a hand grip that repetitively and rapidly (20 msec) opened and closed over short distances. The monkeys completed 300 behavioral trials per day (1,100 to 3,000 movement events) with an accuracy of 80 to 90%. A movement control disorder was recorded in both monkeys. Training was continued until the performance accuracy dropped to below 50%. We subsequently conducted an electrophysiologic mapping study of the representations of the hand within the primary somatosensory (SI) cortical zone. The hand representation in the true primary somatosensory cortical field, SI area 3b, was found to be markedly degraded in these monkeys, as characterized by (1) a dedifferentiation of cortical representations of the skin of the hand manifested by receptive fields that were 10 to 20 times larger than normal, (2) the emergence of many receptive fields that covered the entire glabrous surface of individual digits or that extended across the surfaces of two or more digits, (3) a breakdown of the normally sharply segregated area 3b representations of volar glabrous and dorsal hairy skin of the hand, and (4) a breakdown of the local shifted-overlap receptive field topography of area 3b, with many digital receptive fields overlapping the fields of neurons sampled in cortical penetrations up to more than four times farther apart than normal. Thus, rapid, repetitive, highly stereotypic movements applied in a learning context can actively degrade cortical representations of sensory information guiding fine motor hand movements. This cortical plasticity/learning-based dedifferentiation of sensory feedback information from the hand contributes to the genesis of occupationally derived repetitive strain injuries, including focal dystonia of the hand. Successful treatment of patients with RSI will plausibly require learning-based restoration of differentiated representations of sensory feedback information from the hand.

Animals↗

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↗

Representation of a species-specific vocalization in the primary auditory cortex of the common marmoset: temporal and spectral characteristics.

1. The temporal and spectral characteristics of neural representations of a behaviorally important species-specific vocalization were studied in neuronal populations of the primary auditory cortex (A1) of barbiturate-anesthetized adult common marmosets (Callithrix jacchus), using both natural and synthetic vocalizations. The natural vocalizations used in electrophysiological experiments were recorded from the animals under study or from their conspecifics. These calls were frequently produced in vocal exchanges between members of our marmoset colony and are part of the well-defined and highly stereotyped vocal repertoire of this species. 2. The spectrotemporal discharge pattern of spatially distributed neuron populations in cortical field A1 was found to be correlated with the spectrotemporal acoustic pattern of a complex natural vocalization. However, the A1 discharge pattern was not a faithful replication of the acoustic parameters of a vocalization stimulus, but had been transformed into a more abstract representation than that in the auditory periphery. 3. Subpopulations of A1 neurons were found to respond selectively to natural vocalizations as compared with synthetic variations that had the same spectral but different temporal characteristics. A subpopulation responding selectively to a given monkey's call shared some but not all of its neuronal memberships with other individual-call-specific neuronal subpopulations. 4. In the time domain, responses of individual A1 units were phase-locked to the envelope of a portion of a complex vocalization, which was centered around a unit's characteristic frequency (CF). As a whole, discharges of A1 neuronal populations were phase-locked to discrete stimulus events but not to their rapidly changing spectral contents. The consequence was a reduction in temporal complexity and an increase in cross-population response synchronization. 5. In the frequency domain, major features of the stimulus spectrum were reflected in rate-CF profiles. The spectral features of a natural call were equally or more strongly represented by a subpopulation of A1 neurons that responded selectively to that call as compared with the entire responding A1 population. 6. Neuronal responses to a complex call were distributed very widely across cortical field A1. At the same time, the responses evoked by a vocalization scattered in discrete cortical patches were strongly synchronized to stimulus events and to each other. As a result, at any given time during the course of a vocalization, a coherent representation of the integrated spectrotemporal characteristics of a particular vocalization was present in a specific neuronal population. 7. These results suggest that the representation of behaviorally important and spectrotemporally complex species-specific vocalizations in A1 is 1) temporally integrated and 2) spectrally distributed in nature, and that the representation is carried by spatially dispersed and synchronized cortical cell assemblies that correspond to each individual's vocalizations in a specific and abstracted way.

Acoustic Stimulation↗

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↗