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Effects of Dextromethorphan/Quinidine on Auditory Event-Related Potentials in Multiple Sclerosis Patients With Pseudobulbar Affect

Haiman, Guy MSc*†‡; Pratt, Hillel PhD†‡; Miller, Ariel MD, PhD*‡

Journal of Clinical Psychopharmacology: October 2009 - Volume 29 - Issue 5 - p 444-452
doi: 10.1097/JCP.0b013e3181b5ae5c
Original Contributions
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The purpose of this study was to characterize the brain activity and associated cortical structures involved in pseudobulbar affect (PBA), a condition characterized by uncontrollable episodes of laughing and/or crying in patients with multiple sclerosis before and after treatment with dextromethorphan/quinidine (DM/Q).

Behavioral responses and event-related potentials (ERPs) in response to subjectively significant and neutral verbal stimuli were recorded from 2 groups: 6 multiple sclerosis patients with PBA before (PBA-preTx) and after (PBA-DM/Q) treatment with DM/Q and 6 healthy control (HC) subjects. Statistical nonparametric mapping comparisons of ERP source current density distributions between groups were conducted for subjectively significant and neutral stimuli separately before and after treatment with DM/Q. Treatment with DM/Q had a normalizing effect on the behavioral responses of PBA patients. Event-related potential waveform comparisons of PBA-preTx and PBA-DM/Q with HC, for both neutral and subjectively significant stimuli, revealed effects on early ERP components. Comparisons between PBA-preTx and HC, in response to subjectively significant stimuli, revealed both early and late effects. Source analysis comparisons between PBA-preTx and PBA-DM/Q indicated distinct activations in areas involved in emotional processing and high-level and associative visual processing in response to neutral stimuli and in areas involved in emotional, somatosensory, primary, and premotor processing in response to subjectively significant stimuli. In most cases, stimuli evoked higher current density in PBA-DM/Q compared with the other groups. In conclusion, differences in brain activity were observed before and after medication. Also, DM/Q administration resulted in normalization of behavioral and electrophysiological measures.

From the *Department of Neurology, Multiple Sclerosis and Brain Research Center, Carmel Medical Center; †Evoked Potentials Laboratory, and ‡Rappaport Family Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.

Received December 1, 2008; accepted after revision July 1, 2009.

Reprints: Guy Haiman, MSc, Evoked Potentials Laboratory, Gutwirth Building, Technion-Israel Institute of Technology, Haifa, 32000, Israel (e-mail: guyhaiman@gmail.com); or Ariel Miller, MD, PhD, Department of Neurology, Multiple Sclerosis & Brain Research Center, Carmel Medical Center; Technion, Haifa 34362, Israel (email: millera@tx.technion.ac.il).

This research was partially supported by the Eli and Yona Sternheim Research Fund, the Rappaport Institute for Research in the Medical Sciences, and the V.P.R. fund of the Technion-Israel Institute of Technology, Haifa, Israel.

© 2009 Lippincott Williams & Wilkins, Inc.