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overview My basic interest is in understanding how cognitive processes arise from the dynamics of neural systems. In my research I use human electrophysiology (time-frequency EEG measures and event-related brain potentials [ERPs]) and computational modeling to investigate the neural bases of sensory processing, perception, and executive control in healthy individuals as well as schizophrenia patients. I am interested in schizophrenia because it is characterized by neural circuitry abnormalities that may be manifested in particular brain oscillations, and behaviorally by various kinds of cognitive dysfunction (e.g., hallucinations, thought disorder, attention and working memory deficits). With the recent convergence of evidence concerning the neural circuit mechanisms underlying oscillations and neural circuitry abnormalities in schizophrenia, there is an excellent opportunity to testing hypotheses concerning neural circuitry and cognitive function. Bridging these domains promises to lead to new insights into the neural bases of healthy and disordered cognition and to improved treatments for schizophrenia, as well as other neuropsychiatric disorders. The work in my laboratory (http://ndl.hms.harvard.edu) on oscillatory brain dynamics in schizophrenia currently focuses on two areas: sensory-evoked and perception-related gamma (30-100 Hz) oscillations. In the area of sensory-evoked oscillations we are delineating the factors underlying the deficits in the early auditory- and visual-evoked gamma oscillations and the auditory steady-state response (ASSR) in schizophrenia. Important questions we are examining include the degree to which the deficits in these oscillations reflect intrinsic circuit abnormalities versus dysfunctional input signals to their cortical sources. For instance, the visual-evoked gamma deficit in schizophrenia might reflect the failure of top-down attentional modulation of visual cortex rather than circuit abnormalities within the visual cortex itself. We are also studying the dynamics underlying these oscillation deficits such as modulation by other ongoing rhythms, and whether these deficits involve interactions with other brain areas using source localization methods. In the area of perception-related oscillations, we discovered a gamma oscillation that is elicited by illusory visual objects and is phase-locked to individuals’ reaction times, suggesting that it indexes processes related to conscious perception. In schizophrenia patients, this response-locked oscillation (RLO) occurs at a lower frequency than in healthy individuals, and its phase-locking aspect is correlated with the patients’ visual hallucination and thought disorder ratings. A major direction of our research is to determine the functional significance of this oscillation in healthy individuals, and to understand the nature of the reduced frequency and clinical symptom correlations in individuals with schizophrenia. Finally, we are using computational models of neural circuits to examine how the microcircuit abnormalities found in neuropathological studies of schizophrenia patients may relate to the gamma abnormalities found in EEG studies. With a deeper understanding of the mechanisms of brain oscillations and their dysfunction in schizophrenia, it may be possible to design new therapeutics that target particular neural circuit abnormalities and to assess their efficacy.
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.