title: Modulation of Cortical Oscillations by Low-Frequency Direct Cortical Stimulation Is State-Dependent.
abstract: Cortical oscillations play a fundamental role in organizing large-scale functional brain networks. Noninvasive brain stimulation with temporally patterned waveforms such as repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) have been proposed to modulate these oscillations. Thus, these stimulation modalities represent promising new approaches for the treatment of psychiatric illnesses in which these oscillations are impaired. However, the mechanism by which periodic brain stimulation alters endogenous oscillation dynamics is debated and appears to depend on brain state. Here, we demonstrate with a static model and a neural oscillator model that recurrent excitation in the thalamo-cortical circuit, together with recruitment of cortico-cortical connections, can explain the enhancement of oscillations by brain stimulation as a function of brain state. We then performed concurrent invasive recording and stimulation of the human cortical surface to elucidate the response of cortical oscillations to periodic stimulation and support the findings from the computational models. We found that (1) stimulation enhanced the targeted oscillation power, (2) this enhancement outlasted stimulation, and (3) the effect of stimulation depended on behavioral state. Together, our results show successful target engagement of oscillations by periodic brain stimulation and highlight the role of nonlinear interaction between endogenous network oscillations and stimulation. These mechanistic insights will contribute to the design of adaptive, more targeted stimulation paradigms.
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Sankaraleengam
authors.initials: S
authors.lastname: Alagapan
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.|UNC/NCSU Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Schmidt
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.|Department of Mathematics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Lefebvre
authors.affiliation: Department of Neurosurgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Eldad
authors.initials: E
authors.lastname: Hadar
authors.affiliation: Department of Neurosurgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.|Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Hae Won
authors.initials: HW
authors.lastname: Shin
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.|UNC/NCSU Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.|Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.|Neurobiology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.|Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.|Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Flavio
authors.initials: F
authors.lastname: Frӧhlich
mesh_terms: D001683:Biological Clocks; D058256:Brain Waves; D002540:Cerebral Cortex / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D050781:Transcranial Magnetic Stimulation