Cognitive influences on the affective representation of touch and the sight of touch in the human brain

We show that the affective experience of touch and the sight of touch can be modulated by cognition, and investigate in an fMRI study where top-down cognitive modulations of bottom-up somatosensory and visual processing of touch and its affective value occur in the human brain. The cognitive modulation was produced by word labels, ‘Rich moisturizing cream’ or ‘Basic cream’, while cream was being applied to the forearm, or was seen being applied to a forearm. The subjective pleasantness and richness were modulated by the word labels, as were the fMRI activations to touch in parietal cortex area 7, the insula and ventral striatum. The cognitive labels influenced the activations to the sight of touch and also the correlations with pleasantness in the pregenual cingulate/orbitofrontal cortex and ventral striatum. Further evidence of how the orbitofrontal cortex is involved in affective aspects of touch was that touch to the forearm [which has C fiber Touch (CT) afferents sensitive to light touch] compared with touch to the glabrous skin of the hand (which does not) revealed activation in the mid-orbitofrontal cortex. This is of interest as previous studies have suggested that the CT system is important in affiliative caress-like touch between individuals.     

The affective and cognitive processing of touch, oral texture, and temperature in the brain

Some of the principles of the representation of affective touch in the brain are described. Positively affective touch and temperature are represented in parts of the orbitofrontal and pregenual cingulate cortex. The orbitofrontal cortex is implicated in some of the affective aspects of touch that may be mediated through C fibre touch afferents, in that it is activated more by light touch to the forearm (a source of C-tactile (CT) afferents) than by light touch to the glabrous skin of the hand. Oral somatosensory afferents implicated in sensing the texture of food including fat in the mouth also activate the orbitofrontal and pregenual cingulate cortex, as well as the insular taste cortex. Top-down cognitive modulation of the representation of affective touch produced by word labels is found in parietal cortex area 7, the insula and ventral striatum. The cognitive labels also influence activations to the sight of touch and also the correlations with pleasantness in the pregenual cingulate/orbitofrontal cortex and ventral striatum.     

Distinct portions of anterior cingulate cortex and medial prefrontal cortex are activated by reward processing in separable phases of decision-making cognition.

BACKGROUND: Choosing between actions associated with uncertain rewards and punishments is mediated by neural circuitry encompassing the orbitofrontal cortex, anterior cingulate cortex (ACC), and striatum; however, the precise conditions under which these different components are activated during decision-making cognition remain uncertain. METHODS: Fourteen healthy volunteers completed an event-based functional magnetic resonance imaging protocol to investigate blood-oxygenation-level-dependent (BOLD) responses during independently modeled phases of choice cognition. In the "decision phase," participants decided which of two simultaneous visually presented gambles they wished to play for monetary reward. The gambles differed in their magnitude of gains, magnitude of losses, and the probabilities with which these outcomes were delivered. In the "outcome phase," the result of each choice was indicated on the visual display. RESULTS: In the decision phase, choices involving large gains were associated with increased BOLD responses in the pregenual ACC, paracingulate, and right posterior orbitolateral cortex compared with choices involving small gains. In the outcome phase, good outcomes were associated with increased BOLD responses in the posterior orbitomedial cortex, subcallosal ACC, and ventral striatum compared with negative outcomes. There was only limited overlap between reward-related activity in ACC and orbitofrontal cortex during the decision and outcome phases. CONCLUSIONS: Neural activity within the medial and lateral orbitofrontal cortex, pregenual ACC, and striatum mediate distinct representations of reward-related information that are deployed at different stages during a decision-making episode.     

Selective attention to affective value alters how the brain processes taste stimuli

How does selective attention to affect influence sensory processing? In an fMRI investigation, when subjects were instructed to remember and rate the pleasantness of a taste stimulus, 0.1 m monosodium glutamate, activations were greater in the medial orbitofrontal and pregenual cingulate cortex than when subjects were instructed to remember and rate the intensity of the taste. When the subjects were instructed to remember and rate the intensity, activations were greater in the insular taste cortex. An interaction analysis showed that this dissociation of taste processing, depending on whether attention to pleasantness or intensity was relevant, was highly significant (P < 0.0002). Thus, depending on the context in which tastes are presented and whether affect is relevant, the brain responds to a taste differently. These findings show that, when attention is paid to affective value, the brain systems engaged to represent the sensory stimulus of taste are different from those engaged when attention is directed to the physical properties of a stimulus such as its intensity. This differential biasing of brain regions engaged in processing a sensory stimulus, depending on whether the cognitive demand is for affect‐related vs. more sensory‐related processing, may be an important aspect of cognition and attention. This has many implications for understanding the effects not only of taste but also of other sensory stimuli.     

