Executive dysfunction, including working memory deficits, is prominent in posttraumatic stress disorder (PTSD) and can impede treatment effectiveness. Intervention approaches that target executive dysfunction alongside standard PTSD treatments could boost clinical response. The current study reports secondary analyses from a randomized controlled trial testing combined PTSD treatment with a computerized training program to improve executive dysfunction. We assessed if pre-treatment neurocognitive substrates of executive functioning predicted clinical response to this novel intervention.

Treatment-seeking veterans with PTSD (N = 60) completed a working memory task during functional magnetic resonance imaging prior to being randomized to six weeks of computerized executive function training (five 30-minute sessions each week) plus twelve 50-minute sessions of cognitive processing therapy (CEFT + CPT) or placebo training plus CPT (PT + CPT). Using linear mixed effects models, we examined the extent to which the neurocognitive substrates of executive functioning predicted PTSD treatment response.

Results indicated that veterans with greater activation of working memory regions (e.g. lateral prefrontal and cingulate cortex) had better PTSD symptom improvement trajectories in CEFT + CPT v. PT + CPT. Those with less neural activation during working memory showed similar trajectories of PTSD symptom change regardless of treatment condition.

Greater activity of frontal regions implicated in working memory may serve as a biomarker of response to a novel treatment in veterans with PTSD. Individuals with greater regional responsiveness benefited more from treatment that targeted cognitive dysfunction than treatment that did not include active cognitive training. Clinically, findings could inform our understanding of treatment mechanisms and may contribute to better personalization of treatment.

Auditory system plasticity is a promising target for neuromodulation, cognitive rehabilitation and therapeutic development in schizophrenia (SZ). Auditory-based targeted cognitive training (TCT) is a ‘bottom up’ intervention designed to enhance the speed and accuracy of auditory information processing, which has been shown to improve neurocognition in certain SZ patients. However, the dynamics of TCT learning as a function of training exercises and their impact on neurocognitive functioning and therapeutic outcomes are unknown.

Forty subjects (SZ, n = 21; healthy subjects (HS), n = 19) underwent comprehensive clinical, cognitive, and auditory assessments, including measurements of auditory processing speed (APS) at baseline and after 1-h of TCT. SZ patients additionally completed 30-hours of TCT and repeated assessments ~10–12 weeks later.

SZ patients were deficient in APS at baseline (d = 0.96, p < 0.005) relative to HS. After 1-h of TCT, analyses revealed significant main effects of diagnosis (d = 1.75, p = 0.002) and time (d = 1.04, p < 0.001), and a diagnosis × time interaction (d = 0.85, p = 0.02) on APS. APS learning effects were robust after 1-h in SZ patients (d = 1.47, p < 0.001) and persisted throughout the 30-h of training. Baseline APS was associated with verbal learning gains after 30-h of TCT (r = 0.51, p = 0.02) in SZ.

TCT learning metrics may have prognostic utility and aid in the prospective identification of individuals likely to benefit from TCT. Future experimental medicine studies may advance predictive algorithms that enhance TCT-related clinical, cognitive and functional outcomes.

Cognition in MCI has responded poorly to pharmacological interventions, leading to use of computerized training. Combining computerized cognitive training (CCT) and functional skills training software (FUNSAT) produced improvements in 6 functional skills in MCI, with effect sizes >0.75. However, 4% of HC and 35% of MCI participants failed to master all 6 tasks. We address early identification of characteristics that identify participants who do not graduate, to improve later interventions.

NC participants (n = 72) received FUNSAT and MCI (n = 92) participants received FUNSAT alone or combined FUNSAT and CCT on a fully remote basis. Participants trained twice a week for up to 12 weeks. Participants “graduated” each task when they made one or fewer errors on all 3–6 subtasks per task. Tasks were no longer trained after graduation.

Between-group comparisons of graduation status on baseline completion time and errors found that failure to graduate was associated with more baseline errors on all tasks but no longer completion times. A discriminant analysis found that errors on the first task (Ticket purchase) uniquely separated the groups, F = 41.40, p < .001, correctly classifying 94% of graduators. An ROC analysis found an AUC of .83. MOCA scores did not increase classification accuracy.

