Genetic influences of cortical gray matter in language-related regions in healthy controls and schizophrenia

Purpose To compare regional brain volumes in adult long-term survivors of childhood acute lymphoblastic leukemia (ALL) and healthy controls. Patients and Methods We investigated 130 survivors of childhood ALL diagnosed between 1970 and 2002 with magnetic resonance imaging (MRI) and neuropsychological testing at a median of 22.5 years after diagnosis. Morphometric analyses including whole-brain segmentation were performed using a validated automated procedure; 130 healthy adults served as controls. Results Compared with healthy controls, ALL survivors showed significantly smaller volumes of cortical gray matter, cerebral white matter, amygdala, caudate, hippocampus, thalamus, and estimated intracranial volume. Effect sizes ranged from small to medium. The strongest effect was found for the caudate, which on average was 5.2% smaller in ALL survivors. Caudate volumes were also smaller when controlling for intracranial volume, suggesting a specific effect. Neither age at diagnosis nor treatment variables such as radiation therapy or drug dose had a major impact on neuroanatomic volumes. Neuropsychological assessment revealed reduced processing speed, executive function, and verbal learning/memory in survivors compared with controls but no difference in estimated general intellectual ability. In ALL survivors, but not in controls, neuropsychological test results correlated with volumes of cortical gray matter, caudate, and thalamus as well as intracranial volume. Conclusion Structural MRI of long-term survivors of childhood ALL demonstrated smaller volumes of multiple brain structures compared with healthy controls. Because of possible selection biases, these results must be interpreted with caution. Future studies are required to clarify the significance of these findings and the neurobiologic mechanisms involved.

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Ovarian aging is associated with gray matter volume and disability in women with MS

Neurology ◽

10.1212/wnl.0000000000004843 ◽

2017 ◽

Vol 90 (3) ◽

pp. e254-e260 ◽

Cited By ~ 8

Author(s):

Jennifer S. Graves ◽

Roland G. Henry ◽

Bruce A.C. Cree ◽

Geralyn Lambert-Messerlian ◽

Ruth M. Greenblatt ◽

...

Keyword(s):

Gray Matter ◽

Disease Duration ◽

Longitudinal Research ◽

Gray Matter Volume ◽

Healthy Controls ◽

Linear Regression Models ◽

Matter Volume ◽

Ovarian Aging ◽

Cortical Gray Matter ◽

Gray Matter Loss

ObjectiveTo determine if ovarian aging as measured by levels of anti-Müllerian hormone (AMH) is associated with pattern of multiple sclerosis (MS) progression in women.MethodsWomen with MS and healthy controls were included from a longitudinal research cohort with up to 10 years follow-up. Plasma AMH levels were measured by ELISA for baseline and years 3, 5, and 8–10. Mixed effects logistic and linear regression models were employed, with adjustments for age, disease duration, and other covariables as appropriate.ResultsAMH levels were similar (0.98-fold difference, 95% confidence interval [CI] 0.69–1.37, p = 0.87) in women with MS (n = 412, mean age 42.6 years) and healthy controls (n = 180, mean age 44 years). In a multivariable model of women with MS, including adjustments for age, body mass index, and disease duration, 10-fold lower AMH level was associated with 0.43-higher Expanded Disability Status Scale (EDSS) score (95% CI 0.15–0.70, p = 0.003), 0.25-unit worse MS Functional Composite z score (95% CI −0.40 to −0.10, p = 0.0015), and 7.44 mm3 lower cortical gray matter volume (95% CI −14.6 to −0.30; p = 0.041) at baseline. In a multivariable random-intercept–random-slope model using all observations over time, 10-fold decrease in AMH was associated with a 0.27 increase in EDSS (95% CI 0.11–0.43, p = 0.006) and 5.48 mm3 (95% CI 11.3–0.33, p = 0.065) and 4.55 mm3 (95% CI 9.33–0.23, p = 0.062) decreases in total gray and cortical gray matter, respectively.ConclusionAs a marker of ovarian aging, lower AMH levels were associated with greater disability and gray matter loss in women with MS independent of chronological age and disease duration.

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Supplemental Material for Cortical Gray Matter Atrophy in Healthy Aging Cannot Be Explained by Undetected Incipient Cognitive Disorders: A Comment on Burgmans et al. (2009)

Neuropsychology ◽

10.1037/a0018827.supp ◽

2010 ◽

Keyword(s):

Gray Matter ◽

Healthy Aging ◽

Cognitive Disorders ◽

Gray Matter Atrophy ◽

Cortical Gray Matter

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Slowing of Cortical Gray Matter Atrophy with Teriflunomide is Associated with Delayed Conversion to Clinically Definite MS

SSRN Electronic Journal ◽

10.2139/ssrn.3288899 ◽

2018 ◽

Author(s):

Robert Zivadinov ◽

Michael G. Dwyer ◽

Ellen Carl ◽

Elizabeth M. Poole ◽

Steve Cavalier ◽

...

Keyword(s):

Gray Matter ◽

Gray Matter Atrophy ◽

Cortical Gray Matter

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Reduced cortical gray matter volume in male adolescents with substance and conduct problems

Drug and Alcohol Dependence ◽

10.1016/j.drugalcdep.2011.04.006 ◽

2011 ◽

Vol 118 (2-3) ◽

pp. 295-305 ◽

Cited By ~ 42

Author(s):

Manish Dalwani ◽

Joseph T. Sakai ◽

Susan K. Mikulich-Gilbertson ◽

Jody Tanabe ◽

Kristen Raymond ◽

...

