scholarly journals The Functional Connectivity Between the Nucleus Accumbens and the Ventromedial Prefrontal Cortex as an Endophenotype for Bipolar Disorder

2018 ◽  
Vol 84 (11) ◽  
pp. 803-809 ◽  
Author(s):  
Joseph R. Whittaker ◽  
Sonya F. Foley ◽  
Edward Ackling ◽  
Kevin Murphy ◽  
Xavier Caseras
Keyword(s):  
Bipolar Disorder ◽  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Functional Connectivity ◽  
Ventromedial Prefrontal Cortex

Age differences in ventromedial prefrontal cortex functional connectivity during socioemotional content processing

2020 ◽  
Vol 48 (7) ◽  
pp. 1-19
Author(s):  
Ryan T. Daley ◽  
Holly J. Bowen ◽  
Eric C. Fields ◽  
Angela Gutchess ◽  
Elizabeth A. Kensinger
Keyword(s):  
Prefrontal Cortex ◽  
Functional Connectivity ◽  
Inferior Frontal Gyrus ◽  
Age Groups ◽  
Emotional Content ◽  
Ventromedial Prefrontal Cortex ◽  
Anterior Cingulate ◽  
Supramarginal Gyrus ◽  
Age Related ◽  
Content Processing

Self-relevance effects are often confounded by the presence of emotional content, rendering it difficult to determine how brain networks functionally connected to the ventromedial prefrontal cortex (vmPFC) are affected by the independent contributions of self-relevance and emotion. This difficulty is complicated by age-related changes in functional connectivity between the vmPFC and other default mode network regions, and regions typically associated with externally oriented networks. We asked groups of younger and older adults to imagine placing emotional and neutral objects in their home or a stranger's home. An age-invariant vmPFC cluster showed increased activation for self-relevant and emotional content processing. Functional connectivity analyses revealed age × self-relevance interactions in vmPFC connectivity with the anterior cingulate cortex. There were also age × emotion interactions in vmPFC functional connectivity with the anterior insula, orbitofrontal gyrus, inferior frontal gyrus, and supramarginal gyrus. Interactions occurred in regions with the greatest differences between the age groups, as revealed by conjunction analyses. Implications of the findings are discussed.

scholarly journals L-DOPA modulates activity in the vmPFC, nucleus accumbens, and VTA during threat extinction learning in humans

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Roland Esser ◽  
Christoph W Korn ◽  
Florian Ganzer ◽  
Jan Haaker
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Prediction Error ◽  
Computational Modelling ◽  
Ventromedial Prefrontal Cortex ◽  
Adaptive Behaviour ◽  
Extinction Learning ◽  
Behavioural Treatment ◽  
Related Pathway ◽  
Time Point

Learning to be safe is central for adaptive behaviour when threats are no longer present. Detecting the absence of an expected threat is key for threat extinction learning and an essential process for the behavioural treatment of anxiety-related disorders. One possible mechanism underlying extinction learning is a dopaminergic mismatch signal that encodes the absence of an expected threat. Here we show that such a dopamine-related pathway underlies extinction learning in humans. Dopaminergic enhancement via administration of L-DOPA (vs. Placebo) was associated with reduced retention of differential psychophysiological threat responses at later test, which was mediated by activity in the ventromedial prefrontal cortex that was specific to extinction learning. L-DOPA administration enhanced signals at the time-point of an expected, but omitted threat in extinction learning within the nucleus accumbens, which were functionally coupled with the ventral tegmental area and the amygdala. Computational modelling of threat expectancies further revealed prediction error encoding in nucleus accumbens that was reduced when L-DOPA was administered. Our results thereby provide evidence that extinction learning is influenced by L-DOPA and provide a mechanistic perspective to augment extinction learning by dopaminergic enhancement in humans.

scholarly journals Keeping weight off: Mindfulness-Based Stress Reduction alters amygdala functional connectivity during weight loss maintenance in a randomized control trial

