Serotonin Modulates Early Cortical Auditory Processing in Healthy Subjects. Evidence from MEG with Acute Tryptophan Depletion

Abstract

We studied the effects of acute tryptophan depletion (ATD) on early cortical auditory processing. Middle-latency auditory evoked fields (MAEF) were investigated in 14 healthy subjects after 5 h of ATD or control mixture ingestion in a randomized, double-blinded, controlled cross-over design study. MAEFs to monaural click stimuli (0.1-ms duration) were recorded with a 122-channel neuromagnetometer. Total plasma tryptophan (Trp), free Trp, and large neutral amino acid (LNAA) concentrations were determined by using high-performance liquid chromatography. ATD lowered the total plasma Trp levels by 75%, free Trp level by 47%, and the ratio Trp/ΣLNAA by 92%. The control mixture increased total Trp level by 45% and free Trp by 32%, and decreased the ratio Trp/ΣLNAA by 35%. The ratio tyrosine/ΣLNAA did not differ between ATD and control experiment. ATD resulted in a significant main effect on Pam latencies and a near-significant main effect on Pam amplitudes. A significant Mixture ingestion X Sex interaction on Nbm amplitude and a significant Mixture ingestion X Sex X Hemisphere interaction on Pam latency were observed. ATD did not affect the MAEF source dipoles. The Pam latencies in both hemispheres had a significant negative relationship with the extent of ATD. The results suggest that the neurotransmitter serotonin is involved in early auditory cortical processing. Further, the serotonin modulation may be different in males and females.