Toward clinical translation of TMS-EEG: an integrative review of multidimensional neurophysiological measures

Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) has emerged as a promising noninvasive approach for probing cortical reactivity and network dynamics with millisecond temporal resolution, with growing relevance for mechanistic and clinical neuroscience. However, despite rapid expansion of the field, TMS-EEG findings remain difficult to interpret because of substantial inter-individual variability and fragmentation across distinct analytical domains, including time-domain, spatially integrated, and time-frequency measures. These issues limit cross-study comparability and hinder clinical translation. In this review, we summarize the conceptual basis of TEPs, the physiological interpretation of canonical components (e.g., N15, P30), and commonly adopted analytical considerations. We further synthesize spatially integrated measures, including global and local mean field power (GMFP and LMFP), which quantify distributed cortical responses across multiple electrodes. Time-frequency indices, such as time-related spectral perturbation (TRSP) and inter-trial phase coherence (ITPC), are also reviewed to characterize TMS-induced oscillatory modulations. Drawing on the existing TMS-EEG literature in humans, we outline representative applications of these multidimensional metrics in neuropsychiatric and neurological conditions, including Alzheimer's disease, depression, epilepsy, and stroke. Finally, we discuss key methodological and translational challenges, such as stimulation-related artifacts, inter-individual variability, state-dependency of baseline oscillatory activity, and limited standardization, and highlight how these issues complicate the interpretation of TMS-EEG findings across studies and individuals. Together, this review aims to provide a structured reference framework for integrating and interpreting multidimensional TMS-EEG measures, thereby supporting more consistent understanding of the literature and informing future efforts toward harmonization and clinical translation.