scholarly journals Blunted medial prefrontal cortico-limbic reward-related effective connectivity and depression

Brain ◽  
2020 ◽  
Vol 143 (6) ◽  
pp. 1946-1956 ◽  
Author(s):  
Samuel Rupprechter ◽  
Liana Romaniuk ◽  
Peggy Series ◽  
Yoriko Hirose ◽  
Emma Hawkins ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Basal Ganglia ◽  
Medial Prefrontal Cortex ◽  
Symptom Severity ◽  
Effective Connectivity ◽  
Reward Learning ◽  
Community Based ◽  
Major Depressive ◽  
Mood Symptoms ◽  
Depressive Symptom Severity

Abstract Major depressive disorder is a leading cause of disability and significant mortality, yet mechanistic understanding remains limited. Over the past decade evidence has accumulated from case-control studies that depressive illness is associated with blunted reward activation in the basal ganglia and other regions such as the medial prefrontal cortex. However it is unclear whether this finding can be replicated in a large number of subjects. The functional anatomy of the medial prefrontal cortex and basal ganglia has been extensively studied and the former has excitatory glutamatergic projections to the latter. Reduced effect of glutamatergic projections from the prefrontal cortex to the nucleus accumbens has been argued to underlie motivational disorders such as depression, and many prominent theories of major depressive disorder propose a role for abnormal cortico-limbic connectivity. However, it is unclear whether there is abnormal reward-linked effective connectivity between the medial prefrontal cortex and basal ganglia related to depression. While resting state connectivity abnormalities have been frequently reported in depression, it has not been possible to directly link these findings to reward-learning studies. Here, we tested two main hypotheses. First, mood symptoms are associated with blunted striatal reward prediction error signals in a large community-based sample of recovered and currently ill patients, similar to reports from a number of studies. Second, event-related directed medial prefrontal cortex to basal ganglia effective connectivity is abnormally increased or decreased related to the severity of mood symptoms. Using a Research Domain Criteria approach, data were acquired from a large community-based sample of subjects who participated in a probabilistic reward learning task during event-related functional MRI. Computational modelling of behaviour, model-free and model-based functional MRI, and effective connectivity dynamic causal modelling analyses were used to test hypotheses. Increased depressive symptom severity was related to decreased reward signals in areas which included the nucleus accumbens in 475 participants. Decreased reward-related effective connectivity from the medial prefrontal cortex to striatum was associated with increased depressive symptom severity in 165 participants. Decreased striatal activity may have been due to decreased cortical to striatal connectivity consistent with glutamatergic and cortical-limbic related theories of depression and resulted in reduced direct pathway basal ganglia output. Further study of basal ganglia pathophysiology is required to better understand these abnormalities in patients with depressive symptoms and syndromes.

In Vivo Effective Connectivity Between Mouse Ventral Hippocampal Projections and Medial Prefrontal Cortex Microcircuits

2021 ◽  
Vol 89 (9) ◽  
pp. S121-S122
Author(s):  
David Kupferschmidt ◽  
Thomas Clarity ◽  
Rachel Mikofsky ◽  
Kirsten Gilchrist ◽  
Maxym Myroshnychenko ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Effective Connectivity

scholarly journals Patient-reported outcomes before and after treatment of major depressive disorder

2014 ◽  
Vol 16 (2) ◽  
pp. 171-183 ◽  
Keyword(s):  
Depressive Symptom ◽  
Symptom Severity ◽  
Patient Reported Outcomes ◽  
Burden Of Illness ◽  
Major Depressive ◽  
Patient Reported ◽  
Before And After ◽  
Depressive Symptom Severity ◽  
The Impact ◽  
Level 2

Patient reported outcomes (PROs) of quality of life (QoL), functioning, and depressive symptom severity are important in assessing the burden of illness of major depressive disorder (MDD) and to evaluate the impact of treatment. We sought to provide a detailed analysis of PROs before and after treatment of MDD from the large Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. This analysis examines PROs before and after treatment in the second level of STAR*D. The complete data on QoL, functioning, and depressive symptom severity, were analyzed for each STAR*D level 2 treatment. PROs of QoL, functioning, and depressive symptom severity showed substantial impairments after failing a selective serotonin reuptake inhibitor trial using citalopram (level 1). The seven therapeutic options in level 2 had positive statistically (P values) and clinically (Cohen's standardized differences [Cohen's d]) significant impact on QoL, functioning, depressive symptom severity, and reduction in calculated burden of illness. There were no statistically significant differences between the interventions. However, a substantial proportion of patients still suffered from patient-reported QoL and functioning impairment after treatment, an effect that was more pronounced in nonremitters. PROs are crucial in understanding the impact of MDD and in examining the effects of treatment interventions, both in research and clinical settings.

scholarly journals Molecular mechanism of reward treatment ameliorating chronic stress-induced depressive-like behavior assessed by sequencing miRNA and mRNA in medial prefrontal cortex

2020 ◽  
Author(s):  
Tingting An ◽  
Zhenhua Song ◽  
Jin-Hui Wang
Keyword(s):  
Major Depressive Disorder ◽  
Prefrontal Cortex ◽  
Depressive Disorder ◽  
Molecular Mechanism ◽  
Chronic Stress ◽  
Medial Prefrontal Cortex ◽  
Differentially Expressed ◽  
Mild Stress ◽  
Major Depressive ◽  
Differentially Expressed Mirnas

