Obesity and addiction: neurobiological overlaps

In the paper

“a recent study of siblings discordant for their addiction to stimulant drugs (78) showed brain differences in the morphology of the OFC, which were significantly smaller in the addicted sibling than in controls, whereas in the non-addicted siblings, the OFC did not differ from that of controls (79).”

What the sources say

• Not checked yetcites [78] Ersche KD Jones PS Williams GB Turton AJ Robbins TW Bullmore ET Abnormal brain structure implicated in stimulant drug addiction Science 2012 335 601 604 22301321 source
• ?Could not verify

  The Methods (section 2.1; page unavailable) describe participants with cocaine use disorders and healthy controls, not siblings discordant for addiction. The Results report ERP responses, and searches for OFC morphology and non-addicted siblings found no passage addressing the claimed anatomical comparison. (LLM, conf=0.78)

  cites [79] Parvaz MA Maloney T Moeller SJ Sensitivity to monetary reward is most severely compromised in recently abstaining cocaine addicted individuals: a cross-sectional ERP study Psychiatry Res 2012 203 75 82 22841343 PMC3444645 sourceExperimental — accuracy not yet measured

In the paper

“stress is not only associated with increased consumption of palatable foods and weight gain, but acute stress also uncovers a strong correlation between BMI and a potentiated activation in response to milkshake consumption in the OFC (59)”

What the sources say

• Partly supported

  The Introduction reports an association of stress with palatable-food intake and weight gain. The Results (Neuroimaging) find a positive BMI–OFC relationship during stress-related milkshake consumption, but call the correlation “small but significant,” not strong. The study also tested overweight women, a qualification absent from the claim. (LLM, conf=0.88)

  cites [59] Rudenga KJ Sinha R Small DM Acute stress potentiates brain response to milkshake as a function of body weight and chronic stress Int J Obes (Lond) 2012 [Epub ahead of print] PMC3381866 22430303 sourceExperimental — accuracy not yet measured

In the paper

“in non-obese individuals with BED, we documented higher than normal release of DA in dorsal striatum (caudate) when exposed to food cues and this increase predicted the severity of the binge eating behaviours (95).”

What the sources say

• Not checked yetcites [95] Wang GJ Geliebter A Volkow ND Enhanced striatal dopamine release during food stimulation in binge eating disorder Obesity 2011 19 1601 1608 21350434 PMC3144277 source

In the paper

“this property of palatable foods used to be advantageous in environments where food sources were scarce and/or unreliable because it ensured that food was eaten when available, enabling energy to be stored in the body (as fat) for future use. However, in societies like ours, where food is plentiful and ubiquitous, this adaptation has become a dangerous liability.”

In the paper

“the debate over whether obesity reflects ‘food addiction’ fails to consider the dimensional nature of these two disorders.”

In the paper

“Disruption of the DA reward circuit has been implicated in the loss of control seen in both addiction and obesity (2), although the physiological mechanisms that disrupt the function of the DA striatal circuits, including those implicated in reward (ventral striatum) and in habit formation (dorsal striatum), present clear divergences (3).”

What the sources say

• Not checked yetcites [2] Volkow ND Wang GJ Fowler JS Tomasi D Baler R Food and drug reward: overlapping circuits in human obesity and addiction Curr Top Behav Neurosci 2011 11 1 24 22016109 source
• Not checked yetcites [3] Ziauddeen H Fletcher P Is food addiction a valid and useful concept? Obes Rev 2012 in press PMC3561707 23057499

In the paper

“just as most individuals that consume drugs are not addicted, most individuals that eat excessively retain control over their food intake in some instances but not in others.”

