Drugs, games, and devices for enhancing cognition: implications for work and society.

As work environments change, the demands on working people change. Cognitive abilities in particular are becoming progressively more important for work performance and successful competition in a global environment. However, work-related stress, performance over long hours, lack of sleep, shift work, and jet lag affect cognitive functions. Therefore, an increasing number of healthy people are reported to use cognitive-enhancing drugs, as well as other interventions, such as noninvasive brain stimulation, to maintain or improve work performance. This review summarizes research on pharmacological and technical methods as well as cognitive training, including game apps for the brain, in healthy people. In neuropsychiatric disorders, impairments in cognitive functions can drastically reduce the chances of returning to work; therefore, this review also summarizes findings from pharmacological and cognitive-training studies in neuropsychiatric disorders.All cited psychopharmacological work from Professor Sahakian laboratory was funded by a Wellcome Trust Grant (089589/Z/09/Z) awarded to T.W. Robbins, B.J. Everitt, A.C. Roberts, J.W. Dalley, and B.J. Sahakian, and it was conducted at the Behavioural and Clinical Neuroscience Institute, which is supported by a joint award from the Medical Research Council and Wellcome Trust (G00001354). ABB was supported by a grant from the The Wallitt Foundation.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/nyas.1304

Making sense of real-time functional magnetic resonance imaging (rtfMRI) and rtfMRI neurofeedback

This review explains the mechanism of functional magnetic resonance imaging in general and specifically introduces real-time functional magnetic resonance imaging as a method for training self-regulation of brain activity. Using real-time functional magnetic resonance imaging neurofeedback, participants can acquire control over their own brain activity. In patients with neuropsychiatric disorders, this control can potentially have therapeutic implications. In this review, the technical requirements are presented and potential applications and limitations are discussed

Neuroethical issues in cognitive enhancement: Modafinil as the example of a workplace drug?

The use of cognitive-enhancing drugs by healthy individuals has been a feature for much of recorded history. Cocaine and amphetamine are modern cases of drugs initially enthusiastically acclaimed for enhancing cognition and mood. Today, an increasing number of healthy people are reported to use cognitive-enhancing drugs, as well as other interventions, such as non-invasive brain stimulation, to maintain or improve work performance. Cognitive-enhancing drugs, such as methylphenidate and modafinil, which were developed as treatments, are increasingly being used by healthy people. Modafinil not only affects 'cold' cognition, but also improves 'hot' cognition, such as emotion recognition and task-related motivation. The lifestyle use of 'smart drugs' raises both safety concerns as well as ethical issues, including coercion and increasing disparity in society. As a society, we need to consider which forms of cognitive enhancement (e.g. pharmacological, exercise, lifelong learning) are acceptable and for which groups under what conditions and by what methods we would wish to improve and flourish

Neuroethical issues in cognitive enhancement: Modafinil as the example of a workplace drug?

The use of cognitive-enhancing drugs by healthy individuals has been a feature for much of recorded history. Cocaine and amphetamine are modern cases of drugs initially enthusiastically acclaimed for enhancing cognition and mood. Today, an increasing number of healthy people are reported to use cognitive-enhancing drugs, as well as other interventions, such as non-invasive brain stimulation, to maintain or improve work performance. Cognitive-enhancing drugs, such as methylphenidate and modafinil, which were developed as treatments, are increasingly being used by healthy people. Modafinil not only affects 'cold' cognition, but also improves 'hot' cognition, such as emotion recognition and task-related motivation. The lifestyle use of 'smart drugs' raises both safety concerns as well as ethical issues, including coercion and increasing disparity in society. As a society, we need to consider which forms of cognitive enhancement (e.g. pharmacological, exercise, lifelong learning) are acceptable and for which groups under what conditions and by what methods we would wish to improve and flourish

Psychiatry in the Digital Age: A Blessing or a Curse?

