Psychological constructs related to health outcomes and well-being, such as metacognitive beliefs, have been linked to executive functions in general, and cognitive flexibility more specifically. However, such effects have previously only been discussed on a theoretical level and behavioral flexibility has most often been measured through self-report, only approximating information processing capacities. Objectively measured executive functions may be a more potent predictor of health outcomes. We set out to test whether cognitive flexibility capacity was associated with sick leave in a medium sized company. We included 111 subjects of widely different occupations and assessed their executive functions using Delis-Kaplan Executive Function System test battery (D-KEFS). To assess cognitive flexibility capacity, we included Design Fluency (DF) and Verbal Fluency (VF) and computed these into an index of cognitive flexibility (DFVF). Detailed information on sick leave for the last 5 years was gathered from the company. Our results showed that there was a significant negative correlation between DFVF and sick leave [rs(109) = −0.23, p = 0.015] in the full group as well as in the group that had at least 1 day of sick leave [rs(72) = −0.25, p = 0.03]. The results withstood adjustment for sex, age, occupation, and several core executive functions as well as autistic and ADHD-traits. The results remained for separate analyses using DF or VF. Our main findings were conceptually replicated in a group of bipolar disorder patients. This study shows that objectively measured capacity of cognitive flexibility is associated with key health outcomes such as sick leave.

IntroductionVaccination-related conspiracy ideation is related to reduced compliance with public health advice globally. Such beliefs have previously been linked to the delusion-proneness trait. However, it is not known how this extends to getting vaccinated.MethodsHere, we examined how delusion-proneness, as assessed by Peters et al. Delusions Inventory (PDI), is associated with COVID-19 vaccination in a sample of 273 subjects. We also examined whether delusion-proneness predicted the time to get vaccinated, after the vaccine became available.ResultsUnvaccinated subjects were more delusion-prone than vaccinated subjects (W=2225.5, p<0.001, effect-size=0.27). Among vaccinated subjects, higher delusion-proneness was related to longer time to get vaccinated (rs=0.27, p<0.001). These effects remained after adjusting for anxiety, ADHD, and ASD (Autism Spectrum Disorder) traits as well as for psychiatric diagnoses and sex. Path analyses indicated that the effect of delusion-proneness on vaccination rate was strongly mediated through COVID-19 conspiracy ideation, suggesting that delusion prone individuals first develop specific delusion-like ideas regarding vaccination, which then delays vaccination. An exploratory analysis of written text by subjects instructed to explain why they had vaccinated or not, revealed a difference in reasoning between the groups. Unvaccinated individuals were primarily motivated by concerns about personal safety and potential side effects, while vaccinated individuals stated a desire to protect themselves and others as the primary reasons to get vaccinated. DiscussionOur results suggest that delusion-proneness is a key factor for attaining conspiracy beliefs, at least in relation to COVID-19 pandemic, and associated with lower vaccination rates as well as longer time to get vaccinated.

It has long been speculated that psychedelic use could provoke the onset of psychosis, but there is little evidence to support this conjecture. Using a longitudinal research design with samples representative of the US and UK adult populations with regard to sex, age, and ethnicity (n = 9732), we investigated associations between psychedelic use and change in the number of psychotic symptoms during the two-month study period. In covariate-adjusted regression models, psychedelic use during the study period was not associated with a change in the number of psychotic symptoms unless it interacted with a personal or family history of bipolar disorder, in which case the number of symptoms increased, or with a personal (but not family) history of psychotic disorders, in which case the number of symptoms decreased. Taken together, these findings indicate that psychedelic use may affect psychotic symptoms in individuals with a personal or family history of certain disorders characterized by psychotic symptomatology.

Previous research has suggested that classical psychedelics can foster significant and enduring changes in personality traits and subjective wellbeing. Despite the lack of evidence for adverse effects on mental health stemming from psychedelic use, concerns persist regarding the capacity of these substances to modulate information processing and attitudes towards factual data. The aim of the present study was to investigate the propensity for accepting alternative facts and the general treatment of knowledge within a sample of 392 participants, 233 of whom reported at least a single incidence of psychedelic use in their lifetime. To do this, we leveraged step-wise methods of linear modelling investigating effects of demographics, psychiatric conditions and concomitant drug use. Our findings revealed a moderate positive association between psychedelic use and beliefs in alternative facts, as well as the specific belief that facts are politically influenced. However, no links were found for favouring intuition over evidence when confirming facts. Among other investigated drugs, only alcohol was negatively associated with beliefs in alternative facts. Taken together, our results support the link between psychedelic use and non-conformist thinking styles, which can be attributed to the psychological effects of the drugs themselves, but may also mirror a common trait related to unconventional beliefs and illicit substance use.

