scholarly journals Common variants contribute to intrinsic human brain functional networks

2020 ◽  
Author(s):  
Bingxin Zhao ◽  
Tengfei Li ◽  
Stephen M. Smith ◽  
Di Xiong ◽  
Xifeng Wang ◽  
...  
Keyword(s):  
Human Brain ◽  
Genetic Variants ◽  
Brain Function ◽  
Brain Activity ◽  
Well Being ◽  
Central Executive ◽  
Common Variants ◽  
Default Mode ◽  
Common Genetic Variants ◽  
Intrinsic Brain Activity

AbstractThe human brain remains active in the absence of explicit tasks and forms networks of correlated activity. Resting-state functional magnetic resonance imaging (rsfMRI) measures brain activity at rest, which has been linked with both cognitive and clinical outcomes. The genetic variants influencing human brain function are largely unknown. Here we utilized rsfMRI from 44,190 individuals of multiple ancestries (37,339 in the UK Biobank) to discover and validate the common genetic variants influencing intrinsic brain activity. We identified hundreds of novel genetic loci associated with intrinsic functional signatures (P < 2.8 × 10−11), including associations to the central executive, default mode, and salience networks involved in the triple network model of psychopathology. A number of intrinsic brain activity associated loci colocalized with brain disorder GWAS (e.g., Alzheimer’s disease, Parkinson’s disease, schizophrenia) and cognition, such as 19q13.32, 17q21.31, and 2p16.1. Particularly, we detected a colocalization between one (rs429358) of the two variants in the APOE ε4 locus and function of the default mode, central executive, attention, and visual networks. Genetic correlation analysis demonstrated shared genetic influences between brain function and brain structure in the same regions. We also detected significant genetic correlations with 26 other complex traits, such as ADHD, major depressive disorder, schizophrenia, intelligence, education, sleep, subjective well-being, and neuroticism. Common variants associated with intrinsic brain activity were enriched within regulatory element in brain tissues.

scholarly journals The Impact of Cannabidiol on Human Brain Function: A Systematic Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Albert Batalla ◽  
Julian Bos ◽  
Amber Postma ◽  
Matthijs G. Bossong
Keyword(s):  
Systematic Review ◽  
Psychiatric Disorder ◽  
Human Brain ◽  
Healthy Volunteers ◽  
Resting State ◽  
Brain Function ◽  
Brain Activity ◽  
Autism Spectrum ◽  
Cognitive Tasks ◽  
Therapeutic Effects

Background: Accumulating evidence suggests that the non-intoxicating cannabinoid compound cannabidiol (CBD) may have antipsychotic and anxiolytic properties, and thus may be a promising new agent in the treatment of psychotic and anxiety disorders. However, the neurobiological substrates underlying the potential therapeutic effects of CBD are still unclear. The aim of this systematic review is to provide a detailed and up-to-date systematic literature overview of neuroimaging studies that investigated the acute impact of CBD on human brain function.Methods: Papers published until May 2020 were included from PubMed following a comprehensive search strategy and pre-determined set of criteria for article selection. We included studies that examined the effects of CBD on brain function of healthy volunteers and individuals diagnosed with a psychiatric disorder, comprising both the effects of CBD alone as well as in direct comparison to those induced by ∆9-tetrahydrocannabinol (THC), the main psychoactive component of Cannabis.Results: One-ninety four studies were identified, of which 17 met inclusion criteria. All studies investigated the acute effects of CBD on brain function during resting state or in the context of cognitive tasks. In healthy volunteers, acute CBD enhanced fronto-striatal resting state connectivity, both compared to placebo and THC. Furthermore, CBD modulated brain activity and had opposite effects when compared to THC following task-specific patterns during various cognitive paradigms, such as emotional processing (fronto-temporal), verbal memory (fronto-striatal), response inhibition (fronto-limbic-striatal), and auditory/visual processing (temporo-occipital). In individuals at clinical high risk for psychosis and patients with established psychosis, acute CBD showed intermediate brain activity compared to placebo and healthy controls during cognitive task performance. CBD modulated resting limbic activity in subjects with anxiety and metabolite levels in patients with autism spectrum disorders.Conclusion: Neuroimaging studies have shown that acute CBD induces significant alterations in brain activity and connectivity patterns during resting state and performance of cognitive tasks in both healthy volunteers and patients with a psychiatric disorder. This included modulation of functional networks relevant for psychiatric disorders, possibly reflecting CBD’s therapeutic effects. Future studies should consider replication of findings and enlarge the inclusion of psychiatric patients, combining longer-term CBD treatment with neuroimaging assessments.

