Pain-related opioidergic and dopaminergic neurotransmission: Dual Meta-Analyses of PET Radioligand Studies

AbstractMolecular mechanisms of the interaction between pain and reward associated with pain relief processes in the human brain are still incompletely understood. This is partially due to the invasive nature of the available techniques to visualize and measure metabolic activity. Positron Emission Tomography (PET) radioligand studies using radioactive substances are still the only available modality to date that allows for the investigation of the molecular mechanisms in the human brain. For pain and reward studies, the most commonly studied PET radiotracers are [11C]-carfentanil (CFN) and [11C]- or [18F]-diprenorphine (DPN), which bind to opioid receptors, and [11C]-raclopride (RAC) and [18F]-fallypride (FAL) tracers, which bind to dopamine receptors. The current meta-analysis looks at 15 pain-related studies using opioid radioligands and 8 studies using dopamine radioligands in an effort to consolidate the available data into the most likely activated regions. Our primary goal was to identify regions of shared opioid/dopamine neurotransmission during pain-related experiences. SDM analysis of previously published voxel coordinate data showed that opioidergic activations were strongest in the bilateral caudate, thalamus, right putamen, cingulate gyrus, midbrain, inferior frontal gyrus, and left superior temporal gyrus. The dopaminergic studies showed that the bilateral caudate, thalamus, right putamen, cingulate gyrus, and left putamen had the highest activations. We were able to see a clear overlap between opioid and dopamine activations in a majority of the regions during pain-related processing, though there were some unique areas of dopaminergic activation such as the left putamen. Regions unique to opioidergic activation include the midbrain, inferior frontal gyrus, and left superior temporal gyrus. By investigating the regions of dopaminergic and opioidergic activation, we can potentially provide more targeted treatment to these sets of receptors in patients with pain conditions. These findings could eventually assist in the development of more targeted medication in order to help treat pain conditions and simultaneously prevent physical dependency.

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Striatal molecular alterations in HD gene carriers: a systematic review and meta-analysis of PET studies

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2017-316633 ◽

2017 ◽

Vol 89 (2) ◽

pp. 185-196 ◽

Cited By ~ 14

Author(s):

Flavia Niccolini ◽

Gennaro Pagano ◽

Paolo Fusar-Poli ◽

Andrew Wood ◽

Ladislav Mrzljak ◽

...

Keyword(s):

Pet Imaging ◽

Meta Analysis ◽

Random Effect ◽

Cochrane Library ◽

Imaging Studies ◽

Molecular Changes ◽

Molecular Alterations ◽

Positron Emission ◽

Meta Analyses ◽

Hd Gene

BackgroundOver the past years, positron emission tomography (PET) imaging studies have investigated striatal molecular changes in premanifest and manifest Huntington’s disease (HD) gene expansion carriers (HDGECs), but they have yielded inconsistent results.ObjectiveTo systematically examine the evidence of striatal molecular alterations in manifest and premanifest HDGECs as measured by PET imaging studies.MethodsMEDLINE, ISI Web of Science, Cochrane Library and Scopus databases were searched for articles published until 7 June 2017 that included PET studies in manifest and premanifest HDGECs. Meta-analyses were conducted with random effect models, and heterogeneity was addressed with I2 index, controlling for publication bias and quality of study. The primary outcome was the standardised mean difference (SMD) of PET uptakes in the whole striatum, caudate and putamen in manifest and premanifest HDGECs compared with healthy controls (HCs).ResultsTwenty-four out of 63 PET studies in premanifest (n=158) and manifest (n=191) HDGECs and HCs (n=333) were included in the meta-analysis. Premanifest and manifest HDGECs showed significant decreases in dopamine D2 receptors in caudate (SMD=−1.233, 95% CI −1.753 to −0.713, p<0.0001; SMD=−5.792, 95% CI −7.695 to −3.890, p<0.0001) and putamen (SMD=−1.479, 95% CI −1.965 to −0.992, p<0.0001; SMD=−5.053, 95% CI −6.558 to −3.549, p<0.0001), in glucose metabolism in caudate (SMD=−0.758, 95% CI −1.139 to −0.376, p<0.0001; SMD=−3.738, 95% CI −4.880 to −2.597, p<0.0001) and putamen (SMD=−2.462, 95% CI −4.208 to −0.717, p=0.006; SMD=−1.650, 95% CI −2.842 to −0.458, p<0.001) and in striatal PDE10A binding (SMD=−1.663, 95% CI −2.603 to −0.723, p=0.001; SMD=−2.445, 95% CI −3.371 to −1.519, p<0.001).ConclusionsPET imaging has the potential to detect striatal molecular changes even at the early premanifest stage of HD, which are relevant to the neuropathological mechanisms underlying the development of the disease.

