Causal effects of atrial fibrillation on brain white and gray matter volume: a Mendelian randomization study

Abstract Background Atrial fibrillation (AF) and brain volume loss are prevalent in older individuals. We aimed to assess the causal effect of atrial fibrillation on brain volume phenotypes by Mendelian randomization (MR) analysis. Methods The genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis (15,993 AF patients and 113,719 controls of European ancestry). The outcome summary statistics for head-size-normalized white or gray matter volume measured by magnetic resonance imaging were provided by a previous GWAS of 33,224 white British participants in the UK Biobank. Two-sample MR by the inverse variance–weighted method was performed, supported by pleiotropy-robust MR sensitivity analysis. The causal estimates for the effect of AF on ischemic stroke were also investigated in a dataset that included the findings from the MEGASTROKE study (34,217 stroke patients and 406,111 controls of European ancestry). The direct effects of AF on brain volume phenotypes adjusted for the mediating effect of ischemic stroke were studied by multivariable MR. Results A higher genetic predisposition for AF was significantly associated with lower grey matter volume [beta −0.040, standard error (SE) 0.017, P=0.017], supported by pleiotropy-robust MR sensitivity analysis. Significant causal estimates were identified for the effect of AF on ischemic stroke (beta 0.188, SE 0.026, P=1.03E−12). The total effect of AF on lower brain grey matter volume was attenuated by adjusting for the effect of ischemic stroke (direct effects, beta −0.022, SE 0.033, P=0.528), suggesting that ischemic stroke is a mediator of the identified causal pathway. The causal estimates were nonsignificant for effects on brain white matter volume as an outcome. Conclusions This study identified that genetic predisposition for AF is significantly associated with lower gray matter volume but not white matter volume. The results indicated that the identified total effect of AF on gray matter volume may be mediated by ischemic stroke.

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Causal effect of atrial fibrillation on brain white or grey matter volume: A Mendelian randomization study

10.1101/2020.12.17.20248314 ◽

2020 ◽

Author(s):

Sehoon Park ◽

Soojin Lee ◽

Yaerim Kim ◽

Semin Cho ◽

Kwangsoo Kim ◽

...

Keyword(s):

Atrial Fibrillation ◽

White Matter ◽

Grey Matter ◽

Mendelian Randomization ◽

Brain Volume ◽

Causal Effect ◽

Grey Matter Volume ◽

Volume Loss ◽

White Matter Volume ◽

Matter Volume

AbstractBackgroundAtrial fibrillation (AF) and brain volume loss are prevalent in older individuals. Further study investigating the causal effect of AF on brain volume is warranted.MethodsThis study was a Mendelian randomization (MR) analysis. The genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis and included 537,409 individuals of European ancestry. The outcome summary statistics for quantile-normalized white or grey matter volume measured by magnetic resonance imaging were provided by the previous GWAS of 8426 white British UK Biobank participants. The main MR method was the inverse variance weighted method, supported by sensitivity MR analysis including MR-Egger regression and the weighted median method. The causal estimates from AF to white or grey matter volume were further adjusted for effects of any stroke or ischemic stroke by multivariable MR analysis.ResultsA higher genetic predisposition for AF (one standard deviation increase) was significantly associated with lower white matter volume [beta −0.128 (−0.208, −0.048)] but not grey matter volume [beta −0.041 (−0.101, 0.018)], supported by all utilized sensitivity MR analyses. The multivariable MR analysis indicated that AF is causally linked to lower white matter volume independent of the stroke effect.ConclusionsAF is a causative factor for white matter volume loss. The effect of AF on grey matter volume was inapparent in this study. A future trial is necessary to confirm whether appropriate AF management can be helpful in preventing cerebral white matter volume loss or related brain disorders in AF patients.

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Income is associated with hippocampal/amygdala and education with cingulate cortex grey matter volume

Scientific Reports ◽

10.1038/s41598-020-75809-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

M. Lotze ◽

M. Domin ◽

C. O. Schmidt ◽

N. Hosten ◽

H. J. Grabe ◽

...

