Biomedical subjects

M M Merzenich

Publications and source records attributed to M M Merzenich.

At least 19 recordsLinked to original sources

PubMed2005

Perinatal anoxia degrades auditory system function in rats.

Little is known about the neural bases of the reduced auditory and cortical processing speeds that have been recorded in language-impaired, autistic, schizophrenic, and other disabled human populations. Although there is strong evidence for genetic contributions to etiologies, epigenetic factors such as perinatal anoxia (PA) have been argued to be contributors, or causal, in a significant proportion of cases. In this article, we explored the consequences of PA on this elementary aspect of auditory behavior and on auditory system function in rats that were briefly perinatally anoxic. PA rats had increased acoustic thresholds and reduced processing efficiencies recorded in an auditory behavioral task. These rats had modestly increased interpeak intervals in their auditory brainstem responses, and substantially longer latencies in poststimulus time histogram responses recorded in the primary auditory cortex. The latter were associated with degraded primary auditory cortex receptive fields and a disrupted tonotopy. These processing deficits are consistent with the parallel behavioral and physiological deficits recorded in children and adults with a history of language-learning impairment and autism.

Acoustic Stimulation↗

PubMed2004

Effects of sensorimotor restriction and anoxia on gait and motor cortex organization: implications for a rodent model of cerebral palsy.

Chronic or acute perinatal asphyxia (PA) has been correlated with the subsequent development of cerebral palsy (CP), a developmental neurological disorder characterized by spasticity and motor abnormalities often associated with cognitive deficits. Despite the prevalence of CP, an animal model that mimics the lifetime hypertonic motor deficits is still not available. In the present study, the consequences of PA on motor behavior, gait and organization of the primary motor cortex were examined in rats, and compared with the behavioral and neurological consequences of early postnatal movement-restriction with or without oxygen deprivation. Rats subjected to PA had mild increases in muscular tone accompanied by subtle differences in walking patterns, paralleled by significantly altered but relatively modest disorganization of their primary motor cortices. Movement-restricted rats, suffering PA or not, had reduced body growth rate, markedly increased muscular tone at rest and with active flexion and extension around movement-restricted joints that resulted in abnormal walking patterns and in a profoundly distorted representation of the hind limbs in the primary motor cortex. Within the sensorimotor-restricted groups, non-anoxic rats presented the most abnormal pattern and the greatest cortical representational degradation. This outcome further supports the argument that PA per se may represent a substrate for subtle altered motor behaviors, and that PA alone is sufficient to alter the organization of the primary motor cortex. At the same time, they also show that early experience-dependent movements play a crucial role in shaping normal behavioral motor abilities, and can make a powerful contribution to the genesis of aberrant movement abilities.

Animals↗

PubMed2003

Model of autism: increased ratio of excitation/inhibition in key neural systems.

Autism is a severe neurobehavioral syndrome, arising largely as an inherited disorder, which can arise from several diseases. Despite recent advances in identifying some genes that can cause autism, its underlying neurological mechanisms are uncertain. Autism is best conceptualized by considering the neural systems that may be defective in autistic individuals. Recent advances in understanding neural systems that process sensory information, various types of memories and social and emotional behaviors are reviewed and compared with known abnormalities in autism. Then, specific genetic abnormalities that are linked with autism are examined. Synthesis of this information leads to a model that postulates that some forms of autism are caused by an increased ratio of excitation/inhibition in sensory, mnemonic, social and emotional systems. The model further postulates that the increased ratio of excitation/inhibition can be caused by combinatorial effects of genetic and environmental variables that impinge upon a given neural system. Furthermore, the model suggests potential therapeutic interventions.

Animals↗

PubMed2003

Somatosensory representation of the digits and clinical performance in patients with focal hand dystonia.

