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Two decades of studies suggest that computerized cognitive training (CCT) has an effect on cognitive improvement and the restoration of brain activity. Nevertheless, individual response to CCT remains heterogenous, and the predictive potential of neuroimaging in gauging response to CCT remains unknown. We employed multivariate pattern analysis (MVPA) on whole-brain resting-state functional connectivity (rsFC) to (neuro)monitor clinical outcome defined as psychosis-likeness change after 10-hours of CCT in recent onset psychosis (ROP) patients. Additionally, we investigated if sensory processing (SP) change during CCT is associated with individual psychosis-likeness change and cognitive gains after CCT. 26 ROP patients were divided into maintainers and improvers based on their SP change during CCT. A support vector machine (SVM) classifier separating 56 healthy controls (HC) from 35 ROP patients using rsFC (balanced accuracy of 65.5%, P < 0.01) was built in an independent sample to create a naturalistic model representing the HC-ROP hyperplane. This model was out-of-sample cross-validated in the ROP patients from the CCT trial to assess associations between rsFC pattern change, cognitive gains and SP during CCT. Patients with intact SP threshold at baseline showed improved attention despite psychosis status on the SVM hyperplane at follow-up (p < 0.05). Contrarily, the attentional gains occurred in the ROP patients who showed impaired SP at baseline only if rsfMRI diagnosis status shifted to the healthy-like side of the SVM continuum. Our results reveal the utility of MVPA for elucidating treatment response neuromarkers based on rsFC-SP change and pave the road to more personalized interventions.

Background: Access and engagement with psychosocial interventions for people with psychotic disorders (PD) remain limited. This is because these interventions require specially trained therapists, are often not available in clinical settings, and have a high scheduling burden, requiring a commitment of hours of clinic visits per week for several months. Delivering interventions remotely via mobile devices increases scalability and facilitates access, while also improving scheduling flexibility and decreasing burden, thus improving adherence to intervention requirements. To address these needs, we designed CLIMB, a digital intervention that aims to enhance social functioning in people with PD. CLIMB consists of 2 treatment components: a computerized social cognition training (SCT) program and optimized remote group therapy—an innovative treatment that combines remote group therapy with group texting. In this pilot study, we investigated the feasibility of delivering 6 weeks of CLIMB remotely to people with PD and explored effects on outcomes. We recruited, screened and enrolled participants online, and delivered assessments and intervention remotely using provided iPads. Participants were asked to complete 18 hours of SCT and to attend 6 remote group therapy sessions. Methods: To assess feasibility, we evaluated adherence to study procedures, attrition rates, engagement metrics, and reported acceptability of the intervention. We also explored changes on measures of social cognition, quality of life, and symptoms. Results: Twenty-seven participants were enrolled. Remote assessments were completed successfully on 96% of enrolled participants. Retention in the trial was 77.7%. Ninety-five percent of the iPads were returned undamaged after intervention. Participants on average attended 84% of the group tele-therapy sessions, completed a median of 9.5 hours of SCT, and posted a median of 5.2 messages per week on the group text chat. Participants rated CLIMB in the medium

The rapidly expanding field of mobile health (mHealth) seeks to harness increasingly affordable and ubiquitous mobile digital technologies including smartphones, tablets, apps and wearable devices to enhance clinical care. Accumulating evidence suggests that mHealth interventions are increasingly being adopted and valued by people living with serious mental illnesses such as schizophrenia and bipolar disorder, as a means of better understanding and managing their condition. We draw on experiences from three geographically and methodologically distinct mHealth studies to provide a pragmatic overview of the key challenges and considerations relating to the process of developing digital interventions for this population.

Background Blunted facial affect is a common negative symptom of schizophrenia. Additionally, assessing the trustworthiness of faces is a social cognitive ability that is impaired in schizophrenia. Currently available pharmacological agents are ineffective at improving either of these symptoms, despite their clinical significance. The hypothalamic neuropeptide oxytocin has multiple prosocial effects when administered intranasally to healthy individuals and shows promise in decreasing negative symptoms and enhancing social cognition in schizophrenia. Although two small studies have investigated oxytocin's effects on ratings of facial trustworthiness in schizophrenia, its effects on facial expressivity have not been investigated in any population. Method We investigated the effects of oxytocin on facial emotional expressivity while participants performed a facial trustworthiness rating task in 33 individuals with schizophrenia and 35 age-matched healthy controls using a double-blind, placebo-controlled, cross-over design. Participants rated the trustworthiness of presented faces interspersed with emotionally evocative photographs while being video-recorded. Participants' facial expressivity in these videos was quantified by blind raters using a well-validated manualized approach (i.e. the Facial Expression Coding System; FACES). Results While oxytocin administration did not affect ratings of facial trustworthiness, it significantly increased facial expressivity in individuals with schizophrenia (Z =Â-2.33, p = 0.02) and at trend level in healthy controls (Z =Â-1.87, p = 0.06). Conclusions These results demonstrate that oxytocin administration can increase facial expressivity in response to emotional stimuli and suggest that oxytocin may have the potential to serve as a treatment for blunted facial affect in schizophrenia.

