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1.
Int J Obes (Lond) ; 42(4): 785-793, 2018 04.
Article in English | MEDLINE | ID: mdl-28894291

ABSTRACT

BACKGROUND/OBJECTIVES: Despite the effectiveness of bariatric surgery, there is still substantial variability in long-term weight outcomes and few factors with predictive power to explain this variability. Neuroimaging may provide a novel biomarker with utility beyond other commonly used variables in bariatric surgery trials to improve prediction of long-term weight-loss outcomes. The purpose of this study was to evaluate the effects of sleeve gastrectomy (SG) on reward and cognitive control circuitry postsurgery and determine the extent to which baseline brain activity predicts weight loss at 12-month postsurgery. SUBJECTS/METHODS: Using a longitudinal design, behavioral, hormone and neuroimaging data (during a desire for palatable food regulation paradigm) were collected from 18 patients undergoing SG at baseline (<1 month prior) and 12-month post-SG. RESULTS: SG patients lost an average of 29.0% of their weight (percentage of total weight loss (%TWL)) at 12-month post-SG, with significant variability (range: 16.0-43.5%). Maladaptive eating behaviors (uncontrolled, emotional and externally cued eating) improved (P<0.01), in parallel with reductions in fasting hormones (acyl ghrelin, leptin, glucose, insulin; P<0.05). Brain activity in the nucleus accumbens (NAcc), caudate, pallidum and amygdala during desire for palatable food enhancement vs regulation decreased from baseline to 12 months (P (family-wise error (FWE))<0.05). Dorsolateral and dorsomedial prefrontal cortex activity during desire for palatable food regulation (vs enhancement) increased from baseline to 12 months (P(FWE)<0.05). Baseline activity in the NAcc and hypothalamus during desire for palatable food enhancement was significantly predictive of %TWL at 12 months (P (FWE)<0.05), superior to behavioral and hormone predictors, which did not significantly predict %TWL (P>0.10). Using stepwise linear regression, left NAcc activity accounted for 54% of the explained variance in %TWL at 12 months. CONCLUSIONS: Consistent with previous obesity studies, reward-related neural circuit activity may serve as an objective, relatively robust predictor of postsurgery weight loss. Replication in larger studies is necessary to determine true effect sizes for outcome prediction.


Subject(s)
Bariatric Surgery/statistics & numerical data , Brain/physiology , Feeding Behavior/physiology , Weight Loss/physiology , Adult , Brain/diagnostic imaging , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged , Neuroimaging , Treatment Outcome
2.
Neuroscience ; 250: 733-42, 2013 Oct 10.
Article in English | MEDLINE | ID: mdl-23891965

ABSTRACT

Decades of clinical and basic research indicate significant links between altered hypothalamic-pituitary-adrenal (HPA)-axis hormone dynamics and major depressive disorder (MDD). Recent neuroimaging studies of MDD highlight abnormalities in stress response circuitry regions which play a role in the regulation of the HPA-axes. However, there is a dearth of research examining these systems in parallel, especially as related to potential trait characteristics. The current study addresses this gap by investigating neural responses to a mild visual stress challenge with real-time assessment of adrenal hormones in women with MDD in remission and controls. Fifteen women with recurrent MDD in remission (rMDD) and 15 healthy control women were scanned on a 3T Siemens MR scanner while viewing neutral and negative (stress-evoking) stimuli. Blood samples were obtained before, during, and after scanning for the measurement of HPA-axis hormone levels. Compared to controls, rMDD women demonstrated higher anxiety ratings, increased cortisol levels, and hyperactivation in the amygdala and hippocampus, p<0.05, family-wise error (FWE)-corrected in response to the stress challenge. Among rMDD women, amygdala activation was negatively related to cortisol changes and positively associated with the duration of remission. Findings presented here provide evidence for differential effects of altered HPA-axis hormone dynamics on hyperactivity in stress response circuitry regions elicited by a well-validated stress paradigm in women with recurrent MDD in remission.


Subject(s)
Depressive Disorder, Major/physiopathology , Hypothalamic Hormones/physiology , Hypothalamo-Hypophyseal System/physiology , Pituitary Hormones/physiology , Stress, Psychological/physiopathology , Adrenocorticotropic Hormone/metabolism , Adult , Affect/physiology , Anxiety/psychology , Brain Mapping , Depressive Disorder, Major/psychology , Female , Humans , Hydrocortisone/blood , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Middle Aged , Nerve Net/physiopathology , Prospective Studies , Psychiatric Status Rating Scales , Socioeconomic Factors , Stress, Psychological/psychology
3.
Int J Obes (Lond) ; 36(5): 638-47, 2012 May.
Article in English | MEDLINE | ID: mdl-22024642

ABSTRACT

BACKGROUND: The majority of research on obesity (OB) has focused primarily on clinical features (eating behavior, adiposity measures) or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions that are associated with appetite-regulatory hormones are also involved in the development and maintenance of OB. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic OB. Simple (non-PWS) OB represents an OB-control state. OBJECTIVE: This study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (that is, hypothalamus, amygdala) and prefrontal regions associated with cognitive control (that is, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC) after eating. DESIGN AND PARTICIPANTS: A total of 14 individuals with PWS, 14 BMI- and age-matched individuals with OB, and 15 age-matched healthy-weight controls viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC and DLPFC. RESULTS: Compared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in the hypothalamus and hippocampus in response to food (vs non-food) images pre-meal. Post meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared with OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control. CONCLUSION: In PWS, compared with OB per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple OB.


