Drive, reward sensitivity and the flattening of both.
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626 to 650 of 1,483Delay of smoking gratification as a laboratory model of relapse: effects of incentives for not smoking, and relationship with measures of executive function.
Nineteen nicotine-deprived cigarette smokers received monetary rewards for each minute they chose not to initiate smoking in 2-h laboratory sessions followed by a 30-min period of enforced abstinence from smoking. Reinforcer amounts were delivered according to one of three schedules: increasing, decreasing, and constant. Relapse time (time until first cigarette) was shortest in the decreasing condition, longest in the increasing condition, and intermediate in the constant condition. All differences were significant except in the constant-decreasing comparison. The relationships between a battery of baseline assessments and relapse times were examined. Relapse times were predicted by delay-discounting coefficients (k) for $10 and $1000 in money and for $1000 of cigarettes. Relapse times were also predicted by the number of cigarettes smoked daily and a Wisconsin Card Sorting Test score. P…
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Coherent gamma oscillations couple the amygdala and striatum during learning.
The basolateral amygdala (BLA) mediates the facilitating effects of emotions on memory. The BLA's enhancing influence extends to various types of memories, including striatal-dependent habit formation. To shed light on the underlying mechanisms, we carried out unit and local field potential (LFP) recordings in BLA, striatum, auditory cortex and intralaminar thalamus in cats trained on a stimulus-response task in which the presentation of one of two tones predicted reward delivery. The coherence of BLA, but not of cortical or thalamic, LFPs was highest with striatal gamma activity, and intra-BLA muscimol infusions selectively reduced striatal gamma power. Moreover, coupling of BLA-striatal unit activity increased when LFP gamma power was augmented. Early in training, the rewarded and unrewarded tones elicited a modest increase in coherent BLA-striatal gamma. As learning progressed, this g…
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Stipanovich A, Valjent E, Matamales M, Nishi A, Ahn JH, Maroteaux M, Bertran-Gonzalez J, Brami-Cherrier K, Enslen H, Corbillé AG, Filhol O, Nairn AC, Greengard P, Hervé D, Girault JA (2008)MEDLINE-indexed journal, not yet read by usNature181 citations A phosphatase cascade by which rewarding stimuli control nucleosomal response.
Dopamine orchestrates motor behaviour and reward-driven learning. Perturbations of dopamine signalling have been implicated in several neurological and psychiatric disorders, and in drug addiction. The actions of dopamine are mediated in part by the regulation of gene expression in the striatum, through mechanisms that are not fully understood. Here we show that drugs of abuse, as well as food reinforcement learning, promote the nuclear accumulation of 32-kDa dopamine-regulated and cyclic-AMP-regulated phosphoprotein (DARPP-32). This accumulation is mediated through a signalling cascade involving dopamine D1 receptors, cAMP-dependent activation of protein phosphatase-2A, dephosphorylation of DARPP-32 at Ser 97 and inhibition of its nuclear export. The nuclear accumulation of DARPP-32, a potent inhibitor of protein phosphatase-1, increases the phosphorylation of histone H3, an important c…
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Schmidt L, d'Arc BF, Lafargue G, Galanaud D, Czernecki V, Grabli D, Schüpbach M, Hartmann A, Lévy R, Dubois B, Pessiglione M (2008)MEDLINE-indexed journal, not yet read by usBrain : a journal of neurology145 citations Disconnecting force from money: effects of basal ganglia damage on incentive motivation.
Bilateral basal ganglia lesions have been reported to induce a particular form of apathy, termed auto-activation deficit (AAD), principally defined as a loss of self-driven behaviour that is reversible with external stimulation. We hypothesized that AAD reflects a dysfunction of incentive motivation, a process that translates an expected reward (or goal) into behavioural activation. To investigate this hypothesis, we designed a behavioural paradigm contrasting an instructed (externally driven) task, in which subjects have to produce different levels of force by squeezing a hand grip, to an incentive (self-driven) task, in which subjects can win, depending on their hand grip force, different amounts of money. Skin conductance was simultaneously measured to index affective evaluation of monetary incentives. Thirteen AAD patients with bilateral striato-pallidal lesions were compared to thir…
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Ströhle A, Stoy M, Wrase J, Schwarzer S, Schlagenhauf F, Huss M, Hein J, Nedderhut A, Neumann B, Gregor A, Juckel G, Knutson B, Lehmkuhl U, Bauer M, Heinz A (2008)MEDLINE-indexed journal, not yet read by usNeuroImage247 citations Reward anticipation and outcomes in adult males with attention-deficit/hyperactivity disorder.
