Potential risk groups and psychological, psychosocial, and health behavioral predictors of pharmacological neuroenhancement among university students in Germany.

Aiming to develop and implement intervention strategies targeting pharmacological neuroenhancement (PN) among university students more specifically, we (1) assessed the prevalence of PN among German university students, (2) identified potential sociodemographic and study-related risk groups, and (3) investigated sociodemographic, psychological, study-related psychosocial, general psychosocial and health behavior related factors predicting the 12-month prevalence of PN. Therefore, a cross-sectional online survey was administered to students of the University of Mainz, Germany. A binary logistic regression with stepwise inclusion of the five variable groups was performed to predict PN. A total number of 4351 students out of 31,213 registered students (13.9%) participated in the survey, of which N = 3984 answered the question concerning PN. Of these, 10.4% had used one substance for PN at least once in the past 12 months. The regression analysis revealed 13 variables that were significantly related to the 12-month prevalence of PN. Specifically, the group of health behavior related variables showed the strongest relationship with PN. Therefore, an approach to the prevention of PN should be multifactorial so that it addresses social conditions, as well as education on substance use and healthy behaviors in terms of non-pharmacological strategies as alternatives of PN.

Broadening Your Mind to Include Others: The relationship between serotonergic psychedelic experiences and maladaptive narcissism.

RATIONALE: Recent research has shown that classical serotonergic psychedelic (CSP) drugs may be used to ameliorate certain health issues and disorders. Here we hypothesised that CSP experiences, through their ability to induce awe and ego-dissolution, may result in a reduction of maladaptive narcissistic personality traits, such as a strong sense of entitlement and lack of empathy. OBJECTIVES: Our objective was to investigate whether high levels of awe and ego dissolution during recent CSP experiences are associated with currently lower levels of maladaptive narcissism. METHODS: In this pre-registered high-powered (N = 414) study, we used an online retrospective survey asking participants to describe their 'most awe-inspiring, impressive, significant, or emotionally intense experience', as well as several validated scales to test our hypothesis. RESULTS: A statistically significant mediation model indicated that recent CSP-induced experiences were associated with currently increased feelings of connectedness and affective empathetic drive, which in turn were associated with decreased exploitative-entitled narcissism. This relationship held even when taking into account sensation-seeking personality features. We found no evidence for feelings of ego dissolution to have the same effect. CONCLUSIONS: Feelings of awe, but not ego dissolution, during recent CSP experiences were associated with increased feelings of connectedness and empathy, which in turn were associated with decreased levels of maladaptive narcissism personality features. This suggests that CSPs hold therapeutic potential for disorders involving connectedness and empathy, such as the treatment of pathological narcissism, and that the induction of connectedness through awe appears to be the driving force behind this potential.

Percolating ideas: The effects of caffeine on creative thinking and problem solving.

Caffeine is the most widely consumed psychotropic drug in the world, with numerous studies documenting the effects of caffeine on people's alertness, vigilance, mood, concentration, and attentional focus. The effects of caffeine on creative thinking, however, remain unknown. In a randomized placebo-controlled between-subject double-blind design the present study investigated the effect of moderate caffeine consumption on creative problem solving (i.e., convergent thinking) and creative idea generation (i.e., divergent thinking). We found that participants who consumed 200 mg of caffeine (approximately one 12 oz cup of coffee, n = 44), compared to those in the placebo condition (n = 44), showed significantly enhanced problem-solving abilities. Caffeine had no significant effects on creative generation or on working memory. The effects remained after controlling for participants' caffeine expectancies, whether they believed they consumed caffeine or a placebo, and changes in mood. Possible mechanisms and future directions are discussed.

Methylphenidate does not affect convergent and divergent creative processes in healthy adults.

