Psychiatry - Research Publications
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ItemGenetic Influences on Cost-Efficient Organization of Human Cortical Functional Networks(SOC NEUROSCIENCE, 2011-03-02)The human cerebral cortex is a complex network of functionally specialized regions interconnected by axonal fibers, but the organizational principles underlying cortical connectivity remain unknown. Here, we report evidence that one such principle for functional cortical networks involves finding a balance between maximizing communication efficiency and minimizing connection cost, referred to as optimization of network cost-efficiency. We measured spontaneous fluctuations of the blood oxygenation level-dependent signal using functional magnetic resonance imaging in healthy monozygotic (16 pairs) and dizygotic (13 pairs) twins and characterized cost-efficient properties of brain network functional connectivity between 1041 distinct cortical regions. At the global network level, 60% of the interindividual variance in cost-efficiency of cortical functional networks was attributable to additive genetic effects. Regionally, significant genetic effects were observed throughout the cortex in a largely bilateral pattern, including bilateral posterior cingulate and medial prefrontal cortices, dorsolateral prefrontal and superior parietal cortices, and lateral temporal and inferomedial occipital regions. Genetic effects were stronger for cost-efficiency than for other metrics considered, and were more clearly significant in functional networks operating in the 0.09-0.18 Hz frequency interval than at higher or lower frequencies. These findings are consistent with the hypothesis that brain networks evolved to satisfy competitive selection criteria of maximizing efficiency and minimizing cost, and that optimization of network cost-efficiency represents an important principle for the brain's functional organization.
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ItemGABA concentration in sensorimotor cortex following high-intensity exercise and relationship to lactate levels(WILEY, 2018-02-15)KEY POINTS: Magnetic resonance spectroscopy was conducted before and after high-intensity interval exercise. Sensorimotor cortex GABA concentration increased by 20%. The increase was positively correlated with the increase in blood lactate. There was no change in dorsolateral prefrontal cortex. There were no changes in the glutamate-glutamine-glutathione peak. ABSTRACT: High-intensity exercise increases the concentration of circulating lactate. Cortical uptake of blood borne lactate increases during and after exercise; however, the potential relationship with changes in the concentration of neurometabolites remains unclear. Although changes in neurometabolite concentration have previously been demonstrated in primary visual cortex after exercise, it remains unknown whether these changes extend to regions such as the sensorimotor cortex (SM) or executive regions such as the dorsolateral prefrontal cortex (DLPFC). In the present study, we explored the acute after-effects of high-intensity interval training (HIIT) on the concentration of gamma-Aminobutyric acid (GABA) and the combined glutamate-glutamine-glutathione (Glx) spectral peak in the SM and DLPFC, as well as the relationship with blood lactate levels. Following HIIT, there was a robust increase in GABA concentration in the SM, as evident across the majority of participants. This change was not observed in the DLPFC. Furthermore, the increase in SM GABA was positively correlated with an increase in blood lactate. There were no changes in Glx concentration in either region. The observed increase in SM GABA concentration implies functional relevance, whereas the correlation with lactate levels may relate to the metabolic fate of exercise-derived lactate that crosses the blood-brain barrier.
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ItemReduced Willingness to Expend Effort for Reward in Obesity: Link to Adherence to a 3-Month Weight Loss Intervention.(Wiley, 2017-10)OBJECTIVE: This study aimed to (1) compare the willingness to expend effort for rewards between young adults with healthy weight, overweight, and obesity; and (2) to examine how individual differences in the willingness to expend effort for rewards predict adherence to weight loss treatment. METHODS: Seventy-three participants completed the Effort Expenditure for Rewards Task (EEfRT). Of those 73 participants, 42 young adults with excess weight took part in a 3-month weight loss treatment after completing the EEfRT. Generalized estimating equation models were used to compare the groups with healthy weight, overweight, and obesity in the EEfRT. Logistic regression models, including the proportion of hard-task choices for each reward probability condition as predictors (12%, 50%, and 88%), were conducted to longitudinally predict adherence in the treatment. RESULTS: Young adults with obesity were significantly less willing to expend effort for high-magnitude rewards compared with participants with overweight (P = 0.05). The willingness to expend effort for uncertain rewards (50% probability) was distinguished between completers and dropouts in the weight loss treatment (χ2 = 5.04, P < 0.02). CONCLUSIONS: Young adults with obesity, compared with their counterparts with overweight, have diminished motivation to expend effort for obtaining high-magnitude rewards. Less willingness to expend effort for the most uncertain rewards predicts poor adherence to weight loss treatment.
