Using positron emission scanning and brain MRI, neuroanatomical correlates of hunger and satiety have been investigated. Importantly, recent analyses of this collected data has indicated that the left dorsolateral prefrontal cortex, an area of the brain important in reward processing, may be a satiety center. Neuronal activation in the left dorsolateral prefrontal cortex following a meal is consistently lower in this area in obese versus lean individuals, in both men and women. To investigate the effect of stimulation of the left dorsolateral prefrontal cortex on food intake, a randomized study using trans-cranial direct current stimulation (TDCS) was designed. Obese volunteers are randomized to TDCS versus sham therapy. Volunteers will receive treatment 3 days in a row as inpatients on the clinical research unit, while eating ad-libitum from computerized vending machines. Volunteers will then be additionally randomized to behavioral weight loss intervention versus standard dietary instruction. Volunteers will continue to receive TDCS for an additional 4 weeks to investigate the effects of this treatment on weight loss. Whether behavioral therapy has an additive effect on top of TDCS will also be investigated. Recruitment is currently ongoing for this protocol. In addition we have found from previous neuroimaging data an association between the satiety hormone PYY and activity in gray matter volume and cerebral blood flow in the caudate nuclei. As the caudate is involved in reward related behavior via its effect on striatal, thalamic and cortical pathways. In our analysis caudate activity was associated with acitivity in these regions. Thus, peripheral PYY may modulate food intake by modulating caudate activity which in turn modulates higher level brain regions.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Weise, Christopher M; Mouton, Peter R; Eschbacher, Jennifer et al. (2015) A post-mortem stereological study of striatal cell number in human obesity. Obesity (Silver Spring) 23:100-4
Weise, Christopher M; Thiyyagura, Pradeep; Reiman, Eric M et al. (2015) A potential role for the midbrain in integrating fat-free mass determined energy needs: An H2 (15) O PET study. Hum Brain Mapp 36:2406-15
Gluck, Marci E; Alonso-Alonso, Miguel; Piaggi, Paolo et al. (2015) Neuromodulation targeted to the prefrontal cortex induces changes in energy intake and weight loss in obesity. Obesity (Silver Spring) 23:2149-56
Weise, Christopher M; Thiyyagura, Pradeep; Reiman, Eric M et al. (2013) Fat-free body mass but not fat mass is associated with reduced gray matter volume of cortical brain regions implicated in autonomic and homeostatic regulation. Neuroimage 64:712-21
Weise, Christopher M; Thiyyagura, Pradeep; Reiman, Eric M et al. (2012) Postprandial plasma PYY concentrations are associated with increased regional gray matter volume and rCBF declines in caudate nuclei--a combined MRI and H2(15)O PET study. Neuroimage 60:592-600