Efficacy of Low-frequency rTMS in Aphasia

Study Overview
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Brief Summary
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In a randomized controlled trial, efficacy of low-frequency, inhibitory rTMS will be examined in rehabilitation of acquired aphasia. Two cortical sites will be targeted: Right-hemispheric homologues of Broca's and Wernicke's areas. In addition to cognitive screening prior to onset of rTMS, language assessments will be conducted before, during and after the intervention. An eyetracking-while-listening experiment will also be conducted before and after the intervention to investigate morphosyntactic processing.

Detailed Description
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Efficacy of low-frequency (1hz), inhibitory rTMS will be examined in rehabilitation of acquired aphasia. Two cortical sites will be targeted: Right-hemispheric homologues of Broca's and Wernicke's areas. In other words, right frontal and right temporal sites will be targeted. In addition to cognitive screening prior to onset of rTMS, language assessments will be conducted before, during and after the intervention. The language assessment will be conducted using the Turkish Aphasia Language Assessment Test (ADD) and sets of pictures used to assess naming performance. ADD will be carried out before and after the intervention. Six picture sets will be used, one at baseline, four on different days during the intervention, and the last one immediately after the last day of the intervention. Cognitive screening will be conducted at baseline using the digit span test and Raven's colored progressive matrices. In addition, a pre- and post-treatment eyetracking-while-listening experiment will be conducted to investigate morphosyntactic processing in Turkish and to examine whether the two brain stimulation interventions differentially affect online (dynamic, time-dependent) measures of morphosyntactic processing. The eyetracking paradigm will request the participants to listen to Turkish sentences varying in morphosyntactic complexity (canonical versus noncanonical sentences) and to look at the picture (out of two pictures presented on the screen) corresponding to the sentence they are listening to.

Official Title
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Efficacy of Low-frequency Repetitive Transcranial Magnetic Stimulation on Rehabilitation of Aphasia

Conditions
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Aphasia

Intervention / Treatment
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* Device: rTMS over right frontal target
* Device: rTMS over right temporal target


