Viewing images of foods evokes taste quality-specific activity in gustatory insular cortex.

Previous studies have shown that the conceptual representation of food involves brain regions associated with taste perception. The specificity of this response, however, is unknown. Does viewing pictures of food produce a general, nonspecific response in taste-sensitive regions of the brain? Or is the response specific for how a particular food tastes? Building on recent findings that specific tastes can be decoded from taste-sensitive regions of insular cortex, we asked whether viewing pictures of foods associated with a specific taste (e.g., sweet, salty, and sour) can also be decoded from these same regions, and if so, are the patterns of neural activity elicited by the pictures and their associated tastes similar? Using ultrahigh-resolution functional magnetic resonance imaging at high magnetic field strength (7-Tesla), we were able to decode specific tastes delivered during scanning, as well as the specific taste category associated with food pictures within the dorsal mid-insula, a primary taste responsive region of brain. Thus, merely viewing food pictures triggers an automatic retrieval of specific taste quality information associated with the depicted foods, within gustatory cortex. However, the patterns of activity elicited by pictures and their associated tastes were unrelated, thus suggesting a clear neural distinction between inferred and directly experienced sensory events. These data show how higher-order inferences derived from stimuli in one modality (i.e., vision) can be represented in brain regions typically thought to represent only low-level information about a different modality (i.e., taste).

Taste Quality Representation in the Human Brain.

In the mammalian brain, the insula is the primary cortical substrate involved in the perception of taste. Recent imaging studies in rodents have identified a "gustotopic" organization in the insula, whereby distinct insula regions are selectively responsive to one of the five basic tastes. However, numerous studies in monkeys have reported that gustatory cortical neurons are broadly-tuned to multiple tastes, and tastes are not represented in discrete spatial locations. Neuroimaging studies in humans have thus far been unable to discern between these two models, though this may be because of the relatively low spatial resolution used in taste studies to date. In the present study, we examined the spatial representation of taste within the human brain using ultra-high resolution functional magnetic resonance imaging (MRI) at high magnetic field strength (7-tesla). During scanning, male and female participants tasted sweet, salty, sour, and tasteless liquids, delivered via a custom-built MRI-compatible tastant-delivery system. Our univariate analyses revealed that all tastes (vs tasteless) activated primary taste cortex within the bilateral dorsal mid-insula, but no brain region exhibited a consistent preference for any individual taste. However, our multivariate searchlight analyses were able to reliably decode the identity of distinct tastes within those mid-insula regions, as well as brain regions involved in affect and reward, such as the striatum, orbitofrontal cortex, and amygdala. These results suggest that taste quality is not represented topographically, but by a distributed population code, both within primary taste cortex as well as regions involved in processing the hedonic and aversive properties of taste.SIGNIFICANCE STATEMENT The insula is the primary cortical substrate involved in taste perception, yet some question remains as to whether this region represents distinct tastes topographically or via a population code. Using high field (7-tesla), high-resolution functional magnetic resonance imaging in humans, we examined the representation of different tastes delivered during scanning. All tastes activated primary taste cortex within the bilateral mid-insula, but no brain region exhibited any consistent taste preference. However, multivariate analyses reliably decoded taste quality within the bilateral mid-insula as well as the striatum, orbitofrontal cortex, and bilateral amygdala. This suggests that taste quality is represented by a spatial population code within regions involved in sensory and appetitive properties of taste.

Appetite changes reveal depression subgroups with distinct endocrine, metabolic, and immune states.

There exists little human neuroscience research to explain why some individuals lose their appetite when they become depressed, while others eat more. Answering this question may reveal much about the various pathophysiologies underlying depression. The present study combined neuroimaging, salivary cortisol, and blood markers of inflammation and metabolism collected prior to scanning. We compared the relationships between peripheral endocrine, metabolic, and immune signaling and brain activity to food cues between depressed participants experiencing increased (N = 23) or decreased (N = 31) appetite and weight in their current depressive episode and healthy control participants (N = 42). The two depression subgroups were unmedicated and did not differ in depression severity, anxiety, anhedonia, or body mass index. Depressed participants experiencing decreased appetite had higher cortisol levels than subjects in the other two groups, and their cortisol values correlated inversely with the ventral striatal response to food cues. In contrast, depressed participants experiencing increased appetite exhibited marked immunometabolic dysregulation, with higher insulin, insulin resistance, leptin, CRP, IL-1RA, and IL-6, and lower ghrelin than subjects in other groups, and the magnitude of their insulin resistance correlated positively with the insula response to food cues. These findings provide novel evidence linking aberrations in homeostatic signaling pathways within depression subtypes to the activity of neural systems that respond to food cues and select when, what, and how much to eat. In conjunction with prior work, the present findings strongly support the existence of pathophysiologically distinct depression subtypes for which the direction of appetite change may be an easily measured behavioral marker.

