F.M. van der Veen

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

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.

Serotonin and Cognitive Flexibility: Neuroimaging Studies into the Effect of Acute Tryptophan Depletion in Healthy Volunteers

Cognitive flexibility is the ability to adjust behavior to changes in the environment or task conditions. Previous research suggested that serotonin (5-HT) is involved in cognitive flexibility. Disturbed 5-HT functioning in animals, psychiatric patients and healthy volunteers leads to more rigid behavior. A well recognized method to manipulate levels of brain 5-HT is acute tryptophan depletion (ATD). This method induces a transient and reversible lowering of plasma tryptophan that has been shown to result in decreased brain 5-HT. Only recently has ATD research been combined with functional Magnetic Resonance Imaging (fMRI). In this review, we discuss recent investigations into the effect of ATD on the Blood Oxygen Level Dependent (BOLD) response during tasks that require cognitive flexibility, in healthy volunteers. Functional MRI studies have shown that ATD changes brain activation during tasks that require cognitive flexibility. It is hypothesized that ATD changes the processing of negative feedback, rather than impairing response inhibition, impairing the response to an error or the loss of cognitive control during response interference. Although the results of these studies are intriguing, they are sometimes contradictory. This could be the result of the different paradigms that have been used. Importantly, these studies strongly suggest that future multidisciplinary research should evaluate the mechanisms underlying individual differences and control for variables that have been shown to interact with the effect of ATD on cognitive flexibility and the related brain activation.

Drug-free patients with major depression show an increased electrophysiological response to valid and invalid feedback.

BACKGROUND Depressed patients are biased in their response to negative information. They have been found to show a maladaptive behavioral and aberrant electrophysiological response to negative feedback. The aim of this study was to investigate the behavioral and electrophysiological response to feedback validity in drug-free depressed patients. METHOD Fifteen drug-free in-patients with unipolar major depression disorder (MDD) and 30 demographically matched controls performed a time-estimation task in which they received valid and invalid (i.e. related and unrelated to performance) positive and negative feedback. The number of behavioral adjustments to the feedback and the feedback-related negativity (FRN) were measured. RESULTS Patients made fewer correct adjustments after valid negative feedback than controls, and their FRNs were larger. Neither patients nor controls adjusted their time estimates following invalid negative feedback. CONCLUSIONS The FRN results suggest that depressed drug-free in-patients have an atypical rostral anterior cingulate response to feedback that is independent of feedback validity. Their behavioral response to invalid negative feedback, however, is not impaired. This study confirms the notion that the behavioral responses of depressed individuals to negative feedback are context dependent.

The Effects of Acute Tryptophan Depletion on Brain Activation During Cognition and Emotional Processing in Healthy Volunteers

Acute tryptophan depletion (ATD), a method to temporarily lower central serotonin levels, has been used to study the functioning of the serotonergic system. Relatively recent studies that examined the effects of ATD on brain activation associated with cognitive and emotional processing in healthy volunteers are reviewed. An overview of the findings in healthy volunteers is important for the interpretation of the effect of ATD on brain activation in patients with an affective disorder, such as major depression. These studies show that during response control and negative feedback processing ATD modulates the BOLD response in the inferior/orbitofrontal cortex, the anterior cingulate cortex and the dorsomedial prefrontal cortex. During emotional processing, it is consistently found that ATD modulates the BOLD response in the amygdala. These brain regions also show abnormal activation in depressed patients. However, at the moment it remains unclear if the changes induced by ATD are related to decreased basal serotonin (5-HT) release or the result of other biochemical changes that are mediated by ATD. Future studies should implement methodological improvements, explore the possibilities of new promising imaging techniques and expand investigations into the effects of ATD on basal 5-HT release and other biochemical mechanisms that might be modulated by ATD.

Why don't you like me? Midfrontal theta power in response to unexpected peer rejection feedback

Abstract Social connectedness theory posits that the brain processes social rejection as a threat to survival. Recent electrophysiological evidence suggests that midfrontal theta (4–8 Hz) oscillations in the EEG provide a window on the processing of social rejection. Here we examined midfrontal theta dynamics (power and inter‐trial phase synchrony) during the processing of social evaluative feedback. We employed the Social Judgment paradigm in which 56 undergraduate women (mean age=19.67 years) were asked to communicate their expectancies about being liked vs. disliked by unknown peers. Expectancies were followed by feedback indicating social acceptance vs. rejection. Results revealed a significant increase in EEG theta power to unexpected social rejection feedback. This EEG theta response could be source‐localized to brain regions typically reported during activation of the saliency network (i.e., dorsal anterior cingulate cortex, insula, inferior frontal gyrus, frontal pole, and the supplementary motor area). Theta phase dynamics mimicked the behavior of the time‐domain averaged feedback‐related negativity (FRN) by showing stronger phase synchrony for feedback that was unexpected vs. expected. Theta phase, however, differed from the FRN by also displaying stronger phase synchrony in response to rejection vs. acceptance feedback. Together, this study highlights distinct roles for midfrontal theta power and phase synchrony in response to social evaluative feedback. Our findings contribute to the literature by showing that midfrontal theta oscillatory power is sensitive to social rejection but only when peer rejection is unexpected, and this theta response is governed by a widely distributed neural network implicated in saliency detection and conflict monitoring. HighlightsMidfrontal theta oscillatory dynamics are examined during social feedback processing.Theta power reacts most strongly to unexpected social rejection feedback.Inter‐trial theta phase synchrony is sensitive to both prediction error and rejection feedback.Source‐localization of theta power yielded the ACC as main probable source.Theta power during unexpected rejection feedback was localized to sources within the saliency network.