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Altered neural activities during response inhibition in adults with addiction: a voxel-wise meta-analysis

Psychological Medicine ◽

10.1017/s0033291721000362 ◽

2021 ◽

pp. 1-13

Author(s):

Zeguo Qiu ◽

Junjing Wang

Keyword(s):

Response Inhibition ◽

Substance Dependence ◽

Brain Activity ◽

Meta Analysis ◽

Inferior Frontal Gyrus ◽

Activity Patterns ◽

Behavioral Addiction ◽

Middle Temporal Gyrus ◽

Precentral Gyrus ◽

Meta Analyses

Abstract Background Previous literature has extensively investigated the brain activity during response inhibition in adults with addiction. Inconsistent results including both hyper- and hypo-activities in the fronto-parietal network (FPN) and the ventral attention network (VAN) have been found in adults with addictions, compared with healthy controls (HCs). Methods Voxel-wise meta-analyses of abnormal task-evoked regional activity were conducted for adults with substance dependence (SD) and behavioral addiction during response inhibition tasks to solve previous inconsistencies. Twenty-three functional magnetic resonance imaging studies including 479 substance users, 38 individuals with behavioral addiction and 494 HCs were identified. Results Compared with HCs, all addictions showed hypo-activities in regions within FPN (inferior frontal gyrus and supramarginal gyrus) and VAN (inferior frontal gyrus, middle temporal gyrus, temporal pole and insula), and hyper-activities in the cerebellum during response inhibition. SD subgroup showed almost the same activity patterns, with an additional hypoactivation of the precentral gyrus, compared with HCs. Stronger activation of the cerebellum was associated with longer addiction duration for adults with SD. We could not conduct meta-analytic investigations into the behavioral addiction subgroup due to the small number of datasets. Conclusion This meta-analysis revealed altered activation of FPN, VAN and the cerebellum in adults with addiction during response inhibition tasks using non-addiction-related stimuli. Although FPN and VAN showed lower activity, the cerebellum exhibited stronger activity. These results may help to understand the neural pathology of response inhibition in addiction.

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Convergent and divergent brain structural and functional abnormalities associated with developmental dyslexia

eLife ◽

10.7554/elife.69523 ◽

2021 ◽

Vol 10 ◽

Author(s):

Xiaohui Yan ◽

Ke Jiang ◽

Hui Li ◽

Ziyi Wang ◽

Kyle Perkins ◽

...

Keyword(s):

Developmental Dyslexia ◽

Grey Matter ◽

Meta Analysis ◽

Inferior Frontal Gyrus ◽

Brain Activation ◽

Superior Temporal Gyrus ◽

Brain Regions ◽

Middle Temporal Gyrus ◽

Grey Matter Volume ◽

Matter Volume

Brain abnormalities in the reading network have been repeatedly reported in individuals with developmental dyslexia (DD); however, it is still not totally understood where the structural and functional abnormalities are consistent/inconsistent across languages. In the current multimodal meta-analysis, we found convergent structural and functional alterations in the left superior temporal gyrus across languages, suggesting a neural signature of DD. We found greater reduction in grey matter volume and brain activation in the left inferior frontal gyrus in morpho-syllabic languages (e.g. Chinese) than in alphabetic languages, and greater reduction in brain activation in the left middle temporal gyrus and fusiform gyrus in alphabetic languages than in morpho-syllabic languages. These language differences are explained as consequences of being DD while learning a specific language. In addition, we also found brain regions that showed increased grey matter volume and brain activation, presumably suggesting compensations and brain regions that showed inconsistent alterations in brain structure and function. Our study provides important insights about the etiology of DD from a cross-linguistic perspective with considerations of consistency/inconsistency between structural and functional alterations.