Abstract Background Major depressive disorder (MDD) is a disease that seriously endangers human health and mental state. Chronic stress and lack of reward may reduce the function of the brain's reward circuits, leading to major depressive disorder. The effect of reward treatment on chronic stress-induced depression-like behaviors and its molecular mechanism in the brain remain unclear.Methods Mice were divided into the groups of control, chronic unpredictable mild stress (CUMS), and CUMS-companion. Mice of CUMS group was performed by CUMS for 4 weeks, and CUMS-companion group was treated by CUMS accompanied with companion. The tests of sucrose preference, Y-maze, and forced swimming were conducted to assess depression-like behaviors or resilience. High-throughput sequencing was used to analyze mRNA and miRNA profiles in the medial prefrontal cortex harvested from control, CUMS-MDD (mice with depression-like behaviors in CUMS group), Reward-MDD (mice with depression-like behaviors in CUMS-companion group), CUMS-resilience (resilient mice in CUMS group), Reward-resilience (resilient mice in CUMS-companion group) mice.Results The results provided evidence that accompanying with companion ameliorated CUMS-induced depression-like behaviors in mice. 45 differentially expressed genes (DEGs) are associated with depression-like behaviors, 8 DEGs are associated with resilience and 59 DEGs are associated with nature reward (companion) were identified. Furthermore, 196 differentially expressed miRNAs were found to be associated with companion. Based on the differentially expressed miRNAs and DEGs data, miRNA-mRNA network was established to be associated with companion.Conclusion Taken together, our data here provided a method to ameliorate depression-like behaviors, and numerous potential drug targets for the prevention or treatment of depression.

252. Major Depressive Disorder is Associated With Blunted Learning Signals in Medial Prefrontal Cortex and Putamen When Seeking Monetary Reward

2018 ◽  
Vol 83 (9) ◽  
pp. S101-S102
Author(s):  
Jenna Reinen ◽  
Alexis Whitton ◽  
Diego Pizzagalli ◽  
Mark Silfstein ◽  
Anissa Abi-Dargham ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Prefrontal Cortex ◽  
Depressive Disorder ◽  
Medial Prefrontal Cortex ◽  
Monetary Reward ◽  
Major Depressive

Relationship between depressive symptom severity and amygdala volume in a large community-based sample

2019 ◽  
Vol 283 ◽  
pp. 77-82 ◽  
Author(s):  
Shivani Daftary ◽  
Erin Van Enkevort ◽  
Alexandra Kulikova ◽  
Michael Legacy ◽  
E. Sherwood Brown
Keyword(s):  
Depressive Symptom ◽  
Symptom Severity ◽  
Community Based ◽  
Large Community ◽  
Depressive Symptom Severity ◽  
Amygdala Volume

scholarly journals Context-invariant neural dynamics underlying the encoding of Bayesian uncertainty, but not confidence

2019 ◽  
Author(s):  
Vincenzo G. Fiore ◽  
Xiaosi Gu
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Effective Connectivity ◽  
Sensory Information ◽  
Anterior Insula ◽  
Anterior Cingulate ◽  
Neural Dynamics ◽  
Network Computing ◽  
Evidence Accumulation ◽  
Healthy Humans

AbstractBeliefs about action-outcomes contingencies are often updated in opaque environments where feedbacks might be inaccessible and agents might need to rely on other information for evidence accumulation. It remains unclear, however, whether and how the neural dynamics subserving confidence and uncertainty during belief updating might be context-dependent. Here, we applied a Bayesian model to estimate uncertainty and confidence in healthy humans (n=28) using two multi-option fMRI tasks, one with and one without feedbacks. We found that across both tasks, uncertainty was computed in the anterior insular, anterior cingulate, and dorsolateral prefrontal cortices, whereas confidence was encoded in anterior hippocampus, amygdala and medial prefrontal cortex. However, dynamic causal modelling (DCM) revealed a critical divergence between how effective connectivity in these networks was modulated by the available information. Specifically, there was directional influence from the anterior insula to other regions during uncertainty encoding, independent of outcome availability. Conversely, the network computing confidence was driven either by the anterior hippocampus when outcomes were not available, or by the medial prefrontal cortex and amygdala when feedbacks were immediately accessible. These findings indicate that confidence encoding might largely rely on evidence accumulation and therefore dynamically changes as a function of the available sensory information (i.e. symbolic sequences monitored by the hippocampus, and monetary feedbacks computed by amygdala and medial prefrontal cortex). In contrast, uncertainty could be triggered by any information that disputes existing beliefs (i.e. processed in the insula), independent of its content.Significance StatementOur choices are guided by our beliefs about action-outcome contingencies. In environments where only one action leads to a desired outcome, high estimated action-outcome probabilities result in confidence, whereas low probabilities distributed across multiple choices result in uncertainty. These estimations are continuously updated, sometimes based on feedbacks provided by the environment, but sometimes this update takes place in opaque environments where feedbacks are not readily available. Here, we show that uncertainty computations are driven by the anterior insula, independent of feedback availability. Conversely, confidence encoding dynamically adapts to the information available, as we found it was driven either by the anterior hippocampus, when feedback was absent, or by the medial prefrontal cortex and amygdala, otherwise.

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