Vagal Nerve Stimulation To Enhance Cognition and Learning

Evaluation of Vagus Nerve Stimulation Paired With Cognitive Training to Enhance Learning and Memory and Neural Plasticity in Post-Stroke Patients

The purpose of this study is to find out whether pairing vagus nerve stimulation (VNS) with cognitive training can improve memory and language learning in people who have previously used VNS therapy for movement rehabilitation after a stroke. VNS has been previously used to support motor recovery after stroke, but its effect on cognitive learning is not yet fully understood. This study is enrolling individuals who already have a VNS device implanted and have successfully completed VNS-assisted movement therapy. The investigators aim to explore whether continuing to use the device during a language learning program may also support memory and cognitive improvement. This is a research study, which means the use of VNS for cognitive enhancement is experimental and not currently part of standard treatment. An exploratory MRI/fMRI component also will assess whether VNS-paired language learning is associated with changes in task-based activation and resting-state functional connectivity in language, memory, salience/arousal, and frontoparietal cognitive-control networks. The information learned may help guide future approaches to stroke rehabilitation and cognitive recovery.

Study Overview

• Status: Enrolling by invitation
• Conditions: Stroke; Vagus Nerve Stimulation; Cognitive Assessment; Language Acquisition
• Intervention / Treatment: Device: VNS for Cognition

Detailed Description

Stroke survivors frequently experience persistent cognitive, memory, and language-related difficulties that can affect independence and quality of life. VNS paired with rehabilitation has been shown to enhance motor recovery after stroke, and paired stimulation may support experience-dependent neural plasticity. This study extends that approach to cognitive and language learning by pairing VNS with structured foreign-language vocabulary training.

Eligible participants will be adults with prior stroke who are scheduled to receive, or have received, clinically indicated Vivistim VNS implantation for rehabilitation and who are able to participate in the language-learning intervention. Participants will be randomized to active VNS or sham stimulation during daily language-learning sessions over approximately six weeks. The active stimulation group will receive programmed VNS paired with language-learning stimuli; the sham group will undergo the same language-learning procedures with stimulation amplitude set to zero or otherwise configured according to the sham protocol. Participants will be blinded to group assignment when feasible.

The neuroimaging sub-study will include MRI/fMRI at up to three time points: pre-surgery baseline, when feasible before clinically indicated implantation; post-surgery/pre-language-training baseline; and post-training. The post-surgery/pre-training scan is the key baseline for the language-learning intervention, particularly for participants who already have the device implanted. MRI sessions will include structural MRI, resting-state fMRI, and a task-based foreign-word semantic matching paradigm. The primary task-based fMRI contrast will examine changes in neural responses to future-trained versus trained foreign words compared with never-trained foreign words. Resting-state analyses will examine changes in functional connectivity across language, memory, salience/arousal, frontoparietal cognitive control, and stroke recovery networks. A brief optional 0-back/1-back working-memory fMRI task may be included if scan time and participant tolerance allow.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11790
      • Stony Brook University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 22 years or older
• History of stroke
• Implanted with a Vivistim™ VNS device
• Monolingual in English
• Home-dwelling and independent in activities of daily living
• No prior language training in the selected language of learning
• Tolerated 6 weeks of movement therapy at 0.8 mA without incident and has used the device for at-home stimulation without incident
• Willing and able to participate in a six-week at-home intervention
• Clinically stable, without major concurrent medical conditions that would interfere with study participation

Exclusion Criteria:

• Severe aphasia
• Unable to read and/or write in English
• Significant uncorrected hearing or visual impairment
• Unable to commit to 6 weeks of therapy
• Pregnancy
• Prisoner or ward of the state
• Any medical condition that, in the investigator's judgment, would make participation unsafe
• Younger than 22 years of age

