The 3,4-methylenedioxymethamphetamine enhances early visual processing for salient socio-emotional stimuli.

The 3,4-methylenedioxymethamphetamine (MDMA) has long been used non-medically, and it is currently under investigation for its potential therapeutic benefits. Both uses may be related to its ability to enhance empathy, sociability, emotional processing and its anxiolytic effects. However, the neural mechanisms underlying these effects, and their specificity to MDMA compared to other stimulants, are not yet fully understood. Here, using electroencephalography (EEG), we investigated the effects of MDMA and a prototypic stimulant, methamphetamine (MA), on early visual processing of socio-emotional stimuli in an oddball emotional faces paradigm. Specifically, we examined whether MDMA or MA enhance the processing of facial expressions, compared to placebo, during the early stages of visual perception. MDMA enhanced an event-related component that is sensitive to detecting faces (N170), specifically for happy and angry expressions compared to neutral faces. MA did not affect this measure, and neither drug altered other components of the response to emotional faces. These findings provide novel insights into the neural mechanisms underlying the effects of MDMA on socio-emotional processing and may have implications for the therapeutic use of MDMA in the treatment of social anxiety and other psychiatric disorders.

Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine.

Neural complexity correlates with one's level of consciousness. During coma, anesthesia, and sleep, complexity is reduced. During altered states, including after lysergic acid diethylamide (LSD), complexity is increased. In the present analysis, we examined whether low doses of LSD (13 and 26 µg) were sufficient to increase neural complexity in the absence of altered states of consciousness. In addition, neural complexity was assessed after doses of two other drugs that significantly altered consciousness and mood: delta-9-tetrahydrocannabinol (THC; 7.5 and 15 mg) and methamphetamine (MA; 10 and 20 mg). In three separate studies (N = 73; 21, LSD; 23, THC; 29, MA), healthy volunteers received placebo or drug in a within-subjects design over three laboratory visits. During anticipated peak drug effects, resting state electroencephalography (EEG) recorded Limpel-Ziv complexity and spectral power. LSD, but not THC or MA, dose-dependently increased neural complexity. LSD also reduced delta and theta power. THC reduced, and MA increased, alpha power, primarily in frontal regions. Neural complexity was not associated with any subjective drug effect; however, LSD-induced reductions in delta and theta were associated with elation, and THC-induced reductions in alpha were associated with altered states. These data inform relationships between neural complexity, spectral power, and subjective states, demonstrating that increased neural complexity is not necessary or sufficient for altered states of consciousness. Future studies should address whether greater complexity after low doses of LSD is related to cognitive, behavioral, or therapeutic outcomes, and further examine the role of alpha desynchronization in mediating altered states of consciousness.

Lack of effect of methamphetamine on reward-related brain activity in healthy adults.

INTRODUCTION: Stimulant drugs are thought to alter processing of rewarding stimuli. However, the mechanisms by which they do this are not fully understood. METHOD: In this study we used EEG to assess effects of single doses of methamphetamine (MA) on neural responses during anticipation and receipt of reward in healthy volunteers. Healthy young men and women (N = 28) completed three sessions in which they received placebo, a low MA dose (10 mg) or a higher MA dose (20 mg) under double blind conditions. Subjective and cardiovascular measures were obtained, and EEG was used to assess brain activity during an electrophysiological version of the Monetary Incentive Delay (eMID) task. RESULTS: EEG measures showed expected patterns during anticipation and receipt of reward, and MA produced its expected effects on mood and cardiovascular function. However, MA did not affect EEG responses during either anticipation or receipt of rewards. CONCLUSIONS: These findings suggest that the effects of MA on EEG signals of reward processing are subtle, and not related to the drug's effects on subjective feelings of well-being. The findings contribute to our understanding of the neural effects of MA during behaviors related to reward.

Ketamine treatment for refractory anxiety: A systematic review.

There is a growing interest in the psychiatric properties of the dissociative anaesthetic ketamine, as single doses have been shown to have fast-acting mood-enhancing and anxiolytic effects, which persist for up to a week after the main psychoactive symptoms have diminished. Therefore, ketamine poses potential beneficial effects in patients with refractory anxiety disorders, where other conventional anxiolytics have been ineffective. Ketamine is a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) glutamate receptor, which underlies its induction of pain relief and anaesthesia. However, the role of NMDA receptors in anxiety reduction is still relatively unknown. To fill this paucity in the literature, this systematic review assesses the evidence that ketamine significantly reduces refractory anxiety and discusses to what extent this may be mediated by NMDA receptor antagonism and other receptors. We highlight the temporary nature of the anxiolytic effects and discuss the high discrepancy among the study designs regarding many fundamental factors such as administration routes, complementary treatments and other treatments.