2020 ◽  
Author(s):  
Serhiy Y. Chumachenko ◽  
Ryan Cali ◽  
Milagros C. Rosal ◽  
Jeroan Allison ◽  
Sharina Person ◽  
...  
Keyword(s):  
Weight Loss ◽  
Prefrontal Cortex ◽  
Functional Connectivity ◽  
Stress Reduction ◽  
Behavioral Interventions ◽  
Weight Loss Maintenance ◽  
Ventromedial Prefrontal Cortex ◽  
Depression Symptoms ◽  
Significant Group ◽  
Mindfulness Based Stress Reduction

AbstractObesity is associated with significant comorbidities and financial costs. While behavioral interventions produce clinically meaningful weight loss, weight loss maintenance is challenging. The objective was to improve understanding of the neural and psychological mechanisms modified by mindfulness that may predict clinical outcomes.Individuals who intentionally recently lost weight were randomized to Mindfulness-Based Stress Reduction (MBSR) or a control healthy living course. Anthropometric and psychological factors were measured at baseline, 8 weeks and 6 months. Functional connectivity (FC) analysis was performed at baseline and 8 weeks to examine FC changes between regions of interest selected a priori, and independent components identified by independent component analysis. The association of pre-post FC changes with 6-month weight and psychometric outcomes was then analyzed.Significant group x time interaction was found for FC between the amygdala and ventromedial prefrontal cortex, such that FC increased in the MBSR group and decreased in controls. Non-significant changes in weight were observed at 6 months, where the mindfulness group maintained their weight while the controls showed a weight increase of 3.4% in BMI. Change in FC at 8-weeks between ventromedial prefrontal cortex and several ROIs was associated with change in depression symptoms but not weight at 6 months. This pilot study provides preliminary evidence of neural mechanisms that may be involved in MBSR’s impact on weight loss maintenance that may be useful for designing future clinical trials and mechanistic studies.

scholarly journals Genetic risk for bipolar disorder and schizophrenia predicts structure and function of the ventromedial prefrontal cortex

2021 ◽  
Vol 46 (4) ◽  
pp. E441-E450
Author(s):  
Christoph Abé ◽  
Predrag Petrovic ◽  
William Ossler ◽  
William H. Thompson ◽  
Benny Liberg ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Prefrontal Cortex ◽  
Genetic Risk ◽  
Psychotic Disorders ◽  
Structure And Function ◽  
Ventromedial Prefrontal Cortex ◽  
Risk Scores ◽  
Polygenic Risk ◽  
And Function ◽  
Structural Brain

Background: Bipolar disorder is highly heritable and polygenic. The polygenic risk for bipolar disorder overlaps with that of schizophrenia, and polygenic scores are normally distributed in the population. Bipolar disorder has been associated with structural brain abnormalities, but it is unknown how these are linked to genetic risk factors for psychotic disorders. Methods: We tested whether polygenic risk scores for bipolar disorder and schizophrenia predict structural brain alterations in 98 patients with bipolar disorder and 81 healthy controls. We derived brain cortical thickness, surface area and volume from structural MRI scans. In post-hoc analyses, we correlated polygenic risk with functional hub strength, derived from resting-state functional MRI and brain connectomics. Results: Higher polygenic risk scores for both bipolar disorder and schizophrenia were associated with a thinner ventromedial prefrontal cortex (vmPFC). We found these associations in the combined group, and separately in patients and drug-naive controls. Polygenic risk for bipolar disorder was correlated with the functional hub strength of the vmPFC within the default mode network. Limitations: Polygenic risk is a cumulative measure of genomic burden. Detailed genetic mechanisms underlying brain alterations and their cognitive consequences still need to be determined. Conclusion: Our multimodal neuroimaging study linked genomic burden and brain endophenotype by demonstrating an association between polygenic risk scores for bipolar disorder and schizophrenia and the structure and function of the vmPFC. Our findings suggest that genetic factors might confer risk for psychotic disorders by influencing the integrity of the vmPFC, a brain region involved in self-referential processes and emotional regulation. Our study may also provide an imaging–genetics vulnerability marker that can be used to help identify individuals at risk for developing bipolar disorder.

