FTO variant is associated with changes in BMI, ghrelin and brain function following bariatric surgery.

BACKGROUND: A polymorphism in the fat mass and obesity-associated gene (FTO) is linked to enhanced neural sensitivity to food-cues and attenuated ghrelin suppression. Risk allele carriers regain more weight than non-carriers after bariatric surgery. It remains unclear how FTO variation affects brain function and ghrelin following surgery. METHODS: Resting-state functional magnetic resonance imaging (RS-fMRI) and cue-reactivity fMRI with high-/low-caloric food-cues were performed at pre-surgery and 1-, 6-, and 12-months post-surgery to examine brain function in 16 carriers with one copy of the rs9939609 A allele (AT) and 26 non-carriers (TT). Behavioral assessments up to five years post-surgery were also conducted. RESULTS: AT relative to TT group had smaller BMI-loss at 12 to 60 months post-surgery and lower resting-state activity in posterior cingulate cortex following LSG (group-by-time interaction effects). Meanwhile, AT relative to TT group showed greater food-cue responses in dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC) and insula (group effects). There were negative associations of weight-loss with ghrelin and greater activation in DLPFC, DMPFC and insula in AT but not TT group. CONCLUSION: These findings indicate that FTO variation is associated with the evolution of ghrelin signaling and brain function after bariatric surgery, which might hinder weight-loss.

Sleep deprivation effects on brain state dynamics are associated with dopamine D2 receptor availability via network control theory.

BACKGROUND: Sleep deprivation (SD) negatively affects brain function. Most brain imaging studies have investigated the effects of SD on 'static' brain function. SD effects on functional brain dynamics and their relationship with molecular changes remain relatively unexplored. METHODS: We used functional MRI to examine resting brain state dynamics after one night of SD compared to rested wakefulness (RW) and assessed their association with striatal brain dopamine D2 receptor availability (D2R) measured by PET-[11C]raclopride using network control theory. RESULTS: SD reduced dwell time and persistence probabilities with the strongest effects in two brain states, one characterized by high default mode network and low dorsal attention network activity and the other by high frontal parietal network and low somatomotor network activity. Using network control theory, we showed that after SD there was an overall increase in the control energy required for brain state transitions with effects varying for different brain state transitions. Control energy requirement was negatively associated with transition probabilities under SD and RW and accounted for SD-induced changes in transition probabilities. Alteration in the energy landscape was associated with SD-induced changes in striatal D2R distribution. CONCLUSIONS: These findings demonstrate altered occurrence of internally and externally oriented brain states following acute SD and suggest an association with energy requirements for brain state transitions modulated by striatal D2R.

Seasonality in regional brain glucose metabolism.

BACKGROUND: Daylength and the rates of changes in daylength have been associated with seasonal fluctuations in psychiatric symptoms and in cognition and mood in healthy adults. However, variations in human brain glucose metabolism in concordance with seasonal changes remain under explored. METHODS: In this cross-sectional study, we examined seasonal effects on brain glucose metabolism, which we measured using 18F-fluorodeoxyglucose-PET in 97 healthy participants. To maximize the sensitivity of regional effects, we computed relative metabolic measures by normalizing the regional measures to white matter metabolism. Additionally, we explored the role of rest-activity rhythms/sleep-wake activity measured with actigraphy in the seasonal variations of regional brain metabolic activity. RESULTS: We found that seasonal variations of cerebral glucose metabolism differed across brain regions. Glucose metabolism in prefrontal regions increased with longer daylength and with greater day-to-day increases in daylength. The cuneus and olfactory bulb had the maximum and minimum metabolic values around the summer and winter solstice respectively (positively associated with daylength), whereas the temporal lobe, brainstem, and postcentral cortex showed maximum and minimum metabolic values around the spring and autumn equinoxes, respectively (positively associated with faster daylength gain). Longer daylength was associated with greater amplitude and robustness of diurnal activity rhythms suggesting circadian involvement. CONCLUSIONS: The current findings advance our knowledge of seasonal patterns in a key indicator of brain function relevant for mood and cognition. These data could inform treatment interventions for psychiatric symptoms that peak at specific times of the year.