OBJECTIVE: The purpose of this study was to incorporate magnetoencephalography and clinical testing to describe differences in somatosensory organization and sensorimotor function of the hand in patients with focal hand dystonia, a target-specific disorder of voluntary movement that interferes with fine motor control during the performance of rapid, repetitive, skilled movements. DESIGN: This descriptive study included prospective, quasi-experimental comparisons between groups. RESULTS: Patients with focal hand dystonia demonstrated deficits in physical variables, sensory processing, and motor control when compared with age- and sex-matched controls. They also had altered patterns of firing (amplitude and latency integrated over time) and abnormal somatosensory representations on magnetoencephalography. CONCLUSIONS: These study findings suggest that there are alterations in both somatosensory representation of the digits and clinical performance in patients with focal hand dystonia. Future studies to determine if alterations in the sensorimotor feedback loop contribute to the development of focal hand dystonia are indicated. If so, intervention strategies may need to include specific types of somatosensory retraining as part of the rehabilitation program for patients with focal hand dystonia.

Adult↗

PubMed2001

Speech comprehension is correlated with temporal response patterns recorded from auditory cortex.

Speech comprehension depends on the integrity of both the spectral content and temporal envelope of the speech signal. Although neural processing underlying spectral analysis has been intensively studied, less is known about the processing of temporal information. Most of speech information conveyed by the temporal envelope is confined to frequencies below 16 Hz, frequencies that roughly match spontaneous and evoked modulation rates of primary auditory cortex neurons. To test the importance of cortical modulation rates for speech processing, we manipulated the frequency of the temporal envelope of speech sentences and tested the effect on both speech comprehension and cortical activity. Magnetoencephalographic signals from the auditory cortices of human subjects were recorded while they were performing a speech comprehension task. The test sentences used in this task were compressed in time. Speech comprehension was degraded when sentence stimuli were presented in more rapid (more compressed) forms. We found that the average comprehension level, at each compression, correlated with (i) the similarity between the frequencies of the temporal envelopes of the stimulus and the subject's cortical activity ("stimulus-cortex frequency-matching") and (ii) the phase-locking (PL) between the two temporal envelopes ("stimulus-cortex PL"). Of these two correlates, PL was significantly more indicative for single-trial success. Our results suggest that the match between the speech rate and the a priori modulation capacities of the auditory cortex is a prerequisite for comprehension. However, this is not sufficient: stimulus-cortex PL should be achieved during actual sentence presentation.

Auditory Cortex↗

PubMed2001

Basal forebrain stimulation changes cortical sensitivities to complex sound.

Experience affects how brains respond to sound. Here, we examined how the sensitivity and selectivity of auditory cortical neuronal responses were affected in adult rats by the repeated presentation of a complex sound that was paired with basal forebrain stimulation. The auditory cortical region that was responsive to complex sound was 2-5 five times greater in area in paired-stimulation rats than in naive rats. Magnitudes of neuronal responses evoked by complex sounds were also greatly increased by associative pairing, as were the percentages of neurons that responded selectively to the specific spectrotemporal features that were paired with stimulation. These findings demonstrate that feature selectivity within the auditory cortex can be flexibly altered in adult mammals through appropriate intensive training.

Acoustic Stimulation↗

PubMed2001

Cortical remodelling induced by activity of ventral tegmental dopamine neurons.

Representations of sensory stimuli in the cerebral cortex can undergo progressive remodelling according to the behavioural importance of the stimuli. The cortex receives widespread projections from dopamine neurons in the ventral tegmental area (VTA), which are activated by new stimuli or unpredicted rewards, and are believed to provide a reinforcement signal for such learning-related cortical reorganization. In the primary auditory cortex (AI) dopamine release has been observed during auditory learning that remodels the sound-frequency representations. Furthermore, dopamine modulates long-term potentiation, a putative cellular mechanism underlying plasticity. Here we show that stimulating the VTA together with an auditory stimulus of a particular tone increases the cortical area and selectivity of the neural responses to that sound stimulus in AI. Conversely, the AI representations of nearby sound frequencies are selectively decreased. Strong, sharply tuned responses to the paired tones also emerge in a second cortical area, whereas the same stimuli evoke only poor or non-selective responses in this second cortical field in naive animals. In addition, we found that strong long-range coherence of neuronal discharge emerges between AI and this secondary auditory cortical area.

Acoustic Stimulation↗

PubMed2001

Disrupted neural responses to phonological and orthographic processing in dyslexic children: an fMRI study.

