*3.2. Taste Response*

Sex/gender differences in neuroimaging taste perception in people with obesity are an underexplored research area. This is partially due to the difficulty in firmly identifying regions in the human brain associated with taste (recently reviewed in Kure Liu et al., 2019 [49]). It has been established that the anterior insula/frontal operculum is the primary taste cortex [50–54]. However, Avery et al. (2020) reported that taste quality is more accurately analyzed using a combinatorial spatial code, in which taste perception is distributed throughout the sensory network [55]. In this model, taste quality refers to the unique pattern of activation throughout the primary taste cortex and regions involved in processing hedonic and aversive tastes for each individual in a population [55]. This contrasts with a topographic perspective in which activated regions are attributed to each separate taste component [55]. The type of taste (i.e., salty, bitter, sweet, sour, or umami) has also been found to influence brain activation differences between sexes/genders [15]. The diversity of responses to taste prevent researchers from finding a specific and reliable way to pinpoint regions activated by taste using neuroimaging.

Despite these existing limitations, related studies can shed light on neural taste perception in men and women with obesity (Table 3). Specifically, sex/gender differences in anticipation of taste may improve our understanding of underlying neural differences leading to obesity. For example, Cornier et al. (2015) examined taste anticipation in men and women who were identified as obese prone or obese resistant based on a history of diet and weight gain but not current BMI [56]. After undergoing a cue reactivity fMRI task associating sucrose and artificial saliva with visual cues, males in both populations displayed greater neuronal response to the sucrose-associated visual cue in the right caudate nucleus relative to women [56]. The study supports that there are brain activation sex/gender differences in anticipation of receiving sugar but not the receipt of the sugar itself, emphasizing the importance of sex/gender differences in conditioning in obesity. Geliebter et al. (2013) presented a related analysis of sex/gender differences in obese individuals [57]. When presented with high- instead of low-energy dense auditory food cues, male participants with obesity portrayed brain activation in supplementary motor areas (precentral gyrus) in a sated state. Female participants, though, showed activation in cognitive-related regions (parahippocampal gyrus) in a fasted state [57]. The same obese population further demonstrated that otherwise healthy men and women displayed different patterns of functional connectivity in the amygdala and ventral striatum when responding to food cues in both a sated and hungry state [58]. When the subjects were in a sated state, men tended to show greater connectivity in the amygdala than women, while women displayed greater connectivity in the angular gyrus and precentral gyrus than men [58]. However, in the fasted state, the motor/visual processing centers and emotion/reward-related regions (supplementary motor area, precentral gyrus, precuneus, cuneus) in men were more highly connected, while women had greater connectivity in areas involving response inhibition and cognitive control (i.e., inferior frontal gyrus). Atalayer et al. (2014) suggest their results support the hypothesis that men may process hunger in relation to emotional cues, while women relate it to cognitive processing. The combination of findings from these studies illustrate how satiety and food anticipation may impact brain activation differently in men and women [56–58].

Preliminary evidence suggests that bariatric surgery can impact taste reward anticipation in both sex/genders. In one study, 13 patients with obesity who had undergone a gastric bypass experienced an expected weight loss, in addition to changes in the neural response to the expectation of tastants from before surgery to one-month post-operative [59]. Anticipation of sweet and salty stimuli evoked responses in reward regions, including the NAcc, caudate, VTA, OFC, and prefrontal cortex, as measured by fMRI [59]. While this neural response decreased from baseline to 1-month post-operative in anticipation of sucrose, it increased in anticipation of sodium chloride.

However, lean control participants, who did not have a gastric bypass and were scanned 1 month apart also had a similar decrease in reward response to sucrose but no change in response to sodium chloride, and so it is unclear if this change in sucrose anticipation is due to habituation or the gastric bypass [59]. Some sex/gender differences have also been identified regarding changes in taste response following bariatric surgery. Another group found men (*n* = 35) exhibited a greater decrease in taste and smell ability than women (*n* = 120) as assessed using a subjective taste questionnaire five years post-sleeve gastrectomy operation, especially among those with type-2 diabetes [60]. The authors did not report sex/gender differences in starting BMI, nor what type of taste changes the subjects underwent. Further, there were no sex/gender differences following roux-en-Y gastric bypass in taste or taste aversion [60]. Since these are pilot results, their replication as well as clarification of what types of taste changes occur following bariatric surgery and how they differ between sexes/genders are still needed.



Mar 1991.

Research in a lean population analyzing sex/gender differences in taste also contributes valuable insight on how weight and taste interact between sexes/genders. While maintaining insignificant differences in BMI (23.15 kg/m<sup>2</sup> average for men and 22.76 kg/m<sup>2</sup> average for women), one cohort displayed notable sex/gender differences in the neural response to the transition from hunger to satiety to four different taste types: Sour, bitter, sweet, and salty [15]. fMRI results indicated greater brain activation decreases in men compared to women in the middle frontal gyrus, insula, and cerebellum when changing from a hunger to satiety state for all four tastes [15]. The middle frontal gyrus has been identified as an area critical to dual-task performance and decision-making [61,62]. Since women demonstrated consistently high activation through both hunger and satiety while men experienced a decrease in activation following satiety, Haase et al. (2011) speculated that women exhibit greater top-down functioning regarding taste salience [15]. In other words, female brains may process taste input more cognitively than males' brains since they were activated even when sated. In comparison, male brains displayed less activation after feeling full, suggesting their taste processing is built up from a small piece of sensory information, which dissipates after it has been resolved. Compared to women, men also displayed greater activation changes in reaction to sucrose, citric acid, and caffeine in the inferior frontal gyrus; sucrose and NaCl within the parahippocampal gyrus, entorhinal cortex, perirhinal cortex, and amygdala; and sucrose within the dorsal striatum (caudate, putamen) and posterior cingulate [15]. Because these areas are involved in reward and memory processing, these findings imply that women encode and learn about their food differently than men [63–65]. However, how these neural differences play out behaviorally in obese and overweight populations remains unclear.

Another study examined first-year college students and found that weight gain over the first eight months of school was associated with concurrent taste changes: For every 1% body weight increase, male students displayed a decrease in their tasting ability for sweetness (by ≤ 11.0%) and saltiness (by 7.5%) [66]. This finding aligns with similar studies that observed a decrease in sweet and salty perception accompanying weight gain in male more than in female students [67,68]. In comparison, female students did not display this taste decrease, and instead displayed a 6.5% increase in sourness perception ability for every 1% gain in body weight [66]. However, this correlational study cannot conclude a causal relationship between weight gain and changes in taste perception. While the authors suggested that taste differences between sexes/genders are due to hormonal effects, the neural findings from Haase et al. (2011) suggest that functional differences in the limbic system also contribute to differences in taste perception [15,66,69].
