Recovery From Post-Stroke Aphasia With rTMS Targeting Left or Right Anterior Temporal Lobe (ATLAS)

Recovery From Post-Stroke Aphasia With rTMS Targeting the Anterior Temporal Lobe: Interhemispheric Activation Changes and Lesion-Connectome-Based Predictive Outcomes

This project aims to tailor repetitive Transcranial Magnetic Stimulation (rTMS) target to the clinical profile of post-stroke aphasia, specifically focusing on lexicosemantic impairments, to enhance recovery. Functional Magnetic Resonance Imaging (fMRI) will provide critical insights into the effects of facilitatory versus inhibitory stimulation on interhemispheric balance. Additionally, this study will generate new data on how lesion localization and brain connectivity influence individual responses to rTMS, explaining variability in treatment efficacy.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Aphasia
• Intervention / Treatment: Device: continuous Theta Burst Stimulation; Behavioral: Semantic Feature Analysis; Device: intermittent Theta Burst Stimulation; Device: Transcranial Magnetic Stimulation Sham

Detailed Description

Background and aims In the United States, 18 to 66% of individuals who experience a stroke will suffer from language impairment, referred to as aphasia. Aphasia profoundly impacts quality of life by restricting participation in social, familial, and professional spheres. While the gold standard for aphasia rehabilitation is Speech and Language Therapy (SLT), it often does not lead to complete recovery. Repetitive Transcranial Magnetic Stimulation (rTMS) or Transcranial Direct Current Stimulation (tDCS) are non-invasive brain stimulation techniques that could enhance post-stroke aphasia recovery. Most rTMS and tDCS studies in post-stroke aphasia following left hemispheric strokes have applied inhibitory stimulation targeting the right Inferior Frontal Gyrus (IFG) or facilitatory stimulation targeting the left IFG (i.e., Broca's area and its right homologue).

Aim 1: Focusing solely on the IFG for all participants with post-stroke aphasia may be inefficient, as the language system is widespread and complex, and involves large, interconnected networks also linked to non-linguistic cognitive functions such as working memory or executive functions. Previous research indicated that individuals with different language impairments may have varied recovery paths, and using the same cortical target for non-invasive brain stimulation might be ineffective or even impair recovery. Interestingly, rTMS targeting the motor cortex of the lips in people with phonological impairments improved accuracy and decreased phonological errors in a Picture Naming Task. This improvement likely resulted from rTMS modulating not only the targeted motor cortex but also the connected dorsal phonological stream via intra- and interhemispheric connections. Building on this principle, a pilot study was conducted using inhibitory rTMS targeting the right Anterior Temporal Lobe (ATL) in people with post-stroke aphasia suffering from lexicosemantic impairments, with improvement in Picture Naming for all participants. Lexicosemantic difficulties manifest as anomia and/or semantic errors (e.g., saying tea instead of coffee) and can result from deficits in lexical access or within the semantic system itself. Lexicosemantic processes involve a complex brain network. According to the hub-and-spokes theory, the ATL serves as a central amodal semantic hub that integrates information from various modalities. Other theories emphasize its multimodal and potentially lexical sensibility. This study hypothesizes that rTMS targeting the ATL will modulate the ventral stream of language, resulting in improvements in people with lexicosemantic impairments. This RCT aims to combine ATL stimulation with Semantic Feature Analysis (SFA) rehabilitation, which strengthens lexicosemantic links. This approach was expected to enhance the effect of rTMS on lexicosemantic processes.

Aim 2 and 3.3: Furthermore, the facilitation of the left hemisphere and the inhibition of the right undamaged hemisphere are based on the theory of transcallosal interhemispheric imbalance, where brain lesion leads to hyperactivation of the undamaged hemisphere and hypoactivation of the damaged hemisphere. The undamaged right hemisphere could play a maladaptive role in post-stroke aphasia recovery. However, the role of right hemisphere activation in post-stroke aphasia recovery remains unclear, as it may support recovery in certain participants during both the subacute and chronic phases. More research is needed to better understand the underlying mechanisms of facilitatory and inhibitory stimulation targeting respectively the undamaged and damaged hemispheres.

Aim 3: While non-invasive brain stimulation has been shown to be effective in post-stroke aphasia, certain people with post-stroke aphasia respond better than others. The previous sections highlighted the impact cortical target and stimulation parameters, but recent studies have also proposed that participant's aphasia type or lesion localization may influence their response. Further research, particularly using rTMS, is needed to clarify how lesion localization and disconnections contribute to recovery, as these factors may explain chronic post-stroke language impairments and predict rTMS efficacy. Since the ATL serves as a central hub in the ventral lexicosemantic stream, and rTMS modulates other brain areas through both inter- and intra-hemispheric connectivity, the hypothesis was as follow: a preserved connectivity between the ATL and the posterior temporal lobe will be a strong predictor of rTMS effectiveness.

