Putting measurement-based care into action: A mixed methods study of the benefits of integrating routine client feedback in coordinated specialty care programs for early psychosis.

Background: Measurement-based care (MBC) is an effective tool in the delivery of evidence-based practices (EBPs). MBC utilizes feedback loops to share information and drive changes throughout a learning healthcare system. Few studies have demonstrated this practice in team-based care for people with early psychosis. This paper describes the development of a personalized feedback report derived from routine assessments that is shared with clients and clinicians as part of a MBC process. Methods: We used a quasi pre-post comparison design with mixed methods to evaluate the implementation of a personalized feedback report at 5 early psychosis coordinated specialty care programs (CSC). We compared clients enrolled in CSC who did and did not receive a feedback report over the first 6 months of treatment. The sample included 204 clients: 146 who did not receive the feedback report and were enrolled over 2 years, and 58 who received the feedback report. A subset of 67 clients completed measures at both intake and 6-month follow-up, including 42 who received the report and 25 who did not. We compared the two groups with regard to self-reported symptoms, likelihood of completing treatment, and perception of shared decision making. We conducted qualitative interviews with 5 clients and 5 clinicians to identify the benefits and challenges associated with the personalized feedback report. Results: People who received a personalized feedback report reported significant improvements in shared decision-making and had greater improvements over time in their intent to attend future treatment sessions. They engaged in more sessions for Supported Employment and Education (SEE), case management, and peer support, and fewer medication visits over the first 6 months of treatment. Both groups showed significant improvement in symptoms and functioning. Results from the qualitative analysis indicated that the experience of receiving the reports was valuable and validating for both patients and clinicians. Conclusions: A personalized feedback report was integrated into standard of care for early psychosis programs. This process may improve shared decision-making, strengthen the likelihood to stay in treatment, and increase engagement in psychosocial interventions. We posit that this process facilitates strengths-focused discussions, enhances intrinsic motivation, and strengthens the therapeutic alliance.

Linking social motivation, general motivation, and social cognition to interpersonal functioning in schizophrenia: insights from exploratory graph analysis.

Motivation in general, and social motivation in particular are important for interpersonal functioning in individuals with schizophrenia. Still, their roles after accounting for social cognition, are not well understood. The sample consisted of 147 patients with schizophrenia. General motivation was measured using the Behavioral inhibition/activation scale (BIS/BAS). Social motivation was measured by Passive social withdrawal and Active social avoidance items from PANSS. Interpersonal functioning was evaluated with Birchwood's Social Functioning Scale (SFS). We used Exploratory Graph Analysis for network estimation and community detection. Active social avoidance, passive social withdrawal, and social withdrawal/engagement (from SFS) were the most important nodes. In addition, three distinct communities were identified: Social cognition, Social motivation, and Interpersonal functioning. Notably, the BIS and BAS measures of general motivation were not part of any community. BAS showed stronger links to functioning than BIS. Passive social withdrawal was more strongly linked to interpersonal functioning than social cognitive abilities. Results suggest that social motivation, especially social approach, is more closely related to interpersonal functioning in schizophrenia than general motivation. In contrast, we found that general motivation was largely unrelated to social motivation. This pattern highlights the importance of type of motivation for understanding variability in interpersonal difficulties in schizophrenia.

The Effects of Remote Cognitive Training Combined With a Mobile App Intervention on Psychosis: Double-Blind Randomized Controlled Trial.

