Explore the vast range of titles available.

Serotonin is implicated in multiple executive functions including goal-directed learning, cognitive flexibility, response inhibition and emotional regulation. These functions are impaired in several psychiatric disorders, such as depression and obsessive–compulsive disorder. We tested the cognitive effects of the selective serotonin reuptake inhibitor escitalopram, using an acute and clinically relevant dose (20 mg), in 66 healthy male and female volunteers in a double-blind, placebo-controlled study. Participants performed a cognitive test battery including a probabilistic and reversal learning task, the CANTAB intra-dimensional/extra-dimensional shift test of cognitive flexibility, a response inhibition task with interleaved stop-signal and No-Go trials and tasks measuring emotional processing. We showed that acute escitalopram administration impaired learning and cognitive flexibility, but improved the ability to inhibit responses in stop-signal trials while leaving unaffected acute emotional processing. Our findings suggest a dissociation of effects of acute escitalopram on cognitive functions, possibly mediated by differential modulation of brain serotonin levels in distinct functional neural circuits.

In the 24-month MS-STAT phase 2 trial, we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive multiple sclerosis (SPMS). We now describe the results of the MS-STAT cognitive substudy, in which we investigated the treatment effect on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures. We did a secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1:1) to either 80 mg simvastatin (n=70) or placebo (n=70). The cognitive assessments done were the National Adult Reading Test, Wechsler Abbreviated Scale of Intelligence, Graded Naming Test, Birt Memory and Information Processing Battery (BMIPB), Visual Object and Space Perception battery (cube analysis), Frontal Assessment Battery (FAB), and Paced Auditory Serial Addition Test. Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Questionnaire. HRQoL was assessed using the self-reported 36-Item Short Form Survey (SF-36) version 2. Assessments were done at study entry, 12 months, and 24 months. Patients, treating physicians, and outcome assessors were masked to treatment allocation. Analyses were by intention to treat. MS-STAT is registered with ClinicalTrials.gov, number NCT00647348. Baseline assessment revealed impairments in 60 (45%) of 133 patients on the test of frontal lobe function (FAB), and in between 13 (10%) and 43 (33%) of 130 patients in tests of non-verbal and verbal memory (BMIPB). Over the entire trial, we noted significant worsening on tests of verbal memory (T score decline of 5·7 points, 95% CI 3·6–7·8; p<0·0001) and non-verbal memory (decline of 6·8 points, 4·8–8·7; p<0·0001). At 24 months, the FAB score was 1·2 points higher in the simvastatin-treated group than in the placebo group (95% CI 0·2–2·3). The simvastatin group also had a 2·5 points better mean physical component score of the SF-36 (95% CI 0·3–4·8; p=0·028). A treatment effect was not noted for any other outcomes. To our knowledge, this SPMS cohort is the largest studied to date with comprehensive longitudinal cognitive, neuropsychiatric, and HRQoL assessments. We found evidence of a positive effect of simvastatin on frontal lobe function and a physical quality-of-life measure. Although we found no effect of simvastatin on the other outcome measures, these potential effects warrant confirmation and underline the importance of fully assessing cognition and quality of life in progressive multiple sclerosis treatment trials. The Moulton Foundation, the Berkeley Foundation, the Multiple Sclerosis Trials Collaboration, the Rosetrees Trust, a personal contribution from A W Pidgley CBE, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre and University College London.

Recent research indicates that the hypothalamic neuropeptide hormone oxytocin is a key central nervous system factor in the regulation of food intake and weight. However, the mechanisms underlying the anorexigenic effects of oxytocin in humans are unknown and critical to study to consider oxytocin as a neurohormonal weight loss treatment. We performed a randomized, double-blind, placebo-controlled crossover study with single-dose intranasal oxytocin (24 IU) in ten overweight or obese, otherwise healthy men. Following oxytocin/placebo administration, participants completed an established functional magnetic resonance imaging food motivation paradigm. We hypothesized that oxytocin would reduce the blood oxygenation level-dependent (BOLD) signal to high-calorie food vs non-food visual stimuli in the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic reward system. Following oxytocin administration, compared to placebo, participants showed bilateral VTA hypoactivation to high-calorie food stimuli. A secondary exploratory whole-brain analysis revealed hypoactivation in additional hedonic (orbitofrontal cortex, insula, globus pallidus, putamen, hippocampus, and amygdala) and homeostatic (hypothalamus) food motivation and hyperactivation in cognitive control (anterior cingulate and frontopolar cortex) brain regions following oxytocin administration vs placebo. Oxytocin administration reduces the BOLD signal in reward-related food motivation brain regions, providing a potential neurobiological mechanism for the anorexigenic oxytocin effects in humans. Furthermore, our data indicate that oxytocin administration reduces activation in homeostatic and increases activation in cognitive control brain regions critically involved in regulating food intake and resolving affective conflict, respectively. Future studies are required to link these changes in brain activation to oxytocin effects on food intake and weight.

