• Adrian Curtin, Shanbao Tong, Junfeng Sun, Jijun Wang, Banu Onaral, and Hasan Ayaz.
• Drexel University, School of Biomedical Engineering, Science and Health Systems, Philadelphia, PA, United States.
• Front Neurosci. 2019 Jan 1; 13: 84.

AbstractBackground: The capacity for TMS to elicit neural activity and manipulate cortical excitability has created significant expectation regarding its use in both cognitive and clinical neuroscience. However, the absence of an ability to quantify stimulation effects, particularly outside of the motor cortex, has led clinicians and researchers to pair noninvasive brain stimulation with noninvasive neuroimaging techniques. fNIRS, as an optical and wearable neuroimaging technique, is an ideal candidate for integrated use with TMS. Together, TMS+fNIRS may offer a hybrid alternative to "blind" stimulation to assess NIBS in therapy and research. Objective: In this systematic review, the current body of research into the transient and prolonged effects of TMS on fNIRS-based cortical hemodynamic measures while at rest and during tasks are discussed. Additionally, studies investigating the relation of fNIRS to measures of cortical excitability as produced by TMS-evoked Motor-Evoked-Potential (MEP) are evaluated. The aim of this review is to outline the integrated use of TMS+fNIRS and consolidate findings related to use of fNIRS to monitor changes attributed to TMS and the relationship of fNIRS to cortical excitability itself. Methods: Key terms were searched in PubMed and Web-of-Science to identify studies investigating the use of both fNIRS and TMS. Works from Google-Scholar and referenced works in identified papers were also assessed for relevance. All published experimental studies using both fNIRS and TMS techniques in the study methodology were included. Results: A combined literature search of neuroimaging and neurostimulation studies identified 53 papers detailing the joint use of fNIRS and TMS. 22/53 investigated the immediate effects of TMS at rest in the DLPFC and M1 as measured by fNIRS. 21/22 studies reported a significant effect in [HbO] for 40/54 stimulation conditions with 14 resulting an increase and 26 in a decrease. While 15/22 studies also reported [HbR], only 5/37 conditions were significant. Task effects of fNIRS+TMS were detailed in 16 studies, including 10 with clinical populations. Most studies only reported significant changes in [HbO] related measures. Studies comparing fNIRS to changes in MEP-measured cortical excitability suggest that fNIRS measures may be spatially more diffuse but share similar traits. Conclusion: This review summarizes the progress in the development of this emerging hybrid neuroimaging & neurostimulation methodology and its applications. Despite encouraging progress and novel applications, a lack of replicated works, along with highly disparate methodological approaches, highlight the need for further controlled studies. Interpretation of current research directions, technical challenges of TMS+fNIRS, and recommendations regarding future works are discussed.

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