Attention-deficit/hyperactivity disorder (ADHD) has been suggested to involve deficits in reward processing. We used functional magnetic resonance imaging (fMRI) to compare the neural responses to reward anticipation and outcomes in 10 adults with ADHD and 10 controls as they played a monetary incentive delay task. Adults with ADHD were unmedicated, and groups were matched for age, verbal IQ and smoking habits. Adults with ADHD showed decreased activation in the ventral striatum during the anticipation of gain, but increased activation of the orbitofrontal cortex in response to gain outcomes. Ventral striatal activation in adults with ADHD during gain anticipation was negatively correlated with self-rated symptoms of hyperactivity and impulsivity. These findings suggest that male adults with ADHD show neural signs of abnormal reward processing. Future studies will have to investigate whe…
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Neural responses to taxation and voluntary giving reveal motives for charitable donations.
Civil societies function because people pay taxes and make charitable contributions to provide public goods. One possible motive for charitable contributions, called "pure altruism," is satisfied by increases in the public good no matter the source or intent. Another possible motive, "warm glow," is only fulfilled by an individual's own voluntary donations. Consistent with pure altruism, we find that even mandatory, tax-like transfers to a charity elicit neural activity in areas linked to reward processing. Moreover, neural responses to the charity's financial gains predict voluntary giving. However, consistent with warm glow, neural activity further increases when people make transfers voluntarily. Both pure altruism and warm-glow motives appear to determine the hedonic consequences of financial transfers to the public good.
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Chimpanzee (Pan troglodytes) anticipation of food return: coping with waiting time in an exchange task.
Despite controversial expectations that animals achieve reciprocal altruism, it is unclear if nonhuman species possess the necessary cognitive abilities. For reciprocal altruism, individuals must anticipate the loss of a commodity and accept a delay before some return. The authors investigated the abilities of 5 chimpanzees (Pan troglodytes) to cope with increasing waiting duration in exchange tasks. Subjects had to keep a small cookie before returning it to a human partner to obtain a larger piece. For a piece 2, 4, or 8 times the size of the small piece, 3 of the 5 subjects waited for up to 4 min. For a piece 40 times larger, 4 of the 5 subjects waited up to 8 min. At long time lag, renouncement to wait occurred earlier than predicted by subjects' general waiting capacity, suggesting that the decision to wait was based on a trade-off between reward quantity and expected costs of the wa…
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Tonic dopamine: opportunity costs and the control of response vigor.
Rationale: Dopamine neurotransmission has long been known to exert a powerful influence over the vigor, strength, or rate of responding. However, there exists no clear understanding of the computational foundation for this effect; predominant accounts of dopamine's computational function focus on a role for phasic dopamine in controlling the discrete selection between different actions and have nothing to say about response vigor or indeed the free-operant tasks in which it is typically measured.
Objectives: We seek to accommodate free-operant behavioral tasks within the realm of models of optimal control and thereby capture how dopaminergic and motivational manipulations affect response vigor.
Methods: We construct an average reward reinforcement learning model in which subjects choose both which action to perform and also the latency with which to perform it. Optimal control balances t…
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Maintenance of delay of gratification by four chimpanzees (Pan troglodytes): the effects of delayed reward visibility, experimenter presence, and extended delay intervals.
Previous research in our laboratory has demonstrated that chimpanzees can delay gratification by inhibiting consumption of available food items for as long as 3 min as an experimenter transfers additional food items from a transparent container to a bowl placed in front of the subject. In this study, we examined the influence of the visibility of the food source, as well as the presence of the experimenter, on four chimpanzees' self-control in this paradigm. In Experiment 1 an experimenter transferred 15 preferred food items between a distant opaque container and a bowl placed in front of the subject. In Experiment 2 we tested the chimpanzees with an automated system that (in the absence of the experimenter) transferred up to 36 highly preferred food items from a universal food dispenser to a container located either inside or outside of the subject's enclosure. There were no differences…
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Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning.
The anterior cingulate and orbital cortices and the ventral striatum process different aspects of reward evaluation, whereas the dorsolateral prefrontal cortex and the dorsal striatum are involved in cognitive function. Collectively, these areas are critical to decision making. We mapped the striatal area that receives information about reward evaluation. We also explored the extent to which terminals from reward-related cortical areas converge in the striatum with those from cognitive regions. Using three-dimensional-rendered reconstructions of corticostriatal projection fields along with two-dimensional chartings, we demonstrate the reward and cognitive territories in the primate striatum and show the convergence between these cortical inputs. The results show two labeling patterns: a focal projection field that consists of densely distributed terminal patches, and a diffuse projection…
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Regan JL (2016)case reportMEDLINE-indexed journal, not yet read by usDementia (London, England)20 citations Ethnic minority, young onset, rare dementia type, depression: A case study of a Muslim male accessing UK dementia health and social care services.
