Impact of Apolipoprotein E4 Polymorphism on the Gray Matter Volume and the White Matter Integrity in Subjective Memory Impairment without White Matter Hyperintensities: Voxel-Based Morphometry and Tract-Based Spatial Statistics Study under 3-Tesla MRI.

PubMed

Lee, Young-Min; Ha, Ji-Kyung; Park, Je-Min; Lee, Byung-Dae; Moon, EunSoo; Chung, Young-In; Kim, Ji-Hoon; Kim, Hak-Jin; Mun, Chi-Woong; Kim, Tae-Hyung; Kim, Young-Hoon

2016-01-01

The aim of this study is to compare gray matter (GM) volume and white matter (WM) integrity in Apolipoprotein E4 (ApoE ε4) carriers with that of ApoE ε4 noncarriers using the voxel-based morphometry and diffusion tensor imaging (DTI) to investigate the effect of the ApoE ε4 on brain structures in subjective memory impairment (SMI) without white matter hyperintensities (WMH). Altogether, 26 participants with SMI without WMH were finally recruited from the Memory impairment clinics of Pusan National University Hospital in Korea. All participants were ApoE genotyped (ApoE ε4 carriers: n = 13, matched ApoE ε4 noncarriers: n = 13) and underwent 3-tesla magnetic resonance imaging (MRI) including 3-dimensional volumetric images for GM volume and DTI for WM integrity. ApoE ε4 carriers compared with noncarriers in SMI without WMH showed the atrophy of GM in inferior temporal gyrus, inferior parietal lobule, anterior cingulum, middle frontal gyrus, and precentral gyrus and significantly lower fractional anisotropy WM values in the splenium of corpus callosum and anterior corona radiate. Our findings suggest that the ApoE ε4 is associated with both atrophy of GM volume and disruption of WM integrity in SMI without WMH. Copyright © 2015 by the American Society of Neuroimaging.

Cognitive correlates of gray matter abnormalities in adolescent siblings of patients with childhood-onset schizophrenia

PubMed Central

Wagshal, Dana; Knowlton, Barbara Jean; Cohen, Jessica Rachel; Bookheimer, Susan Yost; Bilder, Robert Martin; Fernandez, Vindia Gisela; Asarnow, Robert Franklin

2015-01-01

Patients with childhood onset schizophrenia (COS) display widespread gray matter (GM) structural brain abnormalities. Healthy siblings of COS patients share some of these structural abnormalities, suggesting that GM abnormalities are endophenotypes for schizophrenia. Another possible endophenotype for schizophrenia that has been relatively unexplored is corticostriatal dysfunction. The corticostriatal system plays an important role in skill learning. Our previous studies have demonstrated corticostriatal dysfunction in COS siblings with a profound skill learning deficit and abnormal pattern of brain activation during skill learning. This study investigated whether structural abnormalities measured using volumetric brain morphometry (VBM) were present in siblings of COS patients and whether these were related to deficits in cognitive skill learning. Results revealed smaller GM volume in COS siblings relative to controls in a number of regions, including occipital, parietal, and subcortical regions including the striatum, and greater GM volume relative to controls in several subcortical regions. Volume in the right superior frontal gyrus and cerebellum were related to performance differences between groups on the weather prediction task, a measure of cognitive skill learning. Our results support the idea that corticostriatal and cerebellar impairment in unaffected siblings of COS patients are behaviorally relevant and may reflect genetic risk for schizophrenia. PMID:25541139

Reduced Gray Matter Volume of the Thalamus and Hippocampal Region in Elderly Healthy Adults with no Impact of APOE ɛ4: A Longitudinal Voxel-Based Morphometry Study.

PubMed

Squarzoni, Paula; Duran, Fabio Luis Souza; Busatto, Geraldo F; Alves, Tania Correa Toledo de Ferraz

2018-01-01

Many cross-sectional voxel-based morphometry (VBM) investigations have shown significant inverse correlations between chronological age and gray matter (GM) volume in several brain regions in healthy humans. However, few VBM studies have documented GM decrements in the healthy elderly with repeated MRI measurements obtained in the same subjects. Also, the extent to which the APOE ɛ4 allele influences longitudinal findings of GM reduction in the healthy elderly is unclear. Verify whether regional GM changes are associated with significant decrements in cognitive performance taking in account the presence of the APOE ɛ4 allele. Using structural MRI datasets acquired in 55 cognitively intact elderly subjects at two time-points separated by approximately three years, we searched for voxels showing significant GM reductions taking into account differences in APOE genotype. We found global GM reductions as well as regional GM decrements in the right thalamus and left parahippocampal gyrus (p < 0.05, family-wise error corrected for multiple comparisons over the whole brain). These findings were not affected by APOE ɛ4. Irrespective of APOE ɛ4, longitudinal VBM analyses show that the hippocampal region and thalamus are critical sites where GM shrinkage is greater than the degree of global volume reduction in healthy elderly subjects.

Abnormal subcortical nuclei shapes in patients with type 2 diabetes mellitus.

PubMed

Chen, Ji; Zhang, Junxiang; Liu, Xuebing; Wang, Xiaoyang; Xu, Xiangjin; Li, Hui; Cao, Bo; Yang, Yanqiu; Lu, Jingjing; Chen, Ziqian

2017-10-01

Type 2 diabetes mellitus (T2DM) increases the risk of brain atrophy and dementia. We aimed to elucidate deep grey matter (GM) structural abnormalities and their relationships with T2DM cognitive deficits by combining region of interest (ROI)-based volumetry, voxel-based morphometry (VBM) and shape analysis. We recruited 23 T2DM patients and 24 age-matched healthy controls to undergo T1-weighted structural MRI scanning. Images were analysed using the three aforementioned methods to obtain deep GM structural shapes and volumes. Biochemical and cognitive assessments were made and were correlated with the resulting metrics. Shape analysis revealed that T2DM is associated with focal atrophy in the bilateral caudate head and dorso-medial part of the thalamus. ROI-based volumetry only detected thalamic volume reduction in T2DM when compared to the controls. No significant between-group differences were found by VBM. Furthermore, a worse performance of cognitive processing speed correlated with more severe GM atrophy in the bilateral dorso-medial part of the thalamus. Also, the GM volume in the bilateral dorso-medial part of the thalamus changed negatively with HbA 1c . Shape analysis is sensitive in identifying T2DM deep GM structural abnormalities and their relationships with cognitive impairments, which may greatly assist in clarifying the neural substrate of T2DM cognitive dysfunction. • Type 2 diabetes mellitus is accompanied with brain atrophy and cognitive dysfunction • Deep grey matter structures are essential for multiple cognitive processes • Shape analysis revealed local atrophy in the dorso-medial thalamus and caudatum in patients • Dorso-medial thalamic atrophy correlated to cognitive processing speed slowing and high HbA1c. • Shape analysis has advantages in unraveling neural substrates of diabetic cognitive deficits.

Regional gray matter atrophy in relapsing remitting multiple sclerosis: baseline analysis of multi-center data.

PubMed

Datta, Sushmita; Staewen, Terrell D; Cofield, Stacy S; Cutter, Gary R; Lublin, Fred D; Wolinsky, Jerry S; Narayana, Ponnada A

2015-03-01

Regional gray matter (GM) atrophy in multiple sclerosis (MS) at disease onset and its temporal variation can provide objective information regarding disease evolution. An automated pipeline for estimating atrophy of various GM structures was developed using tensor based morphometry (TBM) and implemented on a multi-center sub-cohort of 1008 relapsing remitting MS (RRMS) patients enrolled in a Phase 3 clinical trial. Four hundred age and gender matched healthy controls were used for comparison. Using the analysis of covariance, atrophy differences between MS patients and healthy controls were assessed on a voxel-by-voxel analysis. Regional GM atrophy was observed in a number of deep GM structures that included thalamus, caudate nucleus, putamen, and cortical GM regions. General linear regression analysis was performed to analyze the effects of age, gender, and scanner field strength, and imaging sequence on the regional atrophy. Correlations between regional GM volumes and expanded disability status scale (EDSS) scores, disease duration (DD), T2 lesion load (T2 LL), T1 lesion load (T1 LL), and normalized cerebrospinal fluid (nCSF) were analyzed using Pearson׳s correlation coefficient. Thalamic atrophy observed in MS patients compared to healthy controls remained consistent within subgroups based on gender and scanner field strength. Weak correlations between thalamic volume and EDSS (r=-0.133; p<0.001) and DD (r=-0.098; p=0.003) were observed. Of all the structures, thalamic volume moderately correlated with T2 LL (r=-0.492; P-value<0.001), T1 LL (r=-0.473; P-value<0.001) and nCSF (r=-0.367; P-value<0.001). Copyright © 2015 Elsevier B.V. All rights reserved.

Regional brain gray and white matter changes in perinatally HIV-infected adolescents☆

PubMed Central

Sarma, Manoj K.; Nagarajan, Rajakumar; Keller, Margaret A.; Kumar, Rajesh; Nielsen-Saines, Karin; Michalik, David E.; Deville, Jaime; Church, Joseph A.; Thomas, M. Albert

2013-01-01

Despite the success of antiretroviral therapy (ART), perinatally infected HIV remains a major health problem worldwide. Although advance neuroimaging studies have investigated structural brain changes in HIV-infected adults, regional gray matter (GM) and white matter (WM) volume changes have not been reported in perinatally HIV-infected adolescents and young adults. In this cross-sectional study, we investigated regional GM and WM changes in 16 HIV-infected youths receiving ART (age 17.0 ± 2.9 years) compared with age-matched 14 healthy controls (age 16.3 ± 2.3 years) using magnetic resonance imaging (MRI)-based high-resolution T1-weighted images with voxel based morphometry (VBM) analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC), bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain. PMID:24380059

Extraction of dynamic functional connectivity from brain grey matter and white matter for MCI classification.

PubMed

Chen, Xiaobo; Zhang, Han; Zhang, Lichi; Shen, Celina; Lee, Seong-Whan; Shen, Dinggang

2017-10-01

Brain functional connectivity (FC) extracted from resting-state fMRI (RS-fMRI) has become a popular approach for diagnosing various neurodegenerative diseases, including Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI). Current studies mainly construct the FC networks between grey matter (GM) regions of the brain based on temporal co-variations of the blood oxygenation level-dependent (BOLD) signals, which reflects the synchronized neural activities. However, it was rarely investigated whether the FC detected within the white matter (WM) could provide useful information for diagnosis. Motivated by the recently proposed functional correlation tensors (FCT) computed from RS-fMRI and used to characterize the structured pattern of local FC in the WM, we propose in this article a novel MCI classification method based on the information conveyed by both the FC between the GM regions and that within the WM regions. Specifically, in the WM, the tensor-based metrics (e.g., fractional anisotropy [FA], similar to the metric calculated based on diffusion tensor imaging [DTI]) are first calculated based on the FCT and then summarized along each of the major WM fiber tracts connecting each pair of the brain GM regions. This could capture the functional information in the WM, in a similar network structure as the FC network constructed for the GM, based only on the same RS-fMRI data. Moreover, a sliding window approach is further used to partition the voxel-wise BOLD signal into multiple short overlapping segments. Then, both the FC and FCT between each pair of the brain regions can be calculated based on the BOLD signal segments in the GM and WM, respectively. In such a way, our method can generate dynamic FC and dynamic FCT to better capture functional information in both GM and WM and further integrate them together by using our developed feature extraction, selection, and ensemble learning algorithms. The experimental results verify that the dynamic FCT can provide valuable functional information in the WM; by combining it with the dynamic FC in the GM, the diagnosis accuracy for MCI subjects can be significantly improved even using RS-fMRI data alone. Hum Brain Mapp 38:5019-5034, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Regional heterogeneity in limbic maturational changes: evidence from integrating cortical thickness, volumetric and diffusion tensor imaging measures.

PubMed

Grieve, Stuart M; Korgaonkar, Mayuresh S; Clark, C Richard; Williams, Leanne M

2011-04-01

Magnetic resonance imaging (MRI) studies of structural brain development have suggested that the limbic system is relatively preserved in comparison to other brain regions with healthy aging. The goal of this study was to systematically investigate age-related changes of the limbic system using measures of cortical thickness, volumetric and diffusion characteristics. We also investigated if the "relative preservation" concept is consistent across the individual sub-regions of the limbic system. T1 weighted structural MRI and Diffusion Tensor Imaging data from 476 healthy participants from the Brain Resource International Database was used for this study. Age-related changes in grey matter (GM)/white matter (WM) volume, cortical thickness, diffusional characteristics for the pericortical WM and for the fiber tracts associated with the limbic regions were quantified. A regional variability in the aging patterns across the limbic system was present. Four important patterns of age-related changes were highlighted for the limbic sub-regions: 1. early maturation of GM with late loss in the hippocampus and amygdala; 2. an extreme pattern of GM preservation in the entorhinal cortex; 3. a flat pattern of reduced GM loss in the anterior cingulate and the parahippocampus and; 4. accelerated GM loss in the isthmus and posterior cingulate. The GM volumetric data and cortical thickness measures proved to be internally consistent, while the diffusional measures provided complementary data that seem consistent with the GM trends identified. This heterogeneity can be hypothesized to be associated with age-related changes of cognitive function specialized for that region and direct connections to the other brain regions sub-serving these functions. Copyright © 2011 Elsevier Inc. All rights reserved.

Gray matter volume is associated with rate of subsequent skill learning after a long term training intervention

PubMed Central

Sampaio-Baptista, Cassandra; Scholz, Jan; Jenkinson, Mark; Thomas, Adam G.; Filippini, Nicola; Smit, Gabrielle; Douaud, Gwenaëlle; Johansen-Berg, Heidi

2014-01-01

The ability to predict learning performance from brain imaging data has implications for selecting individuals for training or rehabilitation interventions. Here, we used structural MRI to test whether baseline variations in gray matter (GM) volume correlated with subsequent performance after a long-term training of a complex whole-body task. 44 naïve participants were scanned before undertaking daily juggling practice for 6 weeks, following either a high intensity or a low intensity training regime. To assess performance across the training period participants' practice sessions were filmed. Greater GM volume in medial occipito-parietal areas at baseline correlated with steeper learning slopes. We also tested whether practice time or performance outcomes modulated the degree of structural brain change detected between the baseline scan and additional scans performed immediately after training and following a further 4 weeks without training. Participants with better performance had higher increases in GM volume during the period following training (i.e., between scans 2 and 3) in dorsal parietal cortex and M1. When contrasting brain changes between the practice intensity groups, we did not find any straightforward effects of practice time though practice modulated the relationship between performance and GM volume change in dorsolateral prefrontal cortex. These results suggest that practice time and performance modulate the degree of structural brain change evoked by long-term training regimes. PMID:24680712

Brain Structural Differences between Normal and Obese Adults and their Links with Lack of Perseverance, Negative Urgency, and Sensation Seeking.

PubMed

Wang, Haifeng; Wen, Baohong; Cheng, Jingliang; Li, Hongpeng

2017-01-16

In order to examine the difference in brain structure between obese and normal weight individuals, and to explore the relationship between the neuroanatomical changes and impulsivity traits, this study used a voxel-based morphometry method to examine gray matter (GM) volume alterations related to impulsive personality traits in obese individuals relative to normal weight. Eighty adults that completed the UPPS-P Impulsive Behavior Scale were analyzed. Possible GM volume alterations were first analyzed at the whole brain level, and then the relationship between regional GM volume differences and UPPS-P scores were examined in selected regions of interest. Reduced GM volumes were found in the frontal and limbic regions in the obese group compared to normal weight individuals. In the normal weight group, lack of perseverance was negatively correlated with GM volume in the anterior cingulate cortex, and negative urgency was negatively correlated with GM volume in the insula. In the obese group, sensation seeking was negatively correlated with GM volume in the left amygdala and right pallidum. These findings might improve our understanding of the relationship between lack of perseverance, negative urgency, and sensation seeking and body weight fluctuations.

Brain Structural Differences between Normal and Obese Adults and their Links with Lack of Perseverance, Negative Urgency, and Sensation Seeking

PubMed Central

Wang, Haifeng; Wen, Baohong; Cheng, Jingliang; Li, Hongpeng

2017-01-01

In order to examine the difference in brain structure between obese and normal weight individuals, and to explore the relationship between the neuroanatomical changes and impulsivity traits, this study used a voxel-based morphometry method to examine gray matter (GM) volume alterations related to impulsive personality traits in obese individuals relative to normal weight. Eighty adults that completed the UPPS-P Impulsive Behavior Scale were analyzed. Possible GM volume alterations were first analyzed at the whole brain level, and then the relationship between regional GM volume differences and UPPS-P scores were examined in selected regions of interest. Reduced GM volumes were found in the frontal and limbic regions in the obese group compared to normal weight individuals. In the normal weight group, lack of perseverance was negatively correlated with GM volume in the anterior cingulate cortex, and negative urgency was negatively correlated with GM volume in the insula. In the obese group, sensation seeking was negatively correlated with GM volume in the left amygdala and right pallidum. These findings might improve our understanding of the relationship between lack of perseverance, negative urgency, and sensation seeking and body weight fluctuations. PMID:28091559

Anosmia leads to a loss of gray matter in cortical brain areas.

PubMed

Bitter, Thomas; Gudziol, Hilmar; Burmeister, Hartmut Peter; Mentzel, Hans-Joachim; Guntinas-Lichius, Orlando; Gaser, Christian

2010-06-01

Chronic olfactory disorders, including the complete loss of the sense of smell (anosmia), are common. Using voxel-based morphometry (VBM) in magnetic resonance imaging (MRI), structural changes in the cerebral gray matter (GM) of a group of patients with anosmia compared with a normosmic, healthy control group were evaluated. Patients with anosmia presented a significant decrease of GM volume mainly in the nucleus accumbens with adjacent subcallosal gyrus, in the medial prefrontal cortex (MPC) including the middle and anterior cingulate cortices, and in the dorsolateral prefrontal cortex (dlPFC). These areas are part of the limbic loop of the basal ganglia and except the dlPFC secondary olfactory areas. They also play an important role in many neurological diseases. Furthermore, volume decreases in smaller areas like the piriform cortex, insular cortex, orbitofrontal cortex, hippocampus, parahippocampal gyrus, supramarginal gyrus, and cerebellum could be seen. Longer disease duration was associated with a stronger atrophy in the described areas. No local increases in the GM volume could be observed. A comparison with results of an additionally executed functional MRI study on olfaction in healthy subjects was performed to evaluate the significance of the observed atrophy areas in cerebral olfactory processing. To our knowledge, this is the first study on persisting structural changes in cortical GM volume after complete olfactory loss.

Subtle gray matter changes in temporo-parietal cortex associated with cardiovascular risk factors.

PubMed

de Toledo Ferraz Alves, Tânia Corrêa; Scazufca, Márcia; Squarzoni, Paula; de Souza Duran, Fábio Luiz; Tamashiro-Duran, Jaqueline Hatsuko; Vallada, Homero P; Andrei, Anna; Wajngarten, Mauricio; Menezes, Paulo R; Busatto, Geraldo F

2011-01-01

Vascular risk factors may play an important role in the pathophysiology of Alzheimer's disease (AD). While there is consistent evidence of gray matter (GM) abnormalities in earlier stages of AD, the presence of more subtle GM changes associated with vascular risk factors in the absence of clinically significant vascular events has been scarcely investigated. This study aimed to examine GM changes in elderly subjects with cardiovascular risk factors. We predicted that the presence of cardiovascular risk would be associated with GM abnormalities involving the temporal-parietal cortices and limbic structures. We recruited 248 dementia-free subjects, age range 66-75 years, from the population-based "São Paulo Ageing and Health Study", classified in accordance to their Framingham Coronary Heart Disease Risk (FCHDR) score to undergo an MRI scan. We performed an overall analysis of covariance, controlled to total GM and APOE4 status, to investigate the presence of regional GM abnormalities in association with FCHDR subgroups (high-risk, medium-risk, and low-risk), and followed by post hoc t-test. We also applied a co-relational design in order to investigate the presence of linear progression of the GM vulnerability in association with cardiovascular risk factor. Voxel-based morphometry showed that the presence of cardiovascular risk factors were associated with regional GM loss involving the temporal cortices bilaterally. Those results retained statistical significance after including APOE4 as a covariate of interest. We also observed that there was a negative correlation between FCHDR scores and rGM distribution in the parietal cortex. Subclinical cerebrovascular abnormalities involving GM loss may provide an important link between cardiovascular risk factors and AD.

Concurrent white and gray matter degeneration of disease-specific networks in early-stage Alzheimer's disease and behavioral variant frontotemporal dementia.

PubMed

Steketee, Rebecca M E; Meijboom, Rozanna; de Groot, Marius; Bron, Esther E; Niessen, Wiro J; van der Lugt, Aad; van Swieten, John C; Smits, Marion

2016-07-01

This study investigates regional coherence between white matter (WM) microstructure and gray matter (GM) volume and perfusion measures in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) using a correlational approach. WM-GM coherence, compared with controls, was stronger between cingulum WM and frontotemporal GM in AD, and temporoparietal GM in bvFTD. In addition, in AD compared with controls, coherence was stronger between inferior fronto-occipital fasciculus WM microstructure and occipital GM perfusion. In this first study assessing regional WM-GM coherence in AD and bvFTD, we show that WM microstructure and GM volume and perfusion measures are coherent, particularly in regions implicated in AD and bvFTD pathology. This indicates concurrent degeneration in disease-specific networks. Our methodology allows for the detection of incipient abnormalities that go undetected in conventional between-group analyses. Copyright © 2016 Elsevier Inc. All rights reserved.

Altered white matter and cortical structure in neonates with antenatally diagnosed isolated ventriculomegaly.

PubMed

Lockwood Estrin, G; Kyriakopoulou, V; Makropoulos, A; Ball, G; Kuhendran, L; Chew, A; Hagberg, B; Martinez-Biarge, M; Allsop, J; Fox, M; Counsell, S J; Rutherford, M A

2016-01-01

Ventriculomegaly (VM) is the most common central nervous system abnormality diagnosed antenatally, and is associated with developmental delay in childhood. We tested the hypothesis that antenatally diagnosed isolated VM represents a biological marker for altered white matter (WM) and cortical grey matter (GM) development in neonates. 25 controls and 21 neonates with antenatally diagnosed isolated VM had magnetic resonance imaging at 41.97(± 2.94) and 45.34(± 2.14) weeks respectively. T2-weighted scans were segmented for volumetric analyses of the lateral ventricles, WM and cortical GM. Diffusion tensor imaging (DTI) measures were assessed using voxel-wise methods in WM and cortical GM; comparisons were made between cohorts. Ventricular and cortical GM volumes were increased, and WM relative volume was reduced in the VM group. Regional decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were demonstrated in WM of the VM group compared to controls. No differences in cortical DTI metrics were observed. At 2 years, neurodevelopmental delays, especially in language, were observed in 6/12 cases in the VM cohort. WM alterations in isolated VM cases may be consistent with abnormal development of WM tracts involved in language and cognition. Alterations in WM FA and MD may represent neural correlates for later neurodevelopmental deficits.

A structural model of age, grey matter volumes, education, and personality traits.

PubMed

Kitamura, Soichiro; Yasuno, Fumihiko; Yamamoto, Akihide; Kazui, Hiroaki; Kudo, Takashi; Matsuoka, Kiwamu; Kiuchi, Kuniaki; Kosaka, Jun; Nagatsuka, Kazuyuki; Iida, Hidehiro; Kishimoto, Toshifumi

2016-01-01

When the relationship between ageing and changes in personality traits is considered, it is important to know how they are influenced by biological and environmental factors. The present study examined the relationships between various factors associated with the effect of ageing on personality traits, including structural changes of the brain and environmental factors such as education. We recruited 41 healthy subjects. We administered the NEO Five-Factor Inventory to assess personality factors. Magnetic resonance imaging was performed, and regional grey matter (GM) volumes were obtained. We identified associations in the correlation analysis of age, cerebral GM volume, years of education, and the personality trait of openness. Path analysis was used to estimate the relationships among these factors. The path analysis model of age, GM volume, years of education, and the personality trait of openness revealed that age has an indirect negative association with openness through GM volume and years of education. Ageing was related to a decrease in GM volume, which was in turn related to a decrease in the openness score. Older subjects generally had fewer years of education, which was related to a lower openness score. Maintaining openness against the effects of ageing is desirable, and our results imply that interventions against age-related cerebral atrophy and the promotion of opportunities for higher education may contribute to the development and stability of a healthy personality during the adult life course. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

Long-term effects of marijuana use on the brain

PubMed Central

Filbey, Francesca M.; Aslan, Sina; Calhoun, Vince D.; Spence, Jeffrey S.; Damaraju, Eswar; Caprihan, Arvind; Segall, Judith

2014-01-01

Questions surrounding the effects of chronic marijuana use on brain structure continue to increase. To date, however, findings remain inconclusive. In this comprehensive study that aimed to characterize brain alterations associated with chronic marijuana use, we measured gray matter (GM) volume via structural MRI across the whole brain by using voxel-based morphology, synchrony among abnormal GM regions during resting state via functional connectivity MRI, and white matter integrity (i.e., structural connectivity) between the abnormal GM regions via diffusion tensor imaging in 48 marijuana users and 62 age- and sex-matched nonusing controls. The results showed that compared with controls, marijuana users had significantly less bilateral orbitofrontal gyri volume, higher functional connectivity in the orbitofrontal cortex (OFC) network, and higher structural connectivity in tracts that innervate the OFC (forceps minor) as measured by fractional anisotropy (FA). Increased OFC functional connectivity in marijuana users was associated with earlier age of onset. Lastly, a quadratic trend was observed suggesting that the FA of the forceps minor tract initially increased following regular marijuana use but decreased with protracted regular use. This pattern may indicate differential effects of initial and chronic marijuana use that may reflect complex neuroadaptive processes in response to marijuana use. Despite the observed age of onset effects, longitudinal studies are needed to determine causality of these effects. PMID:25385625

Censoring distances based on labeled cortical distance maps in cortical morphometry.

PubMed

Ceyhan, Elvan; Nishino, Tomoyuki; Alexopolous, Dimitrios; Todd, Richard D; Botteron, Kelly N; Miller, Michael I; Ratnanather, J Tilak

2013-01-01

It has been demonstrated that shape differences in cortical structures may be manifested in neuropsychiatric disorders. Such morphometric differences can be measured by labeled cortical distance mapping (LCDM) which characterizes the morphometry of the laminar cortical mantle of cortical structures. LCDM data consist of signed/labeled distances of gray matter (GM) voxels with respect to GM/white matter (WM) surface. Volumes and other summary measures for each subject and the pooled distances can help determine the morphometric differences between diagnostic groups, however they do not reveal all the morphometric information contained in LCDM distances. To extract more information from LCDM data, censoring of the pooled distances is introduced for each diagnostic group where the range of LCDM distances is partitioned at a fixed increment size; and at each censoring step, the distances not exceeding the censoring distance are kept. Censored LCDM distances inherit the advantages of the pooled distances but also provide information about the location of morphometric differences which cannot be obtained from the pooled distances. However, at each step, the censored distances aggregate, which might confound the results. The influence of data aggregation is investigated with an extensive Monte Carlo simulation analysis and it is demonstrated that this influence is negligible. As an illustrative example, GM of ventral medial prefrontal cortices (VMPFCs) of subjects with major depressive disorder (MDD), subjects at high risk (HR) of MDD, and healthy control (Ctrl) subjects are used. A significant reduction in laminar thickness of the VMPFC in MDD and HR subjects is observed compared to Ctrl subjects. Moreover, the GM LCDM distances (i.e., locations with respect to the GM/WM surface) for which these differences start to occur are determined. The methodology is also applicable to LCDM-based morphometric measures of other cortical structures affected by disease.

From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study

PubMed Central

Aghakhanyan, Gayane; Bonanni, Paolo; Randazzo, Giovanna; Nappi, Sara; Tessarotto, Federica; De Martin, Lara; Frijia, Francesca; De Marchi, Daniele; De Masi, Francesco; Kuppers, Beate; Lombardo, Francesco; Caramella, Davide; Montanaro, Domenico

2016-01-01

Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS. PMID:27626634

Brain morphological changes in adolescent and adult patients with anorexia nervosa.

PubMed

Seitz, J; Herpertz-Dahlmann, B; Konrad, K

2016-08-01

Gray matter (GM) and white matter (WM) volume loss occur in the brains of patients with acute anorexia nervosa (AN) and improve again upon weight restoration. Adolescence is an important time period for AN to begin. However, little is known about the differences between brain changes in adolescents vs adults. We used a meta-analysis and a qualitative review of all MRI studies regarding acute structural brain volume changes and their recovery in adolescents and adults with AN. 29 studies with 473 acute, 121 short-term weight-recovered and 255 long-term recovered patients with AN were included in the meta-analysis. In acute AN, GM and WM were reduced compared to healthy controls. Acute adolescent patients showed a significantly greater GM reduction than adults (-8.4 vs -3.1 %), the difference in WM (-4.0 vs -2.1 %) did not reach significance. Short-term weight-recovered patients showed a remaining GM deficit of 3.6 % and a non-significant WM reduction of 0.9 % with no age differences. Following 1.5-8 years of remission, GM and WM were no longer significantly reduced in adults (GM -0.4 %, WM -0.7 %); long-term studies for adolescents were scarce. The qualitative review showed that GM volume loss was correlated with cognitive deficits and three studies found GM regions, cerebellar deficits and WM to be predictive of outcome. GM and WM are strongly reduced in acute AN and even more pronounced in adolescence. Long-term recovery appears to be complete for adults while no conclusions can be drawn for adolescents, thus caution remains.

Grey-matter network disintegration as predictor of cognitive and motor function with aging.

PubMed

Koini, Marisa; Duering, Marco; Gesierich, Benno G; Rombouts, Serge A R B; Ropele, Stefan; Wagner, Fabian; Enzinger, Christian; Schmidt, Reinhold

2018-06-01

Loss of grey-matter volume with advancing age affects the entire cortex. It has been suggested that atrophy occurs in a network-dependent manner with advancing age rather than in independent brain areas. The relationship between networks of structural covariance (SCN) disintegration and cognitive functioning during normal aging is not fully explored. We, therefore, aimed to (1) identify networks that lose GM integrity with advancing age, (2) investigate if age-related impairment of integrity in GM networks associates with cognitive function and decreasing fine motor skills (FMS), and (3) examine if GM disintegration is a mediator between age and cognition and FMS. T1-weighted scans of n = 257 participants (age range: 20-87) were used to identify GM networks using independent component analysis. Random forest analysis was implemented to examine the importance of network integrity as predictors of memory, executive functions, and FMS. The associations between GM disintegration, age and cognitive performance, and FMS were assessed using mediation analyses. Advancing age was associated with decreasing cognitive performance and FMS. Fourteen of 20 GM networks showed integrity changes with advancing age. Next to age and education, eight networks (fronto-parietal, fronto-occipital, temporal, limbic, secondary somatosensory, cuneal, sensorimotor network, and a cerebellar network) showed an association with cognition and FMS (up to 15.08%). GM networks partially mediated the effect between age and cognition and age and FMS. We confirm an age-related decline in cognitive functioning and FMS in non-demented community-dwelling subjects and showed that aging selectively affects the integrity of GM networks. The negative effect of age on cognition and FMS is associated with distinct GM networks and is partly mediated by their disintegration.

Comparison of the brain development trajectory between Chinese and U.S. children and adolescents

PubMed Central

Xie, Wanze; Richards, John E.; Lei, Du; Lee, Kang; Gong, Qiyong

2015-01-01

This current study investigated brain development of Chinese and American children and adolescents from 8 to 16 years of age using structural magnetic resonance imaging (MRI) techniques. Analyses comparing Chinese and U.S. children brain/head MR images were performed to explore similarities and differences in the trajectory of brain development between these two groups. Our results revealed regional and age differences in both brain/head morphological and tissue level development between Chinese and U.S. children. Chinese children's brains and heads were shorter, wider, and taller than those of U.S. children. There were significant differences in the gray matter (GM) and white matter (WM) intensity between the two nationalities. Development trajectories for cerebral volume, GM, and several key brain structures were also distinct between these two populations. PMID:25698941

Whole brain volume changes and its correlation with clinical symptom severity in patients with schizophrenia: A DARTEL-based VBM study.

PubMed

Kim, Gwang-Won; Kim, Yun-Hyeon; Jeong, Gwang-Woo

2017-01-01

The purpose of this study was to evaluate gray matter (GM) and white matter (WM) volume alterations in whole-brain structures in patients with schizophrenia and healthy controls using voxel-based morphometry (VBM), and further to assess the correlation between GM and WM volume variations and symptom severity in schizophrenia. A total of 22 patients with schizophrenia and 22 age-matched healthy controls participated. Magnetic resonance image data were processed using SPM8 software with diffeomorphic anatomical registration via an exponentiated Lie algebra (DARTEL) algorithm. Patients with schizophrenia exhibited significantly decreased GM volumes of the insula, superior temporal gyrus (STG), gyrus rectus, and anterior cingulate cortex (ACC) compared with healthy controls. The GM volumes of the STG and gyrus rectus were negatively correlated with the positive scales on the Positive and Negative Syndrome Scale (PANSS) and those of the STG and ACC were negatively correlated with the negative scales. The durations of illness in schizophrenia were negatively correlated with the GM volumes of the insula, STG, and ACC. Patients with schizophrenia exhibited significantly decreased WM volumes of the superior frontal gyrus, inferior temporal gyrus, and STG. The WM volumes of the STG were negatively correlated with the duration of illness. Our findings suggest that GM and WM volume abnormalities in the STG are associated with the psychopathology of schizophrenia.

Cerebellar gray matter and lobular volumes correlate with core autism symptoms

PubMed Central

D'Mello, Anila M.; Crocetti, Deana; Mostofsky, Stewart H.; Stoodley, Catherine J.

2015-01-01

Neuroanatomical differences in the cerebellum are among the most consistent findings in autism spectrum disorder (ASD), but little is known about the relationship between cerebellar dysfunction and core ASD symptoms. The newly-emerging existence of cerebellar sensorimotor and cognitive subregions provides a new framework for interpreting the functional significance of cerebellar findings in ASD. Here we use two complementary analyses — whole-brain voxel-based morphometry (VBM) and the SUIT cerebellar atlas — to investigate cerebellar regional gray matter (GM) and volumetric lobular measurements in 35 children with ASD and 35 typically-developing (TD) children (mean age 10.4 ± 1.6 years; range 8–13 years). To examine the relationships between cerebellar structure and core ASD symptoms, correlations were calculated between scores on the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview (ADI) and the VBM and volumetric data. Both VBM and the SUIT analyses revealed reduced GM in ASD children in cerebellar lobule VII (Crus I/II). The degree of regional and lobular gray matter reductions in different cerebellar subregions correlated with the severity of symptoms in social interaction, communication, and repetitive behaviors. Structural differences and behavioral correlations converged on right cerebellar Crus I/II, a region which shows structural and functional connectivity with fronto-parietal and default mode networks. These results emphasize the importance of the location within the cerebellum to the potential functional impact of structural differences in ASD, and suggest that GM differences in cerebellar right Crus I/II are associated with the core ASD profile. PMID:25844317

Brain Volumetric Correlates of Autism Spectrum Disorder Symptoms in Attention Deficit/Hyperactivity Disorder

PubMed Central

O’Dwyer, Laurence; Tanner, Colby; van Dongen, Eelco V.; Greven, Corina U.; Bralten, Janita; Zwiers, Marcel P.; Franke, Barbara; Oosterlaan, Jaap; Heslenfeld, Dirk; Hoekstra, Pieter; Hartman, Catharina A.; Rommelse, Nanda; Buitelaar, Jan K.

2014-01-01

Autism spectrum disorder (ASD) symptoms frequently occur in subjects with attention deficit/hyperactivity disorder (ADHD). While there is evidence that both ADHD and ASD have differential structural correlates, no study to date has investigated these structural correlates within a framework that robustly accounts for the phenotypic overlap between the two disorders. The presence of ASD symptoms was measured by the parent-reported Children’s Social and Behavioural Questionnaire (CSBQ) in ADHD subjects (n = 180), their unaffected siblings (n = 118) and healthy controls (n = 146). ADHD symptoms were assessed by a structured interview (K-SADS-PL) and the Conners’ ADHD questionnaires. Whole brain T1-weighted MPRAGE images were acquired and the structural MRI correlates of ASD symptom scores were analysed by modelling ASD symptom scores against white matter (WM) and grey matter (GM) volumes using mixed effects models which controlled for ADHD symptom levels. ASD symptoms were significantly elevated in ADHD subjects relative to both controls and unaffected siblings. ASD scores were predicted by the interaction between WM and GM volumes. Increasing ASD score was associated with greater GM volume. Equivocal results from previous structural studies in ADHD and ASD may be due to the fact that comorbidity has not been taken into account in studies to date. The current findings stress the need to account for issues of ASD comorbidity in ADHD. PMID:24979066

Orbitofrontal Gray Matter Relates to Early Morning Awakening: A Neural Correlate of Insomnia Complaints?

PubMed Central

Stoffers, Diederick; Moens, Sarah; Benjamins, Jeroen; van Tol, Marie-José; Penninx, Brenda W. J. H.; Veltman, Dick J.; Van der Wee, Nic J. A.; Van Someren, Eus J. W.

2012-01-01

Sleep complaints increase profoundly with age; prevalence estimates of insomnia in the elderly reach up to 37%. The three major types of nocturnal complaints are difficulties initiating (DIS) and maintaining (DMS) sleep and early morning awakening (EMA), of which the latter appears most characteristic for aging. The neural correlates associated with these complaints have hardly been investigated, hampering the development of rational treatment and prevention. A recent study on structural brain correlates of insomnia showed that overall severity, but not duration, of insomnia complaints is associated with lower gray matter (GM) density in part of the left orbitofrontal cortex (OFC). Following up on this, we investigated, in an independent sample of people not diagnosed with insomnia, whether individual differences in GM density are associated with differences in DIS, DMS, and EMA. Sixty five healthy participants (mean age = 41 years, range 18–56) filled out questionnaires and underwent structural magnetic resonance imaging. Three compound Z-scores were computed for questionnaire items relating to DIS, DMS, and EMA. Whole-brain voxel-based morphometry was used to investigate their association with GM density. Results show that participants with lower GM density in a region where the left inferior OFC borders the insula report more EMA, but not DIS or DMS. This is the first study to investigate structural brain correlates of specific sleep characteristics that can translate into complaints in insomniacs. The selective association of EMA with orbitofrontal GM density makes our findings particularly relevant to elderly people, where EMA represents the most characteristic complaint. It is hypothesized that low GM density in aforementioned orbitofrontal area affects its role in sensing comfort. An intact ability to evaluate comfort may be crucial to maintain sleep, especially at the end of the night when sleep is vulnerable because homeostatic sleep propensity has dissipated. PMID:23060850

Sex Differences in Parietal Lobe Morphology: Relationship to Mental Rotation Performance

ERIC Educational Resources Information Center

Koscik, Tim; O'Leary, Dan; Moser, David J.; Andreasen, Nancy C.; Nopoulos, Peg

2009-01-01

Structural magnetic resonance imaging (MRI) studies of the human brain have reported evidence for sexual dimorphism. In addition to sex differences in overall cerebral volume, differences in the proportion of gray matter (GM) to white matter (WM) volume have been observed, particularly in the parietal lobe. To our knowledge there have been no…

Gray matter alteration in isolated congenital anosmia patient: a voxel-based morphometry study.

PubMed

Yao, Linyin; Yi, Xiaoli; Wei, Yongxiang

2013-09-01

Decreased volume of gray matter (GM) was observed in olfactory loss in patients with neurodegenerative disorder. However, GM volume has not yet been investigated in isolated congenital anosmia (ICA) people. We herewith investigated the volume change of gray matter of an ICA boy by morphometric analysis of magnetic resonance images (voxel-based morphometry), and compared with that of 20 age-matched healthy controls. ICA boy presented a significant decrease in GM volume in the orbitofrontal cortex, anterior cingulate cortex, middle cingulate cortex, thalamus, insular cortex, cerebellum, precuneus, gyrus rectus, subcallosal gyrus, middle temporal gyrus, fusiform gyrus and piriform cortex. No significant GM volume increase was detected in other brain areas. The pattern of GM atrophy was similar as previous literature reported. Our results identified similar GM volume alterations regardless of the causes of olfactory impairment. Decreased GM volume was not only shown in olfactory bulbs, olfactory tracts and olfactory sulcus, also in primary olfactory cortex and the secondary cerebral olfactory areas in ICA people. This is the first study to evaluate GM volume alterations in ICA people.

Structural neuroplasticity in expert pianists depends on the age of musical training onset.

PubMed

Vaquero, Lucía; Hartmann, Karl; Ripollés, Pablo; Rojo, Nuria; Sierpowska, Joanna; François, Clément; Càmara, Estela; van Vugt, Floris Tijmen; Mohammadi, Bahram; Samii, Amir; Münte, Thomas F; Rodríguez-Fornells, Antoni; Altenmüller, Eckart

2016-02-01

In the last decade, several studies have investigated the neuroplastic changes induced by long-term musical training. Here we investigated structural brain differences in expert pianists compared to non-musician controls, as well as the effect of the age of onset (AoO) of piano playing. Differences with non-musicians and the effect of sensitive periods in musicians have been studied previously, but importantly, this is the first time in which the age of onset of music-training was assessed in a group of musicians playing the same instrument, while controlling for the amount of practice. We recruited a homogeneous group of expert pianists who differed in their AoO but not in their lifetime or present amount of training, and compared them to an age-matched group of non-musicians. A subset of the pianists also completed a scale-playing task in order to control for performance skill level differences. Voxel-based morphometry analysis was used to examine gray-matter differences at the whole-brain level. Pianists showed greater gray matter (GM) volume in bilateral putamen (extending also to hippocampus and amygdala), right thalamus, bilateral lingual gyri and left superior temporal gyrus, but a GM volume shrinkage in the right supramarginal, right superior temporal and right postcentral gyri, when compared to non-musician controls. These results reveal a complex pattern of plastic effects due to sustained musical training: a network involved in reinforcement learning showed increased GM volume, while areas related to sensorimotor control, auditory processing and score-reading presented a reduction in the volume of GM. Behaviorally, early-onset pianists showed higher temporal precision in their piano performance than late-onset pianists, especially in the left hand. Furthermore, early onset of piano playing was associated with smaller GM volume in the right putamen and better piano performance (mainly in the left hand). Our results, therefore, reveal for the first time in a single large dataset of healthy pianists the link between onset of musical practice, behavioral performance, and putaminal gray matter structure. In summary, skill-related plastic adaptations may include decreases and increases in GM volume, dependent on an optimization of the system caused by an early start of musical training. We believe our findings enrich the plasticity discourse and shed light on the neural basis of expert skill acquisition. Copyright © 2015 Elsevier Inc. All rights reserved.

Gray Matter Atrophy in the Cerebellum-Evidence of Increased Vulnerability of the Crus and Vermis with Advancing Age.

PubMed

Yu, Teresa; Korgaonkar, Mayuresh S; Grieve, Stuart M

2017-04-01

This study examined patterns of cerebellar volumetric gray matter (GM) loss across the adult lifespan in a large cross-sectional sample. Four hundred and seventy-nine healthy participants (age range: 7-86 years) were drawn from the Brain Resource International Database who provided T1-weighted MRI scans. The spatially unbiased infratentorial template (SUIT) toolbox in SPM8 was used for normalisation of the cerebellum structures. Global volumetric and voxel-based morphometry analyses were performed to evaluate age-associated trends and gender-specific age-patterns. Global cerebellar GM shows a cross-sectional reduction with advancing age of 2.5 % per decade-approximately half the rate seen in the whole brain. The male cerebellum is larger with a lower percentage of GM, however, after controlling for total brain volume, no gender difference was detected. Analysis of age-related changes in GM volume revealed large bilateral clusters involving the vermis and cerebellar crus where regional loss occurred at nearly twice the average cerebellar rate. No gender-specific patterns were detected. These data confirm that regionally specific GM loss occurs in the cerebellum with age, and form a solid base for further investigation to find functional correlates for this global and focal loss.

Structural brain abnormalities in adolescent anorexia nervosa before and after weight recovery and associated hormonal changes.

PubMed

Mainz, Verena; Schulte-Rüther, Martin; Fink, Gereon R; Herpertz-Dahlmann, Beate; Konrad, Kerstin

2012-01-01

The neurobiological mechanisms of structural brain abnormalities in patients with anorexia nervosa (AN) remain poorly understood. In particular, little is known about the changes in and the recovery of gray matter (GM) volumes after weight gain and the relation to hormonal normalization in adolescent patients with AN. Nineteen female patients aged 12 to 17 years were assessed using magnetic resonance imaging at the time of admission to the hospital (T1) and after weight recovery (T2). Patients were compared with typically developing girls matched for age and intelligence quotient. Structural brain images were analyzed using a voxel-based morphometric approach. Circulating levels of cortisol and gonadotropins were assessed in blood samples. Compared with controls, patients with AN showed reduced GM in several brain regions along the cortical midline, reaching from the occipital cortex to the medial frontal areas. These GM reductions were mostly reversible at T1. Patients showed a GM increase from T1 to T2 along the cortical midline and in the occipital, temporal, parietal, and frontal lobes. GM increases at T2 correlated inversely with cortisol levels at T1 and positively with weight gain at T2. The strongest associations between regional GM increase and weight gain were found in the cerebellum. In addition, increases in GM volumes at T2 in the thalamus, hippocampus, and amygdala were associated with increases in follicle-stimulating hormone. Our data suggest that brain alterations in adolescents with acute AN are mostly reversible at T1 and that GM recovery in specific brain regions is associated with weight and hormonal normalization.

Identification of Amnestic Mild Cognitive Impairment Using Multi-Modal Brain Features: A Combined Structural MRI and Diffusion Tensor Imaging Study.

PubMed

Xie, Yunyan; Cui, Zaixu; Zhang, Zhongmin; Sun, Yu; Sheng, Can; Li, Kuncheng; Gong, Gaolang; Han, Ying; Jia, Jianping

2015-01-01

Identifying amnestic mild cognitive impairment (aMCI) is of great clinical importance because aMCI is a putative prodromal stage of Alzheimer's disease. The present study aimed to explore the feasibility of accurately identifying aMCI with a magnetic resonance imaging (MRI) biomarker. We integrated measures of both gray matter (GM) abnormalities derived from structural MRI and white matter (WM) alterations acquired from diffusion tensor imaging at the voxel level across the entire brain. In particular, multi-modal brain features, including GM volume, WM fractional anisotropy, and mean diffusivity, were extracted from a relatively large sample of 64 Han Chinese aMCI patients and 64 matched controls. Then, support vector machine classifiers for GM volume, FA, and MD were fused to distinguish the aMCI patients from the controls. The fused classifier was evaluated with the leave-one-out and the 10-fold cross-validations, and the classifier had an accuracy of 83.59% and an area under the curve of 0.862. The most discriminative regions of GM were mainly located in the medial temporal lobe, temporal lobe, precuneus, cingulate gyrus, parietal lobe, and frontal lobe, whereas the most discriminative regions of WM were mainly located in the corpus callosum, cingulum, corona radiata, frontal lobe, and parietal lobe. Our findings suggest that aMCI is characterized by a distributed pattern of GM abnormalities and WM alterations that represent discriminative power and reflect relevant pathological changes in the brain, and these changes further highlight the advantage of multi-modal feature integration for identifying aMCI.

Gray Matter Increase in Motor Cortex in Pediatric ADHD: A Voxel-Based Morphometry Study.

PubMed

Sutcubasi Kaya, Bernis; Metin, Baris; Tas, Zeynep Cubukcuoglu; Buyukaslan, Ayse; Soysal, Aysegul; Hatiloglu, Deniz; Tarhan, Nevzat

2018-05-01

Several studies report that ADHD is associated with reduced gray matter (GM), whereas others report no differences in GM volume between ADHD patients and controls, and some even report more GM volume in individuals with ADHD. These conflicting findings suggest that reduced GM is not a universal finding in ADHD, and that more research is needed to delineate with greater accuracy the range of GM alterations. The present study aimed to identify GM alterations in ADHD using pediatric templates. 19 drug-naïve ADHD patients and 18 controls, all aged 7 to 14 years, were scanned using magnetic resonance imaging. Relative to the controls, the ADHD patients had more GM, predominantly in the precentral and supplementary motor areas. Moreover, there were positive correlations between GM volume in these areas and ADHD scale scores. The clinical and pathophysiological significance of increased GM in the motor areas remains to be elucidated by additional research.

Regional brain volumetry and brain function in severely brain-injured patients.

PubMed

Annen, Jitka; Frasso, Gianluca; Crone, Julia Sophia; Heine, Lizette; Di Perri, Carol; Martial, Charlotte; Cassol, Helena; Demertzi, Athena; Naccache, Lionel; Laureys, Steven

2018-04-01

The relationship between residual brain tissue in patients with disorders of consciousness (DOC) and the clinical condition is unclear. This observational study aimed to quantify gray (GM) and white matter (WM) atrophy in states of (altered) consciousness. Structural T1-weighted magnetic resonance images were processed for 102 severely brain-injured and 52 healthy subjects. Regional brain volume was quantified for 158 (sub)cortical regions using Freesurfer. The relationship between regional brain volume and clinical characteristics of patients with DOC and conscious brain-injured patients was assessed using a linear mixed-effects model. Classification of patients with unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) using regional volumetric information was performed and compared to classification using cerebral glucose uptake from fluorodeoxyglucose positron emission tomography. For validation, the T1-based classifier was tested on independent datasets. Patients were characterized by smaller regional brain volumes than healthy subjects. Atrophy occurred faster in UWS compared to MCS (GM) and conscious (GM and WM) patients. Classification was successful (misclassification with leave-one-out cross-validation between 2% and 13%) and generalized to the independent data set with an area under the receiver operator curve of 79% (95% confidence interval [CI; 67-91.5]) for GM and 70% (95% CI [55.6-85.4]) for WM. Brain volumetry at the single-subject level reveals that regions in the default mode network and subcortical gray matter regions, as well as white matter regions involved in long range connectivity, are most important to distinguish levels of consciousness. Our findings suggest that changes of brain structure provide information in addition to the assessment of functional neuroimaging and thus should be evaluated as well. Ann Neurol 2018;83:842-853. © 2018 American Neurological Association.

Brain volumes in healthy adults aged 40 years and over: a voxel-based morphometry study.

PubMed

Riello, Roberta; Sabattoli, Francesca; Beltramello, Alberto; Bonetti, Matteo; Bono, Giorgio; Falini, Andrea; Magnani, Giuseppe; Minonzio, Giorgio; Piovan, Enrico; Alaimo, Giuseppina; Ettori, Monica; Galluzzi, Samantha; Locatelli, Enrico; Noiszewska, Malgorzata; Testa, Cristina; Frisoni, Giovanni B

2005-08-01

Gender and age effect on brain morphology have been extensively investigated. However, the great variety in methods applied to morphology partly explain the conflicting results of linear patterns of tissue changes and lateral asymmetry in men and women. The aim of the present study was to assess the effect of age, gender and laterality on the volumes of gray matter (GM) and white matter (WM) in a large group of healthy adults by means of voxel-based morphometry. This technique, based on observer-independent algorithms, automatically segments the 3 types of tissue and computes the amount of tissue in each single voxel. Subjects were 229 healthy subjects of 40 years of age or older, who underwent magnetic resonance (MR) for reasons other than cognitive impairment. MR images were reoriented following the AC-PC line and, after removing the voxels below the cerebellum, were processed by Statistical Parametric Mapping (SPM99). GM and WM volumes were normalized for intracranial volume. Women had more fractional GM and WM volumes than men. Age was negatively correlated with both fractional GM and WM, and a gender x age interaction effect was found for WM, men having greater WM loss with advancing age. Pairwise differences between left and right GM were negative (greater GM in right hemisphere) in men, and positive (greater GM in left hemisphere) in women (-0.56+/-4.2 vs 0.99+/-4.8; p=0.019). These results support side-specific accelerated WM loss in men, and may help our better understanding of changes in regional brain structures associated with pathological aging.

Playing Super Mario induces structural brain plasticity: gray matter changes resulting from training with a commercial video game.

PubMed

Kühn, S; Gleich, T; Lorenz, R C; Lindenberger, U; Gallinat, J

2014-02-01

Video gaming is a highly pervasive activity, providing a multitude of complex cognitive and motor demands. Gaming can be seen as an intense training of several skills. Associated cerebral structural plasticity induced has not been investigated so far. Comparing a control with a video gaming training group that was trained for 2 months for at least 30 min per day with a platformer game, we found significant gray matter (GM) increase in right hippocampal formation (HC), right dorsolateral prefrontal cortex (DLPFC) and bilateral cerebellum in the training group. The HC increase correlated with changes from egocentric to allocentric navigation strategy. GM increases in HC and DLPFC correlated with participants' desire for video gaming, evidence suggesting a predictive role of desire in volume change. Video game training augments GM in brain areas crucial for spatial navigation, strategic planning, working memory and motor performance going along with evidence for behavioral changes of navigation strategy. The presented video game training could therefore be used to counteract known risk factors for mental disease such as smaller hippocampus and prefrontal cortex volume in, for example, post-traumatic stress disorder, schizophrenia and neurodegenerative disease.

Altered structural covariance of the striatum in functional dyspepsia patients.

PubMed

Liu, P; Zeng, F; Yang, F; Wang, J; Liu, X; Wang, Q; Zhou, G; Zhang, D; Zhu, M; Zhao, R; Wang, A; Gong, Q; Liang, F

2014-08-01

Functional dyspepsia (FD) is thought to be involved in dysregulation within the brain-gut axis. Recently, altered striatum activation has been reported in patients with FD. However, the gray matter (GM) volumes in the striatum and structural covariance patterns of this area are rarely explored. The purpose of this study was to examine the GM volumes and structural covariance patterns of the striatum between FD patients and healthy controls (HCs). T1-weighted magnetic resonance images were obtained from 44 FD patients and 39 HCs. Voxel-based morphometry (VBM) analysis was adopted to examine the GM volumes in the two groups. The caudate- or putamen-related regions identified from VBM analysis were then used as seeds to map the whole brain voxel-wise structural covariance patterns. Finally, a correlation analysis was used to investigate the effects of FD symptoms on the striatum. The results showed increased GM volumes in the bilateral putamen and right caudate. Compared with the structural covariance patterns of the HCs, the FD-related differences were mainly located in the amygdala, hippocampus/parahippocampus (HIPP/paraHIPP), thalamus, lingual gyrus, and cerebellum. And significant positive correlations were found between the volumes in the striatum and the FD duration in the patients. These findings provided preliminary evidence for GM changes in the striatum and different structural covariance patterns in patients with FD. The current results might expand our understanding of the pathophysiology of FD. © 2014 John Wiley & Sons Ltd.

Prenatal cocaine effects on brain structure in early infancy.

PubMed

Grewen, Karen; Burchinal, Margaret; Vachet, Clement; Gouttard, Sylvain; Gilmore, John H; Lin, Weili; Johns, Josephine; Elam, Mala; Gerig, Guido

2014-11-01

Prenatal cocaine exposure (PCE) is related to subtle deficits in cognitive and behavioral function in infancy, childhood and adolescence. Very little is known about the effects of in utero PCE on early brain development that may contribute to these impairments. The purpose of this study was to examine brain structural differences in infants with and without PCE. We conducted MRI scans of newborns (mean age = 5 weeks) to determine cocaine's impact on early brain structural development. Subjects were three groups of infants: 33 with PCE co-morbid with other drugs, 46 drug-free controls and 40 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without cocaine. Infants with PCE exhibited lesser total gray matter (GM) volume and greater total cerebral spinal fluid (CSF) volume compared with controls and infants with non-cocaine drug exposure. Analysis of regional volumes revealed that whole brain GM differences were driven primarily by lesser GM in prefrontal and frontal brain regions in infants with PCE, while more posterior regions (parietal, occipital) did not differ across groups. Greater CSF volumes in PCE infants were present in prefrontal, frontal and parietal but not occipital regions. Greatest differences (GM reduction, CSF enlargement) in PCE infants were observed in dorsal prefrontal cortex. Results suggest that PCE is associated with structural deficits in neonatal cortical gray matter, specifically in prefrontal and frontal regions involved in executive function and inhibitory control. Longitudinal study is required to determine whether these early differences persist and contribute to deficits in cognitive functions and enhanced risk for drug abuse seen at school age and in later life. Copyright © 2014 Elsevier Inc. All rights reserved.

Lifelong Bilingualism Contributes to Cognitive Reserve against White Matter Integrity Declines in Aging

PubMed Central

Gold, Brian T.; Johnson, Nathan F.; Powell, David K.

2013-01-01

Recent evidence suggests that lifelong bilingualism may contribute to cognitive reserve (CR) in normal aging. However, there is currently no neuroimaging evidence to suggest that lifelong bilinguals can retain normal cognitive functioning in the face of age-related neurodegeneration. Here we explored this issue by comparing white matter (WM) integrity and gray matter (GM) volumetric patterns of older adult lifelong bilinguals (N = 20) and monolinguals (N = 20). The groups were matched on a range of relevant cognitive test scores and on the established CR variables of education, socioeconomic status and intelligence. Participants underwent high-resolution structural imaging for assessment of GM volume and diffusion tensor imaging (DTI) for assessment of WM integrity. Results indicated significantly lower microstructural integrity in the bilingual group in several WM tracts. In particular, compared to their monolingual peers, the bilingual group showed lower fractional anisotropy and/or higher radial diffusivity in the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus bilaterally, the fornix, and multiple portions of the corpus callosum. There were no group differences in GM volume. Our results suggest that lifelong bilingualism contributes to CR against WM integrity declines in aging. PMID:24103400

A Voxel Based Morphometry Study of Brain Gray Matter Volumes in Juvenile Obsessive Compulsive Disorder.

PubMed

Jayarajan, Rajan Nishanth; Agarwal, Sri Mahavir; Viswanath, Biju; Kalmady, Sunil V; Venkatasubramanian, Ganesan; Srinath, Shoba; Chandrashekar, C R; Janardhan Reddy, Y C

2015-01-01

Adult patients with Obsessive Compulsive Disorder (OCD) have been shown to have gray matter (GM) volume differences from healthy controls in multiple regions - the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), medial frontal gyri (MFG), striatum, thalamus, and superior parietal lobule. However, there is paucity of data with regard to juvenile OCD. Hence, we examined GM volume differences between juvenile OCD patients and matched healthy controls using voxel based morphometry (VBM) with the above apriori regions of interest. Fifteen right handed juvenile patients with OCD and age- sex- handedness- matched healthy controls were recruited after administering the Mini International Neuropsychiatric Interview-KID and the Children's Yale-Brown Obsessive Compulsive Scale, and scanned using a 3 Tesla magnetic resonance imaging scanner. VBM methodology was followed. In comparison with healthy controls, patients had significantly smaller GM volumes in left ACC. YBOCS total score (current) showed significant negative correlation with GM volumes in bilateral OFC, and left superior parietal lobule. These findings while reiterating the important role of the orbito-fronto-striatal circuitry, also implicate in the parietal lobe - especially the superior parietal lobule as an important structure involved in the pathogenesis of OCD.

The neural correlates of apathy in schizophrenia: An exploratory investigation.

PubMed

Caravaggio, Fernando; Fervaha, Gagan; Menon, Mahesh; Remington, Gary; Graff-Guerrero, Ariel; Gerretsen, Philip

2017-10-25

Motivational deficits represent a core negative symptom in patients with schizophrenia. Previous morphology studies have demonstrated that apathy in patients with schizophrenia is associated with reduced frontal grey matter (GM). We attempted to replicate this previous finding, and explored whether it was distinct from potential associations with a distinct subdomain of negative symptoms, namely Affective Flattening, and GM. Twenty medicated patients with schizophrenia provided structural T1-weighted images acquired on a 3-Tesla MRI scanner and negative symptoms were evaluated using the Scale for the Assessment of Negative Symptoms. Voxel-based morphometry (VBM) was used to explore the correlations between whole-brain GM and i) Apathy, and ii) Affective Flattening, respectively. Apathy scores were negatively correlated with several GM clusters in frontal regions, including the frontal inferior operculum and the left dorsal anterior cingulate cortex. Only positive correlations with GM clusters were observed for Affective Flattening, particularly in the inferior temporal lobe. Notably, the regions associated with apathy scores were distinct from those associated with Affective Flattening, and these findings remained after controlling for antipsychotic medication dosage. We replicated previous associations between reduced frontal GM and apathy in patients with schizophrenia. Moreover, we demonstrated that these GM associations are distinct from those with Affective Flattening. The present findings set the stage for future larger-scale studies confirming the structural and neurochemical substrates of apathy in schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gray Matter-White Matter De-Differentiation on Brain Computed Tomography Predicts Brain Death Occurrence.

PubMed

Vigneron, C; Labeye, V; Cour, M; Hannoun, S; Grember, A; Rampon, F; Cotton, F

2016-01-01

Previous studies have shown that a loss of distinction between gray matter (GM) and white matter (WM) on unenhanced CT scans was predictive of poor outcome after cardiac arrest. The aim of this study was to identify a marker/predictor of imminent brain death. In this retrospective study, 15 brain-dead patients after anoxia and cardiac arrest were included. Patients were paired (1:1) with normal control subjects. Only patients' unenhanced CT scans performed before brain death and during the 24 hours after initial signs were analyzed. WM and GM densities were measured in predefined regions of interest (basal ganglia level, centrum semi-ovale level, high convexity level, brainstem level). At each level, GM and WM density and GM/WM ratio for brain-dead patients and normal control subjects were compared using the Wilcoxon signed-rank test. At each level, a lower GM/WM ratio and decreased GM and WM densities were observed in brain-dead patients' CT scans when compared with normal control subject CT scans. A cut-off value of 1.21 at the basal ganglia level was identified, below which brain death systematically occurred. GM/WM dedifferentiation on unenhanced CT scan is measurable before the occurrence of brain death, highlighting its importance in brain death prediction. The mechanism of GM/WM differentiation loss could be explained by the lack of oxygen caused by ischemia initially affecting the mitochondrial system. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantifying cerebellum grey matter and white matter perfusion using pulsed arterial spin labeling.

PubMed

Li, Xiufeng; Sarkar, Subhendra N; Purdy, David E; Briggs, Richard W

2014-01-01

To facilitate quantification of cerebellum cerebral blood flow (CBF), studies were performed to systematically optimize arterial spin labeling (ASL) parameters for measuring cerebellum perfusion, segment cerebellum to obtain separate CBF values for grey matter (GM) and white matter (WM), and compare FAIR ASST to PICORE. Cerebellum GM and WM CBF were measured with optimized ASL parameters using FAIR ASST and PICORE in five subjects. Influence of volume averaging in voxels on cerebellar grey and white matter boundaries was minimized by high-probability threshold masks. Cerebellar CBF values determined by FAIR ASST were 43.8 ± 5.1 mL/100 g/min for GM and 27.6 ± 4.5 mL/100 g/min for WM. Quantitative perfusion studies indicated that CBF in cerebellum GM is 1.6 times greater than that in cerebellum WM. Compared to PICORE, FAIR ASST produced similar CBF estimations but less subtraction error and lower temporal, spatial, and intersubject variability. These are important advantages for detecting group and/or condition differences in CBF values.

The thalamus and multiple sclerosis

PubMed Central

Minagar, Alireza; Barnett, Michael H.; Benedict, Ralph H.B.; Pelletier, Daniel; Pirko, Istvan; Sahraian, Mohamad Ali; Frohman, Elliott

2013-01-01

The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process. PMID:23296131

The thalamus and multiple sclerosis: modern views on pathologic, imaging, and clinical aspects.

PubMed

Minagar, Alireza; Barnett, Michael H; Benedict, Ralph H B; Pelletier, Daniel; Pirko, Istvan; Sahraian, Mohamad Ali; Frohman, Elliott; Zivadinov, Robert

2013-01-08

The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process.

Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain.

PubMed

Hoekzema, Elseline; Schagen, Sebastian E E; Kreukels, Baudewijntje P C; Veltman, Dick J; Cohen-Kettenis, Peggy T; Delemarre-van de Waal, Henriette; Bakker, Julie

2015-05-01

The sexual differentiation of the brain is primarily driven by gonadal hormones during fetal development. Leading theories on the etiology of gender dysphoria (GD) involve deviations herein. To examine whether there are signs of a sex-atypical brain development in GD, we quantified regional neural gray matter (GM) volumes in 55 female-to-male and 38 male-to-female adolescents, 44 boys and 52 girls without GD and applied both univariate and multivariate analyses. In girls, more GM volume was observed in the left superior medial frontal cortex, while boys had more volume in the bilateral superior posterior hemispheres of the cerebellum and the hypothalamus. Regarding the GD groups, at whole-brain level they differed only from individuals sharing their gender identity but not from their natal sex. Accordingly, using multivariate pattern recognition analyses, the GD groups could more accurately be automatically discriminated from individuals sharing their gender identity than those sharing their natal sex based on spatially distributed GM patterns. However, region of interest analyses indicated less GM volume in the right cerebellum and more volume in the medial frontal cortex in female-to-males in comparison to girls without GD, while male-to-females had less volume in the bilateral cerebellum and hypothalamus than natal boys. Deviations from the natal sex within sexually dimorphic structures were also observed in the untreated subsamples. Our findings thus indicate that GM distribution and regional volumes in GD adolescents are largely in accordance with their respective natal sex. However, there are subtle deviations from the natal sex in sexually dimorphic structures, which can represent signs of a partial sex-atypical differentiation of the brain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Temporal and frontal cortical thickness associations with M100 auditory activity and attention in healthy controls and individuals with schizophrenia

PubMed Central

Edgar, J. Christopher; Hunter, Michael A.; Huang, Mingxiong; Smith, Ashley K.; Chen, Yuhan; Sadek, Joseph; Lu, Brett Y; Miller, Gregory A.; Cañive, José M.

2012-01-01

Background Although gray matter (GM) abnormalities are frequently observed in individuals with schizophrenia (SCZ), the functional consequences of these structural abnormalities are not yet understood. The present study sought to better understand GM abnormalities in SCZ by examining associations between GM and two putative functional SCZ biomarkers: weak 100 ms (M100) auditory responses and impairment on tests of attention. Methods Data were available from 103 subjects (healthy controls=52, SCZ=51). GM cortical thickness measures were obtained for superior temporal gyrus (STG) and prefrontal cortex (PFC). Magnetoencephalography (MEG) provided measures of left and right STG M100 source strength. Subjects were administered the Trail Making Test A and the Connors’ Continuous Performance Test to assess attention. Results A strong trend indicated less GM cortical thickness in SCZ than controls in both regions and in both hemispheres (p=0.06). Individuals with SCZ had weaker M100 responses than controls bilaterally, and individuals with SCZ performed more poorly than controls on tests of attention. Across groups, left STG GM was positively associated with left M00 source strength. In SCZ only, less left and right STG and PFC GM predicted poorer performance on tests of attention. After removing variance in attention associated with age, associations between GM and attention remained significant only in left and right STG. Conclusions Reduced GM cortical thickness may serve as a common substrate for multiple functional abnormalities in SCZ, with structural-functional abnormalities in STG GM especially prominent. As suggested by others, functional abnormalities in SCZ may be a consequence of elimination of the neuropil (dendritic arbors and associated synaptic infrastructure) between neuron bodies. PMID:22766129

Exploring the relationship between white matter and gray matter damage in early primary progressive multiple sclerosis: an in vivo study with TBSS and VBM.

PubMed

Bodini, Benedetta; Khaleeli, Zhaleh; Cercignani, Mara; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

2009-09-01

We investigated the relationship between the damage occurring in the brain normal-appearing white matter (NAWM) and in the gray matter (GM) in patients with early Primary Progressive multiple sclerosis (PPMS), using Tract-Based Spatial Statistics (TBSS) and an optimized voxel-based morphometry (VBM) approach. Thirty-five patients with early PPMS underwent diffusion tensor and conventional imaging and were clinically assessed. TBSS and VBM were employed to localize regions of lower fractional anisotropy (FA) and lower GM volume in patients compared with controls. Areas of anatomical and quantitative correlation between NAWM and GM damage were detected. Multiple regression analyses were performed to investigate whether NAWM FA or GM volume of regions correlated with clinical scores independently from the other and from age and gender. In patients, we found 11 brain regions that showed an anatomical correspondence between reduced NAWM FA and GM atrophy; of these, four showed a quantitative correlation (i.e., the right sensory motor region with the adjacent corticospinal tract, the left and right thalamus with the corresponding thalamic radiations and the left insula with the adjacent WM). Either the NAWM FA or the GM volume in each of these regions correlated with disability. These results demonstrate a link between the pathological processes occurring in the NAWM and in the GM in PPMS in specific, clinically relevant brain areas. Longitudinal studies will determine whether the GM atrophy precedes or follows the NAWM damage. The methodology that we described may be useful to investigate other neurological disorders affecting both the WM and the GM. 2009 Wiley-Liss, Inc.

Voxel-based mapping of grey matter volume and glucose metabolism profiles in amyotrophic lateral sclerosis.

PubMed

Buhour, M-S; Doidy, F; Mondou, A; Pélerin, A; Carluer, L; Eustache, F; Viader, F; Desgranges, B

2017-12-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease of the nervous system involving both upper and lower motor neurons. The patterns of structural and metabolic brain alterations are still unclear. Several studies using anatomical MRI yielded a number of discrepancies in their results, and a few PET studies investigated the effect of ALS on cerebral glucose metabolism. The aim of this study was threefold: to highlight the patterns of grey matter (GM) atrophy, hypometabolism and hypermetabolism in patients with ALS, then to understand the neurobehavioral significance of hypermetabolism and, finally, to investigate the regional differences between the morphologic and functional changes in ALS patients, using a specially designed voxel-based method. Thirty-seven patients with ALS and 37 age- and sex-matched healthy individuals underwent both structural MRI and 18 [F]-fluorodeoxyglucose (FDG) PET examinations. PET data were corrected for partial volume effects. Structural and metabolic abnormalities were examined in ALS patients compared with control subjects using two-sample t tests in statistical parametric mapping (SPM). Then, we extracted the metabolic values of clusters presenting hypermetabolism to correlate with selected cognitive scores. Finally, GM atrophy and hypometabolism patterns were directly compared with a one-paired t test in SPM. We found GM atrophy as well as hypometabolism in motor and extra motor regions and hypermetabolism in medial temporal lobe and cerebellum. We observed negative correlations between the metabolism of the right and left parahippocampal gyri and episodic memory and between the metabolism of right temporal pole and cognitive theory of mind. GM atrophy predominated in the temporal pole, left hippocampus and right thalamus, while hypometabolism predominated in a single cluster in the left frontal superior medial cortex. Our findings provide direct evidence of regional variations in the hierarchy and relationships between GM atrophy and hypometabolism in ALS. Moreover, the 18 FDG-PET investigation suggests that cerebral hypermetabolism is deleterious to cognitive function in ALS.

Cognitive Severity-Specific Neuronal Degenerative Network in Charcoal Burning Suicide-Related Carbon Monoxide Intoxication

PubMed Central

Chen, Nai-Ching; Huang, Chi-Wei; Huang, Shu-Hua; Chang, Wen-Neng; Chang, Ya-Ting; Lui, Chun-Chung; Lin, Pin-Hsuan; Lee, Chen-Chang; Chang, Yen-Hsiang; Chang, Chiung-Chih

2015-01-01

Abstract While carbon monoxide (CO) intoxication often triggers multiple intraneuronal immune- or inflammatory-related cascades, it is not known whether the pathological processes within the affected regions evolve equally in the long term. To understand the neurodegenerative networks, we examined 49 patients with a clinical diagnosis of CO intoxication related to charcoal burning suicide at the chronic stage and compared them with 15 age- and sex-matched controls. Reconstructions of degenerative networks were performed using T1 magnetic resonance imaging, diffusion-tensor imaging, and fluorodeoxyglucose positron emission tomography (PET). Tract-specific fractional anisotropy (FA) quantification of 11 association fibers was performed while the clinical significance of the reconstructed structural or functional networks was determined by correlating them with the cognitive parameters. Compared with the controls, the patients had frontotemporal gray matter (GM) atrophy, diffuse white matter (WM) FA decrement, and axial diffusivity (AD) increment. The patients were further stratified into 3 groups based on the cognitive severities. The spatial extents within the frontal-insular-caudate GM as well as the prefrontal WM AD increment regions determined the cognitive severities among 3 groups. Meanwhile, the prefrontal WM FA values and PET signals also correlated significantly with the patient's Mini-Mental State Examination score. Frontal hypometabolic patterns in PET analysis, even after adjusted for GM volume, were highly coherent to the GM atrophic regions, suggesting structural basis of functional alterations. Among the calculated major association bundles, only the anterior thalamic radiation FA values correlated significantly with all chosen cognitive scores. Our findings suggest that fronto-insular-caudate areas represent target degenerative network in CO intoxication. The topography that occurred at a cognitive severity-specific level at the chronic phase suggested the clinical roles of frontal areas. Although changes in FA are also diffusely distributed, different regional changes in AD suggested unequal long-term compensatory capacities among WM bundles. As such, the affected WM regions showing irreversible changes may exert adverse impacts to the interconnected GM structures. PMID:25984663

Population variation in neuroendocrine activity is associated with behavioral inhibition and hemispheric brain structure in young rhesus monkeys

PubMed Central

Short, Sarah J.; Lubach, Gabriele R.; Shirtcliff, Elizabeth A.; Styner, Martin A.; Gilmore, John H.; Coe, Christopher L.

2014-01-01

Summary Population variation in hypothalamic-pituitary-adrenal (HPA) activity and reactivity was assessed in a healthy sample of 48 juvenile rhesus monkeys. Cluster analysis of the HPA profiles revealed four distinct neuroendocrine phenotypes based on six indices of HPA functioning. Behavioral reactivity was also evaluated in response to novel stimuli, and revealed marked differences between animals in the highest- and lowest-cortisol clusters. Specifically, animals in the high-cortisol cluster showed larger stress-induced cortisol responses and blunted feedback sensitivity to dexamethasone. They were also emotionally reactive, displayed more aggressive behaviors, and were less likely to approach novel objects. In contrast, monkeys in the low-cortisol cluster were more likely to approach and explore novel objects. Representative animals with high or low cortisol profiles were scanned with Magnetic Resonance Imaging to evaluate structural differences in global and regional gray matter (GM) and white matter (WM) volumes. Monkeys with higher cortisol reactivity evinced less hemispheric brain asymmetry, due to decreased GM in the right hemisphere. Stress reactivity was inversely related to global GM and positively related to total cerebrospinal fluid volume. This inverse relationship was also observed in several stress-sensitive regions, including prefrontal and frontal cortices. Our study demonstrates that population variation in pituitary-adrenal activity is related to behavioral disposition and cerebral structure in this nonhuman primate species. PMID:24954302

Polymorphism of DCDC2 Reveals Differences in Cortical Morphology of Healthy Individuals—A Preliminary Voxel Based Morphometry Study

PubMed Central

Gelernter, Joel; Gruen, Jeffrey R.; Calhoun, Vince D.; Meng, Haiying; Cope, Natalie A.; Pearlson, Godfrey D.

2008-01-01

Objective The purpose of this investigation was to determine whether there is an association between the putative reading disability (RD) susceptibility gene Doublecortin Domain Containing 2 (DCDC2), and gray matter (GM) distribution in the brain, in a sample of healthy control individuals. Method Fifty-six control subjects were genotyped for an RD-associated deletion in intron 2 of DCDC2. Voxel based morphometry (VBM) was used to examine structural magnetic resonance imaging (MRI) scans to assess GM differences between the two groups. Results Individuals heterozygous for the deletion exhibited significantly higher GM volumes in reading/language and symbol-decoding related brain regions including superior, medial and inferior temporal, fusiform, hippocampal/para-hippocampal, inferior occipito-parietal, inferior and middle frontal gyri, especially in the left hemisphere. GM values correlated with published data on regional DCDC2 expression in a lateralized manner. Conclusions These data suggest a role for DCDC2 in GM distribution in language-related brain regions in healthy individuals. PMID:19096528

Structural correlates of cognitive deficit and elevated gamma noise power in schizophrenia.

PubMed

Suazo, Vanessa; Díez, Álvaro; Montes, Carlos; Molina, Vicente

2014-03-01

The aim of this study was to assess the relation between cognition, gray matter (GM) volumes and gamma noise power (amount of background oscillatory activity in the gamma band) in schizophrenia. We explored the relation between cognitive performance and regional GM volumes using voxel-based morphometry (VBM), in order to discover if the association between gamma noise power (an electroencephalography measurement of background activity in the gamma band) and cognition is observed through structural deficits related to the disease. Noise power, magnetic resonance imaging and cognitive assessments were obtained in 17 drug-free paranoid patients with schizophrenia and 13 healthy controls. In comparison with controls, patients showed GM deficits at posterior cingulate (bilateral),left inferior parietal (supramarginal gyrus) and left inferior dorsolateral prefrontal regions. Patients exhibited a direct association between performance in working memory and right temporal (superior and inferior gyri) GM densities. They also displayed a negative association between right anterior cerebellum volume and gamma noise power at the frontal midline (Fz) site. A structural deficit in the cerebellum may be involved in gamma activity disorganization in schizophrenia. Temporal structural deficits may relate to cognitive dysfunction in this illness. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Multivariate pattern analysis of obsessive-compulsive disorder using structural neuroanatomy.

PubMed

Hu, Xinyu; Liu, Qi; Li, Bin; Tang, Wanjie; Sun, Huaiqiang; Li, Fei; Yang, Yanchun; Gong, Qiyong; Huang, Xiaoqi

2016-02-01

Magnetic resonance imaging (MRI) studies have revealed brain structural abnormalities in obsessive-compulsive disorder (OCD) patients, involving both gray matter (GM) and white matter (WM). However, the results of previous publications were based on average differences between groups, which limited their usages in clinical practice. Therefore, the aim of this study was to examine whether the application of multivariate pattern analysis (MVPA) to high-dimensional structural images would allow accurate discrimination between OCD patients and healthy control subjects (HCS). High-resolution T1-weighted images were acquired from 33 OCD patients and 33 demographically matched HCS in a 3.0 T scanner. Differences in GM and WM volume between OCD and HCS were examined using two types of well-established MVPA techniques: support vector machine (SVM) and Gaussian process classifier (GPC). We also drew a receiver operating characteristic (ROC) curve to evaluate the performance of each classifier. The classification accuracies for both classifiers using GM and WM anatomy were all above 75%. The highest classification accuracy (81.82%, P<0.001) was achieved with the SVM classifier using WM information. Regional brain anomalies with high discriminative power were based on three distributed networks including the fronto-striatal circuit, the temporo-parieto-occipital junction and the cerebellum. Our study illustrated that both GM and WM anatomical features may be useful in differentiating OCD patients from HCS. WM volume using the SVM approach showed the highest accuracy in our population for revealing group differences, which suggested its potential diagnostic role in detecting highly enriched OCD patients at the level of the individual. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

A voxel based comparative analysis using magnetization transfer imaging and T1-weighted magnetic resonance imaging in progressive supranuclear palsy

PubMed Central

Sandhya, Mangalore; Saini, Jitender; Pasha, Shaik Afsar; Yadav, Ravi; Pal, Pramod Kumar

2014-01-01

Aims: In progressive supranuclear palsy (PSP) tissue damage occurs in specific cortical and subcortical regions. Voxel based analysis using T1-weighted images depict quantitative gray matter (GM) atrophy changes. Magnetization transfer (MT) imaging depicts qualitative changes in the brain parenchyma. The purpose of our study was to investigate whether MT imaging could indicate abnormalities in PSP. Settings and Design: A total of 10 patients with PSP (9 men and 1 woman) and 8 controls (5 men and 3 women) were studied with T1-weighted magnetic resonance imaging (MRI) and 3DMT imaging. Voxel based analysis of T1-weighted MRI was performed to investigate brain atrophy while MT was used to study qualitative abnormalities in the brain tissue. We used SPM8 to investigate group differences (with two sample t-test) using the GM and white matter (WM) segmented data. Results: T1-weighted imaging and MT are equally sensitive to detect changes in GM and WM in PSP. Magnetization transfer ratio images and magnetization-prepared rapid acquisition of gradient echo revealed extensive bilateral volume and qualitative changes in the orbitofrontal, prefrontal cortex and limbic lobe and sub cortical GM. The prefrontal structures involved were the rectal gyrus, medial, inferior frontal gyrus (IFG) and middle frontal gyrus (MFG). The anterior cingulate, cingulate gyrus and lingual gyrus of limbic lobe and subcortical structures such as caudate, thalamus, insula and claustrum were also involved. Cerebellar involvement mainly of anterior lobe was also noted. Conclusions: The findings suggest that voxel based MT imaging permits a whole brain unbiased investigation of central nervous system structural integrity in PSP. PMID:25024571

Sex differences and the impact of steroid hormones on the developing human brain.

PubMed

Neufang, Susanne; Specht, Karsten; Hausmann, Markus; Güntürkün, Onur; Herpertz-Dahlmann, Beate; Fink, Gereon R; Konrad, Kerstin

2009-02-01

Little is known about the hormonal effects of puberty on the anatomy of the developing human brain. In a voxel-based morphometry study, sex-related differences in gray matter (GM) volume were examined in 46 subjects aged 8-15 years. Males had larger GM volumes in the left amygdala, whereas females had larger right striatal and bilateral hippocampal GM volumes than males. Sexually dimorphic areas were related to Tanner stages (TS) of pubertal development and to circulating level of steroid hormones in a subsample of 30 subjects. Regardless of sex, amygdala and hippocampal volumes varied as a function of TS and were associated with circulating testosterone (TEST) levels. By contrast, striatal GM volumes were unrelated to pubertal development and circulating steroid hormones. Whole-brain regression analyses revealed positive associations between circulating estrogen levels and parahippocampal GM volumes as well as between TEST levels and diencephalic brain structures. In addition, a negative association was found between circulating TEST and left parietal GM volumes. These data suggest that GM development in certain brain regions is associated with sexual maturation and that pubertal hormones might have organizational effects on the developing human brain.

Fractal-dimension analysis detects cerebral changes in preterm infants with and without intrauterine growth restriction.

PubMed

Esteban, Francisco J; Padilla, Nelly; Sanz-Cortés, Magdalena; de Miras, Juan Ruiz; Bargalló, Núria; Villoslada, Pablo; Gratacós, Eduard

2010-12-01

In the search for a useful parameter to detect and quantify subtle brain abnormalities in infants with intrauterine growth restriction (IUGR), we hypothesised that the analysis of the structural complexity of grey matter (GM) and white matter (WM) using the fractal dimension (FD), a measurement of the topological complexity of an object, could be established as a useful tool for quantitative studies of infant brain morphology. We studied a sample of 18 singleton IUGR premature infants, (12.72 months corrected age (CA), range: 12 months-14 months), 15 preterm infants matched one-to-one for gestational age (GA) at delivery (12.6 months; range: 12 months-14 months), and 15 neonates born at term (12.4 months; range: 11 months-14 months). The neurodevelopmental outcome was assessed in all subjects at 18 months CA according to the Bayley Scale for Infant and Toddler Development - Third edition (BSID-III). For MRI acquisition and processing, the infants were scanned at 12 months CA, in a TIM TRIO 3T scanner, sleeping naturally. Images were pre-processed using the SPM5 toolbox, the GM and WM segmented under the VBM5 toolbox, and the box-counting method was applied for FD calculation of normal and skeletonized segmented images. The results showed a significant decrease of the FD of the brain GM and WM in the IUGR group when compared to the preterm or at-term controls. We also identified a significant linear tendency of both GM and WM FD from IUGR to preterm and term groups. Finally, multiple linear analyses between the FD of the GM or WM and the neurodevelopmental scales showed a significant regression of the language and motor scales with the FD of the GM. In conclusion, a decreased FD of the GM and WM in IUGR infants could be a sensitive indicator for the investigation of structural brain abnormalities in the IUGR population at 12 months of age, which can also be related to functional disorders. Copyright © 2010 Elsevier Inc. All rights reserved.

Brain grey and white matter predictors of verbal ability traits in older age: The Lothian Birth Cohort 1936.

PubMed

Hoffman, Paul; Cox, Simon R; Dykiert, Dominika; Muñoz Maniega, Susana; Valdés Hernández, Maria C; Bastin, Mark E; Wardlaw, Joanna M; Deary, Ian J

2017-08-01

Cerebral grey and white matter MRI parameters are related to general intelligence and some specific cognitive abilities. Less is known about how structural brain measures relate specifically to verbal processing abilities. We used multi-modal structural MRI to investigate the grey matter (GM) and white matter (WM) correlates of verbal ability in 556 healthy older adults (mean age = 72.68 years, s.d. = .72 years). Structural equation modelling was used to decompose verbal performance into two latent factors: a storage factor that indexed participants' ability to store representations of verbal knowledge and an executive factor that measured their ability to regulate their access to this information in a flexible and task-appropriate manner. GM volumes and WM fractional anisotropy (FA) for components of the language/semantic network were used as predictors of these verbal ability factors. Volume of the ventral temporal cortices predicted participants' storage scores (β = .12, FDR-adjusted p = .04), consistent with the theory that this region acts as a key substrate of semantic knowledge. This effect was mediated by childhood IQ, suggesting a lifelong association between ventral temporal volume and verbal knowledge, rather than an effect of cognitive decline in later life. Executive ability was predicted by FA fractional anisotropy of the arcuate fasciculus (β = .19, FDR-adjusted p = .001), a major language-related tract implicated in speech production. This result suggests that this tract plays a role in the controlled retrieval of word knowledge during speech. At a more general level, these data highlight a basic distinction between information representation, which relies on the accumulation of tissue in specialised GM regions, and executive control, which depends on long-range WM pathways for efficient communication across distributed cortical networks. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of low-level sarin and cyclosarin exposure and Gulf War Illness on brain structure and function: a study at 4T.

PubMed

Chao, Linda L; Abadjian, Linda; Hlavin, Jennifer; Meyerhoff, Deiter J; Weiner, Michael W

2011-12-01

More than 100,000 US troops were potentially exposed to chemical warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at Khamisiyah, Iraq was destroyed during the 1991 Persian Gulf War (GW). We previously found reduced total gray matter (GM) volume in 40 GW veterans with suspected GB/GF exposure relative to 40 matched, unexposed GW veterans on a 1.5T MR scanner. In this study, we reexamine the relationship between GB/GF exposure and volumetric measurements of gross neuroanatomical structures in a different cohort of GW veterans on a 4T MR scanner. Neuropsychological and magnetic resonance imaging (MRI) data from a cross sectional study on Gulf War Illness performed between 2005 and 2010 were used in this study. 4T MRI data were analyzed using automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). Binary comparisons of 64 GB/GF exposed veterans and 64 'matched', unexposed veterans revealed reduced GM (p=0.03) and WM (p=0.03) volumes in the exposed veterans. Behaviorally, exposed veterans committed more errors of omission (p=0.02) and tended to have slower responses (p=0.05) than unexposed veterans on the Continuous Performance Test (CPT), a measure sustained and selective attention. Regression analyses confirmed that GB/GF exposure status predicted GM (β=-0.11, p=0.02) and WM (β=-0.14, p=0.03) volumes, and number of CPT omission errors (β=0.22, p=0.02) over and above potentially confounding demographic, clinical, and psychosocial variables. There was no dose-response relationship between estimated levels of GB/GF exposure and brain volume. However, we did find an effect of Gulf War Illness/Chronic Multisymptom Illness on both GM and WM volume in the GB/GF exposed veterans. These findings confirm previous reports by our group and others of central nervous system pathology in GW veterans with suspected exposure to low levels of GB/GF two decades after the exposure. Copyright © 2011 Elsevier Inc. All rights reserved.

Baseline Gray- and White Matter Volume Predict Successful Weight Loss in the Elderly

PubMed Central

Mokhtari, Fatemeh; Paolini, Brielle M.; Burdette, Jonathan H.; Marsh, Anthony P.; Rejeski, W. Jack; Laurienti, Paul J.

2016-01-01

Objective The purpose of this study is to investigate if structural brain phenotypes can be used to predict weight loss success following behavioral interventions in older adults that are overweight or obese and have cardiometabolic dysfunction. Methods A support vector machine (SVM) with a repeated random subsampling validation approach was used to classify participants into the upper and lower halves of the weight loss distribution following 18 months of a weight loss intervention. Predictions were based on baseline brain gray matter (GM) and white matter (WM) volume from 52 individuals that completed the intervention and a magnetic resonance imaging session. Results The SVM resulted in an average classification accuracy of 72.62 % based on GM and WM volume. A receiver operating characteristic analysis indicated that classification performance was robust based on an area under the curve of 0.82. Conclusions Our findings suggest that baseline brain structure is able to predict weight loss success following 18 months of treatment. The identification of brain structure as a predictor of successful weight loss is an innovative approach to identifying phenotypes for responsiveness to intensive lifestyle interventions. This phenotype could prove useful in future research focusing on the tailoring of treatment for weight loss. PMID:27804273

Structural brain correlates associated with professional handball playing.

PubMed

Hänggi, Jürgen; Langer, Nicolas; Lutz, Kai; Birrer, Karin; Mérillat, Susan; Jäncke, Lutz

2015-01-01

There is no doubt that good bimanual performance is very important for skilled handball playing. The control of the non-dominant hand is especially demanding since efficient catching and throwing needs both hands. We investigated training-induced structural neuroplasticity in professional handball players using several structural neuroimaging techniques and analytic approaches and also provide a review of the literature about sport-induced structural neuroplastic alterations. Structural brain adaptations were expected in regions relevant for motor and somatosensory processing such as the grey matter (GM) of the primary/secondary motor (MI/supplementary motor area, SMA) and somatosensory cortex (SI/SII), basal ganglia, thalamus, and cerebellum and in the white matter (WM) of the corticospinal tract (CST) and corpus callosum, stronger in brain regions controlling the non-dominant left hand. Increased GM volume in handball players compared with control subjects were found in the right MI/SI, bilateral SMA/cingulate motor area, and left intraparietal sulcus. Fractional anisotropy (FA) and axial diffusivity were increased within the right CST in handball players compared with control women. Age of handball training commencement correlated inversely with GM volume in the right and left MI/SI and years of handball training experience correlated inversely with radial diffusivity in the right CST. Subcortical structures tended to be larger in handball players. The anatomical measures of the brain regions associated with handball playing were positively correlated in handball players, but not interrelated in control women. Training-induced structural alterations were found in the somatosensory-motor network of handball players, more pronounced in the right hemisphere controlling the non-dominant left hand. Correlations between handball training-related measures and anatomical differences suggest neuroplastic adaptations rather than a genetic predisposition for a ball playing affinity. Investigations of neuroplasticity specifically in sportsmen might help to understand the neural mechanisms of expertise in general.