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Functional MRI-Specific Alterations in Salience Network in Mild Cognitive Impairment: An ALE Meta-Analysis

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.695210 ◽

2021 ◽

Vol 13 ◽

Author(s):

Yu Song ◽

Wenwen Xu ◽

Shanshan Chen ◽

Guanjie Hu ◽

Honglin Ge ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Meta Analysis ◽

Low Frequency ◽

Superior Temporal Gyrus ◽

Frequency Fluctuation ◽

Imaging Biomarkers ◽

Salience Network ◽

Cingulate Gyrus ◽

Amnestic Mci

Background Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. Amnestic MCI (aMCI) and non-amnestic MCI are the two subtypes of MCI with the former having a higher risk for progressing to Alzheimer's disease (AD). Compared with healthy elderly adults, individuals with MCI have specific functional alterations in the salience network (SN). However, no consistent results are documenting these changes. This meta-analysis aimed to investigate the specific functional alterations in the SN in MCI and aMCI.Methods: We systematically searched PubMed, Embase, and Web of Science for scientific neuroimaging literature based on three research methods, namely, functional connectivity (FC), regional homogeneity (ReHo), and the amplitude of low-frequency fluctuation or fractional amplitude of low-frequency fluctuation (ALFF/fALFF). Then, we conducted the coordinate-based meta-analysis by using the activation likelihood estimation algorithm.Results: In total, 30 functional neuroimaging studies were included. After extracting the data and analyzing it, we obtained specific changes in some brain regions in the SN including decreased ALFF/fALFF in the left superior temporal gyrus, the insula, the precentral gyrus, and the precuneus in MCI and aMCI; increased FC in the thalamus, the caudate, the superior temporal gyrus, the insula, and the cingulate gyrus in MCI; and decreased ReHo in the anterior cingulate gyrus in aMCI. In addition, as to FC, interactions of the SN with other networks including the default mode network and the executive control network were also observed mainly in the middle frontal gyrus and superior frontal gyrus in MCI and inferior frontal gyrus in aMCI.Conclusions: Specific functional alternations in the SN and interactions of the SN with other networks in MCI could be useful as potential imaging biomarkers for MCI or aMCI. Meanwhile, it provided a new insight in predicting the progression of health to MCI or aMCI and novel targets for proper intervention to delay the progression.Systematic Review Registration: [PROSPERO], identifier [No. CRD42020216259].

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Common and distinct patterns of intrinsic brain activity alterations in major depression and bipolar disorder: voxel-based meta-analysis

Translational Psychiatry ◽

10.1038/s41398-020-01036-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jiaying Gong ◽

Junjing Wang ◽

Shaojuan Qiu ◽

Pan Chen ◽

Zhenye Luo ◽

...

Keyword(s):

Bipolar Disorder ◽

Major Depression ◽

Brain Activity ◽

Meta Analysis ◽

Inferior Frontal Gyrus ◽

Superior Temporal Gyrus ◽

Occipital Cortex ◽

Anterior Cingulate ◽

The Right ◽

Intrinsic Brain Activity

Abstract Identification of intrinsic brain activity differences and similarities between major depression (MDD) and bipolar disorder (BD) is necessary. However, results have not yet yielded consistent conclusions. A meta-analysis of whole-brain resting-state functional MRI (rs-fMRI) studies that explored differences in the amplitude of low-frequency fluctuation (ALFF) between patients (including MDD and BD) and healthy controls (HCs) was conducted using seed-based d mapping software. Systematic literature search identified 50 studies comparing 1399 MDD patients and 1332 HCs, and 15 studies comparing 494 BD patients and 593 HCs. MDD patients displayed increased ALFF in the right superior frontal gyrus (SFG) (including the medial orbitofrontal cortex, medial prefrontal cortex [mPFC], anterior cingulate cortex [ACC]), bilateral insula extending into the striatum and left supramarginal gyrus and decreased ALFF in the bilateral cerebellum, bilateral precuneus, and left occipital cortex compared with HCs. BD showed increased ALFF in the bilateral inferior frontal gyrus, bilateral insula extending into the striatum, right SFG, and right superior temporal gyrus (STG) and decreased ALFF in the bilateral precuneus, left cerebellum (extending to the occipital cortex), left ACC, and left STG. In addition, MDD displayed increased ALFF in the left lingual gyrus, left ACC, bilateral precuneus/posterior cingulate gyrus, and left STG and decreased ALFF in the right insula, right mPFC, right fusiform gyrus, and bilateral striatum relative to BD patients. Conjunction analysis showed increased ALFF in the bilateral insula, mPFC, and decreased ALFF in the left cerebellum in both disorders. Our comprehensive meta-analysis suggests that MDD and BD show a common pattern of aberrant regional intrinsic brain activity which predominantly includes the insula, mPFC, and cerebellum, while the limbic system and occipital cortex may be associated with spatially distinct patterns of brain function, which provide useful insights for understanding the underlying pathophysiology of brain dysfunction in affective disorders, and developing more targeted and efficacious treatment and intervention strategies.

