Nonlinear modulation of interacting between COMT and depression on brain function

2017 ◽  
Vol 45 ◽  
pp. 6-13 ◽  
Author(s):  
L. Gong ◽  
C. He ◽  
Y. Yin ◽  
Q. Ye ◽  
F. Bai ◽  
...  

AbstractBackground:The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear.Methods:Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function.Results:We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease × COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system).Conclusion:Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD.

2021 ◽  
Author(s):  
Patrik Wikman ◽  
Mona Moisala ◽  
Artturi Ylinen ◽  
Jallu Lindblom ◽  
Sointu Leikas ◽  
...  

Previous studies have examined the neural correlates of receiving negative feedback from peers during virtual social interaction in young people. However, there is a lack of studies using platforms adolescents use in daily life. In the present study, 92 participants ages 17 to 20 performed a task that involved receiving positive and negative feedback from peers in a Facebook-like platform, while brain activity was measured using functional magnetic resonance imaging (fMRI). We also studied the effects of real-life habits of social media use on neural sensitivity to negative feedback. Peer feedback was shown to activate clusters in the ventrolateral prefrontal cortex (VLPFC), the medial prefrontal cortex (MPFC), superior temporal gyrus and sulcus (STG/STS), and occipital cortex (OC). Negative feedback was related to greater activity in the VLPFC, MPFC, and anterior insula than positive feedback, replicating previous findings on peer feedback and social rejection. Habits of social media use did not correlate with brain responses to negative feedback.


2018 ◽  
Vol 67 (3) ◽  
pp. 185-202 ◽  
Author(s):  
Jill R. Glausier ◽  
Anisha Konanur ◽  
David A. Lewis

Electron microscopy (EM) studies of the postmortem human brain provide a level of resolution essential for understanding brain function in both normal and disease states. However, processes associated with death can impair the cellular and organelle ultrastructural preservation required for quantitative EM studies. Although postmortem interval (PMI), the time between death and preservation of tissue, is thought to be the most influential factor of ultrastructural quality, numerous other factors may also influence tissue preservation. The goal of the present study was to assess the effects of pre- and postmortem factors on multiple components of ultrastructure in the postmortem human prefrontal cortex. Tissue samples from 30 subjects were processed using standard EM histochemistry. The primary dependent measure was number of identifiable neuronal profiles, and secondary measures included presence and/or integrity of synapses, mitochondria, and myelinated axonal fibers. Number of identifiable neuronal profiles was most strongly affected by the interaction of PMI and pH, such that short PMIs and neutral pH values predicted the best preservation. Secondary measures were largely unaffected by pre- and postmortem factors. Together, these data indicate that distinct components of the neuropil are differentially affected by PMI and pH in postmortem human brain.


2020 ◽  
Author(s):  
Parnian Rafei ◽  
Tara Rezapour ◽  
Seyed Amir Hossein Batouli ◽  
Antonio Verdejo-Garcia ◽  
Valentina Lorenzetti ◽  
...  

Background: Episodic Future Thinking (EFT) is a cognitive function that allows individuals to imagine novel experiences that may happen in the future. Prior studies show that EFT is impaired in different groups of substance users, such as alcohol and heroin users. However, there is no evidence regarding the neurobiological mechanisms of EFT in cannabis users.Aim: We aimed to compare brain activations of regular cannabis users and non-using controls during an EFT fMRI task. Exploratory analyses were also conducted to investigate the association between EFT and cannabis use variables (e.g., duration of use, age-onset, etc.).Method: Twenty current cannabis-users and 22 non-users underwent a single session fMRI while completing a task involving envisioning future-related events and retrieval of past memories as a control condition. The EFT fMRI task was adapted from the autobiographical interview and composed of 20 auditory cue sentences (10 cues for past and 10 cues for future events). Participants were asked to recall a past or generate a future event, in response to the cues, and then rated their vividness after each response. Results: We found that cannabis-users compared to non-user controls had lower activation within the cerebellum, medial, and superior temporal gyrus, lateral occipital cortex, and occipital fusiform gyrus while envisioning future events. Cannabis-users rated the vividness of past events significantly lower than non-users (P<0.005). There were no significant group differences for rating the vividness of future events (P=0.052). Conclusion: Cannabis users, compared to drug-naïve controls, have lower brain activation in EFT relevant regions. Thus, any attempts to improve aberrant EFT performance in cannabis-users may benefit from EFT training.


2004 ◽  
Vol 16 (10) ◽  
pp. 1746-1772 ◽  
Author(s):  
Kevin N. Ochsner ◽  
Kyle Knierim ◽  
David H. Ludlow ◽  
Josh Hanelin ◽  
Tara Ramachandran ◽  
...  