Quantifying Cerebellum Grey Matter and White Matter Perfusion Using Pulsed Arterial Spin Labeling

PubMed Central

Li, Xiufeng; Sarkar, Subhendra N.; Purdy, David E.; Briggs, Richard W.

2014-01-01

To facilitate quantification of cerebellum cerebral blood flow (CBF), studies were performed to systematically optimize arterial spin labeling (ASL) parameters for measuring cerebellum perfusion, segment cerebellum to obtain separate CBF values for grey matter (GM) and white matter (WM), and compare FAIR ASST to PICORE. Cerebellum GM and WM CBF were measured with optimized ASL parameters using FAIR ASST and PICORE in five subjects. Influence of volume averaging in voxels on cerebellar grey and white matter boundaries was minimized by high-probability threshold masks. Cerebellar CBF values determined by FAIR ASST were 43.8 ± 5.1 mL/100 g/min for GM and 27.6 ± 4.5 mL/100 g/min for WM. Quantitative perfusion studies indicated that CBF in cerebellum GM is 1.6 times greater than that in cerebellum WM. Compared to PICORE, FAIR ASST produced similar CBF estimations but less subtraction error and lower temporal, spatial, and intersubject variability. These are important advantages for detecting group and/or condition differences in CBF values. PMID:24949416

Dyslexia and Voxel-Based Morphometry: Correlations between Five Behavioural Measures of Dyslexia and Gray and White Matter Volumes

ERIC Educational Resources Information Center

Tamboer, Peter; Scholte, H. Steven; Vorst, Harrie C. M.

2015-01-01

In voxel-based morphometry studies of dyslexia, the relation between causal theories of dyslexia and gray matter (GM) and white matter (WM) volume alterations is still under debate. Some alterations are consistently reported, but others failed to reach significance. We investigated GM alterations in a large sample of Dutch students (37 dyslexics…

Accurate GM atrophy quantification in MS using lesion-filling with co-registered 2D lesion masks☆

PubMed Central

Popescu, V.; Ran, N.C.G.; Barkhof, F.; Chard, D.T.; Wheeler-Kingshott, C.A.; Vrenken, H.

2014-01-01

Background In multiple sclerosis (MS), brain atrophy quantification is affected by white matter lesions. LEAP and FSL-lesion_filling, replace lesion voxels with white matter intensities; however, they require precise lesion identification on 3DT1-images. Aim To determine whether 2DT2 lesion masks co-registered to 3DT1 images, yield grey and white matter volumes comparable to precise lesion masks. Methods 2DT2 lesion masks were linearly co-registered to 20 3DT1-images of MS patients, with nearest-neighbor (NNI), and tri-linear interpolation. As gold-standard, lesion masks were manually outlined on 3DT1-images. LEAP and FSL-lesion_filling were applied with each lesion mask. Grey (GM) and white matter (WM) volumes were quantified with FSL-FAST, and deep gray matter (DGM) volumes using FSL-FIRST. Volumes were compared between lesion mask types using paired Wilcoxon tests. Results Lesion-filling with gold-standard lesion masks compared to native images reduced GM overestimation by 1.93 mL (p < .001) for LEAP, and 1.21 mL (p = .002) for FSL-lesion_filling. Similar effects were achieved with NNI lesion masks from 2DT2. Global WM underestimation was not significantly influenced. GM and WM volumes from NNI, did not differ significantly from gold-standard. GM segmentation differed between lesion masks in the lesion area, and also elsewhere. Using the gold-standard, FSL-FAST quantified as GM on average 0.4% of the lesion area with LEAP and 24.5% with FSL-lesion_filling. Lesion-filling did not influence DGM volumes from FSL-FIRST. Discussion These results demonstrate that for global GM volumetry, precise lesion masks on 3DT1 images can be replaced by co-registered 2DT2 lesion masks. This makes lesion-filling a feasible method for GM atrophy measurements in MS. PMID:24567908

Fusing DTI and FMRI Data: A Survey of Methods and Applications

PubMed Central

Zhu, Dajiang; Zhang, Tuo; Jiang, Xi; Hu, Xintao; Chen, Hanbo; Yang, Ning; Lv, Jinglei; Han, Junwei; Guo, Lei; Liu, Tianming

2014-01-01

The relationship between brain structure and function has been one of the centers of research in neuroimaging for decades. In recent years, diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) techniques have been widely available and popular in cognitive and clinical neurosciences for examining the brain’s white matter (WM) micro-structures and gray matter (GM) functions, respectively. Given the intrinsic integration of WM/GM and the complementary information embedded in DTI/fMRI data, it is natural and well-justified to combine these two neuroimaging modalities together to investigate brain structure and function and their relationships simultaneously. In the past decade, there have been remarkable achievements of DTI/fMRI fusion methods and applications in neuroimaging and human brain mapping community. This survey paper aims to review recent advancements on methodologies and applications in incorporating multimodal DTI and fMRI data, and offer our perspectives on future research directions. We envision that effective fusion of DTI/fMRI techniques will play increasingly important roles in neuroimaging and brain sciences in the years to come. PMID:24103849

Cerebral gray matter volume in patients with chronic migraine: correlations with clinical features.

PubMed

Coppola, Gianluca; Petolicchio, Barbara; Di Renzo, Antonio; Tinelli, Emanuele; Di Lorenzo, Cherubino; Parisi, Vincenzo; Serrao, Mariano; Calistri, Valentina; Tardioli, Stefano; Cartocci, Gaia; Ambrosini, Anna; Caramia, Francesca; Di Piero, Vittorio; Pierelli, Francesco

2017-12-08

To date, few MRI studies have been performed in patients affected by chronic migraine (CM), especially in those without medication overuse. Here, we performed magnetic resonance imaging (MRI) voxel-based morphometry (VBM) analyses to investigate the gray matter (GM) volume of the whole brain in patients affected by CM. Our aim was to investigate whether fluctuations in the GM volumes were related to the clinical features of CM. Twenty untreated patients with CM without a past medical history of medication overuse underwent 3-Tesla MRI scans and were compared to a group of 20 healthy controls (HCs). We used SPM12 and the CAT12 toolbox to process the MRI data and to perform VBM analyses of the structural T1-weighted MRI scans. The GM volume of patients was compared to that of HCs with various corrected and uncorrected thresholds. To check for possible correlations, patients' clinical features and GM maps were regressed. Initially, we did not find significant differences in the GM volume between patients with CM and HCs (p < 0.05 corrected for multiple comparisons). However, using more-liberal uncorrected statistical thresholds, we noted that compared to HCs, patients with CM exhibited clusters of regions with lower GM volumes including the cerebellum, left middle temporal gyrus, left temporal pole/amygdala/hippocampus/pallidum/orbitofrontal cortex, and left occipital areas (Brodmann areas 17/18). The GM volume of the cerebellar hemispheres was negatively correlated with the disease duration and positively correlated with the number of tablets taken per month. No gross morphometric changes were observed in patients with CM when compared with HCs. However, using more-liberal uncorrected statistical thresholds, we observed that CM is associated with subtle GM volume changes in several brain areas known to be involved in nociception/antinociception, multisensory integration, and analgesic dependence. We speculate that these slight morphometric impairments could lead, at least in a subgroup of patients, to the development and continuation of maladaptive acute medication usage.

Alterations of brain grey matter density and olfactory bulb volume in patients with olfactory loss after traumatic brain injury.

PubMed

Han, Pengfei; Winkler, Nicole; Hummel, Cornelia; Hähner, Antje; Gerber, Johannes; Hummel, Thomas

2018-04-27

Olfactory loss and traumatic brain injury (TBI) both lead to anatomical brain alterations in humans. Little research has been done on the structural brain changes for TBI patients with olfactory loss. Using voxel-based morphometry, the grey matter (GM) density was examined for twenty-two TBI patients with hyposmia, twenty-four TBI patients with anosmia, and twenty-two age-matched controls. Olfactory bulb (OB) volumes were measured by manual segmentation of acquired T2 weighted coronal slices using a standardized protocol. Brain lesions in the olfactory relevant areas were also examined for TBI patients. Results showed that patients with anosmia have more frequent lesions in the OB, orbitofrontal cortex (OFC) and the temporal lobe pole, as compared to patients with hyposmia. GM density in the primary olfactory area was decreased in both groups of patients. In addition, compared to controls, patients with anosmia showed GM density reduction in several secondary olfactory eloquent regions, including the gyrus rectus, medial OFC, anterior cingulate cortex, insula, and cerebellum. However, patients with hyposmia showed a lesser degree of GM reduction compared to healthy controls. Smaller OB volumes were found for patients with olfactory loss as compared to controls. TBI patients with anosmia had the smallest OB volumes which were caused by the lesions for OB. In addition, post-TBI duration was negatively correlated with GM density in the secondary olfactory areas in patients with hyposmia, but was positively correlated with GM density in the frontal and temporal gyrus in patients with anosmia. The GM density and OB volume reduction among TBI patients with olfactory loss was largely depend on the location and severity of brain lesions in olfactory relevant regions. Longer post-TBI duration had an impact on brain GM density changes, which indicate a decreased olfactory function in patients with hyposmia and possible compensatory mechanisms in patients with anosmia.

2D phase sensitive inversion recovery imaging to measure in-vivo spinal cord gray and white matter areas in clinically feasible acquisition times

PubMed Central

Papinutto, N.; Schlaeger, R.; Panara, V.; Caverzasi, E.; Ahn, S.; Johnson, K.J.; Zhu, A.H.; Stern, W.A.; Laub, G.; Hauser, S.L.; Henry, R.G.

2018-01-01

PURPOSE In-vivo assessment of spinal cord gray matter (GM) and white matter (WM) could become pivotal to study various neurological diseases, but it is challenging because of insufficient GM/WM contrast provided by conventional MRI. Here we present and assess a procedure for measurement of spinal cord total cross-sectional area (TCA) and GM areas based on phase sensitive inversion recovery imaging (PSIR). MATERIALS AND METHODS We acquired 2D PSIR images at 3T at each disc level of the spinal axis on 10 healthy subjects and measured TCA, cord diameters, WM and GM area, and GM area/TCA ratio. We secondly investigated 32 healthy subjects at 4 selected levels (C2–C3, C3–C4, T8–T9, T9–T10, total acquisition time <8 minutes) and generated normative reference values of TCA and GM areas. We assessed test-retest, intra- and inter-operator reliability of the acquisition strategy and measurement steps. RESULTS The measurement procedure based on 2D PSIR imaging allowed TCA and GM area assessments along the entire spinal cord axis. The tests we performed revealed high test-retest/intra-operator reliability (mean coefficient of variation (COV) at C2–C3: TCA=0.41%, GM area=2.75%) and inter-operator reliability of the measurements (mean COV on the 4 levels: TCA=0.44%, GM area= 4.20%; mean intra-class correlation coefficient: TCA=0.998, GM area=0.906). CONCLUSION 2D PSIR allows reliable in-vivo assessment of spinal cord TCA, GM and WM areas in clinically feasible acquisition times. The area measurements presented here are in agreement with previous MRI and post-mortem studies. PMID:25483607

Diminished gray matter in the hippocampus of cannabis users: possible protective effects of cannabidiol.

PubMed

Demirakca, Traute; Sartorius, Alexander; Ende, Gabriele; Meyer, Nadja; Welzel, Helga; Skopp, Gisela; Mann, Karl; Hermann, Derik

2011-04-01

Chronic cannabis use has been associated with memory deficits and a volume reduction of the hippocampus, but none of the studies accounted for different effects of tetrahydrocannabinol (THC) and cannabidiol (CBD). Using a voxel based morphometry approach optimized for small subcortical structures (DARTEL) gray matter (GM) concentration and volume of the hippocampus were measured in 11 chronic recreational cannabis users and 13 healthy controls, and correlated with THC and CBD from hair analyses. GM volume was calculated by modulating VBM using Jacobian determinants derived from the spatial normalization. Cannabis users showed lower GM volume located in a cluster of the right anterior hippocampus (P(uncorr)=0.002; effect size Cohen's d=1.34). In a regression analysis an inverse correlation of the ratio THC/CBD with the volume of the right hippocampus (P(uncorr) p<0.001, Cohen's d=3.43) was observed. Furthermore Cannabidiol correlated positively with GM concentration (unmodulated VBM data), but not with GM volume (modulated VBM) in the bilateral hippocampus (P=0.03 after correction for hippocampal volume; left hippocampus Cohen's d=4.37 and right hippocampus 4.65). Lower volume in the right hippocampus in chronic cannabis users was corroborated. Higher THC and lower CBD was associated with this volume reduction indicating neurotoxic effects of THC and neuroprotective effects of CBD. This confirms existing preclinical and clinical results. As a possible mechanism the influence of cannabinoids on hippocampal neurogenesis is suggested. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Multicenter Study of Brain Volume Abnormalities in Children and Adolescent-Onset Psychosis

PubMed Central

Reig, Santiago; Parellada, Mara; Castro-Fornieles, Josefina; Janssen, Joost; Moreno, Dolores; Baeza, Inmaculada; Bargalló, Nuria; González-Pinto, Ana; Graell, Montserrat; Ortuño, Felipe; Otero, Soraya; Arango, Celso; Desco, Manuel

2011-01-01

The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of “schizophrenia” or “other psychosis” showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents. PMID:20478821

Focal Gray Matter Plasticity as a Function of Long Duration Head-down Tilt Bed Rest

NASA Technical Reports Server (NTRS)

Koppelmans, V.; DeDios, Y. E.; Wood, S. J.; Reuter-Lorenz, P. A.; Kofman, I.; Bloomberg, J. J.; Mulavara, A. P.; Koppelmans, V.

2014-01-01

Long duration spaceflight (i.e., > or = 22 days) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes. Whether these sensorimotor changes may be related to structural and functional brain changes is yet unknown. However, experimental studies revealed changes in the gray matter (GM) of the brain after simulated microgravity. Thus, it is possible that spaceflight may affect brain structure and thereby cognitive functioning and motor behavior. Long duration head-down tilt bed rest has been suggested as an exclusionary analog to study microgravity effects on the sensorimotor system. Bed rest mimics microgravity in body unloading and bodily fluid shifts. In consideration of the health and performance of crewmembers both in- and post-flight, we are conducting a prospective longitudinal 70-day bed rest study as an analog to investigate the effects of microgravity on the brain. VBM analysis revealed a progressive decrease from pre- to in- bed rest in GM volume in bilateral areas including the frontal medial cortex, the insular cortex and the caudate. Over the same time period, there was a progressive increase in GM volume in the cerebellum, occipital-, and parietal cortex, including the precuneus. The majority of these changes did not fully recover during the post-bed rest period. Analysis of lobular GM volumes obtained with BRAINS showed significantly increased volume from pre-bed rest to in-bed rest in GM of the parietal lobe and the third ventricle. Temporal GM volume at 70 days in bed rest was smaller than that at the first pre-bed rest measurement. Trend analysis showed significant positive linear and negative quadratic relationships between parietal GM and time, a positive linear relationship between third ventricle volume and time, and a negative linear relationship between cerebellar GM volume and time. FM performance improved from pre-bed rest session 1 to session 2. From the second pre-bed rest measure to the last-day-in-bed rest, there was a significant decrease in performance that only partially recovered post-bed rest. No significant association was observed between changes in brain volume and changes in functional mobility. Extended bed rest, which is an analog for microgravity, can result in local volumetric GM increase and decrease and adversely affect functional mobility. These changes in brain structure and performance were not related in this sample. Whether the effects of bed rest dissipate at longer times post-bed rest, and if they are associated with behavior are important questions that warrant further research including more subjects and longer follow-up times.

Structural Brain Changes Following Left Temporal Low-Frequency rTMS in Patients with Subjective Tinnitus

PubMed Central

Langguth, Berthold; Poeppl, Timm B.; Rupprecht, Rainer; Hajak, Göran; Landgrebe, Michael; Schecklmann, Martin

2014-01-01

Repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been used to treat patients with subjective tinnitus. While rTMS is known to induce morphological changes in healthy subjects, no study has investigated yet whether rTMS treatment induces grey matter (GM) changes in tinnitus patients as well, whether these changes are correlated with treatment success, and whether GM at baseline is a useful predictor for treatment outcome. Therefore, we examined magnetic resonance images of 77 tinnitus patients who were treated with rTMS of the left temporal cortex (10 days, 2000 stimuli/day, 1 Hz). At baseline and after the last treatment session high-resolution structural images of the brain were acquired and tinnitus severity was assessed. For a subgroup of 41 patients, additional brain scans were done after a follow-up period of 90 days. GM changes were analysed by means of voxel based morphometry. Transient GM decreases were detectable in several brain regions, especially in the insula and the inferior frontal cortex. These changes were not related to treatment outcome though. Baseline images correlated with change in tinnitus severity in the frontal cortex and the lingual gyrus, suggesting that GM at baseline might hold potential as a possible predictor for treatment outcome. PMID:24991438

Grey Matter Changes Associated with Heavy Cannabis Use: A Longitudinal sMRI Study.

PubMed

Koenders, Laura; Cousijn, Janna; Vingerhoets, Wilhelmina A M; van den Brink, Wim; Wiers, Reinout W; Meijer, Carin J; Machielsen, Marise W J; Veltman, Dick J; Goudriaan, Anneke E; de Haan, Lieuwe

2016-01-01

Cannabis is the most frequently used illicit drug worldwide. Cross-sectional neuroimaging studies suggest that chronic cannabis exposure and the development of cannabis use disorders may affect brain morphology. However, cross-sectional studies cannot make a conclusive distinction between cause and consequence and longitudinal neuroimaging studies are lacking. In this prospective study we investigate whether continued cannabis use and higher levels of cannabis exposure in young adults are associated with grey matter reductions. Heavy cannabis users (N = 20, age baseline M = 20.5, SD = 2.1) and non-cannabis using healthy controls (N = 22, age baseline M = 21.6, SD = 2.45) underwent a comprehensive psychological assessment and a T1- structural MRI scan at baseline and 3 years follow-up. Grey matter volumes (orbitofrontal cortex, anterior cingulate cortex, insula, striatum, thalamus, amygdala, hippocampus and cerebellum) were estimated using the software package SPM (VBM-8 module). Continued cannabis use did not have an effect on GM volume change at follow-up. Cross-sectional analyses at baseline and follow-up revealed consistent negative correlations between cannabis related problems and cannabis use (in grams) and regional GM volume of the left hippocampus, amygdala and superior temporal gyrus. These results suggests that small GM volumes in the medial temporal lobe are a risk factor for heavy cannabis use or that the effect of cannabis on GM reductions is limited to adolescence with no further damage of continued use after early adulthood. Long-term prospective studies starting in early adolescence are needed to reach final conclusions.

Grey Matter Changes Associated with Heavy Cannabis Use: A Longitudinal sMRI Study

PubMed Central

Cousijn, Janna; Vingerhoets, Wilhelmina A. M.; van den Brink, Wim; Wiers, Reinout W.; Meijer, Carin J.; Machielsen, Marise W. J.; Veltman, Dick J.; Goudriaan, Anneke E.; de Haan, Lieuwe

2016-01-01

Cannabis is the most frequently used illicit drug worldwide. Cross-sectional neuroimaging studies suggest that chronic cannabis exposure and the development of cannabis use disorders may affect brain morphology. However, cross-sectional studies cannot make a conclusive distinction between cause and consequence and longitudinal neuroimaging studies are lacking. In this prospective study we investigate whether continued cannabis use and higher levels of cannabis exposure in young adults are associated with grey matter reductions. Heavy cannabis users (N = 20, age baseline M = 20.5, SD = 2.1) and non-cannabis using healthy controls (N = 22, age baseline M = 21.6, SD = 2.45) underwent a comprehensive psychological assessment and a T1- structural MRI scan at baseline and 3 years follow-up. Grey matter volumes (orbitofrontal cortex, anterior cingulate cortex, insula, striatum, thalamus, amygdala, hippocampus and cerebellum) were estimated using the software package SPM (VBM-8 module). Continued cannabis use did not have an effect on GM volume change at follow-up. Cross-sectional analyses at baseline and follow-up revealed consistent negative correlations between cannabis related problems and cannabis use (in grams) and regional GM volume of the left hippocampus, amygdala and superior temporal gyrus. These results suggests that small GM volumes in the medial temporal lobe are a risk factor for heavy cannabis use or that the effect of cannabis on GM reductions is limited to adolescence with no further damage of continued use after early adulthood. Long-term prospective studies starting in early adolescence are needed to reach final conclusions. PMID:27224247

Age-related changes in tissue signal properties within cortical areas important for word understanding in 12- to 19-month-old infants.

PubMed

Travis, Katherine E; Curran, Megan M; Torres, Christina; Leonard, Matthew K; Brown, Timothy T; Dale, Anders M; Elman, Jeffrey L; Halgren, Eric

2014-07-01

Recently, our laboratory has shown that the neural mechanisms for encoding lexico-semantic information in adults operate functionally by 12-18 months of age within left frontotemporal cortices (Travis et al., 2011. Spatiotemporal neural dynamics of word understanding in 12- to 18-month-old-infants. Cereb Cortex. 8:1832-1839). However, there is minimal knowledge of the structural changes that occur within these and other cortical regions important for language development. To identify regional structural changes taking place during this important period in infant development, we examined age-related changes in tissue signal properties of gray matter (GM) and white matter (WM) intensity and contrast. T1-weighted surface-based measures were acquired from 12- to 19-month-old infants and analyzed using a general linear model. Significant age effects were observed for GM and WM intensity and contrast within bilateral inferior lateral and anterovental temporal regions, dorsomedial frontal, and superior parietal cortices. Region of interest (ROI) analyses revealed that GM and WM intensity and contrast significantly increased with age within the same left lateral temporal regions shown to generate lexico-semantic activity in infants and adults. These findings suggest that neurophysiological processes supporting linguistic and cognitive behaviors may develop before cellular and structural maturation is complete within associative cortices. These results have important implications for understanding the neurobiological mechanisms relating structural to functional brain development. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Sexual dimorphism in the parietal substrate associated with visuospatial cognition independent of general intelligence.

PubMed

Hänggi, Jürgen; Buchmann, Andreas; Mondadori, Christian R A; Henke, Katharina; Jäncke, Lutz; Hock, Christoph

2010-01-01

Sex differences in visuospatial cognition (VSC) with male advantage are frequently reported in the literature. There is evidence for sexual dimorphisms in the human brain, one of which postulates more gray matter (GM) in females and more white matter (WM) in males relative to total intracranial volume. We investigated the neuroanatomy of VSC independent of general intelligence (g) in sex-separated populations, homogenous in age, education, memory performance, a memory- and brain morphology-related gene, and g. VSC and g were assessed with the Wechsler adult intelligence scale. The influence of g on VSC was removed using a hierarchical factor analysis and the Schmid-Leiman solution. Structural high-resolution magnetic resonance images were acquired and analyzed with voxel-based morphometry. As hypothesized, the clusters of positive correlations between local volumes and VSC performance independent of g were found mainly in parietal areas, but also in pre- and postcentral regions, predominantly in the WM in males, whereas in females these correlations were located in parietal and superior temporal areas, predominantly in the GM. Our results suggest that VSC depends more strongly on parietal WM structures in males and on parietal GM structures in females. This sex difference might have to do with the increased axonal and decreased somatodendritic tissue in males relative to females. Whether such sex-specific implementations of the VSC network can be explained genetically as suggested in investigations into the Turner syndrome or as a result of structural neural plasticity upon different experience and usage remains to be shown.

Rapid treatment-induced brain changes in pediatric CRPS.

PubMed

Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa; Serrano, Paul; Pielech, Melissa; Prabhu, Sanjay; Becerra, Lino; Borsook, David

2016-03-01

To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex- and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray, two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation.

Structural Hippocampal Anomalies in a Schizophrenia Population Correlate with Navigation Performance on a Wayfinding Task

PubMed Central

Ledoux, Andrée-Anne; Boyer, Patrice; Phillips, Jennifer L.; Labelle, Alain; Smith, Andra; Bohbot, Véronique D.

2014-01-01

Episodic memory, related to the hippocampus, has been found to be impaired in schizophrenia. Further, hippocampal anomalies have also been observed in schizophrenia. This study investigated whether average hippocampal gray matter (GM) would differentiate performance on a hippocampus-dependent memory task in patients with schizophrenia and healthy controls. Twenty-one patients with schizophrenia and 22 control participants were scanned with an MRI while being tested on a wayfinding task in a virtual town (e.g., find the grocery store from the school). Regressions were performed for both groups individually and together using GM and performance on the wayfinding task. Results indicate that controls successfully completed the task more often than patients, took less time, and made fewer errors. Additionally, controls had significantly more hippocampal GM than patients. Poor performance was associated with a GM decrease in the right hippocampus for both groups. Within group regressions found an association between right hippocampi GM and performance in controls and an association between the left hippocampi GM and performance in patients. A second analysis revealed that different anatomical GM regions, known to be associated with the hippocampus, such as the parahippocampal cortex, amygdala, medial, and orbital prefrontal cortices, covaried with the hippocampus in the control group. Interestingly, the cuneus and cingulate gyrus also covaried with the hippocampus in the patient group but the orbital frontal cortex did not, supporting the hypothesis of impaired connectivity between the hippocampus and the frontal cortex in schizophrenia. These results present important implications for creating intervention programs aimed at measuring functional and structural changes in the hippocampus in schizophrenia. PMID:24672451

Structural hippocampal anomalies in a schizophrenia population correlate with navigation performance on a wayfinding task.

PubMed

Ledoux, Andrée-Anne; Boyer, Patrice; Phillips, Jennifer L; Labelle, Alain; Smith, Andra; Bohbot, Véronique D

2014-01-01

Episodic memory, related to the hippocampus, has been found to be impaired in schizophrenia. Further, hippocampal anomalies have also been observed in schizophrenia. This study investigated whether average hippocampal gray matter (GM) would differentiate performance on a hippocampus-dependent memory task in patients with schizophrenia and healthy controls. Twenty-one patients with schizophrenia and 22 control participants were scanned with an MRI while being tested on a wayfinding task in a virtual town (e.g., find the grocery store from the school). Regressions were performed for both groups individually and together using GM and performance on the wayfinding task. Results indicate that controls successfully completed the task more often than patients, took less time, and made fewer errors. Additionally, controls had significantly more hippocampal GM than patients. Poor performance was associated with a GM decrease in the right hippocampus for both groups. Within group regressions found an association between right hippocampi GM and performance in controls and an association between the left hippocampi GM and performance in patients. A second analysis revealed that different anatomical GM regions, known to be associated with the hippocampus, such as the parahippocampal cortex, amygdala, medial, and orbital prefrontal cortices, covaried with the hippocampus in the control group. Interestingly, the cuneus and cingulate gyrus also covaried with the hippocampus in the patient group but the orbital frontal cortex did not, supporting the hypothesis of impaired connectivity between the hippocampus and the frontal cortex in schizophrenia. These results present important implications for creating intervention programs aimed at measuring functional and structural changes in the hippocampus in schizophrenia.

Externalizing personality traits, empathy, and gray matter volume in healthy young drinkers

PubMed Central

Charpentier, Judith; Dzemidzic, Mario; West, John; Oberlin, Brandon G.; Eiler, William J.A.; Saykin, Andrew J.; Kareken, David A.

2016-01-01

Externalizing psychopathology has been linked to prefrontal abnormalities. While clinically diagnosed subjects show altered frontal gray matter, it is unknown if similar deficits relate to externalizing traits in non-clinical populations. We used voxel-based morphometry (VBM) to retrospectively analyze the cerebral gray matter volume of 176 young adult social to heavy drinkers (mean age= 24.0 ± 2.9, male= 83.5%) from studies of alcoholism risk. We hypothesized that prefrontal gray matter volume and externalizing traits would be correlated. Externalizing personality trait components— Boredom Susceptibility-Impulsivity (BS/IMP) and Empathy/Low Antisocial Behaviors (EMP/LASB)— were tested for correlations with gray matter partial volume estimates (gmPVE). Significantly large clusters (pFWE < 0.05, family-wise whole-brain corrected) of gmPVE correlated with EMP/LASB in dorsolateral and medial prefrontal regions, and in occipital cortex. BS/IMP did not correlate with gmPVE, but one scale of impulsivity (Eysenck I7) correlated positively with bilateral inferior frontal/orbitofrontal, and anterior insula gmPVE. In this large sample of community-dwelling young adults, antisocial behavior/low empathy corresponded with reduced prefrontal and occipital gray matter, while impulsivity correlated with increased inferior frontal and anterior insula cortical volume. These findings add to a literature indicating that externalizing personality features involve altered frontal architecture. PMID:26778367

Frequent Seizures Are Associated with a Network of Gray Matter Atrophy in Temporal Lobe Epilepsy with or without Hippocampal Sclerosis

PubMed Central

Coan, Ana C.; Campos, Brunno M.; Yasuda, Clarissa L.; Kubota, Bruno Y.; Bergo, Felipe PG.; Guerreiro, Carlos AM.; Cendes, Fernando

2014-01-01

Objective Patients with temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) have diffuse subtle gray matter (GM) atrophy detectable by MRI quantification analyses. However, it is not clear whether the etiology and seizure frequency are associated with this atrophy. We aimed to evaluate the occurrence of GM atrophy and the influence of seizure frequency in patients with TLE and either normal MRI (TLE-NL) or MRI signs of HS (TLE-HS). Methods We evaluated a group of 172 consecutive patients with unilateral TLE-HS or TLE-NL as defined by hippocampal volumetry and signal quantification (122 TLE-HS and 50 TLE-NL) plus a group of 82 healthy individuals. Voxel-based morphometry was performed with VBM8/SPM8 in 3T MRIs. Patients with up to three complex partial seizures and no generalized tonic-clonic seizures in the previous year were considered to have infrequent seizures. Those who did not fulfill these criteria were considered to have frequent seizures. Results Patients with TLE-HS had more pronounced GM atrophy, including the ipsilateral mesial temporal structures, temporal lobe, bilateral thalami and pre/post-central gyri. Patients with TLE-NL had more subtle GM atrophy, including the ipsilateral orbitofrontal cortex, bilateral thalami and pre/post-central gyri. Both TLE-HS and TLE-NL showed increased GM volume in the contralateral pons. TLE-HS patients with frequent seizures had more pronounced GM atrophy in extra-temporal regions than TLE-HS with infrequent seizures. Patients with TLE-NL and infrequent seizures had no detectable GM atrophy. In both TLE-HS and TLE-NL, the duration of epilepsy correlated with GM atrophy in extra-hippocampal regions. Conclusion Although a diffuse network GM atrophy occurs in both TLE-HS and TLE-NL, this is strikingly more evident in TLE-HS and in patients with frequent seizures. These findings suggest that neocortical atrophy in TLE is related to the ongoing seizures and epilepsy duration, while thalamic atrophy is more probably related to the original epileptogenic process. PMID:24475055

Longitudinal Brain Changes Associated with Prophylactic Cranial Irradiation in Lung Cancer.

PubMed

Simó, Marta; Vaquero, Lucía; Ripollés, Pablo; Gurtubay-Antolin, Ane; Jové, Josep; Navarro, Arturo; Cardenal, Felipe; Bruna, Jordi; Rodríguez-Fornells, Antoni

2016-04-01

The toxic effects of prophylactic cranial irradiation (PCI) and platinum-based chemotherapy on cognition in the lung cancer population have not yet been well established. In the present study we examined the longitudinal neuropsychological and brain structural changes observed in patients with lung cancer who were undergoing these treatments. Twenty-two patients with small cell lung cancer (SCLC) who underwent platinum-based chemotherapy and PCI were compared with two control groups: an age- and education-matched group of healthy controls (n = 21) and a group of patients with non-SCLC (NSCLC, n = 13) who underwent platinum-based chemotherapy. All groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging: T1-weighted and diffusion tensor imaging at baseline (before PCI for SCLC and chemotherapy for NSCLC) and at 3 months after treatment. T1 voxel-based morphometry and tract-based spatial statistics were used to analyze microstructural changes in gray matter (GM) and white matter (WM). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire was also completed. Patients with SCLC exhibited cognitive deterioration in verbal fluency over time. Structural magnetic resonance imaging showed decreases in GM at 3 months in the right subcortical regions, bilateral insular cortex, and superior temporal gyrus in patients with SCLC compared with both control groups. Additionally, patients with SCLC showed decreases in GM over time in the aforementioned regions plus in the right parahippocampal gyrus and hippocampus, together with changes in the WM microstructure of the entire corpus callosum. These changes had a limited impact on responses to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire, however. Patients with NSCLC showed no cognitive or brain structural differences after chemotherapy. This longitudinal study documents moderate neuropsychological deficits together with notable brain-specific structural changes (in GM and WM) in patients with SCLC after chemotherapy and PCI, suggesting that chemotherapy and especially PCI are associated with the development of cognitive and structural brain toxic effects. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

White matter lesion extension to automatic brain tissue segmentation on MRI.

PubMed

de Boer, Renske; Vrooman, Henri A; van der Lijn, Fedde; Vernooij, Meike W; Ikram, M Arfan; van der Lugt, Aad; Breteler, Monique M B; Niessen, Wiro J

2009-05-01

A fully automated brain tissue segmentation method is optimized and extended with white matter lesion segmentation. Cerebrospinal fluid (CSF), gray matter (GM) and white matter (WM) are segmented by an atlas-based k-nearest neighbor classifier on multi-modal magnetic resonance imaging data. This classifier is trained by registering brain atlases to the subject. The resulting GM segmentation is used to automatically find a white matter lesion (WML) threshold in a fluid-attenuated inversion recovery scan. False positive lesions are removed by ensuring that the lesions are within the white matter. The method was visually validated on a set of 209 subjects. No segmentation errors were found in 98% of the brain tissue segmentations and 97% of the WML segmentations. A quantitative evaluation using manual segmentations was performed on a subset of 6 subjects for CSF, GM and WM segmentation and an additional 14 for the WML segmentations. The results indicated that the automatic segmentation accuracy is close to the interobserver variability of manual segmentations.

Database of normal human cerebral blood flow measured by SPECT: II. Quantification of I-123-IMP studies with ARG method and effects of partial volume correction.

PubMed

Inoue, Kentaro; Ito, Hiroshi; Shidahara, Miho; Goto, Ryoi; Kinomura, Shigeo; Sato, Kazunori; Taki, Yasuyuki; Okada, Ken; Kaneta, Tomohiro; Fukuda, Hiroshi

2006-02-01

The limited spatial resolution of SPECT causes a partial volume effect (PVE) and can lead to the significant underestimation of regional tracer concentration in the small structures surrounded by a low tracer concentration, such as the cortical gray matter of an atrophied brain. The aim of the present study was to determine, using 123I-IMP and SPECT, normal CBF of elderly subjects with and without PVE correction (PVC), and to determine regional differences in the effect of PVC and their association with the regional tissue fraction of the brain. Quantitative CBF SPECT using 123I-IMP was performed in 33 healthy elderly subjects (18 males, 15 females, 54-74 years old) using the autoradiographic method. We corrected CBF for PVE using segmented MR images, and analyzed quantitative CBF and regional differences in the effect of PVC using tissue fractions of gray matter (GM) and white matter (WM) in regions of interest (ROIs) placed on the cortical and subcortical GM regions and deep WM regions. The mean CBF in GM-ROIs were 31.7 +/- 6.6 and 41.0 +/- 8.1 ml/100 g/min for males and females, and in WM-ROIs, 18.2 +/- 0.7 and 22.9 +/- 0.8 ml/100 g/min for males and females, respectively. The mean CBF in GM-ROIs after PVC were 50.9 +/- 12.8 and 65.8 +/- 16.1 ml/100 g/min for males and females, respectively. There were statistically significant differences in the effect of PVC among ROIs, but not between genders. The effect of PVC was small in the cerebellum and parahippocampal gyrus, and it was large in the superior frontal gyrus, superior parietal lobule and precentral gyrus. Quantitative CBF in GM recovered significantly, but did not reach values as high as those obtained by invasive methods or in the H2(15)O PET study that used PVC. There were significant regional differences in the effect of PVC, which were considered to result from regional differences in GM tissue fraction, which is more reduced in the frontoparietal regions in the atrophied brain of the elderly.

Regional Gray Matter Volumes Are Related to Concern About Falling in Older People: A Voxel-Based Morphometric Study.

PubMed

Tuerk, Carola; Zhang, Haobo; Sachdev, Perminder; Lord, Stephen R; Brodaty, Henry; Wen, Wei; Delbaere, Kim

2016-01-01

Concern about falling is common in older people. Various related psychological constructs as well as poor balance and slow gait have been associated with decreased gray matter (GM) volume in old age. The current study investigates the association between concern about falling and voxel-wise GM volumes. A total of 281 community-dwelling older people aged 70-90 years underwent structural magnetic resonance imaging. Concern about falling was assessed using Falls Efficacy Scale-International (FES-I). For each participant, voxel-wise GM volumes were generated with voxel-based morphometry and regressed on raw FES-I scores (p < .05 family-wise error corrected on cluster level). FES-I scores were negatively correlated with total brain volume (r = -.212; p ≤ .001), GM volume (r = -.210; p ≤ .001), and white matter volume (r = -.155; p ≤ .001). Voxel-based morphometry analysis revealed significant negative associations between FES-I and GM volumes of (i) left cerebellum and bilateral inferior occipital gyrus (voxels-in-cluster = 2,981; p < .001) and (ii) bilateral superior frontal gyrus and left supplementary motor area (voxels-in-cluster = 1,900; p = .004). Additional adjustment for vision and physical fall risk did not alter these associations. After adjustment for anxiety, only left cerebellum and bilateral inferior occipital gyrus remained negatively associated with FES-I scores (voxels-in-cluster = 2,426; p < .001). Adjustment for neuroticism removed all associations between FES-I and GM volumes. Our study findings show that concern about falling is negatively associated with brain volumes in areas important for emotional control and for motor control, executive functions and visual processing in a large sample of older men and women. Regression analyses suggest that these relationships were primarily accounted for by psychological factors (generalized anxiety and neuroticism) and not by physical fall risk or vision. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Investigating structural brain changes of dehydration using voxel-based morphometry.

PubMed

Streitbürger, Daniel-Paolo; Möller, Harald E; Tittgemeyer, Marc; Hund-Georgiadis, Margret; Schroeter, Matthias L; Mueller, Karsten

2012-01-01

Dehydration can affect the volume of brain structures, which might imply a confound in volumetric and morphometric studies of normal or diseased brain. Six young, healthy volunteers were repeatedly investigated using three-dimensional T(1)-weighted magnetic resonance imaging during states of normal hydration, hyperhydration, and dehydration to assess volume changes in gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). The datasets were analyzed using voxel-based morphometry (VBM), a widely used voxel-wise statistical analysis tool, FreeSurfer, a fully automated volumetric segmentation measure, and SIENAr a longitudinal brain-change detection algorithm. A significant decrease of GM and WM volume associated with dehydration was found in various brain regions, most prominently, in temporal and sub-gyral parietal areas, in the left inferior orbito-frontal region, and in the extra-nuclear region. Moreover, we found consistent increases in CSF, that is, an expansion of the ventricular system affecting both lateral ventricles, the third, and the fourth ventricle. Similar degrees of shrinkage in WM volume and increase of the ventricular system have been reported in studies of mild cognitive impairment or Alzheimer's disease during disease progression. Based on these findings, a potential confound in GM and WM or ventricular volume studies due to the subjects' hydration state cannot be excluded and should be appropriately addressed in morphometric studies of the brain.

Investigating Structural Brain Changes of Dehydration Using Voxel-Based Morphometry

PubMed Central

Streitbürger, Daniel-Paolo; Möller, Harald E.; Tittgemeyer, Marc; Hund-Georgiadis, Margret; Schroeter, Matthias L.; Mueller, Karsten

2012-01-01

Dehydration can affect the volume of brain structures, which might imply a confound in volumetric and morphometric studies of normal or diseased brain. Six young, healthy volunteers were repeatedly investigated using three-dimensional T 1-weighted magnetic resonance imaging during states of normal hydration, hyperhydration, and dehydration to assess volume changes in gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). The datasets were analyzed using voxel-based morphometry (VBM), a widely used voxel-wise statistical analysis tool, FreeSurfer, a fully automated volumetric segmentation measure, and SIENAr a longitudinal brain-change detection algorithm. A significant decrease of GM and WM volume associated with dehydration was found in various brain regions, most prominently, in temporal and sub-gyral parietal areas, in the left inferior orbito-frontal region, and in the extra-nuclear region. Moreover, we found consistent increases in CSF, that is, an expansion of the ventricular system affecting both lateral ventricles, the third, and the fourth ventricle. Similar degrees of shrinkage in WM volume and increase of the ventricular system have been reported in studies of mild cognitive impairment or Alzheime s disease during disease progression. Based on these findings, a potential confound in GM and WM or ventricular volume studies due to the subjects’ hydration state cannot be excluded and should be appropriately addressed in morphometric studies of the brain. PMID:22952926

Functional MRI registration with tissue-specific patch-based functional correlation tensors.

PubMed

Zhou, Yujia; Zhang, Han; Zhang, Lichi; Cao, Xiaohuan; Yang, Ru; Feng, Qianjin; Yap, Pew-Thian; Shen, Dinggang

2018-06-01

Population studies of brain function with resting-state functional magnetic resonance imaging (rs-fMRI) rely on accurate intersubject registration of functional areas. This is typically achieved through registration using high-resolution structural images with more spatial details and better tissue contrast. However, accumulating evidence has suggested that such strategy cannot align functional regions well because functional areas are not necessarily consistent with anatomical structures. To alleviate this problem, a number of registration algorithms based directly on rs-fMRI data have been developed, most of which utilize functional connectivity (FC) features for registration. However, most of these methods usually extract functional features only from the thin and highly curved cortical grey matter (GM), posing great challenges to accurate estimation of whole-brain deformation fields. In this article, we demonstrate that additional useful functional features can also be extracted from the whole brain, not restricted to the GM, particularly the white-matter (WM), for improving the overall functional registration. Specifically, we quantify local anisotropic correlation patterns of the blood oxygenation level-dependent (BOLD) signals using tissue-specific patch-based functional correlation tensors (ts-PFCTs) in both GM and WM. Functional registration is then performed by integrating the features from different tissues using the multi-channel large deformation diffeomorphic metric mapping (mLDDMM) algorithm. Experimental results show that our method achieves superior functional registration performance, compared with conventional registration methods. © 2018 Wiley Periodicals, Inc.

Dyslexia susceptibility genes influence brain atrophy in frontotemporal dementia.

PubMed

Paternicó, Donata; Premi, Enrico; Alberici, Antonella; Archetti, Silvana; Bonomi, Elisa; Gualeni, Vera; Gasparotti, Roberto; Padovani, Alessandro; Borroni, Barbara

2015-10-01

In this study, we evaluated whether variations within genes specifically associated with dyslexia, namely KIAA0319, DCDC2, and CNTNAP2, were associated with greater damage of language-related regions in patients with frontotemporal dementia (FTD) and primary progressive aphasia (PPA) in particular. A total of 118 patients with FTD, 84 with the behavioral variant of FTD (bvFTD) and 34 with PPA, underwent neuropsychological examination, genetic analyses, and brain MRI. KIAA0319 rs17243157 G/A, DCDC2 rs793842 A/G, and CNTNAP2 rs17236239 A/G genetic variations were assessed. Patients were grouped according to clinical phenotype and genotype status (GA/AA or GG). Gray matter (GM) and white matter (WM) differences were assessed by voxel-based morphometry and structural intercorrelation pattern analyses. Patients carrying KIAA0319 A* (GA or AA) showed greater GM and WM atrophy in the left middle and inferior temporal gyri, as compared with KIAA0319 GG (p < 0.001). The effect of KIAA0319 polymorphism was mainly reported in patients with PPA. In patients with PPA carrying at-risk polymorphism, temporal damage led to loss of interhemispheric and intrahemispheric GM and WM structural association. No effect of DCDC2 and CNTNAP2 was found. Genes involved in dyslexia susceptibility, such as KIAA0319, result in language network vulnerability in FTD, and in PPA in particular.

Normalization of Cortical Gray Matter Deficits in Nonpsychotic Siblings of Patients with Childhood-Onset Schizophrenia

ERIC Educational Resources Information Center

Mattai, Anand A.; Weisinger, Brian; Greenstein, Deanna; Stidd, Reva; Clasen, Liv; Miller, Rachel; Tossell, Julia W.; Rapoport, Judith L.; Gogtay, Nitin

2011-01-01

Objective: Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to…

Predicting Prodromal Alzheimer's Disease in Subjects with Mild Cognitive Impairment Using Machine Learning Classification of Multimodal Multicenter Diffusion-Tensor and Magnetic Resonance Imaging Data.

PubMed

Dyrba, Martin; Barkhof, Frederik; Fellgiebel, Andreas; Filippi, Massimo; Hausner, Lucrezia; Hauenstein, Karlheinz; Kirste, Thomas; Teipel, Stefan J

2015-01-01

Alzheimer's disease (AD) patients show early changes in white matter (WM) structural integrity. We studied the use of diffusion tensor imaging (DTI) in assessing WM alterations in the predementia stage of mild cognitive impairment (MCI). We applied a Support Vector Machine (SVM) classifier to DTI and volumetric magnetic resonance imaging data from 35 amyloid-β42 negative MCI subjects (MCI-Aβ42-), 35 positive MCI subjects (MCI-Aβ42+), and 25 healthy controls (HC) retrieved from the European DTI Study on Dementia. The SVM was applied to DTI-derived fractional anisotropy, mean diffusivity (MD), and mode of anisotropy (MO) maps. For comparison, we studied classification based on gray matter (GM) and WM volume. We obtained accuracies of up to 68% for MO and 63% for GM volume when it came to distinguishing between MCI-Aβ42- and MCI-Aβ42+. When it came to separating MCI-Aβ42+ from HC we achieved an accuracy of up to 77% for MD and a significantly lower accuracy of 68% for GM volume. The accuracy of multimodal classification was not higher than the accuracy of the best single modality. Our results suggest that DTI data provide better prediction accuracy than GM volume in predementia AD. Copyright © 2015 by the American Society of Neuroimaging.

Gray matter-changes and correlates of disease severity in schizophrenia: a statistical parametric mapping study.

PubMed

Wilke, M; Kaufmann, C; Grabner, A; Pütz, B; Wetter, T C; Auer, D P

2001-05-01

Voxel-based morphometry has recently been used successfully to detect gray matter volume reductions in schizophrenic patients. The aim of the present study was to confirm the findings on gray-matter changes and to complement these by applying the methodology to CSF-differences. Also, we wanted to determine whether a correlation exists between a clinically defined parameter of disease severity and brain morphology in schizophrenic patients. We investigated 48 schizophrenic patients and compared them with 48 strictly age- and sex-matched controls. High-resolution whole-brain MR-images were segmented and analyzed using SPM99. In a further analysis, the covariate effect of the global assessment of functioning-score (GAF) was calculated. Main findings were (i) left-dominant frontal, temporal, and insular GM-reductions and (ii) GM-increases in schizophrenic patients in the right basal ganglia and bilaterally in the superior cerebellum; (iii) CSF-space increases in patients complementary to some GM-reductions; (iv) a correlation between the GAF-score and local GM-volume in the left inferior frontal and inferior parietal lobe of schizophrenic patients. This study confirms and extends some earlier findings on GM-reduction and detected distinct GM-increases in schizophrenic patients. These changes were corroborated by complementary CSF-increases. Most importantly, a correlation could be established between two particular gray matter-regions and the overall disease severity, with more severely ill patients displaying a local GM-deficit. These findings may be of potentially large importance for both the future interpretation and design of neuroimaging studies in schizophrenia and the further elucidation of possible pathophysiological processes occurring in this disease. Copyright 2001 Academic Press.

175.4 The Relationship of Aging and Inflammatory Biomarkers to Gray Matter Volume and Episodic Memory Performance in Schizophrenia: Evidence of Pathological Accelerated Aging

PubMed Central

Gama, Clarissa

2017-01-01

Abstract Background: Schizophrenia (SZ) is associated with increased somatic morbidity and mortality, in addition to cognitive impairments similar to those seen in normal aging, which may suggest that pathological accelerated aging occurs in SZ. Therefore, we aim to evaluate the relationships of age, telomere length (TL) and CCL11 (aging and inflammatory biomarkers), and gray matter volumes (GM) to episodic memory performance in individuals with SZ compared to healthy controls (HC). Methods: 112 participants (48 SZ and 64 HC) underwent clinical and memory assessments, structural MRI, and had their peripheral blood drawn for biomarkers analysis. Comparisons of group means and correlations were performed. Results: Participants with SZ had decreased TL and GM residual volume, increased CCL11, and worse memory performance compared to HC. In SZ, shorter TL was related to increased CCL11, and they were both related to reduced GM residual volume, all of which were related to worse memory performance. Older age was only associated with reduced GM, but longer duration of illness was related with all the aforementioned variables. Younger age of disease onset was related with increased CCL11 levels and worse memory performance. In HC, there were no significant correlations except for between memory and GM. Conclusion: Our results are consistent with accelerated aging in SZ. These results may indicate that it is not age itself, but the impact of the disease associated with a pathological accelerated aging that leads to impaired outcomes in SZ. Akira Sawa, johns Hopkins University, Johns Hopkins Hospital and Medical Institutions

Short-Term Plasticity of Gray Matter Associated with Leptin Deficiency and Replacement

PubMed Central

Berman, Steven M.; Chakrapani, Shruthi; Delibasi, Tuncay; Monterosso, John; Erol, H. Kutlu; Paz-Filho, Gilberto; Wong, Ma-Li; Licinio, Julio

2011-01-01

Context: Leptin affects neurogenesis, neuronal growth, and viability. We previously reported that leptin supplementation increased gray matter (GM) concentration in the anterior cingulate gyrus (ACG), cerebellum, and inferior parietal lobule, areas that are also involved in food intake. Objective: The aim of this study was to report the changes in brain structure at different states of leptin supplementation. Design: We conducted a nonrandomized trial. Setting and Patients: We studied three adults with congenital leptin deficiency due to a mutation in the leptin gene. Intervention: Patients received treatment with recombinant methionyl human leptin, with annual 11- to 36-d periods of treatment withholding followed by treatment restoration over 3 yr. Main Outcome Measures: GM concentration (by voxel-based morphometry analysis of magnetic resonance scans) was correlated with body mass index (BMI) and leptin supplementation. Results: Annually withholding leptin supplementation for several weeks increased BMI and reversed the original effects of leptin in the cerebellum and ACG. The changes in the ACG were consistent with an indirect effect of leptin mediated through increased BMI. In the cerebellum, where leptin receptors are most dense, GM changes appeared to be direct effects of leptin. Leptin restoration did not lead to recovery of GM in the short term but did lead to an unexpected GM increase in the posterior half of the left thalamus, particularly the pulvinar nucleus. Conclusion: These findings provide the first in vivo evidence of remarkably plastic, reversible, and regionally specific effects of leptin on human brain morphology. They suggest that leptin may have therapeutic value in modulating plasticity-dependent brain functions. PMID:21613360

Sex differences of gray matter morphology in cortico-limbic-striatal neural system in major depressive disorder.

PubMed

Kong, Lingtao; Chen, Kaiyuan; Womer, Fay; Jiang, Wenyan; Luo, Xingguang; Driesen, Naomi; Liu, Jie; Blumberg, Hilary; Tang, Yanqing; Xu, Ke; Wang, Fei

2013-06-01

Sex differences are observed in both epidemiological and clinical aspects of major depressive disorder (MDD). The cortico-limbic-striatal neural system, including the prefrontal cortex, amygdala, hippocampus, and striatum, have shown sexually dimorphic morphological features and have been implicated in the dysfunctional regulation of mood and emotion in MDD. In this study, we utilized a whole-brain, voxel-based approach to examine sex differences in the regional distribution of gray matter (GM) morphological abnormalities in medication-naïve participants with MDD. Participants included 29 medication-naïve individuals with MDD (16 females and 13 males) and 33 healthy controls (HC) (17 females and 16 males). Gray matter morphology of the cortico-limbic-striatal neural system was examined using voxel-based morphometry analyzes of high-resolution structural magnetic resonance imaging scans. The main effect of diagnosis and interaction effect of diagnosis by sex on GM morphology were statistically significant (p < 0.05, corrected) in the left ventral prefrontal cortex, right amygdala, right hippocampus and bilateral caudate when comparing the MDD and HC groups. Posthoc analyzes showed that females with MDD had significant GM decreases in limbic regions (p < 0.05, corrected), compared to female HC; while males with MDD demonstrated significant GM reduction in striatal regions, (p < 0.05, corrected), compared to HC males. The observed sex-related patterns of abnormalities within the cortico-limbic-strial neural system, such as predominant prefrontal-limbic abnormalities in MDD females vs. predominant prefrontal-striatal abnormalities in MDD males, suggest differences in neural circuitry that may mediate sex differences in the clinical presentation of MDD and potential targets for sex-differentiated treatment of the disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dyslexia and voxel-based morphometry: correlations between five behavioural measures of dyslexia and gray and white matter volumes.

PubMed

Tamboer, Peter; Scholte, H Steven; Vorst, Harrie C M

2015-10-01

In voxel-based morphometry studies of dyslexia, the relation between causal theories of dyslexia and gray matter (GM) and white matter (WM) volume alterations is still under debate. Some alterations are consistently reported, but others failed to reach significance. We investigated GM alterations in a large sample of Dutch students (37 dyslexics and 57 non-dyslexics) with two analyses: group differences in local GM and total GM and WM volume and correlations between GM and WM volumes and five behavioural measures. We found no significant group differences after corrections for multiple comparisons although total WM volume was lower in the group of dyslexics when age was partialled out. We presented an overview of uncorrected clusters of voxels (p < 0.05, cluster size k > 200) with reduced or increased GM volume. We found four significant correlations between factors of dyslexia representing various behavioural measures and the clusters found in the first analysis. In the whole sample, a factor related to performances in spelling correlated negatively with GM volume in the left posterior cerebellum. Within the group of dyslexics, a factor related to performances in Dutch-English rhyme words correlated positively with GM volume in the left and right caudate nucleus and negatively with increased total WM volume. Most of our findings were in accordance with previous reports. A relatively new finding was the involvement of the caudate nucleus. We confirmed the multiple cognitive nature of dyslexia and suggested that experience greatly influences anatomical alterations depending on various subtypes of dyslexia, especially in a student sample.

Are morphological changes necessary to mediate the therapeutic effects of electroconvulsive therapy?

PubMed

Nickl-Jockschat, Thomas; Palomero Gallagher, Nicola; Kumar, Vinod; Hoffstaedter, Felix; Brügmann, Elisabeth; Habel, Ute; Eickhoff, Simon B; Grözinger, Michael

2016-04-01

The neurotrophic hypothesis has become the favorite model to explain the antidepressant properties of electroconvulsive therapy (ECT). It is based on the assumption that a restoration of previously defective neural networks drives therapeutic effects. Recent data in rather young patients suggest that neurotrophic effects of ECT might be detectable by diffusion tensor imaging. We here aimed to investigate whether the therapeutic response to ECT necessarily goes along with mesoscopic effects in gray matter (GM) or white matter (WM) in our patients in advanced age. Patients (n = 21, 15 males and 7 females) suffering from major depressive disorder were treated with ECT. Before the start of treatment and after the completion of the index series, they underwent magnetic resonance imaging, including a diffusion-weighed sequence. We used voxel-based morphometry to assess GM changes and tract-based spatial statistics and an SPM-based whole-brain analysis to detect WM changes in the course of treatment. Patients significantly improved clinically during the course of ECT. This was, however, not accompanied by GM or WM changes. This result challenges the notion that mesoscopic brain structure changes are an obligatory prerequisite for the antidepressant effects of ECT.

Brain gray matter phenotypes across the psychosis dimension

PubMed Central

Ivleva, Elena I.; Bidesi, Anup S.; Thomas, Binu P.; Meda, Shashwath A.; Francis, Alan; Moates, Amanda F.; Witte, Bradley; Keshavan, Matcheri S.; Tamminga, Carol A.

2013-01-01

This study sought to examine whole brain and regional gray matter (GM) phenotypes across the schizophrenia (SZ)–bipolar disorder psychosis dimension using voxel-based morphometry (VBM 8.0 with DARTEL segmentation/normalization) and semi-automated regional parcellation, FreeSurfer (FS 4.3.1/64 bit). 3T T1 MPRAGE images were acquired from 19 volunteers with schizophrenia (SZ), 16 with schizoaffective disorder (SAD), 17 with psychotic bipolar I disorder (BD-P) and 10 healthy controls (HC). Contrasted with HC, SZ showed extensive cortical GM reductions, most pronounced in fronto-temporal regions; SAD had GM reductions overlapping with SZ, albeit less extensive; and BD-P demonstrated no GM differences from HC. Within the psychosis dimension, BD-P showed larger volumes in fronto-temporal and other cortical/subcortical regions compared with SZ, whereas SAD showed intermediate GM volumes. The two volumetric methodologies, VBM and FS, revealed highly overlapping results for cortical GM, but partially divergent results for subcortical volumes (basal ganglia, amygdala). Overall, these findings suggest that individuals across the psychosis dimension show both overlapping and unique GM phenotypes: decreased GM, predominantly in fronto-temporal regions, is characteristic of SZ but not of psychotic BD-P, whereas SAD display GM deficits overlapping with SZ, albeit less extensive. PMID:23177922

Brain gray matter phenotypes across the psychosis dimension.

PubMed

Ivleva, Elena I; Bidesi, Anup S; Thomas, Binu P; Meda, Shashwath A; Francis, Alan; Moates, Amanda F; Witte, Bradley; Keshavan, Matcheri S; Tamminga, Carol A

2012-10-30

This study sought to examine whole brain and regional gray matter (GM) phenotypes across the schizophrenia (SZ)-bipolar disorder psychosis dimension using voxel-based morphometry (VBM 8.0 with DARTEL segmentation/normalization) and semi-automated regional parcellation, FreeSurfer (FS 4.3.1/64 bit). 3T T1 MPRAGE images were acquired from 19 volunteers with schizophrenia (SZ), 16 with schizoaffective disorder (SAD), 17 with psychotic bipolar I disorder (BD-P) and 10 healthy controls (HC). Contrasted with HC, SZ showed extensive cortical GM reductions, most pronounced in fronto-temporal regions; SAD had GM reductions overlapping with SZ, albeit less extensive; and BD-P demonstrated no GM differences from HC. Within the psychosis dimension, BD-P showed larger volumes in fronto-temporal and other cortical/subcortical regions compared with SZ, whereas SAD showed intermediate GM volumes. The two volumetric methodologies, VBM and FS, revealed highly overlapping results for cortical GM, but partially divergent results for subcortical volumes (basal ganglia, amygdala). Overall, these findings suggest that individuals across the psychosis dimension show both overlapping and unique GM phenotypes: decreased GM, predominantly in fronto-temporal regions, is characteristic of SZ but not of psychotic BD-P, whereas SAD display GM deficits overlapping with SZ, albeit less extensive. Published by Elsevier Ireland Ltd.

Magnetic resonance brain tissue segmentation based on sparse representations

NASA Astrophysics Data System (ADS)

Rueda, Andrea

2015-12-01

Segmentation or delineation of specific organs and structures in medical images is an important task in the clinical diagnosis and treatment, since it allows to characterize pathologies through imaging measures (biomarkers). In brain imaging, segmentation of main tissues or specific structures is challenging, due to the anatomic variability and complexity, and the presence of image artifacts (noise, intensity inhomogeneities, partial volume effect). In this paper, an automatic segmentation strategy is proposed, based on sparse representations and coupled dictionaries. Image intensity patterns are singly related to tissue labels at the level of small patches, gathering this information in coupled intensity/segmentation dictionaries. This dictionaries are used within a sparse representation framework to find the projection of a new intensity image onto the intensity dictionary, and the same projection can be used with the segmentation dictionary to estimate the corresponding segmentation. Preliminary results obtained with two publicly available datasets suggest that the proposal is capable of estimating adequate segmentations for gray matter (GM) and white matter (WM) tissues, with an average overlapping of 0:79 for GM and 0:71 for WM (with respect to original segmentations).

Fully automatic detection of deep white matter T1 hypointense lesions in multiple sclerosis

NASA Astrophysics Data System (ADS)

Spies, Lothar; Tewes, Anja; Suppa, Per; Opfer, Roland; Buchert, Ralph; Winkler, Gerhard; Raji, Alaleh

2013-12-01

A novel method is presented for fully automatic detection of candidate white matter (WM) T1 hypointense lesions in three-dimensional high-resolution T1-weighted magnetic resonance (MR) images. By definition, T1 hypointense lesions have similar intensity as gray matter (GM) and thus appear darker than surrounding normal WM in T1-weighted images. The novel method uses a standard classification algorithm to partition T1-weighted images into GM, WM and cerebrospinal fluid (CSF). As a consequence, T1 hypointense lesions are assigned an increased GM probability by the standard classification algorithm. The GM component image of a patient is then tested voxel-by-voxel against GM component images of a normative database of healthy individuals. Clusters (≥0.1 ml) of significantly increased GM density within a predefined mask of deep WM are defined as lesions. The performance of the algorithm was assessed on voxel level by a simulation study. A maximum dice similarity coefficient of 60% was found for a typical T1 lesion pattern with contrasts ranging from WM to cortical GM, indicating substantial agreement between ground truth and automatic detection. Retrospective application to 10 patients with multiple sclerosis demonstrated that 93 out of 96 T1 hypointense lesions were detected. On average 3.6 false positive T1 hypointense lesions per patient were found. The novel method is promising to support the detection of hypointense lesions in T1-weighted images which warrants further evaluation in larger patient samples.

Increased microglial catalase activity in multiple sclerosis grey matter.

PubMed

Gray, Elizabeth; Kemp, Kevin; Hares, Kelly; Redondo, Julianna; Rice, Claire; Scolding, Neil; Wilkins, Alastair

2014-04-22

Chronic demyelination, on-going inflammation, axonal loss and grey matter neuronal injury are likely pathological processes that contribute to disease progression in multiple sclerosis (MS). Although the precise contribution of each process and their aetiological substrates is not fully known, recent evidence has implicated oxidative damage as a major cause of tissue injury in MS. The degree of tissue injury caused by oxidative molecules, such as reactive oxygen species (ROS), is balanced by endogenous anti-oxidant enzymes which detoxify ROS. Understanding endogenous mechanisms which protect the brain against oxidative injury in MS is important, since enhancing anti-oxidant responses is a major therapeutic strategy for preventing irreversible tissue injury in the disease. Our aims were to determine expression and activity levels of the hydrogen peroxide-reducing enzyme catalase in MS grey matter (GM). In MS GM, a catalase enzyme activity was elevated compared to control GM. We measured catalase protein expression by immune dot-blotting and catalase mRNA by a real-time polymerase chain reaction (RT-PCR). Protein analysis studies showed a strong positive correlation between catalase and microglial marker IBA-1 in MS GM. In addition, calibration of catalase mRNA level with reference to the microglial-specific transcript AIF-1 revealed an increase in this transcript in MS. This was reflected by the extent of HLA-DR immunolabeling in MS GM which was significantly elevated compared to control GM. Collectively, these observations provide evidence that microglial catalase activity is elevated in MS grey matter and may be an important endogenous anti-oxidant defence mechanism in MS. Copyright © 2014 Elsevier B.V. All rights reserved.

White Matter Tract Injury is Associated with Deep Gray Matter Iron Deposition in Multiple Sclerosis.

PubMed

Bergsland, Niels; Tavazzi, Eleonora; Laganà, Maria Marcella; Baglio, Francesca; Cecconi, Pietro; Viotti, Stefano; Zivadinov, Robert; Baselli, Giuseppe; Rovaris, Marco

2017-01-01

With respect to healthy controls (HCs), increased iron concentrations in the deep gray matter (GM) and decreased white matter (WM) integrity are common findings in multiple sclerosis (MS) patients. The association between these features of the disease remains poorly understood. We investigated the relationship between deep iron deposition in the deep GM and WM injury in associated fiber tracts in MS patients. Sixty-six MS patients (mean age 50.0 years, median Expanded Disability Status Scale 5.25, mean disease duration 19.1 years) and 29 HCs, group matched for age and sex were imaged on a 1.5T scanner. Susceptibility-weighted imaging and diffusion tensor imaging (DTI) were used for assessing high-pass filtered phase values in the deep GM and normal appearing WM (NAWM) integrity in associated fiber tracts, respectively. Correlation analyses investigated the associations between filtered phase values (suggestive of iron content) and WM damage. Areas indicative of increased iron levels were found in the left and right caudates as well as in the left thalamus. MS patients presented with decreased DTI-derived measures of tissue integrity in the associated WM tracts. Greater mean, axial and radial diffusivities were associated with increased iron levels in all three GM areas (r values .393 to .514 with corresponding P values .003 to <.0001). Global NAWM diffusivity measures were not related to mean filtered phase values within the deep GM. Increased iron concentration in the deep GM is associated with decreased tissue integrity of the connected WM in MS patients. Copyright © 2016 by the American Society of Neuroimaging.

Grey matter alterations in migraine: A systematic review and meta-analysis.

PubMed

Jia, Zhihua; Yu, Shengyuan

2017-01-01

To summarize and meta-analyze studies on changes in grey matter (GM) in patients with migraine. We aimed to determine whether there are concordant structural changes in the foci, whether structural changes are concordant with functional changes, and provide further understanding of the anatomy and biology of migraine. We searched PubMed and Embase for relevant articles published between January 1985 and November 2015, and examined the references within relevant primary articles. Following exclusion of unsuitable studies, meta-analysis were performed using activation likelihood estimation (ALE). Eight clinical studies were analyzed for structural changes, containing a total of 390 subjects (191 patients and 199 controls). Five functional studies were enrolled, containing 93 patients and 96 controls. ALE showed that the migraineurs had concordant decreases in the GM volume (GMV) in the bilateral inferior frontal gyri, the right precentral gyrus, the left middle frontal gyrus and the left cingulate gyrus. GMV decreases in right claustrum, left cingulated gyrus, right anterior cingulate, amygdala and left parahippocampal gyrus are related to estimated frequency of headache attack . Activation was found in the somatosensory, cingulate, limbic lobe, basal ganglia and midbrain in migraine patients. GM changes in migraineurs may indicate the mechanism of pain processing and associated symptoms. Changes in the frontal gyrus may predispose a person to pain conditions. The limbic regions may be accumulated damage due to the repetitive occurrence of pain-related processes. Increased activation in precentral gyrus and cingulate opposed to GMV decrease might suggest increased effort duo to disorganization of these areas and/or the use of compensatory strategies involving pain processing in migraine. Knowledge of these structural and functional changes may be useful for monitoring disease progression as well as for therapeutic interventions.

Structural neuroplasticity in the sensorimotor network of professional female ballet dancers.

PubMed

Hänggi, Jürgen; Koeneke, Susan; Bezzola, Ladina; Jäncke, Lutz

2010-08-01

Evidence suggests that motor, sensory, and cognitive training modulates brain structures involved in a specific practice. Functional neuroimaging revealed key brain structures involved in dancing such as the putamen and the premotor cortex. Intensive ballet dance training was expected to modulate the structures of the sensorimotor network, for example, the putamen, premotor cortex, supplementary motor area (SMA), and the corticospinal tracts. We investigated gray (GM) and white matter (WM) volumes, fractional anisotropy (FA), and mean diffusivity (MD) using magnetic resonance-based morphometry and diffusion tensor imaging in 10 professional female ballet dancers compared with 10 nondancers. In dancers compared with nondancers, decreased GM volumes were observed in the left premotor cortex, SMA, putamen, and superior frontal gyrus, and decreased WM volumes in both corticospinal tracts, both internal capsules, corpus callosum, and left anterior cingulum. FA was lower in the WM underlying the dancers' left and right premotor cortex. There were no significant differences in MD between the groups. Age of dance commencement was negatively correlated with GM and WM volume in the right premotor cortex and internal capsule, respectively, and positively correlated with WM volume in the left precentral gyrus and corpus callosum. Results were not influenced by the significantly lower body mass index of the dancers. The present findings complement the results of functional imaging studies in experts that revealed reduced neural activity in skilled compared with nonskilled subjects. Reductions in brain activity are accompanied by local decreases in GM and WM volumes and decreased FA. 2009 Wiley-Liss, Inc.

Dynamics of organic matter, nitrogen and phosphorus removal and their interactions in a tidal operated constructed wetland.

PubMed

Li, Chunyan; Wu, Shubiao; Dong, Renjie

2015-03-15

This paper demonstrates the potential of tidal flow operated constructed wetland application for the removal dynamics of organic matter, nitrogen and phosphorus. Near-complete removal of organic matter was achieved with a constant removal efficiency of 95%, irrespective of TOC influent loadings ranged from 10 g/m(2) · d to 700 g/m(2) · d. High NH4(+)-N removal at 95% efficiency under influent loading of 17 g/m(2) · d, was stably obtained and was not negatively influenced by increasing influent organic carbon loading rate. Increased influent TOC loading (350 g/m(2) · d to 700 g/m(2) · d) significantly enhanced denitrification capacity and increased TN removal from 30% to 95%. Under tidal flow operation, a higher carbon supply (C/N = 20) for complete TN removal was demonstrated as comparing to that observed in traditional CWs approaches. In addition, the removal of phosphorus was strongly influenced by organic loadings. However, further investigations are needed to elucidate the detailed mechanism that would explain the role of organic loading in phosphorus removal. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association of GSK3beta polymorphisms with brain structural changes in major depressive disorder.

PubMed

Inkster, Becky; Nichols, Thomas E; Saemann, Philipp G; Auer, Dorothee P; Holsboer, Florian; Muglia, Pierandrea; Matthews, Paul M

2009-07-01

Indirect evidence suggests that the glycogen synthase kinase-3beta (GSK3beta) gene might be implicated in major depressive disorder (MDD). We evaluated 15 GSK3beta single-nucleotide polymorphisms (SNPs) to test for associations with regional gray matter (GM) volume differences in patients with recurrent MDD. We then used the defined regions of interest based on significant associations to test for MDD x genotype interactions by including a matched control group without any psychiatric disorder, including MDD. General linear model with nonstationary cluster-based inference. Munich, Germany. Patients with recurrent MDD (n = 134) and age-, sex-, and ethnicity-matched healthy controls (n = 143). Associations between GSK3beta polymorphisms and regional GM volume differences. Variation in GM volume was associated with GSK3beta polymorphisms; the most significant associations were found for rs6438552, a putative functional intronic SNP that showed 3 significant GM clusters in the right and left superior temporal gyri and the right hippocampus (P < .001, P = .02, and P = .02, respectively, corrected for multiple comparisons across the whole brain). Similar results were obtained with rs12630592, an SNP in high linkage disequilibrium. A significant SNP x MDD status interaction was observed for the effect on GM volumes in the right hippocampus and superior temporal gyri (P < .001 and P = .01, corrected, respectively). The GSK3beta gene may have a role in determining regional GM volume differences of the right hippocampus and bilateral superior temporal gyri. The association between genotype and brain structure was specific to the patients with MDD, suggesting that GSK3beta genotypes might interact with MDD status. We speculate that this is a consequence of regional neocortical, glial, or neuronal growth or survival. In considering core cognitive features of MDD, the association of GSK3beta polymorphisms with structural variation in the temporal lobe and hippocampus is of particular interest in the context of other evidence for structural and functional abnormalities in the hippocampi of patients with MDD.

Structural Brain Correlates Associated with Professional Handball Playing

PubMed Central

Hänggi, Jürgen; Langer, Nicolas; Lutz, Kai; Birrer, Karin; Mérillat, Susan; Jäncke, Lutz

2015-01-01

Background There is no doubt that good bimanual performance is very important for skilled handball playing. The control of the non-dominant hand is especially demanding since efficient catching and throwing needs both hands. Methodology/Hypotheses We investigated training-induced structural neuroplasticity in professional handball players using several structural neuroimaging techniques and analytic approaches and also provide a review of the literature about sport-induced structural neuroplastic alterations. Structural brain adaptations were expected in regions relevant for motor and somatosensory processing such as the grey matter (GM) of the primary/secondary motor (MI/supplementary motor area, SMA) and somatosensory cortex (SI/SII), basal ganglia, thalamus, and cerebellum and in the white matter (WM) of the corticospinal tract (CST) and corpus callosum, stronger in brain regions controlling the non-dominant left hand. Results Increased GM volume in handball players compared with control subjects were found in the right MI/SI, bilateral SMA/cingulate motor area, and left intraparietal sulcus. Fractional anisotropy (FA) and axial diffusivity were increased within the right CST in handball players compared with control women. Age of handball training commencement correlated inversely with GM volume in the right and left MI/SI and years of handball training experience correlated inversely with radial diffusivity in the right CST. Subcortical structures tended to be larger in handball players. The anatomical measures of the brain regions associated with handball playing were positively correlated in handball players, but not interrelated in control women. Discussion/Conclusion Training-induced structural alterations were found in the somatosensory-motor network of handball players, more pronounced in the right hemisphere controlling the non-dominant left hand. Correlations between handball training-related measures and anatomical differences suggest neuroplastic adaptations rather than a genetic predisposition for a ball playing affinity. Investigations of neuroplasticity specifically in sportsmen might help to understand the neural mechanisms of expertise in general. PMID:25915906

Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord

PubMed Central

Vue, Tou Yia; Kim, Euiseok J.; Parras, Carlos M.; Guillemot, Francois; Johnson, Jane E.

2014-01-01

Glia constitute the majority of cells in the mammalian central nervous system and are crucial for neurological function. However, there is an incomplete understanding of the molecular control of glial cell development. We find that the transcription factor Ascl1 (Mash1), which is best known for its role in neurogenesis, also functions in both astrocyte and oligodendrocyte lineages arising in the mouse spinal cord at late embryonic stages. Clonal fate mapping in vivo reveals heterogeneity in Ascl1-expressing glial progenitors and shows that Ascl1 defines cells that are restricted to either gray matter (GM) or white matter (WM) as astrocytes or oligodendrocytes. Conditional deletion of Ascl1 post-neurogenesis shows that Ascl1 is required during oligodendrogenesis for generating the correct numbers of WM but not GM oligodendrocyte precursor cells, whereas during astrocytogenesis Ascl1 functions in balancing the number of dorsal GM protoplasmic astrocytes with dorsal WM fibrous astrocytes. Thus, in addition to its function in neurogenesis, Ascl1 marks glial progenitors and controls the number and distribution of astrocytes and oligodendrocytes in the GM and WM of the spinal cord. PMID:25249462

Large-scale brain network abnormalities in Huntington's disease revealed by structural covariance.

PubMed

Minkova, Lora; Eickhoff, Simon B; Abdulkadir, Ahmed; Kaller, Christoph P; Peter, Jessica; Scheller, Elisa; Lahr, Jacob; Roos, Raymund A; Durr, Alexandra; Leavitt, Blair R; Tabrizi, Sarah J; Klöppel, Stefan

2016-01-01

Huntington's disease (HD) is a progressive neurodegenerative disorder that can be diagnosed with certainty decades before symptom onset. Studies using structural MRI have identified grey matter (GM) loss predominantly in the striatum, but also involving various cortical areas. So far, voxel-based morphometric studies have examined each brain region in isolation and are thus unable to assess the changes in the interrelation of brain regions. Here, we examined the structural covariance in GM volumes in pre-specified motor, working memory, cognitive flexibility, and social-affective networks in 99 patients with manifest HD (mHD), 106 presymptomatic gene mutation carriers (pre-HD), and 108 healthy controls (HC). After correction for global differences in brain volume, we found that increased GM volume in one region was associated with increased GM volume in another. When statistically comparing the groups, no differences between HC and pre-HD were observed, but increased positive correlations were evident for mHD, relative to pre-HD and HC. These findings could be explained by a HD-related neuronal loss heterogeneously affecting the examined network at the pre-HD stage, which starts to dominate structural covariance globally at the manifest stage. Follow-up analyses identified structural connections between frontoparietal motor regions to be linearly modified by disease burden score (DBS). Moderator effects of disease load burden became significant at a DBS level typically associated with the onset of unequivocal HD motor signs. Together with existing findings from functional connectivity analyses, our data indicates a critical role of these frontoparietal regions for the onset of HD motor signs. © 2015 Wiley Periodicals, Inc.

Gray matter anomalies in pedophiles with and without a history of child sexual offending

PubMed Central

Schiffer, B; Amelung, T; Pohl, A; Kaergel, C; Tenbergen, G; Gerwinn, H; Mohnke, S; Massau, C; Matthias, W; Weiß, S; Marr, V; Beier, K M; Walter, M; Ponseti, J; Krüger, T H C; Schiltz, K; Walter, H

2017-01-01

Pedophilia is a psychiatric disorder that is inter-related with but distinct from child sexual offending (CSO). Neural alterations reportedly contribute to both pedophilia and CSO, but until now, no study has distinguished the brain structural anomalies associated with pedophilia from those specifically associated with CSO in pedophilic men. Using high-resolution T1-weighted brain images and voxel-based morphometry, we analyzed the gray matter (GM) volume of the following 219 men recruited at four acquisition sites in Germany: 58 pedophiles with a history of CSO, 60 pedophiles without any history of CSO and 101 non-pedophilic, non-offending controls to control for the effects of age, education level, verbal IQ, sexual orientation and the acquisition site. Although there were no differences in the relative GM volume of the brain specifically associated with pedophilia, statistical parametric maps revealed a highly significant and CSO-related pattern of above vs below the ‘normal’ GM volume in the right temporal pole, with non-offending pedophiles exhibiting larger volumes than offending pedophiles. Moreover, regression analysis revealed that the lower GM volume of the dorsomedial prefrontal or anterior cingulate cortex was associated with a higher risk of re-offending in pedophilic child molesters. We believe our data provide the first evidence that CSO in pedophilia rather than pedophilia alone is associated with GM anomalies and thus shed new light on the results of previous studies on this topic. These results indicate the need for new neurobehavioral theories on pedophilia and CSO and may be potentially useful for treatment or prevention approaches that aim to reduce the risk of (re)offending in pedophilia. PMID:28509903

Gray matter anomalies in pedophiles with and without a history of child sexual offending.

PubMed

Schiffer, B; Amelung, T; Pohl, A; Kaergel, C; Tenbergen, G; Gerwinn, H; Mohnke, S; Massau, C; Matthias, W; Weiß, S; Marr, V; Beier, K M; Walter, M; Ponseti, J; Krüger, T H C; Schiltz, K; Walter, H

2017-05-16

Pedophilia is a psychiatric disorder that is inter-related with but distinct from child sexual offending (CSO). Neural alterations reportedly contribute to both pedophilia and CSO, but until now, no study has distinguished the brain structural anomalies associated with pedophilia from those specifically associated with CSO in pedophilic men. Using high-resolution T1-weighted brain images and voxel-based morphometry, we analyzed the gray matter (GM) volume of the following 219 men recruited at four acquisition sites in Germany: 58 pedophiles with a history of CSO, 60 pedophiles without any history of CSO and 101 non-pedophilic, non-offending controls to control for the effects of age, education level, verbal IQ, sexual orientation and the acquisition site. Although there were no differences in the relative GM volume of the brain specifically associated with pedophilia, statistical parametric maps revealed a highly significant and CSO-related pattern of above vs below the 'normal' GM volume in the right temporal pole, with non-offending pedophiles exhibiting larger volumes than offending pedophiles. Moreover, regression analysis revealed that the lower GM volume of the dorsomedial prefrontal or anterior cingulate cortex was associated with a higher risk of re-offending in pedophilic child molesters. We believe our data provide the first evidence that CSO in pedophilia rather than pedophilia alone is associated with GM anomalies and thus shed new light on the results of previous studies on this topic. These results indicate the need for new neurobehavioral theories on pedophilia and CSO and may be potentially useful for treatment or prevention approaches that aim to reduce the risk of (re)offending in pedophilia.

Functional consequences of neurite orientation dispersion and density in humans across the adult lifespan.

PubMed

Nazeri, Arash; Chakravarty, M Mallar; Rotenberg, David J; Rajji, Tarek K; Rathi, Yogesh; Michailovich, Oleg V; Voineskos, Aristotle N

2015-01-28

As humans age, a characteristic pattern of widespread neocortical dendritic disruption coupled with compensatory effects in hippocampus and other subcortical structures is shown in postmortem investigations. It is now possible to address age-related effects on gray matter (GM) neuritic organization and density in humans using multishell diffusion-weighted MRI and the neurite-orientation dispersion and density imaging (NODDI) model. In 45 healthy individuals across the adult lifespan (21-84 years), we used a multishell diffusion imaging and the NODDI model to assess the intraneurite volume fraction and neurite orientation-dispersion index (ODI) in GM tissues. We also determined the functional correlates of variations in GM microstructure by obtaining resting-state fMRI and behavioral data. We found a significant age-related deficit in neocortical ODI (most prominently in frontoparietal regions), whereas increased ODI was observed in hippocampus and cerebellum with advancing age. Neocortical ODI outperformed cortical thickness and white matter fractional anisotropy for the prediction of chronological age in the same individuals. Higher GM ODI sampled from resting-state networks with known age-related susceptibility (default mode and visual association networks) was associated with increased functional connectivity of these networks, whereas the task-positive networks tended to show no association or even decreased connectivity. Frontal pole ODI mediated the negative relationship of age with executive function, whereas hippocampal ODI mediated the positive relationship of age with executive function. Our in vivo findings align very closely with the postmortem data and provide evidence for vulnerability and compensatory neural mechanisms of aging in GM microstructure that have functional and cognitive impact in vivo. Copyright © 2015 the authors 0270-6474/15/351753-10$15.00/0.

Gender differences in brain development in Chinese children and adolescents: a structural MRI study

NASA Astrophysics Data System (ADS)

Guo, Xiaojuan; Jin, Zhen; Chen, Kewei; Peng, Danling; Yao, Li

2008-03-01

Using optimized voxel-based morphometry (VBM), this study systematically investigated gender differences in brain development through magnetic resonance imaging (MRI) data in 158 Chinese normal children and adolescents aged 7.26 to 22.80 years (mean age 15.03+/-4.70 years, 78 boys and 80 girls). Gender groups were matched for measures of age, handedness, education level. The customized brain templates, including T I-weighted image and gray matter (GM)/white matter (WM)/cerebro-spinal fluid (CSF) prior probability maps, were created from all participants. Results showed that the total intracranial volume (TIV), global absolute GM and global WM volume in girls were significantly smaller than those in boys. The hippocampus grew faster in girls than that in boys, but the amygdala grew faster in boys than that in girls. The rate of regional GM decreases with age was steeper in the left superior parietal lobule, bilateral inferior parietal lobule, left precuneus, and bilateral supramarginal gyrus in boys compared to girls, which was possibly related to better spatial processing ability in boys. Regional GM volumes were greater in bilateral superior temporal gyrus, bilateral inferior frontal gyrus and bilateral middle frontal gyrus in girls. Regional WM volumes were greater in the left temporal lobe, right inferior parietal and bilateral middle frontal gyrus in girls. The gender differences in the temporal and frontal lobe maybe be related to better language ability in girls. These findings may aid in understanding the differences in cognitive function between boys and girls.

Post-adolescent developmental changes in cortical complexity.

PubMed

Sandu, Anca-Larisa; Izard, Edouard; Specht, Karsten; Beneventi, Harald; Lundervold, Arvid; Ystad, Martin

2014-11-27

Post-adolescence is known to be a period of general maturation and development in the human brain. In brain imaging, volumetric and morphologic cortical grey-matter changes can easily be assessed, but the analysis of cortical complexity seems to have been broadly neglected for this age interval. Magnetic resonance imaging (MRI) was used to acquire structural brain images. The study involved 17 adolescents (mean age 14.1 ± 0.27, 11 girls) who were compared with 14 young adults (mean age 24.24 ± 2.76, 7 women) for measures of brain complexity (fractal dimension--FD), grey matter (GM) volume and surface-area of cortical ribbon. FD was calculated using box-counting and Minkowski-Bouligand methods; FD and GM volume were measured for the whole brain, each hemisphere and lobes: frontal, occipital, parietal and temporal. The results show that the adults have a lower cortical complexity than the adolescents, which was significant for whole brain, left and right hemisphere, frontal and parietal lobes for both genders; and only for males in left temporal lobe. The GM volume was smaller in men than in boys for almost all measurements, and smaller in women than in girls just for right parietal lobe. A significant Pearson correlation was found between FD and GM volume for whole brain and each hemisphere in both genders. The decrease of the GM surface-area was significant in post-adolescence for males, not for females. During post-adolescence there are common changes in cortical complexity in the same regions for both genders, but there are also gender specific changes in some cortical areas. The sex differences from different cortical measurements (FD, GM volume and surface-area of cortical ribbon) could suggest a maturation delay in specific brain regions for each gender in relation to the other and might be explained through the functional role of the corresponding regions reflected in gender difference of developed abilities.

The social network-network: size is predicted by brain structure and function in the amygdala and paralimbic regions

PubMed Central

Von Der Heide, Rebecca; Vyas, Govinda

2014-01-01

The social brain hypothesis proposes that the large size of the primate neocortex evolved to support complex and demanding social interactions. Accordingly, recent studies have reported correlations between the size of an individual’s social network and the density of gray matter (GM) in regions of the brain implicated in social cognition. However, the reported relationships between GM density and social group size are somewhat inconsistent with studies reporting correlations in different brain regions. One factor that might account for these discrepancies is the use of different measures of social network size (SNS). This study used several measures of SNS to assess the relationships SNS and GM density. The second goal of this study was to test the relationship between social network measures and functional brain activity. Participants performed a social closeness task using photos of their friends and unknown people. Across the VBM and functional magnetic resonance imaging analyses, individual differences in SNS were consistently related to structural and functional differences in three regions: the left amygdala, right amygdala and the right entorhinal/ventral anterior temporal cortex. PMID:24493846

Brain tissue segmentation based on DTI data

PubMed Central

Liu, Tianming; Li, Hai; Wong, Kelvin; Tarokh, Ashley; Guo, Lei; Wong, Stephen T.C.

2008-01-01

We present a method for automated brain tissue segmentation based on the multi-channel fusion of diffusion tensor imaging (DTI) data. The method is motivated by the evidence that independent tissue segmentation based on DTI parametric images provides complementary information of tissue contrast to the tissue segmentation based on structural MRI data. This has important applications in defining accurate tissue maps when fusing structural data with diffusion data. In the absence of structural data, tissue segmentation based on DTI data provides an alternative means to obtain brain tissue segmentation. Our approach to the tissue segmentation based on DTI data is to classify the brain into two compartments by utilizing the tissue contrast existing in a single channel. Specifically, because the apparent diffusion coefficient (ADC) values in the cerebrospinal fluid (CSF) are more than twice that of gray matter (GM) and white matter (WM), we use ADC images to distinguish CSF and non-CSF tissues. Additionally, fractional anisotropy (FA) images are used to separate WM from non-WM tissues, as highly directional white matter structures have much larger fractional anisotropy values. Moreover, other channels to separate tissue are explored, such as eigenvalues of the tensor, relative anisotropy (RA), and volume ratio (VR). We developed an approach based on the Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm that combines these two-class maps to obtain a complete tissue segmentation map of CSF, GM, and WM. Evaluations are provided to demonstrate the performance of our approach. Experimental results of applying this approach to brain tissue segmentation and deformable registration of DTI data and spoiled gradient-echo (SPGR) data are also provided. PMID:17804258

Use of Brain MRI Atlases to Determine Boundaries of Age-Related Pathology: The Importance of Statistical Method

PubMed Central

Dickie, David Alexander; Job, Dominic E.; Gonzalez, David Rodriguez; Shenkin, Susan D.; Wardlaw, Joanna M.

2015-01-01

Introduction Neurodegenerative disease diagnoses may be supported by the comparison of an individual patient’s brain magnetic resonance image (MRI) with a voxel-based atlas of normal brain MRI. Most current brain MRI atlases are of young to middle-aged adults and parametric, e.g., mean ±standard deviation (SD); these atlases require data to be Gaussian. Brain MRI data, e.g., grey matter (GM) proportion images, from normal older subjects are apparently not Gaussian. We created a nonparametric and a parametric atlas of the normal limits of GM proportions in older subjects and compared their classifications of GM proportions in Alzheimer’s disease (AD) patients. Methods Using publicly available brain MRI from 138 normal subjects and 138 subjects diagnosed with AD (all 55–90 years), we created: a mean ±SD atlas to estimate parametrically the percentile ranks and limits of normal ageing GM; and, separately, a nonparametric, rank order-based GM atlas from the same normal ageing subjects. GM images from AD patients were then classified with respect to each atlas to determine the effect statistical distributions had on classifications of proportions of GM in AD patients. Results The parametric atlas often defined the lower normal limit of the proportion of GM to be negative (which does not make sense physiologically as the lowest possible proportion is zero). Because of this, for approximately half of the AD subjects, 25–45% of voxels were classified as normal when compared to the parametric atlas; but were classified as abnormal when compared to the nonparametric atlas. These voxels were mainly concentrated in the frontal and occipital lobes. Discussion To our knowledge, we have presented the first nonparametric brain MRI atlas. In conditions where there is increasing variability in brain structure, such as in old age, nonparametric brain MRI atlases may represent the limits of normal brain structure more accurately than parametric approaches. Therefore, we conclude that the statistical method used for construction of brain MRI atlases should be selected taking into account the population and aim under study. Parametric methods are generally robust for defining central tendencies, e.g., means, of brain structure. Nonparametric methods are advisable when studying the limits of brain structure in ageing and neurodegenerative disease. PMID:26023913

Neuroanatomy of Individual Differences in Language in Adult Males with Autism

PubMed Central

Lai, Meng-Chuan; Lombardo, Michael V.; Ecker, Christine; Chakrabarti, Bhismadev; Suckling, John; Bullmore, Edward T.; Happé, Francesca; Murphy, Declan G. M.; Baron-Cohen, Simon

2015-01-01

One potential source of heterogeneity within autism spectrum conditions (ASC) is language development and ability. In 80 high-functioning male adults with ASC, we tested if variations in developmental and current structural language are associated with current neuroanatomy. Groups with and without language delay differed behaviorally in early social reciprocity, current language, but not current autistic features. Language delay was associated with larger total gray matter (GM) volume, smaller relative volume at bilateral insula, ventral basal ganglia, and right superior, middle, and polar temporal structures, and larger relative volume at pons and medulla oblongata in adulthood. Despite this heterogeneity, those with and without language delay showed significant commonality in morphometric features when contrasted with matched neurotypical individuals (n = 57). In ASC, better current language was associated with increased GM volume in bilateral temporal pole, superior temporal regions, dorsolateral fronto-parietal and cerebellar structures, and increased white matter volume in distributed frontal and insular regions. Furthermore, current language–neuroanatomy correlation patterns were similar across subgroups with or without language delay. High-functioning adult males with ASC show neuroanatomical variations associated with both developmental and current language characteristics. This underscores the importance of including both developmental and current language as specifiers for ASC, to help clarify heterogeneity. PMID:25249409

Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord.

