Elevated peripheral inflammation is associated with attenuated striatal reward anticipation in major depressive disorder

BackgroundMajor depressive disorder (MDD) is the leading cause of years lived with disability worldwide, and up to 40% of individuals with MDD do not respond to current treatments. Studies suggest that peripheral inflammation plays an important role in the striatal mesolimbic dopamine pathway and corticostriatal reward circuitry in MDD. Although MDD patients show blunted striatal responses to reward, the link between degree of inflammation and attenuation of reward processing is unclear. We investigated whether MDD patients with elevated peripheral inflammation exhibit attenuated reward responses to enhance our understanding of MDD pathophysiology and develop more effective treatments for current non-responders.MethodsMDD subjects varying on serum C-reactive protein (CRP) concentrations (MDD-High CRP, >3 mg/L, n = 44; MDD-Low CRP, <3 mg/L, n = 44) and healthy comparisons (HC, n = 44) completed a monetary incentive delay (MID) task and provided blood samples to measure inflammation-related markers. MDD-High and MDD-Low were propensity score-matched on age, sex, body mass index (BMI), smoking status, exercise and MID task head motion. Percent change in blood oxygen level-dependent (BOLD) signal during anticipation of wins and losses was extracted from bilateral nucleus accumbens, dorsal caudate and dorsolateral putamen regions of interest (ROIs). A linear mixed-effects model was used to test group (MDD-High, MDD-Low and HC), condition (large-win, small-win and no win), and their interaction for these ROIs as well as whole-brain voxelwise data. Analyses also tested group differences in inflammatory mediators. Correlations were used to explore the relationship between inflammatory mediators and brain regions showing differences between MDD-High and MDD-Low.ResultsMDD-High exhibited: (a) lower BOLD signal change in dorsal caudate, thalamus, left insula and left precuneus during anticipation of small wins than MDD-Low; and (b) higher serum soluble intercellular adhesion molecule 1 (sICAM-1) and interleukin 6 (IL-6) concentrations than MDD-Low and HC. MDD as a whole, regardless of CRP-based inflammation, exhibited: (a) lower precuneus BOLD signal change to large wins than HC; and (b) higher Interleukin 1 receptor antagonist (IL-1ra), macrophage-derived chemokine (MDC) and macrophage inflammatory protein-1 alpha (MIP-1α) concentrations than HC. Higher serum sICAM-1 concentrations were associated with lower caudate BOLD signal change to small wins only within the MDD-High group.ConclusionWithin MDD patients, high inflammation (CRP, sICAM-1) was linked to reduced striatal activation recruited to discriminate intermediate reward magnitudes. These findings support an association between levels of peripheral inflammation and the degree of reward-related activation in individuals with MDD.Registration of clinical trialsThe ClinicalTrials.gov identifier for the clinical protocol associated with data published in this current paper is NCT02450240, “Latent Structure of Multi-level Assessments and Predictors of Outcomes in Psychiatric Disorders.”     

Food motivation circuitry hypoactivation related to hedonic and nonhedonic aspects of hunger and satiety in women with active anorexia nervosa and weight-restored women with anorexia nervosa

Background: Previous studies have provided evidence of food motivation circuitry dysfunction in individuals with anorexia nervosa. However, methodological limitations present challenges to the development of a cohesive neurobiological model of anorexia nervosa. Our goal was to investigate the neural circuitry of appetite dysregulation across states of hunger and satiety in active and weight-restored phases of anorexia nervosa using robust methodology to advance our understanding of potential neural circuitry abnormalities related to hedonic and nonhedonic state and trait. Methods: We scanned women with active anorexia nervosa, weight-restored women with anorexia nervosa and healthy-weight controls on a 3-T Siemens magnetic resonance scanner while they viewed images of high- and low-calorie foods and objects before (premeal) and after (postmeal) eating a 400 kcal meal. Results: We enrolled 12 women with active disease, 10 weight-restored women with anorexia nervosa and 11 controls in our study. Compared with controls, both weight-restored women and those with active disease demonstrated hypoactivity premeal in the hypothalamus, amygdala and anterior insula in response to high-calorie foods (v. objects). Postmeal, hypoactivation in the anterior insula persisted in women with active disease. Percent signal change in the anterior insula was positively correlated with food stimuli ratings and hedonic and nonhedonic appetite ratings in controls, but not women with active disease. Limitations: Our findings are limited by a relatively small sample size, which prevented the use of an analysis of variance model and exploration of interaction effects, although our substantial effect sizes of between-group differences suggest adequate power for our statistical analysis approach. Participants taking psychotropic medications were included. Conclusion: Our data provide evidence of potential state and trait hypoactivations in food motivation regions involved in the assessment of food's reward value and integration of these with interoceptive signalling of one's internal state of well-being, with important relations between brain activity and homeostatic and hedonic aspects of appetite. Our findings give novel evidence of disruption in neurobiological circuits and stress the importance of examining both state and trait characteristics in the investigation of brain phenotypes in individuals with anorexia nervosa.     

