# Deficient Neural Plasticity and its Functional Consequences in Schizophrenia

> **NIH VA IK2** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2022 · —

## Abstract

While antipsychotic medications are useful for ameliorating psychotic symptoms of schizophrenia, they
have little effect on cognitive dysfunction, which is a core feature of the illness and a major determinant of
functional disability and poor community outcomes. Although recent research has shown some promise in
using cognitive training and cognitive-behavioral techniques to target cognition and clinical symptoms,
responses to these interventions are highly variable and likely depend on intact basic mechanisms of
neuroplasticity to achieve success. Several recent theoretical perspectives and observations implicate
abnormalities in basic mechanisms of neuroplasticity in the pathophysiology of schizophrenia, contributing to
cognitive deficits and potentially interfering with the efficacy of cognition-based interventions. Specifically, N-
methyl-D-aspartate receptor (NMDAr)-dependent long-term potentiation (LTP), which is a mechanism of
experience-dependent synaptic plasticity and a leading candidate cellular mechanism of learning and memory,
is predicted to be compromised in schizophrenia based on NMDAr hypofunction models of the disorder.
Recently, sensory stimulation paradigms have been developed that allow for the assessment of LTP-like
plasticity in humans in vivo. Analogous to electrical stimulation in animals, repeated visual stimulation can
induce repetitive synchronous afferent activity that results in LTP-like effects, including persistent potentiation
of scalp-recorded visual evoked potentials (VEPs). A few studies using variants of this paradigm have now
demonstrated deficient LTP-like visual plasticity in schizophrenia as well as mood disorders, reflected by
reduced potentiation of VEPs relative to healthy individuals. Despite these promising initial findings, however,
further work is needed to both optimize and validate the visual stimulation paradigm as a probe of the integrity
of LTP-like plasticity in schizophrenia.
 Accordingly, this Career Development Award study aims to further optimize and validate the visual
stimulation paradigm as a probe of LTP-like visual plasticity and examine the clinical and functional
consequences of deficient LTP-like plasticity in Veterans with schizophrenia. The training plan will further
develop the Principal Investigator's expertise in psychiatric neuroimaging through a tailored combination of
coursework, methodological workshops, and collaboration with established investigators with expertise in
schizophrenia and the integration of functional neuroimaging methods. This study combines neuroimaging
modalities (EEG and fMRI) to achieve four specific aims: 1) to identify when and where LTP-like visual
plasticity effects, and their deficiencies in schizophrenia, occur in the brain; 2) to test the hypothesis that
variation in LTP-like visual plasticity is associated with variation in visual perceptual learning; 3) to examine
whether the integrity of LTP-like visual plasticity predicts gains following co...

## Key facts

- **NIH application ID:** 10407526
- **Project number:** 5IK2CX001878-04
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** Holly K Hamilton
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10407526

## Citation

> US National Institutes of Health, RePORTER application 10407526, Deficient Neural Plasticity and its Functional Consequences in Schizophrenia (5IK2CX001878-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10407526. Licensed CC0.

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