Objective: Individuals at clinical high risk (CHR) for psychosis demonstrate cognitive impairments that predict later psychotic transition and real-world functioning. Cognitive training has shown benefits in schizophrenia, but has not yet been adequately tested in the CHR population. Methods: In this double-blind randomized controlled trial, CHR individuals (N = 83) were given laptop computers and trained at home on 40 hours of auditory processing-based exercises designed to target verbal learning and memory operations, or on computer games (CG). Participants were assessed with neurocognitive tests based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS) battery and rated on symptoms and functioning. Groups were compared before and after training using a mixed-effects model with restricted maximum likelihood estimation, given the high study attrition rate (42%). Results: Participants in the targeted cognitive training group showed a significant improvement in Verbal Memory compared to CG participants (effect size = 0.61). Positive and Total symptoms improved in both groups over time. Conclusions: CHR individuals showed patterns of training-induced cognitive improvement in verbal memory consistent with prior observations in schizophrenia. This is a particularly vulnerable domain in individuals at-risk for psychosis that predicts later functioning and psychotic transition. Ongoing follow-up of this cohort will assess the durability of training effects in CHR individuals, as well as the potential impact on symptoms and functioning over time.

Background: Individuals with schizophrenia have heterogeneous impairments of the auditory processing system that likely mediate differences in the cognitive gains induced by auditory training (AT). Mismatch negativity (MMN) is an event-related potential component reflecting auditory echoic memory, and its amplitude reduction in schizophrenia has been linked to cognitive deficits. Therefore, MMN may predict response to AT and identify individuals with schizophrenia who have the most to gain from AT. Furthermore, to the extent that AT strengthens auditory deviance processing, MMN may also serve as a readout of the underlying changes in the auditory system induced by AT. Methods: Fifty-six individuals early in the course of a schizophrenia-spectrum illness (ESZ) were randomly assigned to 40 h of AT or Computer Games (CG). Cognitive assessments and EEG recordings during a multi-deviant MMN paradigm were obtained before and after AT and CG. Changes in these measures were compared between the treatment groups. Baseline and trait-like MMN data were evaluated as predictors of treatment response. MMN data collected with the same paradigm from a sample of Healthy Controls (HC; n = 105) were compared to baseline MMN data from the ESZ group. Results: Compared to HC, ESZ individuals showed significant MMN reductions at baseline (p = .003). Reduced Double-Deviant MMN was associated with greater general cognitive impairment in ESZ individuals (p = .020). Neither ESZ intervention group showed significant change in MMN. We found high correlations in all MMN deviant types (rs = .59-.68, all ps < .001) between baseline and post-intervention amplitudes irrespective of treatment group, suggesting trait-like stability of the MMN signal. Greater deficits in trait-like Double-Deviant MMN predicted greater cognitive improvements in the AT group (p = .02), but not in the CG group. Conclusions: In this sample of ESZ individuals, AT had no effect on auditory deviance processing as assessed

Background: Even after successful detoxification, 20-40% of subjects presenting chronic migraine with symptomatic medication overuse (CMwMO) relapse into medication overuse within one year. In this restrospective analysis on subjects referred to our center for detoxification, we investigated whether personality traits, dependency-like behaviors and pain coping styles predicted those who relapsed into medication overuse within the 12 months following the detoxification and those who did not.Methods: 63 patients with CMwMO were assessed for personality traits, mood and anxiety, pain coping styles and dependency-like behaviors prior-to and one year after a detoxification program.Results: Of the 42 subjects who attended 1-year follow-up interviews, 11 relapsed into medication overuse despite a temporary benefit from detoxification and did not show clinical or psychological improvement, instead reporting increased anxiety and unmodified perpetuation of severe dependency-like behaviors. In contrast, subjects who did not relapse into medication overuse had clinical improvements that generalized to untreated domains, including decreased depressive symptoms and dependency-like behaviors, although showing unmodified low internal control over pain.Conclusions: Subjects who did not fall into medication overuse throughout the 12 months following the detoxification showed improved clinical, affective and dependence-related outcomes, but not pain coping strategies. Conversely, subjects who relapsed within one year into CMwMO continued to experience significant disability, pain intensity, and dependency-like behaviors. We believe that the persistence of maladaptive pain coping strategies and residual symptomatology increase the risk for recurrent relapses, against which pharmacological interventions are only partially effective. Further studies investigating predictors of relapse are needed to inform multi-disciplinary interventions for CMwMO.