In the paper

“neurotransmitters implicated in drug-seeking behaviours are also implicated in food intake and, conversely, that peptides that regulate food intake also influence the reinforcing effects of drugs”

What the sources say

• Not checked yetcites Tables 1 and 2

In the paper

“the regulation of eating behaviours and hence the responses to food, are modulated by multiple peripheral and central mechanisms that directly or indirectly convey information to the brain’s DA reward pathway with a particular prominent role of the hypothalamus”

What the sources say

• Not checked yetcites Fig. 1

In the paper

“Eating behaviours present a great example of this architecture where the hypothalamus subserves the ‘knot’ of the metabolic bowtie (Fig. 3a) and the DA pathways subserve the ‘knot’ for reactivity to salient external stimuli (including drugs and food) and internal signals”

What the sources say

• Not checked yetcites Fig. 3a

In the paper

“studies are also delineating differences between them that centre on the key role that peripheral signals involved with homeostatic control exert on food intake.”

In the paper

“certain foods, particularly those rich in sugars and fat, are potently rewarding (13) and can trigger addictive-like behaviours in laboratory animals (14,15).”

What the sources say

• Not checked yetcites [13] Lenoir M Serre F Cantin L Ahmed SH Intense sweetness surpasses cocaine reward Plos ONE 2007 2 e698 17668074 PMC1931610 source
• Not checked yetcites [14] Avena NM Rada P Hoebel BG Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake Neurosci Biobehav Rev 2008 32 20 39 17617461 PMC2235907 source
• Not checked yetcites [15] Avena NM Rada P Hoebel BG Sugar and fat bingeing have notable differences in addictive-like behavior J Nutr 2009 139 623 628 19176748 PMC2714381 source

In the paper

“It is when these patterns (loss of control and compulsive intake) become rigid and dictate the behaviour and choices of the individual, despite their adverse consequences, that a pathological state akin to the concept of addiction can be invoked.”

In the paper

“High-calorie foods can promote over-eating (i.e. eating that is uncoupled from energetic needs) and trigger learned associations between the stimulus and the reward (conditioning).”

In the paper

“The overwhelming urge to seek and consume a drug is one of the hallmarks of addiction.”

In the paper

“there are impairments in circuits involved with self-control and decision-making, interoception and mood and stress regulation (8).”

What the sources say

• Not checked yetcites [8] Volkow ND Wang GJ Fowler JS Tomasi D Telang F Baler R Addiction: decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain’s control circuit BioEssay 2010 32 748 755 PMC2948245 20730946 source

In the paper

“brain imaging studies are beginning to uncover common features between these two conditions and delineate some of the overlapping brain circuits whose dysfunctions may underlie the observed deficits.”

In the paper

“these two diseases share neurobiological processes that, when disrupted, can result in compulsive consumption and loss of control in a dimensional continuum, while also involving unique neurobiological processes”

In the paper

“the response to foods in humans, is far more complex, and is influenced not just by its palatability but also by its availability (the patterns of restriction plus overeating, referred to as the eating topography (16)), its visual appeal, economics and incentives (i.e., ‘super sizing’ offers, soda combos), social routines for eating, alternative reinforcement and advertisements (17).”

What the sources say

• Not checked yetcites [16] Corsica JA Pelchat ML Food addiction: true or false? Curr Opin Gastroenterol 2010 26 165 169 20042860 source
• Not checked yetcites [17] Garber AK Lustig RH Is fast food addictive? Curr Drug Abuse Rev 2011 4 146 162 21999689 source

In the paper

“evidence has been accumulating that comparable dopaminergic responses are linked with food reward and that these mechanisms are likely to play a role in excessive food consumption and obesity.”

In the paper

“Drugs of abuse act on the reward and ancillary circuits through different mechanisms; however, they all lead to sharp DA increases in the NAc.”

In the paper

“healthy human volunteers show robust striatal activation upon receipt of a milkshake, and that frequent ice cream consumption blunts the striatal responses (46).”

What the sources say

• Not checked yetcites [46] Burger KS Stice E Frequent ice cream consumption is associated with reduced striatal response to receipt of an ice cream-based milkshake Am J Clin Nutr 2012 95 810 817 22338036 PMC3302359 source

In the paper

“whereas inherently rewarding novel stimuli engage ventral regions of the striatum (NAc), with repeated exposure, the cues associated with the reward then trigger DA increases in dorsal regions of the striatum (50).”

