Altered neural reward and loss processing and prediction error signalling in depression

Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression.     

A close relationship between verbal memory and SN/VTA integrity in young and older adults

Age-related dysfunction in dopaminergic neuromodulation is assumed to contribute to age-associated memory impairment. However, to date there are no in vivo data on how structural parameters of the substantia nigra/ventral tegmental area (SN/VTA), the main origin of dopaminergic projections, relate to memory performance in healthy young and older adults. We investigated this relationship in a cross-sectional study including data from the hippocampus and frontal white matter (FWM) and also assessing working memory span and attention. In groups of young and older adults matched for the variance of their age distribution, gender and body mass index, we observed a robust positive correlation between Magnetization Transfer Ratio (MTR) - a measure of structural integrity - of the SN/VTA and FWM with verbal learning and memory performance among older adults, while there was a negative correlation in the young. Two additional imaging parameters, anisotropy of diffusion and diffusion coefficient, suggested that in older adults FWM changes reflected vascular pathology while SN/VTA changes pointed towards neuronal loss and loss of water content. The negative correlation in the young possibly reflected maturational changes. Multiple regression analyses indicated that in both young and older adults, SN/VTA MTR explained more variance of verbal learning and memory than FWM MTR or hippocampal MTR, and contributed less to explaining variance of working memory span. Together these findings indicate that structural integrity in the SN/VTA has a relatively selective impact on verbal learning and memory and undergoes specific changes from young adulthood to older age that qualitatively differ from changes in the FWM and hippocampus.     

Altered neural function during episodic memory encoding and retrieval in major depression

Memory impairments are common in major depression. Neural processing during non‐emotional episodic memory in depressed patients has only sparsely been investigated, since the majority of studies have focused on emotional stimuli. The aim of this study was to explore neural correlates of episodic memory in depressive patients and to assess brain regions related to subsequent memory performance. Forty‐six participants (23 depressed patients) performed a non‐emotional episodic memory encoding and retrieval task while brain activation was measured with functional magnetic resonance imaging. Patients with depression showed decreased activation in the right prefrontal cortex and right cingulate cortex during memory encoding, but increased activation in the right inferior frontal gyrus (IFG) during recognition memory. While a strong association between hippocampal and parahippocampal activation during memory encoding with subsequent memory performance became evident in healthy controls, this relationship was absent in patients with depression. Taken together, these findings demonstrate that memory related brain regions are affected in their appropriate functioning during memory encoding in depressed patients. Therefore, patients with depression may rely to a greater degree on other brain regions such as the IFG during episodic memory retrieval. Hum Brain Mapp 35:4293–4302, 2014. © 2014 Wiley Periodicals, Inc .     

Neural changes in reward processing following approach-avoidance training for depression

Altered approach motivation is hypothesized to be critical for the maintenance of depression. Computer-administered approach-avoidance training programs to increase approach action tendencies toward positive stimuli produce beneficial outcomes. However, there have been few studies examining neural changes following approach-avoidance training. Participants with major depressive disorder were randomized to an approach-avoidance training (AAT) manipulation intended to increase approach tendencies for positive social cues (n = 13) or a control procedure (n = 15). We examined changes in neural activation (primary outcome) and connectivity patterns using Group Iterative Multiple Model Estimation during a social reward anticipation task (exploratory). A laboratory-based social affiliation task was also administered following the manipulation to measure affect during anticipation of real-world social activity. Individuals in the AAT group demonstrated increased activation in reward processing regions during social reward anticipation relative to the control group from pre- to post-training. Following training, connectivity patterns across reward regions were observed in the full sample and connectivity between the medial prefrontal cortex and caudate was associated with anticipatory positive affect before the social interaction. Preliminary evidence of differential connectivity patterns between the two groups also emerged. Results support models whereby modifying approach-oriented behavioral tendencies with computerized training lead to alterations in reward circuitry ({"type":"clinical-trial","attrs":{"text":"NCT02330744","term_id":"NCT02330744"}}NCT02330744).     