BACKGROUND: Impairments in cognition and motivation are core features of psychosis and strong predictors of social and occupational functioning. Accumulating evidence indicates that cognitive deficits in psychosis can be improved by computer-based cognitive training programs; however, barriers include access and adherence to cognitive training exercises. Limited evidence-based methods have been established to enhance motivated behavior. In this study, we tested the effects of web-based targeted cognitive and social cognitive training (TCT) delivered in conjunction with an innovative digital smartphone app called Personalized Real-Time Intervention for Motivational Enhancement (PRIME). The PRIME app provides users with a motivational coach to set personalized goals and secure social networking for peer support. OBJECTIVE: This study investigated whether deficits in cognition and motivation in people with a psychosis spectrum disorder (N=100) can be successfully addressed with 30 hours of TCT+PRIME as compared with 30 hours of a computer games control condition (CG) plus PRIME (CG+PRIME). Here, we describe our study procedures, the feasibility and acceptability of the intervention, and the results on all primary outcomes. METHODS: In this double-blind randomized controlled trial, English-speaking participants completed all cognitive training, PRIME activities, and assessments remotely. Participants completed a diagnostic interview and remote cognitive, clinical, and self-report measures at baseline, posttraining, and at a 6-month follow-up. RESULTS: This study included participants from 27 states across the United States and 8 countries worldwide. The study population was 58% (58/100) female, with a mean age of 33.77 (SD 10.70) years. On average, participants completed more than half of the cognitive training regimen (mean 18.58, SD 12.47 hours of training), and logged into the PRIME app 4.71 (SD 1.58) times per week. The attrition rate of 22% (22/100) was lower than that reported in our previous studies on remote cognitive training. The total sample showed significant gains in global cognition (P=.03) and attention (P<.001). The TCT+PRIME participants showed significantly greater gains in emotion recognition (P<.001) and global cognition at the trend level (P=.09), although this was not statistically significant, relative to the CG+PRIME participants. The total sample also showed significant improvements on multiple indices of motivation (P=.02-0.05), in depression (P=.04), in positive symptoms (P=.04), and in negative symptoms at a trend level (P=.09), although this was not statistically significant. Satisfaction with the PRIME app was rated at 7.74 (SD 2.05) on a scale of 1 to 10, with higher values indicating more satisfaction. CONCLUSIONS: These results demonstrate the feasibility and acceptability of remote cognitive training combined with the PRIME app and that this intervention can improve cognition, motivation, and symptoms in individuals with psychosis. TCT+PRIME appeared more effective in improving emotion recognition and global cognition than CG+PRIME. Future analyses will test the relationship between hours of cognitive training completed; PRIME use; and changes in cognition, motivation, symptoms, and functioning. TRIAL REGISTRATION: ClinicalTrials.gov NCT02782442; https://clinicaltrials.gov/study/NCT02782442.

Abnormal Information Flow in Schizophrenia Is Linked to Psychosis.

BACKGROUND AND HYPOTHESIS: Prior research has shown that patients with schizophrenia (SZ) show disruption in brain network connectivity that is thought to underlie their cognitive and psychotic symptoms. However, most studies examining functional network disruption in schizophrenia have focused on the temporally correlated coupling of the strength of network connections. Here, we move beyond correlative metrics to assay causal computations of connectivity changes in directed neural information flow, assayed from a neural source to a target in SZ. STUDY DESIGN: This study describes a whole-brain magnetoencephalography-imaging approach to examine causal computations of connectivity changes in directed neural information flow between brain regions during resting states, quantified by phase-transfer entropy (PTE) metrics, assayed from a neural source to an endpoint, in 21 SZ compared with 21 healthy controls (HC), and associations with cognitive and clinical psychotic symptoms in SZ. STUDY RESULTS: We found that SZ showed significant disruption in information flow in alpha (8-12 Hz) and beta (12-30 Hz) frequencies, compared to HC. Reduced information flow in alpha frequencies from the precuneus to the medio-ventral occipital cortex was associated with more severe clinical psychopathology (ie, positive psychotic symptoms), while reduced information flow between insula and middle temporal gyrus was associated with worsening cognitive symptoms. CONCLUSIONS: The present findings highlight the importance of delineating dysfunction in neural information flow in specific oscillatory frequencies between distinct regions that underlie the cognitive and psychotic symptoms in SZ, and provide potential neural biomarkers that could lead to innovations in future neuromodulation treatment development.

Changes in emotion processing and social cognition with auditory versus visual neuroscience-informed cognitive training in individuals with schizophrenia.

BACKGROUND: Neuroscience-informed cognitive training has been used to remediate cognitive deficits in schizophrenia, but their effect on emotion processing and social cognition deficits, which may involve auditory and visual impairments, remain relatively unknown. In this study, we compared the efficacy of auditory versus visual neuroscience-informed cognitive training on emotion processing and social cognition in individuals with schizophrenia. METHODS: In this randomised, double-blind clinical trial, 79 participants with chronic schizophrenia performed 40-hours auditory or visual dynamically equivalent computerised cognitive training. We assessed emotion processing and social cognition using Emotion Recognition, Affective Go-NoGo, Mayer-Salovey-Caruso Emotional-Intelligence, Theory of mind, and Hinting tests before and after 20 h and 40 h of training. RESULTS: After training, participants from both groups decreased their reaction time for facial emotion recognition (p = 3 × 10-6, d = 0.9). This was more remarkable for the auditory group when analysing individual emotions. Both groups also reduced omissions in the affective go-no go (p = 0.01, d = 0.6), which was also attributed, post hoc, to the auditory group. Trends for improvement were observed in theory of mind (p = 0.06, d = 0.6) for both groups. Improvement in emotion processing was associated with improvement in reasoning and problem solving and global cognition and improvement in theory of mind was associated with improvement in attention and global cognition. CONCLUSIONS: Both the auditory and the visual neuroscience-informed cognitive training were efficacious at improving emotion processing and social cognition in individuals with schizophrenia, although improvement was more remarkable for the auditory training group. These improvements were related to cognitive - but not symptom - improvement.

