White matter diffusion estimates in obsessive-compulsive disorder across 1653 individuals: machine learning findings from the ENIGMA OCD Working Group.

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) "OCD vs. healthy controls" (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) "unmedicated OCD vs. healthy controls" (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) "medicated OCD vs. unmedicated OCD" (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6-79.1 in adults; 35.9-63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.

Food go/no-go training alters neural circuits for food evaluation for appetite reduction.

Food go/no-go training has been traditionally categorized as a type of inhibitory training that decreases the desire for high-calorie food consumption. This training requires participants to either respond or withhold their responses to presented items with go cues or food items with no-go cues, respectively. Recent findings have suggested that this training may devalue food items associated with no-go cues instead of facilitating inhibitory control, leading to reduced food consumption. We thus hypothesized that food go/no-go training would alter the brain response to food items with no-go cues in food evaluation regions. To examine this hypothesis, we conducted a repeated measures functional magnetic resonance imaging using food images in healthy participants, who underwent 3 weeks of food go/no-go training (n = 26) using high- and low-calorie food items paired with no-go cues (no-go food) and go cues (go food), respectively, and control training (n = 24). The food go/no-go training reduced the ratings for the desire to eat no-go foods and increased the ratings for go foods. The reduction in no-go food rating was positively associated with a decrease in daily snack intake. The neural responses in the food evaluation regions increased for go foods. Moreover, the functional connectivity of those regions was altered. The food go/no-go training did not decrease impulsivity traits or increase restrained eating, which are associated with inhibitory control. Overall, food go/no-go training influenced the brain regions associated with food evaluation, thus devaluating no-go foods and reducing the daily snack intake. Accordingly, food go/no-go training could promote healthier food choices.

Pragmatic Deficits in Attention Deficit/Hyperactivity Disorder: Systematic Review and Meta-Analysis.

INTRODUCTION: While poorer pragmatic language skills have been found in attention-deficit/hyperactivity disorder (ADHD) populations, there has been no conclusive evidence of this. We aimed to conduct a meta-analysis of pragmatic language abilities in ADHD populations to definitively demonstrate the extent of pragmatic language deficits in these populations as compared to typically developing (TD) populations. METHODS: Studies were identified using the search terms ((attention deficit) OR (adhd)) AND (pragmatics), and those studies were screened and reviewed for inclusion criteria, descriptive information, and outcome variables in order to conduct a meta-analysis. RESULTS: A total of 14 studies (5,772 participants) met the criteria for quantitative synthesis. Meta-analysis indicated that ADHD populations exhibited significantly poorer pragmatic language skills than TD populations, with a very large overall effect size of -1.55. These results indicate that pragmatic language is significantly impaired in ADHD populations. CONCLUSION: It is suggested that pragmatic language skills may deserve greater surveillance considering the importance of pragmatic language in socio-emotional development, daily life, and academic success.

Arcuate Fasciculus Microstructure Predicts Alcohol Dependence Risk through Higher IQ.

IQ has been found to correlate with alcohol consumption, with a higher IQ being a risk for alcohol misuse. Furthermore, recent research has shown that the microstructure of the arcuate fasciculus is associated with IQ. This study therefore aimed to examine the association between the arcuate fasciculus microstructure, IQ, and alcohol dependence risk. In this study, we performed probabilistic tractography between Wernicke's and Broca's areas in the left and right hemispheres to examine the association of the arcuate fasciculus's integrity with IQ and alcohol dependence risk, using DTI data from 344 individuals. Data regarding IQ were obtained from the Wechsler Abbreviated Scale of Intelligence (WASI-II). Alcohol substance involvement (SI) score was derived using the National Institute on Drug Abuse (NIDA) Quick Screen and was used as an index for alcohol dependence risk. Both the left arcuate fasciculus and IQ were found to have a significant association with alcohol dependence risk. A mediation analysis revealed that this association between the left arcuate fasciculus microstructure and an alcohol dependence risk was mediated by IQ. It is suggested that the left arcuate fasciculus microstructure is associated with IQ which is associated with alcohol dependence risk. While alcohol consumption is known to be robustly toxic to the brain, the left arcuate fasciculus shows exceptional characteristics in which its microstructure integrity is positively associated with an alcohol dependence risk through higher IQ. Clinical implications are discussed.

Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis.

