Event-Related Spatio-Spectral Perturbation (ERSSP): A Scalp-Wide EEG Analysis Framework for Capturing Extralemniscal Thalamocortical Activity, Validated Using a Fragile X Syndrome Model

The extralemniscal thalamocortical pathway regulates large-scale modulation of cortical states but remains inaccessible to traditional EEG analysis due to its diffuse, variable, and asynchronous nature. To address this, we introduce the Event-Related Spatio-Spectral Perturbation (ERSSP) framework, which quantifies spatially distributed time-frequency responses. ERSSP summarizes the number of channels exhibiting significant spectral perturbations, capturing diffuse cortical dynamics from sensor-space EEG. We validated this approach using a passive auditory habituation task in individuals with Fragile X Syndrome (FXS), a condition marked by disrupted thalamocortical modulation. ERSSP revealed enhanced spatial extent of power increases (but not phase-locking) in FXS compared to controls. Results also showed expected gender differences, further supporting biological sensitivity of ERSSP. ERSSP provides a conceptually simple and computationally efficient method for quantifying broadly distributed sensory modulation and may enable new insights into thalamocortical function in both basic and clinical neuroscience.