# Temporal Dynamics of Neurophysiological Patterns as Treatment Targets in Scz

> **NIH NIH R01** · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · 2020 · $743,052

## Abstract

This project responds to PAR 14-153, Temporal Dynamics of Neurophysiological Patterns as Potential
Targets for Treating Cognitive Deficits in Brain Disorders.  As described in the RFA, a rich body of evidence
suggests that cognitive processes are associated with particular patterns of neural activity. These data
indicate that oscillatory rhythms, their co-modulation across frequency bands, spike-phase correlations,
spike population dynamics, and other patterns might be useful drivers of therapeutic development for
cognitive improvement in neuropsychiatric disorders. This project uses parallel human and non-human
primate (NHP) investigations to evaluate effects of transcranial direct current stimulation
(tDCS)/transcranial alternating current stimulation (tACS) on neural oscillatory patterns underlying auditory
cognitive impairments in schizophrenia (Sz), with particular emphasis on impairments in theta and delta
phase reset mechanisms and delta/gamma phase amplitude coupling. In addition it evaluates the role of N-
methyl-D-aspartate receptors (NMDAR) in the etiology of oscillatory dysfunction in Sz, as well as the ability
of tDCS/tACS to reverse NMDAR antagonist-induced impairments in NHP as a model for future therapeutic
development. The project addresses Topic 1 of the RFA by mapping neuro-oscillatory patterns underlying
impaired auditory information processing in Sz using parallel human and NHP studies; Topic 2 by
investigating mechanisms underlying NMDAR antagonist-induced effects; Topic 3 by evaluating
tDCS/tACS effects on neuro-oscillatory function in both NHP and Sz; and Topic 4 by evaluating relative
effects of high definition (HD-tDCS) and conventional tDCS using neurocomputational mapping
approaches. The project includes active manipulations in both humans and NHP, and tests specific
hypotheses regarding low frequency (delta, theta) oscillation and cross-frequency (e.g. delta/gamma)
phase-amplitude coupling impairments as a basic mechanism of neurocognitive impairment in Sz. The
recording methods detect neural activity directly using multichannel surface/intracranial electrodes in
humans and NHP, respectively, and employ spectral analyses of EEG data along with quantitative
behavioral measures as the primary outcome variables. Auditory dysfunction, as reflected both
behaviorally and by impaired generation of mismatch negativity (MMN) and other auditory potentials is a
prominent and severe feature of Sz and contributes directly to global functional outcome via direct impact
on processes such as auditory hallucinations, phonological processing impairments and social cognition.
Deficits in MMN generation, moreover, predict conversion to psychosis among at risk individuals. The
proposed stimulation approaches including HD- tDCS and delta frequency tACS are highly novel and will
have direct, real-world impact not only on neurocognitive dysfunction in Sz, but also on related forms of
neurocognitive impairments across relevant associated neur...

## Key facts

- **NIH application ID:** 9858446
- **Project number:** 5R01MH109289-06
- **Recipient organization:** NATHAN S. KLINE INSTITUTE FOR PSYCH RES
- **Principal Investigator:** DANIEL C. JAVITT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $743,052
- **Award type:** 5
- **Project period:** 2016-02-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858446

## Citation

> US National Institutes of Health, RePORTER application 9858446, Temporal Dynamics of Neurophysiological Patterns as Treatment Targets in Scz (5R01MH109289-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9858446. Licensed CC0.

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