Cortical gradient perturbation in attention deficit hyperactivity disorder correlates with neurotransmitter-, cell type-specific and chromosome- transcriptomic signatures.

AIMS: This study aimed to illuminate the neuropathological landscape of attention deficit hyperactivity disorder (ADHD) by a multiscale macro-micro-molecular perspective from in vivo neuroimaging data. METHODS: The "ADHD-200 initiative" repository provided multi-site high-quality resting-state functional connectivity (rsfc-) neuroimaging for ADHD children and matched typically developing (TD) cohort. Diffusion mapping embedding model to derive the functional connectome gradient detecting biologically plausible neural pattern was built, and the multivariate partial least square method to uncover the enrichment of neurotransmitomic, cellular and chromosomal gradient-transcriptional signatures of AHBA enrichment and meta-analytic decoding. RESULTS: Compared to TD, ADHD children presented connectopic cortical gradient perturbations in almost all the cognition-involved brain macroscale networks (all pBH <0.001), but not in the brain global topology. As an intermediate phenotypic variant, such gradient perturbation was spatially enriched into distributions of GABAA/BZ and 5-HT2A receptors (all pBH <0.01) and co-varied with genetic transcriptional expressions (e.g. DYDC2, ATOH7, all pBH <0.01), associated with phenotypic variants in episodic memory and emotional regulations. Enrichment models demonstrated such gradient-transcriptional variants indicated the risk of both cell-specific and chromosome- dysfunctions, especially in enriched expression of oligodendrocyte precursors and endothelial cells (all pperm <0.05) as well enrichment into chromosome 18, 19 and X (pperm <0.05). CONCLUSIONS: Our findings bridged brain macroscale neuropathological patterns to microscale/cellular biological architectures for ADHD children, demonstrating the neurobiologically pathological mechanism of ADHD into the genetic and molecular variants in GABA and 5-HT systems as well brain-derived enrichment of specific cellular/chromosomal expressions.

Sex-based differences in fairness norm compliance and neural circuitry.

Human behavior often aligns with fairness norms, either voluntarily or under external pressure, like sanctions. Prior research has identified distinct neural activation patterns associated with voluntary and sanction-based compliance or non-compliance with fairness norms. However, an investigation gap exists into potential neural connectivity patterns and sex-based differences. To address this, we conducted a study using a monetary allocation game and functional magnetic resonance imaging to examine how neural activity and connectivity differ between sexes across three norm compliance conditions: voluntary, sanction-based, and voluntary post-sanctions. Fifty-five adults (27 females) participated, revealing that punishment influenced decisions, leading to strategic calculations and reduced generosity in voluntary compliance post-sanctions. Moreover, there were sex-based differences in neural activation and connectivity across the different compliance conditions. Specifically, the connectivity between the right dorsolateral prefrontal cortex and right dorsal anterior insular appeared to mediate intuitive preferences, with variations across norm compliance conditions and sexes. These findings imply potential sex-based differences in intuitive motivation for diverse norm compliance conditions. Our insights contribute to a better understanding of the neural pathways involved in fairness norm compliance and clarify sex-based differences, offering implications for future investigations into psychiatric and neurological disorders characterized by atypical socialization and mentalizing.

Gender-specific resting-state rDMPFC-centric functional connectivity underpinnings of intertemporal choice.

Although studies have observed gender differences in intertemporal choice, the neural bases of these differences require further research. The current study used resting state functional connectivity (rsFC) to explore the gender-specific neural basis of intertemporal choice in three independent samples (n1 = 86, n2 = 297, n3 = 172). Behaviorally, three samples (S1, S2, and S3) consistently demonstrated that men had larger delay discounting rate (log k) than women. Then, whole-brain functional connectivity analyses were performed for different genders in S2 and S3 using the right dorsomedial prefrontal cortex (rDMPFC) as a region of interest. By subtracting the common rsFC patterns of different genders, we identified gender-specific log k-related rsFC patterns with significant gender differences in S2. This was verified in an independent sample (S3). Specifically, in women, log k was found to be positively correlated with the rsFC between rDMPFC and anterior cingulate cortex/right orbitofrontal cortex. In contrast, in men, log k was negatively correlated with rsFC between rDMPFC and left orbitofrontal cortex/right precuneus. These gender differences were confirmed by slope tests. The findings highlight how gender may differ when engaging in intertemporal choice. They improve the understanding of gender differences in decision impulsivity and its underlying neural bases.

Sampling inequalities affect generalization of neuroimaging-based diagnostic classifiers in psychiatry.

