Computerized cognitive training and functional recovery in major depressive disorder: A meta-analysis

Motter J.N., Devanand D.P., Doraiswamy P.M., Sneed J.R.

Manning K.J., Alexopoulos G.S., Banerjee S., Morimoto S.S., Seirup J.K., Klimstra S.A., Yuen G., Kanellopoulos T., Gunning-Dixon F.

Executive dysfunction may play a key role in the pathophysiology of late-life depression. Executive dysfunction can be assessed with cognitive tests and subjective report of difficulties with executive skills. The present study investigated the association between subjective report of executive functioning complaints and time to escitalopram treatment response in older adults with major depressive disorder (MDD).100 older adults with MDD (58 with executive functioning complaints and 42 without executive functioning complaints) completed a 12-week trial of escitalopram. Treatment response over 12 weeks, as measured by repeated Hamilton Depression Rating Scale scores, was compared for adults with and without executive complaints using mixed-effects modeling.Mixed effects analysis revealed a significant group × time interaction, F(1, 523.34) = 6.00, p = 0.01. Depressed older adults who reported executive functioning complaints at baseline demonstrated a slower response to escitalopram treatment than those without executive functioning complaints.Self-report of executive functioning difficulties may be a useful prognostic indicator for subsequent speed of response to antidepressant medication.

Siegle G.J., Price R.B., Jones N.P., Ghinassi F., Painter T., Thase M.E.

Treatments for severe depression have moderate success rates, often take many weeks to yield responses, and are often followed by relapse or recurrence. Neurobehavioral interventions address these limitations by targeting mechanisms of cognitive and emotional dysregulation directly. This study extends data and observations from a pilot study examining effects of 2 weeks (6 sessions) of adjunctive cognitive control training exercises added to medication and psychotherapy in severely depressed patients. We examined acute effects and predictors of change in rumination, and long-term effects on service utilization. Compared with treatment as usual, exercises were associated with decreases in rumination and decreased use of intensive outpatient services in the following year. Responses were strongest among patients who displayed physiological indicators (pupillary oscillations at the task frequency) of task engagement before the intervention. These indices changed following intervention, suggesting that the intervention required capitalization on relevant attentional mechanisms and addressed fundamental emotional processes through their cognitive substrates.

Segrave R.A., Arnold S., Hoy K., Fitzgerald P.B.

Major depressive disorder (MDD) is frequently associated with underactivity of the dorsolateral prefrontal cortex (DLPFC) which has led to this brain region being identified as an important target for the development of neurobiological treatments. Transcranial direct current stimulation (tDCS) administered to the DLPFC has antidepressant efficacy, however the magnitude of antidepressant outcomes are limited. Concurrent cognitive activity has been shown to enhance tDCS induced stimulation effects. Cognitive control training (CCT) is a new cognitive therapy for MDD that aims to enhance DLPFC activity via behavioral methods.We tested the hypothesis that co-administration of DLPFC tDCS and CCT would result in a greater reduction in depressive symptomology than administration of tDCS or CCT alone.27 adult participants with MDD were randomized into a three-arm sham-controlled between-groups pilot study comparing the efficacy of 2 mA tDCS + CCT, sham tDCS + CCT and sham CCT + 2 mA tDCS (5 sessions administered on consecutive working days). Blinded assessments of depression severity and cognitive control were conducted at baseline, end of treatment and a three week follow up review.All three treatment conditions were associated with a reduction in depression severity at the end of five treatment sessions. However, only administration of tDCS + CCT resulted in sustained antidepressant response at follow up, the magnitude of which was greater than that observed immediately following conclusion of the treatment course.The results provide preliminary evidence that concurrent CCT enhances antidepressant outcomes from tDCS. In the current sample, participants receiving concurrent tDCS and CCT continued to improve following cessation of treatment. The clinical superiority of a combined therapeutic approach was apparent even in a small sample and following a relatively short treatment course.

Rapport M.D., Orban S.A., Kofler M.J., Friedman L.M.