Keyword(s):

Socioeconomic Status ◽

Anterior Cingulate Cortex ◽

Gray Matter ◽

Gray Matter Volume ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Grey Matter Volume ◽

Life Outcomes ◽

Matter Volume ◽

The Relationship

Abstract Income and education are both elements of a person’s socioeconomic status, which is predictive of a broad range of life outcomes. The brain’s gray matter volume (GMV) is influenced by socioeconomic status and mediators related to an unhealthy life style. We here investigated two independent general population samples comprising 2838 participants (all investigated with the same MRI-scanner) with regard to the association of indicators of the socioeconomic status and gray matter volume. Voxel-based morphometry without prior hypotheses revealed that years of education were positively associated with GMV in the anterior cingulate cortex and net-equivalent income with gray matter volume in the hippocampus/amygdala region. Analyses of possible mediators (alcohol, cigarettes, body mass index (BMI), stress) revealed that the relationship between income and GMV in the hippocampus/amygdala region was partly mediated by self-reported stressors, and the association of years of education with GMV in the anterior cingulate cortex by BMI. These results corrected for whole brain effects (and therefore not restricted to certain brain areas) do now offer possibilities for more detailed hypotheses-driven approaches.

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0315 Gray Matter Volume of the Rostral Medial Prefrontal Cortex is Associated with Resilience to Mood Decline During Overnight Sleep Deprivation

SLEEP ◽

10.1093/sleep/zsaa056.312 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A119-A119

Author(s):

I Anlap ◽

E Taylor ◽

M A Grandner ◽

W D Killgore

Keyword(s):

Prefrontal Cortex ◽

Sleep Deprivation ◽

Medial Prefrontal Cortex ◽

Gray Matter ◽

Cognitive Task ◽

Gray Matter Volume ◽

Grey Matter Volume ◽

Matter Volume ◽

Cluster Threshold ◽

Subjective Alertness

Abstract Introduction Vulnerability to sleep deprivation (SD) has been attributed to inter-individual trait-like differences in the ability to sustain vigilance and subjective alertness, which may have distinct neurobiological substrates. We have previously shown that reduced suppression of the Default Mode Network (DMN) during a cognitive task was predictive of global vulnerability to SD. However, little is known about vulnerability to mood decrements during SD and the underlying neurobiological mechanisms. Using voxel-based morphometry (VBM), we assessed structural differences in gray matter volume (GMV) of a region of the anterior DMN, the medial prefrontal cortex and its association with self-reported mood during 29 hours of SD. Methods 45 healthy participants (23 male; Ages 20-43) underwent 3T structural magnetic resonance imaging (MRI). Within 4 days, participants underwent an overnight SD session (29 hours awake total) which included hourly mood assessments with several visual analog mood scales (VAMS) assessing positive and negative affect. Hourly VAMS data were converted into a comparative metric of percent worsening of mood scores from 19:00 until noon the next day. These scores were averaged to determine a “mood resilience” score, with higher scores indicating greater mood sustainment. Using SPM12, the mean mood resilience scores were correlated with whole-brain gray matter volume, restricted to the medial prefrontal cortex, p<.05, FWE corrected, with a cluster threshold of 137 voxels. Results Overnight mood resilience was significantly correlated with greater grey matter volume in right rostral medial prefrontal cortex (p<.05, corrected; k=137). Conclusion Individuals with greater gray matter volume within a circumscribed region of the right medial prefrontal cortex demonstrated greater resilience to mood degradation over 29 hours of continuous wakefulness. This same region of the brain has been shown to be critical for the passive maintenance of emotions. We speculate that greater GMV could protect against mood decline by better sustaining emotional state during SD. Support Defense Advanced Research Projects Agency Young Faculty Award: DARPA-12-12-11-YFA11-FP-029

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Age-specific adult rat brain MRI templates and tissue probability maps

10.31219/osf.io/htgqn ◽

2021 ◽

Cited By ~ 1

Author(s):

Eilidh MacNicol ◽

Paul Wright ◽

Eugene Kim ◽

Irene Brusini ◽

Oscar Esteban ◽

...