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ItemTranscriptional signatures of connectomic subregions of the human striatum(WILEY, 2017-09)Functionally distinct regions of the brain are thought to possess a characteristic connectional fingerprint - a profile of incoming and outgoing connections that defines the function of that area. This observation has motivated efforts to subdivide brain areas using their connectivity patterns. However, it remains unclear whether these connectomically-defined subregions can be distinguished at the molecular level. Here, we combine high-resolution diffusion-weighted magnetic resonance imaging with transcriptomic data to show that connectomically-defined subregions of the striatum carry distinct transcriptional signatures. Using data-driven clustering of diffusion tractography, seeded from the striatum in 100 healthy individuals, we identify a tripartite organization of the caudate and putamen that comprises ventral, dorsal and caudal subregions. We then use microarray data of gene expression levels in 19 343 genes, taken from 98 tissue samples distributed throughout the striatum, to accurately discriminate the three connectomically-defined subregions with 80-90% classification accuracy using linear support vector machines. This classification accuracy was robust at the group and individual level and was superior for our parcellation of the striatum when compared with parcellations based on anatomical boundaries or other criteria. Genes contributing strongly to classification were enriched for gene ontology categories including dopamine signaling, glutamate secretion, response to amphetamine and metabolic pathways, and were implicated in risk for disorders such as schizophrenia, autism and Parkinson's disease. Our findings highlight a close link between regional variations in transcriptional activity and inter-regional connectivity in the brain, and suggest that there may be a strong genomic signature of connectomically-defined subregions of the brain.
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ItemCognitive Control as a Moderator of Temperamental Motivations Toward Adolescent Risk-Taking Behavior(WILEY, 2016)Few studies have directly examined whether cognitive control can moderate the influence of temperamental positive and negative affective traits on adolescent risk-taking behavior. Using a combined multimethod, latent variable approach to the assessment of adolescent risk-taking behavior and cognitive control, this study examined whether cognitive control moderates the influence of temperamental surgency and frustration on risk-taking behavior in a sample of 177 adolescents (Mage = 16.12 years, SD = 0.69). As predicted, there was a significant interaction between cognitive control and frustration, but not between cognitive control and surgency, in predicting risk-taking behavior. These findings have important implications and suggest that the determinants of adolescent risk taking depend on the valence of the affective motivation for risk-taking behavior.
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ItemCognitive neuroscience can support public health approaches to minimise the harm of 'losses disguised as wins' in multiline slot machines(WILEY, 2019-08)Video slot machines are associated with both accelerated transition into problematic forms of gambling, as well as psychosocial harm above and beyond other forms of gambling. A growing body of evidence is uncovering how key design features of multiline slot machines produce an inflated experience of reward, despite the fact that these features offer no overall financial benefit to the player. A pernicious example of this are 'losses disguised as wins' (LDWs), which occur when simultaneous bets placed on multiple lines result in a winning combination that returns an amount greater than zero, but less the total wager. These events are usually accompanied by the same celebratory sounds and animations that accompany true wins. We argue that LDWs may leverage neuropsychological phenomena that underlie reinforcement learning and contribute to extended or repetitive use and gambling-related harm. While other characteristics of slot machine gambling have been examined by cognitive neuroscientists, this feature has not yet received attention. Neuroscientific methods can be used to assess the impact of LDWs on the human reward system, to assess the claim that these events are a reinforcing and contributing factor in the development of harmful play. Positive findings would provide further persuasive evidence in support of strategies to minimise gambling harm through the regulation of machine design.
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ItemAlteration to hippocampal volume and shape confined to cannabis dependence: a multi-site study(WILEY, 2019-07)Cannabis use is highly prevalent and often considered to be relatively harmless. Nonetheless, a subset of regular cannabis users may develop dependence, experiencing poorer quality of life and greater mental health problems relative to non-dependent users. The neuroanatomy characterizing cannabis use versus dependence is poorly understood. We aimed to delineate the contributing role of cannabis use and dependence on morphology of the hippocampus, one of the most consistently altered brain regions in cannabis users, in a large multi-site dataset aggregated across four research sites. We compared hippocampal volume and vertex-level hippocampal shape differences (1) between 121 non-using controls and 140 cannabis users; (2) between 106 controls, 50 non-dependent users and 70 dependent users; and (3) between a subset of 41 controls, 41 non-dependent users and 41 dependent users, matched on sample characteristics and cannabis use pattern (onset age and dosage). Cannabis users did not differ from controls in hippocampal volume or shape. However, cannabis-dependent users had significantly smaller right and left hippocampi relative to controls and non-dependent users, irrespective of cannabis dosage. Shape analysis indicated localized deflations in the superior-medial body of the hippocampus. Our findings support neuroscientific theories postulating dependence-specific neuroadaptations in cannabis users. Future efforts should uncover the neurobiological risk and liabilities separating dependent and non-dependent use of cannabis.