From affective value to decision-making in the prefrontal cortex

Representing the affective value of a reward on a continuous scale may occur separately from making a binary, for example yes vs no, decision about whether to choose the reward. To investigate whether these are separable processes, we used functional magnetic resonance imaging to measure activations produced by pleasant warm, unpleasant cold, and affectively complex combinations of these stimuli applied to the hand. On some trials the affective value was rated on a continuous scale, and on different trials a yes-no decision was made about whether the stimulus should be repeated in future. Decision-making contrasted with just rating the affective stimuli revealed activations in the medial prefrontal cortex area 10, implicating this area in binary decision-making. Activations related to the pleasantness ratings and which were not influenced when a binary decision was made were found in the pregenual cingulate and parts of the orbitofrontal cortex, implicating these regions in the continuous representation of affective value. When a decision was yes vs. no, effects were found in the dorsal cingulate cortex, agranular (anterior) insula and ventral tegmental area, implicating these areas in initiating actions to obtain goals.     

Different representations of pleasant and unpleasant odours in the human brain

Odours are important in emotional processing; yet relatively little is known about the representations of the affective qualities of odours in the human brain. We found that three pleasant and three unpleasant odours activated dissociable parts of the human brain. Pleasant but not unpleasant odours were found to activate a medial region of the rostral orbitofrontal cortex. Further, there was a correlation between the subjective pleasantness ratings of the six odours given during the investigation with activation of a medial region of the rostral orbitofrontal cortex. In contrast, a correlation between the subjective unpleasantness ratings of the six odours was found in regions of the left and more lateral orbitofrontal cortex. Moreover, a double dissociation was found with the intensity ratings of the odours, which were not correlated with the BOLD signal in the orbitofrontal cortex, but were correlated with the signal in medial olfactory cortical areas including the pyriform and anterior entorhinal cortex. Activation was also found in the anterior cingulate cortex, with a middle part of the anterior cingulate activated by both pleasant and unpleasant odours, and a more anterior part of the anterior cingulate cortex showing a correlation with the subjective pleasantness ratings of the odours. Thus the results suggest that there is a hedonic map of the sense of smell in brain regions such as the orbitofrontal cortex, and these results have implications for understanding the psychiatric and related problems that follow damage to these brain areas.     

Differential pattern of functional brain plasticity after compassion and empathy training

Although empathy is crucial for successful social interactions, excessive sharing of others’ negative emotions may be maladaptive and constitute a source of burnout. To investigate functional neural plasticity underlying the augmentation of empathy and to test the counteracting potential of compassion, one group of participants was first trained in empathic resonance and subsequently in compassion. In response to videos depicting human suffering, empathy training, but not memory training (control group), increased negative affect and brain activations in anterior insula and anterior midcingulate cortex—brain regions previously associated with empathy for pain. In contrast, subsequent compassion training could reverse the increase in negative effect and, in contrast, augment self-reports of positive affect. In addition, compassion training increased activations in a non-overlapping brain network spanning ventral striatum, pregenual anterior cingulate cortex and medial orbitofrontal cortex. We conclude that training compassion may reflect a new coping strategy to overcome empathic distress and strengthen resilience.     

