Cognitive enhancement: Effects of methylphenidate, modafinil, and caffeine on latent memory and resting state functional connectivity in healthy adults

Stimulants like methylphenidate, modafinil, and caffeine have repeatedly shown to enhance cognitive processes such as attention and memory. However, brain-functional mechanisms underlying such cognitive enhancing effects of stimulants are still poorly characterized. Here, we utilized behavioral and resting-state fMRI data from a double-blind randomized placebocontrolled study of methylphenidate, modafinil, and caffeine in 48 healthy male adults. The results show that performance in different memory tasks is enhanced, and functional connectivity (FC) specifically between the frontoparietal network (FPN) and default mode network (DMN) is modulated by the stimulants in comparison to placebo. Decreased negative connectivity between right prefrontal and medial parietal but also between medial temporal lobe and visual brain regions predicted stimulant-induced latent memory enhancement. We discuss dopamine's role in attention and memory as well as its ability to modulate FC between large-scale neural networks (e.g., FPN and DMN) as a potential cognitive enhancement mechanism

REM sleep in acutely traumatized individuals and interventions for the secondary prevention of post-traumatic stress disorder

Increasing evidence supports a close link between REM sleep and the consolidation of emotionally toned memories such as traumatic experiences. In order to investigate the role of sleep for the development of symptoms related to traumatic experiences, beyond experimental models in the laboratory, sleep of acutely traumatised individuals may be examined on the first night after trauma. This might allow us to identify EEG variables predicting the development of posttraumatic stress disorder (PTSD) symptoms, and guide the way to novel sleep interventions to prevent PTSD. Based on our experience, patients' acceptance of polysomnography in the first hours after treatment in an emergency room poses obstacles to such a strategy. Wearable, self-applicable sleep recorders might be an option for the investigation of sleep in the aftermath of trauma. They would considerably decrease the perceived burden for patients and thus increase the likelihood of successful patient recruitment. As one potential sleep intervention, sleep deprivation directly after trauma has been suggested to reduce the consolidation of traumatic memories and hence act as a secondary preventive measure. However, experimental data from sleep deprivation studies in healthy volunteers with the trauma film paradigm have been inconclusive regarding the beneficial or detrimental effects of sleep on traumatic memory processing. Depending on further insights into the role of sleep in traumatic memory consolidation through observational and experimental studies, several options for therapeutic sleep interventions are conceivable: besides behavioural sleep deprivation, selective REM sleep suppression or enhancement by a pharmacological intervention into the serotonergic, noradrenergic or cholinergic systems might provide novel therapeutic options. While REM-modulating drugs have been used with some success for the prevention of PTSD after trauma, they have never been tried before the first night of sleep. In conclusion, more experimental and observational research is needed before sleep interventions are performed in actual trauma victim

Cognitive enhancement effects of stimulants: a randomized controlled trial testing methylphenidate, modafinil, and caffeine

Rational: At all times humans have made attempts to improve their cognitive abilities by different means, among others, with the use of stimulants. Widely available stimulants such as caffeine, but also prescription substances such as methylphenidate and modafinil, are being used by healthy individuals to enhance cognitive performance. Objectives: There is a lack of knowledge on the effects of prescription stimulants when taken by healthy individuals (as compared with patients) and especially on the effects of different substances across different cognitive domains. Methods: We conducted a pilot study with three arms in which male participants received placebo and one of three stimulants (caffeine, methylphenidate, modafinil) and assessed cognitive performance with a test battery that captures various cognitive domains. Results: Our study showed some moderate effects of the three stimulants tested. Methylphenidate had positive effects on self-reported fatigue as well as on declarative memory 24 hours after learning; caffeine had a positive effect on sustained attention; there was no significant effect of modafinil in any of the instruments of our test battery. All stimulants were well tolerated, and no trade-off negative effects on other cognitive domains were found. Conclusions: The few observed significant positive effects of the tested stimulants were domain-specific and of rather low magnitude. The results can inform the use of stimulants for cognitive enhancement purposes as well as direct further research to investigate the effects of stimulants on specific cognitive domains that seem most promising, possibly by using tasks that are more demanding

A Central Clearing Clinic to Provide Mental Health Services for Refugees in Germany