What the sources say

• Not checked yetcites [50] Robbins TW Cador M Taylor JR Everitt BJ Limbic-striatal interactions in reward-related processes Neurosci Biobehav Rev 1989 13 155 162 2682402 source

In the paper

“peripheral signals that modulate food intake exert their actions in part by hypothalamic signalling to VTA but also by their direct effects on the VTA DA meso-accumbens and meso-limbic pathways.”

In the paper

“In humans, there have been reports of an inverse relationship between body mass index (BMI) and recent illicit drug use (35) and of an association between obesity and a lower risk for substance use disorders (36).”

What the sources say

• Not checked yetcites [35] Bluml V Kapusta N Vyssoki B Kogoj D Walter H Lesch OM Relationship between substance use and body mass index in young males Am J Addict 2012 21 72 77 22211349 source
• Not checked yetcites [36] Simon G Von Korff M Saunders K Association between obesity and psychiatric disorders in the US adult population Arch Gen Psychiatry 2006 63 824 830 16818872 PMC1913935 source

In the paper

“once conditioning has occurred, DA signals act as a predictor of reward (49), incentivizing the animal to perform the behaviour that will result in consuming the expected reward (drug or food).”

What the sources say

• Not checked yetcites [49] Schultz W Dopamine signals for reward value and risk: basic and recent data Behav Brain Funct 2010 6 24 20416052 PMC2876988 source

In the paper

“stimuli that cause fast and large increases in DA induce conditioned responses and elicit incentive motivation to procure them (48).”

What the sources say

• Not checked yetcites [48] Owesson-White CA Ariansen J Stuber GD Neural encoding of cocaine-seeking behavior is coincident with phasic dopamine release in the accumbens core and shell Eur J Neurosci 2009 30 1117 1127 19735286 PMC3107700 source

In the paper

“This is consistent with preclinical (40) and clinical (41) studies showing dynamic associations between the changes in neuroendocrine hormones (e.g. insulin, leptin, ghrelin) triggered by food restriction and brain DA signalling and those of recent reports of a relationship between addictive personality and maladaptive eating behaviours following bariatric surgery (42,43).”

What the sources say

• Not checked yetcites [40] Thanos PK Michaelides M Piyis YK Wang GJ Volkow ND Food restriction markedly increases dopamine D2 receptor (D2R) in a rat model of obesity as assessed with in-vivo muPET imaging ([11C] raclopride) and in-vitro ([3H] spiperone) autoradiography Synapse 2008 62 50 61 17960763 source
• Not checked yetcites [41] Dunn JP Kessler RM Feurer ID Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity Diabetes Care 2012 35 1105 1111 22432117 PMC3329842 source
• Not checked yetcites [42] Lent MR Swencionis C Addictive personality and maladaptive eating behaviors in adults seeking bariatric surgery Eat Behav 2012 13 67 70 22177401 source
• Not checked yetcites [43] King WC Chen JY Mitchell JE Prevalence of alcohol use disorders before and after bariatric surgery JAMA 2012 307 2516 2525 22710289 PMC3682834 source

In the paper

“downstream adaptations are likely to be involved in the loss of control over food intake just as is the case for drug intake.”

In the paper

“anorexigenic peptides (e.g. insulin, leptin, PYY) decrease the sensitivity of the brain reward system to food reward, whereas orexigenic ones (e.g. ghrelin) increase it (see review (47)).”

What the sources say

• Not checked yetcites [47] Volkow ND Wang GJ Baler RD Reward, dopamine and the control of food intake: implications for obesity Trends Cogn Sci 2011 15 37 46 21109477 PMC3124340 source

In the paper

“Orexigenic peptides/hormones increase the activity of VTA DA cells and increase DA release in NAc (main target of VTA DA neurons) when exposed to food stimuli, whereas anorexigenic ones inhibit DA firing and decrease DA release (23).”

What the sources say

• Not checked yetcites [23] Opland DM Leinninger GM Myers MG Jr Modulation of the mesolimbic dopamine system by leptin Brain Res 2011 1350 65 70 20417193 PMC2921997 source

In the paper

“obese individuals show lower rates of nicotine (37) and marijuana abuse (38) than non-obese individuals.”