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: VNS Group; Group that was implanted with VNS and will receive stimulations	Device: VNS for Cognition; Subjects previously implanted with VNS will undergo second language acquisition
Sham Comparator: Sham Group; Group that will receive sham stimulations	Device: VNS for Cognition; Subjects previously implanted with VNS will undergo second language acquisition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Foreign-Language Vocabulary Learning Accuracy	Vocabulary learning will be assessed using trained foreign-language vocabulary items. The outcome is the percentage of trained vocabulary items correctly recalled, recognized, or translated. Scores range from 0% to 100%, with higher scores indicating better vocabulary learning.	Baseline and 6 weeks
Change in Foreign-Language Sentence Learning Accuracy	Sentence learning will be assessed using trained short foreign-language sentences. The outcome is the percentage of trained sentence items correctly understood, completed, recalled, or translated. Scores range from 0% to 100%, with higher scores indicating better sentence learning.	Baseline and 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Global Cognition on the Montreal Cognitive Assessment (MoCA)	Global cognition will be measured using the Montreal Cognitive Assessment total score. Scores range from 0 to 30, with higher scores indicating better cognitive function.	6 weeks
Change in Verbal Learning on the Rey Auditory Verbal Learning Test	Verbal learning will be measured as the total number of words recalled across Rey Auditory Verbal Learning Test learning trials. Scores range from 0 to 75, with higher scores indicating better verbal learning.	6 weeks
Change in Delayed Verbal Memory on the Rey Auditory Verbal Learning Test	Delayed verbal memory will be measured as the number of words recalled after a delay on the Rey Auditory Verbal Learning Test. Scores range from 0 to 15, with higher scores indicating better delayed verbal memory.	6 weeks
Change in Verbal Learning on the Hopkins Verbal Learning Test-Revised	Verbal learning will be measured as the total number of words recalled across Hopkins Verbal Learning Test-Revised immediate recall trials. Scores range from 0 to 36, with higher scores indicating better verbal learning.	6 weeks
Change in Delayed Verbal Memory on the Hopkins Verbal Learning Test-Revised	Delayed verbal memory will be measured as the number of words recalled after a delay on the Hopkins Verbal Learning Test-Revised. Scores range from 0 to 12, with higher scores indicating better delayed verbal memory.	6 weeks
Change in Language Function on the Western Aphasia Battery	Language function will be measured using the Western Aphasia Battery Aphasia Quotient. Scores range from 0 to 100, with higher scores indicating better language function.	6 weeks
Change in Story Recall on the Automatic Story Recall Test	Story recall will be measured using the Automatic Story Recall Test score. Scores will be reported as the percentage of story content correctly recalled, ranging from 0% to 100%, with higher scores indicating better story recall.	6 weeks
Change in Working Memory on the Digit Span Task	Working memory will be measured using the Digit Span Task total raw score. Scores range from 0 to 48 if using the WAIS-IV Digit Span version, with higher scores indicating better working memory.	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Resting-State Functional Connectivity Between Language and Memory Networks	Resting-state functional connectivity between predefined language and memory networks will be measured. The outcome will be reported as change in Fisher z-transformed correlation coefficients between these networks. Higher values indicate stronger functional connectivity.	Pre-surgery baseline, post-surgery/pre-training baseline, and immediately after the 6-week language-training intervention
Change in Resting-State Functional Connectivity Between Language and Salience/Arousal Networks	Resting-state functional connectivity between predefined language and salience/arousal networks will be measured. The outcome will be reported as change in Fisher z-transformed correlation coefficients between these networks. Higher values indicate stronger functional connectivity.	Pre-surgery baseline, post-surgery/pre-training baseline, and immediately after the 6-week language-training intervention
Change in Resting-State Functional Connectivity Between Language and Default Mode Networks	Resting-state functional connectivity between predefined language and default mode networks will be measured. The outcome will be reported as change in Fisher z-transformed correlation coefficients between these networks. Higher values indicate stronger functional connectivity.	Pre-surgery baseline, post-surgery/pre-training baseline, and immediately after the 6-week language-training intervention
Change in Resting-State Functional Connectivity Between Language and Frontoparietal Cognitive-Control Networks	Resting-state functional connectivity between predefined language and frontoparietal cognitive-control networks will be measured. The outcome will be reported as change in Fisher z-transformed correlation coefficients between these networks. Higher values indicate stronger functional connectivity.	Pre-surgery baseline, post-surgery/pre-training baseline, and immediately after the 6-week language-training intervention
Change in Task-Based fMRI Activation During Foreign-Word Processing	Task-based fMRI activation will be measured during presentation of trained, future-trained, and never-trained foreign words. The outcome will be reported as change in blood-oxygen-level-dependent activation, measured by contrast estimate or percent signal change, for trained and future-trained words compared with never-trained words. Higher values indicate greater task-related activation.	Pre-surgery baseline, post-surgery/pre-training baseline, and immediately after the 6-week language-training intervention.

Collaborators and Investigators

• Sponsor: Stony Brook University

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: July 17, 2026
• First Posted (Actual): July 22, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 17, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: fMRI; neuromodulation; stroke rehabilitation; VNS; VNS for learning and cognition
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: IRB2025-00209

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Within one year of study completion
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes