**1. Introduction**

Obesity is a growing public health condition associated with significant co-morbidities, including diabetes, heart disease, cancer, and depression [1,2]. Consequently, it carries an enormous economic and public health burden [3]. Traditional remedies to reduce the prevalence of overweight and obesity, such as diet and physical activity, are often successful, but most post-obese individuals fail to maintain a healthy body weight in the long run [4]. In the past decade, the clinical construct of addiction to food and eating (i.e., food addiction; FA) has been suggested to explain why some obese individuals are resistant to conventional weight management regimens. The concept of addiction to food is not under a consensus though, and it is not yet recognized in the Diagnostic and Statistical Manual of Mental Disorders (DSM). Proponents of FA posit that there are psychophysiological commonalities between obesity and substance or behavioral addiction [5], while opponents claim that this construct is highly related to binge-eating disorder (BED) [6,7], and that the term "addiction" is inappropriate since food is a legitimate necessity, not a substance individuals can abstain from [8,9]. Nevertheless, eating behavior commonly seen in individuals with overweight and obesity may resemble symptoms of substance or behavioral addiction, as specified in the DSM. This has led researchers to propose FA, by extrapolating criteria for addiction diagnosis in the DSM and translating them to the food and eating behavior domain [10]. These symptoms include frequent and excessive cravings for rewarding

food [11], associated with an urgency to relieve stress and negative affect; hypersensitivity to external cues signaling the rewarding food [12]; impulsivity [13] and disinhibition of eating restraint in response to the cues [14]; recurrent overeating past the point of satiety [15], and reduced inhibitory control over eating [16], despite being conscious to the adverse consequences of the behavior [17]. Individuals with these symptoms may experience binge-eating episodes, but many do not satisfy the diagnostic criteria for BED, such as eating binges that occur in a 2-h time window [18]. In fact, in a sample of obese treatment seeking BED patients, only a subset of them met FA criteria [19,20]. Therefore, addictive-like eating symptoms may accelerate chronic obesity rates, above and beyond the incidence of BED.

The psychobiological mechanisms of recurrent overeating in overweight and obesity are partially characterized. A decade of research in this area has been channeled into several theories to explain excessive overeating for reward [21]. The incentive sensitization theory, for example, posits that by repeatedly overconsuming rewarding food, regardless of metabolic hunger, a conditioned food-reward response is formed. The rewarding food is commonly hyperpalatable, high in calories, ultra-processed fat, sugar, and/or salt, and it is considered to have an addictive potential [22,23]. With excessive repetition of this behavior, the conditioned response transfers from a consummatory to an anticipatory food reward (i.e., the reward associated with anticipating the consumption of this food) [24]. In this way, a food cue, such as its olfactory or visual properties, is paired with an anticipatory reward in a conditioned learning mechanism, which stems from neurobiological changes in the mesolimbic dopaminergic system [12]. The anticipatory reward from consuming hyperpalatable food can elicit intense cravings in response to the relevant cue [25]. These food cravings are associated attention bias (AB), or the allocation of attentional resources to the relevant cue. Indeed, multiple studies have confirmed the heightened allocation of attentional systems to food cues in obese, compared with lean individuals [26–28].

Another theory that may explain recurrent overeating in obesity is the inhibitory control deficit theory. This theory emphasizes that individuals keep overeating due to dysfunctional activity in brain regions involved in higher-order control functions, which are under the command of inhibitory control regions in the prefrontal cortex (PFC). According to this theory, a dysfunctional PFC activity may accelerate repeated overconsumption of highly rewarding food, even in the absence of metabolic hunger, due to reduced inhibitory control over eating [15].

The two neurocognitive theories described herein are in line with the approach-avoidance motivational direction theory, according to which individuals with left-sided brain prefrontal asymmetry (i.e., greater left, compared with right, PFC activity) are more likely to be responsive to reward, and/or seek out experiences generating a reward [29]. Left-brain asymmetry is also associated with impaired ability to avoid (or inhibit) behaviors generating undesirable consequences. Differently, individuals with right-sided brain prefrontal asymmetry (i.e., greater right, compared with left, PFC activity) are more likely to avoid experiences generating punishment or disgust, and/or keep away from those generating a reward.

In line with the asymmetry hypothesis of obesity [30], a growing body of literature suggests that left-brain asymmetry may be a neurocognitive characteristic of uncontrollable hedonic overeating (i.e., the overconsumption of highly rewarding food in the absence of hunger), and impaired inhibitory control over food consumption [31,32]. There is evidence in females ranging from lean to obese for the presence of left PFC asymmetry as a possible mediator of the association between AB to highly rewarding food and a high BMI [33]. Moreover, participants with obesity and BED, compared with obesity only, display greater left-hemispheric regional cerebral blood flow in response to rewarding food [34]. These studies support the hypothesis that left-brain asymmetry is a neuronal mechanism that preserves aberrant eating behavior in obesity and BED, but no study to date examined this neurobiological feature directly in FA.

The neurocognitive features of heightened attentional sensitivity to an addictive rewarding cue, coupled with inhibitory control deficits over the addictive behavior, and left-brain asymmetry traits, are commonly seen in Substance Use Disorder (SUD) and behavioral addiction [35–37]. Therefore, there is some support for similarities between FA and other types of addiction. In an fMRI study of participants ranging from lean to obese, a correlation between FA scores and increased reward circuitry reactivity was found in the Anterior Cingulate Cortex (ACC), medial orbitofrontal cortex (OFC), and amygdala during anticipation of chocolate milkshake consumption [38]. This was observed jointly with reduced inhibitory control activation in the dorsolateral prefrontal cortex (DLPFC) and the caudate in response to the actual consumption of the food, when comparing participants with high vs. low FA scores. Similar neuronal alterations have been identified in classical addiction, in anticipation and the actual intake of the substance [39–42].

Previous studies have identified reward responsiveness and AB to highly rewarding food cues in FA. For example, reward-responsive eating mediated the relationship between elevated dopamine signaling and FA scores [43]. Moreover, in female overweight adults with FA, AB to rewarding food was identified in an eye-tracking paradigm following a negative mood induction, but the neurobiological mechanisms have not been studied [44]. Therefore, no study thus far examined brain asymmetry and neuronal correlates of AB to highly rewarding food in FA, to empirically test these aspects of neurocognition. Moreover, no study to date examined the specific psychobiological distinction between overweight/obesity with FA relative to overweight/obesity without FA.

To address the knowledge gap in the FA literature, we measured brain asymmetry at rest, cue-reactivity to images of rewarding food in a Stroop Task while measuring EEG, and several psycho-behavioral parameters, including eating behavior (emotional, uncontrollable, restraint, and binge-eating behavior), and depressive symptoms. We compared these parameters between overweight/obese adults with and without FA (FAOB and NFAOB, respectively), as well as lean controls. We hypothesized that the FAOB group, compared with the other two groups, shows greater left-brain asymmetry at rest and AB to food cues, along with heightened evoked electrophysiological responses, in the Stroop task. We also hypothesized greater depressive, uncontrollable and emotional eating, and binge-eating symptoms in the FAOB group, compared with the other two groups.
