scholarly journals Cortical remodelling in childhood is associated with genes enriched for neurodevelopmental disorders

2019 ◽  
Author(s):  
G. Ball ◽  
J. Seidlitz ◽  
R. Beare ◽  
M.L. Seal
Keyword(s):  
Gene Expression ◽  
Cortical Thickness ◽  
Neurodevelopmental Disorders ◽  
Cortical Neurons ◽  
Childhood And Adolescence ◽  
Phenotypic Marker ◽  
Genetic Organisation ◽  
Childhood Population ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Changes

AbstractCortical development during childhood and adolescence has been characterised in recent years using metrics derived from Magnetic Resonance Imaging (MRI). Changes in cortical thickness are greatest in the first two decades of life and recapitulate the genetic organisation of the cortex, highlighting the potential early impact of gene expression on differences in cortical architecture over the lifespan. It is important to further our understanding of the possible neurobiological mechanisms that underlie these changes as differences in cortical thickness may act as a potential phenotypic marker of several common neurodevelopmental and psychiatric disorders.In this study, we combine MRI acquired from a large typically-developing childhood population (n=768) with comprehensive human gene expression databases to test the hypothesis that disrupted mechanisms common to neurodevelopmental disorders are encoded by genes expressed early in development and nested within those associated with typical cortical remodelling in childhood.We find that differential rates of thinning across the developing cortex are associated with spatially-varying gradients of gene expression. Genes that are expressed highly in regions of accelerated thinning are expressed predominantly in cortical neurons, involved in synaptic remodeling, and associated with common cognitive and neurodevelopmental disorders. Further, we identify subsets of genes that are highly expressed in the prenatal period and jointly associated with both developmental cortical morphology and neurodevelopmental disorders.

scholarly journals Serial magnetic resonance imaging findings during severe attacks of familial hemiplegic migraine type 2: a case report

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
David Fear ◽  
Misha Patel ◽  
Ramin Zand
Keyword(s):  
Magnetic Resonance Imaging ◽  
Family History ◽  
Magnetic Resonance ◽  
Familial Hemiplegic Migraine ◽  
Imaging Findings ◽  
Resonance Imaging ◽  
Hemiplegic Migraine ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Changes

Abstract Background Hemiplegic migraines represent a heterogeneous disorder with various presentations. Hemiplegic migraines are classified as sporadic or familial based on the presence of family history, but both subtypes have an underlying genetic etiology. Mutations in the ATP1A2 gene are responsible for Familial Hemiplegic type 2 (FHM2) or the sporadic hemiplegic migraine (SHM) counterpart if there is no family history of the disorder. Manifestations include migraine with aura and hemiparesis along with a variety of other symptoms likely dependent upon the specific mutation(s) present. Case presentation We report the case of an adult man who presented with headache, aphasia, and right-sided weakness. Workup for stroke and various infectious agents was unremarkable during the patient’s extended hospital stay. We emphasize the changes in the Magnetic Resonance Imaging (MRI) over time and the delay from onset of symptoms to MRI changes in Isotropic Diffusion Map (commonly referred to as Diffusion Weighted Imaging (DWI)) as well as Apparent Diffusion Coefficient (ADC). Conclusions We provide a brief review of imaging findings correlated with signs/symptoms and specific mutations in the ATP1A2 gene reported in the literature. Description of the various mutations and consequential presentations may assist neurologists in identifying cases of Hemiplegic Migraine, which may include transient changes in ADC and DWI imaging throughout the course of an attack.

scholarly journals LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models

2021 ◽  
Vol 7 (11) ◽  
pp. eaba1187
Author(s):  
Rina Baba ◽  
Satoru Matsuda ◽  
Yuuichi Arakawa ◽  
Ryuji Yamada ◽  
Noriko Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Specific Inhibitor ◽  
Autism Spectrum ◽  
Poly I:C ◽  
Control Of Gene Expression ◽  
Epigenetic Machinery ◽  
The Brain