Associated Changes in E-cigarette Puff Duration and Cigarettes Smoked per Day.

INTRODUCTION: To examine whether changes in select measures of e-cigarette puffing topography are associated with changes in smoking behavior. METHODS: Sixteen current cigarette smokers were instructed to completely switch from smoking combustible cigarettes to using e-cigarettes over a 2-week period. The study was completed in the Southern Midwestern region of the United States. Measures included demographics, smoking history, and cigarette dependence, as well as baseline and 2-week follow-up self-reported cigarettes per day, cigarette craving and urges, exhaled carbon monoxide readings, and e-cigarette usage data (puff number, puffing time, and average puff duration) collected via the e-cigarette built-in puff counter. RESULTS: Over the 2-week switching period, participants significantly reduced their cigarettes per day (~80% reduction, p < .0001). Although the number of e-cigarette puffs/day remained relatively stable (p > .05), the average total e-cigarette daily puffing time increased significantly (p = .001). Users' average puff duration increased by 91 ms/puff/d (p < .001). The percentage decrease in cigarettes smoked per day was significantly and directly related to the slope of subjects' average puff duration over time (r(13) = .62, p = .01), such that as cigarettes per day decreased, puff duration increased. Self-reported smoking urges remained relatively stable from baseline to the end of the 2-week period (p > .05). CONCLUSIONS: Among smokers switching to an e-cigarette, greater increases in e-cigarette puff duration was associated with greater reductions in cigarette smoking. IMPLICATIONS: The current study is one of the first to examine changes in smokers' e-cigarette puffing behavior and associated changes in cigarette consumption as they attempt to completely switch to e-cigarettes. During a 2-week switching period, participants reduced their cigarettes per day. Moreover, although e-cigarette puffs per day remained relatively stable, users' average puff duration increased significantly. Greater increases in e-cigarette puff duration were associated with greater reductions in cigarette smoking. Understanding how to effectively use an e-cigarette to best reduce and eventually quit smoking will be necessary as smokers increasingly turn to these products to facilitate possible cessation.

Appetite change profiles in depression exhibit differential relationships between systemic inflammation and activity in reward and interoceptive neurocircuitry.

Appetite change is a defining feature of major depressive disorder (MDD), yet little neuroscientific evidence exists to explain why some individuals experience increased appetite when they become depressed while others experience decreased appetite. Previous research suggests depression-related appetite changes can be indicative of underlying neural and inflammatory differences among MDD subtypes. The present study explores the relationship between systemic inflammation and brain circuitry supporting food hedonics for individuals with MDD. Sixty-four participants (31 current, unmedicated MDD and 33 healthy controls [HC]) provided blood samples for analysis of an inflammatory marker, C-reactive protein (CRP), and completed a functional magnetic resonance imaging (fMRI) scan in which they rated the perceived pleasantness of various food stimuli. Random-effects multivariate modeling was used to explore group differences in the relationship between CRP and the coupling between brain activity and inferred food pleasantness (i.e., strength of the relationship between activity and pleasantness ratings). Results revealed that for MDD with increased appetite, higher CRP in blood related to greater coupling between orbitofrontal cortex and anterior insula activity and inferred food pleasantness. Compared to HC, all MDD exhibited a stronger positive association between CRP and coupling between activity in striatum and inferred food pleasantness. These findings suggest that for individuals with MDD, systemic low-grade inflammation is associated with differences in reward and interoceptive-related neural circuitry when making hedonic inferences about food stimuli. In sum, altered immunologic states may affect appetite and inferences about food reward in individuals with MDD and provide evidence for physiological subtypes of MDD.