Objective: To determine migration related distress pattern in refugees and feasibility of a de novo established, central low-threshold outpatient clinic serving more than 80,000 newly arrived refugees in the metropole of Berlin. Methods: In an observational cohort study the relative prevalence of major psychiatric disorders by age, place of living within berlin, language and region of origin were assessed in a refugee cohort from 63 nationalities speaking 36 languages. Findings: Within 18 months, a total of 3,096 cases with a mean age of 29.7 years (11.7) have been referred from all 12 districts and 165 of 182 subdistricts of Berlin to the CCC. 33.7% of the patients were female. The three most frequent diagnoses were unipolar depression (40.4%), posttraumatic stress disorder (24.3%), and adjustment disorder (19.6%). Conclusion: The present data gives insight into the distribution of mental disorders in a large sample of refugees and provides evidence that a CCC is an effective service to quickly and broadly provide psychiatric consultations and thus to overcome classical barriers refugees usually experience in the host communities. In Berlin, Germany, and Europe treatment resources for this population should focus on stress and trauma related disorders

Moral Psychopharmacology Needs Moral Inquiry: The Case of Psychedelics

The revival of psychedelic research coincided and more recently conjoined with psychopharmacological research on how drugs affect moral judgments and behaviors. This article makes the case for a moral psychopharmacology of psychedelics that examines whether psychedelics serve as non-specific amplifiers that enable subjects to (re-)connect with their values, or whether they promote specific moral-political orientations such as liberal and anti-authoritarian views, as recent psychopharmacological studies suggest. This question gains urgency from the fact that the return of psychedelics from counterculture and underground laboratories to mainstream science and society has been accompanied by a diversification of their users and uses. We propose bringing the pharmacological and neuroscientific literature into a conversation with historical and anthropological scholarship documenting the full spectrum of moral and political views associated with the uses of psychedelics. This paper sheds new light on the cultural plasticity of drug action and has implications for the design of psychedelic pharmacopsychotherapies. It also raises the question of whether other classes of psychoactive drugs have an equally rich moral and political life

Hacking the Brain: Dimensions of Cognitive Enhancement

In an increasingly complex information society, demands for cognitive functioning are growing steadily. In recent years, numerous strategies to augment brain function have been proposed. Evidence for their efficacy (or lack thereof) and side effects has prompted discussions about ethical, societal, and medical implications. In the public debate, cognitive enhancement is often seen as a monolithic phenomenon. On a closer look, however, cognitive enhancement turns out to be a multifaceted concept: There is not one cognitive enhancer that augments brain function per se, but a great variety of interventions that can be clustered into biochemical, physical, and behavioral enhancement strategies. These cognitive enhancers differ in their mode of action, the cognitive domain they target, the time scale they work on, their availability and side effects, and how they differentially affect different groups of subjects. Here we disentangle the dimensions of cognitive enhancement, review prominent examples of cognitive enhancers that differ across these dimensions, and thereby provide a framework for both theoretical discussions and empirical research

Navigating the enhancement landscape: ethical issues in research on cognitive enhancers for healthy individuals

Research into the efficacy and safety of cognitive enhancers for recreational or lifestyle use has not been done. Should society pay for studies that might improve the lives of already healthy people

Innovative mechanisms of action for pharmaceutical cognitive enhancement: A systematic review

International audiencePharmacological cognitive enhancement refers to improvement in cognitive functions after drug use in healthy individuals. This popular topic attracts attention both from the general public and the scientific community. The objective was to explore innovative mechanisms of psychostimulant's action, whose potential effectiveness was assessed in randomized placebo-controlled trials (RCTs). A systematic review was carried out, using the words "attention", "memory", "learning", "executive functions", and "vigilance/wakefulness" combined to "cognitive enhancer" or "smart drug". Methylphenidate, amphetamines, modafinil, nicotine, acetylcholine esterase inhibitors and antidepressants were extensively studied in previous meta-analyses and were not included in the present work. Drugs were classified according to their primary mode of action, namely catecholaminergic drugs (tolcapone, pramipexole, guanfacine), cholinergic drugs (anticholinergics), glutamatergic drugs (ampakines), histaminergic drugs, and non-specified (glucocorticoids). Overall, 50 RCTs were included in the present review. In conclusion, a number of new active drugs were found to improve some cognitive functions, in particular verbal episodic memory. However the number of RCTs was limited, and most of the studies found negative results. Future studies should assess both effectiveness and tolerance of repeated doses administration, and individual variability in dose response (including baseline characteristics and potential genetic polymorphisms). One explanation for the limited number of recent RCTs with new psychostimulants seems to be the ethical debate surrounding pharmaceutical cognitive enhancement in healthy subjects