Children with ADHD are characterized frequently as possessing underdeveloped executive functions and sustained attentional abilities, and recent commercial claims suggest that computer-based cognitive training can remediate these impairments and provide significant and lasting improvement in their attention, impulse control, social functioning, academic performance, and complex reasoning skills. The present review critically evaluates these claims through meta-analysis of 25 studies of facilitative intervention training (i.e., cognitive training) for children with ADHD. Random effects models corrected for publication bias and sampling error revealed that studies training short-term memory alone resulted in moderate magnitude improvements in short-term memory (d=0.63), whereas training attention did not significantly improve attention and training mixed executive functions did not significantly improve the targeted executive functions (both nonsignificant: 95% confidence intervals include 0.0). Far transfer effects of cognitive training on academic functioning, blinded ratings of behavior (both nonsignificant), and cognitive tests (d=0.14) were nonsignificant or negligible. Unblinded raters (d=0.48) reported significantly larger benefits relative to blinded raters and objective tests (both p

Anguera J.A., Boccanfuso J., Rintoul J.L., Al-Hashimi O., Faraji F., Janowich J., Kong E., Larraburo Y., Rolle C., Johnston E., Gazzaley A.

Training with a multitasking video game is shown to improve cognitive control abilities that decline with age, revealing the plasticity of the ageing brain; these behavioural improvements were accompanied by underlying neural changes that predicted the training-induced boost in sustained attention and enhanced multitasking performance 6 months later. Our ability to multitask and our capacity for cognitive control decline linearly as we age. A new study shows that cognitive training can help repair this decline. In older adults aged between 60 and 85 who trained at home by playing NeuroRacer, a custom-designed 3D video game, both multitasking and cognitive control improved, with effects persisting for six months. The benefits of this training extended to untrained cognitive functions such as sustained attention and working memory. These findings suggest that the ageing brain may be more robustly plastic than previously thought, allowing for cognitive enhancement using appropriately designed strategies. Cognitive control is defined by a set of neural processes that allow us to interact with our complex environment in a goal-directed manner1. Humans regularly challenge these control processes when attempting to simultaneously accomplish multiple goals (multitasking), generating interference as the result of fundamental information processing limitations2. It is clear that multitasking behaviour has become ubiquitous in today’s technologically dense world3, and substantial evidence has accrued regarding multitasking difficulties and cognitive control deficits in our ageing population4. Here we show that multitasking performance, as assessed with a custom-designed three-dimensional video game (NeuroRacer), exhibits a linear age-related decline from 20 to 79 years of age. By playing an adaptive version of NeuroRacer in multitasking training mode, older adults (60 to 85 years old) reduced multitasking costs compared to both an active control group and a no-contact control group, attaining levels beyond those achieved by untrained 20-year-old participants, with gains persisting for 6 months. Furthermore, age-related deficits in neural signatures of cognitive control, as measured with electroencephalography, were remediated by multitasking training (enhanced midline frontal theta power and frontal–posterior theta coherence). Critically, this training resulted in performance benefits that extended to untrained cognitive control abilities (enhanced sustained attention and working memory), with an increase in midline frontal theta power predicting the training-induced boost in sustained attention and preservation of multitasking improvement 6 months later. These findings highlight the robust plasticity of the prefrontal cognitive control system in the ageing brain, and provide the first evidence, to our knowledge, of how a custom-designed video game can be used to assess cognitive abilities across the lifespan, evaluate underlying neural mechanisms, and serve as a powerful tool for cognitive enhancement.

Porter R.J., Bowie C.R., Jordan J., Malhi G.S.

Objective: There is considerable literature regarding the effectiveness of cognitive remediation (CR) in schizophrenia and in conditions such as stroke and traumatic brain injury. Patients with major depressive disorder (MDD) present with significant cognitive impairment which in many cases may not resolve with treatment. Neurobiological data suggest that this may relate to underlying dysfunction of pre-frontal cortical areas of the brain and their connections with limbic structures. There has been limited research into specific CR to activate these areas and target impaired cognitive function in MDD. We therefore review current evidence, examine the theoretical basis for and present a rationale for research into CR in MDD. In addition, we will examine important methodological issues in developing such an approach. Method: Based on preliminary studies using CR-based techniques, data from CR in schizophrenia, data regarding baseline and residual cognitive impairment in depression, and knowledge of the neurobiology of MDD, we examine the possible utility of CR strategies in the treatment of MDD and make recommendations for research in this area. Results: A small number of previous studies have examined specific CR in MDD. The studies are small and inconclusive. However, data on the neuropsychological function and neurobiology of MDD suggest that this is an approach that deserves further attention and research. Conclusions: Further research is required in carefully selected populations, using well-defined CR techniques and some form of comparator treatment.

