Real-time fMRI-based neurofeedback to restore brain function in substance use disorders: A systematic review of the literature.

INTRODUCTION: Real-time functional magnetic resonance based-neurofeedback (fMRI-neurofeedback) is a neuromodulation tool where individuals self-modulate brain function based on real-time feedback of their brain activity. fMRI-neurofeedback has been used to target brain dysfunction in substance use disorders (SUDs) and to reduce craving, but a systematic synthesis of up-to-date literature is lacking. METHOD: Following PRISMA guidelines, we conducted a systematic review of all the literature that examined the effects of fMRI-neurofeedback on individuals with regular psychoactive substance use (PROSPERO pre-registration = CRD42023401137). RESULTS: The literature included 16 studies comprising 446 participants with SUDs involving alcohol, tobacco, and cocaine. There is consistent between-condition (e.g., fMRI-neurofeedback versus control), less consistent pre-to-post fMRI-neurofeedback, and little intervention-by-time effects on brain function in prefrontal-striatal regions and craving. CONCLUSION: The evidence for changes in brain function/craving was early and inconsistent. More rigorous experiments including repeated measure designs with placebo control conditions, are required to confirm the efficacy of fMRI-neurofeedback in reducing brain alterations and craving in SUDs.

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 (ß = -0.16, p = 0.005). Poorer performance monitoring at baseline predicted higher AE at 3-month follow-up (ß = -0.16, p = 0.004), and more reward-related attentional capture at 3-months predicted higher AE at 6-month follow-up (ß = 0.14, p = 0.033). Less reward-related attentional capture (ß = -0.14, p = 0.003) and less risk-taking under ambiguity (ß = -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.

Multiscale heterogeneity of white matter morphometry in psychiatric disorders.

Background: Inter-individual variability in neurobiological and clinical characteristics in mental illness is often overlooked by classical group-mean case-control studies. Studies using normative modelling to infer person-specific deviations of grey matter volume have indicated that group means are not representative of most individuals. The extent to which this variability is present in white matter morphometry, which is integral to brain function, remains unclear. Methods: We applied Warped Bayesian Linear Regression normative models to T1-weighted magnetic resonance imaging data and mapped inter-individual variability in person-specific white matter volume deviations in 1,294 cases (58% male) diagnosed with one of six disorders (attention-deficit/hyperactivity, autism, bipolar, major depressive, obsessive-compulsive and schizophrenia) and 1,465 matched controls (54% male) recruited across 25 scan sites. We developed a framework to characterize deviation heterogeneity at multiple spatial scales, from individual voxels, through inter-regional connections, specific brain regions, and spatially extended brain networks. Results: The specific locations of white matter volume deviations were highly heterogeneous across participants, affecting the same voxel in fewer than 8% of individuals with the same diagnosis. For autism and schizophrenia, negative deviations (i.e., areas where volume is lower than normative expectations) aggregated into common tracts, regions and large-scale networks in up to 35% of individuals. Conclusions: The prevalence of white matter volume deviations was lower than previously observed in grey matter, and the specific location of these deviations was highly heterogeneous when considering voxel-wise spatial resolution. Evidence of aggregation within common pathways and networks was apparent in schizophrenia and autism but not other disorders.

Photocatalyst Au@Ni-MOFs with Different Plasmonic Coverages for Improved Hydrogen Evolution from Water.

Plasmonic materials are fundamental photosensitizer materials for photocatalytic reactions. Various structures, including core-shell types, satellite types, and distribution types, have been designed and prepared for the optimization of photocatalytic reactions. However, understanding the profound enhancement mechanism of various structures is still challenging. Thus, the plasmonic coverage is considered to be an index for analyzing the influence mechanism. Here, Au@Ni-MOF core-shell flower sphere-like photocatalysts are prepared, and the size of the flower sphere can be precisely regulated by varying the amount of Au. Thus, different plasmonic coverages are realized through the tuning of spheres of different sizes. The high plasmonic coverage of catalysts can enhance visible light absorption, facilitate the generation of photogenerated electron-hole pairs, and shorten the photogenerated carrier transport distance. Moreover, the exponential relationship between the photocatalytic hydrogen production performance and the plasmonic coverage can also be used as a guide for material design. As a result, a photocatalytic hydrogen production rate of 3389 µmol·g-1·h-1 is achieved in the Au@Ni-MOF sample with high plasmonic coverage, which will advance the plasmonic application in photocatalytic reactions.