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Right-handedness, Normal or corrected-to-normal vision and hearing, Aphasia following cerebrovascular accident, Cerebrovascular accident at least 6 months prior to enrolment in the study, Satisfying current TMS safety guidelines (Rossi et al. 2009, 2021), which are: No previous history of epilepsy, No implant (e.g., cochlear implant) or stimulator (e.g., deep brain stimulation) in the head which may interact with the magnetic field, No use of central nervous system active drugs that lower seizure threshold (as listed in the aforementioned guidelines) Exclusion Criteria: Left-handedness, ambidexterity, Impaired and uncorrected vision or hearing, No aphasia symptoms following cerebrovascular accident, Time since cerebrovascular accident less than 6 months, Violating current TMS safety guidelines (Rossi et al. 2009, 2021). In other words: Having a previous history of epilepsy, Having an implant (e.g., cochlear implant) or stimulator (e.g., deep brain stimulation) in the head which may interact with the magnetic field, Taking central nervous system active drugs that lower seizure threshold (as listed in the aforementioned guidelines)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The two groups receive one of the two treatments: right frontal versus right temporal stimulation.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Right frontal 1 Hz rTMS<br>Low-frequency (1 Hz) inhibitory rTMS will be administered to right inferior frontal gyrus with the following parameters: Frequency: 1 Hz Stimulation site: Right IFG (as determined using EEG 10-20 system) Intensity: 100% of motor threshold Dosage: 20 minutes per day Duration: 10 days over 2 weeks (no stimulation during weekends) | Device: rTMS over right frontal target<br>* Low frequency (1 Hz) rTMS over right inferior frontal gyrus<br>|
| Active Comparator: Right temporal 1 Hz rTMS<br>Low-frequency (1 Hz) inhibitory rTMS will be administered to right posterior superior temporal gyrus with the following parameters: Frequency: 1 Hz Stimulation site: Right posterior superior temporal gyrus (as determined using EEG 10-20 system) Intensity: 100% of motor threshold Dosage: 20 minutes per day Duration: 10 days over 2 weeks (no stimulation during weekends) | Device: rTMS over right temporal target<br>* Low frequency (1 Hz) rTMS over right posterior superior temporal gyrus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Turkish Aphasia Language Assessment Test Scores Time 1 (pre-treatment) | Baseline scores obtained from the Turkish Aphasia Language Assessment Test (ADD) Minimum score: 0 points Maximum score: 292 points Higher scores indicate a better outcome | Immediately before the intervention (Day 0) | 
| Turkish Aphasia Language Assessment Test Scores Time 2 (during treatment) | Scores obtained from the Turkish Aphasia Language Assessment Test (ADD) at the end of the first week of treatment Minimum score: 0 points Maximum score: 292 points Higher scores indicate a better outcome | At the end of the first week of intervention (Day 5) | 
| Turkish Aphasia Language Assessment Test Scores Time 3 (post-treatment short-term) | Post-treatment scores obtained from the Turkish Aphasia Language Assessment Test (ADD) at the end of the treatment Minimum score: 0 points Maximum score: 292 points Higher scores indicate a better outcome | Immediately after the intervention (Day 10) | 
| Turkish Aphasia Language Assessment Test Scores Time 4 (post-treatment medium-term) | Post-treatment scores obtained from the Turkish Aphasia Language Assessment Test (ADD) one month after the end of the treatment Minimum score: 0 points Maximum score: 292 points Higher scores indicate a better outcome | 1 month after the intervention | 
| Turkish Aphasia Language Assessment Test Scores Time 5 (post-treatment long-term) | Post-treatment scores obtained from the Turkish Aphasia Language Assessment Test (ADD) six months after the end of the treatment Minimum score: 0 points Maximum score: 292 points Higher scores indicate a better outcome | 6 months after the intervention | 
| Picture Naming Scores Time 1 (pre-treatment) | Picture naming performance (number of accurately named pictures & naming latency for correctly named pictures) There are 20 pictures in total, of which half are objects and half actions. Minimum score: 0 points Maximum score: 20 points Higher scores indicate a better outcome | Immediately before the intervention (Day 0) | 
| Picture Naming Scores Time 2 (during treatment) | Picture naming performance (number of accurately named pictures & naming latency for correctly named pictures) There are 20 pictures in total, of which half are objects and half actions. Minimum score: 0 points Maximum score: 20 points Higher scores indicate a better outcome | At the end of the first week of intervention (Day 5) | 
| Picture Naming Scores Time 3 (post-treatment short-term) | Picture naming performance (number of accurately named pictures & naming latency for correctly named pictures) There are 20 pictures in total, of which half are objects and half actions. Minimum score: 0 points Maximum score: 20 points Higher scores indicate a better outcome | Immediately after the intervention (Day 10) | 
| Picture Naming Scores Time 4 (post-treatment medium-term) | Picture naming performance (number of accurately named pictures & naming latency for correctly named pictures) There are 20 pictures in total, of which half are objects and half actions. Minimum score: 0 points Maximum score: 20 points Higher scores indicate a better outcome | 1 month after the intervention | 
| Picture Naming Scores Time 5 (post-treatment long-term) | Picture naming performance (number of accurately named pictures & naming latency for correctly named pictures) There are 20 pictures in total, of which half are objects and half actions. Minimum score: 0 points Maximum score: 20 points Higher scores indicate a better outcome | 6 months after the intervention | 
| Eye movements Time 1 (pre-treatment) | An eyetracking-while-listening paradigm will be used to determine proportions of dwell time on the correct picture (out of two alternatives) corresponding to auditorily presented Turkish sentences varying in morphosyntactic complexity. | Immediately before the intervention (Day 0) | 
| Eye movements Time 2 (post-treatment) | An eyetracking-while-listening paradigm will be used to determine proportions of dwell time on the correct picture (out of two alternatives) corresponding to auditorily presented Turkish sentences varying in morphosyntactic complexity. | Immediately after the intervention (Day 10) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Repetitive transcranial magnetic stimulation, Aphasia