Holt R.I., Phillips D.I., Jameson K.A., Cooper C., Dennison E.M., Peveler R.C.

Previous studies suggest a link between depression, anxiety and cardiovascular disease (CVD). The aim of the study was to determine the relationship between depressive and anxiety symptoms and CVD in a population based cohort. In total 1578 men and 1,417 women from the Hertfordshire Cohort Study were assessed for CVD at baseline and after 5.9±1.4 years. Depressive and anxiety symptoms were measured using the HADS scale. Baseline HAD-D score, but not HAD-A, was significantly associated with baseline plasma triglycerides , glucose and insulin resistance (men only) and HDL cholesterol (women only). After adjustment for CVD risk factors , higher baseline HAD-D scores were associated with increased odds ratios for CVD (men: 1.162 [95% CI 1.096–1.231]; women: 1.107 [1.038–1.181]). Higher HAD-A scores associated with increased CVD in men only. High HAD-D scores predicted incident CVD (adjusted OR 1.130 [1.034–1.235]), all-cause mortality (adjusted HR 1.081, [1.012–1.154]) and cardiovascular mortality (adjusted HR 1.109 [1.002–1.229]) in men but not in women. The use of a self-report measure of depressive and anxiety symptoms, ‘healthy’ responder bias and the low number of cardiovascular events are all limitations. Depressive and anxiety symptoms are commoner in people with CVD. These symptoms are independent predictors of CVD in men. Although HAD-D score was significantly associated with several cardiovascular risk factors, this did not fully explain the association between HAD-D and CVD.

Bowie C.R., Gupta M., Holshausen K., Jokic R., Best M., Milev R.

AbstractNeurocognitive impairments are observed in depression and associated with poor functioning. This study examined the efficacy and the effectiveness of cognitive remediation with supplemental Internet-based homework in treatment-resistant depression. Participants were randomized to treatment or wait list control conditions. Treatment consisted of 10 weeks of weekly group sessions and daily online cognitive exercises completed at home. The participants were assessed on cognitive, mood, motivation, and functioning measures. There was a significant time by treatment interaction for attention/processing speed and verbal memory. Changes in functioning were not significant, although improved cognition predicted improvements in functioning. Number of minutes of online exercise was associated with greater cognitive improvements. Cognitive deficits are malleable with behavioral treatment in a mood disorder characterized by severe and persistent symptoms.

Rutherford B.R., Roose S.P.

Placebo response in clinical trials of antidepressant medications is substantial and has been increasing. High placebo response rates hamper efforts to detect signals of efficacy for new antidepressant medications, contributing to trial failures and delaying the delivery of new treatments to market. Media reports seize upon increasing placebo response and modest advantages for active drugs as reasons to question the value of antidepressant medication, which may further stigmatize treatments for depression and dissuade patients from accessing mental health care. Conversely, enhancing the factors responsible for placebo response may represent a strategy for improving available treatments for major depressive disorder. A conceptual framework describing the causes of placebo response is needed in order to develop strategies for minimizing placebo response in clinical trials, maximizing placebo response in clinical practice, and talking with depressed patients about the risks and benefits of antidepressant medications. In this review, the authors examine contributors to placebo response in antidepressant clinical trials and propose an explanatory model. Research aimed at reducing placebo response should focus on limiting patient expectancy and the intensity of therapeutic contact in antidepressant clinical trials, while the optimal strategy in clinical practice may be to combine active medication with a presentation and level of therapeutic contact designed to enhance treatment response.

Preiss M., Shatil E., Čermáková R., Cimermanová D., Ram I.

Patients with unipolar depressive disorder and in the depressive phase of bipolar disorder often manifest psychological distress and cognitive deficits, notably in Executive Control. We used computerized cognitive training in anattempt to reduce psychological affliction, improve everyday coping and cognitive function. We asked one group of patients (intervention group) to engage in cognitive training three times a week, for 20 minutes each time, for eight consecutive weeks. A second group of patients (control group) received standard care only. Before the onset of training we administered to all patients self-report questionnaires of mood, mental and psychological health, and everyday coping. We also assessed Executive Control using a broad computerized neurocognitive battery of tests which yielded, among others, scores in Working Memory, Shifting, Inhibition, Visuomotor Vigilance, Divided Attention, Memory Span and a Global Executive Function score. All questionnaires and tests were re-administered to the patients who adhered to the study at the end of training. When we compared the groups (between-group comparisons) on the amount of change that had taken place from baseline to post-training, we found improvements in Executive Control. Further exploration of the data showed that the cognitive improvements did not predict the improvements in everyday coping, and mood. Single-group data (within-group comparisons) show that patients in the intervention group were reporting fewer cognitive failures, fewer dysexecutive incidents and less difficulty in everyday coping. This group had also improved significantly on the six Executive Control tests and on the Global Executive Control score. By contrast, the control group improved only on the reports of cognitive failure and on working memory.