scholarly journals Concordance Among Indices of Intrinsic Brain Function: Insights from Inter-Individual Variation and Temporal Dynamics

2016 ◽  
Author(s):  
Chao-Gan Yan ◽  
Zhen Yang ◽  
Stanley J. Colcombe ◽  
Xi-Nian Zuo ◽  
Michael P. Milham
Keyword(s):  
Individual Variation ◽  
Brain Function ◽  
Temporal Dynamics ◽  
Brain Activity ◽  
Low Frequency ◽  
Resting State Fmri ◽  
Surrogate Data ◽  
Linear Increase ◽  
Intrinsic Brain Activity ◽  
High Degree

ABSTRACTVarious resting-state fMRI (R-fMRI) measures have been developed to characterize intrinsic brain activity. While each of these measures has gained a growing presence in the literature, questions remain regarding the common and unique aspects these indices capture. The present work provided a comprehensive examination of inter-individual variation and intra-individual temporal variation for commonly used measures, including fractional amplitude of low frequency fluctuations, regional homogeneity, voxel-mirrored homotopic connectivity, network centrality and global signal correlation. Regardless of whether examining intra-individual or inter-individual variation, we found that these definitionally distinct R-fMRI indices tend to exhibit a relatively high degree of covariation, which doesn’t exist in phase randomized surrogate data. As a measure of intrinsic brain function, concordance for R-fMRI indices was negatively correlated with age across individuals (i.e., concordance among functional indices decreased with age). To understand the functional significance of concordance, we noted that higher concordance was generally associated with higher strengths of R-fMRI indices, regardless of whether looking through the lens of inter-individual (i.e., high vs. low concordance participants) or intra-individual (i.e., high vs. low concordance states identified via temporal dynamic analyses) differences. We also noted a linear increase in functional concordance together with the R-fMRI indices through the scan, which may suggest a decrease in arousal. The current study demonstrated an enriched picture regarding the relationship among the R-fMRI indices, as well as provided new insights in examining dynamic states within and between individuals.

scholarly journals Searching through functional space reveals distributed visual, auditory, and semantic coding in the human brain

2020 ◽  
Author(s):  
Sreejan Kumar ◽  
Cameron T. Ellis ◽  
Thomas O’Connell ◽  
Marvin M Chun ◽  
Nicholas B. Turk-Browne
Keyword(s):  
Human Brain ◽  
Language Processing ◽  
Brain Function ◽  
Computational Models ◽  
Brain Activity ◽  
Functional Space ◽  
Semantic Features ◽  
Brain Functions ◽  
Auditory Features ◽  
The Brain

AbstractThe extent to which brain functions are localized or distributed is a foundational question in neuroscience. In the human brain, common fMRI methods such as cluster correction, atlas parcellation, and anatomical searchlight are biased by design toward finding localized representations. Here we introduce the functional searchlight approach as an alternative to anatomical searchlight analysis, the most commonly used exploratory multivariate fMRI technique. Functional searchlight removes any anatomical bias by grouping voxels based only on functional similarity and ignoring anatomical proximity. We report evidence that visual and auditory features from deep neural networks and semantic features from a natural language processing model are more widely distributed across the brain than previously acknowledged. This approach provides a new way to evaluate and constrain computational models with brain activity and pushes our understanding of human brain function further along the spectrum from strict modularity toward distributed representation.

scholarly journals Cell Type-Specific Annotation and Fine Mapping of Variants Associated With Brain Disorders

2020 ◽  
Vol 11 ◽  
Author(s):  
Abolfazl Doostparast Torshizi ◽  
Iuliana Ionita-Laza ◽  
Kai Wang
Keyword(s):  
Genetic Variants ◽  
Open Chromatin ◽  
Genome Wide Association Studies ◽  
Brain Disorders ◽  
Common Variants ◽  
Cell Type ◽  
Tissue Specific ◽  
Common Genetic Variants ◽  
Functional Consequences ◽  
Context Free