The representation of oral fat texture in the human somatosensory cortex

How fat is sensed in the mouth and represented in the brain is important in relation to the pleasantness of food, appetite control, and the design of foods that reproduce the mouthfeel of fat yet have low energy content. We show that the human somatosensory cortex (SSC) is involved in oral fat processing via functional coupling to the orbitofrontal cortex (OFC), where the pleasantness of fat texture is represented. Using functional MRI, we found that activity in SSC was more strongly correlated with the OFC during the consumption of a high fat food with a pleasant (vanilla) flavor compared to a low fat food with the same flavor. This effect was not found in control analyses using high fat foods with a less pleasant flavor or pleasant‐flavored low fat foods. SSC activity correlated with subjective ratings of fattiness, but not of texture pleasantness or flavor pleasantness, indicating a representation that is not involved in hedonic processing per se. Across subjects, the magnitude of OFC‐SSC coupling explained inter‐individual variation in texture pleasantness evaluations. These findings extend known SSC functions to a specific role in the processing of pleasant‐flavored oral fat, and identify a neural mechanism potentially important in appetite, overeating, and obesity. Hum Brain Mapp 35:2521–2530, 2014. © 2013 Wiley Periodicals, Inc .     

Functional connectivity between the amygdala and prefrontal cortex in medication-naive individuals with major depressive disorder

Background

Convergent evidence suggests dysfunction within the prefrontal cortex (PFC) and amygdala, important components of a neural system that subserves emotional processing, in individuals with major depressive disorder (MDD). Abnormalities in this system in the left hemisphere and during processing of negative emotional stimuli are especially implicated. In this study, we used functional magnetic resonance imaging (fMRI) to investigate amygdala–PFC functional connectivity during emotional face processing in medication-naive individuals with MDD.

Methods

Individuals with MDD and healthy controls underwent fMRI scanning while processing 3 types of emotional face stimuli. We compared the strength of functional connectivity from the amygdala between the MDD and control groups.

Results

Our study included 28 individuals with MDD and 30 controls. Decreased amygdala–left rostral PFC (rPFC) functional connectivity was observed in the MDD group compared with controls for the fear condition (p < 0.05, corrected). No significant differences were found in amygdala connectivity to any cerebral regions between the MDD and control groups for the happy or neutral conditions.

Limitations

All participants with MDD were experiencing acute episodes, therefore the findings could not be generalized to the entire MDD population.

Conclusion

Medication-naive individuals with MDD showed decreased amygdala–left rPFC functional connectivity in response to negative emotional stimuli, suggesting that abnormalities in amygdala–left rPFC neural circuitry responses to negative emotional stimuli might play an important role in the pathophysiology of MDD.     

A double dissociation of ventromedial prefrontal cortical responses to sad and happy stimuli in depressed and healthy individuals.

BACKGROUND: The ventromedial prefrontal cortex (VMPFC) is a region implicated in the assessment of the rewarding potential of stimuli and may be dysfunctional in major depressive disorder (MDD). The few studies examining prefrontal cortical responses to emotive stimuli in MDD have indicated increased VMPFC responses to pleasant images but decreased responses to sad mood provocation when compared with healthy individuals. We wished to corroborate these results by examining neural responses to personally relevant happy and sad stimuli in MDD and healthy individuals within the same paradigm. METHODS: Neural responses to happy and sad emotional stimuli (autobiographical memory prompts and congruent facial expressions) were measured using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in MDD (n = 12) and healthy (n = 12) individuals. RESULTS: Increased and decreased responses in VMPFC were observed in MDD and healthy individuals, respectively, to happy stimuli, whereas the pattern was reversed for MDD and healthy individual responses to sad stimuli. These findings were not explained by medication effects in depressed individuals. CONCLUSIONS: These findings indicate a double dissociation of the pattern of VMPFC response to happy and sad stimuli in depressed and healthy individuals and suggest abnormal reward processing in MDD.     

