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.

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.

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.

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.

Brain functional and structural magnetic resonance imaging of obesity and weight loss interventions.

Obesity has tripled over the past 40 years to become a major public health issue, as it is linked with increased mortality and elevated risk for various physical and neuropsychiatric illnesses. Accumulating evidence from neuroimaging studies suggests that obesity negatively affects brain function and structure, especially within fronto-mesolimbic circuitry. Obese individuals show abnormal neural responses to food cues, taste and smell, resting-state activity and functional connectivity, and cognitive tasks including decision-making, inhibitory-control, learning/memory, and attention. In addition, obesity is associated with altered cortical morphometry, a lowered gray/white matter volume, and impaired white matter integrity. Various interventions and treatments including bariatric surgery, the most effective treatment for obesity in clinical practice, as well as dietary, exercise, pharmacological, and neuromodulation interventions such as transcranial direct current stimulation, transcranial magnetic stimulation and neurofeedback have been employed and achieved promising outcomes. These interventions and treatments appear to normalize hyper- and hypoactivations of brain regions involved with reward processing, food-intake control, and cognitive function, and also promote recovery of brain structural abnormalities. This paper provides a comprehensive literature review of the recent neuroimaging advances on the underlying neural mechanisms of both obesity and interventions, in the hope of guiding development of novel and effective treatments.

Associations among body mass index, working memory performance, gray matter volume, and brain activation in healthy children.

To investigate the neural mechanisms underlying the association between poorer working memory performance and higher body mass index (BMI) in children. We employed structural-(sMRI) and functional magnetic resonance imaging (fMRI) with a 2-back working memory task to examine brain abnormalities and their associations with BMI and working memory performance in 232 children with overweight/obesity (OW/OB) and 244 normal weight children (NW) from the Adolescent Brain Cognitive Development dataset. OW/OB had lower working memory accuracy, which was associated with higher BMI. They showed smaller gray matter (GM) volumes in the left superior frontal gyrus (SFG_L), dorsal anterior cingulate cortex, medial orbital frontal cortex, and medial superior frontal gyrus, which were associated with lower working memory accuracy. During the working memory task, OW/OB relative to NW showed weaker activation in the left superior temporal pole, amygdala, insula, and bilateral caudate. In addition, caudate activation mediated the relationship between higher BMI and lower working memory accuracy. Higher BMI is associated with smaller GM volumes and weaker brain activation in regions involved with working memory. Task-related caudate dysfunction may account for lower working memory accuracy in children with higher BMI.

Obesity is associated with decreased gray matter volume in children: a longitudinal study.

Childhood obesity has become a global health problem. Previous studies showed that childhood obesity is associated with brain structural differences relative to controls. However, few studies have been performed with longitudinal evaluations of brain structural developmental trajectories in childhood obesity. We employed voxel-based morphometry (VBM) analysis to assess gray matter (GM) volume at baseline and 2-year follow-up in 258 obese children (OB) and 265 normal weight children (NW), recruited as part of the National Institutes of Health Adolescent Brain and Cognitive Development study. Significant group × time effects on GM volume were observed in the prefrontal lobe, thalamus, right precentral gyrus, caudate, and parahippocampal gyrus/amygdala. OB compared with NW had greater reductions in GM volume in these regions over the 2-year period. Body mass index (BMI) was negatively correlated with GM volume in prefrontal lobe and with matrix reasoning ability at baseline and 2-year follow-up. In OB, Picture Test was positively correlated with GM volume in the left orbital region of the inferior frontal gyrus (OFCinf_L) at baseline and was negatively correlated with reductions in OFCinf_L volume (2-year follow-up vs. baseline). These findings indicate that childhood obesity is associated with GM volume reduction in regions involved with reward evaluation, executive function, and cognitive performance.

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.

Habenular connectivity predict weight loss and negative emotional-related eating behavior after laparoscopic sleeve gastrectomy.

Habenular (Hb) processes negative emotions that may drive compulsive food-intake. Its functional changes were reported following laparoscopic-sleeve-gastrectomy (LSG). However, structural connectivity (SC) of Hb-homeostatic/hedonic circuits after LSG remains unclear. We selected regions implicated in homeostatic/hedonic regulation that have anatomical connections with Hb as regions-of-interest (ROIs), and used diffusion-tensor-imaging with probabilistic tractography to calculate SC between Hb and these ROIs in 30 obese participants before LSG (PreLSG) and at 12-month post-LSG (PostLSG12) and 30 normal-weight controls. Three-factor-eating-questionnaire (TFEQ) and Dutch-eating-behavior-questionnaire (DEBQ) were used to assess eating behaviors. LSG significantly decreased weight, negative emotion, and improved self-reported eating behavior. LSG increased SC between the Hb and homeostatic/hedonic regions including hypothalamus (Hy), bilateral superior frontal gyri (SFG), left amygdala (AMY), and orbitofrontal cortex (OFC). TFEQ-hunger negatively correlated with SC of Hb-Hy at PostLSG12; and increased SC of Hb-Hy correlated with reduced depression and DEBQ-external eating. TFEQ-disinhibition negatively correlated with SC of Hb-bilateral SFG at PreLSG. Increased SC of Hb-left AMY correlated with reduced DEBQ-emotional eating. Higher percentage of total weight-loss negatively correlated with SC of Hb-left OFC at PreLSG. Enhanced SC of Hb-homeostatic/hedonic regulatory regions post-LSG may contribute to its beneficial effects in improving eating behaviors including negative emotional eating, and long-term weight-loss.

Sex differences in methylphenidate-induced dopamine increases in ventral striatum.

Sex differences in the prevalence of dopamine-related neuropsychiatric diseases and in the sensitivity to dopamine-boosting drugs such as stimulants is well recognized. Here we assessed whether there are sex differences in the brain dopamine system in humans that could contribute to these effects. We analyzed data from two independent [11C]raclopride PET brain imaging studies that measured methylphenidate-induced dopamine increases in the striatum using different routes of administration (Cohort A = oral 60 mg; Cohort B = intravenous 0.5 mg/kg; total n = 95; 65 male, 30 female), in blinded placebo-controlled designs. Females when compared to males reported stronger feeling of "drug effects" and showed significantly greater dopamine release in the ventral striatum (where nucleus accumbens is located) to both oral and intravenous methylphenidate. In contrast, there were no significant differences in methylphenidate-induced increases in dorsal striatum for either oral or intravenous administration nor were there differences in levels of methylphenidate in plasma. The greater dopamine increases with methylphenidate in ventral but not dorsal striatum in females compared to males suggests an enhanced sensitivity specific to the dopamine reward system that might underlie sex differences in the vulnerability to substance use disorders and to attention-deficit/hyperactivity disorder (ADHD).