scholarly journals Task-independent acute effects of delta-9-tetrahydrocannabinol on human brain function and its relationship with cannabinoid receptor gene expression: a neuroimaging meta-regression analysis

2021 ◽  
Author(s):  
Brandon Gunasekera ◽  
Cathy Davies ◽  
Grace Blest-Hopley ◽  
Mattia Veronese ◽  
Nick F Ramsey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Repeated Measures ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Brain Atlas ◽  
Angular Gyrus ◽  
Protein Distribution ◽  
Middle Temporal ◽  
Repeated Measures Design

Background: The neurobiological mechanisms underlying the effects of delta-9-tetrahydrocannabinol (THC) remain unclear. Here, we examined the spatial acute effect of THC on human on regional brain activation or blood flow (hereafter called 'activation signal') in a 'core' network of brain regions that subserve a multitude of processes. We also investigated whether the neuromodulatory effects of THC are related to the local expression of its key molecular target, cannabinoid-type-1 (CB1R) but not type-2 (CB2R) receptor. Methods: A systematic search was conducted of acute THC-challenge studies using fMRI, PET, and arterial spin labelling in accordance with established guidelines. Using pooled summary data from 372 participants, tested using a within-subject repeated measures design under experimental conditions, we investigated the effects of a single dose (6-42mg) of THC, compared to placebo, on brain signal. Findings: As predicted, THC augmented the activation signal, relative to placebo, in the anterior cingulate, superior frontal cortices, middle temporal and middle and inferior occipital gyri, striatum, amygdala, thalamus, and cerebellum crus II and attenuated it in the middle temporal gyrus (spatially distinct from the cluster with THC-induced increase in activation signal), superior temporal gyrus, angular gyrus, precuneus, cuneus, inferior parietal lobule, and the cerebellum lobule IV/V. Using post-mortem gene expression data from an independent cohort from the Allen Human Brain atlas, we found a direct relationship between the magnitude of THC-induced brain signal change, indexed using pooled effect-size estimates, and CB1R gene expression, a proxy measure of CB1R protein distribution, but not CB2R expression. A dose-response relationship was observed with THC dose in certain brain regions. Interpretation: These meta-analytic findings shed new light on the localisation of the effects of THC in the human brain, suggesting that THC has neuromodulatory effects in regions central to many cognitive tasks and processes, with greater effects in regions with higher levels of CB1R expression.

scholarly journals A pH-eQTL interaction at the RIT2-SYT4 Parkinson's disease risk locus in the substantia nigra

2020 ◽  
Author(s):  
Sejal Patel ◽  
Derek Howard ◽  
Leon French
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Human Brain ◽  
Disease Risk ◽  
Brain Regions ◽  
Dopamine Neurons ◽  
Postmortem Human Brain ◽  
Increased Risk

BACKGROUND: Parkinson's disease (PD) causes severe motor and cognitive disabilities that result from the progressive loss of dopamine neurons in the substantia nigra. The rs12456492 variant in the RIT2 gene has been repeatedly associated with increased risk for Parkinson's disease. From a transcriptomic perspective, a meta-analysis found that RIT2 gene expression is correlated with pH in the human brain. OBJECTIVE: To assess pH associations at the RIT2-SYT4 locus. METHODS: Linear models to examine two datasets that assayed rs12456492, gene expression, and pH in the postmortem human brain. RESULTS: Using the BrainEAC dataset, we replicate the positive correlation between RIT2 gene expression and pH in the human brain. Furthermore, we found that the relationship between expression and pH is influenced by rs12456492. When tested across ten brain regions, this interaction is specifically found in the substantia nigra. A similar association was found for the co-localized SYT4 gene. In addition, SYT4 associations are stronger in a combined model with both genes, and the SYT4 interaction appears to be specific to males. In the GTEx dataset, the pH associations involving rs12456492 and expression of either SYT4 and RIT2 was not seen. This null finding may be due to the short postmortem intervals (PMI) of the GTEx tissue samples. In the BrainEAC data, we tested the effect of PMI and only observed the interactions in the longer PMI samples. CONCLUSIONS: These previously unknown associations suggest novel mechanistic roles for rs12456492, RIT2, and SYT4 in the regulation of pH in the substantia nigra.