A case study comprised of formal interviews, formal observations and informal discussions investigated the motivations and experiences accessing dementia care health and social care services for a Muslim, Pakistani male with dementia. Motivations derived from 'desperation' and an inability to access support from family or religious community. Experiences of accessing services were mostly negative. Dementia services were ill-informed about how to support persons with young onset dementia, with pre-existing mental health conditions, from an ethnic minority. Education and training to remove barriers to all dementia care services is required for persons with dementia, their families and within dementia services and religious communities.
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The use of a vodcast to support eating and reduce anxiety in people with eating disorder: A case series.
Individuals with eating disorders have difficulty controlling obsessive intrusions and ritualistic behaviours relating to food and exercise. An imagery-based intervention using a vodcast (small video file played on a mobile phone or portable media device), with visual and aural components, was designed to target eating related psychopathology in a consecutive series of four patients. The vodcast was used to support consumption of a smoothie, both as a behavioural experiment and at home, in naturalistic circumstances. More of the smoothie was drunk in a shorter time when the smoothie was offered with the vodcast (mean of 218 g, SD = 64) than in the comparison condition (mean of 160 g, SD = 71). The vodcast condition was associated with reduced anxiety in three out of four patients. Three out of four patients used the vodcasts at home and found they provided them with support and motivatio…
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Cai H, Chow IHI, Lei SM, Lok GKI, Su Z, Cheung T, Peshkovskaya A, Tang YL, Jackson T, Ungvari GS, Zhang L, Xiang YT (2023)MEDLINE-indexed journal, not yet read by usJournal of affective disorders24 citations Inter-relationships of depressive and anxiety symptoms with suicidality among adolescents: A network perspective.
Background: Persons with suicidality including suicidal ideation (SI), suicide plans (SP) and/or suicide attempts (SA) are at higher risk for future suicide than those without suicidality. To reduce the risk of future suicide, it is important to understand symptoms of emotional distress that have the strongest links with SI, SP and SA. This network analysis examined item-level relations of depressive and anxiety symptoms with suicidality among adolescents during the COVID-19 pandemic.
Methods: Adolescents between 12 and 20 years of age were assessed with the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and individual binary reponse (no/yes) items assessing SI, SP, and SA during the pandemic. The structure of depressive symptoms, anxiety symptoms and suicidality was characterized using "Expected Influence" and "Bridge Expected Influence" as centrality …
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He Y, Wu C, LeMoult J, Huang J, Zhao Y, Liang K, Chen S, Wang E, Huang L, Chi X (2023)MEDLINE-indexed journal, not yet read by usBMC psychiatry27 citations Exploring symptom-level associations between anxiety and depression across developmental stages of adolescence: a network analysis approach.
Background: Anxiety and depression often co-occur during adolescence, but the associations between symptoms of these two disorders in this developmental period are not yet fully understood. Network analysis provides a valuable approach to uncover meaningful associations among symptoms and offers insights for prevention and intervention strategies. This study aimed to investigate symptom-level associations between anxiety and depression using network analysis and to identify core symptoms, bridge symptoms, and differences in network structure across different stages of adolescence.
Methods: The cross-sectional study was conducted in March 2022 in Shenzhen, China. Participants completed the Generalized Anxiety Disorder Scale-7 and Patient Health Questionnaire Depression Scale, along with demographic questionnaires assessing age and gender. Chinese adolescents aged 10 to 17 who were in Grad…
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The factor structure of the Edinburgh Postnatal Depression Scale among perinatal high-risk and community samples in London.
Timely and accurate detection of perinatal mental health problems is essential for the wellbeing of both mother and child. Growing evidence has suggested that the Edinburgh Postnatal Depression Scale (EPDS) is not a unidimensional measure of perinatal depression, but can be used to screen for anxiety disorders. We aimed to assess the factor structure of the EPDS in 3 different groups of women: n = 266 pregnant women at high-risk of depression ("Perinatal Stress Study"), n = 471 pregnant women from a community sample, and n = 637 early postnatal women from a community sample ("developing Human Connectome Project"). Exploratory factor analysis (40% of each sample) and confirmatory factor analysis (60% of each sample) were performed. The relationship between EPDS scores and history of mental health concerns was investigated. Results suggested that a 3-factor model (depression, anxiety, and …
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Identifying the presence and timing of discrete mood states prior to therapy.