What the sources say

• Not checked yetcites [37] Blendy JA Strasser A Walters CL Reduced nicotine reward in obesity: cross-comparison in human and mouse Psychopharmacology (Berl) 2005 180 306 315 15719224 source
• Not checked yetcites [38] Warren M Frost-Pineda K Gold M Body mass index and marijuana use J Addict Dis 2005 24 95 100 16186086 source

In the paper

“inhibition of striatal D2R or activation of D1R-expressing striatal neurons (which mediate signalling in the striatal direct pathway) enhance the sensitivity to the rewarding effects of drugs (71–73).”

What the sources say

• Not checked yetcites [71] Ferguson SM Eskenazi D Ishikawa M Transient neuronal inhibition reveals opposing roles of indirect and direct pathways in sensitization Nat Neurosci 2010 14 22 24 21131952 PMC3058296 source
• Not checked yetcites [72] Hikida T Kimura K Wada N Funabiki K Nakanishi S Distinct roles of synaptic transmission in direct and indirect striatal pathways to reward and aversive behavior Neuron 2010 66 896 907 20620875 source
• Not checked yetcites [73] Lobo MK Covington HE3rd Chaudhury D Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward Science 2010 330 385 390 20947769 PMC3011229 source

In the paper

“when non-obese male subjects were asked to inhibit their craving for food while being exposed to food cues, they exhibited decreased metabolic activity in amygdala and OFC (as well as in hippocampus), insula and striatum, and that the decreases in OFC were associated with reductions in food craving (56).”

What the sources say

• Not checked yetcites [56] Wang GJ Volkow ND Telang F Evidence of gender differences in the ability to inhibit brain activation elicited by food stimulation Proc Natl Acad Sci U S A 2009 106 1249 1254 19164587 PMC2633545 source

In the paper

“The dependence of the responses to food cues on the nutrition status (60,61) highlights the role of the homeostatic network in the control of the reward network, which in turn is also influenced by neuronal pathways that process stress.”

What the sources say

• Not checked yetcites [60] Bragulat V Dzemidzic M Bruno C Food-related odor probes of brain reward circuits during hunger: a pilot FMRI study Obesity (Silver Spring) 2012 18 1566 1571 20339365 source
• Not checked yetcites [61] Stockburger J Schmalzle R Flaisch T Bublatzky F Schupp HT The impact of hunger on food cue processing: an event-related brain potential study Neuroimage 2009 47 1819 1829 19409497 source

In the paper

“Both preclinical and clinical studies have provided evidence of decreases in striatal D2R, which, through the NAc, are linked with reward and through the dorsal striatum with the establishment of habits and routines in obesity (80–82).”

What the sources say

• Not checked yetcites [80] Geiger BM Haburcak M Avena NM Moyer MC Hoebel BG Pothos EN Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity Neuroscience 2009 159 1193 1199 19409204 PMC2677693 source
• Not checked yetcites [81] Wang GJ Volkow ND Logan J Brain dopamine and obesity Lancet 2001 357 354 357 11210998 source
• Not checked yetcites [82] de Weijer BA van de Giessen E van Amelsvoort TA Lower striatal dopamine D2/3 receptor availability in obese compared with non-obese subjects EJNMMI Res 2012 1 37 22214469 PMC3265412 source

In the paper

“because impairments in OFC and ACC are associated with compulsive behaviours and impulsivity, DA’s impaired modulation of these regions is likely to contribute to the compulsive and impulsive drug intake seen in addiction (76).”

What the sources say

• Not checked yetcites [76] Goldstein RZ Volkow ND Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex Am J Psychiatry 2002 159 1642 1652 12359667 PMC1201373 source

In the paper

“In the striatum, D2Rs mediate signalling in the striatal indirect pathway that modulates frontal cortical regions; and their down-regulation enhances sensitization to the effects of drugs in animal models (68), whereas their up-regulation interferes with drug consumption (69,70).”

