Multivariate empirical mode decomposition reveals markers of Alzheimer’s Disease in the oscillatory response to transcranial magnetic stimulation

• Published in: Clinical neurophysiology Vol. 176; p. 2110756
• Main Authors: Bernardi, Davide, Casula, Elias P., Rocchi, Lorenzo, Fadiga, Luciano, Koch, Giacomo, Papo, David
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2025
• Subjects: Alzheimer’s Disease; Brain oscillations; EEG; Multivariate empirical mode decomposition; Neurology; Transcranial magnetic stimulation; ADCS - ADL; NPPT; AD; IMF; Alzheimer’s Disease; Transcranial magnetic stimulation; DLPFC; EEG; FAB; NPI; MSO; MEMD; AM; MEG; CDR; ADAS - COG; SCD; Brain oscillations; MMSE; RMT; HC; TMS; Multivariate empirical mode decomposition; TEP; Intrinsic Mode Function; Neuropsychiatric Inventory; Clinical Dementia Rating; Electroencephalography; Transcranial Magnetic Stimulation; Frontal Assessment Battery; Non-parametric permutation test; Multivariate Empirical Mode Decomposition; Amplitude Modulation; Alzheimer’s Disease Assessment Scale - Cognitive Subscale; Scalp-to-cortex Distance; TMS-evoked potential; Magnetoencephalography; Healthy Control; Alzheimer’s Disease Cooperative Study - Activities of Daily Living; Maximum Stimulator Output; Resting Motor Threshold; Dorsolateral Prefrontal Cortex; Mini-Mental State Examination
• ISSN: 1388-2457; 1872-8952; 1872-8952
• DOI: 10.1016/j.clinph.2025.2110756

To investigate EEG activity following transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex of Alzheimer’s Disease (AD) patients and control subjects using a data-driven characterization of brain oscillatory activity without prescribed frequency bands. We employed multivariate empirical mode decomposition (MEMD) to analyze the TMS-EEG response of 38 AD patients and 21 control subjects. We used the distinct features of EEG oscillatory modes to train a classification algorithm, a support vector machine. AD patients exhibited a weakened slow-frequency response. Faster oscillatory modes displayed a biphasic response pattern in controls, characterized by an early increase followed by a widespread suppression, which was reduced in AD patients. Classification achieved robust discrimination performance (85%/23% true/false positive rate). AD causes an impairment in the oscillatory response to TMS that has distinct features in different frequency ranges. These features uncovered by MEMD could serve as an effective EEG diagnostic marker. Early detection of AD requires diagnostic tools that are both effective and accessible. Combining EEG with TMS shows great promise. Our results and method enhance TMS-EEG both as a practical diagnostic tool, and as a way to further our understanding of AD pathophysiology. •New EEG markers of Alzheimer’s Disease in the response to transcranial magnetic stimulation of the dorsolateral prefrontal cortex.•Impairment in early low-frequency and late high-frequency responses observed in Alzheimer’s Disease patients.•Robust algorithmic discrimination between patients and controls based on neurobiologically interpretable markers.