Systematic Review and Meta-Analysis on the Impact of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cortical Activity - Functional Near-Infrared Spectroscopy (fNIRS) Evaluation

Background

Repetitive transcranial magnetic stimulation (rTMS) is a device that induces currents within the cerebral cortex through the generation of a magnetic field, aiming to achieve neuroregulation effects, thereby enhancing cortical excitability or inducing inhibitory effects. This technique not only locally affects cortical excitability at the stimulation site but also influences the brain regions on the opposite side through complex neural networks and reciprocal projections. Its applications are broad, primarily used for treating major depressive disorder, neuropathic pain, and post-stroke motor function recovery.

In recent years, functional near-infrared spectroscopy (fNIRS), as an optical neuroimaging method, has been used in conjunction with rTMS due to its advantages in detecting changes in cortical hemodynamic responses, aiming to evaluate and fine-tune the effects of different rTMS protocols on the cortex. However, the specific impacts of rTMS on cortical activity remain controversial. Therefore, this study aims to reveal the effects of rTMS on cortical hemodynamic responses in the primary motor cortex (M1) through a systematic review and meta-analysis.

Research Origin

This study was conducted by Shao-yu Chen, Meng-hsuan Tsou, Kuan-yu Chen, Yan-ci Liu, and Meng-ting Lin, with Yan-ci Liu and Meng-ting Lin as corresponding authors. The research is affiliated with National Taiwan University Hospital and National Taiwan University College of Medicine. The paper was published in the 2024 edition of the Journal of NeuroEngineering and Rehabilitation.

Research Methodology

Systematic Review Process

The study systematically searched the PubMed, Embase, and Scopus databases for literature related to rTMS from the inception of the databases until April 2024. Keywords included terms related to “fNIRS” or “NIRS” or “near-infrared spectroscopy” or “optical tomography” together with “rTMS” or “transcranial magnetic stimulation” and “motor cortex” or “Broca area 4” or “M1”. The screening process was independently evaluated by two medical researchers, ultimately identifying 14 articles for qualitative review and 7 articles for meta-analysis.

Inclusion Criteria

The inclusion criteria included: (1) research subjects being healthy individuals of any age or gender, with no history of neurological or psychiatric disorders; (2) applying rTMS to stimulate the M1 cortex, combined with fNIRS to evaluate cortical activity. Exclusion criteria included: (1) single-pulse TMS studies; (2) studies where the target area of stimulation was not the M1 cortex.

Risk of Bias Assessment

Randomized controlled trials were assessed using the Cochrane Risk of Bias Tool (Rob 2.0), and other observational studies were assessed using the Newcastle-Ottawa Scale (NOS). Two reviewers independently evaluated the risk of bias and reached a consensus through discussion. Any disagreements were resolved by consulting the corresponding author.

Meta-Analysis

Data such as the number of participants, means, and standard deviations were extracted from 7 studies and analyzed using RevMan software. The analyzed data included cortical hemoglobin concentrations ([Hb]), oxygenated hemoglobin concentrations ([HbO]), and deoxygenated hemoglobin concentrations ([HbD]).

Research Results

Study Characteristics

• Total Number of Studies: 312
• Finally Included: 14 (qualitative review), 7 (meta-analysis)
• Subjects: Healthy adults
• rTMS Protocols: Traditional rTMS (10 studies), quadripulse stimulation (QPS) (2 studies), theta burst stimulation (TBS) (3 studies)
• Measurement Indicators: fNIRS recorded Cerebral Blood Flow (CBF), [Hb], [HbO], and [HbD]
• Many studies recorded both online effects and post-stimulation effects; only a few studies recorded fNIRS measurements during functional tasks (e.g., finger-tapping tasks).

fNIRS Measurement Results

• Inhibitory rTMS: Low-frequency (1Hz) rTMS observed a decrease in [HbO] concentration in the ipsilateral M1 cortex, with the range extending to the contralateral cortex.
• Excitatory rTMS: Excitatory rTMS, such as high-frequency rTMS (>5Hz) and short-interval QPS (e.g., QPS-5), generally caused an increase in [HbO] concentration in the ipsilateral cortex.

Meta-Analysis Results

Meta-analysis found a trend of increased [HbO] in the contralateral cortex and decreased [HbO] in the ipsilateral cortex during low-frequency inhibitory rTMS. However, due to the high heterogeneity among the studies, further research is needed to fully understand the changes in brain activity induced by rTMS.

Discussion

Differences in Effects of High-Frequency and Low-Frequency Stimulation

Different frequencies of rTMS protocols have varying impacts on cortical excitability: low-frequency rTMS decreases cortical excitability, while high-frequency rTMS increases cortical excitability. TBS and QPS can also affect brain activity through short-term and long-term neuroplasticity.

Equipment Configuration and Potential Interference

Interference can arise between rTMS stimulation and fNIRS measurement; studies have adjusted the distance and power of the devices. These factors may introduce additional signal noise or false signals, which need special attention in data analysis.

Limitations

This study mainly includes preliminary observational studies with small sample sizes, limited fNIRS channels, and significant variation in study design and rTMS parameters, which may affect the accuracy of the results. The broad differences among these studies require cautious interpretation of the results. The high heterogeneity also indicates the need for further standardized research.

Conclusion

Despite differences in study design and parameters, the trend of increased [HbO] in the contralateral cortex and decreased [HbO] in the ipsilateral cortex during low-frequency inhibitory rTMS was consistently supported in the meta-analysis. These observations suggest dense interactions and interhemispheric regulatory effects within the cortical regions. Future research should continue to explore the mechanisms of rTMS-induced changes in brain activity to provide a theoretical foundation for neurorehabilitation.