Biomedical subjects

M M Merzenich

Publications and source records attributed to M M Merzenich.

At least 37 records · Page 2Linked to original sources

PubMed1999

Distributed representation of spectral and temporal information in rat primary auditory cortex.

Modulations of amplitude and frequency are common features of natural sounds, and are prominent in behaviorally important communication sounds. The mammalian auditory cortex is known to contain representations of these important stimulus parameters. This study describes the distributed representations of tone frequency and modulation rate in the rat primary auditory cortex (A1). Detailed maps of auditory cortex responses to single tones and tone trains were constructed from recordings from 50-60 microelectrode penetrations introduced into each hemisphere. Recorded data demonstrated that the cortex uses a distributed coding strategy to represent both spectral and temporal information in the rat, as in other species. Just as spectral information is encoded in the firing patterns of neurons tuned to different frequencies, temporal information appears to be encoded using a set of filters covering a range of behaviorally important repetition rates. Although the average A1 repetition rate transfer function (RRTF) was low-pass with a sharp drop-off in evoked spikes per tone above 9 pulses per second (pps), individual RRTFs exhibited significant structure between 4 and 10 pps, including substantial facilitation or depression to tones presented at specific rates. No organized topography of these temporal filters could be determined.

Acoustic Stimulation↗

PubMed1999

Strategies to improve electrode positioning and safety in cochlear implants.

An injection-molded internal supporting rib has been produced to control the flexibility of silicone rubber encapsulated electrodes designed to electrically stimulate the auditory nerve in human subjects with severe to profound hearing loss. The rib molding dies, and molds for silicone rubber encapsulation of the electrode, were designed and machined using AutoCad and MasterCam software packages in a PC environment. After molding, the prototype plastic ribs were iteratively modified based on observations of the performance of the rib/silicone composite insert in a clear plastic model of the human scala tympani cavity. The rib-based electrodes were reliably inserted farther into these models, required less insertion force and were positioned closer to the target auditory neural elements than currently available cochlear implant electrodes. With further design improvements the injection-molded rib may also function to accurately support metal stimulating contacts and wire leads during assembly to significantly increase the manufacturing efficiency of these devices. This method to reliably control the mechanical properties of miniature implantable devices with multiple electrical leads may be valuable in other areas of biomedical device design.

Animals↗

PubMed1998

Single-cell correlates of a representational boundary in rat somatosensory cortex.

In primary somatosensory cortex (S1), the transition from one representation to the next is typically abrupt when assayed physiologically. However, the extent of anatomical projections to and within the cortex do not strictly respect these physiologically defined transitions. Physiological properties, such as synaptic strengths or intracortical inhibition, have been hypothesized to account for the functionally defined precision of these representational borders. Because these representational borders can be translocated across the cortex by manipulations or behaviors that change the activity patterns of inputs to the cortex, understanding the physiological mechanisms that delimit representations is also an important starting point for understanding cortical plasticity. A novel in vivo and in vitro preparation has been developed to examine the cellular and synaptic mechanisms that underlie representational borders in the rat. In vivo, a short segment of the border between the forepaw-lower jaw representations in rat S1 was mapped using standard electrophysiological methods and was visibly marked using iontophoresis of pontamine sky blue dye. Slices were then obtained from this marked region and maintained in vitro. Intracellularly recorded responses to electrical stimulation of supragranular cortex were obtained from single neurons near the border in response to stimulation within the representational zone or across the border. Both excitatory and inhibitory responses were smaller when evoked by stimuli that activated projections that crossed borders, as compared with stimuli to projections that did not. These findings indicate that intracortical network properties are contributing to the expressions of representational discontinuities in the cortex.

2-Amino-5-phosphonovalerate↗

PubMed1998

Optimizing sound features for cortical neurons.

The brain's cerebral cortex decomposes visual images into information about oriented edges, direction and velocity information, and color. How does the cortex decompose perceived sounds? A reverse correlation technique demonstrates that neurons in the primary auditory cortex of the awake primate have complex patterns of sound-feature selectivity that indicate sensitivity to stimulus edges in frequency or in time, stimulus transitions in frequency or intensity, and feature conjunctions. This allows the creation of classes of stimuli matched to the processing characteristics of auditory cortical neurons. Stimuli designed for a particular neuron's preferred feature pattern can drive that neuron with higher sustained firing rates than have typically been recorded with simple stimuli. These data suggest that the cortex decomposes an auditory scene into component parts using a feature-processing system reminiscent of that used for the cortical decomposition of visual images.

