Cognitive impairment features in neuropsychiatric conditions and when undiagnosed can have a severe impact on the affected individual's safety and ability to perform daily tasks. Virtual Reality (VR) ...systems are increasingly being explored for the recognition, diagnosis and treatment of cognitive impairment. In this paper, we describe novel VR-derived measures of cognitive performance and show their correspondence with clinically-validated cognitive performance measures. We use an immersive VR environment called VStore where participants complete a simulated supermarket shopping task. People with psychosis (k=26) and non-patient controls (k=128) participated in the study, spanning ages 20-79 years. The individuals were split into two cohorts, a homogeneous non-patient cohort (k=99 non-patient participants) and a heterogeneous cohort (k=26 patients, k=29 non-patient participants). Participants' spatio-temporal behaviour in VStore is used to extract four features, namely, route optimality score, proportional distance score, execution error score, and hesitation score using the Traveling Salesman Problem and explore-exploit decision mathematics. These extracted features are mapped to seven validated cognitive performance scores, via linear regression models. The most statistically important feature is found to be the hesitation score. When combined with the remaining extracted features, the multiple linear regression model resulted in statistically significant results with R2 = 0.369, F-Stat = 7.158, p(F-Stat) = 0.000128.
Background
Aspects of cognitive function decline with age. This phenomenon is referred to as age-related cognitive decline (ARCD). Improving the understanding of these changes that occur as part of ...the ageing process can serve to enhance the detection of the more incapacitating neurodegenerative disorders such as Alzheimer’s disease (AD). In this study, we employ novel methods to assess ARCD by exploring the utility of the alpha3/alpha2 electroencephalogram (EEG) power ratio – a marker of AD, and a novel virtual reality (VR) functional cognition task – VStore, in discriminating between young and ageing healthy adults.
Materials and methods
Twenty young individuals aged 20–30, and 20 older adults aged 60–70 took part in the study. Participants underwent resting-state EEG and completed VStore and the Cogstate Computerised Cognitive Battery. The difference in alpha3/alpha2 power ratios between the age groups was tested using
t
-test. In addition, the discriminatory accuracy of VStore and Cogstate were compared using logistic regression and overlying receiver operating characteristic (ROC) curves. Youden’s J statistic was used to establish the optimal threshold for sensitivity and specificity and model performance was evaluated with the DeLong’s test. Finally, alpha3/alpha2 power ratios were correlated with VStote and Cogstate performance.
Results
The difference in alpha3/alpha2 power ratios between age cohorts was not statistically significant. On the other hand, VStore discriminated between age groups with high sensitivity (94%) and specificity (95%) The Cogstate Pre-clinical Alzheimer’s Battery achieved a sensitivity of 89% and specificity of 60%, and Cogstate Composite Score achieved a sensitivity of 83% and specificity of 85%. The differences between the discriminatory accuracy of VStore and Cogstate models were statistically significant. Finally, high alpha3/alpha2 power ratios correlated strongly with VStore (
r
= 0.73), the Cogstate Pre-clinical Alzheimer’s Battery (
r
= -0.67), and Cogstate Composite Score (
r
= -0.76).
Conclusion
While we did not find evidence that the alpha3/alpha2 power ratio is elevated in healthy ageing individuals compared to young individuals, we demonstrated that VStore can classify age cohorts with high accuracy, supporting its utility in the assessment of ARCD. In addition, we found preliminary evidence that elevated alpha3/alpha2 power ratio may be linked to lower cognitive performance.
Individuals with schizophrenia have difficulty in extracting salient information from faces. Eye-tracking studies have reported that these individuals demonstrate reduced exploratory viewing ...behaviour (i.e. reduced number of fixations and shorter scan paths) compared to healthy controls. Oxytocin has previously been demonstrated to exert pro-social effects and modulate eye gaze during face exploration. In this study, we tested whether oxytocin has an effect on visual attention in patients with schizophrenia.