Persistent epigenetic dysregulation may underlie the pathophysiology of neurodevelopmental disorders, such as autism spectrum disorder (ASD). Here, we show that the inhibition of lysine-specific demethylase 1 (LSD1) enzyme activity normalizes aberrant epigenetic control of gene expression in neurodevelopmental disorders. Maternal exposure to valproate or poly I:C caused sustained dysregulation of gene expression in the brain and ASD-like social and cognitive deficits after birth in rodents. Unexpectedly, a specific inhibitor of LSD1 enzyme activity, 5-((1R,2R)-2-((cyclopropylmethyl)amino)cyclopropyl)-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide hydrochloride (TAK-418), almost completely normalized the dysregulated gene expression in the brain and ameliorated some ASD-like behaviors in these models. The genes modulated by TAK-418 were almost completely different across the models and their ages. These results suggest that LSD1 enzyme activity may stabilize the aberrant epigenetic machinery in neurodevelopmental disorders, and the inhibition of LSD1 enzyme activity may be the master key to recover gene expression homeostasis. TAK-418 may benefit patients with neurodevelopmental disorders.

scholarly journals Actionable and incidental neuroradiological findings in twins with neurodevelopmental disorders

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lynnea Myers ◽  
Mai-Lan Ho ◽  
Elodie Cauvet ◽  
Karl Lundin ◽  
Torkel Carlsson ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Copy Number Variants ◽  
Cross Sectional Study ◽  
Autism Spectrum ◽  
Molecular Signaling ◽  
Mri Findings ◽  
Cross Sectional ◽  
Increased Risk ◽  
Magnetic Resonance Imaging Mri ◽  
Morphological Variants

AbstractWhile previous research has investigated neuroradiological findings in autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), the entire range of neurodevelopmental disorders (NDDs) has not yet been well-studied using magnetic resonance imaging (MRI). Considering the overlap among NDDs and simultaneous development of the brain and face, guided by molecular signaling, we examined the relationship of actionable and incidental (non-actionable) MRI findings and NDD diagnoses together with facial morphological variants and genetic copy number variants (CNVs). A cross-sectional study was conducted with a twin cohort 8–36 years of age (57% monozygotic, 40% dizygotic), including 372 subjects (46% with NDDs; 47% female) imaged by MRI, 280 with data for facial morphological variants, and 183 for CNVs. Fifty-one percent of participants had MRI findings. Males had a statistically significantly higher percentage of MRI findings (57.7%) compared with females (43.8%, p = 0.03). Twin zygosity was not statistically significantly correlated with incidence or severity of specific MRI findings. No statistically significant association was found between MRI findings and any NDD diagnosis or facial morphological variants; however, MRI findings were statistically significantly associated with the number of CNVs (OR 1.20, 95% CI 1.00–1.44, p = 0.05, adjusted OR for sex 1.24, 95% CI 1.03–1.50, p = 0.02). When combining the presence of MRI findings, facial morphological variants, and CNVs, statistically significant relationships were found with ASD and ADHD diagnoses (p = 0.0006 and p = 0.002, respectively). The results of this study demonstrate that the ability to identify NDDs from combined radiology, morphology, and CNV assessments may be possible. Additionally, twins do not appear to be at increased risk for neuroradiological variants.

Voxelwise analysis of conventional magnetic resonance imaging to predict future disability in early relapsing–remitting multiple sclerosis

2012 ◽  
Vol 18 (11) ◽  
pp. 1585-1591 ◽  
Author(s):  
Delphine Wybrecht ◽  
Françoise Reuter ◽  
Wafaa Zaaraoui ◽  
Anthony Faivre ◽  
Lydie Crespy ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Physical Disability ◽  
Conventional Magnetic Resonance Imaging ◽  
Global Approach ◽  
Resonance Imaging ◽  
Conventional Magnetic Resonance ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Changes

Background: The ability of conventional magnetic resonance imaging (MRI) to predict subsequent physical disability and cognitive deterioration after a clinically isolated syndrome (CIS) is weak. Objectives: We aimed to investigate whether conventional MRI changes over 1 year could predict cognitive and physical disability 5 years later in CIS. We performed analyses using a global approach (T2 lesion load, number of T2 lesions), but also a topographic approach. Methods: This study included 38 patients with a CIS. At inclusion, 10 out of 38 patients fulfilled the 2010 revised McDonald’s criteria for the diagnosis of multiple sclerosis. Expanded Disability Status Scale (EDSS) evaluation was performed at baseline, year 1 and year 5, and cognitive evaluation at baseline and year 5. T2-weighted MRI was performed at baseline and year 1. We used voxelwise analysis to analyse the predictive value of lesions location for subsequent disability. Results: Using the global approach, no correlation was found between MRI and clinical data. The occurrence or growth of new lesions in the brainstem was correlated with EDSS changes over the 5 years of follow-up. The occurrence or growth of new lesions in cerebellum, thalami, corpus callosum and frontal lobes over 1 year was correlated with cognitive impairment at 5 years. Conclusion: The assessment of lesion location at the first stage of multiple sclerosis may be of value to predict future clinical disability.

