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Original Article
Neuropsychopharmacology (2002) 27 862-868.10.1038/S0893-133X(02)00357-3

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

Seppo Kähkönen1,2, Jyrki Ahveninen2, Sirpa Pennanen3, Jyrki Liesivuori3, Risto J Ilmoniemi1 and Iiro P Jääskeläinen2,4
1BioMag Laboratory, Engineering Centre, Helsinki University Central Hospital, Helsinki, Finland
2Cognitive Brain Research Unit, Department of Psychology, University of Helsinki, Helsinki, Finland
3Department of Pharmacology and Toxicology, University of Kuopio, Helsinki, Finland
4Massachusetts General Hospital-NMR Center, Harvard Medical School, Charlestown, MA, USA

Correspondence: Seppo Kähkönen, BioMag Laboratory, Engineering Centre, Helsinki University Central Hospital, P.O. Box 340, FIN-00029 HUS, Helsinki, Finland. Tel.: +358 9 47175542; Fax: +358 9 47175781 E-mail: seppo.kahkonen@helsinki.fi

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/SigmaLNAA by 92%. The control mixture increased total Trp level by 45% and free Trp by 32%, and decreased the ratio Trp/SigmaLNAA by 35%. The ratio tyrosine/SigmaLNAA 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.

Keywords: Auditory; Event-related magnetic field; Magnetoencephalography (MEG); Middle-latency auditory magnetic field (MAEF); Serotonin; Tryptophan depletion
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