Efficacy of Low-frequency Repetitive Transcranial Magnetic Stimulation on Rehabilitation of Aphasia
Phase: NA
Conditions: Aphasia
Sponsor: Medipol University

 
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STUDY PROTOCOL  
AND  
STATISTICAL ANALYSIS PLAN 
 
 
 
Study Title: 
Efficacy of Low-frequency Repetitive Transcranial Magnetic Stimulation on 
Rehabilitation of Aphasia 
 
 
 
Study Design  
: Randomized Controlled Trial 
 
Research Center 
: İstanbul Medipol University, Speech, Language and Swallowing 
Therapy and Research Center (MEDKOM) 
 
Document Date 
: 28.06.2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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RESEARCH TEAM 
 
Principal Investigator 
Name  
 
: Talat BULUT 
Title / Expertise 
: Assist. Prof. / Cognitive Neuroscience 
Area of expertise 
: Cognitive Neuroscience 
Institution 
 
: Istanbul Medipol University 
Email  
 
: tbulut@medipol.edu.tr; buluttalat@gmail.com  
 
Investigator 
Name  
 
: Meryem Bilge TOPRAK 
Title / Expertise 
: Speech and Language Therapist / Speech and Language Therapy 
Institution 
 
: Istanbul Medipol University 
Email  
 
: mrymblgtprk@gmail.com  
 
Investigator 
Name  
 
: N. Evra GÜNHAN ŞENOL 
Title / Expertise 
: Assist. Prof. / Speech and Language Therapy 
Institution 
 
: Istanbul Medipol University  
Email  
 
: negunhan@medipol.edu.tr  
 
Investigator 
Name  
 
: Lütfü HANOĞLU 
Title / Expertise 
: Prof. Dr. / Neurology 
Institution 
 
: Istanbul Medipol University 
Email  
 
: lhanoglu@medipol.edu.tr  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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STUDY PROTOCOL  
AND  
STATISTICAL ANALYSIS PLAN 
 
1. 
PURPOSE 
The purpose of the study is to compare effectiveness of two repetitive transcranial magnetic 
stimulation (rTMS) protocols in rehabilitation of aphasia:  
1. Inhibitory, low-frequency stimulation of right inferior frontal gyrus, 
2. Inhibitory, low-frequency stimulation of right posterior superior temporal gyrus. 
 
2. 
METHODS 
Research Design 
Randomized controlled trial 
Population 
People with aphasia aged between 18-80 whose native language is Turkish 
Sample, Inclusion and Exclusion Criteria 
20 participants 
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., 2021, 2009), which are: 
o No previous history of epilepsy, 
o No implants (e.g., cochlear implant) or stimulators (e.g., deep brain stimulation) 
in the head which may interact with the magnetic field, 
o No use of central nervous system (CNS) 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., 2021, 2009). In other words: 
o Having a previous history of epilepsy, 

 
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o Having an implant (e.g., cochlear implant) or a stimulator (e.g., deep brain 
stimulation) in the head which may interact with the magnetic field, 
o Taking central nervous system (CNS) active drugs that lower seizure threshold 
(as listed in the aforementioned guidelines) 
rTMS Interventions 
Intervention 1: Right frontal (inferior frontal gyrus) 1 Hz rTMS 
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) 
Intervention 2: Right temporal (posterior superior temporal gyrus) 1 Hz rTMS 
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) 
Outcome Measurements 
1. ADD Scores 
Baseline and post-treatment scores obtained from the Turkish Aphasia Language Assessment 
Test (ADD) 
Time Frame: Immediately before and immediately after the intervention 
2. Naming Scores 
Naming performance (% accurately named pictures & naming latency for correctly named 
pictures) on the IPNP picture sets 
Time Frame: Immediately before, during and immediately after the intervention 
3. Eye movements 
An eye tracking-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 which vary in morphosyntactic complexity. 

 
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Time Frame: Immediately before and immediately after the intervention 
 
3. 
STATISTICAL ANALYSES 
The statistical analyses will be conducted in R (R Core Team, 2013) using the lme4 
package (Bates, Mächler, Bolker, & Walker, 2015). Numeric dependent variables (tests scores, 
naming latency, dwell time) will be analyzed using linear mixed-effects models (LMM), and 
binary data (accuracy) will be analyzed using generalized linear mixed-effects models (GLMM) 
with a binomial link function.  
The following fixed effects will be entered into the models:  
• rTMS interventions (right frontal, right temporal),  
• Assessment time (pre, intermediate, post),  
• Interaction between rTMS protocol and assessment time.  
Participants and items will be included in the models as random effects. 
The lmerTest package (Kuznetsova, Brockhoff, & Christensen, 2017) in R will be used to 
calculate the p values (alpha level at .05). 
 
4. 
REFERENCES 
 
Bates, D., Mächler, M., Bolker, B., & Walker, S. (2015). Fitting Linear Mixed-Effects Models 
Using lme4. Journal of Statistical Software, 67(1). https://doi.org/10.18637/jss.v067.i01 
Kuznetsova, A., Brockhoff, P. B., & Christensen, R. H. B. (2017). lmerTest Package: Tests in 
Linear Mixed Effects Models. Journal of Statistical Software, 82(13). 
https://doi.org/10.18637/JSS.V082.I13 
R Core Team. (2013). R: A language and environment for statistical computing. R Foundation 
for Statistical Computing, Vienna, Austria. 
Rossi, S., Antal, A., Bestmann, S., Bikson, M., Brewer, C., Brockmöller, J., … Hallett, M. 
(2021). Safety and recommendations for TMS use in healthy subjects and patient 
populations, with updates on training, ethical and regulatory issues: Expert Guidelines. 
Clinical Neurophysiology, 132(1), 269–306. https://doi.org/10.1016/j.clinph.2020.10.003 
Rossi, S., Hallett, M., Rossini, P. M., Pascual-Leone, A., Avanzini, G., Bestmann, S., … 
Ziemann, U. (2009). Safety, ethical considerations, and application guidelines for the use 
of transcranial magnetic stimulation in clinical practice and research. Clinical 
Neurophysiology, 120(12), 2008–2039. https://doi.org/10.1016/j.clinph.2009.08.016