StrokeATLASNCT07608588
Recovery From Post-Stroke Aphasia With rTMS Targeting Left or Right Anterior Temporal Lobe
A study testing continuous Theta Burst Stimulation, intermittent Theta Burst Stimulation and Semantic Feature Analysis in people with Stroke and Aphasia, run by University of South Carolina at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- continuous Theta Burst Stimulation, intermittent Theta Burst Stimulation and Semantic Feature Analysis
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 15 May 2026to 30 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- Illiteracy
- Known neurodegenerative disorders
- Severe uncorrected visual or hearing impairments
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
McCausland Center
Columbia, South Carolina, 29203
Makayla Gibson, PhD, 803-777-0169, mjgibson@email.sc.edu
Sophie Arheix-Parras, PhD
About this study
Official title: 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.
Read the 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.
- Being tested
- continuous Theta Burst Stimulation, intermittent Theta Burst Stimulation, Transcranial Magnetic Stimulation Sham, Semantic Feature Analysis
- Keywords
- aphasia, stroke, rTMS, brain stimulation, speech and language therapy
- Medical subject headings
- Stroke, Aphasia, Communication Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
continuous Theta Burst StimulationDevice
Also called rTMS, repetitive Transcranial Magnetic 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
intermittent Theta Burst StimulationDevice
Also called rTMS, repetitive Transcranial Magnetic 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
Transcranial Magnetic Stimulation ShamDevice
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.
Semantic Feature AnalysisBehavioural
Also called Speech and Language Therapy, SFA
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).
| Study group | Role | What they receive |
|---|---|---|
| Inhibitory rTMS | Experimental | 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. Receives: Device: continuous Theta Burst Stimulation; Behavioral: Semantic Feature Analysis |
| Facilitatory rTMS | Experimental | 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. Receives: Device: intermittent Theta Burst Stimulation; Behavioral: Semantic Feature Analysis |
| Sham rTMS | Sham comparator | 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. Receives: Device: Transcranial Magnetic Stimulation Sham; Behavioral: Semantic Feature Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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 outcomes (12)
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.
Measured: 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).
Measured: 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.
Measured: 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)
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2026
- Study start15 May 2026
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by University of South CarolinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- We will conduct a superiority randomized controlled trial. Participants will be randomly assigned in a 1:1:1 ratio to one of three parallel groups: (1) inhibitory continuous Theta Burst Stimulation (cTBS) targeting the right ATL; (2) the facilitatory intermittent Theta Burst Stimulation (iTBS) targeting the left ATL; (3) sham stimulation, targeting either the left or right ATL with allocation balanced across participants. In all three groups, participants will receive rTMS five times per week for two consecutive weeks (10 sessions in total). Each rTMS session will be immediately followed by Speech and Language Therapy (SLT) using the Semantic Feature Analysis (SFA) protocol. Assessments will be conducted at baseline, immediately post-intervention, and at one-month follow-up. Participants will also undergo fMRI scanning at S1 and S2.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- Responsible party
- Principal investigator, Sophie Arheix-Parras, University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07608588
- Sponsor's protocol ID
- STUDY00000481
- Other IDs
- K99DC023302
- Acronym
- ATLAS
- Status last verified
- May 2026
- First submitted
- 22 Apr 2026
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: 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)
Publications
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.
PubMed 30208415Arheix-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.
PubMed 33862065Hilari 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.
PubMed 12855827Nippold 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).
PubMed 17456896Rossi 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.
PubMed 33243615Arheix-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.
PubMed 41594838
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Recovery From Post-Stroke Aphasia With rTMS Targeting the Anterior Temporal Lobe: Interhemispheric Activation Changes and Lesion-Connectome-Based Predictive Outcomes
- ClinicalTrials.gov ID
- NCT07608588
- Acronym / sponsor ID
- ATLAS / STUDY00000481
- Keywords
- aphasia, stroke, rTMS, brain stimulation, speech and language therapy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- University of South CarolinaUniversity, hospital or other
- Collaborators
- National Institute on Deafness and Other Communication Disorders (NIDCD)
- Study start
- 15 May 2026 (actual)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 30 Jul 2027 (estimated)
- First posted
- 27 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
- Model description
- We will conduct a superiority randomized controlled trial. Participants will be randomly assigned in a 1:1:1 ratio to one of three parallel groups: (1) inhibitory continuous Theta Burst Stimulation (cTBS) targeting the right ATL; (2) the facilitatory intermittent Theta Burst Stimulation (iTBS) targeting the left ATL; (3) sham stimulation, targeting either the left or right ATL with allocation balanced across participants. In all three groups, participants will receive rTMS five times per week for two consecutive weeks (10 sessions in total). Each rTMS session will be immediately followed by Speech and Language Therapy (SLT) using the Semantic Feature Analysis (SFA) protocol. Assessments will be conducted at baseline, immediately post-intervention, and at one-month follow-up. Participants will also undergo fMRI scanning at S1 and S2.
| Arm | Type | Receives |
|---|---|---|
| Inhibitory rTMS | Experimental | Device: continuous Theta Burst Stimulation, Behavioral: Semantic Feature AnalysisParticipants 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. |
| Facilitatory rTMS | Experimental | Device: intermittent Theta Burst Stimulation, Behavioral: Semantic Feature AnalysisParticipants 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. |
| Sham rTMS | Sham comparator | Device: Transcranial Magnetic Stimulation Sham, Behavioral: Semantic Feature AnalysisParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| continuous Theta Burst StimulationAlso: rTMS, repetitive Transcranial Magnetic StimulationWe will use continuous Theta Burst Stimulation (600 pulses, burst frequency at 5 Hz, burst of three pulses at 50Hz) targeting the right ATL | Device | Inhibitory rTMS |
| intermittent Theta Burst StimulationAlso: rTMS, repetitive Transcranial Magnetic StimulationWe 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 | Device | Facilitatory rTMS |
| Transcranial Magnetic Stimulation ShamWe 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. | Device | Sham rTMS |
| Semantic Feature AnalysisAlso: Speech and Language Therapy, SFAParticipants 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). | Behavioural | Facilitatory rTMS, Inhibitory rTMS, Sham rTMS |
Primary outcome
Picture Naming task accuracy
Time frame: 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
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).
12 secondary outcomes
Picture Naming Reaction time
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2026.
- Background: PubMed 30208415Quique 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.
- Background: PubMed 33862065Arheix-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.
- Background: PubMed 12855827Hilari 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.
- Background: PubMed 17456896Nippold 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).
- Background: PubMed 33243615Rossi 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.
- Background: PubMed 41594838Arheix-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.
- Individual participant dataSharing planned: Yes. 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)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing continuous Theta Burst Stimulation, intermittent Theta Burst Stimulation and Semantic Feature Analysis in people with Stroke and Aphasia, run by University of South Carolina at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sophie Arheix-Parras, PhD (803-467-8018, sophie.arheix-parras@sc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Picture Naming task accuracy (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07608588, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2026.