PubMed

Vue, Tou Yia; Kim, Euiseok J; Parras, Carlos M; Guillemot, Francois; Johnson, Jane E

2014-10-01

Glia constitute the majority of cells in the mammalian central nervous system and are crucial for neurological function. However, there is an incomplete understanding of the molecular control of glial cell development. We find that the transcription factor Ascl1 (Mash1), which is best known for its role in neurogenesis, also functions in both astrocyte and oligodendrocyte lineages arising in the mouse spinal cord at late embryonic stages. Clonal fate mapping in vivo reveals heterogeneity in Ascl1-expressing glial progenitors and shows that Ascl1 defines cells that are restricted to either gray matter (GM) or white matter (WM) as astrocytes or oligodendrocytes. Conditional deletion of Ascl1 post-neurogenesis shows that Ascl1 is required during oligodendrogenesis for generating the correct numbers of WM but not GM oligodendrocyte precursor cells, whereas during astrocytogenesis Ascl1 functions in balancing the number of dorsal GM protoplasmic astrocytes with dorsal WM fibrous astrocytes. Thus, in addition to its function in neurogenesis, Ascl1 marks glial progenitors and controls the number and distribution of astrocytes and oligodendrocytes in the GM and WM of the spinal cord. © 2014. Published by The Company of Biologists Ltd.

Integration of Intention and Outcome for Moral Judgment in Frontotemporal Dementia: Brain Structural Signatures.

PubMed

Baez, Sandra; Kanske, Philipp; Matallana, Diana; Montañes, Patricia; Reyes, Pablo; Slachevsky, Andrea; Matus, Cristian; Vigliecca, Nora Silvana; Torralva, Teresa; Manes, Facundo; Ibanez, Agustin

2016-01-01

Moral judgment has been proposed to rely on a distributed brain network. This function is impaired in behavioral variant frontotemporal dementia (bvFTD), a condition involving damage to some regions of this network. However, no studies have investigated moral judgment in bvFTD via structural neuroimaging. We compared the performance of 21 bvFTD patients and 19 controls on a moral judgment task involving scenarios that discriminate between the contributions of intentions and outcomes. Voxel-based morphometry was used to assess (a) the atrophy pattern in bvFTD patients, (b) associations between gray matter (GM) volume and moral judgments, and (c) structural differences between bvFTD subgroups (patients with relatively preserved moral judgment and patients with severer moral judgment impairments). Patients judged attempted harm as more permissible and accidental harm as less permissible than controls. The groups' performance on accidental harm was associated with GM volume in the precuneus. In controls, it was al- so associated with the ventromedial prefrontal cortex (VMPFC). Also, both groups' performance on attempted harm was associated with GM volume in the temporoparietal junction. Patients exhibiting worse performance displayed smaller GM volumes in the precuneus and temporal pole. Results suggest that moral judgment abnormalities in bvFTD are associated with impaired integration of intentions and outcomes, which depends on an extended brain network. In bvFTD, moral judgment seems to critically depend on areas beyond the VMPFC. © 2016 S. Karger AG, Basel.

Orbitofrontal structural markers of negative affect in alcohol dependence and their associations with heavy relapse-risk at 6 months post-treatment.

PubMed

Zois, E; Vollstädt-Klein, S; Hoffmann, S; Reinhard, I; Charlet, K; Beck, A; Jorde, A; Kirsch, M; Walter, H; Heinz, A; Kiefer, F

2017-10-01

Alcohol relapse is often occurring to regulate negative affect during withdrawal. On the neurobiological level, alcoholism is associated with gray matter (GM) abnormalities in regions that regulate emotional experience such as the orbitofrontal cortex (OFC). However, no study to our knowledge has investigated the neurobiological unpinning of affect in alcoholism at early withdrawal and the associations of OFC volume with long-term relapse risk. One hundred and eighty-two participants were included, 95 recently detoxified alcohol dependent patients (ADP) and 87 healthy controls (HC). We measured affective states using the positive and negative affect schedule (PANAS). We collected T1-weighted brain structural images and performed Voxel-based morphometry (VBM). Findings revealed GM volume decrease in alcoholics in the prefrontal cortex (including medial OFC), anterior cingulate gyrus, and insula. GM volume in the medial OFC was positively associated with NA in the ADP group. Cox regression analysis predicted that risk to heavy relapse at 6 months increases with decreased GM volume in the medial OFC. Negative affect during alcohol withdrawal was positively associated with OFC volume. What is more, increased GM volume in the OFC also moderated risk to heavy relapse at 6 months. Reduced GM in the OFC poses as risk to recovery from alcohol dependence and provides valuable insights into transient negative affect states during withdrawal that can trigger relapse. Implications exist for therapeutic interventions signifying the OFC as a neurobiological marker to relapse and could explain the inability of ADP to regulate internal negative affective states. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The volumetric and shape changes of the putamen and thalamus in first episode, untreated major depressive disorder.

PubMed

Lu, Yi; Liang, Hongmin; Han, Dan; Mo, Yin; Li, Zongfang; Cheng, Yuqi; Xu, Xiufeng; Shen, Zonglin; Tan, Chunyan; Zhao, Wei; Zhu, Yun; Sun, Xuejin

2016-01-01

Previous MRI studies confirmed abnormalities in the limbic-cortical-striatal-pallidal-thalamic (LCSPT) network or limbic-cortico-striatal-thalamic-cortical (LCSTC) circuits in patients with major depressive disorder (MDD), but few studies have investigated the subcortical structural abnormalities. Therefore, we sought to determine whether focal subcortical grey matter (GM) changes might be present in MDD at an early stage. We recruited 30 first episode, untreated patients with major depressive disorder (MDD) and 26 healthy control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetric and shape analyses were used to assess volume and shape changes of the subcortical GM structures, respectively. In addition, probabilistic tractography methods were used to demonstrate the relationship between the subcortical and the cortical GM. Compared to healthy controls, MDD patients had significant volume reductions in the bilateral putamen and left thalamus (FWE-corrected, p < 0.05). Meanwhile, the vertex-based shape analysis showed regionally contracted areas on the dorsolateral and ventromedial aspects of the bilateral putamen, and on the dorsal and ventral aspects of left thalamus in MDD patients (FWE-corrected, p < 0.05). Additionally, a negative correlation was found between local atrophy in the dorsal aspects of the left thalamus and clinical variables representing severity. Furthermore, probabilistic tractography demonstrated that the area of shape deformation of the bilateral putamen and left thalamus have connections with the frontal and temporal lobes, which were found to be related to major depression. Our results suggested that structural abnormalities in the putamen and thalamus might be present in the early stages of MDD, which support the role of subcortical structure in the pathophysiology of MDD. Meanwhile, the present study showed that these subcortical structural abnormalities might be the potential trait markers of MDD.

Fractal Dimension Analysis of Subcortical Gray Matter Structures in Schizophrenia

PubMed Central

Sehatpour, Pejman; Long, Jun; Gui, Weihua; Qiao, Jianping; Javitt, Daniel C.; Wang, Zhishun

2016-01-01

A failure of adaptive inference—misinterpreting available sensory information for appropriate perception and action—is at the heart of clinical manifestations of schizophrenia, implicating key subcortical structures in the brain including the hippocampus. We used high-resolution, three-dimensional (3D) fractal geometry analysis to study subtle and potentially biologically relevant structural alterations (in the geometry of protrusions, gyri and indentations, sulci) in subcortical gray matter (GM) in patients with schizophrenia relative to healthy individuals. In particular, we focus on utilizing Fractal Dimension (FD), a compact shape descriptor that can be computed using inputs with irregular (i.e., not necessarily smooth) surfaces in order to quantify complexity (of geometrical properties and configurations of structures across spatial scales) of subcortical GM in this disorder. Probabilistic (entropy-based) information FD was computed based on the box-counting approach for each of the seven subcortical structures, bilaterally, as well as the brainstem from high-resolution magnetic resonance (MR) images in chronic patients with schizophrenia (n = 19) and age-matched healthy controls (n = 19) (age ranges: patients, 22.7–54.3 and healthy controls, 24.9–51.6 years old). We found a significant reduction of FD in the left hippocampus (median: 2.1460, range: 2.07–2.18 vs. median: 2.1730, range: 2.15–2.23, p<0.001; Cohen’s effect size, U3 = 0.8158 (95% Confidence Intervals, CIs: 0.6316, 1.0)), the right hippocampus (median: 2.1430, range: 2.05–2.19 vs. median: 2.1760, range: 2.12–2.21, p = 0.004; U3 = 0.8421 (CIs: 0.5263, 1)), as well as left thalamus (median: 2.4230, range: 2.40–2.44, p = 0.005; U3 = 0.7895 (CIs: 0.5789, 0.9473)) in schizophrenia patients, relative to healthy individuals. Our findings provide in-vivo quantitative evidence for reduced surface complexity of hippocampus, with reduced FD indicating a less complex, less regular GM surface detected in schizophrenia. PMID:27176232

Factors influencing U.S. consumer support for genetic modification to prevent crop disease.

PubMed

McComas, Katherine A; Besley, John C; Steinhardt, Joseph

2014-07-01

This study examines support for the genetic modification (GM) of crops in the context of preventing "late blight," a devastating potato and tomato disease that caused the Irish Potato Famine in the 1850s and results in substantial crop loss today. We surveyed U.S. adults who do the primary grocery shopping in their household (n = 859). Half of the respondents were randomly assigned to read a vignette describing late blight before responding to questions about GM, whereas the other half read a vignette about generic crop disease before responding to questions. We also examine how the perceived fairness of decision makers relates to GM support and the perceived legitimacy of GM decision making. We found that disease specificity mattered less to support and legitimacy than the perceived fairness of decision makers. The perceived risks of GM to human and environmental health negatively related to GM support and legitimacy, whereas the perceived benefits (e.g. reduced threats to crops and a more secure food supply) positively related to support and legitimacy. Objective knowledge about GM had a small, negative relationship with legitimacy whereas self-assessed familiarity with GM had a positive relationship. Overall, the results offer additional confirmation of past findings from more localized settings that perceived fairness of decision makers matters to support for GM and underscore the importance of considering how risk managers' behaviors and actions are perceived alongside individuals' perceptions about the risks and benefits. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cortical reorganization in recent-onset tinnitus patients by the Heidelberg Model of Music Therapy

PubMed Central

Krick, Christoph M.; Grapp, Miriam; Daneshvar-Talebi, Jonas; Reith, Wolfgang; Plinkert, Peter K.; Bolay, Hans Volker

2015-01-01

Pathophysiology and treatment of tinnitus still are fields of intensive research. The neuroscientifically motivated Heidelberg Model of Music Therapy, previously developed by the German Center for Music Therapy Research, Heidelberg, Germany, was applied to explore its effects on individual distress and on brain structures. This therapy is a compact and fast application of nine consecutive 50-min sessions of individualized therapy implemented over 1 week. Clinical improvement and long-term effects over several years have previously been published. However, the underlying neural basis of the therapy's success has not yet been explored. In the current study, the therapy was applied to acute tinnitus patients (TG) and healthy active controls (AC). Non-treated patients were also included as passive controls (PTC). As predicted, the therapeutic intervention led to a significant decrease of tinnitus-related distress in TG compared to PTC. Before and after the study week, high-resolution MRT scans were obtained for each subject. Assessment by repeated measures design for several groups (Two-Way ANOVA) revealed structural gray matter (GM) increase in TG compared to PTC, comprising clusters in precuneus, medial superior frontal areas, and in the auditory cortex. This pattern was further applied as mask for general GM changes as induced by the therapy week. The therapy-like procedure in AC also elicited similar GM increases in precuneus and frontal regions. Comparison between structural effects in TG vs. AC was calculated within the mask for general GM changes to obtain specific effects in tinnitus patients, yielding GM increase in right Heschl's gyrus, right Rolandic operculum, and medial superior frontal regions. In line with recent findings on the crucial role of the auditory cortex in maintaining tinnitus-related distress, a causative relation between the therapy-related GM alterations in auditory areas and the long-lasting therapy effects can be assumed. PMID:25745385

The role of gray and white matter segmentation in quantitative proton MR spectroscopic imaging.

PubMed

Tal, Assaf; Kirov, Ivan I; Grossman, Robert I; Gonen, Oded

2012-12-01

Since the brain's gray matter (GM) and white matter (WM) metabolite concentrations differ, their partial volumes can vary the voxel's ¹H MR spectroscopy (¹H-MRS) signal, reducing sensitivity to changes. While single-voxel ¹H-MRS cannot differentiate between WM and GM signals, partial volume correction is feasible by MR spectroscopic imaging (MRSI) using segmentation of the MRI acquired for VOI placement. To determine the magnitude of this effect on metabolic quantification, we segmented a 1-mm³ resolution MRI into GM, WM and CSF masks that were co-registered with the MRSI grid to yield their partial volumes in approximately every 1 cm³ spectroscopic voxel. Each voxel then provided one equation with two unknowns: its i- metabolite's GM and WM concentrations C(i) (GM) , C(i) (WM) . With the voxels' GM and WM volumes as independent coefficients, the over-determined system of equations was solved for the global averaged C(i) (GM) and C(i) (WM) . Trading off local concentration differences offers three advantages: (i) higher sensitivity due to combined data from many voxels; (ii) improved specificity to WM versus GM changes; and (iii) reduced susceptibility to partial volume effects. These improvements made no additional demands on the protocol, measurement time or hardware. Applying this approach to 18 volunteered 3D MRSI sets of 480 voxels each yielded N-acetylaspartate, creatine, choline and myo-inositol C(i) (GM) concentrations of 8.5 ± 0.7, 6.9 ± 0.6, 1.2 ± 0.2, 5.3 ± 0.6 mM, respectively, and C(i) (WM) concentrations of 7.7 ± 0.6, 4.9 ± 0.5, 1.4 ± 0.1 and 4.4 ± 0.6mM, respectively. We showed that unaccounted voxel WM or GM partial volume can vary absolute quantification by 5-10% (more for ratios), which can often double the sample size required to establish statistical significance. Copyright © 2012 John Wiley & Sons, Ltd.

Correspondence Between Aberrant Intrinsic Network Connectivity and Gray-Matter Volume in the Ventral Brain of Preterm Born Adults.

PubMed

Bäuml, Josef G; Daamen, Marcel; Meng, Chun; Neitzel, Julia; Scheef, Lukas; Jaekel, Julia; Busch, Barbara; Baumann, Nicole; Bartmann, Peter; Wolke, Dieter; Boecker, Henning; Wohlschläger, Afra M; Sorg, Christian

2015-11-01

Widespread brain changes are present in preterm born infants, adolescents, and even adults. While neurobiological models of prematurity facilitate powerful explanations for the adverse effects of preterm birth on the developing brain at microscale, convincing linking principles at large-scale level to explain the widespread nature of brain changes are still missing. We investigated effects of preterm birth on the brain's large-scale intrinsic networks and their relation to brain structure in preterm born adults. In 95 preterm and 83 full-term born adults, structural and functional magnetic resonance imaging at-rest was used to analyze both voxel-based morphometry and spatial patterns of functional connectivity in ongoing blood oxygenation level-dependent activity. Differences in intrinsic functional connectivity (iFC) were found in cortical and subcortical networks. Structural differences were located in subcortical, temporal, and cingulate areas. Critically, for preterm born adults, iFC-network differences were overlapping and correlating with aberrant regional gray-matter (GM) volume specifically in subcortical and temporal areas. Overlapping changes were predicted by prematurity and in particular by neonatal medical complications. These results provide evidence that preterm birth has long-lasting effects on functional connectivity of intrinsic networks, and these changes are specifically related to structural alterations in ventral brain GM. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Relationship between Iron Accumulation and White Matter Injury in Multiple Sclerosis: A Case-Control Study

PubMed Central

Raz, Eytan; Branson, Brittany; Jensen, Jens H.; Bester, Maxim; Babb, James S.; Herbert, Joseph; Grossman, Robert I.; Inglese, Matilde

2015-01-01

PURPOSE Despite the increasing development and applications of iron imaging, the pathophysiology of iron accumulation in multiple sclerosis (MS), and its role in disease progression and development of clinical disability, is poorly understood. The aims of our study were to determine the presence and extent of iron in T2 visible lesions and gray and white matter using magnetic field correlation (MFC) MRI and correlate with microscopic white matter (WM) injury as measured by diffusion tensor imaging (DTI). MATERIALS AND METHODS This is a case-control study incuding a series of 31 patients with clinically definite MS. The mean age was 39 years [standard deviation (SD)=9.55], they were 11 males and 20 females, with a disease duration average of 3 years (range 0-13) and a median EDSS of 2 (0-4.5). Seventeen healthy volunteers (6 males and 11 females) with a mean age of 36 years (SD=11.4) were recruited. All subjects underwent MR imaging on a 3T scanner using T2-weighted sequence, 3D T1 MPRAGE, MFC, single-shot DTI and postcontrast T1. T2-lesion volumes, brain volumetry, DTI parameters and iron quantification were calculated and multiple correlations were exploited. RESULTS Increased MFC was found in the putamen (p=0.061), the thalamus (p=0.123), the centrum semiovale (p=0.053), globus pallidus (p=0.008) and gray matter (GM) (p=0.004) of MS patients compared to controls. The mean lesional MFC was 121 s−2 (SD=67), significantly lower compared to the GM MFC (<0.0001). The GM mean diffusivity (MD) was inversely correlated with the MFC in the centrum semiovale (p<0.001), and in the splenium of the corpus callosum (p<0.001). CONCLUSION Patients with MS have increased iron in the globus pallidus, putamen and centrum with a trend toward increased iron in all the brain structures. Quantitative iron evaluation of WM and GM may improve the understanding of MS pathophysiology, and might serve as a surrogate marker of disease progression. PMID:25416468

Whole brain analysis of postmortem density changes of grey and white matter on computed tomography by statistical parametric mapping.

PubMed

Nishiyama, Yuichi; Kanayama, Hidekazu; Mori, Hiroshi; Tada, Keiji; Yamamoto, Yasushi; Katsube, Takashi; Takeshita, Haruo; Kawakami, Kazunori; Kitagaki, Hajime

2017-06-01

This study examined the usefulness of statistical parametric mapping (SPM) for investigating postmortem changes on brain computed tomography (CT). This retrospective study included 128 patients (23 - 100 years old) without cerebral abnormalities who underwent unenhanced brain CT before and after death. The antemortem CT (AMCT) scans and postmortem CT (PMCT) scans were spatially normalized using our original brain CT template, and postmortem changes of CT values (in Hounsfield units; HU) were analysed by the SPM technique. Compared with AMCT scans, 58.6 % and 98.4 % of PMCT scans showed loss of the cerebral sulci and an unclear grey matter (GM)-white matter (WM) interface, respectively. SPM analysis revealed a significant decrease in cortical GM density within 70 min after death on PMCT scans, suggesting cytotoxic brain oedema. Furthermore, there was a significant increase in the density of the WM, lenticular nucleus and thalamus more than 120 min after death. The SPM technique demonstrated typical postmortem changes on brain CT scans, and revealed that the unclear GM-WM interface on early PMCT scans is caused by a rapid decrease in cortical GM density combined with a delayed increase in WM density. SPM may be useful for assessment of whole brain postmortem changes. • The original brain CT template achieved successful normalization of brain morphology. • Postmortem changes in the brain were independent of sex. • Cortical GM density decreased rapidly after death. • WM and deep GM densities increased following cortical GM density change. • SPM could be useful for assessment of whole brain postmortem changes.

Grey matter damage and overall cognitive impairment in primary progressive multiple sclerosis.

PubMed

Tur, C; Penny, S; Khaleeli, Z; Altmann, D R; Cipolotti, L; Ron, M; Thompson, A J; Ciccarelli, O

2011-11-01

To identify associations between cognitive impairment and imaging measures in a cross-sectional study of patients with primary progressive multiple sclerosis (PPMS). Neuropsychological tests were administered to 27 patients with PPMS and 31 controls. Patients underwent brain conventional magnetic resonance imaging (MRI) sequences, volumetric scans and magnetization transfer (MT) imaging; MT ratio (MTR) parameters, grey matter (GM) and normal-appearing white matter (NAWM) volumes, and WM T2 lesion load (T2LL) were obtained. In patients, multiple linear regression models identified the imaging measure associated with the abnormal cognitive tests independently from the other imaging variables. Partial correlation coefficients (PCC) were reported. Patients performed worse on tests of attention/speed of visual information processing, delayed verbal memory, and executive function, and had a worse overall cognitive performance index, when compared with controls. In patients, a lower GM peak location MTR was associated with worse overall cognitive performance (p < 0.001, PCC = 0.77). GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline (p < 0.001, PCC = -0.62), and executive function (p < 0.001, PCC = 0.79). NAWM volume was associated with attention/speed of visual information processing (p < 0.001, PCC = 0.74), while T2LL was associated with delayed verbal memory (p = 0.007, PCC = -0.55). The finding of strong associations between GM MTR, NAWM volume and T2LL and specific cognitive impairments suggests that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both GM and WM. However, GM MTR appears to be the main correlate of overall cognitive dysfunction, underlining the role of abnormal GM integrity in determining cognitive impairment in PPMS.

Similar cortical but not subcortical gray matter abnormalities in women with posttraumatic stress disorder with versus without dissociative identity disorder.

PubMed

Chalavi, Sima; Vissia, Eline M; Giesen, Mechteld E; Nijenhuis, Ellert R S; Draijer, Nel; Barker, Gareth J; Veltman, Dick J; Reinders, Antje A T S

2015-03-30

Neuroanatomical evidence on the relationship between posttraumatic stress disorder (PTSD) and dissociative disorders is still lacking. We acquired brain structural magnetic resonance imaging (MRI) scans from 17 patients with dissociative identity disorder (DID) and co-morbid PTSD (DID-PTSD) and 16 patients with PTSD but without DID (PTSD-only), and 32 healthy controls (HC), and compared their whole-brain cortical and subcortical gray matter (GM) morphological measurements. Associations between GM measurements and severity of dissociative and depersonalization/derealization symptoms or lifetime traumatizing events were evaluated in the patient groups. DID-PTSD and PTSD-only patients, compared with HC, had similarly smaller cortical GM volumes of the whole brain and of frontal, temporal and insular cortices. DID-PTSD patients additionally showed smaller hippocampal and larger pallidum volumes relative to HC, and larger putamen and pallidum volumes relative to PTSD-only. Severity of lifetime traumatizing events and volume of the hippocampus were negatively correlated. Severity of dissociative and depersonalization/derealization symptoms correlated positively with volume of the putamen and pallidum, and negatively with volume of the inferior parietal cortex. Shared abnormal brain structures in DID-PTSD and PTSD-only, small hippocampal volume in DID-PTSD, more severe lifetime traumatizing events in DID-PTSD compared with PTSD-only, and negative correlations between lifetime traumatizing events and hippocampal volume suggest a trauma-related etiology for DID. Our results provide neurobiological evidence for the side-by-side nosological classification of PTSD and DID in the DSM-5. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Automatic cortical segmentation in the developing brain.

PubMed

Xue, Hui; Srinivasan, Latha; Jiang, Shuzhou; Rutherford, Mary; Edwards, A David; Rueckert, Daniel; Hajnal, Jo V

2007-01-01

The segmentation of neonatal cortex from magnetic resonance (MR) images is much more challenging than the segmentation of cortex in adults. The main reason is the inverted contrast between grey matter (GM) and white matter (WM) that occurs when myelination is incomplete. This causes mislabeled partial volume voxels, especially at the interface between GM and cerebrospinal fluid (CSF). We propose a fully automatic cortical segmentation algorithm, detecting these mislabeled voxels using a knowledge-based approach and correcting errors by adjusting local priors to favor the correct classification. Our results show that the proposed algorithm corrects errors in the segmentation of both GM and WM compared to the classic EM scheme. The segmentation algorithm has been tested on 25 neonates with the gestational ages ranging from approximately 27 to 45 weeks. Quantitative comparison to the manual segmentation demonstrates good performance of the method (mean Dice similarity: 0.758 +/- 0.037 for GM and 0.794 +/- 0.078 for WM).

Differences in Cortical Representation and Structural Connectivity of Hands and Feet between Professional Handball Players and Ballet Dancers

PubMed Central

Meier, Jessica; Topka, Marlene Sofie; Hänggi, Jürgen

2016-01-01

It is known that intensive training and expertise are associated with functional and structural neuroadaptations. Most studies, however, compared experts with nonexperts; hence it is, specifically for sports, unclear whether the neuroplastic adaptations reported are sport-specific or sport-general. Here we aimed at investigating sport-specific adaptations in professional handball players and ballet dancers by focusing on the primary motor and somatosensory grey matter (GM) representation of hands and feet using voxel-based morphometry as well as on fractional anisotropy (FA) of the corticospinal tract by means of diffusion tensor imaging-based fibre tractography. As predicted, GM volume was increased in hand areas of handball players, whereas ballet dancers showed increased GM volume in foot areas. Compared to handball players, ballet dancers showed decreased FA in both fibres connecting the foot and hand areas, but they showed lower FA in fibres connecting the foot compared to their hand areas, whereas handball players showed lower FA in fibres connecting the hand compared to their foot areas. Our results suggest that structural adaptations are sport-specific and are manifested in brain regions associated with the neural processing of sport-specific skills. We believe this enriches the plasticity research in general and extends our knowledge of sport expertise in particular. PMID:27247805

Differences in Cortical Representation and Structural Connectivity of Hands and Feet between Professional Handball Players and Ballet Dancers.

PubMed

Meier, Jessica; Topka, Marlene Sofie; Hänggi, Jürgen

2016-01-01

It is known that intensive training and expertise are associated with functional and structural neuroadaptations. Most studies, however, compared experts with nonexperts; hence it is, specifically for sports, unclear whether the neuroplastic adaptations reported are sport-specific or sport-general. Here we aimed at investigating sport-specific adaptations in professional handball players and ballet dancers by focusing on the primary motor and somatosensory grey matter (GM) representation of hands and feet using voxel-based morphometry as well as on fractional anisotropy (FA) of the corticospinal tract by means of diffusion tensor imaging-based fibre tractography. As predicted, GM volume was increased in hand areas of handball players, whereas ballet dancers showed increased GM volume in foot areas. Compared to handball players, ballet dancers showed decreased FA in both fibres connecting the foot and hand areas, but they showed lower FA in fibres connecting the foot compared to their hand areas, whereas handball players showed lower FA in fibres connecting the hand compared to their foot areas. Our results suggest that structural adaptations are sport-specific and are manifested in brain regions associated with the neural processing of sport-specific skills. We believe this enriches the plasticity research in general and extends our knowledge of sport expertise in particular.

Age-Related Gray and White Matter Changes in Normal Adult Brains

PubMed Central

Farokhian, Farnaz; Yang, Chunlan; Beheshti, Iman; Matsuda, Hiroshi; Wu, Shuicai

2017-01-01

Normal aging is associated with both structural changes in many brain regions and functional declines in several cognitive domains with advancing age. Advanced neuroimaging techniques enable explorative analyses of structural alterations that can be used as assessments of such age-related changes. Here we used voxel-based morphometry (VBM) to investigate regional and global brain volume differences among four groups of healthy adults from the IXI Dataset: older females (OF, mean age 68.35 yrs; n=69), older males (OM, 68.43 yrs; n=66), young females (YF, 27.09 yrs; n=71), and young males (YM, 27.91 yrs; n=71), using 3D T1-weighted MRI data. At the global level, we investigated the influence of age and gender on brain volumes using a two-way analysis of variance. With respect to gender, we used the Pearson correlation to investigate global brain volume alterations due to age in the older and young groups. At the regional level, we used a flexible factorial statistical test to compare the means of gray matter (GM) and white matter (WM) volume alterations among the four groups. We observed different patterns in both the global and regional GM and WM alterations in the young and older groups with respect to gender. At the global level, we observed significant influences of age and gender on global brain volumes. At the regional level, the older subjects showed a widespread reduction in GM volume in regions of the frontal, insular, and cingulate cortices compared to the young subjects in both genders. Compared to the young subjects, the older subjects showed a widespread WM decline prominently in the thalamic radiations, in addition to increased WM in pericentral and occipital areas. Knowledge of these observed brain volume differences and changes may contribute to the elucidation of mechanisms underlying aging as well as age-related brain atrophy and disease. PMID:29344423

Disability-Specific Atlases of Gray Matter Loss in Relapsing-Remitting Multiple Sclerosis.

PubMed

MacKenzie-Graham, Allan; Kurth, Florian; Itoh, Yuichiro; Wang, He-Jing; Montag, Michael J; Elashoff, Robert; Voskuhl, Rhonda R

2016-08-01

Multiple sclerosis (MS) is characterized by progressive gray matter (GM) atrophy that strongly correlates with clinical disability. However, whether localized GM atrophy correlates with specific disabilities in patients with MS remains unknown. To understand the association between localized GM atrophy and clinical disability in a biology-driven analysis of MS. In this cross-sectional study, magnetic resonance images were acquired from 133 women with relapsing-remitting MS and analyzed using voxel-based morphometry and volumetry. A regression analysis was used to determine whether voxelwise GM atrophy was associated with specific clinical deficits. Data were collected from June 28, 2007, to January 9, 2014. Voxelwise correlation of GM change with clinical outcome measures (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores). Among the 133 female patients (mean [SD] age, 37.4 [7.5] years), worse performance on the Multiple Sclerosis Functional Composite correlated with voxelwise GM volume loss in the middle cingulate cortex (P < .001) and a cluster in the precentral gyrus bilaterally (P = .004). In addition, worse performance on the Paced Auditory Serial Addition Test correlated with volume loss in the auditory and premotor cortices (P < .001), whereas worse performance on the 9-Hole Peg Test correlated with GM volume loss in Brodmann area 44 (Broca area; P = .02). Finally, voxelwise GM loss in the right paracentral lobulus correlated with bowel and bladder disability (P = .03). Thus, deficits in specific clinical test results were directly associated with localized GM loss in clinically eloquent locations. These biology-driven data indicate that specific disabilities in MS are associated with voxelwise GM loss in distinct locations. This approach may be used to develop disability-specific biomarkers for use in future clinical trials of neuroprotective treatments in MS.

Tensor-based morphometry of cannabis use on brain structure in individuals at elevated genetic risk of schizophrenia.

PubMed

Welch, K A; Moorhead, T W; McIntosh, A M; Owens, D G C; Johnstone, E C; Lawrie, S M

2013-10-01

Schizophrenia is associated with various brain structural abnormalities, including reduced volume of the hippocampi, prefrontal lobes and thalami. Cannabis use increases the risk of schizophrenia but reports of brain structural abnormalities in the cannabis-using population have not been consistent. We used automated image analysis to compare brain structural changes over time in people at elevated risk of schizophrenia for familial reasons who did and did not use cannabis. Magnetic resonance imaging (MRI) scans were obtained from subjects at high familial risk of schizophrenia at entry to the Edinburgh High Risk Study (EHRS) and approximately 2 years later. Differential grey matter (GM) loss in those exposed (n=23) and not exposed to cannabis (n=32) in the intervening period was compared using tensor-based morphometry (TBM). Cannabis exposure was associated with significantly greater loss of right anterior hippocampal (pcorrected=0.029, t=3.88) and left superior frontal lobe GM (pcorrected=0.026, t=4.68). The former finding remained significant even after the exclusion of individuals who had used other drugs during the inter-scan interval. Using an automated analysis of longitudinal data, we demonstrate an association between cannabis use and GM loss in currently well people at familial risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.

Subjects harboring presenilin familial Alzheimer’s disease mutations exhibit diverse white matter biochemistry alterations

PubMed Central

Roher, Alex E; Maarouf, Chera L; Malek-Ahmadi, Michael; Wilson, Jeffrey; Kokjohn, Tyler A; Daugs, Ian D; Whiteside, Charisse M; Kalback, Walter M; Macias, MiMi P; Jacobson, Sandra A; Sabbagh, Marwan N; Ghetti, Bernardino; Beach, Thomas G

2013-01-01

Alzheimer’s disease (AD) dementia impacts all facets of higher order cognitive function and is characterized by the presence of distinctive pathological lesions in the gray matter (GM). The profound alterations in GM structure and function have fostered the view that AD impacts are primarily a consequence of GM damage. However, the white matter (WM) represents about 50% of the cerebrum and this area of the brain is substantially atrophied and profoundly abnormal in both sporadic AD (SAD) and familial AD (FAD). We examined the WM biochemistry by ELISA and Western blot analyses of key proteins in 10 FAD cases harboring mutations in the presenilin genes PSEN1 and PSEN2 as well as in 4 non-demented control (NDC) individuals and 4 subjects with SAD. The molecules examined were direct substrates of PSEN1 such as Notch-1 and amyloid precursor protein (APP). In addition, apolipoproteins, axonal transport molecules, cytoskeletal and structural proteins, neurotrophic factors and synaptic proteins were examined. PSEN-FAD subjects had, on average, higher amounts of WM amyloid-beta (Aβ) peptides compared to SAD, which may play a role in the devastating dysfunction of the brain. However, the PSEN-FAD mutations we examined did not produce uniform increases in the relative proportions of Aβ42 and exhibited substantial variability in total Aβ levels. These observations suggest that neurodegeneration and dementia do not depend solely on enhanced Aβ42 levels. Our data revealed additional complexities in PSEN-FAD individuals. Some direct substrates of γ-secretase, such as Notch, N-cadherin, Erb-B4 and APP, deviated substantially from the NDC group baseline for some, but not all, mutation types. Proteins that were not direct γ-secretase substrates, but play key structural and functional roles in the WM, likewise exhibited varied concentrations in the distinct PSEN mutation backgrounds. Detailing the diverse biochemical pathology spectrum of PSEN mutations may offer valuable insights into dementia progression and the design of effective therapeutic interventions for both SAD and FAD. PMID:24093083

Grey matter damage in progressive multiple sclerosis versus amyotrophic lateral sclerosis: a voxel-based morphometry MRI study.

PubMed

Tavazzi, Eleonora; Laganà, Maria Marcella; Bergsland, Niels; Tortorella, Paola; Pinardi, Giovanna; Lunetta, Christian; Corbo, Massimo; Rovaris, Marco

2015-03-01

Primary progressive multiple sclerosis (PPMS) and amyotrophic lateral sclerosis (ALS) seem to share some clinical and pathological features. MRI studies revealed the presence of grey matter (GM) atrophy in both diseases, but no comparative data are available. The objective was to compare the regional patterns of GM tissue loss in PPMS and ALS with voxel-based morphometry (VBM). Eighteen PPMS patients, 20 ALS patients, and 31 healthy controls (HC) were studied with a 1.5 Tesla scanner. VBM was performed to assess volumetric GM differences with age and sex as covariates. Threshold-free cluster enhancement analysis was used to obtain significant clusters. Group comparisons were tested with family-wise error correction for multiple comparisons (p < 0.05) except for HC versus MND which was tested at a level of p < 0.001 uncorrected and a cluster threshold of 20 contiguous voxels. Compared to HC, ALS patients showed GM tissue reduction in selected frontal and temporal areas, while PPMS patients showed a widespread bilateral GM volume decrease, involving both deep and cortical regions. Compared to ALS, PPMS patients showed tissue volume reductions in both deep and cortical GM areas. This preliminary study confirms that PPMS is characterized by a more diffuse cortical and subcortical GM atrophy than ALS and that, in the latter condition, brain damage is present outside the motor system. These results suggest that PPMS and ALS may share pathological features leading to GM tissue loss.

Cerebral blood flow and carbon dioxide reactivity in children with bacterial meningitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashwal, S.; Stringer, W.; Tomasi, L.

1990-10-01

We examined total and regional cerebral blood flow (CBF) by stable xenon computed tomography in 20 seriously ill children with acute bacterial meningitis to determine whether CBF was reduced and to examine the changes in CBF during hyperventilation. In 13 children, total CBF was normal (62 +/- 20 ml/min/100 gm) but marked local variability of flow was seen. In five other children, total CBF was significantly reduced (26 +/- 10 ml/min/100 gm; p less than 0.05), with flow reduced more in white matter (8 +/- 5 ml/min/100 gm) than in gray matter (30 +/- 15 ml/min/100 gm). Autoregulation of CBFmore » appeared to be present in these 18 children within a range of mean arterial blood pressure from 56 to 102 mm Hg. In the remaining two infants, brain dead within the first 24 hours, total flow was uniformly absent, averaging 3 +/- 3 ml/min/100 gm. In seven children, CBF was determined at two carbon dioxide tension (PCO2) levels: 40 (+/- 3) mm Hg and 29 (+/- 3) mm Hg. In six children, total CBF decreased 33%, from 52 (+/- 25) to 35 (+/- 15) ml/min/100 gm; the mean percentage of change in CBF per millimeter of mercury of PCO2 was 3.0%. Regional variability of perfusion to changes in PCO2 was marked in all six children. The percentage of change in CBF per millimeter of mercury of PCO2 was similar in frontal gray matter (3.1%) but higher in white matter (4.5%). In the seventh patient a paradoxical response was observed; total and regional CBF increased 25% after hyperventilation. Our findings demonstrate that (1) CBF in children with bacterial meningitis may be substantially decreased globally, with even more variability noted regionally, (2) autoregulation of CBF is preserved, (3) CBF/CO2 responsitivity varies among patients and in different regions of the brain in the same patient, and (4) hyperventilation can reduce CBF below ischemic thresholds.« less

No adverse effect of genetically modified antifungal wheat on decomposition dynamics and the soil fauna community--a field study.

PubMed

Duc, Caroline; Nentwig, Wolfgang; Lindfeld, Andreas

2011-01-01

The cultivation of genetically modified (GM) plants has raised several environmental concerns. One of these concerns regards non-target soil fauna organisms, which play an important role in the decomposition of organic matter and hence are largely exposed to GM plant residues. Soil fauna may be directly affected by transgene products or indirectly by pleiotropic effects such as a modified plant metabolism. Thus, ecosystem services and functioning might be affected negatively. In a litterbag experiment in the field we analysed the decomposition process and the soil fauna community involved. Therefore, we used four experimental GM wheat varieties, two with a race-specific antifungal resistance against powdery mildew (Pm3b) and two with an unspecific antifungal resistance based on the expression of chitinase and glucanase. We compared them with two non-GM isolines and six conventional cereal varieties. To elucidate the mechanisms that cause differences in plant decomposition, structural plant components (i.e. C∶N ratio, lignin, cellulose, hemicellulose) were examined and soil properties, temperature and precipitation were monitored. The most frequent taxa extracted from decaying plant material were mites (Cryptostigmata, Gamasina and Uropodina), springtails (Isotomidae), annelids (Enchytraeidae) and Diptera (Cecidomyiidae larvae). Despite a single significant transgenic/month interaction for Cecidomyiidae larvae, which is probably random, we detected no impact of the GM wheat on the soil fauna community. However, soil fauna differences among conventional cereal varieties were more pronounced than between GM and non-GM wheat. While leaf residue decomposition in GM and non-GM wheat was similar, differences among conventional cereals were evident. Furthermore, sampling date and location were found to greatly influence soil fauna community and decomposition processes. The results give no indication of ecologically relevant adverse effects of antifungal GM wheat on the composition and the activity of the soil fauna community.

No Adverse Effect of Genetically Modified Antifungal Wheat on Decomposition Dynamics and the Soil Fauna Community – A Field Study

PubMed Central

Duc, Caroline; Nentwig, Wolfgang; Lindfeld, Andreas

2011-01-01

The cultivation of genetically modified (GM) plants has raised several environmental concerns. One of these concerns regards non-target soil fauna organisms, which play an important role in the decomposition of organic matter and hence are largely exposed to GM plant residues. Soil fauna may be directly affected by transgene products or indirectly by pleiotropic effects such as a modified plant metabolism. Thus, ecosystem services and functioning might be affected negatively. In a litterbag experiment in the field we analysed the decomposition process and the soil fauna community involved. Therefore, we used four experimental GM wheat varieties, two with a race-specific antifungal resistance against powdery mildew (Pm3b) and two with an unspecific antifungal resistance based on the expression of chitinase and glucanase. We compared them with two non-GM isolines and six conventional cereal varieties. To elucidate the mechanisms that cause differences in plant decomposition, structural plant components (i.e. C∶N ratio, lignin, cellulose, hemicellulose) were examined and soil properties, temperature and precipitation were monitored. The most frequent taxa extracted from decaying plant material were mites (Cryptostigmata, Gamasina and Uropodina), springtails (Isotomidae), annelids (Enchytraeidae) and Diptera (Cecidomyiidae larvae). Despite a single significant transgenic/month interaction for Cecidomyiidae larvae, which is probably random, we detected no impact of the GM wheat on the soil fauna community. However, soil fauna differences among conventional cereal varieties were more pronounced than between GM and non-GM wheat. While leaf residue decomposition in GM and non-GM wheat was similar, differences among conventional cereals were evident. Furthermore, sampling date and location were found to greatly influence soil fauna community and decomposition processes. The results give no indication of ecologically relevant adverse effects of antifungal GM wheat on the composition and the activity of the soil fauna community. PMID:22043279

Inter-Vendor Reproducibility of Pseudo-Continuous Arterial Spin Labeling at 3 Tesla

PubMed Central

Mutsaerts, Henri J. M. M.; Steketee, Rebecca M. E.; Heijtel, Dennis F. R.; Kuijer, Joost P. A.; van Osch, Matthias J. P.; Majoie, Charles B. L. M.; Smits, Marion; Nederveen, Aart J.

2014-01-01

Purpose Prior to the implementation of arterial spin labeling (ASL) in clinical multi-center studies, it is important to establish its status quo inter-vendor reproducibility. This study evaluates and compares the intra- and inter-vendor reproducibility of pseudo-continuous ASL (pCASL) as clinically implemented by GE and Philips. Material and Methods 22 healthy volunteers were scanned twice on both a 3T GE and a 3T Philips scanner. The main difference in implementation between the vendors was the readout module: spiral 3D fast spin echo vs. 2D gradient-echo echo-planar imaging respectively. Mean and variation of cerebral blood flow (CBF) were compared for the total gray matter (GM) and white matter (WM), and on a voxel-level. Results Whereas the mean GM CBF of both vendors was almost equal (p = 1.0), the mean WM CBF was significantly different (p<0.01). The inter-vendor GM variation did not differ from the intra-vendor GM variation (p = 0.3 and p = 0.5 for GE and Philips respectively). Spatial inter-vendor CBF and variation differences were observed in several GM regions and in the WM. Conclusion These results show that total GM CBF-values can be exchanged between vendors. For the inter-vendor comparison of GM regions or WM, these results encourage further standardization of ASL implementation among vendors. PMID:25090654

Inter-vendor reproducibility of pseudo-continuous arterial spin labeling at 3 Tesla.

PubMed

Mutsaerts, Henri J M M; Steketee, Rebecca M E; Heijtel, Dennis F R; Kuijer, Joost P A; van Osch, Matthias J P; Majoie, Charles B L M; Smits, Marion; Nederveen, Aart J

2014-01-01

Prior to the implementation of arterial spin labeling (ASL) in clinical multi-center studies, it is important to establish its status quo inter-vendor reproducibility. This study evaluates and compares the intra- and inter-vendor reproducibility of pseudo-continuous ASL (pCASL) as clinically implemented by GE and Philips. 22 healthy volunteers were scanned twice on both a 3T GE and a 3T Philips scanner. The main difference in implementation between the vendors was the readout module: spiral 3D fast spin echo vs. 2D gradient-echo echo-planar imaging respectively. Mean and variation of cerebral blood flow (CBF) were compared for the total gray matter (GM) and white matter (WM), and on a voxel-level. Whereas the mean GM CBF of both vendors was almost equal (p = 1.0), the mean WM CBF was significantly different (p<0.01). The inter-vendor GM variation did not differ from the intra-vendor GM variation (p = 0.3 and p = 0.5 for GE and Philips respectively). Spatial inter-vendor CBF and variation differences were observed in several GM regions and in the WM. These results show that total GM CBF-values can be exchanged between vendors. For the inter-vendor comparison of GM regions or WM, these results encourage further standardization of ASL implementation among vendors.

Gray matter abnormalities associated with fibromyalgia: A meta-analysis of voxel-based morphometric studies.

PubMed

Shi, HaiCun; Yuan, CongHu; Dai, ZhenYu; Ma, HaiRong; Sheng, LiQin

2016-12-01

Studies employing voxel-based morphometry (VBM) have reported inconsistent findings on the association of gray matter (GM) abnormalities with fibromyalgia. The aim of the present study is to identify the most prominent and replicable GM areas that involved in fibromyalgia. A systematic search of the PubMed database from January 2000 to September 2015 was performed to identify eligible whole-brain VBM studies. Comprehensive meta-analyses to investigate regional GM abnormalities in fibromyalgia were conducted with the Seed-based d Mapping software package. Seven studies, reporting nine comparisons and including a grand total of 180 fibromyalgia patients and 126 healthy controls, were included in the meta-analyses. In fibromyalgia patients compared with healthy controls, regional GM decreases were consistently found in the bilateral anterior cingulate/paracingulate cortex/medial prefrontal cortex, the bilateral posterior cingulate/paracingulate cortex, the left parahippocampal gyrus/fusiform cortex, and the right parahippocampal gyrus/hippocampus. Regional GM increases were consistently found in the left cerebellum. Meta-regression demonstrated that age was correlated with GM anomalies in fibromyalgia patients. The current meta-analysis identified a characteristic pattern of GM alterations within the medial pain system, default mode network, and cerebro-cerebellar circuits, which further supports the concept that fibromyalgia is a symptom complex involving brain areas beyond those implicated in chronic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of gray matter reductions on theory of mind abilities in patients with schizophrenia.

PubMed

Koelkebeck, Katja; Hirao, Kazuyuki; Miyata, Jun; Kawada, Ryosaku; Saze, Teruyasu; Dannlowski, Udo; Ubukata, Shiho; Ohrmann, Patricia; Bauer, Jochen; Pedersen, Anya; Fukuyama, Hidenao; Sawamoto, Nobukatsu; Takahashi, Hidehiko; Murai, Toshiya

2013-01-01

To identify the brain regions involved in the interpretation of intentional movement by patients with schizophrenia, we investigated the association between cerebral gray matter (GM) volumes and performance on a theory of mind (ToM) task using voxel-based morphometry. Eighteen patients with schizophrenia and thirty healthy controls participated in the study. Participants were given a moving shapes task that employs the interpretation of intentional movement. Verbal descriptions were rated according to intentionality. ToM performance deficits in patients were found to be positively correlated with GM volume reductions in the superior temporal sulcus and medial prefrontal cortex. Our findings confirm that divergent brain regions contribute to mentalizing abilities and that GM volume reductions impact behavioral deficits in patients with schizophrenia.

Association of change in brain structure to objectively measured physical activity and sedentary behavior in older adults: Age, Gene/Environment Susceptibility-Reykjavik Study.

PubMed

Arnardottir, Nanna Yr; Koster, Annemarie; Domelen, Dane R Van; Brychta, Robert J; Caserotti, Paolo; Eiriksdottir, Gudny; Sverrisdottir, Johanna E; Sigurdsson, Sigurdur; Johannsson, Erlingur; Chen, Kong Y; Gudnason, Vilmundur; Harris, Tamara B; Launer, Lenore J; Sveinsson, Thorarinn

2016-01-01

Many studies have examined the hypothesis that greater participation in physical activity (PA) is associated with less brain atrophy. Here we examine, in a sub-sample (n=352, mean age 79.1 years) of the Age, Gene/Environment Susceptibility-Reykjavik Study cohort, the association of the baseline and 5-year change in magnetic resonance imaging (MRI)-derived volumes of gray matter (GM) and white matter (WM) to active and sedentary behavior (SB) measured at the end of the 5-year period by a hip-worn accelerometer for seven consecutive days. More GM (β=0.11; p=0.044) and WM (β=0.11; p=0.030) at baseline was associated with more total physical activity (TPA). Also, when adjusting for baseline values, the 5-year change in GM (β=0.14; p=0.0037) and WM (β=0.11; p=0.030) was associated with TPA. The 5-year change in WM was associated with SB (β=-0.11; p=0.0007). These data suggest that objectively measured PA and SB late in life are associated with current and prior cross-sectional measures of brain atrophy, and that change over time is associated with PA and SB in expected directions. Copyright © 2015 Elsevier B.V. All rights reserved.

Structural MRI research in patients with nasopharyngeal carcinoma following radiotherapy: A DTI and VBM study.

PubMed

Leng, Xi; Fang, Peng; Lin, Huan; An, Jie; Tan, Xin; Zhang, Chi; Wu, Donglin; Shen, Wen; Qiu, Shijun

2017-11-01

The aim of the present study was to investigate the microstructural characteristics of the brain lobes following radiotherapy (RT) for patients with nasopharyngeal carcinoma (NPC) at distinct times. Diffusion tensor imaging (DTI) and 3D-T1-weighted imaging was performed in 70 age- and sex-matched subjects, 24 of whom were pre-treatment patients. The patients were divided into three groups, according to the time following completion of RT. Fractional anisotropy (FA) and gray matter (GM) volume were determined. The DTI data were analyzed using tract-based spatial statistics and the GM volume was analyzed using voxel-based morphometry (VBM). Compared with the pre-RT group, the mean FA values in the left parietal lobe white matter (WM) and right cerebellum decreased significantly in the post-RT 0-6 month group (P<0.05). In addition, the mean FA values in the right parietal lobe WM decreased significantly in the post-RT 6-12 month group (P<0.05), compared with the pre-RT group. The FA level in the right temporal lobe remained significantly decreased, compared with that in the pre-RT group (P<0.05) for 1 year after RT. Furthermore, compared with pre-RT group, the GM volume in the bilateral frontal lobe, right occipital lobe, left parietal lobe, right temporal lobe and left cerebellum decreased significantly in the post-RT 0-6 month group (P<0.05), and in the bilateral temporal lobe, parietal lobe, right frontal lobe and left cerebellum, the GM volume decreased significantly in the post-RT 6-12 month group (P<0.05). The GM volume in the right temporal lobe, bilateral frontal lobe and bilateral cerebellum remained significantly decreased compared with that in the pre-RT group (P<0.05) for 1 year after RT. A combination of DTI and VBM may be used to determine radiation-induced brain injury in patients treated for NPC.

Application of Quantitative MRI for Brain Tissue Segmentation at 1.5 T and 3.0 T Field Strengths

PubMed Central

West, Janne; Blystad, Ida; Engström, Maria; Warntjes, Jan B. M.; Lundberg, Peter

2013-01-01

Background Brain tissue segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) are important in neuroradiological applications. Quantitative Mri (qMRI) allows segmentation based on physical tissue properties, and the dependencies on MR scanner settings are removed. Brain tissue groups into clusters in the three dimensional space formed by the qMRI parameters R1, R2 and PD, and partial volume voxels are intermediate in this space. The qMRI parameters, however, depend on the main magnetic field strength. Therefore, longitudinal studies can be seriously limited by system upgrades. The aim of this work was to apply one recently described brain tissue segmentation method, based on qMRI, at both 1.5 T and 3.0 T field strengths, and to investigate similarities and differences. Methods In vivo qMRI measurements were performed on 10 healthy subjects using both 1.5 T and 3.0 T MR scanners. The brain tissue segmentation method was applied for both 1.5 T and 3.0 T and volumes of WM, GM, CSF and brain parenchymal fraction (BPF) were calculated on both field strengths. Repeatability was calculated for each scanner and a General Linear Model was used to examine the effect of field strength. Voxel-wise t-tests were also performed to evaluate regional differences. Results Statistically significant differences were found between 1.5 T and 3.0 T for WM, GM, CSF and BPF (p<0.001). Analyses of main effects showed that WM was underestimated, while GM and CSF were overestimated on 1.5 T compared to 3.0 T. The mean differences between 1.5 T and 3.0 T were -66 mL WM, 40 mL GM, 29 mL CSF and -1.99% BPF. Voxel-wise t-tests revealed regional differences of WM and GM in deep brain structures, cerebellum and brain stem. Conclusions Most of the brain was identically classified at the two field strengths, although some regional differences were observed. PMID:24066153

What is special about the adolescent (JME) brain?

PubMed

Craiu, Dana

2013-07-01

Juvenile myoclonic epilepsy (JME) involves cortico-thalamo-cortical networks. Thalamic, frontal gray matter, connectivity, and neurotransmitter disturbances have been demonstrated by structural/functional imaging studies. Few patients with JME show mutations in genes coding ion channels or GABAA (gamma-aminobutyric acid) receptor subunits. Recent research points to EFHC1 gene mutations leading to microdysgenesis and possible aberrant circuitry. Imaging studies have shown massive structural/functional changes of normally developing adolescent brain structures maturing at strikingly different rates and times. Gray matter (GM) volume diminishes in cortical areas (frontal and parietal) and deep structures (anterior thalamus, putamen, and caudate). Diffusion tensor imaging (DTI) findings support continued microstructural change in WM (white matter) during late adolescence with robust developmental changes in thalamocortical connectivity. The GABAA receptor distribution and specific receptor subunits' expression patterns change with age from neonate to adolescent/adult, contributing to age-related changes in brain excitability. Hormonal influence on brain structure development during adolescence is presented. Possible implications of brain changes during adolescence on the course of JME are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Learning-based 3T brain MRI segmentation with guidance from 7T MRI labeling.

PubMed

Deng, Minghui; Yu, Renping; Wang, Li; Shi, Feng; Yap, Pew-Thian; Shen, Dinggang

2016-12-01

Segmentation of brain magnetic resonance (MR) images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) is crucial for brain structural measurement and disease diagnosis. Learning-based segmentation methods depend largely on the availability of good training ground truth. However, the commonly used 3T MR images are of insufficient image quality and often exhibit poor intensity contrast between WM, GM, and CSF. Therefore, they are not ideal for providing good ground truth label data for training learning-based methods. Recent advances in ultrahigh field 7T imaging make it possible to acquire images with excellent intensity contrast and signal-to-noise ratio. In this paper, the authors propose an algorithm based on random forest for segmenting 3T MR images by training a series of classifiers based on reliable labels obtained semiautomatically from 7T MR images. The proposed algorithm iteratively refines the probability maps of WM, GM, and CSF via a cascade of random forest classifiers for improved tissue segmentation. The proposed method was validated on two datasets, i.e., 10 subjects collected at their institution and 797 3T MR images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Specifically, for the mean Dice ratio of all 10 subjects, the proposed method achieved 94.52% ± 0.9%, 89.49% ± 1.83%, and 79.97% ± 4.32% for WM, GM, and CSF, respectively, which are significantly better than the state-of-the-art methods (p-values < 0.021). For the ADNI dataset, the group difference comparisons indicate that the proposed algorithm outperforms state-of-the-art segmentation methods. The authors have developed and validated a novel fully automated method for 3T brain MR image segmentation. © 2016 American Association of Physicists in Medicine.

Learning-based 3T brain MRI segmentation with guidance from 7T MRI labeling.

PubMed

Deng, Minghui; Yu, Renping; Wang, Li; Shi, Feng; Yap, Pew-Thian; Shen, Dinggang

2016-12-01

Segmentation of brain magnetic resonance (MR) images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) is crucial for brain structural measurement and disease diagnosis. Learning-based segmentation methods depend largely on the availability of good training ground truth. However, the commonly used 3T MR images are of insufficient image quality and often exhibit poor intensity contrast between WM, GM, and CSF. Therefore, they are not ideal for providing good ground truth label data for training learning-based methods. Recent advances in ultrahigh field 7T imaging make it possible to acquire images with excellent intensity contrast and signal-to-noise ratio. In this paper, the authors propose an algorithm based on random forest for segmenting 3T MR images by training a series of classifiers based on reliable labels obtained semiautomatically from 7T MR images. The proposed algorithm iteratively refines the probability maps of WM, GM, and CSF via a cascade of random forest classifiers for improved tissue segmentation. The proposed method was validated on two datasets, i.e., 10 subjects collected at their institution and 797 3T MR images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Specifically, for the mean Dice ratio of all 10 subjects, the proposed method achieved 94.52% ± 0.9%, 89.49% ± 1.83%, and 79.97% ± 4.32% for WM, GM, and CSF, respectively, which are significantly better than the state-of-the-art methods (p-values < 0.021). For the ADNI dataset, the group difference comparisons indicate that the proposed algorithm outperforms state-of-the-art segmentation methods. The authors have developed and validated a novel fully automated method for 3T brain MR image segmentation.

A multiparametric evaluation of regional brain damage in patients with primary progressive multiple sclerosis.

PubMed

Ceccarelli, Antonia; Rocca, Maria A; Valsasina, Paola; Rodegher, Mariaemma; Pagani, Elisabetta; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

2009-09-01

The purpose of this study is to define the topographical distribution of gray matter (GM) and white matter (WM) damage in patients with primary progressive multiple sclerosis (PPMS), using a multiparametric MR-based approach. Using a 3 Tesla scanner, dual-echo, 3D fast-field echo (FFE), and diffusion tensor (DT) MRI scans were acquired from 18 PPMS patients and 17 matched healthy volunteers. An optimized voxel-based (VB) analysis was used to investigate the patterns of regional GM density changes and to quantify GM and WM diffusivity alterations of the entire brain. In PPMS patients, GM atrophy was found in the thalami and the right insula, while mean diffusivity (MD) changes involved several cortical-subcortical structures in all cerebral lobes and the cerebellum. An overlap between decreased WM fractional anisotropy (FA) and increased WM MD was found in the corpus callosum, the cingulate gyrus, the left short temporal fibers, the right short frontal fibers, the optic radiations, and the middle cerebellar peduncles. Selective MD increase, not associated with FA decrease, was found in the internal capsules, the corticospinal tracts, the superior longitudinal fasciculi, the fronto-occipital fasciculi, and the right cerebral peduncle. A discrepancy was found between regional WM diffusivity changes and focal lesions because several areas had DT MRI abnormalities but did not harbor T2-visible lesions. Our study allowed to detect tissue damage in brain areas associated with motor and cognitive functions, which are known to be impaired in PPMS patients. Combining regional measures derived from different MR modalities may be a valuable tool to improve our understanding of PPMS pathophysiology. 2009 Wiley-Liss, Inc.

Effects of ANK3 variation on gray and white matter in bipolar disorder.

PubMed

Lippard, E T C; Jensen, K P; Wang, F; Johnston, J A Y; Spencer, L; Pittman, B; Gelernter, J; Blumberg, H P

2017-09-01

The single-nucleotide polymorphism rs9804190 in the Ankyrin G (ANK3) gene has been reported in genome-wide association studies to be associated with bipolar disorder (BD). However, the neural system effects of rs9804190 in BD are not known. We investigated associations between rs9804190 and gray and white matter (GM and WM, respectively) structure within a frontotemporal neural system implicated in BD. A total of 187 adolescent and adult European Americans were studied: a group homozygous for the C allele (52 individuals with BD and 56 controls) and a T-carrier group, carrying the high-risk T allele (38 BD and 41 controls). Subjects participated in high-resolution structural magnetic resonance imaging and diffusion tensor imaging (DTI) scanning. Frontotemporal region of interest (ROI) and whole-brain exploratory analyses were conducted. DTI ROI-based analysis revealed a significant diagnosis by genotype interaction within the uncinate fasciculus (P⩽0.05), with BD subjects carrying the T (risk) allele showing decreased fractional anisotropy compared with other subgroups, independent of age. Genotype effects were not observed in frontotemporal GM volume. These findings support effects of rs9804190 on frontotemporal WM in adolescents and adults with BD and suggest a mechanism contributing to WM pathology in BD.

A voxel-based morphometry study of anosmic patients

PubMed Central

Peng, P; Xiao, W; Si, L F; Wang, J F; Wang, S K; Zhai, R Y; Wei, Y X

2013-01-01

Objective: The aim of our study was to compare volume change in grey matter (GM) and white matter (WM) in a group of subjects with anosmia and a healthy control group. We tried to find a regular pattern of atrophy within and between GM and WM and to determine whether any particular areas are more sensitive to olfactory injury. Methods: There were 19 anosmic patients and 20 age- and sex-matched control subjects. We acquired MR images on a 3-T scanner and performed voxel-based morphometry using the VBM8 toolbox and SPM8 in a MATLAB® (MathWorks®, Natick, MA) environment. Results: Patients with anosmia showed a significant decrease in GM volume, mainly in the anterior cingulate cortex, middle temporal gyrus, superior temporal gyrus, fusiform gyrus, supramarginal gyrus, superior frontal gyrus, middle frontal gyrus, middle occipital gyrus, anterior insular cortex and cerebellum. In addition, we observed volume decreases in smaller areas such as the piriform cortex, the inferior temporal gyrus, the precuneus and the subcallosal gyrus. All WM areas with atrophy were near those GM areas that experienced volume loss. There was more volume atrophy in GM areas corresponding to WM areas with more volume loss. Atrophy increased with disease duration. Conclusion: There is simultaneous atrophy in GM and WM, and the degree of atrophy is greater with longer disease duration. Different GM and WM areas have different sensitivities to olfactory injury. Advances in knowledge: This study examines the atrophy pattern in and between GM and WM—a subject that has not been widely researched previously. PMID:24133057

Is there any difference in Amide and NOE CEST effects between white and gray matter at 7 T?

NASA Astrophysics Data System (ADS)

Khlebnikov, Vitaliy; Siero, Jeroen C. W.; Wijnen, Jannie; Visser, Fredy; Luijten, Peter R.; Klomp, Dennis W. J.; Hoogduin, Hans

2016-11-01

Measurement of Chemical Exchange Saturation Transfer (CEST) is providing tissue physiology dependent contrast, e.g. by looking at Amide and NOE (Nuclear Overhauser Enhancement) effects. CEST is unique in providing quantitative metabolite information at high imaging resolution. However, direct comparison of Amide and NOE effects between different tissues may result in wrong conclusions on the metabolite concentration due to the additional contributors to the observed CEST contrast, such as water content (WC) and water T1 relaxation (T1w). For instance, there are multiple contradictory reports in the literature on Amide and NOE effects in white matter (WM) and gray matter (GM) at 7 T. This study shows that at 7 T, tissue water T1 relaxation is a stronger contributor to CEST contrasts than WC. After water T1 correction, there was no difference in Amide effects between WM and GM, whereas WM/GM contrast was enhanced for NOE effects.

The connectomes of males and females with autism spectrum disorder have significantly different white matter connectivity densities

PubMed Central

Irimia, Andrei; Torgerson, Carinna M.; Jacokes, Zachary J.; Van Horn, John D.

2017-01-01

Autism spectrum disorder (ASD) encompasses a set of neurodevelopmental conditions whose striking sex-related disparity (with an estimated male-to-female ratio of 4:1) remains unknown. Here we use magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) to identify the brain structure correlates of the sex-by-ASD diagnosis interaction in a carefully selected cohort of 110 ASD patients (55 females) and 83 typically-developing (TD) subjects (40 females). The interaction was found to be predicated primarily upon white matter connectivity density innervating, bilaterally, the lateral aspect of the temporal lobe, the temporo-parieto-occipital junction and the medial parietal lobe. By contrast, regional gray matter (GM) thickness and volume are not found to modulate this interaction significantly. When interpreted in the context of previous studies, our findings add considerable weight to three long-standing hypotheses according to which the sex disparity of ASD incidence is (A) due to WM connectivity rather than to GM differences, (B) modulated to a large extent by temporoparietal connectivity, and (C) accompanied by brain function differences driven by these effects. Our results contribute substantially to the task of unraveling the biological mechanisms giving rise to the sex disparity in ASD incidence, whose clinical implications are significant. PMID:28397802

Catlas: An magnetic resonance imaging-based three-dimensional cortical atlas and tissue probability maps for the domestic cat (Felis catus).

PubMed

Stolzberg, Daniel; Wong, Carmen; Butler, Blake E; Lomber, Stephen G

2017-10-15

Brain atlases play an important role in effectively communicating results from neuroimaging studies in a standardized coordinate system. Furthermore, brain atlases extend analysis of functional magnetic resonance imaging (MRI) data by delineating regions of interest over which to evaluate the extent of functional activation as well as measures of inter-regional connectivity. Here, we introduce a three-dimensional atlas of the cat cerebral cortex based on established cytoarchitectonic and electrophysiological findings. In total, 71 cerebral areas were mapped onto the gray matter (GM) of an averaged T1-weighted structural MRI acquired at 7 T from eight adult domestic cats. In addition, a nonlinear registration procedure was used to generate a common template brain as well as GM, white matter, and cerebral spinal fluid tissue probability maps to facilitate tissue segmentation as part of the standard preprocessing pipeline for MRI data analysis. The atlas and associated files can also be used for planning stereotaxic surgery and for didactic purposes. © 2017 Wiley Periodicals, Inc.

Childhood abuse and deprivation are associated with distinct sex-dependent differences in brain morphology

PubMed Central

Everaerd, Daphne; Klumpers, Floris; Zwiers, Marcel; Guadalupe, Tulio; Franke, Barbara; van Oostrom, Iris; Schene, Aart; Fernández, Guillén; Tendolkar, Indira

2016-01-01

Childhood adversity (CA) has been associated with long-term structural brain alterations and an increased risk for psychiatric disorders. Evidence is emerging that subtypes of CA, varying in the dimensions of threat and deprivation, lead to distinct neural and behavioral outcomes. However, these specific associations have yet to be established without potential confounders such as psychopathology. Moreover, differences in neural development and psychopathology necessitate the exploration of sexual dimorphism. Young healthy adult subjects were selected based on history of CA from a large database to assess gray matter (GM) differences associated with specific subtypes of adversity. We compared voxel-based morphometry data of subjects reporting specific childhood exposure to abuse (n=127) or deprivation (n=126) and a similar sized group of controls (n=129) without reported CA. Subjects were matched on age, gender, and educational level. Differences between CA subtypes were found in the fusiform gyrus and middle occipital gyrus, where subjects with a history of deprivation showed reduced GM compared with subjects with a history of abuse. An interaction between sex and CA subtype was found. Women showed less GM in the visual posterior precuneal region after both subtypes of CA than controls. Men had less GM in the postcentral gyrus after childhood deprivation compared with abuse. Our results suggest that even in a healthy population, CA subtypes are related to specific alterations in brain structure, which are modulated by sex. These findings may help understand neurodevelopmental consequences related to CA. PMID:26576924

Childhood abuse and deprivation are associated with distinct sex-dependent differences in brain morphology.

PubMed

Everaerd, Daphne; Klumpers, Floris; Zwiers, Marcel; Guadalupe, Tulio; Franke, Barbara; van Oostrom, Iris; Schene, Aart; Fernández, Guillén; Tendolkar, Indira

2016-06-01

Childhood adversity (CA) has been associated with long-term structural brain alterations and an increased risk for psychiatric disorders. Evidence is emerging that subtypes of CA, varying in the dimensions of threat and deprivation, lead to distinct neural and behavioral outcomes. However, these specific associations have yet to be established without potential confounders such as psychopathology. Moreover, differences in neural development and psychopathology necessitate the exploration of sexual dimorphism. Young healthy adult subjects were selected based on history of CA from a large database to assess gray matter (GM) differences associated with specific subtypes of adversity. We compared voxel-based morphometry data of subjects reporting specific childhood exposure to abuse (n=127) or deprivation (n=126) and a similar sized group of controls (n=129) without reported CA. Subjects were matched on age, gender, and educational level. Differences between CA subtypes were found in the fusiform gyrus and middle occipital gyrus, where subjects with a history of deprivation showed reduced GM compared with subjects with a history of abuse. An interaction between sex and CA subtype was found. Women showed less GM in the visual posterior precuneal region after both subtypes of CA than controls. Men had less GM in the postcentral gyrus after childhood deprivation compared with abuse. Our results suggest that even in a healthy population, CA subtypes are related to specific alterations in brain structure, which are modulated by sex. These findings may help understand neurodevelopmental consequences related to CA.

Grey matter atrophy is associated with disability increase in natalizumab-treated patients.

PubMed

Ciampi, Ethel; Pareto, Deborah; Sastre-Garriga, Jaume; Vidal-Jordana, Angela; Tur, Carmen; Río, Jordi; Tintoré, Mar; Auger, Cristina; Rovira, Alex; Montalban, Xavier

2017-04-01

Brain volume loss (BVL) is a key outcome in multiple sclerosis (MS) trials. Natalizumab is highly effective on inflammation with moderate impact on atrophy. To explore BVL in patients receiving natalizumab with an emphasis on grey matter (GM). We performed a retrospective post hoc analysis of BVL in 38 patients receiving natalizumab for 3 years using longitudinal voxel-based morphometry (VBM) and FreeSurfer. Significant BVL was observed during first year: brain parenchymal fraction (BPF): -1.12% ( p < 0.001); white matter fraction (WMF): -0.9% ( p = 0.001); grey matter fraction (GMF): -1.28% ( p = 0.002). GM loss was found using VBM in bilateral cerebellum, cingulum, left > right fronto-parietal cortex, right > left hippocampus and left caudate. FreeSurfer showed significant volume losses in subcortical GM, brainstem and cerebellum, and cortical thinning in the left insula. In the second year, only WMF decrease (-0.6%; p = 0.015) was observed with no VBM changes, although FreeSurfer detected significant volume loss in thalamus, hippocampus and cerebellum. Baseline gadolinium enhancement influenced WMF and BPF changes during the first year, but not GMF. Patients with confirmed Expanded Disability Status Scale (EDSS) worsening at 3 years had lower baseline GMF and left thalamus volume and greater BVL over follow-up. BVL develops mainly during the first year of natalizumab therapy. GM changes are independent of baseline inflammation and correlate with disability.

Differences in and correlations between cognitive abilities and brain volumes in healthy control, mild cognitive impairment, and Alzheimer disease groups.

PubMed

Chung, Soon-Cheol; Choi, Mi-Hyun; Kim, Hyung-Sik; Lee, Jung-Chul; Park, Sung-Jun; Jeong, Ul-Ho; Baek, Ji-Hye; Gim, Seon-Young; Choi, Young Chil; Lee, Beob-Yi; Lim, Dae-Woon; Kim, Boseong

2016-05-01

The purpose of this study is to investigate differences in and correlations between cognitive abilities and brain volumes in healthy control (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD) groups. The Korean Version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K), which is used to diagnose AD, was used to measure the cognitive abilities of the study subjects, and the volumes of typical brain components related to AD diagnosis-cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM)-were acquired. Of the CERAD-K subtests, the Boston Naming Test distinguished significantly among the HC, MCI, and AD groups. GM and WM volumes differed significantly among the three groups. There was a significant positive correlation between Boston Naming Test scores and GM and WM volumes. In conclusion, the Boston Naming Test and GM and WM brain volumes differentiated the three tested groups accurately, and there were strong correlations between Boston Naming Test scores and GM and WM volumes. These results will help to establish a test method that differentiates the three groups accurately and is economically feasible. © 2016 Wiley Periodicals, Inc.

DR-TAMAS: Diffeomorphic Registration for Tensor Accurate alignMent of Anatomical Structures

PubMed Central

Irfanoglu, M. Okan; Nayak, Amritha; Jenkins, Jeffrey; Hutchinson, Elizabeth B.; Sadeghi, Neda; Thomas, Cibu P.; Pierpaoli, Carlo

2016-01-01

In this work, we propose DR-TAMAS (Diffeomorphic Registration for Tensor Accurate alignMent of Anatomical Structures), a novel framework for intersubject registration of Diffusion Tensor Imaging (DTI) data sets. This framework is optimized for brain data and its main goal is to achieve an accurate alignment of all brain structures, including white matter (WM), gray matter (GM), and spaces containing cerebrospinal fluid (CSF). Currently most DTI-based spatial normalization algorithms emphasize alignment of anisotropic structures. While some diffusion-derived metrics, such as diffusion anisotropy and tensor eigenvector orientation, are highly informative for proper alignment of WM, other tensor metrics such as the trace or mean diffusivity (MD) are fundamental for a proper alignment of GM and CSF boundaries. Moreover, it is desirable to include information from structural MRI data, e.g., T1-weighted or T2-weighted images, which are usually available together with the diffusion data. The fundamental property of DR-TAMAS is to achieve global anatomical accuracy by incorporating in its cost function the most informative metrics locally. Another important feature of DR-TAMAS is a symmetric time-varying velocity-based transformation model, which enables it to account for potentially large anatomical variability in healthy subjects and patients. The performance of DR-TAMAS is evaluated with several data sets and compared with other widely-used diffeomorphic image registration techniques employing both full tensor information and/or DTI-derived scalar maps. Our results show that the proposed method has excellent overall performance in the entire brain, while being equivalent to the best existing methods in WM. PMID:26931817

DR-TAMAS: Diffeomorphic Registration for Tensor Accurate Alignment of Anatomical Structures.

PubMed

Irfanoglu, M Okan; Nayak, Amritha; Jenkins, Jeffrey; Hutchinson, Elizabeth B; Sadeghi, Neda; Thomas, Cibu P; Pierpaoli, Carlo

2016-05-15

In this work, we propose DR-TAMAS (Diffeomorphic Registration for Tensor Accurate alignMent of Anatomical Structures), a novel framework for intersubject registration of Diffusion Tensor Imaging (DTI) data sets. This framework is optimized for brain data and its main goal is to achieve an accurate alignment of all brain structures, including white matter (WM), gray matter (GM), and spaces containing cerebrospinal fluid (CSF). Currently most DTI-based spatial normalization algorithms emphasize alignment of anisotropic structures. While some diffusion-derived metrics, such as diffusion anisotropy and tensor eigenvector orientation, are highly informative for proper alignment of WM, other tensor metrics such as the trace or mean diffusivity (MD) are fundamental for a proper alignment of GM and CSF boundaries. Moreover, it is desirable to include information from structural MRI data, e.g., T1-weighted or T2-weighted images, which are usually available together with the diffusion data. The fundamental property of DR-TAMAS is to achieve global anatomical accuracy by incorporating in its cost function the most informative metrics locally. Another important feature of DR-TAMAS is a symmetric time-varying velocity-based transformation model, which enables it to account for potentially large anatomical variability in healthy subjects and patients. The performance of DR-TAMAS is evaluated with several data sets and compared with other widely-used diffeomorphic image registration techniques employing both full tensor information and/or DTI-derived scalar maps. Our results show that the proposed method has excellent overall performance in the entire brain, while being equivalent to the best existing methods in WM. Copyright © 2016 Elsevier Inc. All rights reserved.

White matter lesions characterise brain involvement in moderate to severe chronic obstructive pulmonary disease, but cerebral atrophy does not.

PubMed

Spilling, Catherine A; Jones, Paul W; Dodd, James W; Barrick, Thomas R

2017-06-19

Brain pathology is relatively unexplored in chronic obstructive pulmonary disease (COPD). This study is a comprehensive investigation of grey matter (GM) and white matter (WM) changes and how these relate to disease severity and cognitive function. T1-weighted and fluid-attenuated inversion recovery images were acquired for 31 stable COPD patients (FEV 1 52.1% pred., PaO 2 10.1 kPa) and 24 age, gender-matched controls. T1-weighted images were segmented into GM, WM and cerebrospinal fluid (CSF) tissue classes using a semi-automated procedure optimised for use with this cohort. This procedure allows, cohort-specific anatomical features to be captured, white matter lesions (WMLs) to be identified and includes a tissue repair step to correct for misclassification caused by WMLs. Tissue volumes and cortical thickness were calculated from the resulting segmentations. Additionally, a fully-automated pipeline was used to calculate localised cortical surface and gyrification. WM and GM tissue volumes, the tissue volume ratio (indicator of atrophy), average cortical thickness, and the number, size, and volume of white matter lesions (WMLs) were analysed across the whole-brain and regionally - for each anatomical lobe and the deep-GM. The hippocampus was investigated as a region-of-interest. Localised (voxel-wise and vertex-wise) variations in cortical gyrification, GM density and cortical thickness, were also investigated. Statistical models controlling for age and gender were used to test for between-group differences and within-group correlations. Robust statistical approaches ensured the family-wise error rate was controlled in regional and local analyses. There were no significant differences in global, regional, or local measures of GM between patients and controls, however, patients had an increased volume (p = 0.02) and size (p = 0.04) of WMLs. In patients, greater normalised hippocampal volume positively correlated with exacerbation frequency (p = 0.04), and greater WML volume was associated with worse episodic memory (p = 0.05). A negative relationship between WML and FEV 1 % pred. approached significance (p = 0.06). There was no evidence of cerebral atrophy within this cohort of stable COPD patients, with moderate airflow obstruction. However, there were indications of WM damage consistent with an ischaemic pathology. It cannot be concluded whether this represents a specific COPD, or smoking-related, effect.

Atypical anorexia nervosa is not related to brain structural changes in newly diagnosed adolescent patients.

PubMed

Olivo, Gaia; Solstrand Dahlberg, Linda; Wiemerslage, Lyle; Swenne, Ingemar; Zhukovsky, Christina; Salonen-Ros, Helena; Larsson, Elna-Marie; Gaudio, Santino; Brooks, Samantha J; Schiöth, Helgi B

2018-01-01

Patients with atypical anorexia nervosa (AN) have many features overlapping with AN in terms of genetic risk, age of onset, psychopathology and prognosis of outcome, although the weight loss may not be a core factor. While brain structural alterations have been reported in AN, there are currently no data regarding atypical AN patients. We investigated brain structure through a voxel-based morphometry analysis in 22 adolescent females newly-diagnosed with atypical AN, and 38 age- and sex-matched healthy controls (HC). ED-related psychopathology, impulsiveness and obsessive-compulsive traits were assessed with the Eating Disorder Examination Questionnaire (EDE-Q), Barratt Impulsiveness Scale (BIS-11) and Obsessive-compulsive Inventory Revised (OCI-R), respectively. Body mass index (BMI) was also calculated. Patients and HC differed significantly on BMI (p < .002), EDE-Q total score (p < .000) and OCI-R total score (p < .000). No differences could be detected in grey matter (GM) regional volume between groups. The ED-related cognitions in atypical AN patients would suggest that atypical AN and AN could be part of the same spectrum of restrictive-ED. However, contrary to previous reports in AN, our atypical AN patients did not show any GM volume reduction. The different degree of weight loss might play a role in determining such discrepancy. Alternatively, the preservation of GM volume might indeed differentiate atypical AN from AN. © 2017 Wiley Periodicals, Inc.

Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity

PubMed Central

Mueller, Karsten; Möller, Harald E.; Horstmann, Annette; Busse, Franziska; Lepsien, Jöran; Blüher, Matthias; Stumvoll, Michael; Villringer, Arno; Pleger, Burkhard

2015-01-01

Previous cross-sectional studies on body-weight-related alterations in brain structure revealed profound changes in the gray matter (GM) and white matter (WM) that resemble findings obtained from individuals with advancing age. This suggests that obesity may lead to structural brain changes that are comparable with brain aging. Here, we asked whether weight-loss-dependent improved metabolic and neurotrophic functioning parallels the reversal of obesity-related alterations in brain structure. To this end we applied magnetic resonance imaging (MRI) together with voxel-based morphometry and diffusion-tensor imaging in overweight to obese individuals who participated in a fitness course with intensive physical training twice a week over a period of 3 months. After the fitness course, participants presented, with inter-individual heterogeneity, a reduced body mass index (BMI), reduced serum leptin concentrations, elevated high-density lipoprotein-cholesterol (HDL-C), and alterations of serum brain-derived neurotrophic factor (BDNF) concentrations suggesting changes of metabolic and neurotrophic function. Exercise-dependent changes in BMI and serum concentration of BDNF, leptin, and HDL-C were related to an increase in GM density in the left hippocampus, the insular cortex, and the left cerebellar lobule. We also observed exercise-dependent changes of diffusivity parameters in surrounding WM structures as well as in the corpus callosum. These findings suggest that weight-loss due to physical exercise in overweight to obese participants induces profound structural brain plasticity, not primarily of sensorimotor brain regions involved in physical exercise, but of regions previously reported to be structurally affected by an increased body weight and functionally implemented in gustation and cognitive processing. PMID:26190989

Effect of Early Adversity and Childhood Internalizing Symptoms on Brain Structure in Young Men.

PubMed

Jensen, Sarah K G; Dickie, Erin W; Schwartz, Deborah H; Evans, C John; Dumontheil, Iroise; Paus, Tomáš; Barker, Edward D

2015-10-01

Early adversity is an important risk factor that relates to internalizing symptoms and altered brain structure. To assess the direct effects of early adversity and child internalizing symptoms (ie, depression, anxiety) on cortical gray matter (GM) volume, as well as the extent to which early adversity associates with variation in cortical GM volume indirectly via increased levels of internalizing symptoms. A prospective investigation of associations between adversity within the first 6 years of life, internalizing symptoms during childhood and early adolescence, and altered brain structure in late adolescence (age, 18-21 years) was conducted in a community-based birth cohort in England (Avon Longitudinal Study of Parents and Children). Participants from the cohort included 494 mother-son pairs monitored since the mothers were pregnant (estimated date of delivery between April 1, 1991, and December 31, 1992). Data collection for the present study was conducted between April 1, 1991, and November 30, 2010; the neuroimaging data were collected between September 1, 2010, and November 30, 2012, and data analyses for the present study occurred between January 25, 2013, and February 15, 2015. Risk factors were adversity within the first 6 years of the child's life (including prenatal exposure) and the child's internalizing symptoms between age 7 and 13 years. Early childhood adversity. The main outcome was GM volume of cortical regions previously associated with major depression measured through T1-weighted magnetic resonance images collected in late adolescence. Among 494 young men included in this analysis, early adversity was directly associated with lower GM volumes in the anterior cingulate cortex (β = -.18; P = .01) and higher GM volume in the precuneus (β = .18; P = .009). Childhood internalizing symptoms were associated with lower GM volume in the right superior frontal gyrus (β = -.20; P = .002). Early adversity was also associated with higher levels of internalizing symptoms (β = .37; P < .001), which, in turn, were associated with lower superior frontal gyrus volume (ie, an indirect effect) (β = -.08; 95% CI, -0.14 to -0.01; P = .02). Adversity early in life was associated with higher levels of internalizing symptoms as well as with altered brain structure. Early adversity was related to variation in brain structure both directly and via increased levels of internalizing symptoms. These findings may suggest that some of the structural variation often attributed to depression might be associated with early adversity in addition to the effect of depression.

3T deep gray matter T2 hypointensity correlates with disability over time in stable relapsing-remitting multiple sclerosis: a 3-year pilot study.

PubMed

Zhang, Y; Metz, L M; Yong, V W; Mitchell, J R

2010-10-15

Abnormally decreased deep gray matter (GM) signal intensity on T2-weighted MRI (T2 hypointensity) is associated with brain atrophy and disability progression in patients with multiple sclerosis (MS) and is believed to represent excessive iron deposition. We investigated the time course of deep GM T2 hypointensity and its relationship with disability at 3T in 8 stable relapsing-remitting (RR) MS patients treated with minocycline over 3years. MRI and disability measurements were compared at baseline, 6, 12, 24, and 36months. Grand mean deep GM T2 hypointensity was negatively correlated with EDSS over time (r=-0.94, P=0.02). This correlation was strongest in the head of caudate (r=-0.95, P=0.01) and putamen (r=-0.89, P=0.04). Additionally, baseline grand mean deep GM T2 hypointensity appears to predict third year EDSS (r=-0.72, P=0.04). These results suggest that iron associated deep GM injury correlates with patient disability in stable RRMS. Measurements of deep GM T2 hypointensity at high field MRI may prove to be useful in monitoring individuals with MS. Further studies are required to confirm these results in a large sample and to determine if T2 hypointensity changes in clinically active MS patients. Copyright 2010 Elsevier B.V. All rights reserved.

Progression in disability and regional grey matter atrophy in relapsing-remitting multiple sclerosis.

PubMed

Hofstetter, Louis; Naegelin, Yvonne; Filli, Lukas; Kuster, Pascal; Traud, Stefan; Smieskova, Renata; Mueller-Lenke, Nicole; Kappos, Ludwig; Gass, Achim; Sprenger, Till; Penner, Iris-Katharina; Nichols, Thomas E; Vrenken, Hugo; Barkhof, Frederik; Polman, Chris; Radue, Ernst-Wilhelm; Borgwardt, Stefan J; Bendfeldt, Kerstin

2014-02-01

In multiple sclerosis (MS) regional grey matter (GM) atrophy has been associated with disability progression. The aim of this study was to compare regional GM volume changes in relapsing-remitting MS (RRMS) patients with progressive and stable disability, using voxel-based morphometry (VBM). We acquired baseline and 1-year follow-up 3-dimensional (3D) T1-weighted magnetic resonance imaging (MRI) data of RRMS patients, using two 1.5-Tesla scanners. Patients were matched pair-wise with respect to age, gender, disease duration, medication, scanner and baseline Expanded Disability Status Scale (EDSS) into 13 pairs, with either progressive EDSS (≥ 1 point change y(-1)) or stable EDSS, as well as into 29 pairs with either progressive Multiple Sclerosis Functional Composite (MSFC) at ≥ 0.25% decrease in y(-1) in any component, or stable MSFC. We analysed longitudinal regional differences in GM volumes in the progressive and stable EDSS and MSFC groups, respectively, using VBM. Significant GM volume reductions occurred in the right precuneus, in the progressive EDSS group. Differential between-group effects occurred in the right precuneus and in the postcentral gyrus. Further longitudinal GM volume reductions occurred in the right orbicular gyrus, in the progressive MSFC group, but no between-group differences were observed (non-stationary cluster-wise inference, all P(corrected) < 0.05). These results suggested a direct association of disability progression and regional GM atrophy in RRMS.

Regional patterns of grey matter atrophy and magnetisation transfer ratio abnormalities in multiple sclerosis clinical subgroups: a voxel-based analysis study.

PubMed

Mallik, Shahrukh; Muhlert, Nils; Samson, Rebecca S; Sethi, Varun; Wheeler-Kingshott, Claudia A M; Miller, David H; Chard, Declan T

2015-04-01

In multiple sclerosis (MS), demyelination and neuro-axonal loss occur in the brain grey matter (GM). We used magnetic resonance imaging (MRI) measures of GM magnetisation transfer ratio (MTR) and volume to assess the regional localisation of reduced MTR (reflecting demyelination) and atrophy (reflecting neuro-axonal loss) in relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS). A total of 98 people with MS (51 RRMS, 28 SPMS, 19 PPMS) and 29 controls had T1-weighted volumetric and magnetisation transfer scans. SPM8 was used to undertake voxel-based analysis (VBA) of GM tissue volumes and MTR. MS subgroups were compared with controls, adjusting for age and gender. A voxel-by-voxel basis correlation analysis between MTR and volume within each subject group was performed, using biological parametric mapping. MTR reduction was more extensive than atrophy. RRMS and SPMS patients showed proportionately more atrophy in the deep GM. SPMS and PPMS patients showed proportionately greater cortical MTR reduction. RRMS patients demonstrated the most correlation of MTR reduction and atrophy in deep GM. In SPMS and PPMS patients, there was less extensive correlation. These results suggest that in the deep GM of RRMS patients, demyelination and neuro-axonal loss may be linked, while in SPMS and PPMS patients, neuro-axonal loss and demyelination may occur mostly independently. © The Author(s), 2014.

The effect of gender on the neuroanatomy of children with autism spectrum disorders: a support vector machine case-control study.

PubMed

Retico, Alessandra; Giuliano, Alessia; Tancredi, Raffaella; Cosenza, Angela; Apicella, Fabio; Narzisi, Antonio; Biagi, Laura; Tosetti, Michela; Muratori, Filippo; Calderoni, Sara

2016-01-01

Genetic, hormonal, and environmental factors contribute since infancy to sexual dimorphism in regional brain structures of subjects with typical development. However, the neuroanatomical differences between male and female children with autism spectrum disorders (ASD) are an intriguing and still poorly investigated issue. This study aims to evaluate whether the brain of young children with ASD exhibits sex-related structural differences and if a correlation exists between clinical ASD features and neuroanatomical underpinnings. A total of 152 structural MRI scans were analysed. Specifically, 76 young children with ASD (38 males and 38 females; 2-7 years of age; mean = 53 months, standard deviation = 17 months) were evaluated employing a support vector machine (SVM)-based analysis of the grey matter (GM). Group comparisons consisted of 76 age-, gender- and non-verbal-intelligence quotient-matched children with typical development or idiopathic developmental delay without autism. For both genders combined, SVM showed a significantly increased GM volume in young children with ASD with respect to control subjects, predominantly in the bilateral superior frontal gyrus (Brodmann area -BA- 10), bilateral precuneus (BA 31), bilateral superior temporal gyrus (BA 20/22), whereas less GM in patients with ASD was found in right inferior temporal gyrus (BA 37). For the within gender comparisons (i.e., females with ASD vs. controls and males with ASD vs. controls), two overlapping regions in bilateral precuneus (BA 31) and left superior frontal gyrus (BA 9/10) were detected. Sex-by-group analyses revealed in males with ASD compared to matched controls two male-specific regions of increased GM volume (left middle occipital gyrus-BA 19-and right superior temporal gyrus-BA 22). Comparisons in females with and without ASD demonstrated increased GM volumes predominantly in the bilateral frontal regions. Additional regions of significantly increased GM volume in the right anterior cingulate cortex (BA 32) and right cerebellum were typical only of females with ASD. Despite the specific behavioural correlates of sex-dimorphism in ASD, brain morphology as yet remains unclear and requires future dedicated investigations. This study provides evidence of structural brain gender differences in young children with ASD that possibly contribute to the different phenotypic disease manifestations in males and females.

