Acute tryptophan depletion attenuates brain-heart coupling following external feedback

Abstract

External and internal performance feedback triggers neural and visceral modulations such as reactions in the medial prefrontal cortex and insulae or changes of heart period (HP). The functional coupling of neural and cardiac responses following feedback (cortico-cardiac connectivity) is not well understood. While linear time-lagged within-subjects correlations of single-trial EEG and HP (cardio-electroencephalographic covariance tracing, CECT) indicate a robust negative coupling of EEG magnitude 300 ms after presentation of an external feedback stimulus with subsequent alterations of heart period (the so-called N300H phenomenon), the neurotransmitter systems underlying feedback-evoked cortico-cardiac connectivity are largely unknown. Because it has been shown that acute tryptophan depletion (ATD), attenuating brain serotonin (5-HT), decreases cardiac but not neural correlates of feedback processing, we hypothesized that 5-HT may be involved in feedback-evoked cortico-cardiac connectivity. In a placebo-controlled double-blind cross-over design, 12 healthy male participants received a tryptophan-free amino-acid drink at one session (TRP−) and a balanced amino-acid control-drink (TRP+) on another and twice performed a time-estimation task with feedback presented after each trial. N300H magnitude and plasma tryptophan levels were assessed. Results indicated a robust N300H after TRP+, which was significantly attenuated following TRP−. Moreover, plasma tryptophan levels during TRP+ were correlated with N300H amplitude such that individuals with lower tryptophan levels showed reduced N300H. Together, these findings indicate that 5-HT is important for feedback-induced covariation of cortical and cardiac activity. Because individual differences in anxiety have previously been linked to 5-HT, cortico-cardiac coupling and feedback processing, the present findings may be particularly relevant for futures studies on the relationship between 5-HT and anxiety.

Panic Disorder and Serotonin Reuptake Inhibitors Predict Coupling of Cortical and Cardiac Activity

“…Because by blocking the reuptake of 5-HT, SRIs induce an increase in extrasynaptic 5-HT availability, the potentially SRI-induced elevation of N300H converges with (a) the general involvement of 5-HT in central control of the heart (Jordan, 2005) and (b) prior findings of a positive relationship between 5-HT and N300H (Mueller et al, 2012;Mueller et al, 2013). Moreover, the effect of SRIs on brain-heart coupling may explain altered heart rate variability in humans with long-term SRI treatments (Licht et al, 2010) and potentiated cardiovascular responses to acute stress in rats with chronic fluoxetine administration (Grippo et al, 2006).…”

“…CECTs were computed as in prior studies (Mueller et al, 2012;Mueller et al, 2013;Mueller et al, 2010;Panitz et al, 2013). To allow CECT computation across the 350-420 trials available for analysis per individual after artifact screening, EEG segments were divided into 50 bins of 15.625 ms each, ranging from 0 ms (stimulus onset) to 781.25 ms. HP segments were divided into 10 bins of 500 ms, ranging from 0-5 s. Next, CECTs were computed by correlating (Pearson's r) each EEG bin with each HP bin across trials within subjects, resulting in a 10 Â 50 cross-correlation CECT matrix.…”

“…Finally, there is evidence for a prominent role of serotonin (5-HT) in both, brain-heart communication (Jordan, 2005;Mueller et al, 2012;Mueller et al, 2013) and PD (Neumeister et al, 2004). Because serotonin reuptake inhibitors (SRIs) are commonly prescribed for PD and MD, we tested whether current SRI intake correlates with N300H.…”

“…The CECT method assesses time-lagged within-subject covariation of evoked single-trial EEG and heart period (HP) after an external stimulus. CECTs recently demonstrated that centromedial brain activity 300 ms after presentation of motivationally meaningful stimuli (eg, win/loss feedback in gambling tasks) predicts subsequent HP alterations (Mueller et al, 2012;Mueller et al, 2013;Mueller et al, 2010): the larger the EEG amplitude at this latency, the shorter the HP (ie, more acceleration) at subsequent beats. This phenomenon has been labeled 'N300H' to indicate a negative (N) association between EEG amplitude at 300 ms and HP.…”

“…Because serotonin reuptake inhibitors (SRIs) are commonly prescribed for PD and MD, we tested whether current SRI intake correlates with N300H. As both, pharmacological (Mueller et al, 2012) and genetically driven reductions of 5-HT signaling (David et al, 2005;Mueller et al, 2013), attenuate N300H, we expected that SRIs, by increasing 5-HT availability should elevate N300H.…”