Roberta Sellaro

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.

Transcutaneous Vagal Nerve Stimulation (tVNS): a new neuromodulation tool in healthy humans?

The idea that we can influence neurons with electricity is not new. Earlier this century patients were treated, and still are, with electro convulsive therapy as a treatment for severe depression (Fink, 1984). Fortunately, new devices were invented that use electricity to influence neuronal activity in a less invasive way: transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and vagus nerve stimulation (VNS). In contrast to imaging techniques, which are only correlational, by means of these techniques it is possible to infer a causal relation between the stimulated neurotransmitter/brain area and a related cognitive function. Recently, Cerbomed (Erlangen, Germany) engineered a noninvasive, transcutaneous (through the skin) VNS device (tVNS) that stimulates the afferent auricular branch of the vagus nerve located medial of the tragus at the entry of the acoustic meatus (Kreuzer et al., 2012). This device has received CE approval as indication that it complies with essential health and safety requirements. Thus, tVNS is safe and accompanied only by minor side effects such as slight pain, burning, tingling, or itching sensation under the electrodes. Nevertheless, as specified in the instructions manual, the use of the device is contraindicated in the case of pregnancy, cardiac diseases, head trauma, alcoholism, migraine, medication or drug use, neurological or psychiatric disorders, metal pieces in the body (pacemaker), active implants such as a cochlear implant, wounds and diseased skin. A number of studies using high intensity tVNS have not found any major side-effects (Kraus et al., 2007; Dietrich et al., 2008). Given that the right vagal nerve has efferent fibers to the heart, tVNS is safe to be performed only in the left ear (Sperling et al., 2010; Kreuzer et al., 2012). Following Kraus et al. (2007), a clever way to create a sham condition using tVNS is by attaching the stimulation electrodes to the center of the left ear lobe, which is known to be free of cutaneous vagal innervation (Peuker and Filler, 2002), see Figure ​Figure1.1. Indeed, a recent functional magnetic resonance imaging (fMRI) study showed that this sham condition produced no activation in the cortex and brain stem (Kraus et al., 2013). Figure 1 Positioning of the stimulation electrodes in the active (left) and in the sham (right) condition. So far, VNS has been used to study cognitive functioning only in patients with epilepsy and major depression (Vonck et al., 2014). However, the focus of the present opinion article is not on clinical populations but on healthy humans and how tVNS may be a useful tool to further investigate the neuromodulation of cognitive processes related to norepinephrine (NE), gamma-aminobutyric acid (GABA) and Acetylcholine (ACh), the three main neurotransmitters targeted by VNS. To this end we discuss a number of NE, GABA, and ACh-related cognitive functions that could be modulated by tVNS. This is by no means an exhaustive list; the aim of this opinion article is rather to point out and highlight some theoretically driven links that may help to improve designing future tVNS studies. So far, the studies discussed below have not yet been investigated in combination with tVNS in healthy humans. However, based on literature that details their relation to NE and GABA functions we argue that these studies will prove fertile for future research.

Eating to stop: Tyrosine supplementation enhances inhibitory control but not response execution

Animal studies and research in humans have shown that the supplementation of tyrosine, or tyrosine-containing diets, increase the plasma tyrosine and enhance brain dopamine (DA). However, the strategy of administering tyrosine (and the role of DA therein) to enhance cognition is unclear and heavily debated. We studied, in a healthy population, whether tyrosine supplementation improves stopping overt responses, a core cognitive-control function. In a double-blind, placebo-controlled, within-subject design, one hour following the administration of tyrosine (corresponding to the beginning of the 1h-peak of the plasma concentration) or placebo, participants performed a stop-signal task-which taps into response inhibition and response execution speed. Participants in the Tyrosine condition were more efficient in inhibiting unwanted action tendencies but not in reacting to go signals. This is the first demonstration that the supplementation of tyrosine selectively targets, and reliably improves the ability to stop overt responses.

Working Memory Reloaded: Tyrosine Repletes Updating in the N-Back Task

In this study we tested the idea that the food supplement l-Tyrosine (TYR) repletes resources required for cognitive-control operations. We investigated whether the “updating” (and monitoring) of working memory (WM) representations, a key cognitive-control function, can be promoted by administering TYR, the biochemical precursor of dopamine. Participants performed an N-back task where we compared the WM-demanding 2-back condition with the WM-undemanding 1-back condition. As expected, TYR promoted performance in the more demanding (2-back) but not in the easier (1-back) condition, suggesting that TYR selectively targets cognitive-control operations. This result suggests that TYR can replete cognitive resources when more control is needed and, more generally, that food can act as a cognitive enhancer.

