# Neural Bases of Recovery of Language in the First Year after Stroke

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $608,307

## Abstract

Aphasia is among the most common and disabling consequences of stroke. Language rehabilitation is
frequently effective, but recovery is often incomplete and slow. A few small studies have shown that
medications, including cholinesterase inhibitors and selective serotonin reuptake inhibtors (SSRIs), can
augment language rehabilitation to enhance aphasia recovery. These investigations have been based on
strong theoretical grounds, as cholinesterase inhibitors and SSRIs increase the availability of neurotransmitters
that are essential for neuroplasticity. But results have been inconsistent, with small effects. Aphasia
treatment could be substantially advanced by a large randomized trial showing clinically significant benefit of
specific medications, along with language intervention. However, clinical trials are premature because the
most effective medications and the characteristics of individuals most likely to respond have not yet been
identified. In previous funding cycles, we have shown that the volume and location of stroke, other medications
that might block the effect of the tested medication, and the health of the uninfarcted tissue might strongly
affect the response to treatment. Furthermore, it is essential to base the timing of intervention on empirical
evidence regarding the time at which intervention has the greatest effect. We propose to obtain all of this
essential information to design a rational randomized trial of medications (versus placebo), along with
language therapy, that will have the greatest probability of identifying clinically important and reliable effects.
We will obtain this new information in a prospective, longitudinal study of language recovery and multimodality
brain imaging at four time points after stroke (Week 1, Month 3, Month 6, and Month 12). We will not attempt
to manipulate medications, as there are insufficient data on their effects. Rather, medication use (prescribed at
the discretion of the physician team) will be recorded at each visit, and confirmed through pharmacy records
and pill counting. Our progress and record of enrolling large numbers of participants show that we will have
sufficient power to find any significant effects. The structural and resting state fMRI studies will help us
understand the mechanisms of recovery (or decline) after stroke. We hypothesize that beneficial medications
will enhance connectivity between critical nodes in the language network, while medications with a negative
effect (by blocking neurotransmitters or their receptors) will be associated with decrease in connectivity
between these nodes. The brain imaging and behavioral data together will also help us achieve another
important goal, aligned with the mission of NIDCD, to improve prognosis for aphasia recovery at an individual
level. Identifying lesion and brain characteristics, medications, demographics, and number of rehabilitation
sessions that independently contribute to aphasia recovery will allow us to better p...

## Key facts

- **NIH application ID:** 9880281
- **Project number:** 5R01DC005375-18
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Argye E. Hillis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $608,307
- **Award type:** 5
- **Project period:** 2002-07-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880281

## Citation

> US National Institutes of Health, RePORTER application 9880281, Neural Bases of Recovery of Language in the First Year after Stroke (5R01DC005375-18). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9880281. Licensed CC0.

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