Metabotropic glutamate receptor 2 and corticotrophin-releasing factor receptor-1 gene expression is differently regulated by BDNF in rat primary cortical neurons

Synapse ◽  
2013 ◽  
Vol 67 (11) ◽  
pp. 794-800 ◽  
Author(s):  
Christinna V. Jørgensen ◽  
Anders B. Klein ◽  
Mona EL-Sayed ◽  
Gitte M. Knudsen ◽  
Jens D. Mikkelsen
Keyword(s):  
Gene Expression ◽  
Glutamate Receptor ◽  
Cortical Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Primary Cortical Neurons ◽  
Metabotropic Glutamate ◽  
Corticotrophin Releasing Factor

scholarly journals Neuronal activity enhances aryl hydrocarbon receptor-mediated gene expression and dioxin neurotoxicity in cortical neurons

2008 ◽  
Vol 104 (5) ◽  
pp. 1415-1429 ◽  
Author(s):  
Chun-Hua Lin ◽  
Shu-Hui Juan ◽  
Chen Yu Wang ◽  
Yu-Yo Sun ◽  
Chih-Ming Chou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aryl Hydrocarbon Receptor ◽  
Neuronal Activity ◽  
Cortical Neurons ◽  
Aryl Hydrocarbon

scholarly journals Dynamical consequences of regional heterogeneity in the brain’s transcriptional landscape

2020 ◽  
Author(s):  
Gustavo Deco ◽  
Kevin Aquino ◽  
Aurina Arnatkevičiūtė ◽  
Stuart Oldham ◽  
Kristina Sabaroedin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Brain Regions ◽  
Biophysical Model ◽  
Neuronal Dynamics ◽  
Regional Heterogeneity ◽  
Magnetic Resonance Imaging Mri

AbstractBrain regions vary in their molecular and cellular composition, but how this heterogeneity shapes neuronal dynamics is unclear. Here, we investigate the dynamical consequences of regional heterogeneity using a biophysical model of whole-brain functional magnetic resonance imaging (MRI) dynamics in humans. We show that models in which transcriptional variations in excitatory and inhibitory receptor (E:I) gene expression constrain regional heterogeneity more accurately reproduce the spatiotemporal structure of empirical functional connectivity estimates than do models constrained by global gene expression profiles and MRI-derived estimates of myeloarchitecture. We further show that regional heterogeneity is essential for yielding both ignition-like dynamics, which are thought to support conscious processing, and a wide variance of regional activity timescales, which supports a broad dynamical range. We thus identify a key role for E:I heterogeneity in generating complex neuronal dynamics and demonstrate the viability of using transcriptional data to constrain models of large-scale brain function.

scholarly journals Taste quality representation in the human brain

2019 ◽  
Author(s):  
Jason A. Avery ◽  
Alexander G. Liu ◽  
John E. Ingeholm ◽  
Cameron D. Riddell ◽  
Stephen J. Gotts ◽  
...  
Keyword(s):  
Human Brain ◽  
Cortical Neurons ◽  
Brain Regions ◽  
Taste Quality ◽  
7 Tesla ◽  
Mammalian Brain ◽  
High Magnetic Field Strength ◽  
Magnetic Resonance Imaging Mri ◽  
Spatial Locations ◽  
Univariate Analyses