Acoustic Stimulation↗

PubMed1998

Cortical map reorganization enabled by nucleus basalis activity.

Little is known about the mechanisms that allow the cortex to selectively improve the neural representations of behaviorally important stimuli while ignoring irrelevant stimuli. Diffuse neuromodulatory systems may facilitate cortical plasticity by acting as teachers to mark important stimuli. This study demonstrates that episodic electrical stimulation of the nucleus basalis, paired with an auditory stimulus, results in a massive progressive reorganization of the primary auditory cortex in the adult rat. Receptive field sizes can be narrowed, broadened, or left unaltered depending on specific parameters of the acoustic stimulus paired with nucleus basalis activation. This differential plasticity parallels the receptive field remodeling that results from different types of behavioral training. This result suggests that input characteristics may be able to drive appropriate alterations of receptive fields independently of explicit knowledge of the task. These findings also suggest that the basal forebrain plays an active instructional role in representational plasticity.

Acetylcholine↗

PubMed1998

Practice-related improvements in somatosensory interval discrimination are temporally specific but generalize across skin location, hemisphere, and modality.

This paper concerns the characterization of performance and perceptual learning of somatosensory interval discrimination. The purposes of this study were to define (1) the performance characteristics for interval discrimination in the somatosensory system by naive adult humans, (2) the normal capacities for improvement in somatosensory interval discrimination, and (3) the extent of generalization of interval discrimination learning. In a two-alternative forced choice procedure, subjects were presented with two pairs of vibratory pulses. One pair was separated in time by a fixed base interval; a second pair was separated by a target interval that was always longer than the base interval. Subjects indicated which pair was separated by the target interval. The length of the target interval was varied adaptively to determine discrimination thresholds. After initial determination of naive abilities, subjects were trained for 900 trials per day at base intervals of either 75 or 125 msec for 10-15 d. Significant improvements in thresholds resulted from training. Learning at the trained base interval generalized completely across untrained skin locations on the trained hand and to the corresponding untrained skin location in the contralateral hand. The learning partially generalized to untrained base intervals similar to the trained one, but not to more distant base intervals. Learning with somatosensory stimuli generalized to auditory stimuli presented at comparable base intervals. These results demonstrate temporal specificity in somatosensory interval discrimination learning that generalizes across skin location, hemisphere, and modality.

Adult↗

PubMed1998

Language learning impairments: integrating basic science, technology, and remediation.

One of the fundamental goals of the modern field of neuroscience is to understand how neuronal activity gives rise to higher cortical function. However, to bridge the gap between neurobiology and behavior, we must understand higher cortical functions at the behavioral level at least as well as we have come to understand neurobiological processes at the cellular and molecular levels. This is certainly the case in the study of speech processing, where critical studies of behavioral dysfunction have provided key insights into the basic neurobiological mechanisms relevant to speech perception and production. Much of this progress derives from a detailed analysis of the sensory, perceptual, cognitive, and motor abilities of children who fail to acquire speech, language, and reading skills normally within the context of otherwise normal development. Current research now shows that a dysfunction in normal phonological processing, which is critical to the development of oral and written language, may derive, at least in part, from difficulties in perceiving and producing basic sensory-motor information in rapid succession--within tens of ms (see Tallal et al. 1993a for a review). There is now substantial evidence supporting the hypothesis that basic temporal integration processes play a fundamental role in establishing neural representations for the units of speech (phonemes), which must be segmented from the (continuous) speech stream and combined to form words, in order for the normal development of oral and written language to proceed. Results from magnetic resonance imaging (MRI) and positron emission tomography (PET) studies, as well as studies of behavioral performance in normal and language impaired children and adults, will be reviewed to support the view that the integration of rapidly changing successive acoustic events plays a primary role in phonological development and disorders. Finally, remediation studies based on this research, coupled with neuroplasticity research, will be presented.

Dominance, Cerebral↗

PubMed1998

Plasticity of temporal information processing in the primary auditory cortex.

Neurons in the rat primary auditory cortex (A1) generally cannot respond to tone sequences faster than 12 pulses per second (pps). To test whether experience can modify this maximum following rate in adult rats, trains of brief tones with random carrier frequency but fixed repetition rate were paired with electrical stimulation of the nucleus basalis (NB) 300 to 400 times per day for 20-25 days. Pairing NB stimulation with 5-pps stimuli markedly decreased the cortical response to rapidly presented stimuli, whereas pairing with 15-pps stimuli significantly increased the maximum cortical following rate. In contrast, pairing with fixed carrier frequency 15-pps trains did not significantly increase the mean maximum following rate. Thus this protocol elicits extensive cortical remodeling of temporal response properties and demonstrates that simple differences in spectral and temporal features of the sensory input can drive very different cortical reorganizations.