Convergent gustatory and viscerosensory processing in the human dorsal mid-insula.

The homeostatic regulation of feeding behavior requires an organism to be able to integrate information from its internal environment, including peripheral visceral signals about the body's current energy needs, with information from its external environment, such as the palatability of energy-rich food stimuli. The insula, which serves as the brain's primary sensory cortex for representing both visceral signals from the body and taste signals from the mouth and tongue, is a likely candidate region in which this integration might occur. However, to date it has been unclear whether information from these two homeostatically critical faculties is merely co-represented in the human insula, or actually integrated there. Recent functional neuroimaging evidence of a common substrate for visceral interoception and taste perception within the human dorsal mid-insula suggests a model whereby a single population of neurons may integrate viscerosensory and gustatory signals. To test this model, we used fMRI-Adaptation to identify whether insula regions that exhibit repetition suppression following repeated interoception trials would then also exhibit adapted responses to subsequent gustatory stimuli. Multiple mid and anterior regions of the insula exhibited adaptation to interoceptive trials specifically, but only the dorsal mid-insula regions exhibited an adapted gustatory response following interoception. The discovery of this gustatory-interoceptive convergence within the neurons of the human insula supports the existence of a heretofore-undocumented neural pathway by which visceral signals from the periphery modulate the activity of brain regions involved in feeding behavior. Hum Brain Mapp 38:2150-2164, 2017. © 2017 Wiley Periodicals, Inc.

Influence of Visceral Interoceptive Experience on the Brain's Response to Food Images in Anorexia Nervosa.

OBJECTIVE: The aim of the study was to determine how visceral sensations affect responses to food stimuli in anorexia nervosa (AN). METHODS: Twenty weight-restored, unmedicated adolescent and young adult women with AN and twenty healthy control participants completed an interoceptive attention task during which they focused on sensations from the heart, stomach, and bladder and made ratings of these sensations. They then underwent functional magnetic resonance imaging scanning while viewing pictures of food and nonfood objects. Between-groups t tests were employed to investigate group differences in the relationship between interoceptive sensation ratings and brain hemodynamic response to food pictures and, specifically, to highly palatable foods. RESULTS: In response to food pictures, AN participants exhibited a positive relationship between stomach sensation ratings and posterior insula activation (peak t = 4.30). AN participants displayed negative relationships between stomach sensation ratings and amygdala activation (peak t = -4.05) and heart sensation ratings and ventromedial prefrontal cortex activation (peak t = -3.52). In response to highly palatable foods, AN was associated with positive relationships between stomach sensation ratings and activity in the subgenual anterior cingulate (peak t = 3.88) and amygdala (peak t = 4.83), and negative relationships in the ventral pallidum (peak t = -3.99) and ventral tegmental area (peak t = -4.03). AN participants also exhibited negative relationships between cardiac sensations and activation in response to highly palatable foods in the putamen (peak t = -3.41) and ventromedial prefrontal cortex (peak t = -3.61). Healthy participants exhibited the opposite pattern in all of these regions. CONCLUSIONS: Hedonic and interoceptive inferences made by individuals with AN at the sight of food may be influenced by atypical visceral interoceptive experience, which could contribute to restrictive eating.

A common gustatory and interoceptive representation in the human mid-insula.

The insula serves as the primary gustatory and viscerosensory region in the mammalian cortex. It receives visceral and gustatory afferent projections through dedicated brainstem and thalamic nuclei, which suggests a potential role as a site for homeostatic integration. For example, while human neuroimaging studies of gustation have implicated the dorsal mid-insular cortex as one of the primary gustatory regions in the insula, other recent studies have implicated this same region of the insula in interoception. This apparent convergence of gustatory and interoceptive information could reflect a common neural representation in the insula shared by both interoception and gustation. This idea finds support in translational studies in rodents, and may constitute a medium for integrating homeostatic information with feeding behavior. To assess this possibility, healthy volunteers were asked to undergo fMRI while performing tasks involving interoceptive attention to visceral sensations as well as a gustatory mapping task. Analysis of the unsmoothed, high-resolution fMRI data confirmed shared representations of gustatory and visceral interoception within the dorsal mid-insula. Group conjunction analysis revealed overlapping patterns of activation for both tasks in the dorsal mid-insula, and region-of-interest analyses confirmed that the dorsal mid-insula regions responsive for visceral interoception also exhibit strong responses to tastants.