Association of Deep Gray Matter Damage With Cortical and Spinal Cord Degeneration in Primary Progressive Multiple Sclerosis.

PubMed

Ruggieri, Serena; Petracca, Maria; Miller, Aaron; Krieger, Stephen; Ghassemi, Rezwan; Bencosme, Yadira; Riley, Claire; Howard, Jonathan; Lublin, Fred; Inglese, Matilde

2015-12-01

The investigation of cortical gray matter (GM), deep GM nuclei, and spinal cord damage in patients with primary progressive multiple sclerosis (PP-MS) provides insights into the neurodegenerative process responsible for clinical progression of MS. To investigate the association of magnetic resonance imaging measures of cortical, deep GM, and spinal cord damage and their effect on clinical disability. Cross-sectional analysis of 26 patients with PP-MS (mean age, 50.9 years; range, 31-65 years; including 14 women) and 20 healthy control participants (mean age, 51.1 years; range, 34-63 years; including 11 women) enrolled at a single US institution. Clinical disability was measured with the Expanded Disability Status Scale, 9-Hole Peg Test, and 25-Foot Walking Test. We collected data from January 1, 2012, through December 31, 2013. Data analysis was performed from January 21 to April 10, 2015. Cortical lesion burden, brain and deep GM volumes, spinal cord area and volume, and scores on the Expanded Disability Status Scale (score range, 0 to 10; higher scores indicate greater disability), 9-Hole Peg Test (measured in seconds; longer performance time indicates greater disability), and 25-Foot Walking Test (test covers 7.5 m; measured in seconds; longer performance time indicates greater disability). The 26 patients with PP-MS showed significantly smaller mean (SD) brain and spinal cord volumes than the 20 control group patients (normalized brain volume, 1377.81 [65.48] vs 1434.06 [53.67] cm3 [P = .003]; normalized white matter volume, 650.61 [46.38] vs 676.75 [37.02] cm3 [P = .045]; normalized gray matter volume, 727.20 [40.74] vs 757.31 [38.95] cm3 [P = .02]; normalized neocortical volume, 567.88 [85.55] vs 645.00 [42.84] cm3 [P = .001]; normalized spinal cord volume for C2-C5, 72.71 [7.89] vs 82.70 [7.83] mm3 [P < .001]; and normalized spinal cord volume for C2-C3, 64.86 [7.78] vs 72.26 [7.79] mm3 [P =.002]). The amount of damage in deep GM structures, especially with respect to the thalamus, was correlated with the number and volume of cortical lesions (mean [SD] thalamus volume, 8.89 [1.10] cm3; cortical lesion number, 12.6 [11.7]; cortical lesion volume, 0.65 [0.58] cm3; r = -0.52; P < .01). Thalamic atrophy also showed an association with cortical lesion count in the frontal cortex (mean [SD] thalamus volume, 8.89 [1.1] cm3; cortical lesion count in the frontal lobe, 5.0 [5.7]; r = -0.60; P < .01). No association was identified between magnetic resonance imaging measures of the brain and spinal cord damage. In this study, the neurodegenerative process occurring in PP-MS appeared to spread across connected structures in the brain while proceeding independently in the spinal cord. These results support the relevance of anatomical connectivity for the propagation of MS damage in the PP phenotype.

Age, gender and normalization covariates for spinal cord gray matter and total cross-sectional areas at cervical and thoracic levels: A 2D phase sensitive inversion recovery imaging study.

PubMed

Papinutto, Nico; Schlaeger, Regina; Panara, Valentina; Zhu, Alyssa H; Caverzasi, Eduardo; Stern, William A; Hauser, Stephen L; Henry, Roland G

2015-01-01

The source of inter-subject variability and the influence of age and gender on morphometric characteristics of the spinal cord, such as the total cross-sectional area (TCA), the gray matter (GM) and white matter (WM) areas, currently remain under investigation. Understanding the effect of covariates such as age, gender, brain volumes, and skull- and vertebra-derived metrics on cervical and thoracic spinal cord TCA and GM areas in healthy subjects would be fundamental for exploring compartment specific changes in neurological diseases affecting the spinal cord. Using Magnetic Resonance Imaging at 3T we investigated 32 healthy subjects using a 2D phase sensitive inversion recovery sequence and we measured TCA, GM and WM areas at 4 cervical and thoracic levels of the spinal cord. We assessed age and gender relationships of cord measures and explored associations between cord measures and a) brain volumes and b) skull- and vertebra-derived metrics. Age and gender had a significant effect on TCA, WM and GM areas (with women and elderly having smaller values than men and younger people respectively), but not on the GM area/TCA ratio. The total intracranial volume and C3 vertebra dimensions showed the highest correlations with cord measures. When used in multi-regression models, they reduced cord areas group variability by approximately a third. Age and gender influences on cord measures and normalization strategies here presented might be of use in the study of compartment specific changes in various neurological diseases affecting the spinal cord.

Multivariate pattern analysis reveals subtle brain anomalies relevant to the cognitive phenotype in neurofibromatosis type 1.

PubMed

Duarte, João V; Ribeiro, Maria J; Violante, Inês R; Cunha, Gil; Silva, Eduardo; Castelo-Branco, Miguel

2014-01-01

Neurofibromatosis Type 1 (NF1) is a common genetic condition associated with cognitive dysfunction. However, the pathophysiology of the NF1 cognitive deficits is not well understood. Abnormal brain structure, including increased total brain volume, white matter (WM) and grey matter (GM) abnormalities have been reported in the NF1 brain. These previous studies employed univariate model-driven methods preventing detection of subtle and spatially distributed differences in brain anatomy. Multivariate pattern analysis allows the combination of information from multiple spatial locations yielding a discriminative power beyond that of single voxels. Here we investigated for the first time subtle anomalies in the NF1 brain, using a multivariate data-driven classification approach. We used support vector machines (SVM) to classify whole-brain GM and WM segments of structural T1 -weighted MRI scans from 39 participants with NF1 and 60 non-affected individuals, divided in children/adolescents and adults groups. We also employed voxel-based morphometry (VBM) as a univariate gold standard to study brain structural differences. SVM classifiers correctly classified 94% of cases (sensitivity 92%; specificity 96%) revealing the existence of brain structural anomalies that discriminate NF1 individuals from controls. Accordingly, VBM analysis revealed structural differences in agreement with the SVM weight maps representing the most relevant brain regions for group discrimination. These included the hippocampus, basal ganglia, thalamus, and visual cortex. This multivariate data-driven analysis thus identified subtle anomalies in brain structure in the absence of visible pathology. Our results provide further insight into the neuroanatomical correlates of known features of the cognitive phenotype of NF1. Copyright © 2012 Wiley Periodicals, Inc.

Improving Functional MRI Registration Using Whole-Brain Functional Correlation Tensors.

PubMed

Zhou, Yujia; Yap, Pew-Thian; Zhang, Han; Zhang, Lichi; Feng, Qianjin; Shen, Dinggang

2017-09-01

Population studies of brain function with resting-state functional magnetic resonance imaging (rs-fMRI) largely rely on the accurate inter-subject registration of functional areas. This is typically achieved through registration of the corresponding T1-weighted MR images with more structural details. However, accumulating evidence has suggested that such strategy cannot well-align functional regions which are not necessarily confined by the anatomical boundaries defined by the T1-weighted MR images. To mitigate this problem, various registration algorithms based directly on rs-fMRI data have been developed, most of which have utilized functional connectivity (FC) as features for registration. However, most of the FC-based registration methods usually extract the functional features only from the thin and highly curved cortical grey matter (GM), posing a great challenge in accurately estimating the whole-brain deformation field. In this paper, we demonstrate that the additional useful functional features can be extracted from brain regions beyond the GM, particularly, white-matter (WM) based on rs-fMRI, for improving the overall functional registration. Specifically, we quantify the local anisotropic correlation patterns of the blood oxygenation level-dependent (BOLD) signals, modeled by functional correlation tensors (FCTs), in both GM and WM. Functional registration is then performed based on multiple components of the whole-brain FCTs using a multichannel Large Deformation Diffeomorphic Metric Mapping (mLDDMM) algorithm. Experimental results show that our proposed method achieves superior functional registration performance, compared with other conventional registration methods.

Amygdala atrophy affects emotion-related activity in face-responsive regions in frontotemporal degeneration.

PubMed

De Winter, François-Laurent; Van den Stock, Jan; de Gelder, Beatrice; Peeters, Ronald; Jastorff, Jan; Sunaert, Stefan; Vanduffel, Wim; Vandenberghe, Rik; Vandenbulcke, Mathieu

2016-09-01

In the healthy brain, modulatory influences from the amygdala commonly explain enhanced activation in face-responsive areas by emotional facial expressions relative to neutral expressions. In the behavioral variant frontotemporal dementia (bvFTD) facial emotion recognition is impaired and has been associated with atrophy of the amygdala. By combining structural and functional MRI in 19 patients with bvFTD and 20 controls we investigated the neural effects of emotion in face-responsive cortex and its relationship with amygdalar gray matter (GM) volume in neurodegeneration. Voxel-based morphometry revealed decreased GM volume in anterior medio-temporal regions including amygdala in patients compared to controls. During fMRI, we presented dynamic facial expressions (fear and chewing) and their spatiotemporally scrambled versions. We found enhanced activation for fearful compared to neutral faces in ventral temporal cortex and superior temporal sulcus in controls, but not in patients. In the bvFTD group left amygdalar GM volume correlated positively with emotion-related activity in left fusiform face area (FFA). This correlation was amygdala-specific and driven by GM in superficial and basolateral (BLA) subnuclei, consistent with reported amygdalar-cortical networks. The data suggests that anterior medio-temporal atrophy in bvFTD affects emotion processing in distant posterior areas. Copyright © 2016 Elsevier Ltd. All rights reserved.

Longitudinal decline in speech production in Parkinson's disease spectrum disorders.

PubMed

Ash, Sharon; Jester, Charles; York, Collin; Kofman, Olga L; Langey, Rachel; Halpin, Amy; Firn, Kim; Dominguez Perez, Sophia; Chahine, Lama; Spindler, Meredith; Dahodwala, Nabila; Irwin, David J; McMillan, Corey; Weintraub, Daniel; Grossman, Murray

2017-08-01

We examined narrative speech production longitudinally in non-demented (n=15) and mildly demented (n=8) patients with Parkinson's disease spectrum disorder (PDSD), and we related increasing impairment to structural brain changes in specific language and motor regions. Patients provided semi-structured speech samples, describing a standardized picture at two time points (mean±SD interval=38±24months). The recorded speech samples were analyzed for fluency, grammar, and informativeness. PDSD patients with dementia exhibited significant decline in their speech, unrelated to changes in overall cognitive or motor functioning. Regression analysis in a subset of patients with MRI scans (n=11) revealed that impaired language performance at Time 2 was associated with reduced gray matter (GM) volume at Time 1 in regions of interest important for language functioning but not with reduced GM volume in motor brain areas. These results dissociate language and motor systems and highlight the importance of non-motor brain regions for declining language in PDSD. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain Volume as an Integrated Marker for the Risk of Death in a Community-Based Sample: Age Gene/Environment Susceptibility--Reykjavik Study.

PubMed

Van Elderen, Saskia S G C; Zhang, Qian; Sigurdsson, Sigudur; Haight, Thaddeus J; Lopez, Oscar; Eiriksdottir, Gudny; Jonsson, Palmi; de Jong, Laura; Harris, Tamara B; Garcia, Melissa; Gudnason, Vilmundar; van Buchem, Mark A; Launer, Lenore J

2016-01-01

Total brain volume is an integrated measure of health and may be an independent indicator of mortality risk independent of any one clinical or subclinical disease state. We investigate the association of brain volume to total and cause-specific mortality in a large nondemented stroke-free community-based cohort. The analysis includes 3,543 men and women (born 1907-1935) participating in the Age, Gene, Environment Susceptibility-Reykjavik Study. Participants with a known brain-related high risk for mortality (cognitive impairment or stroke) were excluded from these analyses. Quantitative estimates of total brain volume, white matter, white matter lesions, total gray matter (GM; cortical GM and subcortical GM separately), and focal cerebral vascular disease were generated from brain magnetic resonance imaging. Brain atrophy was expressed as brain tissue volume divided by total intracranial volume, yielding a percentage. Mean follow-up duration was 7.2 (0-10) years, with 647 deaths. Cox regression was used to analyze the association of mortality to brain atrophy, adjusting for demographics, cardiovascular risk factors, and cerebral vascular disease. Reduced risk of mortality was significantly associated with higher total brain volume (hazard ratio, 95% confidence interval = 0.71, 0.65-0.78), white matter (0.85, 0.78-0.93), total GM (0.74, 0.68-0.81), and cortical GM (0.78, 0.70-0.87). Overall, the associations were similar for cardiovascular and noncardiovascular-related deaths. Independent of multiple risk factors and cerebral vascular damage, global brain volume predicts mortality in a large nondemented stroke-free community-dwelling older cohort. Total brain volume may be an integrated measure reflecting a range of health and with further investigation could be a useful clinical tool when assessing risk for mortality. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

Brain tissue volumes in the general elderly population. The Rotterdam Scan Study.

PubMed

Ikram, M Arfan; Vrooman, Henri A; Vernooij, Meike W; van der Lijn, Fedde; Hofman, Albert; van der Lugt, Aad; Niessen, Wiro J; Breteler, Monique M B

2008-06-01

We investigated how volumes of cerebrospinal fluid (CSF), grey matter (GM) and white matter (WM) varied with age, sex, small vessel disease and cardiovascular risk factors in the Rotterdam Scan Study. Participants (n=490; 60-90 years) were non-demented and 51.0% had hypertension, 4.9% had diabetes mellitus, 17.8% were current smoker and 54.0% were former smoker. We segmented brain MR-images into GM, normal WM, white matter lesion (WML) and CSF. Brain infarcts were rated visually. Volumes were expressed as percentage of intra-cranial volume. With increasing age, volumes of total brain, normal WM and total WM decreased; that of GM remained unchanged; and that of WML increased, in both men and women. Excluding persons with infarcts did not alter these results. Persons with larger load of small vessel disease had smaller brain volume, especially normal WM volume. Diastolic blood pressure, diabetes mellitus and current smoking were also related to smaller brain volume. In the elderly, higher age, small vessel disease and cardiovascular risk factors are associated with smaller brain volume, especially WM volume.

Neuroanatomical correlates of performance in a state-wide test of math achievement.

PubMed

Wilkey, Eric D; Cutting, Laurie E; Price, Gavin R

2018-03-01

The development of math skills is a critical component of early education and a strong indicator of later school and economic success. Recent research utilizing population-normed, standardized measures of math achievement suggest that structural and functional integrity of parietal regions, especially the intraparietal sulcus, are closely related to the development of math skills. However, it is unknown how these findings relate to in-school math learning. The present study is the first to address this issue by investigating the relationship between regional differences in grey matter (GM) volume and performance in grade-level mathematics as measured by a state-wide, school-based test of math achievement (TCAP math) in children from 3rd to 8th grade. Results show that increased GM volume in the bilateral hippocampal formation and the right inferior frontal gyrus, regions associated with learning and memory, is associated with higher TCAP math scores. Secondary analyses revealed that GM volume in the left angular gyrus had a stronger relationship to TCAP math in grades 3-4 than in grades 5-8 while the relationship between GM volume in the left inferior frontal gyrus and TCAP math was stronger for grades 5-8. These results suggest that the neuroanatomical architecture related to in-school math achievement differs from that related to math achievement measured by standardized tests, and that the most related neural structures differ as a function of grade level. We suggest, therefore, that the use of school-relevant outcome measures is critical if neuroscience is to bridge the gap to education. © 2017 John Wiley & Sons Ltd.

Isotropic non-white matter partial volume effects in constrained spherical deconvolution.

PubMed

Roine, Timo; Jeurissen, Ben; Perrone, Daniele; Aelterman, Jan; Leemans, Alexander; Philips, Wilfried; Sijbers, Jan

2014-01-01

Diffusion-weighted (DW) magnetic resonance imaging (MRI) is a non-invasive imaging method, which can be used to investigate neural tracts in the white matter (WM) of the brain. Significant partial volume effects (PVEs) are present in the DW signal due to relatively large voxel sizes. These PVEs can be caused by both non-WM tissue, such as gray matter (GM) and cerebrospinal fluid (CSF), and by multiple non-parallel WM fiber populations. High angular resolution diffusion imaging (HARDI) methods have been developed to correctly characterize complex WM fiber configurations, but to date, many of the HARDI methods do not account for non-WM PVEs. In this work, we investigated the isotropic PVEs caused by non-WM tissue in WM voxels on fiber orientations extracted with constrained spherical deconvolution (CSD). Experiments were performed on simulated and real DW-MRI data. In particular, simulations were performed to demonstrate the effects of varying the diffusion weightings, signal-to-noise ratios (SNRs), fiber configurations, and tissue fractions. Our results show that the presence of non-WM tissue signal causes a decrease in the precision of the detected fiber orientations and an increase in the detection of false peaks in CSD. We estimated 35-50% of WM voxels to be affected by non-WM PVEs. For HARDI sequences, which typically have a relatively high degree of diffusion weighting, these adverse effects are most pronounced in voxels with GM PVEs. The non-WM PVEs become severe with 50% GM volume for maximum spherical harmonics orders of 8 and below, and already with 25% GM volume for higher orders. In addition, a low diffusion weighting or SNR increases the effects. The non-WM PVEs may cause problems in connectomics, where reliable fiber tracking at the WM-GM interface is especially important. We suggest acquiring data with high diffusion-weighting 2500-3000 s/mm(2), reasonable SNR (~30) and using lower SH orders in GM contaminated regions to minimize the non-WM PVEs in CSD.

Regional grey matter structure differences between transsexuals and healthy controls--a voxel based morphometry study.

PubMed

Simon, Lajos; Kozák, Lajos R; Simon, Viktória; Czobor, Pál; Unoka, Zsolt; Szabó, Ádám; Csukly, Gábor

2013-01-01

Gender identity disorder (GID) refers to transsexual individuals who feel that their assigned biological gender is incongruent with their gender identity and this cannot be explained by any physical intersex condition. There is growing scientific interest in the last decades in studying the neuroanatomy and brain functions of transsexual individuals to better understand both the neuroanatomical features of transsexualism and the background of gender identity. So far, results are inconclusive but in general, transsexualism has been associated with a distinct neuroanatomical pattern. Studies mainly focused on male to female (MTF) transsexuals and there is scarcity of data acquired on female to male (FTM) transsexuals. Thus, our aim was to analyze structural MRI data with voxel based morphometry (VBM) obtained from both FTM and MTF transsexuals (n = 17) and compare them to the data of 18 age matched healthy control subjects (both males and females). We found differences in the regional grey matter (GM) structure of transsexual compared with control subjects, independent from their biological gender, in the cerebellum, the left angular gyrus and in the left inferior parietal lobule. Additionally, our findings showed that in several brain areas, regarding their GM volume, transsexual subjects did not differ significantly from controls sharing their gender identity but were different from those sharing their biological gender (areas in the left and right precentral gyri, the left postcentral gyrus, the left posterior cingulate, precuneus and calcarinus, the right cuneus, the right fusiform, lingual, middle and inferior occipital, and inferior temporal gyri). These results support the notion that structural brain differences exist between transsexual and healthy control subjects and that majority of these structural differences are dependent on the biological gender.

Regional Grey Matter Structure Differences between Transsexuals and Healthy Controls—A Voxel Based Morphometry Study

PubMed Central

Simon, Lajos; Kozák, Lajos R.; Simon, Viktória; Czobor, Pál; Unoka, Zsolt; Szabó, Ádám; Csukly, Gábor

2013-01-01

Gender identity disorder (GID) refers to transsexual individuals who feel that their assigned biological gender is incongruent with their gender identity and this cannot be explained by any physical intersex condition. There is growing scientific interest in the last decades in studying the neuroanatomy and brain functions of transsexual individuals to better understand both the neuroanatomical features of transsexualism and the background of gender identity. So far, results are inconclusive but in general, transsexualism has been associated with a distinct neuroanatomical pattern. Studies mainly focused on male to female (MTF) transsexuals and there is scarcity of data acquired on female to male (FTM) transsexuals. Thus, our aim was to analyze structural MRI data with voxel based morphometry (VBM) obtained from both FTM and MTF transsexuals (n = 17) and compare them to the data of 18 age matched healthy control subjects (both males and females). We found differences in the regional grey matter (GM) structure of transsexual compared with control subjects, independent from their biological gender, in the cerebellum, the left angular gyrus and in the left inferior parietal lobule. Additionally, our findings showed that in several brain areas, regarding their GM volume, transsexual subjects did not differ significantly from controls sharing their gender identity but were different from those sharing their biological gender (areas in the left and right precentral gyri, the left postcentral gyrus, the left posterior cingulate, precuneus and calcarinus, the right cuneus, the right fusiform, lingual, middle and inferior occipital, and inferior temporal gyri). These results support the notion that structural brain differences exist between transsexual and healthy control subjects and that majority of these structural differences are dependent on the biological gender. PMID:24391851

Regional patterns of grey matter atrophy and magnetisation transfer ratio abnormalities in multiple sclerosis clinical subgroups: A voxel-based analysis study

PubMed Central

Muhlert, Nils; Samson, Rebecca S; Sethi, Varun; Wheeler-Kingshott, Claudia AM; Miller, David H; Chard, Declan T

2015-01-01

Background: In multiple sclerosis (MS), demyelination and neuro-axonal loss occur in the brain grey matter (GM). We used magnetic resonance imaging (MRI) measures of GM magnetisation transfer ratio (MTR) and volume to assess the regional localisation of reduced MTR (reflecting demyelination) and atrophy (reflecting neuro-axonal loss) in relapsing–remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS). Methods: A total of 98 people with MS (51 RRMS, 28 SPMS, 19 PPMS) and 29 controls had T1-weighted volumetric and magnetisation transfer scans. SPM8 was used to undertake voxel-based analysis (VBA) of GM tissue volumes and MTR. MS subgroups were compared with controls, adjusting for age and gender. A voxel-by-voxel basis correlation analysis between MTR and volume within each subject group was performed, using biological parametric mapping. Results: MTR reduction was more extensive than atrophy. RRMS and SPMS patients showed proportionately more atrophy in the deep GM. SPMS and PPMS patients showed proportionately greater cortical MTR reduction. RRMS patients demonstrated the most correlation of MTR reduction and atrophy in deep GM. In SPMS and PPMS patients, there was less extensive correlation. Conclusions: These results suggest that in the deep GM of RRMS patients, demyelination and neuro-axonal loss may be linked, while in SPMS and PPMS patients, neuro-axonal loss and demyelination may occur mostly independently. PMID:25145689

Structure impact of two galactomannan fractions on their viscosity properties in dilute solution, unperturbed state and gel state.

PubMed

Gillet, Sébastien; Aguedo, Mario; Petrut, Raul; Olive, Gilles; Anastas, Paul; Blecker, Christophe; Richel, Aurore

2017-03-01

Two fractions of carob galactomannans (GM25 and GM80) were extracted at respectively 25°C and 80°C from crude locust bean gum. Those fractions having slightly different chemical structures, previously characterized, were studied for their viscosity properties over a wide range of concentrations: diluted solution, unperturbed state and gel state. For each of the physical properties, links to the chemical fine structure could be established, expanding knowledge on the topic: in dilute solution, GM25 is more soluble in water while GM80 seems to tend to self-association due to its structure as highlighted by intrinsic viscosity measurements ([η] GM25 =9.96dLg -1 and [η] GM80 =4.04dLg -1 ). In unperturbed state, initial viscosities η 0 were more important for GM80 fractions at 1% and 2% due to greater hyperentanglements (η 0(GM80,1%) =9.9Pas; η 0(GM80,2%) =832.0; Pa.s η 0(GM25,1%) =3.1Pas; η 0(GM25,2%) =45.1Pas). In gel state, hydrogels obtained from GM80 were also stronger (hardness GM80 (2%)=0.51N and hardness GM25 (2%)=0.11N), suggesting a much more important number of junction areas within the gel network. The findings discussed herein demonstrate the potential for new applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of speed and magnitude of weight loss on the development of brain trophic changes in adolescents with anorexia nervosa: a case control study.

PubMed

Bomba, Monica; Riva, Anna; Veggo, Federica; Grimaldi, Marco; Morzenti, Sabrina; Neri, Francesca; Nacinovich, Renata

2013-02-19

Anorexia nervosa commonly arises during adolescence and is associated with more than one medical morbidity. Abnormalities in brain structure (defined as "pseudoatrophy") are common in adolescents with anorexia nervosa; however, their correlations with endocrinological profiles and clinical parameters are still unclear. In particular, no study has described the impact of BMI (body mass index) variations (speed and magnitude of weight loss) on cerebral trophism changes. Eleven adolescents with anorexia nervosa and 8 healthy controls underwent cerebral MRI (magnetic resonance imaging) examination to obtain global and partial volumes (gray matter, white matter and cerebrospinal fluid) and clinical evaluation. The Mann-Whitney U test was used to compare partial volumes and clinical variables between cases and controls. The Spearman non-parametric test was performed in order to explore correlations between the variables studied. The patients diagnosed with AN showed significantly increased cerebrospinal fluid (CSF) volumes and decreased total gray (GM) and white matter (WM) volumes. The degree of weight loss (deltaBMI) correlated inversely with the GM volume; the increase of CSF compartment correlated directly with the rapidity of weight loss (DeltaBMI/disease duration). This study suggests a correlation between cerebral alterations in AN and the speed and magnitude of weight loss, and outlines its importance for the therapeutic treatment.

GM2 gangliosidosis AB variant: novel mutation from India - a case report with a review.

PubMed

Sheth, Jayesh; Datar, Chaitanya; Mistri, Mehul; Bhavsar, Riddhi; Sheth, Frenny; Shah, Krati

2016-07-11

GM2 gangliosidosis-AB variants a rare autosomal recessive neurodegenerative disorder occurring due to deficiency of GM2 activator protein resulting from the mutation in GM2A gene. Only seven mutations in nine cases have been reported from different population except India. Present case is a one year old male born to 3rd degree consanguineous Indian parents from Maharashtra. He was presented with global developmental delay, hypotonia and sensitive to hyperacusis. Horizontal nystagmus and cherry red spot was detected during ophthalmic examination. MRI of brain revealed putaminal hyperintensity and thalamic hypointensity with some unmyelinated white matter in T2/T1 weighted images. Initially he was suspected having Tay-Sachs disease and finally diagnosed as GM2 gangliosidosis, AB variant due to truncated protein caused by nonsense mutation c.472 G > T (p.E158X) in GM2Agene. Children with phenotypic presentation as GM2 gangliosidosis (Tay-Sachs or Sandhoff disease) and normal enzyme activity of β-hexosaminidase-A and -B in leucocytes need to be investigated for GM2 activator protein deficiency.

Deep gray matter volume loss drives disability worsening in multiple sclerosis

PubMed Central

Prados, Ferran; Brownlee, Wallace J.; Altmann, Daniel R.; Tur, Carmen; Cardoso, M. Jorge; De Angelis, Floriana; van de Pavert, Steven H.; Cawley, Niamh; De Stefano, Nicola; Stromillo, M. Laura; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A.; Rovira, Alex; Sastre‐Garriga, Jaume; Vrenken, Hugo; Leurs, Cyra E.; Killestein, Joep; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Wheeler‐Kingshott, Claudia A.M. Gandini; Chard, Declan; Thompson, Alan J.; Alexander, Daniel C.; Barkhof, Frederik; Ciccarelli, Olga

2018-01-01

Objective Gray matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS. Methods We analyzed 3,604 brain high‐resolution T1‐weighted magnetic resonance imaging scans from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome [CIS], 708 relapsing‐remitting [RRMS], 128 secondary‐progressive [SPMS], and 125 primary‐progressive [PPMS]), over an average follow‐up of 2.41 years (standard deviation [SD] = 1.97), and 203 healthy controls (HCs; average follow‐up = 1.83 year; SD = 1.77), attending seven European centers. Disability was assessed with the Expanded Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem, and cerebral white matter. Hierarchical mixed models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time‐to‐EDSS progression. Results SPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time‐to‐EDSS progression (hazard ratio = 0.73; 95% confidence interval, 0.65, 0.82; p < 0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow‐up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (–1.45%), PPMS (–1.66%), and RRMS (–1.34%) than CIS (–0.88%) and HCs (–0.94%; p < 0.01). The rate of temporal GM atrophy in SPMS (–1.21%) was significantly faster than RRMS (–0.76%), CIS (–0.75%), and HCs (–0.51%). Similarly, the rate of parietal GM atrophy in SPMS (–1.24‐%) was faster than CIS (–0.63%) and HCs (–0.23%; all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta = 0.04; p < 0.001). Interpretation This large, multicenter and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions. Ann Neurol 2018;83:210–222 PMID:29331092

Structural but not functional neuroplasticity one year after effective cognitive behaviour therapy for social anxiety disorder.

PubMed

Månsson, Kristoffer N T; Salami, Alireza; Carlbring, Per; Boraxbekk, C-J; Andersson, Gerhard; Furmark, Tomas

2017-02-01

Effective psychiatric treatments ameliorate excessive anxiety and induce neuroplasticity immediately after the intervention, indicating that emotional components in the human brain are rapidly adaptable. Still, the interplay between structural and functional neuroplasticity is poorly understood, and studies of treatment-induced long-term neuroplasticity are rare. Functional and structural magnetic resonance imaging (using 3T MRI) was performed in 13 subjects with social anxiety disorder on 3 occasions over 1year. All subjects underwent 9 weeks of Internet-delivered cognitive behaviour therapy in a randomized cross-over design and independent assessors used the Clinically Global Impression-Improvement (CGI-I) scale to determine treatment response. Gray matter (GM) volume, assessed with voxel-based morphometry, and functional blood-oxygen level-dependent (BOLD) responsivity to self-referential criticism were compared between treatment responders and non-responders using 2×2 (group×time; pretreatment to follow-up) ANOVA. At 1-year follow-up, 7 (54%) subjects were classified as CGI-I responders. Left amygdala GM volume was more reduced in responders relative to non-responders from pretreatment to 1-year follow-up (Z=3.67, Family-Wise Error corrected p=0.02). In contrast to previous short-term effects, altered BOLD activations to self-referential criticism did not separate responder groups at follow-up. The structure and function of the amygdala changes immediately after effective psychological treatment of social anxiety disorder, but only reduced amygdala GM volume, and not functional activity, is associated with a clinical response 1year after CBT. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain lesion correlates of fatigue in individuals with traumatic brain injury.

PubMed

Schönberger, Michael; Reutens, David; Beare, Richard; O'Sullivan, Richard; Rajaratnam, Shantha M W; Ponsford, Jennie

2017-10-01

The purpose of this study was to investigate the neurological correlates of both subjective fatigue as well as objective fatigability in individuals with traumatic brain injury (TBI). The study has a cross-sectional design. Participants (N = 53) with TBI (77% male, mean age at injury 38 years, mean time since injury 1.8 years) underwent a structural magnetic resonance imaging (MRI) scan and completed the Fatigue Severity Scale (FSS), while a subsample (N = 36) was also tested with a vigilance task. While subjective fatigue (FSS) was not related to measures of brain lesions, multilevel analyses showed that a change in the participants' decision time was significantly predicted by grey matter (GM) lesions in the right frontal lobe. The time-dependent development of the participants' error rate was predicted by total brain white matter (WM) lesion volumes, as well as right temporal GM and WM lesion volumes. These findings could be explained by decreased functional connectivity of attentional networks, which results in accelerated exhaustion during cognitive task performance. The disparate nature of objectively measurable fatigability on the one hand and the subjective experience of fatigue on the other needs further investigation.

White matter structural alterations in pediatric obsessive-compulsive disorder: relation to symptom dimensions.

PubMed

Lázaro, L; Ortiz, A G; Calvo, A; Ortiz, A E; Moreno, E; Morer, A; Calvo, R; Bargallo, N

2014-10-03

The aims of this study were to identify gray matter (GM) and white matter (WM) volume abnormalities in pediatric obsessive-compulsive patients, to examine their relationship between these abnormalities and the severity of disorder, and to explore whether they could be explained by the different symptom dimensions. 62 child and adolescent OCD patients (11-18years old) and 46 healthy subjects of the same gender and similar age and estimated intellectual quotient were assessed by means of psychopathological scales and magnetic resonance imaging (MRI). Axial three-dimensional T1-weighted images were obtained in a 3T scanner and analyzed using optimized voxel-based morphometry (VBM). Compared with healthy controls, OCD patients showed lower white matter (WM) volume in the left dorsolateral and cingulate regions involving the superior and middle frontal gyri and anterior cingulate gyrus (t=4.35, p=0.049 FWE (family wise error)-corrected). There was no significant correlation between WM and the severity of obsessive-compulsive symptomatology. There were no regions with lower gray matter (GM) volume in OCD patients than in controls. Compared with healthy controls, only the "harm/checking" OCD dimension showed a cluster with a near significant decrease in WM volume in the right superior temporal gyrus extending into the insula (t=5.61, p=.056 FWE-corrected). The evidence suggests that abnormalities in the dorsolateral prefrontal cortex, anterior cingulate cortex, temporal and limbic regions play a central role in the pathophysiology of OCD. Moreover, regional brain volumes in OCD may vary depending on specific OCD symptom dimensions, indicating the clinical heterogeneity of the condition. Copyright © 2014 Elsevier Inc. All rights reserved.

Longitudinal Study of Neurodegenerative Disorders

ClinicalTrials.gov

2018-01-31

MLD; Krabbe Disease; ALD; MPS I; MPS II; MPS III; Vanishing White Matter Disease; GM3 Gangliosidosis; PKAN; Tay-Sachs Disease; NP Deficiency; Osteopetrosis; Alpha-Mannosidosis; Sandhoff Disease; Niemann-Pick Diseases; MPS IV; Gaucher Disease; GAN; GM1 Gangliosidoses; Morquio Disease; S-Adenosylhomocysteine Hydrolase Deficiency; Batten Disease; Pelizaeus-Merzbacher Disease; Leukodystrophy; Lysosomal Storage Diseases; Purine Nucleoside Phosphorylase Deficiency; Multiple Sulfatase Deficiency Disease

Brain-derived Neurotrophic Factor (BDNF) and gray matter volume in bipolar disorder.

PubMed

Poletti, S; Aggio, V; Hoogenboezem, T A; Ambrée, O; de Wit, H; Wijkhuijs, A J M; Locatelli, C; Colombo, C; Arolt, V; Drexhage, H A; Benedetti, F

2017-02-01

Bipolar Disorder (BD) is a severe psychiatric condition characterized by grey matter (GM) volumes reduction. Neurotrophic factors have been suggested to play a role in the neuroprogressive changes during the illness course. In particular peripheral brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in BD. The aim of our study was to investigate if serum levels of BDNF are associated with GM volumes in BD patients and healthy controls (HC). We studied 36 inpatients affected by a major depressive episode in course of BD type I and 17 HC. Analysis of variance was performed to investigate the effect of diagnosis on GM volumes in the whole brain. Threshold for significance was P<0.05, Family Wise Error (FWE) corrected for multiple comparisons. All the analyses were controlled for the effect of nuisance covariates known to influence GM volumes, such as age, gender and lithium treatment. BD patients showed significantly higher serum BDNF levels compared with HC. Reduced GM volumes in BD patients compared to HC were observed in several brain areas, encompassing the caudate head, superior temporal gyrus, insula, fusiform gyrus, parahippocampal gyrus, and anterior cingulate cortex. The interaction analysis between BDNF levels and diagnosis showed a significant effect in the middle frontal gyrus. HC reported higher BDNF levels associated with higher GM volumes, whereas no association between BDNF and GM volumes was observed in BD. Our study seems to suggest that although the production of BDNF is increased in BD possibly to prevent and repair neural damage, its effects could be hampered by underlying neuroinflammatory processes interfering with the neurodevelopmental role of BDNF. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Measurement of pediatric regional cerebral blood flow from 6 months to 15 years of age in a clinical population.

PubMed

Carsin-Vu, Aline; Corouge, Isabelle; Commowick, Olivier; Bouzillé, Guillaume; Barillot, Christian; Ferré, Jean-Christophe; Proisy, Maia

2018-04-01

To investigate changes in cerebral blood flow (CBF) in gray matter (GM) between 6 months and 15 years of age and to provide CBF values for the brain, GM, white matter (WM), hemispheres and lobes. Between 2013 and 2016, we retrospectively included all clinical MRI examinations with arterial spin labeling (ASL). We excluded subjects with a condition potentially affecting brain perfusion. For each subject, mean values of CBF in the brain, GM, WM, hemispheres and lobes were calculated. GM CBF was fitted using linear, quadratic and cubic polynomial regression against age. Regression models were compared with Akaike's information criterion (AIC), and Likelihood Ratio tests. 84 children were included (44 females/40 males). Mean CBF values were 64.2 ± 13.8 mL/100 g/min in GM, and 29.3 ± 10.0 mL/100 g/min in WM. The best-fit model of brain perfusion was the cubic polynomial function (AIC = 672.7, versus respectively AIC = 673.9 and AIC = 674.1 with the linear negative function and the quadratic polynomial function). A statistically significant difference between the tested models demonstrating the superiority of the quadratic (p = 0.18) or cubic polynomial model (p = 0.06), over the negative linear regression model was not found. No effect of general anesthesia (p = 0.34) or of gender (p = 0.16) was found. we provided values for ASL CBF in the brain, GM, WM, hemispheres, and lobes over a wide pediatric age range, approximately showing inverted U-shaped changes in GM perfusion over the course of childhood. Copyright © 2018 Elsevier B.V. All rights reserved.

The Generation Model of Particle Physics and Galactic Dark Matter

NASA Astrophysics Data System (ADS)

Robson, B. A.

2013-09-01

Galactic dark matter is matter hypothesized to account for the discrepancy of the mass of a galaxy determined from its gravitational effects, assuming the validity of Newton's law of universal gravitation, and the mass calculated from the "luminous matter", stars, gas, dust, etc. observed to be contained within the galaxy. The conclusive observation from the rotation curves of spiral galaxies that the mass discrepancy is greater, the larger the distance scales involved implies that either Newton's law of universal gravitation requires modification or considerably more mass (dark matter) is required to be present in each galaxy. Both the modification of Newton's law of gravitation and the hypothesis of the existence of considerable dark matter in a galaxy are discussed. It is shown that the Generation Model (GM) of particle physics, which leads to a modification of Newton's law of gravitation, is found to be essentially equivalent to that of Milgrom's modified Newtonian dynamics (MOND) theory, with the GM providing a physical understanding of the MOND theory. The continuing success of MOND theory in describing the extragalactic mass discrepancy problems constitutes a strong argument against the existence of undetected dark matter haloes, consisting of unknown nonbaryonic matter, surrounding spiral galaxies.

Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis.

PubMed

Pardini, Matteo; Sudre, Carole H; Prados, Ferran; Yaldizli, Özgür; Sethi, Varun; Muhlert, Nils; Samson, Rebecca S; van de Pavert, Steven H; Cardoso, M Jorge; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A M; Miller, David H; Chard, Declan T

2016-11-01

To assess the association between proximity to the inner (ventricular and aqueductal) and outer (pial) surfaces of the brain and the distribution of normal appearing white matter (NAWM) and grey matter (GM) abnormalities, and white matter (WM) lesions, in multiple sclerosis (MS). 67 people with relapse-onset MS and 30 healthy controls were included in the study. Volumetric T1 images and high-resolution (1 mm 3 ) magnetisation transfer ratio (MTR) images were acquired and segmented into 12 bands between the inner and outer surfaces of the brain. The first and last bands were discarded to limit partial volume effects with cerebrospinal fluid. MTR values were computed for all bands in supratentorial NAWM, cerebellar NAWM and brainstem NA tissue, and deep and cortical GM. Band WM lesion volumes were also measured. Proximity to the ventricular surfaces was associated with progressively lower MTR values in the MS group but not in controls in supratentorial and cerebellar NAWM, brainstem NA and in deep and cortical GM. The density of WM lesions was associated with proximity to the ventricles only in the supratentorial compartment, and no link was found with distance from the pial surfaces. In MS, MTR abnormalities in NAWM and GM are related to distance from the inner and outer surfaces of the brain, and this suggests that there is a common factor underlying their spatial distribution. A similar pattern was not found for WM lesions, raising the possibility that different factors promote their formation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Brain-volume changes in young and middle-aged smokers: a DARTEL-based voxel-based morphometry study.

PubMed

Peng, Peng; Wang, Zhenchang; Jiang, Tao; Chu, Shuilian; Wang, Shuangkun; Xiao, Dan

2017-09-01

Many studies have reported brain volume changes in smokers. However, the volume differences of grey matter (GM) and white matter (WM) in young and middle-aged male smokers with different lifetime tobacco consumption (pack-years) remain uncertain. To examine the brain volume change, especially whether more pack-years smoking would be associated with smaller gray matter and white matter volume in young and middle-aged male smokers. We used a 3T MR scanner and performed Diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL)-based voxel-based morphometry on 53 long-term male smokers (30.72 ± 4.19 years) and 53 male healthy non-smokers (30.83 ± 5.18 years). We separated smokers to light and heavy smokers by pack-years and compared brain volume between different smoker groups and non-smokers. And then we did analysis of covariance (ANCOVA) between smokers and non-smokers by setting pack-years as covariates. Light and heavy smokers all displayed smaller GM and WM volume than non-smokers and more obviously in heavy smokers. The main smaller areas in light and heavy smokers were superior temporal gyrus, insula, middle occipital gyrus, posterior cingulate, precuneus in GM and posterior cingulate, thalamus and midbrain in WM, in addition, we also observed more pack-years smoking was associated with some certain smaller GM and WM volumes by ANCOVA. Young and middle-aged male smokers had many smaller brain areas than non-smokers. Some of these areas' volume had negative correlation with pack-years, while some had not. These may due to different pathophysiological role of smokings. © 2015 John Wiley & Sons Ltd.

Effects of low-level exposure to sarin and cyclosarin during the 1991 Gulf War on brain function and brain structure in US veterans

PubMed Central

Chao, Linda L.; Rothlind, Johannes C.; Cardenas, Valerie A.; Meyerhoff, Dieter J.; Weiner, Michael W.

2010-01-01

Background Potentially more than 100,000 US troops may have been exposed to the organophosphate chemical warfare agents sarin (GB) and cyclosarin (GF) when a munitions dump at Khamisiyah, Iraq was destroyed during the Gulf War (GW) in 1991. Although little is known about the long-term neurobehavioral or neurophysiological effects of low-dose exposure to GB/GF in humans, recent studies of GW veterans from the Devens Cohort suggest decrements in certain cognitive domains and atrophy in brain white matter occur individuals with higher estimated levels of presumed GB/GF exposure. The goal of the current study is to determine the generalizability of these findings in another cohort of GW veterans with suspected GB/GF exposure. Methods Neurobehavioral and imaging data collected in a study on Gulf War Illness between 2002–2007 were used in this study. We focused on the data of 40 GW-deployed veterans categorized as having been exposed to GB/GF at Khamisiyah, Iraq and 40 matched controls. Magnetic resonance images (MRI) of the brain were analyzed using automated and semi-automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM), cerebrospinal fluid (CSF) and hippocampus. Results GW veterans with suspected GB/GF exposure had reduced total GM and hippocampal volumes compared to their unexposed peers (p≤0.01). Although there were no group differences in measures of cognitive function or total WM volume, there were significant, positive correlations between total WM volume and measures of executive function and visuospatial abilities in veterans with suspected GB/GF exposure. Conclusions These findings suggest that low-level exposure to GB/GF can have deleterious effects on brain structure and brain function more than decade later. PMID:20580739

Associations between the self-reported frequency of hearing chemical alarms in theater and regional brain volume in Gulf War Veterans.

PubMed

Chao, Linda L; Reeb, Rosemary; Esparza, Iva L; Abadjian, Linda R

2016-03-01

We previously reported evidence of reduced cortical gray matter (GM), white matter (WM), and hippocampal volume in Gulf War (GW) veterans with predicted exposure to low-levels of nerve agent according to the 2000 Khamisiyah plume model analysis. Because there is suggestive evidence that other nerve agent exposures may have occurred during the Gulf War, we examined the association between the self-reported frequency of hearing chemical alarms sound during deployment in the Gulf War and regional brain volume in GW veterans. Ninety consecutive GW veterans (15 female, mean age: 52±8years) participating in a VA-funded study underwent structural magnetic resonance imaging (MRI) on a 3T scanner. Freesurfer (version 5.1) was used to obtain regional measures of cortical GM, WM, hippocampal, and insula volume. Multiple linear regression was used to determine the association between the self-reported frequencies of hearing chemical alarms during the Gulf War and regional brain volume. There was an inverse association between the self-reported frequency of hearing chemical alarms sound and total cortical GM (adjusted p=0.007), even after accounting for potentially confounding demographic and clinical variables, the veterans' current health status, and other concurrent deployment-related exposures that were correlated with hearing chemical alarms. Post-hoc analyses extended the inverse relationship between the frequency of hearing chemical alarms to GM volume in the frontal (adjusted p=0.02), parietal (adjusted p=0.01), and occipital (adjusted p=0.001) lobes. In contrast, regional brain volumes were not significantly associated with predicted exposure to the Khamisiyah plume or with Gulf War Illness status defined by the Kansas or Centers for Disease Control and Prevention criteria. Many veterans reported hearing chemical alarms sound during the Gulf War. The current findings suggest that exposure to substances that triggered those chemical alarms during the Gulf War likely had adverse neuroanatomical effects. Published by Elsevier B.V.

Associations between the self-reported frequency of hearing chemical alarms in theater and regional brain volume in Gulf War Veterans

PubMed Central

Chao, Linda L.; Reeb, Rosemary; Esparza, Iva L.; Abadjian, Linda R.

2017-01-01

Background We previously reported evidence of reduced cortical gray matter (GM), white matter (WM), and hippocampal volume in Gulf War (GW) veterans with predicted exposure to low-levels of nerve agent according to the 2000 Khamisiyah plume model analysis. Because there is suggestive evidence that other nerve agent exposures may have occurred during the Gulf War, we examined the association between the self-reported frequency of hearing chemical alarms sound during deployment in the Gulf War and regional brain volume in GW veterans. Methods Ninety consecutive GW veterans (15 female, mean age: 52±8 years) participating in a VA-funded study underwent structural magnetic resonance imaging (MRI) on a 3 T scanner. Freesurfer (version 5.1) was used to obtain regional measures of cortical GM, WM, hippocampal, and insula volume. Multiple linear regression was used to determine the association between the self-reported frequencies of hearing chemical alarms during the Gulf War and regional brain volume. Results There was an inverse association between the self-reported frequency of hearing chemical alarms sound and total cortical GM (adjusted p = 0.007), even after accounting for potentially confounding demographic and clinical variables, the veterans’ current health status, and other concurrent deployment-related exposures that were correlated with hearing chemical alarms. Post-hoc analyses extended the inverse relationship between the frequency of hearing chemical alarms to GM volume in the frontal (adjusted p = 0.02), parietal (adjusted p = 0.01), and occipital (adjusted p = 0.001) lobes. In contrast, regional brain volumes were not significantly associated with predicted exposure to the Khamisiyah plume or with Gulf War Illness status defined by the Kansas or Centers for Disease Control and Prevention criteria. Conclusions Many veterans reported hearing chemical alarms sound during the Gulf War. The current findings suggest that exposure to substances that triggered those chemical alarms during the Gulf War likely had adverse neuroanatomical effects. PMID:26920621

Separating generalized anxiety disorder from major depression using clinical, hormonal, and structural MRI data: A multimodal machine learning study.

PubMed

Hilbert, Kevin; Lueken, Ulrike; Muehlhan, Markus; Beesdo-Baum, Katja

2017-03-01

Generalized anxiety disorder (GAD) is difficult to recognize and hard to separate from major depression (MD) in clinical settings. Biomarkers might support diagnostic decisions. This study used machine learning on multimodal biobehavioral data from a sample of GAD, MD and healthy subjects to differentiate subjects with a disorder from healthy subjects (case-classification) and to differentiate GAD from MD (disorder-classification). Subjects with GAD ( n  = 19), MD without GAD ( n  = 14), and healthy comparison subjects ( n  = 24) were included. The sample was matched regarding age, sex, handedness and education and free of psychopharmacological medication. Binary support vector machines were used within a nested leave-one-out cross-validation framework. Clinical questionnaires, cortisol release, gray matter (GM), and white matter (WM) volumes were used as input data separately and in combination. Questionnaire data were well-suited for case-classification but not disorder-classification (accuracies: 96.40%, p  < .001; 56.58%, p  > .22). The opposite pattern was found for imaging data (case-classification GM/WM: 58.71%, p  = .09/43.18%, p  > .66; disorder-classification GM/WM: 68.05%, p  = .034/58.27%, p  > .15) and for cortisol data (38.02%, p  = .84; 74.60%, p  = .009). All data combined achieved 90.10% accuracy ( p  < .001) for case-classification and 67.46% accuracy ( p  = .0268) for disorder-classification. In line with previous evidence, classification of GAD was difficult using clinical questionnaire data alone. Particularly cortisol and GM volume data were able to provide incremental value for the classification of GAD. Findings suggest that neurobiological biomarkers are a useful target for further research to delineate their potential contribution to diagnostic processes.

Attachment Security in Infancy: A Preliminary Study of Prospective Links to Brain Morphometry in Late Childhood

PubMed Central

Leblanc, Élizabel; Dégeilh, Fanny; Daneault, Véronique; Beauchamp, Miriam H.; Bernier, Annie

2017-01-01

A large body of longitudinal research provides compelling evidence for the critical role of early attachment relationships in children’s social, emotional, and cognitive development. It is expected that parent–child attachment relationships may also impact children’s brain development, however, studies linking normative caregiving experiences and brain structure are scarce. To our knowledge, no study has yet examined the associations between the quality of parent–infant attachment relationships and brain morphology during childhood. The aim of this preliminary study was to investigate the prospective links between mother–infant attachment security and whole-brain gray matter (GM) volume and thickness in late childhood. Attachment security toward the mother was assessed in 33 children when they were 15 months old. These children were then invited to undergo structural magnetic resonance imaging at 10–11 years of age. Results indicated that children more securely attached to their mother in infancy had larger GM volumes in the superior temporal sulcus and gyrus, temporo-parietal junction, and precentral gyrus in late childhood. No associations between attachment security and cortical thickness were found. If replicated, these results would suggest that a secure attachment relationship and its main features (e.g., adequate dyadic emotion regulation, competent exploration) may influence GM volume in brain regions involved in social, cognitive, and emotional functioning through experience-dependent processes. PMID:29312029

Regional volumes in brain stem and cerebellum are associated with postural impairments in young brain-injured patients.

PubMed

Drijkoningen, David; Leunissen, Inge; Caeyenberghs, Karen; Hoogkamer, Wouter; Sunaert, Stefan; Duysens, Jacques; Swinnen, Stephan P

2015-12-01

Many patients with traumatic brain injury (TBI) suffer from postural control impairments that can profoundly affect daily life. The cerebellum and brain stem are crucial for the neural control of posture and have been shown to be vulnerable to primary and secondary structural consequences of TBI. The aim of this study was to investigate whether morphometric differences in the brain stem and cerebellum can account for impairments in static and dynamic postural control in TBI. TBI patients (n = 18) and healthy controls (n = 30) completed three challenging postural control tasks on the EquiTest® system (Neurocom). Infratentorial grey matter (GM) and white matter (WM) volumes were analyzed with cerebellum-optimized voxel-based morphometry using the spatially unbiased infratentorial toolbox. Volume loss in TBI patients was revealed in global cerebellar GM, global infratentorial WM, middle cerebellar peduncles, pons and midbrain. In the TBI group and across both groups, lower postural control performance was associated with reduced GM volume in the vermal/paravermal regions of lobules I-IV, V and VI. Moreover, across all participants, worse postural control performance was associated with lower WM volume in the pons, medulla, midbrain, superior and middle cerebellar peduncles and cerebellum. This is the first study in TBI patients to demonstrate an association between postural impairments and reduced volume in specific infratentorial brain areas. Volumetric measures of the brain stem and cerebellum may be valuable prognostic markers of the chronic neural pathology, which complicates rehabilitation of postural control in TBI. © 2015 Wiley Periodicals, Inc.

Brain Swelling and Loss of Gray and White Matter Differentiation in Human Postmortem Cases by Computed Tomography.

PubMed

Shirota, Go; Gonoi, Wataru; Ishida, Masanori; Okuma, Hidemi; Shintani, Yukako; Abe, Hiroyuki; Takazawa, Yutaka; Ikemura, Masako; Fukayama, Masashi; Ohtomo, Kuni

2015-01-01

The purpose of this study was to evaluate the brain by postmortem computed tomography (PMCT) versus antemortem computed tomography (AMCT) using brains from the same patients. We studied 36 nontraumatic subjects who underwent AMCT, PMCT, and pathological autopsy in our hospital between April 2009 and December 2013. PMCT was performed within 20 h after death, followed by pathological autopsy including the brain. Autopsy confirmed the absence of intracranial disorders that might be related to the cause of death or might affect measurements in our study. Width of the third ventricle, width of the central sulcus, and attenuation in gray matter (GM) and white matter (WM) from the same area of the basal ganglia, centrum semiovale, and high convexity were statistically compared between AMCT and PMCT. Both the width of the third ventricle and the central sulcus were significantly shorter in PMCT than in AMCT (P < 0.0001). GM attenuation increased after death at the level of the centrum semiovale and high convexity, but the differences were not statistically significant considering the differences in attenuation among the different computed tomography scanners. WM attenuation significantly increased after death at all levels (P<0.0001). The differences were larger than the differences in scanners. GM/WM ratio of attenuation was significantly lower by PMCT than by AMCT at all levels (P<0.0001). PMCT showed an increase in WM attenuation, loss of GM-WM differentiation, and brain swelling, evidenced by a decrease in the size of ventricles and sulci.

Real-time interactive tractography analysis for multimodal brain visualization tool: MultiXplore

NASA Astrophysics Data System (ADS)

Bakhshmand, Saeed M.; de Ribaupierre, Sandrine; Eagleson, Roy

2017-03-01

Most debilitating neurological disorders can have anatomical origins. Yet unlike other body organs, the anatomy alone cannot easily provide an understanding of brain functionality. In fact, addressing the challenge of linking structural and functional connectivity remains in the frontiers of neuroscience. Aggregating multimodal neuroimaging datasets may be critical for developing theories that span brain functionality, global neuroanatomy and internal microstructures. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are main such techniques that are employed to investigate the brain under normal and pathological conditions. FMRI records blood oxygenation level of the grey matter (GM), whereas DTI is able to reveal the underlying structure of the white matter (WM). Brain global activity is assumed to be an integration of GM functional hubs and WM neural pathways that serve to connect them. In this study we developed and evaluated a two-phase algorithm. This algorithm is employed in a 3D interactive connectivity visualization framework and helps to accelerate clustering of virtual neural pathways. In this paper, we will detail an algorithm that makes use of an index-based membership array formed for a whole brain tractography file and corresponding parcellated brain atlas. Next, we demonstrate efficiency of the algorithm by measuring required times for extracting a variety of fiber clusters, which are chosen in such a way to resemble all sizes probable output data files that algorithm will generate. The proposed algorithm facilitates real-time visual inspection of neuroimaging data to further the discovery in structure-function relationship of the brain networks.

Altered Gray Matter Volume and Resting-State Connectivity in Individuals With Internet Gaming Disorder: A Voxel-Based Morphometry and Resting-State Functional Magnetic Resonance Imaging Study

PubMed Central

Seok, Ji-Woo; Sohn, Jin-Hun

2018-01-01

Neuroimaging studies on the characteristics of individuals with Internet gaming disorder (IGD) have been accumulating due to growing concerns regarding the psychological and social problems associated with Internet use. However, relatively little is known about the brain characteristics underlying IGD, such as the associated functional connectivity and structure. The aim of this study was to investigate alterations in gray matter (GM) volume and functional connectivity during resting state in individuals with IGD using voxel-based morphometry and a resting-state connectivity analysis. The participants included 20 individuals with IGD and 20 age- and sex-matched healthy controls. Resting-state functional and structural images were acquired for all participants using 3 T magnetic resonance imaging. We also measured the severity of IGD and impulsivity using psychological scales. The results show that IGD severity was positively correlated with GM volume in the left caudate (p < 0.05, corrected for multiple comparisons), and negatively associated with functional connectivity between the left caudate and the right middle frontal gyrus (p < 0.05, corrected for multiple comparisons). This study demonstrates that IGD is associated with neuroanatomical changes in the right middle frontal cortex and the left caudate. These are important brain regions for reward and cognitive control processes, and structural and functional abnormalities in these regions have been reported for other addictions, such as substance abuse and pathological gambling. The findings suggest that structural deficits and resting-state functional impairments in the frontostriatal network may be associated with IGD and provide new insights into the underlying neural mechanisms of IGD. PMID:29636704

Brain Structural Correlates of Subclinical Obsessive-Compulsive Symptoms in Healthy Children.

PubMed

Suñol, Maria; Contreras-Rodríguez, Oren; Macià, Dídac; Martínez-Vilavella, Gerard; Martínez-Zalacaín, Ignacio; Subirà, Marta; Pujol, Jesús; Sunyer, Jordi; Soriano-Mas, Carles

2018-01-01

Subclinical obsessive-compulsive (OC) symptoms are frequently observed in children and have been reported to predict a subsequent diagnosis of OC disorder (OCD). Therefore, identifying the putative neurobiological signatures of such risk is crucial, because it would allow for the characterization of the underpinnings of OCD without the interfering effects of chronicity, medication, or comorbidities, especially when interpreted within the context of OCD clinical heterogeneity and taking into account normal neurodevelopmental changes. The present study aimed to identify the brain volumetric features associated with subclinical OC symptoms and the potential modulatory effects of sex and age in a large sample of healthy children. Two hundred fifty-five healthy children were assessed using the Obsessive-Compulsive Inventory-Child Version and underwent a brain structural magnetic resonance examination. The relation between total and symptom-specific scores and regional gray and white matter (GM and WM) volumes was evaluated. Participants were grouped according to sex and age (younger versus older) to assess the effect of these factors on symptom-brain morphometry associations. Ordering symptoms were negatively related to GM volumes in the ventral caudate. Hoarding symptoms were positively associated with GM and WM volumes in the left inferior frontal gyrus, and obsessing symptoms correlated negatively with GM and WM volumes in the right temporal pole. Doubt-checking symptoms correlated positively with WM volumes in the right inferior fronto-occipital fasciculus and the corpus callosum. Sex and age modulated some of these associations. Subclinical OC symptoms are associated with specific brain volumetric features, which could be considered potential neural signatures of increased risk for OCD. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

[Genetically modified food (food derived from biotechnology): current and future trends in public acceptance and safety assessment].

PubMed

Nishiura, Hiroshi; Imai, Hirohisa; Nakao, Hiroyuki; Tsukino, Hiromasa; Kuroda, Yoshiki; Katoh, Takahiko

2002-11-01

Current and future trends regarding genetically modified (GM) crops and food stuffs were reviewed, with a particular focus on public acceptance and safety assessment. While GM foods, foods derived from biotechnology, are popular with growers and producers, they are still a matter of some concern among consumers. In fact, our recent surveys showed that Japanese consumers had become uneasy about the potential health risks of genetically modified foods. Many Japanese consumers have only vague ideas about the actual health risks, and they appear to be making decisions simply by rejecting GM food because of non-informed doubts. Although the debate about GM foods has increased in the mass media and scientific journals, few articles concerning direct studies on the potential toxicity or adverse health effects of GM foods have appeared. The roles of relevant international regulatory bodies in ensuring that GM crops and food are safe are therefore have summarized. Finally, the current debate on use of GM crops in agriculture and future trends for development of GM foods with enriched nutrients, better functionality, and medicinal ingredients, which will be of direct benefit to the consumer, are covered.

Settling flux and origin of particulate organic carbon in a macro-tidal semi-enclosed embayment: Luoyuan Bay, Southeast China coast

NASA Astrophysics Data System (ADS)

Wang, Ai-jun; Ye, Xiang; Xu, Xiao-hui; Yin, Xi-jie; Xu, Yong-hang

2018-06-01

Coastal embayments play a vital role in the global carbon cycle either as sources of organic matter to open sea or as carbon sinks due to the accumulation of organic matter in sediments. This paper describes a study of Luoyuan Bay, a typical semi-enclosed embayment with a total area of approximately 227 km2 in a strong tidal environment. The analysed results indicate that the particulate organic carbon (POC) concentration in suspended particulate matter (SPM) varies from 0.57 mg/L to 1.33 mg/L at the bottom layer (0.5 MAB, meters above bed) and from 0.54 mg/L to 1.25 mg/L at the surface layer (0.5 MBS, meters below surface). The δ13C‰ ranges from -25.52‰ to -23.54‰ and exhibits different variations at the surface and bottom layers in spring and neap tides. The POC content in deposited particulate matter (DPM) varies from 0.62% to 2.95%, increasing from spring to neap tide, and the δ13C and C/N molar ratio are -25.29‰ ∼ -21.41‰ and 4.18-8.53, respectively. The settling fluxes of POC obtained by sediment trap decrease from 2.25 g/m2·tide during the spring tide to 0.55 g/m2·tide during the neap tide with a mean value of 1.41 g/m2·tide during the observation, whereas the settling flux of SPM decreases from 456.76 g/m2·tide during the spring tide to 37.12 g/m2·tide during the neap tide. Combining the δ13C and C/N molar ratio, three end-members are recognized, i.e., freshwater algae and phytoplankton, marine algae and phytoplankton, and kelp-derived detritus. The mean contribution to POC from these three sources is 57.2%, 31.8% and 11.0% in SPM, and 39.9%, 35.0% and 25.1% in DPM, respectively. The POC from freshwater algae, phytoplankton and kelp-derived detritus is controlled by sediment dynamic processes.

Cerebral structural changes in diabetic kidney disease: African American-Diabetes Heart Study MIND.

PubMed

Sink, Kaycee M; Divers, Jasmin; Whitlow, Christopher T; Palmer, Nicholette D; Smith, S Carrie; Xu, Jianzhao; Hugenschmidt, Christina E; Wagner, Benjamin C; Williamson, Jeff D; Bowden, Donald W; Maldjian, Joseph A; Freedman, Barry I

2015-02-01

Albuminuria and reduced kidney function are associated with cognitive impairment. Relationships between nephropathy and cerebral structural changes remain poorly defined, particularly in African Americans (AAs), a population at higher risk for both cognitive impairment and diabetes than European Americans. We examined the relationship between urine albumin:creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and cerebral MRI volumes in 263 AAs with type 2 diabetes. Cross-sectional associations between renal parameters and white matter (WM), gray matter (GM), hippocampal, and WM lesion (WML) volumes were assessed using generalized linear models adjusted for age, education, sex, BMI, hemoglobin A1c (HbA1c) level, and hypertension. Participants had a mean (SD) age of 60.2 years (9.7 years), and 62.7% were female. Mean diabetes duration was 14.3 years (8.9 years), HbA1c level was 8.2% (2.2%; 66 mmol/mol), eGFR was 86.0 mL/min/1.73 m(2) (23.2 mL/min/1.73 m(2)), and UACR was 155.8 mg/g (542.1 mg/g; median 8.1 mg/g). Those with chronic kidney disease (CKD) (eGFR <60 mL/min/1.73 m(2) or UACR >30 mg/g) had smaller GM and higher WML volumes. Higher UACR was significantly associated with higher WML volume and greater atrophy (larger cerebrospinal fluid volumes), and smaller GM and hippocampal WM volumes. A higher eGFR was associated with larger hippocampal WM volumes. Consistent with higher WML volumes, participants with CKD had significantly poorer processing speed and working memory. These findings were independent of glycemic control. We found albuminuria to be a better marker of cerebral structural changes than eGFR in AAs with type 2 diabetes. Relationships between albuminuria and brain pathology may contribute to poorer cognitive performance in patients with mild CKD. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Rumination mediates the relationship between structural variations in ventrolateral prefrontal cortex and sensitivity to negative life events.

PubMed

Qiao, L; Wei, D T; Li, W F; Chen, Q L; Che, X W; Li, B B; Li, Y D; Qiu, J; Zhang, Q L; Liu, Y J

2013-01-01

Individuals have different levels of stress sensitivity. An individual's predisposition to experience negative life events (NLEs) may make him/her more vulnerable to a series of psychopathological and physical diseases. However, the neuroanatomical correlates of individual differences in sensitivity to NLEs remain unknown. In this study, voxel-based morphometry was used to identify the gray matter (GM) associations of individual differences in sensitivity to NLEs measured by adolescent self-rating life events checklist. Results showed that there was a positive association between individual NLEs sensitivity and regional GM volume (rGMV) in the ventrolateral prefrontal cortex (VLPFC). GM was mostly evident in the left frontal operculum and a small part of the left middle frontal gyrus. This region was thought to play an important role in introception. Importantly, our study revealed that rumination served as a mediator between the rGMV of the VLPFC and individual NLEs sensitivity. These findings suggest that people with greater VLPFC might be more inclined to ruminate and the ruminative response style might make them more sensitive to NLEs. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Reduced caudate volume and enhanced striatal-DMN integration in chess experts.

PubMed

Duan, Xujun; He, Sheng; Liao, Wei; Liang, Dongmei; Qiu, Lihua; Wei, Luqing; Li, Yuan; Liu, Chengyi; Gong, Qiyong; Chen, Huafu

2012-04-02

The superior capability of chess experts largely depends on quick automatic processing skills which are considered to be mediated by the caudate nucleus. We asked whether continued practice or rehearsal of the skill over a long period of time can lead to structural changes in this region. We found that, comparing to novice controls, grandmaster and master level Chinese chess players (GM/Ms), who had a mean period of over 10years of tournament and training practice, exhibited significant smaller gray-matter volume in the bilateral caudate nuclei. When these regions were used as seeds in functional connectivity analysis in resting-state fMRI, significantly enhanced integration was found in GM/Ms between the caudate and the default mode network (DMN), a constellation of brain areas important for goal-directed cognitive performance and theory of mind. These findings demonstrate the structural changes in the caudate nucleus in response to its extensive engagement in chess problem solving, and its enhanced functional integration with widely distributed circuitry to better support high-level cognitive control of behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

The effect of ageing on grey and white matter reductions in schizophrenia.

PubMed

Bose, Subrata K; Mackinnon, Toby; Mehta, Mitul A; Turkheimer, Federico E; Howes, Oliver D; Selvaraj, Sudhakar; Kempton, Matthew J; Grasby, Paul M

2009-07-01

Total brain volume and, in particular gray matter (GM) volume is reduced in patients with schizophrenia and recent studies suggest there is greater progressive loss of brain volume in the patients with schizophrenia than in normal controls. However, as the longitudinal studies do not include life-long follow-up, it is not clear if this occurs across the lifespan or only in the early phase of the illness. In this study we investigated this by studying the effects of age on brain tissue volumes in schizophrenia (n=34, age range=27-65 years)to test the prediction that there is a progressive loss in grey matter volume with increasing age in patients compared to healthy controls (n=33, age range=18-73 years). The results showed there was diminished relative GM volume loss with age in patients with schizophrenia compared to controls--in contrast to our prediction. However, there was increased relative white matter (WM) loss with age in schizophrenia. The results also replicated previous findings that patients with schizophrenia have significantly lower total (1509 versus 1596 mm(3)) and regional GM volume (755 versus 822 mm(3)) and increased cerebrospinal fluid (CSF) volume when compared to matched healthy volunteers. Overall these findings indicate that the proportion of grey matter in schizophrenia is reduced compared to controls early in the illness, and this difference diminishes with age; the corresponding effect in the proportion of WM is an increase with age compared to controls. This suggests that illness related factors may differentially affect grey and white matter, with implications for understanding the pathophysiology of schizophrenia and related psychotic disorders.

Frontal gray matter abnormalities predict seizure outcome in refractory temporal lobe epilepsy patients.

PubMed

Doucet, Gaelle E; He, Xiaosong; Sperling, Michael; Sharan, Ashwini; Tracy, Joseph I

2015-01-01

Developing more reliable predictors of seizure outcome following temporal lobe surgery for intractable epilepsy is an important clinical goal. In this context, we investigated patients with refractory temporal lobe epilepsy (TLE) before and after temporal resection. In detail, we explored gray matter (GM) volume change in relation with seizure outcome, using a voxel-based morphometry (VBM) approach. To do so, this study was divided into two parts. The first one involved group analysis of differences in regional GM volume between the groups (good outcome (GO), e.g., no seizures after surgery; poor outcome (PO), e.g., persistent postoperative seizures; and controls, N = 24 in each group), pre- and post-surgery. The second part of the study focused on pre-surgical data only (N = 61), determining whether the degree of GM abnormalities can predict surgical outcomes. For this second step, GM abnormalities were identified, within each lobe, in each patient when compared with an ad hoc sample of age-matched controls. For the first analysis, the results showed larger GM atrophy, mostly in the frontal lobe, in PO patients, relative to both GO patients and controls, pre-surgery. When comparing pre-to-post changes, we found relative GM gains in the GO but not in the PO patients, mostly in the non-resected hemisphere. For the second analysis, only the frontal lobe displayed reliable prediction of seizure outcome. 81% of the patients showing pre-surgical increased GM volume in the frontal lobe became seizure free, post-surgery; while 77% of the patients with pre-surgical reduced frontal GM volume had refractory seizures, post-surgery. A regression analysis revealed that the proportion of voxels with reduced frontal GM volume was a significant predictor of seizure outcome (p = 0.014). Importantly, having less than 1% of the frontal voxels with GM atrophy increased the likelihood of being seizure-free, post-surgery, by seven times. Overall, our results suggest that using pre-surgical GM abnormalities within the frontal lobe is a reliable predictor of seizure outcome post-surgery in TLE. We believe that this frontal GM atrophy captures seizure burden outside the pre-existing ictal temporal lobe, reflecting either the development of epileptogenesis or the loss of a protective, adaptive force helping to control or limit seizures. This study provides evidence of the potential of VBM-based approaches to predict surgical outcomes in refractory TLE candidates.

Frontal gray matter abnormalities predict seizure outcome in refractory temporal lobe epilepsy patients

PubMed Central

Doucet, Gaelle E.; He, Xiaosong; Sperling, Michael; Sharan, Ashwini; Tracy, Joseph I.

2015-01-01

Developing more reliable predictors of seizure outcome following temporal lobe surgery for intractable epilepsy is an important clinical goal. In this context, we investigated patients with refractory temporal lobe epilepsy (TLE) before and after temporal resection. In detail, we explored gray matter (GM) volume change in relation with seizure outcome, using a voxel-based morphometry (VBM) approach. To do so, this study was divided into two parts. The first one involved group analysis of differences in regional GM volume between the groups (good outcome (GO), e.g., no seizures after surgery; poor outcome (PO), e.g., persistent postoperative seizures; and controls, N = 24 in each group), pre- and post-surgery. The second part of the study focused on pre-surgical data only (N = 61), determining whether the degree of GM abnormalities can predict surgical outcomes. For this second step, GM abnormalities were identified, within each lobe, in each patient when compared with an ad hoc sample of age-matched controls. For the first analysis, the results showed larger GM atrophy, mostly in the frontal lobe, in PO patients, relative to both GO patients and controls, pre-surgery. When comparing pre-to-post changes, we found relative GM gains in the GO but not in the PO patients, mostly in the non-resected hemisphere. For the second analysis, only the frontal lobe displayed reliable prediction of seizure outcome. 81% of the patients showing pre-surgical increased GM volume in the frontal lobe became seizure free, post-surgery; while 77% of the patients with pre-surgical reduced frontal GM volume had refractory seizures, post-surgery. A regression analysis revealed that the proportion of voxels with reduced frontal GM volume was a significant predictor of seizure outcome (p = 0.014). Importantly, having less than 1% of the frontal voxels with GM atrophy increased the likelihood of being seizure-free, post-surgery, by seven times. Overall, our results suggest that using pre-surgical GM abnormalities within the frontal lobe is a reliable predictor of seizure outcome post-surgery in TLE. We believe that this frontal GM atrophy captures seizure burden outside the pre-existing ictal temporal lobe, reflecting either the development of epileptogenesis or the loss of a protective, adaptive force helping to control or limit seizures. This study provides evidence of the potential of VBM-based approaches to predict surgical outcomes in refractory TLE candidates. PMID:26594628

Differential effects of intrauterine growth restriction on brain structure and development in preterm infants: a magnetic resonance imaging study.

PubMed

Padilla, Nelly; Falcón, Carles; Sanz-Cortés, Magdalena; Figueras, Francesc; Bargallo, Núria; Crispi, Fátima; Eixarch, Elisenda; Arranz, Angela; Botet, Francesc; Gratacós, Eduard

2011-03-25

Previous evidence suggests that preterm newborns with intrauterine growth restriction (IUGR) have specific neurostructural and neurodevelopmental anomalies, but it is unknown whether these effects persist in early childhood. We studied a sample of 18 preterm IUGR, 15 preterm AGA - born between 26 and 34 weeks of gestational age (GA) - and 15 healthy born-term infants. Infants were scanned at 12 months corrected age (CA), in a 3T scanner, without sedation. Analyses were made by automated lobar volumetry and voxel-based morphometry (VBM). The neurodevelopmental outcome was assessed in all subjects at 18 months CA with the Bayley Scale for Infant and Toddler Development, third edition. IUGR infants had reduced relative volumes for the insular and temporal lobes. According to VBM, IUGR infants had bilateral reduced gray matter (GM) in the temporal, parietal, frontal, and insular regions compared with the other groups. IUGR infants had increased white matter (WM) in temporal regions compared to the AGA group and in frontal, parietal, occipital, and insular regions compared to the term group. They also showed decreased WM in the cerebellum and a non-significant trend in the hippocampus compared to term infants. IUGR infants had reduced neurodevelopmental scores, which were positively correlated with GM in various regions. These data suggest that the IUGR induces a distinct brain pattern of structural changes that persist at 1 year of life and are associated with specific developmental difficulties. Copyright © 2011 Elsevier B.V. All rights reserved.

Voxel-based morphometric multisite collaborative study on schizophrenia.

PubMed

Segall, Judith M; Turner, Jessica A; van Erp, Theo G M; White, Tonya; Bockholt, H Jeremy; Gollub, Randy L; Ho, Beng C; Magnotta, Vince; Jung, Rex E; McCarley, Robert W; Schulz, S Charles; Lauriello, John; Clark, Vince P; Voyvodic, James T; Diaz, Michele T; Calhoun, Vince D

2009-01-01

Regional gray matter (GM) abnormalities are well known to exist in patients with chronic schizophrenia. Voxel-based morphometry (VBM) has been previously used on structural magnetic resonance images (MRI) data to characterize these abnormalities. Two multisite schizophrenia studies, the Functional Biomedical Informatics Research Network and the Mind Clinical Imaging Consortium, which include 9 data collection sites, are evaluating the efficacy of pooling structural imaging data across imaging centers. Such a pooling of data could yield the increased statistical power needed to elucidate effects that may not be seen with smaller samples. VBM analyses were performed to evaluate the consistency of patient versus control gray matter concentration (GMC) differences across the study sites, as well as the effects of combining multisite data. Integration of data from both studies yielded a large sample of 503 subjects, including 266 controls and 237 patients diagnosed with schizophrenia, schizoaffective or schizophreniform disorder. The data were analyzed using the combined sample, as well as analyzing each of the 2 multisite studies separately. A consistent pattern of reduced relative GMC in schizophrenia patients compared with controls was found across all study sites. Imaging center-specific effects were evaluated using a region of interest analysis. Overall, the findings support the use of VBM in combined multisite studies. This analysis of schizophrenics and controls from around the United States provides continued supporting evidence for GM deficits in the temporal lobes, anterior cingulate, and frontal regions in patients with schizophrenia spectrum disorders.

Automatic tissue image segmentation based on image processing and deep learning

NASA Astrophysics Data System (ADS)

Kong, Zhenglun; Luo, Junyi; Xu, Shengpu; Li, Ting

2018-02-01

Image segmentation plays an important role in multimodality imaging, especially in fusion structural images offered by CT, MRI with functional images collected by optical technologies or other novel imaging technologies. Plus, image segmentation also provides detailed structure description for quantitative visualization of treating light distribution in the human body when incorporated with 3D light transport simulation method. Here we used image enhancement, operators, and morphometry methods to extract the accurate contours of different tissues such as skull, cerebrospinal fluid (CSF), grey matter (GM) and white matter (WM) on 5 fMRI head image datasets. Then we utilized convolutional neural network to realize automatic segmentation of images in a deep learning way. We also introduced parallel computing. Such approaches greatly reduced the processing time compared to manual and semi-automatic segmentation and is of great importance in improving speed and accuracy as more and more samples being learned. Our results can be used as a criteria when diagnosing diseases such as cerebral atrophy, which is caused by pathological changes in gray matter or white matter. We demonstrated the great potential of such image processing and deep leaning combined automatic tissue image segmentation in personalized medicine, especially in monitoring, and treatments.

Brain structural correlates of reward sensitivity and impulsivity in adolescents with normal and excess weight.

PubMed

Moreno-López, Laura; Soriano-Mas, Carles; Delgado-Rico, Elena; Rio-Valle, Jacqueline S; Verdejo-García, Antonio

2012-01-01

Neuroscience evidence suggests that adolescent obesity is linked to brain dysfunctions associated with enhanced reward and somatosensory processing and reduced impulse control during food processing. Comparatively less is known about the role of more stable brain structural measures and their link to personality traits and neuropsychological factors on the presentation of adolescent obesity. Here we aimed to investigate regional brain anatomy in adolescents with excess weight vs. lean controls. We also aimed to contrast the associations between brain structure and personality and cognitive measures in both groups. Fifty-two adolescents (16 with normal weight and 36 with excess weight) were scanned using magnetic resonance imaging and completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the UPPS-P scale, and the Stroop task. Voxel-based morphometry (VBM) was used to assess possible between-group differences in regional gray matter (GM) and to measure the putative differences in the way reward and punishment sensitivity, impulsivity and inhibitory control relate to regional GM volumes, which were analyzed using both region of interest (ROI) and whole brain analyses. The ROIs included areas involved in reward/somatosensory processing (striatum, somatosensory cortices) and motivation/impulse control (hippocampus, prefrontal cortex). Excess weight adolescents showed increased GM volume in the right hippocampus. Voxel-wise volumes of the second somatosensory cortex (SII) were correlated with reward sensitivity and positive urgency in lean controls, but this association was missed in excess weight adolescents. Moreover, Stroop performance correlated with dorsolateral prefrontal cortex volumes in controls but not in excess weight adolescents. Adolescents with excess weight have structural abnormalities in brain regions associated with somatosensory processing and motivation.

Irritable Bowel Syndrome in female patients is associated with alterations in structural brain networks

PubMed Central

Labus, Jennifer; Dinov, Ivo D.; Jiang, Zhiguo; Ashe-McNalley, Cody; Zamanyan, Alen; Shi, Yonggang; Hong, Jui-Yang; Gupta, Arpana; Tillisch, Kirsten; Ebrat, Bahar; Hobel, Sam; Gutman, Boris A.; Joshi, Shantanu; Thompson, Paul M.; Toga, Arthur W.; Mayer, Emeran A.

2014-01-01

Alterations in gray matter (GM) density/ volume and cortical thickness (CT) have been demonstrated in small and heterogeneous samples of subjects with different chronic pain syndromes, including irritable bowel syndrome (IBS). Aggregating across 7 structural neuroimaging studies conducted at UCLA between August 2006 and April 2011, we examined group differences in regional GM volume in 201 predominantly premenopausal female subjects (82 IBS, mean age: 32 ± 10 SD, 119 Healthy Controls [HCs], 30± 10 SD). Applying graph theoretical methods and controlling for total brain volume, global and regional properties of large-scale structural brain networks were compared between IBS and HC groups. Relative to HCs, the IBS group had lower volumes in bilateral superior frontal gyrus, bilateral insula, bilateral amygdala, bilateral hippocampus, bilateral middle orbital frontal gyrus, left cingulate, left gyrus rectus, brainstem, and left putamen. Higher volume was found for the left postcentral gyrus. Group differences were no longer significant for most regions when controlling for Early Trauma Inventory global score with the exception of the right amygdala and the left post central gyrus. No group differences were found for measures of global and local network organization. Compared to HCs, the right cingulate gyrus and right thalamus were identified as significantly more critical for information flow. Regions involved in endogenous pain modulation and central sensory amplification were identified as network hubs in IBS. Overall, evidence for central alterations in IBS was found in the form of regional GM volume differences and altered global and regional properties of brain volumetric networks. PMID:24076048

DISRUPTION OF LARGE-SCALE NEURAL NETWORKS IN NON-FLUENT/AGRAMMATIC VARIANT PRIMARY PROGRESSIVE APHASIA ASSOCIATED WITH FRONTOTEMPORAL DEGENERATION PATHOLOGY

PubMed Central

Grossman, Murray; Powers, John; Ash, Sherry; McMillan, Corey; Burkholder, Lisa; Irwin, David; Trojanowski, John Q.

2012-01-01

Non-fluent/agrammatic primary progressive aphasia (naPPA) is a progressive neurodegenerative condition most prominently associated with slowed, effortful speech. A clinical imaging marker of naPPA is disease centered in the left inferior frontal lobe. We used multimodal imaging to assess large-scale neural networks underlying effortful expression in 15 patients with sporadic naPPA due to frontotemporal lobar degeneration (FTLD) spectrum pathology. Effortful speech in these patients is related in part to impaired grammatical processing, and to phonologic speech errors. Gray matter (GM) imaging shows frontal and anterior-superior temporal atrophy, most prominently in the left hemisphere. Diffusion tensor imaging reveals reduced fractional anisotropy in several white matter (WM) tracts mediating projections between left frontal and other GM regions. Regression analyses suggest disruption of three large-scale GM-WM neural networks in naPPA that support fluent, grammatical expression. These findings emphasize the role of large-scale neural networks in language, and demonstrate associated language deficits in naPPA. PMID:23218686

Age-related delay in visual and auditory evoked responses is mediated by white- and grey-matter differences.

PubMed

Price, D; Tyler, L K; Neto Henriques, R; Campbell, K L; Williams, N; Treder, M S; Taylor, J R; Henson, R N A

2017-06-09

Slowing is a common feature of ageing, yet a direct relationship between neural slowing and brain atrophy is yet to be established in healthy humans. We combine magnetoencephalographic (MEG) measures of neural processing speed with magnetic resonance imaging (MRI) measures of white and grey matter in a large population-derived cohort to investigate the relationship between age-related structural differences and visual evoked field (VEF) and auditory evoked field (AEF) delay across two different tasks. Here we use a novel technique to show that VEFs exhibit a constant delay, whereas AEFs exhibit delay that accumulates over time. White-matter (WM) microstructure in the optic radiation partially mediates visual delay, suggesting increased transmission time, whereas grey matter (GM) in auditory cortex partially mediates auditory delay, suggesting less efficient local processing. Our results demonstrate that age has dissociable effects on neural processing speed, and that these effects relate to different types of brain atrophy.

Age-related delay in visual and auditory evoked responses is mediated by white- and grey-matter differences

PubMed Central

Price, D.; Tyler, L. K.; Neto Henriques, R.; Campbell, K. L.; Williams, N.; Treder, M.S.; Taylor, J. R.; Brayne, Carol; Bullmore, Edward T.; Calder, Andrew C.; Cusack, Rhodri; Dalgleish, Tim; Duncan, John; Matthews, Fiona E.; Marslen-Wilson, William D.; Rowe, James B.; Shafto, Meredith A.; Cheung, Teresa; Davis, Simon; Geerligs, Linda; Kievit, Rogier; McCarrey, Anna; Mustafa, Abdur; Samu, David; Tsvetanov, Kamen A.; van Belle, Janna; Bates, Lauren; Emery, Tina; Erzinglioglu, Sharon; Gadie, Andrew; Gerbase, Sofia; Georgieva, Stanimira; Hanley, Claire; Parkin, Beth; Troy, David; Auer, Tibor; Correia, Marta; Gao, Lu; Green, Emma; Allen, Jodie; Amery, Gillian; Amunts, Liana; Barcroft, Anne; Castle, Amanda; Dias, Cheryl; Dowrick, Jonathan; Fair, Melissa; Fisher, Hayley; Goulding, Anna; Grewal, Adarsh; Hale, Geoff; Hilton, Andrew; Johnson, Frances; Johnston, Patricia; Kavanagh-Williamson, Thea; Kwasniewska, Magdalena; McMinn, Alison; Norman, Kim; Penrose, Jessica; Roby, Fiona; Rowland, Diane; Sargeant, John; Squire, Maggie; Stevens, Beth; Stoddart, Aldabra; Stone, Cheryl; Thompson, Tracy; Yazlik, Ozlem; Barnes, Dan; Dixon, Marie; Hillman, Jaya; Mitchell, Joanne; Villis, Laura; Henson, R. N. A.

2017-01-01

Slowing is a common feature of ageing, yet a direct relationship between neural slowing and brain atrophy is yet to be established in healthy humans. We combine magnetoencephalographic (MEG) measures of neural processing speed with magnetic resonance imaging (MRI) measures of white and grey matter in a large population-derived cohort to investigate the relationship between age-related structural differences and visual evoked field (VEF) and auditory evoked field (AEF) delay across two different tasks. Here we use a novel technique to show that VEFs exhibit a constant delay, whereas AEFs exhibit delay that accumulates over time. White-matter (WM) microstructure in the optic radiation partially mediates visual delay, suggesting increased transmission time, whereas grey matter (GM) in auditory cortex partially mediates auditory delay, suggesting less efficient local processing. Our results demonstrate that age has dissociable effects on neural processing speed, and that these effects relate to different types of brain atrophy. PMID:28598417

Normalization of Cortical Gray Matter Deficits in Nonpsychotic Siblings of Patients With Childhood-Onset Schizophrenia

PubMed Central

Mattai, Anand A.; Weisinger, Brian; Greenstein, Deanna; Stidd, Reva; Clasen, Liv; Miller, Rachel; Tossell, Julia W.; Rapoport, Judith L.; Gogtay, Nitin

2012-01-01

Objective Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to “normalize” by age 17 years. Here we present a replication with nonoverlapping groups of healthy full siblings and healthy controls. Method Using an automated measure and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in nonpsychotic full siblings (n = 43, 68 scans; ages 5 through 26 years) of patients with COS, contrasting them with age-, gender-, and scan interval–matched healthy controls (n = 86, 136 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons. Results As in our previous study, young nonpsychotic siblings (<17 years) showed significant GM deficits in bilateral prefrontal and left temporal cortices and, in addition, smaller deficits in the parietal and right inferior temporal cortices. These deficits in nonpsychotic siblings normalized with age with minimal abnormalities remaining by age 17. Conclusions Our results support previous findings showing nonpsychotic siblings of COS probands to have early GM deficits that ameliorate with time. At early ages, prefrontal and/or temporal loss may serve as a familial/trait marker for COS. Late adolescence appears to be a critical period for greatest localization of deficits in probands or normalization in nonpsychotic siblings. PMID:21703497

A voxel-based approach to gray matter asymmetries.

PubMed

Luders, E; Gaser, C; Jancke, L; Schlaug, G

2004-06-01

Voxel-based morphometry (VBM) was used to analyze gray matter (GM) asymmetries in a large sample (n = 60) of male and female professional musicians with and without absolute pitch (AP). We chose to examine these particular groups because previous studies using traditional region-of-interest (ROI) analyses have shown differences in hemispheric asymmetry related to AP and gender. Voxel-based methods may have advantages over traditional ROI-based methods since the analysis can be performed across the whole brain with minimal user bias. After determining that the VBM method was sufficiently sensitive for the detection of differences in GM asymmetries between groups, we found that male AP musicians were more leftward lateralized in the anterior region of the planum temporale (PT) than male non-AP musicians. This confirmed the results of previous studies using ROI-based methods that showed an association between PT asymmetry and the AP phenotype. We further observed that male non-AP musicians revealed an increased leftward GM asymmetry in the postcentral gyrus compared to female non-AP musicians, again corroborating results of a previously published study using ROI-based methods. By analyzing hemispheric GM differences across our entire sample, we were able to partially confirm findings of previous studies using traditional morphometric techniques, as well as more recent, voxel-based analyses. In addition, we found some unusually pronounced GM asymmetries in our musician sample not previously detected in subjects unselected for musical training. Since we were able to validate gender- and AP-related brain asymmetries previously described using traditional ROI-based morphometric techniques, the results of our analyses support the use of VBM for examinations of GM asymmetries.

A Retrospective Belgian Multi-Center MRI Biomarker Study in Alzheimer's Disease (REMEMBER).