How task demands shape brain responses to visual food cues

Several previous imaging studies have aimed at identifying the neural basis of visual food cue processing in humans. However, there is little consistency of the functional magnetic resonance imaging (fMRI) results across studies. Here, we tested the hypothesis that this variability across studies might – at least in part – be caused by the different tasks employed. In particular, we assessed directly the influence of task set on brain responses to food stimuli with fMRI using two tasks (colour vs. edibility judgement, between‐subjects design). When participants judged colour, the left insula, the left inferior parietal lobule, occipital areas, the left orbitofrontal cortex and other frontal areas expressed enhanced fMRI responses to food relative to non‐food pictures. However, when judging edibility, enhanced fMRI responses to food pictures were observed in the superior and middle frontal gyrus and in medial frontal areas including the pregenual anterior cingulate cortex and ventromedial prefrontal cortex. This pattern of results indicates that task sets can significantly alter the neural underpinnings of food cue processing. We propose that judging low‐level visual stimulus characteristics – such as colour – triggers stimulus‐related representations in the visual and even in gustatory cortex (insula), whereas discriminating abstract stimulus categories activates higher order representations in both the anterior cingulate and prefrontal cortex. Hum Brain Mapp 38:2897–2912, 2017. © 2017 Wiley Periodicals, Inc.     

A non-reward attractor theory of depression

A non-reward attractor theory of depression is proposed based on the operation of the lateral orbitofrontal cortex and supracallosal cingulate cortex. The orbitofrontal cortex contains error neurons that respond to non-reward for many seconds in an attractor state that maintains a memory of the non-reward. The human lateral orbitofrontal cortex is activated by non-reward during reward reversal, and by a signal to stop a response that is now incorrect. Damage to the human orbitofrontal cortex impairs reward reversal learning. Not receiving reward can produce depression. The theory proposed is that in depression, this lateral orbitofrontal cortex non-reward system is more easily triggered, and maintains its attractor-related firing for longer. This triggers negative cognitive states, which in turn have positive feedback top-down effects on the orbitofrontal cortex non-reward system. Treatments for depression, including ketamine, may act in part by quashing this attractor. The mania of bipolar disorder is hypothesized to be associated with oversensitivity and overactivity in the reciprocally related reward system in the medial orbitofrontal cortex and pregenual cingulate cortex.     

Aerobic exercise modulates anticipatory reward processing via the μ‐opioid receptor system

Physical exercise modulates food reward and helps control body weight. The endogenous µ‐opioid receptor (MOR) system is involved in rewarding aspects of both food and physical exercise, yet interaction between endogenous opioid release following exercise and anticipatory food reward remains unresolved. Here we tested whether exercise‐induced opioid release correlates with increased anticipatory reward processing in humans. We scanned 24 healthy lean men after rest and after a 1 h session of aerobic exercise with positron emission tomography (PET) using MOR‐selective radioligand [¹¹C]carfentanil. After both PET scans, the subjects underwent a functional magnetic resonance imaging (fMRI) experiment where they viewed pictures of palatable versus nonpalatable foods to trigger anticipatory food reward responses. Exercise‐induced changes in MOR binding in key regions of reward circuit (amygdala, thalamus, ventral and dorsal striatum, and orbitofrontal and cingulate cortices) were used to predict the changes in anticipatory reward responses in fMRI. Exercise‐induced changes in MOR binding correlated negatively with the exercise‐induced changes in neural anticipatory food reward responses in orbitofrontal and cingulate cortices, insula, ventral striatum, amygdala, and thalamus: higher exercise‐induced opioid release predicted higher brain responses to palatable versus nonpalatable foods. We conclude that MOR activation following exercise may contribute to the considerable interindividual variation in food craving and consumption after exercise, which might promote compensatory eating and compromise weight control.     

Dissociation of BOLD responses to reward prediction errors and reward receipt by a model comparison

The representation of reward anticipation and reward prediction errors is the basis for reward-associated learning. The representation of whether or not a reward occurred (reward receipt) is important for decision making. Recent studies suggest that, while reward anticipation and reward prediction errors are encoded in the midbrain and the ventral striatum, reward receipts are encoded in the medial orbitofrontal cortex. In order to substantiate this functional specialization we analyzed data from an fMRI study in which 59 subjects completed two simple monetary reward paradigms. Because reward receipts and reward prediction errors were correlated, a statistical model comparison was applied separating the effects of the two. Reward prediction error fitted BOLD responses significantly better than reward receipt in the midbrain and the ventral striatum. Conversely, reward receipt fitted BOLD responses better in the orbitofrontal cortex. Activation related to reward anticipation was found in the orbitofrontal cortex. The results confirm a functional specialization of behaviorally important aspects of reward processing within the mesolimbic dopaminergic system.     

