scholarly journals Opioid antagonism modulates wanting-related frontostriatal connectivity

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Alexander Soutschek ◽  
Susanna C Weber ◽  
Thorsten Kahnt ◽  
Boris B Quednow ◽  
Philippe N Tobler
Keyword(s):  
Neural Activity ◽  
Dorsolateral Prefrontal Cortex ◽  
Receptor Activation ◽  
Brain Regions ◽  
Neural Processing ◽  
Neural Connectivity ◽  
Double Blind ◽  
Double Blind Clinical Trial ◽  
Dorsolateral Prefrontal ◽  
Pharmacological Manipulations

Theoretical accounts distinguish between motivational ('wanting') and hedonic ('liking') dimensions of rewards. Previous animal and human research linked wanting and liking to anatomically and neurochemically distinct brain mechanisms, but it remains unknown how the different brain regions and neurotransmitter systems interact in processing distinct reward dimensions. Here, we assessed how pharmacological manipulations of opioid and dopamine receptor activation modulate the neural processing of wanting and liking in humans in a randomized, placebo-controlled, double-blind clinical trial. Reducing opioid receptor activation with naltrexone selectively reduced wanting of rewards, which on a neural level was reflected by stronger coupling between dorsolateral prefrontal cortex and the striatum under naltrexone compared with placebo. In contrast, reducing dopaminergic neurotransmission with amisulpride revealed no robust effects on behavior or neural activity. Our findings thus provide insights into how opioid receptors mediate neural connectivity related to specifically motivational, not hedonic, aspects of rewards.

scholarly journals Opioid antagonism reduces wanting by strengthening frontostriatal connectivity

2021 ◽  
Author(s):  
Alexander Soutschek ◽  
Philippe N Tobler ◽  
Thorsten Kahnt ◽  
Boris Quednow ◽  
Susanna Weber
Keyword(s):  
Clinical Trial ◽  
Dorsolateral Prefrontal Cortex ◽  
Receptor Activation ◽  
Brain Regions ◽  
Neural Processing ◽  
Double Blind ◽  
Double Blind Clinical Trial ◽  
Dorsolateral Prefrontal ◽  
Goal Directed Behavior ◽  
Pharmacological Manipulations

Goal-directed behavior depends on both motivational (“wanting”) and hedonic (“liking”) dimensions of rewards. Previous animal and human research linked wanting and liking to anatomically and neurochemically distinct brain mechanisms, but it remains unknown as to how the different brain regions and neurotransmitter systems interact in processing distinct reward dimensions. Here, we assessed how pharmacological manipulations of opioid and dopamine receptor activation modulate the neural processing of wanting and liking in humans in a randomized, placebo-controlled, double-blind clinical trial. Blocking opioid receptor activation with naltrexone selectively reduced wanting of rewards, which on a neural level was reflected by stronger coupling between dorsolateral prefrontal cortex and the striatum under naltrexone compared with placebo. Our findings thus provide insights into how opioid receptors mediate frontostriatal gating of specifically motivational, not hedonic, aspects of rewards.

scholarly journals Spontaneous Neural Activity Changes after Bariatric Surgery: a resting-state fMRI study

2021 ◽  
Author(s):  
Yashar Zeighami ◽  
Sylvain Iceta ◽  
Mahsa Dadar ◽  
Mélissa Pelletier ◽  
Mélanie Nadeau ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Visual Cortex ◽  
Neural Activity ◽  
Dorsolateral Prefrontal Cortex ◽  
Severe Obesity ◽  
Normal Weight ◽  
Post Surgery ◽  
Spontaneous Neural Activity ◽  
Dorsolateral Prefrontal

