Dose-dependent power and connectivity modulation of low frequency oscillations through transcranial magnetic stimulation in non-human primates

Transcranial magnetic stimulation (TMS) is a powerful non-invasive tool for safely modulating neural activity in humans. In particular, the left dorsolateral prefrontal cortex (DLPFC) is a common target site for clinical interventions in disorders such as treatment-resistant depression. Yet, clinical trials investigating the efficacy of TMS often lack neural markers of target engagement of the DLPFC. Local field potentials (LFPs), such as prefrontal theta oscillations, have been implicated in the clinical symptoms of these disorders. However, non-invasive electroencephalography (EEG) recordings in humans are limited by their spatial resolution and challenges of interpreting EEG signals. In this study, we investigate the effects of single-pulse TMS applied to the left prefrontal cortex in non-human primates on LFPs recorded through intracranial EEG. Compared to sham TMS, the intensity of active TMS pulses scaled with LFP power changes in a 1-13 Hz range at contacts close to the stimulation site in the prefrontal cortex (e.g., caudate nucleus, anterior cingulate cortex, insular cortex) as well as contacts that were more distal (e.g., posterior cingulate cortex, temporal lobe). To test how TMS modulates connectivity between these regions, we conducted a phase-based connectivity analysis. TMS pulses initially enhanced and then disrupted connectivity at 1-13 Hz between the stimulation site and other contacts. Connectivity rebounded approximately 1500 ms post-stimulation. Only the initial enhancement in connectivity scaled with TMS intensity. Our results demonstrate a dose-dependent power modulation of low frequency LFPs across prefrontal, parietal and temporal cortical regions by single pulses. Furthermore, they show that TMS applied over the left prefrontal cortex can enhance and interrupt short- and long-range connectivity. Our study advances the understanding of the effects of TMS on brain oscillations and connectivity with direct relevance for clinical applications in neuromodulation therapies.