Developmental dyslexia, characterized by difficulty in reading, has been associated with phonological and orthographic processing deficits. fMRI was performed on dyslexic and normal-reading children (8-12 years old) during phonological and orthographic tasks of rhyming and matching visually presented letter pairs. During letter rhyming, both normal and dyslexic reading children had activity in left frontal brain regions, whereas only normal-reading children had activity in left temporo-parietal cortex. During letter matching, normal-reading children showed activity throughout extrastriate cortex, especially in occipito-parietal regions, whereas dyslexic children had little activity in extrastriate cortex during this task. These results indicate dyslexia may be characterized in childhood by disruptions in the neural bases of both phonological and orthographic processes important for reading.

Child↗

PubMed2001

Spectrotemporal sensitivities in rat auditory cortical neurons.

Studies in several mammalian species have demonstrated that auditory cortical neurons respond strongly to single frequency-modulated (FM) sweeps, and that most responses are selective for sweep direction and/or rate. In the present study, we used extracellular recordings to examine how neurons in the auditory cortices of anesthetized rats respond to continuous, periodic trains of FM sweeps (described previously by deCharms et al., Science 280 (1998) pp. 1439-1444, as moving auditory gratings). Consistent with previous observations in owl monkeys, we found that the majority of cortical neurons responded selectively to trains of either up-sweeps or down-sweeps; selectivity for down-sweeps was most common. Periodic responses were typically evoked only by sweep trains with repetition rates less than 12 sweeps per second. Directional differences in responses were dependent on repetition rate. Our results support the proposal that a combination of both spectral and temporal acoustic features determines the responses of auditory cortical neurons to sound, and add to the growing body of evidence indicating that the traditional view of the auditory cortex as a frequency analyzer is not sufficient to explain how the mammalian brain represents complex sounds.

Acoustic Stimulation↗

PubMed2001

Persistent and specific influences of early acoustic environments on primary auditory cortex.

This study demonstrates that the adult form of 'tonotopic maps' of sound frequency in the rat primary auditory cortex (A1) arises from parallel developmental processes involving two cortical zones: the progressive differentiation and refinement of selectively tone-responsive receptive fields within an initially broadly-tuned posterior zone, and the progressive loss of tone-evoked, short-latency response over an initially large, very broadly tuned anterior zone. The formation of tonotopic maps in A1 was specifically influenced by a rat pup's early acoustic environments. Exposure to pulsed tones resulted in accelerated emergence and an expansion of A1 representations of those specific tone frequencies, as well as a deteriorated tonotopicity and broader-than-normal receptive fields. Thus, auditory experiences during early postnatal development are important in shaping the functional development of auditory cortical representations of specific acoustic environments.

Acoustic Stimulation↗

PubMed2001

Sensory input directs spatial and temporal plasticity in primary auditory cortex.

The cortical representation of the sensory environment is continuously modified by experience. Changes in spatial (receptive field) and temporal response properties of cortical neurons underlie many forms of natural learning. The scale and direction of these changes appear to be determined by specific features of the behavioral tasks that evoke cortical plasticity. The neural mechanisms responsible for this differential plasticity remain unclear partly because important sensory and cognitive parameters differ among these tasks. In this report, we demonstrate that differential sensory experience directs differential plasticity using a single paradigm that eliminates the task-specific variables that have confounded direct comparison of previous studies. Electrical activation of the basal forebrain (BF) was used to gate cortical plasticity mechanisms. The auditory stimulus paired with BF stimulation was systematically varied to determine how several basic features of the sensory input direct plasticity in primary auditory cortex (A1) of adult rats. The distributed cortical response was reconstructed from a dense sampling of A1 neurons after 4 wk of BF-sound pairing. We have previously used this method to show that when a tone is paired with BF activation, the region of the cortical map responding to that tone frequency is specifically expanded. In this report, we demonstrate that receptive-field size is determined by features of the stimulus paired with BF activation. Specifically, receptive fields were narrowed or broadened as a systematic function of both carrier-frequency variability and the temporal modulation rate of paired acoustic stimuli. For example, the mean bandwidth of A1 neurons was increased (+60%) after pairing BF stimulation with a rapid train of tones and decreased (-25%) after pairing unmodulated tones of different frequencies. These effects are consistent with previous reports of receptive-field plasticity evoked by natural learning. The maximum cortical following rate and minimum response latency were also modified as a function of stimulus modulation rate and carrier-frequency variability. The cortical response to a rapid train of tones was nearly doubled if BF stimulation was paired with rapid trains of random carrier frequency, while no following rate plasticity was observed if a single carrier frequency was used. Finally, we observed significant increases in response strength and total area of functionally defined A1 following BF activation paired with certain classes of stimuli and not others. These results indicate that the degree and direction of cortical plasticity of temporal and receptive-field selectivity are specified by the structure and schedule of inputs that co-occur with basal forebrain activation and suggest that the rules of cortical plasticity do not operate on each elemental stimulus feature independently of others.

