Cognitive enhancement.

Cognitive enhancement refers to the improvement of cognitive ability in normal healthy individuals. In this article, we focus on the use of pharmaceutical agents and brain stimulation for cognitive enhancement, reviewing the most common methods of pharmacologic and electronic cognitive enhancement, and the mechanisms by which they are believed to work, the effectiveness of these methods and their prevalence. We note the many gaps in our knowledge of these matters, including open questions about the size, reliability and nature of the enhancing effects, and we conclude with recommendations for further research. WIREs Cogn Sci 2014, 5:95-103. doi: 10.1002/wcs.1250 CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website.

Are prescription stimulants "smart pills"? The epidemiology and cognitive neuroscience of prescription stimulant use by normal healthy individuals.

Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience literatures in search of answers to these questions. Epidemiological issues addressed include the prevalence of nonmedical stimulant use, user demographics, methods by which users obtain prescription stimulants, and motivations for use. Cognitive neuroscience issues addressed include the effects of prescription stimulants on learning and executive function, as well as the task and individual variables associated with these effects. Little is known about the prevalence of prescription stimulant use for cognitive enhancement outside of student populations. Among college students, estimates of use vary widely but, taken together, suggest that the practice is commonplace. The cognitive effects of stimulants on normal healthy people cannot yet be characterized definitively, despite the volume of research that has been carried out on these issues. Published evidence suggests that declarative memory can be improved by stimulants, with some evidence consistent with enhanced consolidation of memories. Effects on the executive functions of working memory and cognitive control are less reliable but have been found for at least some individuals on some tasks. In closing, we enumerate the many outstanding questions that remain to be addressed by future research and also identify obstacles facing this research.

Discussing smart pills versus endorsing smart pills: reply to Swanson, Wigal, and Volkow (2011) and Elliott and Elliott (2011).

We find much of interest, and little to disagree with, in the commentaries on our article. We take issue only with the suggestion that our article was provocative and submit that the attempt to understand the use of stimulants as smart pills does not imply an endorsement of the practice.

First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial.

BACKGROUND: Children with HIV will be on antiretroviral therapy (ART) longer than adults, and therefore the durability of first-line ART and timing of switch to second-line are key questions. We assess the long-term outcome of protease inhibitor and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line ART and viral load switch criteria in children. METHODS: In a randomised open-label factorial trial, we compared effectiveness of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor versus two NRTIs plus an NNRTI and of switch to second-line ART at a viral load of 1000 copies per mL versus 30,000 copies per mL in previously untreated children infected with HIV from Europe and North and South America. Random assignment was by computer-generated sequentially numbered lists stratified by age, region, and by exposure to perinatal ART. Primary outcome was change in viral load between baseline and 4 years. Analysis was by intention to treat, which we defined as all patients that started treatment. This study is registered with ISRCTN, number ISRCTN73318385. FINDINGS: Between Sept 25, 2002, and Sept 7, 2005, 266 children (median age 6.5 years; IQR 2.8-12.9) were randomly assigned treatment regimens: 66 to receive protease inhibitor and switch to second-line at 1000 copies per mL (PI-low), 65 protease inhibitor and switch at 30,000 copies per mL (PI-higher), 68 NNRTI and switch at 1000 copies per mL (NNRTI-low), and 67 NNRTI and switch at 30,000 copies per mL (NNRTI-higher). Median follow-up was 5.0 years (IQR 4.2-6.0) and 188 (71%) children were on first-line ART at trial end. At 4 years, mean reductions in viral load were -3.16 log(10) copies per mL for protease inhibitors versus -3.31 log(10) copies per mL for NNRTIs (difference -0.15 log(10) copies per mL, 95% CI -0.41 to 0.11; p=0.26), and -3.26 log(10) copies per mL for switching at the low versus -3.20 log(10) copies per mL for switching at the higher threshold (difference 0.06 log(10) copies per mL, 95% CI -0.20 to 0.32; p=0.56). Protease inhibitor resistance was uncommon and there was no increase in NRTI resistance in the PI-higher compared with the PI-low group. NNRTI resistance was selected early, and about 10% more children accumulated NRTI mutations in the NNRTI-higher than the NNRTI-low group. Nine children had new CDC stage-C events and 60 had grade 3/4 adverse events; both were balanced across randomised groups. INTERPRETATION: Good long-term outcomes were achieved with all treatments strategies. Delayed switching of protease-inhibitor-based ART might be reasonable where future drug options are limited, because the risk of selecting for NRTI and protease-inhibitor resistance is low. FUNDING: Paediatric European Network for Treatment of AIDS (PENTA) and Pediatric AIDS Clinical Trials Group (PACTG/IMPAACT).

