# Biases in sharp wave-ripple content as a transdiagnostic cognitive process

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2022 · $328,000

## Abstract

PROJECT SUMMARY
Comorbidities between different mood disorders, as well as those with other syndromes such as
schizophrenia, PTSD, and OCD suggest the possibility of shared underlying mechanisms that
could inform development of new treatments. However, a rate-limiting step in uncovering such
mechanisms continues to be the difficulty of studying these disorders in laboratory animals: it may
never be possible to look at the behavior of an animal and know that it is experiencing a mood
disorder.
To side-step this fundamental challenge, we take a different approach: we will establish a neural
assay of negatively biased thought. Many mood disorders are characterized by biased information
processing, including recall biases for negative past events (in major depression) and biases
towards generating negative future scenarios (in generalized anxiety disorder). Cognitive process
theories of learning, memory and decision-making indicate that such biased thought may not only
be a signature of mood disorders, but in fact causally contribute to it.
This work will develop a neural assay of negatively biased thought in mice by focusing on sharp
wave-ripples (SWRs): bursts of internally generated, synchronous neural activity in the
hippocampus that can depict past or upcoming experiences. SWRs are an attractive preclinical
target because (1) SWRs are highly conserved across mammals including rodents and humans,
making it likely that results will translate, and (2) SWR activity can be decoded to reveal their
content, such as retrieval of specific prior experiences. This implies that we can establish an
objective neural assay for negatively biased thought: given a positive and a negative experience,
are both experiences retrieved equally often, equally effective downstream, or is there a bias?
Aim 1 will optimize a behavioral task and neural assay to provide positive and negative
experiences that can be neurally distinguished, yielding for individual subjects and individual
recording sessions a SWR content bias for negative compared to positive events. Next, Aim 2 will
administer drugs known to generate affectively biased information processing in rodents in
humans (amphetamine and pramipexole) and determine their effects on SWR bias and behavior.
Finally, we will probe the mechanisms that link SWR content to motivational/affective systems at
the neural circuit level through their interaction with dopamine in Aim 3.
Taken together, the proposed work is expected to establish SWR content as a candidate
transdiagnostic process that is of broad relevance to a number of mental health disorders.

## Key facts

- **NIH application ID:** 10401925
- **Project number:** 5R01MH123466-03
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Matthijs van der Meer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $328,000
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401925

## Citation

> US National Institutes of Health, RePORTER application 10401925, Biases in sharp wave-ripple content as a transdiagnostic cognitive process (5R01MH123466-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10401925. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*