Acoustic Stimulation↗

PubMed2000

Disruption of the neural response to rapid acoustic stimuli in dyslexia: evidence from functional MRI.

The biological basis for developmental dyslexia remains unknown. Research has suggested that a fundamental deficit in dyslexia is the inability to process sensory input that enters the nervous system rapidly and that deficits in processing rapid acoustic information are associated with impaired reading. Functional magnetic resonance imaging (fMRI) was used to identify the brain basis of rapid acoustic processing in normal readers and to discover the status of that response in dyslexic readers. Normal readers showed left prefrontal activity in response to rapidly changing, relative to slowly changing, nonlinguistic acoustic stimuli. Dyslexic readers showed no differential left frontal response. Two dyslexic readers participated in a remediation program and showed increased activity in left prefrontal cortex after training. These fMRI results identify left prefrontal regions as normally being sensitive to rapid relative to slow acoustic stimulation, insensitive to the difference between such stimuli in dyslexic readers, and plastic enough in adulthood to develop such differential sensitivity after intensive training.

Acoustic Stimulation↗

PubMed2000

Auditory processing parallels reading abilities in adults.

A broad battery of psychoacoustic measures and standard measures of reading and spelling were applied to 102 adults. The test group included individuals with a childhood history of reading difficulties and controls with no reported reading difficulties. Reading scores were variable in both groups. Poor auditory processing abilities were recorded in poor readers; particular difficulties were posed by tasks requiring spectral distinctions, the simplest of which was pure tone frequency discrimination. In absolute terms, the greatest deficits were recorded in tasks in which stimuli were presented in brief forms and in rapid succession. Auditory processing abilities accounted for more than 50% of the reading score variance in the control group, but their correlation with reading scores was lower in the group with childhood histories of reading difficulties. The additional variability in the latter group resulted largely from the prevalence of reading-compensated poor psychoacoustic performers, whose short-term word memory was also typically poor. Taken together, these findings support a link between impaired auditory resolution and poor reading. Psychoacoustic difficulties are largely retained through adulthood and may be the source of the retained reading difficulties.

Adolescent↗

PubMed2000

Computational model of the role of sensory disorganization in focal task-specific dystonia.

We present a new computational model for the development of task-specific focal dystonia. The purpose of the model is to explain how altered sensory representations can lead to abnormal motor behavior. Dystonia is described as the result of excessive gain through a sensorimotor loop. The gain is determined in part by the sensory cortical area devoted to each motor function, and behaviors that lead to abnormal increases in sensory cortical area are predicted to lead to dystonia. Properties of dystonia including muscular co-contraction, overflow movements, and task specificity are predicted by properties of a linear approximation to the loop transformation. We provide simulations of several different mechanisms that can cause the gain to exceed 1 and the motor activity to become sustained and uncontrolled. The model predicts that normal plasticity mechanisms may contribute to worsening of symptoms over time.

Dystonic Disorders↗

PubMed1999

Functional organization of spectral receptive fields in the primary auditory cortex of the owl monkey.

Recent experiments in the cat have demonstrated that several response parameters, including frequency tuning, intensity tuning, and FM selectivity, are spatially segregated across the isofrequency axis. To investigate whether a similar functional organization exists in the primate, we have studied the spatial distribution of pure-tone receptive field parameters across the primary auditory cortex (AI) in six owl monkeys (Aotus trivirgatus). The distributions of binaural interaction types and onset latency were also examined. Consistent with previous studies, the primary auditory cortex contained a clear cochleotopic organization. We demonstrate here that several other properties of the responses to tonal stimuli also showed nonrandom spatial distributions that were largely independent from each other. In particular, the sharpness of frequency tuning to pure tones, intensity tuning and sensitivity, response latency, and binaural interaction types all showed spatial variations that were independent from the representation of characteristic frequency and from each other. Statistical analysis confirmed that these organizations did not reflect random distributions. The overall organizational pattern of overlaying but independent functional maps that emerged was quite similar to that seen in AI of cats and, in general, appears to reflect a fundamental organization principle of primary sensory cortical fields.