An increasing number of healthy people use methylphenidate, a psychostimulant that increases dopamine and noradrenaline transmission in the brain, to help them focus over extended periods of time. While methylphenidate has been shown to facilitate some cognitive functions, like focus and distractor-resistance, the same drug might also contribute to cognitive impairment, for example, in creativity. In this study, we investigated whether acute administration of a low oral dose (20 mg) of methylphenidate affected convergent and divergent creative processes in a sample of young healthy participants. Also, we explored whether such effects depended on individual differences in ADHD symptoms and working memory capacity. Contrary to our expectations, methylphenidate did not affect participants' creative performance on any of the tasks. Also, methylphenidate effects did not depend on individual differences in trait hyperactivity-impulsivity or baseline working memory capacity. Thus, although the effects of methylphenidate on creativity might be underestimated in our study due to several methodological factors, our findings do not suggest that methylphenidate impairs people's ability to be creative.

Cocaine enhances figural, but impairs verbal 'flexible' divergent thinking.

Anecdotal evidence suggests that cocaine use will help overcome creative 'blocks' by enhancing flexible thinking. Given that cocaine is likely to enhance dopamine (DA) levels, which in turn are positively associated with divergent thinking (DT); is a possibility that is tested in the present study. Furthermore, the impact of cocaine is tested on convergent thinking (CT), another aspect of creative thinking, which has been reported to be impaired with high DA levels. It was hypothesized that cocaine would enhance DT and impair CT. A placebo-controlled within-subjects study including 24 healthy poly-drug users was set up to test the influence of oral cocaine (300 mg) on creativity. Verbal CT was assessed with the Remote Associates Task (RAT); figural CT was assessed with the Picture Concepts Task (PCT) and the Tower of London (TOL). Verbal DT was assessed with the Alternative Uses Task (AUT); figural DT was assessed with the Pattern/Line Meanings Task (PLMT). Findings showed that, compared to placebo, cocaine impaired figural CT (TOL) and flexible DT of verbal stimuli (AUT), while it enhanced figural DT (PLMT). No significant effects of cocaine were observed regarding the PCT and RAT. It was demonstrated that cocaine-induced effects on creativity in poly-drug users are stimulus-dependent. Cocaine enhanced performance on figural DT but impaired performance on verbal (flexible) DT. Cocaine impaired CT on only one figural task and but not on the other tasks. As creativity is an important aspect in cognitive therapies, it is important to further understand these discrepancies in creativity task performance.

Replication and extension of a model predicting response to psilocybin.

BACKGROUND: Recent research demonstrated the potential of psychedelic drugs as treatment for depression and death-related anxiety and as an enhancement for well-being. While generally positive, responses to psychedelic drugs can vary according to traits, setting, and mental state (set) before and during ingestion. Most earlier models explain minimal response variation, primarily related to dosage and trust, but a recent study found that states of surrender and preoccupation at the time of ingestion explained substantial variance in mystical and adverse psilocybin experiences. OBJECTIVES: The current study sought to replicate the previous model, extend the model with additional predictors, and examine the role of mystical experience on positive change. METHOD: A hierarchical regression model was created with crowdsourced retrospective data from 183 individuals who had self-administered psilocybin in the past year. Scales explored mental states before, during, and after psilocybin ingestion, relying on open-ended memory prompts at each juncture to trigger recollections. Controlled drug administration was not employed. RESULTS: This study replicated the previous model, finding a state of surrender before ingestion a key predictor of optimal experience and preoccupation a key predictor of adverse experience. Additional predictors added to the explanatory power for optimal and adverse experience. The model supported the importance of mystical experiences to long-term change. CONCLUSION: Mental states of surrender or preoccupation at the time of ingestion explain variance in mystical or adverse psilocybin experiences, and mystical experiences relate to long-term positive change. The capacity to recognize this optimal preparatory mental state may benefit therapeutic use of psilocybin in clinical settings.

A distinct inferential mechanism for delusions in schizophrenia.

