Adult attachment style is associated with cerebral μ‐opioid receptor availability in humans

Human attachment behavior mediates establishment and maintenance of social relationships. Adult attachment characteristically varies on anxiety and avoidance dimensions, reflecting the tendencies to worry about the partner breaking the social bond (anxiety) and feeling uncomfortable about depending on others (avoidance). In primates and other mammals, the endogenous μ‐opioid system is linked to long‐term social bonding, but evidence of its role in human adult attachment remains more limited. We used in vivo positron emission tomography to reveal how variability in μ‐opioid receptor (MOR) availability is associated with adult attachment in humans. We scanned 49 healthy subjects using a MOR‐specific ligand [¹¹C]carfentanil and measured their attachment avoidance and anxiety with the Experiences in Close Relationships‐Revised scale. The avoidance dimension of attachment correlated negatively with MOR availability in the thalamus and anterior cingulate cortex, as well as the frontal cortex, amygdala, and insula. No associations were observed between MOR availability and the anxiety dimension of attachment. Our results suggest that the endogenous opioid system may underlie interindividual differences in avoidant attachment style in human adults, and that differences in MOR availability are associated with the individuals’ social relationships and psychosocial well‐being. Hum Brain Mapp 36:3621–3628, 2015. © 2015 Wiley Periodicals, Inc.     

Low‐ and high‐frequency transcutaneous electrical acupoint stimulation induces different effects on cerebral μ‐opioid receptor availability in rhesus monkeys

Although systematic studies have demonstrated that acupuncture or electroacupuncture (EA) analgesia is based on their accelerating endogenous opioid release to activate opioid receptors and that EA of different frequencies is mediated by different opioid receptors in specific areas of the central nervous system, there is little direct, real‐time evidence to confirm this in vivo. The present study was designed to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS), an analogue of EA, at low and high frequencies on μ‐opioid receptor (MOR) availability in the brain of rhesus monkeys. Monkeys underwent 95‐min positron emission tomography (PET) with ¹¹C‐carfentanil three times randomly while receiving 0, 2, or 100 Hz TEAS, respectively. Each TEAS was administered in the middle 30 min during the 95‐min PET scan, and each session of PET and TEAS was separated by at least 2 weeks. The results revealed that 2 Hz but not 100 Hz TEAS evoked a significant increase in MOR binding potential in the anterior cingulate cortex, the caudate nucleus, the putamen, the temporal lobe, the somatosensory cortex, and the amygdala compared with 0 Hz TEAS. The effect remained after the end of TEAS in the anterior cingulate cortex and the temporal lobe. The selective increase in MOR availability in multiple brain regions related to pain and sensory processes may play a role in mediating low‐frequency TEAS efficacy. © 2014 Wiley Periodicals, Inc.     

The anticipation and outcome phases of reward and loss processing: A neuroimaging meta‐analysis of the monetary incentive delay task

The processing of rewards and losses are crucial to everyday functioning. Considerable interest has been attached to investigating the anticipation and outcome phases of reward and loss processing, but results to date have been inconsistent. It is unclear if anticipation and outcome of a reward or loss recruit similar or distinct brain regions. In particular, while the striatum has widely been found to be active when anticipating a reward, whether it activates in response to the anticipation of losses as well remains ambiguous. Furthermore, concerning the orbitofrontal/ventromedial prefrontal regions, activation is often observed during reward receipt. However, it is unclear if this area is active during reward anticipation as well. We ran an Activation Likelihood Estimation meta‐analysis of 50 fMRI studies, which used the Monetary Incentive Delay Task (MIDT), to identify which brain regions are implicated in the anticipation of rewards, anticipation of losses, and the receipt of reward. Anticipating rewards and losses recruits overlapping areas including the striatum, insula, amygdala and thalamus, suggesting that a generalised neural system initiates motivational processes independent of valence. The orbitofrontal/ventromedial prefrontal regions were recruited only during the reward outcome, likely representing the value of the reward received. Our findings help to clarify the neural substrates of the different phases of reward and loss processing, and advance neurobiological models of these processes.     

