Tuning the brain at 40 Hz: Synergistic effects of combined tACS and auditory steady-state response

Gamma oscillations are altered in several conditions such as schizophrenia, Alzheimers Disease, and Mild Cognitive Impairment. Both 40-Hz transcranial alternating current stimulation (tACS) and 40-Hz auditory steady-state stimulation can entrain gamma oscillations and improve cognitive outcomes, but their combined effects remain unclear. This study tested whether preconditioning gamma activity with tACS enhances the auditory steady-state response (ASSR) to 40-Hz auditory stimulation, reflecting a potential synergistic interaction. In a within-subject, sham-controlled design, EEG was recorded before and after 40-Hz tACS delivered over bilateral sensorimotor areas in 34 healthy participants. 40-Hz auditory stimulation was administered before and after tACS to evaluate potential changes in ASSR. Source-level gamma power was analyzed in temporal and sensorimotor regions using linear mixed-effects models. Compared to sham, real tACS increased ASSR-related gamma activity in the superior temporal gyrus, with no effects elsewhere or between hemispheres. These findings support the use of multimodal gamma entrainment to enhance neural oscillations. To conclude, combining 40-Hz tACS with auditory stimulation enhances gamma activity more than either intervention alone, supporting potential clinical applications for neuropsychiatric conditions with disrupted gamma oscillations.