More baseline errors, but not completion times, predicted failure to master all FUNSAT tasks. Accuracy of identification of eventual mastery was exceptional. Detection of risk to fail to master training tasks is possible in the first 15 minutes of the baseline assessment. This information can guide future enhancements of computerized training.

Everyday affective fluctuations are more extreme and more frequent in adolescence compared to any other time in development. Successful regulation of these affective experiences is important for good mental health and has been proposed to depend on affective control. The present study examined whether improving affective control through a computerised affective control training app (AffeCT) would benefit adolescent mental health.

One-hundred and ninety-nine participants (11–19 years) were assigned to complete 2 weeks of AffeCT or placebo training on an app. Affective control (i.e. affective inhibition, affective updating and affective shifting), mental health and emotion regulation were assessed at pre- and post-training. Mental health and emotion regulation were assessed again one month and one year later.

Compared with the placebo group, the AffeCT group showed significantly greater improvements in affective control on the trained measure. AffeCT did not, relative to placebo, lead to better performance on untrained measures of affective control. Pre- to post-training change in affective control covaried with pre- to post-training change in mental health problems in the AffeCT but not the placebo group. These mental health benefits of AffeCT were only observed immediately following training and did not extend to 1 month or year post-training.

In conclusion, the study provides preliminary evidence that AffeCT may confer short-term preventative benefits for adolescent mental health.

Cognitive development after schizophrenia onset can be shaped by interventions such as cognitive remediation, yet no study to date has investigated whether patterns of early behavioral development may predict later cognitive changes following intervention. We therefore investigated the extent to which premorbid adjustment trajectories predict cognitive remediation gains in schizophrenia.

In a total sample of 215 participants (170 first-episode schizophrenia participants and 45 controls), we classified premorbid functioning trajectories from childhood through late adolescence using the Cannon-Spoor Premorbid Adjustment Scale. For the 62 schizophrenia participants who underwent 6 months of computer-assisted, bottom-up cognitive remediation interventions, we identified MATRICS Consensus Cognitive Battery scores for which participants demonstrated mean changes after intervention, then evaluated whether developmental trajectories predicted these changes.

Growth mixture models supported three premorbid functioning trajectories: stable-good, deteriorating, and stable-poor adjustment. Schizophrenia participants demonstrated significant cognitive remediation gains in processing speed, verbal learning, and overall cognition. Notably, participants with stable-poor trajectories demonstrated significantly greater improvements in processing speed compared to participants with deteriorating trajectories.

This is the first study to our knowledge to characterize the associations between premorbid functioning trajectories and cognitive remediation gains after schizophrenia onset, indicating that 6 months of bottom-up cognitive remediation appears to be sufficient to yield a full standard deviation gain in processing speed for individuals with early, enduring functioning difficulties. Our findings highlight the connection between trajectories of premorbid and postmorbid functioning in schizophrenia and emphasize the utility of considering the lifespan developmental course in personalizing therapeutic interventions.

Cognitive training (CT) and aerobic exercise both show promising moderate impact on cognition and everyday functioning in schizophrenia. Aerobic exercise is hypothesized to increase brain-derived neurotrophic factor (BDNF) and thereby synaptic plasticity, leading to increased learning capacity. Systematic CT should take advantage of increased learning capacity and be more effective when combined with aerobic exercise.

We examined the impact of a 6-month program of cognitive training & exercise (CT&E) compared to cognitive training alone (CT) in 47 first-episode schizophrenia outpatients. All participants were provided the same Posit Science computerized CT, 4 h/week, using BrainHQ and SocialVille programs. The CT&E group also participated in total body circuit training exercises to enhance aerobic conditioning. Clinic and home-based exercise were combined for a target of 150 min per week.

The MATRICS Consensus Cognitive Battery Overall Composite improved significantly more with CT&E than with CT alone (p = 0.04), particularly in the first 3 months (6.5 v. 2.2 T-score points, p < 0.02). Work/school functioning improved substantially more with CT&E than with CT alone by 6 months (p < 0.001). BDNF gain tended to predict the amount of cognitive gain but did not reach significance. The cognitive gain by 3 months predicted the amount of work/school functioning improvement at 6 months. The amount of exercise completed was strongly associated with the degree of cognitive and work/school functioning improvement.

