Stefan Kabisch

Obesity-Related Differences between Women and Men in Brain Structure and Goal-Directed Behavior

Gender differences in the regulation of body-weight are well documented. Here, we assessed obesity-related influences of gender on brain structure as well as performance in the Iowa Gambling Task. This task requires evaluation of both immediate rewards and long-term outcomes and thus mirrors the trade-off between immediate reward from eating and the long-term effect of overeating on body-weight. In women, but not in men, we show that the preference for salient immediate rewards in the face of negative long-term consequences is higher in obese than in lean subjects. In addition, we report structural differences in the left dorsal striatum (i.e., putamen) and right dorsolateral prefrontal cortex for women only. Functionally, both regions are known to play complimentary roles in habitual and goal-directed control of behavior in motivational contexts. For women as well as men, gray matter volume correlates positively with measures of obesity in regions coding the value and saliency of food (i.e., nucleus accumbens, orbitofrontal cortex) as well as in the hypothalamus (i.e., the brains central homeostatic center). These differences between lean and obese subjects in hedonic and homeostatic control systems may reflect a bias in eating behavior toward energy-intake exceeding the actual homeostatic demand. Although we cannot infer from our results the etiology of the observed structural differences, our results resemble neural and behavioral differences well known from other forms of addiction, however, with marked differences between women and men. These findings are important for designing gender-appropriate treatments of obesity and possibly its recognition as a form of addiction.

Exenatide-Induced Reduction in Energy Intake Is Associated With Increase in Hypothalamic Connectivity

OBJECTIVE Glucagon-like peptide-1 receptor agonists such as exenatide are known to influence neural activity in the hypothalamus of animals and to reduce energy intake. In humans, however, significant weight loss has been observed in only a subgroup of patients. Why only some individuals respond with weight loss and others do not remains unclear. In this functional magnetic resonance imaging (fMRI) study, we investigated differences in hypothalamic connectivity between “responders” (reduction in energy intake after exenatide infusion) and “nonresponders.” RESEARCH DESIGN AND METHODS We performed a randomized, double-blinded, placebo-controlled, cross-over fMRI study with intravenous administration of exenatide in obese male volunteers. During brain scanning with continuous exenatide or placebo administration, participants rated food and nonfood images. After each scanning session, energy intake was measured using an ad libitum buffet. Functional hypothalamic connectivity was assessed by eigenvector centrality mapping, a measure of connectedness throughout the brain. RESULTS Responders showed significantly higher connectedness of the hypothalamus, which was specific for the food pictures condition, in the exenatide condition compared with placebo. Nonresponders did not show any significant exenatide-induced changes in hypothalamic connectedness. CONCLUSIONS Our results demonstrate a central hypothalamic effect of peripherally administered exenatide that occurred only in the group that showed an exenatide-dependent anorexigenic effect. These findings indicate that the hypothalamic response seems to be the crucial factor for the effect of exenatide on energy intake.

Contact dermatitis after transcranial direct current stimulation

could improve refractory negative symptoms; (2) ‘‘inhibitory’’ rTMS to the left temporoparietal cortex (l-TPC) could produces sustained reductions in resistant AH. However, these effects were transitory and nonspecific. Transcranial direct current stimulation (tDCS) is a noninvasive technique for brain stimulation increasingly used in the treatment of some neurologic/psychiatric diseases. Using tDCS, cortical neuronal excitability increases in the vicinity of the anodal electrode and is reduced near the cathodal electrode. By acting antagonistically on two brain areas and more precisely by decreasing the l-TPC activity and increasing the l-DLPFC activity, tDCS could constitute a new tool in the treatment of refractory symptoms in schizophrenia. We aimed to treat refractory symptoms in patients with DSM IV schizophrenia. Before starting a large randomized controlled study versus placebo (ClinicalTrials.gov; NCT00870909), we undertook an open pilot study of bifocal tDCS in these indications (l-DLPFC anodal tDCS and l-TPC cathodal tDCS). tDCS was delivered using an Eldith DC stimulator plus (The Magstim Company, Whiteland, Wales, UK) at an intensity of 2 mA for 20 minutes twice a day with a 3-hour interval, for 5 consecutive working days. Clinical assessments were performed before and immediately after treatment as well as 1 and 3 months after tDCS sessions using the Positive And Negative Syndrome Scale (PANSS) and the Auditory Hallucination Rating Scale (AHRS). Two righthanded patients with DSM IV schizophrenia and refractory AH were enrolled. The first patient was 46 years old (baseline: PANSS5 77; AHRS 5 30, medication 5 1245 mg equivalent chlorpromazine/day). tDCS permitted a drastic reduction in AHRS scores (277%; from30 to 7) and a slight improvement in other schizophrenic symptoms (PANSS 220%; positive subscale scores from 28 to 21; negative subscale scores from 17 to 16 and general psychopathology scores from 32 to 25) 3 months after stimulation sessions. The second patient was 29 years old (baseline: PANSS5 88; AHRS 5 28, medication 5 900 mg equivalent chlorpromazine/day). tDCS also permitted a drastic reduction in AHRS score (248%; from 28 to 14) and an improvement of other symptoms (PANSS 249%; positive: from 22 to 12; negative: from 22 to 9; general psychopathology: from 44 to 21) at the end of follow-up (13months). The clinical efficacy appeared immediately after stimulation sessions and was maintained or continued to improve during at least 3 months. We reported no adverse events and the two patients only described a transient mild tingling or a slight itching sensation associated with the onset of stimulation, confirming the safety of this technique. Although limited by small sample size and open labelled design, these results show promising effects for both auditory hallucination and overall symptoms in patients with refractory symptoms. Larger-scale randomized trials comparing tDCS and sham stimulation are indicated. Jerome Brunelin EA 4166, Service du Pr d’Amato CH le vinatier 95 bd Pinel 69677 Bron cedex France E-mail address: jerome.brunelin@ch-le-vinatier.fr