Owens M., Koster E.H., Derakshan N.

Impaired filtering of irrelevant information from working memory is thought to underlie reduced working memory capacity for relevant information in dysphoria. The current study investigated whether training-related gains in working memory performance on the adaptive dual n-back task could result in improved inhibitory function. Efficacy of training was monitored in a change detection paradigm allowing measurement of a sustained event-related potential asymmetry sensitive to working memory capacity and the efficient filtering of irrelevant information. Dysphoric participants in the training group showed training-related gains in working memory that were accompanied by gains in working memory capacity and filtering efficiency compared to an active control group. Results provide important initial evidence that behavioral performance and neural function in dysphoria can be improved by facilitating greater attentional control.

Lohman M.C., Rebok G.W., Spira A.P., Parisi J.M., Gross A.L., Kueider A.M.

Background: Cognitive performance benefits from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study may differ for individuals who exhibit a greater number of depressive symptoms. Method: Using data from ACTIVE memory training and control conditions, we evaluated the effect of depressive symptomatology on memory scores across a 5-year period. Of 1,401 participants, 210 had elevated depressive symptoms at baseline, as measured by a 12-item version of the Center for Epidemiological Studies-Depression Scale (CES-D). Results: Participants with elevated depressive symptoms scored significantly lower at baseline and had faster decline in memory performance than those exhibiting fewer depressive symptoms. Memory score differences among depressive symptom categories did not differ between training conditions. Discussion: Findings suggest that elevated depressive symptoms may predict declines in memory ability over time, but do not attenuate gains from training. Training provides a potential method of improving memory which is robust to effects of depression.

Salminen T., Strobach T., Schubert T.

Recent studies have reported improvements in a variety of cognitive functions following sole working memory (WM) training. In spite of the emergence of several successful training paradigms, the scope of transfer effects has remained mixed. This is most likely due to the heterogeneity of cognitive functions that have been measured and tasks that have been applied. In the present study, we approached this issue systematically by investigating transfer effects from WM training to different aspects of executive functioning. Our training task was a demanding WM task that requires simultaneous performance of a visual and an auditory n-back task, while the transfer tasks tapped WM updating, coordination of the performance of multiple simultaneous tasks (i.e., dual-tasks) and sequential tasks (i.e., task switching), and the temporal distribution of attentional processing. Additionally, we examined whether WM training improves reasoning abilities; a hypothesis that has so far gained mixed support. Following training, participants showed improvements in the trained task as well as in the transfer WM updating task. As for the other executive functions, trained participants improved in a task switching situation and in attentional processing. There was no transfer to the dual-task situation or to reasoning skills. These results therefore confirm previous findings that WM can be trained, and additionally, they show that the training effects can generalize to various other tasks tapping on executive functions.

Alexopoulos G.S., Hoptman M.J., Kanellopoulos D., Murphy C.F., Lim K.O., Gunning F.M.

Abnormalities have been identified in the Cognitive Control Network (CCN) and the Default Mode Network (DMN) during episodes of late-life depression. This study examined whether functional connectivity at rest (FC) within these networks characterizes late-life depression and predicts antidepressant response.26 non-demented, non-MCI older adults were studied. Of these, 16 had major depression and 10 had no psychopathology. Depressed patients were treated with escitalopram (target dose 20 mg) for 12 weeks after a 2-week placebo phase. Resting state time series was determined prior to treatment. FC within the CCN was determined by placing seeds in the dACC and the DLPFC bilaterally. FC within the DMN was assessed from a seed placed in the posterior cingulate.Low resting FC within the CCN and high resting FC within the DMN distinguished depressed from normal elderly subjects. Beyond this "double dissociation", low resting FC within the CCN predicted low remission rate and persistence of depressive symptoms and signs, apathy, and dysexecutive behavior after treatment with escitalopram. In contrast, resting FC within the DMN was correlated with pessimism but did not predict treatment response.If confirmed, these findings may serve as a signature of the brain's functional topography characterizing late-life depression and sustaining its symptoms. By identifying the network abnormalities underlying biologically meaningful characteristics (apathy, dysexecutive behavior, pessimism) and sustaining late-life depression, these findings can provide a novel target on which new somatic and psychosocial treatments can be tested.

