The development and maintenance of addictions can be explained via the incentive salience theory, which couples classical Pavlovian conditioning principles (29, 30) with associative learning mechanisms by automatically generating drug- or gambling-related action and craving (19). Environmental cues that trigger such responses are mediated by subcortical structures of the basal ganglia and its cortical inputs. Specifically, the dopamine-dependent striatum-amygdala neural circuit promotes habitual, incentive-motivational and salient behaviors in response to non-natural rewards [e.g., psychoactive drugs; see (31)], natural rewards (e.g., food, and sexual intercourse) (32) and behavioral cues (33–36).

Addictive substances, including highly palatable foods, can sensitize vulnerable reward systems to food stimuli and lead to hyper–activation. Eating can lead to the release of dopamine in the ventral tegmental area (VTA) and its transmission to the nucleus accumbens (NAcc; a part of the ventral striatum), which in turn, translates it into release of opioid peptides that make people feel good. Learning to expect and subconsciously anticipate such rewards from food consumption induces in some people strong motivational states for food intake, which, if remains unchecked or uninhibited, can drive excess eating (37).

Indeed, increased activation in the amygdala-striatal area has been reported in many fMRI studies that used food-related stimuli. For example, obese individuals had greater activation in brain areas associated with reward processing when exposed to visual food cues compared to lean individuals, but without food stimulation this activation was decreased 38–40. Morris and Dolan (41) reported a PET study according to which the activation of the left amygdala and the right anterior orbitofrontal cortex (OFC) correlated positively with recognition memory for food items and the activation of the right OFC was negatively correlated with recognition memory for non-food items. Ng et al. (42) found that compared to lean people, obese people show higher activity in somatosensory (Rolandic operculum), gustatory (frontal operculum), and reward valuation (amygdala) regions, and in the ventromedial prefrontal cortex (vmPFC) in response to intake and anticipated intake of a milkshake vs. a plain drink. Similarly, He et al. (43) used a food-specific go/nogo task to measure the inhibitory control ability of high BMI participants. Results indicated that high BMI participants responded faster in go trials related to high-calorie food images, compared to the go trials related to low-calorie food images. In nogo trial, these participants expressed stronger difficulty to inhibit their responses. In addition, fMRI results showed that the right striatum was more active in go trials focusing on high-calorie food images, and that the PFC was more active in nogo trials; PFC activation negatively correlated with subjects' BMI. Contrerasrodríguez et al. (44) examined potential abnormal functional connectivity in obese people. They found that over-weight participants displayed increased functional connection between the ventral striatum and the medial prefrontal and parietal cortices; and between the dorsal striatum and the somatosensory cortex. Moreover, these participants' connectivity of the dorsal striatum was associated with food craving and can predict BMI increases. These results support the view that a hyper-responsivity of the impulsive system (and a deficit in the reflective system) may promote excess, impulsive eating behaviors.

Likewise, Coveleskie et al. (45) have examined the structural/anatomical differences between obese women and lean controls. Voxel-Based Morphometry (VBM) analysis revealed significantly greater gray matter volume (GMV) in the NAcc in the high BMI-group compared to the control group. This suggests that brain structures, and specifically increased GMV in the areas associated with the impulsive reward system, may be a marker for obesity and essentially food “addiction.”

Collectively, such studies indicate that the impulsive system likely plays an important role in processes that automatically gauge the value of food-related stimuli and generates motivational consumption states. This motivational state, if not assessed and inhibited properly, may result in problematic eating.

The impulsive system is indeed a key mediator of the “wanting” component during reward anticipation and processing; it creates strong incentive-motivation to act. However, it does not account for controlling the “wanting” and acting upon it. These are regulated by the reflective system, which includes vmPFC, anterior cingulate cortex, dlPFC, and lateral orbitofrontal/inferior frontal gyrus (32). The PFC is involved in decision-making, executive functions, forecasting flexible future outcomes, and controlling the action drives mediated via the impulsive system (46). Indeed, damage to this area impairs decision-making abilities; it results in reckless decisions without sufficient consideration of the consequences of the behavior (47).

The reflective system is based on the integration of two functions that are mediated via two neural sub-systems; “cool” executive functions and “hot” executive functions (48). “Cool” executive functions are mediated via the dorsolateral prefrontal cortex (dlPFC) and anterior cingulate cortex (ACC), and involve inhibitory control, basic working memory, analytical thinking, cognitive flexibility, and the maintenance and updating of new relevant information (49). This view is in congruence with theories of economic decision-making, according to which humans are rational, reflective, and goal-directed decision-makers. In contrast, “Hot” executive functions integrate emotions into decision making, and are mediated by the ventromedial PFC (vmPFC) and the OFC. These structures are involved in eliciting somatic states from memories and knowledge, which in return initiate emotional and affective responses (50), and consequently are based on one's “gut-feeling,” intuition, and heuristics (51). Adequate decision-making often involves an integration of the “cool” cognitive and “hot” emotion-involved systems; it relies on one's ability to more optimally evaluate probable outcomes of an action by weighing short-term gains against long-term, often more uncertain, losses (52, 53).