Hemispheric divergence of interoceptive processing across psychiatric disorders.

Interactions between top-down attention and bottom-up visceral inputs are assumed to produce conscious perceptions of interoceptive states, and while each process has been independently associated with aberrant interoceptive symptomatology in psychiatric disorders, the neural substrates of this interface are unknown. We conducted a preregistered functional neuroimaging study of 46 individuals with anxiety, depression, and/or eating disorders (ADE) and 46 propensity-matched healthy comparisons (HC), comparing their neural activity across two interoceptive tasks differentially recruiting top-down or bottom-up processing within the same scan session. During an interoceptive attention task, top-down attention was voluntarily directed towards cardiorespiratory or visual signals, whereas during an interoceptive perturbation task, intravenous infusions of isoproterenol (a peripherally-acting beta-adrenergic receptor agonist) were administered in a double-blinded and placebo-controlled fashion to drive bottom-up cardiorespiratory sensations. Across both tasks, neural activation converged upon the insular cortex, localizing within the granular and ventral dysgranular subregions bilaterally. However, contrasting hemispheric differences emerged, with the ADE group exhibiting (relative to HCs) an asymmetric pattern of overlap in the left insula, with increased or decreased proportions of co-activated voxels within the left or right dysgranular insula, respectively. The ADE group also showed less agranular anterior insula activation during periods of bodily uncertainty (i.e., when anticipating possible isoproterenol-induced changes that never arrived). Finally, post-task changes in insula functional connectivity were associated with anxiety and depression severity. These findings confirm the dysgranular mid-insula as a key cortical interface where attention and prediction meet real-time bodily inputs, especially during heightened awareness of interoceptive states. Further, the dysgranular mid-insula may indeed be a "locus of disruption" for psychiatric disorders.

Keeping the body in mind: insula functional organization and functional connectivity integrate interoceptive, exteroceptive, and emotional awareness.

Relatively discrete experimental literatures have grown to support the insula's role in the domains of interoception, focal exteroceptive attention and cognitive control, and the experience of anxiety, even as theoretical accounts have asserted that the insula is a critical zone for integrating across these domains. Here we provide the first experimental demonstration that there exists a functional topography across the insula, with distinct regions in the same participants responding in a highly selective fashion for interoceptive, exteroceptive, and affective processing. Although each insular region is associated with areas of differential resting state functional connectivity relative to the other regions, overall their functional connectivity profiles are quite similar, thereby providing a map of how interoceptive, exteroceptive, and emotional awareness are integrated within the insular cortex.

A common neural code for representing imagined and inferred tastes.

Inferences about the taste of foods are a key aspect of our everyday experience of food choice. Despite this, gustatory mental imagery is a relatively under-studied aspect of our mental lives. In the present study, we examined subjects during high-field fMRI as they actively imagined basic tastes and subsequently viewed pictures of foods dominant in those specific taste qualities. Imagined tastes elicited activity in the bilateral dorsal mid-insula, one of the primary cortical regions responsive to the experience of taste. In addition, within this region we reliably decoded imagined tastes according to their dominant quality - sweet, sour, or salty - thus indicating that, like actual taste, imagined taste activates distinct quality-specific neural patterns. Using a cross-task decoding analysis, we found that the neural patterns for imagined tastes and food pictures in the mid-insula were reliably similar and quality-specific, suggesting a common code for representing taste quality regardless of whether explicitly imagined or automatically inferred when viewing food. These findings have important implications for our understanding of the mechanisms of mental imagery and the multimodal nature of presumably primary sensory brain regions like the dorsal mid-insula.

Dietary fat restriction affects brain reward regions in a randomized crossover trial.

