Progress update from the hippocampal subfields group

Introduction: Heterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence. Methods: Our international working group, funded by the EU Joint Programme–Neurodegenerative Disease Research (JPND), is working toward the production of a reliable, validated, harmonized protocol for segmentation of medial temporal lobe regions. The working group uses a novel postmortem data set and online consensus procedures to ensure validity and facilitate adoption. Results: This progress report describes the initial results and milestones that we have achieved to date, including the development of a draft protocol and results from the initial reliability tests and consensus procedures. Discussion: A harmonized protocol will enable the standardization of segmentation methods across laboratories interested in medial temporal lobe research worldwid

The underlying neurobiology of key functional domains in young people with mood and anxiety disorders: a systematic review

BACKGROUND: Mood and anxiety disorders are leading causes of disability and mortality, due largely to their onset during adolescence and young adulthood and broader impact on functioning. Key factors that are associated with disability and these disorders in young people are social and economic participation (e.g. education, employment), physical health, suicide and self-harm behaviours, and alcohol and substance use. A better understanding of the objective markers (i.e. neurobiological parameters) associated with these factors is important for the development of effective early interventions that reduce the impact of disability and illness persistence. METHODS: We systematically reviewed the literature for neurobiological parameters (i.e. neuropsychology, neuroimaging, sleep-wake and circadian biology, neurophysiology and metabolic measures) associated with functional domains in young people (12 to 30 years) with mood and/or anxiety disorders. RESULTS: Of the one hundred and thirty-four studies selected, 7.6 % investigated social and economic participation, 2.1 % physical health, 15.3 % suicide and self-harm behaviours, 6.9 % alcohol and substance use, whereas the majority (68.1 %) focussed on clinical syndrome. CONCLUSIONS: Despite the predominance of studies that solely examine the clinical syndrome of young people the literature also provides evidence of distinct associations among objective measures (indexing various aspects of brain circuitry) and other functional domains. We suggest that a shift in focus towards characterising the mechanisms that underlie and/or mediate multiple functional domains will optimise personalised interventions and improve illness trajectories

Instant grid: A framework for on-demand grid point construction

This paper proposes the InstantGrid framework for ondemand construction of grid points. In contrast to traditional approaches, InstantGrid is designed to substantially simplify software management in grid systems, and is able to instantly turn any computer into a grid-ready platform with the desired execution environment. Experimental results demonstrate that a 256-node grid point with commodity grid middleware can be constructed in five minutes from scratch. © Springer-Verlag 2004.link_to_subscribed_fulltex

Cognitive remediation improves memory and psychosocial functioning in first-episode psychiatric out-patients

BACKGROUND: Cognitive remediation (CR) is an effective treatment for several psychiatric disorders. To date, there have been no published studies examining solely first-episode psychiatric cohorts, despite the merits demonstrated by early intervention CR studies. The current study aimed to assess the effectiveness of CR in patients with a first-episode of either major depression or psychosis. Method Fifty-five patients (mean age = 22.8 years, s.d. = 4.3) were randomly assigned to either CR (n = 28) or treatment as usual (TAU; n = 27). CR involved once-weekly 2-h sessions for a total of 10 weeks. Patients were comprehensively assessed before and after treatment. Thirty-six patients completed the study, and analyses were conducted using an intent-to-treat (ITT) approach with all available data. RESULTS: In comparison to TAU, CR was associated with improved immediate learning and memory controlling for diagnosis and baseline differences. Similarly, CR patients demonstrated greater improvements than TAU patients in psychosocial functioning irrespective of diagnosis. Delayed learning and memory improvements mediated the effect of treatment on psychosocial functioning at a marginal level. CONCLUSIONS: CR improves memory and psychosocial outcome in first-episode psychiatric out-patients for both depression and psychosis. Memory potentially mediated the functional gains observed. Future studies need to build on the current findings in larger samples using blinded allocation and should incorporate longitudinal follow-up and assessment of potential moderators (e.g. social cognition, self-efficacy) to examine sustainability and the precise mechanisms of CR effects respectively

Cognitive inflexibility moderates the relationship between relief-driven drinking motives and alcohol use

INTRODUCTION: Drinking motives and neurocognition play significant roles in predicting alcohol use. There is limited research examining how relief-driven drinking motives interact with neurocognition in alcohol use, which would help to elucidate the neurocognitive-motivational profiles most susceptible to harmful drinking. This study investigated the interactions between neurocognition (response inhibition and cognitive flexibility) and relief-driven drinking, in predicting problem drinking. METHODS: Participants completed the Alcohol Use Disorders Identification Test - Consumption items (AUDIT-C) to measure drinking behaviour, and online cognitive tasks, including the Value-Modulated Attentional Capture and Reversal Task (VMAC-R) and the Stop Signal Task (SST). The sample (N = 368) were individuals who drink alcohol, which included a subsample (N = 52) with problematic drinking, as defined by self-identifying as having a primary drinking problem. Drinking motives were assessed using a binary coping question in the overall sample, and the Habit, Reward, and Fear Scale (HRFS) in the subsample. Moderation analyses were conducted to investigate whether cognitive flexibility and response inhibition moderated relationships between relief-driven motives and drinking. RESULTS: Cognitive flexibility moderated the relationship between relief-driven motives and drinking (overall sample: β = 13.69, p = 0.017; subsample: β = 1.45, p = 0.013). Greater relief-driven motives were associated with heavier drinking for individuals with low cognitive flexibility. There was no significant interaction between response inhibition and relief-driven motives. CONCLUSIONS: Relief-driven drinking motives interact with cognitive inflexibility to drive heavier drinking. Greater understanding of these neurocognitive-motivational mechanisms may help to develop more targeted and effective interventions for reducing harmful drinking

