# Identifying neural mechanisms of aberrant inhibitory processing and salience in patients with schizophrenia

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $25,005

## Abstract

Project Summary
Individuals with schizophrenia (SZ) demonstrate deficits in the ability to filter irrelevant or redundant information
and may misattribute salience to thoughts and events. In turn, these impairments may contribute to higher-
level cognitive dysfunction and clinical symptoms associated with SZ. In EEG studies, inhibitory processing
deficits are reliably observed in SZ during an auditory paired-click paradigm; in healthy comparison (HC)
participants, the P50 component of the event-related potential (ERP) is reliably reduced to the second identical
stimulus in a pair whereas individuals with SZ show reduced inhibition of the P50 to redundant information. In
the same paradigm, individuals with SZ exhibit a decreased N100 ERP response to the initial stimulus relative
to HC participants, which may reflect decreased auditory salience processing. A separate body of research
using fMRI has linked inhibitory and salience monitoring deficits in SZ to insufficient suppression of the default
mode network (DMN), which supports internally-focused cognition and self-referential processing. The salience
network (SN), a higher-order system responsible for monitoring salience, regulates DMN as needed for tasks
requiring attention to external stimuli. Given the shared constructs associated with P50 suppression, N100
attentional response, and the connectivity of DMN and SN, we hypothesize that these measures capture
aspects of dysfunction in SZ within the same mechanism. Using resting-state fMRI, resting-state EEG, and
EEG recorded during the paired-click paradigm from SZ patients (N = 84) and HCs (N = 42), the proposed
research employs a multimodal approach to identify and characterize abnormal inhibitory and salience
processing in SZ. Primary aims of the study are to 1) determine whether DMN suppression represents a
mechanism of inhibitory filtering and evaluate this dysfunction in SZ; and 2) determine whether down-
regulation of DMN by SN represents a mechanism supporting inhibitory processing and salience monitoring
and evaluate the contribution of these processes to dysfunction in patients with SZ. By integrating findings
across modalities to refine our understanding of the neural circuitry involved in aberrant inhibitory processing
and salience in SZ, findings from this project will serve to inform future research into the development of
targeted treatments. In addition to the outlined research objectives, the applicant will pursue coursework,
clinical science training activities, and mentorship in order to develop as an independent researcher with
expertise in the application of clinical neuroscience methods to elucidate mechanisms of cognitive impairment
and clinical symptoms in psychopathology.

## Key facts

- **NIH application ID:** 10156079
- **Project number:** 1F31MH124421-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Anika Maya Guha
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $25,005
- **Award type:** 1
- **Project period:** 2021-02-01 → 2021-08-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10156079

## Citation

> US National Institutes of Health, RePORTER application 10156079, Identifying neural mechanisms of aberrant inhibitory processing and salience in patients with schizophrenia (1F31MH124421-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10156079. Licensed CC0.

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