Action Potentials↗

PubMed1999

A multielectrode implant device for the cerebral cortex.

A new class of brain implant technology was developed that allows the simultaneous recording of voltage signals from many individual neurons in the cerebral cortex during cognitive tasks. The device allows recording from 49 independent positions spanning a 2 x 2-mm region of neural tissue. The recording electrodes are positioned in a square grid with 350 microm spacing, and each microelectrode can be precisely independently vertically positioned using a hydraulic microdrive. The device utilizes ultrafine, sharp iridium microelectrodes that minimize mechanical disturbance of the region near the electrode tip and produce low noise neuronal recordings. The total weight of this device is less than 20 g, and the device is reusable. The implant device has been used for transdural recordings in primary somatosensory and auditory cortices of marmosets, owl monkeys, and rats. On a typical day, one-third of the microelectrodes yield well-discriminated single neuron action potential waveforms. Additional array electrodes yield lower amplitude driven multiunit activity. The average signal-to-noise ratio of discriminated action potential waveforms 6 months after implantation was greater than 9. Simple design alternatives are discussed that can increase the number of electrodes in the array and the depths at which dense array recordings can be achieved.

Animals↗

PubMed1999

Dendritic bias of neurons in rat somatosensory cortex associated with a functional boundary.

Sensory information is encoded throughout the central nervous system by activation of specific groups of neurons. Neurons encoding information from a particular modality are grouped together and constitute an ordered neural representation or "map" of the stimulus. The organization of these representations is not static, but is capable of significant alteration in response to changes in the patterns of inputs delivered to the cortex in the appropriate behavioral context. Therefore, understanding the basic mechanisms that account for discontinuities in cortical representations are important for understanding both information processing in the cortex and plasticity of cortical organization. It is clear that both anatomic and physiologic mechanisms underlie both the genesis and the plasticity of these representations; however, their exact contributions are not fully understood. To examine neuronal anatomy around a representational border in rat primary somatosensory cortex (S1), a novel in vivo/in vitro preparation was used in which the location of the border between the forepaw and lower jaw representations in rat S1 was determined electrophysiologically and marked by dye iontophoresis in vivo. By using in vitro slices from the region in which this border was marked, the morphologies of single cortical layer 2/3 neurons close to and far from the border were determined by intracellular injection of biocytin. Neurons close to the border had dendritic arbors that were significantly biased away from the border; neurons far from the border did not. This bias was due to a decrease in the number of neurites that specifically crossed the border with a concomitant increase in other near-border parts of the neuron, consistent with the ideas that patterns of activity are important for neurite outgrowth and that neurons maintain a relatively constant total neurite extent. These findings confirm the close association of cortical anatomy and physiology and illustrate their relationships with cortical representational discontinuities.

Age Factors↗

PubMed1999

Cortical auditory signal processing in poor readers.

Magnetoencephalographic responses recorded from auditory cortex evoked by brief and rapidly successive stimuli differed between adults with poor vs. good reading abilities in four important ways. First, the response amplitude evoked by short-duration acoustic stimuli was stronger in the post-stimulus time range of 150-200 ms in poor readers than in normal readers. Second, response amplitude to rapidly successive and brief stimuli that were identical or that differed significantly in frequency were substantially weaker in poor readers compared with controls, for interstimulus intervals of 100 or 200 ms, but not for an interstimulus interval of 500 ms. Third, this neurological deficit closely paralleled subjects' ability to distinguish between and to reconstruct the order of presentation of those stimulus sequences. Fourth, the average distributed response coherence evoked by rapidly successive stimuli was significantly weaker in the beta- and gamma-band frequency ranges (20-60 Hz) in poor readers, compared with controls. These results provide direct electrophysiological evidence supporting the hypothesis that reading disabilities are correlated with the abnormal neural representation of brief and rapidly successive sensory inputs, manifested in this study at the entry level of the cortical auditory/aural speech representational system(s).

Acoustic Stimulation↗