Binge eating is associated with right orbitofrontal-insular-striatal atrophy in frontotemporal dementia

Memory and Aging Center, Department of Neurology, University of California San Francisco, 1779 Turk St., San Francisco, CA 94115, USA.
Neurology (Impact Factor: 8.29). 11/2007; 69(14):1424-33. DOI: 10.1212/01.wnl.0000277461.06713.23
Source: PubMed


Neurophysiologic studies on human and nonhuman primates implicate an orbitofrontal-insular-striatal circuit in high-level regulation of feeding. However, the role of these areas in determining feeding disturbances in neurologic patients remains uncertain.
To determine brain structures critical for control of eating behavior, we performed a prospective, laboratory-based, free-feeding study of 18 healthy control subjects and 32 patients with neurodegenerative disease. MR voxel-based morphometry (VBM) was used to identify regions of significant atrophy in patients who overate compared with those who did not.
Despite normal taste recognition, 6 of 32 patients compulsively binged, consuming large quantities of food after reporting appropriate satiety. All six patients who overate were clinically diagnosed with frontotemporal dementia (FTD), a disorder previously associated with disordered eating, while the nonovereaters were diagnosed with FTD, semantic dementia, progressive aphasia, progressive supranuclear palsy, and Alzheimer disease. VBM revealed that binge-eating patients had significantly greater atrophy in the right ventral insula, striatum, and orbitofrontal cortex.
Binge eating can occur despite reported satiety and is associated with damage to a right-sided orbitofrontal-insular-striatal circuit in humans. These findings support a model in which ventral insular and orbitofrontal cortices serve as higher-order gustatory regions and cooperate with the striatum to guide appropriate feeding responses.

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Available from: Joshua D Woolley, Apr 25, 2014
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    • "While no clear chemical map has so far been reported in the human gustatory cortex, future investigations on patients sustaining injury to the insular cortex might eventually reveal that this region contains specialized neuronal circuits differentially controlling chemosensory vs. homeostatic functions associated with food intake and body weight. Whereas atrophy in the anterior ventral region of the insula has been associated with compulsive binge eating in patients with fronto-temporal dementia (Fig. 4a–b; Woolley et al. 2007), a single case study investigated by Small et al. revealed a patient with a posterior insular lesion who reported losing 25 lb without actively attempting to control body weight (Fig. 4c; Mak et al. 2005). Follow-up interviews with this very patient revealed a sustained maintenance of postsurgical weight associated with little effort at controlling appetite. "
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    ABSTRACT: The gustatory aspect of the insular cortex is part of the brain circuit that controls ingestive behaviors based on chemosensory inputs. However, the sensory properties of foods are not restricted to taste and should also include salient features such as odor, texture, temperature, and appearance. Therefore, it is reasonable to hypothesize that specialized circuits within the central taste pathways must be involved in representing several other oral sensory modalities in addition to taste. In this review, we evaluate current evidence indicating that the insular gustatory cortex functions as an integrative circuit, with taste-responsive regions also showing heightened sensitivity to olfactory, somatosensory, and even visual stimulation. We also review evidence for modulation of taste-responsive insular areas by changes in physiological state, with taste-elicited neuronal responses varying according to the nutritional state of the organism. We then examine experimental support for a functional map within the insular cortex that might reflect the various sensory and homeostatic roles associated with this region. Finally, we evaluate the potential role of the taste insular cortex in weight-gain susceptibility. Taken together, the current experimental evidence favors the view that the insular gustatory cortex functions as an orosensory integrative system that not only enables the formation of complex flavor representations but also mediates their modulation by the internal state of the body, playing therefore a central role in food intake regulation.
    Chemosensory Perception 03/2012; 5(1). DOI:10.1007/s12078-012-9117-9 · 1.30 Impact Factor
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    • "Apathy has been related to orbitofrontal, frontomedian, anterior and midcingulate alterations in both FTLD (Franceschi et al., 2005; Le Ber et al., 2006; Peters et al., 2006; Zamboni et al., 2008) and AD (Migneco et al., 2001; Holthoff et al., 2005; Apostolova et al., 2007; Marshall et al., 2007). In FTLD, disinhibition was associated with orbitofrontal, anterior cingulate, and anterior temporal impairments (Franceschi et al., 2005; Le Ber et al., 2006; Peters et al., 2006; Zamboni et al., 2008), whereas abnormal eating behaviors were related to orbitofrontal and right insular atrophy (Whitwell et al., 2007; Woolley et al., 2007). Although these studies revealed interesting results, they have limitations. "
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    ABSTRACT: Behavioral impairments occur frequently in dementia. Studies with magnetic resonance imaging, measuring atrophy, have systematically investigated their neural correlates. Such a systematic approach has not yet been applied to imaging with [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET), although regional hypometabolism may precede and exceed atrophy in dementia. The present study related all behavioral disorders as assessed with the Neuropsychiatric Inventory to reductions in brain glucose utilization as measured by FDG-PET with Statistical Parametric Mapping (SPM5). It included 54 subjects mainly with early Alzheimer's disease, frontotemporal lobar degeneration, and subjective cognitive impairment. Apathy, disinhibition and eating disorders - most frequent in frontotemporal lobar degeneration - correlated significantly with regional brain hypometabolism. Whereas a single regressor analysis and conjunction analysis revealed largely overlapping frontomedian regions that were associated with all three behavioral domains, a disjunction analysis identified three specific neural networks for each behavioral disorder, independent of dementia severity. Apathy was related to the ventral tegmental area, a component of the motivational dopaminergic network; disinhibition to both anterior temporal lobes including the anterior hippocampi and left amygdala, caudate head, orbitofrontal cortex and insulae; and eating disorders to the right lateral (orbito) frontal cortex/insula. Our study contributes to the understanding of behavioral deficits in early dementia and suggests specific diagnostic and therapeutic approaches.
    Psychiatry Research 10/2011; 194(3):235-44. DOI:10.1016/j.pscychresns.2011.06.009 · 2.47 Impact Factor
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    • "The VENs are prime targets of the pathological processes in FTD during the early stage of the illness, which is characterized by the loss of social awareness and empathy (Seeley et al., 2006, 2007, 2008). However, FTD is also frequently associated with compulsive eating (Woolley et al., 2007), and FI is significantly reduced on the right side in the FTD patients who are compulsive overeater (Seeley, 2008). The FTD findings may reflect a basic role for the VENs, fork cells, and related circuitry in the control of appetite. "
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    ABSTRACT: The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex (ACC) in great apes and humans but not other primates. We stereologically counted the VENs in FI and the limbic anterior (LA) area of ACC and found them to be more numerous in humans than in apes. In humans, VENs first appear in small numbers in the 36th week postconception are rare at birth and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than the left in FI and LA in postnatal brains; this may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, containing FI, is related to physiological changes in the body, decision-making, error recognition, and awareness. In a preliminary diffusion tensor imaging study of the connections of FI, we found that the VEN-containing regions connect with the frontal pole as well as with other parts of frontal and insular cortex, the septum, and the amygdala. The VENs and a related cell population, the fork cells, selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing pepide, which signal satiety. The loss of VENs and fork cells may be related to the loss of satiety signaling in patients with frontotemporal dementia who have damage to FI. These cells may be morphological specializations of an ancient population of neurons involved in the control of appetite present in the insular cortex in all mammals.
    American Journal of Human Biology 01/2011; 23(1):5-21. DOI:10.1002/ajhb.21136 · 1.70 Impact Factor
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