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: ß = 13.69, p = 0.017; subsample: ß = 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.

Examining the unique relationships between problematic use of the internet and impulsive and compulsive tendencies: network approach.

BACKGROUND: Both impulsivity and compulsivity have been identified as risk factors for problematic use of the internet (PUI). Yet little is known about the relationship between impulsivity, compulsivity and individual PUI symptoms, limiting a more precise understanding of mechanisms underlying PUI. AIMS: The current study is the first to use network analysis to (a) examine the unique association among impulsivity, compulsivity and PUI symptoms, and (b) identify the most influential drivers in relation to the PUI symptom community. METHOD: We estimated a Gaussian graphical model consisting of five facets of impulsivity, compulsivity and individual PUI symptoms among 370 Australian adults (51.1% female, mean age = 29.8, s.d. = 11.1). Network structure and bridge expected influence were examined to elucidate differential associations among impulsivity, compulsivity and PUI symptoms, as well as identify influential nodes bridging impulsivity, compulsivity and PUI symptoms. RESULTS: Results revealed that four facets of impulsivity (i.e. negative urgency, positive urgency, lack of premeditation and lack of perseverance) and compulsivity were related to different PUI symptoms. Further, compulsivity and negative urgency were the most influential nodes in relation to the PUI symptom community due to their highest bridge expected influence. CONCLUSIONS: The current findings delineate distinct relationships across impulsivity, compulsivity and PUI, which offer insights into potential mechanistic pathways and targets for future interventions in this space. To realise this potential, future studies are needed to replicate the identified network structure in different populations and determine the directionality of the relationships among impulsivity, compulsivity and PUI symptoms.

Cannabis Dependence is Associated with Reduced Hippocampal Subregion Volumes Independently of Sex: Findings from an ENIGMA Addiction Working Group Multi-Country Study.

Background: Males and females who consume cannabis can experience different mental health and cognitive problems. Neuroscientific theories of addiction postulate that dependence is underscored by neuroadaptations, but do not account for the contribution of distinct sexes. Further, there is little evidence for sex differences in the neurobiology of cannabis dependence as most neuroimaging studies have been conducted in largely male samples in which cannabis dependence, as opposed to use, is often not ascertained. Methods: We examined subregional hippocampus and amygdala volumetry in a sample of 206 people recruited from the ENIGMA Addiction Working Group. They included 59 people with cannabis dependence (17 females), 49 cannabis users without cannabis dependence (20 females), and 98 controls (33 females). Results: We found no group-by-sex effect on subregional volumetry. The left hippocampal cornu ammonis subfield 1 (CA1) volumes were lower in dependent cannabis users compared with non-dependent cannabis users (p<0.001, d=0.32) and with controls (p=0.022, d=0.18). Further, the left cornu ammonis subfield 3 (CA3) and left dentate gyrus volumes were lower in dependent versus non-dependent cannabis users but not versus controls (p=0.002, d=0.37, and p=0.002, d=0.31, respectively). All models controlled for age, intelligence quotient (IQ), alcohol and tobacco use, and intracranial volume. Amygdala volumetry was not affected by group or group-by-sex, but was smaller in females than males. Conclusions: Our findings suggest that the relationship between cannabis dependence and subregional volumetry was not moderated by sex. Specifically, dependent (rather than non-dependent) cannabis use may be associated with alterations in selected hippocampus subfields high in cannabinoid type 1 (CB1) receptors and implicated in addictive behavior. As these data are cross-sectional, it is plausible that differences predate cannabis dependence onset and contribute to the initiation of cannabis dependence. Longitudinal neuroimaging work is required to examine the time-course of the onset of subregional hippocampal alterations in cannabis dependence, and their progression as cannabis dependence exacerbates or recovers over time.

A multiscale characterization of cortical shape asymmetries in early psychosis.