The influence of depression on memory

One hundred and fifty-two patients suffering from endogenous depression and receiving electroconvulsive therapy (ECT) were scoredfor depression and for memory function before the first, after thesixth and after the last treatment. One third of the patients werealso studied with regard to Retention by verbal and visual testson the same occasions. For the purpose of calculating possible correlations between the degree of depression and memory function, 10 depressive symptoms were assessed and combined under three headings, (1) Depressive Appearance, (2) Content of Ideas and (3) Agitation, while the memory function was measured by means of WMS comprising seven tests combined under three headings, (1) Mental Control, (2) Verbal Learning and (3) Visual Reproduction, besides the tests for Retention. Correlations were calculated on absolute scores before the treatment and on differences between scores from first to second and from first to third examination during the treatment. It is concluded that endogenous depression clearly impairs memory function as measured by WMS and tests for Retention and that, in accordance with this, recovery from depression eliminates the impairment of memory. Mental Control is slightly more sensitive to depression than the other memory tests. Of the components of depression, especially Agitation, but also Depressive Appearance are of great importance. It is further concluded that other factors, too, are of appreciable significance in the memory function as measured by the aforementioned methods. In this context, the intelligence as well as the attitude towards the patient during the testing must be assumed to be of importance. Age seems to have no influence on the relation between depression and memory. As the WMS has been standardized to WAIS IQ, and as in unilateral ECT a great approximation of the average MQ score to the normal level of intelligence occurs, it may be deduced that the harmful effect of this form of treatment on memory is only very slight. Signs of impaired memory after unilateral ECT may thus be interpreted rather as evidence of the presence of residual depression, especially if “Mental Control” is reduced and depressive symptoms such as “Agitation” and “Depressive Appearance” remain.     

Modulating reconsolidation and extinction to regulate drug reward memory

Drug addiction is an aberrant memory that shares the same memory processes as other memories. Brief exposure to drug‐associated cues could result in reconsolidation, a hypothetical process during which original memory could be updated. In contrast, longer exposure times to drug‐associated cues could trigger extinction, a process that decreases the conditioned responding. In this review, we discuss the pharmacological and non‐pharmacological manipulations on the reconsolidation and extinction that could be used to interfere with drug reward memories. Pharmacological agents such as β‐adrenergic receptor antagonist propranolol can interfere with reconsolidation to disrupt drug reward memory. Pharmacological agents such as the NMDA receptor glycine site agonists d ‐cycloserine and d ‐serine can facilitate extinction and then attenuate the expression of drug reward memory. Besides pharmacological interventions, drug‐free behavioral approaches by utilizing the reconsolidation and extinction, such as ‘post‐retrieval extinction’ and ‘UCS‐retrieval extinction’, are also effective to erase or inhibit the recall of drug reward memory. Taken together, pharmacological modulation and non‐pharmacological modulation of reconsolidation and extinction are promising approaches to regulate drug reward memory and prevent relapse.     

Investigation of mood-congruent false and true memory recognition in depression

The present study investigated the extent of mood-congruent false and true memory recognition in depression. A group of 25 patients with depression and 28 healthy controls completed a variant of the Deese-Roediger McDermott task. Four lists were read to participants in sequence, followed by a recognition task. The words in each list were associated with a central but unmentioned theme word that was either depression-relevant (i.e., loneliness), delusion-relevant (betrayal), positive (holidays), or neutral (window). Whereas it was expected to replicate the conventional mood-congruent effect in depression (better recognition of depression-relevant items), the available literature did not allow strong predictions to be made on the extent of mood-congruent false recognition in depression. Results showed that depressed patients learned emotionally charged material equally well as healthy participants but forgot significantly more neutral material. A conventional mood-congruent memory bias was not found, but relative to healthy controls, patients with depression committed more false recognition errors for emotionally charged words, particularly for depression-relevant items. The results confirm that depressed patients are biased toward emotional material. Reasons for the absence of the expected mood-congruent memory bias are discussed. It is suggested that researchers as well as clinicians should pay more attention to mood-congruent false recollection, because it may undermine the validity of autobiographic reports in depressive patients and may represent a maintenance factor for the disorder.     