The neural substrates of affective processing toward positive and negative affective pictures in patients with major depressive disorder

Previous studies examining neural responses to emotional stimuli in individuals with major depressive disorder (MDD) have indicated increased responses within the left amygdala to sad faces, and increased activity within the visual cortex and striatum to expressions of happiness. Using functional magnetic resonance imaging (fMRI), the current study measured neural responses to neutral, positive and negative pictures of the International Affective Picture System in 15 healthy individuals and 15 patients with MDD. Depressed individuals demonstrated lower activity in the right hippocampus and the right insula to negative affective pictures, whereas they showed lower activity in the right anterior cingulate cortex and the left insula to positive pictures. However, within the MDD group, the severity of depression correlated with the activity of the left amygdala, bilateral inferior orbitofrontal areas, and the left insula to negative pictures, whereas there were no clear indications of association between specific cerebral regions and positive pictures. Our findings indicate that preferential decreases in the left amygdala in response to negative pictures might be involved in the processing of emotional stimuli in depressed individuals. Also, these findings suggest that the bilateral inferior orbitofrontal cortices and left amygdala may be preferentially recruited in MDD patients, but not in healthy individuals.     

Functional centrality of amygdala,striatum and hypothalamus in a “small‐world” network underlying joy: An fMRI study with music

Current knowledge about small‐world networks underlying emotions is sparse, and confined to functional magnetic resonance imaging (fMRI) studies using resting‐state paradigms. This fMRI study applied Eigenvector Centrality Mapping (ECM) and functional connectivity analysis to reveal neural small‐world networks underlying joy and fear. Joy and fear were evoked using music, presented in 4‐min blocks. Results show that the superficial amygdala (SF), laterobasal amygdala (LB), striatum, and hypothalamus function as computational hubs during joy. Out of these computational hubs, the amygdala nuclei showed the highest centrality values. The SF showed functional connectivity during joy with the mediodorsal thalamus (MD) and nucleus accumbens (Nac), suggesting that SF, MD, and Nac modulate approach behavior in response to positive social signals such as joyful music. The striatum was functionally connected during joy with the LB, as well as with premotor cortex, areas 1 and 7a, hippocampus, insula and cingulate cortex, showing that sensorimotor, attentional, and emotional processes converge in the striatum during music perception. The hypothalamus showed functional connectivity during joy with hippocampus and MD, suggesting that hypothalamic endocrine activity is modulated by hippocampal and thalamic activity during sustained periods of music‐evoked emotion. Our study indicates high centrality of the amygdala nuclei groups within a functional network underlying joy, suggesting that these nuclei play a central role for the modulation of emotion‐specific activity within this network. Hum Brain Mapp 35:3485–3498, 2014. © 2013 Wiley Periodicals, Inc .     

Ventral striatal network connectivity reflects reward learning and behavior in patients with Parkinson's disease

A subgroup of Parkinson's disease (PD) patients treated with dopaminergic therapy develop compulsive reward‐driven behaviors, which can result in life‐altering morbidity. The mesocorticolimbic dopamine network guides reward‐motivated behavior; however, its role in this treatment‐related behavioral phenotype is incompletely understood. Here, mesocorticolimbic network function in PD patients who develop impulsive and compulsive behaviors (ICB) in response to dopamine agonists was assessed using BOLD fMRI. The tested hypothesis was that network connectivity between the ventral striatum and the limbic cortex is elevated in patients with ICB and that reward‐learning proficiency reflects the extent of mesocorticolimbic network connectivity. To evaluate this hypothesis, 3.0T BOLD‐fMRI was applied to measure baseline functional connectivity on and off dopamine agonist therapy in age and sex‐matched PD patients with (n = 19) or without (n = 18) ICB. An incentive‐based task was administered to a subset of patients (n = 20) to quantify positively or negatively reinforced learning. Whole‐brain voxelwise analyses and region‐of‐interest‐based mixed linear effects modeling were performed. Elevated ventral striatal connectivity to the anterior cingulate gyrus (P = 0.013), orbitofrontal cortex (P = 0.034), insula (P = 0.044), putamen (P = 0.014), globus pallidus (P < 0.01), and thalamus (P < 0.01) was observed in patients with ICB. A strong trend for elevated amygdala‐to‐midbrain connectivity was found in ICB patients on dopamine agonist. Ventral striatum‐to‐subgenual cingulate connectivity correlated with reward learning (P < 0.01), but not with punishment‐avoidance learning. These data indicate that PD‐ICB patients have elevated network connectivity in the mesocorticolimbic network. Behaviorally, proficient reward‐based learning is related to this enhanced limbic and ventral striatal connectivity. Hum Brain Mapp 39:509–521, 2018. © 2017 Wiley Periodicals, Inc.     

