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SUMMARYInferences 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.

Weight loss diets often target restriction of dietary fat or carbohydrate, macronutrients that are sensed via distinct gut-brain pathways and differentially affect peripheral hormones and metabolism. However, the effects of such diet changes on human brain are unclear. We investigated whether selective isocaloric reductions in dietary fat or carbohydrate 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 to a eucaloric baseline diet. On 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 libitumintake shifted towards foods high in both fat and carbohydrates. These results suggest that dietary fat restriction increases tonic dopamine in brain reward regions and affects food choice in ways that may hamper diet adherence.

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.

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 STATEMENTThe 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.

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.

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).

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, non-specific 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, 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 ultra-high 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).Significance StatementDoes a picture of an apple taste sweet? Previous studies have shown that viewing food pictures activates brain regions involved in taste perception. However, it’s unclear if this response is actually specific to the taste of depicted foods. Using ultra-high resolution functional magnetic resonance imaging and multi-voxel pattern analysis, we decoded specific tastes delivered during scanning, as well as the dominant tastes associated with food pictures within primary taste cortex. Thus, merely viewing pictures of food evokes an automatic retrieval of information about the taste of those foods. These results show how higher-order information from one sensory modality (i.e. vision) can be represented in brain regions thought to represent only low-level information from a different modality (i.e. taste).

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 super-ficial 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).

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.

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.

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 (IER) task to compare interoceptive and exteroceptive recall among 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 fMRI, 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 controls, depressed participants exhibited marked hypo-activation of the right dorsal mid-insula during interoceptive recall. Conclusions In non-depressed 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 hypo-activation 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.

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., Highlights • We explored behavioral reactivity to taste in autism spectrum disorder (ASD). • In ASD subjects, taste reactivity was related to the brain's response to tastants. • Taste reactivity predicted tastant response in gustatory and social brain regions. • Taste reactivity predicted connectivity between gustatory and social brain regions.

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.

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.

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.

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.

Anorexia nervosa (AN) is a devastating psychiatric illness that is associated with significant morbidity and mortality. Aberrant visceral interoceptive processing within the insula has been hypothesized to be an important mechanism in AN's pathophysiology due to the theoretical link between interoception and emotional experience. We therefore utilized functional magnetic resonance imaging (fMRI) to examine whether altered insula functioning underlies visceral interoception in AN. Fifteen females with restricting-type AN and 15 healthy control females underwent fMRI while performing an interoceptive attention task during which they focused on sensations in their heart, stomach, and bladder. Participants also performed an anxious rumination task while in the scanner. AN participants were weight-restored and free of psychotropic medications. Two distinct regions of the insula—anterior insula and dorsal mid-insula—exhibited a significant (p

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.

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 (Johnson et al., 2014). 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 (Avery et al., 2017; Avery et al., 2015; Simmons et al., 2013b). 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 vs. 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.

Trait impulsivity is characterized by behavioral disinhibition and rash decision-making that contribute to many maladaptive behaviors. Previous research demonstrates that trait impulsivity is related to the activity of brain regions underlying reward sensitivity and emotion regulation, but little is known about this relationship in the context of immediately available primary reward. This is unfortunate, as impulsivity in these contexts can lead to unhealthy behaviors, including poor food choices, dangerous drug use and risky sexual practices. In addition, little is known about the relationship between integration of reward and affective neurocircuitry, as measured by resting-state functional connectivity, and trait impulsivity in everyday life, as measured with a commonly used personality inventory. We therefore asked healthy adults to undergo a functional magnetic resonance imaging task in which they saw cues indicating the imminent oral administration of rewarding taste, as well as a resting-state scan. Trait impulsivity was associated with increased activation during anticipation of primary reward in the anterior cingulate cortex (ACC) and amygdala. Additionally, resting-state functional connectivity between the ACC and the right amygdala was negatively correlated with trait impulsivity. These findings demonstrate that trait impulsivity is related not only to ACC-amygdala activation but also to how tightly coupled these regions are to one another.

