Elsevier

NeuroImage

Volume 32, Issue 1, 1 August 2006, Pages 248-255
NeuroImage

Acute tryptophan depletion improves performance and modulates the BOLD response during a Stroop task in healthy females

https://doi.org/10.1016/j.neuroimage.2006.03.026Get rights and content

Abstract

To gain more insight into the effect of low brain serotonin (5-HT) on brain activation related to conflict, the present study examined the effect of acute tryptophan depletion (ATD) on performance and the blood oxygen level dependent (BOLD) response during a combined cognitive and emotional Stroop task. Fifteen healthy female volunteers were tested during a placebo and tryptophan depletion session in an event-related fMRI design. ATD improved performance during Stroop interference. Two effects of ATD on the BOLD response were found. Firstly, ATD increased the BOLD response in the anterior cingulate cortex (ACC) (BA 32) when incongruent color words were compared with congruent color words in the first Stroop block the participants performed. Secondly, ATD increased the BOLD response in the left precuneus (BA 31) and cuneus (BA 18) during congruent color words. ATD did not affect the BOLD response accompanying emotional stimuli. However, we showed that ATD increased the interference of negative words on color naming. This finding was explained in terms of an emotional processing bias in favor of negative words, which leads to stronger interference of these words. In line with previous studies, the present study showed that a temporary reduction of 5-HT improved Stroop performance and changed the underlying brain activation pattern in healthy female participants. Moreover, we replicated our previous finding that ATD modulated the BOLD response in the dorsomedial prefrontal cortex during tasks that require cognitive control.

Introduction

Acute tryptophan depletion (ATD) has been used as a model to study the effects of reduced central 5-HT (Nishizawa et al., 1997, Williams et al., 1999, Young et al., 1999) on cognitive performance and brain activation. In a previous study, our group showed that ATD increased the response in the dorsomedial prefrontal cortex (dmPFC) to negative feedback preceding a switch in response strategy (Evers et al., 2005). Activation in the dmPFC associated with negative feedback has been related to performance monitoring and cognitive control (see Ridderinkhof et al., 2004 for a review). According to one theory (Holroyd and Coles, 2002), the dmPFC response to negative feedback is linked to phasic changes in the midbrain dopamine system related to outcomes that are worse than expected. According to a second theory, dmPFC activation is related to conflict monitoring which becomes necessary when two competing response tendencies become active at the same time (Botvinick et al., 2004). In our previous study (Evers et al., 2005), it was unclear whether the dmPFC response to negative feedback was associated with an outcome that was worse than expected or conflict monitoring. Therefore, the present study examined brain responses to conflict in the absence of negative outcome. This was done in a combined cognitive and emotional Stroop task.

The studies examining the effects of ATD on performance in a Stroop task have been inconclusive thus far. Some studies reported improved performance (Coull et al., 1995, Rosse et al., 1992, Rowley et al., 1997, Schmitt et al., 2000), whereas other studies did not show an effect of ATD on Stroop performance (Gallagher et al., 2003, Horacek et al., 2005, Sobczak et al., 2002). Horacek et al. (2005) showed that ATD increased the blood oxygen level dependent (BOLD) response in the left bilateral mediofrontal, anterior cingulate and dorsolateral prefrontal cortex during Stroop performance in healthy volunteers. A problem with this study is that performance was measured outside the MRI scanner. It is therefore not possible to judge whether the participants carried out the task correctly during scanning. The current study used an event-related design to study the effect of ATD on the BOLD response during Stroop interference. Performance and the BOLD signal were recorded simultaneously.

5-HT has also been related to emotional processing. Previous studies revealed that ATD impaired the processing of positive information in healthy volunteers (Murphy et al., 2002) and remitted depressed patients (Booij et al., 2005). However, Booij et al. (2005) showed no effect of ATD on reaction times (RTs) and interference scores during an emotional Stroop task in currently depressed patients. In general, participants experience more interference from negative than from positive or neutral words (e.g. McKenna and Sharma, 1995) which can be explained by the higher threat caused by negative events in daily live (Mandler, 1975, Oatley and Johnson-Laird, 1987). Compton et al. (2003) showed that ignoring negative versus neutral words activated the bilateral occipito-temporal cortex and decreased the activation in the amygdala. Whalen et al. (1998) reported greater activation in the anterior cingulate cortex (ACC) for negative versus neutral words. However, Compton et al. (2003) did not find brain activation differences between positive and neutral words. To our knowledge, the present study is the first study examining the effect of ATD on the BOLD response during an emotional Stroop task.

To study the effect of ATD on cognitive Stroop interference and interference by emotional words, we designed a combined Stroop task in which congruent color (CC), incongruent color (IC), neutral (e.g. house, bean, coin), positive (e.g. proud, friend, smart) and negative (e.g. murder, bitch, death) words were presented in a semi-randomized order. Based on the studies discussed above, we hypothesized that (i) IC words cause more interference than CC words, (ii) IC words are associated with an increased BOLD response in the ACC, inferior parietal cortex, inferior frontal junction and middle frontal cortex (Laird et al., 2005) and (iii) ATD does not change or decreases Stroop interference and modulates the related BOLD response. With regard to the emotional Stroop part, we hypothesized that (i) RTs are higher for negative than for positive or neutral words because of the higher threat caused by negative events, (ii) the medial PFC, ACC and insula are activated during emotional words (for a review, see Phan et al., 2002) and (iii) ATD impairs performance on emotional words and affects the related brain activation.

