Demonstrating test-retest reliability of electrophysiological measures for healthy adults in a multisite study of biomarkers of antidepressant treatment response

Craig E. Tenkea, Jürgen Kaysera, Pia Pechtelb, Christian A. Webbb, Daniel G. Dillonb, Franziska Goerc, Laura Murrayc, Patricia Deldind, Benji T. Kuriand, Patrick J. McGratha, Ramin Parseyf, Madhukar Trivedie, Maurizio Favab,g, Myrna M. Weissmana, Melvin McInnisd, Karen Abrahama, Jorge E. Alvarengaa, Daniel M. Alschulera, Crystal Coopere, Diego A. Pizzagallib, Gerard E. Brudera

aDepartment of Psychiatry, Columbia University College of Physicians & Surgeons and New York State Psychiatric Institute, New York, NY, USA; bDepartment of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Massachusetts, USA; cCenter For Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts, USA; dDepartments of Psychology and Psychiatry, University of Michigan Health System, Ann Arbor, Michigan, USA; eDepartment of Psychiatry, UT Southwestern Medical Center, Dallas, Texas, USA; fDepartment of Psychiatry, SUNY Stony Brook, Stony Brook, New York, USA; gDepression Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts, USA

Received 2 March 2016; revised 21 April 2016; accepted 17 Aug 2016; published 20 December 2016.

Abstract

Growing evidence suggests that loudness dependency of auditory evoked potentials (LDAEP) and resting EEG alpha and theta may be biological markers for predicting response to antidepressants. In spite of this promise, little is known about the joint reliability of these markers, and thus their clinical applicability. New, standardized procedures were developed to improve the compatibility of data acquired with different EEG platforms, and used to examine test-retest reliability for the three electrophysiological measures selected for a multisite project-Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC). Thirty nine healthy controls across four clinical research sites were tested in two sessions separated by about one week. Resting EEG (eyes-open and eyes-closed conditions) was recorded and LDAEP measured using binaural tones (1000 Hz, 40 ms) at five intensities (60-100 dB SPL). Principal components analysis (PCA) of current source density (CSD) waveforms reduced volume conduction and provided reference-free measures of resting EEG alpha and N1 dipole activity to tones from auditory cortex. Low Resolution Electromagnetic Tomography (LORETA) extracted resting theta current density measures corresponding to rostral anterior cingulate (rACC), which has been implicated in treatment response. There were no significant differences in posterior alpha, N1 dipole or rACC theta across sessions. Test-retest reliability was .84 for alpha, .87 for N1 dipole, and .70 for theta rACC current density. The demonstration of good-to-excellent reliability for these measures provides a template for future EEG/ERP studies from multiple testing sites, and an important step for evaluating them as biomarkers for predicting treatment response.

Key Words: EEG, Evoked potentials, Surface Laplacian, LORETA, Biomarkers, Reliability