Activation likelihood estimation meta‐analysis of brain correlates of placebo analgesia in human experimental pain

Placebo analgesia (PA) is one of the most studied placebo effects. Brain imaging studies published over the last decade, using either positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), suggest that multiple brain regions may play a pivotal role in this process. However, there continues to be much debate as to which areas consistently contribute to placebo analgesia‐related networks. In the present study, we used activation likelihood estimation (ALE) meta‐analysis, a state‐of‐the‐art approach, to search for the cortical areas involved in PA in human experimental pain models. Nine fMRI studies and two PET studies investigating cerebral hemodynamic changes were included in the analysis. During expectation of analgesia, activated foci were found in the left anterior cingulate, right precentral, and lateral prefrontal cortex and in the left periaqueductal gray (PAG). During noxious stimulation, placebo‐related activations were detected in the anterior cingulate and medial and lateral prefrontal cortices, in the left inferior parietal lobule and postcentral gyrus, anterior insula, thalamus, hypothalamus, PAG, and pons; deactivations were found in the left mid‐ and posterior cingulate cortex, superior temporal and precentral gyri, in the left anterior and right posterior insula, in the claustrum and putamen, and in the right thalamus and caudate body. Our results suggest on one hand that the modulatory cortical networks involved in PA largely overlap those involved in the regulation of emotional processes, on the other that brain nociceptive networks are downregulated in parallel with behavioral analgesia. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Acute “binge” cocaine increases mu-opioid receptor mRNA levels in areas of the rat mesolimbic mesocortical dopamine system

Autoradiography studies demonstrated that chronic “binge” cocaine administration increased mu-opioid receptor density in dopaminergically innervated rat brain regions, including the cingulate cortex, the nucleus accumbens, and the basolateral amygdala. The present study investigated the effects of a single day of binge-pattern cocaine administration (3 × 15 mg/kg, intraperitoneally [i.p.] at hourly intervals) on mu-opioid receptor mRNA levels in selected brain regions. Rats were sacrificed 30 min after the third injection and mRNA levels were measured by a quantitative solution hybridization RNase protection assay. Acute binge cocaine administration significantly increased mu-opioid receptor mRNA levels in the frontal cortex, nucleus accumbens, and amygdala, but not in the caudate-putamen, thalamus, hippocampus, and hypothalamus. As has been suggested for other G-protein coupled receptors, the rapid increase of MOR mRNA reported in this study might represent an adaptive response to compensate for a decrease in number of receptors following cocaine-induced opioid peptide release.     

Enhanced affective brain representations of chocolate in cravers vs. non-cravers

To examine the neural circuitry involved in food craving, in making food particularly appetitive and thus in driving wanting and eating, we used fMRI to measure the response to the flavour of chocolate, the sight of chocolate and their combination in cravers vs. non-cravers. Statistical parametric mapping (SPM) analyses showed that the sight of chocolate produced more activation in chocolate cravers than non-cravers in the medial orbitofrontal cortex and ventral striatum. For cravers vs. non-cravers, a combination of a picture of chocolate with chocolate in the mouth produced a greater effect than the sum of the components (i.e. supralinearity) in the medial orbitofrontal cortex and pregenual cingulate cortex. Furthermore, the pleasantness ratings of the chocolate and chocolate-related stimuli had higher positive correlations with the fMRI blood oxygenation level-dependent signals in the pregenual cingulate cortex and medial orbitofrontal cortex in the cravers than in the non-cravers. To our knowledge, this is the first study to show that there are differences between cravers and non-cravers in their responses to the sensory components of a craved food in the orbitofrontal cortex, ventral striatum and pregenual cingulate cortex, and that in some of these regions the differences are related to the subjective pleasantness of the craved foods. Understanding individual differences in brain responses to very pleasant foods helps in the understanding of the mechanisms that drive the liking for specific foods and thus intake of those foods.     