A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to treat adults with major depressive disorder (MDD) in the maintenance phase. This study searched the PubMed, Cochrane Library, and Embase databases and included only double-blind, randomized, placebo-controlled trials with an enrichment design: patients were stabilized on the antidepressant of interest during the open-label study and then randomized to receive the same antidepressant or placebo. The outcomes were the 6-month relapse rate (primary outcome, efficacy), all-cause discontinuation (acceptability), discontinuation due to adverse events (tolerability), and the incidence of individual adverse events. The risk ratio with a 95% credible interval was calculated. The meta-analysis comprised 34 studies (n = 9384, mean age = 43.80 years, and %females = 68.10%) on 20 antidepressants (agomelatine, amitriptyline, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, vilazodone, and vortioxetine) and a placebo. In terms of the 6-month relapse rate, amitriptyline, citalopram, desvenlafaxine, duloxetine, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, and vortioxetine outperformed placebo. Compared to placebo, desvenlafaxine, paroxetine, sertraline, venlafaxine, and vortioxetine had lower all-cause discontinuation; however, sertraline had a higher discontinuation rate due to adverse events. Compared to placebo, venlafaxine was associated with a lower incidence of dizziness, while desvenlafaxine, sertraline, and vortioxetine were associated with a higher incidence of nausea/vomiting. In conclusion, desvenlafaxine, paroxetine, venlafaxine, and vortioxetine had reasonable efficacy, acceptability, and tolerability in the treatment of adults with stable MDD.

Prevalence of hearing loss in college students: a meta-analysis.

Introduction: Hearing loss among college students, specifically noise-induced hearing loss (NIHL), appears to be increasing. This may be particularly challenging for this population as college students are required to listen to lectures in classrooms that may have suboptimal listening environments. College-aged musicians are at a particularly high risk due to repeated and extended exposure to loud noise. Therefore, the purpose of the current study was (1) to examine the prevalence of hearing loss in college students and (2) to emphasize the importance of detecting hearing loss at 6,000 Hz. Methods: A meta-analysis was conducted using the PRISMA model. The literature search yielded 8 studies (1,950 subjects) that tested hearing loss using an audiogram and Distortion Product Otoacoustic Emissions (DPOAEs). All studies used audiologic tests to detect hearing loss among college students between the ages of 17-35 years. Results: Results indicate that the prevalence of hearing loss in college students is 19%. In addition, the prevalence of hearing loss at 6,000 Hz is 85% among student musicians. For this meta-analysis, slight sensorineural hearing loss, or thresholds greater than 20 dB bilaterally or unilaterally, qualified as hearing loss. Discussion: Decreased hearing at 6,000 Hz may lead to an individual's inability to hear important environmental factors and high frequency speech sounds. College students without full auditory function at this frequency may have difficulties performing in class based on decreased attention, comprehension, and memory. Although students may not realize the influence of their 6,000 Hz hearing loss or be unaware of its presence, it could significantly change their likelihood to succeed in college. Therefore, implementing a hearing conservation program may be advised for colleges and universities to help prevent hearing loss in students, particularly for collegiate musicians. In addition, it may be beneficial to screen hearing in college students at 6,000 Hz for better detection of hearing loss overall.

Sleep duration is associated with Caudate volume and executive function.

The ineligible role of the caudate nucleus in sleep has been implicated. Previous literature showed that the caudate volume is associated with longer habitual sleep duration in older adults. However, the association between sleep duration and caudate volume remains unknown in the younger population. In this study, we examined the caudate volume in youth to older adults (10 to 85 years old) with a greater sample size (N = 464). The volumetric size of the caudate nucleus showed significantly positive association with habitual sleep duration, especially in younger population. Sleep duration showed a significant association with executive function performance. However, caudate volume did not significantly predict executive function. Our results suggested that sleep duration is associated with the caudate volume and executive function. It is also suggested that there are some external mechanisms that modulate executive function which prevent the caudate-sleep relation's effect on executive function.

Hippocampal Functional Connectivity in Parkinson's Disease.

BACKGROUND: While the hippocampus is not part of the nigrostriatal dopaminergic pathway, influence of Parkinson's disease (PD) on the hippocampus has been consistently implicated. However, it is not clear how the hippocampal changes contribute to the pathology of PD. OBJECTIVES: We aimed to elucidate the physiological changes of the hippocampus in its orchestration with the rest of the brain. METHODS: Using the resting-state fMRI data from Parkinson's Progression Markers Initiative (PPMI), functional connectivity of the hippocampus was analyzed in 93 individuals with PD and 18 individuals without PD. RESULTS: A whole brain voxel-wise analysis showed that the bilateral paracingulate gyri were less connected to the hippocampus in the PD group compared to the control group. The hippocampus-paracingulate dysconnectivity did not show association with cognitive indices. CONCLUSIONS: The hippocampus in PD shows dysconnectivity to the paracingulate gyri.

Disrupted functional connectivity of the primary auditory cortex in autism.