Umami: a delicious flavor formed by convergence of taste and olfactory pathways in the human brain

Umami taste is produced by glutamate acting on a fifth taste system. However, glutamate presented alone as a taste stimulus is not highly pleasant, and does not act synergistically with other tastes (sweet, salt, bitter and sour). We show here that when glutamate is given in combination with a consonant, savory, odour (vegetable), the resulting flavor can be much more pleasant. Moreover, we showed using functional brain imaging with fMRI that the glutamate taste and savory odour combination produced much greater activation of the medial orbitofrontal cortex and pregenual cingulate cortex than the sum of the activations by the taste and olfactory components presented separately. Supralinear effects were much less (and significantly less) evident for sodium chloride and vegetable odour. Further, activations in these brain regions were correlated with the pleasantness and fullness of the flavor, and with the consonance of the taste and olfactory components. Supralinear effects of glutamate taste and savory odour were not found in the insular primary taste cortex. We thus propose that glutamate acts by the nonlinear effects it can produce when combined with a consonant odour in multimodal cortical taste-olfactory convergence regions. We propose the concept that umami can be thought of as a rich and delicious flavor that is produced by a combination of glutamate taste and a consonant savory odour. Glutamate is thus a flavor enhancer because of the way that it can combine supralinearly with consonant odours in cortical areas where the taste and olfactory pathways converge far beyond the receptors.     

Taste-olfactory convergence, and the representation of the pleasantness of flavour, in the human brain

The functional architecture of the central taste and olfactory systems in primates provides evidence that the convergence of taste and smell information onto single neurons is realized in the caudal orbitofrontal cortex (and immediately adjacent agranular insula). These higher-order association cortical areas thus support flavour processing. Much less is known, however, about homologous regions in the human cortex, or how taste-odour interactions, and thus flavour perception, are implemented in the human brain. We performed an event-related fMRI study to investigate where in the human brain these interactions between taste and odour stimuli (administered retronasally) may be realized. The brain regions that were activated by both taste and smell included parts of the caudal orbitofrontal cortex, amygdala, insular cortex and adjoining areas, and anterior cingulate cortex. It was shown that a small part of the anterior (putatively agranular) insula responds to unimodal taste and to unimodal olfactory stimuli, and that a part of the anterior frontal operculum is a unimodal taste area (putatively primary taste cortex) not activated by olfactory stimuli. Activations to combined olfactory and taste stimuli where there was little or no activation to either alone (providing positive evidence for interactions between the olfactory and taste inputs) were found in a lateral anterior part of the orbitofrontal cortex. Correlations with consonance ratings for the smell and taste combinations, and for their pleasantness, were found in a medial anterior part of the orbitofrontal cortex. These results provide evidence on the neural substrate for the convergence of taste and olfactory stimuli to produce flavour in humans, and where the pleasantness of flavour is represented in the human brain.     

Fasting biases brain reward systems towards high-calorie foods

Nutritional state (e.g. fasted vs. fed) and different food stimuli (e.g. high-calorie vs. low-calorie, or appetizing vs. bland foods) are both recognized to change activity in brain reward systems. Using functional magnetic resonance imaging, we have studied the interaction between nutritional state and different food stimuli on brain food reward systems. We examined how blood oxygen level-dependent activity within a priori regions of interest varied while viewing pictures of high-calorie and low-calorie foods. Pictures of non-food household objects were included as control stimuli. During scanning, subjects rated the appeal of each picture. Twenty non-obese healthy adults [body mass index 22.1 ± 0.5 kg/m² (mean ± SEM), age range 19–35 years, 10 male] were scanned on two separate mornings between 11:00 and 12:00 h, once after eating a filling breakfast ('fed': 1.6 ± 0.1 h since breakfast), and once after an overnight fast but skipping breakfast ('fasted': 15.9 ± 0.3 h since supper) in a randomized cross-over design. Fasting selectively increased activation to pictures of high-calorie over low-calorie foods in the ventral striatum, amygdala, anterior insula, and medial and lateral orbitofrontal cortex (OFC). Furthermore, fasting enhanced the subjective appeal of high-calorie more than low-calorie foods, and the change in appeal bias towards high-calorie foods was positively correlated with medial and lateral OFC activation. These results demonstrate an interaction between homeostatic and hedonic aspects of feeding behaviour, with fasting biasing brain reward systems towards high-calorie foods.     

