Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans.

Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants, Banisteriopsis caapi and Psychotria viridis. It contains the psychedelic 5-HT2A and sigma-1 agonist N,N-dimethyltryptamine (DMT) plus ß-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties. Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor, the molecular target of classical psychedelics, this has not been tested experimentally. Here we wished to study the contribution of the 5-HT2A receptor to the neurophysiological and psychological effects of ayahuasca in humans. We measured drug-induced changes in spontaneous brain oscillations and subjective effects in a double-blind randomized placebo-controlled study involving the oral administration of ayahuasca (0.75mg DMT/kg body weight) and the 5-HT2A antagonist ketanserin (40mg). Twelve healthy, experienced psychedelic users (5 females) participated in four experimental sessions in which they received the following drug combinations: placebo+placebo, placebo+ayahuasca, ketanserin+placebo and ketanserin+ayahuasca. Ayahuasca induced EEG power decreases in the delta, theta and alpha frequency bands. Current density in alpha-band oscillations in parietal and occipital cortex was inversely correlated with the intensity of visual imagery induced by ayahuasca. Pretreatment with ketanserin inhibited neurophysiological modifications, reduced the correlation between alpha and visual effects, and attenuated the intensity of the subjective experience. These findings suggest that despite the chemical complexity of ayahuasca, 5-HT2A activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans.

State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect.

The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation) and between time points (before versus after training) were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression.

Inferior frontal cortex activity is modulated by reward sensitivity and performance variability.

High reward sensitivity has been linked with motivational and cognitive disorders related with prefrontal and striatal brain function during inhibitory control. However, few studies have analyzed the interaction among reward sensitivity, task performance and neural activity. Participants (N=57) underwent fMRI while performing a Go/No-go task with Frequent-go (77.5%), Infrequent-go (11.25%) and No-go (11.25%) stimuli. Task-associated activity was found in inhibition-related brain regions, with different activity patterns for right and left inferior frontal gyri (IFG): right IFG responded more strongly to No-go stimuli, while left IFG responded similarly to all infrequent stimuli. Reward sensitivity correlated with omission errors in Go trials and reaction time (RT) variability, and with increased activity in right and left IFG for No-go and Infrequent-go stimuli compared with Frequent-go. Bilateral IFG activity was associated with RT variability, with reward sensitivity mediating this association. These results suggest that reward sensitivity modulates behavior and brain function during executive control.

Characterizing individual differences in reward sensitivity from the brain networks involved in response inhibition.

A "disinhibited" cognitive profile has been proposed for individuals with high reward sensitivity, characterized by increased engagement in goal-directed responses and reduced processing of negative or unexpected cues, which impairs adequate behavioral regulation after feedback in these individuals. This pattern is manifested through deficits in inhibitory control and/or increases in RT variability. In the present work, we aimed to test whether this profile is associated with the activity of functional networks during a stop-signal task using independent component analysis (ICA). Sixty-one participants underwent fMRI while performing a stop-signal task, during which a manual response had to be inhibited. ICA was used to mainly replicate the functional networks involved in the task (Zhang and Li, 2012): two motor networks involved in the go response, the left and right fronto-parietal networks for stopping, a midline error-processing network, and the default-mode network (DMN), which was further subdivided into its anterior and posterior parts. Reward sensitivity was mainly associated with greater activity of motor networks, reduced activity in the midline network during correct stop trials and, behaviorally, increased RT variability. All these variables explained 36% of variance of the SR scores. This pattern of associations suggests that reward sensitivity involves greater motor engagement in the dominant response, more distractibility and reduced processing of salient or unexpected events, which may lead to disinhibited behavior.

How bilingualism shapes the functional architecture of the brain: A study on executive control in early bilinguals and monolinguals.