Nineteen male participants with schizophrenia received intranasal oxytocin 40UI or placebo in a double-blind, placebo-controlled, crossover fashion during two visits separated by seven days. They engaged in a free-viewing eye-tracking task, exploring images of Caucasian men displaying angry, happy, and neutral emotional expressions; and control images of animate and inanimate stimuli. Eye-tracking parameters included: total number of fixations, mean duration of fixations, dispersion, and saccade amplitudes.
We found a main effect of treatment, whereby oxytocin increased the total number of fixations, dispersion, and saccade amplitudes, while decreasing the duration of fixations compared to placebo. This effect, however, was non-specific to facial stimuli. When restricting the analysis to facial images only, we found the same effect. In addition, oxytocin modulated fixation rates in the eye and nasion regions.
This is the first study to explore the effects of oxytocin on eye gaze in schizophrenia. Oxytocin had enhanced exploratory viewing behaviour in response to both facial and inanimate control stimuli. We suggest that the acute administration of intranasal oxytocin may have the potential to enhance visual attention in schizophrenia.
Cognitive deficits are present in several neuropsychiatric disorders, including Alzheimer disease, schizophrenia, and depression. Assessments used to measure cognition in these disorders are ...time-consuming, burdensome, and have low ecological validity. To address these limitations, we developed a novel virtual reality shopping task-VStore.
This study aims to establish the construct validity of VStore in relation to the established computerized cognitive battery, Cogstate, and explore its sensitivity to age-related cognitive decline.
A total of 142 healthy volunteers aged 20-79 years participated in the study. The main VStore outcomes included verbal recall of 12 grocery items, time to collect items, time to select items on a self-checkout machine, time to make the payment, time to order coffee, and total completion time. Construct validity was examined through a series of backward elimination regression models to establish which Cogstate tasks, measuring attention, processing speed, verbal and visual learning, working memory, executive function, and paired associate learning, in addition to age and technological familiarity, best predicted VStore performance. In addition, 2 ridge regression and 2 logistic regression models supplemented with receiver operating characteristic curves were built, with VStore outcomes in the first model and Cogstate outcomes in the second model entered as predictors of age and age cohorts, respectively.
Overall VStore performance, as indexed by the total time spent completing the task, was best explained by Cogstate tasks measuring attention, working memory, paired associate learning, and age and technological familiarity, accounting for 47% of the variance. In addition, with λ=5.16, the ridge regression model selected 5 parameters for VStore when predicting age (mean squared error 185.80, SE 19.34), and with λ=9.49 for Cogstate, the model selected all 8 tasks (mean squared error 226.80, SE 23.48). Finally, VStore was found to be highly sensitive (87%) and specific (91.7%) to age cohorts, with 94.6% of the area under the receiver operating characteristic curve.
Our findings suggest that VStore is a promising assessment that engages standard cognitive domains and is sensitive to age-related cognitive decline.
Background:
The evidence for safe and effective interventions to treat the negative and cognitive symptoms of schizophrenia is lacking.
Objectives:
Vortioxetine is a novel antidepressant that has ...been used as adjunctive therapy for the treatment of psychosis; however, its effectiveness in clinical practice is relatively unknown. In this study, we aimed to determine the potential clinical effectiveness and safety and tolerability of vortioxetine in psychosis.
Design:
This is a non-interventional, retrospective study on the add-on use of vortioxetine in a group of people with schizophrenia-spectrum disorders in a large UK NHS mental health trust.
Methods:
Clinical effectiveness of vortioxetine was retrospectively assessed through the Clinical Global Impression – Severity (CGI-S) scale at 3 months. Safety and tolerability were evaluated through treatment discontinuation rates at 3, 6, and 12 months, and clinical reasons were evaluated at the primary endpoint of 3 months.