Jeong H.S., Lee Y.W., Rhee T.G., Shim S.R.

Lukka L., Vesterinen M., Salonen A., Bergman V., Torkki P., Palva S., Palva J.M.

Zwalmen Y.V., Koster E.H., Demeester D., Baeken C., Verhaeghe N., Hoorelbeke K.

Yu M., Wang J., Xia Y., Fan Y., Tang Q., Wang S., Ren Q., Tao Y.

Purpose To determine the status of depression and its key influencing factors among Chinese older adults in different living situations. Method Data of 7,092 older adults were obtained from the China Health and Retirement Longitudinal Survey. This study analyzed key variables influencing depressive symptoms using random forest modeling and logistic regression. Results The prevalence of depressive symptoms in older adults is 33.2%, with the highest prevalence of depression in older adults living alone (41.2%). Cognitive functioning and life satisfaction are psychological factors that affect older adults' mental health, whereas self-rated health and child relationship satisfaction are biological and social factors affecting their mental health, respectively. Furthermore, self-rated pain and limitations in activities of daily living were identified as risk factors for their mental health. Key factors affecting older adults' mental health differ between living situations. Conclusion Key factors of depressive symptoms in older adults differ across living situations, providing a priority and reference for differential prevention and precise intervention of depressive symptoms to promote a healthy aging process. Results of the current study may help clinicians better understand the pathogenesis of depression in older adults, guide clinical diagnosis and treatment, and develop individualized depression prevention and management strategies. [ Research in Gerontological Nursing, xx (x), xx–xx.]

Bomyea J., Caudle M.M., Dugas N., Moore R.C., Simmons A.N., Thomas M.L.

Wittmann F.G., Pabst A., Zülke A., Luppa M., Cardona M.I., Boekholt M., Fankhänel T., Weise S., Kosilek R.P., Sanftenberg L., Brettschneider C., Döhring J., Williamson M., Wiese B., Thyrian J.R., et. al.

Background The aim of the study was to analyze the impact of adherence to the intervention components on the effectiveness of AgeWell.de, a multi-domain lifestyle intervention against cognitive decline, on function in everyday activities, quality of life, depressiveness and social isolation. Objective Studying the effect of adherence on health-related outcomes. Methods Participants were aged 60–77 years at baseline and at risk (Cardiovascular Risk Factors, Ageing and Dementia Score (CAIDE) ≥9). Adherence to the components nutrition, enhancement of physical and social activities and cognitive training was analyzed in two ways, first continual within the intervention group (n = 378, mean age = 69.1 years, 52.7% female) and second as dichotomous split (75% adherence) and in reference to the control group (received infomaterial and regular health advice; n = 441, mean age = 69 years, 53% female). Generalized linear regression models were then run on the health outcomes functioning in everyday activities, quality of life, depressive symptoms, and social inclusion. Results Health-related quality of life and depressiveness were improved in participants with better adherence to nutritional counselling and enhancement of physical and social activities. Better adherence to social activities was relevant for function in everyday activities. Effects of high adherence to cognitive training was found for improvements in depressiveness when comparing it to the control group. No effect was found on social inclusion when considering the particular components. Conclusions The extent of adherence to most components influenced health-related outcomes such as health-related quality of life and depressiveness. With this study, the effectiveness of AgeWell.de can be understood in greater depth. Trial Registration German Clinical Trial Register (DRKS; ID: DRKS00013555).

Charvet L., Goldberg J.D., Li X., Best P., Lustberg M., Shaw M., Zhovtis L., Gutman J., Datta A., Bikson M., Pilloni G., Krupp L.