Delusions, a core symptom of psychosis, are false beliefs that are rigidly held with strong conviction despite contradictory evidence. Alterations in inferential processes have long been proposed to underlie delusional pathology, but previous attempts to show this have failed to yield compelling evidence for a specific relationship between inferential abnormalities and delusional severity in schizophrenia. Using a novel, incentivized information-sampling task (a modified version of the beads task), alongside well-characterized decision-making tasks, we sought a mechanistic understanding of delusions in a sample of medicated and unmedicated patients with schizophrenia who exhibited a wide range of delusion severity. In this novel task, participants chose whether to draw beads from one of two hidden jars or to guess the identity of the hidden jar, in order to minimize financial loss from a monetary endowment, and concurrently reported their probability estimates for the hidden jar. We found that patients with higher delusion severity exhibited increased information seeking (i.e. increased draws-to-decision behaviour). This increase was highly specific to delusion severity as compared to the severity of other psychotic symptoms, working-memory capacity, and other clinical and socio-demographic characteristics. Delusion-related increases in information seeking were present in unmedicated patients, indicating that they were unlikely due to antipsychotic medication. In addition, after adjusting for delusion severity, patients as a whole exhibited decreased information seeking relative to healthy individuals, a decrease that correlated with lower socioeconomic status. Computational analyses of reported probability estimates further showed that more delusional patients exhibited abnormal belief updating characterized by stronger reliance on prior beliefs formed early in the inferential process, a feature that correlated with increased information seeking in patients. Other decision-making parameters that could have theoretically explained the delusion effects, such as those related to subjective valuation, were uncorrelated with both delusional severity and information seeking among the patients. In turn, we found some preliminary evidence that subjective valuation (rather than belief updating) may explain group differences in information seeking unrelated to delusions. Together, these results suggest that abnormalities in belief updating, characterized by stronger reliance on prior beliefs formed by incorporating information presented earlier in the inferential process, may be a core computational mechanism of delusional ideation in psychosis. Our results thus provide direct empirical support for an inferential mechanism that naturally captures the characteristic rigidity associated with delusional beliefs.

Patterns of antihypertensive and statin adherence prior to dementia: findings from the adult changes in thought study.

BACKGROUND: Detecting patients with undiagnosed dementia is an important clinical challenge. Changes in medication adherence might represent an early sign of cognitive impairment. We sought to examine antihypertensive and statin adherence trajectories in community-dwelling older adults, comparing people who went on to develop dementia to those who did not. METHODS: We analyzed data from Adult Changes in Thought (ACT), a population-based cohort study embedded within an integrated healthcare delivery system. Analyses included 4368 participants aged ≥65 years who had at least one follow-up visit. Research-quality dementia diagnoses were used to identify cases. We selected non-dementia control visits matched on age, sex, and study cohort that occurred at similar ACT follow-up time as the case's dementia onset; we treated this as the index date. Participants were included if they were prevalent users of either a statin or antihypertensive medication on the first day of follow up - 3 years prior to the index date. Using prescription fill dates and days supply, we calculated daily binary medication availability measures for each participant ('days covered') over 3 years leading up to the index date. We used group-based trajectory models to identify patterns of antihypertensive and statin adherence, and used conditional logistic regression to examine associations between adherence trajectories and dementia. RESULTS: Four trajectories were identified for antihypertensive users (292 cases, 3890 control visits), including near perfect (n = 1877, 36.6% cases, 45.5% controls), high (n = 1840, 43.2% cases, 44.1% controls), moderate (n = 365, 18.5% cases, 8.0% controls) and early poor adherence (n = 100, 1.7% cases, 2.4% controls). Odds of dementia was 3 times greater for those with moderate antihypertensive adherence compared to those with near perfect adherence (adjusted OR 3.0, 95% CI 2.0, 4.3). Four trajectories were identified for statin users (148 cases, 1131 control visits), including high (n = 1004, 75.0% cases, 79.0% controls), moderate (n = 192, 19.6% cases, 14.4% controls), early poor (n = 43, 2.0% cases, 3.5% controls), and delayed poor adherence (n = 40, 3.4% cases, 3.1% controls). No association was detected between statin adherence trajectories and dementia. CONCLUSIONS: Patterns of medication adherence may be useful to identify a subset of people at higher likelihood of developing dementia.

Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting.

INTRODUCTION: Taking microdoses (a mere fraction of normal doses) of psychedelic substances, such as truffles, recently gained popularity, as it allegedly has multiple beneficial effects including creativity and problem-solving performance, potentially through targeting serotonergic 5-HT2A receptors and promoting cognitive flexibility, crucial to creative thinking. Nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing psychedelics, it is impossible to draw definitive conclusions on that matter. Here, our main aim was to quantitatively explore the cognitive-enhancing potential of microdosing psychedelics in healthy adults. METHODS: During a microdosing event organized by the Dutch Psychedelic Society, we examined the effects of psychedelic truffles (which were later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the Picture Concept Task assessing convergent thinking and the Alternative Uses Task assessing divergent thinking. A short version of the Ravens Progressive Matrices task assessed potential changes in fluid intelligence. We tested once before taking a microdose and once while the effects were expected to be manifested. RESULTS: We found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected. CONCLUSION: While this study provides quantitative support for the cognitive-enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results, we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and flexibility. We hope this study will motivate future microdosing studies with more controlled designs to test this hypothesis.

Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution.

RATIONALE: Ayahuasca is a psychotropic plant tea from South America used for religious purposes by indigenous people of the Amazon. Increasing evidence indicates that ayahuasca may have therapeutic potential in the treatment of mental health disorders and can enhance mindfulness-related capacities. Most research so far has focused on acute and sub-acute effects of ayahuasca on mental health-related parameters and less on long-term effects. OBJECTIVES: The present study aimed to assess sub-acute and long-term effects of ayahuasca on well-being and cognitive thinking style. The second objective was to assess whether sub-acute and long-term effects of ayahuasca depend on the degree of ego dissolution that was experienced after consumption of ayahuasca. RESULTS: Ayahuasca ceremony attendants (N = 57) in the Netherlands and Colombia were assessed before, the day after, and 4 weeks following the ritual. Relative to baseline, ratings of depression and stress significantly decreased after the ayahuasca ceremony and these changes persisted for 4 weeks. Likewise, convergent thinking improved post-ayahuasca ceremony up until the 4 weeks follow-up. Satisfaction with life and several aspects of mindfulness increased the day after the ceremony, but these changes failed to reach significance 4 weeks after. Changes in affect, satisfaction with life, and mindfulness were significantly correlated to the level of ego dissolution experienced during the ayahuasca ceremony and were unrelated to previous experience with ayahuasca. CONCLUSION: It is concluded that ayahuasca produces sub-acute and long-term improvements in affect and cognitive thinking style in non-pathological users. These data highlight the therapeutic potential of ayahuasca in the treatment of mental health disorders, such as depression.

Altered Mental Status at High Altitude.

Intrathecal baclofen pumps are commonly used in pediatric patients with spastic cerebral palsy. Baclofen binds to γ-aminobutyric acid receptors to inhibit both monosynaptic and polysynaptic reflexes at the spinal cord level. The blockade stops the release of excitatory transmitters and thereby decreases muscle contraction. It is commonly used for lower limb spasticity and has been shown to improve postural ability and functional status. The US Food and Drug Administration has approved baclofen for the treatment of spasticity of cerebral or spinal origin in adult and pediatric patients 4 years or older. Various complications of baclofen pumps are described in the literature. Immediately after surgery, problems from infection can arise and range from superficial skin infections to meningitis and bacteremia. Another early complication includes cerebrospinal fluid leak that can be observed by notable swelling beneath the lumbar incision. Additional problems that arise later are usually from the mechanics of the pump and catheter. Pump-related complications include failure, migration, and flipping. Catheter-related complications include disconnection, occlusion, fracture, or kink. Most of these complications typically lead to baclofen withdrawal, although there are a few case reports of overdose due to mechanical causes. Here we describe 2 cases of individuals experiencing complications of excessive baclofen exposure after significant changes in the atmospheric pressure due to travel involving ambient altitude change. These cases reflect the need to discuss this potential complication with families and patients with baclofen pumps before travel to high elevations.

