Common and distinct networks underlying reward valence and processing stages: a meta-analysis of functional neuroimaging studies

To better understand the reward circuitry in human brain, we conducted activation likelihood estimation (ALE) and parametric voxel-based meta-analyses (PVM) on 142 neuroimaging studies that examined brain activation in reward-related tasks in healthy adults. We observed several core brain areas that participated in reward-related decision making, including the nucleus accumbens (NAcc), caudate, putamen, thalamus, orbitofrontal cortex (OFC), bilateral anterior insula, anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC), as well as cognitive control regions in the inferior parietal lobule and prefrontal cortex (PFC). The NAcc was commonly activated by both positive and negative rewards across various stages of reward processing (e.g., anticipation, outcome, and evaluation). In addition, the medial OFC and PCC preferentially responded to positive rewards, whereas the ACC, bilateral anterior insula, and lateral PFC selectively responded to negative rewards. Reward anticipation activated the ACC, bilateral anterior insula, and brain stem, whereas reward outcome more significantly activated the NAcc, medial OFC, and amygdala. Neurobiological theories of reward-related decision making should therefore take distributed and interrelated representations of reward valuation and valence assessment into account.     

Orbitomedial prefrontal cortical projections to distinct longitudinal columns of the periaqueductal gray in the rat

We utilised retrograde and anterograde tracing procedures to study the origin and termination of prefrontal cortical (PFC) projections to the periaqueductal gray (PAG) in the rat. A previous study, in the primate, had demonstrated that distinct subgroups of PFC areas project to specific PAG columns. Retrograde tracing experiments revealed that projections to dorsolateral (dlPAG) and ventrolateral (vlPAG) periaqueductal gray columns arose from medial PFC, specifically prelimbic, infralimbic, and anterior cingulate cortices. Injections made in the vlPAG also labeled cells in medial, ventral, and dorsolateral orbital cortex and dorsal and posterior agranular insular cortex. Other orbital and insular regions, including lateral and ventrolateral orbital, ventral agranular insular, and dysgranular and granular insular cortex did not give rise to appreciable projections to the PAG. Anterograde tracing experiments revealed that the projections to different PAG columns arose from specific PFC areas. Projections from the caudodorsal medial PFC (caudal prelimbic and anterior cingulate cortices) terminated predominantly in dlPAG, whereas projections from the rostroventral medial PFC (rostral prelimbic cortex) innervated predominantly the vlPAG. As well, consistent with the retrograde data, projections arising from select orbital and agranular insular cortical areas terminated selectively in the vlPAG. The results indicate: (1) that rat orbital and medial PFC possesses an organisation broadly similar to that of the primate; and (2) that subdivisions within the rat orbital and medial PFC can be recognised on the basis of projections to distinct PAG columns.     

Two systems of resting state connectivity between the insula and cingulate cortex

The insula and cingulate cortices are implicated in emotional, homeostatic/allostatic, sensorimotor, and cognitive functions. Non‐human primates have specific anatomical connections between sub‐divisions of the insula and cingulate. Specifically, the anterior insula projects to the pregenual anterior cingulate cortex (pACC) and the anterior and posterior mid‐cingulate cortex (aMCC and pMCC); the mid‐posterior insula only projects to the posterior MCC (pMCC). In humans, functional neuroimaging studies implicate the anterior insula and pre/subgenual ACC in emotional processes, the mid‐posterior insula with awareness and interoception, and the MCC with environmental monitoring, response selection, and skeletomotor body orientation. Here, we tested the hypothesis that distinct resting state functional connectivity could be identified between (1) the anterior insula and pACC/aMCC; and (2) the entire insula (anterior, middle, and posterior insula) and the pMCC. Functional connectivity was assessed from resting state fMRI scans in 19 healthy volunteers using seed regions of interest in the anterior, middle, and posterior insula. Highly correlated, low‐frequency oscillations (< 0.05 Hz) were identified between specific insula and cingulate subdivisions. The anterior insula was shown to be functionally connected with the pACC/aMCC and the pMCC, while the mid/posterior insula was only connected with the pMCC. These data provide evidence for a resting state anterior insula–pACC/aMCC cingulate system that may integrate interoceptive information with emotional salience to form a subjective representation of the body; and another system that includes the entire insula and MCC, likely involved in environmental monitoring, response selection, and skeletomotor body orientation. Human Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.     