Fatigue is a common and often debilitating feature of multiple sclerosis (MS) that lacks reliably effective treatment options for most patients. Transcranial direct current stimulation (tDCS), a safe and well-tolerated type of noninvasive brain stimulation, is a low-cost and home-based approach with the potential to reduce fatigue in MS. We conducted a double-blind, sham-controlled, randomized clinical trial to compare active vs. low-dose (sham) tDCS paired with computer-based cognitive training, delivered as a home-based intervention, to reduce MS-related fatigue. Participants with MS-related fatigue, but without depression, were stratified by neurologic disability using the Extended Disability Status Scale (EDSS) and randomized to complete 30 daily sessions over six weeks of either active or sham tDCS paired with online cognitive training (BrainHQ). The primary outcome was the change in PROMIS Fatigue score from baseline to the end of the intervention. A total of 117 participants were randomized, with 92% completing all treatment sessions. Both groups showed significant reductions in fatigue, with no significant difference between them. This suggests that tDCS does not provide any additional benefit over cognitive training alone in reducing fatigue, but confirms the feasibility and tolerance of this home-based intervention.

Xu C., Tao Y., Lin Y., Zhu J., Li Z., Li J., Wang M., Huang T., Shi C.

BackgroundIncreasing evidences suggests that depression is a heterogeneous clinical syndrome. Cognitive deficits in depression are associated with poor psychosocial functioning and worse response to conventional antidepressants. However, a consistent profile of neurocognitive abnormalities in depression remains unclear.ObjectiveWe used data-driven parsing of cognitive performance to reveal subgroups present across depressed individuals and then investigate the change pattern of cognitive subgroups across the course in follow-up.MethodWe assessed cognition in 163 patients with depression using The Chinese Brief Cognitive Test(C-BCT) and the scores were compared with those of 196 healthy controls (HCs). 58 patients were reassessed after 8 weeks. We used K-means cluster analysis to identify cognitive subgroups, and compared clinical variables among these subgroups. A linear mixed-effects model, incorporating time and group (with interaction term: time × group) as fixed effects, was used to assess cognitive changes over time. Stepwise logistic regression analysis was conducted to identify risk factors associated with these subgroups.ResultsTwo distinct neurocognitive subgroups were identified: (1) a cognitive-impaired subgroup with global impairment across all domains assessed by the C-BCT, and (2) a cognitive-preserved subgroup, exhibited intact cognitive function, with performance well within the healthy range. The cognitive-impaired subgroup presented with more severe baseline symptoms, including depressed mood, guilt, suicidality, and poorer work performance. Significant group × time interactions were observed in the Trail Making Test Part A (TMT-A) and Continuous Performance Test (CPT), but not in Symbol Coding or Digit Span tests. Despite partial improvement in TMT-A and CPT tests, the cognitive-impaired subgroup's scores remained lower than those of the cognitive-preserved subgroup across all tests at the study endpoint. Multiple regression analysis indicated that longer illness duration, lower educational levels, and antipsychotic medication use may be risk factors for cognitive impairment.ConclusionThis study identifies distinguishable cognitive subgroups in acute depression, thereby confirming the presence of cognitive heterogeneity. The cognitive-impaired subgroup exhibits distinct symptoms and persistent cognitive deficits even after treatment. Screening for cognitive dysfunction may facilitate more targeted interventions.Clinical Trial Registrationhttps://www.chictr.org, identifier ChiCTR2400092796.

Richter T., Shani R., Tal S., Derakshan N., Cohen N., Enock P.M., McNally R.J., Mor N., Daches S., Williams A.D., Yiend J., Carlbring P., Kuckertz J.M., Yang W., Reinecke A., et. al.

Cognitive training is a promising intervention for psychological distress; however, its effectiveness has yielded inconsistent outcomes across studies. This research is a pre-registered individual-level meta-analysis to identify factors contributing to cognitive training efficacy for anxiety and depression symptoms. Machine learning methods, alongside traditional statistical approaches, were employed to analyze 22 datasets with 1544 participants who underwent working memory training, attention bias modification, interpretation bias modification, or inhibitory control training. Baseline depression and anxiety symptoms were found to be the most influential factor, with individuals with more severe symptoms showing the greatest improvement. The number of training sessions was also important, with more sessions yielding greater benefits. Cognitive trainings were associated with higher predicted improvement than control conditions, with attention and interpretation bias modification showing the most promise. Despite the limitations of heterogeneous datasets, this investigation highlights the value of large-scale comprehensive analyses in guiding the development of personalized training interventions.

