Laura Steenbergen

A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood

BACKGROUND Recent insights into the role of the human microbiota in cognitive and affective functioning have led to the hypothesis that probiotic supplementation may act as an adjuvant strategy to ameliorate or prevent depression. OBJECTIVE Heightened cognitive reactivity to normal, transient changes in sad mood is an established marker of vulnerability to depression and is considered an important target for interventions. The present study aimed to test if a multispecies probiotic containing Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58) may reduce cognitive reactivity in non-depressed individuals. DESIGN In a triple-blind, placebo-controlled, randomized, pre- and post-intervention assessment design, 20 healthy participants without current mood disorder received a 4-week probiotic food-supplement intervention with the multispecies probiotics, while 20 control participants received an inert placebo for the same period. In the pre- and post-intervention assessment, cognitive reactivity to sad mood was assessed using the revised Leiden index of depression sensitivity scale. RESULTS Compared to participants who received the placebo intervention, participants who received the 4-week multispecies probiotics intervention showed a significantly reduced overall cognitive reactivity to sad mood, which was largely accounted for by reduced rumination and aggressive thoughts. CONCLUSION These results provide the first evidence that the intake of probiotics may help reduce negative thoughts associated with sad mood. Probiotics supplementation warrants further research as a potential preventive strategy for depression.

Transcutaneous vagus nerve stimulation (tVNS) enhances response selection during action cascading processes

The ever-changing environment we are living in requires us to apply different action control strategies in order to fulfill a task goal. Indeed, when confronted with multiple response options it is fundamental to prioritize and cascade different actions. So far, very little is known about the neuromodulation of action cascading. In this study we assessed the causal role of the gamma-aminobutyric acid (GABA)-ergic and noradrenergic system in modulating the efficiency of action cascading by applying transcutaneous vagus nerve stimulation (tVNS), a new non-invasive and safe method to stimulate the vagus nerve and to increase GABA and norepinephrine concentrations in the brain. A single-blind, sham-controlled, between-group design was used to assess the effect of on-line (i.e., stimulation overlapping with the critical task) tVNS in healthy young volunteers (n=30)-on a stop-change paradigm. Results showed that active, as compared to sham stimulation, enhanced response selection functions during action cascading and led to faster responses when two actions were executed in succession. These findings provide evidence for the important role of the GABA-ergic and noradrenergic system in modulating performance in action cascading.

Tyrosine promotes cognitive flexibility: Evidence from proactive vs. reactive control during task switching performance

Tyrosine (TYR), an amino acid found in various foods, has been shown to increase dopamine (DA) levels in the brain. Recent studies have provided evidence that TYR supplementation can improve facets of cognitive control in situations with high cognitive demands. Here we investigated whether TYR promotes cognitive flexibility, a cognitive-control function that is assumed to be modulated by DA. We tested the effect of TYR on proactive vs. reactive control during task switching performance, which provides a relatively well-established diagnostic of cognitive flexibility. In a double-blind, randomized, placebo-controlled design, 22 healthy adults performed in a task-switching paradigm. Compared to a neutral placebo, TYR promoted cognitive flexibility (i.e. reduced switching costs). This finding supports the idea that TYR can facilitate cognitive flexibility by repleting cognitive resources.

Effects of Concomitant Stimulation of the GABAergic and Norepinephrine System on Inhibitory Control – A Study Using Transcutaneous Vagus Nerve Stimulation

BACKGROUND Inhibitory control processes are a central executive function. Several lines of evidence suggest that the GABAergic and the norepinephrine (NE) system modulate inhibitory control processes. Yet, the effects of conjoint increases in the GABAergic and NE system activity on inhibitory control have not been examined. OBJECTIVE/HYPOTHESIS We examine the conjoint effects of the GABA and NE system for inhibitory control. METHODS We used transcutaneous vagus nerve stimulation (tVNS), which has been shown to modulate both the GABAergic and NE system. We examine the effects of tVNS in two experimental paradigms examining different aspect of inhibitory control; i.e. a backward inhibition paradigm and a response inhibition paradigm modulating working memory load. RESULTS There were no effects of tVNS on backward inhibition processes, but on response inhibition processes. Yet, these only emerged when working memory processes were needed to control response inhibition. Compared to a sham stimulation, tVNS induced better response inhibition performance (i.e. fewer false alarms). CONCLUSIONS A concomitant modulation of the GABAergic and NE system, as induced by tVNS, affects inhibitory control processes, but only when working memory processes play an important role for inhibitory control. Even though both the GABAergic and the NE system are modulated by tVNS, the results suggest that the modulation of the NE system is most important for the emerging effects.

Tryptophan Promotes Interpersonal Trust

“Every kind of peaceful cooperation among men is primarily based on mutual trust and only secondarily on institutions such as courts of justice and police,” Albert Einstein (1950) once said. Indeed, interpersonal trust is an essential element of social life in general and an important determinant of cooperative behavior in particular (Pruitt & Kimmel, 1977; Yamagishi, 1986). After all, most people will cooperate only if they expect others to do so as well, which makes mutual trust an important precondition for establishing mutual cooperation. Pharmacological studies in rats and humans suggest that the neurotransmitter serotonin (5-HT) plays a crucial role in promoting cooperative behavior (Crockett, 2009), which can be enhanced by increasing the 5-HT level through administration of selective serotonin reuptake inhibitors (Knutson et al., 1998; Tse & Bond, 2002) and can be reduced by lowering the 5-HT level through tryptophan depletion (Crockett, Clark, & Robbins, 2009; Crockett, Clark, Tabibnia, Lieberman, & Robbins, 2008; Wood, Rilling, Sanfey, Bhagwagar, & Rogers, 2006). In the experiment reported here, for the first time, we focused on the link between 5-HT and the key precursor to cooperation: interpersonal trust. We tested whether mutual trust can be promoted by administering the food supplement L-tryptophan (TRP), the biochemical precursor of 5-HT. TRP is an essential amino acid contained in food such as fish, soybeans, eggs, and spinach. TRP supplementation is known to increase plasma TRP levels and to influence brain 5-HT synthesis (Markus, Firk, Gerhardt, Kloek, & Smolders, 2008). We expected to find an effect of TRP on interpersonal trust because the medial prefrontal cortex, the brain region associated with trust-related decisions (Delgado, Frank, & Phelps, 2005; McCabe, Houser, Ryan, Smith, & Trouard, 2001), receives serotonergic projections from neurons in the raphe nuclei, the principal source of 5-HT release in the brain. It is thus plausible, if not likely, that the activation of the medial prefrontal cortex is modulated through serotonergic projections— which we aimed to target by supplementation with TRP. Method

