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

Abstract

Serotonin is synthesized from its precursor, tryptophan, by brainstem raphé neurons and their synaptic terminals in limbic regions. The omission of tryptophan from an Acute Tryptophan Depletion (ATD) diet transiently diminishes serotonin synthesis, alters raphé activity, and mimics symptoms of depression. Raphé 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 raphé signals for changes with the ATD 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 raphé at high frequencies (0.25 to 0.125 s −1) during ATD (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 raphé and anterior thalamus at low frequencies during ATD ( P < 0.05). This preliminarily supports using fMRI time-series features to assess pontine raphé function. Whether, and how, high frequency activity oscillations interfere with low frequency signaling requires further study.