Carballo-Marquez A., Ampatzoglou A., Rojas-Rincón J., Garcia-Casanovas A., Garolera M., Fernández-Capo M., Porras-Garcia B.

Executive functions (EFs) are essential cognitive processes involved in concentration, planning, decision-making, and impulse control during adolescence. Executive Dysfunction (ED) can lead to significant academic and socio-emotional difficulties, particularly with impairments in emotion regulation (ER). This study aims to assess a virtual reality (VR) cognitive training intervention on EFs, ER, and internalizing symptoms in adolescents at risk for ED. Thirty-eight adolescents aged 12–14 years, identified as being at moderate to high risk for ED, were randomly assigned to two groups. The experimental group (n = 22) received gamified VR cognitive training, while the control group (n = 16) received VR nature-based relaxation training. Both interventions lasted five weeks, twice a week for 30 min each. Pre- and post-assessments included ER skills, internalizing symptoms, and cognitive performance measures. Two-way mixed ANOVAs showed significant group × time interactions (p < 0.05) in measures of depression and internalizing symptoms. The experimental group showed significant reductions in these symptoms compared with the control group. Significant main effects of time (p < 0.05) were also found on some measures. Both groups experienced reduced anxiety, improved emotional control and cognitive functioning, and VR cognitive training was particularly effective in reducing internalizing symptoms, while both interventions showed promising results in improving some ER skills and cognitive performance. The findings demonstrate the preliminary effects of VR-based cognitive training in improving the psychological and cognitive well-being of adolescents at risk for ED and suggest that integrating VR technologies into educational settings can effectively address the cognitive and emotional challenges faced by these students.

Oudega M.L., Wagenmakers M.J., Palsma T., Hoogendoorn A.W., Vriend C., van den Heuvel O.A., Schouws S., Dols A.

IntroductionUnipolar and bipolar mood disorders in older adults are accompanied by cognitive impairment, including executive dysfunction, with a severe impact on daily life. Up and till now, strategies to improve cognitive functioning in late-life mood disorders (LLMD) are sparse. Therefore, we aimed to assess the efficacy of adaptive, computerized cognitive training (CT) on executive and subjective cognitive functioning in LLMD.MethodsIn this double-blind, randomized controlled study we enrolled patients over the age of 50 with partly remitted LLMD. Over 8 weeks, patients participated in 24 45-minute sessions of computerized multi-domain training (CT) or an active control condition (ACC) (nonspecific cognitive activity). The primary outcome was executive functioning based on the interference score on the STROOP task (not incorporated in the training). Secondary outcomes were subjective cognitive functioning, depressive symptoms and quality of life. Outcomes were assessed before and after training (T1) and at a 3-month follow-up (T2) and analyzed with linear mixed-model analyses.ResultsThirty-eight patients were included in the study, 22 in the experimental CT and 16 in the ACC. Mean age was 67.3 years and 52.6% was female. Linear mixed-model analyses showed small within-group effect sizes, corresponding to no statistically significant improvement of executive functioning or depression severity in either group. In both groups we did observe an improvement on subjective cognitive functioning over time. From T0 to T1 the mean score of the Cognitive Functioning Questionnaire (CFQ) of the CT group decreased from 52.7 to 46.8 points (p=0.003) and the mean CFQ score of the ACC group decreased from 52.7 to 45.7 points (p&lt;0.001). This effect remained in both groups at follow-up (T2); respectively p=0.002 and p&lt;0.001.The patients in the AAC also showed an improvement of quality of life directly after the training (T1); i.e. the mean quality of life scores improved from 53 to 57 points (p=0.011), but this effect did not remain at follow-up.ConclusionsThis study shows no beneficial effect of an 8-week computerized CT on the primary outcome, i.e, executive functioning. Subjective cognitive functioning did improve in both groups, indicating that frequent cognitive training is advantageous. Future studies with more intensive training could be designed to explore this result further.Clinical trial registrationclinicaltrials.gov, identifier NCT04006756.

Bomyea J., Feng S., Moore R.C., Simmons A.N., Thomas M.L.

Repetitive negative thinking (RNT) symptoms, which are characterized by pervasive, uncontrollable negative thoughts, are common in individuals with mood, anxiety, and traumatic stress disorders. Inability to regulate the contents of working memory is a hypothesized etiological factor in RNT, which suggests that training to improve working memory may be beneficial. This study examined the effects of working memory training on resting-state functional connectivity (rsFC) in individuals with elevated RNT and whether such changes would be associated with clinical improvement.