Subject(s)
Functional Neuroimaging/methods , Hunger , Obesity/physiopathology , Prader-Willi Syndrome/physiopathology , Prefrontal Cortex/physiopathology , Satiation , Adult , Brain Mapping , Feeding Behavior/psychology , Female , Humans , Magnetic Resonance Imaging/methods , Male , Obesity/psychology , Photic Stimulation , Postprandial Period , Prader-Willi Syndrome/psychology , Reward , Surveys and Questionnaires
4.
Int J Obes (Lond) ; 34(10): 1494-500, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20440296

ABSTRACT

OBJECTIVE: To investigate the neural mechanisms of food motivation in children and adolescents, and examine brain activation differences between healthy weight (HW) and obese participants. SUBJECTS: Ten HW children (ages 11-16; BMI < 85%ile) and 10 obese children (ages 10-17; BMI >95%ile) matched for age, gender and years of education. MEASUREMENTS: Functional magnetic resonance imaging (fMRI) scans were conducted twice: when participants were hungry (pre-meal) and immediately after a standardized meal (post-meal). During the fMRI scans, the participants passively viewed blocked images of food, non-food (animals) and blurred baseline control. RESULTS: Both groups of children showed brain activation to food images in the limbic and paralimbic regions (PFC/OFC). The obese group showed significantly greater activation to food pictures in the PFC (pre-meal) and OFC (post-meal) than the HW group. In addition, the obese group showed less post-meal reduction of activation (vs pre-meal) in the PFC, limbic and the reward-processing regions, including the nucleus accumbens. CONCLUSION: Limbic and paralimbic activation in high food motivation states was noted in both groups of participants. However, obese children were hyper-responsive to food stimuli as compared with HW children. In addition, unlike HW children, brain activations in response to food stimuli in obese children failed to diminish significantly after eating. This study provides initial evidence that obesity, even among children, is associated with abnormalities in neural networks involved in food motivation, and that the origins of neural circuitry dysfunction associated with obesity may begin early in life.


Subject(s)
Hunger/physiology , Limbic System/physiopathology , Motivation/physiology , Obesity/physiopathology , Adolescent , Child , Feeding Behavior/physiology , Feeding Behavior/psychology , Female , Food , Humans , Magnetic Resonance Imaging , Male , Obesity/psychology , Photic Stimulation/methods , Postprandial Period
5.
Int J Obes (Lond) ; 33(2): 273-83, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19048015

ABSTRACT

BACKGROUND: Differences in behavioral phenotypes between the two most common subtypes of Prader-Willi syndrome (PWS) (chromosome 15q deletions and maternal uniparental disomy 15 (UPD) indicate that distinct neural networks may be affected. Though both subtypes display hyperphagia, the deletion subgroup shows reduced behavioral inhibition around food, whereas those with UPD are generally more able to maintain cognitive control over food intake impulses. OBJECTIVE: To examine the neural basis of phenotypic differences to better understand relationships between genetic subtypes and behavioral outcomes. We predicted greater food motivation circuitry activity in the deletion subtype and greater activity in higher order cognitive regions in the UPD group, especially after eating. DESIGN AND PARTICIPANTS: Nine individuals with PWS due to UPD and nine individuals with PWS due to (type 2) deletion, matched for age, gender and body mass index, underwent functional magnetic resonance imaging (fMRI) while viewing food images during two food motivation states: one before (pre-meal) and one after (post-meal) eating a standardized 500 kcal meal. RESULTS: Both PWS subgroups showed greater activity in response to food pre- and post-meal compared with the healthy-weight group. Compared with UPD, the deletion subtype showed increased food motivation network activation both pre- and post-meal, especially in the medial prefrontal cortex (mPFC) and amygdala. In contrast, the UPD group showed greater activation than the deletion subtype post-meal in the dorsolateral prefrontal cortex (DLPFC) and parahippocampal gyrus (PHG). CONCLUSION: These preliminary findings are the first functional neuroimaging findings to support divergent neural mechanisms associated with behavioral phenotypes in genetic subtypes of PWS. Results are discussed within the framework of genetic mechanisms such as haploinsufficiency and gene dosage effects and their differential influence on deletion and UPD subtypes, respectively.


Subject(s)
Appetite/physiology , Brain/physiopathology , Hyperphagia/physiopathology , Prader-Willi Syndrome/physiopathology , Appetite/genetics , Chromosome Deletion , Chromosomes, Human, Pair 15/genetics , Female , Humans , Hyperphagia/genetics , Hyperphagia/psychology , Magnetic Resonance Imaging , Male , Nerve Net , Phenotype , Photic Stimulation , Prader-Willi Syndrome/genetics , Prader-Willi Syndrome/psychology , Surveys and Questionnaires , Uniparental Disomy/genetics , Young Adult
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