Cognitive control, which is critical for goal‐directed behavior, involves resolving conflicts between competing stimuli and is influenced by neurotransmitter interactions within cortico‐subcortical areas. This study investigated the relationship between baseline amino acid transmitter levels and interference control, focusing on the effects of experimentally enhancing catecholaminergic signaling. Using a double‐blind, placebo‐controlled crossover design with two dosage groups, n = 71 healthy human adults underwent proton magnetic resonance spectroscopy once to assess baseline GABA+ and Glx levels in the anterior cingulate cortex (ACC), striatum, and supplementary motor area (SMA). Participants then performed a subliminally primed flanker task inducing different scales of conflict twice while EEG was recorded: once after receiving a placebo (lactase) and once more under either low (0.25 mg/kg) or medium (0.50 mg/kg) doses of methylphenidate (MPH), which modulates the catecholaminergic and amino acid transmitter systems driving cognitive and interference control. Medium MPH doses were more effective than low doses at reducing subliminal interference effects, highlighting dose‐specific behavioral improvements. Higher striatal GABA+ levels led to better interference control at low doses, while lower ACC GABA+ and GABA+/Glx levels were associated with better interference control at medium doses, suggesting a dose‐dependent shift from striatal to ACC dominance in conflict resolution. Neurophysiological (EEG data) analyses revealed increased theta‐band (TBA) and alpha‐band activity (ABA) overlapping in the mid‐superior‐frontal and inferior‐frontal clusters under conditions of heightened cognitive control demands. The findings highlight that whether and how amino acid transmitter levels in cognitive control‐relevant regions modulate interference conflicts depends on the degree of catecholaminergic signaling. We found medium methylphenidate doses (0.5 mg/kg) to be more effective than low doses (0.25 mg/kg) at reducing subliminal interference effects, with higher striatal GABA+ levels leading to better interference control at low doses, while lower ACC GABA+ and GABA+/Glx levels led to better interference control at medium doses.

Memory and executive function are often impaired in patients with major depression, while cortisol secretion is increased. Mineralocorticoid receptors (MR) are abundantly expressed in the hippocampus and in the prefrontal cortex, brain areas critical for memory, executive function, and cortisol inhibition. Here, we investigated whether MR stimulation with fludrocortisone (1) improves memory and executive function and (2) decreases cortisol secretion in depressed patients and healthy individuals. Twenty-four depressed patients without medication and 24 age-, sex-, and education-matched healthy participants received fludrocortisone (0.4 mg) or placebo in a randomized, double-blind, within-subject cross-over design. We measured verbal memory, visuospatial memory, executive function, psychomotor speed, and salivary cortisol secretion during cognitive testing between 1400 and 1700 hours. For verbal memory and executive function, we found better performance after fludrocortisone compared with placebo across groups. No treatment effect on other cognitive domains emerged. Depressed patients performed worse than healthy individuals in psychomotor speed and executive function. No group effect or group × treatment interaction emerged on other cognitive domains. Fludrocortisone decreased cortisol secretion across groups and there was a significant correlation between cortisol inhibition and verbal memory performance. Our data suggest a crucial role of MR in verbal memory and executive function and demonstrate the possibility to improve cognition in depressed patients and healthy individuals through MR stimulation.

Psychosocial well-being requires effective regulation of emotional responding in context of threat or stress. Neuroimaging studies have focused on instructed, volitional regulation (e.g., reappraisal or distancing), largely ignoring implicit regulation that does not involve purposeful effort to alter emotional experience. These implicit processes may or may not involve the same neural pathways as explicit regulatory strategies. We examined the neurobiology of implicit emotional regulation processes and the impact of the stress hormone cortisol on these processes. Our study task employed composite pictures of faces and places to examine neural activity during implicit emotional processing (of emotional faces), while these responses were implicitly regulated by attention shift away from the emotionally evocative stimuli, and while subjects reflectively appraised their own emotional response to them. Subjects completed the task in an fMRI scanner after random assignment to receive placebo or hydrocortisone (HCT), an orally administered version of cortisol. Implicit emotional processing activated insula/IFG, dACC/dMPFC, midbrain and amygdala. With attention shifting, we saw diminished signal in emotion generating/response regions (e.g., amygdala) and increased activations in task specific attention regions like parahippocampus. With appraisal of emotions, we observed robust activations in medial prefrontal areas, where activation is also seen in instructed reappraisal studies. We observed no main effects of HCT administration on brain, but males and females showed opposing neural effects in prefrontal areas. The data suggest that different types of emotion regulation utilize overlapping circuits, but with some strategy specific activation. Further study of the dimorphic sex response to cortisol is needed.