Acoustic Stimulation↗

PubMed1998

Optical imaging and electrophysiology of rat barrel cortex. I. Responses to small single-vibrissa deflections.

A study was undertaken to investigate the response of the rodent somatosensory barrel cortex to single-whisker, near-threshold vibrissal stimuli. Cortical responses to controlled whisker deflections were recorded by (i) conventional multi-unit extracellular recording within the cytochrome oxidase rich barrels centers and the interbarrel septa, and (ii) intrinsic signal optical imaging, a technique that provides a spatial view of cortical activation thought to be related to the deoxygenation of hemoglobin in activated areas. Barrel cortex neurons responded weakly to whisker deflections of 0.04 degrees. Their response to a series of small stimuli of increasing amplitude was well-fitted by a logarithmic function. Responses to larger stimuli declined monotonically with distance from the center of the barrel column, and were characterized by greater onset and offset firing rates, by greater post-excitatory reduction of firing to below spontaneous levels, and by shorter response latency. In comparison to measurements taken previously from primary vibrissal afferent fibers, we conclude that cortical cells can respond to activity in a very small fraction of first-order sensory neurons.

Animals↗

PubMed1998

Optical imaging and electrophysiology of rat barrel cortex. II. Responses to paired-vibrissa deflections.

A study was undertaken to investigate the response of the rodent somatosensory barrel cortex to paired-whisker stimuli. Cortical responses to controlled whisker deflections were recorded by (i) conventional multi-unit extracellular recording within the cytochrome oxidase rich barrels centers, and (ii) intrinsic signal optical imaging, a technique that measures an optical correlate of neuronal activity thought to be related to the deoxygenation of hemoglobin in activated regions. Stimuli were applied to two whiskers in sequence, at temporal separations ranging from 0 to 60 ms. Over intervals of 10-40 ms, the primary effect of paired-whisker stimulation was suppressive. We suggest that paired-whisker inhibition results from the activation of layer IV fast-spike units within the principle whisker's barrel, by excitatory input arriving from a surround-whisker. Paired-whisker stimulation produces inhibition in intrinsic images, because it results in a net reduction in layer II/III and/or layer IV metabolism. Intra-cortical inhibition may serve to convert the sequence of inputs from the whisker array into a barrel cortex magnitude code that can be read by higher cortical areas.

Animals↗

PubMed1998

Speech modifications algorithms used for training language learning-impaired children.

In this paper, the details of processing algorithms used in a training program with language learning-impaired children (LLI's) are described. The training program utilized computer games, speech/language training exercises, books-on-tape and educational CD-ROM's. Speech tracks in these materials were processed using these algorithms. During a four week training period, recognition of both processed and normal speech in these children continually increased to near age-appropriate levels. We conclude that this form of processed speech is subject to profound perceptual learning effects and exhibits widespread generalization to normal speech. This form of learning and generalization contributes to the rehabilitation of temporal processing deficits and language comprehension in this subject population.

Algorithms↗

PubMed1998

Cortical plasticity: from synapses to maps.

It has been clear for almost two decades that cortical representations in adult animals are not fixed entities, but rather, are dynamic and are continuously modified by experience. The cortex can preferentially allocate area to represent the particular peripheral input sources that are proportionally most used. Alterations in cortical representations appear to underlie learning tasks dependent on the use of the behaviorally important peripheral inputs that they represent. The rules governing this cortical representational plasticity following manipulations of inputs, including learning, are increasingly well understood. In parallel with developments in the field of cortical map plasticity, studies of synaptic plasticity have characterized specific elementary forms of plasticity, including associative long-term potentiation and long-term depression of excitatory postsynaptic potentials. Investigators have made many important strides toward understanding the molecular underpinnings of these fundamental plasticity processes and toward defining the learning rules that govern their induction. The fields of cortical synaptic plasticity and cortical map plasticity have been implicitly linked by the hypothesis that synaptic plasticity underlies cortical map reorganization. Recent experimental and theoretical work has provided increasingly stronger support for this hypothesis. The goal of the current paper is to review the fields of both synaptic and cortical map plasticity with an emphasis on the work that attempts to unite both fields. A second objective is to highlight the gaps in our understanding of synaptic and cellular mechanisms underlying cortical representational plasticity.