What the sources say

• Not checked yetcites [68] Ferguson SM Eskenazi D Ishikawa M Transient neuronal inhibition reveals opposing roles of indirect and direct pathways in sensitization Nat Neurosci 2011 14 22 24 21131952 PMC3058296 source
• Not checked yetcites [69] Thanos PK Michaelides M Umegaki H Volkow ND D2R DNA transfer into the nucleus accumbens attenuates cocaine self-administration in rats Synapse 2008 62 481 486 18418874 PMC2659016 source
• Not checked yetcites [70] Thanos PK Volkow ND Freimuth P Overexpression of dopamine D2 receptors reduces alcohol self-administration J Neurochem 2001 78 1094 1103 11553683 source

In the paper

“A reverse scenario would depend on a pre-existing vulnerability for drug use in prefrontal regions, possibly exacerbated by further decreases in striatal D2R triggered by repeated drug use.”

In the paper

“This suggests that, in these subjects at risk for alcoholism, the normal prefrontal function was linked to enhanced striatal D2R signalling, which in turn may have protected them from alcohol abuse.”

In the paper

“Given that dysfunction in OFC and ACC results in compulsivity (see review (85)), this might be part of the mechanism by which low-striatal D2R signalling facilitates hyperphagia (86,87).”

What the sources say

• Not checked yetcites [85] Fineberg NA Potenza MN Chamberlain SR Probing compulsive and impulsive behaviors, from animal models to endophenotypes: a narrative review Neuropsychopharmacology 2009 35 591 604 19940844 PMC3055606 source
• Not checked yetcites [86] Davis LM Michaelides M Cheskin LJ Bromocriptine administration reduces hyperphagia and adiposity and differentially affects dopamine D2 receptor and transporter binding in leptin-receptor-deficient Zucker rats and rats with diet-induced obesity Neuroendocrinology 2009 89 152 162 18984941 PMC2681080 source
• Not checked yetcites [87] Holsen LM Savage CR Martin LE Importance of reward and prefrontal circuitry in hunger and satiety: Prader-Willi syndrome vs. simple obesity Int J Obes (Lond) 2012 36 638 647 22024642 PMC3270121 source

In the paper

“the negative correlation between BMI and striatal D2R reported in obese (81) and in overweight (96) individuals, as well as the correlation between BMI and decreased blood flow in prefrontal regions in healthy individuals (97,98) and decreased prefrontal metabolism in obese subjects (63) support this.”

What the sources say

• Not checked yetcites [81] Wang GJ Volkow ND Logan J Brain dopamine and obesity Lancet 2001 357 354 357 11210998 source
• Not checked yetcites [96] Haltia LT Rinne JO Merisaari H Effects of intravenous glucose on dopaminergic function in the human brain in vivo Synapse 2007 61 748 756 17568412 source
• Not checked yetcites [97] Willeumier KC Taylor DV Amen DG Elevated BMI is associated with decreased blood flow in the prefrontal cortex using SPECT imaging in healthy adults Obesity (Silver Spring) 2011 19 1095 1097 21311507 PMC3125099 source
• Not checked yetcites [98] Volkow ND Wang GJ Telang F Inverse association between BMI and prefrontal metabolic activity in healthy adults Obesity 2009 17 60 65 18948965 PMC2681079 source

In the paper

“These processes are modulated by D1R and D2R (presumably also D4R) and thus, the decreased activity in PFC, both in addiction and in obesity, is likely to contribute to poor self-control, impulsivity and high compulsivity.”

In the paper

“This suggests a dynamic interaction between the amount of food eaten (reflected in part in the BMI) and the reactivity of reward regions to high-calorie food (reflected in the activation of OFC and ACC) in normal-weight individuals but which was not observed in obese individuals.”

In the paper

“while these studies cannot address the question of whether the emerging association between low D2R and high BMI points to causality”

In the paper

“The prefrontal cortex (PFC) plays a crucial role in executive function, including self-control.”

In the paper

“The lower-than-normal availability of D2R in the striatum of obese individuals, which has been associated with reduced activity in PFC and ACC (63) is therefore likely to contribute to their deficient control over food intake.”