Food advertisements often promote choices that are driven by inferences about the hedonic pleasures of eating a particular food. Given the individual and public health consequences of obesity, it is critical to address unanswered questions about the specific neural systems underlying these hedonic inferences. For example, although regions such as the orbitofrontal cortex (OFC) are frequently observed to respond more to pleasant food images than less hedonically pleasing stimuli, one important hedonic brain region in particular has largely remained conspicuously absent among human studies of hedonic response to food images. Based on rodent research demonstrating that activity in the ventral pallidum underlies the hedonic pleasures experienced upon eating food rewards, one might expect that activity in this important 'hedonic hotspot' might also track inferred food pleasantness. To date, however, no human studies have assessed this question. We thus asked human subjects to undergo fMRI and make item-by-item ratings of how pleasant it would be to eat particular visually perceived foods. Activity in the ventral pallidum was strongly modulated with pleasantness inferences. Additionally, activity within a region of the orbitofrontal cortex that tracks the pleasantness of tastes was also modulated with inferred pleasantness. Importantly, the reliability of these findings is demonstrated by their replication when we repeated the experiment at a new site with new subjects. These two experiments demonstrate that the ventral pallidum, in addition to the OFC, plays a central role in the moment-to-moment hedonic inferences that influence food-related decision-making.

Appetite and weight changes are common but variable diagnostic markers in major depressive disorder: some depressed individuals manifest increased appetite, while others lose their appetite. Many of the brain regions implicated in appetitive responses to food have also been implicated in depression. It is thus remarkable that there exists no published research comparing the neural responses to food stimuli of depressed patients with increased versus decreased appetites.Using functional MRI, brain activity was compared in unmedicated depressed patients with increased or decreased appetite and healthy control subjects while viewing photographs of food and nonfood objects. The authors also measured how resting-state functional connectivity related to subjects' food pleasantness ratings.Within putative reward regions, depressed participants with increased appetites exhibited greater hemodynamic activity to food stimuli than both those reporting appetite decreases and healthy control subjects. In contrast, depressed subjects experiencing appetite loss exhibited hypoactivation within a region of the mid-insula implicated in interoception, with no difference observed in this region between healthy subjects and those with depression-related appetite increases. Mid-insula activity was negatively correlated with food pleasantness ratings of depressed participants with increased appetites, and its functional connectivity to reward circuitry was positively correlated with food pleasantness ratings.Depression-related increases in appetite are associated with hyperactivation of putative mesocorticolimbic reward circuitry, while depression-related appetite loss is associated with hypoactivation of insular regions that support monitoring the body's physiological state. Importantly, the interactions among these regions also contribute to individual differences in the depression-related appetite changes.

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.

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 [Avery et al., 2014; Craig, 2002; Simmons et al., 2013a], 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 [Hanamori et al., 1998; Veldhuizen et al., 2011], other recent studies have implicated this same region of the insula in interoception [Avery et al., 2014; Craig, 2002; Simmons et al., 2013a]. 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 [Hanamori et al., 1998; Veldhuizen et al., 2011], 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.

Background Somatic complaints and altered interoceptive awareness are common features in the clinical presentation of major depressive disorder (MDD). Recently, neurobiological evidence has accumulated demonstrating that the insula is one of the primary cortical structures underlying interoceptive awareness. Abnormal interoceptive representation within the insula may thus contribute to the pathophysiology and symptomatology of MDD. Methods We compared functional magnetic resonance imaging blood oxygenation level-dependent responses between 20 unmedicated adults with MDD and 20 healthy control participants during a task requiring attention to visceral interoceptive sensations and also assessed the relationship of this blood oxygenation level-dependent response to depression severity, as rated using the Hamilton Depression Rating Scale. Additionally, we examined between-group differences in insula resting-state functional connectivity and its relationship to Hamilton Depression Rating Scale ratings of depression severity. Results Relative to the healthy control subjects, unmedicated MDD subjects exhibited decreased activity bilaterally in the dorsal mid-insula cortex (dmIC) during interoception. Activity within the insula during the interoceptive attention task was negatively correlated with both depression severity and somatic symptom severity in depressed subjects. Major depressive disorder also was associated with greater resting-state functional connectivity between the dmIC and limbic brain regions implicated previously in MDD, including the amygdala, subgenual prefrontal cortex, and orbitofrontal cortex. Moreover, functional connectivity between these regions and the dmIC was positively correlated with depression severity. Conclusions Major depressive disorder and the somatic symptoms of depression are associated with abnormal interoceptive representation within the insula.

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. Hum Brain Mapp 34:2944–2958, 2013. © 2012 Wiley Periodicals, Inc.