Vicarious ratings of social touch the effect of age and autistic traits.

Tactile sensitivities are common in Autism Spectrum Conditions (autism). Psychophysically, slow, gentle stroking touch is typically rated as more pleasant than faster or slower touch. Vicarious ratings of social touch results in a similar pattern of velocity dependent hedonic ratings as directly felt touch. Here we investigated whether adults and children's vicarious ratings vary according to autism diagnosis and self-reported autistic traits. Adults' scoring high on the AQ rated stroking touch on the palm as less pleasant than a Low AQ group. However, in contrast to our hypothesis, we did not find any effect of autism diagnosis on children's touch ratings despite parental reports highlighting significant somatosensory sensitivities. These results are discussed in terms of underpinning sensory and cognitive factors.

Children's vicarious ratings of social touch are tuned to the velocity but not the location of a caress.

Affective sharing is a bottom-up process involving automatic processing of sensory inputs that facilitate vicarious experience of another's emotional state. It is grounded directly in the prior experiences of the perceiver. In adults, vicarious ratings of affective touch match the known velocity tuning and hypothesised anatomical distribution of C-tactile afferents (CT), a subclass of C-fibre which respond preferentially to low force/velocity stroking touch, typically perceived as pleasant. Given the centrality of touch to early nurturing interactions, here we examined whether primary school aged children's vicarious ratings of affective touch show the same anatomical and velocity specific patterns reported in adults. Forty-four children aged between 8 and 11 (mean age 9, 24 male) rated a sequence of video clips depicting one individual being touched by another on 5 different upper-body sites (palm, dorsal forearm, ventral forearm, upper-arm and back) at 3 different velocities (static, CT optimal, slow stroking and non-CT optimal, fast stroking). Immediately after viewing each clip, participants were asked to rate how pleasant they perceived the touch to be. While children rated the CT optimal velocity significantly higher than static or non-CT optimal touch, unlike adults their ratings did not vary across skin sites. This difference may reflect the fact children's ratings are grounded in bottom-up affective resonance while adults also draw on top-down cognitive evaluation of the broader social context when rating the stimuli.

The role of the metabotropic glutamate receptor 5 in nicotine addiction.

This review summarizes the evidence for the potential involvement of metabotropic glutamate receptor 5 (mGluR5) in the development of nicotine addiction. Nicotine is consumed worldwide and is highly addictive. Previous research has extensively investigated the role of dopamine in association with reward learning and addiction, which has provided strong evidence for the involvement of dopaminergic neuronal circuitry in nicotine addiction. More recently, researchers focused on glutamatergic transmission after nicotine abuse, and its involvement in the reinforcing and rewarding effects of nicotine addiction. A number of robust preclinical and clinical studies have shown mGluR5 signaling as a facilitating mechanism of nicotine addiction and nicotine withdrawal. Specifically, clinical studies have illustrated lower cortical mGluR5 density in smokers compared to nonsmokers in the human brain. In addition, mGluR5 might selectively regulate craving and withdrawal. This suggests that mGluR5 could be a key receptor in the development of nicotine addiction and therefore clinical trials to examine the therapeutic potential of mGluR5 agents could help to contribute to reduce nicotine addiction in society.

Autistic traits modulate cortical responses to affective but not discriminative touch.

The sense of touch is primarily considered a discriminative and exteroceptive sense, facilitating the detection, manipulation and exploration of objects, via an array of low-threshold mechanoreceptors and fast conducting A-beta (Aß) afferents. However, a class of unmyelinated, low-threshold mechanoreceptors identified in the hairy skin of mammals have been proposed to constitute a second, anatomically distinct system coding the affective qualities of touch. Unlike Aßs, which increase their firing rate linearly with the velocity of a stimulus moving across their receptive field, the response of these C-tactile afferents (CTs) is described by an inverted 'U' curve fit, responding optimally to a skin temperature stimulus moving at between 1 and 10 cm/s. Given the distinct velocity tuning of these fast and slow touch fibres, here we used event-related potentials to compare the time course of neural responses to 1st (fast) and 2nd (slow) touch systems. We identified a higher amplitude P300 in response to fast, Aß-targeted, versus slow CT-targeted, stroking touch. In contrast, we identified a previously described, C-fibre specific, ultra-late potential (ULP) associated with CT-targeted input. Of special note as regards the function of CTs is that the amplitude of the ULP was negatively correlated with self-reported levels of autistic traits, which is consistent with the hypothesized affective and social significance of this response. Taken together, these findings provide further support for distinct discriminative and affective touch systems and suggests the temporal resolution of EEG provides an as yet underutilized tool for exploring individual differences in response sensitivity to CT-targeted touch.