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Meta-analysis of meta-analyses in oncologic positron emission tomography

Nuclear Medicine Communications ◽

10.1097/mnm.0000000000000908 ◽

2018 ◽

Vol 39 (12) ◽

pp. 1150-1155

Author(s):

Kyoungjune Pak ◽

Seunghyeon Shin ◽

So Jung Kim ◽

Keunyoung Kim ◽

Youngduk Seo ◽

...

Keyword(s):

Positron Emission Tomography ◽

Meta Analysis ◽

Emission Tomography ◽

Positron Emission ◽

Meta Analyses

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Voxel-Based Meta-Analysis of Gray Matter Abnormalities in Multiple System Atrophy

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2020.591666 ◽

2020 ◽

Vol 12 ◽

Author(s):

Junyu Lin ◽

Xinran Xu ◽

Yanbing Hou ◽

Jing Yang ◽

Huifang Shang

Keyword(s):

Multiple System Atrophy ◽

Gray Matter ◽

Meta Analysis ◽

Inferior Frontal Gyrus ◽

Superior Temporal Gyrus ◽

Middle Temporal Gyrus ◽

Significant Heterogeneity ◽

Middle Temporal ◽

The Right ◽

Complementary Analysis

Purpose: This study aimed to identify consistent gray matter volume (GMV) changes in the two subtypes of multiple system atrophy (MSA), including parkinsonism subtype (MSA-P), and cerebellar subtype (MSA-C), by conducting a voxel-wise meta-analysis of whole brain voxel-based morphometry (VBM) studies.Method: VBM studies comparing MSA-P or MSA-C and healthy controls (HCs) were systematically searched in the PubMed, Embase, and Web of Science published from 1974 to 20 October 2020. A quantitative meta-analysis of VBM studies on MSA-P or MSA-C was performed using the effect size-based signed differential mapping (ES-SDM) method separately. A complementary analysis was conducted using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) method, which allows a familywise error rate (FWE) correction for multiple comparisons of the results, for further validation of the results.Results: Ten studies were included in the meta-analysis of MSA-P subtype, comprising 136 MSA-P patients and 211 HCs. Five studies were included in the meta-analysis of MSA-C subtype, comprising 89 MSA-C patients and 134 HCs. Cerebellum atrophy was detected in both MSA-P and MSA-C, whereas basal ganglia atrophy was only detected in MSA-P. Cerebral cortex atrophy was detected in both subtypes, with predominant impairment of the superior temporal gyrus, inferior frontal gyrus, temporal pole, insula, and amygdala in MSA-P and predominant impairment of the superior temporal gyrus, middle temporal gyrus, fusiform gyrus, and lingual gyrus in MSA-C. Most of these results survived the FWE correction in the complementary analysis, except for the bilateral amygdala and the left caudate nucleus in MSA-P, and the right superior temporal gyrus and the right middle temporal gyrus in MSA-C. These findings remained robust in the jackknife sensitivity analysis, and no significant heterogeneity was detected.Conclusion: A different pattern of brain atrophy between MSA-P and MSA-C detected in the current study was in line with clinical manifestations and provided the evidence of the pathophysiology of the two subtypes of MSA.

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The metabolic signature of cardiorespiratory fitness: a protocol for a systematic review and meta-analysis

BMJ Open Sport & Exercise Medicine ◽

10.1136/bmjsem-2020-001008 ◽

2021 ◽

Vol 7 (1) ◽

pp. e001008

Author(s):

Justin Carrard ◽

Chiara Guerini ◽

Christian Appenzeller-Herzog ◽

Denis Infanger ◽

Karsten Königstein ◽

...

Keyword(s):

Cardiorespiratory Fitness ◽

Molecular Mechanisms ◽

Tissue Sample ◽

Meta Analysis ◽

Cardiopulmonary Exercise Test ◽

Test Protocol ◽

Tissue Samples ◽

Analytical Technique ◽

Human Tissue Sample ◽

Meta Analyses

IntroductionA low cardiorespiratory fitness (CRF) is a strong and independent predictor of cardiometabolic, cancer and all-cause mortality. To date, the mechanisms linking CRF with reduced mortality remain largely unknown. Metabolomics, which is a powerful metabolic phenotyping technology to unravel molecular mechanisms underlying complex phenotypes, could elucidate how CRF fosters human health.Methods and analysisThis study aims at systematically reviewing and meta-analysing the literature on metabolites of any human tissue sample, which are positively or negatively associated with CRF. Studies reporting estimated CRF will not be considered. No restrictions will be placed on the metabolomics technology used to measure metabolites. PubMed, Web of Science and EMBASE will be searched for relevant articles published until the date of the last search. Two authors will independently screen full texts of selected abstracts. References and citing articles of included articles will be screened for additional relevant publications. Data regarding study population, tissue samples, analytical technique, quality control, data processing, metabolites associated to CRF, cardiopulmonary exercise test protocol and exercise exhaustion criteria will be extracted. Methodological quality will be assessed using a modified version of QUADOMICS. Narrative synthesis as well as tabular/charted presentation of the extracted data will be included. If feasible, meta-analyses will be used to investigate the associations between identified metabolites and CRF. Potential sources of heterogeneity will be explored in meta-regressions.Ethics and disseminationNo ethics approval is required. The results will be published in a peer-reviewed journal and as conference presentation.PROSPERO registration numberCRD42020214375.

