# Neurophysiological biomarkers of cognition in Dup15 syndrome: From mouse models to patients (Project)

> **NIH NIH U54** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $309,026

## Abstract

Project: Abstract 
The proposal is truly translational, as it draws from clinical observation and moves 
towards rigorous quantification of biomarkers of cognitive impairment in both mouse 
models and patients. Such a study will serve as a model for studies of other 
neurodevelopmental disorders in our comprehensive Center. These biomarkers can then, in 
future studies, be directly related to gene expression. First, we will identify a mechanism-based 
electrophysiological biomarker of cognitive dysfunction and potential responsiveness to 
treatment in a genetically well-defined syndrome highly associated with ID. Standardized 
measures of cognition are limited in their ability to quantify subtle individual differences or to 
capture clinical heterogeneity that may inform prognosis and intervention. Our group has 
considerable expertise in the integration of EEG biomarkers with behavior to better characterize 
children with neurodevelopmental disorders. Second, we will perform parallel studies in mouse 
models, in order to validate and better understand the genetic basis of biomarker identified in 
humans and to begin to test treatments that may alter both the cell activation patterns and 
behavior in these mouse models. Specifically we will test how abnormal oscillations disrupt 
information flow in awake behaving animals, allowing us to directly link electrophysiological 
changes to cognition. 
Innovative methods to study electrophysiological markers in both mouse models and 
patients. The human EEG experiments in the Jeste Lab will make use of new analysis 
techniques to measure signal complexity and to quantify resting state spectral power from 
challenging populations. The mouse experiments will make use of custom-made high density 
electrophysiological recordings from hundreds of neurons with silicon probes targeted to 
multiple cortical regions. New attention-based multimodal set shifting task designed in the 
Golshani lab to record the activity of large neuronal populations during flexible decision making 
and attentional set shifting, a cognitive domain that is affected in the disorder. Finally, we will 
use a new generation of miniaturized microscopes to record the activity patterns of large 
populations of hippocampal neurons over days during learning, allowing us for the first time to 
follow population dynamics in the same group of neurons during learning and extinction. 
Importantly, these studies are rooted in gaining a new understanding of ID at a systems level 
with a desire to find convergence in mechanisms and evidence-based treatments for individuals 
with this heterogeneous group of disorder.

## Key facts

- **NIH application ID:** 9836708
- **Project number:** 5U54HD087101-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Shafali Spurling Jeste
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $309,026
- **Award type:** 5
- **Project period:** — → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836708

## Citation

> US National Institutes of Health, RePORTER application 9836708, Neurophysiological biomarkers of cognition in Dup15 syndrome: From mouse models to patients (Project) (5U54HD087101-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9836708. Licensed CC0.

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