Using fMRI to dissociate sensory encoding from cognitive evaluation of heat pain intensity

Neuroimaging studies of painful stimuli in humans have identified a network of brain regions that is more extensive than identified previously in electrophysiological and anatomical studies of nociceptive pathways. This extensive network has been described as a pain matrix of brain regions that mediate the many interrelated aspects of conscious processing of nociceptive input such as perception, evaluation, affective response, and emotional memory. We used functional magnetic resonance imaging in healthy human subjects to distinguish brain regions required for pain sensory encoding from those required for cognitive evaluation of pain intensity. The results suggest that conscious cognitive evaluation of pain intensity in the absence of any sensory stimulation activates a network that includes bilateral anterior insular cortex/frontal operculum, dorsal lateral prefrontal cortex, bilateral medial prefrontal cortex/anterior cingulate cortex, right superior parietal cortex, inferior parietal lobule, orbital prefrontal cortex, and left occipital cortex. Increased activity common to both encoding and evaluation was observed in bilateral anterior insula/frontal operculum and medial prefrontal cortex/anterior cingulate cortex. We hypothesize that these two regions play a crucial role in bridging the encoding of pain sensation and the cognitive processing of sensory input.     

The neurophysiological bases of emotion: An fMRI study of the affective circumplex using emotion-denoting words

Objective: We aimed to study the neural processing of emotion‐denoting words based on a circumplex model of affect, which posits that all emotions can be described as a linear combination of two neurophysiological dimensions, valence and arousal. Based on the circumplex model, we predicted a linear relationship between neural activity and incremental changes in these two affective dimensions. Methods: Using functional magnetic resonance imaging, we assessed in 10 subjects the correlations of BOLD (blood oxygen level dependent) signal with ratings of valence and arousal during the presentation of emotion‐denoting words. Results: Valence ratings correlated positively with neural activity in the left insular cortex and inversely with neural activity in the right dorsolateral prefrontal and precuneus cortices. The absolute value of valence ratings (reflecting the positive and negative extremes of valence) correlated positively with neural activity in the left dorsolateral and medial prefrontal cortex (PFC), dorsal anterior cingulate cortex, posterior cingulate cortex, and right dorsal PFC, and inversely with neural activity in the left medial temporal cortex and right amygdala. Arousal ratings and neural activity correlated positively in the left parahippocampus and dorsal anterior cingulate cortex, and inversely in the left dorsolateral PFC and dorsal cerebellum. Conclusion: We found evidence for two neural networks subserving the affective dimensions of valence and arousal. These findings clarify inconsistencies from prior imaging studies of affect by suggesting that two underlying neurophysiological systems, valence and arousal, may subserve the processing of affective stimuli, consistent with the circumplex model of affect. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

Paralimbic and medial prefrontal cortical involvement in neuroendocrine responses to traumatic stimuli

OBJECTIVE: Hypothalamic-pituitary-adrenal axis activity and cortisol release are consequences of central stress system activation, but they may also influence cognitive and emotional processes within the brain. Despite the importance of central stress response systems, little is known about the specific brain circuits through which psychosocial stimuli activate the hypothalamic-pituitary-adrenal axis and through which cortisol feedback modulates central processing. The authors used [(15)O]H(2)O positron emission tomography (PET) on subjects with posttraumatic stress disorder (PTSD) to study these circuits. METHOD: Participants were combat-PTSD patients, combat-exposed healthy comparison subjects, and noncombat-exposed healthy comparison subjects. Participants were scanned using [(15)O]H(2)O PET while they experienced a series of emotional-induction conditions, which included aversive pictures and autobiographic narratives. Blood samples were obtained 2 minutes before and 5 minutes after each activation scan in order to measure the subjects' plasma adrenocorticotropic hormone and cortisol levels. RESULTS: In voxel-wise analyses, the authors found that adrenocorticotropic hormone responses were covaried with regional cerebral blood flow (rCBF) in the dorsal medial prefrontal cortex, rostral anterior cingulate cortex, and right insula, with some differences between PTSD patients and comparison subjects. Prestimulus cortisol levels covaried with rCBF responses in the rostral anterior cingulate cortex. In combat-PTSD patients only, prestimulus cortisol levels covaried with rCBF in the subgenual anterior cingulate cortex. CONCLUSIONS: These findings provide evidence of cortical involvement in hypothalamic-pituitary-adrenal responses to psychological stimuli, specifically implicating the insula, dorsal medial prefrontal cortex, and rostral anterior cingulate cortex. These findings also show, for the first time, that cortisol may modulate activity in specific brain areas such as the rostral and subgenual anterior cingulate cortices. Differential patterns of covariation between combat veterans with and without PTSD potentially implicate the dorsal medial prefrontal cortex and subgenual anterior cingulate cortex as areas of dysregulation in PTSD.     