Durable Cognitive Gains and Symptom Improvement Are Observed in Individuals With Recent-Onset Schizophrenia 6 Months After a Randomized Trial of Auditory Training Completed Remotely.

OBJECTIVE: Cognitive impairment in schizophrenia predicts functional outcomes and is largely unresponsive to pharmacology or psychotherapy; it is thus a critical unmet treatment need. This article presents the impact of remotely completed, intensive, targeted auditory training (AT) vs control condition computer games (CG) in a double-blind randomized trial in young adults with recent-onset schizophrenia. METHOD: Participants (N = 147) were assessed for cognition, symptoms, and functioning at baseline, post-intervention, and at 6-month follow-up. All participants were provided with laptop computers and were instructed to complete 40 hours remotely of training or computer games. An intent-to-treat analysis (N = 145) was performed using linear mixed models with time modeled as a continuous variable. Planned contrasts tested the change from baseline to post-training, baseline to 6-month follow-up, and post-training to 6-month follow-up. RESULTS: Global Cognition, which had improved in the AT group relative to the CG group at post-training, showed durable gains at 6-month follow-up in an omnibus group-by-time interaction test (F(1,179) = 4.80, P = .030), as did Problem-Solving (F(1,179) = 5.13, P = .025), and Speed of Processing improved at trend level significance (F(1,170) = 3.80, P = .053). Furthermore, the AT group showed significantly greater improvement than the CG group in positive symptoms (F(1,179) = 4.06, P = .045). CONCLUSIONS: These results provide the first evidence of durable cognitive gains and symptom improvement at follow-up of cognitive training (CT) in early schizophrenia completed independently and remotely. While functioning did not show significant improvement, these findings suggest that intensive targeted CT of auditory processing is a promising component of early intervention to promote recovery from psychosis.

Multivariate pattern analysis of brain structure predicts functional outcome after auditory-based cognitive training interventions.

Cognitive gains following cognitive training interventions are associated with improved functioning in people with schizophrenia (SCZ). However, considerable inter-individual variability is observed. Here, we evaluate the sensitivity of brain structural features to predict functional response to auditory-based cognitive training (ABCT) at a single-subject level. We employed whole-brain multivariate pattern analysis with support vector machine (SVM) modeling to identify gray matter (GM) patterns that predicted higher vs. lower functioning after 40 h of ABCT at the single-subject level in SCZ patients. The generalization capacity of the SVM model was evaluated by applying the original model through an out-of-sample cross-validation analysis to unseen SCZ patients from an independent validation sample who underwent 50 h of ABCT. The whole-brain GM volume-based pattern classification predicted higher vs. lower functioning at follow-up with a balanced accuracy (BAC) of 69.4% (sensitivity 72.2%, specificity 66.7%) as determined by nested cross-validation. The neuroanatomical model was generalizable to an independent cohort with a BAC of 62.1% (sensitivity 90.9%, specificity 33.3%). In particular, greater baseline GM volumes in regions within superior temporal gyrus, thalamus, anterior cingulate, and cerebellum predicted improved functioning at the single-subject level following ABCT in SCZ participants. The present findings provide a structural MRI fingerprint associated with preserved GM volumes at a single baseline timepoint, which predicted improved functioning following an ABCT intervention, and serve as a model for how to facilitate precision clinical therapies for SCZ based on imaging data, operating at the single-subject level.

Testing a Novel Web-Based Neurocognitive Battery in the General Community: Validation and Usability Study.