Abstract Objective Placebo effect has been found to be a significant contributor to the outcomes of antidepressant treatment, leading to questions about its overall efficacy. Previous research has shown that global societal trends and events such as economic recessions and pandemics, significantly affect people's mental health. The relationship between the two has not previously been examined. The present study investigated how global social sentiment, as indexed by global suicide rates, is related to the the treatment response in clinical trials of antidepressants. Methods We scrutinized data from a 1979–2016 meta-analysis of antidepressant clinical trials for depression. Outcomes from placebo and active groups, including responders, remitters, and dropouts, were matched with annual global suicide rates. Linear and non-linear methods were leveraged to estimate effect-sizes. Results During periods with high suicide rates, placebo groups displayed fewer responders (r=-0.38,P < 0.001) and remitters (r=-0.42,P < 0.001), and a higher dropout rate (r = 0.56,P < 0.001). Active groups exhibited a similar pattern, but the placebo arms were affected more strongly. The findings held true after applying non-linear methods, alternative metrics, and accounting for initial depression severity, group size, publication year, trial duration, proportion of multi-center studies. Specificity analyses revealed that earlier suicide rates had stronger association with the trial outcomes, and in a subsample of studies conducted in North America suicide rates from more culturally distant countries had weaker association with the outcomes. Conclusions The placebo effects observed in antidepressant treatment are influenced by societal wellbeing, suggesting that socionomic sentiment should be taken into account when assessing the effectiveness of psychopharmacological interventions.

Background The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture. Methods A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research. Discussion This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma.

Abstract Objective Placebo effect has been found to be a significant contributor to the outcomes of antidepressant treatment, leading to questions about its overall efficacy. Previous research has shown that global societal trends and events such as economic recessions and pandemics, significantly affect people's mental health. The relationship between the two has not previously been examined. The present study investigated how global social sentiment, as indexed by global suicide rates, is related to the the treatment response in clinical trials of antidepressants. Methods We scrutinized data from a 1979–2016 meta-analysis of antidepressant clinical trials for depression. Outcomes from placebo and active groups, including responders, remitters, and dropouts, were matched with annual global suicide rates. Linear and non-linear methods were leveraged to estimate effect-sizes. Results During periods with high suicide rates, placebo groups displayed fewer responders (r=-0.38,P < 0.001) and remitters (r=-0.42,P < 0.001), and a higher dropout rate (r = 0.56,P < 0.001). Active groups exhibited a similar pattern, but the placebo arms were affected more strongly. The findings held true after applying non-linear methods, alternative metrics, and accounting for initial depression severity, group size, publication year, trial duration, proportion of multi-center studies. Specificity analyses revealed that earlier suicide rates had stronger association with the trial outcomes, and in a subsample of studies conducted in North America suicide rates from more culturally distant countries had weaker association with the outcomes. Conclusions The placebo effects observed in antidepressant treatment are influenced by societal wellbeing, suggesting that socionomic sentiment should be taken into account when assessing the effectiveness of psychopharmacological interventions.

Balance dysfunction is a disabling symptom in people with Parkinson’s disease (PD). Evidence suggests that exercise can improve balance performance and induce neuroplastic effects. We hypothesised that a 10-week balance intervention (HiBalance) would improve balance, other motor and cognitive symptoms, and alter task-evoked brain activity in people with PD. We performed a double-blind randomised controlled trial (RCT) where 95 participants with PD were randomised to either HiBalance ( n = 48) or a control group ( n = 47). We found no significant group by time effect on balance performance ( b = 0.4 95% CI [−1, 1.9], p = 0.57) or on our secondary outcomes, including the measures of task-evoked brain activity. The findings of this well-powered, double-blind RCT contrast previous studies of the HiBalance programme but are congruent with other double-blind RCTs of physical exercise in PD. The divergent results raise important questions on how to optimise physical exercise interventions for people with PD. Preregistration clinicaltrials.gov: NCT03213873.