1.AbstractBackgroundMetabolic disorders associated with obesity could lead to alterations in brain structure and function. Whether these changes can be reversed after weight loss is unclear. Bariatric surgery provides a unique opportunity to address these questions because it induces marked weight loss and metabolic improvements which in turn may impact the brain in a longitudinal fashion. Previous studies found widespread changes in grey matter (GM) and white matter (WM) after bariatric surgery. However, findings regarding changes in spontaneous neural activity following surgery, as assessed with the fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity of neural activity (ReHo), are scarce and heterogenous. In this study, we used a longitudinal design to examine the changes in spontaneous neural activity after bariatric surgery (comparing pre- to post-surgery), and to determine whether these changes are related to cardiometabolic variables.MethodsThe study included 57 participants with severe obesity (mean BMI=43.1±4.3kg/m2) who underwent sleeve gastrectomy (SG), biliopancreatic diversion with duodenal switch (BPD), or Roux-en-Y gastric bypass (RYGB), scanned prior to bariatric surgery and at follow-up visits of 4 months (N=36), 12 months (N=29), and 24 months (N=14) after surgery. We examined fALFF and ReHo measures across 1022 cortical and subcortical regions (based on combined Schaeffer-Xiao parcellations) using a linear mixed effect model. Voxel-based morphometry (VBM) based on T1-weighted images was also used to measure GM density in the same regions. We also used an independent sample from the Human Connectome Project (HCP) to assess regional differences between individuals who had normal-weight (N=46) or severe obesity (N=46).ResultsWe found a global increase in the fALFF signal with greater increase within dorsolateral prefrontal cortex, precuneus, inferior temporal gyrus, and visual cortex. This effect was more significant 4 months after surgery. The increase within dorsolateral prefrontal cortex, temporal gyrus, and visual cortex was more limited after 12 months and only present in the visual cortex after 24 months. These increases in neural activity measured by fALFF were also significantly associated with the increase in GM density following surgery. Furthermore, the increase in neural activity was significantly related to post-surgery weight loss and improvement in cardiometabolic variables, such as insulin resistance index and blood pressure. In the independent HCP sample, normal-weight participants had higher global and regional fALFF signals, mainly in dorsolateral/medial frontal cortex, precuneus and middle/inferior temporal gyrus compared to the obese participants. These BMI-related differences in fALFF were associated with the increase in fALFF 4 months post-surgery especially in regions involved in control, default mode and dorsal attention networks.ConclusionsBariatric surgery-induced weight loss and improvement in metabolic factors are associated with widespread global and regional increases in neural activity, as measured by fALFF signal. These findings alongside the higher fALFF signal in normal-weight participants compared to participants with severe obesity in an independent dataset suggest an early recovery in the neural activity signal level after the surgery.

scholarly journals Effect of Vitamin D Receptor Activation on the AGE/RAGE System and Myeloperoxidase in Chronic Kidney Disease Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Claudia Torino ◽  
Patrizia Pizzini ◽  
Sebastiano Cutrupi ◽  
Rocco Tripepi ◽  
Antonio Vilasi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Generalized Linear Model ◽  
Receptor Activation ◽  
Advanced Glycation ◽  
Double Blind ◽  
Double Blind Clinical Trial ◽  
Glycation End Products ◽  
Circulating Levels ◽  
Biomarkers Of Oxidative Stress

Vitamin D receptor (VDR) activation has been reported to increase circulating levels of the advanced glycation end products (AGE) and their decoy receptor (RAGE). However, until now, the effect of VDR activation on AGE and RAGE has not been tested in the setting of a randomized, double-blind clinical trial. We have therefore analyzed the effect of VDR activation by paricalcitol on pentosidine, S100A12/ENRAGE, and RAGE and on established biomarkers of oxidative stress like myeloperoxidase in CKD patients in the PENNY trial. At baseline, human S100A12/ENRAGE, RAGE, and myeloperoxidase, but not pentosidine, were intercorrelated, and the association between S100A12/ENRAGE and myeloperoxidase (r=0.71, P<0.001) was the strongest among these correlations. Paricalcitol failed to modify biomarkers of the AGE/RAGE system and myeloperoxidase in unadjusted and adjusted analyses by the generalized linear model (GLM). No effect modification by other risk factors was registered. Paricalcitol does not modify biomarkers of the AGE/RAGE system and myeloperoxidase in CKD patients. The apparent increase in RAGE levels by VDR activation reported in previous uncontrolled studies is most likely due to confounding factors rather than to VDR activation per se. This trial is registered with NCT01680198.

Contribution of Human Prefrontal Cortex to Delay Performance

1998 ◽  
Vol 10 (2) ◽  
pp. 167-177 ◽  
Author(s):  
Linda L. Chao ◽  
Robert T. Knight
Keyword(s):  
Prefrontal Cortex ◽  
Neural Activity ◽  
Dorsolateral Prefrontal Cortex ◽  
Silent Period ◽  
Primary Auditory Cortex ◽  
Association Cortex ◽  
Focal Lesions ◽  
Delay Performance ◽  
Dorsolateral Prefrontal ◽  
Auditory Association Cortex

Neurological patients with focal lesions in the dorsolateral prefrontal cortex and age-matched control subjects were tested on an auditory version of the delayed-match-to-sample task employing environmental sounds. Subjects had to indicate whether a cue (S1) and a subsequent target sound (S2) were identical. On some trials, S1 and S2 were separated by a silent period of 5 sec. On other trials, the 5-sec delay between S1 and S2 was filled with irrelevant tone pips that served as distractors. Behaviorally, frontal patients were impaired by the presence of distractors. Electrophysiologically, patients generated enhanced primary auditory cortex-evoked responses to the tone pips, supporting a failure in inhibitory control of sensory processing after prefrontal damage. Intrahemispheric reductions of neural activity generated in the auditory association cortex and additional intrahemispheric reductions of attention-related frontal activity were also observed in the prefrontal patients. Together, these findings suggest that the dorsolateral prefrontal cortex is crucial for gating distracting information as well as maintaining distributed intrahemispheric neural activity during auditory working memory.