BACKGROUNDWeight-loss diets often target dietary fat or carbohydrates, macronutrients that are sensed via distinct gut-brain pathways and differentially affect peripheral hormones and metabolism. However, the effects of such diet changes on the human brain are unclear. METHODSWe investigated whether selective isocaloric reductions in dietary fat or carbohydrates altered dopamine D2/3 receptor binding potential (D2BP) and neural activity in brain-reward regions in response to visual food cues in 17 inpatient adults with obesity as compared with a eucaloric baseline diet using a randomized crossover design. RESULTSOn the fifth day of dietary fat restriction, but not carbohydrate restriction, both D2BP and neural activity to food cues were decreased in brain-reward regions. After the reduced-fat diet, ad libitum intake shifted toward foods high in both fat and carbohydrates. CONCLUSIONThese results suggest that dietary fat restriction increases tonic dopamine in brain-reward regions and affects food choice in ways that may hamper diet adherence. TRIAL REGISTRATIONClinicalTrials.gov NCT00846040 FUNDING. NIDDK 1ZIADK013037.

Taste Metaphors Ground Emotion Concepts Through the Shared Attribute of Valence.

"Parting is such sweet sorrow." Taste metaphors provide a rich vocabulary for describing emotional experience, potentially serving as an adaptive mechanism for conveying abstract emotional concepts using concrete verbal references to our shared experience. We theorized that the popularity of these expressions results from the close association with hedonic valence shared by these two domains of experience. To explore the possibility that this affective quality underlies the semantic similarity of these domains, we used a behavioral "odd-one-out" task in an online sample of 1059 participants in order to examine the semantic similarity of concepts related to emotion, taste, and color, another rich source of sensory metaphors. We found that the semantic similarity of emotion and taste concepts was greater than that of emotion and color concepts. Importantly, the similarity of taste and emotion concepts was strongly related to their similarity in hedonic valence, a relationship which was also significantly greater than that present between color and emotion. These results suggest that the common core of valence between taste and emotion concepts allows us to bridge the conceptual divide between our shared sensory environment and our internal emotional experience.

Against gustotopic representation in the human brain: There is no Cartesian Restaurant.

The insular cortex is still one of the least understood cortical regions in the human brain. This review will highlight research on taste quality representation within the human insular cortex. Much of the controversy surrounding this topic is based in the ongoing debate over different theories of peripheral taste coding. When translated to the study of gustatory cortex, this has generated a distinct set of theoretical models, namely the topographic (or 'gustotopic') and population coding models of taste organization. Recent investigations into this topic have employed high-resolution functional neuroimaging methods and multivariate analytic approaches to examine taste quality coding in the human brain. Collectively, these recent studies do not support the topographic model of taste quality representation, but rather one where taste quality is represented by distributed patterns of activation within gustatory regions of the insula.

Layer-Specific Contributions to Imagined and Executed Hand Movements in Human Primary Motor Cortex.

The human ability to imagine motor actions without executing them (i.e., motor imagery) is crucial to a number of cognitive functions, including motor planning and learning, and has been shown to improve response times and accuracy of subsequent motor actions [1, 2]. Although these behavioral findings suggest the possibility that imagined movements directly influence primary motor cortex (M1), how this might occur remains unknown [3]. Here, we use a non-blood-oxygen-level-dependent (BOLD) method for collecting fMRI data, called vascular space occupancy (VASO) [4, 5], to measure neural activations across cortical laminae in M1 while participants either tapped their thumb and forefinger together or simply imagined doing so. We report that, whereas executed movements (i.e., finger tapping) evoked neural responses in both the superficial layers of M1 that receive cortical input and the deep layers of M1 that send output to the spinal cord to support movement, imagined movements evoked responses in superficial cortical layers only. Furthermore, we found that finger tapping preceded by both imagined and executed movements showed a reduced response in the superficial layers (repetition suppression) coupled with a heightened response in the deep layers (repetition enhancement). Taken together, our results provide evidence for a mechanism whereby imagined movements can directly affect motor performance and might explain how neural repetition effects lead to improvements in behavior (e.g., repetition priming).