The present study tested a novel, person-specific method for identifying discrete mood profiles from time-series data, and examined the degree to which these profiles could be predicted by lagged mood and anxiety variables and time-based variables, including trends (linear, quadratic, cubic), cycles (12-hr, 24-hr, and 7-day), day of the week, and time of day. We analyzed ambulatory data from 45 individuals with mood and anxiety disorders prior to therapy. Data were collected four-times-daily for at least 30 days. Latent profile analysis was applied person-by-person to discretize each individual's continuous multivariate time series of rumination, worry, fear, anger, irritability, anhedonia, hopelessness, depressed mood, and avoidance. That is, each time point was classified according to its unique blend of emotional states, and latent classes representing discrete mood profiles were iden…
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Antibiotic-induced microbiome depletion is associated with resilience in mice after chronic social defeat stress.
Background: The brain-gut axis plays a role in the pathogenesis of stress-related disorders such as depression. However, the role of brain-gut axis in the resilience versus susceptibility after stress remains unclear. Here, we examined the effects of antibiotic-induced microbiome depletion on an anhedonia-like phenotype in adult mice subjected to chronic social defeat stress (CSDS).
Methods: Using CSDS paradigm, we investigated the effects of antibiotic-induced microbiome depletion on the resilience versus susceptibility in mice.
Results: Treatment with an antibiotic cocktail for 14 days significantly decreased the diversity and composition of the microbiota in the host gut. Proteobacteria were markedly increased after treatment with the antibiotic cocktail. At the genus and species levels, the antibiotic-treated group exhibited marked alterations in the microbiota compared with a contro…
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Moreno-Fernández RD, Pérez-Martín M, Castilla-Ortega E, Rosell Del Valle C, García-Fernández MI, Chun J, Estivill-Torrús G, Rodríguez de Fonseca F, Santín LJ, Pedraza C (2017)MEDLINE-indexed journal, not yet read by usTranslational psychiatry40 citations maLPA1-null mice as an endophenotype of anxious depression.
Anxious depression is a prevalent disease with devastating consequences and a poor prognosis. Nevertheless, the neurobiological mechanisms underlying this mood disorder remain poorly characterized. The LPA1 receptor is one of the six characterized G protein-coupled receptors (LPA1-6) through which lysophosphatidic acid acts as an intracellular signalling molecule. The loss of this receptor induces anxiety and several behavioural and neurobiological changes that have been strongly associated with depression. In this study, we sought to investigate the involvement of the LPA1 receptor in mood. We first examined hedonic and despair-like behaviours in wild-type and maLPA1 receptor null mice. Owing to the behavioural response exhibited by the maLPA1-null mice, the panic-like reaction was assessed. In addition, c-Fos expression was evaluated as a measure of the functional activity, followed by…
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High-Fat Diet Induced Anxiety and Anhedonia: Impact on Brain Homeostasis and Inflammation.
Depression and type 2 diabetes (T2D) are highly comorbid disorders that carry a large public health burden. However, there is a clear lack of knowledge of the neural pathological pathways underlying these illnesses. The present study aims to elucidate the molecular mechanisms by which a diet rich in fat can cause multiple complications in the brain, thereby affecting intracellular signaling and gene expression that underlie anxiety and depressive behaviors. The results show that a high-fat diet (HFD; ~16 weeks) causes anxiety and anhedonic behaviors. Importantly, the results also show that 4 months of HFD causes disruption of intracellular cascades involved in synaptic plasticity and insulin signaling/glucose homeostasis (ie, Akt, extracellular signal-regulated kinase (ERK), P70S6K), as well as increased corticosterone levels and activation of the innate immune system, including elevatio…
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Increased social anhedonia and reduced helping behaviour in young people with high depressive symptomatology.
Background: Social anhedonia, the decreased enjoyment of pleasant social experiences, is associated with depression. However, whether social anhedonia in depression affects prosocial behaviours is unclear. The current study aimed to examine how high levels of depressive symptomatology in young people affect responses to usually rewarding social situations, including helping behaviour.
Methods: We recruited 46 females, 16 scoring high on the Beck Depression Inventory (BDI scores>20, Mage=19; HD) and 30 scoring low (BDI<10, Mage=20; LD). In a social emotion task (SET), participants were presented with social scenarios and asked to rate their expected emotional responses. Subsequently, participants' helping behaviour was measured by dropping a pile of papers near them and recording their responses. Lastly, participants completed the SET again.
