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Daniel C Javitt

Publications and source records attributed to Daniel C Javitt.

60 records · Page 4Linked to original sources

Multisensory auditory-visual interactions during early sensory processing in humans: a high-density electrical mapping study.

Integration of information from multiple senses is fundamental to perception and cognition, but when and where this is accomplished in the brain is not well understood. This study examined the timing and topography of cortical auditory-visual interactions using high-density event-related potentials (ERPs) during a simple reaction-time (RT) task. Visual and auditory stimuli were presented alone and simultaneously. ERPs elicited by the auditory and visual stimuli when presented alone were summed ('sum' ERP) and compared to the ERP elicited when they were presented simultaneously ('simultaneous' ERP). Divergence between the 'simultaneous' and 'sum' ERP indicated auditory-visual (AV) neural response interactions. There was a surprisingly early right parieto-occipital AV interaction, consistent with the finding of an earlier study [J. Cogn. Neurosci. 11 (1999) 473]. The timing of onset of this effect (46 ms) was essentially simultaneous with the onset of visual cortical processing, as indexed by the onset of the visual C1 component, which is thought to represent the earliest cortical visual evoked potential. The coincident timing of the early AV interaction and C1 strongly suggests that AV interactions can affect early visual sensory processing. Additional AV interactions were found within the time course of sensory processing (up to 200 ms post stimulus onset). In total, this system of AV effects over the scalp was suggestive of both activity unique to multisensory processing, and the modulation of 'unisensory' activity. RTs to the stimuli when presented simultaneously were significantly faster than when they were presented alone. This RT facilitation could not be accounted for by probability summation, as evidenced by violation of the 'race' model, providing compelling evidence that auditory-visual neural interactions give rise to this RT effect.

Acoustic Stimulation↗

Pilot-controlled trial of D-cycloserine for the treatment of post-traumatic stress disorder.

Dysfunction of glutamatergic neurotransmission may be relevant to the pathogenesis of post-traumatic stress disorder (PTSD). Preclinical and clinical evidence suggests that PTSD symptoms could be alleviated following enhancement of neurotransmission mediated at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Eleven patients with chronic PTSD participated in a double-blind, placebo-controlled, cross-over trial with 50 mg/d D-cycloserine which acts as a partial agonist at the glycine regulatory site on the NMDA receptor. D-cycloserine treatment resulted in significant improvements in numbing, avoidance, and anxiety symptoms; however, similar effects were also observed during placebo treatment. In addition, D-cycloserine treatment resulted in a significant (p=0.03), reduction in the perseverative error scores as measured by the Wisconsin Card Sorting Test. This pilot study is the first to assess the efficacy of a NMDA receptor modulator for PTSD treatment and its results warrant further, larger-scale investigation.

Adult↗

Auditory-somatosensory multisensory processing in auditory association cortex: an fMRI study.

Using high-field (3 Tesla) functional magnetic resonance imaging (fMRI), we demonstrate that auditory and somatosensory inputs converge in a subregion of human auditory cortex along the superior temporal gyrus. Further, simultaneous stimulation in both sensory modalities resulted in activity exceeding that predicted by summing the responses to the unisensory inputs, thereby showing multisensory integration in this convergence region. Recently, intracranial recordings in macaque monkeys have shown similar auditory-somatosensory convergence in a subregion of auditory cortex directly caudomedial to primary auditory cortex (area CM). The multisensory region identified in the present investigation may be the human homologue of CM. Our finding of auditory-somatosensory convergence in early auditory cortices contributes to mounting evidence for multisensory integration early in the cortical processing hierarchy, in brain regions that were previously assumed to be unisensory.

Acoustic Stimulation↗

Placebo-controlled trial of D-cycloserine added to conventional neuroleptics, olanzapine, or risperidone in schizophrenia.

OBJECTIVE: The authors investigated the clinical effects of D-cycloserine when added to treatment with conventional neuroleptics, olanzapine, or risperidone for treatment-resistant schizophrenia. METHOD: Twenty-four patients participated in a double-blind, placebo-controlled, 6-week crossover trial with D-cycloserine, 50 mg/day, added to their fixed dose of antipsychotic medication. Clinical ratings were performed every 2 weeks. RESULTS: D-Cycloserine treatment was well tolerated and resulted in a significant reduction in negative symptoms (mean=15%). The degree of improvement did not differ between patients treated with conventional neuroleptics and those treated with olanzapine or risperidone. CONCLUSIONS: These data support the efficacy of the addition of 50 mg/day of D-cycloserine to treatment with conventional neuroleptics and suggest that therapeutic benefits may also be attained when D-cycloserine is added to olanzapine or risperidone.

Adult↗

A naturalistic study of risperidone treatment outcome using prognosis-adjusted discharge rates in New York State inpatients.

BACKGROUND: Information concerning the effectiveness of newer atypical antipsychotics is derived largely from controlled clinical trials of relatively short duration. Limited information is available concerning naturalistic outcome of patients selected for clinical treatment with atypical antipsychotics. This study evaluates 1-year discharge rates among all patients treated with risperidone within the New York State inpatient psychiatric hospital system during the calendar years 1994 and 1995 ("period of interest") relative to patients treated with all other antipsychotic medications. METHOD: Data from the Integrated Research Database at Nathan Kline Institute (Orangeburg, N.Y.) were used. This database maintains complete treatment records for all inpatients within the New York State psychiatric inpatient system along with demographic, diagnostic, admission, and discharge information. Patients were identified at admission or first change in antipsychotic during the period of interest, and 1-year outcome was determined. RESULTS: 2198 risperidone-treated patients were identified versus 3259 treated with other antipsychotics. Length of hospitalization prior to treatment initiation was the primary predictor of discharge rate for both risperidone and control groups. When adjustment was made for between-group difference in prognosis (dischargeability), patients treated with risperidone within 30 days of admission were less likely to be discharged than those treated with all other agents (including clozapine), whereas risperidone was more effective in patients who had been hospitalized for 90 days or more prior to switch from another antipsychotic to risperidone. CONCLUSION: When database information is utilized to evaluate treatment effectiveness, adjustment must be made for a priori differences in prognosis or dischargeability. With appropriate methodology, database studies may indicate which patient groups are most likely to benefit from newer atypical antipsychotic agents.

Adult↗

Glycine modulators in schizophrenia.

N-methyl-D-aspartate (NMDA) receptor dysfunction may play a key role in the pathophysiology of schizophrenia. Recent studies have investigated the ability of NMDA/glycine-site modulators to ameliorate persistent negative and cognitive symptoms. Several full or partial glycine-site agonists, including glycine, D-serine and D-cycloserine, have shown effectiveness in small-scale clinical trials. Glycine levels in brain are regulated by GLYT1-type glycine transporters. Recently developed glycine transport inhibitors (GTI) have preclinical behavioral effects similar to those of glycine or D-serine, and may represent a 'next generation' approach to the treatment of the persistent negative and cognitive symptoms of schizophrenia.

Animals↗