PubMed

Niemantsverdriet, Ellis; Ribbens, Annemie; Bastin, Christine; Benoit, Florence; Bergmans, Bruno; Bier, Jean-Christophe; Bladt, Roxanne; Claes, Lene; De Deyn, Peter Paul; Deryck, Olivier; Hanseeuw, Bernard; Ivanoiu, Adrian; Lemper, Jean-Claude; Mormont, Eric; Picard, Gaëtane; Salmon, Eric; Segers, Kurt; Sieben, Anne; Smeets, Dirk; Struyfs, Hanne; Thiery, Evert; Tournoy, Jos; Triau, Eric; Vanbinst, Anne-Marie; Versijpt, Jan; Bjerke, Maria; Engelborghs, Sebastiaan

2018-01-01

Magnetic resonance imaging (MRI) acquisition/processing techniques assess brain volumes to explore neurodegeneration in Alzheimer's disease (AD). We examined the clinical utility of MSmetrix and investigated if automated MRI volumes could discriminate between groups covering the AD continuum and could be used as a predictor for clinical progression. The Belgian Dementia Council initiated a retrospective, multi-center study and analyzed whole brain (WB), grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), cortical GM (CGM) volumes, and WM hyperintensities (WMH) using MSmetrix in the AD continuum. Baseline (n = 887) and follow-up (FU, n = 95) T1-weighted brain MRIs and time-linked neuropsychological data were available. The cohort consisted of cognitively healthy controls (HC, n = 93), subjective cognitive decline (n = 102), mild cognitive impairment (MCI, n = 379), and AD dementia (n = 313). Baseline WB and GM volumes could accurately discriminate between clinical diagnostic groups and were significantly decreased with increasing cognitive impairment. MCI patients had a significantly larger change in WB, GM, and CGM volumes based on two MRIs (n = 95) compared to HC (FU>24months, p = 0.020). Linear regression models showed that baseline atrophy of WB, GM, CGM, and increased CSF volumes predicted cognitive impairment. WB and GM volumes extracted by MSmetrix could be used to define the clinical spectrum of AD accurately and along with CGM, they are able to predict cognitive impairment based on (decline in) MMSE scores. Therefore, MSmetrix can support clinicians in their diagnostic decisions, is able to detect clinical disease progression, and is of help to stratify populations for clinical trials.

Improved longitudinal gray and white matter atrophy assessment via application of a 4-dimensional hidden Markov random field model.

PubMed

Dwyer, Michael G; Bergsland, Niels; Zivadinov, Robert

2014-04-15

SIENA and similar techniques have demonstrated the utility of performing "direct" measurements as opposed to post-hoc comparison of cross-sectional data for the measurement of whole brain (WB) atrophy over time. However, gray matter (GM) and white matter (WM) atrophy are now widely recognized as important components of neurological disease progression, and are being actively evaluated as secondary endpoints in clinical trials. Direct measures of GM/WM change with advantages similar to SIENA have been lacking. We created a robust and easily-implemented method for direct longitudinal analysis of GM/WM atrophy, SIENAX multi-time-point (SIENAX-MTP). We built on the basic halfway-registration and mask composition components of SIENA to improve the raw output of FMRIB's FAST tissue segmentation tool. In addition, we created LFAST, a modified version of FAST incorporating a 4th dimension in its hidden Markov random field model in order to directly represent time. The method was validated by scan-rescan, simulation, comparison with SIENA, and two clinical effect size comparisons. All validation approaches demonstrated improved longitudinal precision with the proposed SIENAX-MTP method compared to SIENAX. For GM, simulation showed better correlation with experimental volume changes (r=0.992 vs. 0.941), scan-rescan showed lower standard deviations (3.8% vs. 8.4%), correlation with SIENA was more robust (r=0.70 vs. 0.53), and effect sizes were improved by up to 68%. Statistical power estimates indicated a potential drop of 55% in the number of subjects required to detect the same treatment effect with SIENAX-MTP vs. SIENAX. The proposed direct GM/WM method significantly improves on the standard SIENAX technique by trading a small amount of bias for a large reduction in variance, and may provide more precise data and additional statistical power in longitudinal studies. Copyright © 2013 Elsevier Inc. All rights reserved.

MRI-based Brain Healthcare Quotients: A bridge between neural and behavioral analyses for keeping the brain healthy

PubMed Central

Nemoto, Kiyotaka; Oka, Hiroki; Fukuda, Hiroki

2017-01-01

Neurological and psychiatric disorders are a burden on social and economic resources. Therefore, maintaining brain health and preventing these disorders are important. While the physiological functions of the brain are well studied, few studies have focused on keeping the brain healthy from a neuroscientific viewpoint. We propose a magnetic resonance imaging (MRI)-based quotient for monitoring brain health, the Brain Healthcare Quotient (BHQ), which is based on the volume of gray matter (GM) and the fractional anisotropy (FA) of white matter (WM). We recruited 144 healthy adults to acquire structural neuroimaging data, including T1-weighted images and diffusion tensor images, and data associated with both physical (BMI, blood pressure, and daily time use) and social (subjective socioeconomic status, subjective well-being, post-materialism and Epicureanism) factors. We confirmed that the BHQ was sensitive to an age-related decline in GM volume and WM integrity. Further analysis revealed that the BHQ was critically affected by both physical and social factors. We believe that our BHQ is a simple yet highly sensitive, valid measure for brain health research that will bridge the needs of the scientific community and society and help us lead better lives in which we stay healthy, active, and sharp. PMID:29077756

Cerebral gray matter volume variation in female-to-male transsexuals: a voxel-based morphometric study.

PubMed

Kim, Tae-Hoon; Kim, Seok-Kwun; Jeong, Gwang-Woo

2015-12-16

Several studies seem to support the hypothesis that brain anatomy is associated with transsexualism. However, these studies were still limited because few neuroanatomical findings have been obtained from female-to-male (FtM) transsexuals. This study compared the cerebral regional volumes of gray matter (GM) between FtM transsexuals and female controls using a voxel-based morphometry. Twelve FtM transsexuals who had undergone sex-reassignment surgery and 15 female controls participated in this study. Both groups were age matched and right-handed, with no history of neurological illness. Fifteen female controls were recruited to determine whether GM volumes in FtM transsexuals more closely resembled individuals who shared their biological sex. MRI data were processed using SPM 8 with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL). FtM transsexuals showed significantly larger volumes of the thalamus, hypothalamus, midbrain, gyrus rectus, head of caudate nucleus, precentral gyrus, and subcallosal area compared with the female controls. However, the female controls showed a significantly larger volume in the superior temporal gyrus including Heschl's gyrus and Rolandic operculum. These findings confirm that the volume difference in brain substructures in FtM transsexuals is likely to be associated with transsexualism and that transsexualism is probably associated with distinct cerebral structures, determining gender identity.

Towards a unified analysis of brain maturation and aging across the entire lifespan: A MRI analysis.

PubMed

Coupé, Pierrick; Catheline, Gwenaelle; Lanuza, Enrique; Manjón, José Vicente

2017-11-01

There is no consensus in literature about lifespan brain maturation and senescence, mainly because previous lifespan studies have been performed on restricted age periods and/or with a limited number of scans, making results instable and their comparison very difficult. Moreover, the use of nonharmonized tools and different volumetric measurements lead to a great discrepancy in reported results. Thanks to the new paradigm of BigData sharing in neuroimaging and the last advances in image processing enabling to process baby as well as elderly scans with the same tool, new insights on brain maturation and aging can be obtained. This study presents brain volume trajectory over the entire lifespan using the largest age range to date (from few months of life to elderly) and one of the largest number of subjects (N = 2,944). First, we found that white matter trajectory based on absolute and normalized volumes follows an inverted U-shape with a maturation peak around middle life. Second, we found that from 1 to 8-10 y there is an absolute gray matter (GM) increase related to body growth followed by a GM decrease. However, when normalized volumes were considered, GM continuously decreases all along the life. Finally, we found that this observation holds for almost all the considered subcortical structures except for amygdala which is rather stable and hippocampus which exhibits an inverted U-shape with a longer maturation period. By revealing the entire brain trajectory picture, a consensus can be drawn since most of the previously discussed discrepancies can be explained. Hum Brain Mapp 38:5501-5518, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Total and regional brain volumes in a population-based normative sample from 4 to 18 years: the NIH MRI Study of Normal Brain Development.

PubMed

2012-01-01

Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5-18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents.

Cortical Changes Across the Autism Lifespan.

PubMed

Osipowicz, Karol; Bosenbark, Danielle D; Patrick, Kristina E

2015-08-01

Although it is widely accepted that autism spectrum disorder (ASD) involves neuroanatomical abnormalities and atypical neurodevelopmental patterns, there is little consensus regarding the precise pattern of neuroanatomical differences or how these differences relate to autism symptomology. Furthermore, there is limited research related to neuroanatomical correlates of autism symptomology in individuals with ASD and the studies that do exist primarily include small samples. This study was the first to investigate gray matter (GM) changes throughout the ASD lifespan, using voxel-based morphometry to determine whether significant differences exist in the GM volumes of a large sample of individuals with ASD compared to age- and IQ-matched typical controls. We examined GM volume across the lifespan in 531 individuals diagnosed with ASD and 571 neurotypical controls, aged 7-64. We compared groups and correlated GM with age and autism severity in the ASD group. Findings suggest bilateral decreased GM volume for individuals with ASD in regions extending from the thalamus to the cerebellum, anterior medial temporal lobes, and orbitofrontal regions. Higher autism severity was associated with decreased GM volumes in prefrontal cortex, inferior parietal and temporal regions, and temporal poles. Similar relationships were found between GM volume and age. ASD diagnosis and severity were not associated with increased GM volumes in any region. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Does the brain shrink as the waist expands?

PubMed

Willette, Auriel A; Kapogiannis, Dimitrios

2015-03-01

Recent studies suggest that being overweight or obese is related to worse cognitive performance, particularly executive function. Obesity may also increase the risk of Alzheimer's disease. Consequently, there has been increasing interest in whether adiposity is related to gray or white matter (GM, WM) atrophy. In this review, we identified and critically evaluated studies assessing obesity and GM or WM volumes either globally or in specific regions of interest (ROIs). Across all ages, higher adiposity was consistently associated with frontal GM atrophy, particularly in prefrontal cortex. In children and adults <40 years of age, most studies found no relationship between adiposity and occipital or parietal GM volumes, whereas findings for temporal lobe were mixed. In middle-aged and aged adults, a majority of studies found that higher adiposity is associated with parietal and temporal GM atrophy, whereas results for precuneus, posterior cingulate, and hippocampus were mixed. Higher adiposity had no clear association with global or regional WM in any age group. We conclude that higher adiposity may be associated with frontal GM atrophy across all ages and parietal and temporal GM atrophy in middle and old age. Published by Elsevier B.V.

Functional analysis of structurally related soybean GmWRKY58 and GmWRKY76 in plant growth and development.

PubMed

Yang, Yan; Chi, Yingjun; Wang, Ze; Zhou, Yuan; Fan, Baofang; Chen, Zhixiang

2016-08-01

WRKY transcription factors constitute a large protein superfamily with a predominant role in plant stress responses. In this study we report that two structurally related soybean WRKY proteins, GmWRKY58 and GmWRKY76, play a critical role in plant growth and flowering. GmWRKY58 and GmWRKY76 are both Group III WRKY proteins with a C2HC zinc finger domain and are close homologs of AtWRKY70 and AtWRKY54, two well-characterized Arabidopsis WRKY proteins with an important role in plant responses to biotic and abiotic stresses. GmWRKY58 and GmWRKY76 are both localized to the nucleus, recognize the TTGACC W-box sequence with a high specificity, and function as transcriptional activators in both yeast and plant cells. Expression of GmWRKY58 and GmWRKY76 was detected at low levels in roots, stem, leaves, flowers, and pods. Expression of the two genes in leaves increased substantially during the first 4 weeks after germination but steadily declined thereafter with increased age. To determine their biological functions, transgenic Arabidopsis plants were generated overexpressing GmWRKY58 or GmWRKY76 Unlike AtWRKY70 and AtWRKY54, overexpression of GmWRKY58 or GmWRKY76 had no effect on disease resistance and only small effects on abiotic stress tolerance of the transgenic plants. Significantly, transgenic Arabidopsis plants overexpressing GmWRKY58 or GmWRKY76 flowered substantially earlier than control plants and this early flowering phenotype was associated with increased expression of several flowering-promoting genes, some of which are enriched in W-box sequences in their promoters recognized by GmWRKY58 and GmWRKY76. In addition, virus-induced silencing of GmWRKY58 and GmWRKY76 in soybean resulted in stunted plants with reduced leaf expansion and terminated stem growth. These results provide strong evidence for functional divergence among close structural homologs of WRKY proteins from different plant species. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Functional analysis of structurally related soybean GmWRKY58 and GmWRKY76 in plant growth and development

PubMed Central

Yang, Yan; Chi, Yingjun; Wang, Ze; Zhou, Yuan; Fan, Baofang; Chen, Zhixiang

2016-01-01

WRKY transcription factors constitute a large protein superfamily with a predominant role in plant stress responses. In this study we report that two structurally related soybean WRKY proteins, GmWRKY58 and GmWRKY76, play a critical role in plant growth and flowering. GmWRKY58 and GmWRKY76 are both Group III WRKY proteins with a C2HC zinc finger domain and are close homologs of AtWRKY70 and AtWRKY54, two well-characterized Arabidopsis WRKY proteins with an important role in plant responses to biotic and abiotic stresses. GmWRKY58 and GmWRKY76 are both localized to the nucleus, recognize the TTGACC W-box sequence with a high specificity, and function as transcriptional activators in both yeast and plant cells. Expression of GmWRKY58 and GmWRKY76 was detected at low levels in roots, stem, leaves, flowers, and pods. Expression of the two genes in leaves increased substantially during the first 4 weeks after germination but steadily declined thereafter with increased age. To determine their biological functions, transgenic Arabidopsis plants were generated overexpressing GmWRKY58 or GmWRKY76. Unlike AtWRKY70 and AtWRKY54, overexpression of GmWRKY58 or GmWRKY76 had no effect on disease resistance and only small effects on abiotic stress tolerance of the transgenic plants. Significantly, transgenic Arabidopsis plants overexpressing GmWRKY58 or GmWRKY76 flowered substantially earlier than control plants and this early flowering phenotype was associated with increased expression of several flowering-promoting genes, some of which are enriched in W-box sequences in their promoters recognized by GmWRKY58 and GmWRKY76. In addition, virus-induced silencing of GmWRKY58 and GmWRKY76 in soybean resulted in stunted plants with reduced leaf expansion and terminated stem growth. These results provide strong evidence for functional divergence among close structural homologs of WRKY proteins from different plant species. PMID:27335454

Genetically modified organisms in the United States: implementation, concerns, and public perception.

PubMed

Oeschger, Max P; Silva, Catherine E

2007-01-01

We examine the state of biotechnology with respect to genetically modified (GM) organisms in agriculture. Our focus is on the USA, where there has been significant progress and implementation but where, to date, the matter has drawn little attention. GM organisms are the result of lateral gene transfers, the transfer of genes from one species to another, or sometimes, from one kingdom to another. The introduction of foreign genes makes some people very uncomfortable, and a small group of activists have grave concerns about the technology. Attempts by activists to build concern in the general public have garnered little attention; however, the producers of GM organisms have responded to their concerns and established extensive testing programs to be applied to each candidate organism that is produced. In the meantime, GM varieties of corn, cotton, soybean and rapeseed have been put into agricultural production and are now extensively planted. These crops, and the other, newer GM crops, have produced no problems and have pioneered a silent agricultural revolution in the USA.

Evidence for Absolute Moral Opposition to Genetically Modified Food in the United States.

PubMed

Scott, Sydney E; Inbar, Yoel; Rozin, Paul

2016-05-01

Public opposition to genetic modification (GM) technology in the food domain is widespread (Frewer et al., 2013). In a survey of U.S. residents representative of the population on gender, age, and income, 64% opposed GM, and 71% of GM opponents (45% of the entire sample) were "absolutely" opposed-that is, they agreed that GM should be prohibited no matter the risks and benefits. "Absolutist" opponents were more disgust sensitive in general and more disgusted by the consumption of genetically modified food than were non-absolutist opponents or supporters. Furthermore, disgust predicted support for legal restrictions on genetically modified foods, even after controlling for explicit risk-benefit assessments. This research suggests that many opponents are evidence insensitive and will not be influenced by arguments about risks and benefits. © The Author(s) 2016.

Distinct neuroanatomical bases of episodic and semantic memory performance in Alzheimer's disease.

PubMed

Hirni, Daniela I; Kivisaari, Sasa L; Monsch, Andreas U; Taylor, Kirsten I

2013-04-01

Alzheimer's disease (AD) neurofibrillary pathology begins in the medial perirhinal cortex (mPRC) before spreading to the entorhinal cortex (ERC) and hippocampus (HP) in anterior medial temporal lobe (aMTL). While the role of the ERC/HP complex in episodic memory formation is well-established, recent research suggests that the PRC is required to form semantic memories of individual objects. We aimed to test whether commonly used clinical measures of episodic and semantic memory are distinctly associated with ERC/HP and mPRC integrity, respectively, in healthy mature individuals and very early AD patients. One hundred thirty normal controls, 32 amnestic mild cognitive impairment patients, some of whom are in the earliest (i.e., preclinical) stages of AD, and ten early-stage AD patients received neuropsychological testing and high-resolution anatomic and diffusion MRI. Voxel-based regression analyses tested for regions where episodic memory (delayed recall scores on the California Verbal Learning and Rey Osterrieth Complex Figure Tests) and semantic memory (Boston Naming Test, category fluency) performance correlated with gray matter (GM) regions of interest and whole-brain fractional anisotropy (FA) voxel values. When controlling for the opposing memory performance, poorer episodic memory performance was associated with reduced bilateral ERC/HP GM volume and related white matter integrity, but not with mPRC GM volume. Poor semantic memory performance was associated with both reduced left mPRC and ERC/HP GM volume, as well as reduced FA values in white matter tracts leading to the PRC. These results indicate a partial division of labor within the aMTL and suggest that mPRC damage in very early AD may be detectable with common clinical tests of semantic memory if episodic memory performance is controlled. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neuroinflammatory component of gray matter pathology in multiple sclerosis.

PubMed

Herranz, Elena; Giannì, Costanza; Louapre, Céline; Treaba, Constantina A; Govindarajan, Sindhuja T; Ouellette, Russell; Loggia, Marco L; Sloane, Jacob A; Madigan, Nancy; Izquierdo-Garcia, David; Ward, Noreen; Mangeat, Gabriel; Granberg, Tobias; Klawiter, Eric C; Catana, Ciprian; Hooker, Jacob M; Taylor, Norman; Ionete, Carolina; Kinkel, Revere P; Mainero, Caterina

2016-11-01

In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with 11 C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal-appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation. Fifteen secondary-progressive MS (SPMS) patients, 12 relapsing-remitting MS (RRMS) patients, and 14 matched healthy controls underwent 11 C-PBR28 MR-PET. MS subjects underwent 7T T2*-weighted imaging for cortical lesion segmentation, and neurological and cognitive evaluation. 11 C-PBR28 binding was measured using normalized 60- to 90-minute standardized uptake values and volume of distribution ratios. Relative to controls, MS subjects exhibited abnormally high 11 C-PBR28 binding across the brain, the greatest increases being in cortex and cortical lesions, thalamus, hippocampus, and NAWM. MS WM lesions showed relatively modest TSPO increases. With the exception of cortical lesions, where TSPO expression was similar, 11 C-PBR28 uptake across the brain was greater in SPMS than in RRMS. In MS, increased 11 C-PBR28 binding in cortex, deep GM, and NAWM correlated with neurological disability and impaired cognitive performance; cortical thinning correlated with increased thalamic TSPO levels. In MS, neuroinflammation is present in the cortex, cortical lesions, deep GM, and NAWM, is closely linked to poor clinical outcome, and is at least partly linked to neurodegeneration. Distinct inflammatory-mediated factors may underlie accumulation of cortical and WM lesions. Quantification of TSPO levels in MS could prove to be a sensitive tool for evaluating in vivo the inflammatory component of GM pathology, particularly in cortical lesions. Ann Neurol 2016;80:776-790. © 2016 American Neurological Association.

Multivariate Classification of Structural MRI Data Detects Chronic Low Back Pain

PubMed Central

Ung, Hoameng; Brown, Justin E.; Johnson, Kevin A.; Younger, Jarred; Hush, Julia; Mackey, Sean

2014-01-01

Chronic low back pain (cLBP) has a tremendous personal and socioeconomic impact, yet the underlying pathology remains a mystery in the majority of cases. An objective measure of this condition, that augments self-report of pain, could have profound implications for diagnostic characterization and therapeutic development. Contemporary research indicates that cLBP is associated with abnormal brain structure and function. Multivariate analyses have shown potential to detect a number of neurological diseases based on structural neuroimaging. Therefore, we aimed to empirically evaluate such an approach in the detection of cLBP, with a goal to also explore the relevant neuroanatomy. We extracted brain gray matter (GM) density from magnetic resonance imaging scans of 47 patients with cLBP and 47 healthy controls. cLBP was classified with an accuracy of 76% by support vector machine analysis. Primary drivers of the classification included areas of the somatosensory, motor, and prefrontal cortices—all areas implicated in the pain experience. Differences in areas of the temporal lobe, including bordering the amygdala, medial orbital gyrus, cerebellum, and visual cortex, were also useful for the classification. Our findings suggest that cLBP is characterized by a pattern of GM changes that can have discriminative power and reflect relevant pathological brain morphology. PMID:23246778

Cortical thickness and VBM in young women at risk for familial depression and their depressed mothers with positive family history.

PubMed

Ozalay, Ozgun; Aksoy, Burcu; Tunay, Sebnem; Simsek, Fatma; Chandhoki, Swati; Kitis, Omer; Eker, Cagdas; Gonul, Ali Saffet

2016-06-30

It has been demonstrated that compared to low-risk subjects, high-risk subjects for depression have structural and functional alterations in their brain scans even before the disease onset. However, it is not known if these alterations are related to vulnerability to depression or epiphenomena. One way to resolve this ambiguity is to detect the structural alterations in the high-risk subjects and determine if the same alterations are present in the probands. In this study, we recruited 24 women with the diagnosis of Major Depressive Disorder (MDD) with recurrent episodes and their healthy daughters (the high-risk for familial depression group; HRFD). We compared structural brain scans of the patients and HRFG group with those of 24 age-matched healthy mothers and their healthy daughters at similar ages to the HRFD group; respectively. Both cortical gray matter (GM) volume and thickness analyses revealed that HRFD daughters and their MDD mothers had similar GM differences in two regions: the right temporoparietal region and the dorsomedial prefrontal cortex. These results suggested that the observed alterations may be related to trait clinical and neurophysiological characteristics of MDD and may present before the onset of illness. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Long-Term Occupational Stress Is Associated with Regional Reductions in Brain Tissue Volumes

PubMed Central

Blix, Eva; Perski, Aleksander; Berglund, Hans; Savic, Ivanka

2013-01-01

There are increasing reports of cognitive and psychological declines related to occupational stress in subjects without psychiatric premorbidity or major life trauma. The underlying neurobiology is unknown, and many question the notion that the described disabilities represent a medical condition. Using PET we recently found that persons suffering from chronic occupational stress had limbic reductions in the 5-HT1A receptor binding potential. Here we examine whether chronic work-related stress is also associated with changes in brain structure. We performed MRI-based voxel-based morphometry and structural volumetry in stressed subjects and unstressed controls focusing on gray (GM) and white matter (WM) volumes, and the volumes of hippocampus, caudate, and putamen – structures known to be susceptible to neurotoxic changes. Stressed subjects exhibited significant reductions in the GM volumes of the anterior cingulate cortex and the dorsolateral prefrontal cortex. Furthermore, their caudate and putamen volumes were reduced, and the volumes correlated inversely to the degree of perceived stress. Our results add to previous data on chronic psychosocial stress, and indicate a morphological involvement of the frontostriatal circuits. The present findings of morphological changes in these regions confirm our previous conclusion that symptoms from occupational stress merit careful investigations and targeted treatment. PMID:23776438

Irritable bowel syndrome in female patients is associated with alterations in structural brain networks.

PubMed

Labus, Jennifer S; Dinov, Ivo D; Jiang, Zhiguo; Ashe-McNalley, Cody; Zamanyan, Alen; Shi, Yonggang; Hong, Jui-Yang; Gupta, Arpana; Tillisch, Kirsten; Ebrat, Bahar; Hobel, Sam; Gutman, Boris A; Joshi, Shantanu; Thompson, Paul M; Toga, Arthur W; Mayer, Emeran A

2014-01-01

Alterations in gray matter (GM) density/volume and cortical thickness (CT) have been demonstrated in small and heterogeneous samples of subjects with differing chronic pain syndromes, including irritable bowel syndrome (IBS). Aggregating across 7 structural neuroimaging studies conducted at University of California, Los Angeles, Los Angeles, CA, USA, between August 2006 and April 2011, we examined group differences in regional GM volume in 201 predominantly premenopausal female subjects (82 IBS, mean age: 32±10 SD, 119 healthy controls [HCs], 30±10 SD). Applying graph theoretical methods and controlling for total brain volume, global and regional properties of large-scale structural brain networks were compared between the group with IBS and the HC group. Relative to HCs, the IBS group had lower volumes in the bilateral superior frontal gyrus, bilateral insula, bilateral amygdala, bilateral hippocampus, bilateral middle orbital frontal gyrus, left cingulate, left gyrus rectus, brainstem, and left putamen. Higher volume was found in the left postcentral gyrus. Group differences were no longer significant for most regions when controlling for the Early Trauma Inventory global score, with the exception of the right amygdala and the left postcentral gyrus. No group differences were found for measures of global and local network organization. Compared to HCs, in patients with IBS, the right cingulate gyrus and right thalamus were identified as being significantly more critical for information flow. Regions involved in endogenous pain modulation and central sensory amplification were identified as network hubs in IBS. Overall, evidence for central alterations in patients with IBS was found in the form of regional GM volume differences and altered global and regional properties of brain volumetric networks. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Brain structural substrates of cognitive procedural learning in alcoholic patients early in abstinence.

PubMed

Ritz, Ludivine; Segobin, Shailendra; Le Berre, Anne Pascale; Lannuzel, Coralie; Boudehent, Céline; Vabret, François; Eustache, Francis; Pitel, Anne Lise; Beaunieux, Hélène

2014-08-01

Procedural learning allows for the acquisition of new behavioral skills. Previous studies have shown that chronic alcoholism is characterized by impaired cognitive procedural learning and brain abnormalities affecting regions that are involved in the automation of new cognitive procedures in healthy individuals. The goal of the present study was to investigate the brain structural substrates of cognitive procedural learning in alcoholic patients (ALs) early in abstinence. Thirty-one ALs and 31 control participants (NCs) performed the Tower of Toronto task (4 daily learning sessions, each comprising 10 trials) to assess cognitive procedural learning. We also assessed episodic and working memory, executive functions, and visuospatial abilities. ALs underwent 1.5T structural magnetic resonance imaging. The initial cognitive phase was longer in the AL group than in the NC group, whereas the autonomous phase was shorter. In ALs, the longer cognitive phase was predicted by poorer planning and visuospatial working memory abilities, and by smaller gray matter (GM) volumes in the angular gyrus and caudate nucleus. ALs' planning abilities correlated with smaller GM volume in the angular gyrus. Cognitive procedural learning was impaired in ALs, with a delayed transition from the cognitive to the autonomous phase. This slowdown in the automation of the cognitive procedure was related to lower planning abilities, which may have hampered the initial generation of the procedure to be learned. In agreement with this neuropsychological finding, a persistent relationship was found between learning performance and the GM volumes of the angular gyrus and caudate nucleus, which are usually regarded as markers of planning and initial learning of the cognitive procedure. Copyright © 2014 by the Research Society on Alcoholism.

Brain structural substrates of cognitive procedural learning in alcoholic patients early in abstinence

PubMed Central

Ritz, Ludivine; Segobin, Shailendra; Le Berre, Anne Pascale; Lannuzel, Coralie; Boudehent, Céline; Vabret, François; Eustache, Francis; Pitel, Anne Lise; Beaunieux, Hélène

2014-01-01

Background Procedural learning allows for the acquisition of new behavioral skills. Previous studies have shown that chronic alcoholism is characterized by impaired cognitive procedural learning and brain abnormalities affecting regions that are involved in the automation of new cognitive procedures in healthy individuals. The goal of the present study was to investigate the brain structural substrates of cognitive procedural learning in alcoholic patients (ALs) early in abstinence. Methods Thirty-one ALs and 31 control participants (NCs) performed the Tower of Toronto task (4 daily learning sessions, each comprising 10 trials) to assess cognitive procedural learning. We also assessed episodic and working memory, executive functions, and visuospatial abilities. ALs underwent 1.5T structural magnetic resonance imaging. Results The initial cognitive phase was longer in the AL group than in the NC group, whereas the autonomous phase was shorter. In ALs, the longer cognitive phase was predicted by poorer planning and visuospatial working memory abilities, and by smaller gray matter (GM) volumes in the angular gyrus and caudate nucleus. ALs’ planning abilities correlated with smaller GM volume in the angular gyrus. Conclusions Cognitive procedural learning was impaired in ALs, with a delayed transition from the cognitive to the autonomous phase. This slowdown in the automation of the cognitive procedure was related to lower planning abilities, which may have hampered the initial generation of the procedure to be learned. In agreement with this neuropsychological finding, a persistent relationship was found between learning performance and the GM volumes of the angular gyrus and caudate nucleus, which are usually regarded as markers of planning and initial learning of the cognitive procedure. PMID:25156613

Gray matter trophism, cognitive impairment, and depression in patients with multiple sclerosis.

PubMed

Pravatà, Emanuele; Rocca, Maria A; Valsasina, Paola; Riccitelli, Gianna C; Gobbi, Claudio; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

2017-12-01

Cognitive impairment and depression frequently affects patients with multiple sclerosis (MS). However, the relationship between the occurrence of depression and cognitive impairment and the development of cortical atrophy has not been fully elucidated yet. To investigate the association of cortical and deep gray matter (GM) volume with depression and cognitive impairment in MS. Three-dimensional (3D) T1-weighted scans were obtained from 126 MS patients and 59 matched healthy controls. Cognitive impairment was assessed using the Brief Repeatable Battery of Neuropsychological Tests and depression with the Montgomery-Asberg Depression Rating Scale (MADRS). Using FreeSurfer and FIRST software, we assessed cortical thickness (CTh) and deep GM volumetry. Magnetic resonance imaging (MRI) variables explaining depression and cognitive impairment were investigated using factorial and classification analysis. Multivariate regression models correlated GM abnormalities with symptoms severity. Compared with controls, MS patients exhibited widespread bilateral cortical thinning involving all brain lobes. Depressed MS showed selective CTh decrease in fronto-temporal regions, whereas cognitive impairment MS exhibited widespread fronto-parietal cortical and subcortical GM atrophy. Frontal cortical thinning was the best predictor of depression ( C-statistic = 0.7), whereas thinning of the right precuneus and high T2 lesion volume best predicted cognitive impairment ( C-statistic = 0.8). MADRS severity correlated with right entorhinal cortex thinning, whereas cognitive impairment severity correlated with left entorhinal and thalamus atrophy. MS-related depression is linked to circumscribed CTh changes in areas deputed to emotional behavior, whereas cognitive impairment is correlated with cortical and subcortical GM atrophy of circuits involved in cognition.

Brain structure and verbal function across adulthood while controlling for cerebrovascular risks.

PubMed

Sanfratello, L; Lundy, S L; Qualls, C; Knoefel, J E; Adair, J C; Caprihan, A; Stephen, J M; Aine, C J

2017-04-08

The development and decline of brain structure and function throughout adulthood is a complex issue, with cognitive aging trajectories influenced by a host of factors including cerebrovascular risk. Neuroimaging studies of age-related cognitive decline typically reveal a linear decrease in gray matter (GM) volume/density in frontal regions across adulthood. However, white matter (WM) tracts mature later than GM, particularly in regions necessary for executive functions and memory. Therefore, it was predicted that a middle-aged group (MC: 35-45 years) would perform best on a verbal working memory task and reveal greater regional WM integrity, compared with both young (YC: 18-25 years) and elder groups (EC: 60+ years). Diffusion tensor imaging (DTI) and magnetoencephalography (MEG) were obtained from 80 healthy participants. Objective measures of cerebrovascular risk and cognition were also obtained. As predicted, MC revealed best verbal working memory accuracy overall indicating some maturation of brain function between YC and MC. However, contrary to the prediction fractional anisotropy values (FA), a measure of WM integrity, were not greater in MC (i.e., there were no significant differences in FA between YC and MC but both groups showed greater FA than EC). An overall multivariate model for MEG ROIs showed greater peak amplitudes for MC and YC, compared with EC. Subclinical cerebrovascular risk factors (systolic blood pressure and blood glucose) were negatively associated with FA in frontal callosal, limbic, and thalamic radiation regions which correlated with executive dysfunction and slower processing speed, suggesting their contribution to age-related cognitive decline. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The Associations between Regional Gray Matter Structural Changes and Changes of Cognitive Performance in Control Groups of Intervention Studies.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Sassa, Yuko; Sekiguchi, Atsushi; Nagase, Tomomi; Nouchi, Rui; Fukushima, Ai; Kawashima, Ryuta

2015-01-01

In intervention studies of cognitive training, the challenging cognitive tests, which were used as outcome measures, are generally completed in more than a few hours. Here, utilizing the control groups' data from three 1-week intervention studies in which young healthy adult subjects underwent a wide range of cognitive tests and T1-weighted magnetic resonance imaging (MRI) before and after the intervention period, we investigated how regional gray matter (GM) density (rGMD) of the subjects changed through voxel-based morphometry (VBM). Statistically significant increases in rGMD were observed in the anatomical cluster that mainly spread around the bilateral dorsal anterior cingulate cortex (dACC) and the right superior frontal gyrus (rSFG). Moreover, mean rGMD within this cluster changes were significantly and positively correlated with performance changes in the Stroop task, and tended to positively correlate with performance changes in a divergent thinking task. Affected regions are considered to be associated with performance monitoring (dACC) and manipulation of the maintained information including generating associations (rSFG), and both are relevant to the cognitive functions measured in the cognitive tests. Thus, the results suggest that even in the groups of the typical "control group" in intervention studies including those of the passive one, experimental or non-experimental factors can result in an increase in the regional GM structure and form the association between such neural changes and improvements related to these cognitive tests. These results suggest caution toward the experimental study designs without control groups.

Constructing graph models for software system development and analysis

NASA Astrophysics Data System (ADS)

Pogrebnoy, Andrey V.

2017-01-01

We propose a concept for creating the instrumentation for functional and structural decisions rationale during the software system (SS) development. We propose to develop SS simultaneously on two models - functional (FM) and structural (SM). FM is a source code of the SS. Adequate representation of the FM in the form of a graph model (GM) is made automatically and called SM. The problem of creating and visualizing GM is considered from the point of applying it as a uniform platform for the adequate representation of the SS source code. We propose three levels of GM detailing: GM1 - for visual analysis of the source code and for SS version control, GM2 - for resources optimization and analysis of connections between SS components, GM3 - for analysis of the SS functioning in dynamics. The paper includes examples of constructing all levels of GM.

Cued recall measure predicts the progression of gray matter atrophy in patients with amnesic mild cognitive impairment.

PubMed

Koric, Lejla; Ranjeva, Jean-Philippe; Felician, Olivier; Guye, Maxime; de Anna, Francesca; Soulier, Elisabeth; Didic, Mira; Ceccaldi, Mathieu

2013-01-01

Amnesic mild cognitive impairment (aMCI) is a heterogeneous syndrome that could be subdivided into distinct neuropsychological variants. To investigate relationships between the neuropsychological profile of memory impairment at baseline and the neuroimaging pattern of grey matter (GM) loss over 18 months, we performed a prospective volumetric brain study on 31 aMCI patients and 29 matched controls. All subjects were tested at baseline using a standardized neuropsychological battery, which included the Free and Cued Selective Recall Reminding Test (FCSRT) for the assessment of verbal declarative memory. Over 18 months, patients with impaired free recall but normal total recall (high index of cueing) on the FCSRT developed subcortical and frontal GM loss, while patients with impaired free and total recall (low index of cueing) developed GM atrophy within the left anterior and lateral temporal lobe. In summary, cued recall deficits are associated with a progression of atrophy that closely parallels the spatiotemporal distribution of neurofibrillary degeneration in early Alzheimer's disease (AD), indicating possible AD pathological changes. © 2013 S. Karger AG, Basel.

Bilingualism provides a neural reserve for aging populations.

PubMed

Abutalebi, Jubin; Guidi, Lucia; Borsa, Virginia; Canini, Matteo; Della Rosa, Pasquale A; Parris, Ben A; Weekes, Brendan S

2015-03-01

It has been postulated that bilingualism may act as a cognitive reserve and recent behavioral evidence shows that bilinguals are diagnosed with dementia about 4-5 years later compared to monolinguals. In the present study, we investigated the neural basis of these putative protective effects in a group of aging bilinguals as compared to a matched monolingual control group. For this purpose, participants completed the Erikson Flanker task and their performance was correlated to gray matter (GM) volume in order to investigate if cognitive performance predicts GM volume specifically in areas affected by aging. We performed an ex-Gaussian analysis on the resulting RTs and report that aging bilinguals performed better than aging monolinguals on the Flanker task. Bilingualism was overall associated with increased GM in the ACC. Likewise, aging induced effects upon performance correlated only for monolinguals to decreased gray matter in the DLPFC. Taken together, these neural regions might underlie the benefits of bilingualism and act as a neural reserve that protects against the cognitive decline that occurs during aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lack of Gender Influence on Cortical and Subcortical Gray Matter Development in Childhood-Onset Schizophrenia

PubMed Central

Weisinger, Brian; Greenstein, Deanna; Mattai, Anand; Clasen, Liv; Lalonde, Francois; Feldman, Sara; Miller, Rachel; Tossell, Julia W.; Vyas, Nora S.; Stidd, Reva; David, Christopher; Gogtay, Nitin

2013-01-01

Background: Progressive cortical gray matter (GM) abnormalities are an established feature of schizophrenia and are more pronounced in rare, severe, and treatment refractory childhood-onset schizophrenia (COS) cases. The effect of sex on brain development in schizophrenia is poorly understood and studies to date have produced inconsistent results. >Methods: Using the largest to date longitudinal sample of COS cases (n = 104, scans = 249, Male/Female [M/F] = 57/47), we compared COS sex differences with sex differences in a sample of matched typically developing children (n = 104, scans = 244, M/F = 57/47), to determine whether or not sex had differential effects on cortical and subcortical brain development in COS. Results: Our results showed no significant differential sex effects in COS for either GM cortical thickness or subcortical volume development (sex × diagnosis × age interaction; false discovery rate q = 0.05). Conclusion: Sex appears to play a similar role in cortical and subcortical GM development in COS as it does in normally developing children. PMID:21613381

White Matter Hyperintensity Associations with Cerebral Blood Flow in Elderly Subjects Stratified by Cerebrovascular Risk.

PubMed

Bahrani, Ahmed A; Powell, David K; Yu, Guoquiang; Johnson, Eleanor S; Jicha, Gregory A; Smith, Charles D

2017-04-01

This study aims to add clarity to the relationship between deep and periventricular brain white matter hyperintensities (WMHs), cerebral blood flow (CBF), and cerebrovascular risk in older persons. Deep white matter hyperintensity (dWMH) and periventricular white matter hyperintensity (pWMH) and regional gray matter (GM) and white matter (WM) blood flow from arterial spin labeling were quantified from magnetic resonance imaging scans of 26 cognitively normal elderly subjects stratified by cerebrovascular disease (CVD) risk. Fluid-attenuated inversion recovery images were acquired using a high-resolution 3-dimensional (3-D) sequence that reduced partial volume effects seen with slice-based techniques. dWMHs but not pWMHs were increased in patients at high risk of CVD; pWMHs but not dWMHs were associated with decreased regional cortical (GM) blood flow. We also found that blood flow in WM is decreased in regions of both pWMH and dWMH, with a greater degree of decrease in pWMH areas. WMHs are usefully divided into dWMH and pWMH regions because they demonstrate differential effects. 3-D regional WMH volume is a potentially valuable marker for CVD based on associations with cortical CBF and WM CBF. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Attitudes of Agricultural Experts Toward Genetically Modified Crops: A Case Study in Southwest Iran.

PubMed

Ghanian, Mansour; Ghoochani, Omid M; Kitterlin, Miranda; Jahangiry, Sheida; Zarafshani, Kiumars; Van Passel, Steven; Azadi, Hossein

2016-04-01

The production of genetically modified (GM) crops is growing around the world, and with it possible opportunities to combat food insecurity and hunger, as well as solutions to current problems facing conventional agriculture. In this regard the use of GMOs in food and agricultural applications has increased greatly over the past decade. However, the development of GM crops has been a matter of considerable interest and worldwide public controversy. This, in addition to skepticism, has stifled the use of this practice on a large scale in many areas, including Iran. It stands to reason that a greater understanding of this practice could be formed after a review of the existing expert opinions surrounding GM crops. Therefore, the purpose of this study was to analyze the predictors that influence agricultural experts' attitudes toward the development of and policies related to GM crops. Using a descriptive correlational research method, questionnaire data was collected from 65 experts from the Agricultural Organization in the Gotvand district in Southwest Iran. Results indicated that agricultural experts were aware of the environmental benefits and possible risks associated with GM crops. The majority of participants agreed that GM crops could improve food security and accelerate rural development, and were proponents of labeling practices for GM crops. Finally, there was a positive correlation between the perception of benefits and attitudes towards GM crops.

Cortical Enhanced Tissue Segmentation of Neonatal Brain MR Images Acquired by a Dedicated Phased Array Coil

PubMed Central

Shi, Feng; Yap, Pew-Thian; Fan, Yong; Cheng, Jie-Zhi; Wald, Lawrence L.; Gerig, Guido; Lin, Weili; Shen, Dinggang

2010-01-01

The acquisition of high quality MR images of neonatal brains is largely hampered by their characteristically small head size and low tissue contrast. As a result, subsequent image processing and analysis, especially for brain tissue segmentation, are often hindered. To overcome this problem, a dedicated phased array neonatal head coil is utilized to improve MR image quality by effectively combing images obtained from 8 coil elements without lengthening data acquisition time. In addition, a subject-specific atlas based tissue segmentation algorithm is specifically developed for the delineation of fine structures in the acquired neonatal brain MR images. The proposed tissue segmentation method first enhances the sheet-like cortical gray matter (GM) structures in neonatal images with a Hessian filter for generation of cortical GM prior. Then, the prior is combined with our neonatal population atlas to form a cortical enhanced hybrid atlas, which we refer to as the subject-specific atlas. Various experiments are conducted to compare the proposed method with manual segmentation results, as well as with additional two population atlas based segmentation methods. Results show that the proposed method is capable of segmenting the neonatal brain with the highest accuracy, compared to other two methods. PMID:20862268

Structural alterations in the prefrontal cortex mediate the relationship between Internet gaming disorder and depressed mood.

PubMed

Choi, Jihye; Cho, Hyun; Kim, Jin-Young; Jung, Dong Jin; Ahn, Kook Jin; Kang, Hang-Bong; Choi, Jung-Seok; Chun, Ji-Won; Kim, Dai-Jin

2017-04-28

Adaptive gaming use has positive effects, whereas depression has been reported to be prevalent in Internet gaming disorder (IGD). However, the neural correlates underlying the association between depression and Internet gaming remain unclear. Moreover, the neuroanatomical profile of the striatum in IGD is relatively less clear despite its important role in addiction. We found lower gray matter (GM) density in the left dorsolateral prefrontal cortex (DLPFC) in the IGD group than in the Internet gaming control (IGC) group and non-gaming control (NGC) group, and the GM density was associated with lifetime usage of Internet gaming, depressed mood, craving, and impulsivity in the gaming users. Striatal volumetric analysis detected a significant reduction in the right nucleus accumbens (NAcc) in the IGD group and its association with lifetime usage of gaming and depression. These findings suggest that alterations in the brain structures involved in the reward system are associated with IGD-related behavioral characteristics. Furthermore, the DLPFC, involved in cognitive control, was observed to serve as a mediator in the association between prolonged gaming and depressed mood. This finding may provide insight into an intervention strategy for treating IGD with comorbid depression.

Structural brain and neuropsychometric changes associated with pediatric bipolar disorder with psychosis.

PubMed

James, Anthony; Hough, Morgan; James, Susan; Burge, Linda; Winmill, Louise; Nijhawan, Sunita; Matthews, Paul M; Zarei, Mojtaba

2011-02-01

To identify neuropsychological and structural brain changes using a combination of high-resolution structural and diffusion tensor imaging in pediatric bipolar disorder (PBD) with psychosis (presence of delusions and or hallucinations). We recruited 15 patients and 20 euthymic age- and gender-matched healthy controls. All subjects underwent high-resolution structural and diffusion tensor imaging. Voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), and probabilistic tractography were used to analyse magnetic resonance imaging data. The PBD subjects had normal overall intelligence with specific impairments in working memory, executive function, language function, and verbal memory. Reduced gray matter (GM) density was found in the left orbitofrontal cortex, left pars triangularis, right premotor cortex, occipital cortex, right occipital fusiform gyrus, and right crus of the cerebellum. TBSS analysis showed reduced fractional anisotropy (FA) in the anterior corpus callosum. Probabilistic tractography from this cluster showed that this region of the corpus callosum is connected with the prefrontal cortices, including those regions whose density is decreased in PBD. In addition, FA change was correlated with verbal memory and working memory, while more widespread reductions in GM density correlated with working memory, executive function, language function, and verbal memory. The findings suggest widespread cortical changes as well as specific involvement of interhemispheric prefrontal tracts in PBD, which may reflect delayed myelination in these tracts. © 2011 John Wiley and Sons A/S.

Broad-spectrum enhanced absorption of graphene-molybdenum disulfide photovoltaic cells in metal-mirror microcavity.

PubMed

Jiang-Tao, Liu; Yun-Kai, Cao; Hong, Tong; Dai-Qiang, Wang; Zhen-Hua, Wu

2018-04-06

The optical absorption of graphene-molybdenum disulfide photovoltaic cells (GM-PVc) in wedge-shaped metal-mirror microcavities (w-MMCs) combined with a spectrum-splitting structure was studied. Results showed that the combination of spectrum-splitting structure and w-MMC can enable the light absorption of GM-PVcs to reach about 65% in the broad spectrum. The influence of processing errors on the absorption of GM-PVcs in w-MMCs was 3-14 times lower than that of GM-PVcs in wedge photonic crystal microcavities. The light absorption of GM-PVcs reached 60% in the broad spectrum, even with the processing errors. The proposed structure is easy to implement and may have potentially important applications in the development of ultra-thin and high-efficiency solar cells and optoelectronic devices.

Broad-spectrum enhanced absorption of graphene-molybdenum disulfide photovoltaic cells in metal-mirror microcavity

NASA Astrophysics Data System (ADS)

Jiang-Tao, Liu; Yun-Kai, Cao; Hong, Tong; Dai-Qiang, Wang; Zhen-Hua, Wu

2018-04-01

The optical absorption of graphene-molybdenum disulfide photovoltaic cells (GM-PVc) in wedge-shaped metal-mirror microcavities (w-MMCs) combined with a spectrum-splitting structure was studied. Results showed that the combination of spectrum-splitting structure and w-MMC can enable the light absorption of GM-PVcs to reach about 65% in the broad spectrum. The influence of processing errors on the absorption of GM-PVcs in w-MMCs was 3-14 times lower than that of GM-PVcs in wedge photonic crystal microcavities. The light absorption of GM-PVcs reached 60% in the broad spectrum, even with the processing errors. The proposed structure is easy to implement and may have potentially important applications in the development of ultra-thin and high-efficiency solar cells and optoelectronic devices.

Effects of low-level exposure to sarin and cyclosarin during the 1991 Gulf War on brain function and brain structure in US veterans.

PubMed

Chao, Linda L; Rothlind, Johannes C; Cardenas, Valerie A; Meyerhoff, Dieter J; Weiner, Michael W

2010-09-01

Potentially more than 100,000 US troops may have been exposed to the organophosphate chemical warfare agents sarin (GB) and cyclosarin (GF) when a munitions dump at Khamisiyah, Iraq was destroyed during the Gulf War (GW) in 1991. Although little is known about the long-term neurobehavioral or neurophysiological effects of low-dose exposure to GB/GF in humans, recent studies of GW veterans from the Devens Cohort suggest decrements in certain cognitive domains and atrophy in brain white matter occur individuals with higher estimated levels of presumed GB/GF exposure. The goal of the current study is to determine the generalizability of these findings in another cohort of GW veterans with suspected GB/GF exposure. Neurobehavioral and imaging data collected in a study on Gulf War Illness between 2002 and 2007 were used in this study. We focused on the data of 40 GW-deployed veterans categorized as having been exposed to GB/GF at Khamisiyah, Iraq and 40 matched controls. Magnetic resonance images (MRI) of the brain were analyzed using automated and semi-automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM), cerebrospinal fluid (CSF) and hippocampus. GW veterans with suspected GB/GF exposure had reduced total GM and hippocampal volumes compared to their unexposed peers (p< or =0.01). Although there were no group differences in measures of cognitive function or total WM volume, there were significant, positive correlations between total WM volume and measures of executive function and visuospatial abilities in veterans with suspected GB/GF exposure. These findings suggest that low-level exposure to GB/GF can have deleterious effects on brain structure and brain function more than decade later. Copyright © 2010 Elsevier Inc. All rights reserved.

Autoimmune comorbidities in multiple sclerosis: what is the influence on brain volumes? A case-control MRI study.

PubMed

Lorefice, Lorena; Fenu, Giuseppe; Pitzalis, Roberta; Scalas, Giulia; Frau, Jessica; Coghe, Giancarlo; Musu, Luigina; Sechi, Vincenzo; Barracciu, Maria Antonietta; Marrosu, Maria Giovanna; Cocco, Eleonora

2018-05-01

Several studies indicated that multiple sclerosis (MS) is frequently associated with other autoimmune diseases. However, it is little known if the coexistence of these conditions may influence the radiologic features of MS, and in particular the brain volumes. To evaluate the effect of autoimmune comorbidities on brain atrophy in a large case-control MS population. A group of MS patients affected by a second autoimmune disorder, and a control MS group without any comorbidity, were recruited. Patients underwent a brain MRI and volumes of whole brain (WB), white matter (WM), and gray matter (GM) with cortical GM were estimated by SIENAX. The sample included 286 MS patients, of which 30 (10.5%) subjects with type 1 diabetes (T1D), 53 (18.5%) with autoimmune thyroiditis (AT) and 4 (0.1%) with celiac disease. Multiple regression analysis found an association between T1D and lower GM (p = 0.038) and cortical GM (p = 0.036) volumes, independent from MS clinical features and related to T1D duration (p < 0.01), while no association was observed with AT and celiac disease. Our data support the importance of considering T1D as possible factors influencing the brain atrophy in MS. Further studies are needed to confirm our data and to clarify the underlying mechanisms.

Evidence for Lipid Packaging in the Crystal Structure of the GM2-Activator Complex with Platelet Activating Factor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wright, Christine S.; Mi, Li-Zhi; Rastinejad, Fraydoon

2010-11-16

GM2-activator protein (GM2-AP) is a lipid transfer protein that has the ability to stimulate the enzymatic processing of gangliosides as well as T-cell activation through lipid presentation. Our previous X-ray crystallographic studies of GM2-AP have revealed a large lipid binding pocket as the central overall feature of the structure with non-protein electron density within this pocket suggesting bound lipid. To extend these studies, we present here the 2 {angstrom} crystal structure of GM2-AP complexed with platelet activating factor (PAF). PAF is a potent phosphoacylglycerol whose toxic patho-physiological effects can be inhibited by GM2-AP. The structure shows an ordered arrangement ofmore » two bound lipids and a fatty acid molecule. One PAF molecule binds in an extended conformation within the hydrophobic channel that has an open and closed conformation, and was seen to contain bound phospholipid in the low pH apo structure. The second molecule is submerged inside the pocket in a U-shaped conformation with its head group near the single polar residue S141. It was refined as lyso-PAF as it lacks electron density for the sn-2 acetate group. The alkyl chains of PAF interact through van der Waals contacts, while the head groups bind in different environments with their phosphocholine moieties in contact with aromatic rings (Y137, F80). The structure has revealed further insights into the lipid binding properties of GM2-AP, suggesting an unexpected unique mode of lipid packaging that may explain the efficiency of GM2-AP in inhibiting the detrimental biological effects of PAF.« less

Gravitational mass of relativistic matter and antimatter

DOE PAGES

Kalaydzhyan, Tigran

2015-10-13

The universality of free fall, the weak equivalence principle (WEP), is a cornerstone of the general theory of relativity, the most precise theory of gravity confirmed in all experiments up to date. The WEP states the equivalence of the inertial, m, and gravitational, m g, masses and was tested in numerous occasions with normal matter at relatively low energies. However, there is no confirmation for the matter and antimatter at high energies. For the antimatter the situation is even less clear – current direct observations of trapped antihydrogen suggest the limits -65 < m g/m <110 not excluding the so-calledmore » antigravity phenomenon, i.e. repulsion of the antimatter by Earth. Here we demonstrate an indirect bound 0.96 < m g/m < 1.04 on the gravitational mass of relativistic electrons and positrons coming from the absence of the vacuum Cherenkov radiation at the Large Electron–Positron Collider (LEP) and stability of photons at the Tevatron collider in presence of the annual variations of the solar gravitational potential. Our result clearly rules out the speculated antigravity. By considering the absolute potential of the Local Supercluster (LS), we also predict the bounds 1 -4 ×10 -7 < m g/m <1 +2 ×10 -7 for an electron and positron. Lastly, we comment on a possibility of performing complementary tests at the future International Linear Collider (ILC) and Compact Linear Collider (CLIC).« less

Anatomy assisted PET image reconstruction incorporating multi-resolution joint entropy

NASA Astrophysics Data System (ADS)

Tang, Jing; Rahmim, Arman

2015-01-01

A promising approach in PET image reconstruction is to incorporate high resolution anatomical information (measured from MR or CT) taking the anato-functional similarity measures such as mutual information or joint entropy (JE) as the prior. These similarity measures only classify voxels based on intensity values, while neglecting structural spatial information. In this work, we developed an anatomy-assisted maximum a posteriori (MAP) reconstruction algorithm wherein the JE measure is supplied by spatial information generated using wavelet multi-resolution analysis. The proposed wavelet-based JE (WJE) MAP algorithm involves calculation of derivatives of the subband JE measures with respect to individual PET image voxel intensities, which we have shown can be computed very similarly to how the inverse wavelet transform is implemented. We performed a simulation study with the BrainWeb phantom creating PET data corresponding to different noise levels. Realistically simulated T1-weighted MR images provided by BrainWeb modeling were applied in the anatomy-assisted reconstruction with the WJE-MAP algorithm and the intensity-only JE-MAP algorithm. Quantitative analysis showed that the WJE-MAP algorithm performed similarly to the JE-MAP algorithm at low noise level in the gray matter (GM) and white matter (WM) regions in terms of noise versus bias tradeoff. When noise increased to medium level in the simulated data, the WJE-MAP algorithm started to surpass the JE-MAP algorithm in the GM region, which is less uniform with smaller isolated structures compared to the WM region. In the high noise level simulation, the WJE-MAP algorithm presented clear improvement over the JE-MAP algorithm in both the GM and WM regions. In addition to the simulation study, we applied the reconstruction algorithms to real patient studies involving DPA-173 PET data and Florbetapir PET data with corresponding T1-MPRAGE MRI images. Compared to the intensity-only JE-MAP algorithm, the WJE-MAP algorithm resulted in comparable regional mean values to those from the maximum likelihood algorithm while reducing noise. Achieving robust performance in various noise-level simulation and patient studies, the WJE-MAP algorithm demonstrates its potential in clinical quantitative PET imaging.

Recurrent granulomatous mastitis mimicking inflammatory breast cancer

PubMed Central

Ergin, Ahmet Bahadir; Cristofanilli, Massimo; Daw, Hamed; Tahan, Gulgun; Gong, Yun

2011-01-01

Granulomatous mastitis (GM) is an uncommon benign breast lesion. Diagnosis is a matter of exclusion from other inflammatory, infectious and granulomatous aetiologies. Here, we presented an atypical GM case, which had clinical and radiologic features overlapping with inflammatory breast cancer (IBC). The disease had multiple recurrences. The patient is a 40-year-old Caucasian woman with a sudden onset of left breast swelling accompanied by diffuse skin redness, especially of the subareolar region and malodorous yellow nipple discharge from the left nipple. The disease progressed on antibiotic treatment and recurred after local resection. A similar lesion developed even after bilateral mastectomy. GM may show clinical/radiologic features suggestive of IBC. Multiple recurrences can be occasionally encountered. GM after recurrence could be much more alarming clinically. Pathology confirmation is the key for accurate diagnosis and a multidisciplinary approach is important to rule out IBC. PMID:22715267

Developmentally Sensitive Interaction Effects of Genes and the Social Environment on Total and Subcortical Brain Volumes.

PubMed

Richards, Jennifer S; Arias Vásquez, Alejandro; Franke, Barbara; Hoekstra, Pieter J; Heslenfeld, Dirk J; Oosterlaan, Jaap; Faraone, Stephen V; Buitelaar, Jan K; Hartman, Catharina A

2016-01-01

Smaller total brain and subcortical volumes have been linked to psychopathology including attention-deficit/hyperactivity disorder (ADHD). Identifying mechanisms underlying these alterations, therefore, is of great importance. We investigated the role of gene-environment interactions (GxE) in interindividual variability of total gray matter (GM), caudate, and putamen volumes. Brain volumes were derived from structural magnetic resonance imaging scans in participants with (N = 312) and without ADHD (N = 437) from N = 402 families (age M = 17.00, SD = 3.60). GxE effects between DAT1, 5-HTT, and DRD4 and social environments (maternal expressed warmth and criticism; positive and deviant peer affiliation) as well as the possible moderating effect of age were examined using linear mixed modeling. We also tested whether findings depended on ADHD severity. Deviant peer affiliation was associated with lower caudate volume. Participants with low deviant peer affiliations had larger total GM volumes with increasing age. Likewise, developmentally sensitive GxE effects were found on total GM and putamen volume. For total GM, differential age effects were found for DAT1 9-repeat and HTTLPR L/L genotypes, depending on the amount of positive peer affiliation. For putamen volume, DRD4 7-repeat carriers and DAT1 10/10 homozygotes showed opposite age relations depending on positive peer affiliation and maternal criticism, respectively. All results were independent of ADHD severity. The presence of differential age-dependent GxE effects might explain the diverse and sometimes opposing results of environmental and genetic effects on brain volumes observed so far.

Developmentally Sensitive Interaction Effects of Genes and the Social Environment on Total and Subcortical Brain Volumes

PubMed Central

Arias Vásquez, Alejandro; Franke, Barbara; Hoekstra, Pieter J.; Heslenfeld, Dirk J.; Oosterlaan, Jaap; Faraone, Stephen V.

2016-01-01

Smaller total brain and subcortical volumes have been linked to psychopathology including attention-deficit/hyperactivity disorder (ADHD). Identifying mechanisms underlying these alterations, therefore, is of great importance. We investigated the role of gene-environment interactions (GxE) in interindividual variability of total gray matter (GM), caudate, and putamen volumes. Brain volumes were derived from structural magnetic resonance imaging scans in participants with (N = 312) and without ADHD (N = 437) from N = 402 families (age M = 17.00, SD = 3.60). GxE effects between DAT1, 5-HTT, and DRD4 and social environments (maternal expressed warmth and criticism; positive and deviant peer affiliation) as well as the possible moderating effect of age were examined using linear mixed modeling. We also tested whether findings depended on ADHD severity. Deviant peer affiliation was associated with lower caudate volume. Participants with low deviant peer affiliations had larger total GM volumes with increasing age. Likewise, developmentally sensitive GxE effects were found on total GM and putamen volume. For total GM, differential age effects were found for DAT1 9-repeat and HTTLPR L/L genotypes, depending on the amount of positive peer affiliation. For putamen volume, DRD4 7-repeat carriers and DAT1 10/10 homozygotes showed opposite age relations depending on positive peer affiliation and maternal criticism, respectively. All results were independent of ADHD severity. The presence of differential age-dependent GxE effects might explain the diverse and sometimes opposing results of environmental and genetic effects on brain volumes observed so far. PMID:27218681

Neurobiological changes of schizotypy: evidence from both volume-based morphometric analysis and resting-state functional connectivity.

PubMed

Wang, Yi; Yan, Chao; Yin, Da-zhi; Fan, Ming-xia; Cheung, Eric F C; Pantelis, Christos; Chan, Raymond C K

2015-03-01

The current study sought to examine the underlying brain changes in individuals with high schizotypy by integrating networks derived from brain structural and functional imaging. Individuals with high schizotypy (n = 35) and low schizotypy (n = 34) controls were screened using the Schizotypal Personality Questionnaire and underwent brain structural and resting-state functional magnetic resonance imaging on a 3T scanner. Voxel-based morphometric analysis and graph theory-based functional network analysis were conducted. Individuals with high schizotypy showed reduced gray matter (GM) density in the insula and the dorsolateral prefrontal gyrus. The graph theoretical analysis showed that individuals with high schizotypy showed similar global properties in their functional networks as low schizotypy individuals. Several hubs of the functional network were identified in both groups, including the insula, the lingual gyrus, the postcentral gyrus, and the rolandic operculum. More hubs in the frontal lobe and fewer hubs in the occipital lobe were identified in individuals with high schizotypy. By comparing the functional connectivity between clusters with abnormal GM density and the whole brain, individuals with high schizotypy showed weaker functional connectivity between the left insula and the putamen, but stronger connectivity between the cerebellum and the medial frontal gyrus. Taken together, our findings suggest that individuals with high schizotypy present changes in terms of GM and resting-state functional connectivity, especially in the frontal lobe. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Multimodal partial volume correction: Application to [11C]PIB PET/MRI myelin imaging in multiple sclerosis.

PubMed

Grecchi, Elisabetta; Veronese, Mattia; Bodini, Benedetta; García-Lorenzo, Daniel; Battaglini, Marco; Stankoff, Bruno; Turkheimer, Federico E

2017-12-01

The [ 11 C]PIB PET tracer, originally developed for amyloid imaging, has been recently repurposed to quantify demyelination and remyelination in multiple sclerosis (MS). Myelin PET imaging, however, is limited by its low resolution that deteriorates the quantification accuracy of white matter (WM) lesions. Here, we introduce a novel partial volume correction (PVC) method called Multiresolution-Multimodal Resolution-Recovery (MM-RR), which uses the wavelet transform and a synergistic statistical model to exploit MRI structural images to improve the resolution of [ 11 C]PIB PET myelin imaging. MM-RR performance was tested on a phantom acquisition and in a dataset comprising [ 11 C]PIB PET and MR T1- and T2-weighted images of 8 healthy controls and 20 MS patients. For the control group, the MM-RR PET images showed an average increase of 5.7% in WM uptake while the grey-matter (GM) uptake remained constant, resulting in +31% WM/GM contrast. Furthermore, MM-RR PET binding maps correlated significantly with the mRNA expressions of the most represented proteins in the myelin sheath (R 2  = 0.57 ± 0.09). In the patient group, MM-RR PET images showed sharper lesion contours and significant improvement in normal-appearing tissue/WM-lesion contrast compared to standard PET (contrast improvement > +40%). These results were consistent with MM-RR performances in phantom experiments.

Mass shedding and partition of the a/m ratio between core and envelope in gravitational collapse

NASA Astrophysics Data System (ADS)

de Felice, F.; Yu, Y.

1986-06-01

The authors show that, even taking into account redistribution of angular momentum, the ratio (a/m) (a/m = cJ/GM2, where J and M are the total angular momentum and gravitational mass) of a collapsing and rotating body varies slowly with the mass, when mass shedding takes place. Thus formation of an extended structure outside a collapsing body, like rings, discs or diffuse matter, is not in general a guarantee that the ratio (a/m) of the inner object is decreased appreciably from its initial value.

Characterization of Intraventricular and Intracerebral Hematomas in Non-Contrast CT

PubMed Central

Nowinski, Wieslaw L; Gomolka, Ryszard S; Qian, Guoyu; Gupta, Varsha; Ullman, Natalie L; Hanley, Daniel F

2014-01-01

Summary Characterization of hematomas is essential in scan reading, manual delineation, and designing automatic segmentation algorithms. Our purpose is to characterize the distribution of intraventricular (IVH) and intracerebral hematomas (ICH) in NCCT scans, study their relationship to gray matter (GM), and to introduce a new tool for quantitative hematoma delineation. We used 289 serial retrospective scans of 51 patients. Hematomas were manually delineated in a two-stage process. Hematoma contours generated in the first stage were quantified and enhanced in the second stage. Delineation was based on new quantitative rules and hematoma profiling, and assisted by a dedicated tool superimposing quantitative information on scans with 3D hematoma display. The tool provides: density maps (40-85HU), contrast maps (8/15HU), mean horizontal/vertical contrasts for hematoma contours, and hematoma contours below a specified mean contrast (8HU). White matter (WM) and GM were segmented automatically. IVH/ICH on serial NCCT is characterized by 59.0HU mean, 60.0HU median, 11.6HU standard deviation, 23.9HU mean contrast, –0.99HU/day slope, and –0.24 skewness (changing over time from negative to positive). Its 0.1st-99.9th percentile range corresponds to 25-88HU range. WM and GM are highly correlated (R 2=0.88; p<10–10) whereas the GM-GS correlation is weak (R 2=0.14; p<10–10). The intersection point of mean GM-hematoma density distributions is at 55.6±5.8HU with the corresponding GM/hematoma percentiles of 88th/40th. Objective characterization of IVH/ICH and stating the rules quantitatively will aid raters to delineate hematomas more robustly and facilitate designing algorithms for automatic hematoma segmentation. Our two-stage process is general and potentially applicable to delineate other pathologies on various modalities more robustly and quantitatively. PMID:24976197

Characterization of intraventricular and intracerebral hematomas in non-contrast CT.

PubMed

Nowinski, Wieslaw L; Gomolka, Ryszard S; Qian, Guoyu; Gupta, Varsha; Ullman, Natalie L; Hanley, Daniel F

2014-06-01

Characterization of hematomas is essential in scan reading, manual delineation, and designing automatic segmentation algorithms. Our purpose is to characterize the distribution of intraventricular (IVH) and intracerebral hematomas (ICH) in NCCT scans, study their relationship to gray matter (GM), and to introduce a new tool for quantitative hematoma delineation. We used 289 serial retrospective scans of 51 patients. Hematomas were manually delineated in a two-stage process. Hematoma contours generated in the first stage were quantified and enhanced in the second stage. Delineation was based on new quantitative rules and hematoma profiling, and assisted by a dedicated tool superimposing quantitative information on scans with 3D hematoma display. The tool provides: density maps (40-85HU), contrast maps (8/15HU), mean horizontal/vertical contrasts for hematoma contours, and hematoma contours below a specified mean contrast (8HU). White matter (WM) and GM were segmented automatically. IVH/ICH on serial NCCT is characterized by 59.0HU mean, 60.0HU median, 11.6HU standard deviation, 23.9HU mean contrast, -0.99HU/day slope, and -0.24 skewness (changing over time from negative to positive). Its 0.1(st)-99.9(th) percentile range corresponds to 25-88HU range. WM and GM are highly correlated (R (2)=0.88; p<10(-10)) whereas the GM-GS correlation is weak (R (2)=0.14; p<10(-10)). The intersection point of mean GM-hematoma density distributions is at 55.6±5.8HU with the corresponding GM/hematoma percentiles of 88(th)/40(th). Objective characterization of IVH/ICH and stating the rules quantitatively will aid raters to delineate hematomas more robustly and facilitate designing algorithms for automatic hematoma segmentation. Our two-stage process is general and potentially applicable to delineate other pathologies on various modalities more robustly and quantitatively.

Reliability of Three Dimentional Pseudo-continuous Arterial Spin Labeling: A Volumetric Cerebral Perfusion Imaging with Different Post-labeling Time and Functional State in Health Adults.

PubMed

Liu, Meng-Qi; Chen, Zhi-Ye; Ma, Lin

2018-03-30

Objective To evaluate the reliability of three dimensional spiral fast spin echo pseudo-continuous arterial spin labeling (3D pc-ASL) in measuring cerebral blood flow (CBF) with different post-labeling delay time (PLD) in the resting state and the right finger taping state. Methods 3D pc-ASL and three dimensional T1-weighted fast spoiled gradient recalled echo (3D T1-FSPGR) sequence were applied to eight healthy subjects twice at the same time each day for one week interval. ASL data acquisition was performed with post-labeling delay time (PLD) 1.5 seconds and 2.0 seconds in the resting state and the right finger taping state respectively. CBF mapping was calculated and CBF value of both the gray matter (GM) and white matter (WM) was automatically extracted. The reliability was evaluated using the intraclass correlation coefficient (ICC) and Bland and Altman plot. Results ICC of the GM (0.84) and WM (0.92) was lower at PLD 1.5 seconds than that (GM, 0.88; WM, 0.94) at PLD 2.0 seconds in the resting state, and ICC of GM (0.88) was higher in the right finger taping state than that in the resting state at PLD 1.5 seconds. ICC of the GM and WM was 0.71 and 0.78 for PLD 1.5 seconds and PLD 2.0 seconds in the resting state at the first scan, and ICC of the GM and WM was 0.83 and 0.79 at the second scan, respectively. Conclusion This work demonstrated that 3D pc-ASL might be a reliable imaging technique to measure CBF over the whole brain at different PLD in the resting state or controlled state.

Quantification of γ-aminobutyric acid (GABA) in 1 H MRS volumes composed heterogeneously of grey and white matter.

PubMed

Mikkelsen, Mark; Singh, Krish D; Brealy, Jennifer A; Linden, David E J; Evans, C John

2016-11-01

The quantification of γ-aminobutyric acid (GABA) concentration using localised MRS suffers from partial volume effects related to differences in the intrinsic concentration of GABA in grey (GM) and white (WM) matter. These differences can be represented as a ratio between intrinsic GABA in GM and WM: r M . Individual differences in GM tissue volume can therefore potentially drive apparent concentration differences. Here, a quantification method that corrects for these effects is formulated and empirically validated. Quantification using tissue water as an internal concentration reference has been described previously. Partial volume effects attributed to r M can be accounted for by incorporating into this established method an additional multiplicative correction factor based on measured or literature values of r M weighted by the proportion of GM and WM within tissue-segmented MRS volumes. Simulations were performed to test the sensitivity of this correction using different assumptions of r M taken from previous studies. The tissue correction method was then validated by applying it to an independent dataset of in vivo GABA measurements using an empirically measured value of r M . It was shown that incorrect assumptions of r M can lead to overcorrection and inflation of GABA concentration measurements quantified in volumes composed predominantly of WM. For the independent dataset, GABA concentration was linearly related to GM tissue volume when only the water signal was corrected for partial volume effects. Performing a full correction that additionally accounts for partial volume effects ascribed to r M successfully removed this dependence. With an appropriate assumption of the ratio of intrinsic GABA concentration in GM and WM, GABA measurements can be corrected for partial volume effects, potentially leading to a reduction in between-participant variance, increased power in statistical tests and better discriminability of true effects. Copyright © 2016 John Wiley & Sons, Ltd.

Food availability to an Adamussium bed during the austral summer 1993/1994 (Terra Nova Bay, Ross Sea)

NASA Astrophysics Data System (ADS)

Albertelli, G.; Cattaneo-Vietti, R.; Chiantore, M.; Pusceddu, A.; Fabiano, M.

1998-11-01

In the framework of the ROSSMIZE Project (Ross Sea Marginal Ice Zone Ecology) of the Italian Antarctic Research Programme (PNRA), the organic matter flux through the water column and its role on benthic communities have been taken in particular account. During the austral Summer 1993-1994, from December 27, 1993 to February 11, 1994, a study on this flux in shallow waters was carried out, in a station close to Terra Nova Bay Italian base (Ross Sea), at 40 m depth. This site is characterized by the filter-feeding Adamussium colbecki, a scallop which reaches high values of density (60 ind/m 2) and biomass (120 g DW/m 2). At the beginning of the sampling period, a sediment trap was positioned on the sea-bottom and samples were collected every 3-5 days, as well as temperature, salinity and fluorescence data from sea surface to bottom. Fluorescence profiles put in evidence a phytoplankton bloom occurring during the maximum water column stratification, in the last decade of January. Organic matter flux through the water column showed rather constant values up to the 24th of January. Immediately after, a sudden increase took place (24-29 January), reaching 13.55 g/m 2/d for TSM, 0.24 g/m 2/d for lipids, 0.53 g/m 2/d for proteins, 0.37 g/m 2/d for carbohydrates, 0.69 g/m 2/d and 0.1 g/m 2/d for POC and PON, respectively, 0.5 and 2.8 mg/m 2/d for chlorophyll- a and phaeopigments, in correspondence to the fluorescence peak occurring in the same period. A large part of the total flux was represented by oval faecal pellets, as accounted by microscopical observations of sedimented material. Most of the pellets were 200-300 μm long, filled mainly by diatom frustules.

Radiation dose reduction using 100-kVp and a sinogram-affirmed iterative reconstruction algorithm in adolescent head CT: Impact on grey-white matter contrast and image noise.

PubMed

Nagayama, Yasunori; Nakaura, Takeshi; Tsuji, Akinori; Urata, Joji; Furusawa, Mitsuhiro; Yuki, Hideaki; Hirarta, Kenichiro; Kidoh, Masafumi; Oda, Seitaro; Utsunomiya, Daisuke; Yamashita, Yasuyuki

2017-07-01

To retrospectively evaluate the image quality and radiation dose of 100-kVp scans with sinogram-affirmed iterative reconstruction (IR) for unenhanced head CT in adolescents. Sixty-nine patients aged 12-17 years underwent head CT under 120- (n = 34) or 100-kVp (n = 35) protocols. The 120-kVp images were reconstructed with filtered back-projection (FBP), 100-kVp images with FBP (100-kVp-F) and sinogram-affirmed IR (100-kVp-S). We compared the effective dose (ED), grey-white matter (GM-WM) contrast, image noise, and contrast-to-noise ratio (CNR) between protocols in supratentorial (ST) and posterior fossa (PS). We also assessed GM-WM contrast, image noise, sharpness, artifacts, and overall image quality on a four-point scale. ED was 46% lower with 100- than 120-kVp (p < 0.001). GM-WM contrast was higher, and image noise was lower, on 100-kVp-S than 120-kVp at ST (p < 0.001). CNR of 100-kVp-S was higher than of 120-kVp (p < 0.001). GM-WM contrast of 100-kVp-S was subjectively rated as better than of 120-kVp (p < 0.001). There were no significant differences in the other criteria between 100-kVp-S and 120-kVp (p = 0.072-0.966). The 100-kVp with sinogram-affirmed IR facilitated dramatic radiation reduction and better GM-WM contrast without increasing image noise in adolescent head CT. • 100-kVp head CT provides 46% radiation dose reduction compared with 120-kVp. • 100-kVp scanning improves subjective and objective GM-WM contrast. • Sinogram-affirmed IR decreases head CT image noise, especially in supratentorial region. • 100-kVp protocol with sinogram-affirmed IR is suited for adolescent head CT.

Fire effects on soil organic matter content, composition, and nutrients in boreal interior Alaska

USGS Publications Warehouse

Neff, J.C.; Harden, J.W.; Gleixner, G.

2005-01-01

Boreal ecosystems contain a substantial fraction of the earth's soil carbon stores and are prone to frequent and severe wildfires. In this study, we examine changes in element and organic matter stocks due to a 1999 wildfire in Alaska. One year after the wildfire, burned soils contained between 1071 and 1420 g/m2 less carbon than unburned soils. Burned soils had lower nitrogen than unburned soils, higher calcium, and nearly unchanged potassium, magnesium, and phosphorus stocks. Burned surface soils tended to have higher concentrations of noncombustible elements such as calcium, potassium, magnesium, and phosphorus compared with unburned soils. Combustion losses of carbon were mostly limited to surface dead moss and fibric horizons, with no change in the underlying mineral horizons. Burning caused significant changes in soil organic matter structure, with a 12% higher ratio of carbon to combustible organic matter in surface burned horizons compared with unburned horizons. Pyrolysis gas chromatography - mass spectroscopy also shows preferential volatilization of polysaccharide-derived organic matter and enrichment of lignin-and lipid-derived compounds in surface soils. The chemistry of deeper soil layers in burned and unburned sites was similar, suggesting that immediate fire impacts were restricted to the surface soil horizon. ?? 2005 NRC.

On the Viability of Diffusion MRI-Based Microstructural Biomarkers in Ischemic Stroke

PubMed Central

Boscolo Galazzo, Ilaria; Brusini, Lorenza; Obertino, Silvia; Zucchelli, Mauro; Granziera, Cristina; Menegaz, Gloria

2018-01-01

Recent tract-based analyses provided evidence for the exploitability of 3D-SHORE microstructural descriptors derived from diffusion MRI (dMRI) in revealing white matter (WM) plasticity. In this work, we focused on the main open issues left: (1) the comparative analysis with respect to classical tensor-derived indices, i.e., Fractional Anisotropy (FA) and Mean Diffusivity (MD); and (2) the ability to detect plasticity processes in gray matter (GM). Although signal modeling in GM is still largely unexplored, we investigated their sensibility to stroke-induced microstructural modifications occurring in the contralateral hemisphere. A more complete picture could provide hints for investigating the interplay of GM and WM modulations. Ten stroke patients and ten age/gender-matched healthy controls were enrolled in the study and underwent diffusion spectrum imaging (DSI). Acquisitions at three and two time points (tp) were performed on patients and controls, respectively. For all subjects and acquisitions, FA and MD were computed along with 3D-SHORE-based indices [Generalized Fractional Anisotropy (GFA), Propagator Anisotropy (PA), Return To the Axis Probability (RTAP), Return To the Plane Probability (RTPP), and Mean Square Displacement (MSD)]. Tract-based analysis involving the cortical, subcortical and transcallosal motor networks and region-based analysis in GM were successively performed, focusing on the contralateral hemisphere to the stroke. Reproducibility of all the indices on both WM and GM was quantitatively proved on controls. For tract-based, longitudinal group analyses revealed the highest significant differences across the subcortical and transcallosal networks for all the indices. The optimal regression model for predicting the clinical motor outcome at tp3 included GFA, PA, RTPP, and MSD in the subcortical network in combination with the main clinical information at baseline. Region-based analysis in the contralateral GM highlighted the ability of anisotropy indices in discriminating between groups mainly at tp1, while diffusivity indices appeared to be altered at tp2. 3D-SHORE indices proved to be suitable in probing plasticity in both WM and GM, further confirming their viability as a novel family of biomarkers in ischemic stroke in WM and revealing their potential exploitability in GM. Their combination with tensor-derived indices can provide more detailed insights of the different tissue modulations related to stroke pathology. PMID:29515362

Automatic segmentation and reconstruction of the cortex from neonatal MRI.

PubMed

Xue, Hui; Srinivasan, Latha; Jiang, Shuzhou; Rutherford, Mary; Edwards, A David; Rueckert, Daniel; Hajnal, Joseph V

2007-11-15

Segmentation and reconstruction of cortical surfaces from magnetic resonance (MR) images are more challenging for developing neonates than adults. This is mainly due to the dynamic changes in the contrast between gray matter (GM) and white matter (WM) in both T1- and T2-weighted images (T1w and T2w) during brain maturation. In particular in neonatal T2w images WM typically has higher signal intensity than GM. This causes mislabeled voxels during cortical segmentation, especially in the cortical regions of the brain and in particular at the interface between GM and cerebrospinal fluid (CSF). We propose an automatic segmentation algorithm detecting these mislabeled voxels and correcting errors caused by partial volume effects. Our results show that the proposed algorithm corrects errors in the segmentation of both GM and WM compared to the classic expectation maximization (EM) scheme. Quantitative validation against manual segmentation demonstrates good performance (the mean Dice value: 0.758+/-0.037 for GM and 0.794+/-0.078 for WM). The inner, central and outer cortical surfaces are then reconstructed using implicit surface evolution. A landmark study is performed to verify the accuracy of the reconstructed cortex (the mean surface reconstruction error: 0.73 mm for inner surface and 0.63 mm for the outer). Both segmentation and reconstruction have been tested on 25 neonates with the gestational ages ranging from approximately 27 to 45 weeks. This preliminary analysis confirms previous findings that cortical surface area and curvature increase with age, and that surface area scales to cerebral volume according to a power law, while cortical thickness is not related to age or brain growth.

In vivo signatures of nonfluent/agrammatic primary progressive aphasia caused by FTLD pathology

PubMed Central

Caso, Francesca; Mandelli, Maria Luisa; Henry, Maya; Gesierich, Benno; Bettcher, Brianne M.; Ogar, Jennifer; Filippi, Massimo; Comi, Giancarlo; Magnani, Giuseppe; Sidhu, Manu; Trojanowski, John Q.; Huang, Eric J.; Grinberg, Lea T.; Miller, Bruce L.; Dronkers, Nina; Seeley, William W.

2014-01-01

Objective: To identify early cognitive and neuroimaging features of sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) caused by frontotemporal lobar degeneration (FTLD) subtypes. Methods: We prospectively collected clinical, neuroimaging, and neuropathologic data in 11 patients with sporadic nfvPPA with FTLD-tau (nfvPPA-tau, n = 9) or FTLD–transactive response DNA binding protein pathology of 43 kD type A (nfvPPA-TDP, n = 2). We analyzed patterns of cognitive and gray matter (GM) and white matter (WM) atrophy at presentation in the whole group and in each pathologic subtype separately. We also considered longitudinal clinical data. Results: At first evaluation, regardless of pathologic FTLD subtype, apraxia of speech (AOS) was the most common cognitive feature and atrophy involved the left posterior frontal lobe. Each pathologic subtype showed few distinctive features. At presentation, patients with nfvPPA-tau presented with mild to moderate AOS, mixed dysarthria with prominent hypokinetic features, clear agrammatism, and atrophy in the GM of the left posterior frontal regions and in left frontal WM. While speech and language deficits were prominent early, within 3 years of symptom onset, all patients with nfvPPA-tau developed significant extrapyramidal motor signs. At presentation, patients with nfvPPA-TDP had severe AOS, dysarthria with spastic features, mild agrammatism, and atrophy in left posterior frontal GM only. Selective mutism occurred early, when general neurologic examination only showed mild decrease in finger dexterity in the right hand. Conclusions: Clinical features in sporadic nfvPPA caused by FTLD subtypes relate to neurodegeneration of GM and WM in frontal motor speech and language networks. We propose that early WM atrophy in nfvPPA is suggestive of FTLD-tau pathology while early selective GM loss might be indicative of FTLD-TDP. PMID:24353332

Assessment of in vivo microstructure alterations in gray matter using DKI in Internet gaming addiction.

PubMed

Sun, Yawen; Sun, Jinhua; Zhou, Yan; Ding, Weina; Chen, Xue; Zhuang, Zhiguo; Xu, Jianrong; Du, Yasong

2014-10-24

The aim of the current study was to investigate the utility of diffusional kurtosis imaging (DKI) in the detection of gray matter (GM) alterations in people suffering from Internet Gaming Addiction (IGA). DKI was applied to 18 subjects with IGA and to 21 healthy controls (HC). Whole-brain voxel-based analyses were performed with the following derived parameters: mean kurtosis metrics (MK), radial kurtosis (K⊥), and axial kurtosis (K//). A significance threshold was set at P <0.05, AlphaSim corrected. Pearson's correlation was performed to investigate the correlations between the Chen Internet Addiction Scale (CIAS) and the DKI-derived metrics of regions that differed between groups. Additionally, we used voxel-based morphometry (VBM) to detect GM-volume differences between the two groups. Compared with the HC group, the IGA group demonstrated diffusional kurtosis parameters that were significantly less in GM of the right anterolateral cerebellum, right inferior and superior temporal gyri, right supplementary motor area, middle occipital gyrus, right precuneus, postcentral gyrus, right inferior frontal gyrus, left lateral lingual gyrus, left paracentral lobule, left anterior cingulate cortex, and median cingulate cortex. The bilateral fusiform gyrus, insula, posterior cingulate cortex (PCC), and thalamus also exhibited less diffusional kurtosis in the IGA group. MK in the left PCC and K⊥ in the right PCC were positively correlated with CIAS scores. VBM showed that IGA subjects had higher GM volume in the right inferior and middle temporal gyri, and right parahippocampal gyrus, and lower GM volume in the left precentral gyrus. The lower diffusional kurtosis parameters in IGA suggest multiple differences in brain microstructure, which may contribute to the underlying pathophysiology of IGA. DKI may provide sensitive imaging biomarkers for assessing IGA severity.

Brain tissue volumes in relation to cognitive function and risk of dementia.

PubMed

Ikram, M Arfan; Vrooman, Henri A; Vernooij, Meike W; den Heijer, Tom; Hofman, Albert; Niessen, Wiro J; van der Lugt, Aad; Koudstaal, Peter J; Breteler, Monique M B

2010-03-01

We investigated in a population-based cohort study the association of global and lobar brain tissue volumes with specific cognitive domains and risk of dementia. Participants (n=490; 60-90 years) were non-demented at baseline (1995-1996). From baseline brain MRI-scans we obtained global and lobar volumes of CSF, GM, normal WM, white matter lesions and hippocampus. We performed neuropsychological testing at baseline to assess information processing speed, executive function, memory function and global cognitive function. Participants were followed for incident dementia until January 1, 2005. Larger volumes of CSF and WML were associated with worse performance on all neuropsychological tests, and an increased risk of dementia. Smaller WM volume was related to poorer information processing speed and executive function. In contrast, smaller GM volume was associated with worse memory function and increased risk of dementia. When investigating lobar GM volumes, we found that hippocampal volume and temporal GM volume were most strongly associated with risk of dementia, even in persons without objective and subjective cognitive deficits at baseline, followed by frontal and parietal GM volumes. Copyright 2008 Elsevier Inc. All rights reserved.

Impact on environment, ecosystem, diversity and health from culturing and using GMOs as feed and food.

PubMed

Tsatsakis, Aristidis M; Nawaz, Muhammad Amjad; Tutelyan, Victor A; Golokhvast, Kirill S; Kalantzi, Olga-Ioanna; Chung, Duck Hwa; Kang, Sung Jo; Coleman, Michael D; Tyshko, Nadia; Yang, Seung Hwan; Chung, Gyuhwa

2017-09-01

Modern agriculture provides the potential for sustainable feeding of the world's increasing population. Up to the present moment, genetically modified (GM) products have enabled increased yields and reduced pesticide usage. Nevertheless, GM products are controversial amongst policy makers, scientists and the consumers, regarding their possible environmental, ecological, and health risks. Scientific-and-political debates can even influence legislation and prospective risk assessment procedure. Currently, the scientifically-assessed direct hazardous impacts of GM food and feed on fauna and flora are conflicting; indeed, a review of literature available data provides some evidence of GM environmental and health risks. Although the consequences of gene flow and risks to biodiversity are debatable. Risks to the environment and ecosystems can exist, such as the evolution of weed herbicide resistance during GM cultivation. A matter of high importance is to provide precise knowledge and adequate current information to regulatory agencies, governments, policy makers, researchers, and commercial GMO-releasing companies to enable them to thoroughly investigate the possible risks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Coordination of Leaf Photosynthesis, Transpiration, and Structural Traits in Rice and Wild Relatives (Genus Oryza)1[W][OA

PubMed Central

Giuliani, Rita; Koteyeva, Nuria; Voznesenskaya, Elena; Evans, Marc A.; Cousins, Asaph B.; Edwards, Gerald E.

2013-01-01

The genus Oryza, which includes rice (Oryza sativa and Oryza glaberrima) and wild relatives, is a useful genus to study leaf properties in order to identify structural features that control CO2 access to chloroplasts, photosynthesis, water use efficiency, and drought tolerance. Traits, 26 structural and 17 functional, associated with photosynthesis and transpiration were quantified on 24 accessions (representatives of 17 species and eight genomes). Hypotheses of associations within, and between, structure, photosynthesis, and transpiration were tested. Two main clusters of positively interrelated leaf traits were identified: in the first cluster were structural features, leaf thickness (Thickleaf), mesophyll (M) cell surface area exposed to intercellular air space per unit of leaf surface area (Smes), and M cell size; a second group included functional traits, net photosynthetic rate, transpiration rate, M conductance to CO2 diffusion (gm), stomatal conductance to gas diffusion (gs), and the gm/gs ratio. While net photosynthetic rate was positively correlated with gm, neither was significantly linked with any individual structural traits. The results suggest that changes in gm depend on covariations of multiple leaf (Smes) and M cell (including cell wall thickness) structural traits. There was an inverse relationship between Thickleaf and transpiration rate and a significant positive association between Thickleaf and leaf transpiration efficiency. Interestingly, high gm together with high gm/gs and a low Smes/gm ratio (M resistance to CO2 diffusion per unit of cell surface area exposed to intercellular air space) appear to be ideal for supporting leaf photosynthesis while preserving water; in addition, thick M cell walls may be beneficial for plant drought tolerance. PMID:23669746

Enhanced Disease Susceptibility1 Mediates Pathogen Resistance and Virulence Function of a Bacterial Effector in Soybean1[C][W][OPEN

PubMed Central

Wang, Jialin; Shine, M.B.; Gao, Qing-Ming; Navarre, Duroy; Jiang, Wei; Liu, Chunyan; Chen, Qingshan; Hu, Guohua; Kachroo, Aardra

2014-01-01

Enhanced disease susceptibility1 (EDS1) and phytoalexin deficient4 (PAD4) are well-known regulators of both basal and resistance (R) protein-mediated plant defense. We identified two EDS1-like (GmEDS1a/GmEDS1b) proteins and one PAD4-like (GmPAD4) protein that are required for resistance signaling in soybean (Glycine max). Consistent with their significant structural conservation to Arabidopsis (Arabidopsis thaliana) counterparts, constitutive expression of GmEDS1 or GmPAD4 complemented the pathogen resistance defects of Arabidopsis eds1 and pad4 mutants, respectively. Interestingly, however, the GmEDS1 and GmPAD4 did not complement pathogen-inducible salicylic acid accumulation in the eds1/pad4 mutants. Furthermore, the GmEDS1a/GmEDS1b proteins were unable to complement the turnip crinkle virus coat protein-mediated activation of the Arabidopsis R protein Hypersensitive reaction to Turnip crinkle virus (HRT), even though both interacted with HRT. Silencing GmEDS1a/GmEDS1b or GmPAD4 reduced basal and pathogen-inducible salicylic acid accumulation and enhanced soybean susceptibility to virulent pathogens. The GmEDS1a/GmEDS1b and GmPAD4 genes were also required for Resistance to Pseudomonas syringae pv glycinea2 (Rpg2)-mediated resistance to Pseudomonas syringae. Notably, the GmEDS1a/GmEDS1b proteins interacted with the cognate bacterial effector AvrA1 and were required for its virulence function in rpg2 plants. Together, these results show that despite significant structural similarities, conserved defense signaling components from diverse plants can differ in their functionalities. In addition, we demonstrate a role for GmEDS1 in regulating the virulence function of a bacterial effector. PMID:24872380

Voxel-based morphometry in Alzheimers disease and mild cognitive impairment: Systematic review of studies addressing the frontal lobe.