Brain connectivity changes to fast versus slow dopamine increases.

The rewarding effects of stimulant drugs such as methylphenidate (MP) depend crucially on how fast they raise dopamine in the brain. Yet how the rate of drug-induced dopamine increases impacts brain network communication remains unresolved. We manipulated route of MP administration to generate fast versus slow dopamine increases. We hypothesized that fast versus slow dopamine increases would result in a differential pattern of global brain connectivity (GBC) in association with regional levels of dopamine D1 receptors, which are critical for drug reward. Twenty healthy adults received MP intravenously (0.5 mg/kg; fast dopamine increases) and orally (60 mg; slow dopamine increases) during simultaneous [11C]raclopride PET-fMRI scans (double-blind, placebo-controlled). We tested how GBC was temporally associated with slow and fast dopamine increases on a minute-to-minute basis. Connectivity patterns were strikingly different for slow versus fast dopamine increases, and whole-brain spatial patterns were negatively correlated with one another (rho = -0.54, pspin < 0.001). GBC showed "fast>slow" associations in dorsal prefrontal cortex, insula, posterior thalamus and brainstem, caudate and precuneus; and "slow>fast" associations in ventral striatum, orbitofrontal cortex, and frontopolar cortex (pFDR < 0.05). "Fast>slow" GBC patterns showed significant spatial correspondence with D1 receptor availability (estimated via normative maps of [11C]SCH23390 binding; rho = 0.22, pspin < 0.05). Further, hippocampal GBC to fast dopamine increases was significantly negatively correlated with self-reported 'high' ratings to intravenous MP across individuals (r(19) = -0.68, pbonferroni = 0.015). Different routes of MP administration produce divergent patterns of brain connectivity. Fast dopamine increases are uniquely associated with connectivity patterns that have relevance for the subjective experience of drug reward.

Ketogenic diet reduces a neurobiological craving signature in inpatients with alcohol use disorder.

Background and aims: Increasing evidence suggests that a ketogenic (high-fat, low-carbohydrate) diet (KD) intervention reduces alcohol withdrawal severity and alcohol craving in individuals with alcohol use disorder (AUD) by shifting brain energetics from glucose to ketones. We hypothesized that the KD would reduce a neurobiological craving signature when individuals undergoing alcohol detoxification treatment were exposed to alcohol cues. Methods: We performed a secondary analysis of functional magnetic resonance data of 33 adults with an AUD who were randomized to a KD (n = 19) or a standard American diet (SA; n = 14) and underwent 3 weeks of inpatient alcohol detoxification treatment. Once per week, participants performed an alcohol cue-reactivity paradigm with functional magnetic resonance imaging. We extracted brain responses to food and alcohol cues and quantified the degree to which each set of brain images shared a pattern of activation with a recently established 'Neurobiological Craving Signature' (NCS). We then performed a group-by-time repeated measures ANOVA to test for differences in craving signature expression between the dietary groups over the three-week treatment period. We also correlated these expression patterns with self-reported wanting ratings for alcohol cues. Results: For alcohol relative to food cues, there was a main effect of group, such that the KD group showed lower NCS expression across all 3 weeks of treatment. The main effect of time and the group-by-time interaction were not significant. Self-reported wanting for alcohol cues reduced with KD compared to SA but did not correlate with the NCS score. Conclusion: A ketogenic diet reduces self-reported alcohol wanting, and induced lower NCS to alcohol cues during inpatient treatment for AUD. However, in the KD group alcohol wanting continued to decrease across the 3 weeks of abstinence while the NCS scores remained stable, suggesting that this cue-induced NCS may not fully capture ongoing, non-cue-induced alcohol desire.

Associations Among Birth Weight, Adrenarche, Brain Morphometry, and Cognitive Function in Preterm Children Ages 9 to 11 Years.

