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<italic>Objective:</italic> Our goal was to analyze the electrophysiological response to direct electrical stimulation (DES) systematically applied at a wide range of parameters and anatomical sites, with particular focus on neural activities associated with memory and cognition. <italic>Methods:</italic> We used a large set of intracranial EEG (iEEG) recordings with DES from 45 subjects with electrodes implanted both subdurally on the cortical surface and subcortically into the brain parenchyma. Subjects were stimulated in blocks of alternating frequency and amplitude parameters during quiet wakefulness. <italic>Results:</italic> Stimulating at different frequencies and amplitudes of electric current revealed a persistent pattern of response in the slow and the fast neural activities. In particular, amplification of the theta (4&#x2013;7 Hz) and attenuation of the gamma (29&#x2013;52 Hz) power-in-band was observed with increasing the stimulation parameters. This opposite effect on the low and high frequency bands was found across a network of selected local and distal sites proportionally to the proximity and magnitude of the electric current. Power increase in the theta and decrease in the gamma band was driven by the total electric charge delivered with either increasing the frequency or amplitude of the stimulation current. This inverse effect on the theta and gamma activities was consistently observed in response to different stimulation frequencies and amplitudes. <italic>Conclusion:</italic> Our results suggest a uniform DES effect of amplifying theta and suppressing gamma neural activities in the human brain. <italic>Significance:</italic> These findings reveal the utility of simple power-in-band features for understanding and optimizing the effects of electrical stimulation on brain functions.

Direct Electrical Stimulation of the Human Brain Has Inverse Effects on the Theta and Gamma Neural Activities