PubMed

Ribeiro, Luís Gustavo; Busatto, Geraldo

2016-01-01

Voxel-based morphometry (VBM) is a useful approach for investigating neurostructural brain changes in dementia. We systematically reviewed VBM studies of Alzheimer's disease (AD) and mild cognitive impairment (MCI), specifically focusing on grey matter (GM) atrophy in the frontal lobe. Two searches were performed on the Pubmed database. A set of exclusion criteria was applied to ensure the selection of only VBM studies that directly investigated GM volume abnormalities in AD and/or MCI patients compared to cognitively normal controls. From a total of 46 selected articles, 35 VBM studies reported GM volume reductions in the frontal lobe. The frontal subregions, where most of the volume reductions were reported, included the inferior, superior and middle frontal gyri, as well as the anterior cingulate gyrus. We also found studies in which reduced frontal GM was detected in MCI patients who converted to AD. In a minority of studies, correlations between frontal GM volumes and behavioural changes or cognitive deficits in AD patients were investigated, with variable findings. Results of VBM studies indicate that the frontal lobe should be regarded as an important brain area when investigating GM volume deficits in association with AD. Frontal GM loss might not be a feature specific to late AD only. Future VBM studies involving large AD samples are warranted to further investigate correlations between frontal volume deficits and both cognitive impairment and neuropsychiatric symptoms.

White Matter Integrity on DTI, Amyloid Load, and Neurodegeneration in Non-demented Elderly

PubMed Central

Kantarci, Kejal; Schwarz, Christopher G.; Reid, Robert; Przybelski, Scott A.; Lesnick, Timothy; Zuk, Samantha M.; Senjem, Matthew L.; Gunter, Jeffrey L.; Lowe, Val; Machulda, Mary M.; Knopman, David S.; Petersen, Ronald C.; Jack, Clifford R.

2016-01-01

Importance Pathophysiologic mechanisms leading to loss of white matter (WM) integrity and the temporal positioning of biomarkers of WM integrity relative to the biomarkers of gray matter (GM) neurodegeneration and amyloid load in the course of AD are poorly understood. Objective To investigate the effects of Alzheimer’s disease (AD)-related GM neurodegeneration and high β-amyloid on white matter (WM) microstructure in non-demented older adults. Design Longitudinal cohort study Setting Population-based Mayo Clinic Study of Aging. Participants Participants (n=701) with MRI/DTI and PET studies diagnosed as cognitively normal (CN; n=570) or mild cognitive impairment (MCI; n=131) were included. CN and MCI subjects were divided into biomarker-negative, amyloid- positive only, neurodegeneration- positive only, and amyloid plus neurodegeneration-positive groups based on their amyloid load on 11C-Pittsburgh compound-B PET, AD hypometabolic pattern on 18F-fluorodeoxyglucose PET and/or hippocampal atrophy on MRI. Main Outcome Measure Fractional anisotrophy (FA) from diffusion tensor imaging (DTI) Results No FA alterations were observed in biomarker-negative MCI, and amyloid-positive only CN and MCI groups. Conversely, neurodegeneration-positive only and amyloid plus neurodegeneration- positive CN and MCI groups consistently had decreased FA in the fornix, which correlated with cognitive performance (Rho=0.38; p<0.001). Patients with MCI had more extensive WM involvement than CN subjects, and greatest FA decreases were observed in the amyloid plus neurodegeneration-positive MCI group. Conclusions and Relevance High amyloid load does not influence DTI-based measures of WM integrity in the absence of co-existent GM neurodegeneration in non-demented older adults. PMID:25347157

Longitudinal Relationships between Caloric Expenditure and Gray Matter in the Cardiovascular Health Study

PubMed Central

Raji, Cyrus A.; Merrill, David A.; Eyre, Harris; Mallam, Sravya; Torosyan, Nare; Erickson, Kirk I.; Lopez, Oscar L.; Becker, James T.; Carmichael, Owen T.; Gach, H. Michael; Thompson, Paul M.; Longstreth, W.T.; Kuller, Lewis H.

2016-01-01

Background: Physical activity (PA) can be neuroprotective and reduce the risk for Alzheimer’s disease (AD). In assessing physical activity, caloric expenditure is a proxy marker reflecting the sum total of multiple physical activity types conducted by an individual. Objective:To assess caloric expenditure, as a proxy marker of PA, as a predictive measure of gray matter (GM) volumes in the normal and cognitively impaired elderly persons. Methods: All subjects in this study were recruited from the Institutional Review Board approved Cardiovascular Health Study (CHS), a multisite population-based longitudinal study in persons aged 65 and older. We analyzed a sub-sample of CHS participants 876 subjects (mean age 78.3, 57.5% F, 42.5% M) who had i) energy output assessed as kilocalories (kcal) per week using the standardized Minnesota Leisure-Time Activities questionnaire, ii) cognitive assessments for clinical classification of normal cognition, mild cognitive impairment (MCI), and AD, and iii) volumetric MR imaging of the brain. Voxel-based morphometry modeled the relationship between kcal/week and GM volumes while accounting for standard covariates including head size, age, sex, white matter hyperintensity lesions, MCI or AD status, and site. Multiple comparisons were controlled using a False Discovery Rate of 5 percent. Results: Higher energy output, from a variety of physical activity types, was associated with larger GM volumes in frontal, temporal, and parietal lobes, as well as hippocampus, thalamus, and basal ganglia. High levels of caloric expenditure moderated neurodegeneration-associated volume loss in the precuneus, posterior cingulate, and cerebellar vermis. Conclusion:Increasing energy output from a variety of physical activities is related to larger gray matter volumes in the elderly, regardless of cognitive status. PMID:26967227

Brain networks in posterior cortical atrophy: a single case tractography study and literature review.

PubMed

Migliaccio, Raffaella; Agosta, Federica; Toba, Monica N; Samri, Dalila; Corlier, Fabian; de Souza, Leonardo C; Chupin, Marie; Sharman, Michael; Gorno-Tempini, Maria L; Dubois, Bruno; Filippi, Massimo; Bartolomeo, Paolo

2012-01-01

Posterior cortical atrophy (PCA) is rare neurodegenerative dementia, clinically characterized by a progressive decline in higher-visual object and space processing. After a brief review of the literature on the neuroimaging in PCA, here we present a study of the brain structural connectivity in a patient with PCA and progressive isolated visual and visuo-motor signs. Clinical and cognitive data were acquired in a 58-years-old patient (woman, right-handed, disease duration 18 months). Brain structural and diffusion tensor (DT) magnetic resonance imaging (MRI) were obtained. A voxel-based morphometry (VBM) study was performed to explore the pattern of gray matter (GM) atrophy, and a fully automatic segmentation was assessed to obtain the hippocampal volumes. DT MRI-based tractography was used to assess the integrity of long-range white matter (WM) pathways in the patient and in six sex- and age-matched healthy subjects. This PCA patient had a clinical syndrome characterized by left visual neglect, optic ataxia, and left limb apraxia, as well as mild visuo-spatial episodic memory impairment. VBM study showed bilateral posterior GM atrophy with right predominance; DT MRI tractography demonstrated WM damage to the right hemisphere only, including the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus, as compared to age-matched controls. The homologous left-hemisphere tracts were spared. No difference was found between left and right hippocampal volumes. These data suggest that selective visuo-spatial deficits typical of PCA might not result from cortical damage alone, but by a right-lateralized network-level dysfunction including WM damage along the major visual pathways. Copyright © 2011 Elsevier Srl. All rights reserved.

GM1 gangliosidosis in a Japanese domestic cat: a new variant identified in Hokkaido, Japan

PubMed Central

UENO, Hiroshi; YAMATO, Osamu; SUGIURA, Takeshi; KOHYAMA, Moeko; YABUKI, Akira; MIYOSHI, Kenjiro; MATSUDA, Kazuya; UCHIDE, Tsuyoshi

2015-01-01

A male Japanese domestic cat with retarded growth in Hokkaido, Japan, showed progressive motor dysfunction, such as ataxia starting at 3 months of age and tremors, visual disorder and seizure after 4 months of age. Finally, the cat died of neurological deterioration at 9 months of age. Approximately half of the peripheral blood lymphocytes had multiple abnormal vacuoles. Magnetic resonance imaging showed bisymmetrical hyperintensity in the white matter of the parietal and occipital lobes in the forebrain on T2-weighted and fluid-attenuated inversion recovery images, and mild encephalatrophy of the olfactory bulbs and temporal lobes. The activity of lysosomal acid β-galactosidase in leukocytes was negligible, resulting in the biochemical diagnosis of GM1 gangliosidosis. Histologically, swollen neurons characterized by accumulation of pale, slightly granular cytoplasmic materials were observed throughout the central nervous system. Dysmyelination or demyelination and gemistocytic astrocytosis were observed in the white matter. Ultrastructually, membranous cytoplasmic bodies were detected in the lysosomes of neurons. However, genetic analysis did not identify the c.1448G>C mutation, which is the single known mutation of feline GM1 gangliosidosis, suggesting that the cat was affected with a new variant of the feline disease. PMID:26234889

Deterioration of abstract reasoning ability in mild cognitive impairment and Alzheimer's disease: correlation with regional grey matter volume loss revealed by diffeomorphic anatomical registration through exponentiated lie algebra analysis.

PubMed

Yoshiura, Takashi; Hiwatashi, Akio; Yamashita, Koji; Ohyagi, Yasumasa; Monji, Akira; Takayama, Yukihisa; Kamano, Norihiro; Kawashima, Toshiro; Kira, Jun-Ichi; Honda, Hiroshi

2011-02-01

To determine which brain regions are relevant to deterioration in abstract reasoning as measured by Raven's Colored Progressive Matrices (CPM) in the context of dementia. MR images of 37 consecutive patients including 19 with Alzheimer's disease (AD) and 18 with amnestic mild cognitive impairment (aMCI) were retrospectively analyzed. All patients were administered the CPM. Regional grey matter (GM) volume was evaluated according to the regimens of voxel-based morphometry, during which a non-linear registration algorithm called Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra was employed. Multiple regression analyses were used to map the regions where GM volumes were correlated with CPM scores. The strongest correlation with CPM scores was seen in the left middle frontal gyrus while a region with the largest volume was identified in the left superior temporal gyrus. Significant correlations were seen in 14 additional regions in the bilateral cerebral hemispheres and right cerebellum. Deterioration of abstract reasoning ability in AD and aMCI measured by CPM is related to GM loss in multiple regions, which is in close agreement with the results of previous activation studies.

Brain plasticity and sensorimotor deterioration as a function of 70 days head down tilt bed rest

PubMed Central

Bloomberg, Jacob J.; De Dios, Yiri E.; Wood, Scott J.; Reuter-Lorenz, Patricia A.; Kofman, Igor S.; Riascos, Roy; Mulavara, Ajitkumar P.; Seidler, Rachael D.

2017-01-01

Background Adverse effects of spaceflight on sensorimotor function have been linked to altered somatosensory and vestibular inputs in the microgravity environment. Whether these spaceflight sequelae have a central nervous system component is unknown. However, experimental studies have shown spaceflight-induced brain structural changes in rodents’ sensorimotor brain regions. Understanding the neural correlates of spaceflight-related motor performance changes is important to ultimately develop tailored countermeasures that ensure mission success and astronauts’ health. Method Head down-tilt bed rest (HDBR) can serve as a microgravity analog because it mimics body unloading and headward fluid shifts of microgravity. We conducted a 70-day 6° HDBR study with 18 right-handed males to investigate how microgravity affects focal gray matter (GM) brain volume. MRI data were collected at 7 time points before, during and post-HDBR. Standing balance and functional mobility were measured pre and post-HDBR. The same metrics were obtained at 4 time points over ~90 days from 12 control subjects, serving as reference data. Results HDBR resulted in widespread increases GM in posterior parietal regions and decreases in frontal areas; recovery was not yet complete by 12 days post-HDBR. Additionally, HDBR led to balance and locomotor performance declines. Increases in a cluster comprising the precuneus, precentral and postcentral gyrus GM correlated with less deterioration or even improvement in standing balance. This association did not survive Bonferroni correction and should therefore be interpreted with caution. No brain or behavior changes were observed in control subjects. Conclusions Our results parallel the sensorimotor deficits that astronauts experience post-flight. The widespread GM changes could reflect fluid redistribution. Additionally, the association between focal GM increase and balance changes suggests that HDBR also may result in neuroplastic adaptation. Future studies are warranted to determine causality and underlying mechanisms. PMID:28767698

Anatomical substrates of cognitive and clinical dimensions in first episode schizophrenia.

PubMed

Rigucci, S; Rossi-Espagnet, C; Ferracuti, S; De Carolis, A; Corigliano, V; Carducci, F; Mancinelli, I; Cicone, F; Tatarelli, R; Bozzao, A; Girardi, P; Comparelli, A

2013-10-01

To explore gray (GM) and white matter (WM) abnormalities and the relationships with neuropsychopathology in first-episode schizophrenia (FES). Nineteen patients with first episode of non-affective psychosis and 18 controls underwent a magnetic resonance voxel-based morphometry. Additionally, WM fractional anisotropy (FA) was calculated. For correlative analysis, symptoms and neuropsychological performances were scored by PANSS and by a comprehensive neuropsychological assessment respectively. Patients showed significantly decreased volume of left temporal lobe and disarray of all major WM tracts. Disorganized PANSS factor was inversely related to left cerebellar GM volume (corrected P = 0.03) and to WM FA of the left cerebellum, inferior fronto-occipital fasciculi (IFOF), and inferior longitudinal fasciculi (corrected P < 0.05). PANSS negative factor was inversely related to FA in the IFOF and superior longitudinal fasciculi (corrected P < 0.05). Impairment in facial emotion identification showed associations with temporo-occipital GM volume decrease (corrected P = 0.003) and WM disarray of superior and middle temporal gyri, anterior thalamic radiation, and superior longitudinal fasciculi (corrected P < 0.05). Speed of processing and visual memory correlated with WM abnormalities in fronto-temporal tracts. These results confirm how the structural development of key brain regions is related to neuropsychopathological dysfunction in FES, consistently with a neurodevelopmentally derived misconnection syndrome. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Image segmentation by EM-based adaptive pulse coupled neural networks in brain magnetic resonance imaging.

PubMed

Fu, J C; Chen, C C; Chai, J W; Wong, S T C; Li, I C

2010-06-01

We propose an automatic hybrid image segmentation model that integrates the statistical expectation maximization (EM) model and the spatial pulse coupled neural network (PCNN) for brain magnetic resonance imaging (MRI) segmentation. In addition, an adaptive mechanism is developed to fine tune the PCNN parameters. The EM model serves two functions: evaluation of the PCNN image segmentation and adaptive adjustment of the PCNN parameters for optimal segmentation. To evaluate the performance of the adaptive EM-PCNN, we use it to segment MR brain image into gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). The performance of the adaptive EM-PCNN is compared with that of the non-adaptive EM-PCNN, EM, and Bias Corrected Fuzzy C-Means (BCFCM) algorithms. The result is four sets of boundaries for the GM and the brain parenchyma (GM+WM), the two regions of most interest in medical research and clinical applications. Each set of boundaries is compared with the golden standard to evaluate the segmentation performance. The adaptive EM-PCNN significantly outperforms the non-adaptive EM-PCNN, EM, and BCFCM algorithms in gray mater segmentation. In brain parenchyma segmentation, the adaptive EM-PCNN significantly outperforms the BCFCM only. However, the adaptive EM-PCNN is better than the non-adaptive EM-PCNN and EM on average. We conclude that of the three approaches, the adaptive EM-PCNN yields the best results for gray matter and brain parenchyma segmentation. Copyright 2009 Elsevier Ltd. All rights reserved.

The Architecture of the Golfer's Brain

PubMed Central

Jäncke, Lutz; Koeneke, Susan; Hoppe, Ariana; Rominger, Christina; Hänggi, Jürgen

2009-01-01

Background Several recent studies have shown practice-dependent structural alterations in humans. Cross-sectional studies of intensive practice of specific tasks suggest associated long-term structural adaptations. Playing golf at a high level of performance is one of the most demanding sporting activities. In this study, we report the relationship between a particular level of proficiency in playing golf (indicated by golf handicap level) and specific neuroanatomical features. Principal Findings Using voxel-based morphometry (VBM) of grey (GM) and white matter (WM) volumes and fractional anisotropy (FA) measures of the fibre tracts, we identified differences between skilled (professional golfers and golfers with an handicap from 1–14) and less-skilled golfers (golfers with an handicap from 15–36 and non-golfer). Larger GM volumes were found in skilled golfers in a fronto-parietal network including premotor and parietal areas. Skilled golfers revealed smaller WM volume and FA values in the vicinity of the corticospinal tract at the level of the internal and external capsule and in the parietal operculum. However, there was no structural difference within the skilled and less-skilled golfer group. Conclusion There is no linear relationship between the anatomical findings and handicap level, amount of practice, and practice hours per year. There was however a strong difference between highly-practiced golfers (at least 800–3,000 hours) and those who have practised less or non-golfers without any golfing practise, thus indicating a step-wise structural and not a linear change. PMID:19277116

Effects of field-grown genetically modified Zoysia grass on bacterial community structure.

PubMed

Lee, Yong-Eok; Yang, Sang-Hwan; Bae, Tae-Woong; Kang, Hong-Gyu; Lim, Pyung-Ok; Lee, Hyo-Yeon

2011-04-01

Herbicide-tolerant Zoysia grass has been previously developed through Agrobacterium-mediated transformation. We investigated the effects of genetically modified (GM) Zoysia grass and the associated herbicide application on bacterial community structure by using culture-independent approaches. To assess the possible horizontal gene transfer (HGT) of transgenic DNA to soil microorganisms, total soil DNAs were amplified by PCR with two primer sets for the bar and hpt genes, which were introduced into the GM Zoysia grass by a callus-type transformation. The transgenic genes were not detected from the total genomic DNAs extracted from 1.5 g of each rhizosphere soils of GM and non-GM Zoysia grasses. The structures and diversities of the bacterial communities in rhizosphere soils of GM and non-GM Zoysia grasses were investigated by constructing 16S rDNA clone libraries. Classifier, provided in the RDP II, assigned 100 clones in the 16S rRNA gene sequences library into 11 bacterial phyla. The most abundant phyla in both clone libraries were Acidobacteria and Proteobacteria. The bacterial diversity of the GM clone library was lower than that of the non- GM library. The former contained four phyla, whereas the latter had seven phyla. Phylogenetic trees were constructed to confirm these results. Phylogenetic analyses of the two clone libraries revealed considerable difference from each other. The significance of difference between clone libraries was examined with LIBSHUFF statistics. LIBSHUFF analysis revealed that the two clone libraries differed significantly (P〈0.025), suggesting alterations in the composition of the microbial community associated with GM Zoysia grass.

Detection of Normal Aging Effects on Human Brain Metabolite Concentrations and Microstructure with Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging.

PubMed

Eylers, V V; Maudsley, A A; Bronzlik, P; Dellani, P R; Lanfermann, H; Ding, X-Q

2016-03-01

Knowledge of age-related physiological changes in the human brain is a prerequisite to identify neurodegenerative diseases. Therefore, in this study whole-brain (1)H-MRS was used in combination with quantitative MR imaging to study the effects of normal aging on healthy human brain metabolites and microstructure. Sixty healthy volunteers, 21-70 years of age, were studied. Brain maps of the metabolites NAA, creatine and phosphocreatine, and Cho and the tissue irreversible and reversible transverse relaxation times T2 and T2' were derived from the datasets. The relative metabolite concentrations and the values of relaxation times were measured with ROIs placed within the frontal and parietal WM, centrum semiovale, splenium of the corpus callosum, hand motor area, occipital GM, putamen, thalamus, pons ventral/dorsal, and cerebellar white matter and posterior lobe. Linear regression analysis and Pearson correlation tests were used to analyze the data. Aging resulted in decreased NAA concentrations in the occipital GM, putamen, splenium of the corpus callosum, and pons ventral and decreased creatine and phosphocreatine concentrations in the pons dorsal and putamen. Cho concentrations did not change significantly in selected brain regions. T2 increased in the cerebellar white matter and decreased in the splenium of the corpus callosum with aging, while the T2' decreased in the occipital GM, hand motor area, and putamen, and increased in the splenium of the corpus callosum. Correlations were found between NAA concentrations and T2' in the occipital GM and putamen and between creatine and phosphocreatine concentrations and T2' in the putamen. The effects of normal aging on brain metabolites and microstructure are region-dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients. © 2016 by American Journal of Neuroradiology.

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nieman, Brian J., E-mail: brian.nieman@utoronto.ca; Department of Medical Biophysics, University of Toronto, Toronto, Ontario; Ontario Institute for Cancer Research, Toronto, Ontario

Purpose: Pediatric patients treated with cranial radiation are at high risk of developing lasting cognitive impairments. We sought to identify anatomical changes in both gray matter (GM) and white matter (WM) in radiation-treated patients and in mice, in which the effect of radiation can be isolated from other factors, the time course of anatomical change can be established, and the effect of treatment age can be more fully characterized. Anatomical results were compared between species. Methods and Materials: Patients were imaged with T{sub 1}-weighted magnetic resonance imaging (MRI) after radiation treatment. Nineteen radiation-treated patients were divided into groups of 7 yearsmore » of age and younger (7−) and 8 years and older (8+) and were compared to 41 controls. C57BL6 mice were treated with radiation (n=52) or sham treated (n=52) between postnatal days 16 and 36 and then assessed with in vivo and/or ex vivo MRI. In both cases, measurements of WM and GM volume, cortical thickness, area and volume, and hippocampal volume were compared between groups. Results: WM volume was significantly decreased following treatment in 7− and 8+ treatment groups. GM volume was unchanged overall, but cortical thickness was slightly increased in the 7− group. Results in mice mostly mirrored these changes and provided a time course of change, showing early volume loss and normal growth. Hippocampal volume showed a decreasing trend with age in patients, an effect not observed in the mouse hippocampus but present in the olfactory bulb. Conclusions: Changes in mice treated with cranial radiation are similar to those in humans, including significant WM and GM alterations. Because mice did not receive any other treatment, the similarity across species supports the expectation that radiation is causative and suggests mice provide a representative model for studying impaired brain development after cranial radiation and testing novel treatments.« less

Aphid-parasitoid community structure on genetically modified wheat.

PubMed

von Burg, Simone; van Veen, Frank J F; Álvarez-Alfageme, Fernando; Romeis, Jörg

2011-06-23

Since the introduction of genetically modified (GM) plants, one of the main concerns has been their potential effect on non-target insects. Many studies have looked at GM plant effects on single non-target herbivore species or on simple herbivore-natural enemy food chains. Agro-ecosystems, however, are characterized by numerous insect species which are involved in complex interactions, forming food webs. In this study, we looked at transgenic disease-resistant wheat (Triticum aestivum) and its effect on aphid-parasitoid food webs. We hypothesized that the GM of the wheat lines directly or indirectly affect aphids and that these effects cascade up to change the structure of the associated food webs. Over 2 years, we studied different experimental wheat lines under semi-field conditions. We constructed quantitative food webs to compare their properties on GM lines with the properties on corresponding non-transgenic controls. We found significant effects of the different wheat lines on insect community structure up to the fourth trophic level. However, the observed effects were inconsistent between study years and the variation between wheat varieties was as big as between GM plants and their controls. This suggests that the impact of our powdery mildew-resistant GM wheat plants on food web structure may be negligible and potential ecological effects on non-target insects limited.

Abnormal development of sensory-motor, visual temporal and parahippocampal cortex in children with learning disabilities and borderline intellectual functioning

PubMed Central

Baglio, Francesca; Cabinio, Monia; Ricci, Cristian; Baglio, Gisella; Lipari, Susanna; Griffanti, Ludovica; Preti, Maria G.; Nemni, Raffaello; Clerici, Mario; Zanette, Michela; Blasi, Valeria

2014-01-01

Borderline intellectual functioning (BIF) is a condition characterized by an intelligence quotient (IQ) between 70 and 85. BIF children present with cognitive, motor, social, and adaptive limitations that result in learning disabilities and are more likely to develop psychiatric disorders later in life. The aim of this study was to investigate brain morphometry and its relation to IQ level in BIF children. Thirteen children with BIF and 14 age- and sex-matched typically developing (TD) children were enrolled. All children underwent a full IQ assessment (WISC-III scale) and a magnetic resonance (MR) examination including conventional sequences to assess brain structural abnormalities and high resolution 3D images for voxel-based morphometry analysis. To investigate to what extent the group influenced gray matter (GM) volumes, both univariate and multivariate generalized linear model analysis of variance were used, and the varimax factor analysis was used to explore variable correlations and clusters among subjects. Results showed that BIF children, compared to controls have increased regional GM volume in bilateral sensorimotor and right posterior temporal cortices and decreased GM volume in the right parahippocampal gyrus. GM volumes were highly correlated with IQ indices. The present work is a case study of a group of BIF children showing that BIF is associated with abnormal cortical development in brain areas that have a pivotal role in motor, learning, and behavioral processes. Our findings, although allowing for little generalization to the general population, contribute to the very limited knowledge in this field. Future longitudinal MR studies will be useful in verifying whether cortical features can be modified over time even in association with rehabilitative intervention. PMID:25360097

Affective mentalizing and brain activity at rest in the behavioral variant of frontotemporal dementia.

PubMed

Caminiti, Silvia P; Canessa, Nicola; Cerami, Chiara; Dodich, Alessandra; Crespi, Chiara; Iannaccone, Sandro; Marcone, Alessandra; Falini, Andrea; Cappa, Stefano F

2015-01-01

bvFTD patients display an impairment in the attribution of cognitive and affective states to others, reflecting GM atrophy in brain regions associated with social cognition, such as amygdala, superior temporal cortex and posterior insula. Distinctive patterns of abnormal brain functioning at rest have been reported in bvFTD, but their relationship with defective attribution of affective states has not been investigated. To investigate the relationship among resting-state brain activity, gray matter (GM) atrophy and the attribution of mental states in the behavioral variant of fronto-temporal degeneration (bvFTD). We compared 12 bvFTD patients with 30 age- and education-matched healthy controls on a) performance in a task requiring the attribution of affective vs. cognitive mental states; b) metrics of resting-state activity in known functional networks; and c) the relationship between task-performances and resting-state metrics. In addition, we assessed a connection between abnormal resting-state metrics and GM atrophy. Compared with controls, bvFTD patients showed a reduction of intra-network coherent activity in several components, as well as decreased strength of activation in networks related to attentional processing. Anomalous resting-state activity involved networks which also displayed a significant reduction of GM density. In patients, compared with controls, higher affective mentalizing performance correlated with stronger functional connectivity between medial prefrontal sectors of the default-mode and attentional/performance monitoring networks, as well as with increased coherent activity in components of the executive, sensorimotor and fronto-limbic networks. Some of the observed effects may reflect specific compensatory mechanisms for the atrophic changes involving regions in charge of affective mentalizing. The analysis of specific resting-state networks thus highlights an intermediate level of analysis between abnormal brain structure and impaired behavioral performance in bvFTD, reflecting both dysfunction and compensation mechanisms.

Binding, Conformational Transition and Dimerization of Amyloid-β Peptide on GM1-Containing Ternary Membrane: Insights from Molecular Dynamics Simulation

PubMed Central

Manna, Moutusi; Mukhopadhyay, Chaitali

2013-01-01

Interactions of amyloid-β (Aβ) with neuronal membrane are associated with the progression of Alzheimer’s disease (AD). Ganglioside GM1 has been shown to promote the structural conversion of Aβ and increase the rate of peptide aggregation; but the exact nature of interaction driving theses processes remains to be explored. In this work, we have carried out atomistic-scale computer simulations (totaling 2.65 µs) to investigate the behavior of Aβ monomer and dimers in GM1-containing raft-like membrane. The oligosaccharide head-group of GM1 was observed to act as scaffold for Aβ-binding through sugar-specific interactions. Starting from the initial helical peptide conformation, a β-hairpin motif was formed at the C-terminus of the GM1-bound Aβ-monomer; that didn’t appear in absence of GM1 (both in fluid POPC and liquid-ordered cholesterol/POPC bilayers and also in aqueous medium) within the simulation time span. For Aβ-dimers, the β-structure was further enhanced by peptide-peptide interactions, which might influence the propensity of Aβ to aggregate into higher-ordered structures. The salt-bridges and inter-peptide hydrogen bonds were found to account for dimer stability. We observed spontaneous formation of intra-peptide D23-K28 salt-bridge and a turn at V24GSN27 region - long been accepted as characteristic structural-motifs for amyloid self-assembly. Altogether, our results provide atomistic details of Aβ-GM1 and Aβ-Aβ interactions and demonstrate their importance in the early-stages of GM1-mediated Aβ-oligomerisation on membrane surface. PMID:23951128

In search of multimodal neuroimaging biomarkers of cognitive deficits in schizophrenia.

PubMed

Sui, Jing; Pearlson, Godfrey D; Du, Yuhui; Yu, Qingbao; Jones, Thomas R; Chen, Jiayu; Jiang, Tianzi; Bustillo, Juan; Calhoun, Vince D

2015-12-01

The cognitive deficits of schizophrenia are largely resistant to current treatments and thus are a lifelong illness burden. The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) provides a reliable and valid assessment of cognition across major cognitive domains; however, the multimodal brain alterations specifically associated with MCCB in schizophrenia have not been examined. The interrelationships between MCCB and the abnormalities seen in three types of neuroimaging-derived maps-fractional amplitude of low-frequency fluctuations (fALFF) from resting-state functional magnetic resonance imaging (MRI), gray matter (GM) density from structural MRI, and fractional anisotropy from diffusion MRI-were investigated by using multiset canonical correlation analysis in data from 47 schizophrenia patients treated with antipsychotic medications and 50 age-matched healthy control subjects. One multimodal component (canonical variant 8) was identified as both group differentiating and significantly correlated with the MCCB composite. It demonstrated 1) increased cognitive performance associated with higher fALFF (intensity of regional spontaneous brain activity) and higher GM volumes in thalamus, striatum, hippocampus, and the mid-occipital region, with co-occurring fractional anisotropy changes in superior longitudinal fascicules, anterior thalamic radiation, and forceps major; 2) higher fALFF but lower GM volume in dorsolateral prefrontal cortex related to worse cognition in schizophrenia; and 3) distinct domains of MCCB might exhibit dissociable multimodal signatures, e.g., increased fALFF in inferior parietal lobule particularly correlated with decreased social cognition. Medication dose did not relate to these findings in schizophrenia. Our results suggest linked functional and structural deficits in distributed cortico-striato-thalamic circuits may be closely related to MCCB-measured cognitive impairments in schizophrenia. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Voxel-based morphometry in Alzheimers disease and mild cognitive impairment: Systematic review of studies addressing the frontal lobe

PubMed Central

Ribeiro, Luís Gustavo; Busatto, Geraldo

2016-01-01

ABSTRACT Voxel-based morphometry (VBM) is a useful approach for investigating neurostructural brain changes in dementia. We systematically reviewed VBM studies of Alzheimer's disease (AD) and mild cognitive impairment (MCI), specifically focusing on grey matter (GM) atrophy in the frontal lobe. Methods: Two searches were performed on the Pubmed database. A set of exclusion criteria was applied to ensure the selection of only VBM studies that directly investigated GM volume abnormalities in AD and/or MCI patients compared to cognitively normal controls. Results: From a total of 46 selected articles, 35 VBM studies reported GM volume reductions in the frontal lobe. The frontal subregions, where most of the volume reductions were reported, included the inferior, superior and middle frontal gyri, as well as the anterior cingulate gyrus. We also found studies in which reduced frontal GM was detected in MCI patients who converted to AD. In a minority of studies, correlations between frontal GM volumes and behavioural changes or cognitive deficits in AD patients were investigated, with variable findings. Conclusion: Results of VBM studies indicate that the frontal lobe should be regarded as an important brain area when investigating GM volume deficits in association with AD. Frontal GM loss might not be a feature specific to late AD only. Future VBM studies involving large AD samples are warranted to further investigate correlations between frontal volume deficits and both cognitive impairment and neuropsychiatric symptoms. PMID:29213441

Where the world stands still: turnaround as a strong test of ΛCDM cosmology

NASA Astrophysics Data System (ADS)

Pavlidou, V.; Tomaras, T. N.

2014-09-01

Our intuitive understanding of cosmic structure formation works best in scales small enough so that isolated, bound, relaxed gravitating systems are no longer adjusting their radius; and large enough so that space and matter follow the average expansion of the Universe. Yet one of the most robust predictions of ΛCDM cosmology concerns the scale that separates these limits: the turnaround radius, which is the non-expanding shell furthest away from the center of a bound structure. We show that the maximum possible value of the turnaround radius within the framework of the ΛCDM model is, for a given mass M, equal to (3GM/Λ c2)1/3, with G Newton's constant and c the speed of light, independently of cosmic epoch, exact nature of dark matter, or baryonic effects. We discuss the possible use of this prediction as an observational test for ΛCDM cosmology. Current data appear to favor ΛCDM over alternatives with local inhomogeneities and no Λ. However there exist several local-universe structures that have, within errors, reached their limiting size. With improved determinations of their turnaround radii and the enclosed mass, these objects may challenge the limit and ΛCDM cosmology.

The Structure of the GM-CSF Receptor Complex Reveals a Distinct Mode of Cytokine Receptor Activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hansen, Guido; Hercus, Timothy R.; McClure, Barbara J.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that controls the production and function of blood cells, is deregulated in clinical conditions such as rheumatoid arthritis and leukemia, yet offers therapeutic value for other diseases. Its receptors are heterodimers consisting of a ligand-specific {alpha} subunit and a {beta}c subunit that is shared with the interleukin (IL)-3 and IL-5 receptors. How signaling is initiated remains an enigma. We report here the crystal structure of the human GM-CSF/GM-CSF receptor ternary complex and its assembly into an unexpected dodecamer or higher-order complex. Importantly, mutagenesis of the GM-CSF receptor at the dodecamer interface andmore » functional studies reveal that dodecamer formation is required for receptor activation and signaling. This unusual form of receptor assembly likely applies also to IL-3 and IL-5 receptors, providing a structural basis for understanding their mechanism of activation and for the development of therapeutics.« less

Lactobacillus plantarum attenuates anxiety-related behavior and protects against stress-induced dysbiosis in adult zebrafish.

PubMed

Davis, Daniel J; Doerr, Holly M; Grzelak, Agata K; Busi, Susheel B; Jasarevic, Eldin; Ericsson, Aaron C; Bryda, Elizabeth C

2016-09-19

The consumption of probiotics has become increasingly popular as a means to try to improve health and well-being. Not only are probiotics considered beneficial to digestive health, but increasing evidence suggests direct and indirect interactions between gut microbiota (GM) and the central nervous system (CNS). Here, adult zebrafish were supplemented with Lactobacillus plantarum to determine the effects of probiotic treatment on structural and functional changes of the GM, as well as host neurological and behavioral changes. L. plantarum administration altered the β-diversity of the GM while leaving the major core architecture intact. These minor structural changes were accompanied by significant enrichment of several predicted metabolic pathways. In addition to GM modifications, L. plantarum treatment also significantly reduced anxiety-related behavior and altered GABAergic and serotonergic signaling in the brain. Lastly, L. plantarum supplementation provided protection against stress-induced dysbiosis of the GM. These results underscore the influence commensal microbes have on physiological function in the host, and demonstrate bidirectional communication between the GM and the host.

Short-term effects of different genetically modified maize varieties on arthropod food web properties: an experimental field assessment.

PubMed

Szénási, Ágnes; Pálinkás, Zoltán; Zalai, Mihály; Schmitz, Oswald J; Balog, Adalbert

2014-06-17

There is concern that genetically modified (GM) plants may have adverse affects on the arthropod biodiversity comprising agricultural landscapes. The present study report on a two year field experimental test of whether four different genotypic lines, some are novel with no previous field tests, of GM maize hybrids alter the structure of arthropod food webs that they harbour, relative to non-GM maize (control) that is widely used in agriculture. The different GM genotypes produced either Bt toxins, conferred glyphosate tolerance or a combination of the two traits. Quantitative food web analysis, based on short-term assessment assigning a total of 243,896 arthropod individuals collected from the treatments to their positions in food webs, revealed that complex and stable food webs persisted in each maize treatment. Moreover, food web structure remained relatively unchanged by the GM-genotype. The results suggest that at least in short-term period these particular GM maize genotypes will not have adverse effects on arthropod biota of agricultural landscapes.

Recommendations for the Use of Automated Gray Matter Segmentation Tools: Evidence from Huntington’s Disease

PubMed Central

Johnson, Eileanoir B.; Gregory, Sarah; Johnson, Hans J.; Durr, Alexandra; Leavitt, Blair R.; Roos, Raymund A.; Rees, Geraint; Tabrizi, Sarah J.; Scahill, Rachael I.

2017-01-01

The selection of an appropriate segmentation tool is a challenge facing any researcher aiming to measure gray matter (GM) volume. Many tools have been compared, yet there is currently no method that can be recommended above all others; in particular, there is a lack of validation in disease cohorts. This work utilizes a clinical dataset to conduct an extensive comparison of segmentation tools. Our results confirm that all tools have advantages and disadvantages, and we present a series of considerations that may be of use when selecting a GM segmentation method, rather than a ranking of these tools. Seven segmentation tools were compared using 3 T MRI data from 20 controls, 40 premanifest Huntington’s disease (HD), and 40 early HD participants. Segmented volumes underwent detailed visual quality control. Reliability and repeatability of total, cortical, and lobular GM were investigated in repeated baseline scans. The relationship between each tool was also examined. Longitudinal within-group change over 3 years was assessed via generalized least squares regression to determine sensitivity of each tool to disease effects. Visual quality control and raw volumes highlighted large variability between tools, especially in occipital and temporal regions. Most tools showed reliable performance and the volumes were generally correlated. Results for longitudinal within-group change varied between tools, especially within lobular regions. These differences highlight the need for careful selection of segmentation methods in clinical neuroimaging studies. This guide acts as a primer aimed at the novice or non-technical imaging scientist providing recommendations for the selection of cohort-appropriate GM segmentation software. PMID:29066997

Membrane-lipid homeostasis in a prodromal rat model of Alzheimer's disease: Characteristic profiles in ganglioside distributions during aging detected using MALDI imaging mass spectrometry.

PubMed

Caughlin, Sarah; Maheshwari, Shikhar; Agca, Yuksel; Agca, Cansu; Harris, Aaron J; Jurcic, Kristina; Yeung, Ken K-C; Cechetto, David F; Whitehead, Shawn N

2018-06-01

Accumulation of simple gangliosides GM2 and GM3, and gangliosides with longer long-chain bases (d20:1) have been linked to toxicity and the pathogenesis of Alzheimer's disease (AD). Conversely, complex gangliosides, such as GM1, have been shown to be neuroprotective. Recent evidence using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) has demonstrated that a-series gangliosides are differentially altered during normal aging, yet it remains unclear how simple species are shifting relative to complex gangliosides in the prodromal stages of AD. Ganglioside profiles in wild-type (Wt) and transgenic APP21 Fischer rats were detected and quantified using MALDI-IMS at P0 (birth), 3, 12, and 20 months of age and each species quantified to allow for individual species comparisons. Tg APP21 rats were found to have a decreased level of complex gangliosides in a number of brain regions as compared to Wt rats and showed higher levels of simple gangliosides. A unique pattern of expression was observed in the white matter as compared to gray matter regions, with an age-dependent decrease in GD1 d18:1 species observed and significantly elevated levels of GM3 in Tg APP21 rats. These results are indicative of a pathological shift in ganglioside homeostasis during aging that is exacerbated in Tg APP21 rats. Ganglioside dysregulation may occur in the prodromal stages of neurodegenerative diseases like AD. Copyright © 2018 Elsevier B.V. All rights reserved.

Recommendations for the Use of Automated Gray Matter Segmentation Tools: Evidence from Huntington's Disease.

PubMed

Johnson, Eileanoir B; Gregory, Sarah; Johnson, Hans J; Durr, Alexandra; Leavitt, Blair R; Roos, Raymund A; Rees, Geraint; Tabrizi, Sarah J; Scahill, Rachael I

2017-01-01

The selection of an appropriate segmentation tool is a challenge facing any researcher aiming to measure gray matter (GM) volume. Many tools have been compared, yet there is currently no method that can be recommended above all others; in particular, there is a lack of validation in disease cohorts. This work utilizes a clinical dataset to conduct an extensive comparison of segmentation tools. Our results confirm that all tools have advantages and disadvantages, and we present a series of considerations that may be of use when selecting a GM segmentation method, rather than a ranking of these tools. Seven segmentation tools were compared using 3 T MRI data from 20 controls, 40 premanifest Huntington's disease (HD), and 40 early HD participants. Segmented volumes underwent detailed visual quality control. Reliability and repeatability of total, cortical, and lobular GM were investigated in repeated baseline scans. The relationship between each tool was also examined. Longitudinal within-group change over 3 years was assessed via generalized least squares regression to determine sensitivity of each tool to disease effects. Visual quality control and raw volumes highlighted large variability between tools, especially in occipital and temporal regions. Most tools showed reliable performance and the volumes were generally correlated. Results for longitudinal within-group change varied between tools, especially within lobular regions. These differences highlight the need for careful selection of segmentation methods in clinical neuroimaging studies. This guide acts as a primer aimed at the novice or non-technical imaging scientist providing recommendations for the selection of cohort-appropriate GM segmentation software.

Distributed abnormalities of brain white matter architecture in patients with dominant optic atrophy and OPA1 mutations.

PubMed

Rocca, Maria A; Bianchi-Marzoli, Stefania; Messina, Roberta; Cascavilla, Maria Lucia; Zeviani, Massimo; Lamperti, Costanza; Milesi, Jacopo; Carta, Arturo; Cammarata, Gabriella; Leocani, Letizia; Lamantea, Eleonora; Bandello, Francesco; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

2015-05-01

Using advanced MRI techniques, we investigated the presence and topographical distribution of brain grey matter (GM) and white matter (WM) alterations in dominant optic atrophy (DOA) patients with genetically proven OPA1 mutation as well as their correlation with clinical and neuro-ophthalmologic findings. Nineteen DOA patients underwent neurological, neuro-ophthalmologic and brainstem auditory evoked potentials (BAEP) evaluations. Voxel-wise methods were applied to assess regional GM and WM abnormalities in patients compared to 20 healthy controls. Visual acuity was reduced in 16 patients. Six DOA patients (4 with missense mutations) had an abnormal I peripheral component (auditory nerve) at BAEP. Compared to controls, DOA patients had significant atrophy of the optic nerves (p < 0.0001). Voxel-based morphometry (VBM) analysis showed that, compared to controls, DOA patients had significant WM atrophy of the chiasm and optic tracts; whereas no areas of GM atrophy were found. Tract-based spatial statistics (TBSS) analysis showed that compared to controls, DOA patients had significantly lower mean diffusivity, axial and radial diffusivity in the WM of the cerebellum, brainstem, thalamus, fronto-occipital-temporal lobes, including the cingulum, corpus callosum, corticospinal tract and optic radiation bilaterally. No abnormalities of fractional anisotropy were detected. No correlations were found between volumetric and diffusivity abnormalities quantified with MRI and clinical and neuro-ophthalmologic measures of disease severity. Consistently with pathological studies, tissue loss in DOA patients is limited to anterior optic pathways reflecting retinal ganglion cell degeneration. Distributed abnormalities of diffusivity indexes might reflect abnormal intracellular mitochondrial morphology as well as alteration of protein levels due to OPA1 mutations.

White and gray matter damage in primary progressive MS

PubMed Central

Chard, Declan; Altmann, Daniel R.; Tozer, Daniel; Miller, David H.; Thompson, Alan J.; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

2016-01-01

Objective: The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex (“primary WM damage model”); and (2) cortical abnormalities predict later changes in connected WM tracts (“primary GM damage model”). Methods: Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. Results: The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. Conclusion: These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. PMID:26674332

White and gray matter damage in primary progressive MS: The chicken or the egg?

PubMed

Bodini, Benedetta; Chard, Declan; Altmann, Daniel R; Tozer, Daniel; Miller, David H; Thompson, Alan J; Wheeler-Kingshott, Claudia; Ciccarelli, Olga

2016-01-12

The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex ("primary WM damage model"); and (2) cortical abnormalities predict later changes in connected WM tracts ("primary GM damage model"). Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent variable's baseline MTR; tract lesion load and MTR, spinal cord area, age, and sex were examined for potential confounding. The baseline MTR of most regions was lower in patients than in healthy controls. The tract-cortex pair relationships in the primary WM damage model were significant for the bilateral motor pair and right visual pair, while those in the primary GM damage model were only significant for the right motor pair. Lower lesion MTR at baseline was associated with lower MTR in the same tract normal-appearing WM at 2 years in 3 tracts. These results are consistent with the hypothesis that in early PPMS, cortical damage is for the most part a sequela of normal-appearing WM pathology, which, in turn, is predicted by abnormalities within WM lesions. © 2015 American Academy of Neurology.

MRBrainS Challenge: Online Evaluation Framework for Brain Image Segmentation in 3T MRI Scans.

PubMed

Mendrik, Adriënne M; Vincken, Koen L; Kuijf, Hugo J; Breeuwer, Marcel; Bouvy, Willem H; de Bresser, Jeroen; Alansary, Amir; de Bruijne, Marleen; Carass, Aaron; El-Baz, Ayman; Jog, Amod; Katyal, Ranveer; Khan, Ali R; van der Lijn, Fedde; Mahmood, Qaiser; Mukherjee, Ryan; van Opbroek, Annegreet; Paneri, Sahil; Pereira, Sérgio; Persson, Mikael; Rajchl, Martin; Sarikaya, Duygu; Smedby, Örjan; Silva, Carlos A; Vrooman, Henri A; Vyas, Saurabh; Wang, Chunliang; Zhao, Liang; Biessels, Geert Jan; Viergever, Max A

2015-01-01

Many methods have been proposed for tissue segmentation in brain MRI scans. The multitude of methods proposed complicates the choice of one method above others. We have therefore established the MRBrainS online evaluation framework for evaluating (semi)automatic algorithms that segment gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) on 3T brain MRI scans of elderly subjects (65-80 y). Participants apply their algorithms to the provided data, after which their results are evaluated and ranked. Full manual segmentations of GM, WM, and CSF are available for all scans and used as the reference standard. Five datasets are provided for training and fifteen for testing. The evaluated methods are ranked based on their overall performance to segment GM, WM, and CSF and evaluated using three evaluation metrics (Dice, H95, and AVD) and the results are published on the MRBrainS13 website. We present the results of eleven segmentation algorithms that participated in the MRBrainS13 challenge workshop at MICCAI, where the framework was launched, and three commonly used freeware packages: FreeSurfer, FSL, and SPM. The MRBrainS evaluation framework provides an objective and direct comparison of all evaluated algorithms and can aid in selecting the best performing method for the segmentation goal at hand.

MRBrainS Challenge: Online Evaluation Framework for Brain Image Segmentation in 3T MRI Scans

PubMed Central

Mendrik, Adriënne M.; Vincken, Koen L.; Kuijf, Hugo J.; Breeuwer, Marcel; Bouvy, Willem H.; de Bresser, Jeroen; Alansary, Amir; de Bruijne, Marleen; Carass, Aaron; El-Baz, Ayman; Jog, Amod; Katyal, Ranveer; Khan, Ali R.; van der Lijn, Fedde; Mahmood, Qaiser; Mukherjee, Ryan; van Opbroek, Annegreet; Paneri, Sahil; Pereira, Sérgio; Rajchl, Martin; Sarikaya, Duygu; Smedby, Örjan; Silva, Carlos A.; Vrooman, Henri A.; Vyas, Saurabh; Wang, Chunliang; Zhao, Liang; Biessels, Geert Jan; Viergever, Max A.

2015-01-01

Many methods have been proposed for tissue segmentation in brain MRI scans. The multitude of methods proposed complicates the choice of one method above others. We have therefore established the MRBrainS online evaluation framework for evaluating (semi)automatic algorithms that segment gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) on 3T brain MRI scans of elderly subjects (65–80 y). Participants apply their algorithms to the provided data, after which their results are evaluated and ranked. Full manual segmentations of GM, WM, and CSF are available for all scans and used as the reference standard. Five datasets are provided for training and fifteen for testing. The evaluated methods are ranked based on their overall performance to segment GM, WM, and CSF and evaluated using three evaluation metrics (Dice, H95, and AVD) and the results are published on the MRBrainS13 website. We present the results of eleven segmentation algorithms that participated in the MRBrainS13 challenge workshop at MICCAI, where the framework was launched, and three commonly used freeware packages: FreeSurfer, FSL, and SPM. The MRBrainS evaluation framework provides an objective and direct comparison of all evaluated algorithms and can aid in selecting the best performing method for the segmentation goal at hand. PMID:26759553

Relationship between Brain Age-Related Reduction in Gray Matter and Educational Attainment

PubMed Central

Rzezak, Patricia; Squarzoni, Paula; Duran, Fabio L.; de Toledo Ferraz Alves, Tania; Tamashiro-Duran, Jaqueline; Bottino, Cassio M.; Ribeiz, Salma; Lotufo, Paulo A.; Menezes, Paulo R.; Scazufca, Marcia; Busatto, Geraldo F.

2015-01-01

Inter-subject variability in age-related brain changes may relate to educational attainment, as suggested by cognitive reserve theories. This voxel-based morphometry study investigated the impact of very low educational level on the relationship between regional gray matter (rGM) volumes and age in healthy elders. Magnetic resonance imaging data were acquired in elders with low educational attainment (less than 4 years) (n = 122) and high educational level (n = 66), pulling together individuals examined using either of three MRI scanners/acquisition protocols. Voxelwise group comparisons showed no rGM differences (p<0.05, family-wise error corrected for multiple comparisons). When within-group voxelwise patterns of linear correlation were compared between high and low education groups, there was one cluster of greater rGM loss with aging in low versus high education elders in the left anterior cingulate cortex (p<0.05, FWE-corrected), as well as a trend in the left dorsomedial prefrontal cortex (p<0.10). These results provide preliminary indication that education might exert subtle protective effects against age-related brain changes in healthy subjects. The anterior cingulate cortex, critical to inhibitory control processes, may be particularly sensitive to such effects, possibly given its involvement in cognitive stimulating activities at school or later throughout life. PMID:26474472

Cortical brain development in nonpsychotic siblings of patients with childhood-onset schizophrenia.

PubMed

Gogtay, Nitin; Greenstein, Deanna; Lenane, Marge; Clasen, Liv; Sharp, Wendy; Gochman, Pete; Butler, Philip; Evans, Alan; Rapoport, Judith

2007-07-01

Cortical gray matter (GM) loss is marked and progressive in childhood-onset schizophrenia (COS) during adolescence but becomes more circumscribed by early adulthood. Nonpsychotic siblings of COS probands could help evaluate whether the cortical GM abnormalities are familial/trait markers. To map cortical development in nonpsychotic siblings of COS probands. Using an automated measurement and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in healthy full siblings (n = 52, 113 scans; age 8 through 28 years) of patients with COS, contrasting them with age-, sex-, and scan interval-matched healthy controls (n = 52, 108 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons. An ongoing COS study at the National Institute of Mental Health. Fifty-two healthy full siblings of patients with COS, aged 8 through 28 years, and 52 healthy controls. Longitudinal trajectories of cortical GM development in healthy siblings of patients with COS compared with matched healthy controls and exploratory measure of the relationship between developmental GM trajectories and the overall functioning as defined by the Global Assessment Scale (GAS) score. Younger, healthy siblings of patients with COS showed significant GM deficits in the left prefrontal and bilateral temporal cortices and smaller deficits in the right prefrontal and inferior parietal cortices compared with the controls. These cortical deficits in siblings disappeared by age 20 years and the process of deficit reduction correlated with overall functioning (GAS scores) at the last scan. Prefrontal and temporal GM loss in COS appears to be a familial/trait marker. Amelioration of regional GM deficits in healthy siblings was associated with higher global functioning (GAS scores), suggesting a relationship between brain plasticity and functional outcome for these nonpsychotic, nonspectrum siblings.

Brain-water diffusion coefficients reflect the severity of inherited prion disease

PubMed Central

Hyare, H.; Wroe, S.; Siddique, D.; Webb, T.; Fox, N. C.; Stevens, J.; Collinge, J.; Yousry, T.; Thornton, J. S.

2010-01-01

Objective: Inherited prion diseases are progressive neurodegenerative conditions, characterized by cerebral spongiosis, gliosis, and neuronal loss, caused by mutations within the prion protein (PRNP) gene. We wished to assess the potential of diffusion-weighted MRI as a biomarker of disease severity in inherited prion diseases. Methods: Twenty-five subjects (mean age 45.2 years) with a known PRNP mutation including 19 symptomatic patients, 6 gene-positive asymptomatic subjects, and 7 controls (mean age 54.1 years) underwent conventional and diffusion-weighted MRI. An index of normalized brain volume (NBV) and region of interest (ROI) mean apparent diffusion coefficient (ADC) for the head of caudate, putamen, and pulvinar nuclei were recorded. ADC histograms were computed for whole brain (WB) and gray matter (GM) tissue fractions. Clinical assessment utilized standardized clinical scores. Mann-Whitney U test and regression analyses were performed. Results: Symptomatic patients exhibited an increased WB mean ADC (p = 0.006) and GM mean ADC (p = 0.024) compared to controls. Decreased NBV and increased mean ADC measures significantly correlated with clinical measures of disease severity. Using a stepwise multivariate regression procedure, GM mean ADC was an independent predictor of Clinician's Dementia Rating score (p = 0.001), Barthel Index of activities of daily living (p = 0.001), and Rankin disability score (p = 0.019). Conclusions: Brain volume loss in inherited prion diseases is accompanied by increased cerebral apparent diffusion coefficient (ADC), correlating with increased disease severity. The association between gray matter ADC and clinical neurologic status suggests this measure may prove a useful biomarker of disease activity in inherited prion diseases. GLOSSARY ADAS-Cog = Alzheimer's Disease Assessment Scale–Cognitive subscale; ADC = apparent diffusion coefficient; ADL = Barthel Activities of Daily Living scale; BET = brain extraction tool; BPRS = Brief Psychiatric Rating Scale; BSE = bovine spongiform encephalopathy; CDR = Clinician's Dementia Rating Scale; CGIS = Clinician's Global Impression of Disease; CI = confidence interval; DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; FOV = field of view; GM = gray matter; LC = left head of caudate; LP = left putamen; LPu = left pulvinar; MMSE = Mini-Mental State Examination; NBV = normalized brain volume; PH = peak height; PL = peak location; RC = right head of caudate; RP = right putamen; RPu = right pulvinar; ROI = region of interest; sCJD = sporadic Creutzfeldt-Jakob disease; TE = echo time; TI = inversion time; TR = repetition time; vCJD = variant Creutzfeldt-Jakob disease; WB = whole brain; WM = white matter. PMID:20177119

Serial proton MR spectroscopy of gray and white matter in relapsing-remitting MS

PubMed Central

Kirov, Ivan I.; Tal, Assaf; Babb, James S.; Herbert, Joseph

2013-01-01

Objective: To characterize and follow the diffuse gray and white matter (GM/WM) metabolic abnormalities in early relapsing-remitting multiple sclerosis using proton magnetic resonance spectroscopic imaging (1H-MRSI). Methods: Eighteen recently diagnosed, mildly disabled patients (mean baseline time from diagnosis 32 months, mean Expanded Disability Status Scale [EDSS] score 1.3), all on immunomodulatory medication, were scanned semiannually for 3 years with T1-weighted and T2-weighted MRI and 3D 1H-MRSI at 3 T. Ten sex- and age-matched controls were followed annually. Global absolute concentrations of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and myo-inositol (mI) were obtained for all GM and WM in the 360 cm3 1H-MRSI volume of interest. Results: Patients' average WM Cr, Cho, and mI concentrations (over all time points), 5.3 ± 0.4, 1.6 ± 0.1, and 5.1 ± 0.7 mM, were 8%, 12%, and 11% higher than controls' (p ≤ 0.01), while their WM NAA, 7.4 ± 0.7 mM, was 6% lower (p = 0.07). There were increases with time of patients' WM Cr: 0.1 mM/year, Cho: 0.02 mM/year, and NAA: 0.1 mM/year (all p < 0.05). None of the patients' metabolic concentrations correlated with their EDSS score, relapse rate, GM/WM/CSF fractions, or lesion volume. Conclusions: Diffuse WM glial abnormalities were larger in magnitude than the axonal abnormalities and increased over time independently of conventional clinical or imaging metrics and despite immunomodulatory treatment. In contrast, the axonal abnormalities showed partial recovery, suggesting that patients' lower WM NAA levels represented a dysfunction, which may abate with treatment. Absence of detectable diffuse changes in GM suggests that injury there is minimal, focal, or heterogeneous between cortex and deep GM nuclei. PMID:23175732

[Annual production of moss layer in dark coniferous forests of Ket-Chulym Forest District (by the example of Moss Hylocomium splendens)].

PubMed

Koshurnikova, N N

2007-01-01

The biological production of the moss layer was analyzed in dark coniferous stands in progressive succession in the southern taiga in West Siberia. The rate of organic matter production by mosses changed from 15-22.2 g/(m2 y) in 50-90-year-old fir forests to 51.6 g/(m2 y) in 170-year-old mixed Siberian pine-spruce-fir stands. In forest phytocenosis that were formed with species replacement (after cuttings with understory clearing), the annual moss production (net primary production) ranged from 2.8 to 20.6 g/(m2 y). The annual moss cover production amounted to 35-36% of the moss photosynthetic biomass irrespective of the type of native stand progressive succession and the stand age.

Alzheimer Disease and Behavioral Variant Frontotemporal Dementia: Automatic Classification Based on Cortical Atrophy for Single-Subject Diagnosis.

PubMed

Möller, Christiane; Pijnenburg, Yolande A L; van der Flier, Wiesje M; Versteeg, Adriaan; Tijms, Betty; de Munck, Jan C; Hafkemeijer, Anne; Rombouts, Serge A R B; van der Grond, Jeroen; van Swieten, John; Dopper, Elise; Scheltens, Philip; Barkhof, Frederik; Vrenken, Hugo; Wink, Alle Meije

2016-06-01

Purpose To investigate the diagnostic accuracy of an image-based classifier to distinguish between Alzheimer disease (AD) and behavioral variant frontotemporal dementia (bvFTD) in individual patients by using gray matter (GM) density maps computed from standard T1-weighted structural images obtained with multiple imagers and with independent training and prediction data. Materials and Methods The local institutional review board approved the study. Eighty-four patients with AD, 51 patients with bvFTD, and 94 control subjects were divided into independent training (n = 115) and prediction (n = 114) sets with identical diagnosis and imager type distributions. Training of a support vector machine (SVM) classifier used diagnostic status and GM density maps and produced voxelwise discrimination maps. Discriminant function analysis was used to estimate suitability of the extracted weights for single-subject classification in the prediction set. Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were calculated for image-based classifiers and neuropsychological z scores. Results Training accuracy of the SVM was 85% for patients with AD versus control subjects, 72% for patients with bvFTD versus control subjects, and 79% for patients with AD versus patients with bvFTD (P ≤ .029). Single-subject diagnosis in the prediction set when using the discrimination maps yielded accuracies of 88% for patients with AD versus control subjects, 85% for patients with bvFTD versus control subjects, and 82% for patients with AD versus patients with bvFTD, with a good to excellent AUC (range, 0.81-0.95; P ≤ .001). Machine learning-based categorization of AD versus bvFTD based on GM density maps outperforms classification based on neuropsychological test results. Conclusion The SVM can be used in single-subject discrimination and can help the clinician arrive at a diagnosis. The SVM can be used to distinguish disease-specific GM patterns in patients with AD and those with bvFTD as compared with normal aging by using common T1-weighted structural MR imaging. (©) RSNA, 2015.

Crystallographic structure of human beta-hexosaminidase A: interpretation of Tay-Sachs mutations and loss of GM2 ganglioside hydrolysis.

PubMed

Lemieux, M Joanne; Mark, Brian L; Cherney, Maia M; Withers, Stephen G; Mahuran, Don J; James, Michael N G

2006-06-16

Lysosomal beta-hexosaminidase A (Hex A) is essential for the degradation of GM2 gangliosides in the central and peripheral nervous system. Accumulation of GM2 leads to severely debilitating neurodegeneration associated with Tay-Sachs disease (TSD), Sandoff disease (SD) and AB variant. Here, we present the X-ray crystallographic structure of Hex A to 2.8 A resolution and the structure of Hex A in complex with NAG-thiazoline, (NGT) to 3.25 A resolution. NGT, a mechanism-based inhibitor, has been shown to act as a chemical chaperone that, to some extent, prevents misfolding of a Hex A mutant associated with adult onset Tay Sachs disease and, as a result, increases the residual activity of Hex A to a level above the critical threshold for disease. The crystal structure of Hex A reveals an alphabeta heterodimer, with each subunit having a functional active site. Only the alpha-subunit active site can hydrolyze GM2 gangliosides due to a flexible loop structure that is removed post-translationally from beta, and to the presence of alphaAsn423 and alphaArg424. The loop structure is involved in binding the GM2 activator protein, while alphaArg424 is critical for binding the carboxylate group of the N-acetyl-neuraminic acid residue of GM2. The beta-subunit lacks these key residues and has betaAsp452 and betaLeu453 in their place; the beta-subunit therefore cleaves only neutral substrates efficiently. Mutations in the alpha-subunit, associated with TSD, and those in the beta-subunit, associated with SD are discussed. The effect of NGT binding in the active site of a mutant Hex A and its effect on protein function is discussed.

Complement Factor H and Simian Virus 40 bind the GM1 ganglioside in distinct conformations.

PubMed

Blaum, Bärbel S; Frank, Martin; Walker, Ross C; Neu, Ursula; Stehle, Thilo

2016-05-01

Mammalian cell surfaces are decorated with a variety of glycan chains that orchestrate development and defense and are exploited by pathogens for cellular attachment and entry. While glycosidic linkages are, in principle, flexible, the conformational space that a given glycan can sample is subject to spatial and electrostatic restrictions imposed by its overall chemical structure. Here, we show how the glycan moiety of the GM1 ganglioside, a branched, monosialylated pentasaccharide that serves as a ligand for various proteins, undergoes differential conformational selection in its interactions with different lectins. Using STD NMR and X-ray crystallography, we found that the innate immune regulator complement Factor H (FH) binds a previously not reported GM1 conformation that is not compatible with the GM1-binding sites of other structurally characterized GM1-binding lectins such as the Simian Virus 40 (SV40) capsid. Molecular dynamics simulations of the free glycan in explicit solvent on the 10 μs timescale reveal that the FH-bound conformation nevertheless corresponds to a minimum in the Gibbs free energy plot. In contrast to the GM1 conformation recognized by SV40, the FH-bound GM1 conformation is associated with poor NOE restraints, explaining how it escaped(1)H-(1)H NOE-restrained modeling in the past and highlighting the necessity for ensemble representations of glycan structures. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Voxel-Based Morphometry ALE meta-analysis of Bipolar Disorder

NASA Astrophysics Data System (ADS)

Magana, Omar; Laird, Robert

2012-03-01

A meta-analysis was performed independently to view the changes in gray matter (GM) on patients with Bipolar disorder (BP). The meta-analysis was conducted on a Talairach Space using GingerALE to determine the voxels and their permutation. In order to achieve the data acquisition, published experiments and similar research studies were uploaded onto the online Voxel-Based Morphometry database (VBM). By doing so, coordinates of activation locations were extracted from Bipolar disorder related journals utilizing Sleuth. Once the coordinates of given experiments were selected and imported to GingerALE, a Gaussian was performed on all foci points to create the concentration points of GM on BP patients. The results included volume reductions and variations of GM between Normal Healthy controls and Patients with Bipolar disorder. A significant amount of GM clusters were obtained in Normal Healthy controls over BP patients on the right precentral gyrus, right anterior cingulate, and the left inferior frontal gyrus. In future research, more published journals could be uploaded onto the database and another VBM meta-analysis could be performed including more activation coordinates or a variation of age groups.

Clinical and molecular analysis of GM2 gangliosidosis in two apparent littermate kittens of the Japanese domestic cat.

PubMed

Hasegawa, Daisuke; Yamato, Osamu; Kobayashi, Masanori; Fujita, Michio; Nakamura, Shinichiro; Takahashi, Kimimasa; Satoh, Hiroyuki; Shoda, Toru; Hayashi, Daisuke; Yamasaki, Masahiro; Maede, Yoshimitsu; Arai, Toshiro; Orima, Hiromitsu

2007-06-01

This case report documents clinical and molecular findings in two littermate kittens of the Japanese domestic cat with GM2 gangliosidosis variant 0. Analysis included detailed physical, magnetic resonance imaging, biochemical, pathological and genetic examinations. At first, these littermate kittens showed typical cerebellar signs at approximately 2 months of age. About 2 months later, they progressively showed other neurological signs and subsequently died at about 7 months of age. Magnetic resonance imaging just before the death showed an enlarged ventricular system, T1 hyperintensity in the internal capsule, and T2 hyperintensity in the white matter of the whole brain. Histological findings suggested a type of lysosomal storage disease. Biochemical studies demonstrated that the kittens were affected with GM2 gangliosidosis variant 0, and a DNA assay finally demonstrated that these animals were homozygous for the mutation, which the authors had identified in a different family of the Japanese domestic cat. The findings in the present cases provide useful information about GM2 gangliosidosis variant 0 in Japanese domestic cats.

Impact of seaweed beachings on dynamics of δ(15)N isotopic signatures in marine macroalgae.

PubMed

Lemesle, Stéphanie; Mussio, Isabelle; Rusig, Anne-Marie; Menet-Nédélec, Florence; Claquin, Pascal

2015-08-15

A fine-scale survey of δ(15)N, δ(13)C, tissue-N in seaweeds was conducted using samples from 17 sampling points at two sites (Grandcamp-Maisy (GM), Courseulles/Mer (COU)) along the French coast of the English Channel in 2012 and 2013. Partial triadic analysis was performed on the parameter data sets and revealed the functioning of three areas: one estuary (EstA) and two rocky areas (GM(∗), COU(∗)). In contrast to oceanic and anthropogenic reference points similar temporal dynamics characterized δ(15)N signatures and N contents at GM(∗) and COU(∗). Nutrient dynamics were similar: the N-concentrations in seawater originated from the River Seine and local coastal rivers while P-concentrations mainly from these local rivers. δ(15)N at GM(∗) were linked to turbidity suggesting inputs of autochthonous organic matter from large-scale summer seaweed beachings made up of a mixture of Rhodophyta, Phaeophyta and Chlorophyta species. This study highlights the coupling between seaweed beachings and nitrogen sources of intertidal macroalgae. Copyright © 2015 Elsevier Ltd. All rights reserved.

White Matter Atrophy and Cognitive Dysfunctions in Neuromyelitis Optica

PubMed Central

Blanc, Frederic; Noblet, Vincent; Jung, Barbara; Rousseau, François; Renard, Felix; Bourre, Bertrand; Longato, Nadine; Cremel, Nadjette; Di Bitonto, Laure; Kleitz, Catherine; Collongues, Nicolas; Foucher, Jack; Kremer, Stephane; Armspach, Jean-Paul; de Seze, Jerome

2012-01-01

Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N) to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain) and VBM for focal brain volume (GM and WM), NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54%) had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM) was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in NMO patients, particularly in the WM. PMID:22509264

Neuroprotective effects of yoga practice: age-, experience-, and frequency-dependent plasticity

PubMed Central

Villemure, Chantal; Čeko, Marta; Cotton, Valerie A.; Bushnell, M. Catherine

2015-01-01

Yoga combines postures, breathing, and meditation. Despite reported health benefits, yoga’s effects on the brain have received little study. We used magnetic resonance imaging to compare age-related gray matter (GM) decline in yogis and controls. We also examined the effect of increasing yoga experience and weekly practice on GM volume and assessed which aspects of weekly practice contributed most to brain size. Controls displayed the well documented age-related global brain GM decline while yogis did not, suggesting that yoga contributes to protect the brain against age-related decline. Years of yoga experience correlated mostly with GM volume differences in the left hemisphere (insula, frontal operculum, and orbitofrontal cortex) suggesting that yoga tunes the brain toward a parasympatically driven mode and positive states. The number of hours of weekly practice correlated with GM volume in the primary somatosensory cortex/superior parietal lobule (S1/SPL), precuneus/posterior cingulate cortex (PCC), hippocampus, and primary visual cortex (V1). Commonality analyses indicated that the combination of postures and meditation contributed the most to the size of the hippocampus, precuneus/PCC, and S1/SPL while the combination of meditation and breathing exercises contributed the most to V1 volume. Yoga’s potential neuroprotective effects may provide a neural basis for some of its beneficial effects. PMID:26029093

Synthesis and Evaluation of GM2-Monophosphoryl Lipid A Conjugate as a Fully Synthetic Self-Adjuvant Cancer Vaccine.

PubMed

Zhou, Zhifang; Mandal, Satadru S; Liao, Guochao; Guo, Jiatong; Guo, Zhongwu

2017-09-12

An efficient method was developed for the synthesis of a GM2 derivative suitable for the conjugation with various biomolecules. This GM2 derivative was covalently linked to keyhole limpet hemocyanin (KLH) and monophosphoryl lipid A (MPLA) to form novel therapeutic cancer vaccines. Immunological evaluations of the resultant conjugates in mice revealed that they elicited robust GM2-specific overall and IgG antibody responses. Moreover, the GM2-MPLA conjugate was disclosed to elicit strong immune responses without the use of an adjuvant, proving its self-adjuvant property. The antisera of both conjugates showed strong binding and mediated similarly effective complement-dependent cytotoxicity to GM2-expressing cancer cell line MCF-7. Based on these results, it was concluded that both GM2-MPLA and GM2-KLH are promising candidates as therapeutic cancer vaccines, whereas fully synthetic GM2-MPLA, which has homogeneous and well-defined structure and self-adjuvant property, deserves more attention and studies.

Cognitive correlates of white matter lesion load and brain atrophy

PubMed Central

Dong, Chuanhui; Nabizadeh, Nooshin; Caunca, Michelle; Cheung, Ying Kuen; Rundek, Tatjana; Elkind, Mitchell S.V.; DeCarli, Charles; Sacco, Ralph L.; Stern, Yaakov

2015-01-01

Objective: We investigated white matter lesion load and global and regional brain volumes in relation to domain-specific cognitive performance in the stroke-free Northern Manhattan Study (NOMAS) population. Methods: We quantified white matter hyperintensity volume (WMHV), total cerebral volume (TCV), and total lateral ventricular (TLV) volume, as well as hippocampal and cortical gray matter (GM) lobar volumes in a subgroup. We used general linear models to examine MRI markers in relation to domain-specific cognitive performance, adjusting for key covariates. Results: MRI and cognitive data were available for 1,163 participants (mean age 70 ± 9 years; 60% women; 66% Hispanic, 17% black, 15% white). Across the entire sample, those with greater WMHV had worse processing speed. Those with larger TLV volume did worse on episodic memory, processing speed, and semantic memory tasks, and TCV did not explain domain-specific variability in cognitive performance independent of other measures. Age was an effect modifier, and stratified analysis showed that TCV and WMHV explained variability in some domains above age 70. Smaller hippocampal volume was associated with worse performance across domains, even after adjusting for APOE ε4 and vascular risk factors, whereas smaller frontal lobe volumes were only associated with worse executive function. Conclusions: In this racially/ethnically diverse, community-based sample, white matter lesion load was inversely associated with cognitive performance, independent of brain atrophy. Lateral ventricular, hippocampal, and lobar GM volumes explained domain-specific variability in cognitive performance. PMID:26156514

Effects of Hormone Therapy on Brain Volumes Changes of Postmenopausal Women Revealed by Optimally-Discriminative Voxel-Based Morphometry

PubMed Central

Zhang, Tianhao; Casanova, Ramon; Resnick, Susan M.; Manson, JoAnn E.; Baker, Laura D.; Padual, Claudia B.; Kuller, Lewis H.; Bryan, R. Nick; Espeland, Mark A.; Davatzikos, Christos

2016-01-01

Backgrounds The Women's Health Initiative Memory Study Magnetic Resonance Imaging (WHIMS-MRI) provides an opportunity to evaluate how menopausal hormone therapy (HT) affects the structure of older women’s brains. Our earlier work based on region of interest (ROI) analysis demonstrated potential structural changes underlying adverse effects of HT on cognition. However, the ROI-based analysis is limited in statistical power and precision, and cannot provide fine-grained mapping of whole-brain changes. Methods We aimed to identify local structural differences between HT and placebo groups from WHIMS-MRI in a whole-brain refined level, by using a novel method, named Optimally-Discriminative Voxel-Based Analysis (ODVBA). ODVBA is a recently proposed imaging pattern analysis approach for group comparisons utilizing a spatially adaptive analysis scheme to accurately locate areas of group differences, thereby providing superior sensitivity and specificity to detect the structural brain changes over conventional methods. Results Women assigned to HT treatments had significant Gray Matter (GM) losses compared to the placebo groups in the anterior cingulate and the adjacent medial frontal gyrus, and the orbitofrontal cortex, which persisted after multiple comparison corrections. There were no regions where HT was significantly associated with larger volumes compared to placebo, although a trend of marginal significance was found in the posterior cingulate cortical area. The CEE-Alone and CEE+MPA groups, although compared with different placebo controls, demonstrated similar effects according to the spatial patterns of structural changes. Conclusions HT had adverse effects on GM volumes and risk for cognitive impairment and dementia in older women. These findings advanced our understanding of the neurobiological underpinnings of HT effects. PMID:26974440

Individual structural differences in left inferior parietal area are associated with schoolchildrens' arithmetic scores

PubMed Central

Li, Yongxin; Hu, Yuzheng; Wang, Yunqi; Weng, Jian; Chen, Feiyan

2013-01-01

Arithmetic skill is of critical importance for academic achievement, professional success and everyday life, and childhood is the key period to acquire this skill. Neuroimaging studies have identified that left parietal regions are a key neural substrate for representing arithmetic skill. Although the relationship between functional brain activity in left parietal regions and arithmetic skill has been studied in detail, it remains unclear about the relationship between arithmetic achievement and structural properties in left inferior parietal area in schoolchildren. The current study employed a combination of voxel-based morphometry (VBM) for high-resolution T1-weighted images and fiber tracking on diffusion tensor imaging (DTI) to examine the relationship between structural properties in the inferior parietal area and arithmetic achievement in 10-year-old schoolchildren. VBM of the T1-weighted images revealed that individual differences in arithmetic scores were significantly and positively correlated with the gray matter (GM) volume in the left intraparietal sulcus (IPS). Fiber tracking analysis revealed that the forceps major, left superior longitudinal fasciculus (SLF), bilateral inferior longitudinal fasciculus (ILF) and inferior fronto-occipital fasciculus (IFOF) were the primary pathways connecting the left IPS with other brain areas. Furthermore, the regression analysis of the probabilistic pathways revealed a significant and positive correlation between the fractional anisotropy (FA) values in the left SLF, ILF and bilateral IFOF and arithmetic scores. The brain structure-behavior correlation analyses indicated that the GM volumes in the left IPS and the FA values in the tract pathways connecting left IPS were both related to children's arithmetic achievement. The present findings provide evidence that individual structural differences in the left IPS are associated with arithmetic scores in schoolchildren. PMID:24367320

Language comprehension in nonspeaking children with severe cerebral palsy: Neuroanatomical substrate?

PubMed

Geytenbeek, Joke J; Oostrom, Kim J; Harlaar, Laurike; Becher, Jules G; Knol, Dirk L; Barkhof, Frederik; Pinto, Pedro S; Vermeulen, R Jeroen

2015-09-01

To identify relations between brain abnormalities and spoken language comprehension, MRI characteristics of 80 nonspeaking children with severe CP were examined. MRI scans were analysed for patterns of brain abnormalities and scored for specific MRI measures: white matter (WM) areas; size of lateral ventricles, WM abnormality/reduction, cysts, subarachnoid space, corpus callosum thinning and grey matter (GM) areas; cortical GM abnormalities, thalamus, putamen, globus pallidus and nucleus caudatus and cerebellar abnormalities. Language comprehension was assessed with a new validated instrument (C-BiLLT). MRI scans of 35 children were classified as a basal ganglia necrosis (BGN) pattern, with damage to central GM areas; in 60% of these children damage to WM areas was also found. MRI scans of 13 children were classified as periventricular leukomalacia (PVL) with little concomitant damage to central GM areas, 13 as malformations and 19 as miscellaneous. Language comprehension was best in children with BGN, followed by malformations and miscellaneous, and was poorest in PVL. Linear regression modelling per pattern group (malformations excluded), with MRI measures as independent variables, revealed that corpus callosum thinning in BGN and parieto-occipital WM reduction in PVL were the most important explanatory factors for poor language comprehension. No MRI measures explained outcomes in language comprehension in the miscellaneous group. Comprehension of spoken language differs between MRI patterns of severe CP. In children with BGN and PVL differences in language comprehension performance is attributed to damage in the WM areas. Language comprehension was most affected in children with WM lesions in the subcortical and then periventricular areas, most characteristic for children with PVL. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Use of O-15 water and C-11 butanol to measure cerebral blood flow (CBF) and water permeability with positron emission tomography (PET)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herscovitch, P.; Raichle, M.E.; Kilbourn, M.R.

1985-05-01

Tracers used to measure CBF with PET and the Kety autoradiographic approach should freely cross the blood-brain barrier. 0-15 water, which is not freely permeable, may underestimate CBF, especially at higher flows. The authors determined this under-estimation relative to flow measured with a freely diffusible tracer, C-11 butanol and used these data to calculate the extraction (E) and permeability surface area product (PS) for 0-15 water. Paired flow measurements were made with 0-15 water (CBF-wat) and C-11 butanol (CBF-but) in eight normal human subjects. Average CBF-but, 55.6 ml/(min . 100g) was significantly greater than CBF-water, 47.6 ml/(min . 100g). Themore » ratio of regional gray matter (GM) flow to white matter (WM) flow was significantly greater with C-11 butanol, indicating a greater underestimation of CBF with 0-15 water in the higher flow GM. Average E for water was 0.92 in WM and 0.82 in GM. The mean PS in GM, 148 ml/(min . 100g), was significantly greater than in WM, 94 ml/(min . 100g). Simulation studies demonstrated that a measurement error in CBF-wat or CBF-but causes an approximately equivalent error in E but a considerably larger error in PS due to the sensitivity of the equation, PS=-CBF . ln(1-E), to variations in E. Modest errors in E and PS result from tissue heterogeneity that occurs due to the limited spatial resolution of PET. The authors' measurements of E and PS for water are similar to data obtained by more invasive methods and demonstrate the ability of PET to measure brain water permeability.« less

The relation between gray matter volume and the use of alcohol, tobacco, cocaine and cannabis in male polysubstance users.

PubMed

Kaag, A M; Schulte, M H J; Jansen, J M; van Wingen, G; Homberg, J; van den Brink, W; Wiers, R W; Schmaal, L; Goudriaan, A E; Reneman, L

2018-06-01

Neuroimaging studies have demonstrated gray matter (GM) volume abnormalities in substance users. While the majority of substance users are polysubstance users, very little is known about the relation between GM volume abnormalities and polysubstance use. In this study we assessed the relation between GM volume, and the use of alcohol, tobacco, cocaine and cannabis as well as the total number of substances used, in a sample of 169 males: 15 non-substance users, 89 moderate drinkers, 27 moderate drinkers who also smoke tobacco, 13 moderate drinkers who also smoke tobacco and use cocaine, 10 heavy drinkers who smoke tobacco and use cocaine and 15 heavy drinkers who smoke tobacco, cannabis and use cocaine. Regression analyses showed that there was a negative relation between the number of substances used and volume of the dorsal medial prefrontal cortex (mPFC) and the ventral mPFC. Without controlling for the use of other substances, the volume of the dorsal mPFC was negatively associated with the use of alcohol, tobacco, and cocaine. After controlling for the use of other substances, a negative relation was found between tobacco and cocaine and volume of the thalami and ventrolateral PFC, respectively. These findings indicate that mPFC alterations may not be substance-specific, but rather related to the number of substances used, whereas, thalamic and ventrolateral PFC pathology is specifically associated with tobacco and cocaine use, respectively. These findings are important, as the differential alterations in GM volume may underlie different cognitive deficits associated with substance use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Less Daily Computer Use is Related to Smaller Hippocampal Volumes in Cognitively Intact Elderly.

PubMed

Silbert, Lisa C; Dodge, Hiroko H; Lahna, David; Promjunyakul, Nutta-On; Austin, Daniel; Mattek, Nora; Erten-Lyons, Deniz; Kaye, Jeffrey A

2016-01-01

Computer use is becoming a common activity in the daily life of older individuals and declines over time in those with mild cognitive impairment (MCI). The relationship between daily computer use (DCU) and imaging markers of neurodegeneration is unknown. The objective of this study was to examine the relationship between average DCU and volumetric markers of neurodegeneration on brain MRI. Cognitively intact volunteers enrolled in the Intelligent Systems for Assessing Aging Change study underwent MRI. Total in-home computer use per day was calculated using mouse movement detection and averaged over a one-month period surrounding the MRI. Spearman's rank order correlation (univariate analysis) and linear regression models (multivariate analysis) examined hippocampal, gray matter (GM), white matter hyperintensity (WMH), and ventricular cerebral spinal fluid (vCSF) volumes in relation to DCU. A voxel-based morphometry analysis identified relationships between regional GM density and DCU. Twenty-seven cognitively intact participants used their computer for 51.3 minutes per day on average. Less DCU was associated with smaller hippocampal volumes (r = 0.48, p = 0.01), but not total GM, WMH, or vCSF volumes. After adjusting for age, education, and gender, less DCU remained associated with smaller hippocampal volume (p = 0.01). Voxel-wise analysis demonstrated that less daily computer use was associated with decreased GM density in the bilateral hippocampi and temporal lobes. Less daily computer use is associated with smaller brain volume in regions that are integral to memory function and known to be involved early with Alzheimer's pathology and conversion to dementia. Continuous monitoring of daily computer use may detect signs of preclinical neurodegeneration in older individuals at risk for dementia.

Diffusion tensor imaging of the human cerebellar pathways and their interplay with cerebral macrostructure

PubMed Central

Keser, Zafer; Hasan, Khader M.; Mwangi, Benson I.; Kamali, Arash; Ucisik-Keser, Fehime Eymen; Riascos, Roy F.; Yozbatiran, Nuray; Francisco, Gerard E.; Narayana, Ponnada A.

2015-01-01

Cerebellar white matter (WM) connections to the central nervous system are classified functionally into the Spinocerebellar (SC), vestibulocerebellar (VC), and cerebrocerebellar subdivisions. The SC pathways project from spinal cord to cerebellum, whereas the VC pathways project from vestibular organs of the inner ear. Cerebrocerebellar connections are composed of feed forward and feedback connections between cerebrum and cerebellum including the cortico-ponto-cerebellar (CPC) pathways being of cortical origin and the dentate-rubro-thalamo-cortical (DRTC) pathway being of cerebellar origin. In this study we systematically quantified the whole cerebellar system connections using diffusion tensor magnetic resonance imaging (DT-MRI). Ten right-handed healthy subjects (7 males and 3 females, age range 20–51 years) were studied. DT-MRI data were acquired with a voxel size = 2 mm × 2 mm × 2 mm at a 3.0 Tesla clinical MRI scanner. The DT-MRI data were prepared and analyzed using anatomically-guided deterministic tractography methods to reconstruct the SC, DRTC, fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC) and occipito-ponto-cerebellar (OPC). The DTI-attributes or the cerebellar tracts along with their cortical representation (Brodmann areas) were presented in standard Montréal Neurological Institute space. All cerebellar tract volumes were quantified and correlated with volumes of cerebral cortical, subcortical gray matter (GM), cerebral WM and cerebellar GM, and cerebellar WM. On our healthy cohort, the ratio of total cerebellar GM-to-WM was ~3.29 ± 0.24, whereas the ratio of cerebral GM-to-WM was approximately 1.10 ± 0.11. The sum of all cerebellar tract volumes is ~25.8 ± 7.3 mL, or a percentage of 1.6 ± 0.45 of the total intracranial volume (ICV). PMID:25904851

Combined replacement effects of human modified β-hexosaminidase B and GM2 activator protein on GM2 gangliosidoses fibroblasts.

PubMed

Kitakaze, Keisuke; Tasaki, Chikako; Tajima, Youichi; Hirokawa, Takatsugu; Tsuji, Daisuke; Sakuraba, Hitoshi; Itoh, Kohji

2016-09-01

GM2 gangliosidoses are autosomal recessive lysosomal storage diseases (LSDs) caused by mutations in the HEXA , HEXB and GM2A genes, which encode the human lysosomal β-hexosaminidase (Hex) α- and β-subunits, and GM2 activator protein (GM2A), respectively. These diseases are associated with excessive accumulation of GM2 ganglioside (GM2) in the brains of patients with neurological symptoms. Here we established a CHO cell line overexpressing human GM2A, and purified GM2A from the conditioned medium, which was taken up by fibroblasts derived from a patient with GM2A deficiency, and had the therapeutic effects of reducing the GM2 accumulated in fibroblasts when added to the culture medium. We also demonstrated for the first time that recombinant GM2A could enhance the replacement effect of human modified HexB (modB) with GM2-degrading activity, which is composed of homodimeric altered β-subunits containing a partial amino acid sequence of the α-subunit, including the GSEP loop necessary for binding to GM2A, on reduction of the GM2 accumulated in fibroblasts derived from a patient with Tay-Sachs disease, a HexA (αβ heterodimer) deficiency, caused by HEXA mutations. We predicted the same manner of binding of GM2A to the GSEP loop located in the modified HexB β-subunit to that in the native HexA α-subunit on the basis of the x-ray crystal structures. These findings suggest the effectiveness of combinational replacement therapy involving the human modified HexB and GM2A for GM2 gangliosidoses.

Evaluation of the Effect of Fingolimod Treatment on Microglial Activation Using Serial PET Imaging in Multiple Sclerosis.

PubMed

Sucksdorff, Marcus; Rissanen, Eero; Tuisku, Jouni; Nuutinen, Salla; Paavilainen, Teemu; Rokka, Johanna; Rinne, Juha; Airas, Laura

2017-10-01

Traditionally, multiple sclerosis (MS) has been considered a white matter disease with focal inflammatory lesions. It is, however, becoming clear that significant pathology, such as microglial activation, also takes place outside the plaque areas, that is, in areas of normal-appearing white matter (NAWM) and gray matter (GM). Microglial activation can be detected in vivo using 18-kDa translocator protein (TSPO)-binding radioligands and PET. It is unknown whether fingolimod affects microglial activation in MS. The aim of this study was to investigate whether serial PET can be used to evaluate the effect of fingolimod treatment on microglial activation. Methods: Ten relapsing-remitting MS patients were studied using the TSPO radioligand 11 C-( R )-PK11195. Imaging was performed at baseline and after 8 and 24 wk of fingolimod treatment. Eight healthy individuals were imaged for comparison. Microglial activation was evaluated as distribution volume ratio of 11 C-( R )-PK11195. Results: The patients had MS for an average of 7.9 ± 4.3 y (mean ± SD), their total relapses averaged 4 ± 2.4, and their Expanded Disability Status Scale was 2.7 ± 0.5. The patients were switched to fingolimod because of safety reasons or therapy escalation. The mean washout period before the initiation of fingolimod was 2.3 ± 1.1 mo. The patients were clinically stable on fingolimod. At baseline, microglial activation was significantly higher in the combined NAWM and GM areas of MS patients than in healthy controls ( P = 0.021). 11 C-( R )-PK11195 binding was reduced (-12.31%) within the combined T2 lesion area after 6 mo of fingolimod treatment ( P = 0.040) but not in the areas of NAWM or GM. Conclusion: Fingolimod treatment reduced microglial/macrophage activation at the site of focal inflammatory lesions, presumably by preventing leukocyte trafficking from the periphery. It did not affect the widespread, diffuse microglial activation in the NAWM and GM. The study opens new vistas for designing future therapeutic studies in MS that use the evaluation of microglial activation as an imaging outcome measure. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Decreased glutathione levels predict loss of brain volume in children and adolescents with first-episode psychosis in a two-year longitudinal study.