Study Intervention Participants will be randomly assigned to one of three groups: (1) the inhibitory continuous Theta Burst Stimulation (cTBS) targeting the right ATL, (2) the facilitatory intermittent Theta Burst Stimulation (iTBS) targeting the left ATL, or (3) the sham control TMS group, with sham stimulation targeting either the left or right ATL in half of the participants. The intervention will consist of two weeks of stimulation according to group assignment, five times per week (10 sessions total), followed by 30 minutes of Speech-Language Therapy using the Semantic Feature Analysis method.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sophie Arheix-Parras, PhD; Phone Number: 803-467-8018; Email: sophie.arheix-parras@sc.edu

Study Locations

• United States
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Recruiting
      • McCausland Center
      • Contact: Makayla Gibson, PhD; Phone Number: 803-777-0169; Email: mjgibson@email.sc.edu
      • Principal Investigator: Sophie Arheix-Parras, PhD
      • Sub-Investigator: Chris Rorden, PhD
      • Sub-Investigator: Rutvik H Desai, PhD
      • Sub-Investigator: Leonardo Bonilha, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Right-handedness (assesed using the Edinburgh Handedness Inventory)
• Native English speakers
• Single left hemispheric stroke
• Diagnosis of aphasia and lexicosemantic impairments (e.g., anomia, semantic errors in picture naming or spontaneous speech) confirmed by a Speech and Language Pathologist or Physician

Exclusion Criteria:

• Severely impaired auditory comprehension (WAB Comprehension score of 0 or 1)
• Major phonological impairments (defined as > 2 errors in non-word repetition of one- and two-syllable items on the PALPA, 2)
• Contraindications to rTMS (e.g., uncontrolled epilepsy, history of seizures, intracranial ferromagnetic body, cochlear implant, or factors that lower seizure threshold (see Rossi et al., 2021)
• Contraindication to MRI
• Stroke involving the left ATL
• Severe depression or psychiatric history
• Illiteracy
• Known neurodegenerative disorders
• Severe uncorrected visual or hearing impairments