Childhood trauma is associated with elevated anhedonia and altered core reward circuitry in major depression patients and controls

Childhood trauma (CT) is a well‐established risk factor for major depressive disorder (MDD). However, the underlying mechanism linking CT and MDD remains not fully understood. The present study tested the hypothesis that CT have effects on specific types of anhedonia in depression via reward system. To do so, we evaluated different aspects of anhedonia and resting‐state functional connectivity (FC) in reward system among 66 patients with MDD (44 with moderate‐to‐severe and 22 with no or low CT), and 57 healthy controls (HC; 23 with moderate‐to‐severe and 34 with no or low CT). Results showed that MDD patients with moderate‐to‐severe CT suffered more severe state anhedonic depression than patients with no or low level of CT. Individuals with moderate‐to‐severe CT, irrespective of MDD diagnosis, had elevated physical, social and anticipatory but not consummatory trait anhedonia, and demonstrated decreased left nucleus accumbens (NAcc)‐right orbital frontal cortex (OFC) and left ventral caudate‐left OFC connectivity compared to those with no or low exposure. Left NAcc‐right OFC connectivity mediated relationship between CT and state anhedonia in MDD. The total altered ventral striatum (VS)‐OFC connectivity mediated links between CT and physical trait anhedonia in HC. These findings highlight specific types of anhedonia and the core reward system as targets of CT. Blunted hedonic responses via decreased coupling within core reward system may be involved in the mechanism of depression following CT. Implications for clinical interventions are also discussed.     

Neural correlates of processing emotional prosody in unipolar depression

Major depressive disorder (MDD) is characterized by a biased emotion perception. In the auditory domain, MDD patients have been shown to exhibit attenuated processing of positive emotions expressed by speech melody (prosody). So far, no neuroimaging studies examining the neural basis of altered processing of emotional prosody in MDD are available. In this study, we addressed this issue by examining the emotion bias in MDD during evaluation of happy, neutral, and angry prosodic stimuli on a five‐point Likert scale during functional magnetic resonance imaging (fMRI). As expected, MDD patients rated happy prosody less intense than healthy controls (HC). At neural level, stronger activation in the middle superior temporal gyrus (STG) and the amygdala was found in all participants when processing emotional as compared to neutral prosody. MDD patients exhibited an increased activation of the amygdala during processing prosody irrespective of valence while no significant differences between groups were found for the STG, indicating that altered processing of prosodic emotions in MDD occurs rather within the amygdala than in auditory areas. Concurring with the valence‐specific behavioral effect of attenuated evaluation of positive prosodic stimuli, activation within the left amygdala of MDD patients correlated with ratings of happy, but not neutral or angry prosody. Our study provides first insights in the neural basis of reduced experience of positive information and an abnormally increased amygdala activity during prosody processing.     

The neural correlates of anhedonia in major depressive disorder.

BACKGROUND: Anhedonia is a relative lack of pleasure in response to formerly rewarding stimuli. It is an important diagnostic feature of major depressive disorder (MDD), and predicts antidepressant efficacy. Understanding its neurobiological basis may help to target new treatments and predict treatment outcomes. Using a novel paradigm, we aimed to explore the correlations between anhedonia severity and magnitude of neural responses to happy and sad stimuli in regions previously implicated in studies of human reward processing and depressive anhedonia. METHODS: Neural responses to happy and sad emotional stimuli (autobiographical prompts and mood congruent facial expressions) were measured using blood oxygen level dependent (BOLD) functional magnetic resonance imaging in twelve MDD individuals with varying degrees of anhedonia. RESULTS: In response to happy stimuli, anhedonia, but not depression severity per se, was positively and negatively correlated with ventromedial prefrontal cortex (VMPFC) and amygdala/ventral striatal activity, respectively. State anxiety independently contributed to a VMPFC-subcortical dissociation of response to happy (but not sad) stimuli, which was similar, but different, to anhedonia. CONCLUSIONS: These findings suggest that anhedonia and state anxiety are associated with dysfunction within neural systems underlying the response to, and assessment of, the rewarding potential of emotive stimuli in MDD, and highlight the importance of employing a symptom-dimension-based approach in the examination of the neurobiology of depression.     

Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder

Neuroplasticity may have a core role in the pathophysiology of major depressive disorder (MDD), a concept supported by experimental studies that found that excessive cortisol secretion and/or excessive production of inflammatory cytokines impairs neuronal plasticity and neurogenesis in the hippocampus. The objective of this study was to examine how changes in the glucocorticoid and inflammatory systems may affect hippocampal volumes in MDD. A multimodal approach with structural neuroimaging of hippocampus and amygdala, measurement of peripheral inflammatory proteins interleukin (IL)-6 and C-reactive protein (CRP), glucocorticoid receptor (GR) mRNA expression, and expression of glucocorticoid-inducible genes (glucocorticoid-inducible genes Leucin Zipper (GILZ) and glucocorticoid-inducible kinase-1 (SGK-1)) was used in 40 patients with MDD and 43 healthy controls (HC). Patients with MDD showed smaller hippocampal volumes and increased inflammatory proteins IL-6 and CRP compared with HC. Childhood maltreatment was associated with increased CRP. Patients with MDD, who had less expression of the glucocorticoid-inducible genes GILZ or SGK-1 had smaller hippocampal volumes. Regression analysis showed a strong positive effect of GILZ and SGK-1 mRNA expression, and further inverse effects of IL-6 concentration, on hippocampal volumes. These findings suggest that childhood maltreatment, peripheral inflammatory and glucocorticoid markers and hippocampal volume are interrelated factors in the pathophysiology of MDD. Glucocorticoid-inducible genes GILZ and SGK-1 might be promising candidate markers for hippocampal volume changes relevant for diseases like MDD. Further studies need to explore the possible clinical usefulness of such a blood biomarker, for example, for diagnosis or prediction of therapy response.     

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.     

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.     

抑郁症患者情绪图片反应特征及杏仁核反应模式的研究

目的 探讨抑郁症患者对情感刺激的行为学反应模式及其相关的杏仁核时程反应过程.方法 12例首次发病、未经治疗的抑郁症患者(抑郁症组)和13名健康个体(健康对照组)对观看正性、中性和负性情绪图片的愉悦度等评分;并在被动注视任务下行功能磁共振成像,采用感兴趣区分析方法,比较两组杏仁核在不同情绪图片任务组块间的血氧水平依赖(BOLD)信号时间反应特征.结果 (1)抑郁症组情绪图片愉悦度评分[正性:(6.6 ±0.2)分;中性:(4.7 ±0.1)分]低于健康对照组[分别为(7.7 ±0.2)分和(5.1 ±0.1)分],负性情绪图片评分[(3.4 ±0.3)分]高于健康对照组[(2.2 ±0.2)分;P<0.01].(2)对正性情绪图片任务,两组间右侧杏仁核存在"组×时间"交互作用(P=0.002);抑郁症组杏仁核BOLD信号变化率为(0.02±0.09)%,激活时间后移至Block 2.对负性情绪图片任务,两组间左侧杏仁核有"组×时间"交互作用(P=0.008),右侧杏仁核存在组主效应(P=0.007)和时间主效应(P=0.016),抑郁症组BOLD信号变化率低于(-0.06 ±0.14)%.结论 杏仁核是抑郁症患者丧失愉悦体验和情绪低落的神经基础之一.     

Decreased neural activity in reward circuitry during personal reference in abstinent alcoholics--a fMRI study

Two of the most striking features in alcoholism are the irresistible craving for alcohol and the proceeding neglect of other activities and pleasures that were formerly relevant. Craving has been investigated extensively and is commonly due to a dysfunctional reward system. The neural basis of the neglect of self-relevant interests, which can be described as altered personal reference, and its association to the reward system, however, remains unclear. Using fMRI, we investigated neural activity during a paradigm that tested for both reward and personal reference with regard to the same stimuli, i.e., alcoholic and nonalcoholic pictures, in healthy subjects and abstinent alcoholic patients. Alcoholic patients showed slightly reduced signal changes in the brain stem adjacent to ventral tegmental area (VTA) and in the ventromedial prefrontal cortex (VMPFC) during the reward task, while we found no alterations in the right and left ventral striatum (VS). The same regions (VS, VTA, and VMPFC), however, showed reduced signal changes during personal reference with lack of neural differentiation between high and low referenced stimuli in alcoholic patients. In summary, we demonstrate for the first time neurophysiological alterations in reward circuitry during personal reference in alcoholic patients. Our results underline the important role of the reward circuitry during personal reference in the pathophysiology of alcohol addiction.     