Aerobic exercise significantly enhances the impact of CT on cognition and functional outcome in first-episode schizophrenia, apparently driven by the amount of exercise completed.

There is a need to study therapies that may contribute to the successful rehabilitation of veterans with traumatic brain injury (TBI) and increase their effective interaction with the stressful environment, reduce the severity of symptoms. Combined short-term therapies may have potential.

To analyze the clinical case of combined psychological treatment of TBI in a Ukrainian combat veteran with reduced resilience

The clinical case of Ukrainian combat veteran with TBI is presented. Montreal Cognitive Assessment (MoCA) was used to assess cognitive domains. Neurobehavioral symptom inventory (NSI) was used to assess neurobehavioral symptoms of TBI. CD-RISC was used to assess resilience. In addition to pharmacotherapy, the patient agreed to undergo a combined program of psychological therapy of 3 short-term positive intervention sessions and 3 cognitive training sessions.

MoCA result prior to treatment was 24 p., NSI – 38 p., CD-RISC – 44 p. (lower than in population). After the combined therapy, the results of the assessment with MoCA were 26 points, NSI was 17 points, CD-RISC – 47 points. Subjectively, the patient noted an improvement in emotional state, better resilience, and a significant reduction in the intensity of cognitive symptoms.

Combining positive interventions with cognitive training can have the potential to significantly improve the neurobehavioral and cognitive functioning of war veterans with traumatic brain injury, and also possibly increase resilience. Further research in this direction will be conducted to obtain more reliable results.

Mild cognitive impairment (MCI) becomes increasingly common. It has been demonstrated high risk of progression to dementia. There are no approved medications for treatment of MCI while cognitive intervention might improve cognitive deficits. However, there have been insufficient evidence supporting the effect of the cognitive intervention.

To evaluate the effects of a cognitive rehabilitation training in patients with Mild cognitive impairment

A randomized controlled single-blind trial was conducted. Participants aged ≥ 60 years diagnosed with MCI were recruited and randomly assigned to intervention group (n=32) or waiting list control group (n=32). The intervention was 3-day weekly sessions of multi-component cognitive rehabilitation training for 3 months. Outcomes were assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB) to measure the effects of intervention at baseline, 3-month and 6-month follow up within the intervention group and compare between intervention group and control group.

The intervention showed significant improvements on the visual episodic memory (p<0.05) and on the executive function (p<0.05) at 3-month follow up. There was a trend towards improvement of cognition between the intervention group and control group, but this effect was not significant. At 6-month follow up, the OTS significantly changed from 3-month follow up, which reflect the maintaining effects of the cognitive training.

The cognitive rehabilitation training has demonstrated improvement of the visual episodic memory and the executive function for the elderly with MCI.

Anxiety and depression are leading causes of disability worldwide, yet individuals are often unable to access appropriate treatment. There is a need to develop effective interventions that can be delivered remotely. Previous research has suggested that emotional processing biases are a potential target for intervention, and these may be altered through brief training programs.

We report two experimental medicine studies of emotional bias training in two samples: individuals from the general population (n = 522) and individuals currently taking antidepressants to treat anxiety or depression (n = 212). Participants, recruited online, completed four sessions of EBT from their own home. Mental health and cognitive functioning outcomes were assessed at baseline, immediately post-training, and at 2-week follow-up.

In both studies, our intervention successfully trained participants to perceive ambiguous social information more positively. This persisted at a 2-week follow-up. There was no clear evidence that this change in emotional processing transferred to improvements in symptoms in the primary analyses. However, in both studies, there was weak evidence for improved quality of life following EBT amongst individuals with more depressive symptoms at baseline. No clear evidence of transfer effects was observed for self-reported daily stress, anhedonia or depressive symptoms. Exploratory analyses suggested that younger participants reported greater treatment gains.

These studies demonstrate the effectiveness of delivering a multi-session online training program to promote lasting cognitive changes. Given the inconsistent evidence for transfer effects, EBT requires further development before it can be considered as a treatment for anxiety and depression.

Preliminary evidence suggests beneficial effects of cognitive remediation in depression. An update of the current evidence is needed. The aim was to systematically assess the effectiveness of cognitive remediation in depression on three outcomes.