Results:
Data were available for 40 subjects with a diagnosis of schizophrenia or schizoaffective disorder–prescribed vortioxetine treatment; 30 (75%) remained on treatment at 3 months. At CGI-S assessment, 15 of the 35 evaluated subjects reported at least a 1-point improvement, from 5 at baseline to 4 after 3 months of treatment. Twenty-six (65%) remained on treatment at 1-year follow-up. The main reasons for those discontinuing treatment were inadequate response (10%) and manic switch (7.5%), while one subject refused treatment. Tolerability to treatment was good, and 36 subjects (90%) reported no adverse events specific to vortioxetine treatment.
Conclusion:
Schizophrenia is a complex illness, and there is insufficient treatment response in many individuals. A significant proportion of whom may require adjunctive treatments depending on the nature of the residual symptoms. Vortioxetine could be a potentially safe and effective option in such people, but further controlled studies are required.
Abstract
Background
It is widely accepted that neurocognitive performance is linked to functional outcomes in schizophrenia (Green, Kern, Braff, & Mintz, 2000). Research, however, shows that this ...relationship is likely to be mediated by other factors such as social competence (Brekke, Kay, Lee, & Green, 2005). Indeed, performance on cognitive tasks only explain 20% of the variance in work related skills (Bowie et al., 2008). Furthermore, the composite score generated by the gold standard neurocognitive measure, the MATRICS Consensus Cognitive Battery (MCCB), fails to predict work or education related functioning and independent living (August, Kiwanuka, McMahon, & Gold, 2012). To address these limitations, we developed a novel and ecologically valid virtual reality (VR) task with the aim to simultaneously measure cognition and functional capacity in schizophrenia. The assessment is set in a minimarket environment where participants are required to buy selected items from a shopping list. In this study, our objective was to establish the construct validity of the VR task in relation to the MCCB, and test whether it can predict functional outcomes. In addition, we tested whether app-based cognitive training can improve cognition and/or functional outcomes at follow-up as an exploratory objective.
Methods
Thirty patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited from South London. At baseline, participants completed the VR task and MCCB, the Positive and Negative Syndrome Scale (PANSS), and various functional capacity/outcome measures including the Global Assessment of Functioning (GAF), Social and Occupational Functioning Assessment Scale (SOFAS), UCSD Performance-Based Skills Assessment-Brief (UPSA-B), and World Health Organization Disability Assessment Schedule II (WHODAS-II). A subset of participants was randomly allocated to receive a 4-week long, app-based training; either playing with an immersive or a 2D spatial memory training game. Those who completed the training were invited back for a follow-up visit. Construct validity of the VR task will be assessed through a series of bivariate correlations. The predictive ability of the VR task for functional outcomes will be tested through linear regression models. Finally, the efficacy of spatial memory training will be assessed using repeated measures ANOVA.
Results
Data analysis is currently ongoing, and results will be presented at the conference.
Discussion
This study will provide the first indication whether VR can be employed to test cognition and functional capacity simultaneously in patients with schizophrenia. Given the current lack of reliable and ecologically valid functional outcome measures, new assessments that are sensitive to clinically meaningful cognitive improvements are desperately needed.
Abstract
Background
High-resolution structural MRI has been widely used in clinical research to detect and quantify subtle brain changes in patient populations. Findings from prospective, ...longitudinal studies show structural brain abnormalities as well as progressive gray matter changes over time in individuals at clinical high risk for psychosis compared to healthy subjects. In recent years, research in this field has seen an increase in multicentre neuroimaging projects, such as EU-GEI, PSYSCAN, PRONIA and NAPLS. Additional sources of variance, alongside known technological and biological factors, may be introduced when MRI images are acquired and combined from different sites. It is imperative for longitudinal multicentre studies to determine the accuracy of quantitative MRI measurements and account for systematic differences both between scanners and across scanning sessions. This is particularly true within psychosis research where morphometric changes as small as 3% or less are expected.
