The main objective of this Scientist Development Award for Clinicians (SDAC) is to establish the Principal Investigator, Dr. Krystal, as an independent clinical researcher in neuropsychiatry with skill in quantitative EEG analysis. Richard D. Weiner, M.D., Ph.D., Associate Professor of Psychiatry at DUMC, Director of the DUMC ECT Program and Quantitative EEG Laboratory, and Chairman of the American Psychiatric Association Task Force on ECT will serve as Sponsor. The main objective will be met through: (1) course work in multivariate statistics, signal analysis, non-linear systems dynamics, and system modelling; (2) tutorials in research methodology, instruments for diagnosing major depression, measuring outcome of electroconvulsive therapy, clinical decision analysis, signal processing, non-linear dynamics, modeling, and quantitative EEG; (3) expert consultation; and (4) a supervised research experience. The proposed two-stage research program is designed to develop ictal electroencephalographic (EEG) markers of electroconvulsive therapy (ECT) treatment adequacy, which will allow ECT to be delivered in a safer and more effective manner. Stage I consists of 2 retrospective pilot analyses of data already collected, in which (1) a multivariate ictal EEG model of treatment adequacy based on manual ratings is developed for 2 channel data, and (2) existing 21-channel computer ictal EEG data are analyzed to determine an optimal recording electrode set for prediction of treatment adequacy. In the latter case, the electrode choice will be achieved by studying the inter-electrode relationships of ictal EEG data to choose the set of electrodes that records as much of the information available in the 21 channel data as possible, while minimizing redundancy. Stage II, building on the results of Stage I and three promising pilot studies, uses prospectively recorded ictal EEG data in depressed subjects receiving ECT to develop, refine, and test both computer derived and manually rated multivariate models of ECT seizure adequacy for their ability to predict therapeutic response. The final models will be compared for overall clinical utility taking into account simplicity, capacity for automation, and ability to predict treatment outcome.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Unknown (K20)
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Treatment Assessment Review Committee (TA)
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Duke University
Schools of Medicine
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Krystal, Andrew D; Weiner, Richard D; Dean, Margaret D et al. (2003) Comparison of seizure duration, ictal EEG, and cognitive effects of ketamine and methohexital anesthesia with ECT. J Neuropsychiatry Clin Neurosci 15:27-34
Zoldi, S M; Krystal, A; Greenside, H S (2000) Stationarity and redundancy of multichannel EEG data recorded during generalized tonic-clonic seizures. Brain Topogr 12:187-200
Krystal, A D; Dean, M D; Weiner, R D et al. (2000) ECT stimulus intensity: are present ECT devices too limited? Am J Psychiatry 157:963-7
Krystal, A D; Holsinger, T; Weiner, R D et al. (2000) Prediction of the utility of a switch from unilateral to bilateral ECT in the elderly using treatment 2 ictal EEG indices. J ECT 16:327-37
Krystal, A D; Weiner, R D; Lindahl, V et al. (2000) The development and retrospective testing of an electroencephalographic seizure quality-based stimulus dosing paradigm with ECT. J ECT 16:338-49
Krystal, A D; Watts, B V; Weiner, R D et al. (1998) The use of flumazenil in the anxious and benzodiazepine-dependent ECT patient. J ECT 14:5-14
Krystal, A D; Coffey, C E; Weiner, R D et al. (1998) Changes in seizure threshold over the course of electroconvulsive therapy affect therapeutic response and are detected by ictal EEG ratings. J Neuropsychiatry Clin Neurosci 10:178-86
Krystal, A D; Zaidman, C; Greenside, H S et al. (1997) The largest Lyapunov exponent of the EEG during ECT seizures as a measure of ECT seizure adequacy. Electroencephalogr Clin Neurophysiol 103:599-606
Krystal, A D; Coffey, C E (1997) Neuropsychiatric considerations in the use of electroconvulsive therapy. J Neuropsychiatry Clin Neurosci 9:283-92
Krystal, A D; Weiner, R D; Coffey, C E et al. (1996) Effect of ECT treatment number on the ictal EEG. Psychiatry Res 62:179-89

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