What the sources say

• Not checked yetcites [63] Volkow ND Wang GJ Telang F Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors Neuroimage 2008 42 1537 1543 18598772 PMC2659013 source

In the paper

“decreased striatal D2R availability has been linked to compulsive food intake in obese rodents (84) and with decreased metabolic activity in OFC and ACC in obese humans (63).”

What the sources say

• Not checked yetcites [84] Johnson PM Kenny PJ Dopamine D2 receptors in addictionlike reward dysfunction and compulsive eating in obese rats Nat Neurosci 2010 13 635 641 20348917 PMC2947358 source
• Not checked yetcites [63] Volkow ND Wang GJ Telang F Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors Neuroimage 2008 42 1537 1543 18598772 PMC2659013 source

In the paper

“An enhanced activity in brain regions that process palatability could make obese subjects favour food over other natural reinforcers, whereas decreased activation of dopaminergic targets by the actual food consumption might lead to overconsumption as a means to compensate for weak D2R-mediated signalling (93).”

What the sources say

• Not checked yetcites [93] Stice E Spoor S Bohon C Small DM Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele Science 2008 322 449 452 18927395 PMC2681095 source

In the paper

“since decreased striatal D2R-related signalling is also likely to reduce the sensitivity to other natural rewards, this deficit in obese individuals may also contribute to compensatory overeating (88).”

What the sources say

• Not checked yetcites [88] Geiger BM Behr GG Frank LE Evidence for defective mesolimbic dopamine exocytosis in obesity-prone rats FASEB J 2008 22 2740 2746 18477764 PMC2728544 source

In the paper

“obese individuals exhibited less activation of reward circuits from actual food consumption (consummatory food reward) than lean individuals, whereas they showed greater activation of somatosensory cortical regions that process palatability when they anticipated consumption (91).”

What the sources say

• Not checked yetcites [91] Stice E Spoor S Bohon C Veldhuizen MG Small DM Relation of reward from food intake and anticipated food intake to obesity: a functional magnetic resonance imaging study J Abnorm Psychol 2008 117 924 935 19025237 PMC2681092 source

In the paper

“PET studies with FDG to measure brain glucose metabolism in normal-weight individuals reported that exposure to food cues increased metabolic activity in OFC, which was associated with the desire for the food (117).”

What the sources say

• Not checked yetcites [117] Wang GJ Volkow ND Telang F Exposure to appetitive food stimuli markedly activates the human brain Neuroimage 2004 21 1790 1797 15050599 source

In the paper

“For example, an MRI study done in elderly women, using voxel-based morphometry, found a negative correlation between BMI and grey matter volumes (including frontal regions), which, in the OFC, was associated with impaired executive function (126).”

What the sources say

• Not checked yetcites [126] Walther K Birdsill AC Glisky EL Ryan L Structural brain differences and cognitive functioning related to body mass index in older females Hum Brain Mapp 2010 31 1052 1064 19998366 PMC6870943 source

In the paper

“Moreover, when the responses to i.v. methylphenidate are compared between cocaine-addicted and non-addicted individuals, the former responded with increased metabolism in ventral ACC and medial OFC (an effect associated with craving), while the latter showed decreased metabolism in these regions (114).”

What the sources say

• Not checked yetcites [114] Volkow ND Wang GJ Ma Y Activation of orbital and medial prefrontal cortex by methylphenidate in cocaine-addicted subjects but not in controls: relevance to addiction J Neurosci 2005 25 3932 3939 15829645 PMC6724925 source

In the paper

“The enhanced OFC activation by the food stimulation is likely to reflect downstream dopaminergic effects and participate in DA’s involvement in the drive for food consumption.”

In the paper

“Another study found no differences in grey matter volumes between obese and lean subjects; however, it did record a positive correlation between white matter volume in basal brain structures and waist to hip ratios, a trend that was partially reversed by dieting (129).”

What the sources say

• Not checked yetcites [129] Haltia LT Viljanen A Parkkola R Brain white matter expansion in human obesity and the recovering effect of dieting J Clin Endocrinol Metab 2007 92 3278 3284 17536002 source

In the paper

“Because drug taking becomes the main motivational drive in drug addiction (110), addicted subjects are aroused and motivated by the process of obtaining the drug but tend to become withdrawn and apathetic when exposed to non–drug-related activities.”

