Neuroimaging-Guided TMS–EEG for Real-Time Cortical Network Mapping

The cerebral cortex is organized into structurally and functionally segregated networks, enabling the human brain to process information highly efficiently. Transcranial magnetic stimulation (TMS), in combination with electroencephalography (EEG), offers a non-invasive approach to probing brain networks, revealing cortical excitability and causal connectivity. However, this method faces two significant challenges: (a) ensuring the quality of TMS-evoked potentials (TEPs) to maximize information gain, often requiring comprehensive cortical mapping, and (b) eliciting the response from the network of interest and not from adjacent cortical sites. Existing TMS targeting approaches frequently fail to precisely stimulate functionally relevant cortical areas, hindering treatment efficacy and the identification of biomarkers. The presented protocol integrates precise cortical mapping to acquire artifact-free TEPs, enabling reliable and reproducible measurements of early TEP components. This precision improves sensitivity to subtle neurophysiological variations and strengthens correlations with clinical phenotypes, supporting biomarker discovery in neuropsychiatric disorders. The proposed protocol utilizes structural, functional, and diffusion magnetic resonance imaging (MRI) to identify cortical patches belonging to the network of interest. Anatomical parcellation, functional connectivity, and real-time tractography are applied to locate areas with strong connectivity to other brain regions associated with the target network. The resulting personalized cortical clusters define the initial stimulation targets. TMS-EEG mapping is then employed to optimize TMS parameters by localizing cortical areas with high excitability, enhancing neuronal response magnitude while reducing non-neuronal noise, including muscle artifacts, decay, and other confounding factors affecting early TMS-EEG responses. A systematic exploration of the cortical mantle is conducted, adjusting stimulation location, orientation, and intensity, with continuous data quality monitoring through real-time visualization of averaged TEPs. TMS parameters producing artifact-free responses with clearly discernible early TEP components are selected for data collection. This article introduces the neuroimaging-guided TMS-EEG mapping technique and highlights the methodological advancements and benefits achievable through its application.