Phase synchronized 6 Hz transcranial electric and magnetic stimulation boosts frontal theta activity and enhances working memory.

Network-level synchronization of theta oscillations in the cerebral cortex is linked to many vital cognitive functions across daily life, such as executive functions or regulation of arousal and consciousness. However, while neuroimaging has uncovered the ubiquitous functional relevance of theta rhythms in cognition, there remains a limited set of techniques for externally enhancing and stabilizing theta in the human brain non-invasively. Here, we developed and employed a new phase-synchronized low-intensity electric and magnetic stimulation technique to induce and stabilize narrowband 6-Hz theta oscillations in a group of healthy human adult participants, and then demonstrated how this technique also enhances cognitive processing by assaying working memory. Our findings demonstrate a technological advancement of brain stimulation methods, while also validating the causal link between theta activity and concurrent cognitive behavior, which may ultimately help to not only explain mechanisms, but offer perspectives for restoring deficient theta-band network activity observed in neuropsychiatric diseases.

External induction and stabilization of brain oscillations in the human.

BACKGROUND: Neural oscillations in the cerebral cortex are associated with a range of cognitive processes and neuropsychiatric disorders. However, non-invasively modulating oscillatory activity remains technically challenging, due to limited strength, duration, or non-synchronization of stimulation waveforms with endogenous rhythms. OBJECTIVE: We hypothesized that applying controllable phase-synchronized repetitive transcranial magnetic stimulation pulses (rTMS) with alternating currents (tACS) may induce and stabilize neuro-oscillatory resting-state activity at targeted frequencies. METHODS: Using a novel circuit to precisely synchronize rTMS pulses with phase of tACS, we empirically tested whether combined, 10-Hz prefrontal bilateral stimulation could induce and stabilize 10-Hz oscillations in the bilateral prefrontal cortex (PFC). 25 healthy participants took part in a repeated-measures design. Whole-brain resting-state EEG in eyes-open (EO) and eyes-closed (EC) was recorded before (baseline), immediately (1-min), and 15- and 30-min after stimulation. Bilateral, phase-synchronized rTMS aligned to the positive tACS peak was compared with rTMS at tACS trough, with bilateral tACS or rTMS on its own, and to sham. RESULTS: 10-Hz resting-state PFC power increased significantly with peak-synchronized rTMS + tACS (EO: 44.64%, EC: 46.30%, p < 0.05) compared to each stimulation protocol on its own, and sham, with effects spanning between prefrontal and parietal regions and sustaining throughout 30-min. No effects were observed with the sham protocol. Moreover, rTMS timed to the negative tACS trough did not induce local or global changes in oscillations. CONCLUSION: Phase-synchronizing rTMS with tACS may be a viable approach for inducing and stabilizing neuro-oscillatory activity, particularly in scenarios where endogenous oscillatory tone is attenuated, such as disorders of consciousness or major depression.