Reduced striatal activation in females with major depression during the processing of affective stimuli

The extent to which affective reactivity and associated neural underpinnings are altered by depression remains equivocal. This study assessed striatal activation in fifty-one unmedicated female participants meeting DSM-IV criteria for Major Depressive Disorder (MDD) and 61 age-matched healthy females (HC) aged 17–63 years. Participants completed an affective reactivity functional magnetic resonance imaging task. Data were preprocessed using SPM8, and region-of-interest analyses were completed using MarsBaR to extract caudate, putamen, and nucleus accumbens (NAcc) activation. General linear repeated measure ANOVAs were used to assess group differences and correlational analyses were used to measure the association between activation, depression severity, and anhedonia. Main effects of hemisphere, valence, and group status were observed, with MDD participants demonstrating decreased striatal activation compared with HC. Across groups and valence types, the left hemisphere demonstrated greater activation than the right hemisphere in the putamen and nucleus accumbens, whereas the right hemisphere demonstrated greater activation than the left in the caudate. Additionally, unpleasant stimuli elicited greater activation than pleasant and neutral stimuli in the caudate and putamen, and unpleasant stimuli elicited greater activation than neutral stimuli in the NAcc. There were no significant associations between activation, depression severity, and anhedonia. Overall, depression was characterized by reduced affective reactivity in the striatum, regardless of stimuli valence, supporting the emotion context insensitivity model of depression.     

In-hospital levels of C-reactive protein and IL-6 predict post-operative depressive symptoms among patients undergoing total knee replacement surgery

Behavioral changes observed following immune system activation are similar to many of the hallmark symptoms of major depressive disorder (MDD), including appetite change, lethargy, fatigue, negative mood and anhedonia. Acute phase proteins, such as interleukin-6 (IL-6) and C-reactive protein (CRP) have been implicated in the production of sickness behavior, and research has revealed significant differences in the levels of these acute phase proteins between depressed and non-depressed individuals. The current study examined whether early post-operative IL-6 and CRP levels predicted subsequent depressive symptoms in 110 patients undergoing total knee replacement surgery (TKR). In-hospital levels of IL-6 and CRP predicted depressive symptoms at three-months following surgery, as indicated by significant main effects and a significant interaction term. Specifically, lower levels of in-hospital CRP and higher levels of IL-6 in-hospital predicted more depressive symptoms three-months following surgery. The finding that levels of acute phase proteins soon after surgery predict subsequent depressive symptoms, if replicated, extends prior research on the relationships between IL-6, CRP, and depression. Further, this predictive relationship suggests the possibility of early identification of individuals at risk for the subsequent development of post-operative depression.     

Amygdala functional connectivity in female patients with major depressive disorder with and without suicidal ideation

Background

Major depressive disorder (MDD) is a known major risk factor for suicide and is one of the most common mental disorders. Meanwhile, gender differences in suicidal behavior have long been recognized including the finding that women have higher rates of suicidal ideation and/or suicidal behavior than men. The mechanism underlying suicide ideation in female patients with MDD remains poorly understood. The aim of the present study was to examine possible suicidal behavior-related neural circuitry in female MDD.

Methods

In this study, 15 female participants with the first-episode MDD with suicidal ideation and 24 participants with the first-episode MDD without suicidal ideation as well as 39 female participants in a healthy control (HC) group, ranging in age from 18 to 50 years, underwent resting-state functional magnetic resonance imaging. The whole-brain amygdala resting-state functional connectivity (rsFC) was compared among these three groups.

Results

Compared with female participants with the first-episode MDD without suicidal ideation and those in the HC group, female participants with the first-episode MDD with suicidal ideation showed a significant difference in rsFC between the amygdala and precuneus/cuneus (p?<?0.05, corrected). No significant difference in amygdala–precuneus/cuneus rsFC was observed between female patients with the first-episode MDD without suicidal ideation and the HC group (p?<?0.05, corrected).

Conclusions

Our findings suggest that suicidal ideation in female patients with the first-episode MDD may be related to an abnormality in amygdala neural circuitry. The abnormality in amygdala–precuneus/cuneus functional connectivity might present the trait feature for suicide in women with the first-episode MDD. The precuneus/cuneus may be an important region related to suicide and require future study.