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Establishing a Role of the Semantic Control Network in Social Cognitive Processing: A Meta-analysis of Functional Neuroimaging Studies

10.1101/2021.04.01.437961 ◽

2021 ◽

Author(s):

Richard J Binney ◽

Veronica Diveica ◽

Kami Koldewyn

Keyword(s):

Cognitive Processing ◽

Social Cognitive ◽

Functional Neuroimaging ◽

Meta Analysis ◽

Inferior Frontal Gyrus ◽

Brain Regions ◽

Middle Temporal Gyrus ◽

Neural Activation ◽

Control Mechanisms ◽

Meta Analyses

Most leading models of socio-cognitive processing devote little discussion to the nature and neuroanatomical correlates of cognitive control mechanisms. Recently, it has been proposed that the regulation of social behaviours could rely on brain regions specialised in the controlled retrieval of semantic information, namely the anterior inferior frontal gyrus (IFG) and posterior middle temporal gyrus. Accordingly, we set out to investigate whether the neural activation commonly found in social functional neuroimaging studies extends to these semantic control regions. We conducted five coordinate-based meta-analyses to combine results of over 500 fMRI/PET experiments and identified the brain regions consistently involved in semantic control, as well as four social abilities: theory of mind, trait inference, empathy and moral reasoning. This allowed an unprecedented parallel review of the neural networks associated with each of these cognitive domains. The results confirmed that the anterior left IFG region involved in semantic control is reliably engaged in all four social domains. This suggests that social cognition could be partly regulated by the neurocognitive system underpinning semantic control.

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Pairwise genetic meta-analyses between schizophrenia and substance dependence phenotypes reveals novel association signals

10.1101/2021.09.12.21263471 ◽

2021 ◽

Author(s):

Laura A. Greco ◽

William R. Reay ◽

Christopher V. Dayas ◽

Murray J. Cairns

Keyword(s):

Substance Use ◽

Molecular Mechanisms ◽

Substance Dependence ◽

System Development ◽

Causal Effect ◽

Meta Analysis ◽

Nervous System Development ◽

Cannabis Use ◽

Individual Substance ◽

Meta Analyses

AbstractAlmost half of individuals diagnosed with schizophrenia also present with a substance use disorder, however, little is known about potential molecular mechanisms underlying this comorbidity. We used genetic analyses to enhance our understanding of the molecular overlap between these conditions. Our analyses revealed a positive genetic correlation between schizophrenia and the following dependence phenotypes: alcohol (rg = 0.3685, SE = 0.0768, P = 1.61 × 10−06), cannabis use disorder (rg = 0.309, SE = 0.0332, P = 1.19 × 10−20) and nicotine dependence (rg = 0.1177, SE = 0.0436, P = 7.0 × 10-03), as well as lifetime cannabis use (rg = 0.234, SE = 0.0298, P = 3.73 × 10−15) and drinks per week (rg = 0.0688, SE = 0.0217, P = 1.5 × 10−03). We further constructed latent causal variable (LCV) models to test for partial genetic causality and found evidence for a potential causal relationship between alcohol dependence and schizophrenia (GCP = 0.6, SE = 0.22, P = 1.6 × 10−03). This putative causal effect with schizophrenia was not seen using a continuous phenotype of drinks consumed per week, suggesting that distinct molecular mechanisms underlying dependence are involved in the relationship between alcohol and schizophrenia. To localise the specific genetic overlap between schizophrenia and substance use disorders, we conducted a gene-based and gene-set pairwise meta-analysis between schizophrenia and each of the four individual substance dependence phenotypes in up to 790,806 individuals. These bivariate meta-analyses identified 44 associations not observed in the individual GWAS, including five shared genes that play a key role in early central nervous system development. These genes may play an important role in substance dependence in schizophrenia, and, as a result, could represent important targets for future treatment or early intervention, as comorbid substance dependence is associated with poor treatment adherence, greater chronicity and increased mortality.

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