A growing body of fMRI studies has examined the abnormal function of the reflective system in obese people. Le et al. (54) compared the activation of the left dlPFC in lean and obese people following a meal. They discovered lower activity in obese people. A meta-analysis conducted by (55) examined the most common functional differences between normal-weight and obese people responding to food stimuli. The results indicated that obese participants had increased activation in the left dorsomedial prefrontal cortex, right parahippocampal gyrus, right precentral gyrus, and right anterior cingulate cortex, as well as reduced activation in the left dlPFC and left insular cortex. This decreased activation may be indicative of the notion that obese people have weaker inhibitory control and interoceptive awareness when exposed to food-related stimuli, compared to people in the normal weight range. Combining such inhibitory deficits with high sensitivity to food stimuli, often presented by obese people, can provide a neurocognitive account for problematic eating and consequent obesity.

An fMRI study investigating unhealthy food choices (43) found that increased activity in the PFC and reduced activity of the insula were positively correlated with high consumption of vegetables. In contrast, consumption of high calorie foods correlated with reduced activity of the PFC and elevated activity of the insula. These results indicated that in order to make healthy food choices, people have to spend more cognitive resources encapsulated in the reflective system. Moreover, Verdejo-Román et al. (56) found less effective functional connectivity between frontal areas responsible for cognitive control and striatal areas involved in reward anticipation and processing in obese individuals who performed a food-based reward task. This suggests that the reward circuitry of obese people is incongruent with the cognitive control areas, thus making obese individuals' self-regulation ability poor when trying to control consumption of palatable foods.

Structural imaging studies using VBM also support this perspective (57, 58). Specifically, a longitudinal study (59) examined a total of 292 obese and normal weight subjects over two time-points, 5 years apart. Obese subjects had significantly smaller total brain volumes (with no difference in white matter; or cerebrospinal fluid). The most robust finding in their study was the reduced GMV in dlPFC in obese people, which can be indicative of poor foresight and risk assessment, and is common in other addictions (60).

Taken together, these studies indicate that obese individuals may have a hypo-functioning reflective system, which can manifest structurally through decreased GMV in key regions of the reflective system. This again points to possible similarities between problematic eating and other addictive behaviors.

The third and final component in the tripartite model is an interoceptive awareness system, which is primarily insular cortex dependent. This system is reciprocally connected to several limbic regions including the vmPFC, the amygdala, and the ventral striatum (61). Besides being the primary taste area in the brain (4), it has recently been argued that the insular cortex may contribute to the onset and maintenance of addiction by integrating and translating interoceptive, somatic signals into subjective experiences like the feeling of anticipation, desires, urges, or cravings (53). These interoceptive manifestations can potentiate the activity of the impulsive system, and simultaneously weaken the goal-driven cognitive functions mediated by the reflective system. In other words, interoceptive signals can “hijack” the cognitive resources of the reflective system that are required for executing inhibitory control over tempting behaviors, such as eating high-calorie dense foods.

This view is supported by fMRI studies showing increased insular activity in response to food-related stimuli. According to Simmons et al. (62) and Frank et al. (63), when presented with high calorie pictures of food, subjects show increased activity in the insular cortex and the OFC. In a recent review article (64), neural responses to visual food cues according to weight status were analyzed. Findings indicated that both the insula and OFC have increased activity in obese subjects in a majority of the sixty fMRI studies they reviewed. In addition, increased brain response to appetitive tastes in both the insula and the amygdala have been demonstrated in satiated obese compared with satiated healthy weight children (65). Deficient emotion regulation can also be associated with obesity. Steward et al. (66) asked participants to modulate their negative emotions induced by negative pictures. Overweight participants continuously displayed high activation in the right insula. Functional connectivity between the right insula and right dorsal lateral PFC and dorsal medial PFC was less effective in overweigh participants compared to normal-weight participants.

Studies of adolescent obesity indicated that the activation of the insula was positively correlated with interoceptive sensitivity in obese adolescents, but negatively correlated with interoceptive sensitivity in healthy-weight adolescents. While in healthy weight adolescents insular activation negatively correlated with external eating, it positively correlated with external eating in obese adolescents (67). Although the insula activated in both healthy and overweight adolescents, it reflected different mechanisms in these groups. The interoceptive insensitivity in obese people may explain increased food consumption; this consumption serves as a means to achieve equal satiation to this experienced by normal weight individuals.

VBM studies also support the hypothesis that obese or individuals with disordered eating have similar structural differences in the GMV and white matter in the insular cortex as substance addicts. Both Shott et al. (68) and Jauchchara et al. (69) studied gray and white matter densities in obese cases vs. lean controls. They both found that areas associated with the impulsive system (striatum and putamen) and the interoceptive awareness system (the insula) had reduced GMV [and associated white matter in (68)] in obese subjects. Smucny et al. (70) however, have shown that the reduction in insular GMV also can be seen in lower ranges of BMI. After controlling for age, sex, and total GMV, the results showed that obesity-prone people had reduced GMV in the OFC and insula compared to obesity-resistant subjects. They also found that GM volume in the insula was inversely correlated with reported ratings of hunger after a meal and inversely correlated with plasma leptin concentration. These findings illuminate the importance of and associations between GMV, homeostatic and hormonal responses, as related to food intake.

Other than obesity, studies also showed that the following factors can be associated with differences in the activity of the insula; and indirectly influence impulsive and reflective system functions.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.