Understanding one's own and other individual's emotional states is essential for maintaining emotional equilibrium and strong social bonds. Although the neural substrates supporting reflection upon one's own feelings have been investigated, no studies have directly examined attributions about the internal emotional states of others to determine whether common or distinct neural systems support these abilities. The present study sought to directly compare brain regions involved in judging one's own, as compared to another individual's, emotional state. Thirteen participants viewed mixed valence blocks of photos drawn from the International Affective Picture System while whole-brain fMRI data were collected. Preblock cues instructed participants to evaluate either their emotional response to each photo, the emotional state of the central figure in each photo, or (in a baseline condition) whether the photo was taken indoors or outdoors. Contrasts indicated (1) that both self and other judgments activated the medial prefrontal cortex (MPFC), the superior temporal gyrus, and the posterior cingulate/precuneus, (2) that self judgments selectively activated subregions of the MPFC and the left temporal cortex, whereas (3) other judgments selectively activated the left lateral prefrontal cortex (including Broca's area) and the medial occipital cortex. These results suggest (1) that self and other evaluation of emotion rely on a network of common mechanisms centered on the MPFC, which has been hypothesized to support mental state attributions in general, and (2) that medial and lateral PFC regions selectively recruited by self or other judgments may be involved in attention to, and elaboration of, internally as opposed to externally generated information.


2021 ◽  
pp. 1-7
Author(s):  
Dylan J. Terstege ◽  
Debra S. MacDonald ◽  
R. Andrew Tasker

Abstract Objective: Ginsenosides, biologically active components of the root of Panax ginseng, have been reported to have therapeutic benefits in a number of disease states including psychiatric conditions such as major depressive disorder. Our objective was to determine if a standardised commercial ginseng extract, G115®, could reduce the signs of behavioural despair commonly observed in animal models of depression either alone or in combination with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Methods: Male Sprague-Dawley (SD) rats (N = 51) were divided into four groups: vehicle control, G115® ginseng root extract, fluoxetine and fluoxetine plus G115®. Rats were trained to voluntarily consume treatments twice daily for 14 days and were then tested in an open field (OF), elevated plus maze (EPM) and forced swim test (FST). Post-mortem hippocampal and prefrontal cortex tissue was analysed for expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) by western blot. Results: One-way Analysis of Variance revealed no significant group differences in the OF or plus-maze performance on any variable examined. In the FST, fluoxetine significantly reduced immobility time and increased latency to immobility. The effects of fluoxetine were further significantly potentiated by co-administration of G115®. Post-mortem tissue analysis revealed significant group differences in BDNF expression in the left hippocampus and left prefrontal cortex without any accompanying changes in TrkB expression. Conclusions: We conclude that oral G115® significantly potentiates the antidepressant-like effect of fluoxetine in the FST in the absence of potentially confounding effects on locomotion and anxiety.


2012 ◽  
Vol 23 (10) ◽  
pp. 2309-2321 ◽  
Author(s):  
P. C. Garell ◽  
H. Bakken ◽  
J. D. W. Greenlee ◽  
I. Volkov ◽  
R. A. Reale ◽  
...  

2020 ◽  
Author(s):  
Nazia Jassim ◽  
Simon Baron-Cohen ◽  
John Suckling

Sensory sensitivities occur in up to 90% of autistic individuals. With the recent inclusion of sensory symptoms in the diagnostic criteria for autism, there is a current need to develop neural hypotheses related to autistic sensory perception. Using activation likelihood estimation (ALE), we meta-analysed 52 task-based fMRI studies investigating differences between autistic (n=891) and control (n=967) participants during non-social sensory perception. During complex perception, autistic groups showed more activity in the secondary somatosensory and occipital cortices, insula, caudate, superior temporal gyrus, and inferior parietal lobule, while control groups showed more activity in the frontal and parietal regions. During basic sensory processing, autistic groups showed hyperactivity in the lateral occipital cortex, primary somatosensory and motor cortices, insula, caudate, and thalamus, while controls showed heightened activity in the precentral gyrus, middle frontal gyrus, precuneus, and anterior cingulate cortex. We conclude that autistic individuals, on average, show distinct engagement of sensory-related brain networks during sensory perception. These findings may help guide future research to focus on relevant neurobiological mechanisms underpinning the autistic experience.


2019 ◽  
Author(s):  
Erlend S. Dørum ◽  
Tobias Kaufmann ◽  
Dag Alnæs ◽  
Geneviève Richard ◽  
Knut K. Kolskår ◽  
...  