Keyword(s):

White Matter ◽

Rat Brain ◽

Grey Matter ◽

Brain Volume ◽

Grey Matter Volume ◽

Total Brain Volume ◽

Adult Rat ◽

Matter Volume ◽

Probability Maps ◽

Total Brain

Age-specific resources mitigate biases in human MRI processing arising from structural changes across the lifespan. There are fewer age-specific resources for preclinical imaging, and they only represent developmental periods rather than adulthood. Since rats recapitulate many facets of human aging, it was hypothesized that brain volume and each tissue’s relative contribution to total brain volume would change with age in the adult rat. However, the currently available tissue probability maps, which provide a priori information for tissue volume estimation, provide inaccurate grey matter probabilities in subcortical structures, particularly the thalamus. Consequently, age-specific templates and tissue probability maps were generated from a longitudinal study that scanned a cohort of rats at 3, 5, 11, and 17 months old. Mixed-effects models assessed the effect of age on brain, grey matter, white matter, and CSF volumes, and the relative tissue proportions. Grey and white matter volume increased with age, and the tissue proportions relative to total brain volume varied throughout adulthood. Furthermore, we present evidence of a systematic underestimation of thalamic grey matter volume with existing resources, which is mitigated with the use of age-specific tissue probability maps since the derived estimates better matched histological evidence. To reduce age-related biases in image pre-processing, a set of rat brain resources from across the adult lifespan is consequently released to expand the preclinical MRI community’s fundamental resources.

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Usefulness of two-dimensional measurements for the evaluation of brain volume and disability in multiple sclerosis

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/20552173211070749 ◽

2022 ◽

Vol 8 (1) ◽

pp. 205521732110707

Author(s):

Satori Ajitomi ◽

Juichi Fujimori ◽

Ichiro Nakashima

Keyword(s):

Multiple Sclerosis ◽

Processing Speed ◽

Lateral Ventricle ◽

Grey Matter ◽

Brain Volume ◽

Grey Matter Volume ◽

Two Dimensional ◽

Whole Brain ◽

Brain Volumes ◽

Matter Volume

Background Two-dimensional (2D) measures have been proposed as potential proxies for whole-brain volume in multiple sclerosis (MS). Objective To verify whether 2D measurements by routine MRI are useful in predicting brain volume or disability in MS. Methods In this cross-sectional analysis, eighty-five consecutive Japanese MS patients—relapsing-remitting MS (81%) and progressive MS (19%)—underwent 1.5 Tesla T1-weighted 3D MRI examinations to measure whole-brain and grey matter volume. 2D measurements, namely, third ventricle width, lateral ventricle width (LVW), brain width, bicaudate ratio, and corpus callosum index (CCI), were obtained from each scan. Correlations between 2D measurements and 3D measurements, the Expanded Disability Status Scale (EDSS), or processing speed were analysed. Results The third and lateral ventricle widths were well-correlated with the whole-brain volume ( p < 0.0001), grey matter volume ( p < 0.0001), and EDSS scores ( p = 0.0001, p = .0004, respectively).The least squares regression model revealed that 78% of the variation in whole-brain volume could be explained using five explanatory variables, namely, LVW, CCI, age, sex, and disease duration. By contrast, the partial correlation coefficient excluding the effect of age showed that the CCI was significantly correlated with the EDSS and processing speed ( p < 0.0001). Conclusion Ventricle width correlated well with brain volumes, while the CCI correlated well with age-independent (i.e. disease-induced) disability.

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The neurobiology of smartphone addiction in emerging adults evaluated using brain morphometry and resting-state functional MRI

Neuroscience Research Notes ◽

10.31117/neuroscirn.v4i4.107 ◽

2021 ◽

Vol 4 (4) ◽

pp. 19-28

Author(s):

Aida Abdul Rashid ◽

Subapriya Suppiah ◽

Nisha Syed Nasser ◽

Hamed Sharifat ◽

Mazlyfarina Mohamad ◽

...

Keyword(s):