A comprehensive evaluation of the neurocognitive predictors of problematic alcohol use, eating, pornography, and internet use: A 6-month longitudinal study

BACKGROUND AND AIMS: Cognitive control and reward-related abnormalities are centrally implicated in addiction. However, findings from longitudinal studies addressing neurocognitive predictors of addictive behaviors are mixed. Further, little work has been conducted predicting non-substance-related addictive behaviors. Our study aimed to assess predictors of substance and non-substance addictive behaviors in a community sample, systematically evaluating each neurocognitive function's independent influence on addictive behavior. METHODS: Australians (N = 294; 51.7% female; M[SD] age = 24.8[4.7] years) completed online neurocognitive tasks and surveys at baseline and 3-month follow-up. Self-report scales assessed problematic alcohol use, addictive eating (AE), problematic pornography use (PPU), and problematic internet use (PUI) at 3- and 6-month follow-ups. Linear regressions with bootstrapping assessed neurocognitive predictors for each addictive behavior across a 6-month period. RESULTS: Neurocognition at baseline did not predict AE or PUI severity at 6-month follow-up. Less delay discounting at baseline predicted higher PPU at 6-month follow-up (β = -0.16, p = 0.005). Poorer performance monitoring at baseline predicted higher AE at 3-month follow-up (β = -0.16, p = 0.004), and more reward-related attentional capture at 3-months predicted higher AE at 6-month follow-up (β = 0.14, p = 0.033). Less reward-related attentional capture (β = -0.14, p = 0.003) and less risk-taking under ambiguity (β = -0.11, p = 0.029) at baseline predicted higher PUI at 3-month follow-up. All findings were of small effect size. None of the neurocognitive variables predicted problematic alcohol use. DISCUSSION AND CONCLUSIONS: We were unable to identify a core set of specific neurocognitive functions that reliably predict multiple addictive behavior types. However, our findings indicate both cognitive control and reward-related functions predict non-substance addictive behaviors in different ways. Findings suggest that there may be partially distinct neurocognitive mechanisms contributing to addiction depending on the specific addictive behavior

The Relationship between Sleep-Wake Cycle and Cognitive Functioning in Young People with Affective Disorders

Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16-30 years; 66% female) with primary diagnoses of affective disorders, and 69 healthy controls (18-30 years; 57% female). Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a 'long sleep' cluster, a 'disrupted sleep' cluster, and a 'delayed and disrupted sleep' cluster. Circadian clusters included a 'strong circadian' cluster, a 'weak circadian' cluster, and a 'delayed circadian' cluster. Medication use differed between clusters. The 'long sleep' cluster displayed significantly worse visual memory performance compared to the 'disrupted sleep' cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments and improvement of functioning in young adults early in the course of affective illness

Clinical, neurocognitive and demographic factors associated with functional impairment in the Australian Brain and Mind Youth Cohort Study (2008-2016)

OBJECTIVES: We sought to determine the unique and shared contributions of clinical, neurocognitive and demographic factors to functional impairment in a large, transdiagnostic, clinical cohort of adolescents and young adults. DESIGN: Cross-sectional baseline data from a prospective, cohort study. SETTING: Help-seeking youth referred from outpatient services were recruited to the Brain and Mind Youth Cohort (2008-2016) in Sydney, Australia. PARTICIPANTS: In total, 1003 outpatients were recruited, aged between 12 and 36 years (mean= 20.4 years, 54% female), with baseline diagnoses of affective, psychotic, developmental or behavioural disorders. INTERVENTIONS: Treatment as usual. PRIMARY OUTCOME MEASURES: Social and occupational functioning was used to index level of functional impairment. Structural equation modelling was used to examine associations between neurocognition, core clinical symptoms and alcohol and substance use, and clinician-rated and researcher-rated functional impairment. Moderator analyses were conducted to determine the potential influence of demographic and clinical factors (eg, medication exposure). RESULTS: Independent of diagnosis, we found that neurocognitive impairments, and depressive, anxiety and negative symptoms, were significantly associated with functioning. The association of neurocognition with social and occupational functioning remained significant even when constraining for age (15-25-year-olds only) or diagnosis (affective disorders only) in the final model. CONCLUSIONS: This study demonstrated that, in a clinically representative sample of youth, the key determinants of functioning may not be disorder specific. Further, evidence of neurocognitive dysfunction suggests that interventions that target cognition and functioning should not necessarily be reserved just for older adults with established illness