Antidepressant efficacy of high-frequency transcranial magnetic stimulation over the left dorsolateral prefrontal cortex in double-blind sham-controlled designs: a meta-analysis

2008 ◽  
Vol 39 (1) ◽  
pp. 65-75 ◽  
Author(s):  
D. J. L. G. Schutter
Keyword(s):  
Prefrontal Cortex ◽  
Transcranial Magnetic Stimulation ◽  
Effect Size ◽  
High Frequency ◽  
Magnetic Stimulation ◽  
Dorsolateral Prefrontal Cortex ◽  
Meta Analysis ◽  
Double Blind ◽  
Left Dlpfc ◽  
Dorsolateral Prefrontal

BackgroundFor more than a decade high-frequency repetitive transcranial magnetic stimulation (rTMS) has been applied to the left dorsolateral prefrontal cortex (DLPFC) in search of an alternative treatment for depression. The aim of this study was to provide an update on its clinical efficacy by performing a meta-analysis involving double-blind sham-controlled studies.MethodA literature search was conducted in the databases PubMed and Web of Science in the period between January 1980 and November 2007 with the search terms ‘depression’ and ‘transcranial magnetic stimulation’. Thirty double-blind sham-controlled parallel studies with 1164 patients comparing the percentage change in depression scores from baseline to endpoint of activeversussham treatment were included. A random effects meta-analysis was performed to investigate the clinical efficacy of fast-frequency rTMS over the left DLPFC in depression.ResultsThe test for heterogeneity was not significant (QT=30.46,p=0.39). A significant overall weighted mean effect size,d=0.39 [95% confidence interval (CI) 0.25–0.54], for active treatment was observed (z=6.52,p<0.0001). Medication resistance and intensity of rTMS did not play a role in the effect size.ConclusionsThese findings show that high-frequency rTMS over the left DLPFC is superior to sham in the treatment of depression. The effect size is robust and comparable to at least a subset of commercially available antidepressant drug agents. Current limitations and future prospects are discussed.

scholarly journals Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex

2020 ◽  
Author(s):  
Kristen R. Maynard ◽  
Leonardo Collado-Torres ◽  
Lukas M. Weber ◽  
Cedric Uytingco ◽  
Brianna K. Barry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Web Application ◽  
Dorsolateral Prefrontal Cortex ◽  
Large Scale ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Sequencing Data ◽  
Dorsolateral Prefrontal ◽  
Transcriptomics Data

AbstractWe used the 10x Genomics Visium platform to define the spatial topography of gene expression in the six-layered human dorsolateral prefrontal cortex (DLPFC). We identified extensive layer-enriched expression signatures, and refined associations to previous laminar markers. We overlaid our laminar expression signatures onto large-scale single nuclei RNA sequencing data, enhancing spatial annotation of expression-driven clusters. By integrating neuropsychiatric disorder gene sets, we showed differential layer-enriched expression of genes associated with schizophrenia and autism spectrum disorder, highlighting the clinical relevance of spatially-defined expression. We then developed a data-driven framework to define unsupervised clusters in spatial transcriptomics data, which can be applied to other tissues or brain regions where morphological architecture is not as well-defined as cortical laminae. We lastly created a web application for the scientific community to explore these raw and summarized data to augment ongoing neuroscience and spatial transcriptomics research (http://research.libd.org/spatialLIBD).

scholarly journals Regional heterogeneity in gene expression, regulation and coherence in hippocampus and dorsolateral prefrontal cortex across development and in schizophrenia

2018 ◽  
Author(s):  
L Collado-Torres ◽  
EE Burke ◽  
A Peterson ◽  
JH Shin ◽  
RE Straub ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Brain Region ◽  
Dorsolateral Prefrontal Cortex ◽  
Large Scale ◽  
Brain Regions ◽  
Second Phase ◽  
Regional Heterogeneity ◽  
Surrogate Variable Analysis ◽  
Dorsolateral Prefrontal

AbstractRecent large-scale genomics efforts have better characterized the molecular correlates of schizophrenia in postmortem human neocortex, but not hippocampus which is a brain region prominently implicated in its pathogenesis. Here in the second phase of the BrainSeq Consortium (Phase II), we have generated RiboZero RNA-seq data for 900 samples across both the dorsolateral prefrontal cortex (DLPFC) and the hippocampus (HIPPO) for 551 individuals (286 affected by schizophrenia disorder: SCZD). We identify substantial regional differences in gene expression, in both pre- and post-natal life, and find widespread differences in how genes are regulated across development. By extending quality surrogate variable analysis (qSVA) to multiple brain regions, we identified 48 and 245 differentially expressed genes (DEG) by SCZD diagnosis (FDR<5%) in HIPPO and DLPFC, respectively, with surprisingly minimal overlap in DEG between the two brain regions. We further identified 205,618 brain region-dependent eQTLs (FDR<1%) and found that 124 GWAS risk loci contain eQTLs in at least one of the regions. We also identify potential molecular correlates of in vivo evidence of altered prefrontal-hippocampal functional coherence in schizophrenia. These results underscore the complexity and regional heterogeneity of the transcriptional correlates of schizophrenia, and suggest future schizophrenia therapeutics may need to target molecular pathologies localized to specific brain regions.

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