Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography

Abstract

The central role of the hypothalamus in the origination and/or processing of feeding-related stimuli may be modulated by the activity of other functional areas of the brain including the insular cortex (involved in enteroceptive monitoring) and the prefrontal cortex (involved in the inhibition of inappropriate response tendencies). Regional cerebral blood flow (rCBF), a marker of neuronal activity, was measured in 11 healthy, normal-weight men by using positron emission tomography in a state of hunger (after 36-h fast) and a state of satiation (after a liquid meal). Hunger was associated with significantly increased rCBF in the vicinity of the hypothalamus and insular cortex and in additional paralimbic and limbic areas (orbitofrontal cortex, anterior cingulate cortex, and parahippocampal and hippocampal formation), thalamus, caudate, precuneus, putamen, and cerebellum. Satiation was associated with increased rCBF in the vicinity of the ventromedial prefrontal cortex, dorsolateral prefrontal cortex, and inferior parietal lobule. Changes in plasma insulin concentrations in response to the meal were negatively correlated with changes in rCBF in the insular and orbitofrontal cortex. Changes in plasma free fatty acid concentrations in response to the meal were negatively correlated with changes in rCBF in the anterior cingulate and positively correlated with changes in rCBF in the dorsolateral prefrontal cortex. In conclusion, these findings raise the possibility that several regions of the brain participate in the regulation of hunger and satiation and that insulin and free fatty acids may be metabolic modulators of postprandial brain neuronal events. Although exploratory, the present study provides a foundation for investigating the human brain regions and cognitive operations that respond to nutritional stimuli.

Figure 1

Images of brain activation in response to hunger and satiation. Brain regions with significant increase in rCBF in response to hunger are shown in blue; brain regions with significant increase in rCBF in response to satiation are shown in yellow. Images were generated by using PET and MRI data from 11 healthy, lean individuals. Color-coded images are superimposed onto an average of the subjects’ brain MRIs (grayscale image). Horizontal brain sections correspond to the coordinates of the Talairach and Tournoux brain atlas (27). The number under each section reflects the distance in mm superior (+) or inferior (−) to a horizontal plane between the anterior and posterior commissures. The right hemisphere in each section is on the reader’s right. Compared with satiation, hunger was associated with significantly increased rCBF (P < 0.005 uncorrected for multiple comparisons) in the hypothalamus (hy), thalamus (th), anterior cingulate (ac), insula/claustrum (in), orbitofrontal and temporal cortex (of/at), hippocampus/parahippocampul gyrus (hi/pa), precuneus (pcu), caudate/ventricle (ca/v), putamen (pu), and cerebellum (ce). Compared with hunger, satiation was associated with increased rCBF (P < 0.005 uncorrected for multiple comparisons) in the ventromedial prefrontal cortex (vmpf), dorsolateral prefrontal cortex (dlpf), ventrolateral prefrontal cortex (alpf), and inferior parietal lobule (ipa). The location and magnitude of maximal difference are shown in Tables 2 and 3.

Figure 2

Correlations between changes in plasma insulin concentrations elicited by satiation and changes in normalized PET counts in the left insular cortex centered around Talairach atlas coordinates (x = −40, y = 12, z = 5; Upper) and left orbitofrontal cortex centered around Talairach atlas coordinates (x = −28, y = 16, z = −12; Lower).

Figure 3

Correlations between changes in plasma free fatty acids concentrations elicited by satiation and changes in normalized PET counts in the anterior cingulate centered around Talairach atlas coordinates (x = 0, y = 25, z = 18; Upper) and left dorsolateral prefrontal cortex centered around Talairach atlas coordinates (x = −52, y = 32, z = 22; Lower).