What the sources say

• Not checked yetcites [110] Volkow ND Fowler JS Wang GJ The addicted human brain: insights from imaging studies J Clin Invest 2003 111 1444 1451 12750391 PMC155054 source

In the paper

“This suggests that the activation of these prefrontal regions with drug exposure may be specific to addiction and associated with the enhanced desire for the drug.”

In the paper

“In contrast, when tasting sucrose, subjects who have recovered from anorexia nervosa show less insular activation and no association with feelings of pleasantness as observed in controls (145).”

What the sources say

• Not checked yetcites [145] Wagner A Aizenstein H Mazurkewicz L Altered insula response to taste stimuli in individuals recovered from restricting-type anorexia nervosa Neuropsychopharmacology 2008 33 513 523 17487228 source

In the paper

“The insula, particularly its more anterior regions, is reciprocally connected to several limbic regions (e.g. ventromedial prefrontal cortex, amygdala, and ventral striatum) and appears to have an interoceptive function, integrating the autonomic and visceral information with emotion and motivation, thus providing conscious awareness of these urges (135).”

What the sources say

• Not checked yetcites [135] Naqvi NH Bechara A The hidden island of addiction: the insula Trends Neurosci 2009 32 56 67 18986715 PMC3698860 source

In the paper

“For example, when normal-weight women tasted a sweetener with calories (sucrose), both the insula and dopaminergic midbrain areas became activated, whereas tasting a calorie-free sweetener (sucralose) only activated the insula (144).”

What the sources say

• Not checked yetcites [144] Frank GK Oberndorfer TA Simmons AN Sucrose activates human taste pathways differently from artificial sweetener Neuroimage 2008 39 1559 1569 18096409 source

In the paper

“The observed changes suggest excessive input from the amygdala and insula; these, in turn could trigger exaggerated stimulus-response learning and incentive motivation to food cues in the dorsal caudate nucleus, which could become overwhelming in light of weak inhibitory control by fronto-cortical regions.”

In the paper

“Similar antireward responses (including increased stress reactivity, negative mood and discomfort) may also contribute to excessive food consumption in obesity and to the high propensity to relapse when dieting after exposure to a stressful or frustrating event.”

In the paper

“A highly palatable food diet can induce obesity in rats, with the weight increases correlating with increases in m-opioid peptide binding in the basolateral and basomedial amygdala.”

What the sources say

• Not checked yetcites [157] Smith SL Harrold JA Williams G Diet-induced obesity increases mu opioid receptor binding in specific regions of the rat brain Brain Res 2002 953 215 222 12384255 source

In the paper

“Moreover, neurons in the rostromedial tegmental nucleus, which receive a major input from the lateral habenula, project to VTA DA neurons and are activated after food deprivation (158).”

What the sources say

• Not checked yetcites [158] Jhou TC Fields HL Baxter MG Saper CB Holland PC The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine neurons, encodes aversive stimuli and inhibits motor responses Neuron 2009 61 786 800 19285474 PMC2841475 source

In the paper

“The many mechanistic and behavioural parallels identified between addiction and obesity suggest the value of multipronged parallel therapeutic approaches for both of these disorders.”

In the paper

“The picture that is emerging is that obesity, similar to drug addiction (226), appears to result from imbalanced processing in a range of regions implicated in reward/saliency, motivation/drive, emotion/stress reactivity, memory/conditioning, executive function/self-control and interoception, in addition to possible imbalances in the homeostatic regulation of food intake.”

What the sources say

• Not checked yetcites [226] Carnell S Gibson C Benson L Ochner CN Geliebter A Neuroimaging and obesity: current knowledge and future directions Obes Rev 2011 13 43 56 21902800 PMC3241905 source

In the paper

“Also, whether tested during early or protracted periods of abstinence/ dieting, addicted/obese subjects show lower D2R in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (OFC) and inhibitory control (ACC and DLPFC), whose disruption results in compulsivity and impulsivity.”