The effect of oxytocin on group formation and strategic thinking in men.

Decision-making in groups is a remarkable and decisive element of human societies. Humans are able to organize themselves in groups, engage in collaborative decision-making processes and arrive at a binding agreement, even in the absence of unanimous consent. However, the transfer of decision-making autonomy requires a willingness to deliberately expose oneself to the decisions of others. A lack of trust in the abilities of others or of the underlying decision-making process, i.e. public trust, can lead to a breakdown of organizations in political or economic domains. Recent studies indicate that the biological basis of trust on an individual level is related to Oxytocin, an endogenous neuropeptide and hormone, which is also associated with pro-social behavior and positive conflict resolution. However, little is known about the effects of Oxytocin on the inclination of individuals to form or join groups and to deliberately engage in collaborative decision-making processes. Here, we show that intranasal administration of Oxytocin (n = 60) compared to placebo (n = 60) in males causes an adverse effect on the choice for forming groups in the presence of a competitive environment. In particular, Oxytocin negatively affects the willingness to work collaboratively in a p-Beauty contest game, whereas the effect is most pronounced for participants with relatively high strategic sophistication. Since our data provide initial evidence that Oxytocin has a positive effect on strategic thinking and performance in the p-Beauty contest game, we argue that the adverse effect on group formation might be rooted in an enhanced strategic sophistication of participants treated with Oxytocin.

The effects of cannabidiol on persecutory ideation and anxiety in a high trait paranoid group.

BACKGROUND: Previous studies have suggested that cannabidiol has anxiolytic and antipsychotic properties, raising hopes that cannabidiol will translate to the psychiatric clinic. Cannabidiol may be particularly useful for anxiety and paranoia in those at-risk of major mental illness. METHODS: Immersion in a controlled 3D virtual-reality scenario was used to assay persecutory ideation and anxiety in a sample of non-clinical volunteers ( n=32) pre-selected for high paranoid traits. Participants were randomised to receive oral cannabidiol (600 mg) or placebo 130 min prior to entering virtual-reality. Well-validated rating scales were used to assay persecutory thinking and anxiety. Salivary cortisol concentration, heart rate and blood pressure were measured over the course of the experimental session. RESULTS: Immersion in the virtual-reality session elicited anxiety as indexed by the Beck's anxiety inventory ( p<0.005), and increased cortisol concentration ( p=0.05), heart rate ( p<0.05) and systolic blood pressure ( p<0.05). However, cannabidiol had no impact upon any of these effects, except for a strong trend to increase anxiety ( p=0.09). Cannabidiol had no effect on persecutory ideation as assayed by the Community Assessment of Psychic Experiences questionnaire or the State Social Paranoia Scale. CONCLUSIONS: In contrast to previous studies, there was no evidence of any benefits of cannabidiol on anxiety or persecutory ideation in healthy volunteers with high trait paranoia. However, a larger sample will be required for a definitive study.

The effect of methylphenidate treatment on suspiciousness in children with ADHD alone or comorbid with ODD.