Psychosis has often been linked to abnormal cortical asymmetry, but prior results have been inconsistent. Here, we applied a novel spectral shape analysis to characterize cortical shape asymmetries in patients with early psychosis across different spatial scales. We used the Human Connectome Project for Early Psychosis dataset (aged 16-35), comprising 56 healthy controls (37 males, 19 females) and 112 patients with early psychosis (68 males, 44 females). We quantified shape variations of each hemisphere over different spatial frequencies and applied a general linear model to compare differences between healthy controls and patients with early psychosis. We further used canonical correlation analysis to examine associations between shape asymmetries and clinical symptoms. Cortical shape asymmetries, spanning wavelengths from about 22 to 75 mm, were significantly different between healthy controls and patients with early psychosis (Cohen's d = 0.28-0.51), with patients showing greater asymmetry in cortical shape than controls. A single canonical mode linked the asymmetry measures to symptoms (canonical correlation analysis r = 0.45), such that higher cortical asymmetry was correlated with more severe excitement symptoms and less severe emotional distress. Significant group differences in the asymmetries of traditional morphological measures of cortical thickness, surface area, and gyrification, at either global or regional levels, were not identified. Cortical shape asymmetries are more sensitive than other morphological asymmetries in capturing abnormalities in patients with early psychosis. These abnormalities are expressed at coarse spatial scales and are correlated with specific symptom domains.

Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study.

INTRODUCTION: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool. METHODS: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables. RESULTS: Compared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges' g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses. CONCLUSION: EOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

The neurocognitive correlates of non-substance addictive behaviors.

Neurocognitive deficits have been implicated as transdiagnostic risk markers of substance use disorders. However, these have yet to be comprehensively evaluated in other, non-substance addictions. In a large, general community sample (N = 475) the present study evaluated the neurocognitive correlates of problem alcohol use and three non-substance-related addictive behaviors: addictive eating (AE), problematic pornography use (PPU), and problematic use of the internet (PUI), to identify potential shared and distinct neurocognitive correlates. A sample of Australian residents (54.4 % female M[SD] age = 32.4[11.9] years) completed a comprehensive online assessment of neurocognitive tasks tapping into eight distinct expert-endorsed domains purportedly associated with addiction. Multiple linear regressions with bootstrapping were used to examine associations among each addictive behavior of interest and neurocognition, trait impulsivity, and compulsivity, as well as key covariates. Neurocognition was differentially associated with each addictive behavior. None of the neurocognitive domains were significantly associated with problematic alcohol use or AE (p >.05), poorer performance monitoring was significantly associated with higher levels of PPU and PUI (ß = -0.10, p =.049; ß = -0.09, p =.028), and a preference for delayed gratification was associated with more severe PUI (ß = -0.10, p =.025). Our findings have theoretical implications for how we understand non-substance addiction and suggest the need for a more nuanced approach to studying addictive behaviors that take into account the underlying neurocognitive mechanisms associated with each type of addiction.

Neuroimaging Insights: Kava's (Piper methysticum) Effect on Dorsal Anterior Cingulate Cortex GABA in Generalized Anxiety Disorder.

Generalised Anxiety Disorder (GAD) is a prevalent, chronic mental health disorder. The measurement of regional brain gamma-aminobutyric acid (GABA) offers insight into its role in anxiety and is a potential biomarker for treatment response. Research literature suggests Piper methysticum (Kava) is efficacious as an anxiety treatment, but no study has assessed its effects on central GABA levels. This study investigated dorsal anterior cingulate (dACC) GABA levels in 37 adult participants with GAD. GABA was measured using proton magnetic resonance spectroscopy (1H-MRS) at baseline and following an eight-week administration of Kava (standardised to 120 mg kavalactones twice daily) (n = 20) or placebo (n = 17). This study was part of the Kava for the Treatment of GAD (KGAD; ClinicalTrials.gov: NCT02219880), a 16-week intervention study. Compared with the placebo group, the Kava group had a significant reduction in dACC GABA (p = 0.049) at eight weeks. Baseline anxiety scores on the HAM-A were positively correlated with GABA levels but were not significantly related to treatment. Central GABA reductions following Kava treatment may signal an inhibitory effect, which, if considered efficacious, suggests that GABA levels are modulated by Kava, independent of reported anxiety symptoms. dACC GABA patterns suggest a functional role of higher levels in clinical anxiety but warrants further research for symptom benefit. Findings suggest that dACC GABA levels previously un-examined in GAD could serve as a biomarker for diagnosis and treatment response.

