Grant: Discovery Launch Supplement

Excitability refers to neural reactivity to stimuli, plays a crucial role in information processing, and is disrupted in various neuropsychiatric conditions. Transcranial Magnetic Stimulation (TMS) is the primary method for assessing excitability, but it has inherent limitations regarding spatial and temporal sampling as well as depth penetration. Excitability is intricately linked to the excitation/inhibition (E/I) balance, which refers to the equilibrium between excitatory and inhibitory activity in neural circuits. Recent evidence suggests that E/I can be estimated from resting state electromagnetic and hemodynamic signals recorded with electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), respectively. Several features, such as EEG phase synchronization, entropy, exponent of the power spectrum; and fMRI amplitude of low-frequency fluctuations, spatial homogeneity, and Hurst exponent, have been linked to E/I. Nevertheless, the interplay between E/I estimates and excitability remains to be understood. Our long-term objective is to develop innovative methodologies for non-invasive, high-resolution, whole-head, and TMS-independent EEG and fMRI excitability mapping. We hypothesize that it is possible to map cortical excitability from EEG and fMRI estimates of E/I by addressing the relationship between excitability and E/I. The proposed research program in the short term aims to enhance our comprehension of cortical excitability and its relationship with E/I in the human brain. We will accomplish this with the following three specific objectives: Objective 1: To map EEG-based E/I and its relationship with excitability; Objective 2: To map fMRI-based E/I and its relationship with excitability; Objective 3: Fusion of the output of Objective 1 and 2, using advanced statistical modeling. Our research strategy relies on the controlled manipulation of cortical excitability through neuromodulation techniques, complemented by assessment of E/I and excitability using both neuroimages and TMS (Objectives 1 and 2). We will jointly model results from Objectives 1 and 2 to obtain comprehensive excitability estimates, leveraging the complementarity of EEG and fMRI (Objective 3). Impact This research has implications for comprehending brain function and offers an inclusive, cost-effective, non-invasive, and stimulus-independent approach for mapping cortical excitability with high resolution, simultaneously across superficial and deep regions. The output of this research has a translational potential, as excitability is a biomarker in neuropsychiatric conditions. Applying combined multimodal neuroimaging and brain stimulation will overcome methodological challenges. This research promotes collaborations among international experts and fosters a valuable training environment. Data, code, and procedures developed throughout this project will be made openly available, further enhancing its impact within the neuroscience community.