BACKGROUND: In recent years, there has been increased interest in the development of remote psychological assessments. These platforms increase accessibility and allow clinicians to monitor important health metrics, thereby informing patient-centered treatment. OBJECTIVE: In this study, we report the properties and usability of a new web-based neurocognitive assessment battery and present a normative data set for future use. METHODS: A total of 781 participants completed a portion of 8 tasks that captured performance in auditory processing, visual-spatial working memory, visual-spatial learning, cognitive flexibility, and emotional processing. A subset of individuals (n=195) completed a 5-question survey measuring the acceptability of the tasks. RESULTS: Between 252 and 426 participants completed each task. Younger individuals outperformed their older counterparts in 6 of the 8 tasks. Therefore, central tendency data metrics were presented using 7 different age bins. The broad majority of participants found the tasks interesting and enjoyable and endorsed some interest in playing them at home. Only 1 of 195 individuals endorsed not at all for the statement, "I understood the instructions." Older individuals were less likely to understand the instructions; however, 72% (49/68) of individuals over the age of 60 years still felt that they mostly or very much understood the instructions. CONCLUSIONS: Overall, the tasks were found to be widely acceptable to the participants. The use of web-based neurocognitive tasks such as these may increase the ability to deploy precise data-informed interventions to a wider population.

Response to targeted cognitive training may be neuroprotective in patients with early schizophrenia.

Individuals with schizophrenia exhibit widespread cortical thinning associated with illness severity and deficits in cognition. However, intact cortical thickness (CTh) may serve as a protective factor. The current study sought to examine changes in CTh in response to auditory targeted cognitive training (TCT) in individuals with recent onset schizophrenia. Participants underwent MRI scanning and a cognitive assessment before and after being randomly assigned to 40 h of either TCT (N = 21) or a computer games control condition (CG; N = 22) over 16 weeks. Groups did not differ at baseline on demographic variables or measures of CTh. At the level of group averages, neither group showed significant pre-post changes in CTh in any brain region. However, changes in CTh related to individual differences in treatment outcome, as improved global cognition in the TCT group corresponded to reduced cortical thinning in frontal, temporal, parietal, and occipital lobes. These relationships were not observed in the CG group. The current findings suggest that TCT may be neuroprotective in early schizophrenia, such that individuals who improved in response to training also showed a reduction in cortical thinning that may be otherwise hastened due to age and illness.

Online Social Cognition Training in Schizophrenia: A Double-Blind, Randomized, Controlled Multi-Site Clinical Trial.

Social cognition (SC), the mental operations underlying social functioning, are impaired in schizophrenia. Their direct link to functional outcome and illness status have made them an important therapeutic target. However, no effective treatment for these deficits is currently applied as a standard of care. To address this need, we have developed SocialVille-an online, plasticity-based training program that targets SC deficits in schizophrenia. Here we report the outcomes of a double-blind, controlled, randomized, multi-site clinical trial of SocialVille. Outpatients with schizophrenia were randomized to complete 40 sessions of either SocialVille (N = 55 completers) or active control (computer games; N = 53 completers) from home. The a priori co-primary outcome measures were a social cognitive composite and a functional capacity outcome (UCSD Performance-based Skills Assessment [UPSA-2]). Secondary outcomes included a virtual functional capacity measure (VRFCAT), social functioning, quality of life, and motivation. Linear mixed models revealed a group × time interaction favoring the treatment group for the social cognitive composite (b = 2.81; P < .001) but not for the UPSA-2 measure. Analysis of secondary outcome measures showed significant group × time effects favoring the treatment group on SC and social functioning, on the virtual functional capacity measure and a motivation subscale, although these latter findings were nonsignificant with FDR correction. These results provide support for the efficacy of a remote, plasticity-based social cognitive training program in improving SC and social functioning in schizophrenia. Such treatments may serve as a cost-effective adjunct to existing psychosocial treatments. Trial Registration: NCT02246426.

A Neural Biomarker for Hallucinations: Medial Prefrontal Aberrations in Neural Connectivity Predict Self-Agency Deficits and Hallucination Severity in Schizophrenia.

