# Anxiety and aversive learning: Neural mechanics of generalization and patterns of disorder pathology

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2020 · $190,625

## Abstract

Project Summary
 Emotional dysfunction is at the core of many psychiatric disorders, with epidemiological studies noting
the growing prevalence of fear, anxiety, post-traumatic, and mood disorders in the United States. The overall
goal of the proposed project is to characterize the neural mechanisms that underlie dysfunctional aversive
learning in anxiety disorder patients. The failure to discriminate between threatening and safe contexts is at
the core of many psychiatric problems, with overgeneralization proposed as a defining feature of anxiety
disorders. In this project, we (1) translate a robust basic science paradigm testing different modes of
aversive learning into the clinical arena, and (2) establish a quantitative approach for measuring inter-
individual differences in aversive learning. The approach relies on a robust index of aversive learning -- the
steady state visual evoked potential (ssVEP) -- which is measured by presenting a visual cue at a specific
frequency (e.g., 15 times per second, 15 Hz) that then elicits neural activity at the same driving frequency.
When a cue is reliably followed by an aversive event (i.e. CS+), the amplitude of the ssVEP is heightened,
compared to the amplitude of the frequency at which a safe cue (i.e. CS-) is presented, providing an exquisite
measure of fear learning.
 The current project assesses generalization learning in anxiety disorder patients, by presenting an
aversively conditioned CS+ together with "safe" cues that vary in similarity to the CS+. Pilot data with healthy
participants shows neural sharpening (i.e., good discrimination of CS+) in sensors placed over occipital
cortex, and neural generalization (enhanced responses to safe cues most similar to the CS+) over parietal
cortex, and the proposed study measures aversive learning in 100 participants (80 anxiety disorder patients
and 20 healthy controls). Using the ssVEP (as well as startle and self-reports), aversive sharpening and
generalization are computed for each participant and for each dependent measure using the norm (Euclidian
distance) of the difference between weights modeling sharpening or generalization functions and each
participant's z-transformed means across "safe" cues that vary in similarity to the CS+, producing a single
quantitative index indicating the degree of generalization and sharpening for each measure. The project
explores the overarching hypothesis that inter-individual differences in the generalization of aversive learning-
- quantitatively elucidated using the ssVEP-- are dimensionally related to key features of psychopathology
across diagnostic groups. Taken together, this project will provide key information regarding dysfunction in
aversive learning, which plays a role in the etiology and maintenance of anxiety, as well as form the basis for
developing a novel technique useful in clinical assessment and post-treatment contexts.

## Key facts

- **NIH application ID:** 9978957
- **Project number:** 5R21MH120829-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Andreas Keil
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $190,625
- **Award type:** 5
- **Project period:** 2019-07-16 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978957

## Citation

> US National Institutes of Health, RePORTER application 9978957, Anxiety and aversive learning: Neural mechanics of generalization and patterns of disorder pathology (5R21MH120829-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9978957. Licensed CC0.

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