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Biomedical subjects

J C Arezzo

Publications and source records attributed to J C Arezzo.

At least 37 records · Page 2Linked to original sources
PubMed1996

Role of cortical N-methyl-D-aspartate receptors in auditory sensory memory and mismatch negativity generation: implications for schizophrenia.

Working memory refers to the ability of the brain to store and manipulate information over brief time periods, ranging from seconds to minutes. As opposed to long-term memory, which is critically dependent upon hippocampal processing, critical substrates for working memory are distributed in a modality-specific fashion throughout cortex. N-methyl-D-aspartate (NMDA) receptors play a crucial role in the initiation of long-term memory. Neurochemical mechanisms underlying the transient memory storage required for working memory, however, remain obscure. Auditory sensory memory, which refers to the ability of the brain to retain transient representations of the physical features (e.g., pitch) of simple auditory stimuli for periods of up to approximately 30 sec, represents one of the simplest components of the brain working memory system. Functioning of the auditory sensory memory system is indexed by the generation of a well-defined event-related potential, termed mismatch negativity (MMN). MMN can thus be used as an objective index of auditory sensory memory functioning and a probe for investigating underlying neurochemical mechanisms. Monkeys generate cortical activity in response to deviant stimuli that closely resembles human MMN. This study uses a combination of intracortical recording and pharmacological micromanipulations in awake monkeys to demonstrate that both competitive and noncompetitive NMDA antagonists block the generation of MMN without affecting prior obligatory activity in primary auditory cortex. These findings suggest that, on a neurophysiological level, MMN represents selective current flow through open, unblocked NMDA channels. Furthermore, they suggest a crucial role of cortical NMDA receptors in the assessment of stimulus familiarity/unfamiliarity, which is a key process underlying working memory performance.

Animals↗
PubMed1996

CSF-1 deficiency in mice results in abnormal brain development.

Colony stimulating factor-1 (CSF-1) was initially identified as a growth factor for mononuclear phagocytes. This study examines the role of CSF-1 in the development of the central nervous system (CNS). CSF-1 treatment of neurons cultured from embryonic brain promoted survival and process outgrowth in a dose-dependent manner. By contrast, CSF-1 treatment of neurons cultured from the osteopetrotic (op/op) mouse, a null mutant for CSF-1, promoted significantly less process outgrowth, suggesting that there are neural abnormalities in op/op animals. Nuclease protection assays were used to determine whether CSF-1 and its receptor are expressed at times appropriate to regulate neural development. Both CSF-1 and its receptor are expressed in developing mouse brain, with a unique pattern of CSF-1 mRNA splice variant expression encoding secreted, and not membrane-bound, growth factor. To determine whether brain function is altered by null mutation of CSF-1, op/op mice were examined using electrophysiologic assays. Brainstem auditory and visual evoked potentials were both abnormal in op/op mice. Further, intracortical recordings revealed aberrant neuronal function within visual cortex and alterations in the cortical circuitry that balances excitation and inhibition. Daily CSF-1 injection of postnatal op/op mice largely rescued the abnormal neural phenotype, confirming that the absence of CSF-1 during development is responsible for the abnormalities. The effects of CSF-1 on cultured embryonic neural cells, the developmentally appropriate expression of CSF-1 and its receptor, and the neurological abnormalities in op/op mice suggest a role for CSF-1 in brain development.

Animals↗
PubMed1995

Tonotopic organization of responses reflecting stop consonant place of articulation in primary auditory cortex (A1) of the monkey.

Current source density and multiunit activity elicited by stop consonant-vowel syllables were examined in primary auditory cortex of an awake monkey. Relative amplitudes of the speech-evoked responses were determined by the onset spectra of the consonants and the tonotopic organization. This finding supports the psychoacoustic hypothesis that the onset spectra of stop consonants are important determinants for the discrimination of place of articulation.

Animals↗
PubMed1995

Physiologic correlates of the voice onset time boundary in primary auditory cortex (A1) of the awake monkey: temporal response patterns.