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ItemProlonged Cannabidiol Treatment Effects on Hippocampal Subfield Volumes in Current Cannabis Users.(Mary Ann Liebert Inc, 2018)Introduction: Chronic cannabis use is associated with neuroanatomical alterations in the hippocampus. While adverse impacts of cannabis use are generally attributed to Δ9-tetrahydrocannabinol, emerging naturalistic evidence suggests cannabidiol (CBD) is neuroprotective and may ameliorate brain harms associated with cannabis use, including protection from hippocampal volume loss. This study examined whether prolonged administration of CBD to regular cannabis users within the community could reverse or reduce the characteristic hippocampal harms associated with chronic cannabis use. Materials and Methods: Eighteen regular cannabis users participated in an ∼10-week open-label pragmatic trial involving daily oral administration of 200 mg CBD, with no change to their ongoing cannabis use requested. Participants were assessed at baseline and post-CBD treatment using structural magnetic resonance imaging. Automated longitudinal hippocampal segmentation was performed to assess volumetric change over the whole hippocampus and within 12 subfields. Results: No change was observed in left or right hippocampus as a whole. However, left subicular complex (parasubiculum, presubiculum, and subiculum) volume significantly increased from baseline to post-treatment (p=0.017 uncorrected) by 1.58% (Cohen's d=0.63; 2.83% in parasubiculum). Heavy cannabis users demonstrated marked growth in the left subicular complex, predominantly within the presubiculum, and right cornu ammonis (CA)1 compared to lighter users. Associations between greater right subicular complex and total hippocampal volume and higher plasma CBD concentration were evident, particularly in heavy users. Conclusions: Our findings suggest a restorative effect of CBD on the subicular and CA1 subfields in current cannabis users, especially those with greater lifetime exposure to cannabis. While replication is required in a larger, placebo-controlled trial, these findings support a protective role of CBD against brain structural harms conferred by chronic cannabis use. Furthermore, these outcomes suggest that CBD may be a useful adjunct in treatments for cannabis dependence and may be therapeutic for a range of clinical disorders characterized by hippocampal pathology (e.g., schizophrenia, Alzheimer's disease, and major depressive disorder).
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ItemTherapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial.(Mary Ann Liebert Inc, 2018)Introduction: Chronic cannabis use has been associated with impaired cognition and elevated psychological symptoms, particularly psychotic-like experiences. While Δ9-tetrahydrocannabinol (THC) is thought to be primarily responsible for these deleterious effects, cannabidiol (CBD) is purported to have antipsychotic properties and to ameliorate cognitive, symptomatic, and brain harms in cannabis users. However, this has never been tested in a prolonged administration trial in otherwise healthy cannabis users. Here, we report the first study of prolonged CBD administration to a community sample of regular cannabis users in a pragmatic trial investigating potential restorative effects of CBD on psychological symptoms and cognition. Materials and Methods: Twenty frequent cannabis users (16 male, median age 25 years) underwent a 10-week open-label trial of 200 mg of daily oral CBD treatment, while continuing to use cannabis as usual. The majority of participants were daily cannabis users who had used cannabis for several years (median 5.5 years of regular use). Participants underwent psychological and cognitive assessments at baseline (BL) and post-treatment (PT) and were monitored weekly throughout the trial. Results: CBD was well tolerated with no reported side effects; however, participants retrospectively reported reduced euphoria when smoking cannabis. No impairments to cognition were found, nor were there deleterious effects on psychological function. Importantly, participants reported significantly fewer depressive and psychotic-like symptoms at PT relative to BL, and exhibited improvements in attentional switching, verbal learning, and memory. Increased plasma CBD concentrations were associated with improvements in attentional control and beneficial changes in psychological symptoms. Greater benefits were observed in dependent than in nondependent cannabis users. Conclusions: Prolonged CBD treatment appears to have promising therapeutic effects for improving psychological symptoms and cognition in regular cannabis users. Our findings require replication given the lack of a placebo control in this pragmatic trial, but suggest that CBD may be a useful adjunct treatment for cannabis dependence.
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ItemManifesto for a European research network into Problematic Usage of the Internet.(Elsevier BV, 2018-11)The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.