BACKGROUND: Preterm infants with low birth weight are at heightened risk of developmental sequelae, including neurological and cognitive dysfunction that can persist into adolescence or adulthood. In addition, preterm birth and low birth weight can provoke changes in endocrine and metabolic processes that likely impact brain health throughout development. However, few studies have examined associations among birth weight, pubertal endocrine processes, and long-term neurological and cognitive development. METHODS: We investigated the associations between birth weight and brain morphometry, cognitive function, and onset of adrenarche assessed 9 to 11 years later in 3571 preterm and full-term children using the ABCD (Adolescent Brain Cognitive Development) Study dataset. RESULTS: The preterm children showed lower birth weight and early adrenarche, as expected. Birth weight was positively associated with cognitive function (all Cohen's d > 0.154, p < .005), global brain volumes (all Cohen's d > 0.170, p < .008), and regional volumes in frontal, temporal, and parietal cortices in preterm and full-term children (all Cohen's d > 0.170, p < .0007); cortical volume in the lateral orbitofrontal cortex partially mediated the effect of low birth weight on cognitive function in preterm children. In addition, adrenal score and cortical volume in the lateral orbitofrontal cortex mediated the associations between birth weight and cognitive function only in preterm children. CONCLUSIONS: These findings highlight the impact of low birth weight on long-term brain structural and cognitive function development and show important associations with early onset of adrenarche during the puberty. This understanding may help with prevention and treatment.

Stimulant medications in children with ADHD normalize the structure of brain regions associated with attention and reward.

Children with ADHD show abnormal brain function and structure. Neuroimaging studies found that stimulant medications may improve brain structural abnormalities in children with ADHD. However, prior studies on this topic were conducted with relatively small sample sizes and wide age ranges and showed inconsistent results. In this cross-sectional study, we employed latent class analysis and linear mixed-effects models to estimate the impact of stimulant medications using demographic, clinical measures, and brain structure in a large and diverse sample of children aged 9-11 from the Adolescent Brain and Cognitive Development Study. We studied 273 children with low ADHD symptoms and received stimulant medication (Stim Low-ADHD), 1002 children with high ADHD symptoms and received no medications (No-Med ADHD), and 5378 typically developing controls (TDC). After controlling for the covariates, compared to Stim Low-ADHD and TDC, No-Med ADHD showed lower cortical thickness in the right insula (INS, d = 0.340, PFDR = 0.003) and subcortical volume in the left nucleus accumbens (NAc, d = 0.371, PFDR = 0.003), indicating that high ADHD symptoms were associated with structural abnormalities in these brain regions. In addition, there was no difference in brain structural measures between Stim Low-ADHD and TDC children, suggesting that the stimulant effects improved both ADHD symptoms and ADHD-associated brain structural abnormalities. These findings together suggested that children with ADHD appear to have structural abnormalities in brain regions associated with saliency and reward processing, and treatment with stimulant medications not only improve the ADHD symptoms but also normalized these brain structural abnormalities.

Obesity is associated with alterations in anatomical connectivity of frontal-corpus callosum.

Obesity has been linked to abnormal frontal function, including the white matter fibers of anterior portion of the corpus callosum, which is crucial for information exchange within frontal cortex. However, alterations in white matter anatomical connectivity between corpus callosum and cortical regions in patients with obesity have not yet been investigated. Thus, we enrolled 72 obese and 60 age-/gender-matched normal weight participants who underwent clinical measurements and diffusion tensor imaging. Probabilistic tractography with connectivity-based classification was performed to segment the corpus callosum and quantify white matter anatomical connectivity between subregions of corpus callosum and cortical regions, and associations between corpus callosum-cortex white matter anatomical connectivity and clinical behaviors were also assessed. Relative to normal weight individuals, individuals with obesity exhibited significantly greater white matter anatomical connectivity of corpus callosum-orbitofrontal cortex, which was positively correlated with body mass index and self-reported disinhibition of eating behavior, and lower white matter anatomical connectivity of corpus callosum-prefrontal cortex, which was significantly negatively correlated with craving for high-calorie food cues. The findings show that alterations in white matter anatomical connectivity between corpus callosum and frontal regions involved in reward and executive control are associated with abnormal eating behaviors.

Preterm birth associated alterations in brain structure, cognitive functioning and behavior in children from the ABCD dataset.