PubMed

Fraguas, David; Gonzalez-Pinto, Ana; Micó, Juan Antonio; Reig, Santiago; Parellada, Mara; Martínez-Cengotitabengoa, Mónica; Castro-Fornieles, Josefina; Rapado-Castro, Marta; Baeza, Immaculada; Janssen, Joost; Desco, Manuel; Leza, Juan Carlos; Arango, Celso

2012-05-01

Progressive loss of cortical gray matter (GM), as measured by magnetic resonance imaging, has been described early in the course of first-episode psychosis. This study aims to assess the relationship between oxidative balance and progression of cortical GM changes in a multicenter sample of first-episode early-onset psychosis (EOP) patients from baseline to two-year follow-up. A total of 48 patients (13 females, mean age 15.9±1.5 years) and 56 age- and gender-matched healthy controls (19 females, 15.3±1.5 years) were assessed. Magnetic resonance imaging (MRI) scans performed both at the time of the first psychotic episode and 2 years later were used for volumetric measurements of left and right gray matter regions (frontal, parietal, and temporal lobes) and total sulcal cerebrospinal fluid (CSF). Total glutathione (GSH) blood levels were determined at baseline. In patients, after controlling for possible confounding variables, lower baseline GSH levels were significantly associated with greater volume decrease in left frontal (B=0.034, 95% confidence interval (CI): 0.011 to 0.056, r=0.620, p=0.006), parietal (B=0.039, 95% CI: 0.020 to 0.059, r=0.739, p=0.001), temporal (B=0.026, 95% CI: 0.016 to 0.036, r=0.779, p<0.001), and total (B=0.022, 95% CI: 0.014 to 0.031, r=0.803, p<0.001) gray matter, and with greater increase in total CSF (B=-0.560, 95% CI: -0.270 to -0.850, r=-0.722, p=0.001). Controls did not show significant associations between brain volume changes and GSH levels. GSH deficit during the first psychotic episode was related to greater loss of cortical GM two years later in patients with first-episode EOP, suggesting that oxidative damage may contribute to the progressive loss of cortical GM found in patients with first-episode psychosis. Copyright © 2012 Elsevier B.V. All rights reserved.

Differential Hemispheric Predilection of Microstructural White Matter and Functional Connectivity Abnormalities between Respectively Semantic and Behavioral Variant Frontotemporal Dementia.

PubMed

Meijboom, Rozanna; Steketee, Rebecca M E; Ham, Leontine S; van der Lugt, Aad; van Swieten, John C; Smits, Marion

2017-01-01

Semantic dementia (SD) and behavioral variant frontotemporal dementia (bvFTD), subtypes of frontotemporal dementia, are characterized by distinct clinical symptoms and neuroimaging features, with predominant left temporal grey matter (GM) atrophy in SD and bilateral or right frontal GM atrophy in bvFTD. Such differential hemispheric predilection may also be reflected by other neuroimaging features, such as brain connectivity. This study investigated white matter (WM) microstructure and functional connectivity differences between SD and bvFTD, focusing on the hemispheric predilection of these differences. Eight SD and 12 bvFTD patients, and 17 controls underwent diffusion tensor imaging and resting state functional MRI at 3T. Whole-brain WM microstructure was assessed to determine distinct WM tracts affected in SD and bvFTD. For these tracts, diffusivity measures and lateralization indices were calculated. Functional connectivity was established for GM regions affected in early stage SD or bvFTD. Results of a direct comparison between SD and bvFTD are reported. Whole-brain WM microstructure abnormalities were more pronounced in the left hemisphere in SD and bilaterally- with a slight predilection for the right- in bvFTD. Lateralization of tract-specific abnormalities was seen in SD only, toward the left hemisphere. Functional connectivity of disease-specific regions was mainly decreased bilaterally in SD and in the right hemisphere in bvFTD. SD and bvFTD show WM microstructure and functional connectivity abnormalities in different regions, that are respectively more pronounced in the left hemisphere in SD and in the right hemisphere in bvFTD. This indicates differential hemispheric predilection of brain connectivity abnormalities between SD and bvFTD.

Using Correlative Properties of Neighboring Pixels to Enhance Contrast-to-Noise Ratio of Abnormal Hippocampus in Patients With Intractable Epilepsy and Mesial Temporal Sclerosis.

PubMed

Parsons, Matthew S; Sharma, Aseem; Hildebolt, Charles

2018-06-12

To test whether an image-processing algorithm can aid in visualization of mesial temporal sclerosis on magnetic resonance imaging by selectively increasing contrast-to-noise ratio (CNR) between abnormal hippocampus and normal brain. In this Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, baseline coronal fluid-attenuated inversion recovery images of 18 adults (10 females, eight males; mean age 41.2 years) with proven mesial temporal sclerosis were processed using a custom algorithm to produce corresponding enhanced images. Average (Hmean) and maximum (Hmax) CNR for abnormal hippocampus were calculated relative to normal ipsilateral white matter. CNR values for normal gray matter (GM) were similarly calculated using ipsilateral cingulate gyrus as the internal control. To evaluate effect of image processing on visual conspicuity of hippocampal signal alteration, a neuroradiologist masked to the side of hippocampal abnormality rated signal intensity (SI) of hippocampi on baseline and enhanced images using a five-point scale (definitely abnormal to definitely normal). Differences in Hmean, Hmax, GM, and SI ratings for abnormal hippocampi on baseline and enhanced images were assessed for statistical significance. Both Hmean and Hmax were significantly higher in enhanced images as compared to baseline images (p < 0.0001 for both). There was no significant difference in the GM between baseline and enhanced images (p = 0.9375). SI ratings showed a more confident identification of abnormality on enhanced images (p = 0.0001). Image-processing resulted in increased CNR of abnormal hippocampus without affecting the CNR of normal gray matter. This selective increase in conspicuity of abnormal hippocampus was associated with more confident identification of hippocampal signal alteration. Copyright © 2018 Academic Radiology. Published by Elsevier Inc. All rights reserved.

Characterizing Brain Structures and Remodeling after TBI Based on Information Content, Diffusion Entropy

PubMed Central

Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P.; Zhang, Zheng Gang; Lehman, Norman L.; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

2013-01-01

Background To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Methods Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Results Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Conclusions Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease. PMID:24143186

Characterizing brain structures and remodeling after TBI based on information content, diffusion entropy.

PubMed

Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P; Zhang, Zheng Gang; Lehman, Norman L; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

2013-01-01

To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease.

Effect of structural modifications of ganglioside GM2 on intra-molecular carbohydrate-to-carbohydrate interaction and enzymatic susceptibility.

PubMed

Li, Yu-Teh; Li, Su-Chen; Kiso, Makoto; Ishida, Hideharu; Mauri, Laura; Raimondi, Laura; Bernardi, Anna; Sonnino, Sandro

2008-03-01

The effect of inter-molecular carbohydrate-to-carbohydrate interaction on basic cell biological processes has been well documented and appreciated. In contrast, very little is known about the intra-molecular carbohydrate-to-carbohydrate interaction. The presence of an interaction between the GalNAc and the Neu5Ac in GM2 detected by NMR spectroscopy represents a well-defined intra-molecular carbohydrate-to-carbohydrate interaction. This intriguing interaction is responsible for the GM2-epitope, GalNAcbeta1-->4(Neu5Acalpha2-->3)Gal-, to exhibit a rigid and compact conformation. We hypothesized that this compact conformation may be the cause for both the GalNAc and the Neu5Ac in GM2 to be refractory to enzymatic hydrolysis and the GM2 activator protein is able to interact with the compact trisaccharide GM2-epitope, rendering the GalNAc and the Neu5Ac accessible to beta-hexosaminidase A and sialidase. We have used a series of structurally modified GM2 to study the effect of modifications of sugar chains on the conformation and enzymatic susceptibility of this ganglioside. Our hypothesis was borne out by the fact that when the GalNAcbeta1-->4Gal linkage in GM2 was converted to the GalNAcbeta1-->6Gal, both the GalNAc and the Neu5Ac became susceptible to beta-hexosaminidase A and sialidase, respectively, without GM2 activator protein. We hope our work will engender interest in identifying other intra-molecular carbohydrate-to-carbohydrate interactions in glycoconjugates.

Evolution and Structural Analyses of Glossina morsitans (Diptera; Glossinidae) Tetraspanins

PubMed Central

Murungi, Edwin K.; Kariithi, Henry M.; Adunga, Vincent; Obonyo, Meshack; Christoffels, Alan

2014-01-01

Tetraspanins are important conserved integral membrane proteins expressed in many organisms. Although there is limited knowledge about the full repertoire, evolution and structural characteristics of individual members in various organisms, data obtained so far show that tetraspanins play major roles in membrane biology, visual processing, memory, olfactory signal processing, and mechanosensory antennal inputs. Thus, these proteins are potential targets for control of insect pests. Here, we report that the genome of the tsetse fly, Glossina morsitans (Diptera: Glossinidae) encodes at least seventeen tetraspanins (GmTsps), all containing the signature features found in the tetraspanin superfamily members. Whereas six of the GmTsps have been previously reported, eleven could be classified as novel because their amino acid sequences do not map to characterized tetraspanins in the available protein data bases. We present a model of the GmTsps by using GmTsp42Ed, whose presence and expression has been recently detected by transcriptomics and proteomics analyses of G. morsitans. Phylogenetically, the identified GmTsps segregate into three major clusters. Structurally, the GmTsps are largely similar to vertebrate tetraspanins. In view of the exploitation of tetraspanins by organisms for survival, these proteins could be targeted using specific antibodies, recombinant large extracellular loop (LEL) domains, small-molecule mimetics and siRNAs as potential novel and efficacious putative targets to combat African trypanosomiasis by killing the tsetse fly vector. PMID:26462947

Where the world stands still: turnaround as a strong test of ΛCDM cosmology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pavlidou, V.; Tomaras, T.N., E-mail: pavlidou@physics.uoc.gr, E-mail: tomaras@physics.uoc.gr

Our intuitive understanding of cosmic structure formation works best in scales small enough so that isolated, bound, relaxed gravitating systems are no longer adjusting their radius; and large enough so that space and matter follow the average expansion of the Universe. Yet one of the most robust predictions of ΛCDM cosmology concerns the scale that separates these limits: the turnaround radius, which is the non-expanding shell furthest away from the center of a bound structure. We show that the maximum possible value of the turnaround radius within the framework of the ΛCDM model is, for a given mass M, equalmore » to (3GM/Λ c{sup 2}){sup 1/3}, with G Newton's constant and c the speed of light, independently of cosmic epoch, exact nature of dark matter, or baryonic effects. We discuss the possible use of this prediction as an observational test for ΛCDM cosmology. Current data appear to favor ΛCDM over alternatives with local inhomogeneities and no Λ. However there exist several local-universe structures that have, within errors, reached their limiting size. With improved determinations of their turnaround radii and the enclosed mass, these objects may challenge the limit and ΛCDM cosmology.« less

Hierarchical brain tissue segmentation and its application in multiple sclerosis and Alzheimer's disease

NASA Astrophysics Data System (ADS)

Lei, Tianhu; Udupa, Jayaram K.; Moonis, Gul; Schwartz, Eric; Balcer, Laura

2005-04-01

Based on Fuzzy Connectedness (FC) object delineation principles and algorithms, a hierarchical brain tissue segmentation technique has been developed for MR images. After MR image background intensity inhomogeneity correction and intensity standardization, three FC objects for cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) are generated via FC object delineation, and an intracranial (IC) mask is created via morphological operations. Then, the IC mask is decomposed into parenchymal (BP) and CSF masks, while the BP mask is separated into WM and GM masks. WM mask is further divided into pure and dirty white matter masks (PWM and DWM). In Multiple Sclerosis studies, a severe white matter lesion (LS) mask is defined from DWM mask. Based on the segmented brain tissue images, a histogram-based method has been developed to find disease-specific, image-based quantitative markers for characterizing the macromolecular manifestation of the two diseases. These same procedures have been applied to 65 MS (46 patients and 19 normal subjects) and 25 AD (15 patients and 10 normal subjects) data sets, each of which consists of FSE PD- and T2-weighted MR images. Histograms representing standardized PD and T2 intensity distributions and their numerical parameters provide an effective means for characterizing the two diseases. The procedures are systematic, nearly automated, robust, and the results are reproducible.

The Neuroanatomical Correlates of Training-Related Perceptuo-Reflex Uncoupling in Dancers

PubMed Central

Nigmatullina, Yuliya; Hellyer, Peter J.; Nachev, Parashkev; Sharp, David J.; Seemungal, Barry M.

2015-01-01

Sensory input evokes low-order reflexes and higher-order perceptual responses. Vestibular stimulation elicits vestibular-ocular reflex (VOR) and self-motion perception (e.g., vertigo) whose response durations are normally equal. Adaptation to repeated whole-body rotations, for example, ballet training, is known to reduce vestibular responses. We investigated the neuroanatomical correlates of vestibular perceptuo-reflex adaptation in ballet dancers and controls. Dancers' vestibular-reflex and perceptual responses to whole-body yaw-plane step rotations were: (1) Briefer and (2) uncorrelated (controls' reflex and perception were correlated). Voxel-based morphometry showed a selective gray matter (GM) reduction in dancers' vestibular cerebellum correlating with ballet experience. Dancers' vestibular cerebellar GM density reduction was related to shorter perceptual responses (i.e. positively correlated) but longer VOR duration (negatively correlated). Contrastingly, controls' vestibular cerebellar GM density negatively correlated with perception and VOR. Diffusion-tensor imaging showed that cerebral cortex white matter (WM) microstructure correlated with vestibular perception but only in controls. In summary, dancers display vestibular perceptuo-reflex dissociation with the neuronatomical correlate localized to the vestibular cerebellum. Controls' robust vestibular perception correlated with a cortical WM network conspicuously absent in dancers. Since primary vestibular afferents synapse in the vestibular cerebellum, we speculate that a cerebellar gating of perceptual signals to cortical regions mediates the training-related attenuation of vestibular perception and perceptuo-reflex uncoupling. PMID:24072889

Quantitative analysis of multiple sclerosis: a feasibility study

NASA Astrophysics Data System (ADS)

Li, Lihong; Li, Xiang; Wei, Xinzhou; Sturm, Deborah; Lu, Hongbing; Liang, Zhengrong

2006-03-01

Multiple Sclerosis (MS) is an inflammatory and demyelinating disorder of the central nervous system with a presumed immune-mediated etiology. For treatment of MS, the measurements of white matter (WM), gray matter (GM), and cerebral spinal fluid (CSF) are often used in conjunction with clinical evaluation to provide a more objective measure of MS burden. In this paper, we apply a new unifying automatic mixture-based algorithm for segmentation of brain tissues to quantitatively analyze MS. The method takes into account the following effects that commonly appear in MR imaging: 1) The MR data is modeled as a stochastic process with an inherent inhomogeneity effect of smoothly varying intensity; 2) A new partial volume (PV) model is built in establishing the maximum a posterior (MAP) segmentation scheme; 3) Noise artifacts are minimized by a priori Markov random field (MRF) penalty indicating neighborhood correlation from tissue mixture. The volumes of brain tissues (WM, GM) and CSF are extracted from the mixture-based segmentation. Experimental results of feasibility studies on quantitative analysis of MS are presented.

Carbon accumulation and storage capacity in mangrove sediments three decades after deforestation within a eutrophic bay.

PubMed

Pérez, A; Machado, W; Gutiérrez, D; Borges, A C; Patchineelam, S R; Sanders, C J

2018-01-01

A dated sediment core from an eutrophic mangrove area presented non-significant differences in carbon accumulation rates before (55.7±10.2gm -2 yr -1 ) and after three decades of deforestation (59.7±7.2gm -2 yr -1 ). Although eutrophication effects appear to compensate the loss of mangrove organic matter input, the results in this work show a threefold lower carbon accumulation than the global averages estimated for mangrove sediments. The effects of increasing eutrophication and enhanced sediment dry bulk density observed after deforestation (~30% higher) did not result in higher carbon stocks. Moreover, the lower TOC:OP (<400) and C:N (~20) molar ratios, as well as increased nutrient accumulation, reflect the dominance of phytoplankton-derived organic matter after deforestation, resulting in less-efficient sedimentary carbon sinks. These results indicate that the organic material deposited from eutrophication may not compensate mangrove deforestation losses on carbon accumulation in mangrove ecosystems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical and MRI correlates of disease progression in a case of nonfluent/agrammatic variant of primary progressive aphasia due to progranulin (GRN) Cys157LysfsX97 mutation.

PubMed

Caso, Francesca; Agosta, Federica; Magnani, Giuseppe; Galantucci, Sebastiano; Spinelli, Edoardo G; Galimberti, Daniela; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

2014-07-15

Little is known about the longitudinal changes of brain damage in patients with sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) and in progranulin (GRN) mutation carriers. This study reports the clinical and MRI longitudinal data of a patient with nfvPPA carrying GRN Cys157LysfsX97 mutation (GRN+). Voxel-based morphometry, tensor-based morphometry and diffusion tensor MRI were applied to evaluate gray matter (GM) and white matter (WM) changes over three years. The prominent clinical feature was motor speech impairment associated with only mild agrammatism. MRI demonstrated a progressive and severe GM atrophy of inferior fronto-insular-temporo-parietal regions with focal damage to frontotemporal and frontoparietal WM connections. This is the first report of longitudinal MRI data in a nfvPPA- GRN+ patient and this report offers new insights into the pathophysiology of the disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway

PubMed Central

Todeschini, Adriane Regina; Dos Santos, Jose Nilson; Handa, Kazuko; Hakomori, Sen-itiroh

2008-01-01

Ganglioside GM2 complexed with tetraspanin CD82 in glycosynaptic microdomain of HCV29 and other epithelial cells inhibits hepatocyte growth factor-induced cMet tyrosine kinase. In addition, adhesion of HCV29 cells to extracellular matrix proteins also activates cMet kinase through “cross-talk” of integrins with cMet, leading to inhibition of cell motility and growth. Present studies indicate that cell motility and growth are greatly influenced by expression of GM2, GM3, or GM2/GM3 complexes, which affect cMet kinase activity of various types of cells, based on the following series of observations: (i) Cells expressing CD82, cultured with GM2 and GM3 cocoated on silica nanospheres, displayed stronger and more consistent motility inhibition than those cultured with GM2 or GM3 alone or with other glycosphingolipids. (ii) GM2-GM3, in the presence of Ca2+ form a heterodimer, as evidenced by electrospray ionization (ESI) mass spectrometry and by specific reactivity with mAb 8E11, directed to GM2/GM3 dimer structure. (iii) Cells expressing cMet and CD82 were characterized by enhanced motility associated with HGF-induced cMet activation. Both cMet and motility were strongly inhibited by culturing cells with GM2/GM3 dimer coated on nanospheres. (iv) Adhesion of HCV29 or YTS-1/CD82 cells to laminin-5-coated plate activated cMet kinase in the absence of HGF, whereas GM2/GM3 dimer inhibited adhesion-induced cMet kinase activity and inhibited cell motility. (v) Inhibited cell motility as in i, iii, and iv was restored to normal level by addition of mAb 8E11, which blocks interaction of GM2/GM3 dimer with CD82. Signaling through Src and MAP kinases is activated or inhibited in close association with cMet kinase, in response to GM2/GM3 dimer interaction with CD82. Thus, a previously uncharacterized GM2/GM3 heterodimer complexed with CD82 inhibits cell motility through CD82-cMet or integrin-cMet pathway. PMID:18272501

Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway.

PubMed

Todeschini, Adriane Regina; Dos Santos, Jose Nilson; Handa, Kazuko; Hakomori, Sen-itiroh

2008-02-12

Ganglioside GM2 complexed with tetraspanin CD82 in glycosynaptic microdomain of HCV29 and other epithelial cells inhibits hepatocyte growth factor-induced cMet tyrosine kinase. In addition, adhesion of HCV29 cells to extracellular matrix proteins also activates cMet kinase through "cross-talk" of integrins with cMet, leading to inhibition of cell motility and growth. Present studies indicate that cell motility and growth are greatly influenced by expression of GM2, GM3, or GM2/GM3 complexes, which affect cMet kinase activity of various types of cells, based on the following series of observations: (i) Cells expressing CD82, cultured with GM2 and GM3 cocoated on silica nanospheres, displayed stronger and more consistent motility inhibition than those cultured with GM2 or GM3 alone or with other glycosphingolipids. (ii) GM2-GM3, in the presence of Ca2+ form a heterodimer, as evidenced by electrospray ionization (ESI) mass spectrometry and by specific reactivity with mAb 8E11, directed to GM2/GM3 dimer structure. (iii) Cells expressing cMet and CD82 were characterized by enhanced motility associated with HGF-induced cMet activation. Both cMet and motility were strongly inhibited by culturing cells with GM2/GM3 dimer coated on nanospheres. (iv) Adhesion of HCV29 or YTS-1/CD82 cells to laminin-5-coated plate activated cMet kinase in the absence of HGF, whereas GM2/GM3 dimer inhibited adhesion-induced cMet kinase activity and inhibited cell motility. (v) Inhibited cell motility as in i, iii, and iv was restored to normal level by addition of mAb 8E11, which blocks interaction of GM2/GM3 dimer with CD82. Signaling through Src and MAP kinases is activated or inhibited in close association with cMet kinase, in response to GM2/GM3 dimer interaction with CD82. Thus, a previously uncharacterized GM2/GM3 heterodimer complexed with CD82 inhibits cell motility through CD82-cMet or integrin-cMet pathway.

Modulation of the Fecal Microbiota in Sprague-Dawley Rats Using Genetically Modified and Isogenic Corn Lines.

PubMed

Li, Penggao; Yang, Chun; Yue, Rong; Zhen, Yaping; Zhuo, Qin; Piao, Jianhua; Yang, Xiaoguang; Xiao, Rong

2018-01-17

This study investigated the composition and proportions of fecal microbiota in Sprague-Dawley rats after consuming two genetically modified (GM) corn lines in comparison with the isogenic corn and the AIN93G standard feed for 10 weeks using bar-coded 16S rRNA gene sequencing. As a result, GM corn did not significantly alter the overall health and alpha-diversity of fecal microbiota. Fecal microbiota structures could be separated into noncorn and corn but not non-GM and GM corn subgroups. Both non-GM and GM corn caused the increase in bacterial populations related to carbohydrates utilization, such as Lactobacillus, Barnesiella, and Bifidobacterium, and the reduction in potentially pathogenic populations, such as Tannerella and Moraxellaceae. In conclusion, similar effects on the fecal microbiota were observed after consuming a GM- and non-GM-corn-based diet for long periods. Further studies are warranted to elucidate the functional relevance of the changes in the proportions of bacterial populations in these diets.

In vivo measurements of T1 relaxation times in mouse brain associated with different modes of systemic administration of manganese chloride.

PubMed

Kuo, Yu-Ting; Herlihy, Amy H; So, Po-Wah; Bhakoo, Kishore K; Bell, Jimmy D

2005-04-01

To measure regional T1 and T2 values for normal C57Bl/6 mouse brain and changes in T1 after systemic administration of manganese chloride (MnCl2) at 9.4 T. C57Bl/6 mice were anesthetized and baseline T1 and T2 measurements obtained prior to measurement of T1 after administration of MnCl2 at 9.4 T. MnCl2 was administered systemically either by the intravenous (IV), intraperitoneal (IP), or subcutaneous (SC) routes. T1 and T2 maps for each MRI transverse slice were generated using commercial software, and T1 and T2 values of white matter (WM), gray matter (GM), pituitary gland, and lateral ventricle were obtained. When compared with baseline values at low-field, significant lengthening of the T1 values was shown at 9.4 T, while no significant change was seen for T2 values. Significant T1 shortening of the normal mouse brain was observed following IV, IP, and SC administration of MnCl2, with IV and IP showing similar acute effects. Significant decreases in T1 values were seen for the pituitary gland and the ventricles 15 minutes after either IV or IP injection. GM showed greater uptake of the contrast agent than WM at 15 and 45 minutes after either IV or IP injections. Although both structures are within the blood-brain barrier (BBB), GM and WM revealed a steady decrease in T1 values at 24 and 72 hours after MnCl2 injection regardless of the route of administration. Systemic administration of MnCl2 by IV and IP routes induced similar time-course of T1 changes in different regions of the mouse brain. Acute effects of MnCl2 administration were mainly influenced by either the presence or absence of BBB. SC injection also provided significant T1 change at subacute stage after MnCl2 administration. Copyright 2005 Wiley-Liss, Inc.

Changes in plant biomass and species composition of alpine Kobresia meadows along altitudinal gradient on the Qinghai-Tibetan Plateau.

PubMed

Wang, ChangTing; Cao, GuangMin; Wang, QiLan; Jing, ZengChun; Ding, LuMing; Long, RuiJun

2008-01-01

Alpine Kobresia meadows are major vegetation types on the Qinghai-Tibetan Plateau. There is growing concern over their relationships among biodiversity, productivity and environments. Despite the importance of species composition, species richness, the type of different growth forms, and plant biomass structure for Kobresia meadow ecosystems, few studies have been focused on the relationship between biomass and environmental gradient in the Kobresia meadow plant communities, particularly in relation to soil moisture and edaphic gradients. We measured the plant species composition, herbaceous litter, aboveground and belowground biomass in three Kobresia meadow plant communities in Haibei Alpine Meadow Ecosystem Research Station from 2001 to 2004. Community differences in plant species composition were reflected in biomass distribution. The total biomass showed a decrease from 13196.96+/-719.69 g/m(2) in the sedge-dominated K. tibetica swamp to 2869.58+/-147.52 g/m(2) in the forb and sedge dominated K. pygmaea meadow, and to 2153.08+/-141.95 g/m(2) in the forbs and grasses dominated K. humilis along with the increase of altitude. The vertical distribution of belowground biomass is distinct in the three meadow communities, and the belowground biomass at the depth of 0-10 cm in K. tibetica swamp meadow was significantly higher than that in K. humilis and K. pygmaea meadows (P<0.01). The herbaceous litter in K. tibetica swamp was significantly higher than those in K. pygnaeca and K. humilis meadows. The effects of plant litter are enhanced when ground water and soil moisture levels are raised. The relative importance of litter and vegetation may vary with soil water availability. In the K. tibetica swamp, total biomass was negatively correlated to species richness (P<0.05); aboveground biomass was positively correlated to soil organic matter, soil moisture, and plant cover (P<0.05); belowground biomass was positively correlated with soil moisture (P<0.05). However, in the K. pygnaeca and K. humilis meadow communities, aboveground biomass was positively correlated to soil organic matter and soil total nitrogen (P<0.05). This suggests that the distribution of biomass coincided with soil moisture and edaphic gradient in alpine meadows.

Structural Abnormalities in Early Tourette Syndrome Children: A Combined Voxel-Based Morphometry and Tract-Based Spatial Statistics Study

PubMed Central

Wang, Jieqiong; Gao, Peiyi; Yin, Guangheng; Zhang, Liping; Lv, Chuankai; Ji, Zhiying; Yu, Tong; Sabel, B. A.; He, Huiguang; Peng, Yun

2013-01-01

Tourette Syndrome (TS) is characterized with chronic motor and vocal tics beginning in childhood. Abnormality of both gray (GM) and white matter (WM) has been observed in cortico-striato-thalamo-cortical circuits and sensory-motor cortex of adult TS patient. It is not clear if these morphological changes are also present in TS children and if there are any microstructural changes of WM. To understand the developmental cause of such changes, we investigated volumetric changes of GM and WM using VBM and microstructural changes of WM using DTI, and correlated these changes with tic severity and duration. T1 images and Diffusion Tensor Images (DTI) from 21 TS children were compared with 20 age and gender matched health control children using a 1.5T Philips scanner. All of the 21 TS children met the DSM-IV-TR criteria. T1 images were analyzed using DARTEL-VBM in conjunction with statistical parametric mapping (SPM). Diffusion tensor imaging (DTI) analysis was performed using Tract-Based Spatial Statistics (TBSS). Brain volume changes were found in left superior temporal gyrus, left and right paracentral gyrus, right precuneous cortex, right pre- and post- central gyrus, left temporal occipital fusiform cortex, right frontal pole, and left lingual gyrus. Significant axial diffusivity (AD) and mean diffusivity (MD) increases were found in anterior thalamic radiation, right cingulum bundle projecting to the cingulate gurus and forceps minor. Decreases in white matter volume (WMV) in the right frontal pole were inversely related with tic severity (YGTSS), and increases in AD and MD were positively correlated with tic severity and duration, respectively. These changes in TS children can be interpreted as signs of neural plasticity in response to the experiential demand. Our findings may suggest that the morphological and microstructural measurements from structural MRI and DTI can potentially be used as a biomarker of the pathophysiologic pattern of early TS children. PMID:24098769

Structural abnormalities in early Tourette syndrome children: a combined voxel-based morphometry and tract-based spatial statistics study.

PubMed

Liu, Yue; Miao, Wen; Wang, Jieqiong; Gao, Peiyi; Yin, Guangheng; Zhang, Liping; Lv, Chuankai; Ji, Zhiying; Yu, Tong; Sabel, B A; He, Huiguang; Peng, Yun

2013-01-01

Tourette Syndrome (TS) is characterized with chronic motor and vocal tics beginning in childhood. Abnormality of both gray (GM) and white matter (WM) has been observed in cortico-striato-thalamo-cortical circuits and sensory-motor cortex of adult TS patient. It is not clear if these morphological changes are also present in TS children and if there are any microstructural changes of WM. To understand the developmental cause of such changes, we investigated volumetric changes of GM and WM using VBM and microstructural changes of WM using DTI, and correlated these changes with tic severity and duration. T1 images and Diffusion Tensor Images (DTI) from 21 TS children were compared with 20 age and gender matched health control children using a 1.5T Philips scanner. All of the 21 TS children met the DSM-IV-TR criteria. T1 images were analyzed using DARTEL-VBM in conjunction with statistical parametric mapping (SPM). Diffusion tensor imaging (DTI) analysis was performed using Tract-Based Spatial Statistics (TBSS). Brain volume changes were found in left superior temporal gyrus, left and right paracentral gyrus, right precuneous cortex, right pre- and post-central gyrus, left temporal occipital fusiform cortex, right frontal pole, and left lingual gyrus. Significant axial diffusivity (AD) and mean diffusivity (MD) increases were found in anterior thalamic radiation, right cingulum bundle projecting to the cingulate gurus and forceps minor. Decreases in white matter volume (WMV) in the right frontal pole were inversely related with tic severity (YGTSS), and increases in AD and MD were positively correlated with tic severity and duration, respectively. These changes in TS children can be interpreted as signs of neural plasticity in response to the experiential demand. Our findings may suggest that the morphological and microstructural measurements from structural MRI and DTI can potentially be used as a biomarker of the pathophysiologic pattern of early TS children.

Discriminative analysis of schizophrenia using support vector machine and recursive feature elimination on structural MRI images.

PubMed

Lu, Xiaobing; Yang, Yongzhe; Wu, Fengchun; Gao, Minjian; Xu, Yong; Zhang, Yue; Yao, Yongcheng; Du, Xin; Li, Chengwei; Wu, Lei; Zhong, Xiaomei; Zhou, Yanling; Fan, Ni; Zheng, Yingjun; Xiong, Dongsheng; Peng, Hongjun; Escudero, Javier; Huang, Biao; Li, Xiaobo; Ning, Yuping; Wu, Kai

2016-07-01

Structural abnormalities in schizophrenia (SZ) patients have been well documented with structural magnetic resonance imaging (MRI) data using voxel-based morphometry (VBM) and region of interest (ROI) analyses. However, these analyses can only detect group-wise differences and thus, have a poor predictive value for individuals. In the present study, we applied a machine learning method that combined support vector machine (SVM) with recursive feature elimination (RFE) to discriminate SZ patients from normal controls (NCs) using their structural MRI data. We first employed both VBM and ROI analyses to compare gray matter volume (GMV) and white matter volume (WMV) between 41 SZ patients and 42 age- and sex-matched NCs. The method of SVM combined with RFE was used to discriminate SZ patients from NCs using significant between-group differences in both GMV and WMV as input features. We found that SZ patients showed GM and WM abnormalities in several brain structures primarily involved in the emotion, memory, and visual systems. An SVM with a RFE classifier using the significant structural abnormalities identified by the VBM analysis as input features achieved the best performance (an accuracy of 88.4%, a sensitivity of 91.9%, and a specificity of 84.4%) in the discriminative analyses of SZ patients. These results suggested that distinct neuroanatomical profiles associated with SZ patients might provide a potential biomarker for disease diagnosis, and machine-learning methods can reveal neurobiological mechanisms in psychiatric diseases.

Effects of genetically modified maize events expressing Cry34Ab1, Cry35Ab1, Cry1F, and CP4 EPSPS proteins on arthropod complex food webs.

PubMed

Pálinkás, Zoltán; Kiss, József; Zalai, Mihály; Szénási, Ágnes; Dorner, Zita; North, Samuel; Woodward, Guy; Balog, Adalbert

2017-04-01

Four genetically modified (GM) maize ( Zea mays L.) hybrids (coleopteran resistant, coleopteran and lepidopteran resistant, lepidopteran resistant and herbicide tolerant, coleopteran and herbicide tolerant) and its non-GM control maize stands were tested to compare the functional diversity of arthropods and to determine whether genetic modifications alter the structure of arthropods food webs. A total number of 399,239 arthropod individuals were used for analyses. The trophic groups' number and the links between them indicated that neither the higher magnitude of Bt toxins (included resistance against insect, and against both insects and glyphosate) nor the extra glyphosate treatment changed the structure of food webs. However, differences in the average trophic links/trophic groups were detected between GM and non-GM food webs for herbivore groups and plants. Also, differences in characteristic path lengths between GM and non-GM food webs for herbivores were observed. Food webs parameterized based on 2-year in-field assessments, and their properties can be considered a useful and simple tool to evaluate the effects of Bt toxins on non-target organisms.

Affective mentalizing and brain activity at rest in the behavioral variant of frontotemporal dementia

PubMed Central

Caminiti, Silvia P.; Canessa, Nicola; Cerami, Chiara; Dodich, Alessandra; Crespi, Chiara; Iannaccone, Sandro; Marcone, Alessandra; Falini, Andrea; Cappa, Stefano F.

2015-01-01

Background bvFTD patients display an impairment in the attribution of cognitive and affective states to others, reflecting GM atrophy in brain regions associated with social cognition, such as amygdala, superior temporal cortex and posterior insula. Distinctive patterns of abnormal brain functioning at rest have been reported in bvFTD, but their relationship with defective attribution of affective states has not been investigated. Objective To investigate the relationship among resting-state brain activity, gray matter (GM) atrophy and the attribution of mental states in the behavioral variant of fronto-temporal degeneration (bvFTD). Methods We compared 12 bvFTD patients with 30 age- and education-matched healthy controls on a) performance in a task requiring the attribution of affective vs. cognitive mental states; b) metrics of resting-state activity in known functional networks; and c) the relationship between task-performances and resting-state metrics. In addition, we assessed a connection between abnormal resting-state metrics and GM atrophy. Results Compared with controls, bvFTD patients showed a reduction of intra-network coherent activity in several components, as well as decreased strength of activation in networks related to attentional processing. Anomalous resting-state activity involved networks which also displayed a significant reduction of GM density. In patients, compared with controls, higher affective mentalizing performance correlated with stronger functional connectivity between medial prefrontal sectors of the default-mode and attentional/performance monitoring networks, as well as with increased coherent activity in components of the executive, sensorimotor and fronto-limbic networks. Conclusions Some of the observed effects may reflect specific compensatory mechanisms for the atrophic changes involving regions in charge of affective mentalizing. The analysis of specific resting-state networks thus highlights an intermediate level of analysis between abnormal brain structure and impaired behavioral performance in bvFTD, reflecting both dysfunction and compensation mechanisms. PMID:26594631

Chimeric HIV-1 Envelope Glycoproteins with Potent Intrinsic Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Activity*

PubMed Central

Boot, Maikel; Cobos Jiménez, Viviana; Kootstra, Neeltje A.; Sanders, Rogier W.

2013-01-01

HIV-1 acquisition can be prevented by broadly neutralizing antibodies (BrNAbs) that target the envelope glycoprotein complex (Env). An ideal vaccine should therefore be able to induce BrNAbs that can provide immunity over a prolonged period of time, but the low intrinsic immunogenicity of HIV-1 Env makes the elicitation of such BrNAbs challenging. Co-stimulatory molecules can increase the immunogenicity of Env and we have engineered a soluble chimeric Env trimer with an embedded granulocyte-macrophage colony-stimulating factor (GM-CSF) domain. This chimeric molecule induced enhanced B and helper T cell responses in mice compared to Env without GM-CSF. We studied whether we could optimize the activity of the embedded GM-CSF as well as the antigenic structure of the Env component of the chimeric molecule. We assessed the effect of truncating GM-CSF, removing glycosylation-sites in GM-CSF, and adjusting the linker length between GM-CSF and Env. One of our designed EnvGM-CSF chimeras improved GM-CSF-dependent cell proliferation by 6-fold, reaching the same activity as soluble recombinant GM-CSF. In addition, we incorporated GM-CSF into a cleavable Env trimer and found that insertion of GM-CSF did not compromise Env cleavage, while Env cleavage did not compromise GM-CSF activity. Importantly, these optimized EnvGM-CSF proteins were able to differentiate human monocytes into cells with a macrophage-like phenotype. Chimeric EnvGM-CSF should be useful for improving humoral immunity against HIV-1 and these studies should inform the design of other chimeric proteins. PMID:23565193

PETPVC: a toolbox for performing partial volume correction techniques in positron emission tomography

NASA Astrophysics Data System (ADS)

Thomas, Benjamin A.; Cuplov, Vesna; Bousse, Alexandre; Mendes, Adriana; Thielemans, Kris; Hutton, Brian F.; Erlandsson, Kjell

2016-11-01

Positron emission tomography (PET) images are degraded by a phenomenon known as the partial volume effect (PVE). Approaches have been developed to reduce PVEs, typically through the utilisation of structural information provided by other imaging modalities such as MRI or CT. These methods, known as partial volume correction (PVC) techniques, reduce PVEs by compensating for the effects of the scanner resolution, thereby improving the quantitative accuracy. The PETPVC toolbox described in this paper comprises a suite of methods, both classic and more recent approaches, for the purposes of applying PVC to PET data. Eight core PVC techniques are available. These core methods can be combined to create a total of 22 different PVC techniques. Simulated brain PET data are used to demonstrate the utility of toolbox in idealised conditions, the effects of applying PVC with mismatched point-spread function (PSF) estimates and the potential of novel hybrid PVC methods to improve the quantification of lesions. All anatomy-based PVC techniques achieve complete recovery of the PET signal in cortical grey matter (GM) when performed in idealised conditions. Applying deconvolution-based approaches results in incomplete recovery due to premature termination of the iterative process. PVC techniques are sensitive to PSF mismatch, causing a bias of up to 16.7% in GM recovery when over-estimating the PSF by 3 mm. The recovery of both GM and a simulated lesion was improved by combining two PVC techniques together. The PETPVC toolbox has been written in C++, supports Windows, Mac and Linux operating systems, is open-source and publicly available.

Effects of river flow regime on cottonwood leaf litter dynamics in semi-arid northwestern Colorado

USGS Publications Warehouse

Andersen, D.C.; Nelson, S.M.

2003-01-01

We compared production and breakdown of Fremont cottonwood (Populus deltoides wislizenii) leaf litter at matched floodplain sites on the regulated Green River and unregulated Yampa River in semi-arid northwestern Colorado. Litter production under trees was similar at sites in 1999 (250 g/m2, oven-dry) but lower in 2000 (215 and 130 g/m2), a drought year that also featured an outbreak of defoliating beetles at the Yampa River site. Our production values were similar to the few others reported for riparian forests within semi-arid or arid areas. Leaf litter in portions of the floodplain not inundated during the spring flood lost organic matter at the same rate as leaves placed in upland sites in 1998 and 2000: 35 to 50% of organic matter during an approximately 160-day spring and summer period. Inundated litter lost 55 to 90% of its organic matter during the same period. Organic matter loss from inundated leaves increased with duration of inundation and with deposition of fine sediment. Pooled across locations, leafpack data suggested that nitrogen concentration (mg N/kg organic matter) increased until about 65% of the initial organic matter was lost. This increase likely reflected the buildup of microbial decomposer populations. The role of insects and other macroinvertebrates in litter breakdown apparently was minor at both sites. Large spatial and temporal variation in litter dynamics in aridland floodplain settings is ensured by microtopographic variation in the alluvial surface coupled with year-to-year variation associated with most natural flood regimes. Factors reducing flood flow frequency or magnitude will reduce overall breakdown rates on the floodplain towards those found in drier upland environments.

Effect of structural modifications of ganglioside GM2 on intra-molecular carbohydrate-to-carbohydrate interaction and enzymatic susceptibility

PubMed Central

Li, Yu-Teh; Li, Su-Chen; Kiso, Makoto; Ishida, Hideharu; Mauri, Laura; Raimondi, Laura; Bernardi, Anna; Sonnino, Sandro

2008-01-01

Summary The effect of inter-molecular carbohydrate-to-carbohydrate interaction on basic cell biological processes has been well documented and appreciated. In contrast, very little is known about the intra-molecular carbohydrate-to-carbohydrate interaction. The presence of an interaction between the GalNAc and the Neu5Ac in GM2 detected by NMR spectroscopy represents a well-defined intra-molecular carbohydrate-to-carbohydrate interaction. This intriguing interaction is responsible for the GM2-epitope, GalNAcβ1Π4(Neu5Acα2Π3)Gal-, to exhibit a rigid and compact conformation. We hypothesized that this compact conformation may be the cause for both the GalNAc and the Neu5Ac in GM2 to be refractory to enzymatic hydrolysis and the GM2 activator protein is able to interact with the compact trisaccharide GM2-epitope, rendering the GalNAc and the Neu5Ac accessible to β-hexosaminidase A and sialidase. We have used a series of structurally modified GM2 to study the effect of modifications of sugar chains on the conformation and enzymatic susceptibility of this ganglioside. Our hypothesis was borne out by the fact that when the GalNAcβ1Π4Gal linkage in GM2 was converted to the GalNAcβ1Π6Gal, both the GalNAc and the Neu5Ac became susceptible to β-hexosaminidase A and sialidase, respectively, without GM2 activator protein. We hope our work will engender interest in identifying other intra-molecular carbohydrate-to-carbohydrate interactions in glycoconjugates. PMID:17967427

Brain structure correlates of urban upbringing, an environmental risk factor for schizophrenia.

PubMed

Haddad, Leila; Schäfer, Axel; Streit, Fabian; Lederbogen, Florian; Grimm, Oliver; Wüst, Stefan; Deuschle, Michael; Kirsch, Peter; Tost, Heike; Meyer-Lindenberg, Andreas

2015-01-01

Urban upbringing has consistently been associated with schizophrenia, but which specific environmental exposures are reflected by this epidemiological observation and how they impact the developing brain to increase risk is largely unknown. On the basis of prior observations of abnormal functional brain processing of social stress in urban-born humans and preclinical evidence for enduring structural brain effects of early social stress, we investigated a possible morphological correlate of urban upbringing in human brain. In a sample of 110 healthy subjects studied with voxel-based morphometry, we detected a strong inverse correlation between early-life urbanicity and gray matter (GM) volume in the right dorsolateral prefrontal cortex (DLPFC, Brodmann area 9). Furthermore, we detected a negative correlation of early-life urbanicity and GM volumes in the perigenual anterior cingulate cortex (pACC) in men only. Previous work has linked volume reductions in the DLPFC to the exposure to psychosocial stress, including stressful experiences in early life. Besides, anatomical and functional alterations of this region have been identified in schizophrenic patients and high-risk populations. Previous data linking functional hyperactivation of pACC during social stress to urban upbringing suggest that the present interaction effect in brain structure might contribute to an increased risk for schizophrenia in males brought up in cities. Taken together, our results suggest a neural mechanism by which early-life urbanicity could impact brain architecture to increase the risk for schizophrenia. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Magnetic resonance findings of the corpus callosum in canine and feline lysosomal storage diseases.

PubMed

Hasegawa, Daisuke; Tamura, Shinji; Nakamoto, Yuya; Matsuki, Naoaki; Takahashi, Kimimasa; Fujita, Michio; Uchida, Kazuyuki; Yamato, Osamu

2013-01-01

Several reports have described magnetic resonance (MR) findings in canine and feline lysosomal storage diseases such as gangliosidoses and neuronal ceroid lipofuscinosis. Although most of those studies described the signal intensities of white matter in the cerebrum, findings of the corpus callosum were not described in detail. A retrospective study was conducted on MR findings of the corpus callosum as well as the rostral commissure and the fornix in 18 cases of canine and feline lysosomal storage diseases. This included 6 Shiba Inu dogs and 2 domestic shorthair cats with GM1 gangliosidosis; 2 domestic shorthair cats, 2 familial toy poodles, and a golden retriever with GM2 gangliosidosis; and 2 border collies and 3 chihuahuas with neuronal ceroid lipofuscinoses, to determine whether changes of the corpus callosum is an imaging indicator of those diseases. The corpus callosum and the rostral commissure were difficult to recognize in all cases of juvenile-onset gangliosidoses (GM1 gangliosidosis in Shiba Inu dogs and domestic shorthair cats and GM2 gangliosidosis in domestic shorthair cats) and GM2 gangliosidosis in toy poodles with late juvenile-onset. In contrast, the corpus callosum and the rostral commissure were confirmed in cases of GM2 gangliosidosis in a golden retriever and canine neuronal ceroid lipofuscinoses with late juvenile- to early adult-onset, but were extremely thin. Abnormal findings of the corpus callosum on midline sagittal images may be a useful imaging indicator for suspecting lysosomal storage diseases, especially hypoplasia (underdevelopment) of the corpus callosum in juvenile-onset gangliosidoses.

Magnetic Resonance Findings of the Corpus Callosum in Canine and Feline Lysosomal Storage Diseases

PubMed Central

Hasegawa, Daisuke; Tamura, Shinji; Nakamoto, Yuya; Matsuki, Naoaki; Takahashi, Kimimasa; Fujita, Michio; Uchida, Kazuyuki; Yamato, Osamu

2013-01-01

Several reports have described magnetic resonance (MR) findings in canine and feline lysosomal storage diseases such as gangliosidoses and neuronal ceroid lipofuscinosis. Although most of those studies described the signal intensities of white matter in the cerebrum, findings of the corpus callosum were not described in detail. A retrospective study was conducted on MR findings of the corpus callosum as well as the rostral commissure and the fornix in 18 cases of canine and feline lysosomal storage diseases. This included 6 Shiba Inu dogs and 2 domestic shorthair cats with GM1 gangliosidosis; 2 domestic shorthair cats, 2 familial toy poodles, and a golden retriever with GM2 gangliosidosis; and 2 border collies and 3 chihuahuas with neuronal ceroid lipofuscinoses, to determine whether changes of the corpus callosum is an imaging indicator of those diseases. The corpus callosum and the rostral commissure were difficult to recognize in all cases of juvenile-onset gangliosidoses (GM1 gangliosidosis in Shiba Inu dogs and domestic shorthair cats and GM2 gangliosidosis in domestic shorthair cats) and GM2 gangliosidosis in toy poodles with late juvenile-onset. In contrast, the corpus callosum and the rostral commissure were confirmed in cases of GM2 gangliosidosis in a golden retriever and canine neuronal ceroid lipofuscinoses with late juvenile- to early adult-onset, but were extremely thin. Abnormal findings of the corpus callosum on midline sagittal images may be a useful imaging indicator for suspecting lysosomal storage diseases, especially hypoplasia (underdevelopment) of the corpus callosum in juvenile-onset gangliosidoses. PMID:24386203

Genes in food--why the furore?

PubMed

Dixon, Bernard

2003-04-01

Although unprecedented and perhaps unique in its irrationality, the recent furore over genetically modified (GM) food holds extremely important lessons for scientists. Some sections of the media undoubtedly bear a heavy responsibility for giving the expression 'GM' threatening connotations that are quite unwarranted. However, influential contributions to the hysteria have come from a surprising range of other sources, including some scientists. The research community has failed in its responsibility to society in three ways. Firstly, plant scientists did not appreciate that certain techniques (such as the use of antibiotic resistance genes as markers during plant transformation) would inevitably provoke public consternation. As a result, they took no steps to address such concerns. Secondly, researchers overlooked, minimized or in some cases simply dismissed the significance of public fears that they were 'interfering with Nature' or 'playing God'. Thirdly, plant breeders apparently saw no need to take pro-active measures with regard to the media and public in placing potential environmental and nutritional benefits of GM crops on the agenda in a positive fashion. Partly because of this failure, GM food is now firmly established in the public mind as wholly objectionable. One measure of how far we have travelled down that road is that it hardly matters any more whether objections are based on alleged environmental risks of cultivating GM crops or alleged toxicological hazards of eating them. 'Genetically modified organism', like 'radioactivity', has become an odious, generic shibboleth. Given that millions of people throughout the world are already benefiting from pharmaceuticals made by GM organisms, this is bizarre.

Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage.

PubMed

Filippi, Massimo; Rocca, Maria A; Pagani, Elisabetta; De Stefano, Nicola; Jeffery, Douglas; Kappos, Ludwig; Montalban, Xavier; Boyko, Alexei N; Comi, Giancarlo

2014-08-01

In Assessment of OraL Laquinimod in PrEventing ProGRession in Multiple SclerOsis (ALLEGRO), a phase III study in relapsing-remitting multiple sclerosis (RRMS), oral laquinimod slowed disability and brain atrophy progression, suggesting laquinimod may reduce tissue damage in MS. MRI techniques sensitive to the most destructive aspects of the disease were used to further investigate laquinimod's potential effects on inflammation and neurodegeneration. 1106 RRMS patients were randomised 1:1 to receive once-daily oral laquinimod (0.6 mg) or placebo for 24 months. White matter (WM), grey matter (GM) and thalamic fractions were derived at months 0, 12 and 24. Also assessed were evolution of gadolinium-enhancing and/or new T2 lesions into permanent black holes (PBH); magnetisation transfer ratio (MTR) of normal-appearing brain tissue (NABT), WM, GM and T2 lesions; and N-acetylaspartate/creatine (NAA/Cr) levels in WM. Compared with placebo, laquinimod-treated patients showed lower rates of WM at months 12 and 24 (p=0.004 and p=0.035) and GM (p=0.004) atrophy at month 12 and a trend for less GM atrophy at month 24 (p=0.078). Laquinimod also slowed thalamic atrophy at month 12 (p=0.005) and month 24 (p=0.003) and reduced the number of PBH at 12 and 24 months evolving from active lesions (all p<0.05). By month 24, MTR decreased significantly in NABT (p=0.015), WM (p=0.011) and GM (p=0.034) in placebo-treated patients, but not in laquinimod-treated patients. WM NAA/Cr tended to increase with laquinimod and decrease with placebo at 24 months (p=0.179). Oral laquinimod may reduce (at least in the initial phase of treatment) some of the more destructive pathological processes in RRMS patients. The ALLEGRO trial identifier number with clinicaltrials.gov is NCT00509145. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Ganglioside-Lipid and Ganglioside-Protein Interactions Revealed by Coarse-Grained and Atomistic Molecular Dynamics Simulations.

PubMed

Gu, Ruo-Xu; Ingólfsson, Helgi I; de Vries, Alex H; Marrink, Siewert J; Tieleman, D Peter

2017-04-20

Gangliosides are glycolipids in which an oligosaccharide headgroup containing one or more sialic acids is connected to a ceramide. Gangliosides reside in the outer leaflet of the plasma membrane and play a crucial role in various physiological processes such as cell signal transduction and neuronal differentiation by modulating structures and functions of membrane proteins. Because the detailed behavior of gangliosides and protein-ganglioside interactions are poorly known, we investigated the interactions between the gangliosides GM1 and GM3 and the proteins aquaporin (AQP1) and WALP23 using equilibrium molecular dynamics simulations and potential of mean force calculations at both coarse-grained (CG) and atomistic levels. In atomistic simulations, on the basis of the GROMOS force field, ganglioside aggregation appears to be a result of the balance between hydrogen bond interactions and steric hindrance of the headgroups. GM3 clusters are slightly larger and more ordered than GM1 clusters due to the smaller headgroup of GM3. The different structures of GM1 and GM3 clusters from atomistic simulations are not observed at the CG level based on the Martini model, implying a difference in driving forces for ganglioside interactions in atomistic and CG simulations. For protein-ganglioside interactions, in the atomistic simulations, GM1 lipids bind to specific sites on the AQP1 surface, whereas they are depleted from WALP23. In the CG simulations, the ganglioside binding sites on the AQP1 surface are similar, but ganglioside aggregation and protein-ganglioside interactions are more prevalent than in the atomistic simulations. Using the polarizable Martini water model, results were closer to the atomistic simulations. Although experimental data for validation is lacking, we proposed modified Martini parameters for gangliosides to more closely mimic the sizes and structures of ganglioside clusters observed at the atomistic level.

Ganglioside-Lipid and Ganglioside-Protein Interactions Revealed by Coarse-Grained and Atomistic Molecular Dynamics Simulations

PubMed Central

2016-01-01

Gangliosides are glycolipids in which an oligosaccharide headgroup containing one or more sialic acids is connected to a ceramide. Gangliosides reside in the outer leaflet of the plasma membrane and play a crucial role in various physiological processes such as cell signal transduction and neuronal differentiation by modulating structures and functions of membrane proteins. Because the detailed behavior of gangliosides and protein-ganglioside interactions are poorly known, we investigated the interactions between the gangliosides GM1 and GM3 and the proteins aquaporin (AQP1) and WALP23 using equilibrium molecular dynamics simulations and potential of mean force calculations at both coarse-grained (CG) and atomistic levels. In atomistic simulations, on the basis of the GROMOS force field, ganglioside aggregation appears to be a result of the balance between hydrogen bond interactions and steric hindrance of the headgroups. GM3 clusters are slightly larger and more ordered than GM1 clusters due to the smaller headgroup of GM3. The different structures of GM1 and GM3 clusters from atomistic simulations are not observed at the CG level based on the Martini model, implying a difference in driving forces for ganglioside interactions in atomistic and CG simulations. For protein-ganglioside interactions, in the atomistic simulations, GM1 lipids bind to specific sites on the AQP1 surface, whereas they are depleted from WALP23. In the CG simulations, the ganglioside binding sites on the AQP1 surface are similar, but ganglioside aggregation and protein-ganglioside interactions are more prevalent than in the atomistic simulations. Using the polarizable Martini water model, results were closer to the atomistic simulations. Although experimental data for validation is lacking, we proposed modified Martini parameters for gangliosides to more closely mimic the sizes and structures of ganglioside clusters observed at the atomistic level. PMID:27610460

SIZE-FRACTIONATED AMBIENT PARTICULATE MATTER INDUCES GM-CSF IN HUMAN BRONCHIAL EPITHELIAL CELLS BY MAPK PATHWAYS. (R827351C003)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Anti-GM1 antibodies as a model of the immune response to self-glycans.

PubMed

Nores, Gustavo A; Lardone, Ricardo D; Comín, Romina; Alaniz, María E; Moyano, Ana L; Irazoqui, Fernando J

2008-03-01

Glycans are a class of molecules with high structural variability, frequently found in the plasma membrane facing the extracellular space. Because of these characteristics, glycans are often considered as recognition molecules involved in cell social functions, and as targets of pathogenic factors. Induction of anti-glycan antibodies is one of the early events in immunological defense against bacteria that colonize the body. Because of this natural infection, antibodies recognizing a variety of bacterial glycans are found in sera of adult humans and animals. The immune response to glycans is restricted by self-tolerance, and no antibodies to self-glycans should exist in normal subjects. However, antibodies recognizing structures closely related to self-glycans do exist, and can lead to production of harmful anti-self antibodies. Normal human sera contain low-affinity anti-GM1 IgM-antibodies. Similar antibodies with higher affinity or different isotype are found in some neuropathy patients. Two hypotheses have been developed to explain the origin of disease-associated anti-GM1 antibodies. According to the "molecular mimicry" hypothesis, similarity between GM1 and Campylobacter jejuni lipopolysaccharide carrying a GM1-like glycan is the cause of Guillain-Barré syndrome associated with anti-GM1 IgG-antibodies. According to the "binding site drift" hypothesis, IgM-antibodies associated with disease originate through changes in the binding site of normally occurring anti-GM1 antibodies. We now present an "integrated" hypothesis, combining the "mimicry" and "drift" concepts, which satisfactorily explains most of the published data on anti-GM1 antibodies.

The GM2 Glycan Serves as a Functional Coreceptor for Serotype 1 Reovirus

PubMed Central

Liu, Yan; Blaum, Bärbel S.; Reiter, Dirk M.; Feizi, Ten; Dermody, Terence S.; Stehle, Thilo

2012-01-01

Viral attachment to target cells is the first step in infection and also serves as a determinant of tropism. Like many viruses, mammalian reoviruses bind with low affinity to cell-surface carbohydrate receptors to initiate the infectious process. Reoviruses disseminate with serotype-specific tropism in the host, which may be explained by differential glycan utilization. Although α2,3-linked sialylated oligosaccharides serve as carbohydrate receptors for type 3 reoviruses, neither a specific glycan bound by any reovirus serotype nor the function of glycan binding in type 1 reovirus infection was known. We have identified the oligosaccharide portion of ganglioside GM2 (the GM2 glycan) as a receptor for the attachment protein σ1 of reovirus strain type 1 Lang (T1L) using glycan array screening. The interaction of T1L σ1 with GM2 in solution was confirmed using NMR spectroscopy. We established that GM2 glycan engagement is required for optimal infection of mouse embryonic fibroblasts (MEFs) by T1L. Preincubation with GM2 specifically inhibited type 1 but not type 3 reovirus infection of MEFs. To provide a structural basis for these observations, we defined the mode of receptor recognition by determining the crystal structure of T1L σ1 in complex with the GM2 glycan. GM2 binds in a shallow groove in the globular head domain of T1L σ1. Both terminal sugar moieties of the GM2 glycan, N-acetylneuraminic acid and N-acetylgalactosamine, form contacts with the protein, providing an explanation for the observed specificity for GM2. Viruses with mutations in the glycan-binding domain display diminished hemagglutination capacity, a property dependent on glycan binding, and reduced capacity to infect MEFs. Our results define a novel mode of virus-glycan engagement and provide a mechanistic explanation for the serotype-dependent differences in glycan utilization by reovirus. PMID:23236285

The GM2 glycan serves as a functional coreceptor for serotype 1 reovirus.

PubMed

Reiss, Kerstin; Stencel, Jennifer E; Liu, Yan; Blaum, Bärbel S; Reiter, Dirk M; Feizi, Ten; Dermody, Terence S; Stehle, Thilo

2012-01-01

Viral attachment to target cells is the first step in infection and also serves as a determinant of tropism. Like many viruses, mammalian reoviruses bind with low affinity to cell-surface carbohydrate receptors to initiate the infectious process. Reoviruses disseminate with serotype-specific tropism in the host, which may be explained by differential glycan utilization. Although α2,3-linked sialylated oligosaccharides serve as carbohydrate receptors for type 3 reoviruses, neither a specific glycan bound by any reovirus serotype nor the function of glycan binding in type 1 reovirus infection was known. We have identified the oligosaccharide portion of ganglioside GM2 (the GM2 glycan) as a receptor for the attachment protein σ1 of reovirus strain type 1 Lang (T1L) using glycan array screening. The interaction of T1L σ1 with GM2 in solution was confirmed using NMR spectroscopy. We established that GM2 glycan engagement is required for optimal infection of mouse embryonic fibroblasts (MEFs) by T1L. Preincubation with GM2 specifically inhibited type 1 but not type 3 reovirus infection of MEFs. To provide a structural basis for these observations, we defined the mode of receptor recognition by determining the crystal structure of T1L σ1 in complex with the GM2 glycan. GM2 binds in a shallow groove in the globular head domain of T1L σ1. Both terminal sugar moieties of the GM2 glycan, N-acetylneuraminic acid and N-acetylgalactosamine, form contacts with the protein, providing an explanation for the observed specificity for GM2. Viruses with mutations in the glycan-binding domain display diminished hemagglutination capacity, a property dependent on glycan binding, and reduced capacity to infect MEFs. Our results define a novel mode of virus-glycan engagement and provide a mechanistic explanation for the serotype-dependent differences in glycan utilization by reovirus.

Effects of CaMSRB2-Expressing Transgenic Rice Cultivation on Soil Microbial Communities.

PubMed

Sohn, Soo-In; Oh, Young-Ju; Kim, Byung-Yong; Cho, Hyun-Suk

2016-07-28

Although many studies on the effects of genetically modified (GM) crops on soil microorganisms have been carried out over the past decades, they have provided contradictory information, even for the same GM crop, owing to the diversity of the soil environments in which they were conducted. This inconsistency in results suggests that the effects of GM crops on soil microorganisms should be considered from many aspects. In this study, we investigated the effects of the GM drought-tolerant rice MSRB2-Bar-8, which expresses the CaMSRB2 gene, on soil microorganisms based on the culture-dependent and culture-independent methods. To this end, rhizosphere soils of GM and non-GM (IM) rice were analyzed for soil chemistry, population densities of soil microorganisms, and microbial community structure (using pyrosequencing technology) at three growth stages (seedling, tillering, and maturity). There was no significant difference in the soil chemistry between GM and non-GM rice. The microbial densities of the GM soils were found to be within the range of those of the non-GM rice. In the pyrosequencing analyses, Proteobacteria and Chloroflexi were dominant at the seedling stage, while Chloroflexi showed dominance over Proteobacteria at the maturity stage in both the GM and non-GM soils. An UPGMA dendrogram showed that the soil microbial communities were clustered by growth stage. Taken together, the results from this study suggest that the effects of MSRB2-Bar-8 cultivation on soil microorganisms are not significant.

Attitudes of agricultural scientists in Indonesia towards genetically modified foods.

PubMed

Februhartanty, Judhiastuty; Widyastuti, Tri Nisa; Iswarawanti, Dwi Nastiti

2007-01-01

Conflicting arguments and partial truths on genetically modified (GM) foods have left confusion. Although studies of consumer acceptance of GM foods are numerous, the study of scientists is limited. Therefore, the main objective of this study was to assess the attitudes of scientists towards GM foods. The study was a cross sectional study. A total of 400 scientists (involved in at least one of teaching, research and consultancy) in the Bogor Agricultural Institute, Indonesia were selected randomly from its faculties of agriculture, veterinary, fishery, animal husbandry, forestry, agricultural technology, mathematics and science, and the post graduate department. Data collection was done by face-to-face interview using a structured questionnaire and self-administered questionnaire. The result showed that the majority (72.8%) of the respondents were favorably disposed towards GM foods, 14.8% were neutral, and only 12.5% were against them. The majority (78.3%) stated that they would try GM food if offered. Most (71%) reported that they were aware of the term "GM foods". Only half of the respondents felt that they had a basic understanding about GM foods. However, based on a knowledge test, 69.8% had a good knowledge score. Nearly 50% indicated that they were more exposed to news which supported GM foods. Over 90% said that there should be some form of labeling to distinguish food containing GM ingredients from non-GM foods. Attitudes were significantly associated with willingness to try GM foods if offered, restrictions on GM foods, and exposure to media reports about the pros and cons of GM foods.

Cortical Thickness, Surface Area and Subcortical Volume Differentially Contribute to Cognitive Heterogeneity in Parkinson's Disease.

PubMed

Gerrits, Niels J H M; van Loenhoud, Anita C; van den Berg, Stan F; Berendse, Henk W; Foncke, Elisabeth M J; Klein, Martin; Stoffers, Diederick; van der Werf, Ysbrand D; van den Heuvel, Odile A

2016-01-01

Parkinson's disease (PD) is often associated with cognitive deficits, although their severity varies considerably between patients. Recently, we used voxel-based morphometry (VBM) to show that individual differences in gray matter (GM) volume relate to cognitive heterogeneity in PD. VBM does, however, not differentiate between cortical thickness (CTh) and surface area (SA), which might be independently affected in PD. We therefore re-analyzed our cohort using the surface-based method FreeSurfer, and investigated (i) CTh, SA, and (sub)cortical GM volume differences between 93 PD patients and 45 matched controls, and (ii) the relation between these structural measures and cognitive performance on six neuropsychological tasks within the PD group. We found cortical thinning in PD patients in the left pericalcarine gyrus, extending to cuneus, precuneus and lingual areas and left inferior parietal cortex, bilateral rostral middle frontal cortex, and right cuneus, and increased cortical surface area in the left pars triangularis. Within the PD group, we found negative correlations between (i) CTh of occipital areas and performance on a verbal memory task, (ii) SA and volume of the frontal cortex and visuospatial memory performance, and, (iii) volume of the right thalamus and scores on two verbal fluency tasks. Our primary findings illustrate that i) CTh and SA are differentially affected in PD, and ii) VBM and FreeSurfer yield non-overlapping results in an identical dataset. We argue that this discrepancy is due to technical differences and the subtlety of the PD-related structural changes.

Developmental trajectories of the fronto-temporal lobes from infancy to early adulthood in healthy individuals.

PubMed

Tanaka, Chiaki; Matsui, Mie; Uematsu, Akiko; Noguchi, Kyo; Miyawaki, Toshio

2012-01-01

Brain development during early life in healthy individuals is rapid and dynamic, indicating that this period plays a very important role in neural and functional development. The frontal and temporal lobes are known to play a particularly important role in cognition. The study of healthy frontal and temporal lobe development in children is therefore of considerable importance. A better understanding of how these brain regions develop could also aid in the diagnosis and treatment of neurodevelopmental disorders. Some developmental studies have used magnetic resonance imaging (MRI) to examine infant brains, but it remains the case that relatively little is known about cortical brain development in the first few years of life. In the present study we examined whole brain, temporal lobe and frontal lobe developmental trajectories from infancy to early adulthood in healthy individuals, considering gender and brain hemisphere differences. We performed a cross-sectional, longitudinal morphometric MRI study of 114 healthy individuals (54 females and 60 males) aged 1 month to 25 years old (mean age ± SD 8.8 ± 6.9). We measured whole brain, temporal and frontal lobe gray matter (GM)/white matter (WM) volumes, following previously used protocols. There were significant non-linear age-related volume changes in all regions. Peak ages of whole brain, temporal lobe and frontal lobe development occurred around pre-adolescence (9-12 years old). GM volumes for all regions increased significantly as a function of age. Peak age was nevertheless lobe specific, with a pattern of earlier peak ages for females in both temporal and frontal lobes. Growth change in whole brain GM volume was larger in males than in females. However, GM volume growth changes for the temporal and frontal lobes showed a somewhat different pattern. GM volume for both temporal and frontal lobes showed a greater increase in females until around 5-6 years old, at which point this tendency reversed (GM volume changes in males became greater), with male GM volume increasing for a longer time than that of females. WM volume growth changes were similar across regions, all increasing rapidly until early childhood but slowing down thereafter. All regions displayed significant rightward volumetric asymmetry regardless of sex. Furthermore, the right temporal and frontal lobes showed a greater volumetric increase than the left for the first several years, with this tendency reversing at around 6 years of age. In addition, the left frontal and temporal lobes increased in volume for a longer period of time. Taken together, these findings indicated that brain developmental trajectories differ depending on brain region, sex and brain hemisphere. Gender-related factors such as sex hormones and functional laterality may affect brain development. Copyright © 2012 S. Karger AG, Basel.

Newborn Insula Gray Matter Volume is Prospectively Associated With Early Life Adiposity Gain

PubMed Central

Rasmussen, Jerod M.; Entringer, Sonja; Kruggel, Frithjof; Cooper, Dan M.; Styner, Martin; Gilmore, John H.; Potkin, Steven G.; Wadhwa, Pathik D.; Buss, Claudia

2017-01-01

Background The importance of energy homeostasis brain circuitry in the context of obesity is well established, however, the developmental ontogeny of this circuitry in humans is currently unknown. Here, we investigate the prospective association between newborn gray matter (GM) volume in the insula, a key brain region underlying energy homeostasis, and change in percent body fat accrual over the first six months of postnatal life, an outcome that represents among the most reliable infant predictors of childhood obesity risk. Methods 52 infants (29 male, 23 female, gestational age at birth=39[1.5] weeks) were assessed using structural MRI shortly after birth (postnatal age at MRI scan=25.9[12.2] days), and serial Dual X-Ray Absorptiometry shortly after birth (postnatal age at DXA scan 1=24.6[11.4] days) and at six months of age (postnatal age at DXA scan 2=26.7[3.3] weeks). Results Insula GM volume was inversely associated with change in percent body fat from birth to six-months postnatal age and accounted for 19% of its variance (β=-3.6%/S.D., p=0.001). This association was driven by the central-posterior portion of the insula, a region of particular importance for gustation and interoception. The direction of this effect is in concordance with observations in adults, and the results remained statistically significant after adjusting for relevant covariates and potential confounding variables. Conclusions Together, these findings suggest an underlying neural basis of childhood obesity that precedes the influence of the postnatal environment. The identification of plausible brain-related biomarkers of childhood obesity risk that predate the influence of the postnatal obesogenic environment may contribute to an improved understanding of propensity for obesity, early identification of at-risk individuals, and intervention targets for primary prevention. PMID:28487552

Sex Effects on Smoking Cue Perception in Non-Smokers, Smokers, and Ex-Smokers: A Pilot Study.

PubMed

Zanchi, Davide; Brody, Arthur; Borgwardt, Stefan; Haller, Sven

2016-01-01

Recent neuroimaging research suggests sex-related brain differences in smoking addiction. In the present pilot study, we assessed gender-related differences in brain activation in response to cigarette-related video cues, investigating non-smokers, smokers, and ex-smokers. First, we compared 29 females (28.6 ± 5.3) vs. 23 males (31.5 ± 6.4), regardless of current smoking status to assess global gender-related effects. Second, we performed a post hoc analysis of non-smokers (9 females and 8 males), smokers (10 females and 8 males), and ex-smokers (10 females and 7 males). Participants performed a block-design functional magnetic resonance imaging paradigm contrasting smoking with control cue video exposures. Data analyses included task-related general linear model, voxel-based morphometry of gray matter (GM), and tract-based spatial statistics of white matter (WM). First, the global effect regardless of current smoking status revealed higher activation in the bilateral superior frontal gyrus and anterior cingulate cortex (ACC) for females compared to males. Second, the analysis according to current smoking status demonstrated higher activation in female vs. male smokers vs. non-smokers in the superior frontal gyrus, anterior and posterior cingulate cortex, and precuneus, and higher activation in female vs. male ex-smokers vs. non-smokers in the right precentral gyrus, in the right insula and ACC. No structural differences were found in GM or WM. The current study identifies gender-related brain functional differences in smokers and ex-smokers compared to non-smokers. The current work can be considered as a starting point for future investigations into gender differences in brain responses to cigarette-related cues.

[Survival pronostic factors in Mexican patients with multiforme glioblastoma].

PubMed

Hernández-Reyna, Ricardo; Medellín-Sánchez, Roberto; Cerda-Flores, Ricardo M; Calderón-Garcidueñas, Ana Laura

2010-01-01

To study the pre- and transoperative factors that influence patients' survival with GM. Clinical and pathological records of all confirmed cases of GM diagnosed between 2000 and 2006 were included. Postoperative survival was divided in less or more than 8 months. χ2 test was used. One hundred and twenty patients (45 women and 75 men) were studied. Age range was from 7 to 85 years, 3.3% were 16 years old or younger and 12.5% were 70 years old or older. Headache was the most frequent complain, 40 patients developed hemiparesia and 6 had parestesias. Predominance of white matter hemispheric lesions was observed: right hemispheric tumors 65 (54%), left lesions 30 (25%) and bilateral tumors 7%. Histologically, 1.6% of GM had a sarcomatous component; 35% of patients survived less than 8 months. A difference between patients survival was the preoperative Karnofsky Performance Scale Score and the degree of cerebral edema during the surgical procedure. Pre-operative Karnofsky evaluation and edema during the surgical procedure were significant prognostic factors for survival.

Genetics Home Reference: GM2-gangliosidosis, AB variant

MedlinePlus

... link) National Institute of Neurological Disorders and Stroke: Lipid Storage Diseases Fact Sheet Educational Resources (3 links) ... Chen B, Rigat B, Curry C, Mahuran DJ. Structure of the GM2A gene: identification of an exon ...

An automated tool for cortical feature analysis: Application to differences on 7 Tesla T2* -weighted images between young and older healthy subjects.

PubMed

Doan, Nhat Trung; van Rooden, Sanneke; Versluis, Maarten J; Buijs, Mathijs; Webb, Andrew G; van der Grond, Jeroen; van Buchem, Mark A; Reiber, Johan H C; Milles, Julien

2015-07-01

High field T 2 * -weighted MR images of the cerebral cortex are increasingly used to study tissue susceptibility changes related to aging or pathologies. This paper presents a novel automated method for the computation of quantitative cortical measures and group-wise comparison using 7 Tesla T 2 * -weighted magnitude and phase images. The cerebral cortex was segmented using a combination of T 2 * -weighted magnitude and phase information and subsequently was parcellated based on an anatomical atlas. Local gray matter (GM)/white matter (WM) contrast and cortical profiles, which depict the magnitude or phase variation across the cortex, were computed from the magnitude and phase images in each parcellated region and further used for group-wise comparison. Differences in local GM/WM contrast were assessed using linear regression analysis. Regional cortical profiles were compared both globally and locally using permutation testing. The method was applied to compare a group of 10 young volunteers with a group of 15 older subjects. Using local GM/WM contrast, significant differences were revealed in at least 13 of 17 studied regions. Highly significant differences between cortical profiles were shown in all regions. The proposed method can be a useful tool for studying cortical changes in normal aging and potentially in neurodegenerative diseases. Magn Reson Med 74:240-248, 2015. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

The effect of future time perspective on delay discounting is mediated by the gray matter volume of vmPFC.

PubMed

Guo, Yiqun; Chen, Zhiyi; Feng, Tingyong

2017-07-28

Although several previous studies have shown that individuals' attitude towards time could affect their intertemporal preference, little is known about the neural basis of the relation between time perspective (TP) and delay discounting. In the present study, we quantified the gray matter (GM) cortical volume using voxel-based morphometry (VBM) methods to investigate the effect of TP on delay discounting (DD) across two independent samples. For group 1 (102 healthy college students; 46 male; 20.40 ± 1.87 years), behavioral results showed that only Future TP was a significant predictor of DD, and higher scores on Future TP were related to lower discounting rates. Whole-brain analysis revealed that steeper discounting correlated with greater GM volume in the ventromedial prefrontal cortex (vmPFC) and ventral part of posterior cingulate cortex (vPCC). Also, GM volume of a cluster in the vmPFC was correlated with Future TP. Interestingly, there was an overlapping region in vmPFC that was correlated with both DD and Future TP. Region-of-interest analysis further indicated that the overlapping region of vmPFC played a partially mediating role in the relation between Future TP and DD in the other independent dataset (Group 2, 36 healthy college students; 14 male; 20.18±1.80 years). Taken together, our results provide a new perspective from neural basis for explaining the relation between DD and future TP. Copyright © 2017 Elsevier Ltd. All rights reserved.

GM1-gangliosidosis in Alaskan huskies: clinical and pathologic findings.

PubMed

Müller, G; Alldinger, S; Moritz, A; Zurbriggen, A; Kirchhof, N; Sewell, A; Baumgärtner, W

2001-05-01

Three Alaskan Huskies, two females and one male, were diagnosed with GM1-gangliosidosis. Clinically, diseased animals exhibited proportional dwarfism and developed progressive neurologic impairment with signs of cerebellar dysfunction at the age of 5-7 months. Skeletal lesions characterized by retarded enchondral ossification of vertebral epiphyses were revealed by radiographs of the male dog at 5.5 months of age. Histologic examination of the central nervous system (CNS) revealed that most neurons were enlarged with a foamy to granular cytoplasm due to tightly packed vacuoles that displaced the Nissl substance. Vacuoles in paraffin-embedded sections stained positively with Luxol fast blue and Grocott's method, and in frozen sections vacuoles were periodic acid-Schiff positive. Foamy vacuolation also occurred within neurons of the autonomic ganglia. Extracerebral cells such as macrophages and peripheral lymphocytes also displayed foamy cytoplasm and vacuolation. In the CNS of diseased animals, a mild demyelination and axonal degeneration was accompanied by a significant astrogliosis (P < 0.05) in the gray matter as compared with age- and sex-matched control dogs. There was also a significant loss (P < 0.05) of oligodendrocytes in the gray and white matter of affected animals as compared with controls. Ultrastructurally, the neuronal storage material consisted of numerous circular to concentric whorls of lamellated membranes or stacks of membranes in parallel arrays. GM1-gangliosidosis in Alaskan Huskies resembles beta-galactosidase deficiency in other canine breeds, and these CNS disorders may be a consequence of neuronal storage and disturbed myelin processing.

Requirement of GM2 ganglioside activator for phospholipase D activation

PubMed Central

Nakamura, Shun-ichi; Akisue, Toshihiro; Jinnai, Hitoshi; Hitomi, Tomohiro; Sarkar, Sukumar; Miwa, Noriko; Okada, Taro; Yoshida, Kimihisa; Kuroda, Shun’ichi; Kikkawa, Ushio; Nishizuka, Yasutomi

1998-01-01

Sequence analysis of a heat-stable protein necessary for the activation of ADP ribosylation factor-dependent phospholipase D (PLD) reveals that this protein has a structure highly homologous to the previously known GM2 ganglioside activator whose deficiency results in the AB-variant of GM2 gangliosidosis. The heat-stable activator protein indeed has the capacity to enhance enzymatic conversion of GM2 to GM3 ganglioside that is catalyzed by β-hexosaminidase A. Inversely, GM2 ganglioside activator purified separately from tissues as described earlier [Conzelmann, E. & Sandhoff, K. (1987) Methods Enzymol. 138, 792–815] stimulates ADP ribosylation factor-dependent PLD in a dose-dependent manner. At higher concentrations of ammonium sulfate, the PLD activator protein apparently substitutes for protein kinase C and phosphatidylinositol 4,5-bisphosphate, both of which are known as effective stimulators of the PLD reaction. The mechanism of action of the heat-stable PLD activator protein remains unknown. PMID:9770472

STrategically Acquired Gradient Echo (STAGE) imaging, part I: Creating enhanced T1 contrast and standardized susceptibility weighted imaging and quantitative susceptibility mapping.

PubMed

Chen, Yongsheng; Liu, Saifeng; Wang, Yu; Kang, Yan; Haacke, E Mark

2018-02-01

To provide whole brain grey matter (GM) to white matter (WM) contrast enhanced T1W (T1WE) images, multi-echo quantitative susceptibility mapping (QSM), proton density (PD) weighted images, T1 maps, PD maps, susceptibility weighted imaging (SWI), and R2* maps with minimal misregistration in scanning times <5min. Strategically acquired gradient echo (STAGE) imaging includes two fully flow compensated double echo gradient echo acquisitions with a resolution of 0.67×1.33×2.0mm 3 acquired in 5min for 64 slices. Ten subjects were recruited and scanned at 3 Tesla. The optimum pair of flip angles (6° and 24° with TR=25ms at 3T) were used for both T1 mapping with radio frequency (RF) transmit field correction and creating enhanced GM/WM contrast (the T1WE). The proposed T1WE image was created from a combination of the proton density weighted (6°, PDW) and T1W (24°) images and corrected for RF transmit field variations. Prior to the QSM calculation, a multi-echo phase unwrapping strategy was implemented using the unwrapped short echo to unwrap the longer echo to speed up computation. R2* maps were used to mask deep grey matter and veins during the iterative QSM calculation. A weighted-average sum of susceptibility maps was generated to increase the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR). The proposed T1WE image has a significantly improved CNR both for WM to deep GM and WM to cortical GM compared to the acquired T1W image (the first echo of 24° scan) and the T1MPRAGE image. The weighted-average susceptibility maps have 80±26%, 55±22%, 108±33% SNR increases across the ten subjects compared to the single echo result of 17.5ms for the putamen, caudate nucleus, and globus pallidus, respectively. STAGE imaging offers the potential to create a standardized brain imaging protocol providing four pieces of quantitative tissue property information and multiple types of qualitative information in just 5min. Published by Elsevier Inc.

The use of whole food animal studies in the safety assessment of genetically modified crops: limitations and recommendations.

PubMed

Bartholomaeus, Andrew; Parrott, Wayne; Bondy, Genevieve; Walker, Kate

2013-11-01

There is disagreement internationally across major regulatory jurisdictions on the relevance and utility of whole food (WF) toxicity studies on GM crops, with no harmonization of data or regulatory requirements. The scientific value, and therefore animal ethics, of WF studies on GM crops is a matter addressable from the wealth of data available on commercialized GM crops and WF studies on irradiated foods. We reviewed available GM crop WF studies and considered the extent to which they add to the information from agronomic and compositional analyses. No WF toxicity study was identified that convincingly demonstrated toxicological concern or that called into question the adequacy, sufficiency, and reliability of safety assessments based on crop molecular characterization, transgene source, agronomic characteristics, and/or compositional analysis of the GM crop and its near-isogenic line. Predictions of safety based on crop genetics and compositional analyses have provided complete concordance with the results of well-conducted animal testing. However, this concordance is primarily due to the improbability of de novo generation of toxic substances in crop plants using genetic engineering practices and due to the weakness of WF toxicity studies in general. Thus, based on the comparative robustness and reliability of compositional and agronomic considerations and on the absence of any scientific basis for a significant potential for de novo generation of toxicologically significant compositional alterations as a sole result of transgene insertion, the conclusion of this review is that WF animal toxicity studies are unnecessary and scientifically unjustifiable.

Overexpression of the Transcription Factors GmSHN1 and GmSHN9 Differentially Regulates Wax and Cutin Biosynthesis, Alters Cuticle Properties, and Changes Leaf Phenotypes in Arabidopsis.

PubMed

Xu, Yangyang; Wu, Hanying; Zhao, Mingming; Wu, Wang; Xu, Yinong; Gu, Dan

2016-04-21

SHINE (SHN/WIN) clade proteins, transcription factors of the plant-specific APETALA 2/ethylene-responsive element binding factor (AP2/ERF) family, have been proven to be involved in wax and cutin biosynthesis. Glycine max is an important economic crop, but its molecular mechanism of wax biosynthesis is rarely characterized. In this study, 10 homologs of Arabidopsis SHN genes were identified from soybean. These homologs were different in gene structures and organ expression patterns. Constitutive expression of each of the soybean SHN genes in Arabidopsis led to different leaf phenotypes, as well as different levels of glossiness on leaf surfaces. Overexpression of GmSHN1 and GmSHN9 in Arabidopsis exhibited 7.8-fold and 9.9-fold up-regulation of leaf cuticle wax productions, respectively. C31 and C29 alkanes contributed most to the increased wax contents. Total cutin contents of leaves were increased 11.4-fold in GmSHN1 overexpressors and 5.7-fold in GmSHN9 overexpressors, mainly through increasing C16:0 di-OH and dioic acids. GmSHN1 and GmSHN9 also altered leaf cuticle membrane ultrastructure and increased water loss rate in transgenic Arabidopsis plants. Transcript levels of many wax and cutin biosynthesis and leaf development related genes were altered in GmSHN1 and GmSHN9 overexpressors. Overall, these results suggest that GmSHN1 and GmSHN9 may differentially regulate the leaf development process as well as wax and cutin biosynthesis.

Overexpression of the Transcription Factors GmSHN1 and GmSHN9 Differentially Regulates Wax and Cutin Biosynthesis, Alters Cuticle Properties, and Changes Leaf Phenotypes in Arabidopsis

PubMed Central

Xu, Yangyang; Wu, Hanying; Zhao, Mingming; Wu, Wang; Xu, Yinong; Gu, Dan

2016-01-01

SHINE (SHN/WIN) clade proteins, transcription factors of the plant-specific APETALA 2/ethylene-responsive element binding factor (AP2/ERF) family, have been proven to be involved in wax and cutin biosynthesis. Glycine max is an important economic crop, but its molecular mechanism of wax biosynthesis is rarely characterized. In this study, 10 homologs of Arabidopsis SHN genes were identified from soybean. These homologs were different in gene structures and organ expression patterns. Constitutive expression of each of the soybean SHN genes in Arabidopsis led to different leaf phenotypes, as well as different levels of glossiness on leaf surfaces. Overexpression of GmSHN1 and GmSHN9 in Arabidopsis exhibited 7.8-fold and 9.9-fold up-regulation of leaf cuticle wax productions, respectively. C31 and C29 alkanes contributed most to the increased wax contents. Total cutin contents of leaves were increased 11.4-fold in GmSHN1 overexpressors and 5.7-fold in GmSHN9 overexpressors, mainly through increasing C16:0 di-OH and dioic acids. GmSHN1 and GmSHN9 also altered leaf cuticle membrane ultrastructure and increased water loss rate in transgenic Arabidopsis plants. Transcript levels of many wax and cutin biosynthesis and leaf development related genes were altered in GmSHN1 and GmSHN9 overexpressors. Overall, these results suggest that GmSHN1 and GmSHN9 may differentially regulate the leaf development process as well as wax and cutin biosynthesis. PMID:27110768

Increased resting cerebral blood flow in adult Fabry disease: MRI arterial spin labeling study.

PubMed

Phyu, Po; Merwick, Aine; Davagnanam, Indran; Bolsover, Fay; Jichi, Fatima; Wheeler-Kingshott, Claudia; Golay, Xavier; Hughes, Deralynn; Cipolotti, Lisa; Murphy, Elaine; Lachmann, Robin H; Werring, David John

2018-04-17

To assess resting cerebral blood flow (CBF) in the whole-brain and cerebral white matter (WM) and gray matter (GM) of adults with Fabry disease (FD), using arterial spin labeling (ASL) MRI, and to investigate CBF correlations with WM hyperintensity (WMH) volume and the circulating biomarker lyso-Gb3. This cross-sectional, case-control study included 25 patients with genetically confirmed FD and 18 age-matched healthy controls. We quantified resting CBF using Quantitative Signal Targeting With Alternating Radiofrequency Labeling of Arterial Regions (QUASAR) ASL MRI. We measured WMH volume using semiautomated software. We measured CBF in regions of interest in whole-brain, WM, and deep GM, and assessed correlations with WMH volume and plasma lyso-Gb3. The mean age (% male) for FD and healthy controls was 42.2 years (44%) and 37.1 years (50%). Mean whole-brain CBF was 27.56 mL/100 mL/min (95% confidence interval [CI] 23.78-31.34) for FD vs 22.39 mL/100 mL/min (95% CI 20.08-24.70) for healthy controls, p = 0.03. In WM, CBF was higher in FD (22.42 mL/100 mL/min [95% CI 17.72-27.12] vs 16.25 mL/100 mL/min [95% CI 14.03-18.48], p = 0.05). In deep GM, CBF was similar between groups (40.41 mL/100 mL/min [95% CI 36.85-43.97] for FD vs 37.46 mL/100 mL/min [95% CI 32.57-42.35], p = 0.38). In patients with FD with WMH (n = 20), whole-brain CBF correlated with WMH volume ( r = 0.59, p = 0.006), not with plasma lyso-Gb3. In FD, resting CBF is increased in WM but not deep GM. In FD, CBF correlates with WMH, suggesting that cerebral perfusion changes might contribute to, or result from, WM injury. © 2018 American Academy of Neurology.

A Quantized Metric As an Alternative to Dark Matter

NASA Astrophysics Data System (ADS)

Maker, Joel

2010-03-01

The cosmological spherical symmetry background metric coefficient (g44≡) g00= 1-2GM/c^2r should be inserted into a Dirac equation σμ(gμμγ^μψ/xμ)-φψ = 0 (1,Maker) to make it generally covariant. The spin of this cosmological Dirac object is nearly unobservable due to inertial frame dragging and has rotational L(L+1) δɛ and oscillatory ɛ interactions with external objects at distance away r>>10^10 LY. The inside and outside frequencies φ match at the boundary allowing the outside metric eigenvalues to propagate inside. To include the correct 3 lepton masses in this Dirac equation we must use ansatz goo= e^i(2ɛ+δɛ) with ɛ=.06, δɛ=.00058. For local metric effects our ansatz is goo=e^iδɛ. Here the metric coefficient goo levels off to the quantized value e^iδɛ in the galaxy halo: goo=1-2GM/rc^2-> rel(e^iδɛ) =cos(δɛ)= 1-(δɛ)^2/2 ->(δɛ)^2/2=2GM/rc^2 for this circular motion v^2/r=GM/r^2=c^2(δɛ)^2/4r ->v^2 =c^2(δɛ)^2/4 =87km/sec)^2 100km/sec)^2. So the metric acts to quantize v. Note also there is rotational energy quantization for the δɛ rotational states that goes as: (L(L+1)) .5ex1 -.1em/ -.15em.25ex2 mv^2 ->√L(L+1) v. Thus differences in v are proportional to L, L being an integer. Therefore δv = kL so v = 1k, v = 2k, v = 3k, v = 4k. v=N (the above ˜100km/sec) with dark matter then not required to give these high halo velocities. Recent nearby galaxy Doppler halo velocity data strongly support this velocity quantization result.

The brain effects of cannabis in healthy adolescents and in adolescents with schizophrenia: a systematic review.

PubMed

James, Anthony; James, Christine; Thwaites, Thomas

2013-12-30

Cannabis is widely used in adolescence; however, the effects of cannabis on the developing brain remain unclear. Cannabis might be expected to have increased effects upon brain development and cognition during adolescence. There is extensive re-organisation of grey (GM) and white matter (WM) at this time, while the endocannabinoid (eCB) system, which is involved in the normal physiological regulation of neural transmission, is still developing. In healthy adolescent cannabis users there is a suggestion of greater memory loss and hippocampal volume changes. Functional studies point to recruitment of greater brain areas under cognitive load. Structural and DTI studies are few, and limited by comorbid drug and alcohol use. The studies of cannabis use in adolescent-onset schizophrenia (AOS) differ, with one study pointing to extensive GM and WM changes. There is an intriguing suggestion that the left parietal lobe may be more vulnerable to the effects of cannabis in AOS. As in adult schizophrenia cognition does not appear to be adversely affected in AOS following cannabis use. Given the limited number of studies it is not possible to draw firm conclusions. There is a need for adequately powered, longitudinal studies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The effect of future time perspective on procrastination: the role of parahippocampal gyrus and ventromedial prefrontal cortex.

