Time series fMRI measures detect changes in pontine raphe following acute tryptophan depletion

Serotonin is synthesized from its precursor, tryptophan, by brainstem raphe neurons and their synaptic terminals in limbic regions. The omission of tryptophan from an Acute Tryptophan Depletion (ATD) diet transiently diminishes serotonin synthesis, alters raphe activity, and mimics symptoms of depression. Raphe functional magnetic resonance imaging (fMRI) poses challenges using signal-averaging analyses. Time-series properties of fMRI blood oxygenation level dependent (BOLD) signals may hold promise, so we analyzed raphe signals for changes with the AID diet. Eleven remitted (previously depressed) patients were awake with eyes-closed during seven-minute resting scans with 0.5 s(-1) sampling. BOLD signal time-series data were frequency-filtered using wavelet transforms, yielding three octave-width frequency bands from 0.25 to 0.03 s(-1) and an unbounded band below 0.03 s(-1). Spectral power, reflecting signal information, increased in pontine raphe at high frequencies (0.25 to 0.125 s(-1)) during AID (compared to control, balanced, diet, P<0.004) but was unchanged at other frequencies. Functional connectivity, the correlation between time-series data from pairs of regions, weakened between pontine raphe and anterior thalamus at low frequencies during AID (P<0.05). This preliminarily supports using fMRI time-series features to assess pontine raphe function. Whether, and how, high frequency activity oscillations interfere with low frequency signaling requires further study. (C) 2010 Elsevier Ireland Ltd. All rights reserved.