AbstractA cerebral stroke is characterized by compromised brain function due to an interruption in cerebrovascular blood supply. Although stroke incurs focal damage determined by the vascular territory affected, clinical symptoms commonly involve multiple functions and cognitive faculties that are insufficiently explained by the focal damage alone. Functional connectivity (FC) refers to the synchronous activity between spatially remote brain regions organized in a network of interconnected brain regions. Functional magnetic resonance imaging (fMRI) has advanced this system-level understanding of brain function, elucidating the complexity of stroke outcomes, as well as providing information useful for prognostic and rehabilitation purposes.We tested for differences in brain network connectivity between a group of patients with minor ischemic strokes in sub-acute phase (n=44) and matched controls (n=100). As neural network configuration is dependent on cognitive effort, we obtained fMRI data during rest and two load levels of a multiple object tacking (MOT) task. Network nodes and time-series were estimated using independent component analysis (ICA) and dual regression, with network edges defined as the partial temporal correlations between node pairs. The full set of edgewise FC went into a cross-validated regularized linear discriminant analysis (rLDA) to classify groups and cognitive load.MOT task performance and cognitive tests revealed no significant group differences. While multivariate machine learning revealed high sensitivity to experimental condition, with classification accuracies between rest and attentive tracking approaching 100%, group classification was at chance level, with negligible differences between conditions. Repeated measures ANOVA showed significantly stronger synchronization between a temporal node and a sensorimotor node in patients across conditions. Overall, the results revealed high sensitivity of FC indices to task conditions, and suggest relatively small brain network-level disturbances after clinically mild strokes.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S10-S10
Author(s):  
Margaret Niznikiewicz ◽  
Kana Okano ◽  
Clemens Bauer ◽  
Paul Nestor ◽  
Elizabetta Del Re ◽  
...  

Abstract Background Auditory hallucinations (AH) are one of the core symptoms of schizophrenia (SZ) and constitute a significant source of suffering and disability. One third of SZ patients experience pharmacology-resistant AH, so an alternative/complementary treatment strategy is needed to alleviate this debilitating condition. In this study, real-time functional Magnetic Resonance Imaging neurofeedback (rt-fMRI NFB), a non-invasive technique, was used to help 10 SZ patients modulate their brain activity in key brain regions belonging to the network involved in the experience of auditory hallucinations. In two experiments we selected two different brain targets. 1. the superior temporal gyrus (STG) and 2. default mode network (DMN)-central executive network (CEN) connectivity. STG is a key area in the neurophysiology of AH. Hyperactivation of the default mode network (DMN) and of the superior temporal gyrus (STG) in SZ has been shown in imaging studies. Furthermore, several studies point to reduced anticorrelation between the DMN and the central executive network (CEN). Finally, DMN hyperconnectivity has been associated with positive symptoms such as AHs while reduced DMN anticorrelations have been associated with cognitive impairment. Methods In the STG-focused NFB experiment, subjects were trained to upregulate the STG activity while listening to their own voice recording and downregulate it while ignoring a stranger’s voice recording in the course of 21 min NFB session. Visual feedback was provided to subjects at the end of each run from their own STG activity in the form of a thermometer. AH were assessed with auditory hallucination scale pre-NFB and within a week after the NFB session. The DMN-CEN focused NFB experiment was conducted about 1 month later to minimize the carry over effects from the STG-focused NFB and was designed to help SZ patients modulate their DMN and CEN networks. DMN and CEN networks were defined individually for each subject. The goal of the task was to increase CEN-DMN anti-correlations. To achieve that patients were provided with meditation strategies to guide their performance. Feedback was provided in the form of a ball that traveled up if the modulation of DMN-CEN connectivity was successful and traveled down if it was not successful. AH measures were taken before the NFB session and within a week after the session. Results In the STG-focused NFB task, significant STG activation reduction was found in the comparison of pre- relative to post-NFB in the condition of ignoring another person’s voice (p<0.05), FWE-TFCE corrected. AH were also significantly reduced (p<0.01). Importantly, significant correlation was found between reductions in the STG activation and AH reductions (r=.83). In the DMN-CEN focused NFB task, significant increase in the anti-correlations between medial prefrontal cortex (mPFC) and dorsolateral prefrontal cortex (DLPFC) (p<0.05) was observed as well as significant reduction in the mPFC-PCC connectivity (p <0.05), in the pre-post NFB comparisons. AH were significantly reduced in post- relative to pre-NFB comparison (p<0.02). Finally, there was a significant correlation between individual scores in mPFC-STG connectivity and AH reductions. Discussion These the two experiments suggest that targeting both the STG BOLD activation and DMN-CEN connectivity in NFB tasks aimed at AH reduction result both in brain changes and in AH reductions. Together, these results provide strong preliminary support for the NFB use as a means to impact brain function leading to reductions in AH in SZ. Importantly, these results suggest that AH result from brain abnormalities in a network of brain regions and that targeting a brain region belonging to this network will lead to AH symptom reduction.


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