Sex Differences in Resting-State Functional Connectivity of the Cerebellum in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is more prevalent in males than females, but the underlying neurobiology of this sex bias remains unclear. Given its involvement in ASD, its role in sensorimotor, cognitive, and socio-affective processes, and its developmental sensitivity to sex hormones, the cerebellum is a candidate for understanding this sex difference. The current study used resting-state functional magnetic resonance imaging (fMRI) to investigate sex-dependent differences in cortico-cerebellar organization in ASD. We collected resting-state fMRI scans from 47 females (23 ASD, 24 controls) and 120 males (56 ASD, 65 controls). Using a measure of global functional connectivity (FC), we ran a linear mixed effects analysis to determine whether there was a sex-by-diagnosis interaction in resting-state FC. Subsequent seed-based analyses from the resulting clusters were run to clarify the global connectivity effects. Two clusters in the bilateral cerebellum exhibited a diagnosis-by-sex interaction in global connectivity. These cerebellar clusters further showed a pattern of interaction with regions in the cortex, including bilateral fusiform, middle occipital, middle frontal, and precentral gyri, cingulate cortex, and precuneus. Post hoc tests revealed a pattern of cortico-cerebellar hyperconnectivity in ASD females and a pattern of hypoconnectivity in ASD males. Furthermore, cortico-cerebellar FC in females more closely resembled that of control males than that of control females. These results shed light on the sex-specific pathophysiology of ASD and are indicative of potentially divergent neurodevelopmental trajectories for each sex. This sex-dependent, aberrant cerebellar connectivity in ASD might also underlie some of the motor and/or socio-affective difficulties experienced by members of this population, but the symptomatic correlate(s) of these brain findings remain unknown. Clinical Trial Registration: www.ClinicalTrials.gov, NIH Clinical Study Protocol 10-M-0027 (ZIA MH002920-09) identifier #NCT01031407.

Neural correlates of taste reactivity in autism spectrum disorder.

Selective or 'picky' eating habits are common among those with autism spectrum disorder (ASD). These behaviors are often related to aberrant sensory experience in individuals with ASD, including heightened reactivity to food taste and texture. However, very little is known about the neural mechanisms that underlie taste reactivity in ASD. In the present study, food-related neural responses were evaluated in 21 young adult and adolescent males diagnosed with ASD without intellectual disability, and 21 typically-developing (TD) controls. Taste reactivity was assessed using the Adolescent/Adult Sensory Profile, a clinical self-report measure. Functional magnetic resonance imaging was used to evaluate hemodynamic responses to sweet (vs. neutral) tastants and food pictures. Subjects also underwent resting-state functional connectivity scans.The ASD and TD individuals did not differ in their hemodynamic response to gustatory stimuli. However, the ASD subjects, but not the controls, exhibited a positive association between self-reported taste reactivity and the response to sweet tastants within the insular cortex and multiple brain regions associated with gustatory perception and reward. There was a strong interaction between diagnostic group and taste reactivity on tastant response in brain regions associated with ASD pathophysiology, including the bilateral anterior superior temporal sulcus (STS). This interaction of diagnosis and taste reactivity was also observed in the resting state functional connectivity between the anterior STS and dorsal mid-insula (i.e., gustatory cortex).These results suggest that self-reported heightened taste reactivity in ASD is associated with heightened brain responses to food-related stimuli and atypical functional connectivity of primary gustatory cortex, which may predispose these individuals to maladaptive and unhealthy patterns of selective eating behavior. Trial registration: (clinicaltrials.gov identifier) NCT01031407. Registered: December 14, 2009.

The Neural Bases of Interoceptive Encoding and Recall in Healthy Adults and Adults With Depression.