Animals↗

PubMed1998

Plasticity of primary somatosensory cortex paralleling sensorimotor skill recovery from stroke in adult monkeys.

Adult owl and squirrel monkeys were trained to master a small-object retrieval sensorimotor skill. Behavioral observations along with positive changes in the cortical area 3b representations of specific skin surfaces implicated specific glabrous finger inputs as important contributors to skill acquisition. The area 3b zones over which behaviorally important surfaces were represented were destroyed by microlesions, which resulted in a degradation of movements that had been developed in the earlier skill acquisition. Monkeys were then retrained at the same behavioral task. They could initially perform it reasonably well using the stereotyped movements that they had learned in prelesion training, although they acted as if key finger surfaces were insensate. However, monkeys soon initiated alternative strategies for small object retrieval that resulted in a performance drop. Over several- to many-week-long period, monkeys again used the fingers for object retrieval that had been used successfully before the lesion, and reacquired the sensorimotor skill. Detailed maps of the representations of the hands in SI somatosensory cortical fields 3b, 3a, and 1 were derived after postlesion functional recovery. Control maps were derived in the same hemispheres before lesions, and in opposite hemispheres. Among other findings, these studies revealed the following 1) there was a postlesion reemergence of the representation of the fingertips engaged in the behavior in novel locations in area 3b in two of five monkeys and a less substantial change in the representation of the hand in the intact parts of area 3b in three of five monkeys. 2) There was a striking emergence of a new representation of the cutaneous fingertips in area 3a in four of five monkeys, predominantly within zones that had formerly been excited only by proprioceptive inputs. This new cutaneous fingertip representation disproportionately represented behaviorally crucial fingertips. 3) There was an approximately two times enlargement of the representation of the fingers recorded in cortical area 1 in postlesion monkeys. The specific finger surfaces employed in small-object retrieval were differentially enlarged in representation. 4) Multiple-digit receptive fields were recorded at a majority of emergent, cutaneous area 3a sites in all monkeys and at a substantial number of area 1 sites in three of five postlesion monkeys. Such fields were uncommon in area 1 in control maps. 5) Single receptive fields and the component fields of multiple-digit fields in postlesion representations were within normal receptive field size ranges. 6) No significant changes were recorded in the SI hand representations in the opposite (untrained, intact) control hemisphere. These findings are consistent with "substitution" and "vicariation" (adaptive plasticity) models of recovery from brain damage and stroke.

Analysis of Variance↗

PubMed1998

Net interaction between different forms of short-term synaptic plasticity and slow-IPSPs in the hippocampus and auditory cortex.

Paired-pulse plasticity is typically used to study the mechanisms underlying synaptic transmission and modulation. An important question relates to whether, under physiological conditions in which various opposing synaptic properties are acting in parallel, the net effect is facilitatory or depressive, that is, whether cells further or closer to threshold. For example, does the net sum of paired-pulse facilitation (PPF) of excitatory postsynaptic potentials (EPSPs), paired-pulse depression (PPD) of inhibitory postsynaptic potentials (IPSPs), and the hyperpolarizing slow IPSP result in depression or facilitation? Here we examine how different time-dependent properties act in parallel and examine the contribution of gamma-aminobutyric acid-B (GABAB) receptors that mediate two opposing processes, the slow IPSP and PPD of the fast IPSP. Using intracellular recordings from rat CA3 hippocampal neurons and L-II/III auditory cortex neurons, we examined the postsynaptic responses to paired-pulse stimulation (with intervals between 50 and 400 ms) of the Schaffer collaterals and white matter, respectively. Changes in the amplitude, time-to-peak (TTP), and slope of each EPSP were analyzed before and after application of the GABAB antagonist CGP-55845. In both CA3 and L-II/III neurons the peak amplitude of the second EPSP was generally depressed (further from threshold) compared with the first at the longer intervals; however, these EPSPs were generally broader and exhibited a longer TTP that could result in facilitation by enhancing temporal summation. At the short intervals CA3 neurons exhibited facilitation of the peak EPSP amplitude in the absence and presence of CGP-55845. In contrast, on average L-II/III cells did not exhibit facilitation at any interval, in the absence or presence of CGP-55845. CGP-55845 generally "erased" short-term plasticity, equalizing the peak amplitude and TTP of the first and second EPSPs at longer intervals in the hippocampus and auditory cortex. These results show that it is necessary to consider all time-dependent properties to determine whether facilitation or depression will dominate under intact pharmacological conditions. Furthermore our results suggest that GABAB-dependent properties may be the major contributor to short-term plasticity on the time scale of a few hundred milliseconds and are consistent with the hypothesis that the balance of different time-dependent processes can modulate the state of networks in a complex manner and could contribute to the generation of temporally sensitive neural responses.