Individual differences and the neural representations of reward expectation and reward prediction error

Reward expectation and reward prediction errors are thoughtto be critical for dynamic adjustments in decision-making andreward-seeking behavior, but little is known about their representationin the brain during uncertainty and risk-taking. Furthermore,little is known about what role individual differences mightplay in such reinforcement processes. In this study, it is shownbehavioral and neural responses during a decision-making taskcan be characterized by a computational reinforcement learningmodel and that individual differences in learning parametersin the model are critical for elucidating these processes. Inthe fMRI experiment, subjects chose between high- and low-riskrewards. A computational reinforcement learning model computedexpected values and prediction errors that each subject mightexperience on each trial. These outputs predicted subjects’trial-to-trial choice strategies and neural activity in severallimbic and prefrontal regions during the task. Individual differencesin estimated reinforcement learning parameters proved criticalfor characterizing these processes, because models that incorporatedindividual learning parameters explained significantly morevariance in the fMRI data than did a model using fixed learningparameters. These findings suggest that the brain engages areinforcement learning process during risk-taking and that individualdifferences play a crucial role in modeling this process.     

Frontopolar cortical inefficiency may underpin reward and working memory dysfunction in bipolar disorder

Abstract

Objectives. Emotional dysregulation in bipolar disorder is thought to arise from dysfunction within prefrontal cortical regions involved in cognitive control coupled with increased or aberrant activation within regions engaged in emotional processing. The aim of this study was to determine the common and distinct patterns of functional brain abnormalities during reward and working memory processing in patients with bipolar disorder. Methods. Participants were 36 euthymic bipolar disorder patients and 37 healthy comparison subjects matched for age, sex and IQ. Functional magnetic resonance imaging (fMRI) was conducted during the Iowa Gambling Task (IGT) and the n-back working memory task. Results. During both tasks, patients with bipolar disorder demonstrated a pattern of inefficient engagement within the ventral frontopolar prefrontal cortex with evidence of segregation along the medial-lateral dimension for reward and working memory processing, respectively. Moreover, patients also showed greater activation in the anterior cingulate cortex during the Iowa Gambling Task and in the insula during the n-back task. Conclusions. Our data implicate ventral frontopolar dysfunction as a core abnormality underpinning bipolar disorder and confirm that overactivation in regions involved in emotional arousal is present even in tasks that do not typically engage emotional systems.     

Neural correlates of reward and loss sensitivity in psychopathy

Psychopathy is a personality disorder associated with callous and impulsive behavior and criminal recidivism. It has long been theorized that psychopaths have deficits in processing reward and punishment. Here, we use structural and functional magnetic resonance imaging to examine the neural correlates of reward and loss sensitivity in a group of criminal psychopaths. Forty-one adult male prison inmates (n = 18 psychopaths and n = 23 non-psychopaths) completed a functional magnetic resonance imaging task involving the gain or loss of money. Across the entire sample of participants, monetary gains elicited robust activation within the ventral striatum (VS). Although psychopaths and non-psychopaths did not significantly differ with respect to overall levels of VS response to reward vs loss, we observed significantly different correlations between VS responses and psychopathy severity within each group. Volumetric analyses of striatal subregions revealed a similar pattern of correlations, specifically for the right accumbens area within VS. In a separate sample of inmates (n = 93 psychopaths and n = 117 non-psychopaths) who completed a self-report measure of appetitive motivation, we again found that the correlation with psychopathy severity differed between groups. These convergent results offer novel insight into the neural substrates of reward and loss processing in psychopathy.     