Neurofunctional Effects of Cannabis on Response Inhibition

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
S. Borgwardt ◽  
P. Allen ◽  
S. Bhattacharyya ◽  
P. Fusar-Poli ◽  
J.A. Crippa ◽  
...  
Keyword(s):  
Response Inhibition ◽  
Repeated Measures ◽  
Temporal Cortex ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Psychotic Symptoms ◽  
Double Blind ◽  
Subject Design ◽  
Mediate Response ◽  
The Right

Background:This study examined the effect of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on brain activation during a motor inhibition task.Methods:Functional magnetic resonance imaging and behavioural measures were recorded while 15 healthy volunteers performed a Go/No-Go task following administration of either THC or CBD or placebo in a double-blind, pseudo-randomized, placebo-controlled repeated measures within-subject design.Results:Relative to placebo, THC attenuated activation in the right inferior frontal and the anterior cingulate gyrus. In contrast, CBD deactivated the left temporal cortex and insula. These effects were not related to changes in anxiety, intoxication, sedation, and psychotic symptoms.Conclusions:These data suggest that THC attenuates the engagement of brain regions that mediate response inhibition. CBD modulated function in regions not usually implicated in response inhibition.

scholarly journals The neural basis of temporal individuation and its capacity limits in the human brain

2017 ◽  
Vol 118 (5) ◽  
pp. 2601-2613
Author(s):  
Claire K. Naughtin ◽  
Benjamin J. Tamber-Rosenau ◽  
Paul E. Dux
Keyword(s):  
Human Brain ◽  
Premotor Cortex ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Repetition Blindness ◽  
Neural Basis ◽  
Related Factors ◽  
Regional Patterns ◽  
Repetition Suppression ◽  
Capacity Limit

Individuation refers to individualsʼ use of spatial and temporal properties to register objects as distinct perceptual events relative to other stimuli. Although behavioral studies have examined both spatial and temporal individuation, neuroimaging investigations have been restricted to the spatial domain and at relatively late stages of information processing. Here, we used univariate and multivoxel pattern analyses of functional MRI data to identify brain regions involved in individuating temporally distinct visual items and the neural consequences that arise when this process reaches its capacity limit (repetition blindness, RB). First, we found that regional patterns of blood-oxygen-level-dependent activity across the cortex discriminated between instances where repeated and nonrepeated stimuli were successfully individuated—conditions that placed differential demands on temporal individuation. These results could not be attributed to repetition suppression or other stimulus-related factors, task difficulty, regional activation differences, other capacity-limited processes, or artifacts in the data or analyses. Contrary to current theoretical models, this finding suggests that temporal individuation is supported by a distributed set of brain regions, rather than a single neural correlate. Second, conditions that reflect the capacity limit of individuation—instances of RB—lead to changes in the spatial patterns within this network, as well as amplitude changes in the left hemisphere premotor cortex, superior medial frontal cortex, anterior cingulate cortex, and bilateral parahippocampal place area. These findings could not be attributed to response conflict/ambiguity and likely reflect the core brain regions and mechanisms that underlie the capacity-limited process that gives rise to RB.NEW & NOTEWORTHY We present novel findings into the neural bases of temporal individuation and repetition blindness (RB)—the perceptual deficit that arises when this process reaches its capacity limit. Specifically, we found that temporal individuation is a widely distributed process in the brain and identified a number of candidate brain regions that appear to underpin RB. These findings enhance our understanding of how these fundamental perceptual processes are reflected in the human brain.

scholarly journals Homologous laminar organization of the mouse and human subiculum

2019 ◽  
Author(s):  
Michael S. Bienkowski ◽  
Farshid Sepehrband ◽  
Nyoman D. Kurniawan ◽  
Jim Stanis ◽  
Laura Korobkova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hippocampal Formation ◽  
Expression Patterns ◽  
Pyramidal Cells ◽  
Longitudinal Axis ◽  
Brain Regions ◽  
Brain Atlas ◽  
Fiber Density ◽  
Laminar Organization ◽  
Hybridization Data

SummaryThe subiculum is the major output structure of the hippocampal formation and one of the brain regions most affected by Alzheimer’s disease. Our previous work revealed a hidden laminar architecture within the mouse subiculum. However, the rotation of the hippocampal longitudinal axis across species makes it unclear how the laminar organization is represented in human subiculum. Using in situ hybridization data from the Allen Human Brain Atlas, we demonstrate that the human subiculum also contains complementary laminar gene expression patterns similar to the mouse. In addition, we provide evidence that the molecular domain boundaries in human subiculum correspond to microstructural differences observed in high resolution MRI and fiber density imaging. Finally, we show both similarities and differences in the gene expression profile of subiculum pyramidal cells within homologous lamina. Overall, we present a new 3D model of the anatomical organization of human subiculum and its evolution from the mouse.