Behavioral studies in animals support the view that categorical, phonetic phenomena are based upon specific response properties of the auditory system. This study investigated physiologic responses reflecting the phonetic parameter of voice onset time (VOT). We examined multiunit activity (MUA) in the primary auditory cortex (A1) of awake monkeys elicited by the consonant-vowel syllables /da/ and /ta/ that varied in VOT from 0 to 60 msec. Two temporal response patterns encode VOT. The first pattern contains responses time-locked to stimulus onset and to the onset of voicing. In 10 of 17 electrode penetrations that display this pattern, MUA reflects the VOT perceptual boundary by containing a prominent response to voicing onset only for /ta/ stimuli. The second pattern contains responses phase-locked to the periodic portion of the syllables. MUA exhibiting this temporal pattern does not display categorical-like properties. We conclude that specific temporal response patterns in A1 reflect the perceptual boundary for VOT and may represent a physiologic correlate for categorical perception of this phonetic parameter.

Animals↗
PubMed1995

Neural generators of early cortical somatosensory evoked potentials in the awake monkey.

Controversy continues to exist regarding the generators of the initial cortical components of the somatosensory evoked potential (SEP). This issue was explored by detailed epidural and intracortical mapping of somatosensory evoked activity in Old World monkeys. In depth recordings, 3 complementary procedures were utilized: (1) the intracortical and subcortical distribution of SEPs was determined from approximately 4000 locations; (2) concomitant profiles of multiple unit activity (MUA) were recorded as an estimate of local action potential profiles; (3) 1-dimensional calculations of current source density (CSD) were used to outline the timing and pattern of regional transmembrane current flow. Our analysis confirms the participation of multiple cortical areas, located on either side of the central sulcus, in the generation of the initial cortical SEP components. Earliest activity P10, was localized to area 3, followed within milliseconds by activation of areas 1, 2 (P12), and 4 (P13). In SI (Brodmann's areas 3, 1 and 2), the initial SEP components reflect the depolarization of lamina 4 stellate cells and the subsequent activation of adjacent pyramidal cells in laminae 3 and 5. The genesis of later cortical components (P20, N45) represents the composite of activity distributed across multiple cortical laminae and the interaction of overlapping excitatory and inhibitory events. These findings have direct implications for the clinical interpretation of SEP waveforms.

Animals↗
PubMed1995

Didanosine (ddl) and stavudine (d4T): absence of peripheral neurotoxicity in rabbits.

Some 20 male New Zealand White rabbits (five/group) were given either didanosine (ddl) or stavudine (d4T) at 750 and 1500 mg/kg body weight/day by oral intubation for 24 wk. An additional group was given 300 mg/kg body weight/day zidovudine (AZT) as a negative control. After 13 weeks the high dose of ddl was lowered from 1500 to 1000 mg/kg body weight/day following the death of one rabbit and continued inappetence in the dose group. The rabbits were observed daily, plasma drug levels were monitored, and electrophysiological measurements of peripheral nerve conduction were performed during the study. Additionally, body weight and food intake were recorded, and clinicopathological parameters were evaluated. Sections of selected peripheral nerves, and dorsal and ventral spinal nerve roots were examined by light and transmission electron microscopy. Although peripheral neuropathy has been reported in rabbits with the nucleoside analogue zalcitabine (ddC), based on clinical observations, electrophysiological measurements, and light and electron microscopy, no evidence of peripheral neurotoxicity was observed in rabbits given either ddl of d4T.

Animals↗
PubMed1995

Electrophysiological evidence for overlapping dominant and latent inputs to somatosensory cortex in squirrel monkeys.

1. The pattern of reorganization in area 3b of adult primates after median or ulnar nerve section suggests that somatic afferents from the dorsum of the hand, carried by the radial nerve, have preferential access to the cortical territories normally expressing glabrous inputs carried by the median and ulnar nerves. A likely mechanism underlying preferential access is preexisting, but silent, radial nerve inputs to the glabrous region of cortex. 2. We tested this by comparing the effects of electrical stimulation of median or ulnar versus radial nerves, on responses in the hand representation of area 3b. Laminar current source density and multiunit activity profiles were sampled with the use of linear array multicontact electrodes spanning the laminae of area 3b. Data were obtained from three squirrel monkeys anesthetized during recording. 3. Compared with colocated median or ulnar nerve responses, the radial nerve response had 1) an initial short-latency response in the middle laminae that was subtle; there was a small transmembrane current flow component without a discernable multiunit activity correlate; and 2) a laminar sequence and distribution of activity that was similar to those of the median or ulnar nerve responses (i.e., initial activation of the middle, followed by upper and lower laminae), but the significant current flow and multiunit response to radial nerve stimulation occurs 12-15 ms later. 4. Normal corepresentation of nondominant dorsum hand (radial) inputs with the dominant (median or ulnar) inputs in the glabrous hand surface representation provides a clear vehicle for the biased patterns of reorganization occurring after peripheral nerve section. The initial, "subtle" activity phase in the nondominant response is believed to reflect intracortical inhibition, and the later "significant" response phase, a rebound excitation, possibly compounded by an indirect or extralemniscal input. The spatiotemporal pattern of nondominant input is proposed to play a role in normal somatosensory perception.