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.     

Changes in regional cerebral blood flow following antidepressant treatment in late-life depression

OBJECTIVE: Reversible/irreversible abnormalities of regional cerebral blood flow (rCBF) are seen in patients with depression. However, in late-life depression there is little evidence of a longitudinal change in rCBF through remission. We examined whether the decreased rCBF in individuals with late-life depression resolves following treatment. METHODS: Twenty-five depressed patients older than 55 years completed the Hamilton Rating Scale for Depression and single photon emission computed tomography before and after a mean of 13.7 weeks of pharmacotherapy. Quantitative analyses were performed using the Statistical Parametric Mapping procedure. RESULTS: Patients with depression demonstrated decreased rCBF in the anterior ventral and dorsal medial prefrontal cortex (PFC), including anterior cingulate cortices, bilateral ventrolateral PFC to temporal cortices, and bilateral medial to lateral parieto-occipital lobes relative to healthy controls. No particular areas showed increased rCBF. Following pharmacotherapy, rCBF significantly increased in the left dorsolateral PFC to precentral areas and the right parieto-occipital regions. However, decreased rCBF at baseline in the anterior ventral/dorsal medial PFC, bilateral ventrolateral PFC, bilateral temporal lobes, and bilateral parietal lobes did not show significant improvement after treatment. CONCLUSIONS: Remarkable improvements in rCBF in the left dorsolateral PFC to precentral regions are consistent with the hypothesis that neuronetworks including the left frontal cortex may be functionally and reversibly involved in late-life unipolar major depression (state-dependent). In contrast, neural circuits including bilateral medial, dorsolateral, and parietal areas may reflect underlying and continuous pathognomonic brain dysfunction of depression (trait-dependent).     

Brain structural basis of cognitive reappraisal and expressive suppression

Cognitive reappraisal and expressive suppression, two major emotion regulation strategies, are differentially related to emotional well-being. The aim of this study was to test the association of individual differences in these two emotion regulation strategies with gray matter volume of brain regions that have been shown to be involved in the regulation of emotions. Based on high-resolution magnetic resonance images of 96 young adults voxel-based morphometry was used to analyze the gray matter volumes of the a priori regions of interest, including amygdala, insula, dorsal anterior cingulate and paracingulate cortex, medial and lateral prefrontal cortex (PFC) and their association with cognitive reappraisal and expressive suppression usage as well as neuroticism. A positive association of cognitive reappraisal with right and tendentially left amygdala volume and of neuroticism with left amygdala volume (marginally significant) was found. Expressive suppression was related to dorsal anterior cingulate/paracingulate cortex and medial PFC gray matter volume. The results of this study emphasize the important role of the amygdala in individual differences in cognitive reappraisal usage as well as neuroticism. Additionally, the association of expressive suppression usage with larger volumes of the medial PFC and dorsal anterior/paracingulate cortex underpins the role of these regions in regulating emotion-expressive behavior.     

An fMRI study of the interface between affective and cognitive neural circuitry in pediatric bipolar disorder

The pathophysiology of pediatric bipolar disorder (PBD) impacts both affective and cognitive brain systems. Understanding disturbances in the neural circuits subserving these abilities is critical for characterizing developmental aberrations associated with the disorder and developing improved treatments. Our objective is to use functional neuroimaging with pediatric bipolar disorder patients employing a task that probes the functional integrity of attentional control and affect processing. Ten euthymic unmedicated pediatric bipolar patients and healthy controls matched for age, sex, race, socioeconomic status, and IQ were scanned using functional magnetic resonance imaging. In a pediatric color word matching paradigm, subjects were asked to match the color of a word with one of two colored circles below. Words had a positive, negative or neutral emotional valence, and were presented in 30-s blocks. In the negative affect condition, relative to the neutral condition, patients with bipolar disorder demonstrated greater activation of bilateral pregenual anterior cingulate cortex and left amygdala, and less activation in right rostral ventrolateral prefrontal cortex (PFC) and dorsolateral PFC at the junction of the middle frontal and inferior frontal gyri. In the positive affect condition, there was no reduced activation of PFC or increased amygdala activation. The pattern of reduced activation of ventrolateral PFC and greater amygdala activation in bipolar children in response to negative stimuli suggests both disinhibition of emotional reactivity in the limbic system and reduced function in PFC systems that regulate those responses. Higher cortical cognitive areas such as the dorsolateral PFC may also be adversely affected by exaggerated emotional responsivity to negative emotions. This pattern of functional alteration in affective and cognitive circuitry may contribute to the reduced capacity for affect regulation and behavioral self-control in pediatric bipolar disorder.     