Prior studies have shown that the medial prefrontal cortex (mPFC) represents one neural substrate that mediates judgments of self-agency (i.e., the awareness that 'I am the originator of my actions'). Patients with schizophrenia (SZ) manifest cardinal self-agency deficits that contribute to debilitating psychotic symptoms (e.g. hallucinations) and distort reality monitoring. This is the first study in which we examine across 2 SZ samples, the mPFC site that underlies self-agency deficits during an explicit reality-monitoring task (i.e., while subjects distinguish self-generated information from externally-derived information) in one SZ sample, and link intrinsic functional connectivity (iFC) during rest within this a priori task-evoked self-agency seed with hallucination symptoms in a different SZ sample. In particular, we examined the iFC between the mPFC site that underlies self-agency deficits with all other brain regions in SZ using resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI data were collected from 32 SZ and 28 age, gender, and education-matched healthy control (HC) subjects. Functional connectivity maps were computed for each subject and compared between the HC and SZ groups. Within-group and between-group analyses revealed that aberrant iFC in this a priori-defined mPFC 'self-agency seed' predicted hallucination severity. The present findings reveal that the neural aberrations in this mPFC site represents one cardinal biomarker that underlies explicit self-agency deficits during a reality-monitoring task in one SZ sample that generalized to aberrant iFC differences in a different SZ sample and predicted worsening psychotic hallucinatory experiences. This region may represent a key neurobiological target for treatment avenues to improve hallucinatory symptoms.

Specificity and Durability of Changes in Auditory Processing Efficiency After Targeted Cognitive Training in Individuals With Recent-Onset Psychosis.

BACKGROUND: We previously demonstrated that the high heterogeneity of response to computerized Auditory Training (AT) in psychosis can be ascribed to individual differences in sensory processing efficiency and neural plasticity. In particular, we showed that Auditory Processing Speed (APS) serves as a behavioral measure of target engagement, with faster speed predicting greater transfer effects to untrained cognitive domains. Here, we investigate whether the ability of APS to function as a proxy for target engagement is unique to AT, or if it applies to other training interventions, such as Executive Functioning Training (EFT). Additionally, we examine whether changes in APS are durable after these two forms of training. METHODS: One hundred and twenty-five participants with Recent Onset Psychosis (ROP) were randomized to AT (n = 66) and EFT (n = 59), respectively. APS was captured at baseline, after treatment, and at 6-month follow-up. Mixed models repeated measures analysis with restricted maximum likelihood was used to examine whether training condition differentiated APS trajectories. Within-group correlational analyses were used to study the relationship between APS and performance improvements in each of the training exercises. RESULTS: The two groups were matched for age, gender, education, and baseline APS. Participants showed high inter-individual variability in APS at each time point. The mixed model showed a significant effect of time (F = 5.99, p = .003) but not a significant group-by-time effect (F = .73, p = .48). This was driven by significant APS improvements AT patients after treatment (d = .75) that were maintained after 6 months (d = .63). Conversely, in EFT patients, APS improvements did not reach statistical significance after treatment (p = .33) or after 6 months (p = .24). In AT patients, baseline APS (but not APS change) highly predicted peak performance for each training exercise (all r's >.42). CONCLUSIONS: Participant-specific speed in processing basic auditory stimuli greatly varies in ROP, and strongly influences the magnitude of response to auditory but not executive functioning training. Importantly, enhanced auditory processing efficiency persists 6 months after AT, suggesting the durability of neuroplasticity processes induced by this form of training. Future studies should aim to identify markers of target engagement and durability for cognitive training interventions that target sensory modalities beyond the auditory domain.

Deficits in Auditory and Visual Sensory Discrimination Reflect a Genetic Liability for Psychosis and Predict Disruptions in Global Cognitive Functioning.

Sensory discrimination thresholds (i.e., the briefest stimulus that can be accurately perceived) can be measured using tablet-based auditory and visual sweep paradigms. These basic sensory functions have been found to be diminished in patients with psychosis. However, the extent to which worse sensory discrimination characterizes genetic liability for psychosis, and whether it is related to clinical symptomatology and community functioning remains unknown. In the current study we compared patients with psychosis (PSY; N=76), their first-degree biological relatives (REL; N=44), and groups of healthy controls (CON; N=13 auditory and visual/N=275 auditory/N=267 visual) on measures of auditory and visual sensory discrimination, and examined relationships with a battery of symptom, cognitive, and functioning measures. Sound sweep thresholds differed among the PSY, REL, and CON groups, driven by higher thresholds in the PSY compared to CON group, with the REL group showing intermediate thresholds. Visual thresholds also differed among the three groups, driven by higher thresholds in the REL versus CON group, and no significant differences between the REL and PSY groups. Across groups and among patients, higher thresholds (poorer discrimination) for both sound and visual sweeps strongly correlated with lower global cognitive scores. We conclude that low-level auditory and visual sensory discrimination deficits in psychosis may reflect genetic liability for psychotic illness. Critically, these deficits relate to global cognitive disruptions that are a hallmark of psychotic illnesses such as schizophrenia.