Action Potentials↗
PubMed1994

Detection of stimulus deviance within primate primary auditory cortex: intracortical mechanisms of mismatch negativity (MMN) generation.

Mismatch negativity (MMN) is a cognitive, auditory event-related potential (AEP) that reflects preattentive detection of stimulus deviance and indexes the operation of the auditory sensory ('echoic') memory system. MMN is elicited most commonly in an auditory oddball paradigm in which a sequence of repetitive standard stimuli is interrupted infrequently and unexpectedly by a physically deviant 'oddball' stimulus. Electro- and magnetoencephalographic dipole mapping studies have localized the generators of MMN to supratemporal auditory cortex in the vicinity of Heschl's gyrus, but have not determined the degree to which MMN reflects activation within primary auditory cortex (AI) itself. The present study, using moveable multichannel electrodes inserted acutely into superior temporal plane, demonstrates a significant contribution of AI to scalp-recorded MMN in the monkey, as reflected by greater response of AI to loud or soft clicks presented as deviants than to the same stimuli presented as repetitive standards. The MMN-like activity was localized primarily to supragranular laminae within AI. Thus, standard and deviant stimuli elicited similar degrees of initial, thalamocortical excitation. In contrast, responses within supragranular cortex were significantly larger to deviant stimuli than to standards. No MMN-like activity was detected in a limited number to passes that penetrated anterior and medial to AI. AI plays a well established role in the decoding of the acoustic properties of individual stimuli. The present study demonstrates that primary auditory cortex also plays an important role in processing the relationships between stimuli, and thus participates in cognitive, as well as purely sensory, processing of auditory information.

Acoustic Stimulation↗
PubMed1994

Nerve growth factor administration protects against experimental diabetic sensory neuropathy.

Small fiber sensory neuropathy is one of the most common complications of diabetes mellitus. Currently there is no adequate therapy to prevent this often debilitating problem. Nerve growth factor (NGF) is a protein that promotes the survival and integrity of a large percentage of sensory neurons including the small fiber pain transmitting neurons which are often prominently affected in diabetic neuropathy. We report here that exogenously administered NGF is capable of preventing the behavioral and biochemical manifestations of diabetic sensory neuropathy in a streptozocin induced rat model. NGF administration prevented the elevation of tailflick threshold (a measure of the rat's response to a thermal noxious stimulus) which occurred in streptozocin-induced diabetic rats. Further, it prevented the induced reduction in levels of the neuropeptides substance P and calcitonin gene related peptide measured from cervical dorsal root ganglia. Finally, NGF did not ameliorate the prolonged latency of the compound action potentials measured from the caudal nerve of the tail. In view of these results, a clinical trial of NGF in diabetic neuropathy has now commenced.

Action Potentials↗
PubMed1994

Contribution of extrastriate area V4 to the surface-recorded flash VEP in the awake macaque.

This study compared striate and extrastriate contributions to the surface-recorded flash VEP. Laminar visual evoked potential, current source density and multiunit activity profiles were obtained with multicontact electrodes from areas V1 and V4 in three awake macaques. As found earlier, the major striate contribution is to early (N40, P55-80) components. Major contributions to the later (N95, P120, Late Negativity) components arise from V4. Early, afferent-triggered inhibition in V4 also produces a small contribution to N40. Response latencies in V4 vs V1 suggest an input to V4, bypassing V1, emphasizing a parallel processing component of visual system organization.

Action Potentials↗
PubMed1994

Speech-evoked activity in primary auditory cortex: effects of voice onset time.

Neural encoding of temporal speech features is a key component of acoustic and phonetic analyses. We examined the temporal encoding of the syllables /da/ and /ta/, which differ along the temporally based, phonetic parameter of voice onset time (VOT), in primary auditory cortex (A1) of awake monkeys using concurrent multilaminar recordings of auditory evoked potentials (AEP), the derived current source density, and multiunit activity. A general sequence of A1 activation consisting of a lamina-specific profile of parallel and sequential excitatory and inhibitory processes is described. VOT is encoded in the temporal response patterns of phase-locked activity to the periodic speech segments and by "on" responses to stimulus and voicing onset. A transformation occurs between responses in the thalamocortical (TC) fiber input and A1 cells. TC fibers are more likely to encode VOT with "on" responses to stimulus onset followed by phase-locked responses during the voiced segment, whereas A1 responses are more likely to exhibit transient responses both to stimulus and voicing onset. Relevance to subcortical speech processing, the human AEP and speech psychoacoustics are discussed. A mechanism for categorical differentiation of voiced and unvoiced consonants is proposed.