Common genetic variants confer susceptibility to a large number of complex brain disorders. Given that such variants predominantly localize in non-coding regions of the human genome, there is a significant challenge to predict and characterize their functional consequences. More importantly, most available computational methods, generally defined as context-free methods, output prediction scores regarding the functionality of genetic variants irrespective of the context, i.e., the tissue or cell-type affected by a disease, limiting the ability to predict the functional consequences of common variants on brain disorders. In this study, we introduce a comparative multi-step pipeline to investigate the relative effectiveness of context-specific and context-free approaches to prioritize disease causal variants. As an experimental case, we focused on schizophrenia (SCZ), a debilitating neuropsychiatric disease for which a large number of susceptibility variants is identified from genome-wide association studies. We tested over two dozen available methods and examined potential associations between the cell/tissue-specific mapping scores and open chromatin accessibility, and provided a prioritized map of SCZ risk loci for in vitro or in-vivo functional analysis. We found extensive differences between context-free and tissue-specific approaches and showed how they may play complementary roles. As a proof of concept, we found a few sets of genes, through a consensus mapping of both categories, including FURIN to be among the top hits. We showed that the genetic variants in this gene and related genes collectively dysregulate gene expression patterns in stem cell-derived neurons and characterize SCZ phenotypic manifestations, while genes which were not shared among highly prioritized candidates in both approaches did not demonstrate such characteristics. In conclusion, by combining context-free and tissue-specific predictions, our pipeline enables prioritization of the most likely disease-causal common variants in complex brain disorders.

scholarly journals Seasonality in human cognitive brain responses

2016 ◽  
Vol 113 (11) ◽  
pp. 3066-3071 ◽  
Author(s):  
Christelle Meyer ◽  
Vincenzo Muto ◽  
Mathieu Jaspar ◽  
Caroline Kussé ◽  
Erik Lambot ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Function ◽  
Brain Activity ◽  
Memory Task ◽  
Cognitive Changes ◽  
Attention Task ◽  
Cross Sectional ◽  
Brain Physiology ◽  
Annual Rhythms ◽  
Brain Responses

Daily variations in the environment have shaped life on Earth, with circadian cycles identified in most living organisms. Likewise, seasons correspond to annual environmental fluctuations to which organisms have adapted. However, little is known about seasonal variations in human brain physiology. We investigated annual rhythms of brain activity in a cross-sectional study of healthy young participants. They were maintained in an environment free of seasonal cues for 4.5 d, after which brain responses were assessed using functional magnetic resonance imaging (fMRI) while they performed two different cognitive tasks. Brain responses to both tasks varied significantly across seasons, but the phase of these annual rhythms was strikingly different, speaking for a complex impact of season on human brain function. For the sustained attention task, the maximum and minimum responses were located around summer and winter solstices, respectively, whereas for the working memory task, maximum and minimum responses were observed around autumn and spring equinoxes. These findings reveal previously unappreciated process-specific seasonality in human cognitive brain function that could contribute to intraindividual cognitive changes at specific times of year and changes in affective control in vulnerable populations.

scholarly journals The Default Mode of Human Brain Function Primes the Intentional Stance

2015 ◽  
Vol 27 (6) ◽  
pp. 1116-1124 ◽  
Author(s):  
Robert P. Spunt ◽  
Meghan L. Meyer ◽  
Matthew D. Lieberman
Keyword(s):  
Human Brain ◽  
Brain Function ◽  
Mental States ◽  
Social World ◽  
Brain Regions ◽  
Social Stimulus ◽  
Intentional Stance ◽  
Default Mode ◽  
Human Tendency ◽  
The Mind

Humans readily adopt an intentional stance to other people, comprehending their behavior as guided by unobservable mental states such as belief, desire, and intention. We used fMRI in healthy adults to test the hypothesis that this stance is primed by the default mode of human brain function present when the mind is at rest. We report three findings that support this hypothesis. First, brain regions activated by actively adopting an intentional rather than nonintentional stance to a social stimulus were anatomically similar to those demonstrating default responses to fixation baseline in the same task. Second, moment-to-moment variation in default activity during fixation in the dorsomedial PFC was related to the ease with which participants applied an intentional—but not nonintentional—stance to a social stimulus presented moments later. Finally, individuals who showed stronger dorsomedial PFC activity at baseline in a separate task were generally more efficient when adopting the intentional stance and reported having greater social skills. These results identify a biological basis for the human tendency to adopt the intentional stance. More broadly, they suggest that the brain's default mode of function may have evolved, in part, as a response to life in a social world.

