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

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.

• 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]