OBJECTIVE: To assess the level of the suspiciousness in children with attention deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder (ODD) in comparison to ADHD alone and the response of suspiciousness symptoms to methylphenidate (MPH) treatment. METHODS: In this open-label comparative study, children with DSM-IV-TR ADHD, aged 8-18 years, with (N = 30) or without (N = 30) ODD received MPH treatment for 12 weeks. The severity of ODD symptoms was assessed by the Kiddie-Schedule for Affective Disorders and Schizophrenia. The severity of ADHD symptoms was assessed by the ADHD-Rating-Scale-IV and suspiciousness was assessed at baseline and at endpoint by a scale designed especially for assessment of suspiciousness and named Suspiciousness Rating Scale (SRS). RESULTS: Significant reductions in SRS scores were detected in both groups following MPH treatment (before and after: p = .0012 and p = .0273, respectively). Only in the ADHD/ODD group a significant correlation was found between the rate of improvement in ADHD, as assessed by the ADHD-RS, and the reduction in suspiciousness, as assessed by the SRS (Spearman r = 0.48, p = .0066). CONCLUSIONS: In addition to the beneficial effect of MPH treatment on ADHD and ODD symptoms it also diminishes suspiciousness. However, due to the small sample size further studies are needed to confirm the present results.

S-Ketamine-Induced NMDA Receptor Blockade during Natural Speech Production and Its Implications for Formal Thought Disorder in Schizophrenia: A Pharmaco-fMRI Study.

Structural and functional changes in the lateral temporal language areas have been related to formal thought disorder (FTD) in schizophrenia. Continuous, natural speech production activates the right lateral temporal lobe in schizophrenia, as opposed to the left in healthy subjects. Positive and negative FTD can be elicited in healthy subjects by glutamatergic NMDA blockade with ketamine. It is unclear whether the glutamate system is related to the reversed hemispheric lateralization during speaking in patients. In a double-blind, crossover, placebo-controlled study, 15 healthy, male, right-handed volunteers overtly described 7 pictures for 3 min each while BOLD signal changes were acquired with fMRI. As a measure of linguistic demand, the number of words within 20 s epochs was correlated with BOLD responses. Participants developed S-ketamine-induced psychotic symptoms, particularly positive FTD. Ketamine vs placebo was associated with enhanced neural responses in the right middle and inferior temporal gyri. Similar to a previous fMRI study in schizophrenia patients vs healthy controls applying the same design, S-ketamine reversed functional lateralization during speech production in healthy subjects. Results demonstrate an association between glutamatergic imbalance, dysactivations in lateral temporal brain areas, and FTD symptom formation.

Effects of tryptophan depletion on selective serotonin reuptake inhibitor-remitted patients with obsessive compulsive disorder.

BACKGROUND: Serotonergic antidepressants are first-line medication therapies for obsessive-compulsive disorder, however it is not known if synaptic serotonin availability is important for selective serotonin reuptake inhibitor efficacy. The present study tested the hypothesis that temporary reduction in central serotonin transmission, through acute tryptophan depletion, would result in an increase in anxiety in selective serotonin reuptake inhibitor-remitted obsessive-compulsive disorder patients. METHODS: Eight patients (four males) with obsessive-compulsive disorder who showed sustained clinical improvement with selective serotonin reuptake inhibitor treatment underwent acute tryptophan depletion in a randomized, double-blind, placebo-controlled, within-subjects design, over two days one week apart. Five hours after consumption of the depleting/sham drink the participants performed a personalized obsessive-compulsive disorder symptom exposure task. Psychological responses were measured using the Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and Visual Analogue Scales. RESULTS: Free plasma tryptophan to large neutral amino acid ratio decreased by 93% on the depletion day and decreased by 1% on the sham day, as anticipated. Psychological rating scores as measured by Visual Analogue Scale showed a significant decrease in perceived control and increase in interfering thoughts at the time of provocation on the depletion day but not on the sham day. A measure of convergent validity, namely Visual Analogue Scale Similar to past, was significantly higher at the time of provocation on both the depletion and sham days. Both the depletion and time of provocation scores for Visual Analogue Scale Anxiety, Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and blood pressure were not significant. CONCLUSIONS: Acute tryptophan depletion caused a significant decrease in perceived control and increase in interfering thoughts at the time of provocation. Acute tryptophan depletion had no effect on the Spielberger State Anxiety Inventory or Visual Analogue Scale Anxiety measures, which suggests that the mechanism of action of selective serotonin reuptake inhibitors may be different to that seen in panic, social anxiety and post-traumatic stress disorder. Successful selective serotonin reuptake inhibitor treatment of obsessive-compulsive disorder may involve the ability of serotonin to switch habitual responding to goal-directed behaviour.