Neural mechanisms of reward and loss processing in a low-income sample of at-risk adolescents

Adolescence is a time of engagement in risky, reward-driven behaviors, with concurrent developmental changes within reward-related neural systems. As previous research has recruited mostly higher socioeconomic, European and European American participants, therefore limiting generalizability to the US population, especially for populations of color or low-income populations. The current study provided one of the first opportunities to examine the neural correlates of reward and loss functioning in a population-based sample of adolescents at increased risk for poverty-related adversities. The study investigated neural reward and loss processing and whether age, pubertal status and the social constructs of gender and race predicted individual differences in reward- and loss-related brain function. One hundred and twenty-eight primarily low-income adolescents (mean age: 15.9 years, 75% African American) from urban environments completed a modified monetary incentive delay task during functional magnetic resonance imaging (fMRI). Consistent with the previous research, reward and loss anticipation recruited similar motivational circuitry including striatal, insular, thalamic and supplementary motor areas. Race and gender were not associated with reward- or loss-related neural reactivity. Age and pubertal development were associated with differences in neural reactivity to reward and loss, suggesting that older and more mature adolescents had increased activity in sensory and motivational circuits, but decreased activity in regions responsible for error detection and behavior modification.     

Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression.

BACKGROUND: A large number of studies suggest the presence of deficits in dorsolateral prefrontal cortex function during performance of working memory tasks in individuals with schizophrenia. However, working memory deficits may also present in other psychiatric disorders, such as major depression. It is not clear whether people with major depression also demonstrate impaired prefrontal activation during performance of working memory tasks. METHODS: We used functional magnetic resonance imaging to assess the patterns of cortical activation associated with the performance of a 2-back version of the N-Back task (working memory) in 38 individuals with schizophrenia and 14 with major depression. RESULTS: We found significant group differences in the activation of dorsolateral prefrontal cortex associated with working memory performance. Consistent with prior research, participants with schizophrenia failed to show activation of right dorsolateral prefrontal cortex in response to working memory tasks demands, whereas those with major depression showed clear activation of right and left dorsolateral prefrontal cortex as well as bilateral activation of inferior and superior frontal cortex. CONCLUSIONS: During performance of working memory tasks, deficits in prefrontal activation, including dorsolateral regions, are more severe in participants with schizophrenia (most of whom were recently released outpatients) than in unmedicated outpatients with acute nonpsychotic major depression.     

Association between reward‐related activation in the ventral striatum and trait reward sensitivity is moderated by dopamine transporter genotype

The impact of individual differences on human reward processing has been a focus of research in recent years, particularly, as they are associated with a variety of neuropsychiatric diseases including addiction and attention‐deficit/hyperactivity disorder. Studies exploring the neural basis of individual differences in reward sensitivity have consistently implicated the ventral striatum (VS) as a core component of the human reward system. However, the mechanisms of dopaminergic neurotransmission underlying ventral striatal activation as well as trait reward sensitivity remain speculative. We addressed this issue by investigating the triadic interplay between VS reactivity during reward anticipation using functional magnetic resonance imaging, trait reward sensitivity, and dopamine (DA) transporter genotype (40‐bp 3′VNTR of DAT, SLC6A3) affecting synaptic DA neurotransmission. Our results show that DAT variation moderates the association between VS‐reactivity and trait reward sensitivity. Specifically, homozygote carriers of the DAT 10‐repeat allele exhibit a strong positive correlation between reward sensitivity and reward‐related VS activity whereas this relationship is absent in the DAT 9‐repeat allele carriers. We discuss the possibility that this moderation of VS‐trait relation might arise from DAT‐dependent differences in DA availability affecting synaptic plasticity within the VS. Generally, studying the impact of dopaminergic gene variations on the relation between reward‐related brain activity and trait reward sensitivity might facilitate the investigation of complex mechanisms underlying disorders linked to dysregulation of DA neurotransmission. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

首发抑郁症患者字母工作记忆fMRI研究

目的探讨首发抑郁症患者字母工作记忆的脑激活特征。方法12例首发抑郁症患者与12名健康对照配对进行字母工作记忆任务的功能磁共振成像(fMRI)。以AFNI软件对fMRI数据进行定位与定量分析。结果①两组任务执行正确率均大于75%,患者组字母工作记忆2-back任务正确率低于对照组[(0.79±0.04)%vs(0.83±0.03)%,t=4.69,P<0.05];②两组字母工作记忆激活的感兴趣脑区(ROI)均为左侧Broca区BA44/45、双侧前额叶腹侧BA9/46、顶叶后部BA7/40、前运动区BA6及辅助运动区(SMA)BA6/8(P<0.05);③患者组在右侧与左侧BA9/46、右侧与左侧BA6及左侧Broca区的激活强度分别为:1.38%、1.69%、1.21%、1.32%及0.52%,低于对照组的2.42%、3.53%、2.95%、3.51%及1.62%(P<0.05)。结论首发抑郁症患者存在字母工作记忆损害,而语音环路的双侧BA9/46、BA6与左侧Broca区激活减弱可能为其病理机制之一。     