Regional, circuit and network heterogeneity of brain abnormalities in psychiatric disorders.

The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case-control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive-compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience-ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks.

A Novel, Expert-Endorsed, Neurocognitive Digital Assessment Tool for Addictive Disorders: Development and Validation Study.

BACKGROUND: Many people with harmful addictive behaviors may not meet formal diagnostic thresholds for a disorder. A dimensional approach, by contrast, including clinical and community samples, is potentially key to early detection, prevention, and intervention. Importantly, while neurocognitive dysfunction underpins addictive behaviors, established assessment tools for neurocognitive assessment are lengthy and unengaging, difficult to administer at scale, and not suited to clinical or community needs. The BrainPark Assessment of Cognition (BrainPAC) Project sought to develop and validate an engaging and user-friendly digital assessment tool purpose-built to comprehensively assess the main consensus-driven constructs underpinning addictive behaviors. OBJECTIVE: The purpose of this study was to psychometrically validate a gamified battery of consensus-based neurocognitive tasks against standard laboratory paradigms, ascertain test-retest reliability, and determine their sensitivity to addictive behaviors (eg, alcohol use) and other risk factors (eg, trait impulsivity). METHODS: Gold standard laboratory paradigms were selected to measure key neurocognitive constructs (Balloon Analogue Risk Task [BART], Stop Signal Task [SST], Delay Discounting Task [DDT], Value-Modulated Attentional Capture [VMAC] Task, and Sequential Decision-Making Task [SDT]), as endorsed by an international panel of addiction experts; namely, response selection and inhibition, reward valuation, action selection, reward learning, expectancy and reward prediction error, habit, and compulsivity. Working with game developers, BrainPAC tasks were developed and validated in 3 successive cohorts (total N=600) and a separate test-retest cohort (N=50) via Mechanical Turk using a cross-sectional design. RESULTS: BrainPAC tasks were significantly correlated with the original laboratory paradigms on most metrics (r=0.18-0.63, P<.05). With the exception of the DDT k function and VMAC total points, all other task metrics across the 5 tasks did not differ between the gamified and nongamified versions (P>.05). Out of 5 tasks, 4 demonstrated adequate to excellent test-retest reliability (intraclass correlation coefficient 0.72-0.91, P<.001; except SDT). Gamified metrics were significantly associated with addictive behaviors on behavioral inventories, though largely independent of trait-based scales known to predict addiction risk. CONCLUSIONS: A purpose-built battery of digitally gamified tasks is sufficiently valid for the scalable assessment of key neurocognitive processes underpinning addictive behaviors. This validation provides evidence that a novel approach, purported to enhance task engagement, in the assessment of addiction-related neurocognition is feasible and empirically defensible. These findings have significant implications for risk detection and the successful deployment of next-generation assessment tools for substance use or misuse and other mental disorders characterized by neurocognitive anomalies related to motivation and self-regulation. Future development and validation of the BrainPAC tool should consider further enhancing convergence with established measures as well as collecting population-representative data to use clinically as normative comparisons.

Brain volumes in alcohol use disorder: Do females and males differ? A whole-brain magnetic resonance imaging mega-analysis.

Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole-brain, voxel-based, multi-tissue mega-analytic approach, thereby extending our recent surface-based region of interest findings on a nearly matching sample using a complementary methodological approach. T1-weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel-based morphometry. The effects of group, sex, group-by-sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group-by-sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group-by-sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo-occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD.

COP9 Signalosome Promotes Neointimal Hyperplasia via Deneddylation and CSN5-Mediated Nuclear Export.