Neural circuitry underlying voluntary suppression of sadness.

BACKGROUND: The ability to voluntarily self-regulate negative emotion is essential to a healthy psyche. Indeed, a chronic incapacity to suppress negative emotion might be a key factor in the genesis of depression and anxiety. Regarding the neural underpinnings of emotional self-regulation, a recent functional neuroimaging study carried out by our group has revealed that the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex are involved in voluntary suppression of sexual arousal. As few things are known, still, with respect to the neural substrate underlying volitional self-regulation of basic emotions, here we used functional magnetic resonance imaging to identify the neural circuitry associated with the voluntary suppression of sadness. METHODS: Twenty healthy female subjects were scanned during a Sad condition and a Suppression condition. In the Sad condition, subjects were instructed to react normally to sad film excerpts whereas, in the Suppression condition, they were asked to voluntarily suppress any emotional reaction in response to comparable stimuli. RESULTS: Transient sadness was associated with significant loci of activation in the anterior temporal pole and the midbrain, bilaterally, as well as in the left amygdala, left insula, and right ventrolateral prefrontal cortex (VLPFC) (Brodmann area [BA] 47). Correlational analyses carried out between self-report ratings of sadness and regional blood oxygen level dependent (BOLD) signal changes revealed the existence of positive correlations in the right VLPFC (BA 47), bilaterally, as well as in the left insula and the affective division of the left anterior cingulate gyrus (BA 24/32). In the Suppression condition, significant loci of activation were noted in the right DLPFC (BA 9) and the right orbitofrontal cortex (OFC) (BA 11), and positive correlations were found between the self-report ratings of sadness and BOLD signal changes in the right OFC (BA 11) and right DLPFC (BA 9). CONCLUSIONS: These results confirm the key role played by the DLPFC in emotional self-regulation. They also indicate that the right DLPFC and right OFC are components of a neural circuit implicated in voluntary suppression of sadness.     

Topography of descending projections from anterior insular and medial prefrontal regions to the lateral habenula of the epithalamus in the rat

The epithalamic lateral nucleus of the habenula (LHb) plays a key role in regulating firing of dopamine and serotonin neurons in the midbrain and is thereby involved in various cognitive and affective behaviors. It is not yet clear, however, from where the LHb receives cognitive and affective information relevant to its regulation of the midbrain monoaminergic systems. The prefrontal cortex would be among the ideal sources. Here, using anterograde and retrograde tracer injections in the rat brain, we characterized the topography of the corticohabenular projections. Following injections of cholera toxin subunit B into the LHb, retrogradely labeled neurons were produced in the anterior insular, cingulate, prelimbic and infralimbic cortices. Consistent with this retrograde tracing, injections of biotinylated dextran amine (BDA) into these cortical regions labeled robust terminals in the LHb. Our quantification of the BDA-impregnated varicosities revealed that projections from the anterior insula terminated mainly in the intersection regions of the lateral and ventral two-thirds of the LHb, while projections from the cingulate cortex terminated mainly in the lateral two-thirds of the LHb. By comparison, BDA-labeled terminals originating from the medial prefrontal regions were contained mainly in the medial plus ventral one-third of LHb. Based on these data, we hypothesize that LHb provides a link for conveying cognitive and affective information from prefrontal and insular regions to the midbrain monoaminergic centers.     