Shared genetic etiology between anxiety disorders and psychiatric and related intermediate phenotypes

2019 ◽  
Vol 50 (4) ◽  
pp. 692-704 ◽  
Author(s):  
Kazutaka Ohi ◽  
Takeshi Otowa ◽  
Mihoko Shimada ◽  
Tsukasa Sasaki ◽  
Hisashi Tanii
Keyword(s):  
Anxiety Disorders ◽  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Large Scale ◽  
Genetic Correlations ◽  
Well Being ◽  
Subjective Well Being ◽  
Intermediate Phenotypes ◽  
Genome Wide ◽  
Common Genetic Variants

AbstractBackgroundPsychiatric disorders and related intermediate phenotypes are highly heritable and have a complex, overlapping polygenic architecture. A large-scale genome-wide association study (GWAS) of anxiety disorders identified genetic variants that are significant on a genome-wide. The current study investigated the genetic etiological overlaps between anxiety disorders and frequently cooccurring psychiatric disorders and intermediate phenotypes.MethodsUsing case–control and factor score models, we investigated the genetic correlations of anxiety disorders with eight psychiatric disorders and intermediate phenotypes [the volumes of seven subcortical brain regions, childhood cognition, general cognitive ability and personality traits (subjective well-being, loneliness, neuroticism and extraversion)] from large-scale GWASs (n= 7556–298 420) by linkage disequilibrium score regression.ResultsAmong psychiatric disorders, the risk of anxiety disorders was positively genetically correlated with the risks of major depressive disorder (MDD) (rg± standard error = 0.83 ± 0.16,p= 1.97 × 10−7), schizophrenia (SCZ) (0.28 ± 0.09,p= 1.10 × 10−3) and attention-deficit/hyperactivity disorder (ADHD) (0.34 ± 0.13,p= 8.40 × 10−3). Among intermediate phenotypes, significant genetic correlations existed between the risk of anxiety disorders and neuroticism (0.81 ± 0.17,p= 1.30 × 10−6), subjective well-being (−0.73 ± 0.18,p= 4.89 × 10−5), general cognitive ability (−0.23 ± 0.08,p= 4.70 × 10−3) and putamen volume (−0.50 ± 0.18,p= 5.00 × 10−3). No other significant genetic correlations between anxiety disorders and psychiatric or intermediate phenotypes were observed (p> 0.05). The case–control model yielded stronger genetic effect sizes than the factor score model.ConclusionsOur findings suggest that common genetic variants underlying the risk of anxiety disorders contribute to elevated risks of MDD, SCZ, ADHD and neuroticism and reduced quality of life, putamen volume and cognitive performance. We suggest that the comorbidity of anxiety disorders is partly explained by common genetic variants.

scholarly journals Movie viewing elicits rich and reliable brain state dynamics

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Johan N. van der Meer ◽  
Michael Breakspear ◽  
Luke J. Chang ◽  
Saurabh Sonkusare ◽  
Luca Cocchi
Keyword(s):  
Resting State ◽  
Brain Function ◽  
Temporal Dynamics ◽  
Brain Activity ◽  
State Transitions ◽  
Brain State ◽  
The Social ◽  
Brain States ◽  
Functional States ◽  
Intrinsic Brain Activity

Abstract Adaptive brain function requires that sensory impressions of the social and natural milieu are dynamically incorporated into intrinsic brain activity. While dynamic switches between brain states have been well characterised in resting state acquisitions, the remodelling of these state transitions by engagement in naturalistic stimuli remains poorly understood. Here, we show that the temporal dynamics of brain states, as measured in fMRI, are reshaped from predominantly bistable transitions between two relatively indistinct states at rest, toward a sequence of well-defined functional states during movie viewing whose transitions are temporally aligned to specific features of the movie. The expression of these brain states covaries with different physiological states and reflects subjectively rated engagement in the movie. In sum, a data-driven decoding of brain states reveals the distinct reshaping of functional network expression and reliable state transitions that accompany the switch from resting state to perceptual immersion in an ecologically valid sensory experience.

