# Stressed heart-brain communication in Veterans with schizophrenia: neurovascular and autonomic mechanisms

> **NIH VA IK2** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2023 · —

## Abstract

Schizophrenia is a debilitating psychiatric illness that also increases the risk of cardiovascular disease.
Cardiovascular and metabolic disease is the leading cause of premature death for veterans with schizophrenia.
Although cellular and genetic studies have suggested that metabolic impairments may underlie neural and
cardiac dysfunction, studies in clinical neuroscience are limited. Functional magnetic resonance imaging (fMRI)
is widely used as a clinical research tool and has identified aberrant activity across brain networks that may
underlie psychiatric symptoms. Aberrant brain activity in schizophrenia is inefficient: excessive hemodynamic
recruitment at rest and deficient hemodynamic recruitment during cognitively demanding tasks. However, fMRI
does not assay neural activity directly, and instead, reflects slow changes in the regional level of blood oxygen
(hemodynamics) commonly interpreted as a surrogate for neural activity. Moreover, these vascular brain
signals are influenced by systemic physiology, including cardiac activity under the control of the autonomic
nervous system (ANS). Therefore, brain inefficiency in schizophrenia (as measured using fMRI) might reflect
cardiovascular dysfunction or inefficiency in the coupling of neural activity to vascular blood flow. In turn, brain
inefficiency may underlie cognitive deficits, the leading cause of functional impairment in schizophrenia.
 Vascular signals from fMRI are typically modeled to reflect neurovascular coupling, the recruitment of
blood and oxygen to support active neural tissue. Stress signals within the ANS delay neurovascular coupling
in the brain and increase heart rate, blood pressure and cardiac output to meet behavioral demands. In
schizophrenia, ANS signals are dysregulated, and neurovascular coupling is delayed, while at rest. The
relationships between neural, hemodynamic, and ANS activity are unknown in schizophrenia; new approaches
are needed to understand neurovascular coupling and the relationship to ANS stress physiology.
Electroencephalography (EEG) can measure neural activity directly, and when used concurrently with fMRI
(EEG-fMRI), is a promising research tool for examining neurovascular coupling. Continuous blood pressure
monitoring (CBP) can be used to examine the ANS function, but links between CBP derived measure of ANS
function and neurovascular coupling in the brain are unknown. This CDA-2 proposal hypothesizes that
neurovascular coupling is inefficient in schizophrenia, can be measured using simultaneous CBP-EEG-fMRI
and is mediated by dysregulated ANS activity as assayed by CBP.
 This CDA-2 enables a path to scientific independence by examining the role of neurovascular and
autonomic function in relation to cognitive and clinical symptoms in schizophrenia. Treatments targeting
underlying pathology in schizophrenia are lacking and current pharmacotherapies exacerbate metabolic
disease. Measures of neurovascular coupling may serve as a biomarker to guide...

## Key facts

- **NIH application ID:** 10589714
- **Project number:** 1IK2CX002457-01A2
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** Michael Jacob
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10589714

## Citation

> US National Institutes of Health, RePORTER application 10589714, Stressed heart-brain communication in Veterans with schizophrenia: neurovascular and autonomic mechanisms (1IK2CX002457-01A2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10589714. Licensed CC0.

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