Overgeneral autobiographical memory and depression in older adults: a systematic review

Objectives: Overgeneral autobiographical memory (OGM) is a well-researched phenomenon in working age adults with depression. However, the relevance and importance of OGM in older adult depression is not well established. The aim of this review was to synthesise existing literature on OGM and depressive symptoms in older adults under the framework of the Capture and Rumination, Functional Avoidance and Impaired Executive Control (CaR-FA-X) model.

Method: Literature searches were conducted using PsychINFO, PubMed and Web of Knowledge. Eighteen articles were reviewed.

Results: OGM is elevated in healthy older adults compared to adults of working age, and further elevated in older adults with depression. Evidence supports the role of impaired executive function as a mechanism for OGM in older adults with depression, but no studies measured other components of the CaR-FA-X model (i.e. functional avoidance and rumination).

Conclusion: OGM is prevalent in older adults and more so for those with depression; however, there is no clear understanding of the underpinning mechanisms. It is recommended that future research looks at the role of functional avoidance and rumination, and at the use of memory specificity interventions being developed in the working age adult literature.     

Sleep-related memory consolidation in depression: an emerging field of research

Sleep-related memory consolidation has received increasing attention in recent years. Because previous research has focused on healthy young adults, only very few studies have been conducted in patients with psychiatric disorders so far. The investigation of sleep-related memory consolidation in depression offers a wide range of future research opportunities and can therefore be regarded as an emerging field of research. This article gives a short overview of current knowledge of sleep-related memory consolidation in healthy young adults and builds a bridge to psychiatry and depression, where further research is urgently needed.     

Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder.

BACKGROUND: Although abnormalities in reward processing have been proposed to underlie attention-deficit/hyperactivity disorder (ADHD), this link has not been tested explicitly with neural probes. METHODS: This hypothesis was tested by using fMRI to compare neural activity within the striatum in individuals with ADHD and healthy controls during a reward-anticipation task that has been shown previously to produce reliable increases in ventral striatum activity in healthy adults and healthy adolescents. Eleven adolescents with ADHD (5 off medication and 6 medication-na?ve) and 11 healthy controls (ages 12-17 y) were included. Groups were matched for age, gender, and intelligence quotient. RESULTS: We found reduced ventral striatal activation in adolescents with ADHD during reward anticipation, relative to healthy controls. Moreover, ventral striatal activation was negatively correlated with parent-rated hyperactive/impulsive symptoms across the entire sample. CONCLUSIONS: These findings provide neural evidence that symptoms of ADHD, and impulsivity or hyperactivity in particular, may involve diminished reward anticipation, in addition to commonly observed executive dysfunction.     

Memory-related hippocampal activation during sleep and temporal memory in toddlers

Nonhuman research has implicated developmental processes within the hippocampus in the emergence and early development of episodic memory, but research in humans has been constrained by the difficulty of examining hippocampal function during early development. In the present study, we assessed 48 2-year-olds with a novel paradigm in which participants completed two games on a tablet that required remembering associations between unique characters, the places they visited, and the temporal order with which they did so. At the completion of each game, a unique, novel song played. Toddlers remembered spatial locations better than temporal order during an immediate test, after a 20-minute delay, and after a week delay. After the last behavioral session, toddlers underwent an fMRI task during natural nocturnal sleep evaluating hippocampal activation in response to learned and novel songs. We found that the extent of hippocampal activation for learned songs compared to novel songs during sleep was correlated with memory for temproal order across all time delays, but not with memory for spatial locations. The results confirm that that the functional contribution of the hippocampus to early memory can be assessed during sleep and suggest that assessment of temporal aspects of memory in the current task best capture this contribution.