Anticipating control over aversive stimuli is mediated by the medial prefrontal cortex: An fMRI study with healthy adults

The anticipation of control over aversive events in life is relevant for our mental health. Insights on the underlying neural mechanisms remain limited. We developed a new functional magnetic resonance imaging (fMRI) task that uses auditory stimuli to explore the neural correlates of (1) the anticipation of control over aversion and (2) the processing of aversion. In a sample of 25 healthy adults, we observed increased neural activation in the medial prefrontal cortex (ventromedial prefrontal cortex and rostral anterior cingulate cortex), other brain areas relevant for reward anticipation (ventral striatum, brainstem [ventral tegmental area], midcingulate cortex), and the posterior cingulate cortex when they anticipated control over aversion compared with anticipating no control (1). The processing of aversive sounds compared to neutral sounds (2) was associated with increased neural activation in the bilateral posterior insula. Our findings provide evidence for the important role of medial prefrontal regions in control anticipation and highlight the relevance of conceiving the neural mechanisms involved within a reward‐based framework.     

Sex differences in neural responses to stress and alcohol context cues

Stress and alcohol context cues are each associated with alcohol-related behaviors, yet neural responses underlying these processes remain unclear. This study investigated the neural correlates of stress and alcohol context cue experiences and examined sex differences in these responses. Using functional magnetic resonance imaging, brain responses were examined while 43 right-handed, socially drinking, healthy individuals (23 females) engaged in brief guided imagery of personalized stress, alcohol-cue, and neutral-relaxing scenarios. Stress and alcohol-cue exposure increased activity in the cortico-limbic-striatal circuit (P < 0.01, corrected), encompassing the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), left anterior insula, striatum, and visuomotor regions (parietal and occipital lobe, and cerebellum). Activity in the left dorsal striatum increased during stress, while bilateral ventral striatum activity was evident during alcohol-cue exposure. Men displayed greater stress-related activations in the mPFC, rostral ACC, posterior insula, amygdala, and hippocampus than women, whereas women showed greater alcohol-cue-related activity in the superior and middle frontal gyrus (SFG/MFG) than men. Stress-induced anxiety was positively associated with activity in emotion-modulation regions, including the medial OFC, ventromedial PFC, left superior-mPFC, and rostral ACC in men, but in women with activation in the SFG/MFG, regions involved in cognitive processing. Alcohol craving was significantly associated with the striatum (encompassing dorsal, and ventral) in men, supporting its involvement in alcohol "urge" in healthy men. These results indicate sex differences in neural processing of stress and alcohol-cue experiences and have implications for sex-specific vulnerabilities to stress- and alcohol-related psychiatric disorders.     

Regional cerebral glucose metabolic abnormalities in bipolar II depression.

BACKGROUND: Functional neuroimaging studies of bipolar disorder (BD) performed in conjunction with antidepressant treatment trials generally require that patients remain on mood stabilizers to reduce the risk of inducing mania; yet, it is unknown whether the metabolic abnormalities evident in unmedicated BD depressives remain detectable in patients receiving mood stabilizers. This study investigated whether cerebral metabolic abnormalities previously reported in unmedicated BD subjects are evident in depressed bipolar disorder type II (BD II) subjects receiving lithium or divalproex. METHODS: Using [18F]-fluorodeoxyglucose-positron-emission tomography, cerebral glucose metabolism was compared between 13 depressed BD II subjects on therapeutic doses of lithium or divalproex and 18 healthy control subjects. Regional metabolism was compared between groups in predefined regions of interest. RESULTS: Metabolism was increased in the bilateral amygdala, accumbens area, and anteroventral putamen, left orbitofrontal cortex and right pregenual anterior cingulate cortex in depressives versus control subjects. Post hoc exploratory analysis additionally revealed increased metabolism in left parahippocampal, posterior cingulate, and right anterior insular cortices in depressives versus control subjects. Correlational analyses showed multiple limbic-cortical-striatal interactions in the BD sample not evident in the control sample, permitting sensitive and specific classification of subjects by discriminant analysis. CONCLUSIONS: These results confirm previous reports that bipolar depression is associated with abnormally increased metabolism in the amygdala, ventral striatum, orbitofrontal cortex, anterior cingulate, and anterior insula, and extend these results to bipolar disorder type II depressives on lithium or divalproex. They also implicate an extended functional anatomical network known to modulate visceromotor function in the pathophysiology of BD II depression.     