BACKGROUND: The development of machine learning models for aiding in the diagnosis of mental disorder is recognized as a significant breakthrough in the field of psychiatry. However, clinical practice of such models remains a challenge, with poor generalizability being a major limitation. METHODS: Here, we conducted a pre-registered meta-research assessment on neuroimaging-based models in the psychiatric literature, quantitatively examining global and regional sampling issues over recent decades, from a view that has been relatively underexplored. A total of 476 studies (n = 118,137) were included in the current assessment. Based on these findings, we built a comprehensive 5-star rating system to quantitatively evaluate the quality of existing machine learning models for psychiatric diagnoses. RESULTS: A global sampling inequality in these models was revealed quantitatively (sampling Gini coefficient (G) = 0.81, p < .01), varying across different countries (regions) (e.g., China, G = 0.47; the USA, G = 0.58; Germany, G = 0.78; the UK, G = 0.87). Furthermore, the severity of this sampling inequality was significantly predicted by national economic levels (ß = - 2.75, p < .001, R2adj = 0.40; r = - .84, 95% CI: - .41 to - .97), and was plausibly predictable for model performance, with higher sampling inequality for reporting higher classification accuracy. Further analyses showed that lack of independent testing (84.24% of models, 95% CI: 81.0-87.5%), improper cross-validation (51.68% of models, 95% CI: 47.2-56.2%), and poor technical transparency (87.8% of models, 95% CI: 84.9-90.8%)/availability (80.88% of models, 95% CI: 77.3-84.4%) are prevailing in current diagnostic classifiers despite improvements over time. Relating to these observations, model performances were found decreased in studies with independent cross-country sampling validations (all p < .001, BF10 > 15). In light of this, we proposed a purpose-built quantitative assessment checklist, which demonstrated that the overall ratings of these models increased by publication year but were negatively associated with model performance. CONCLUSIONS: Together, improving sampling economic equality and hence the quality of machine learning models may be a crucial facet to plausibly translating neuroimaging-based diagnostic classifiers into clinical practice.

Neural differences of food-specific inhibitory control in people with healthy vs higher BMI.

Consistent with the idea that deficits in inhibition limit resistance to tempting, tasty, high-calorie foods, and might result in a higher BMI, we test whether people with higher BMIs (BMI >25 kg/m2) present inefficient inhibitory control over food-related responses. To unpack this association, we also examine individual differences in the neural mechanisms of food inhibitory control in healthy vs higher BMI individuals. We test these aspects with a sample of 109 participants (49 with higher BMI and 60 with healthy BMI) and the food stop-signal task, which was used to examine individuals' inhibitory control. Results demonstrated that people with higher BMI had significantly poorer food inhibitory control than healthy BMI individuals. fMRI results showed that, in both Go (Go_food vs Go_nature) and Stop conditions (Stop_food vs Stop_nature), compared to healthy BMI individuals, individuals with higher BMI had lower activation in the superior frontal gyrus, precuneus, precentral gyrus, and supramarginal gyrus in the food stimulus condition. Moreover, ROI analysis results showed that under the Stop_food condition, the activation in the inferior frontal gyrus in the higher BMI group was significantly negatively correlated with inhibitory control abilities. These results suggest that people with a higher BMI have limited ability to inhibit food impulsions, and that the prefrontal regions and parietal cortex may contribute to the progression of inhibitory control limitations in relation to food.

From fears of evaluation to social anxiety: The longitudinal relationships and neural basis in healthy young adults

Background: Social anxiety disorder (SAD) is a common mental health problem, and its core cognitive manifestation is the persistent fear of being evaluated, including both negatively (FNE) and positively (FPE). This study aimed to examine the longitudinal relationships of FNE, FPE and SAD and explore their neural basis. Methods: Three samples were retrieved in this study. First, the data of 649 college students who completed a survey and fMRI scan were used to explore the neural basis of FNE, FPE, and SAD symptoms. Next, the data of 450 participants who completed the same survey twice were used to examine the longitudinal relationships of the variables. Finally, the overlapping of the two samples (N = 288) who completed two surveys and the fMRI scan were used to establish a brain-behavior model. Results: Both FNE and FPE predicted SAD, and SAD also predicted FPE. The neural signals of subregions in prefrontal cortex were correlated with the scores of FNE, FPE and SAD. Abnormal prefrontal signals influenced SAD symptoms via fears of evaluation. Conclusions: Our findings explain the behavioral and neural underpinnings of social anxiety from a fear of evaluation angle. This contributes to a better theorical understanding of SAD and clinical practice. (AU)

Risk aversion in risk-taking tasks: Combined effects of feedback attributes and cognitive reflection ability.