The existence of a behavioral advantage of bilinguals over monolinguals during executive tasks is controversial. A new approach to this issue is to investigate the effect of bilingualism on neural control when performing these tasks as a window to understand when behavioral differences are produced. Here, we tested if early bilinguals use more language-related networks than monolinguals while performing a go/no-go task that includes infrequent no-go and go trials. The RTs and accuracy in both groups did not differ. An independent component analyses (ICA) revealed, however, that bilinguals used the left fronto-parietal network and the salience network more than monolinguals while processing go infrequent cues and no-go cues, respectively. It was noteworthy that the modulation of these networks had opposite correlates with performance in bilinguals and monolinguals, which suggests that between-group differences were more qualitative than quantitative. Our results suggest that bilinguals may differently develop the involvement of the executive control networks that comprise the left inferior frontal gyrus during cognitive control tasks than monolinguals.

Reward sensitivity modulates brain activity in the prefrontal cortex, ACC and striatum during task switching.

Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS) sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies.

Differential neural control in early bilinguals and monolinguals during response inhibition.

We tested the hypothesis that early bilinguals and monolinguals use different brain areas when performing nonlinguistic executive control tasks. For this, we explored brain activity of early bilinguals and monolinguals during a manual stop-signal paradigm. Behaviorally, bilinguals and monolinguals did not show significant differences in the task, which led us to compare brain activation that cannot be attributed to differences in performance. Analyses demonstrated that monolinguals activated the anterior cingulate cortex more than bilinguals when performing the stop-signal task. These results offer direct support for the notion that early bilingualism exerts an effect on neural circuitry responsible for executive control. Consistent with recent reports, we found that bilinguals used the anterior cingulate more efficiently than monolinguals to monitor nonlinguistic cognitive conflicts.

A functional magnetic resonance imaging assessment of small animals' phobia using virtual reality as a stimulus.

BACKGROUND: To date, still images or videos of real animals have been used in functional magnetic resonance imaging protocols to evaluate the brain activations associated with small animals' phobia. OBJECTIVE: The objective of our study was to evaluate the brain activations associated with small animals' phobia through the use of virtual environments. This context will have the added benefit of allowing the subject to move and interact with the environment, giving the subject the illusion of being there. METHODS: We have analyzed the brain activation in a group of phobic people while they navigated in a virtual environment that included the small animals that were the object of their phobia. RESULTS: We have found brain activation mainly in the left occipital inferior lobe (P<.05 corrected, cluster size=36), related to the enhanced visual attention to the phobic stimuli; and in the superior frontal gyrus (P<.005 uncorrected, cluster size=13), which is an area that has been previously related to the feeling of self-awareness. CONCLUSIONS: In our opinion, these results demonstrate that virtual stimulus can enhance brain activations consistent with previous studies with still images, but in an environment closer to the real situation the subject would face in their daily lives.

Bilinguals use language-control brain areas more than monolinguals to perform non-linguistic switching tasks.

We tested the hypothesis that early bilinguals use language-control brain areas more than monolinguals when performing non-linguistic executive control tasks. We do so by exploring the brain activity of early bilinguals and monolinguals in a task-switching paradigm using an embedded critical trial design. Crucially, the task was designed such that the behavioural performance of the two groups was comparable, allowing then to have a safer comparison between the corresponding brain activity in the two groups. Despite the lack of behavioural differences between both groups, early bilinguals used language-control areas--such as left caudate, and left inferior and middle frontal gyri--more than monolinguals, when performing the switching task. Results offer direct support for the notion that, early bilingualism exerts an effect in the neural circuitry responsible for executive control. This effect partially involves the recruitment of brain areas involved in language control when performing domain-general executive control tasks, highlighting the cross-talk between these two domains.

Spontaneous brain activity predicts learning ability of foreign sounds.