BACKGROUND: Preterm birth is a global health problem and associated with increased risk of long-term developmental impairments, but findings on the adverse outcomes of prematurity have been inconsistent. METHODS: Data were obtained from the baseline session of the ongoing longitudinal Adolescent Brain and Cognitive Development (ABCD) Study. We identified 1706 preterm children and 1865 matched individuals as Control group and compared brain structure (MRI data), cognitive function and mental health symptoms. RESULTS: Results showed that preterm children had higher psychopathological risk and lower cognitive function scores compared to controls. Structural MRI analysis indicated that preterm children had higher cortical thickness in the medial orbitofrontal cortex, parahippocampal gyrus, temporal and occipital gyrus; smaller volumes in the temporal and parietal gyrus, cerebellum, insula and thalamus; and smaller fiber tract volumes in the fornix and parahippocampal-cingulum bundle. Partial correlation analyses showed that gestational age and birth weight were associated with ADHD symptoms, picvocab, flanker, reading, fluid cognition composite, crystallized cognition composite and total cognition composite scores, and measures of brain structure in regions involved with emotional regulation, attention and cognition. CONCLUSIONS: These findings suggest a complex interplay between psychopathological risk and cognitive deficits in preterm children that is associated with changes in regional brain volumes, cortical thickness, and structural connectivity among cortical and limbic brain regions critical for cognition and emotional well-being.

Disrupted brain state dynamics in opioid and alcohol use disorder: attenuation by nicotine use.

Substance use disorder (SUD) is a chronic relapsing disorder with long-lasting changes in brain intrinsic networks. While most research to date has focused on static functional connectivity, less is known about the effect of chronic drug use on dynamics of brain networks. Here we investigated brain state dynamics in individuals with opioid use (OUD) and alcohol use disorder (AUD) and assessed how concomitant nicotine use, which is frequent among individuals with OUD and AUD, affects brain dynamics. Resting-state functional magnetic resonance imaging data of 27 OUD, 107 AUD, and 137 healthy participants were included in the analyses. To identify recurrent brain states and their dynamics, we applied a data-driven clustering approach that determines brain states at a single time frame. We found that OUD and AUD non-smokers displayed similar changes in brain state dynamics including decreased fractional occupancy or dwell time in default mode network (DMN)-dominated brain states and increased appearance rate in visual network (VIS)-dominated brain states, which were also reflected in transition probabilities of related brain states. Interestingly, co-use of nicotine affected brain states in an opposite manner by lowering VIS-dominated and enhancing DMN-dominated brain states in both OUD and AUD participants. Our finding revealed a similar pattern of brain state dynamics in OUD and AUD participants that differed from controls, with an opposite effect for nicotine use suggesting distinct effects of various drugs on brain state dynamics. Different strategies for treating SUD may need to be implemented based on patterns of co-morbid drug use.

Examining the role of dopamine in methylphenidate's effects on resting brain function.

The amplitude of low-frequency fluctuations (ALFF) and global functional connectivity density (gFCD) are fMRI (Functional MRI) metrics widely used to assess resting brain function. However, their differential sensitivity to stimulant-induced dopamine (DA) increases, including the rate of DA rise and the relationship between them, have not been investigated. Here we used, simultaneous PET-fMRI to examine the association between dynamic changes in striatal DA and brain activity as assessed by ALFF and gFCD, following placebo, intravenous (IV), or oral methylphenidate (MP) administration, using a within-subject double-blind placebo-controlled design. In putamen, MP significantly reduced D2/3 receptor availability and strongly reduced ALFF and increased gFCD in the brain for IV-MP (Cohen's d > 1.6) but less so for oral-MP (Cohen's d < 0.6). Enhanced gFCD was associated with both the level and the rate of striatal DA increases, whereas decreased ALFF was only associated with the level of DA increases. These findings suggest distinct representations of neurovascular activation with ALFF and gFCD by stimulant-induced DA increases with differential sensitivity to the rate and the level of DA increases. We also observed an inverse association between gFCD and ALFF that was markedly enhanced during IV-MP, which could reflect an increased contribution from MP's vasoactive properties.