Neurochemical and brain functional changes in the ventromedial prefrontal cortex of first-episode psychosis patients: A combined functional magnetic resonance imaging—proton magnetic resonance spectroscopy study

2020 ◽  
Vol 54 (5) ◽  
pp. 519-527 ◽  
Author(s):  
Haixin Cen ◽  
Jiale Xu ◽  
Zhilei Yang ◽  
Li Mei ◽  
Tianyi Chen ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Magnetic Resonance ◽  
Functional Connectivity ◽  
Proton Magnetic Resonance ◽  
Proton Magnetic Resonance Spectroscopy ◽  
First Episode Psychosis ◽  
Ventromedial Prefrontal Cortex ◽  
First Episode ◽  
Gaba Level ◽  
Episode Psychosis

Objective: Previous studies showed alterations of brain function in the ventromedial prefrontal cortex of schizophrenia patients. Also, neurochemical changes, especially GABA level alteration, have been found in the medial prefrontal cortex of schizophrenia patients. However, the relationship between GABA level in the ventromedial prefrontal cortex and brain functional activity in schizophrenia patients remains unexplored. Methods: In total, 23 drug-naïve, first-episode psychosis patients and 26 matched healthy controls completed the study. The single voxel proton magnetic resonance spectroscopy data were acquired in ventromedial prefrontal cortex region, which was used as the seed region for resting-state functional connectivity analysis. The proton magnetic resonance spectroscopy data were processed to quantify the concentrations of GABA+, glutamine and glutamate, and N-acetylaspartate in ventromedial prefrontal cortex. Spearman correlation analysis was used to examine the relationship between metabolite concentration, functional connectivity and clinical variables. Pearson correlation analysis was used to examine the relationship between GABA+ concentration and functional connectivity value. Results: In first-episode psychosis patients, GABA+ level in ventromedial prefrontal cortex was higher and was positively correlated with ventromedial prefrontal cortex-left middle orbital frontal cortex functional connectivity. N-acetylaspartate level was positively correlated with positive symptoms, and the functional connectivity between ventromedial prefrontal cortex and left precuneus was negatively associated with negative symptoms of first-episode psychosis patients. Conclusion: Our results indicated that ventromedial prefrontal cortex functional connectivity changes were positively correlated with higher local GABA+ level in first-episode psychosis patients. The altered neurochemical concentration and functional connectivity provide insights into the pathology of schizophrenia.

scholarly journals Differential protein expression of DARPP-32 versus Calcineurin in the prefrontal cortex and nucleus accumbens in schizophrenia and bipolar disorder

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yasuto Kunii ◽  
Mizuki Hino ◽  
Junya Matsumoto ◽  
Atsuko Nagaoka ◽  
Hiroyuki Nawa ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Enzyme Linked Immunosorbent Assay ◽  
Differential Protein Expression ◽  
Expression Ratio ◽  
Expression Levels ◽  
Positive Correlations

Abstract Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32) integrates dopaminergic signaling into that of several other neurotransmitters. Calcineurin (CaN), located downstream of dopaminergic pathways, inactivates DARPP-32 by dephosphorylation. Despite several studies have examined their expression levels of gene and protein in postmortem patients’ brains, they rendered inconsistent results. In this study, protein expression levels of DARPP-32 and CaN were measured by enzyme-linked immunosorbent assay (ELISA) in the prefrontal cortex (PFC), and nucleus accumbens (NAc) of 49 postmortem samples from subjects with schizophrenia, bipolar disorder, and normal controls. We also examined the association between this expression and genetic variants of 8 dopaminergic system-associated molecules for 55 SNPs in the same postmortem samples. In the PFC of patients with schizophrenia, levels of DARPP-32 were significantly decreased, while those of CaN tended to increase. In the NAc, both of DARPP-32 and CaN showed no significant alternations in patients with schizophrenia or bipolar disorder. Further analysis of the correlation of DARPP-32 and CaN expressions, we found that positive correlations in controls and schizophrenia in PFC, and schizophrenia in NAc. In PFC, the expression ratio of DARPP-32/CaN were significantly lower in schizophrenia than controls. We also found that several of the aforementioned SNPs may predict protein expression, one of which was confirmed in a second independent sample set. This differential expression of DARPP-32 and CaN may reflect potential molecular mechanisms underlying the pathogenesis of schizophrenia and bipolar disorder, or differences between these two major psychiatric diseases.

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