When we enhance cognition with Adderall, do we sacrifice creativity? A preliminary study.

RATIONALE: Adderall (mixed amphetamine salts) is used by healthy normal individuals to enhance attention. Research with healthy normal participants and those with attention deficit hyperactivity disorder indicate a possible inverse relationship between attentional function and creativity. This raises the possibility that Adderall could decrease creativity in people using it for cognitive enhancement. OBJECTIVE: This study was designed to find out whether Adderall impairs creativity in healthy young adults. MATERIAL AND METHODS: In a double-blind placebo-controlled study, the effects of Adderall on the performance of 16 healthy young adults were measured on four tests of creativity from the psychological literature: two tasks requiring divergent thought and two requiring convergent thought. RESULTS: Adderall affected performance on the convergent tasks only, in one case enhancing it, particularly for lower-performing individuals, and in the other case enhancing it for the lower-performing and impairing it for higher-performing individuals. CONCLUSION: The preliminary evidence is inconsistent with the hypothesis that Adderall has an overall negative effect on creativity. Its effects on divergent creative thought cannot be inferred with confidence from this study because of the ambiguity of null results. Its effects on convergent creative thought appear to be dependent on the baseline creativity of the individual. Those in the higher range of the normal distribution may be unaffected or impaired, whereas those in the lower range of the normal distribution experience enhancement.

Brain imaging and brain privacy: a realistic concern?

Functional neuroimaging has been used to study a wide array of psychological traits, including aspects of personality and intelligence. Progress in identifying the neural correlates of individual differences in such traits, for the sake of basic science, has moved us closer to the applied science goal of measuring them and thereby raised ethical concerns about privacy. How realistic are such concerns given the current state of the art? In this article, we describe the statistical basis of the measurement of psychological traits using functional neuroimaging and examine the degree to which current functional neuroimaging protocols could be used for this purpose. By analyzing the published data from 16 studies, we demonstrate that the use of imaging to gather information about an individual's psychological traits is already possible, but to an extremely limited extent.

Efficacy, safety and tolerability of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents.

OBJECTIVE: To evaluate the efficacy, safety and tolerability of ritonavir-boosted tipranavir (TPV/r) in HIV-1-infected pediatric patients. DESIGN: Open-label randomized pediatric trial (1182.14/PACTG1051) comparing TPV/r at two doses including an optimized background regimen. METHODS: HIV-1-infected patients (2-18 years) with plasma viral load 1500 copies/ml or more were randomized to TPV/r 290/115 or 375/150 mg/m twice-daily oral solution and optimized background regimen. Week 48 efficacy, safety and tolerability results were evaluated. RESULTS: Children (n = 115; 97% treatment experienced) were randomized to low or high dose therapy. Eighty-eight remained on-treatment through 48 weeks. Baseline characteristics were similar between dose groups. At study entry, half of the HIV-1 isolates were resistant to all protease inhibitors. At 48 weeks, 39.7% low-dose and 45.6% high-dose TPV/r recipients had viral load less than 400 copies/ml and 34.5 and 35.1%, respectively, achieved viral load less than 50 copies/ml. Vomiting, cough and diarrhea were the most frequent adverse events. Grade 3 alanine aminotransferase elevations were observed in 6.3% of patients. No grade 4 alanine aminotransferase or grade 3/4 aspartate aminotransferase elevations were reported. CONCLUSIONS: TPV/r achieved a sustained virologic response, showed a good safety profile and was well tolerated at either dose. In pediatric patients with high baseline resistance profiles, high-dose TPV/r tended to demonstrate a better sustained response.