Neuroimaging in Adolescents: Post-Traumatic Stress Disorder and Risk for Substance Use Disorders.

Trauma in childhood and adolescence has long-term negative consequences in brain development and behavior and increases the risk for psychiatric disorders. Among them, post-traumatic stress disorder (PTSD) during adolescence illustrates the connection between trauma and substance misuse, as adolescents may utilize substances to cope with PTSD. Drug misuse may in turn lead to neuroadaptations in learning processes that facilitate the consolidation of traumatic memories that perpetuate PTSD. This reflects, apart from common genetic and epigenetic modifications, overlapping neurocircuitry engagement triggered by stress and drug misuse that includes structural and functional changes in limbic brain regions and the salience, default-mode, and frontoparietal networks. Effective strategies to prevent PTSD are needed to limit the negative consequences associated with the later development of a substance use disorder (SUD). In this review, we will examine the link between PTSD and SUDs, along with the resulting effects on memory, focusing on the connection between the development of an SUD in individuals who struggled with PTSD in adolescence. Neuroimaging has emerged as a powerful tool to provide insight into the brain mechanisms underlying the connection of PTSD in adolescence and the development of SUDs.

Neural circuit selective for fast but not slow dopamine increases in drug reward.

The faster a drug enters the brain, the greater its addictive potential, yet the brain circuits underlying the rate dependency to drug reward remain unresolved. With simultaneous PET-fMRI we linked dynamics of dopamine signaling, brain activity/connectivity, and self-reported 'high' in 20 adults receiving methylphenidate orally (results in slow delivery) and intravenously (results in fast delivery) (trial NCT03326245). We estimated speed of striatal dopamine increases to oral and IV methylphenidate and then tested where brain activity was associated with slow and fast dopamine dynamics (primary endpoint). We then tested whether these brain circuits were temporally associated with individual 'high' ratings to methylphenidate (secondary endpoint). A corticostriatal circuit comprising the dorsal anterior cingulate cortex and insula and their connections with dorsal caudate was activated by fast (but not slow) dopamine increases and paralleled 'high' ratings. These data provide evidence in humans for a link between dACC/insula activation and fast but not slow dopamine increases and document a critical role of the salience network in drug reward.

Ketogenic diet reduces a neurobiological craving signature in alcohol use disorder.

Background and Aims: Increasing evidence suggests that a ketogenic (high-fat, low-carbohydrate) diet intervention reduces alcohol withdrawal severity and alcohol craving in individuals with alcohol use disorder (AUD) by shifting brain energetics from glucose to ketones. We hypothesized that the ketogenic diet would reduce a brain craving signature when individuals undergoing alcohol detoxification treatment were exposed to alcohol cues. Methods: We performed a secondary analysis of functional magnetic resonance data of n=33 adults with an AUD were randomized to a ketogenic diet (n=19) or a standard American diet (n=14) and underwent three weeks of inpatient alcohol detoxification treatment. Once per week, participants performed an alcohol cue-reactivity paradigm with functional magnetic resonance imaging. We extracted brain responses to food and alcohol cues and quantified the degree to which each set of brain images shared a pattern of activation with a recently validated 'Neurobiological Craving Signature' (NCS). We then performed a group-by-time repeated measures ANOVA to test for differences in craving signature expression between the dietary groups over the three-week treatment period. We also correlated these expression patterns with self-reported wanting ratings for alcohol cues. Results: For alcohol relative to food cues, there was a main effect of group, such that the ketogenic diet group showed lower NCS expression across all three weeks of treatment. The main effect of time and the group-by-time interaction were not significant. Self-reported wanting for alcohol cues reduced with KD compared to SA but did not correlate with the NCS score. Conclusions: A ketogenic diet reduces self-reported alcohol wanting, and induced lower brain craving signatures to alcohol cues during inpatient treatment for AUD.

Neurological, Behavioral, and Pathophysiological Characterization of the Co-Occurrence of Substance Use and HIV: A Narrative Review.

