# Neurophysiologic and Connectivity Changes Associated with SlowedProcessing Speed and Working Memory Impairments in Multiple Sclerosis

> **NIH NIH F31** · UNIVERSITY OF TEXAS DALLAS · 2020 · $41,144

## Abstract

Abstract
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that can impair both motor
and cognitive ability. Upwards of 70% of MS patients experience cognitive impairment with processing speed
and memory ability as the most prominent neuropsychological deficits observed. Processing speed, defined as
the amount of time needed to process elementary cognitive operations may be especially important for
cognitive functions that are widely distributed across brain regions. Current models of working memory posit
that it is a widely distributed system involving persistent neural activity in various brain regions during memory
delays. For instance, the completion of a working memory task requires persistent neural activity in sensory,
executive, motor, and associative cortical areas, and functional connectivity between these areas. MS is known
to degrade the white matter microstructure that mediates neural-vascular communication and functioning, also
known as neural-vascular coupling. I hypothesize that poor neural-vascular coupling impedes the ability of
neurons to fire persistently and maintain memory traces in brain regions needed for working memory tasks.
Timely coordination between brain areas is also critical for executing working memory tasks. Therefore, any
impediment to the persistent neural activity required within a region could affect connectivity between working
memory-related brain regions. Thus, I hypothesize that, due to altered neural-vascular coupling within working
memory regions, functional connectivity between working memory-related regions is adversely affected. In Aim
1, I will test the hypothesis that abnormal neural-vascular coupling in working memory regions is related to
slower processing speed in MS. In Aim 2, I will test the hypothesis that abnormal neural-vascular coupling in
working memory regions leads to altered functional connectivity between working memory-related brain
regions. To assess the Aim 1 hypotheses, I will use advanced dual-echo functional magnetic resonance
imaging to obtain measures of blood-oxygen-level-dependent (BOLD) signal, cerebral blood flow, maximum
blood-oxygen capacity (the factor M), and cerebral metabolic rate of oxygen in MS and healthy controls during
a Sternberg-type Working Memory Task (SWMT). To assess the Aim 2 hypotheses, I will use resting-state and
task-based functional connectivity analyses along with structural diffusion imaging analyses to investigate the
functional and structural connectivity between working memory-related regions associated with the SWMT.
Achieving these grant aims will yield new knowledge about MS-related neurophysiologic alterations, MS-
related connectivity changes, and how these changes may be associated with interactions between processing
speed and working memory impairments in MS.

## Key facts

- **NIH application ID:** 9992985
- **Project number:** 1F31NS115361-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Mark Daniel Zuppichini
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $41,144
- **Award type:** 1
- **Project period:** 2020-05-15 → 2022-05-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992985

## Citation

> US National Institutes of Health, RePORTER application 9992985, Neurophysiologic and Connectivity Changes Associated with SlowedProcessing Speed and Working Memory Impairments in Multiple Sclerosis (1F31NS115361-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9992985. Licensed CC0.

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