scholarly journals Gene expression heterogeneity during brain development and aging: temporal changes and functional consequences

2019 ◽  
Author(s):  
Ulaş Işıldak ◽  
Mehmet Somel ◽  
Janet M. Thornton ◽  
Handan Melike Dönertaş
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Meta Analysis ◽  
Brain Regions ◽  
Genetic Alterations ◽  
Individual Heterogeneity ◽  
Brain Functions ◽  
Aging Period ◽  
Gene Expression Heterogeneity ◽  
Development And Aging

AbstractCells in largely non-mitotic tissues such as the brain are prone to stochastic (epi-)genetic alterations that may cause increased variability between cells and individuals over time. Although increased inter-individual heterogeneity in gene expression was previously reported, whether this process starts during development or if it is restricted to the aging period has not yet been studied. The regulatory dynamics and functional significance of putative aging-related heterogeneity are also unknown. Here we address these by a meta-analysis of 19 transcriptome datasets from diverse human brain regions. We observed a significant increase in inter-individual heterogeneity during aging (20+ years) compared to postnatal development (0 to 20 years). Increased heterogeneity during aging was consistent among different brain regions at the gene level and associated with lifespan regulation and neuronal functions. Overall, our results show that increased expression heterogeneity is a characteristic of aging human brain, and may influence aging-related changes in brain functions.

scholarly journals Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

2014 ◽  
pp. 154-161 ◽  
Author(s):  
Julio Cesar Montoya ◽  
Dianora Fajardo ◽  
Ángela Peña ◽  
Adalberto Sánchez ◽  
Martha C Domínguez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Down Syndrome ◽  
Human Brain ◽  
Critical Region ◽  
Expression Profiles ◽  
Brain Atlas ◽  
Normal Human Brain ◽  
Normal Human ◽  
The Brain ◽  
Brain Homeostasis

Background: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. Objective: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. Methods: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Results: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously idenjpgied brain structures play a crucial role in the learning process, in different class of memory and in motor skills. Conclusion: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition.

scholarly journals Association of Protein Distribution and Gene Expression Revealed by PET and Post-Mortem Quantification in the Serotonergic System of the Human Brain

2016 ◽  
Vol 27 (1) ◽  
pp. 117-130 ◽  
Author(s):  
A. Komorowski ◽  
G. M. James ◽  
C. Philippe ◽  
G. Gryglewski ◽  
A. Bauer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Serotonergic System ◽  
Post Mortem ◽  
Protein Distribution

scholarly journals Unhealthy yet Avoidable—How Cognitive Bias Modification Alters Behavioral and Brain Responses to Food Cues in Individuals with Obesity

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 874 ◽  
Author(s):  
Nora Mehl ◽  
Filip Morys ◽  
Arno Villringer ◽  
Annette Horstmann
Keyword(s):  
Cognitive Bias ◽  
Brain Connectivity ◽  
Inferior Frontal Gyrus ◽  
Brain Regions ◽  
Cognitive Bias Modification ◽  
Anterior Cingulate ◽  
Angular Gyrus ◽  
Unhealthy Food ◽  
Food Cues ◽  
Bias Modification

Obesity is associated with automatically approaching problematic stimuli, such as unhealthy food. Cognitive bias modification (CBM) could beneficially impact problematic approach behavior. However, it is unclear which mechanisms are targeted by CBM in obesity. Candidate mechanisms include: (1) altering reward value of food stimuli; and (2) strengthening inhibitory abilities. Thirty-three obese adults completed either CBM or sham training during functional magnetic resonance imaging (fMRI) scanning. CBM consisted of implicit training to approach healthy and avoid unhealthy foods. At baseline, approach tendencies towards food were present in all participants. Avoiding vs. approaching food was associated with higher activity in the right angular gyrus (rAG). CBM resulted in a diminished approach bias towards unhealthy food, decreased activation in the rAG, and increased activation in the anterior cingulate cortex. Relatedly, functional connectivity between the rAG and right superior frontal gyrus increased. Analysis of brain connectivity during rest revealed training-related connectivity changes of the inferior frontal gyrus and bilateral middle frontal gyri. Taken together, CBM strengthens avoidance tendencies when faced with unhealthy foods and alters activity in brain regions underpinning behavioral inhibition.