Keyword(s):

Conduct Problems ◽

Gray Matter ◽

Gray Matter Volume ◽

Male Adolescents ◽

Matter Volume ◽

Cortical Gray Matter

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The Role of Electrode Size on the Incidence of Spreading Depression and on Cortical Cerebral Blood Flow as Measured by H2 Clearance

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1992.33 ◽

1992 ◽

Vol 12 (2) ◽

pp. 230-237 ◽

Cited By ~ 37

Author(s):

Marleen J. Verhaegen ◽

Michael M. Todd ◽

David S. Warner ◽

Bruce James ◽

Julie B. Weeks

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Gray Matter ◽

Spreading Depression ◽

Insertion Depth ◽

Flow Measurements ◽

Electrode Size ◽

Cortical Gray Matter ◽

The Right

Cerebral blood flow was measured by the H2 clearance method 30 and 60 min after the implantation of 300, 250, 125, or 50 μm diameter platinum–iridium electrodes 2 mm deep into the right parietal cortex of normothermic, normocarbic halothane-anesthetized rats. Another group of animals had 50 μm electrodes inserted 1 mm. In all animals, the presence or absence of a wave of spreading depression (SD) was noted at the time of implantation, with recordings made with glass micropipettes. H2 flow values were compared with those measured in gray matter from the same anatomical region (but from different rats), using [3H]nicotine. The incidence of SD ranged from 60% following insertion of 300 μm electrodes to 0% with 50 μm electrodes. H2 clearance flows also varied with electrode size, from 77 ± 21 ml 100 g−1 min−1 (mean ± standard deviation) with 300 μm electrodes to 110 ± 31 and 111 ± 16 ml 100 g−1 min−1 with 125 and 50 μm electrodes, respectively (insertion depth of 2 mm). A CBF value of 155 ± 60 ml 100 g−1 min−1 was obtained with 50 μm electrodes inserted only 1 mm. Cortical gray matter blood flow measured with [3H]nicotine was 154 ± 35 ml 100 g−1 min−1. When the role of SD in subsequent flow measurements was examined, there was a gradual increase in CBF between 30 and 60 min after electrode insertion in those animals with SD, while no such change was seen in rats without SD. These results indicate that the choice of electrode size and implantation depth influences the measurement of CBF by H2 clearance. CBF values equivalent to those obtained with isotopic techniques can be acutely obtained with small (50 μm diameter) electrodes inserted 1 mm into the cortex. While the occurrence of SD does influence CBF in the period immediately after implantation, a relationship between electrode size and measured flow is present that is independent of SD.

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Early cortical gray matter loss and cognitive correlates in non-demented Parkinson's patients

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2013.07.018 ◽

2013 ◽

Vol 19 (12) ◽

pp. 1088-1093 ◽

Cited By ~ 39

Author(s):

Eun-Young Lee ◽

Suman Sen ◽

Paul J. Eslinger ◽

Daymond Wagner ◽

Michele L. Shaffer ◽

...

Keyword(s):

Gray Matter ◽

Cognitive Correlates ◽

Cortical Gray Matter ◽

Gray Matter Loss

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Association of Age at Onset With Gray Matter Volume and White Matter Microstructural Abnormalities in People With Multiple Sclerosis

Neurology ◽

10.1212/wnl.0000000000012869 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012869

Author(s):

Raffaello Bonacchi ◽

Alessandro Meani ◽

Elisabetta Pagani ◽

Olga Marchesi ◽

Andrea Falini ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Gray Matter ◽

Linear Models ◽

Gray Matter Volume ◽

Age At Onset ◽

Healthy Controls ◽

Compensatory Mechanisms ◽

Cross Sectional ◽

Matter Volume

Objective:To investigate whether age at onset influences brain gray matter volume (GMV) and white matter (WM) microstructural abnormalities in adult multiple sclerosis (MS) patients, given its influence on clinical phenotype and disease course.Method:In this hypothesis-driven cross-sectional study, we enrolled 67 pediatric-onset MS (POMS) patients and 143 sex- and disease duration (DD)-matched randomly-selected adult-onset MS (AOMS) patients, together with 208 healthy controls. All subjects underwent neurological evaluation and 3T MRI acquisition. MRI variables were standardized based on healthy controls, to remove effects of age and sex. Associations with DD in POMS and AOMS patients were studied with linear models. Time to reach clinical and MRI milestones was assessed with product-limit approach.Results:At DD=1 year, GMV and WM fractional anisotropy (FA) were abnormal in AOMS but not in POMS patients. Significant interaction of age at onset (POMS vs AOMS) into the association with DD was found for GMV and WM FA. The crossing point of regression lines in POMS and AOMS patients was at 20 years of DD for GMV and 14 for WM FA. For POMS and AOMS patients, median DD was 29 and 19 years to reach Expanded Disability Status Scale=3 (p<0.001), 31 and 26 years to reach abnormal Paced Auditory Serial Addition Task-3 (p=0.01), 24 and 18 years to reach abnormal GMV (p=0.04), and 19 and 17 years to reach abnormal WM FA (p=0.36).Conclusions:Younger patients are initially resilient to MS-related damage. Then, compensatory mechanisms start failing with loss of WM integrity, followed by GM atrophy and finally disability.

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