scholarly journals Common Variants in 22 Genes Regulate Response to Metformin Intervention in Children with Obesity: A Pharmacogenetic Study of a Randomized Controlled Trial

2019 ◽  
Vol 8 (9) ◽  
pp. 1471 ◽  
Author(s):  
Augusto Anguita-Ruiz ◽  
Belén Pastor-Villaescusa ◽  
Rosaura Leis ◽  
Gloria Bueno ◽  
Raúl Hoyos ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Genetic Variants ◽  
Controlled Trial ◽  
Common Variants ◽  
Oral Antidiabetic Agent ◽  
Double Blind ◽  
Pharmacogenetic Study ◽  
Randomized Controlled ◽  
Common Genetic Variants ◽  
Wide Range

Metformin is a first-line oral antidiabetic agent that has shown additional effects in treating obesity and metabolic syndrome. Inter-individual variability in metformin response could be partially explained by the genetic component. Here, we aimed to test whether common genetic variants can predict the response to metformin intervention in obese children. The study was a multicenter and double-blind randomized controlled trial that was stratified according to sex and pubertal status in 160 children with obesity. Children were randomly assigned to receive either metformin (1g/d) or placebo for six months after meeting the defined inclusion criteria. We conducted a post hoc genotyping study in 124 individuals (59 placebo, 65 treated) comprising finally 231 genetic variants in candidate genes. We provide evidence for 28 common variants as promising pharmacogenetics regulators of metformin response in terms of a wide range of anthropometric and biochemical outcomes, including body mass index (BMI) Z-score, and glucose, lipid, and inflammatory traits. Although no association remained statistically significant after multiple-test correction, our findings support previously reported variants in metformin transporters or targets as well as identify novel and promising loci, such as the ADYC3 and the BDNF genes, with plausible biological relation to the metformin’s action mechanism. Trial Registration: Registered on the European Clinical Trials Database (EudraCT, ID: 2010-023061-21) on 14 November 2011 (URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-023061-21/ES).

scholarly journals Emergence and organization of adult brain function throughout child development

2020 ◽  
Author(s):  
Tristan S. Yates ◽  
Cameron T. Ellis ◽  
Nicholas B. Turk-Browne
Keyword(s):  
Human Brain ◽  
Brain Function ◽  
Brain Activity ◽  
Inferior Frontal Gyrus ◽  
Developmental Trajectory ◽  
Adult Brain ◽  
Data Driven ◽  
Age Related ◽  
Data Driven Approach ◽  
The Brain

AbstractAdult cognitive neuroscience has guided the study of human brain development by identifying regions associated with cognitive functions at maturity. The activity, connectivity, and structure of a region can be compared across ages to characterize the developmental trajectory of the corresponding function. However, observed developmental differences may not only reflect the maturation of the function but also its organization across the brain. That is, a function may be mature in children but supported by different brain regions and thus underestimated by focusing on adult regions. To test these possibilities, we investigated the presence, maturity, and localization of adult functions in children using probabilistic shared response modeling, a machine learning approach for functional alignment. After learning a lower-dimensional feature space from fMRI activity as adults watched a movie, we translated these shared features into the anatomical brain space of children 3–12 years old. To evaluate functional maturity, we correlated this reconstructed activity with the children’s actual fMRI activity as they watched the same movie. We found reliable correlations throughout cortex, even in the youngest children. The strength of the correlation in the precuneus, inferior frontal gyrus, and lateral occipital cortex increased over development and predicted chronological age. These age-related changes were driven by three types of developmental trajectories across distinct features of adult function: emergence from absence to presence, consistency in anatomical expression, and reorganization from one anatomical region to another. This data-driven approach to studying brain-wide function during naturalistic perception provides an abstract description of cognitive development throughout childhood.Significance StatementWhen watching a movie, your brain processes many types of information—plotlines, characters, locations, etc. A child watching this movie receives the same input, but some of their cognitive abilities (e.g., motion detection) are more developed than others (e.g., emotional reasoning). Beyond anatomical differences, when does the child brain begin to function like an adult brain? We used a data-driven approach to extract different aspects of brain activity from adults while they watched a movie during fMRI. We then predicted what the brain activity of a child would look like if they had processed the movie the same way. Comparing this prediction with actual brain activity from children allowed us to track the development of human brain function.

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