Cognitive symptoms in psychiatric disorders are associated with changes in the temporal structure of brain activity. For example, altered rhythmic activity in the gamma frequency band (>30 Hz) in the cortex is implicated in psychiatric symptoms such as hallucinations, reduced sensory gating, and impaired cognitive control. Despite growing recognition of the functional roles of oscillations in cortex, the dynamics that govern the occurrence of different rhythmic activity states (i.e. cortical state dynamics) remain unknown. Since states with fast rhythms likely enhance sensory processing while states with slow rhythms disconnect cortex from sensory input during rest, understanding cortical state dynamics has broad implications for the study and treatment of cognitive symptoms in schizophrenia, autism, and attention-deficit disorder such as impaired attention and perception. The long-term goal is to understand the electrophysiological signatures and behavioral correlates of cortical state dynamics and to develop individualized brain stimulation to treat mental illness by modulating cortical state dynamics. The objective of the proposed research is to understand cortical state dynamics in response to sensory input and to modulate these dynamics with feedback stimulation using non-invasive transcranial current stimulation in humans. The central hypothesis of this work is that cortical networks exhibit spontaneous and induced transitions between slow and fast oscillatory activity states that can be controlled with non-invasive brain stimulation. In order to test this hypothesis, this work utilizes an interdisciplinary approach that integrates computer simulations, in vivo ferret electrophysiology, and non-invasive transcranial current stimulation coupled with electroen- cephalography (EEG) in healthy human subjects to pursue the following three specific aims: (1) to determine the electrophysiological substrate of cortical states during rest and sensory stimulation, (2) to identify optimal waveforms for transcranial current stimulation as a function of cortical state, an (3) to develop and evaluate feedback transcranial brain stimulation to control cortical state dynamics and modulate their behavioral correlates in humans. This work is significant because feedback brain stimulation radically differs from today's prevalent brain stimulation that utilizes generic, pre-programmed stimulation waveforms. The results of this work are intended to catalyze a paradigm shift in the treatment of mental illnesses to- wards effective, individualized brain stimulation based on rational design.
The proposed research is relevant to public health because the development of feedback brain stimulation will lead to novel, non-pharmacological treatment options for psychiatric illnesses that have the potential of higher efficacy and lower side-effect risk than current treatment options. Thus, the proposed research is relevant to the NIMH's mission to use innovative research to transform the way mental illness is treated.
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