Single-Dose Testosterone Administration Impairs Cognitive Reflection in Men.

In nonhumans, the sex steroid testosterone regulates reproductive behaviors such as fighting between males and mating. In humans, correlational studies have linked testosterone with aggression and disorders associated with poor impulse control, but the neuropsychological processes at work are poorly understood. Building on a dual-process framework, we propose a mechanism underlying testosterone's behavioral effects in humans: reduction in cognitive reflection. In the largest study of behavioral effects of testosterone administration to date, 243 men received either testosterone or placebo and took the Cognitive Reflection Test (CRT), which estimates the capacity to override incorrect intuitive judgments with deliberate correct responses. Testosterone administration reduced CRT scores. The effect remained after we controlled for age, mood, math skills, whether participants believed they had received the placebo or testosterone, and the effects of 14 additional hormones, and it held for each of the CRT questions in isolation. Our findings suggest a mechanism underlying testosterone's diverse effects on humans' judgments and decision making and provide novel, clear, and testable predictions.

Attentional Lapses in Attention-Deficit/Hyperactivity Disorder: Blank Rather Than Wandering Thoughts.

People with attention-deficit/hyperactivity disorder (ADHD) have difficulties sustaining their attention on external tasks. Such attentional lapses have often been characterized as the simple opposite of external sustained attention, but the different types of attentional lapses, and the subjective experiences to which they correspond, remain unspecified. In this study, we showed that unmedicated children (ages 6-12) with ADHD, when probed during a standard go/no-go task, reported more mind blanking (a mental state characterized by the absence of reportable content) than did control participants. This increase in mind blanking happened at the expense of both focused and wandering thoughts. We also found that methylphenidate reverted the level of mind blanking to baseline (i.e., the level of mind blanking reported by control children without ADHD). However, this restoration led to mind wandering more than to focused attention. In a second experiment, we extended these findings to adults who had subclinical ADHD. These results suggest that executive functions impaired in ADHD are required not only to sustain external attention but also to maintain an internal train of thought.

The effect of the muscarinic M1 receptor antagonist biperiden on cognition in medication free subjects with psychosis.

The acetylcholine muscarinic M1 receptor has been implicated in both psychosis and cognition. Post-mortem research has shown reduced muscarinic M1 receptor density in 25% of chronic patients with schizophrenia. It is unknown whether reduced M1 receptor density is related to cognitive symptoms of psychosis. We investigated the role of the M1 receptor in separate cognitive domains in subjects with a psychotic disorder using a muscarinic M1 antagonist as an acute pharmacological challenge. 33 young subjects with a psychotic disorder and 30 gender, age and IQ matched healthy controls were enrolled. All participants completed a comprehensive cognitive test battery twice: once after placebo and once after oral administration of 4mg. biperiden (M1 antagonist). The order of drug administration was counterbalanced. Biperiden significantly negatively influenced both verbal (p< 0.001 and p=0.032) and visual learning and memory (p=0.028) in both groups. A medication x group interaction effect was found for reasoning and problem solving (p=0.005). No main or interaction effects were found for other cognitive domains. These results provide further in-vivo evidence that the M1 receptor is involved in cognitive functioning, particularly verbal and visual memory processes. Lack of differential effects of biperiden between psychotic subjects and healthy controls may suggest that decreased M1 receptor density is only present in chronic, older schizophrenia patients. However, it remains possible that differential effects of biperiden would be present in more severe cognitive impaired subjects with psychosis after several doses of biperiden instead of a single administration.