Neuronal correlates of reward and loss in Cluster B personality disorders: a functional magnetic resonance imaging study

Decision making is guided by the likely consequences of behavioural choices. Neuronal correlates of financial reward have been described in a number of functional imaging studies in humans. Areas implicated in reward include ventral striatum, dopaminergic midbrain, amygdala and orbitofrontal cortex. Response to loss has not been as extensively studied but may involve prefrontal and medial temporal cortices. It has been proposed that increased sensitivity to reward and reduced sensitivity to punishment underlie some of the psychopathology in impulsive personality disordered individuals. However, few imaging studies using reinforcement tasks have been conducted in this group. In this fMRI study, we investigate the effects of positive (monetary reward) and negative (monetary loss) outcomes on BOLD responses in two target selection tasks. The experimental group comprised eight people with Cluster B (antisocial and borderline) personality disorder, whilst the control group contained fourteen healthy participants. A key finding was the absence of prefrontal responses and reduced BOLD signal in the subcortical reward system in the PD group during positive reinforcement. Impulsivity scores correlated negatively with prefrontal responses in the PD but not the control group during both, reward and loss. Our results suggest dysfunctional responses to rewarding and aversive stimuli in Cluster B personality disordered individuals but do not support the notion of hypersensitivity to reward and hyposensitivity to loss.     

Spatial migration of human reward processing with functional development: Evidence from quantitative meta‐analyses

Functional magnetic resonance imaging (fMRI) studies have shown notable age‐dependent differences in reward processing. We analyzed data from a total of 554 children, 1,059 adolescents, and 1,831 adults from 70 articles. Quantitative meta‐analyses results show that adults engage an extended set of regions that include anterior and posterior cingulate gyri, insula, basal ganglia, and thalamus. Adolescents engage the posterior cingulate and middle frontal gyri as well as the insula and amygdala, whereas children show concordance in right insula and striatal regions almost exclusively. Our data support the notion of reorganization of function over childhood and adolescence and may inform current hypotheses relating to decision‐making across age.     

Effective connectivity of a reward network in obese women

Exaggerated reactivity to food cues in obese women appears to be mediated in part by a hyperactive reward system that includes the nucleus accumbens, amygdala, and orbitofrontal cortex. The present study used functional magnetic resonance imaging (fMRI) to investigate whether differences between 12 obese and 12 normal-weight women in reward-related brain activation in response to food images can be explained by changes in the functional interactions between key reward network regions. A two-step path analysis/General Linear Model approach was used to test whether there were group differences in network connections between nucleus accumbens, amygdala, and orbitofrontal cortex in response to high- and low-calorie food images. There was abnormal connectivity in the obese group in response to both high- and low-calorie food cues compared to normal-weight controls. Compared to controls, the obese group had a relative deficiency in the amygdala's modulation of activation in both orbitofrontal cortex and nucleus accumbens, but excessive influence of orbitofrontal cortex's modulation of activation in nucleus accumbens. The deficient projections from the amygdala might relate to suboptimal modulation of the affective/emotional aspects of a food's reward value or an associated cue's motivational salience, whereas increased orbitofrontal cortex to nucleus accumbens connectivity might contribute to a heightened drive to eat in response to a food cue. Thus, it is possible that not only greater activation of the reward system, but also differences in the interaction of regions in this network may contribute to the relatively increased motivational value of foods in obese individuals.     

It’s in the eye of the beholder: selective attention to drink properties during tasting influences brain activation in gustatory and reward regions

Statements regarding pleasantness, taste intensity or caloric content on a food label may influence the attention consumers pay to such characteristics during consumption. There is little research on the effects of selective attention on taste perception and associated brain activation in regular drinks. The aim of this study was to investigate the effect of selective attention on hedonics, intensity and caloric content on brain responses during tasting drinks. Using functional MRI brain responses of 27 women were measured while they paid attention to the intensity, pleasantness or caloric content of fruit juice, tomato juice and water. Brain activation during tasting largely overlapped between the three selective attention conditions and was found in the rolandic operculum, insula and overlying frontal operculum, striatum, amygdala, thalamus, anterior cingulate cortex and middle orbitofrontal cortex (OFC). Brain activation was higher during selective attention to taste intensity compared to calories in the right middle OFC and during selective attention to pleasantness compared to intensity in the right putamen, right ACC and bilateral middle insula. Intensity ratings correlated with brain activation during selective attention to taste intensity in the anterior insula and lateral OFC. Our data suggest that not only the anterior insula but also the middle and lateral OFC are involved in evaluating taste intensity. Furthermore, selective attention to pleasantness engaged regions associated with food reward. Overall, our results indicate that selective attention to food properties can alter the activation of gustatory and reward regions. This may underlie effects of food labels on the consumption experience of consumers.     