Emerging Adults ◽

Functional Mri ◽

Gray Matter ◽

Resting State ◽

Gray Matter Volume ◽

Smartphone Addiction ◽

Grey Matter Volume ◽

Precentral Gyrus ◽

Matter Volume ◽

Psychosocial Wellbeing

The characteristics of smartphone addiction (SPA) can be evaluated by neuroimaging studies. Information on the brain structural alterations, and effects on psychosocial wellbeing, however, have not been concurrently evaluated. The aim of this study was to identify abnormalities in gray matter volume using voxel-based morphometry (VBM) and neuronal functional alterations using resting-state functional MRI (rs-fMRI) in emerging adults with SPA. We correlated the neuroimaging parameters with indices for psychosocial wellbeing such as depression, anxiety, stress, and impulsivity. Forty participants (20 SPA and 20 age-matched healthy controls) were assessed using VBM and rs-fMRI. The smartphone addiction scale – Malay version (SAS-M) questionnaire scores were used to categorize the SPA and healthy control groups. DASS-21 and BIS-11 questionnaires were used to assess for psychosocial wellbeing and impulsivity, respectively. VBM identified the SPA group to have reduced gray matter volume in the insula and precentral gyrus; and increased grey matter volume in the precuneus relative to controls. Moderate correlation was observed between the precuneus volume and the SAS-M scores. Individuals with SPA showed significant rs-fMRI activations in the precuneus, and posterior cingulate cortex (FWE uncorrected, p<0.001). The severity of SPA was correlated with depression. Anxiety score was moderately correlated with reduced GMV at the precentral gyrus. Collectively, these results can be used to postulate that the structural and neuronal functional changes in the insula are linked to the neurobiology of SPA that shares similarities with other behavioural addictions.

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Global and regional volume changes in the brains of patients with phenylketonuria

Neurology ◽

10.1212/01.wnl.0000204415.39853.4a ◽

2006 ◽

Vol 66 (7) ◽

pp. 1074-1078 ◽

Cited By ~ 22

Author(s):

B. Pérez-Dueñas ◽

J. Pujol ◽

C. Soriano-Mas ◽

H. Ortiz ◽

R. Artuch ◽

...

Keyword(s):

White Matter ◽

Gray Matter ◽

Premotor Cortex ◽

Gray Matter Volume ◽

Relative Increase ◽

Volume Reduction ◽

Periventricular White Matter ◽

White Matter Volume ◽

Volume Changes ◽

Matter Volume

Background: Although phenylketonuria is a treatable disease, patients with late or nonoptimal phenylalanine-restricted diet may experience brain damage. The authors used tridimensional MRI and a voxelwise analysis method to investigate possible volume changes in the brain parenchyma of patients with phenylketonuria.Methods: The authors assessed 27 treated patients (mean age ± SD, 20 ± 7 years) and 27 matched control subjects. Global tissue volumes were compared, and statistical parametric maps of between-group regional volume differences were obtained for gray and white matter. Anatomic data were correlated with relevant clinical and biochemical variables.Results: Patients with phenylketonuria showed smaller gray matter volumes that were associated with lower IQ and older age at diagnosis. Voxel-based maps revealed that significant gray matter volume reduction occurred in motor and premotor cortex and thalamus. A relative increase in gray matter volume was observed in the ventral part of the striatum. The authors found no group differences for global white matter measurements. Higher recent phenylalanine levels, however, were associated with larger global white matter volume in early-treated patients. Voxel-based maps showed a relative volume reduction in periventricular white matter and a relative increase in the region of the internal capsule, extending to the adjacent thalamus and striatum.Conclusions: Treated patients may show significant gray and white matter volume changes related to the duration and strict observation of dietary treatment. Further studies are needed to investigate whether the presence of neurologic symptoms may be explained by specific anatomic alterations.

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0307 Gray Matter Volume Correlates of Psychomotor Vigilance Speed During Sleep Deprivation

SLEEP ◽

10.1093/sleep/zsaa056.304 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A116-A116

Author(s):

C E Meinhausen ◽

J R Vanuk ◽

M A Grandner ◽

W D Killgore

Keyword(s):