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inhibitory rTMS; Participants will receive inhibitory continuous Theta Burst Stimulation (cTBS) targeting the right ATL 5 times a week for 2 weeks. Each stimulation session will be followed by 30-min of Speech and Language Therapy using the Semantic Feature Analysis protocol.	Device: continuous Theta Burst Stimulation; We will use continuous Theta Burst Stimulation (600 pulses, burst frequency at 5 Hz, burst of three pulses at 50Hz) targeting the right ATL; Other Names: rTMS; repetitive Transcranial Magnetic Stimulation; Behavioral: Semantic Feature Analysis; Participants will receive 30 minutes of Semantic Feature Analysis therapy administered by a Speech and Language Pathologist. On a computer screen, participants will see an image of an object and will be cued to retrieve the object's name by describing various features of the object, including its physical properties, typical location, personal associations, category, use and actions involving the object (Quique et al., 2019).; Other Names: SFA; Speech and Language Therapy
Experimental: Facilitatory rTMS; Participants will receive facilitatory intermittent Theta Burst Stimulation (iTBS) targeting the left ATL 5 times a week for 2 weeks. Each stimulation session will be followed by 30-min of Speech and Language Therapy using the Semantic Feature Analysis protocol.	Behavioral: Semantic Feature Analysis; Participants will receive 30 minutes of Semantic Feature Analysis therapy administered by a Speech and Language Pathologist. On a computer screen, participants will see an image of an object and will be cued to retrieve the object's name by describing various features of the object, including its physical properties, typical location, personal associations, category, use and actions involving the object (Quique et al., 2019).; Other Names: SFA; Speech and Language Therapy; Device: intermittent Theta Burst Stimulation; We will use intermittent Theta Burst Stimulation (600 pulses, burst frequency at 5 Hz, burst of three pulses at 50Hz, interval intertrain of 8 sec, 10 pulses in train) targeting the left ATL; Other Names: rTMS; repetitive Transcranial Magnetic Stimulation
Sham Comparator: Sham rTMS; Participants will receive sham stimulation targeting either the left or right ATL with allocation balanced across participants, 5 times a week for 2 weeks. Each stimulation session will be followed by 30-min of Speech and Language Therapy using the Semantic Feature Analysis protocol.	Behavioral: Semantic Feature Analysis; Participants will receive 30 minutes of Semantic Feature Analysis therapy administered by a Speech and Language Pathologist. On a computer screen, participants will see an image of an object and will be cued to retrieve the object's name by describing various features of the object, including its physical properties, typical location, personal associations, category, use and actions involving the object (Quique et al., 2019).; Other Names: SFA; Speech and Language Therapy; Device: Transcranial Magnetic Stimulation Sham; We will use sham stimulation using the same coil but flipped over, with the left ATL targeted in half of the participant and the right ATL in the other half. The placebo coil will replicate the auditory sensations produced by active stimulation. In addition, we will use electrical stimulation of the scalp (via electrodes placed over specific muscles) in the Sham group to mimic the sensory effects of active stimulation. Participants will have no prior rTMS experience before inclusion in the protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Picture Naming task accuracy	The primary outcome is improvement in accuracy of the a Picture Naming task. Participants will complete a Picture Naming tasks based on the Older Adult Naming Test. Participants will name items from pictures as quickly and accurately as possible. Items will include mid-frequency words and 10 pictures of middle-to-late age-of-acquisition words (mean = 10.01 years, SD = 1.16).	Baseline assessment conducted within 7 days prior to intervention Post-intervention assessment conducted within 3 days after the final intervention session Follow-up assessment conducted 1 month after the end of the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Picture Naming Reaction time	Reaction times will also be recorded for the picture naming task using E-Prime software (version 3.0). A decrease in reaction time for the picture naming task will be considered as an improvement.	Baseline assessment conducted within 7 days prior to intervention Post-intervention assessment conducted within 3 days after the final intervention session Follow-up assessment conducted 1 month after the end of the intervention
Auditory Description Naming accuracy	Participants will complete an Auditory Description Naming based on the Older Adult Naming Test. Participants will name items from verbal descriptions as quickly and accurately as possible. Items will include mid-frequency words supplemented with 10 descriptions of middle to high-frequency abstract words (mean frequency = 3.45, SD = 0.90).	Baseline assessment conducted within 7 days prior to intervention Post-intervention assessment conducted within 3 days after the final intervention session Follow-up assessment conducted 1 month after the end of the intervention
Auditory Description Naming reaction time	Reaction times will also be recorded using E-Prime software (version 3.0) for the auditory description naming task. A decrease in Reaction Time will be considered as improvement.	Baseline assessment conducted within 7 days prior to intervention Post-intervention assessment conducted within 3 days after the final intervention session Follow-up assessment conducted 1 month after the end of the intervention
Comprehensive Aphasia Test - aphasia impact questionnaire	Online version of the Comprehensive Aphasia Test (CAT): Aphasia Impact Questionnaire score (124-item scale; higher scores indicate a greater impact of aphasia on the participant's life, meaning worse outcome).	Baseline assessment conducted within 7 days prior to intervention Post-intervention assessment conducted within 3 days after the final intervention session Follow-up assessment conducted 1 month after the end of the intervention
Similarity task Accuracy	Participants will be asked whether pairs of items are similar or dissimilar in meaning (for example, coffee and tea are similar in meaning, whereas cat and cup are not). Accuracy will be recorded.	Baseline assessment conducted within 7 days prior to intervention Post-intervention assessment conducted within 3 days after the final intervention session Follow-up assessment conducted 1 month after the end of the intervention
Similarity task - reaction time	We will also measure Reaction time for this task.	Baseline assessment conducted within 7 days prior to intervention Post-intervention assessment conducted within 3 days after the final intervention session Follow-up assessment conducted 1 month after the end of the intervention
Verb naming task accuracy	Verb naming will be assessed using video clips from the T-DAV 20. Only the number of correct answers will be recorded as an outcome measure.	Baseline assessment conducted within 7 days prior to intervention Post-intervention assessment conducted within 3 days after the final intervention session Follow-up assessment conducted 1 month after the end of the intervention
Digit span	Digit span (WAIS-IV) for the working memory and the total score will be reported.	Baseline assessment conducted within 7 days prior to intervention Post-intervention assessment conducted within 3 days after the final intervention session Follow-up assessment conducted 1 month after the end of the intervention
Flanker task	Using an E-Prime script, inhibitory processes will be measured with the Flanker task. Accuracy will be used as the outcome measure.	Baseline assessment conducted within 7 days prior to intervention Post-intervention assessment conducted within 3 days after the final intervention session Follow-up assessment conducted 1 month after the end of the intervention
Flexibility - Trail Making Test	Flexibility will be measured using the Trail Making Test, and the reaction time difference between Parts B and A will be used as the outcome measure.	Baseline assessment conducted within 7 days prior to intervention Post-intervention assessment conducted within 3 days after the final intervention session Follow-up assessment conducted 1 month after the end of the intervention
Comprehensive Aphasia Test - cognitive screening	Online version of the Comprehensive Aphasia Test (CAT): cognitive screening score (scale /49, higher meaning better outcome)	Baseline assessment conducted within 7 days prior to intervention Post-intervention assessment conducted within 3 days after the final intervention session Follow-up assessment conducted 1 month after the end of the intervention
Comprehensive Aphasia Test - language score	Online version of the Comprehensive Aphasia Test (CAT): language comprehension (spoken and written words, sentences, and paragraphs) and expressive language (repetition, picture description, reading aloud, writing) (Total scale /402, higher meaning better outcome).	Baseline assessment conducted within 7 days prior to intervention Post-intervention assessment conducted within 3 days after the final intervention session Follow-up assessment conducted 1 month after the end of the intervention