Delusional beliefs consist of strong priors characterized by resistance to change even when evidence supporting another view is overwhelming. Such bias against disconfirmatory evidence (BADE) has been experimentally demonstrated in patients with psychosis as well as in delusion proneness. In this fMRI-study, we tested for similar resistance to change and associated brain processes in extinction of fear learning, involving a well-described mechanism dependent of evidence updating. A social fear conditioning paradigm was used in which four faces had either been coupled to an unconditioned aversive stimulus (CS+) or not (CS-). For two of the faces, instructions had been given about the fear contingencies (iCS+/iCS-) while for two other faces no such instructions had been given (niCS+/niCS-). Interaction analysis suggested that individuals who score high on delusion-proneness (hDP; n = 20) displayed less extinction of evaluative fear compared to those with low delusion proneness (lDP; n = 23; n = 19 in fMRI-analysis) for non-instructed faces (F = 5.469, P = .024). The resistance to extinction was supported by a difference in extinction related activity between the two groups in medial prefrontal cortex and its connectivity with amygdala, as well as in a cortical network supporting fear processing. For instructed faces no extinction was noted, but there was a larger evaluative fear (F = 5.048, P = 0.03) and an increased functional connectivity between lateral orbitofrontal cortex and fear processing regions for hDP than lDP. Our study links previous explored BADE-effects in delusion associated phenotypes to fear extinction, and suggest that effects of instructions on evaluative fear learning are more pronounced in delusion prone subjects.

The stock market is a bellwether of socio-economic changes that may directly affect individual well-being. Using large-scale UK-biobank data generated over 14 years, we applied specification curve analysis to rigorously identify significant associations between the local stock market index (FTSE100) and 479,791 UK residents’ mood, as well as their alcohol intake and blood pressure adjusting the results for a large number of potential confounders, including age, sex, linear and non-linear effects of time, research site, other stock market indexes. Furthermore, we found similar associations between FTSE100 and volumetric measures of affective brain regions in a subsample (n=39,755; measurements performed over 5.5 years), which were particularly strong around phase transitions characterized by maximum volatility in the market. The main findings did not depend on applied effect-size estimation criteria (linear methods or mutual information criterion) and were replicated in two independent US-based studies (Parkinson’s Progression Markers Initiative; n=424; performed over 2,5 years and MyConnectome; n=1; 81 measurements over 1,5 years). Our results suggest that phase transitions in the society, indexed by stock market, exhibit close relationships with human mood, health and the affective brain from an individual to population level.

The rapid spread of conspiracy ideas associated with the recent COVID-19 pandemic represents a major threat to the ongoing and coming vaccination programs. Yet, the cognitive factors underlying the pandemic-related conspiracy beliefs are not well described. We hypothesized that such cognitive style is driven by delusion proneness, a trait phenotype associated with formation of delusion-like beliefs that exists on a continuum in the normal population. To probe this hypothesis, we developed a COVID-19 conspiracy questionnaire (CCQ) and assessed 577 subjects online. Their responses clustered into three factors that included Conspiracy, Distrust and Fear/Action as identified using principal component analysis. We then showed that CCQ (in particular the Conspiracy and Distrust factors) related both to general delusion proneness assessed with Peter's Delusion Inventory (PDI) as well as resistance to belief update using a Bias Against Disconfirmatory Evidence (BADE) task. Further, linear regression and pathway analyses suggested a specific contribution of BADE to CCQ not directly explained by PDI. Importantly, the main results remained significant when using a truncated version of the PDI where questions on paranoia were removed (in order to avoid circular evidence), and when adjusting for ADHD- and autistic traits (that are known to be substantially related to delusion proneness). Altogether, our results strongly suggest that pandemic-related conspiracy ideation is associated with delusion proneness trait phenotype.

VO 2 max (maximal oxygen consumption), a validated measure of aerobic fitness, has been associated with better cerebral artery compliance and measures of brain morphology, such as higher cortical thickness (CT) in frontal, temporal and cingular cortices, and larger grey matter volume (GMV) of the middle temporal gyrus, hippocampus, orbitofrontal cortex and cingulate cortex. Single sessions of physical exercise can promptly enhance cognitive performance and brain activity during executive tasks. However, the immediate effects of exercise on macro-scale properties of the brain’s grey matter remain unclear. We investigated the impact of one session of moderate-intensity physical exercise, compared with rest, on grey matter volume, cortical thickness, working memory performance, and task-related brain activity in older adults. Cross-sectional associations between brain measures and VO 2 max were also tested. Exercise did not induce statistically significant changes in brain activity, grey matter volume, or cortical thickness. Cardiovascular fitness, measured by VO 2 max, was associated with lower grey matter blood flow in the left hippocampus and thicker cortex in the left superior temporal gyrus. Cortical thickness was reduced at post-test independent of exercise/rest. Our findings support that (1) fitter individuals may need lower grey matter blood flow to meet metabolic oxygen demand, and (2) have thicker cortex.