Social distancing and the shortage of healthcare professionals during the COVID-19 pandemic, the impact of population aging on the healthcare system, as well as the rapid pace of digital innovation are catalyzing the development and implementation of new technologies and digital services in psychiatry. Is this transformation a blessing or a curse for psychiatry? To answer this question, we conducted a literature review covering a broad range of new technologies and eHealth services, including telepsychiatry; computer-, internet-, and app-based cognitive behavioral therapy; virtual reality; digital applied games; a digital medicine system; omics; neuroimaging; machine learning; precision psychiatry; clinical decision support; electronic health records; physician charting; digital language translators; and online mental health resources for patients. We found that eHealth services provide effective, scalable, and cost-efficient options for the treatment of people with limited or no access to mental health care. This review highlights innovative technologies spearheading the way to more effective and safer treatments. We identified artificially intelligent tools that relieve physicians from routine tasks, allowing them to focus on collaborative doctor-patient relationships. The transformation of traditional clinics into digital ones is outlined, and the challenges associated with the successful deployment of digitalization in psychiatry are highlighted

Levetiracetam as an adjunctive treatment for mania: a double-blind, randomized, placebo-controlled trial

BACKGROUND: Levetiracetam is an anticonvulsant with a low side effect profile and favorable properties for individuals with bipolar I disorder during their manic phase. Despite initial promising results until about 2008, it appears that this track of research has not been followed-up. To counter this, we tested the influence of adjuvant levetiracetam on acute mania, compared to placebo. More specifically, we performed a randomized, double-blind, placebo-controlled clinical trial among inpatients with bipolar disorder I during their acute phase of mania. METHODS: A total of 72 inpatients (mean age: 33.98 years; 23.6% females) with diagnosed bipolar disorder I and during their acute manic phase were randomly assigned either to the adjuvant levetiracetam (250 mg to a maximum of 1,500 mg) or to the placebo condition. Standard medication was lithium at therapeutic dosages. At baseline, participants completed a series of self-rating questionnaires covering sociodemographic information and subjective sleep. Subjective sleep was re-assessed 24 days later at the end of the study. Experts rated participants' acute state of mania with the Young Mania Rating Scale at baseline and at day 12 and day 24. Participants' cognitive performance was assessed at baseline and at day 24 at the end of the study. RESULTS: Over time, mania scores significantly decreased (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (medium effect size). Likewise, over time, subjective sleep improved (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (large effect size). Over time, cognitive performance improved (large effect size), irrespective of the study condition. CONCLUSIONS: Compared to placebo, adjuvant levetiracetam to lithium improved symptoms of mania, as rated by experts, and subjective sleep quality. Adjuvant levetiracetam had no further favorable (or detrimental) impact on cognitive performance

Disentangling craving‐ and valence‐related brain responses to smoking cues in individuals with nicotine use disorder

Tobacco smoking is one of the leading causes of preventable death and disease worldwide. Most smokers want to quit, but relapse rates are high. To improve current smoking cessation treatments, a better understanding of the underlying mechanisms of nicotine dependence and related craving behaviour is needed. Studies on cue-driven cigarette craving have been a particularly useful tool for investigating the neural mechanisms of drug craving. Here, functional neuroimaging studies in humans have identified a core network of craving-related brain responses to smoking cues that comprises of amygdala, anterior cingulate cortex, orbitofrontal cortex, posterior cingulate cortex and ventral striatum. However, most functional Magnetic Resonance Imaging (fMRI) cue-reactivity studies do not adjust their stimuli for emotional valence, a factor assumed to confound craving-related brain responses to smoking cues. Here, we investigated the influence of emotional valence on key addiction brain areas by disentangling craving- and valence-related brain responses with parametric modulators in 32 smokers. For one of the suggested key regions for addiction, the amygdala, we observed significantly stronger brain responses to the valence aspect of the presented images than to the craving aspect. Our results emphasize the need for carefully selecting stimulus material for cue-reactivity paradigms, in particular with respect to emotional valence. Further, they can help designing future research on teasing apart the diverse psychological dimensions that comprise nicotine dependence and, therefore, can lead to a more precise mapping of craving-associated brain areas, an important step towards more tailored smoking cessation treatments. Keywords: craving; cue-reactivity; functional Magnetic Resonance Imaging; neuroimaging; nicotine use disorder; smoking

Influence of modafinil on early ejaculation - Results from a double-blind randomized clinical trial