The Visual Word Form Area compensates for auditory working memory dysfunction in schizophrenia.

Auditory working memory impairments feature prominently in schizophrenia. However, the existence of altered and perhaps compensatory neural dynamics, sub-serving auditory working memory, remains largely unexplored. We compared the dynamics of induced high gamma power (iHGP) across cortex in humans during speech-sound working memory in individuals with schizophrenia (SZ) and healthy comparison subjects (HC) using magnetoencephalography (MEG). SZ showed similar task performance to HC while utilizing different brain regions. During encoding of speech sounds, SZ lacked the correlation of iHGP with task performance in posterior superior temporal gyrus (STGp) that was observed in healthy subjects. Instead, SZ recruited the visual word form area (VWFA) during both stimulus encoding and response preparation. Importantly, VWFA activity during encoding correlated with the magnitude of SZ hallucinations, task performance and an independent measure of verbal working memory. These findings suggest that VWFA plasticity is harnessed to compensate for STGp dysfunction in schizophrenia patients with hallucinations.

Cognitive Training for Very High Risk Incarcerated Adolescent Males.

OBJECTIVE: Persistent violent and antisocial behavior, as manifested in conduct disorder (CD) traits, are associated with a range of cognitive deficits. Individuals with more severe cognitive deficits are more likely to commit violent crimes. Currently, no treatments target improving cognition in high-risk CD youth. This pilot study tests the feasibility and efficacy of delivering intensive tablet-based cognitive training (CT) to adolescent males incarcerated in a youth maximum-security prison. METHODS: Participants were fourteen adolescent males, diagnosed with CD. All participants completed up to 30 h of unsupervised, intensive, adaptive CT exercises that targeted multiple neurocognitive domains, as well as a battery of standardized neurocognitive measures and computerized assessments at baseline and post-training. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: At baseline, participants exhibited significant impairments on neurocognitive measures, relative to age-matched healthy controls. Twelve participants completed training and showed evidence of target engagement, as indexed by improvement in cognitive processing speed. Significant gains were observed in measures of global cognition, with additional gains in cognitive flexibility at trend level significance. Improvements in these measures were positively related to total training time. In summary, both assessments and intervention appear to be feasible, tolerable, and acceptable in incarcerated youth. Intensive CT shows preliminary efficacy in improving neurocognitive performance in key domains, with large effect sizes, and significant performance improvement associations with the time in training.

Auditory versus visual neuroscience-informed cognitive training in schizophrenia: Effects on cognition, symptoms and quality of life.

BACKGROUND: Cognitive impairments are related to deficits in primary auditory and visual sensory processes in schizophrenia. These impairments can be remediated by neuroscience-informed computerized cognitive trainings that target auditory and visual processes. However, it is not clear which modality results in greater improvements in cognition, symptoms and quality of life. We aimed to investigate the impact of training auditory versus visual cognitive processes in global cognition in patients with schizophrenia. METHODS: Seventy-nine schizophrenia participants were randomly assigned to either 40 h of auditory or visual computerized training. Auditory and visual exercises were chosen to be dynamically equivalent and difficulties increased progressively during the training. We evaluated cognition, symptoms and quality of life before, after 20 h, and after 40 h of training. ClinicalTrials.gov (1R03TW009002-01). RESULTS: Participants who received the visual training showed significant improvements in global cognition compared to the auditory training group. The visual training significantly improved attention and reasoning and problem-solving, while the auditory training improved reasoning and problem-solving only. Schizophrenia symptoms improved after training in both groups, whereas quality of life remained unchanged. Interestingly, there was a significant and positive correlation between improvements in attention and symptoms in the visual training group. CONCLUSIONS: We conclude that the visual training and the auditory training are differentially efficient at remediating cognitive deficits and symptoms of clinically stable schizophrenia patients. Ongoing follow-up of participants will evaluate the durability of training effects on cognition and symptoms, as well as the potential impact on quality of life over time.

Early- Versus Adult-Onset Schizophrenia as a Predictor of Response to Neuroscience-Informed Cognitive Training.