Autism Spectrum Disorder (ASD) has been found to influence hearing and sensory integration, while brain functional connectivity in ASD has been repeatedly shown to be atypical. However, functional connectivity of the auditory cortex in ASD has not been well studied. In the current study, we used resting-state functional magnetic resonance imaging data, provided by the Autism Brain Imaging Data Exchange (ABIDE), to examine functional connectivity of the primary auditory cortex in ASD. The study subjects included 68 individuals with ASD and 77 individuals without ASD. In the primary dataset, the ASD group showed lesser functional connectivity between the auditory cortex and four regions: the medial occipital cortex, primary motor cortex, insular cortex, and Wernicke's area. In the replication dataset (44 individuals with ASD and 39 individuals without ASD), reduced connectivity to the medial occipital cortex and primary motor cortex was replicated among these four regions, which have previously been shown to be influenced by ASD. Thus, the reduced functional connectivity to these indicated regions may partly explain deficient sensory integration associated with ASD.

The interhemispheric auditory white matter tract is associated with impulsivity.

The association between auditory processing and impulsivity has been consistently shown. However, the exact mechanism and pathological relations are not clear. The bilateral auditory cortices are interhemispherically connected through the corpus callosum. We hypothesized that this Interhemispheric Auditory white matter Tract (IAT) is associated with impulsivity. We first isolated the IAT and tested the association between IAT's integrity and impulsivity using diffusion tensor imaging (DTI) data from Nathan Kline Institute - Rockland Sample. Fractional Anisotropy (FA) was used as an index of white matter integrity. Out of 446 individuals, probabilistic tractography of IAT was successful in 390 individuals. FA of the IAT showed positive association with impulsivity scale, measured by UPPS (urgency, premeditation, perseverance, and sensation seeking) Impulsive Behavior Scale total score. Among five UPPS subscales, sensation seeking showed positive association with IAT FA. Our results showed that higher IAT FA is associated with higher impulsivity, especially with higher sensation seeking. It is suggested that stronger interhemispheric auditory integration is associated with greater impulsivity and sensation seeking.

Pharmacological treatment for bipolar mania: a systematic review and network meta-analysis of double-blind randomized controlled trials.

A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.

The human raphe-hippocampal tract and affective sensitivity: a probabilistic tractography study.

Serotonergic system plays critical roles in modulating affective control. The raphe nucleus has been known to be the origin of forebrain 5-HT afferents. Specifically, the Raphe-Hippocampal projection has been shown to modulate affective sensitivity in rodents. However, the human Raphe-Hippocampal tract is not well studied. We aimed to segment the Raphe-Hippocampal tract using probabilistic tractography on diffusion tensor imaging data from 502 subjects. The Raphe-Hippocampal tracts were successfully isolated in 464 individuals. There was a significant association between integrity of the Raphe-Hippocampal tract and affective sensitivity. To our best knowledge, this is the first study that isolated the human Raphe-Hippocampal tract. The integrity of the tract showed consistent characteristics with rodent findings, where affective sensitivity is modulated by the Raphe-Hippocampal projection. This study provides a technique to segment the human Raphe-Hippocampal tract and a translational knowledge that the tract in a human possesses consistent characteristics that have been found in rodent studies.

Disrupted functional connectivity between the nucleus accumbens and posterior cingulate cortex in autism spectrum disorder.

OBJECTIVES: Dysfunctions in the basal ganglia have been repeatedly found in autism spectrum disorder (ASD). The nucleus accumbens (NAcc) is known for its central role in social functions and also in its abnormality in ASD. In this study, whole-brain functional connectivity of the NAcc was examined to isolate brain regions that are differently connected to the NAcc in autism, using resting-state functional MRI (rs-fMRI) data. METHODS: In the initial dataset, 68 individuals with ASD (13.13 ± 2.41 years old) and 77 typically developing individuals (14.79 ± 3.57 years old) were compared. RESULTS: The precuneus cortex, lingual gyrus, thalamus, dorsal striatum, anterior cingulate cortex and posterior cingulate cortex showed weaker connectivity to the NAcc in the group with ASD. Among these regions, dysconnectivity of the posterior cingulate cortex (PCC) was replicated in the replication dataset, with 78 individuals with ASD and 105 without ASD. CONCLUSIONS: This study suggests that the dysconnectivity between the NAcc and PCC may account for social dysfunctions in ASD.

Efficacy and safety of antipsychotic treatments for schizophrenia: A systematic review and network meta-analysis of randomized trials in Japan.