The social evaluation of faces: a meta-analysis of functional neuroimaging studies

Neuroscience research on the social evaluation of faces has accumulated over the last decade, yielding divergent results. We used a meta-analytic technique, multi-level kernel density analysis (MKDA), to analyze 29 neuroimaging studies on face evaluation. Across negative face evaluations, we observed the most consistent activations in bilateral amygdala. Across positive face evaluations, we observed the most consistent activations in medial prefrontal cortex, pregenual anterior cingulate cortex (pgACC), medial orbitofrontal cortex (mOFC), left caudate and nucleus accumbens (NAcc). Based on additional analyses comparing linear and non-linear responses, we propose a ventral/dorsal dissociation within the amygdala, wherein separate populations of neurons code for face valence and intensity, respectively. Finally, we argue that some of the differences between studies are attributable to differences in the typicality of face stimuli. Specifically, extremely attractive faces are more likely to elicit responses in NAcc/caudate and mOFC.     

Ventral striatum/nucleus accumbens activation to smoking-related pictorial cues in smokers and nonsmokers: a functional magnetic resonance imaging study.

BACKGROUND: Converging evidence from several theories of the development of incentive-sensitization to smoking-related environmental stimuli suggests that the ventral striatum plays an important role in the processing of smoking-related cue reactivity. METHODS: Twenty-six healthy right-handed volunteers (14 smokers and 12 nonsmoking controls) underwent functional magnetic resonance imaging (fMRI) during which neutral and smoking-related images were presented. Region of interest analyses were performed within the ventral striatum/nucleus accumbens (VS/NAc) for the contrast between smoking-related (SR) and nonsmoking related neutral (N) cues. RESULTS: Group activation for SR versus N cues was observed in smokers but not in nonsmokers in medial orbitofrontal cortex, superior frontal gyrus, anterior cingulate cortex, and posterior fusiform gyrus using whole-brain corrected Z thresholds and in the ventral VS/NAc using uncorrected Z-statistics (smokers Z = 3.2). Region of interest analysis of signal change within ventral VS/NAc demonstrated significantly greater activation to SR versus N cues in smokers than controls. CONCLUSIONS: This is the first demonstration of greater VS/NAc activation in addicted smokers than nonsmokers presented with smoking-related cues using fMRI. Smokers, but not controls, demonstrated activation to SR versus N cues in a distributed reward signaling network consistent with cue reactivity studies of other drugs of abuse.     

Microstimulation of primate neocortex targeting striosomes induces negative decision‐making

Here, we combined MRI‐guided electrical microstimulation and viral tracing to examine the function of a corticostriatal circuit implicated by previous cortical microstimulation as modulating affective judgment and decision‐making. Local microstimulation of a small part of the pregenual anterior cingulate cortex (pACC) was found to increase avoidance decisions in a cost‐benefit decision‐making task (Ap‐Av task) in which differing amounts of “good” and “bad” options were given simultaneously. No effect of such stimulation was found when the monkeys performed a task in which both offers were rewarding, but given in different amounts. We asked whether we could identify the targets of such corticostriatal circuits when the cortical microstimulation sites were explicitly identified as affecting approach or avoidance in the Ap‐Av task. We explored the pACC and caudal orbitofrontal cortex (cOFC) to look for such sites. For each cortical region, we found sites at which microstimulation induced increased avoidance behavior. After identifying these sites, we injected viral tracers carrying constructs allowing subsequent track‐tracing post‐mortem. For each site identified behaviorally as increasing avoidance choices, we found strong fiber projections to the anterior striatum with large parts of these targeting striosomes subsequently identified by serial section immunohistochemistry. With fMRI, we demonstrated that microstimulation in an anesthetized monkey at sites pre‐identified as affecting Ap‐Av choices induced blood oxygen level dependent activation of the anterior striatum, confirming that the microstimulation method that we applied was effective in activating the striatum. These findings outline circuits leading from pACC/cOFC to striosomes and causally modulating decision‐making under emotional conflict.