BACKGROUND For men, early ejaculation is a serious health concern. Here, we tested the influence of modafinil (Profinil®) on early ejaculation. To this end, we performed a double-blind randomized clinical trial among men with early ejaculation. METHODS A total of 46 men with early ejaculation (mean age: 37.35 years) and in stable marital relationships with regular weekly penile-vaginal intercourse were randomly assigned either to the modafinil (100 mg) or to the placebo condition. Compounds were taken about 4-6h before intended penile-vaginal intercourse. At baseline and four weeks later at the end of the study, participants completed a series of self-rating questionnaires covering early ejaculation. Female partners also rated their male partners' early ejaculation profile. RESULTS Dimensions of early ejaculation improved over time, but only so in the modafinil condition, while no improvements were observed in the placebo condition. CONCLUSIONS Among male adults in stable marital relationships with regular weekly penile-vaginal intercourse modafinil improved dimensions of early ejaculation, always compared to placebo. Given the strong effect of modafinil on cognitive-executive processes, it is conceivable, that modafinil acted both via physiological and cognitive-executive pathways

“Hot” and “Cold” Cognition in Users of Club Drugs/Novel Psychoactive Substances

Novel psychoactive substances (NPS) are popular “club/party” drugs that first attracted attention in the UK in 2009 and remained legal until the 2016 Psychoactive Substances Act criminalized their distribution. Unlike “traditional” illicit drugs, very little is known about the influence of their analogs on neuropsychological functioning. We characterized the cognitive and emotional profile of NPS/polydrug users using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and EMOTICOM test battery in adult male (aged 20–49 years) recreational users without psychiatric comorbidities (n = 27; “psychonauts”), service users attending a UK specialist “Club Drug” Clinic for problematic use (n = 20) and healthy control volunteers without significant drug-taking histories (n = 35). Tasks were selected to distinguish “hot” cognitive processes that are highly influenced by emotion from “cold” cognitive processes that are largely independent of emotional influence. Both user groups reported significantly higher sensation-seeking traits compared with non-users. Recreational NPS users demonstrated more risk-taking behavior compared with controls and treatment-seeking NPS users showed poorer learning, episodic memory and response inhibition compared with the other two groups. These effects persisted, when controlling for age, intelligence, alcohol and cannabis use severity, nicotine dependence, trait anxiety, depression, childhood adversity, impulsivity, and sensation seeking. Overall, recreational NPS users showed elevated “hot” (emotion-laden) cognition in the absence of “cold” (non-emotional) cognitive deficits, whereas “cold” cognitive dysfunction was pronounced in individuals seeking treatment for problematic NPS use. High trait impulsivity and poor self-control may confer additional risk to NPS/polydrug use severity and separate those seeking treatment from those using NPS recreationally

Acute anxiety and autonomic arousal induced by CO 2 inhalation impairs prefrontal executive functions in healthy humans

Funder: The Wallitt Foundation; Eton College; and NIHR Cambridge Biodmedical Centre (BRC) Mental Health theme.Funder: Cambridge Vice-Chanchellor's Award and Fitzwilliam College scholarshipFunder: Medical Research Council (G1000183)Abstract: Acute anxiety impacts cognitive performance. Inhalation of air enriched with carbon dioxide (CO2) in healthy humans provides a novel experimental model of generalised anxiety, but has not previously been used to assess cognition. We used inhalation of 7.5% CO2 to induce acute anxiety and autonomic arousal in healthy volunteers during neuropsychological tasks of cognitive flexibility, emotional processing and spatial working memory in a single-blind, placebo-controlled, randomized, crossover, within-subjects study. In Experiment 1 (n = 44), participants made significantly more extra-dimensional shift errors on the Cambridge Neuropsychological Test Automated Battery (CANTAB) Intra-Extra Dimensional Set Shift task under CO2 inhalation compared with ‘normal’ air. Participants also had slower latencies when responding to positive words and made significantly more omission errors for negative words on the CANTAB Affective Go/No-go task. In Experiment 2 (n = 28), participants made significantly more total errors and had poorer heuristic search strategy on the CANTAB Spatial Working Memory task. In both experiments, CO2 inhalation significantly increased negative affect; state anxiety and fear; symptoms of panic; and systolic blood pressure/heart rate. Overall, CO2 inhalation produced robust anxiogenic effects and impaired fronto-executive functions of cognitive flexibility and working memory. Effects on emotional processing suggested a mood-congruent slowing in processing speed in the absence of a negative attentional bias. State-dependent effects of anxiety on cognitive-emotional interactions in the prefrontal cortex warrant further investigation