Methods
Six healthy participants were scanned on four separate occasions over a two-month period at King’s College London; twice on a GE SIGNA HDx 3T scanner used locally in the EU-GEI High Risk Study and twice on a GE MR750 3T scanner used locally in the PSYSCAN study. Both scanners implemented the ADNI-2 T1 protocol which is used globally across the EU-GEI and PSYSCAN consortia. Structural imaging data was segmented using the FreeSurfer 6.0 longitudinal pipeline. Intraclass correlation coefficients (ICCs) with a two-way mixed effects model of absolute agreement were calculated to assess intra- and inter-scanner reliability of brain morphometry. For volumetric studies, ICC values greater than 0.9 indicate ‘excellent’ reliability. Reliability analyses of key regions implicated in psychosis included gray matter volume estimates of the hippocampus, insula, lateral ventricle, orbitofrontal cortex and anterior cingulate cortex, and average cortical thickness measurements of the whole brain, parahippocampus and superior frontal cortex.
Results
Gray matter volume estimates of all structures yielded ‘excellent’ reliability for both intra-scanner (ICCs of 0.979 – 0.998) and inter-scanner analyses (ICCs of 0.976 – 0.999). Intra-scanner reliability for mean cortical thickness measurements was ‘excellent’ for right total cortex, resulting in an ICC of 0.901, but otherwise ‘good’ for left and total cortex, parahippocampus, superior frontal cortex (ICCs of 0.754 – 0.875). Inter-scanner reliability for mean cortical thickness estimates were most variable across the brain structures. Here, results demonstrated ‘excellent’ reliability for the parahippocampus and left total cortex (ICCs of 0.907 – 0.965), ‘good’ for total cortex (ICC of 0.835), ‘moderate’ for right total cortex, right and total superior frontal cortex (ICCs of 0.520 – 0.676), and ‘poor’ for the left superior frontal cortex which produced an ICC of 0.470. Overall, mean cortical thickness estimates of the superior frontal cortex from two different MR scanners showed the least reliability.
Discussion
Results confirmed highly reliable estimates for gray matter volumes in all brain structures, both from images acquired within the same scanner and across two different scanners. However, the findings indicated increased variability of mean cortical thickness estimates, particularly between scanners, which should be considered when interpreting study findings. Multicentre structural neuroimaging within the field of psychosis is becoming more common and it must be acknowledged that combining MRI data in multicentre studies will contribute additional sources of variance and potential bias with certain brain regions affected more than others.
Background: Individuals with schizophrenia have difficulty in extracting salient information from faces. Eye-tracking studies have reported that these individuals demonstrate reduced exploratory ...viewing behaviour (i.e.reduced number offixations and shorter scan paths) compared to healthy controls. Oxytocin has previouslybeen demonstrated to exert pro-social effects and modulate eye gaze during face exploration. In this study, wetested whether oxytocin has an effect on visual attention in patients with schizophrenia.Methods: Nineteen male participants with schizophrenia received intranasal oxytocin 40UI or placebo in adouble-blind, placebo-controlled, crossover fashion during two visits separated by seven days. They engagedin a free-viewing eye-tracking task, exploring images of Caucasian men displaying angry, happy, and neutralemotional expressions; and control images of animate and inanimate stimuli. Eye-tracking parameters included:total number offixations, mean duration offixations, dispersion, and saccade amplitudes.Results: We found a main effect of treatment, whereby oxytocin increased the total number offixations, dispersion, and saccade amplitudes, while decreasing the duration offixations compared to placebo. This effect, how-ever, was non-specific to facial stimuli. When restricting the analysis to facial images only, we found the sameeffect. In addition, oxytocin modulatedfixation rates in the eye and nasion regions.Discussion: This is thefirst study to explore the effects of oxytocin on eye gaze in schizophrenia. Oxytocin had enhanced exploratory viewing behaviour in response to both facial and inanimate control stimuli. We suggest thatthe acute administration of intranasal oxytocin may have the potential to enhance visual attention inschizophrenia.
Worldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with ...high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group.