The neural basis of mood-congruent processing biases in depression

BACKGROUND: Mood-congruent processing biases are among the most robust research findings in neuropsychological studies of depression. Depressed patients show preferential processing of negatively toned stimuli across a range of cognitive tasks. The present study aimed to determine whether these behavioral abnormalities are associated with specific neural substrates. METHODS: Ten depressed patients and 11 healthy control subjects underwent scanning during performance of an emotional go/no-go task using functional magnetic resonance imaging. The task allowed comparison among neural response to happy, sad, and neutral words, in the context of these words as targets (ie, stimuli to which subjects were required to make a motor response) or distractors (ie, stimuli to which the motor response was withheld). RESULTS: Depressed patients showed attenuated neural responses to emotional relative to neutral targets in ventral cingulate and posterior orbitofrontal cortices. However, patients showed elevated responses specific to sad targets in rostral anterior cingulate extending to anterior medial prefrontal cortex. Unlike controls, patients showed differential neural response to emotional, particularly sad, distractors in the lateral orbitofrontal cortex. CONCLUSIONS: These findings suggest a distinct neural substrate for mood-congruent processing biases in performance. The medial and orbital prefrontal regions may play a key role in mediating the interaction between mood and cognition in affective disorder.     

Heightened central affective response to visceral sensations of pain and discomfort in IBS

Background Typically, conventional functional imaging methods involve repeated exposures to sensory stimulation. In rectal distension (RD) studies that involve multiple distensions, however, it is difficult to disambiguate the central response to RD from pathological alterations in peripheral neural responses associated with relaxation and accommodation of the rectum. Methods This study addressed potential confounders found in previous imaging studies by collecting functional magnetic resonance imaging studies (fMRI) data during a single slow ramp‐tonic distension paradigm and analysing fMRI signal changes using independent component analysis. Key Results Compared with controls, IBS participants showed increased activation of the anterior cingulate cortices, insula and ventral medial prefrontal regions suggesting heightened affective responses to painful visceral stimuli. In addition, the failure by IBS patients to down‐regulate activity within ventral medial prefrontal and the posterior cingulate/precuneus regions was suggestive of reduced sensitivity to somatic changes and delayed shifts away from rest in `default network' activity patterns. Controls showed heightened activation of the thalamus, striatal regions and dorsolateral prefrontal cortex suggesting greater arousal and salience‐driven sustained attention reactions and greater modulation of affective responses to discomfort and pain. Conclusion&Inferences This work points to alterations in the central response to visceral pain and discomfort in IBS, highlighting diminished modulation and heightened internalization of affective reactions.     

Neural correlates of developmental differences in risk estimation and feedback processing

The primary aim of this study was to compare the neural substrates of decision-making in middle-aged children and adults. To this end, we collected fMRI data while 9-12-year-olds and 18-26-year-olds performed a simple gambling task. The task was designed to tap two important aspects of decision-making: risk estimation and feedback processing. We examined how orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC) contributed to risk estimation, and how ventrolateral and medial prefrontal cortices (VLPFC and medial PFC) contributed to negative feedback processing in children and adults. Region of interest analyses revealed differences in brain activation between children and adults for ACC and lateral OFC. ACC was recruited more for high-risk than for low-risk trials, and this difference was larger for children than for adults. In contrast, children and adults did not differ in activation for OFC or DLPFC. These data suggest that children's decision-making under uncertainty is associated with a high degree of response conflict. Both age groups exhibited bilateral VLPFC (BA 47) and medial PFC/ACC (BA 6/ BA 32 (dorsal) and 24 (ventral)) activation associated with negative feedback processing. Relative to adults, children engaged lateral OFC more strongly for negative relative to positive feedback. These results indicate that children may find negative feedback more aversive than adults do. In summary, children aged 9-12 years and adults recruit similar brain regions during risk-estimation and feedback processing, but some key differences between the groups provide insight into the factors contributing to developmental changes in decision-making.     

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.     

The salient characteristics of the central effects of acupuncture needling: limbic-paralimbic-neocortical network modulation