Mapping neurotransmitter networks with PET: An example on serotonin and opioid systems

All functions of the human brain are consequences of altered activity of specific neural pathways and neurotransmitter systems. Although the knowledge of “system level” connectivity in the brain is increasing rapidly, we lack “molecular level” information on brain networks and connectivity patterns. We introduce novel voxel‐based positron emission tomography (PET) methods for studying internal neurotransmitter network structure and intercorrelations of different neurotransmitter systems in the human brain. We chose serotonin transporter and μ‐opioid receptor for this analysis because of their functional interaction at the cellular level and similar regional distribution in the brain. Twenty‐one healthy subjects underwent two consecutive PET scans using [¹¹C]MADAM, a serotonin transporter tracer, and [¹¹C]carfentanil, a μ‐opioid receptor tracer. First, voxel‐by‐voxel “intracorrelations” (hub and seed analyses) were used to study the internal structure of opioid and serotonin systems. Second, voxel‐level opioid–serotonin intercorrelations (between neurotransmitters) were computed. Regional μ‐opioid receptor binding potentials were uniformly correlated throughout the brain. However, our analyses revealed nonuniformity in the serotonin transporter intracorrelations and identified a highly connected local network (midbrain–striatum–thalamus–amygdala). Regionally specific intercorrelations between the opioid and serotonin tracers were found in anteromedial thalamus, amygdala, anterior cingulate cortex, dorsolateral prefrontal cortex, and left parietal cortex, i.e., in areas relevant for several neuropsychiatric disorders, especially affective disorders. This methodology enables in vivo mapping of connectivity patterns within and between neurotransmitter systems. Quantification of functional neurotransmitter balances may be a useful approach in etiological studies of neuropsychiatric disorders and also in drug development as a biomarker‐based rationale for targeted modulation of neurotransmitter networks. Hum Brain Mapp 35:1875–1884, 2014. © 2013 Wiley Periodicals, Inc.     

Imaging studies of kleptomania in a middle‐aged woman with obsessive–compulsive disorder: a case report

A 57‐year‐old woman who had been arrested for shoplifting visited our hospital. She was diagnosed with kleptomania. She had previously been diagnosed with CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome and obsessive–compulsive disorder. Cranial magnetic resonance imaging showed mild atrophy of the bilateral dorsolateral prefrontal cortices, left hippocampus, and occipital cortex, as well as diffuse mild T₂ hyperintensity in the deep and subcortical white matter, including the frontal region. During a single‐photon emission computed tomography scan, significant hyperperfusion was observed in the right ventral striatum, including the nucleus accumbens, ventral thalamus, and right ventrolateral prefrontal areas. Patchy hypoperfusion was found in the bilateral posterior cingulate, parietal, and occipital regions. The patient's neurocognitive function was normal, except for slight impairment of her executive function. Her symptoms and neuroimaging findings were not suggestive of a specific neurocognitive disorder. Hyperactivity of the right ventral striatum may contribute to both obsessive–compulsive disorder and kleptomania. Although frontotemporal lobar degeneration is a major neurocognitive disorder related to illegal behaviours, CREST syndrome‐induced white matter microstructural damage in the orbitofrontal lobe could have caused our patient's kleptomania.     

Reduced functional connectivity within the limbic cortico‐striato‐thalamo‐cortical loop in unmedicated adults with obsessive‐compulsive disorder

Cortico‐striato‐thalamo‐cortical (CSTC) loops project from the cortex to the striatum, then from the striatum to the thalamus via the globus pallidus, and finally from the thalamus back to the cortex again. These loops have been implicated in Obsessive‐Compulsive Disorder (OCD) with particular focus on the limbic CSTC loop, which encompasses the orbitofrontal and anterior cingulate cortices, as well as the ventral striatum. Resting state functional‐connectivity MRI (rs‐fcMRI) studies, which examine temporal correlations in neural activity across brain regions at rest, have examined CSTC loop connectivity in patients with OCD and suggest hyperconnectivity within these loops in medicated adults with OCD. We used rs‐fcMRI to examine functional connectivity within CSTC loops in unmedicated adults with OCD (n = 23) versus healthy controls (HCs) (n = 20). Contrary to prior rs‐fcMRI studies in OCD patients on medications that report hyperconnectivity in the limbic CSTC loop, we found that compared with HCs, unmedicated OCD participants had reduced connectivity within the limbic CSTC loop. Exploratory analyses revealed that reduced connectivity within the limbic CSTC loop correlated with OCD symptom severity in the OCD group. Our finding of limbic loop hypoconnectivity in unmedicted OCD patients highlights the potential confounding effects of antidepressants on connectivity measures and the value of future examinations of the effects of pharmacological and/or behavioral treatments on limbic CSTC loop connectivity. Hum Brain Mapp 35:2852–2860, 2014. © 2013 Wiley Periodicals, Inc .     

