Transcranial magnetic vs intracranial electric stimulation: a direct comparison of their effects via scalp EEG recordings

• Published in: Brain stimulation Vol. 18; no. 5; pp. 1444 - 1454
• Main Authors: Comolatti, Renzo, Hassan, Gabriel, Mikulan, Ezequiel, Russo, Simone, Colombo, Michele A., Litterio, Elisabetta, Furregoni, Giulia, D'Ambrosio, Sasha, Fecchio, Matteo, Parmigiani, Sara, Sartori, Ivana, Casarotto, Silvia, Pigorini, Andrea, Massimini, Marcello
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2025; Elsevier
• Subjects: Complexity; e-field simulation; EEG; intracranial electrical stimulation; Neuronal bistability; Sleep; Transcranial magnetic stimulation; Transcranial magnetic stimulation; Sleep; EEG; Neuronal bistability; intracranial electrical stimulation; e-field simulation; Complexity
• ISSN: 1935-861X; 1876-4754; 1876-4754
• DOI: 10.1016/j.brs.2025.07.016

Single-pulse Transcranial Magnetic Stimulation (TMS) and Intracranial Electrical Stimulation (IES) are widely used to probe cortical excitability and connectivity, but their electrophysiological effects have never been compared. This study aims to fill this gap by using high-density scalp electroencephalogram (hd-EEG) as a common read-out to compare human brain responses to TMS and IES. The dataset includes TMS-evoked potentials (TEPs) acquired from healthy subjects (n = 22) and IES-evoked potentials (IEPs) recorded from drug-resistant epileptic patients (n = 31) during wakefulness. In a subset of subjects TEPs (n = 12) and IEPs (n = 13) were also recorded during NREM sleep. Amplitude, spectral, and spatiotemporal features of TMS and IES responses, as well as their estimated electrical fields, were compared. We observed marked differences between TMS and IES responses. During wakefulness, IEPs are considerably larger, slower and associated with a suppression of cortical activity, whereas TEPs are characterized by multiple waves of recurrent activation. These differences are attenuated in NREM, during which both TMS and IES elicit large EEG responses associated with a prominent suppression of cortical activity. At the global level, the spatiotemporal complexity of the responses to both TMS and IES decreases consistently following the transition from wakefulness to NREM sleep. Despite the limitations due to different subject populations (healthy vs pathological), our findings provide a first reference to parallel non-invasive and invasive brain stimulation and to interpret their differential effects. They also offer important insight on how cortical responsiveness is shaped by inhibition and adaptation mechanisms depending on input parameters and brain states. •IES evokes higher signal-to-noise EEG responses than TMS.•IES responses are larger, slower, and lead to cortical suppression.•TMS elicits faster recurrent waves, with no suppression during wakefulness.•Both TMS and IES converge to similar patterns during NREM sleep.