Results: The SET at time 1 revealed that HD ind…
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Depression and employment status in primary and tertiary care settings.
Objective: Major depressive disorder (MDD) is a leading cause of disability. Impairment in work function considerably adds to symptom burden and increases the economic impact of this disorder. Our study aimed to investigate the factors associated with work status in MDD within primary and tertiary care.
Method: We used data from 2 large databases for our analysis--Study 1: the InSight database, a chart review of MDD patients treated by primary care physicians across Canada (n=986); and Study 2: the International Mood Disorders Collaborative Project, a cross-sectional study of mood disorder patients (Canadian data only: n=274).
Results: Both studies demonstrated high rates of unemployment and disability (30.3% to 42.1%). Quebec showed the highest rate of unemployment (21%) and British Columbia had the greatest percentage of patients on disability (15%). Employed and unemployed groups were…
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Couch Y, Anthony DC, Dolgov O, Revischin A, Festoff B, Santos AI, Steinbusch HW, Strekalova T (2013)MEDLINE-indexed journal, not yet read by usBrain, behavior, and immunity145 citations Microglial activation, increased TNF and SERT expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia.
A chronic stress paradigm comprising exposure to predation, tail suspension and restraint induces a depressive syndrome in C57BL/6J mice that occurs in some, but not all, animals. Here, we sought to extend our behavioural studies to investigate how susceptibility (sucrose preference<65%) or resilience (sucrose preference>65%) to stress-induced anhedonia affects the 5HT system and the expression of inflammation-related genes. All chronically stressed animals, displayed increased level of anxiety, but susceptible mice exhibited an increased propensity to float in the forced swim test and demonstrate hyperactivity under stressful lighting conditions. These changes were not present in resilient or acutely stressed animals. Compared to resilient animals, susceptible mice showed elevated expression of tumour necrosis factor alpha (TNF) and the 5-HT transporter (SERT) in the pre-frontal area. E…
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Social deprivation stress is a triggering factor for the emergence of anxiety- and depression-like behaviours and leads to reduced brain BDNF levels in C57BL/6J mice.
Stress is a main risk factor that can trigger psychiatric disorders, including anxiety and major depression. Neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF), have been identified as neuroendocrine effectors involved in the response to stress and in the neurobehavioural changes associated with depression. Aim of this paper was to study the relationship between neuroendocrine activation (circulating corticosterone and brain BDNF levels) and a wide array of depression- and anxiety-like behaviours (anhedonia, behavioural despair, generalised and social anxiety) resulting from exposure to chronic stress. To this end, 3-month-old C57BL/6J male mice were exposed to either chronic disruption of the social structure (SS), to a stable social structure (SG) or to social deprivation (SD), a condition lacking social stimuli. Results show that, despite not developing anhedonia (decreas…
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Chronic juvenile stress produces corticolimbic dendritic architectural remodeling and modulates emotional behavior in male and female rats.
Nearly 12% of US children are exposed to intense adverse experiences. Research has demonstrated that these experiences can negatively impact adult health, often resulting in psychopathology. Less attention, however, is given to the impact of childhood adverse experiences on childhood health and wellbeing. Using a rodent model of chronic juvenile stress (restraint 6 h daily from postnatal day 20 to 41), we report that chronic stress has significant immediate morbidities in both males and females during this developmental window. Specifically, we demonstrate that chronic juvenile stress produces depressive-like behavior and significant neuronal remodeling of brain regions likely involved in these behavioral alterations: the hippocampus, prefrontal cortex and amygdala. Chronically stressed males and females exhibit anhedonia, increased locomotion when exposed to novelty, and altered coping …
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Anhedonia requires MC4R-mediated synaptic adaptations in nucleus accumbens.
Chronic stress is a strong diathesis for depression in humans and is used to generate animal models of depression. It commonly leads to several major symptoms of depression, including dysregulated feeding behaviour, anhedonia and behavioural despair. Although hypotheses defining the neural pathophysiology of depression have been proposed, the critical synaptic adaptations in key brain circuits that mediate stress-induced depressive symptoms remain poorly understood. Here we show that chronic stress in mice decreases the strength of excitatory synapses on D1 dopamine receptor-expressing nucleus accumbens medium spiny neurons owing to activation of the melanocortin 4 receptor. Stress-elicited increases in behavioural measurements of anhedonia, but not increases in measurements of behavioural despair, are prevented by blocking these melanocortin 4 receptor-mediated synaptic changes in vivo.…
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