Thumbs up or thumbs down? Effects of neuroticism and depressive symptoms on psychophysiological responses to social evaluation in healthy students

The effects of neuroticism and depressive symptoms on psychophysiological responses in a social judgment task were examined in a sample of 101 healthy young adults. Participants performed a social judgment task in which they had to predict whether or not a virtual peer presented on a computer screen liked them. After the prediction, the actual judgment was shown, and behavioral, electrocortical, and cardiac responses to this judgment were measured. The feedback-related negativity (FRN) was largest after unexpected feedback. The largest P3 was found after the expected “like” judgments, and cardiac deceleration was largest following unexpected “do not like” judgments. Both the P3 and cardiac deceleration were affected by gender—that is, only males showed differential P3 responses to social judgments, and males showed stronger cardiac decelerations. Time–frequency analyses were performed to explore theta and delta oscillations. Theta oscillations were largest following unexpected outcomes and correlated with FRN amplitudes. Delta oscillations were largest following expected “like” judgments and correlated with P3 amplitudes. Self-reported trait neuroticism was significantly related to social evaluative predictions and cardiac reactivity to social feedback, but not to the electrocortical responses. That is, higher neuroticism scores were associated with a more negative prediction bias and with smaller cardiac responses to judgments for which a positive outcome was predicted. Depressive symptoms did not affect the behavioral and psychophysiological responses in this study. The results confirmed the differential sensitivities of various outcome measures to different psychological processes, but the found individual differences could only partly be ascribed to the collected subjective measures.

Grapheme-color synesthesia interferes with color perception in a standard Stroop task

This study examined the proposed automatic and involuntary nature of synesthetic experiences in grapheme-color synesthetes by comparing behavioral and blood-oxygen level dependent (BOLD) responses in a synesthetic and a standard version of the Stroop task. Clear interference effects in terms of slower reaction times and stronger BOLD responses in the rostral cingulate zone (RCZ) were found in synesthetes performing the synesthetic version of the Stroop task. Surprisingly, less interference was found in synesthetes compared with controls performing the standard Stroop task. This smaller interference effect, expressed as the difference in reaction time between incongruent and neutral stimuli, was explained in terms of experienced interference during the neutral condition of the Stroop task in synesthetes. This was confirmed by stronger BOLD responses in the RCZ for synesthetes specifically in the neutral condition. To the best of our knowledge, this is the first study to show different performance of synesthetes in a standard Stroop task and the presented data can be seen as strong evidence for the automatic and involuntary nature of synesthetic experiences.

Acute tryptophan depletion selectively attenuates cardiac slowing in an Eriksen flanker task

In the present study, the effects of transiently lowering central serotonin levels by means of acute tryptophan depletion on measures of cognitive flexibility were examined. Flexible behaviour was measured in an Eriksen flanker task, and cardiac and electro-cortical responses to errors and congruent and incongruent stimuli were measured. The depletion was successful in lowering tryptophan levels and, as expected, it did not affect subjective mood. Depletion did not affect performance and electro-cortical measures and selectively affected cardiac measures. Depletion attenuated cardiac slowing to incongruent flanker stimuli but did not affect cardiac responses to congruent stimuli and errors. The selective effect on cardiac responses as compared to performance and electro-cortical measures was in accordance with earlier findings, as well as the attenuation of cardiac slowing. The selective effect on the cardiac response to incongruent stimuli was unexpected. Detailed analyses showed a close connection to the earlier reported attenuation of the cardiac response to negative feedback, and the effect is explained in terms of reduced anticipation of the feedback stimulus due to enhanced punishment prediction.

Validation of the cocaine versions of the Obsessive Compulsive Drug Use Scale and the Desires for Drug Questionnaire

Abstract Background: The Obsessive Compulsive Drug Use Scale (OCDUS) and the Desires for Drug Questionnaire (DDQ) are two frequently used drug craving questionnaires. Although both heroin and cocaine versions of the questionnaires exist, only the heroin versions have been psychometrically evaluated. The present study was conducted to evaluate the psychometric qualities of the cocaine versions of the OCDUS (OCDUS-C) and DDQ (DDQ-C). Methods: Cocaine-dependent inpatients (n = 101) completed both scales as well as a Visual Analogue Craving Scale (VACS), an alternative, one-item index for assessing momentary craving. We examined the reliability (internal consistency), construct validity (factor structure), and concurrent validity (correlations among both questionnaires, the VACS, and indicators of severity of dependence). A subsample also completed the OCDUS-C and DDQ-C for a second time, one week after the initial administration to obtain a preliminary investigation of the test-retest reliability. Results: In general, both questionnaires displayed good internal consistency, test-retest reliability, and concurrent validity. Further, the construct validity of both the DDQ and OCDUS was demonstrated by means of confirmatory factor analyses showing the expected three-factor models. Conclusion: Our results indicate that the OCDUS and DDQ for cocaine are both easy to administer and reliable instruments to assist the clinical practitioner or researcher to measure craving in cocaine dependent subjects. Moreover, the factor structure for the cocaine versions were similar to the heroin versions, indicating the OCDUS and the DDQ can be reliably used to measure craving for both substances, enabling a direct comparison between heroin and cocaine craving.