     

The influence of insulin on anticipation and consummatory reward to food intake: A functional imaging study on healthy normal weight and overweight subjects employing intranasal insulin delivery

Aberrant responses within homeostatic, hedonic and cognitive systems contribute to poor appetite control in those with an overweight phenotype. The hedonic system incorporates limbic and meso‐limbic regions involved in learning and reward processing, as well as cortical regions involved in motivation, decision making and gustatory processing. Equally important within this complex, multifaceted framework are the cognitive systems involved in inhibitory control and valuation of food choices. Regions within these systems display insulin receptors and pharmacologically increasing central insulin concentrations using intranasal administration (IN‐INS) has been shown to significantly reduce appealing food cue responsiveness and also food intake. In this work we describe a placebo‐controlled crossover pharmacological functional magnetic resonance imaging (fMRI) study that looks at how IN‐INS (160 IU) affects anticipatory and consummatory responses to sweet stimuli and importantly how these responses differ between healthy normal weight and overweight male individuals. This work shows that age matched normal weight and overweight (not obese) individuals respond similarly to both the anticipation and receipt of sweet stimuli under placebo conditions. However, increased central insulin concentrations produce marked differences between groups when anticipating sweet stimuli within the prefrontal cortex and midbrain as well as observed differences in the amygdala during consummatory responses.     

Overnight changes in waking auditory evoked potential amplitude reflect altered sleep homeostasis in major depression

Goldstein MR, Plante DT, Hulse BK, Sarasso S, Landsness EC, Tononi G, Benca RM. Overnight changes in waking auditory evoked potential amplitude reflect altered sleep homeostasis in major depression. Objective: Sleep homeostasis is altered in major depressive disorder (MDD). Pre‐ to postsleep decline in waking auditory evoked potential (AEP) amplitude has been correlated with sleep slow wave activity (SWA), suggesting that overnight changes in waking AEP amplitude are homeostatically regulated in healthy individuals. This study investigated whether the overnight change in waking AEP amplitude and its relation to SWA is altered in MDD. Method: Using 256‐channel high‐density electroencephalography, all‐night sleep polysomnography and single‐tone waking AEPs pre‐ and postsleep were collected in 15 healthy controls (HC) and 15 non‐medicated individuals with MDD. Results: N1 and P2 amplitudes of the waking AEP declined after sleep in the HC group, but not in MDD. The reduction in N1 amplitude also correlated with fronto‐central SWA in the HC group, but a comparable relationship was not found in MDD, despite equivalent SWA between groups. No pre‐ to postsleep differences were found for N1 or P2 latencies in either group. These findings were not confounded by varying levels of alertness or differences in sleep variables between groups. Conclusion: MDD involves altered sleep homeostasis as measured by the overnight change in waking AEP amplitude. Future research is required to determine the clinical implications of these findings.     

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.     

Trait anhedonia is associated with reduced reactivity and connectivity of mesolimbic and paralimbic reward pathways

Anhedonia is the inability to experience pleasure from normally pleasant stimuli. Although anhedonia is a prominent feature of many psychiatric disorders, trait anhedonia is also observed dimensionally in healthy individuals. Currently, the neurobiological basis of anhedonia is poorly understood because it has been mainly investigated in patients with psychiatric disorders. Thus, previous studies have not been able to adequately disentangle the neural correlates of anhedonia from other clinical symptoms. In this study, trait anhedonia was assessed in well-characterized healthy participants with no history of Axis I psychiatric illness. Functional magnetic resonance imaging with musical stimuli was used to examine brain responses and effective connectivity in relation to individual differences in anhedonia. We found that trait anhedonia was negatively correlated with pleasantness ratings of music stimuli and with activation of key brain structures involved in reward processing, including nucleus accumbens (NAc), basal forebrain and hypothalamus which are linked by the medial forebrain bundle to the ventral tegmental area (VTA). Brain regions important for processing salient emotional stimuli, including anterior insula and orbitofrontal cortex were also negatively correlated with trait anhedonia. Furthermore, effective connectivity between NAc, VTA and paralimbic areas, that regulate emotional reactivity to hedonic stimuli, was negatively correlated with trait anhedonia. Our results indicate that trait anhedonia is associated with reduced reactivity and connectivity of mesolimbic and related limbic and paralimbic systems involved in reward processing. Critically, this association can be detected even in individuals without psychiatric illness. Our findings have important implications both for understanding the neurobiological basis of anhedonia and for the treatment of anhedonia in psychiatric disorders.