This is a phase II, randomised, double-blind, placebo-controlled, parallel-group clinical trial taking place in two sites in the UK: the South West of England and London. Ninety-six recently detoxified alcoholics, with comorbid depressive symptoms, will be randomised to one of four treatment arms. Patients will receive either three sessions of ketamine (0.8 mg/kg administered intravenously (IV) over 40 minutes) or placebo (50 ml saline 0.9% IV over 40 minutes) plus either seven sessions of manualised psychological therapy or an alcohol education control. Patients will be assessed at 3 and 6 months on a range of psychological and biological variables. The primary endpoints are (1) relapse rates at 6 months and (2) percentage days abstinent at 6 months. Secondary endpoints include 3 and 6 month percentage days abstinence, tolerability (indicated by dropout), adverse events, depressive symptoms, craving and quality of life.
This study will provide important information on a new combined psychological and pharmacological intervention aimed at reducing relapse rates in alcoholics. The findings would have broad application given the worldwide prevalence of alcoholism and its associated medical, psychological and social problems.
ClinicalTrials.gov, NCT02649231 . Registered on 5 January 2016.
Abstract
Background
Deficits in social cognition often develop during the prodromal stages of psychosis, remain stable over the course of the illness, and have a dramatic impact on daily functioning ...(Fett et al., 2011). Social cue processing, particularly face perception, plays a critical role in social cognitive functioning. Patients with schizophrenia struggle to extract information from faces and interpret facial expressions (Kohler et al., 2010). These deficits may be explained by restricted visual attention. Indeed, eye-tracking studies have demonstrated that people with schizophrenia show reduced exploratory behaviour (i.e. reduced number of fixations and longer fixation durations) in response to facial stimuli compared to healthy controls (e.g. Manor et al., 1999). Oxytocin has been demonstrated to exert pro-social effects on behaviour and modulate eye gaze during perception of faces. In the present study, we tested whether the neuropeptide, oxytocin, has a compensatory effect on visual processing of human faces.
Methods
Twenty right-handed male subjects with schizophrenia (n = 16) or schizoaffective disorder (n = 4) were administered intranasal oxytocin 40UI or placebo in a double-blind, placebo-controlled, cross-over fashion during two visits separated by 7 days. Participants engaged in a free-viewing eye-tracking task, during which they were looking at 6 facial images of two Caucasian men displaying angry, happy, and neutral facial expressions, and 6 control images in a random order. Eye-tracking measures including 1) total number of fixations, 2) dispersion, 3) saccade amplitude, and 4) mean duration of fixations were captured using the EyeLink 1000 system (SR Research Ltd, Ottawa, Ontario, Canada). Four separate 2 x 4 repeated-measures analysis of variance (ANOVA) were carried out to evaluate the within-subject effects of treatment, stimuli, and the interactions between stimuli and treatment (p < .05, two-tailed).
Results
We found a main effect of treatment (F1,17 = 16.139, p = .001), but not a main effect of stimuli (F3,51 = 1.479, p > .231) on total number of fixations. There was a main effect of treatment on duration of fixation, (F1,13 = 5.455, p = .036) but not a main effect of stimuli (F3,39 = 1.267, p = .299). For dispersion, there was a significant main effect of stimuli (F3,51 = 3.424, p = .024) but no main effect of treatment (F1,17 = 3.170, p = .093). Analysis of saccade amplitudes revealed no main effect of treatment (F1,17 = 2.666, p = .121) or stimuli (F3,51 = 0.289, p = .833). None of the interactions reached significance.
Discussion
To our knowledge, this is the first study to explore the effects of oxytocin on eye movements in individuals with schizophrenia. We found that oxytocin increased exploratory viewing behaviour in response to affective facial stimuli by significantly increasing the total number and duration of fixations compared to placebo. While previous findings regarding oxytocin have been inconsistent, our findings are in line with research showing that the intranasal administration of 40UI oxytocin may improve social cognitive deficits in schizophrenia (e.g. Davis et al., 2013). Future experiments may wish to explore the correlation between eye movement changes induced by oxytocin and facial affect recognition in larger samples.
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