The meta-analysis was pre-registered on PROSPERO (CRD42019124316). PubMed, PsycINFO, Embase and Cochrane Library were searched on 2 February 2019 and 8 November 2020 for peer-reviewed published articles. We included randomized and non-randomized clinical trials comparing cognitive remediation to control conditions in adults with primary depression. Random-effects models were used to calculate Hedges' g, and moderators were assessed using mixed-effects subgroup analyses and meta-regression. Main outcome categories were post-treatment depressive symptomatology (DS), cognitive functioning (CF) and daily functioning (DF).

We identified 5221 records and included 21 studies reporting on 24 comparisons, with 438 depressed patients receiving cognitive remediation and 540 patients in a control condition. We found a small effect on DS (g = 0.28, 95% CI 0.09–0.46, I2 40%), a medium effect on CF (g = 0.60, 95% CI 0.37–0.83, I2 44%) and a small effect on DF (g = 0.22, 95% CI 0.06–0.39, I2 3%). There were no significant effects at follow-up. Confounding bias analyses indicated possible overestimation of the DS and DF effects in the original studies.

Cognitive remediation in depression improves CF in the short term. The effects on DS and DF may have been overestimated. Baseline depressive symptom severity should be considered when administering cognitive remediation.

Auditory frequency modulation learning (‘auditory learning’) is a key component of targeted cognitive training (TCT) for schizophrenia. TCT can be effective in enhancing neurocognition and function in schizophrenia, but such gains require significant time and effort and elude many patients.

As a strategy to increase and/or accelerate TCT-induced clinical gains, we tested the dose- and time-course effects of the pro-attentional drug, amphetamine (AMPH; placebo, 2.5, 5 or 10 mg po; within-subject double-blind, order balanced) on auditory learning in schizophrenia patients [n = 32; M:F = 19:13; age 42.0 years (24–55)]. To understand predictors and/or mechanisms of AMPH-enhanced TCT, we also measured auditory fidelity (words-in-noise (WIN), quick speech-in-noise (QuickSIN)) and neurocognition (MATRICS comprehensive cognitive battery (MCCB)). Some measures were also acquired from age-matched healthy subjects (drug free; n = 10; M:F = 5:5).

Patients exhibited expected deficits in neurocognition. WIN and QuickSIN performance at low signal intensities was impaired in patients with low v. high MCCB attention/vigilance (A/V) scores; these deficits were corrected by AMPH, maximally at 2.5–5 mg (d's = 0.79–1.29). AMPH also enhanced auditory learning, with maximal effects at 5 mg (d = 0.93), and comparable effects 60 and 210 min post pill. ‘Pro-learning’ effects of AMPH and AMPH-induced gains in auditory fidelity were most evident in patients with low MCCB A/V scores.

These findings advance our understanding of the impact of pro-attentional interventions on auditory information processing and suggest dose- and time-course parameters for studies that assess the ability of AMPH to enhance the clinical benefits of TCT in schizophrenia patients.

Cognitive deficits at the first episode of schizophrenia are predictive of functional outcome. Interventions that improve cognitive functioning early in schizophrenia are critical if we hope to prevent or limit long-term disability in this disorder.

We completed a 12-month randomized controlled trial of cognitive remediation and of long-acting injectable (LAI) risperidone with 60 patients with a recent first episode of schizophrenia. Cognitive remediation involved programs focused on basic cognitive processes as well as more complex, life-like situations. Healthy behavior training of equal treatment time was the comparison group for cognitive remediation, while oral risperidone was the comparator for LAI risperidone in a 2 × 2 design. All patients were provided supported employment/education to encourage return to work or school.

Both antipsychotic medication adherence and cognitive remediation contributed to cognitive improvement. Cognitive remediation was superior to healthy behavior training in the LAI medication condition but not the oral medication condition. Cognitive remediation was also superior when medication adherence and protocol completion were covaried. Both LAI antipsychotic medication and cognitive remediation led to significantly greater improvement in work/school functioning. Effect sizes were larger than in most prior studies of first-episode patients. In addition, cognitive improvement was significantly correlated with work/school functional improvement.

These results indicate that consistent antipsychotic medication adherence and cognitive remediation can significantly improve core cognitive deficits in the initial period of schizophrenia. When combined with supported employment/education, cognitive remediation and LAI antipsychotic medication show separate significant impact on improving work/school functioning.