Two is better than one: bilingual education promotes the flexible mind

The interest in the influence of bilingualism on our daily life is constantly growing. Speaking two languages (or more) requires people to develop a flexible mindset to rapidly switch back and forth between languages. This study investigated whether and to what extent attending bilingual education benefits cognitive control. We tested two groups of Dutch high-school students who either followed regular classes in Dutch or were taught in both English and Dutch. They performed on a global–local switching paradigm that provides well-established measures of cognitive flexibility and attentional processing style. As predicted, the bilingually educated group showed smaller switching costs (i.e., greater cognitive flexibility) and a decreased global precedence effect than the regular group. Our findings support the idea that bilingual education promotes cognitive flexibility and a bias towards a more focused “scope” of attention.

γ-Aminobutyric acid (GABA) administration improves action selection processes: a randomised controlled trial

In order to accomplish a task goal, real-life environments require us to develop different action control strategies in order to rapidly react to fast-moving visual and auditory stimuli. When engaging in complex scenarios, it is essential to prioritise and cascade different actions. Recent studies have pointed to an important role of the gamma-aminobutyric acid (GABA)-ergic system in the neuromodulation of action cascading. In this study we assessed the specific causal role of the GABA-ergic system in modulating the efficiency of action cascading by administering 800 mg of synthetic GABA or 800 mg oral of microcrystalline cellulose (placebo). In a double-blind, randomised, between-group design, 30 healthy adults performed a stop-change paradigm. Results showed that the administration of GABA, compared to placebo, increased action selection when an interruption (stop) and a change towards an alternative response were required simultaneously, and when such a change had to occur after the completion of the stop process. These findings, involving the systemic administration of synthetic GABA, provide the first evidence for a possible causal role of the GABA-ergic system in modulating performance in action cascading.

Effects of l-Tyrosine on working memory and inhibitory control are determined by DRD2 genotypes: A randomized controlled trial.

l-Tyrosine (TYR), the precursor of dopamine (DA), has been shown to enhance facets of cognitive control in situations with high cognitive demands. However some previous outcomes were mixed: some studies reported significant improvements, while other did not. Given that TYR increases DA level in the brain, we investigated, in a double-blind, randomized, placebo-controlled design, whether the C957T genotypes of a functional synonymous polymorphism in the human dopamine D2 receptor (DRD2) gene (rs6277) contribute to individual differences in the reactivity to TYR administration and whether this factor predicts the magnitude of TYR-induced performance differences on inhibiting behavioral responses in a stop-signal task and working memory (WM) updating in a N-back task. Our findings show that T/T homozygotes (i.e., individuals potentially associated with lower striatal DA level) showed larger beneficial effects of TYR supplementation than C/C homozygotes (i.e., individuals potentially associated with higher striatal DA level), suggesting that genetically determined differences in DA function may explain inter-individual differences in response to TYR supplementation. These findings reinforce the idea that genetic predisposition modulates the effect of TYR in its role as cognitive enhancer.

Tryptophan supplementation modulates social behavior: A review.

Tryptophan (TRP), the precursor of serotonin (5-HT), is one of the most investigated amino-acids. TRP supplementation can increase 5-HT levels in the brain and for this reason numerous studies have investigated whether administration of TRP can positively influence social behavior that relies on serotonergic function. Here we review the available studies on TRP, to clarify if and under what circumstances TRP supplementation might modulate social behavior. TRP supplementation seems to improve control over social behavior in patients and individuals suffering from disorders or behaviors associated with dysfunctions in serotonergic functioning. In contrast, in healthy humans TRP supplementation seems to promote social behavior. Although more research is needed to disentangle and understand the relations between individual differences, TRP effectivity, 5-HT functioning, social interactions, and context, we conclude TRP can be a promising tool for modulating social behavior.

No role of beta receptors in cognitive flexibility: Evidence from a task-switching paradigm in a randomized controlled trial

There is evidence that noradrenergic coeruleo-cortical projections are involved in different forms of cognitive flexibility. So far, no studies in humans have investigated the involvement of beta receptors on task-switching performance, a well-established measure of cognitive flexibility. The present study investigated whether the administration of propranolol (a central and peripheral beta-adrenergic antagonist) affected switching costs (i.e., the increase of reaction time in task-switching trials relative to task-repetition trials). Sixteen healthy adult human subjects performed a global-local task-switching paradigm in a double-blind, within-subjects design study investigating the effects of 80mg of propranolol hydrochloride (a β1 and β2 adrenergic receptor antagonist) vs. an oral dose of microcrystalline cellulose (placebo pill). The acute administration of propranolol did not affect the size of switching costs compared to the intake of the neutral placebo. Our results, corroborated by Bayesian inference, suggest that beta receptors do not modulate cognitive flexibility as measured by task-switching performance.