Combined antiretroviral therapy (cART) has greatly reduced the severity of HIV-associated neurocognitive disorders in people living with HIV (PLWH); however, PLWH are more likely than the general population to use drugs and suffer from substance use disorders (SUDs) and to exhibit risky behaviors that promote HIV transmission and other infections. Dopamine-boosting psychostimulants such as cocaine and methamphetamine are some of the most widely used substances among PLWH. Chronic use of these substances disrupts brain function, structure, and cognition. PLWH with SUD have poor health outcomes driven by complex interactions between biological, neurocognitive, and social factors. Here we review the effects of comorbid HIV and psychostimulant use disorders by discussing the distinct and common effects of HIV and chronic cocaine and methamphetamine use on behavioral and neurological impairments using evidence from rodent models of HIV-associated neurocognitive impairments (Tat or gp120 protein expression) and clinical studies. We also provide a biopsychosocial perspective by discussing behavioral impairment in differentially impacted social groups and proposing interventions at both patient and population levels.

Risk Assessment of Maladaptive Behaviors in Adolescents: Nutrition, Screen Time, Prenatal Exposure, Childhood Adversities - Adolescent Brain Cognitive Development Study.

PURPOSE: We aimed to identify significant contributing factors to the risk of maladaptive behaviors, such as alcohol use disorder or obesity, in children. To achieve this, we utilized the extensive adolescent brain cognitive development data set, which encompasses a wide range of environmental, social, and nutritional factors. METHODS: We divided our sample into equal sets (test, validation; n = 3,415 each). On exploratory factor analysis, six factor domains were identified as most significant (fat/sugar intake, screen time, and prenatal alcohol exposure, parental aggressiveness, hyperactivity, family violence, parental education, and family income) and used to stratify the children into low- (n = 975), medium- (n = 967), high- (n = 977) risk groups. Regression models were used to analyze the relationship between identified risk groups, and differences in reward sensitivity, and behavioral problems at 2-year follow-up. RESULTS: The functional magnetic resonance imaging analyses showed reduced activation in several brain regions during reward or loss anticipation in high/medium-risk (vs. low-risk) children on a monetary incentive delay task. High-risk children exhibited heightened middle frontal cortex activity when receiving large rewards. They also displayed increased impulsive and motivated reward-seeking behaviors, along with behavioral problems. These findings replicated in our validation set, and a negative correlation between middle frontal cortexthickness and impulsivity behavior was observed in high-risk children. DISCUSSION: Our findings show altered reward function and increased impulsiveness in high-risk adolescents. This study has implications for early risk identification and the development of prevention strategies for maladaptive behaviors in children, particularly those at high risk.

Hippocampal volume loss in individuals with a history of non-fatal opioid overdose.

Incidence of opioid-related overdoses in the United States has increased dramatically over the past two decades. Despite public emphasis on overdose fatalities, most overdose cases are not fatal. Although there are case reports of amnestic syndromes and acute injury to the hippocampus following non-fatal opioid overdose, the effects of such overdoses on brain structure are poorly understood. Here, we investigated the neuroanatomical correlates of non-fatal opioid overdoses by comparing hippocampal volume in opioid use disorder (OUD) patients who had experienced an opioid overdose (OD; N = 17) with those who had not (NOD; N = 32). Voxel-based morphometry showed lower hippocampal volume in the OD group than in the NOD group, which on post hoc analysis was evident in the left but not the right hippocampus. These findings strengthen the evidence that hippocampal injury is associated with non-fatal opioid overdose, which is hypothesized to underlie overdose-related amnestic syndrome.

Habenula Volume and Functional Connectivity Changes Following Laparoscopic Sleeve Gastrectomy for Obesity Treatment.