Vander Zwalmen Y., Hoorelbeke K., Demeester D., Koster E.H.

Background Cognitive control training (CCT) has gained attention in recent years as a preventative intervention in the context of major depressive disorder. To date, uncertainty exists around the working mechanisms of CCT and how its effects unfold overtime. Objective This study aimed to examine cognitive and affective transfer effects following an unusually high number of training sessions. Methods This case report presents data of a participant completing a large amount of training sessions (n=55) over the course of 1 year in 2 training phases: 10 initial sessions, followed by 45 additional sessions. Reliable change indices were calculated for several self-report questionnaires, measuring cognitive and affective functioning. Results Cognitive task performance suggests improved cognitive functioning after training (accuracy scores increased from 43/181, 24% at baseline to 110/181, 61% shortly after training), which was maintained at follow-up (accuracy scores around 50%). Reliable change indices suggest a decrease in depressive symptoms (Beck Depression Inventory-II score decreased from 23 at baseline to 3 following initial training). Similarly, burnout symptoms following CCT showed a similar decrease. Maladaptive emotion regulation strategies displayed high variability, decreasing after periods of training but increasing when no training was performed. However, no changes in repetitive negative thinking were observed. Thematic analysis from an in-depth interview focusing on CCT adherence and user experience pointed to the importance of independency and accessibility of CCT in perceived agency, as well as the need for clear feedback mechanisms following training. Conclusions Training task performance indicates further increases in performance beyond typical amounts of training sessions (10-20 sessions), hinting that more sessions could be beneficial for continued improvement in cognitive functioning. In line with previous research, CCT decreased depressive symptomatology. However, its effects on emotion regulation remain unclear. Further mechanistic studies into the temporal unfolding of CCT effects are necessary to investigate potential working mechanisms. Trial Registration ClinicalTrials.gov NCT05166798; https://clinicaltrials.gov/study/NCT05166798

Wang X., Zhou J., Zhu K., Wang Y., Ma X., Ren L., Guo C., Zhang Z., Lu P., Zhang Q.

This randomized, open-label study examined the therapeutic effects of Neurocognitive Adaptive Training for Depression (NCAT-D) combined with selective serotonin reuptake inhibitors (SSRIs) on cognitive impairment among patients with late-life depression (LLD). Study data were collected from May 5, 2021, to April 21, 2023. Outpatients who met the diagnostic criteria for major depressive disorder according to the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (i.e., a total score on the 17-item Hamilton Depression Rating Scale (HAMD-17) ≥ 18 and a total score on the Montreal Cognitive Assessment scale (MOCA) < 26) were recruited at Beijing Anding Hospital. These participants were randomly assigned to receive up to 12 weeks of NCAT-D and SSRIs treatment (n = 57) or SSRIs with a control treatment (n = 61). Primary outcomes included changes in Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores from baseline to week 12 between the two groups. Assessments were conducted at baseline, after 2 weeks, 4 weeks, 8 weeks, and at 12 weeks. Mixed model repeated measures (MMRM) analysis was performed on modified intention-to-treat (mITT) and completer populations. The full analysis set (FAS) included 118 patients (NCAT-D and SSRIs group, n = 57; SSRIs and Control group, n = 61). During the 12-week study period, MMRM analysis revealed a significantly greater reduction in cognitive function (as indicated by ADAS-cog total scores) from baseline to post-treatment in the NCAT-D and SSRIs group compared to the SSRIs and Control groups [(F (1,115) = 13.65, least-squares mean difference [95% CI]: −2.77 [− 3.73, − 1.81], p < 0.001)]. The intervention group showed a significantly greater reduction in HAMD-17 scores compared to the control group [MMRM, estimated mean difference (SE) between groups: −3.59 [− 5.02, − 2.15], p < 0.001]. There was no significant difference in the incidence of adverse events between the two groups. NCAT-D combined with SSRIs was efficacious and well tolerated in LLD patients with cognitive impairment. Registered on October 18, 2022, at ClinicalTrials.gov Identifier: (#NCT05588102).

Stamatis C.A., Heusser A., Ala'ilima T., Flannery J.E., Simon T.J., Kollins S.H.