Spatially resolved EEG reveals theta-band network modulation following iTBS in aging and mild cognitive impairment

Neuromodulation shows promise as a general strategy for non-pharmacological intervention in a range of psychiatric and neurodegenerative brain disorders. Two major challenges in making neuromodulation methods clinically viable are (1) Assessing brain network changes induced by the stimulation, and (2) Optimizing stimulation protocols by adjusting the locations and spectral content of the stimulation. Spatially resolved electroencephalography (EEG) provides solutions to both by characterizing whole brain frequency-dependent brain electrical networks (BENs) with high spatial and temporal resolution. In this paper, we describe our novel SPatially resolved EEG Constrained with Tissue properties by Regularized Entropy (SPECTRE) method, the first to reconstruct whole-brain, high spatially and temporally resolved brain electrical networks (BENs) from standard EEG data. We apply SPECTRE to a sham-controlled transcranial magnetic stimulation (TMS) intervention in older adults spanning cognitively normal (CN) aging and mild cognitive impairment (MCI). In this pilot case series, SPECTRE detected consistent theta-band BEN changes associated with active intermittent theta-burst stimulation(iTBS) relative to sham, suggesting the potential for TMS to modulate affected deep brain regions in older adults. These preliminary results warrant replication in larger samples. This study further suggests that accelerated iTBS might function by targeting compensatory networks in MCI. SPECTRE Overall, the present results support the feasibility of using SPECTRE-enhanced EEG to track stimulation-associated network changes and motivate future work testing whether such measures can inform individualized neuromodulation protocols.