Prefrontal Cortex ◽

Sleep Deprivation ◽

Gray Matter ◽

Inferior Frontal Gyrus ◽

Gray Matter Volume ◽

Sleep Loss ◽

Grey Matter Volume ◽

Matter Volume ◽

The Right ◽

Psychomotor Vigilance

Abstract Introduction Sleep deprivation has often been associated with decreased cognitive control, including deficits in the ability to sustain attention. Psychomotor vigilance speed slows following a period of fatigue, and can lead to disastrous results in daily life. In order to determine the brain areas correlated with reduced psychomotor vigilance speed, as a result of diminished sleep, a voxel-based morphometry analysis was performed prior to a period of monitored sleep deprivation. The mean speed of response time during the final 17 hours of a 29-hour sleep deprivation was then measured with the Psychomotor Vigilance Test (PVT), a reaction-timed task that measures the speed participants respond to a visual stimulus. Methods 45 healthy individuals (male=23 female=22) between the ages of 20-43 years (M=25.4 SD=5.6) participated in the study. Structural neuroimaging data were collected using a T3 magnetic resonance imaging scanner following a typical night’s sleep. Mean PVT speed was monitored with an hourly 10-minute PVT assessment during a monitored overnight sleep deprivation session. Speed was defined as the reciprocal of reaction time (1/RT). Results PVT speed was negatively correlated with grey matter volume (P<.05 FWE-corrected) in the prefrontal cortex, specifically the right posterior inferior frontal gyrus (p=.030; MNI coordinates = 36, 12, 26). Conclusion Our findings indicate that gray matter within the right posterior inferior frontal gyrus is greater in individuals who are more vulnerable to slowing of PVT responses during an overnight period of sleep deprivation. These findings suggest that inter-individual differences in the ability to sustain psychomotor vigilance during sleep loss may be related to increased gray matter in the right lateral prefrontal cortex and could have implications for understanding the neurobiological substrates of vulnerability and resilience to sleep loss. Support

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Optic neuritis interferes with optical coherence tomography and magnetic resonance imaging correlations

Multiple Sclerosis Journal ◽

10.1177/1352458512457844 ◽

2012 ◽

Vol 19 (4) ◽

pp. 443-450 ◽

Cited By ~ 81

Author(s):

Hanna Zimmermann ◽

Alina Freing ◽

Falko Kaufhold ◽

Gunnar Gaede ◽

Elena Bohn ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Optic Neuritis ◽

Grey Matter ◽

Brain Volume ◽

Retinal Nerve Fibre Layer ◽

Grey Matter Volume ◽

Optical Coherence ◽

Cross Sectional ◽

Matter Volume ◽

Retinal Examination

Background: Retinal nerve fibre layer (RNFL) thinning is associated with brain atrophy in multiple sclerosis (MS). An influence of optic neuritis is well documented but sparsely investigated. Recently, the retinal ganglion cell layer (GCL) has been shown to provide superior information regarding visual function and retinal neurodegeneration as compared with RNFL. Objective: To investigate the association of white and grey matter brain volume with peripapillary RNFL and macular GCL in MS patients with and without a history of optic neuritis. Methods: 63 patients with relapsing–remitting MS were included in a two-centre cross-sectional prospective study. All patients underwent retinal examination with spectral domain optical coherence tomography and 1.5 T MRI for determination of normalized brain volume (NBV), white matter volume (NWMV) and grey matter volume (NGMV). Results: Both RNFL and GCL were associated with NBV, NWMV and NGMV in eyes without previous optic neuritis. This association is disrupted in the case of NGMV following optic neuritis. Conclusions: Both RNFL and GCL as parameters of neuro-axonal damage are comparably linked to whole brain as well as white and grey matter atrophy. An event of optic neuritis interferes with this relation, adding further damage to the optic nerve and disrupting especially an association with grey matter.

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Neuromorphological changes following selection for tameness and aggression in the Russian fox-farm experiment

10.1101/2020.11.21.390229 ◽

2020 ◽

Author(s):

Erin E. Hecht ◽

Anna Kukekova ◽

David A. Gutman ◽

Greg Acland ◽

Todd M. Preuss ◽

...

Keyword(s):

Gray Matter ◽

Brain Volume ◽

Gray Matter Volume ◽

Aggressive Response ◽

Neural Mechanisms ◽

Brain Morphology ◽

Controlled Study ◽

Matter Volume ◽

Selection For ◽

Dog Domestication

AbstractThe Russian fox-farm experiment is an unusually long-running and well-controlled study designed to replicate wolf-to-dog domestication. As such, it offers an unprecedented window onto the neural mechanisms governing the evolution of behavior. Here we report adaptations to gray matter morphology resulting from selection for tameness vs. aggressive response toward humans. Contrasting with prior work in other domesticated species, tame foxes did not show reduced brain volume. Rather, gray matter volume in both the tame and aggressive strains was increased relative to foxes bred without selection on behavior. Furthermore, tame- and aggressive-enlarged regions overlapped substantially, including portions of motor, somatosensory, and prefrontal cortex, amygdala, hippocampus, and cerebellum. We also observed differential morphological covariation across distributed gray matter networks. In one prefrontal-hypothalamic network, this covariation differentiated the tame and aggressive foxes together from the conventional strain. These findings indicate that selection for opposite behaviors can influence brain morphology in a similar way.

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