Animals↗
PubMed1994

Effects of a frontal lesion on the cortical potentials associated with voluntary movement in the awake monkey.

An accidental, punctate lesion to a medial portion of the frontal lobe, including supplementary motor cortex and anterior commissure, produced a change in the cortical potentials preceding voluntary movement in a cynomolgus monkey. At the time of the lesion, the animal was highly trained in a repetitive voluntary movement task, and baseline mapping of specific movement-related potentials (MRPs) was complete. Prelesion MRPs were characterized by a well-defined N2 response, which began approximately 100 msec before the onset of movement. This response was centered over the contralateral precentral gyrus and believed to reflect the phasic portion of the corticospinal discharge. After the lesion, the animal fully recovered the ability to perform the movement task. However, the amplitude of N2 on the side ipsilateral to the lesion was significantly reduced. This decrease was not associated with any deficit in movement execution. EMG measurements did not exhibit any diminished or abnormal patterns of activity. These data suggest that portions of the frontal lobe not directly involved in the genesis of MRPs may still provide a supportive role in organizing the sequence and pattern of neuroelectric activity associated with movement. Furthermore, the findings document the sensitivity of MRPs for detecting subtle changes in the pattern of efferent electrical activity associated with a lesion within the brain, even in the absence of overt movement disorders.

Animals↗
PubMed1994

MRI monitoring of vigabatrin-induced intramyelinic edema in dogs.

Chronic administration of vigabatrin (gamma-vinyl GABA) in dogs produces reversible microvacuolation (intramyelinic edema) in discrete brain regions. Histologic changes are most notable in the columns of the fornix and regions of the hypothalamus, thalamus, optic tract, and hippocampus. In an attempt to image these changes in vivo, we performed high-field MRI on seven treated and four control dogs at baseline and after 15 weeks of dosing with vigabatrin (300 mg/kg/d). All dogs underwent parallel electrophysiologic assessment to determine the effects of vigabatrin on afferent conduction. At 15 weeks, all treated dogs showed increased T2- and decreased T1-weighted signals, with changes from baseline most prominent in the columns of the fornix and to a lesser degree in the surrounding hypothalamus and thalamus. MRIs performed on control dogs were unremarkable. We then perfused a random selection of four treated and two control dogs and imaged their brains ex vivo prior to sectioning. Ex vivo imaging confirmed the in vivo findings and strongly correlated with both electrophysiologic and subsequent histopathologic findings. Imaging was repeated in the surviving dogs 5 and 12 weeks after discontinuation of dosing. Signal abnormalities in the treated dogs progressively diminished during recovery, paralleling the electrophysiologic and histopathologic results. These findings demonstrate that MRI can detect signal changes anatomically congruent with vigabatrin-induced intramyelinic edema and suggest that MRI may provide a useful noninvasive tool for monitoring patients during clinical trials.

4-Aminobutyrate Transaminase↗
PubMed1993

Effects of administration of ciliary neurotrophic factor on normal motor and sensory peripheral nerves in vivo.

Ciliary neurotrophic factor (CNTF) has a variety of effects on different neuronal populations in vitro, but little has been reported concerning its effects in vivo. This study examined the effects of CNTF administration on peripheral nerves both in young growing rats and in more mature animals. In both young and fully grown rats, CNTF stimulated levels of substance P and calcitonin gene related peptide in sensory spinal ganglia. In immature rats, CNTF increased compound nerve conduction velocity and motor nerve conduction velocity. By contrast, electrophysiological measurements were not affected in fully grown animals. There was a biphasic dose response to CNTF for the electrophysiologic changes with larger changes noted at a dose of 0.1 micrograms/g body weight than at a dose of 0.25 micrograms/g. There were no behavioral changes noted at either dose of the factor. These observations indicate that CNTF administration in vivo can influence neural physiology, and suggest that the factor may be useful for the treatment of disorders involving either sensory or motor peripheral nerves.

Aging↗