Can learning capacity of the human brain be predicted from initial spontaneous functional connectivity (FC) between brain areas involved in a task? We combined task-related functional magnetic resonance imaging (fMRI) and resting-state fMRI (rs-fMRI) before and after training with a Hindi dental-retroflex nonnative contrast. Previous fMRI results were replicated, demonstrating that this learning recruited the left insula/frontal operculum and the left superior parietal lobe, among other areas of the brain. Crucially, resting-state FC (rs-FC) between these two areas at pretraining predicted individual differences in learning outcomes after distributed (Experiment 1) and intensive training (Experiment 2). Furthermore, this rs-FC was reduced at posttraining, a change that may also account for learning. Finally, resting-state network analyses showed that the mechanism underlying this reduction of rs-FC was mainly a transfer in intrinsic activity of the left frontal operculum/anterior insula from the left frontoparietal network to the salience network. Thus, rs-FC may contribute to predict learning ability and to understand how learning modifies the functioning of the brain. The discovery of this correspondence between initial spontaneous brain activity in task-related areas and posttraining performance opens new avenues to find predictors of learning capacities in the brain using task-related fMRI and rs-fMRI combined.

Bilateral inferior frontal language-related activation correlates with verbal recall in patients with left temporal lobe epilepsy and typical language distribution.

Language fMRI has been used in the presurgical evaluation of drug-resistant temporal lobe epilepsy patients. Previous studies have demonstrated that left temporal lobe epilepsy (LTLE) patients with atypical language lateralization are at lower risk of postsurgical verbal memory decline, hypothesizing co-occurrence of verbal memory and language reorganization presurgically. Furthermore, it has been proposed that the recruitment of right frontal language-related areas is associated with the preservation of verbal memory performance in these patients. However, less is known about the correlation between these functions specifically in LTLE patients with left language dominance, although they are more prone to postsurgical verbal memory decline. The aim of the present study was to investigate whether the relationship between verbal memory scores and frontal language activation is also observed in LTLE patients with typical language dominance. Eighteen healthy controls, 12 right temporal lobe epilepsy patients and 12 LTLE patients with typical language distribution as assessed by an fMRI verbal fluency task were selected. Verbal memory scores were obtained from the patients' neuropsychological presurgical evaluation. Our results showed a positive correlation between verbal recall and activation of bilateral inferior frontal areas in LTLE patients. These results support the hypothesis of a link between language representation in inferior frontal areas and hippocampal functioning, and indicate that both hemispheres are related to the preservation of verbal memory in patients with hippocampal damage and typical language dominance.

Frontostriatal response to set switching is moderated by reward sensitivity.

The reinforcement sensitivity theory (RST) relates individual differences in reward sensitivity to the activation of the behavioral approach system (BAS). Dopamine-related brain structures have been repeatedly associated with reward processing, but also with cognitive processes such as task switching. In the present study, we examined the association between reward sensitivity and the event-related fMRI BOLD response with set switching in 31 males. As expected, the right inferior frontal cortex (rIFG) and the striatum (i.e. the left putamen) were involved in set-switching activity for the overall sample. Interindividual differences in Gray's reward sensitivity were related to stronger activity in the rIFG and the ventral striatum. Thus, trait reward sensitivity contributed to the modulation of brain responsiveness in set-switching tasks. Having considered previous research, we propose that higher BAS activity is associated with a stronger reward to process a better implementation of goal-directed tasks and the diminished processing of secondary cues.

The sentence verification task: a reliable fMRI protocol for mapping receptive language in individual subjects.

OBJECTIVE: To test the capacity of a sentence verification (SV) task to reliably activate receptive language areas. Presurgical evaluation of language is useful in predicting postsurgical deficits in patients who are candidates for neurosurgery. Productive language tasks have been successfully elaborated, but more conflicting results have been found in receptive language mapping. MATERIALS AND METHODS: Twenty-two right-handed healthy controls made true-false semantic judgements of brief sentences presented auditorily. RESULTS: Group maps showed reliable functional activations in the frontal and temporoparietal language areas. At the individual level, the SV task showed activation located in receptive language areas in 100% of the participants with strong left-sided distributions (mean lateralisation index of 69.27). CONCLUSION: The SV task can be considered a useful tool in evaluating receptive language function in individual subjects. This study is a first step towards designing the fMRI task which may serve to presurgically map receptive language functions.