BACKGROUND: Neointimal hyperplasia (NH) is a common pathological response to vascular injury and mediated primarily by vascular smooth muscle cell (VSMC) migration and proliferation. The COP9 signalosome (CSN) is formed by 8 canonical subunits (CSN1 through CSN8) with its deneddylation activity residing in CSN5. Each or some of CSN subunits may have deneddylation-independent function. Despite strong evidence linking the CSN to cell cycle regulation in cancer cells, the role of the CSN in vascular biology remains obscure. METHODS: Neointimal CSN5 expression in the lung tissue of pulmonary hypertension (PAH) patients was assessed with immunohistochemistry. Adult mice with smooth muscle cell-restricted CSN5 knockout (CSN5-SMKO) or CSN8 hypomorphism (CSN8-hypo) and cultured mouse VSMCs were studied to determine the role and governing mechanisms of the CSN in NH. NH was induced by ligation of the left common carotid artery (LCCA) and PDGF-BB stimulation was used to mimic the vascular injury in cell cultures. RESULTS: Remarkably higher CSN5 levels were detected in the neointimal VSMCs of the pulmonary arteries of human PAH. LCCA ligation induced NH and significantly increased the mRNA and protein levels of CSN subunits in the LCCA wall of adult wild type mice. CSN5-SMKO impaired Cullin deneddylation and the nuclear export of p27 in vessel walls and markedly inhibited VSMC proliferation in mice. On the contrary, CSN8-hypo significantly exacerbated NH and VSMC proliferation in vivo and in cellulo . Cytoplasmic CSN5 mini-complexes and the nuclear export of p27 were significantly increased in CSN8-hypo mouse vessels and cultured CSN8-hypo VSMCs. Nuclear export inhibition with leptomycin attenuated the PDGF-BB-induced increases in VSMC proliferation in both CSN8-hypo and control VSMCs. Further, genetically disabling CSN5 nuclear export but not disabling CSN5 deneddylase activity suppressed the hyperproliferation and restored p27 nuclear localization in CSN8 hypomorphic VSMCs. Interestingly, CSN deneddylase inhibition by CSN5i-3 did not alter the hyperproliferation of cultured CSN8-hypo VSMCs but suppressed wild type VSMC proliferation in cellulo and in vivo and blocked neointimal formation in wild type mice. CONCLUSION: The CSN promotes VSMC proliferation and NH in injured vessels through deneddylation activity and CSN5-mediated nuclear export.

Individuals with problem gambling and obsessive-compulsive disorder learn through distinct reinforcement mechanisms.

Obsessive-compulsive disorder (OCD) and pathological gambling (PG) are accompanied by deficits in behavioural flexibility. In reinforcement learning, this inflexibility can reflect asymmetric learning from outcomes above and below expectations. In alternative frameworks, it reflects perseveration independent of learning. Here, we examine evidence for asymmetric reward-learning in OCD and PG by leveraging model-based functional magnetic resonance imaging (fMRI). Compared with healthy controls (HC), OCD patients exhibited a lower learning rate for worse-than-expected outcomes, which was associated with the attenuated encoding of negative reward prediction errors in the dorsomedial prefrontal cortex and the dorsal striatum. PG patients showed higher and lower learning rates for better- and worse-than-expected outcomes, respectively, accompanied by higher encoding of positive reward prediction errors in the anterior insula than HC. Perseveration did not differ considerably between the patient groups and HC. These findings elucidate the neural computations of reward-learning that are altered in OCD and PG, providing a potential account of behavioural inflexibility in those mental disorders.

Increased cortical surface area but not altered cortical thickness or gyrification in bipolar disorder following stabilisation from a first episode of mania.

BACKGROUND: Despite reports of altered brain morphology in established bipolar disorder (BD), there is limited understanding of when these morphological abnormalities emerge. Assessment of patients during the early course of illness can help to address this gap, but few studies have examined surface-based brain morphology in patients at this illness stage. METHODS: We completed a secondary analysis of baseline data from a randomised control trial of BD individuals stabilised after their first episode of mania (FEM). The magnetic resonance imaging scans of n = 35 FEM patients and n = 29 age-matched healthy controls were analysed. Group differences in cortical thickness, surface area and gyrification were assessed at each vertex of the cortical surface using general linear models. Significant results were identified at p < 0.05 using cluster-wise correction. RESULTS: The FEM group did not differ from healthy controls with regards to cortical thickness or gyrification. However, there were two clusters of increased surface area in the left hemisphere of FEM patients, with peak coordinates falling within the lateral occipital cortex and pars triangularis. CONCLUSIONS: Cortical thickness and gyrification appear to be intact in the aftermath of a first manic episode, whilst cortical surface area in the inferior/middle prefrontal and occipitoparietal cortex is increased compared to age-matched controls. It is possible that increased surface area in the FEM group is the outcome of abnormalities in a premorbidly occurring process. In contrast, the findings raise the hypothesis that cortical thickness reductions seen in past studies of individuals with more established BD may be more attributable to post-onset factors.