Animals↗

PubMed1997

Context-sensitive synaptic plasticity and temporal-to-spatial transformations in hippocampal slices.

Hippocampal slices are used to show that, as a temporal input pattern of activity flows through a neuronal layer, a temporal-to-spatial transformation takes place. That is, neurons can respond selectively to the first or second of a pair of input pulses, thus transforming different temporal patterns of activity into the activity of different neurons. This is demonstrated using associative long-term potentiation of polysynaptic CA1 responses as an activity-dependent marker: by depolarizing a postsynaptic CA1 neuron exclusively with the first or second of a pair of pulses from the dentate gyrus, it is possible to "tag" different subpopulations of CA3 neurons. This technique allows sampling of a population of neurons without recording simultaneously from multiple neurons. Furthermore, it reflects a biologically plausible mechanism by which single neurons may develop selective responses to time-varying stimuli and permits the induction of context-sensitive synaptic plasticity. These experimental results support the view that networks of neurons are intrinsically able to process temporal information and that it is not necessary to invoke the existence of internal clocks or delay lines for temporal processing on the time scale of tens to hundreds of milliseconds.

Animals↗

PubMed1997

Learning transfer and neuronal plasticity in humans trained in tactile discrimination.

Adult humans were unilaterally trained in a tactile discrimination task of sequentially applied multi-finger stimuli. Magnetic source imaging (MSI) was performed before and after the training to evaluate use-dependent neuronal plasticity. All subjects showed fast improvements in performance and complete transfer of the learned task. MSI recordings revealed an unilateral decrease in current dipole strength in the somatosensory system contralateral to the trained hand. Attenuation of sensory evoked fields and a complete learning transfer indicate learning in associative and secondary cortices rather than perceptual plasticity operating on neuronal populations involved in early sensory processing. This findings are discussed with respect to an equivalent animal model and to learning specificity and generalization.

Adult↗

PubMed1997

Learning and generalization of auditory temporal-interval discrimination in humans.

The sensory encoding of the duration, interval, and order of different stimulus features provides vital information to the nervous system. The present study focuses on the influence of practice on auditory temporal-interval discrimination. The goals of the experiment were to determine (1) whether practice improved the ability to discriminate a standard interval of 100 msec bounded by brief 1 kHz tones from longer intervals, and, if so, (2) whether this improvement generalized to different tonal frequencies or temporal intervals. Learning was examined in 14 human subjects using an adaptive, two-alternative, forced-choice procedure. One hour of training per day for 10 d led to marked improvements in the ability to discriminate between the standard and longer intervals. The generalization of learning was evaluated by independently varying the spectral (tonal frequency) and temporal (interval) components of the stimuli in four conditions tested both before and after the training phase. Remarkably, there was complete generalization to the trained interval of 100 msec bounded by tones at the untrained frequency of 4 kHz, but no generalization to the untrained intervals of 50, 200, or 500 msec bounded by tones at the trained frequency of 1 kHz. Thus, these data show that (1) temporal-interval discrimination using a 100-msec standard undergoes perceptual learning, and (2) the neural mechanisms underlying this learning are temporally, but not spectrally, specific. These results are compared with those from previous investigations of learning in visual spatial tasks, and are discussed in relation to biologically plausible models of temporal processing.

Acoustic Stimulation↗

PubMed1997

Deficits in auditory temporal and spectral resolution in language-impaired children.

Between 3 and 6 per cent of children who are otherwise unimpaired have extreme difficulties producing and understanding spoken language. This disorder is typically labelled specific language impairment. Children diagnosed with specific language impairment often have accompanying reading difficulties (dyslexia), but not all children with reading difficulties have specific language impairment. Some researchers claim that language impairment arises from failures specific to language or cognitive processing. Others hold that language impairment results from a more elemental problem that makes affected children unable to hear the acoustic distinctions among successive brief sounds in speech. Here we report the results of psychophysical tests employing simple tones and noises showing that children with specific language impairment have severe auditory perceptual deficits for brief but not long tones in particular sound contexts. Our data support the view that language difficulties result from problems in auditory perception, and provide further information about the nature of these perceptual problems that should contribute to improving the diagnosis and treatment of language impairment and related disorders.

Analysis of Variance↗