# Novel Cross-Species Neurophysiological Assays of Reward and Cognitive Domains

> **NIH NIH UH3** · MCLEAN HOSPITAL · 2021 · $229,547

## Abstract

Project Summary
Deficits across the domains of reward and cognition are defining characteristics of virtually all neuropsychiatric
disorders, and have deleterious effects on functional recovery, disease chronicity, and morbidity. Development
of effective treatments is hindered by the lack of well-validated preclinical measures of target engagement that
are functionally similar across species. Capitalizing on a partnership among basic and translational
neuroscientists with a strong track record of collaborations, the overarching goal of UH2/UH3 MH109334 is to
develop new translational assessments of reward and cognition in which the neurophysiological and behavioral
metrics are identical across species.
 We have addressed this objective by modifying and validating assessments of reward learning, cognitive
control, and cognitive flexibility, each of which is disrupted across illnesses. During the UH2 phase, we have
developed (or modified), tested and optimized human and rodent versions of a flanker task (cognitive control)
and a probabilistic reversal learning task (PRL; cognitive flexibility), such that task parameters are analogous
between humans and rats. Additionally, we have recorded EEG data in both humans and rats during
performance of each task. In both species, EEG data were analyzed using several techniques, including time-
frequency wavelet analyses and time-domain event-related potential (ERP) analyses. These analyses yielded
a priori EEG and behavioral variables (e.g., theta oscillations, error-related negativity, feedback-related
negativity) that were manipulated in the UH3 phase, which included modafinil (Year 3) and methylphenidate
(Year 4) challenges.
 Due to the COVID-19 pandemic, the human methylphenidate studies could not be started owing to work-
from-home orders from Partners HealthCare and McLean Hospital. Similarly, the preclinical methylphenidate
component at McLean Hospital (target: Flanker Task) was severely affected, with only limited research
activities allowed between mid-March and mid-August. The preclinical methylphenidate component at UCSD
(target: Probabilistic Reversal Learning Task) was also affected, although less severely. The current
administrative supplement requests funding to complete the Year 4 methylphenidate experiments at all sites.
 Ultimately, these studies will provide novel measures of reward and/or cognition in both humans and rats
that show clear parallels in behavior and neurophysiology that can be manipulated with putative treatments
across species. Such tasks will help narrow the existing translational gap between preclinical animal and
human research and will promote the development of urgently needed treatments for reward and cognitive
disorders.

## Key facts

- **NIH application ID:** 10249528
- **Project number:** 3UH3MH109334-04S1
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** Diego A Pizzagalli
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $229,547
- **Award type:** 3
- **Project period:** 2016-04-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249528

## Citation

> US National Institutes of Health, RePORTER application 10249528, Novel Cross-Species Neurophysiological Assays of Reward and Cognitive Domains (3UH3MH109334-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10249528. Licensed CC0.

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