Brain reward system's alterations in response to food and monetary stimuli in overweight and obese individuals

The brain's reward system is crucial to understand obesity in modern society, as increased neural responsivity to reward can fuel the unhealthy food choices that are driving the growing obesity epidemic. Brain's reward system responsivity to food and monetary rewards in individuals with excessive weight (overweight and obese) versus normal weight controls, along with the relationship between this responsivity and body mass index (BMI) were tested. The sample comprised 21 adults with obesity (BMI > 30), 21 with overweight (BMI between 25 and 30), and 39 with normal weight (BMI < 25). Participants underwent a functional magnetic resonance imaging (fMRI) session while performing two tasks that involve the processing of food (Willing to Pay) and monetary rewards (Monetary Incentive Delay). Neural activations within the brain reward system were compared across the three groups. Curve fit analyses were conducted to establish the association between BMI and brain reward system's response. Individuals with obesity had greater food‐evoked responsivity in the dorsal and ventral striatum compared with overweight and normal weight groups. There was an inverted U‐shape association between BMI and monetary‐evoked responsivity in the ventral striatum, medial frontal cortex, and amygdala; that is, individuals with BMIs between 27 and 32 had greater responsivity to monetary stimuli. Obesity is associated with greater food‐evoked responsivity in the ventral and dorsal striatum, and overweight is associated with greater monetary‐evoked responsivity in the ventral striatum, the amygdala, and the medial frontal cortex. Findings suggest differential reactivity of the brain's reward system to food versus monetary rewards in obesity and overweight. Hum Brain Mapp 38:666–677, 2017. © 2016 Wiley Periodicals, Inc.     

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.     

Social,reward, and attention brain networks are involved when online bids for joint attention are met with congruent versus incongruent responses

Joint attention (JA) is a cornerstone of adaptive human social functioning. Little functional magnetic resonance imaging (fMRI) research has examined, in interactive paradigms, neural activation underlying bids for JA, met with a congruent or an incongruent social response. We developed a highly naturalistic fMRI paradigm utilizing eye-tracking to create real-time, contingent social responses to participant-initiated JA. During congruent responses to JA bids, we observed increased activation in the right amygdala, the right fusiform gyrus, anterior and dorsal anterior cingulate cortices, striatum, ventral tegmental area, and posterior parietal cortices. Incongruent responses to JA bids elicited increased activity localized to the right temporoparietal junction (TPJ) and bilateral cerebellum. No differences in eye-gaze patterns were observed during congruent or incongruent trials. Our results highlight the importance of utilizing interactive fMRI paradigms in social neuroscience and the impact of congruency in recruiting integrated social, reward, and attention circuits for processing JA.     

Neurochemical and behavioural indices of exercise reward are independent of exercise controllability

Brain reward circuits are implicated in stress‐related psychiatric disorders. Exercise reduces the incidence of stress‐related disorders, but the contribution of exercise reward to stress resistance is unknown. Exercise‐induced stress resistance is independent of exercise controllability; both voluntary running (VR) and forced running (FR) protect rats against the anxiety‐like and depression‐like behavioural consequences of stress. Voluntary exercise is a natural reward, but whether rats find FR rewarding is unknown. Moreover, the contribution of dopamine (DA) and striatal reward circuits to exercise reward is not well characterized. Adult, male rats were assigned to locked wheels, VR, or FR groups. FR rats were forced to run in a pattern resembling the natural wheel running behavior of rats. Both VR and FR increased the reward‐related plasticity marker ΔFosB in the dorsal striatum and nucleus accumbens, and increased the activity of DA neurons in the lateral ventral tegmental area, as revealed by immunohistochemistry for tyrosine hydroxylase and pCREB. Both VR and FR rats developed conditioned place preference (CPP) to the side of a CPP chamber paired with exercise. Re‐exposure to the exercise‐paired side of the CPP chamber elicited conditioned increases in cfos mRNA in direct‐pathway (dynorphin‐positive) neurons in the dorsal striatum and nucleus accumbens in both VR and FR rats, and in tyrosine hydroxylase‐positive neurons in the lateral ventral tegmental area of VR rats only. The results suggest that the rewarding effects of exercise are independent of exercise controllability and provide insight into the DA and striatal circuitries involved in exercise reward and exercise‐induced stress resistance.