Rationale Cannabidiol (CBD) is increasingly used as a sleep aid for insomnia; yet neurocognitive and subjective state effects following daily therapeutic use are unclear. Objectives To measure the effect of daily CBD use on neurocognitive performance and daily subjective mood in a population with primary insomnia. Methods This study used a randomized, placebo-controlled, parallel design incorporating a single-blind placebo run-in week followed by a two-week double-blind dosing period, during which participants consumed 150 mg CBD ( N  = 15) or placebo ( N  = 15) sublingually 60-minutes daily before bed. Attention, executive function, reasoning, information processing, working and episodic memory were assessed using the CogPro system at the beginning of the placebo run-in, after 1-week and 2-weeks of dosing. Subjective states using visual analogue scales and side effects were recorded daily. Results Cognitive performance was unaffected by nightly CBD supplementation (all p  > 0.05). From baseline to trial conclusion, those receiving CBD reported greater experience of calmness, clear-headedness, coordination and were more likely to report side-effects of dry mouth relative to placebo (all p  < 0.05). Conclusions Relative to placebo, daytime cognitive functioning following nightly supplementation as a therapeutic aid for primary insomnia was preserved under trial conditions. Results suggested an overall favourable safety profile, with larger controlled trials and thorough analyses of varying insomnia phenotypes necessary to corroborate these findings.

Background and aims There is a growing use of novel psychoactive substances (NPSs) including synthetic cannabinoids. Synthetic cannabinoid products have effects similar to those of natural cannabis but the new synthetic cannabinoids are more potent and dangerous and their use has resulted in various adverse effects. The purpose of the study was to assess whether persistent use of synthetic cannabinoids is associating with impairments of executive function in chronic users. Methods A total of 38 synthetic cannabinoids users, 43 recreational cannabis users, and 41 non-user subjects were studied in two centers in Hungary and Israel. Computerized cognitive function tests, the classical Stroop word-color task, n-back task, and a free-recall memory task were used. Results Synthetic cannabinoid users performed significantly worse than both recreational and non-cannabis users on the n-back task (less accuracy), the Stroop task (overall slow responses and less accuracy), and the long-term memory task (less word recall). Additionally, they have also shown higher ratings of depression and anxiety compared with both recreational and non-users groups. Discussion This study showed impairment of executive function in synthetic cannabinoid users compared with recreational users of cannabis and non-users. This may have major implications for our understanding of the long-term consequences of synthetic cannabinoid based drugs.

Purpose The aim of the present study was to examine the acute and chronic effects of wild blueberry supplementation on mood, executive function, and serum biomarkers of neuroplasticity, inflammation, and oxidative stress in emerging adults with moderate-to-severe depressive symptoms. Methods In this double-blind trial, 60 emerging adults ( M age  = 20.0 years, 32% male) with self-reported depressive symptoms were randomly assigned to receive a single blueberry drink (acute phase), followed by 6 weeks of daily blueberry supplementation (chronic phase), or a matched placebo drink. The primary outcome was Beck Depression Inventory-II (BDI-II) scores at 6-week follow-up. Further measures included momentary affect (PANAS-X) and accuracy on an executive function task. The data were analyzed using ANCOVAs adjusted for baseline values, sex, and habitual fruit and vegetable intake. Estimated marginal means were calculated to compare the treatment arms. Results The blueberry drink significantly improved positive affect ( p  = 0.026) and executive function ( p  = 0.025) at 2 h post-ingestion, with change scores being positively correlated in the blueberry group ( r  = 0.424, p  = 0.017). However, after six weeks of supplementation the reduction in BDI-II scores was greater in the placebo group by 5.8 points (95% CI: 0.8–10.7, p  = 0.023). Generalized anxiety and anhedonia also decreased significantly more in the placebo group. No significant differences were found for any of the biomarkers. Conclusions Six weeks of wild blueberry supplementation were inferior to placebo in reducing depressive symptoms. Nevertheless, the correlated improvements in positive affect and executive function after a single dose of blueberries point to a beneficial, albeit transient, psychological effect. These contrasting results suggest a biphasic, hormetic-like response that warrants further investigation. Trial registration : NCT04647019, dated 30 November, 2020.

During physical efforts and sport practice, vigilance is responsible for maintaining an optimal state of activation, guaranteeing the ability to quickly respond and detect unexpected, but critical, stimuli over time. Caffeine and physical exercise are able to modulate the activation state, affecting vigilance performance. The aim of the present work was to assess the specific effects and modulations of caffeine intake and two physical intensities on vigilance components. Participants performed an attentional task (ANTI-Vea) to measure the executive and arousal components of vigilance, in six double-blinded counterbalanced sessions combining caffeine, placebo, or no-ingestion, with light vs. moderate cyclergometer exercise. Exercise at moderate intensity improved executive vigilance with faster overall reaction time (RT), without impairing error rates. Instead, caffeine intake generally improved arousal vigilance. In conclusion, caffeine and acute exercise seems to moderate executive and arousal vigilance in different ways.