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.

Transcutaneous vagus nerve stimulation enhances post-error slowing

People tend to slow down after they commit an error, a phenomenon known as post-error slowing (PES). It has been proposed that slowing after negative feedback or unforeseen errors is linked to the activity of the locus coeruleus–norepinephrine (LC–NE) system, but there is little direct evidence for this hypothesis. Here, we assessed the causal role of the noradrenergic system in modulating PES by applying transcutaneous vagus nerve stimulation (tVNS), a new noninvasive and safe method to stimulate the vagus nerve and to increase NE concentrations in the brain. A single-blind, sham-controlled, between-group design was used to assess the effect of tVNS in healthy young volunteers (n = 40) during two cognitive tasks designed to measure PES. Results showed increased PES during active tVNS, as compared with sham stimulation. This effect was of similar magnitude for the two tasks. These findings provide evidence for an important role of the noradrenergic system in PES.

The joint Simon effect depends on perceived agency, but not intentionality, of the alternative action

A co-actors intentionality has been suggested to be a key modulating factor for joint action effects like the joint Simon effect (JSE). However, in previous studies intentionality has often been confounded with agency defined as perceiving the initiator of an action as being the causal source of the action. The aim of the present study was to disentangle the role of agency and intentionality as modulating factors of the JSE. In Experiment 1, participants performed a joint go/nogo Simon task next to a co-actor who either intentionally controlled a response button with own finger movements (agency+/intentionality+) or who passively placed the hand on a response button that moved up and down on its own as triggered by computer signals (agency−/intentionality−). In Experiment 2, we included a condition in which participants believed that the co-actor intentionally controlled the response button with a Brain-Computer Interface (BCI) while placing the response finger clearly besides the response button, so that the causal relationship between agent and action effect was perceptually disrupted (agency−/intentionality+). As a control condition, the response button was computer controlled while the co-actor placed the response finger besides the response button (agency−/intentionality−). Experiment 1 showed that the JSE is present with an intentional co-actor and causality between co-actor and action effect, but absent with an unintentional co-actor and a lack of causality between co-actor and action effect. Experiment 2 showed that the JSE is absent with an intentional co-actor, but no causality between co-actor and action effect. Our findings indicate an important role of the co-actors agency for the JSE. They also suggest that the attribution of agency has a strong perceptual basis.

The stimulated social brain: effects of transcranial direct current stimulation on social cognition

Transcranial direct current stimulation (tDCS) is an increasingly popular noninvasive neuromodulatory tool in the fields of cognitive and clinical neuroscience and psychiatry. It is an inexpensive, painless, and safe brain‐stimulation technique that has proven to be effective in modulating cognitive and sensory–perceptual functioning in healthy individuals and clinical populations. Importantly, recent findings have shown that tDCS may also be an effective and promising tool for probing the neural mechanisms of social cognition. In this review, we present the state‐of‐the‐art of the field of tDCS research in social cognition. By doing so, we aim to gather knowledge of the potential of tDCS to modulate social functioning and social decision making in healthy humans, and to inspire future research investigations.

Increasing the role of belief information in moral judgments by stimulating the right temporoparietal junction

Morality plays a vital role in our social life. A vast body of research has suggested that moral judgments rely on cognitive processes mediated by the right temporoparietal junction (rTPJ), an area thought to be involved in belief attribution. Here we assessed the role of the rTPJ in moral judgments directly by means of transcranial direct current stimulation (tDCS)--a non-invasive brain stimulation technique that, by applying a weak current to the scalp, allows modulating cortical excitability of the area being stimulated. Participants were randomly and equally assigned to receive anodal stimulation (to increase cortical excitability), cathodal stimulation (to decrease cortical excitability), or sham (placebo) stimulation over the rTPJ before completing a moral judgment task. Participants read stories in which protagonists produced either a negative or a neutral outcome based on either a negative or a neutral belief that they were causing harm or no harm, respectively. Results revealed a selective group difference when judging the moral permissibility of accidental harms (belief neutral, outcome negative), but not intentional harms (belief negative, outcome negative), attempted harms (belief negative, outcome neutral), or neutral acts (belief neutral, outcome neutral). Specifically, participants who received anodal stimulation assigned less blame to accidental harms compared to participants who received cathodal or sham stimulation. These results are consistent with previous findings showing that the degree of rTPJ activation reflects reliance on the agents innocent intention. Crucially, our findings provide direct evidence supporting the critical role of the rTPJ in mediating belief attribution for moral judgment.