BACKGROUND: Neuroimaging studies have revealed alterations in habenular (Hb) structure and functional connectivity (FC) in psychiatric conditions. The Hb plays a particularly critical role in regulating negative emotions, which trigger excessive food intake and obesity. However, obesity and weight loss intervention (i.e., laparoscopic sleeve gastrectomy [LSG])-associated changes in Hb structure and FC have not been studied. METHODS: We used voxel-based morphometry analysis to measure changes in gray matter volume (GMV) in the Hb in 56 patients with obesity at pre-LSG and 12 months post-LSG and in 78 normal-weight (NW) control participants. Then, we conducted Hb seed-based resting-state FC (RSFC) to examine obesity-related and LSG-induced alterations in RSFC. Finally, we used mediation analysis to characterize the interrelationships among Hb GMV, RSFC, and behaviors. RESULTS: Compared with NW participants, Hb GMV was smaller in patients at pre-LSG and increased at 12 months post-LSG to levels equivalent to that of NW; in addition, increases in Hb GMV were correlated with reduced body mass index (BMI). Compared with NW participants, pre-LSG patients showed greater RSFCs of the Hb-insula, Hb-precentral gyrus, and Hb-rolandic operculum and weaker RSFCs of the Hb-thalamus, Hb-hypothalamus, and Hb-caudate; LSG normalized these RSFCs. Decreased RSFC of the Hb-insula was correlated with reduced BMI, Yale Food Addiction Scale rating, and emotional eating; reduced hunger levels were correlated with increased RSFCs of the Hb-thalamus and Hb-hypothalamus; and reduced BMI and Yale Food Addiction Scale ratings were correlated with increased RSFCs of the Hb-thalamus and Hb-hypothalamus, respectively. The bidirectional relationships between Hb GMV and RSFC of the Hb-insula contributed to reduced BMI. CONCLUSIONS: These findings indicate that LSG increased Hb GMV and that its related improvement in RSFC of the Hb-insula may mediate long-term benefits of LSG for eating behaviors and weight loss.

Associations between body mass index, sleep-disordered breathing, brain structure, and behavior in healthy children.

Pediatric overweight/obesity can lead to sleep-disordered breathing (SDB), abnormal neurological and cognitive development, and psychiatric problems, but the associations and interactions between these factors have not been fully explored. Therefore, we investigated the associations between body mass index (BMI), SDB, psychiatric and cognitive measures, and brain morphometry in 8484 children 9-11 years old using the Adolescent Brain Cognitive Development dataset. BMI was positively associated with SDB, and both were negatively correlated with cortical thickness in lingual gyrus and lateral orbitofrontal cortex, and cortical volumes in postcentral gyrus, precentral gyrus, precuneus, superior parietal lobule, and insula. Mediation analysis showed that SDB partially mediated the effect of overweight/obesity on these brain regions. Dimensional psychopathology (including aggressive behavior and externalizing problem) and cognitive function were correlated with BMI and SDB. SDB and cortical volumes in precentral gyrus and insula mediated the correlations between BMI and externalizing problem and matrix reasoning ability. Comparisons by sex showed that obesity and SDB had a greater impact on brain measures, cognitive function, and mental health in girls than in boys. These findings suggest that preventing childhood obesity will help decrease SDB symptom burden, abnormal neurological and cognitive development, and psychiatric problems.

Neural correlates of decreased impulsivity during delay discounting task after laparoscopic sleeve gastrectomy.

OBJECTIVE: The goal of this study was to investigate laparoscopic sleeve gastrectomy (LSG)-induced changes in choice impulsivity and the neural correlates in individuals with obesity (OB). METHODS: The study employed functional magnetic resonance imaging with a delay discounting task in 29 OB tested before and 1 month after LSG. Thirty participants with normal weight matched to OB with gender and age were recruited as the control group and underwent an identical functional magnetic resonance imaging scan. Alterations in activation and functional connectivity between pre- and post-LSG were investigated and compared with participants with normal weight. RESULTS: OB exhibited significantly reduced discounting rate after LSG. During the delay discounting task, hyperactivation in dorsolateral prefrontal cortex, right caudate, and dorsomedial prefrontal cortex decreased in OB after LSG. LSG additionally engaged compensatory effects through increased activation in bilateral posterior insula and functional connectivity between caudate and dorsomedial prefrontal cortex. Those changes were associated with decreased discounting rate and BMI as well as improved eating behaviors. CONCLUSIONS: These findings indicate that decreased choice impulsivity following LSG was associated with the changes in regions involved in executive control, reward evaluation, interoception, and prospection. This study may provide neurophysiological support for the development of nonoperative treatments such as brain stimulation for individuals with obesity and overweight.