Collaborators and Investigators

• Sponsor: University of South Carolina
• Collaborators: National Institute on Deafness and Other Communication Disorders (NIDCD)

Publications and helpful links

General Publications

• Hilari K, Byng S, Lamping DL, Smith SC. Stroke and Aphasia Quality of Life Scale-39 (SAQOL-39): evaluation of acceptability, reliability, and validity. Stroke. 2003 Aug;34(8):1944-50. doi: 10.1161/01.STR.0000081987.46660.ED. Epub 2003 Jul 10.
• Rossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmoller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, Di Lazzaro V, Fox MD, George MS, Gilbert D, Kimiskidis VK, Koch G, Ilmoniemi RJ, Lefaucheur JP, Leocani L, Lisanby SH, Miniussi C, Padberg F, Pascual-Leone A, Paulus W, Peterchev AV, Quartarone A, Rotenberg A, Rothwell J, Rossini PM, Santarnecchi E, Shafi MM, Siebner HR, Ugawa Y, Wassermann EM, Zangen A, Ziemann U, Hallett M; basis of this article began with a Consensus Statement from the IFCN Workshop on "Present, Future of TMS: Safety, Ethical Guidelines", Siena, October 17-20, 2018, updating through April 2020. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol. 2021 Jan;132(1):269-306. doi: 10.1016/j.clinph.2020.10.003. Epub 2020 Oct 24.
• Quique YM, Evans WS, Dickey MW. Acquisition and Generalization Responses in Aphasia Naming Treatment: A Meta-Analysis of Semantic Feature Analysis Outcomes. Am J Speech Lang Pathol. 2019 Mar 11;28(1S):230-246. doi: 10.1044/2018_AJSLP-17-0155.
• Arheix-Parras S, Barrios C, Python G, Cogne M, Sibon I, Engelhardt M, Dehail P, Cassoudesalle H, Moucheboeuf G, Glize B. A systematic review of repetitive transcranial magnetic stimulation in aphasia rehabilitation: Leads for future studies. Neurosci Biobehav Rev. 2021 Aug;127:212-241. doi: 10.1016/j.neubiorev.2021.04.008. Epub 2021 Apr 20.
• Nippold MA, Mansfield TC, Billow JL. Peer conflict explanations in children, adolescents, and adults: examining the development of complex syntax. Am J Speech Lang Pathol. 2007 May;16(2):179-88. doi: 10.1044/1058-0360(2007/022).
• Arheix-Parras S, Moore SR, Desai RH. Improving Lexicosemantic Impairments in Post-Stroke Aphasia Using rTMS Targeting the Right Anterior Temporal Lobe. Brain Sci. 2026 Jan 22;16(1):117. doi: 10.3390/brainsci16010117.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2026
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: April 22, 2026
• First Submitted That Met QC Criteria: May 19, 2026
• First Posted (Actual): May 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: stroke; rTMS; brain stimulation; aphasia; speech and language therapy
• Additional Relevant MeSH Terms: Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Language Disorders; Speech Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Stroke; Aphasia; Communication Disorders; Therapeutics; Patient Care; Rehabilitation; Aftercare; Continuity of Patient Care; Magnetic Field Therapy; Rehabilitation of Speech and Language Disorders; Transcranial Magnetic Stimulation; Speech Therapy
• Other Study ID Numbers: STUDY00000481; K99DC023302 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The expected data types include:

• Behavioral data: Accuracy and reaction times measures for cognitive and language tasks.
• Neuroimaging data: Structural MRI (T1 and T2 weighted) and functional MRI (resting state and task-based, for around 15 minutes per session)

• IPD Sharing Time Frame: Data will be made available upon publication of the respective study. Data will remain accessible for at least 10 years post-publication.

IPD Sharing Access Criteria

Interested research will be able to access the following data : - De-identified behavioral data (reaction time, accuracy, transcription) at be shared publicly using OSF

• Audio recordings will not be shared due to confidentiality risks
• Neuroimaging data (structural and functional MRI) will be shared after de-identification (face removal) in OpenNeuro
• Aggregate results will be disseminated via peer-reviewed publications and conference presentations.
• Study protocol, task descriptions, and analysis pipelines will be documented in manuscripts
• Metadata describing participant demographics (e.g., age, gender, stroke type, lesion location) will be included in shared dataset and available in manuscripts
• Documentation will be provided upon request to facilitate data interpretation

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

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