Human and animal studies suggest that acupuncture produces many beneficial effects through the central nervous system. However, the neural substrates of acupuncture actions are not completely clear to date. fMRI studies at Hegu (LI4) and Zusanli (ST36) indicated that the limbic system may play an important role for acupuncture effects. To test if this finding applies to other major classical acupoints, fMRI was performed on 10 healthy adults during manual acupuncture at Taichong (LV3), Xingjian (LV2), Neiting (ST44), and a sham point on the dorsum of the left foot. Although certain differences could be observed between real and sham points, the hemodynamic response (BOLD signal changes) and psychophysical response (sensory experience) to acupuncture were generally similar for all four points. Acupuncture produced extensive deactivation of the limbic-paralimbic-neocortical system. Clusters of deactivated regions were seen in the medial prefrontal cortex (frontal pole, pregenual cingulate), the temporal lobe (amygdala, hippocampus, and parahippocampus) and the posterior medial cortex (precuneus, posterior cingulate). The sensorimotor cortices (somatosensory cortices, supplementary motor cortex), thalamus and occasional paralimbic structures such as the insula and anterior middle cingulate cortex showed activation. Our results provide additional evidence in support of previous reports that acupuncture modulates the limbic-paralimbic-neocortical network. We hypothesize that acupuncture may mediate its antipain, antianxiety, and other therapeutic effects via this intrinsic neural circuit that plays a central role in the affective and cognitive dimensions of pain as well as in the regulation and integration of emotion, memory processing, autonomic, endocrine, immunological, and sensorimotor functions.     

Anxiety positive subjects show altered processing in the anterior insula during anticipation of negative stimuli

Prior neuroimaging studies support the hypothesis that anticipation, an important component of anxiety, may be mediated by activation within the insular and medial prefrontal cortices including the anterior cingulate cortex. However, there is an insufficient understanding of how affective anticipation differs across anxiety groups in emotional brain loci and networks. We examined 14 anxiety positive (AP) and 14 anxiety normative (AN) individuals completing an affective picture anticipation task during functional magnetic resonance imaging (fMRI). Brain activation was examined across groups for cued anticipation (to aversive or pleasant stimuli). Both groups showed greater activation in the bilateral anterior insula during cued differential anticipation (i.e., aversive vs. pleasant), and activation on the right was significantly higher in AP compared to AN subjects. Functional connectivity showed that the left anterior insula was involved in a similar network during pleasant anticipation in both groups. The left anterior insula during aversive and the right anterior insula during all anticipation conditions coactivated with a cortical network consisting of frontal and parietal lobes in the AP group to a greater degree. These results are consistent with the hypothesis that anxiety is related to greater anticipatory reactivity in the brain and that there may be functional asymmetries in the brain that interact with psychiatric traits.     

Structural integrity of the prefrontal cortex modulates electrocortical sensitivity to reward

The P300 is a known ERP component assessing stimulus value, including the value of a monetary reward. In parallel, the incentive value of reinforcers relies on the PFC, a major cortical projection region of the mesocortical reward pathway. Here we show a significant positive correlation between P300 response to money (vs. no money) with PFC gray matter volume in the OFC, ACC, and dorsolateral and ventrolateral PFC in healthy control participants. In contrast, individuals with cocaine use disorders showed compromises in both P300 sensitivity to money and PFC gray matter volume in the ventrolateral PFC and OFC and their interdependence. These results document for the first time the importance of gray matter structural integrity of subregions of PFC to the reward-modulated P300 response.     

The neural substrate of human empathy: effects of perspective-taking and cognitive appraisal

Whether observation of distress in others leads to empathic concern and altruistic motivation, or to personal distress and egoistic motivation, seems to depend upon the capacity for self-other differentiation and cognitive appraisal. In this experiment, behavioral measures and event-related functional magnetic resonance imaging were used to investigate the effects of perspective-taking and cognitive appraisal while participants observed the facial expression of pain resulting from medical treatment. Video clips showing the faces of patients were presented either with the instruction to imagine the feelings of the patient ("imagine other") or to imagine oneself to be in the patient's situation ("imagine self"). Cognitive appraisal was manipulated by providing information that the medical treatment had or had not been successful. Behavioral measures demonstrated that perspective-taking and treatment effectiveness instructions affected participants' affective responses to the observed pain. Hemodynamic changes were detected in the insular cortices, anterior medial cingulate cortex (aMCC), amygdala, and in visual areas including the fusiform gyrus. Graded responses related to the perspective-taking instructions were observed in middle insula, aMCC, medial and lateral premotor areas, and selectively in left and right parietal cortices. Treatment effectiveness resulted in signal changes in the perigenual anterior cingulate cortex, in the ventromedial orbito-frontal cortex, in the right lateral middle frontal gyrus, and in the cerebellum. These findings support the view that humans' responses to the pain of others can be modulated by cognitive and motivational processes, which influence whether observing a conspecific in need of help will result in empathic concern, an important instigator for helping behavior.