The nematode Caenorhabditis Elegans has become an important model organism for many areas of biological research including genetics, development, and neurobiology. It is the first organism to have its genome sequenced, complete cell ontogeny determined, and nervous system mapped. With all of the information that is available on this simple organism, \emph{C. elegans} may also become the first organism to be accurately and completely modeled in silico. In this work we take a step toward this goal by presenting a biologically accurate, 3-dimensional model of C. elegans. This model takes into account many facets of the organism including size, shape, weight distribution, muscle placement, and muscle force. We also explicitly model the environment of the worm to include factors such as contact, friction, inertia, and gravity. We tuned and validated our model using video recordings taken of the worm and show that our model accurately depicts the physics of undulatory locomotion used to forward crawl on an agarose surface. We also present evidence that suggests that the forces applied by the nematode during locomotion are not uniform, but decrease as the wave is propagated from its head to its tail.

Background and Purpose— Several carotid endarterectomy randomized, controlled trials and series have reported higher perioperative stroke and death rates for women compared with men. The potential for this same relationship with carotid artery stenting was examined in the lead-in phase of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). Methods— CREST compares efficacy of carotid endarterectomy and carotid artery stenting in preventing stroke, myocardial infarction, and death in the periprocedural period and ipsilateral stroke over the follow-up period. CREST included a “lead-in” phase of symptomatic (≥50% stenosis) and asymptomatic (≥70% stenosis) patients. Patients were examined by a neurologist preprocedure, at 24 hours, and at 30 days. Review of stroke and death was by an independent events committee. The association of sex with periprocedural stroke and death was examined in 1564 patients undergoing carotid artery stenting (26.5% symptomatic). Results— Women comprised 37% of the lead-in cohort and did not differ from men by age, symptomatic status, or characteristics of the internal carotid artery. The 30-day stroke and death rate for women was 4.5% (26 of 579; 95% CI, 3.0% to 6.5%) compared with 4.2% (41 of 985; 95% CI, 3.0% to 5.6%) for men. The difference in stroke and death rate was not significant nor were there any significant differences by sex after adjustment for age, arterial characteristics, or cardiovascular risk factors. Conclusions— These results do not provide evidence that women have a higher carotid artery stenting stroke and death rate compared with men. The potential differential periprocedural risk by sex will be prospectively addressed in the randomized phase of CREST.

Prevailing theories hold that the insula is functionally organized along its caudal-to-rostral axis, with posterior regions coding lower-level sensory information, and anterior regions coding higher-level stimulus significance relative to the body’s homeostatic needs. Contrary to predictions of this model, the response of the taste-sensitive region of the caudal, but not rostral, insula to food images was directly related to the body’s homeostatic state as indexed by levels of peripheral glucose.

Social and behavioral scientists have a great deal to offer to public and private sector efforts directed toward health promotion and disease prevention. This chapter focuses on stress, coping, and social support. Research questions in these domains revolve around the interconnections among individuals’ emotions, motivation, goals, cognitions, and social relationships. The utility of such research lies in establishing behavioral predictors of individuals’ likelihood of becoming ill and the ease of their recovery from illness (Clark, 1994). A second contribution lies in the abilities of these fields to inform and guide health promotion and disease prevention intervention.

Purpose: This study was undertaken to determine whether the Adult Identity Mentoring (AIM) project successfully promotes abstinence, delays initiation of sex, and decreases intention to engage in sex. Methods: Twenty middle school classes of African-American seventh graders were randomly assigned to receive either the AIM intervention or a standard health education control curriculum. The AIM is a 10-session curriculum based on the theory of possible selves. Class exercises encourage students to articulate a possible future self-identity and to develop self-promotion skills. Surveys about sexual activity were conducted before the intervention, 19 weeks after baseline, and again at 1 year after the intervention. Results: Hierarchical logistic regression analyses showed significant effects for the intervention on sexual intentions, abstinence, and a trend toward fewer virgins initiating intercourse for the first time, 19 weeks after baseline. Specifically, students who received the intervention showed decreased intention to engage in sex and increased abstinence compared with students not receiving the intervention. Effects for 1-year follow-up, with smaller sample size, showed only that AIM male participants maintained the significant abstinence effect. Conclusions: A new intervention, AIM was evaluated among African-American seventh graders. This program, by focusing students on positive future selves, effectively modified sexual risk without directly providing instruction on sexually explicit topics. © 2005 Society for Adolescent Medicine. All rights reserved.