OBJECTIVE:Pedophilic disorder (PD) is characterized bypersistent, intense sexual attraction to prepubertal children that the individual has acted on, or causes marked distress or interpersonal difficulty. Although prior research suggests that PD has neurodevelopmental underpinnings, the evidence remains sparse. To aid the understanding of etiology and treatment development, we quantified neurobiological and clinical correlates of PD.METHOD:We compared 55 self-referred, help-seeking, non-forensic male patients with DSM-5 PD with 57 age-matched, healthy male controls (HC) on clinical, neuropsychological, and structural brain imaging measures (cortical thickness and surface area, subcortical and white matter volumes). Structural brain measures were related to markers for aberrant neurodevelopment including IQ, and the 2nd to 4th digit ratio (2D:4D).RESULTS:PD was associated with psychiatric disorder comorbidity and ADHD and autism spectrum disorder symptoms. PD patients had lower total IQ than HC. PD individuals exhibited cortical surface area abnormalities in regions belonging to the brain's default mode network and showed abnormal volume of white matter underlying those regions. PD subjects had smaller hippocampi and nuclei accumbens than HC. Findings were not related to history of child-related sexual offending. IQ correlated negatively with global expression of PD-related brain features and 2D:4D correlated with surface area in PD.CONCLUSIONS:In the largest single-center study to date, we delineate psychiatric comorbidity, neurobiological and cognitive correlates of PD. Our morphometric findings, their associations with markers of aberrant neurodevelopment, and psychiatric comorbidities suggest that neurodevelopmental mechanisms are involved in PD. The findings may need consideration in future development of clinical management of PD patients.

Background: Regular physical activity is beneficial for cognitive performance in older age. A single bout of aerobic physical exercise can transiently improve cognitive performance. Researchers have advanced improvements in cerebral circulation as a mediator of long-term effects of aerobic physical exercise on cognition, but the immediate effects of exercise on cognition and cerebral perfusion are not well characterized and the effects in older adults are largely unknown. Methods: Forty-nine older adults were randomized to a 30-min aerobic exercise at moderate intensity or relaxation. Groups were matched on age and cardiovascular fitness (VO2 max). Average Grey Matter Blood Flow (GMBF), measured by a pulsed arterial-spin labeling (pASL) magnetic resonance imaging (MRI) acquisition, and working memory performance, measured by figurative n-back tasks with increasing loads were assessed before and 7 min after exercising/resting. Results: Accuracy on the n-back task increased from before to after exercising/resting regardless of the type of activity. GMBF decreased after exercise, relative to the control (resting) group. In the exercise group, higher n-back performance after exercise was associated with lower GMBF in the right hippocampus, left medial frontal cortex and right orbitofrontal cortex, and higher cardiovascular fitness was associated with lower GMBF. Conclusion: The decrease of GMBF reported in younger adults shortly after exercise also occurs in older adults and relates to cardiovascular fitness, potentially supporting the link between cardiovascular fitness and cerebrovascular reactivity in older age.

We investigated the feasibility aspects of two choice reaction time tasks designed to assess implicit sequence learning and dual task ability in individuals with mild to moderate Parkinson’s disease in comparison to healthy individuals. Twelve individuals with mild to moderate Parkinson’s disease and 12 healthy individuals, all ≥ 60 years of age, were included. A serial reaction time task was used as a measure of implicit sequence learning and a similar task but with the addition of a simple counting task, was used as a measure of dual task ability. We have present thorough descriptive statistics of the data but we have refrained from any inferential statistics due to the small sample size. All participants understood the task instructions and the difficulty level of both tasks was deemed acceptable. There were indications of task fatigue that demand careful choices for how best to analyse the data from such tasks in future trials. Ceiling effects were present in several accuracy outcomes, but not in the reaction time outcomes. Overall, we found both tasks to be feasible to use in samples of individuals with mild to moderate Parkinson’s disease and healthy older individuals.

BackgroundBipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD.MethodsLongitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables.ResultsCompared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex (0.18 < d < 0.22). More (hypo)manic episodes were associated with faster cortical thinning, primarily in the prefrontal cortex.ConclusionsIn the hitherto largest longitudinal MRI study on BD, we did not detect accelerated cortical thinning but noted faster ventricular enlargements in BD. However, abnormal frontocortical thinning was observed in association with frequent manic episodes. Our study yields insights into disease progression in BD and highlights the importance of mania prevention in BD treatment.

