# The Role of Thalamic Circuitry Dysfunction in Cognitive Deficits in Schizophrenia: Wake and Sleep

> **NIH NIH K01** · UNIVERSITY OF IOWA · 2021 · $148,673

## Abstract

Project Summary/Abstract
Cognitive deficits are the strongest predictor of functional outcome in schizophrenia, and even after the florid
psychotic symptoms are treated with antipsychotic drugs, debilitating cognitive deficits persist. Consequently,
only 20% of individuals with schizophrenia can work. Cognitive deficits are also seen in early course, minimally
treated patients and first-degree relatives. Recent studies point to sleep spindle abnormalities as a target for
improving cognitive function in schizophrenia. Patients with schizophrenia have a specific deficit in sleep
spindles that is associated with impaired memory consolidation and symptom severity. Sleep spindle deficits
are seen in non-psychotic first-degree relatives and antipsychotic naïve first episode patients, and constitute
an endophenotype that (i) predates the onset of SZ, (ii) persists throughout its course, and (iii) contributes to
cognitive deficits and symptoms. Sleep spindles are rapid bursts of 12-15 Hz EEG activity characteristic of
Stage 2 non-rapid eye movement sleep that are generated and regulated by the thalamic reticular nucleus
(TRN) and related thalamocortical circuitry. Another endophenotype of SZ, sensory gating, is also regulated by
TRN circuitry. The TRN, by gating the flow of information from the thalamus to the cortex, attenuates the
transmission of redundant and irrelevant sensory stimuli and thereby protects higher cognitive function from
interference. Patients with SZ and their first-degree relatives exhibit sensory gating deficits that correlate with
cognitive function and symptom severity. The goal of the present study is to determine whether sleep spindles
and sensory gating are associated with the same underlying TRN mediated thalamocortical communication
abnormality in schizophrenia and predict memory consolidation deficits and symptom severity. Measurement of
sensory gating is more tractable and will enable large-scale genetic studies to decipher the complex genetic
architecture of TRN dysfunction in schizophrenia, provide clues to mechanism and actionable targets for
treatment.

## Key facts

- **NIH application ID:** 10307155
- **Project number:** 5K01MH114012-05
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Bengi Baran
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $148,673
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10307155

## Citation

> US National Institutes of Health, RePORTER application 10307155, The Role of Thalamic Circuitry Dysfunction in Cognitive Deficits in Schizophrenia: Wake and Sleep (5K01MH114012-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10307155. Licensed CC0.

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