SUMMARYIn the mammalian brain, the insula is the primary cortical substrate involved in the perception of taste. Recent imaging studies in rodents have identified a gustotopic organization in the insula, whereby distinct insula regions are selectively responsive to one of the five basic tastes. However, numerous studies in monkeys have reported that gustatory cortical neurons are broadly-tuned to multiple tastes, and tastes are not represented in discrete spatial locations. Neuroimaging studies in humans have thus far been unable to discern between these two models, though this may be due to the relatively low spatial resolution employed in taste studies to date. In the present study, we examined the spatial representation of taste within the human brain using ultra-high resolution functional magnetic resonance imaging (MRI) at high magnetic field strength (7-Tesla). During scanning, participants tasted sweet, salty, sour and tasteless liquids, delivered via a custom-built MRI-compatible tastant-delivery system. Our univariate analyses revealed that all tastes (vs. tasteless) activated primary taste cortex within the bilateral dorsal mid-insula, but no brain region exhibited a consistent preference for any individual taste. However, our multivariate searchlight analyses were able to reliably decode the identity of distinct tastes within those mid-insula regions, as well as brain regions involved in affect and reward, such as the striatum, orbitofrontal cortex, and amygdala. These results suggest that taste quality is not represented topographically, but by a combinatorial spatial code, both within primary taste cortex as well as regions involved in processing the hedonic and aversive properties of taste.

scholarly journals Longitudinal structural and functional brain development in childhood and adolescence

2018 ◽  
Author(s):  
Kathryn L. Mills ◽  
Christian K. Tamnes
Keyword(s):  
Brain Development ◽  
Animal Studies ◽  
Diffusion Tensor ◽  
Childhood And Adolescence ◽  
Structural Development ◽  
Social Environments ◽  
Brain Structure And Function ◽  
Magnetic Resonance Imaging Mri ◽  
Methodological Considerations ◽  
And Function

The development of the human brain involves a prolonged course of maturation, enabling us to learn to navigate our complex social environments. Here, we give short introductions to post-mortem and animal studies on postnatal brain development and selected methodological considerations for longitudinal developmental neuroimaging. We then describe typical developmental changes in brain structure and function from childhood to adulthood. We focus on measurements derived from magnetic resonance imaging (MRI) and on longitudinal data. Specifically, we discuss brain structural development based on morphometry and diffusion tensor imaging (DTI) studies, and functional development based on resting-state and task-based functional MRI. Finally, we highlight selected current overarching research questions and argue that an important step in answering these questions is to study individual differences in longitudinal brain development.

Abstract T P312: Utility of Early MRI in Intracerebral Hemorrhage

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Sherri A Braksick ◽  
Sara Hocker
Keyword(s):  
Intracerebral Hemorrhage ◽  
Clinical Management ◽  
Older Patients ◽  
Sinus Thrombosis ◽  
Retrospective Chart Review ◽  
Outpatient Setting ◽  
Amyloid Angiopathy ◽  
Non Invasive ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Changes

Introduction: Intracerebral hemorrhage (ICH) causes significant morbidity and mortality. Utility of early magnetic resonance imaging (MRI) is not fully understood. Identifying patients in whom early MRI changes clinical management may improve outcomes in select patients and reduce costs overall by avoiding inpatient MRIs in patients who are unlikely to benefit. Hypothesis: We assessed the hypothesis that early MRI in patients with spontaneous ICH does not alter management acutely in older patients. Methods: We conducted a retrospective chart review of all ICH admitted to our institution from 2006-2012. Patients were excluded if they 1) had a known underlying lesion, 2) were < 18 years, 3) suffered ICH as a result of trauma or 4) did not undergo MRI. Data were evaluated for clinical or radiographic characteristics that resulted in a change in clinical management, including surgical intervention or future avoidance of antithrombotic medications, among others. Results: In total, 248 patients with a median age of 70 years (IQR 58-78) were included. MRI changed management in 79 patients (31.9%). Initial MRI was obtained an average of 10 days after the hemorrhage. Possible structural abnormalities requiring emergent intervention were found in 14 (17.7%) patients, while 64 (81.0%) had findings concerning for other non-emergent/non-surgical anomalies (possible tumor (n=6), cavernoma (n=7), alternate diagnosis (n=1), probable amyloid angiopathy (n=21), evaluation for embolic phenomenon (n=13), evaluation for vasculitis (n=2), abnormal edema/enhancement (n=8), MRI led to additional non-invasive vascular imaging (n=6)). One patient (1.3%) was found to have a venous sinus thrombosis prompting anticoagulation. MRI was more likely to result in a change in management in patients < 55 years of age (47.1% vs 27.9%, p=0.009). Conclusions: MRI after ICH changed management in approximately one-third of patients and resulted in an immediate change in management in a minority of patients. Younger patients are more likely to benefit from early MRI. In older patients suspected of amyloid angiopathy that may preclude future antithrombotic therapy, delayed MRI in the outpatient setting may be reasonable.

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