Section snippets

Participants

Nineteen healthy female volunteers (aged between 19 and 33; mean age 22.3; SE of mean 0.7), mostly pregraduate students, were included in this study, which was approved by the Medical Ethics Committee of Maastricht University Hospital. Participants were recruited by local advertisements. The health status of the participants was checked by a medical questionnaire, which was evaluated by a medical doctor. The participants received no medication at the moment of inclusion, had never used

Results

Fifteen volunteers were successfully tested. Of the original 19 included volunteers, two dropped out after the first session because of nausea and vomiting, one volunteer panicked in the scanner, and imaging data for one participant were lost due to technical problems. Nine participants started in the BAL condition and six started in the TRP− condition.

Discussion

The present study investigated the effect of ATD on performance and the BOLD response during a combined cognitive and emotional Stroop task. In the cognitive part of the Stroop task, we showed first that ATD increased the BOLD signal in the ACC when IC words were compared with CC words in the first block of the Stroop task. Secondly, ATD increased the BOLD response in the left precuneus (BA 31) and cuneus (BA 18) during CC words. At the behavioral level, ATD decreased the interference score for

Acknowledgments

We thank Olga Reneerkens for test and analysis assistance and Jeroen van Deursen for radiographic assistance. This work was supported by a TOP grant (No. 912-02-050) from ZonMW-NWO and a grant from the Dutch Brain Foundation (Hersenstichting Nederland, 11F03(2).41).

References (39)

  • J.T. Coull et al.

    Differential effects of clonidine, haloperidol, diazepam and tryptophan depletion on focused attention and attentional search

    Psychopharmacology (Berlin)

    (1995)
  • E.A. Evers et al.

    Serotonergic modulation of prefrontal cortex during negative feedback in probabilistic reversal learning

    Neuropsychopharmacology

    (2005)
  • P. Gallagher et al.

    Effects of acute tryptophan depletion on executive function in healthy volunteers

    BMC Psychiatry

    (2003)
  • K. Gegenfurtner et al.

    Color vision

    Annu. Rev. Neurosci.

    (2003)
  • C.J. Harmer et al.

    Tryptophan depletion decreases the recognition of fear in female volunteers

    Psychopharmacology (Berlin)

    (2003)
  • C.B. Holroyd et al.

    The neural basis of human error processing: reinforcement learning, dopamine, and the error-related negativity

    Psychol. Rev.

    (2002)
  • J. Horacek et al.

    The effect of tryptophan depletion on brain activation measured by fMRI during the Stroop test in healthy volunteers

    Physiol. Res.

    (2005)
  • J. Kerns et al.

    Anterior cingulate conflict monitoring and adjustments in control

    Science

    (2004)
  • A.R. Laird et al.

    A comparison of label-based review and ALE meta-analysis in the Stroop task

    Hum. Brain Mapp.

    (2005)
  • Cited by (62)

    • Does chronic use of amphetamine-type stimulants impair interference control? – A meta-analysis

      2023, Neuroscience and Biobehavioral Reviews
      Citation Excerpt :

      Yet still, studies investigating the relationship between interference control and ATS are still rather few and partly inconsistent. On the one hand, different studies suggest that interference control is impaired in ATS users, as compared to healthy controls (Farhadian et al., 2017; Ghavidel et al., 2020a; Nestor et al., 2011; Salo et al., 2009c; Sim et al., 2002), but there are also several studies that found no differences between non-users and ATS users (including Back-Madruga et al., 2003; Chang et al., 2005; Dafters, 2006a; Halpern et al., 2011; Wagner et al., 2013), or after long-term abstinence (Benitez-López et al., 2019; Bensmann et al., 2019a; Reneman et al., 2006b). For example, some studies show that cognitive inhibition does not differ between chronic MDMA users and non-users (Dafters, 2006a), or that AMPH users do not show changes in interference control at baseline after six months of abstinence (Benitez-López et al., 2019).

    • The role of serotonin in performance monitoring and cognitive control

      2020, Handbook of Behavioral Neuroscience
      Citation Excerpt :

      With regard to neural markers of response inhibition, serotonergic manipulations were consistently found to affect signals specifically originating from the right lateral frontal cortex, which is known to be involved in behavioral inhibition. This was shown for BOLD responses (Del-Ben et al., 2005; Drueke et al., 2013, 2009; Evers et al., 2006; Macoveanu et al., 2013; Rubia et al., 2005), the lateralized EEG inhibitory N2 (Fischer et al., 2015a), as well as its MEG equivalent (Hughes et al., 2015). In this context, many human tasks may not be sensitive enough to measure inhibitory failures following a subtle challenge of the serotonergic system, whereas reaction times following events that require exerted inhibition appear to be a more sensitive measure.

    • Bright ambient light conditions reduce the effect of tryptophan depletion in healthy females

      2013, Psychiatry Research
      Citation Excerpt :

      We did not include a placebo condition in our study design. However, the biological and behavioral effects of TD have been described in a number of studies and appear to be well-established (Neumeister et al., 2002; Evers et al., 2006; aan het Rot et al., 2008). Further, we were able to include only a small sample number into the two bright light conditions.

    View all citing articles on Scopus
    View full text