scholarly journals Human brain region-specific variably methylated regions (VMRs) are enriched for heritability of distinct neuropsychiatric traits

2021 ◽  
Author(s):  
Lindsay F. Rizzardi ◽  
Peter F. Hickey ◽  
Adrian Idrizi ◽  
Rakel Tryggvadóttir ◽  
Colin M. Callahan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Human Brain ◽  
Brain Region ◽  
Brain Regions ◽  
Differential Methylation ◽  
Anterior Cingulate ◽  
Single Pair ◽  
Regulatory Regions ◽  
Neuronal Nuclei ◽  
The Brain

ABSTRACTBACKGROUNDDNA methylation dynamics in the brain are associated with normal development and neuropsychiatric disease and differ across functionally distinct brain regions. Previous studies of genome-wide methylation differences among human brain regions focused on limited numbers of individuals and one to two brain regions.RESULTSUsing GTEx samples, we have generated a resource of DNA methylation in purified neuronal nuclei from 8 brain regions as well as lung and thyroid tissues from 12-23 donors. We identified differentially methylated regions between brain regions (DMRs) among neuronal nuclei in both CpG (181,146) and non-CpG (264,868) contexts, few of which were unique to a single pair-wise comparison. This significantly expands the knowledge of differential methylation across the brain by 10-fold. In addition, we present the first differential methylation analysis among neuronal nuclei from basal ganglia tissues and identified 2,295 unique CpG DMRs, many associated with ion transport. Consistent with prior studies, CpG DMRs were enriched in regulatory regions while non-CpG DMRs were enriched in intergenic regions. We also identified 81,130 regions of variably CpG methylated regions (VMRs), i.e. variable methylation among individuals in the same brain region, which were enriched in regulatory regions and in CpG DMRs. Many VMRs were unique to a specific brain region, with only 202 common across all brain regions, as well as lung and thyroid. VMRs identified in the amygdala, anterior cingulate cortex, and hippocampus were enriched for heritability of schizophrenia.CONCLUSIONSThese data suggest that epigenetic variation in these particular human brain regions could be associated with the risk for this neuropsychiatric disorder.

scholarly journals NIMG-13. GENETIC, CELLULAR, AND CONNECTOMIC CHARACTERIZATION OF THE ADULT HUMAN BRAIN REGIONS COMMONLY PLAGUED BY GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii149-ii149
Author(s):  
Ayan Mandal ◽  
Rafael Romero-Garcia ◽  
Michael Hart ◽  
John Suckling
Keyword(s):  
Human Brain ◽  
Occipital Lobe ◽  
Brain Regions ◽  
Brain Dysfunction ◽  
Brain Atlas ◽  
Association Cortex ◽  
Low Grade ◽  
Expression Of Genes ◽  
Neuroimaging Data ◽  
Multiple Graph

Abstract For decades, it has been known that gliomas follow a nonrandom spatial distribution, appearing more often in some brain regions (e.g. the insula) compared to others (e.g. the occipital lobe). A better understanding of the glioma localization patterns could lend clues to the origins of these types of tumors, and consequently inform treatment targets. Following hypotheses derived from prior research into neuropsychiatric disease and cancer, gliomas may be expected to localize to brain regions characterized by functional hubness, stem-like cells, and transcription of genetic drivers of gliomagenesis. We combined neuroimaging data from 335 adult patients with high- and low-grade glioma to form a replicable tumor frequency map. Using this map, we demonstrate that glioma frequency is elevated in association cortex and correlated with multiple graph-theoretical metrics of high functional connectedness. Brain regions populated with putative cells-of-origin for glioma, neural stem cells and oligodendrocyte precursor cells, exhibited a high glioma frequency. Leveraging a human brain atlas of post-mortem gene expression, we found that gliomas were localized to brain regions enriched with expression of genes associated with chromatin organization and synaptic signaling. A set of glioma proto-oncogenes was enriched among the transcriptomic correlates of glioma distribution. Finally, a regression model incorporating connectomic, cellular, and genetic factors explained 58% of the variance in glioma frequency. These results add to previous literature reporting the vulnerability of hub regions to neurological disease, as well as provide support for cancer stem cell theories of glioma. Our findings illustrate how factors of diverse scale, from genetic to connectomic, can independently influence the anatomic localization of brain dysfunction.

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