BACKGROUND: Theoretical models assert that the brain's interoceptive network links external stimuli with their interoceptive consequences, thereby supporting later recall of these associations to guide the selection of healthy behaviors. If these accounts are correct, previously reported interoceptive abnormalities in major depressive disorder (MDD) should lead to altered recall of associations between external stimuli and their interoceptive (somatic) consequences. To date, the processes underlying interoceptive recall have never been experimentally investigated. METHODS: We designed and implemented the Interoceptive Encoding and Recall task to compare interoceptive and exteroceptive recall among subjects with MDD (n = 24) and healthy comparison subjects (n = 21). During the encoding phase, subjects learned to pair neutral visual cues (geometric shapes) with aversive interoceptive and exteroceptive stimuli. Later, while undergoing functional magnetic resonance imaging, subjects were prompted to recall the stimulus associated with each shape. RESULTS: Interoceptive recall, relative to exteroceptive recall, was associated with bilateral mid-to-posterior insula activation. Relative to the healthy control participants, participants with depression exhibited marked hypoactivation of the right dorsal mid-insula during interoceptive recall. CONCLUSIONS: In healthy control subjects, simply recalling a stimulus associated with a previous interoceptive challenge activated a key region in the brain's interoceptive network. Although previous research has linked MDD with aberrant processing of interoceptive stimuli, the current study is the first to demonstrate that individuals with MDD exhibit decreased insula activity while recalling interoceptive memories. It is possible that insula hypoactivation during interoceptive recall may affect the representation of prior interoceptive experiences in ways that contribute to depressive symptomology and the relationship between depression and systemic health.

How the Brain Wants What the Body Needs: The Neural Basis of Positive Alliesthesia.

Discontinuing unhealthy behaviors, such as overeating or drug use, depends upon an individual's ability to overcome the influence of environmental reward cues. The strength of that influence, however, varies greatly depending upon the internal state of the body. Characterizing the relationship between interoceptive signaling and shifting drug cue valuation provides an opportunity for understanding the neural bases of how changing internal states alter reward processing more generally. A total of 17 cigarette smokers rated the pleasantness of cigarette pictures when they were nicotine sated or nicotine abstinent. On both occasions, smokers also underwent functional magnetic resonance imaging (fMRI) scanning while performing a visceral interoceptive attention task and a resting-state functional connectivity scan. Hemodynamic, physiological, and behavioral parameters were compared between sated and abstinent scans. The relationships between changes in these parameters across scan sessions were also examined. Smokers rated cigarette pictures as significantly more pleasant while nicotine abstinent than while nicotine sated. Comparing abstinent with sated scans, smokers also exhibited significantly decreased mid-insula, amygdala, and orbitofrontal activity while attending to interoceptive signals from the body. Change in interoceptive activity within the left mid-insula predicted the increase in smoker's pleasantness ratings of cigarette cues. This increase in pleasantness ratings was also correlated with an increase in resting-state functional connectivity between the mid-insula and the ventral striatum and ventral pallidum. These findings support a model wherein interoceptive processing in the mid-insula of withdrawal signals from the body potentiates the motivational salience of reward cues through the recruitment of hedonic 'hot spots' within the brain's reward circuitry.

Obesity is associated with altered mid-insula functional connectivity to limbic regions underlying appetitive responses to foods.

Obesity is fundamentally a disorder of energy balance. In obese individuals, more energy is consumed than is expended, leading to excessive weight gain through the accumulation of adipose tissue. Complications arising from obesity, including cardiovascular disease, elevated peripheral inflammation, and the development of Type II diabetes, make obesity one of the leading preventable causes of morbidity and mortality. Thus, it is of paramount importance to both individual and public health that we understand the neural circuitry underlying the behavioral regulation of energy balance. To this end, we sought to examine obesity-related differences in the resting state functional connectivity of the dorsal mid-insula, a region of gustatory and interoceptive cortex associated with homeostatically sensitive responses to food stimuli. Within the present study, obese and healthy weight individuals completed resting fMRI scans during varying interoceptive states, both while fasting and after a standardized meal. We examined group differences in the pre- versus post-meal functional connectivity of the mid-insula, and how those differences were related to differences in self-reported hunger ratings and ratings of meal pleasantness. Obese and healthy weight individuals exhibited opposing patterns of eating-related functional connectivity between the dorsal mid-insula and multiple brain regions involved in reward, valuation, and satiety, including the medial orbitofrontal cortex, the dorsal striatum, and the ventral striatum. In particular, healthy weight participants exhibited a significant positive relationship between changes in hunger and changes in medial orbitofrontal functional connectivity, while obese participants exhibited a complementary negative relationship between hunger and ventral striatum connectivity to the mid-insula. These obesity-related alterations in dorsal mid-insula functional connectivity patterns may signify a fundamental difference in the experience of food motivation in obese individuals, wherein approach behavior toward food is guided more by reward-seeking than by homeostatically relevant interoceptive information from the body.