INTRODUCTION: Feedback on human choices is important because it can affect risk-taking and rationality in subsequent decisions. In daily life, choices are not always followed by immediate outcomes nor are they always followed by simple, single-dimensional feedback. Here, we seek to extend previous studies on the effects of feedback on subsequent risk-taking in three experiments. METHODS: We examine whether (1) the effect of feedback immediacy on participants' risk-taking exists in tasks containing explicit probabilistic outcome values; (2) increasing feedback dimensionality from one dimension (only about the outcome) to include a second dimension (also about the "rationality" of prior choices) increases feedback effects on risk-taking; and (3) cognitive reflection ability moderates feedback effects on risk-taking. RESULTS: Results showed that feedback reduced risk-taking in tasks containing explicit probabilistic outcomes (Studies 1 and 2). They further showed that two-dimensional feedback produces a stronger reduction in risk-taking compared to single-dimensional feedback (Study 3). Lastly, results suggested that cognitive reflection ability moderates the effects of feedback on risk-taking (Study 4). CONCLUSION: Taken together, the findings extended the understanding of risk-taking and mitigating mechanisms and pave the way for intervention studies aimed at changing risky behaviors.

From fears of evaluation to social anxiety: The longitudinal relationships and neural basis in healthy young adults.

Background: Social anxiety disorder (SAD) is a common mental health problem, and its core cognitive manifestation is the persistent fear of being evaluated, including both negatively (FNE) and positively (FPE). This study aimed to examine the longitudinal relationships of FNE, FPE and SAD and explore their neural basis. Methods: Three samples were retrieved in this study. First, the data of 649 college students who completed a survey and fMRI scan were used to explore the neural basis of FNE, FPE, and SAD symptoms. Next, the data of 450 participants who completed the same survey twice were used to examine the longitudinal relationships of the variables. Finally, the overlapping of the two samples (N = 288) who completed two surveys and the fMRI scan were used to establish a brain-behavior model. Results: Both FNE and FPE predicted SAD, and SAD also predicted FPE. The neural signals of subregions in prefrontal cortex were correlated with the scores of FNE, FPE and SAD. Abnormal prefrontal signals influenced SAD symptoms via fears of evaluation. Conclusions: Our findings explain the behavioral and neural underpinnings of social anxiety from a fear of evaluation angle. This contributes to a better theorical understanding of SAD and clinical practice.

Maladaptive changes in delay discounting in males during the COVID-19 pandemic: the predictive role of functional connectome.

The Coronavirus disease of 2019 (COVID-19) and measures to curb it created population-level changes in male-dominant impulsive and risky behaviors such as violent crimes and gambling. One possible explanation for this is that the pandemic has been stressful, and males, more so than females, tend to respond to stress by altering their focus on immediate versus delayed rewards, as reflected in their delay discounting rates. Delay discounting rates from healthy undergraduate students were collected twice during the pandemic. Discounting rates of males (n=190) but not of females (n=493) increased during the pandemic. Using machine learning, we show that prepandemic functional connectome predict increased discounting rates in males (n=88). Moreover, considering that delay discounting is associated with multiple psychiatric disorders, we found the same neural pattern that predicted increased discounting rates in this study, in secondary datasets of patients with major depression and schizophrenia. The findings point to sex-based differences in maladaptive delay discounting under real-world stress events, and to connectome-based neuromarkers of such effects. They can explain why there was a population-level increase in several impulsive and risky behaviors during the pandemic and point to intriguing questions about the shared underlying mechanisms of stress responses, psychiatric disorders and delay discounting.

Impulsivity and neural mechanisms that mediate preference for immediate food rewards in people with vs without excess weight.

People with excess weight (overweight or obese; body mass index [BMI]>25) are generally characterized as impulsive with regards to food. However, the underlying brain mechanisms of this impulsivity are not fully understood. As such, this study aims at understanding the neural mechanisms underlying impulsivity toward food rewards, as well as differences in delay discounting patterns for hypothetical food between people with vs without excess weight. To this end, participants (79 college students, 33 with excess weight and 46 without) performed a food delay discounting task and completed questionnaires related to food addiction and impulsivity. In the task, we manipulated the magnitude of immediate and delayed rewards and employed event-related fMRI design to measure brain activity. The results showed that people with excess weight, compared to those without, were more impulsive and presented a lower probability of choosing delayed rewards. The higher the BMI was, the lower the probability of choosing delayed rewards was. People with excess weight also had higher impulsivity scores than people with no excess weight. Moreover, people with excess weight had less activation in executive function areas such as the anterior cingulate gyrus, the frontal pole, and the inferior frontal gyrus in both difficult and easy decision-making conditions. These results suggest that hypo-activation of executive function areas may contribute to the progression of decision impulsivity in relation to food, which in turn is associated with excess weight.