In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis.

Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age = 16.6 years, interquartile range (IQR) = 2.14, 46.4% females) and 265 adolescent healthy controls (median age = 16.2 years, IQR = 2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d = 0.37), posterior corona radiata (d = 0.32), and superior fronto-occipital fasciculus (d = 0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.

Research on pharyngeal bacterial flora in transoral atlantoaxial operation and the postoperative follow-up study.

OBJECTIVES: To study the changes of bacterial flora after a series of preoperative oral disinfection and the postoperative recovery of nerve function of patients with craniovertebral junction disorders who were treated with transoral approach operations. METHODS: This research analyzed 20 cases collected from October 2009 to May 2010. All these patients were with CVJ disorders, including 8 males and 12 females, aged 2 to 66 (38.1 on average), and they were all treated with transoral approach operations. The mucosa samples of the posterior pharyngeal wall were sent for bacteria culture. These samples were collected by sterile cotton swabs at four crucial points, including 3 days before operation/before gargling, 3 days after continuous gargling/after anesthesia intubation on the day of operation, after intraoperative cleaning and washing of the mouth, and after intraoperative iodophor immersion. The microflora was stained by means of smear and further counted after an investigation by microscope. The neural function of patients was evaluated by the ASIA classification and the JOA scores. All patients but two with posterior stabilization performed respectively underwent transoral atlantoaxial reduction plate (TARP) fixation consecutively in the same sitting. A regular reexamination of cervical vertebra with lateral and open mouth X-ray, CT and MRI was conducted after operation to evaluate the reduction of atlantoaxial dislocation, internal fixation position, bone graft fusion, inflammatory lesions and tumor recurrence. RESULTS: This bacteriological research showed that the mucosa of the posterior pharyngeal wall of all the patients was in a sterile state after a series of oral preoperative preparations and intraoperative iodophor disinfection, which was considered as type I incision. The bacterial culture results of the mucosa samples of the posterior pharyngeal wall collected at different time points showed significant differences (χ2 = 42.762, P = 0.000). All the patients had improvement in ASIA, and their neural functions were improved to different levels after operation. There was a significant difference in JOA scores before and after operation (t = 8.677, P = 0.000). Postoperative imaging examination showed that the atlantoaxial screw position was good and firm, and the CVJ disorders were treated appropriately. CONCLUSION: It is safe and effective to cut the posterior pharyngeal muscle layer and implant internal fixation by means of transoral approach.

The individuality of shape asymmetries of the human cerebral cortex.

Asymmetries of the cerebral cortex are found across diverse phyla and are particularly pronounced in humans, with important implications for brain function and disease. However, many prior studies have confounded asymmetries due to size with those due to shape. Here, we introduce a novel approach to characterize asymmetries of the whole cortical shape, independent of size, across different spatial frequencies using magnetic resonance imaging data in three independent datasets. We find that cortical shape asymmetry is highly individualized and robust, akin to a cortical fingerprint, and identifies individuals more accurately than size-based descriptors, such as cortical thickness and surface area, or measures of inter-regional functional coupling of brain activity. Individual identifiability is optimal at coarse spatial scales (~37 mm wavelength), and shape asymmetries show scale-specific associations with sex and cognition, but not handedness. While unihemispheric cortical shape shows significant heritability at coarse scales (~65 mm wavelength), shape asymmetries are determined primarily by subject-specific environmental effects. Thus, coarse-scale shape asymmetries are highly personalized, sexually dimorphic, linked to individual differences in cognition, and are primarily driven by stochastic environmental influences.