BACKGROUND: We examined the efficacy and safety of using antipsychotic medication for schizophrenia using only randomized trials of antipsychotic for schizophrenia conducted in Japan to avoid the biological and environmental heterogeneities caused by pooling data from various races and ethnicities. METHODS: We searched for eligible studies on Embase, PubMed, and CENTRAL. Primary outcomes were improvement in Positive and Negative Syndrome Scale total score (PANSS-T) and all-cause discontinuation. Other outcomes were improvement in PANSS subscale scores, discontinuation due to adverse events or inefficacy, and the incidence of 16 adverse events. RESULTS: We calculated mean difference or risk ratios and 95% credible intervals. We identified 34 RCTs (6798 patients; mean study duration, 9.0 ± 4.24 weeks; proportion of male patients, 53.7%; mean age, 43.3 years). Besides placebo, studies included aripiprazole, asenapine, blonanserin, blonanserin-patch, brexpiprazole, clocapramine (no PANSS data), clozapine (no PANSS data), haloperidol, lurasidone, mosapramine, olanzapine, paliperidone, perospirone, quetiapine, and risperidone. Efficacy and safety profiles differed for antipsychotics used with schizophrenia in Japanese patients. All active treatments other than haloperidol and quetiapine outperformed placebo to improve PANSS-T. Asenapine, olanzapine, paliperidone, and risperidone outperformed placebo for all-cause discontinuation. Asenapine, blonanserin, blonanserin-patch, haloperidol, lurasidone, mosapramine, olanzapine, paliperidone, and risperidone outperformed placebo to improve PANSS positive subscale scores. Aripiprazole, asenapine, blonanserin, blonanserin-patch, brexpiprazole, lurasidone, olanzapine, paliperidone, perospirone, and risperidone outperformed placebo to improve PANSS negative subscale scores. The confidence in evidence of most outcomes was low or very low. CONCLUSION: Our results are similar to those of previous network meta-analysis involving various races and ethnicities.

Mood stabilizers and/or antipsychotics for bipolar disorder in the maintenance phase: a systematic review and network meta-analysis of randomized controlled trials.

We searched Embase, PubMed, and CENTRAL from inception until 22 May 2020 to investigate which antipsychotics and/or mood stabilizers are better for patients with bipolar disorder in the maintenance phase. We performed two categorical network meta-analyses. The first included monotherapy studies and studies in which the two drugs used were specified (i.e., aripiprazole, aripiprazole once monthly, aripiprazole+lamotrigine, aripiprazole+valproate, asenapine, carbamazepine, lamotrigine, lamotrigine+valproate, lithium, lithium+oxcarbazepine, lithium+valproate, olanzapine, paliperidone, quetiapine, risperidone long-acting injection, valproate, and placebo). The second included studies on second-generation antipsychotic combination therapies (SGAs) (i.e., aripiprazole, lurasidone, olanzapine, quetiapine, and ziprasidone) with lithium or valproate (LIT/VAL) compared with placebo with LIT/VAL. Outcomes were recurrence/relapse rate of any mood episode (RR-any, primary), depressive episode (RR-dep) and manic/hypomanic/mixed episode (RR-mania), discontinuation, mortality, and individual adverse events. Risk ratios and 95% credible interval were calculated. Forty-one randomized controlled trials were identified (n = 9821; mean study duration, 70.5 ± 36.6 weeks; percent female, 54.1%; mean age, 40.7 years). All active treatments other than carbamazepine, lamotrigine+valproate (no data) and paliperidone outperformed the placebo for RR-any. Aripiprazole+valproate, lamotrigine, lamotrigine+valproate, lithium, olanzapine, and quetiapine outperformed placebo for RR-dep. All active treatments, other than aripiprazole+valproate, carbamazepine, lamotrigine, and lamotrigine+valproate, outperformed placebo for RR-mania. Asenapine, lithium, olanzapine, quetiapine, and valproate outperformed placebo for all-cause discontinuation. All SGAs+LIT/VALs other than olanzapine+LIT/VAL outperformed placebo+LIT/VAL for RR-any. Lurasidone+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for RR-dep. Aripiprazole+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for RR-mania. Lurasidone+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for all-cause discontinuation. Treatment efficacy, tolerability, and safety profiles differed among treatments.

Estimation of Dynamic Bivariate Correlation Using a Weighted Graph Algorithm.

Dynamic correlation is the correlation between two time series across time. Two approaches that currently exist in neuroscience literature for dynamic correlation estimation are the sliding window method and dynamic conditional correlation. In this paper, we first show the limitations of these two methods especially in the presence of extreme values. We present an alternate approach for dynamic correlation estimation based on a weighted graph and show using simulations and real data analyses the advantages of the new approach over the existing ones. We also provide some theoretical justifications and present a framework for quantifying uncertainty and testing hypotheses.