It has previously been demonstrated that short-term foreign language learning can lead to structural brain changes in younger adults. Experience-dependent brain plasticity is known to be possible also in older age, but the specific effect of foreign language learning on brain structure in language-and memory-relevant regions in the old brain remains unknown. In the present study, 160 older Swedish adults (65–75 years) were randomized to complete either an entry-level Italian course or a relaxation course, both with a total duration of 11 weeks. Structural MRI scans were conducted before and after the intervention in a subset of participants to test for differential change in gray matter in the two groups in the inferior frontal gyrus, the superior temporal gyrus, and the hippocampus, and in white matter microstructure in the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), fronto-occipital fasciculus, and the hippocampal (HC) section of the cingulum. The study found no evidence for differential structural change following language training, independent of achieved vocabulary proficiency. However, hippocampal volume and associative memory ability before the intervention were found to be robust predictors of vocabulary proficiency at the end of the language course. The results suggest that having greater hippocampal volume and better associative memory ability benefits vocabulary learning in old age but that the very initial stage of foreign language learning does not trigger detectable changes in brain morphometry in old age.

Despite recently resurrected scientific interest in classical psychedelics, few studies have focused on potential harms associated with abuse of these substances. In particular, the link between psychedelic use and psychotic symptoms has been debated while no conclusive evidence has been presented. Here, we studied an adult population (n = 1032) with a special focus on young (18–35 years) and healthy individuals (n = 701) to evaluate the association of psychedelic drug use with schizotypy and evidence integration impairment typically observed in psychosis-spectrum disorders. Experimental behavioural testing was performed in a subsample of the subjects (n = 39). We observed higher schizotypy scores in psychedelic users in the total sample. However, the effect size was notably small and only marginally significant when considering young and healthy subjects (Cohen’s d = 0.13). Controlling for concomitant drug use, none of our analyses found significant associations between psychedelic use and schizotypal traits. Results from experimental testing showed that total exposure to psychedelics (frequency and temporal proximity of use) was associated with better evidence integration (Cohen’s d = 0.13) and a higher sensitivity of fear responses (Cohen’s d = 1.05) to the effects instructed knowledge in a reversal aversive learning task modelled computationally with skin conductance response and pupillometry. This effect was present even when controlling for demographics and concomitant drug use. On a group level, however, only difference in sensitivity of fear responses to instructed knowledge reached statistical significance. Taken together, our findings suggest that psychedelic drug use is only weakly associated with psychosis-like symptoms, which, in turn, is to a large extent explained by psychiatric comorbidities and use of other psychoactive substances. Our results also suggest that psychedelics may have an effect on flexibility of evidence integration and aversive learning processes, that may be linked to recently suggested therapeutic effects of psychedelic drugs in non-psychotic psychiatric populations.

Genetic and hormonal factors have been suggested to influence human sexual orientation. Previous studied proposed brain differences related to sexual orientation and that these follow cross-sex shifted patterns. However, the neurobiological correlates of sexual orientation and how genetic factors relate to brain structural variation remains largely unexplored. Using the largest neuroimaging-genetics dataset available on same-sex sexual behavior (SSB) (n = 18,645), we employed a data-driven multivariate classification algorithm (PLS) on magnetic resonance imaging data from two imaging modalities to extract brain covariance patterns related to sex. Through analyses of latent variables, we tested for SSB-related cross-sex shifts in such patterns. Using genotype data, polygenic scores reflecting the genetic predisposition for SSB were computed and tested for associations with neuroimaging outcomes. Patterns important for classifying between males and females were less pronounced in non-heterosexuals. Predominantly in non-heterosexual females, multivariate brain patterns as represented by latent variables were shifted toward the opposite sex. Complementary univariate analyses revealed region specific SSB-related differences in both males and females. Polygenic scores for SSB were associated with volume of lateral occipital and temporo-occipital cortices. The present large-scale study demonstrates multivariate neuroanatomical correlates of SSB, and tentatively suggests that genetic factors related to SSB may contribute to structural variation in certain brain structures. These findings support a neurobiological basis to the differences in human sexuality.

The dorsolateral prefrontal cortex (DLPFC) is part of a network important for emotional regulation and the possibility of modulating activity in this region with transcranial direct current stimulation (TDCS) to change mood has gained great interest, particularly for application in clinical populations. Whilst results in major depressive disorder have been promising, less is known about the effects of TDCS on mood in non-clinical populations. We hypothesized that multiple sessions of anodal TDCS applied over the left DLPFC would enhance mood, primarily as measured by the Profile of Mood States questionnaire, in healthy older adults. In addition, in an exploratory analysis, we examined the potentially moderating role of working memory training. Working memory, just like emotional regulation, taxes the DLPFC, which suggests that engaging in a working memory task whilst receiving TDCS may have a different effect on activity in this region and consequently mood. A total of 123 participants between 65 and 75 years of age were randomly assigned to receive either 20 sessions of TDCS, with or without working memory training, or 20 sessions sham stimulation, with or without working memory training. We found no support for enhancement of mood due to TDCS in healthy older adults, with or without cognitive training and conclude that the TDCS protocol used is unlikely to improve mood in non-depressed older individuals.