BACKGROUND: Developmental stages characterized by greater neural plasticity might be critical periods during which the effects of cognitive training (CT) could theoretically be maximized. However, experiencing a first episode of schizophrenia during childhood or adolescence (ie, early-onset schizophrenia [EOS]) may reduce the brain's ability to benefit from CT. This study examined the effects of EOS versus onset at > 18 years of age (ie, adult-onset schizophrenia [AOS]) as a predictor of response to CT and the relationship between duration of illness and cognitive improvements. METHODS: This study is a secondary analysis of data from 2 randomized trials that examined the cognitive effects of neuroscience-informed auditory training (AT) exercises in 84 outpatients with schizophrenia (26 EOS, 58 AOS, recruited between 2004 and 2014). RESULTS: There was a significant effect of time in all cognitive domains (F > 10.22, P < .002). The effect of EOS was significant only for verbal learning and memory (F = 5.79, P = .018). AOS increased the mean change score by 5.70 points in this domain, whereas EOS showed no change (t = -2.280, P = .025). However, the difference between AOS and EOS was no longer statistically significant after control for multiple comparisons. Shorter duration of illness was associated with greater improvement in problem solving in the AOS group (r = -0.27, P = .040). CONCLUSIONS: Auditory training is effective in improving cognition in both EOS and AOS. Treatment effects in all cognitive domains were similar, with the exception of verbal learning and memory. This result requires replication. Cognitive training provided earlier in the course of the illness results in greater improvements in executive functions. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00312962, NCT00694889​​.

Increased global cognition correlates with increased thalamo-temporal connectivity in response to targeted cognitive training for recent onset schizophrenia.

Patients with schizophrenia exhibit disrupted thalamocortical connections that relate to aspects of symptoms and deficits in cognition. Targeted cognitive training (TCT) of the auditory system in schizophrenia has been shown to improve cognition, but its impact on thalamocortical connectivity is not known. Here we examined thalamocortical connections that may be neuroplastic in response to TCT using a region of interest (ROI) approach. Participants were randomly assigned to either 40 h of TCT (N = 24) or an active control condition (CG; N = 20). Participants underwent resting state fMRI and cognitive testing both before and after training. Changes in thalamocortical connectivity were measured in 15 ROIs derived from a previous study comparing a large sample of schizophrenia subjects with healthy controls. A significant group by time interaction was observed in a left superior temporal ROI which was previously found to exhibit thalamocortical hyper-connectivity in patients with schizophrenia. Changes in this ROI reflected thalamic connectivity increases in the TCT group, while the CG group showed decreases. Additionally, the relationship between connectivity change and change in global cognition showed a slope difference between groups, with increases in thalamo-temporal connectivity correlating with improvements in global cognition in TCT. No significant relationships were observed with changes in clinical symptoms or functioning. These findings demonstrate that TCT may influence intrinsic functional connections in young individuals with schizophrenia, such that improvements in cognition correspond to compensatory increases in connectivity in a temporal region previously shown to exhibit thalamic hyper-connectivity.

Six month durability of targeted cognitive training supplemented with social cognition exercises in schizophrenia.

BACKGROUND: Deficits in cognition, social cognition, and motivation are significant predictors of poor functional outcomes in schizophrenia. Evidence of durable benefit following social cognitive training is limited. We previously reported the effects of 70 h of targeted cognitive training supplemented with social cognitive exercises (TCT + SCT) verses targeted cognitive training alone (TCT). Here, we report the effects six months after training. METHODS: 111 participants with schizophrenia spectrum disorders were randomly assigned to TCT + SCT or TCT-only. Six months after training, thirty-four subjects (18 TCT + SCT, 16 TCT-only) were assessed on cognition, social cognition, reward processing, symptoms, and functioning. Intent to treat analyses was used to test the durability of gains, and the association of gains with improvements in functioning and reward processing were tested. RESULTS: Both groups showed durable improvements in multiple cognitive domains, symptoms, and functional capacity. Gains in global cognition were significantly associated with gains in functional capacity. In the TCT + SCT group, participants showed durable improvements in prosody identification and reward processing, relative to the TCT-only group. Gains in reward processing in the TCT + SCT group were significantly associated with improvements in social functioning. CONCLUSIONS: Both TCT + SCT and TCT-only result in durable improvements in cognition, symptoms, and functional capacity six months post-intervention. Supplementing TCT with social cognitive training offers greater and enduring benefits in prosody identification and reward processing. These results suggest that novel cognitive training approaches that integrate social cognitive exercises may lead to greater improvements in reward processing and functioning in individuals with schizophrenia.