Publications (19) View all
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Article: The neuroanatomy of genetic subtype differences in Prader-Willi syndrome.
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ABSTRACT: Despite behavioral differences between genetic subtypes of Prader-Willi syndrome (PWS), no studies have been published characterizing brain structure in these subgroups. Our goal was to examine differences in the brain structure phenotype of common subtypes of PWS [chromosome 15q deletions and maternal uniparental disomy 15 (UPD)]. Fifteen individuals with PWS due to a typical deletion [(DEL) type I; n = 5, type II; n = 10], eight with PWS due to UPD, and 25 age-matched healthy-weight individuals (HWC) participated in structural magnetic resonance imaging (MRI) scans. A custom voxel-based morphometry processing stream was used to examine regional differences in gray and white matter volume (WMV) between groups, covarying for age, sex, and body mass index (BMI). Overall, compared to HWC, PWS individuals had lower gray matter volumes (GMV) that encompassed the prefrontal, orbitofrontal and temporal cortices, hippocampus and parahippocampal gyrus, and lower WMVs in the brain stem, cerebellum, medial temporal, and frontal cortex. Compared to UPD, the DEL subtypes had lower GMV primarily in the prefrontal and temporal cortices, and lower white matter in the parietal cortex. The UPD subtype had more extensive lower gray and WMVs in the orbitofrontal and limbic cortices compared to HWC. These preliminary findings are the first structural neuroimaging findings to support potentially separate neural mechanisms mediating the behavioral differences seen in these genetic subtypes.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 03/2012; 159B(2):243-53. · 3.70 Impact Factor -
Article: Brain hypoactivation, autonomic nervous system dysregulation, and gonadal hormones in depression: a preliminary study.
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ABSTRACT: The comorbidity of major depressive disorder (MDD) and cardiovascular disease (CVD) is among the 10th leading cause of morbidity and mortality worldwide. Thus, understanding the co-occurrence of these disorders will have major public health significance. MDD is associated with an abnormal stress response, manifested in brain circuitry deficits, gonadal dysfunction, and autonomic nervous system (ANS) dysregulation. Contribution of the relationships between these systems to the pathophysiology of MDD is not well understood. The objective of this preliminary study was to investigate, in parallel, relationships between HPG-axis functioning, stress response circuitry activation, and parasympathetic reactivity in healthy controls and women with MDD. Using fMRI with pulse oximetry [from which we calculated the high frequency (HF) component of R-R interval variability (HF-RRV), a measure of parasympathetic modulation] and hormone data, we studied eight women with recurrent MDD in remission and six controls during a stress response paradigm. We demonstrated that hypoactivations of hypothalamus, amygdala, hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and subgenual ACC were associated with lower parasympathetic cardiac modulation in MDD women. Estradiol and progesterone attenuated group differences in the effect of HF-RRV on hypoactivation in the amygdala, hippocampus, ACC, and OFC in MDD women. Findings have implications for understanding the relationship between mood, arousal, heart regulation, and gonadal hormones, and may provide insights into MDD and CVD risk comorbidity.Neuroscience Letters 02/2012; 514(1):57-61. · 2.11 Impact Factor -
Article: Changes in brain activation to food pictures after adjustable gastric banding.
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ABSTRACT: Adjustable gastric banding is an effective weight-loss treatment, but little is known about the neural mechanisms underlying weight loss. The purpose of the present study was to determine whether gastric banding affects brain function in regions previously implicated in food motivation, reward, and cognitive control. The setting for the study was the University of Missouri-Kansas City, Department of Psychology; Hoglund Brain Imaging Center, University of Kansas Medical Center; and private practice in the United States. Ten obese participants were recruited before adjustable gastric banding surgery (mean body mass index before surgery 40.6 ± 1.96 kg/m(2)). Their mean body mass index at 12 weeks after surgery was 36.1 ± 2.32 kg/m(2), with a mean percentage of excess weight loss of 25.21% ± 8.41%. Functional magnetic resonance imaging scans were conducted before and 12 weeks after adjustable gastric banding surgery. At each assessment point, the participants completed questionnaires assessing food motivation and were scanned while hungry (before eating) and immediately after a standardized meal (after eating). During the functional magnetic resonance imaging scans, the participants viewed food pictures, nonfood pictures (animals), and blurred baseline control pictures. The functional magnetic resonance imaging data were analyzed using BrainVoyager QX. After surgery, the participants reported significantly less food motivation and more cognitive restraint. The participants also showed decreased brain activation to food versus nonfood pictures in regions implicated in food motivation and reward, including the parahippocampus, medial prefrontal cortex, insula, and inferior frontal gyrus. In contrast, they demonstrated increased activation to food versus nonfood pictures in anterior prefrontal cortex, a region implicated in cognitive control and inhibition. This is the first study to examine the functional brain changes after gastric banding surgery and 1 of the first studies to longitudinally examine neural changes associated with weight loss. These results have provided preliminary evidence that adjustable gastric banding alters brain function in regions known to regulate reward and cognitive control.Surgery for Obesity and Related Diseases 07/2011; 8(5):602-8. · 3.93 Impact Factor -
Article: Stress response circuitry hypoactivation related to hormonal dysfunction in women with major depression.
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ABSTRACT: Women have approximately twice the risk of major depressive disorder (MDD) than men, yet this difference remains largely unexplained. Previous MDD research suggests high rates of endocrine dysfunction, which may be related to deficits in brain activity in stress response circuitry [hypothalamus, amygdala, hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC)]. This functional magnetic resonance imaging (fMRI) study investigated the relationship between hypothalamic-pituitary-gonadal (HPG)-axis hormones and stress response circuitry dysfunction in MDD in women. During the late follicular/midcycle phase of the menstrual cycle, female participants (10 with extensive histories of MDD, in remission, 10 healthy controls) were scanned while viewing negative and neutral arousal pictures. Group differences in blood oxygen-level dependent (BOLD) signal changes were analyzed using SPM2. Baseline gonadal hormones included estradiol, progesterone, and testosterone. fMRI results showed greater BOLD signal intensity changes in controls versus MDD in hypothalamus, amygdala, hippocampus, OFC, ACC, and subgenual ACC, findings unrelated to medication status. MDD women had a lower serum estradiol and higher serum progesterone compared to controls. Hypoactivations in hypothalamus, subgenual ACC, amygdala and OFC in MDD were associated with low estradiol and high progesterone. Generalizability of our findings is limited by small sample size and restriction to females, although this did not affect the internal validity of the results. Hypoactivation of the stress response circuitry in MDD women is associated with dysregulation of the HPG-axis. Associations between brain activity deficits and hormonal disruption in MDD may ultimately contribute to understanding sex differences in MDD.Journal of affective disorders 12/2010; 131(1-3):379-87. · 3.76 Impact Factor -
Article: Importance of reward and prefrontal circuitry in hunger and satiety: Prader-Willi syndrome vs simple obesity.
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ABSTRACT: 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. 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. 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. 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. 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.International journal of obesity (2005) 10/2011; 36(5):638-47. · 4.34 Impact Factor