PubMed

Liu, Peiwei; Feng, Tingyong

2018-05-09

Procrastination is an almost universal affliction, which occurs across culture and brings serious consequences across multiple fields, such as finance, health and education. Previous research has showed procrastination can be influenced by future time perspective (FTP). However, little is known about the neural basis underlying the impact of FTP on procrastination. To address this question, we used voxel-based morphometry (VBM) based on brain structure. In line with previous findings, the behavioral result indicated that FTP inventory scores were significantly negatively correlated with procrastination inventory scores (r = -0.63, n = 160). The whole-brain VBM results showed that FTP scores were significantly negatively correlated with the grey matter (GM) volumes of the parahippocampal gyrus (paraPHC) and ventromedial prefrontal cortex (vmPFC) after the multiple comparisons correction. Furthermore, mediation analyses revealed that the effect of GM volumes of the paraPHC and vmPFC on procrastination was mediated by FTP. These results suggested that paraPHC and vmPFC, the critical brain regions about episodic future thinking, could be the neural basis responsible for the impact of FTP on procrastination. The present study extends our knowledge on procrastination, and provides a novel perspective to understand the relationship between FTP and procrastination.

Determinants of public attitudes to genetically modified salmon.

PubMed

Amin, Latifah; Azad, Md Abul Kalam; Gausmian, Mohd Hanafy; Zulkifli, Faizah

2014-01-01

The objective of this paper is to assess the attitude of Malaysian stakeholders to genetically modified (GM) salmon and to identify the factors that influence their acceptance of GM salmon using a structural equation model. A survey was carried out on 434 representatives from various stakeholder groups in the Klang Valley region of Malaysia. Public attitude towards GM salmon was measured using self-developed questionnaires with seven-point Likert scales. The findings of this study have confirmed that public attitudes towards GM salmon is a complex issue and should be seen as a multi-faceted process. The most important direct predictors for the encouragement of GM salmon are the specific application-linked perceptions about religious acceptability of GM salmon followed by perceived risks and benefits, familiarity, and general promise of modern biotechnology. Encouragement of GM salmon also involves the interplay among other factors such as general concerns of biotechnology, threatening the natural order of things, the need for labeling, the need for patenting, confidence in regulation, and societal values. The research findings can serve as a database that will be useful for understanding the social construct of public attitude towards GM foods in a developing country.

Determinants of Public Attitudes to Genetically Modified Salmon

PubMed Central

Amin, Latifah; Azad, Md. Abul Kalam; Gausmian, Mohd Hanafy; Zulkifli, Faizah

2014-01-01

The objective of this paper is to assess the attitude of Malaysian stakeholders to genetically modified (GM) salmon and to identify the factors that influence their acceptance of GM salmon using a structural equation model. A survey was carried out on 434 representatives from various stakeholder groups in the Klang Valley region of Malaysia. Public attitude towards GM salmon was measured using self-developed questionnaires with seven-point Likert scales. The findings of this study have confirmed that public attitudes towards GM salmon is a complex issue and should be seen as a multi-faceted process. The most important direct predictors for the encouragement of GM salmon are the specific application-linked perceptions about religious acceptability of GM salmon followed by perceived risks and benefits, familiarity, and general promise of modern biotechnology. Encouragement of GM salmon also involves the interplay among other factors such as general concerns of biotechnology, threatening the natural order of things, the need for labeling, the need for patenting, confidence in regulation, and societal values. The research findings can serve as a database that will be useful for understanding the social construct of public attitude towards GM foods in a developing country. PMID:24489695

The clustering of galaxies in the completed SDSS-III Baryon Oscillation Spectroscopic Survey: constraining modified gravity

NASA Astrophysics Data System (ADS)

Mueller, Eva-Maria; Percival, Will; Linder, Eric; Alam, Shadab; Zhao, Gong-Bo; Sánchez, Ariel G.; Beutler, Florian; Brinkmann, Jon

2018-04-01

We use baryon acoustic oscillation and redshift space distortion from the completed Baryon Oscillation Spectroscopic Survey, corresponding to Data Release 12 of the Sloan Digital Sky Survey, combined sample analysis in combination with cosmic microwave background, supernova, and redshift space distortion measurements from additional spectroscopic surveys to test deviations from general relativity. We present constraints on several phenomenological models of modified gravity: First, we parametrize the growth of structure using the growth index γ, finding γ = 0.566 ± 0.058 (68 per cent C.L.). Secondly, we modify the relation of the two Newtonian potentials by introducing two additional parameters, GM and GL. In this approach, GM refers to modifications of the growth of structure whereas GL to modification of the lensing potential. We consider a power law to model the redshift dependence of GM and GL as well as binning in redshift space, introducing four additional degrees of freedom, GM(z < 0.5), GM(z > 0.5), GL(z < 0.5), and GL(z > 0.5). At 68 per cent C.L., we measure GM = 0.980 ± 0.096 and GL = 1.082 ± 0.060 for a linear model, GM = 1.01 ± 0.36 and GL = 1.31 ± 0.19 for a cubic model as well as GM(z < 0.5) = 1.26 ± 0.32, GM(z > 0.5) = 0.986 ± 0.022, GL(z < 0.5) = 1.067 ± 0.058, and GL(z > 0.5) = 1.037 ± 0.029. Thirdly, we investigate general scalar tensor theories of gravity, finding the model to be mostly unconstrained by current data. Assuming a one-parameter f(R) model, we can constrain B0 < 7.7 × 10-5 (95 per cent C.L). For all models we considered, we find good agreement with general relativity.

Cortical Brain Atrophy and Intra-Individual Variability in Neuropsychological Test Performance in HIV Disease

PubMed Central

HINES, Lindsay J.; MILLER, Eric N.; HINKIN, Charles H.; ALGER, Jeffery R.; BARKER, Peter; GOODKIN, Karl; MARTIN, Eileen M.; MARUCA, Victoria; RAGIN, Ann; SACKTOR, Ned; SANDERS, Joanne; SELNES, Ola; BECKER, James T.

2015-01-01

Objective To characterize the relationship between dispersion-based intra-individual variability (IIVd) in neuropsychological test performance and brain volume among HIV seropositive and seronegative men and to determine the effects of cardiovascular risk and HIV infection on this relationship. Methods Magnetic Resonance Imaging (MRI) was used to acquire high-resolution neuroanatomic data from 147 men age 50 and over, including 80 HIV seropositive (HIV+) and 67 seronegative controls (HIV−) in this cross-sectional cohort study. Voxel Based Morphometry was used to derive volumetric measurements at the level of the individual voxel. These brain structure maps were analyzed using Statistical Parametric Mapping (SPM2). IIVd was measured by computing intra-individual standard deviations (ISD’s) from the standardized performance scores of five neuropsychological tests: Wechsler Memory Scale-III Visual Reproduction I and II, Logical Memory I and II, Wechsler Adult Intelligence Scale-III Letter Number Sequencing. Results Total gray matter (GM) volume was inversely associated with IIVd. Among all subjects, IIVd -related GM atrophy was observed primarily in: 1) the inferior frontal gyrus bilaterally, the left inferior temporal gyrus extending to the supramarginal gyrus, spanning the lateral sulcus; 2) the right superior parietal lobule and intraparietal sulcus; and, 3) dorsal/ventral regions of the posterior section of the transverse temporal gyrus. HIV status, biological, and cardiovascular disease (CVD) variables were not linked to IIVd -related GM atrophy. Conclusions IIVd in neuropsychological test performance may be a sensitive marker of cortical integrity in older adults, regardless of HIV infection status or CVD risk factors, and degree of intra-individual variability links with volume loss in specific cortical regions; independent of mean-level performance on neuropsychological tests. PMID:26303224

New MR imaging assessment tool to define brain abnormalities in very preterm infants at term.

PubMed

Kidokoro, H; Neil, J J; Inder, T E

2013-01-01

WM injury is the dominant form of injury in preterm infants. However, other cerebral structures, including the deep gray matter and the cerebellum, can also be affected by injury and/or impaired growth. Current MR imaging injury assessment scales are subjective and are challenging to apply. Thus, we developed a new assessment tool and applied it to MR imaging studies obtained from very preterm infants at term age. MR imaging scans from 97 very preterm infants (< 30 weeks' gestation) and 22 healthy term-born infants were evaluated retrospectively. The severity of brain injury (defined by signal abnormalities) and impaired brain growth (defined with biometrics) was scored in the WM, cortical gray matter, deep gray matter, and cerebellum. Perinatal variables for clinical risks were collected. In very preterm infants, brain injury was observed in the WM (n=23), deep GM (n=5), and cerebellum (n=23). Combining measures of injury and impaired growth showed moderate to severe abnormalities most commonly in the WM (n=38) and cerebellum (n=32) but still notable in the cortical gray matter (n=16) and deep gray matter (n=11). WM signal abnormalities were associated with a reduced deep gray matter area but not with cerebellar abnormality. Intraventricular and/or parenchymal hemorrhage was associated with cerebellar signal abnormality and volume reduction. Multiple clinical risk factors, including prolonged intubation, prolonged parenteral nutrition, postnatal corticosteroid use, and postnatal sepsis, were associated with increased global abnormality on MR imaging. Very preterm infants demonstrate a high prevalence of injury and growth impairment in both the WM and gray matter. This MR imaging scoring system provides a more comprehensive and objective classification of the nature and extent of abnormalities than existing measures.

Morphological and Glucose Metabolism Abnormalities in Alcoholic Korsakoff's Syndrome: Group Comparisons and Individual Analyses

PubMed Central

Pitel, Anne-Lise; Aupée, Anne-Marie; Chételat, Gaël; Mézenge, Florence; Beaunieux, Hélène; de la Sayette, Vincent; Viader, Fausto; Baron, Jean-Claude; Eustache, Francis; Desgranges, Béatrice

2009-01-01

Background Gray matter volume studies have been limited to few brain regions of interest, and white matter and glucose metabolism have received limited research attention in Korsakoff's syndrome (KS). Because of the lack of brain biomarkers, KS was found to be underdiagnosed in postmortem studies. Methodology/Principal Findings Nine consecutively selected patients with KS and 22 matched controls underwent both structural magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography examinations. Using a whole-brain analysis, the between-group comparisons of gray matter and white matter density and relative glucose uptake between patients with KS and controls showed the involvement of both the frontocerebellar and the Papez circuits, including morphological abnormalities in their nodes and connection tracts and probably resulting hypometabolism. The direct comparison of the regional distribution and degree of gray matter hypodensity and hypometabolism within the KS group indicated very consistent gray matter distribution of both abnormalities, with a single area of significant difference in the middle cingulate cortex showing greater hypometabolism than hypodensity. Finally, the analysis of the variability in the individual patterns of brain abnormalities within our sample of KS patients revealed that the middle cingulate cortex was the only brain region showing significant GM hypodensity and hypometabolism in each of our 9 KS patients. Conclusions/Significance These results indicate widespread brain abnormalities in KS including both gray and white matter damage mainly involving two brain networks, namely, the fronto-cerebellar circuit and the Papez circuit. Furthermore, our findings suggest that the middle cingulate cortex may play a key role in the pathophysiology of KS and could be considered as a potential in vivo brain biomarker. PMID:19936229

Neuroplasticity as a function of second language learning: anatomical changes in the human brain.

PubMed

Li, Ping; Legault, Jennifer; Litcofsky, Kaitlyn A

2014-09-01

The brain has an extraordinary ability to functionally and physically change or reconfigure its structure in response to environmental stimulus, cognitive demand, or behavioral experience. This property, known as neuroplasticity, has been examined extensively in many domains. But how does neuroplasticity occur in the brain as a function of an individual's experience with a second language? It is not until recently that we have gained some understanding of this question by examining the anatomical changes as well as functional neural patterns that are induced by the learning and use of multiple languages. In this article we review emerging evidence regarding how structural neuroplasticity occurs in the brain as a result of one's bilingual experience. Our review aims at identifying the processes and mechanisms that drive experience-dependent anatomical changes, and integrating structural imaging evidence with current knowledge of functional neural plasticity of language and other cognitive skills. The evidence reviewed so far portrays a picture that is highly consistent with structural neuroplasticity observed for other domains: second language experience-induced brain changes, including increased gray matter (GM) density and white matter (WM) integrity, can be found in children, young adults, and the elderly; can occur rapidly with short-term language learning or training; and are sensitive to age, age of acquisition, proficiency or performance level, language-specific characteristics, and individual differences. We conclude with a theoretical perspective on neuroplasticity in language and bilingualism, and point to future directions for research. Copyright © 2014 Elsevier Ltd. All rights reserved.

Water response to ganglioside GM1 surface remodelling.

PubMed

Brocca, P; Rondelli, V; Mallamace, F; Di Bari, M T; Deriu, A; Lohstroh, W; Del Favero, E; Corti, M; Cantu', L

2017-01-01

Gangliosides are biological glycolipids participating in rafts, structural and functional domains of cell membranes. Their headgroups are able to assume different conformations when packed on the surface of an aggregate, more lying or standing. Switching between different conformations is possible, and is a collective event. Switching can be induced, in model systems, by concentration or temperature increase, then possibly involving ganglioside-water interaction. In the present paper, the effect of GM1 ganglioside headgroup conformation on the water structuring and interactions is addressed. Depolarized Rayleigh Scattering, Raman Scattering, Quasielastic Neutron Scattering and NMR measurements were performed on GM1 ganglioside solutions, focusing on solvent properties. All used techniques agree in evidencing differences in the structure and dynamics of solvent water on different time-and-length scales in the presence of either GM1 headgroup conformations. In general, all results indicate that both the structural properties of solvent water and its interactions with the sugar headgroups of GM1 respond to surface remodelling. The extent of this modification is much higher than expected and, interestingly, ganglioside headgroups seem to turn from cosmotropes to chaotropes upon collective rearrangement from the standing- to the lying-conformation. In a biological perspective, water structure modulation could be one of the physico-chemical elements contributing to the raft strategy, both for rafts formation and persistence and for their functional aspects. In particular, the interaction with approaching bodies could be favoured or inhibited or triggered by complex-sugar-sequence conformational switch. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of the topography of brain damage on depression and fatigue in patients with multiple sclerosis.

PubMed

Gobbi, C; Rocca, M A; Riccitelli, G; Pagani, E; Messina, R; Preziosa, P; Colombo, B; Rodegher, M; Falini, A; Comi, G; Filippi, M

2014-02-01

Involvement of selected central nervous system (CNS) regions has been associated with depression and fatigue in MS. We assessed whether specific regional patterns of lesion distribution and atrophy of the gray (GM) and white matter (WM) are associated with these symptoms in MS. Brain dual-echo and 3D T1-weighted images were acquired from 123 MS patients (69 depressed (D), 54 non-depressed (nD), 64 fatigued, 59 non-fatigued) and 90 controls. Lesion distribution, GM and WM atrophy were estimated using VBM and SPM8. Gender, age, disease duration and conventional MRI characteristics did not differ between D-MS and nD-MS patients. Fatigued patients experienced higher EDSS and depression than non-fatigued ones. Lesion distribution and WM atrophy were not related to depression and fatigue. Atrophy of regions in the frontal, parietal and occipital lobes had a combined effect on depression and fatigue. Atrophy of the left middle frontal gyrus and right inferior frontal gyrus were selectively related to depression. No specific pattern of GM atrophy was found to be related to fatigue. Depression in MS is linked to atrophy of cortical regions located in the bilateral frontal lobes. A distributed pattern of GM atrophy contributes to the concomitant presence of depression and fatigue in these patients.

Meditation effects within the hippocampal complex revealed by voxel-based morphometry and cytoarchitectonic probabilistic mapping

PubMed Central

Luders, Eileen; Kurth, Florian; Toga, Arthur W.; Narr, Katherine L.; Gaser, Christian

2013-01-01

Scientific studies addressing anatomical variations in meditators' brains have emerged rapidly over the last few years, where significant links are most frequently reported with respect to gray matter (GM). To advance prior work, this study examined GM characteristics in a large sample of 100 subjects (50 meditators, 50 controls), where meditators have been practicing close to 20 years, on average. A standard, whole-brain voxel-based morphometry approach was applied and revealed significant meditation effects in the vicinity of the hippocampus, showing more GM in meditators than in controls as well as positive correlations with the number of years practiced. However, the hippocampal complex is regionally segregated by architecture, connectivity, and functional relevance. Thus, to establish differential effects within the hippocampal formation (cornu ammonis, fascia dentata, entorhinal cortex, subiculum) as well as the hippocampal-amygdaloid transition area, we utilized refined cytoarchitectonic probabilistic maps of (peri-) hippocampal subsections. Significant meditation effects were observed within the subiculum specifically. Since the subiculum is known to play a key role in stress regulation and meditation is an established form of stress reduction, these GM findings may reflect neuronal preservation in long-term meditators—perhaps due to an attenuated release of stress hormones and decreased neurotoxicity. PMID:23847572

Permeability-diffusivity modeling vs. fractional anisotropy on white matter integrity assessment and application in schizophrenia.

PubMed

Kochunov, P; Chiappelli, J; Hong, L E

2013-01-01

Diffusion tensor imaging (DTI) assumes a single pool of anisotropically diffusing water to calculate fractional anisotropy (FA) and is commonly used to ascertain white matter (WM) deficits in schizophrenia. At higher b-values, diffusion-signal decay becomes bi-exponential, suggesting the presence of two, unrestricted and restricted, water pools. Theoretical work suggests that semi-permeable cellular membrane rather than the presence of two physical compartments is the cause. The permeability-diffusivity (PD) parameters measured from bi-exponential modeling may offer advantages, over traditional DTI-FA, in identifying WM deficits in schizophrenia. Imaging was performed in N = 26/26 patients/controls (age = 20-61 years, average age = 40.5 ± 12.6). Imaging consisted of fifteen b-shells: b = 250-3800 s/mm(2) with 30 directions/shell, covering seven slices of mid-sagittal corpus callosum (CC) at 1.7 × 1.7 × 4.6 mm. 64-direction DTI was also collected. Permeability-diffusivity-index (PDI), the ratio of restricted to unrestricted apparent diffusion coefficients, and the fraction of unrestricted compartment (Mu) were calculated for CC and cingulate gray matter (GM). FA values for CC were calculated using tract-based-spatial-statistics. Patients had significantly reduced PDI in CC (p ≅ 10(- 4)) and cingulate GM (p = 0.002), while differences in CC FA were modest (p ≅ .03). There was no group-related difference in Mu. Additional theoretical-modeling analysis suggested that reduced PDI in patients may be caused by reduced cross-membrane water molecule exchanges. PDI measurements for cerebral WM and GM yielded more robust patient-control differences than DTI-FA. Theoretical work offers an explanation that patient-control PDI differences should implicate abnormal active membrane permeability. This would implicate abnormal activities in ion-channels that use water as substrate for ion exchange, in cerebral tissues of schizophrenia patients.

Linked 4-Way Multimodal Brain Differences in Schizophrenia in a Large Chinese Han Population.

PubMed

Liu, Shengfeng; Wang, Haiying; Song, Ming; Lv, Luxian; Cui, Yue; Liu, Yong; Fan, Lingzhong; Zuo, Nianming; Xu, Kaibin; Du, Yuhui; Yu, Qingbao; Luo, Na; Qi, Shile; Yang, Jian; Xie, Sangma; Li, Jian; Chen, Jun; Chen, Yunchun; Wang, Huaning; Guo, Hua; Wan, Ping; Yang, Yongfeng; Li, Peng; Lu, Lin; Yan, Hao; Yan, Jun; Wang, Huiling; Zhang, Hongxing; Zhang, Dai; Calhoun, Vince D; Jiang, Tianzi; Sui, Jing

2018-04-20

Multimodal fusion has been regarded as a promising tool to discover covarying patterns of multiple imaging types impaired in brain diseases, such as schizophrenia (SZ). In this article, we aim to investigate the covarying abnormalities underlying SZ in a large Chinese Han population (307 SZs, 298 healthy controls [HCs]). Four types of magnetic resonance imaging (MRI) features, including regional homogeneity (ReHo) from resting-state functional MRI, gray matter volume (GM) from structural MRI, fractional anisotropy (FA) from diffusion MRI, and functional network connectivity (FNC) resulted from group independent component analysis, were jointly analyzed by a data-driven multivariate fusion method. Results suggest that a widely distributed network disruption appears in SZ patients, with synchronous changes in both functional and structural regions, especially the basal ganglia network, salience network (SAN), and the frontoparietal network. Such a multimodal coalteration was also replicated in another independent Chinese sample (40 SZs, 66 HCs). Our results on auditory verbal hallucination (AVH) also provide evidence for the hypothesis that prefrontal hypoactivation and temporal hyperactivation in SZ may lead to failure of executive control and inhibition, which is relevant to AVH. In addition, impaired working memory performance was found associated with GM reduction and FA decrease in SZ in prefrontal and superior temporal area, in both discovery and replication datasets. In summary, by leveraging multiple imaging and clinical information into one framework to observe brain in multiple views, we can integrate multiple inferences about SZ from large-scale population and offer unique perspectives regarding the missing links between the brain function and structure that may not be achieved by separate unimodal analyses.

White versus gray matter: fMRI hemodynamic responses show similar characteristics, but differ in peak amplitude

PubMed Central

2012-01-01

Background There is growing evidence for the idea of fMRI activation in white matter. In the current study, we compared hemodynamic response functions (HRF) in white matter and gray matter using 4 T fMRI. White matter fMRI activation was elicited in the isthmus of the corpus callosum at both the group and individual levels (using an established interhemispheric transfer task). Callosal HRFs were compared to HRFs from cingulate and parietal activation. Results Examination of the raw HRF revealed similar overall response characteristics. Finite impulse response modeling confirmed that the WM HRF characteristics were comparable to those of the GM HRF, but had significantly decreased peak response amplitudes. Conclusions Overall, the results matched a priori expectations of smaller HRF responses in white matter due to the relative drop in cerebral blood flow (CBF) and cerebral blood volume (CBV). Importantly, the findings demonstrate that despite lower CBF and CBV, white matter fMRI activation remained within detectable ranges at 4 T. PMID:22852798

A peptidogalactomannan isolated from Cladosporium herbarum induces defense-related genes in BY-2 tobacco cells.

PubMed

Mattos, Bianca Braz; Montebianco, Caroline; Romanel, Elisson; da Franca Silva, Tatiane; Bernabé, Renato Barroso; Simas-Tosin, Fernanda; Souza, Lauro M; Sassaki, Guilherme L; Vaslin, Maite F S; Barreto-Bergter, Eliana

2018-05-01

Cladosporium herbarum is a plant pathogen associated with passion fruit scab and mild diseases in pea and soybean. In this study, a peptidogalactomannan (pGM) of C. herbarum mycelium was isolated and structurally characterized, and its role in plant-fungus interactions was evaluated. C. herbarum pGM is composed of carbohydrates (76%) and contains mannose, galactose and glucose as its main monosaccharides (molar ratio, 52:36:12). Methylation and 13 C-nuclear magnetic resonance ( 13 C-NMR) spectroscopy analysis have shown the presence of a main chain containing (1 → 6)-linked α-D-Manp residues, and β-D-Galf residues are present as (1 → 5)-interlinked side chains. β-Galactofuranose containing similar structures were characterized by our group in A. fumigatus, A. versicolor, A. flavus and C. resinae. Tobacco BY-2 cells were used as a model system to address the question of the role of C. herbarum pGM in cell viability and induction of the expression of plant defense-related genes. Native and partially acid hydrolyzed pGMs (lacking galactofuranosyl side-chain residues) were incubated with BY-2 cell suspensions at different concentrations. Cell viability drastically decreased after exposure to more than 400 μg ml -1 pGM; however no cell viability effect was observed after exposure to a partially acid hydrolyzed pGM. BY-2 cell contact with pGM strongly induce the expression of plant defense-related genes, such as phenylalanine ammonia lyase (PAL) and lipoxygenase (LOX), as well as the pathogen-related PR-1a, PR-2 and PR-3 genes, suggesting that pGM activates defense responses in tobacco cells. Interestingly, contact with partially hydrolyzed pGM also induced defense-related gene expression at earlier times than native pGM. These results show that the side chains of the (1 → 5)-linked β-D-galactofuranosyl units from pGM play an important role in the first line fungus-plant interactions mediating plant responses against C. herbarum. In addition, it was observed that pGM and/or C. herbarum conidia are able to induced HR when in contact with tobacco leaves and in vitro plantlets roots, producing necrotic lesions and peroxidase and NO burst, respectively. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Complete localization of disulfide bonds in GM2 activator protein.

PubMed Central

Schütte, C. G.; Lemm, T.; Glombitza, G. J.; Sandhoff, K.

1998-01-01

Lysosomal degradation of ganglioside GM2 by hexosaminidase A requires the presence of a small, non-enzymatic cofactor, the GM2-activator protein (GM2AP). Lack of functional protein leads to the AB variant of GM2-gangliosidosis, a fatal lysosomal storage disease. Although its possible mode of action and functional domains have been discussed frequently in the past, no structural information about GM2AP is available so far. Here, we determine the complete disulfide bond pattern of the protein. Two of the four disulfide bonds present in the protein were open to classical determination by enzymatic cleavage and mass spectrometry. The direct localization of the remaining two bonds was impeded by the close vicinity of cysteines 136 and 138. We determined the arrangement of these disulfide bonds by MALDI-PSD analysis of disulfide linked peptides and by partial reduction, cyanylation and fragmentation in basic solution, as described recently (Wu F, Watson JT, 1997, Protein Sci 6:391-398). PMID:9568910

Resistance of pathogenic and spoilage microorganisms to disinfectants in the presence of organic matter and their residual effect on stainless steel and polypropylene.

PubMed

Iñiguez-Moreno, Maricarmen

2018-04-23

The effectiveness of disinfectants can vary according to the microorganism, type of residues and surface. Hence, the aim of this study was to determine the effectiveness of four disinfectants in the presence of organic matter and their residual effect on stainless steel grade 304 (SS) and polypropylene B (PP-B). The disinfectant effectiveness in the presence of meat extract, yolk egg and whole milk was determined according to AOAC and UNE-EN 1040:2015; the residual effect was realized according to UNE-EN 13697:2015, using approved strains. The disinfectant effectiveness was affect at different grades depending on the organic matter present; disinfectant A (400μgmL -1 , fifth generation quaternary ammonium compound, QAC) was most effective in the presence of 10% meat extract, while the disinfectant C (200μgmL -1 , peracetic acid) had better activity in the presence of 10% egg yolk and whole milk. In the evaluation of residual effect onto SS and PP-B, the QAC had the better effect, reducing 6 Log 10 CFU mL -1 of Listeria monocytogenes ATCC 19111 24h after their application. Conversely, the disinfectants had no residual effect against Pseudomonas aeruginosa ATCC 15442. The antimicrobial activity of disinfectants tested against pathogenic and spoilage microorganisms was affected according to the type of organic matter. Disinfectant A had a more residual effect than the other disinfectants evaluated. Moreover, the residual effect of a disinfectant is greater on SS than on PP-B and dependent on the microorganism tested. Copyright © 2018. Published by Elsevier Ltd.

In cellulo examination of a beta-alpha hybrid construct of beta-hexosaminidase A subunits, reported to interact with the GM2 activator protein and hydrolyze GM2 ganglioside.

PubMed

Sinici, Incilay; Yonekawa, Sayuri; Tkachyova, Ilona; Gray, Steven J; Samulski, R Jude; Wakarchuk, Warren; Mark, Brian L; Mahuran, Don J

2013-01-01

The hydrolysis in lysosomes of GM2 ganglioside to GM3 ganglioside requires the correct synthesis, intracellular assembly and transport of three separate gene products; i.e., the alpha and beta subunits of heterodimeric beta-hexosaminidase A, E.C. # 3.2.1.52 (encoded by the HEXA and HEXB genes, respectively), and the GM2-activator protein (GM2AP, encoded by the GM2A gene). Mutations in any one of these genes can result in one of three neurodegenerative diseases collectively known as GM2 gangliosidosis (HEXA, Tay-Sachs disease, MIM # 272800; HEXB, Sandhoff disease, MIM # 268800; and GM2A, AB-variant form, MIM # 272750). Elements of both of the hexosaminidase A subunits are needed to productively interact with the GM2 ganglioside-GM2AP complex in the lysosome. Some of these elements have been predicted from the crystal structures of hexosaminidase and the activator. Recently a hybrid of the two subunits has been constructed and reported to be capable of forming homodimers that can perform this reaction in vivo, which could greatly simplify vector-mediated gene transfer approaches for Tay-Sachs or Sandhoff diseases. A cDNA encoding a hybrid hexosaminidase subunit capable of dimerizing and hydrolyzing GM2 ganglioside could be incorporated into a single vector, whereas packaging both subunits of hexosaminidase A into vectors, such as adeno-associated virus, would be impractical due to size constraints. In this report we examine the previously published hybrid construct (H1) and a new more extensive hybrid (H2), with our documented in cellulo (live cell- based) assay utilizing a fluorescent GM2 ganglioside derivative. Unfortunately when Tay-Sachs cells were transfected with either the H1 or H2 hybrid construct and then were fed the GM2 derivative, no significant increase in its turnover was detected. In vitro assays with the isolated H1 or H2 homodimers confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside.

In Cellulo Examination of a Beta-Alpha Hybrid Construct of Beta-Hexosaminidase A Subunits, Reported to Interact with the GM2 Activator Protein and Hydrolyze GM2 Ganglioside

PubMed Central

Sinici, Incilay; Yonekawa, Sayuri; Tkachyova, Ilona; Gray, Steven J.; Samulski, R. Jude; Wakarchuk, Warren; Mark, Brian L.; Mahuran, Don J.

2013-01-01

The hydrolysis in lysosomes of GM2 ganglioside to GM3 ganglioside requires the correct synthesis, intracellular assembly and transport of three separate gene products; i.e., the alpha and beta subunits of heterodimeric beta-hexosaminidase A, E.C. # 3.2.1.52 (encoded by the HEXA and HEXB genes, respectively), and the GM2-activator protein (GM2AP, encoded by the GM2A gene). Mutations in any one of these genes can result in one of three neurodegenerative diseases collectively known as GM2 gangliosidosis (HEXA, Tay-Sachs disease, MIM # 272800; HEXB, Sandhoff disease, MIM # 268800; and GM2A, AB-variant form, MIM # 272750). Elements of both of the hexosaminidase A subunits are needed to productively interact with the GM2 ganglioside-GM2AP complex in the lysosome. Some of these elements have been predicted from the crystal structures of hexosaminidase and the activator. Recently a hybrid of the two subunits has been constructed and reported to be capable of forming homodimers that can perform this reaction in vivo, which could greatly simplify vector-mediated gene transfer approaches for Tay-Sachs or Sandhoff diseases. A cDNA encoding a hybrid hexosaminidase subunit capable of dimerizing and hydrolyzing GM2 ganglioside could be incorporated into a single vector, whereas packaging both subunits of hexosaminidase A into vectors, such as adeno-associated virus, would be impractical due to size constraints. In this report we examine the previously published hybrid construct (H1) and a new more extensive hybrid (H2), with our documented in cellulo (live cell- based) assay utilizing a fluorescent GM2 ganglioside derivative. Unfortunately when Tay-Sachs cells were transfected with either the H1 or H2 hybrid construct and then were fed the GM2 derivative, no significant increase in its turnover was detected. In vitro assays with the isolated H1 or H2 homodimers confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside. PMID:23483939

An α-subunit loop structure is required for GM2 activator protein binding by β-hexosaminidase A

PubMed Central

Zarghooni, Maryam; Bukovac, Scott; Tropak, Michael; Callahan, John; Mahuran, Don

2010-01-01

The α- and/or β-subunits of human β-hexosaminidase A (αβ) and B (ββ) are ~60% identical. In vivo only β-hexosaminidase A can utilize GM2 ganglioside as a substrate, but requires the GM2 activator protein to bind GM2 ganglioside and then interact with the enzyme, placing the terminal GalNAc residue in the active site of the α-subunit. A model for this interaction suggests that two loop structures, present only in the α-subunit, may be critical to this binding. Three amino acids in one of these loops are not encoded in the HEXB gene, while four from the other are removed posttranslationally from the pro-β-subunit. Natural substrate assays with forms of hexosaminidase A containing mutant α-subunits demonstrate that only the site that is removed from the β-subunit during its maturation is critical for the interaction. Our data suggest an unexpected biological role for such proteolytic processing events. PMID:15485660

Prospective longitudinal MRI study of brain volumes and diffusion changes during the first year after moderate to severe traumatic brain injury

PubMed Central

Brezova, Veronika; G⊘ran Moen, Kent; Skandsen, Toril; Vik, Anne; Brewer, James B.; Salvesen, Øyvind; Håberg, Asta K.

2014-01-01

The objectives of this prospective study in 62 moderate–severe TBI patients were to investigate volume change in cortical gray matter (GM), hippocampus, lenticular nucleus, lobar white matter (WM), brainstem and ventricles using a within subject design and repeated MRI in the early phase (1–26 days) and 3 and 12 months postinjury and to assess changes in GM apparent diffusion coefficient (ADC) in normal appearing tissue in the cortex, hippocampus and brainstem. The impact of Glasgow Coma Scale (GCS) score at admission, duration of post-traumatic amnesia (PTA), and diffusion axonal injury (DAI) grade on brain volumes and ADC values over time was assessed. Lastly, we determined if MRI-derived brain volumes from the 3-month scans provided additional, significant predictive value to 12-month outcome classified with the Glasgow Outcome Scale—Extended after adjusting for GCS, PTA and age. Cortical GM loss was rapid, largely finished by 3 months, but the volume reduction was unrelated to GCS score, PTA, or presence of DAI. However, cortical GM volume at 3 months was a significant independent predictor of 12-month outcome. Volume loss in the hippocampus and lenticular nucleus was protracted and statistically significant first at 12 months. Slopes of volume reduction over time for the cortical and subcortical GGM were significantly different. Hippocampal volume loss was most pronounced and rapid in individuals with PTA > 2 weeks. The 3-month volumes of the hippocampus and lentiform nucleus were the best independent predictors of 12-month outcome after adjusting for GCS, PTA and age. In the brainstem, volume loss was significant at both 3 and 12 months. Brainstem volume reduction was associated with lower GCS score and the presence of DAI. Lobar WM volume was significantly decreased first after 12 months. Surprisingly DAI grade had no impact on lobar WM volume. Ventricular dilation developed predominantly during the first 3 months, and was strongly associated with volume changes in the brainstem and cortical GM, but not lobar WM volume. Higher ADC values were detected in the cortex in individuals with severe TBI, DAI and PTA > 2 weeks, from 3 months. There were no associations between ADC values and brain volumes, and ADC values did not predict outcome. PMID:25068105

A discriminative model-constrained EM approach to 3D MRI brain tissue classification and intensity non-uniformity correction

NASA Astrophysics Data System (ADS)

Wels, Michael; Zheng, Yefeng; Huber, Martin; Hornegger, Joachim; Comaniciu, Dorin

2011-06-01

We describe a fully automated method for tissue classification, which is the segmentation into cerebral gray matter (GM), cerebral white matter (WM), and cerebral spinal fluid (CSF), and intensity non-uniformity (INU) correction in brain magnetic resonance imaging (MRI) volumes. It combines supervised MRI modality-specific discriminative modeling and unsupervised statistical expectation maximization (EM) segmentation into an integrated Bayesian framework. While both the parametric observation models and the non-parametrically modeled INUs are estimated via EM during segmentation itself, a Markov random field (MRF) prior model regularizes segmentation and parameter estimation. Firstly, the regularization takes into account knowledge about spatial and appearance-related homogeneity of segments in terms of pairwise clique potentials of adjacent voxels. Secondly and more importantly, patient-specific knowledge about the global spatial distribution of brain tissue is incorporated into the segmentation process via unary clique potentials. They are based on a strong discriminative model provided by a probabilistic boosting tree (PBT) for classifying image voxels. It relies on the surrounding context and alignment-based features derived from a probabilistic anatomical atlas. The context considered is encoded by 3D Haar-like features of reduced INU sensitivity. Alignment is carried out fully automatically by means of an affine registration algorithm minimizing cross-correlation. Both types of features do not immediately use the observed intensities provided by the MRI modality but instead rely on specifically transformed features, which are less sensitive to MRI artifacts. Detailed quantitative evaluations on standard phantom scans and standard real-world data show the accuracy and robustness of the proposed method. They also demonstrate relative superiority in comparison to other state-of-the-art approaches to this kind of computational task: our method achieves average Dice coefficients of 0.93 ± 0.03 (WM) and 0.90 ± 0.05 (GM) on simulated mono-spectral and 0.94 ± 0.02 (WM) and 0.92 ± 0.04 (GM) on simulated multi-spectral data from the BrainWeb repository. The scores are 0.81 ± 0.09 (WM) and 0.82 ± 0.06 (GM) and 0.87 ± 0.05 (WM) and 0.83 ± 0.12 (GM) for the two collections of real-world data sets—consisting of 20 and 18 volumes, respectively—provided by the Internet Brain Segmentation Repository.

Effectiveness of dust control methods for crystalline silica and respirable suspended particulate matter exposure during manual concrete surface grinding.

PubMed

Akbar-Khanzadeh, Farhang; Milz, Sheryl A; Wagner, Cynthia D; Bisesi, Michael S; Ames, April L; Khuder, Sadik; Susi, Pam; Akbar-Khanzadeh, Mahboubeh

2010-12-01

Concrete grinding exposes workers to unacceptable levels of crystalline silica dust, known to cause diseases such as silicosis and possibly lung cancer. This study examined the influence of major factors of exposure and effectiveness of existing dust control methods by simulating field concrete grinding in an enclosed workplace laboratory. Air was monitored during 201 concrete grinding sessions while using a variety of grinders, accessories, and existing dust control methods, including general ventilation (GV), local exhaust ventilation (LEV), and wet grinding. Task-specific geometric mean (GM) of respirable crystalline silica dust concentrations (mg/m³ for LEV:HEPA-, LEV:Shop-vac-, wet-, and uncontrolled-grinding, while GV was off/on, were 0.17/0.09, 0.57/0.13, 1.11/0.44, and 23.1/6.80, respectively. Silica dust concentrations (mg/m³ using 100-125 mm (4-5 inch) and 180 mm (7 inch) grinding cups were 0.53/0.22 and 2.43/0.56, respectively. GM concentrations of silica dust were significantly lower for (1) GV on (66.0%) vs. off, and (2) LEV:HEPA- (99.0%), LEV:Shop-vac- (98.1%) or wet- (94.4%) vs. uncontrolled-grinding. Task-specific GM of respirable suspended particulate matter (RSP) concentrations (mg/m³ for LEV:HEPA-, LEV:Shop-vac-, wet-, and uncontrolled grinding, while GV was off/on, were 1.58/0.63, 7.20/1.15, 9.52/4.13, and 152/47.8, respectively. GM concentrations of RSP using 100-125 mm and 180 mm grinding cups were 4.78/1.62 and 22.2/5.06, respectively. GM concentrations of RSP were significantly lower for (1) GV on (70.2%) vs. off, and (2) LEV:HEPA- (98.9%), LEV:Shop-vac- (96.9%) or wet- (92.6%) vs. uncontrolled grinding. Silica dust and RSP were not significantly affected by (1) orientation of grinding surfaces (vertical vs. inclined); (2) water flow rates for wet grinding; (3) length of task-specific sampling time; or, (4) among cup sizes of 100, 115 or 125 mm. No combination of factors or control methods reduced an 8-hr exposure level to below the recommended criterion of 0.025 mg/m³ for crystalline silica, requiring further refinement in engineering controls, administrative controls, or the use of respirators.

A discriminative model-constrained EM approach to 3D MRI brain tissue classification and intensity non-uniformity correction.

PubMed

Wels, Michael; Zheng, Yefeng; Huber, Martin; Hornegger, Joachim; Comaniciu, Dorin

2011-06-07

We describe a fully automated method for tissue classification, which is the segmentation into cerebral gray matter (GM), cerebral white matter (WM), and cerebral spinal fluid (CSF), and intensity non-uniformity (INU) correction in brain magnetic resonance imaging (MRI) volumes. It combines supervised MRI modality-specific discriminative modeling and unsupervised statistical expectation maximization (EM) segmentation into an integrated Bayesian framework. While both the parametric observation models and the non-parametrically modeled INUs are estimated via EM during segmentation itself, a Markov random field (MRF) prior model regularizes segmentation and parameter estimation. Firstly, the regularization takes into account knowledge about spatial and appearance-related homogeneity of segments in terms of pairwise clique potentials of adjacent voxels. Secondly and more importantly, patient-specific knowledge about the global spatial distribution of brain tissue is incorporated into the segmentation process via unary clique potentials. They are based on a strong discriminative model provided by a probabilistic boosting tree (PBT) for classifying image voxels. It relies on the surrounding context and alignment-based features derived from a probabilistic anatomical atlas. The context considered is encoded by 3D Haar-like features of reduced INU sensitivity. Alignment is carried out fully automatically by means of an affine registration algorithm minimizing cross-correlation. Both types of features do not immediately use the observed intensities provided by the MRI modality but instead rely on specifically transformed features, which are less sensitive to MRI artifacts. Detailed quantitative evaluations on standard phantom scans and standard real-world data show the accuracy and robustness of the proposed method. They also demonstrate relative superiority in comparison to other state-of-the-art approaches to this kind of computational task: our method achieves average Dice coefficients of 0.93 ± 0.03 (WM) and 0.90 ± 0.05 (GM) on simulated mono-spectral and 0.94 ± 0.02 (WM) and 0.92 ± 0.04 (GM) on simulated multi-spectral data from the BrainWeb repository. The scores are 0.81 ± 0.09 (WM) and 0.82 ± 0.06 (GM) and 0.87 ± 0.05 (WM) and 0.83 ± 0.12 (GM) for the two collections of real-world data sets-consisting of 20 and 18 volumes, respectively-provided by the Internet Brain Segmentation Repository.

Using the Moon As A Low-Noise Seismic Detector For Strange Quark Nuggets

NASA Technical Reports Server (NTRS)

Banerdt, W. Bruce; Chui, Talso; Griggs, Cornelius E.; Herrin, Eugene T.; Nakamura, Yosio; Paik, Ho Jung; Penanen, Konstantin; Rosenbaum, Doris; Teplitz, Vigdor L.; Young, Joseph

2006-01-01

Strange quark matter made of up, down and strange quarks has been postulated by Witten [1]. Strange quark matter would be nearly charge neutral and would have density of nuclear matter (10(exp 14) gm/cu cm). Witten also suggested that nuggets of strange quark matter, or strange quark nuggets (SQNs), could have formed shortly after the Big Bang, and that they would be viable candidates for cold dark matter. As suggested by de Rujula and Glashow [2], an SQN may pass through a celestial body releasing detectable seismic energy along a straight line. The Moon, being much quieter seismically than the Earth, would be a favorable place to search for such events. We review previous searches for SQNs to illustrate the parameter space explored by using the Moon as a low-noise detector of SQNs. We also discuss possible detection schemes using a single seismometer, and using an International Lunar Seismic Network.

Soybean TCP transcription factors: Evolution, classification, protein interaction and stress and hormone responsiveness.

PubMed

Feng, Zhi-Juan; Xu, Sheng-Chun; Liu, Na; Zhang, Gu-Wen; Hu, Qi-Zan; Gong, Ya-Ming

2018-06-01

TEOSINTE-BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors, a family of plant-specific proteins, play crucial roles in plant growth and development and stress response. However, systematical information is unknown regarding the TCP gene family in soybean. In the present study, a total of 54 GmTCPs were identified in soybean, which were grouped into 11 groups with the typical TCP conserved domains. Phylogenetic relationship, protein motif and gene structure analyses distinguished the GmTCPs into two homology classes: Class I and Class II. Class II was then differentiated into two subclasses: CIN and CYC/TB1. Unique cis-element number and composition existed in the promoter regions which might be involved in the gene transcriptional regulation of different GmTCPs. Tissue expression analysis demonstrated the diverse spatiotemporal expression profiles of GmTCPs. Furthermore, the interaction protein of one previously functionally unknown TCP protein-GmTCP8 was investigated. Yeast two-hybrid assay showed the interaction between GmTCP8 and an abscisic acid receptor (GmPYL10). QRT-PCR assays indicated the distinct expression profiles of GmTCPs in response to abiotic stresses (heat, drought and salt) and stress-related signals (abscisic acid, brassinolide, salicylicacid and methyl jasmonate). These results will facilitate to uncover the possible roles of GmTCPs under abiotic stress and hormone signal responses in soybean. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Hyperbolically Patterned 3D Graphene Metamaterial with Negative Poisson's Ratio and Superelasticity.

PubMed

Zhang, Qiangqiang; Xu, Xiang; Lin, Dong; Chen, Wenli; Xiong, Guoping; Yu, Yikang; Fisher, Timothy S; Li, Hui

2016-03-16

A hyperbolically patterned 3D graphene metamaterial (GM) with negative Poisson's ratio and superelasticity is highlighted. It is synthesized by a modified hydrothermal approach and subsequent oriented freeze-casting strategy. GM presents a tunable Poisson's ratio by adjusting the structural porosity, macroscopic aspect ratio (L/D), and freeze-casting conditions. Such a GM suggests promising applications as soft actuators, sensors, robust shock absorbers, and environmental remediation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Investigating the neuroanatomical substrate of pathological laughing and crying in amyotrophic lateral sclerosis with multimodal neuroimaging techniques.

PubMed

Christidi, Foteini; Karavasilis, Efstratios; Ferentinos, Panagiotis; Xirou, Sophia; Velonakis, Georgios; Rentzos, Michalis; Zouvelou, Vasiliki; Zalonis, Ioannis; Efstathopoulos, Efstathios; Kelekis, Nikolaos; Evdokimidis, Ioannis

2018-02-01

Pathological laughing and crying (PLC) is common in several neurological and psychiatric diseases and is associated with a distributed network involving the frontal cortex, the brainstem and cortico-pontine-cerebellar circuits. By applying multimodal neuroimaging approach, we examined the neuroanatomical substrate of PLC in a sample of patients with amyotrophic lateral sclerosis (ALS). We studied 56 non-demented ALS patients and 25 healthy controls (HC). PLC was measured in ALS using the Center of Neurologic Study Lability Scale (CNS-LS; cutoff score: 13). All participants underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging at 3T. Voxel-based morphometry and tract-based spatial-statistics analysis was used to examine gray matter (GM) and white matter (WM) differences between ALS patients with and without PLC (ALS-PLC and ALS-nonPLC, respectively). Comparisons were restricted to regions with detected differences between ALS and HC, controlling for age, gender, total intracranial volume and depressive symptoms. In regions with significant differences between ALS and HC, ALS-PLC patients showed decreased GM volume in left orbitofrontal cortex, frontal operculum, and putamen and bilateral frontal poles, compared to ALS-nonPLC. They also had decreased fractional anisotropy in left cingulum bundle and posterior corona radiata. WM abnormalities were additionally detected in WM associative and ponto-cerebellar tracts (using a more liberal threshold). PLC in ALS is driven by both GM and WM abnormalities which highlight the role of circuits rather than isolated centers in the emergence of this condition. ALS is suggested as a useful natural experimental model to study PLC.

Adverse childhood experiences influence the detrimental effect of bipolar disorder and schizophrenia on cortico-limbic grey matter volumes.

PubMed

Poletti, Sara; Vai, Benedetta; Smeraldi, Enrico; Cavallaro, Roberto; Colombo, Cristina; Benedetti, Francesco

2016-01-01

Adverse childhood experiences (ACE) can lead to several negative consequences in adult life, are highly prevalent in psychiatric disorders where they associate with clinical and brain morphological features. Grey matter volume loss is a central characteristic of bipolar disorder (BD) and schizophrenia (SCZ). The aim of this study is to measure the effect of diagnosis and ACE on GM volume in a sample of patients with BD or SCZ compared with healthy controls (HC). We studied 206 depressed BD patients, 96 SCZ patients and 136 healthy subjects. GM volumes were estimated with 3.0 Tesla MRI and analyzed with VBM technique. The effect of diagnosis was investigated in the whole sample and separately exposed to high and low ACE subjects. An effect of diagnosis was observed in orbitofrontal cortex encompassing BA 47 and insula, and in the thalamus. HC had the highest volume and SCZ patients the lowest with BD patients showing an intermediate volume. This pattern persisted only in subjects with high ACE. No differences were observed for low ACE subjects. The three diagnostic groups differ for age and education, previous and current medications, and treatment periods. Our results underline the importance of ACE on the neural underpinnings of psychiatric psychopathology and suggest a major role of exposure to ACE for the GM deficits to reveal in clinical populations. Exposure to early stress is a crucial factor that must be taken in to account when searching for biomarkers of BD and SCZ. Copyright © 2015 Elsevier B.V. All rights reserved.

A diffusional kurtosis imaging study of idiopathic generalized epilepsy with unilateral interictal epileptiform discharges in children.

PubMed

Zhang, Yuzhen; Gao, Yu; Zhou, Minxiong; Wu, Jie; Zee, Chishing; Wang, Dengbin

2016-10-01

To investigate brain abnormalities in children with a clinical diagnosis of idiopathic generalized epilepsy (IGE) and unilateral interictal epileptiform discharges (IED) demonstrated on electroencephalography (EEG) by diffusional kurtosis imaging (DKI). DKI images were obtained from 18 patients (n=9 each in the left and right hemispheres). Fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) maps were estimated through voxel-based analyses, and compared with 18 normal controls matched for age and sex. In the left side group, the significant differences of FA were in the left fusiform gyrus and occipital lobe of the white matter (WM). The significant differences of MD were in the left pons. The significant differences of MK were in the anterior cingulate gyrus, limbic lobe, gray matter (GM) and WM of the right cerebrum. In the right side group, the significant differences of FA were in the WM of the left cerebrum. MD identified differences in the frontal, temporal, occipital, and parietal lobes of both hemispheres, especially in the limbic system, fusiform gyrus, uncus, and parahippocampal gyrus. The significant differences of MK were in the GM of the right cerebrum, particularly in the rolandic operculum and frontal lobe. DKI is sensitive for the detection of diffusion abnormalities in both WM and GM of IGE in children. Secondary brain abnormalities may exist in regions outside the unilateral epileptogenic zone through the limbic epileptic network, and can be detected by DKI indices FA, MD and MK. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Automatic segmentation of MR brain images of preterm infants using supervised classification.

PubMed

Moeskops, Pim; Benders, Manon J N L; Chiţ, Sabina M; Kersbergen, Karina J; Groenendaal, Floris; de Vries, Linda S; Viergever, Max A; Išgum, Ivana

2015-09-01

Preterm birth is often associated with impaired brain development. The state and expected progression of preterm brain development can be evaluated using quantitative assessment of MR images. Such measurements require accurate segmentation of different tissue types in those images. This paper presents an algorithm for the automatic segmentation of unmyelinated white matter (WM), cortical grey matter (GM), and cerebrospinal fluid in the extracerebral space (CSF). The algorithm uses supervised voxel classification in three subsequent stages. In the first stage, voxels that can easily be assigned to one of the three tissue types are labelled. In the second stage, dedicated analysis of the remaining voxels is performed. The first and the second stages both use two-class classification for each tissue type separately. Possible inconsistencies that could result from these tissue-specific segmentation stages are resolved in the third stage, which performs multi-class classification. A set of T1- and T2-weighted images was analysed, but the optimised system performs automatic segmentation using a T2-weighted image only. We have investigated the performance of the algorithm when using training data randomly selected from completely annotated images as well as when using training data from only partially annotated images. The method was evaluated on images of preterm infants acquired at 30 and 40weeks postmenstrual age (PMA). When the method was trained using random selection from the completely annotated images, the average Dice coefficients were 0.95 for WM, 0.81 for GM, and 0.89 for CSF on an independent set of images acquired at 30weeks PMA. When the method was trained using only the partially annotated images, the average Dice coefficients were 0.95 for WM, 0.78 for GM and 0.87 for CSF for the images acquired at 30weeks PMA, and 0.92 for WM, 0.80 for GM and 0.85 for CSF for the images acquired at 40weeks PMA. Even though the segmentations obtained using training data from the partially annotated images resulted in slightly lower Dice coefficients, the performance in all experiments was close to that of a second human expert (0.93 for WM, 0.79 for GM and 0.86 for CSF for the images acquired at 30weeks, and 0.94 for WM, 0.76 for GM and 0.87 for CSF for the images acquired at 40weeks). These results show that the presented method is robust to age and acquisition protocol and that it performs accurate segmentation of WM, GM, and CSF when the training data is extracted from complete annotations as well as when the training data is extracted from partial annotations only. This extends the applicability of the method by reducing the time and effort necessary to create training data in a population with different characteristics. Copyright © 2015 Elsevier Inc. All rights reserved.

Conformation of a Group 2 Late Embryogenesis Abundant Protein from Soybean. Evidence of Poly (l-Proline)-type II Structure1

PubMed Central

Soulages, Jose L.; Kim, Kangmin; Arrese, Estela L.; Walters, Christina; Cushman, John C.

2003-01-01

Late embryogenesis abundant (LEA) proteins are members of a large group of hydrophilic, glycine-rich proteins found in plants, algae, fungi, and bacteria known collectively as hydrophilins that are preferentially expressed in response to dehydration or hyperosmotic stress. Group 2 LEA (dehydrins or responsive to abscisic acid) proteins are postulated to stabilize macromolecules against damage by freezing, dehydration, ionic, or osmotic stress. However, the structural and physicochemical properties of group 2 LEA proteins that account for such functions remain unknown. We have analyzed the structural properties of a recombinant form of a soybean (Glycine max) group 2 LEA (rGmDHN1). Differential scanning calorimetry of purified rGmDHN1 demonstrated that the protein does not display a cooperative unfolding transition upon heating. Ultraviolet absorption and circular dichroism spectroscopy revealed that the protein is in a largely hydrated and unstructured conformation in solution. However, ultraviolet absorption and circular dichroism measurements collected at different temperatures showed that the protein exists in equilibrium between two extended conformational states: unordered and left-handed extended helical or poly (l-proline)-type II structures. It is estimated that 27% of the residues of rGmDHN1 adopt or poly (l-proline)-type II-like helical conformation at 12°C. The content of extended helix gradually decreases to 15% as the temperature is increased to 80°C. Studies of the conformation of the protein in solution in the presence of liposomes, trifluoroethanol, and sodium dodecyl sulfate indicated that rGmDHN1 has a very low intrinsic ability to adopt α-helical structure and to interact with phospholipid bilayers through amphipathic α-helices. The ability of the protein to remain in a highly extended conformation at low temperatures could constitute the basis of the functional role of GmDHN1 in the prevention of freezing, desiccation, ionic, or osmotic stress-related damage to macromolecular structures. PMID:12644649

Resting-State Hyperperfusion of the Supplementary Motor Area in Catatonia

PubMed Central

Schäppi, Lea; Federspiel, Andrea; Bohlhalter, Stephan; Wiest, Roland; Strik, Werner; Stegmayer, Katharina

2017-01-01

Abstract Catatonia is a psychomotor syndrome that not only frequently occurs in the context of schizophrenia but also in other conditions. The neural correlates of catatonia remain unclear due to small-sized studies. We therefore compared resting-state cerebral blood flow (rCBF) and gray matter (GM) density between schizophrenia patients with current catatonia and without catatonia and healthy controls. We included 42 schizophrenia patients and 41 controls. Catatonia was currently present in 15 patients (scoring >2 items on the Bush Francis Catatonia Rating Scale screening). Patients did not differ in antipsychotic medication or positive symptoms. We acquired whole-brain rCBF using arterial spin labeling and GM density. We compared whole-brain perfusion and GM density over all and between the groups using 1-way ANCOVAs (F and T tests). We found a group effect (F test) of rCBF within bilateral supplementary motor area (SMA), anterior cingulate cortex, dorsolateral prefrontal cortex, left interior parietal lobe, and cerebellum. T tests indicated 1 cluster (SMA) to be specific to catatonia. Moreover, catatonia of excited and retarded types differed in SMA perfusion. Furthermore, increased catatonia severity was associated with higher perfusion in SMA. Finally, catatonia patients had a distinct pattern of GM density reduction compared to controls with prominent GM loss in frontal and insular cortices. SMA resting-state hyperperfusion is a marker of current catatonia in schizophrenia. This is highly compatible with a dysregulated motor system in catatonia, particularly affecting premotor areas. Moreover, SMA perfusion was differentially altered in retarded and excited catatonia subtypes, arguing for distinct pathobiology. PMID:27729486

The use of whole food animal studies in the safety assessment of genetically modified crops: Limitations and recommendations

PubMed Central

Bartholomaeus, Andrew; Parrott, Wayne; Bondy, Genevieve

2013-01-01

There is disagreement internationally across major regulatory jurisdictions on the relevance and utility of whole food (WF) toxicity studies on GM crops, with no harmonization of data or regulatory requirements. The scientific value, and therefore animal ethics, of WF studies on GM crops is a matter addressable from the wealth of data available on commercialized GM crops and WF studies on irradiated foods. We reviewed available GM crop WF studies and considered the extent to which they add to the information from agronomic and compositional analyses. No WF toxicity study was identified that convincingly demonstrated toxicological concern or that called into question the adequacy, sufficiency, and reliability of safety assessments based on crop molecular characterization, transgene source, agronomic characteristics, and/or compositional analysis of the GM crop and its near-isogenic line. Predictions of safety based on crop genetics and compositional analyses have provided complete concordance with the results of well-conducted animal testing. However, this concordance is primarily due to the improbability of de novo generation of toxic substances in crop plants using genetic engineering practices and due to the weakness of WF toxicity studies in general. Thus, based on the comparative robustness and reliability of compositional and agronomic considerations and on the absence of any scientific basis for a significant potential for de novo generation of toxicologically significant compositional alterations as a sole result of transgene insertion, the conclusion of this review is that WF animal toxicity studies are unnecessary and scientifically unjustifiable. PMID:24164514

CD1 molecule expression on human monocytes induced by granulocyte-macrophage colony-stimulating factor.

PubMed

Kasinrerk, W; Baumruker, T; Majdic, O; Knapp, W; Stockinger, H

1993-01-15

In this paper we demonstrate that granulocyte-macrophage CSF (GM-CSF) specifically induces the expression of CD1 molecules, CD1a, CD1b and CD1c, upon human monocytes. CD1 molecules appeared upon monocytes on day 1 of stimulation with rGM-CSF, and expression was up-regulated until day 3. Monocytes cultured in the presence of LPS, FMLP, PMA, recombinant granulocyte-CSF, rIFN-gamma, rTNF-alpha, rIL-1 alpha, rIL-1 beta, and rIL-6 remained negative. The induction of CD1 molecules by rGM-CSF was restricted to monocytes, since no such effect was observed upon peripheral blood granulocytes, PBL, and the myeloid cell lines Monomac1, Monomac6, MV4/11, HL60, U937, THP1, KG1, and KG1A. CD1a mRNA was detectable in rGM-CSF-induced monocytes but not in those freshly isolated. SDS-PAGE and immunoblotting analyses of CD1a mAb VIT6 immunoprecipitate from lysate of rGM-CSF-activated monocytes revealed an appropriate CD1a polypeptide band of 49 kDa associated with beta 2-microglobulin. Expression of CD1 molecules on monocytes complements the distribution of these structures on accessory cells, and their specific induction by GM-CSF strengthens the suggestion that CD1 is a family of crucial structures required for interaction between accessory cells and T cells.

Expression of the GM2 activator protein in mouse testis.

PubMed

Li, Yu-Teh; Li, Su-Chen; Chen, I-Li

2017-12-01

The GM2-activator protein (GM2-AP), revealed by Li et al. in 1973 in human liver, was initially identified as a protein cofactor that stimulated β-hexosaminidase A to hydrolyze N-acetylgalactosamine from GM2 ganglioside. This cofactor was found to be missing in human variant AB Tay-Sachs disease. Over the years, the GM2-AP has also been shown to be involved in kidney vesicular transport, lipid presentation by CD1 molecule to T-cells, and interaction of human sperm with zona pellucida. Since the expression of the GM2-AP via mRNA detection in mouse tissues was found to be the highest in testis, we became interested in the localization of the GM2-AP at cellular level in mouse testis during spermatogenesis. Using immunohistochemical analysis and electron microscopy, we found that the GM2-AP was predominantly localized in the basal cytoplasm and the attenuated processes of Sertoli cells. The stained structure appeared to be lysosomes. The most interesting finding was the association of the GM2-AP with the acrosomal apparatus in early spermatids. A modest to intense staining was observed in some acrosomal granules and acrosomal caps. The GM2-AP seemed to disappear from acrosomal caps in the later stage of spermatids, in which the nucleus became elongated and condensed. These results suggest that the GM2-AP may be involved in the normal functions of Sertoli cells and play important roles during the development of acrosomal caps in the early spermatids. Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Deformable Image Registration for Cone-Beam CT Guided Transoral Robotic Base of Tongue Surgery

PubMed Central

Reaungamornrat, S.; Liu, W. P.; Wang, A. S.; Otake, Y.; Nithiananthan, S.; Uneri, A.; Schafer, S.; Tryggestad, E.; Richmon, J.; Sorger, J. M.; Siewerdsen, J. H.; Taylor, R. H.

2013-01-01

Transoral robotic surgery (TORS) offers a minimally invasive approach to resection of base of tongue tumors. However, precise localization of the surgical target and adjacent critical structures can be challenged by the highly deformed intraoperative setup. We propose a deformable registration method using intraoperative cone-beam CT (CBCT) to accurately align preoperative CT or MR images with the intraoperative scene. The registration method combines a Gaussian mixture (GM) model followed by a variation of the Demons algorithm. First, following segmentation of the volume of interest (i.e., volume of the tongue extending to the hyoid), a GM model is applied to surface point clouds for rigid initialization (GM rigid) followed by nonrigid deformation (GM nonrigid). Second, the registration is refined using the Demons algorithm applied to distance map transforms of the (GM-registered) preoperative image and intraoperative CBCT. Performance was evaluated in repeat cadaver studies (25 image pairs) in terms of target registration error (TRE), entropy correlation coefficient (ECC), and normalized pointwise mutual information (NPMI). Retraction of the tongue in the TORS operative setup induced gross deformation >30 mm. The mean TRE following the GM rigid, GM nonrigid, and Demons steps was 4.6, 2.1, and 1.7 mm, respectively. The respective ECC was 0.57, 0.70, and 0.73 and NPMI was 0.46, 0.57, and 0.60. Registration accuracy was best across the superior aspect of the tongue and in proximity to the hyoid (by virtue of GM registration of surface points on these structures). The Demons step refined registration primarily in deeper portions of the tongue further from the surface and hyoid bone. Since the method does not use image intensities directly, it is suitable to multi-modality registration of preoperative CT or MR with intraoperative CBCT. Extending the 3D image registration to the fusion of image and planning data in stereo-endoscopic video is anticipated to support safer, high-precision base of tongue robotic surgery. PMID:23807549

Deformable image registration for cone-beam CT guided transoral robotic base-of-tongue surgery

NASA Astrophysics Data System (ADS)

Reaungamornrat, S.; Liu, W. P.; Wang, A. S.; Otake, Y.; Nithiananthan, S.; Uneri, A.; Schafer, S.; Tryggestad, E.; Richmon, J.; Sorger, J. M.; Siewerdsen, J. H.; Taylor, R. H.

2013-07-01

Transoral robotic surgery (TORS) offers a minimally invasive approach to resection of base-of-tongue tumors. However, precise localization of the surgical target and adjacent critical structures can be challenged by the highly deformed intraoperative setup. We propose a deformable registration method using intraoperative cone-beam computed tomography (CBCT) to accurately align preoperative CT or MR images with the intraoperative scene. The registration method combines a Gaussian mixture (GM) model followed by a variation of the Demons algorithm. First, following segmentation of the volume of interest (i.e. volume of the tongue extending to the hyoid), a GM model is applied to surface point clouds for rigid initialization (GM rigid) followed by nonrigid deformation (GM nonrigid). Second, the registration is refined using the Demons algorithm applied to distance map transforms of the (GM-registered) preoperative image and intraoperative CBCT. Performance was evaluated in repeat cadaver studies (25 image pairs) in terms of target registration error (TRE), entropy correlation coefficient (ECC) and normalized pointwise mutual information (NPMI). Retraction of the tongue in the TORS operative setup induced gross deformation >30 mm. The mean TRE following the GM rigid, GM nonrigid and Demons steps was 4.6, 2.1 and 1.7 mm, respectively. The respective ECC was 0.57, 0.70 and 0.73, and NPMI was 0.46, 0.57 and 0.60. Registration accuracy was best across the superior aspect of the tongue and in proximity to the hyoid (by virtue of GM registration of surface points on these structures). The Demons step refined registration primarily in deeper portions of the tongue further from the surface and hyoid bone. Since the method does not use image intensities directly, it is suitable to multi-modality registration of preoperative CT or MR with intraoperative CBCT. Extending the 3D image registration to the fusion of image and planning data in stereo-endoscopic video is anticipated to support safer, high-precision base-of-tongue robotic surgery.

Structural MRI-based detection of Alzheimer's disease using feature ranking and classification error.

PubMed

Beheshti, Iman; Demirel, Hasan; Farokhian, Farnaz; Yang, Chunlan; Matsuda, Hiroshi

2016-12-01

This paper presents an automatic computer-aided diagnosis (CAD) system based on feature ranking for detection of Alzheimer's disease (AD) using structural magnetic resonance imaging (sMRI) data. The proposed CAD system is composed of four systematic stages. First, global and local differences in the gray matter (GM) of AD patients compared to the GM of healthy controls (HCs) are analyzed using a voxel-based morphometry technique. The aim is to identify significant local differences in the volume of GM as volumes of interests (VOIs). Second, the voxel intensity values of the VOIs are extracted as raw features. Third, the raw features are ranked using a seven-feature ranking method, namely, statistical dependency (SD), mutual information (MI), information gain (IG), Pearson's correlation coefficient (PCC), t-test score (TS), Fisher's criterion (FC), and the Gini index (GI). The features with higher scores are more discriminative. To determine the number of top features, the estimated classification error based on training set made up of the AD and HC groups is calculated, with the vector size that minimized this error selected as the top discriminative feature. Fourth, the classification is performed using a support vector machine (SVM). In addition, a data fusion approach among feature ranking methods is introduced to improve the classification performance. The proposed method is evaluated using a data-set from ADNI (130 AD and 130 HC) with 10-fold cross-validation. The classification accuracy of the proposed automatic system for the diagnosis of AD is up to 92.48% using the sMRI data. An automatic CAD system for the classification of AD based on feature-ranking method and classification errors is proposed. In this regard, seven-feature ranking methods (i.e., SD, MI, IG, PCC, TS, FC, and GI) are evaluated. The optimal size of top discriminative features is determined by the classification error estimation in the training phase. The experimental results indicate that the performance of the proposed system is comparative to that of state-of-the-art classification models. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Synthesis of reticulated hollow spheres structure NiCo2S4 and its application in organophosphate pesticides biosensor.

PubMed

Peng, Lei; Dong, Sheying; Wei, Wenbo; Yuan, Xiaojing; Huang, Tinglin

2017-06-15

Electrode materials play a key role in the development of electrochemical sensors, particularly enzyme-based biosensors. Here, a novel NiCo 2 S 4 with reticulated hollow spheres assembled from rod-like structures was prepared by a one-pot solvothermal method and its formation mechanism was discussed. Moreover, comparison of NiCo 2 S 4 materials from different experiment conditions as biosensors was investigated by electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV), and the best one that was reticulated hollow spheres assembled from rod-like structures NiCo 2 S 4 has been successfully employed as a matrix of AChE immobilization for the special structure, superior conductivity and rich reaction active sites. When using common two kinds of organophosphate pesticides (OPs) as model analyte, the biosensors demonstrated a wide linear range of 1.0×10 -12 -1.0×10 -8 gmL -1 with the detection limit of 4.2×10 -13 gmL -1 for methyl parathion, and 1.0×10 -13 -1.0×10 -10 gmL -1 with the detection limit of 3.5×10 -14 gmL -1 for paraoxon, respectively. The proposed biosensors exhibited many advantages such as acceptable stability and low cost, providing a promising tool for analysis of OPs. Copyright © 2016 Elsevier B.V. All rights reserved.

Functional Analysis of GmCPDs and Investigation of Their Roles in Flowering

PubMed Central

Wang, Miao; Xu, Xin; Zhang, Xinxin; Sun, Shi; Wu, Cunxiang; Hou, Wensheng; Wang, Qingyu; Han, Tianfu

2015-01-01

The onset of floral development is a pivotal switch in the life of soybean. Brassinosteroids (BRs), a group of steroidal phytohormones with essential roles in plant growth and development, are associated with flowering induction. Genes involved in BR biosynthesis have been studied to a great extent in Arabidopsis, but the study of these genes has been limited in soybean. In this study, four CPD homologs (GmCPDs) catalyzing BR synthesis were isolated from soybean. Transcripts were mainly confined to cotyledons and leaves and were down-regulated in response to exogenous BR. Bioinformatic analysis showed strong sequence and structure similarity between GmCPDs and AtCPD as well as CPDs of other species. Overexpression of GmCPDs in an Arabidopsis BR-deficient mutant rescued the phenotype by restoring the biosynthesis pathway, revealing the functional roles of each GmCPDs in. Except for the rescue of root development, leaf expansion and plant type architecture, GmCPDs in expression also complemented the late flowering phenotype of Arabidopsis mutants deficient in CPD. Further evidence in soybean plants is that the expression levels of GmCPDs in are under photoperiod control in Zigongdongdou, a photoperiod-sensitive variety, and show a sudden peak upon floral meristem initiation. Together with increased GmCPDs in expression in the leaves and cotyledons of photoperiod-insensitive early-maturity soybean, it is clear that GmCPDs in contribute to flowering development and are essential in the early stages of flowering regulation. PMID:25734273

Influence of Ganglioside GM1 Concentration on Lipid Clustering and Membrane Properties and Curvature.

PubMed

Patel, Dhilon S; Park, Soohyung; Wu, Emilia L; Yeom, Min Sun; Widmalm, Göran; Klauda, Jeffery B; Im, Wonpil

2016-11-01

Gangliosides are a class of glycosphingolipids (GSLs) with amphiphilic character that are found at the outer leaflet of the cell membranes, where their ability to organize into special domains makes them vital cell membrane components. However, a molecular understanding of GSL-rich membranes in terms of their clustered organization, stability, and dynamics is still elusive. To gain molecular insight into the organization and dynamics of GSL-rich membranes, we performed all-atom molecular-dynamics simulations of bicomponent ganglioside GM1 in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) phospholipid bilayers with varying concentrations of GM1 (10%, 20%, and 30%). Overall, the simulations show very good agreement with available experimental data, including x-ray electron density profiles along the membrane normal, NMR carbohydrate proton-proton distances, and x-ray crystal structures. This validates the quality of our model systems for investigating GM1 clustering through an ordered-lipid-cluster analysis. The increase in GM1 concentration induces tighter lipid packing, driven mainly by inter-GM1 carbohydrate-carbohydrate interactions, leading to a greater preference for the positive curvature of GM1-containing membranes and larger cluster sizes of ordered-lipid clusters (with a composite of GM1 and POPC). These clusters tend to segregate and form a large percolated cluster at a 30% GM1 concentration at 293 K. At a higher temperature of 330 K, however, the segregation is not maintained. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Mass balances of mercury and nitrogen in burned and unburned forested watersheds at Acadia National Park, Maine, USA

USGS Publications Warehouse

Nelson, S.J.; Johnson, K.B.; Kahl, J.S.; Haines, T.A.; Fernandez, I.J.

2007-01-01

Precipitation and streamwater samples were collected from 16 November 1999 to 17 November 2000 in two watersheds at Acadia National Park, Maine, and analyzed for mercury (Hg) and dissolved inorganic nitrogen (DIN, nitrate plus ammonium). Cadillac Brook watershed burned in a 1947 fire that destroyed vegetation and soil organic matter. We hypothesized that Hg deposition would be higher at Hadlock Brook (the reference watershed, 10.2 ??g/m2/year) than Cadillac (9.4 ??g/m2/year) because of the greater scavenging efficiency of the softwood vegetation in Hadlock. We also hypothesized the Hg and DIN export from Cadillac Brook would be lower than Hadlock Brook because of elemental volatilization during the fire, along with subsequently lower rates of atmospheric deposition in a watershed with abundant bare soil and bedrock, and regenerating vegetation. Consistent with these hypotheses, Hg export was lower from Cadillac Brook watershed (0.4 ??g/m2/year) than from Hadlock Brook watershed (1.3 ??g/m2/year). DIN export from Cadillac Brook (11.5 eq/ ha/year) was lower than Hadlock Brook (92.5 eq/ha/year). These data show that ??50 years following a wildfire there was lower atmospheric deposition due to changes in forest species composition, lower soil pools, and greater ecosystem retention for both Hg and DIN. ?? Springer Science + Business Media B.V. 2006.

Distribution of dust during two dust storms in Iceland

NASA Astrophysics Data System (ADS)

Ösp Magnúsdóttir, Agnes; Dagsson-Waldhauserova, Pavla; Arnalds, Ólafur; Ólafsson, Haraldur

2017-04-01

Particulate matter mass concentrations and size fractions of PM1, PM2.5, PM4, PM10, and PM15 measured in transversal horizontal profile of two dust storms in southwestern Iceland are presented. Images from a camera network were used to estimate the visibility and spatial extent of measured dust events. Numerical simulations were used to calculate the total dust flux from the sources as 180,000 and 280,000 tons for each storm. The mean PM15 concentrations inside of the dust plumes varied from 10 to 1600 ?g?m?3 (PM10 = 7 to 583 ?g?m?3). The mean PM1 concentrations were 97-241 ?g?m?3 with a maximum of 261 ?g?m?3 for the first storm. The PM1/PM2.5 ratios of >0.9 and PM1/PM10 ratios of 0.34-0.63 show that suspension of volcanic materials in Iceland causes air pollution with extremely high PM1 concentrations, similar to polluted urban areas in Europe or Asia. Icelandic volcanic dust consists of a higher proportion of submicron particles compared to crustal dust. Both dust storms occurred in relatively densely inhabited areas of Iceland. First results on size partitioning of Icelandic dust presented here should challenge health authorities to enhance research in relation to dust and shows the need for public dust warning systems.

Availability and utility of crop composition data.

PubMed

Kitta, Kazumi

2013-09-04

The safety assessment of genetically modified (GM) crops is mandatory in many countries. Although the most important factor to take into account in these safety assessments is the primary effects of artificially introduced transgene-derived traits, possible unintended effects attributed to the insertion of transgenes must be carefully examined in parallel. However, foods are complex mixtures of compounds characterized by wide variations in composition and nutritional values. Food components are significantly affected by various factors such as cultivars and the cultivation environment including storage conditions after harvest, and it can thus be very difficult to detect potential adverse effects caused by the introduction of a transgene. A comparative approach focusing on the identification of differences between GM foods and their conventional counterparts has been performed to reveal potential safety issues and is considered the most appropriate strategy for the safety assessment of GM foods. This concept is widely shared by authorities in many countries. For the efficient safety assessment of GM crops, an easily accessible and wide-ranging compilation of crop composition data is required for use by researchers and regulatory agencies. Thus, we developed an Internet-accessible food composition database comprising key nutrients, antinutrients, endogenous toxicants, and physiologically active substances of staple crops such as rice and soybeans. The International Life Sciences Institute has also been addressing the same matter and has provided the public a crop composition database of soybeans, maize, and cotton.

Frequency Mapping of Rat Spinal Cord at 7T

NASA Astrophysics Data System (ADS)

Chen, Evan; Rauscher, Alexander; Kozlowski, Piotr; Yung, Andrew

2012-10-01

The spinal cord is an integral part of the nervous system responsible for sensory, motor, and reflex control crucial to all bodily function. Due to its non-invasive nature, MRI is well matched for characterizing and imaging of spinal cord, and is used extensively for clinical applications. Recent developments in magnetic resonance imaging (MRI) at high field (7T) using phase represents a new approach of characterizing spinal cord myelin. Theory suggests that microstructure differences in myelinated white matter (WM) and non-myelinated gray matter (GM) affect MR phase, measurable frequency shifts. Data from pilot experiments using a multi-gradient echo (MGE) sequence to image rat spinal cords placed parallel to main magnetic field B0 has shown frequency shifts between not only between WM and GM, but also between specific WM tracts of the dorsal column, including the fasciculus gracilis, fasciculus cuneatus, and corticospinal tract. Using MGE, frequency maps at multiple echo times (TE) between 4ms and 22ms show a non-linear relationship between WM frequency, contrary to what was previously expected. These results demonstrate the effectiveness of MGE in revealing new information about spinal cord tissue microstructure, and lays important groundwork for in-vivo and human studies.

Automatic brain tissue segmentation based on graph filter.

PubMed

Kong, Youyong; Chen, Xiaopeng; Wu, Jiasong; Zhang, Pinzheng; Chen, Yang; Shu, Huazhong

2018-05-09

Accurate segmentation of brain tissues from magnetic resonance imaging (MRI) is of significant importance in clinical applications and neuroscience research. Accurate segmentation is challenging due to the tissue heterogeneity, which is caused by noise, bias filed and partial volume effects. To overcome this limitation, this paper presents a novel algorithm for brain tissue segmentation based on supervoxel and graph filter. Firstly, an effective supervoxel method is employed to generate effective supervoxels for the 3D MRI image. Secondly, the supervoxels are classified into different types of tissues based on filtering of graph signals. The performance is evaluated on the BrainWeb 18 dataset and the Internet Brain Segmentation Repository (IBSR) 18 dataset. The proposed method achieves mean dice similarity coefficient (DSC) of 0.94, 0.92 and 0.90 for the segmentation of white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF) for BrainWeb 18 dataset, and mean DSC of 0.85, 0.87 and 0.57 for the segmentation of WM, GM and CSF for IBSR18 dataset. The proposed approach can well discriminate different types of brain tissues from the brain MRI image, which has high potential to be applied for clinical applications.

Segmentation of tumor and edema along with healthy tissues of brain using wavelets and neural networks.

PubMed

Demirhan, Ayşe; Toru, Mustafa; Guler, Inan

2015-07-01

Robust brain magnetic resonance (MR) segmentation algorithms are critical to analyze tissues and diagnose tumor and edema in a quantitative way. In this study, we present a new tissue segmentation algorithm that segments brain MR images into tumor, edema, white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). The detection of the healthy tissues is performed simultaneously with the diseased tissues because examining the change caused by the spread of tumor and edema on healthy tissues is very important for treatment planning. We used T1, T2, and FLAIR MR images of 20 subjects suffering from glial tumor. We developed an algorithm for stripping the skull before the segmentation process. The segmentation is performed using self-organizing map (SOM) that is trained with unsupervised learning algorithm and fine-tuned with learning vector quantization (LVQ). Unlike other studies, we developed an algorithm for clustering the SOM instead of using an additional network. Input feature vector is constructed with the features obtained from stationary wavelet transform (SWT) coefficients. The results showed that average dice similarity indexes are 91% for WM, 87% for GM, 96% for CSF, 61% for tumor, and 77% for edema.

Integration of Sparse Multi-modality Representation and Geometrical Constraint for Isointense Infant Brain Segmentation

PubMed Central

Wang, Li; Shi, Feng; Li, Gang; Lin, Weili; Gilmore, John H.; Shen, Dinggang

2014-01-01

Segmentation of infant brain MR images is challenging due to insufficient image quality, severe partial volume effect, and ongoing maturation and myelination process. During the first year of life, the signal contrast between white matter (WM) and gray matter (GM) in MR images undergoes inverse changes. In particular, the inversion of WM/GM signal contrast appears around 6–8 months of age, where brain tissues appear isointense and hence exhibit extremely low tissue contrast, posing significant challenges for automated segmentation. In this paper, we propose a novel segmentation method to address the above-mentioned challenge based on the sparse representation of the complementary tissue distribution information from T1, T2 and diffusion-weighted images. Specifically, we first derive an initial segmentation from a library of aligned multi-modality images with ground-truth segmentations by using sparse representation in a patch-based fashion. The segmentation is further refined by the integration of the geometrical constraint information. The proposed method was evaluated on 22 6-month-old training subjects using leave-one-out cross-validation, as well as 10 additional infant testing subjects, showing superior results in comparison to other state-of-the-art methods. PMID:24505729

Integration of sparse multi-modality representation and geometrical constraint for isointense infant brain segmentation.

PubMed

Wang, Li; Shi, Feng; Li, Gang; Lin, Weili; Gilmore, John H; Shen, Dinggang

2013-01-01

Segmentation of infant brain MR images is challenging due to insufficient image quality, severe partial volume effect, and ongoing maturation and myelination process. During the first year of life, the signal contrast between white matter (WM) and gray matter (GM) in MR images undergoes inverse changes. In particular, the inversion of WM/GM signal contrast appears around 6-8 months of age, where brain tissues appear isointense and hence exhibit extremely low tissue contrast, posing significant challenges for automated segmentation. In this paper, we propose a novel segmentation method to address the above-mentioned challenge based on the sparse representation of the complementary tissue distribution information from T1, T2 and diffusion-weighted images. Specifically, we first derive an initial segmentation from a library of aligned multi-modality images with ground-truth segmentations by using sparse representation in a patch-based fashion. The segmentation is further refined by the integration of the geometrical constraint information. The proposed method was evaluated on 22 6-month-old training subjects using leave-one-out cross-validation, as well as 10 additional infant testing subjects, showing superior results in comparison to other state-of-the-art methods.

Regional gray matter density is associated with achievement motivation: evidence from voxel-based morphometry.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Sekiguchi, Atsushi; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Yokoyama, Ryoichi; Iizuka, Kunio; Hashizume, Hiroshi; Nakagawa, Seishu; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

2014-01-01

Achievement motivation can be defined as a recurrent need to improve one's past performance. Despite previous functional imaging studies on motivation-related functional activation, the relationship between regional gray matter (rGM) morphology and achievement motivation has never been investigated. We used voxel-based morphometry and a questionnaire (achievement motivation scale) to measure individual achievement motivation and investigated the association between rGM density (rGMD) and achievement motivation [self-fulfillment achievement motivation (SFAM) and competitive achievement motivation (CAM) across the brain in healthy young adults (age 21.0 ± 1.8 years, men (n = 94), women (n = 91)]. SFAM and rGMD significantly and negatively correlated in the orbitofrontal cortex (OFC). CAM and rGMD significantly and positively correlated in the right putamen, insula, and precuneus. These results suggest that the brain areas that play central roles in externally modulated motivation (OFC and putamen) also contribute to SFAM and CAM, respectively, but in different ways. Furthermore, the brain areas in which rGMD correlated with CAM are related to cognitive processes associated with distressing emotions and social cognition, and these cognitive processes may characterize CAM.

An empirical test of competing theories of hazard-related trust: the case of GM food.

PubMed

Allum, Nick

2007-08-01

Few scholars doubt the importance of trust in explaining variation in public perception of technological risk. Relatively little, however, is known about the particular types of judgments that people use in granting or withholding trust. This article presents findings from an empirical study that explores several dimensions of trust relevant for citizens' judgments of scientists involved in the development of GM food. The relationship between particular dimensions of trust and perceptions of GM food risk is also explored, using structural equation modeling. Results suggest that trust judgments based on the perception of shared values are most important in relation to GM food risk, but that judgments about scientists' technical competence are also important.

Development of an Immunoassay for Rapid Detection of Ganglioside GM1 Mimicry in Campylobacter jejuni Strains

PubMed Central

Prendergast, Martina M.; Kosunen, Timo U.; Moran, Anthony P.

2001-01-01

Mimicry of peripheral nerve gangliosides by Campylobacter jejuni lipopolysaccharides (LPSs) has been proposed to induce cross-reacting antiganglioside antibodies in Guillain-Barré syndrome (GBS). Because current methods for LPS characterization are labor-intensive and inhibit the screening of large numbers of strains, a rapid GM1 epitope screening assay was developed. Biomass from two agar plates of confluent growth yielded sufficient LPS using a novel phenol-water and ether extraction procedure. Extracts of LPS were reacted with cholera toxin (GM1 ligand), peanut agglutinin (Galβ1→3GalNAc ligand), and anti-GM1 antibodies. After the assay was validated, 12 of 59 (20%) C. jejuni serostrains, including four serotypes that have not previously been associated with GBS, reacted with two or more anti-GM1 ganglioside reagents. Subsequently, LPS extracts from 5 of 7 (71%) C. jejuni isolates and 2 of 3 (67%) C. jejuni culture collection strains bore GM1 structures. Overall, the assay system was reliable, efficient, and reproducible and may be adapted for large-scale epidemiological studies. PMID:11283076

Structural equation modelling reveals factors regulating surface sediment organic carbon content and CO2 efflux in a subtropical mangrove.

PubMed

Ouyang, Xiaoguang; Lee, Shing Yip; Connolly, Rod M

2017-02-01

Mangroves are blue carbon ecosystems that sequester significant carbon but release CO 2 , and to a lesser extent CH 4, from the sediment through oxidation of organic carbon or from overlying water when flooded. Previous studies, e.g. Leopold et al. (2015), have investigated sediment organic carbon (SOC) content and CO 2 flux separately, but could not provide a holistic perspective for both components of blue carbon. Based on field data from a mangrove in southeast Queensland, Australia, we used a structural equation model to elucidate (1) the biotic and abiotic drivers of surface SOC (10cm) and sediment CO 2 flux; (2) the effect of SOC on sediment CO 2 flux; and (3) the covariation among the environmental drivers assessed. Sediment water content, the percentage of fine-grained sediment (<63μm), surface sediment chlorophyll and light condition collectively drive sediment CO 2 flux, explaining 41% of their variation. Sediment water content, the percentage of fine sediment, season, landform setting, mangrove species, sediment salinity and chlorophyll collectively drive surface SOC, explaining 93% of its variance. Sediment water content and the percentage of fine sediment have a negative impact on sediment CO 2 flux but a positive effect on surface SOC content, while sediment chlorophyll is a positive driver of both. Surface SOC was significantly higher in Avicennia marina (2994±186gm -2 , mean±SD) than in Rhizophora stylosa (2383±209gm -2 ). SOC was significantly higher in winter (2771±192gm -2 ) than in summer (2599±211gm -2 ). SOC significantly increased from creek-side (865±89gm -2 ) through mid (3298±137gm -2 ) to landward (3933±138gm -2 ) locations. Sediment salinity was a positive driver of SOC. Sediment CO 2 flux without the influence of biogenic structures (crab burrows, aerial roots) averaged 15.4mmolm -2 d -1 in A. marina stands under dark conditions, lower than the global average dark flux (61mmolm -2 d -1 ) for mangroves. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetically Modified Flax Expressing NAP-SsGT1 Transgene: Examination of Anti-Inflammatory Action

PubMed Central

Matusiewicz, Magdalena; Kosieradzka, Iwona; Zuk, Magdalena; Szopa, Jan

2014-01-01

The aim of the work was to define the influence of dietary supplementation with GM (genetically modified) GT#4 flaxseed cake enriched in polyphenols on inflammation development in mice liver. Mice were given ad libitum isoprotein diets: (1) standard diet; (2) high-fat diet rich in lard, high-fat diet enriched with 30% of (3) isogenic flax Linola seed cake; and (4) GM GT#4 flaxseed cake; for 96 days. Administration of transgenic and isogenic seed cake lowered body weight gain, of transgenic to the standard diet level. Serum total antioxidant status was statistically significantly improved in GT#4 flaxseed cake group and did not differ from Linola. Serum thiobarbituric acid reactive substances, lipid profile and the liver concentration of pro-inflammatory cytokine tumor necrosis factor-α were ameliorated by GM and isogenic flaxseed cake consumption. The level of pro-inflammatory cytokine interferon-γ did not differ between mice obtaining GM GT#4 and non-GM flaxseed cakes. The C-reactive protein concentration was reduced in animals fed GT#4 flaxseed cake and did not differ from those fed non-GM flaxseed cake-based diet. Similarly, the liver structure of mice consuming diets enriched in flaxseed cake was improved. Dietetic enrichment with GM GT#4 and non-GM flaxseed cakes may be a promising solution for health problems resulting from improper diet. PMID:25247574

Coordination of Leaf Photosynthesis, Transpiration, and Structural Traits in Rice and Wild Relatives (Genus Oryza).

PubMed

Giuliani, Rita; Koteyeva, Nuria; Voznesenskaya, Elena; Evans, Marc A; Cousins, Asaph B; Edwards, Gerald E

2013-07-01

The genus Oryza, which includes rice (Oryza sativa and Oryza glaberrima) and wild relatives, is a useful genus to study leaf properties in order to identify structural features that control CO(2) access to chloroplasts, photosynthesis, water use efficiency, and drought tolerance. Traits, 26 structural and 17 functional, associated with photosynthesis and transpiration were quantified on 24 accessions (representatives of 17 species and eight genomes). Hypotheses of associations within, and between, structure, photosynthesis, and transpiration were tested. Two main clusters of positively interrelated leaf traits were identified: in the first cluster were structural features, leaf thickness (Thick(leaf)), mesophyll (M) cell surface area exposed to intercellular air space per unit of leaf surface area (S(mes)), and M cell size; a second group included functional traits, net photosynthetic rate, transpiration rate, M conductance to CO(2) diffusion (g(m)), stomatal conductance to gas diffusion (g(s)), and the g(m)/g(s) ratio.While net photosynthetic rate was positively correlated with gm, neither was significantly linked with any individual structural traits. The results suggest that changes in gm depend on covariations of multiple leaf (S(mes)) and M cell (including cell wall thickness) structural traits. There was an inverse relationship between Thick(leaf) and transpiration rate and a significant positive association between Thick(leaf) and leaf transpiration efficiency. Interestingly, high g(m) together with high g(m)/g(s) and a low S(mes)/g(m) ratio (M resistance to CO(2) diffusion per unit of cell surface area exposed to intercellular air space) appear to be ideal for supporting leaf photosynthesis while preserving water; in addition, thick M cell walls may be beneficial for plant drought tolerance.

Comparison of arterial spin labeling registration strategies in the multi-center GENetic frontotemporal dementia initiative (GENFI).

PubMed

Mutsaerts, Henri J M M; Petr, Jan; Thomas, David L; De Vita, Enrico; Cash, David M; van Osch, Matthias J P; Golay, Xavier; Groot, Paul F C; Ourselin, Sebastien; van Swieten, John; Laforce, Robert; Tagliavini, Fabrizio; Borroni, Barbara; Galimberti, Daniela; Rowe, James B; Graff, Caroline; Pizzini, Francesca B; Finger, Elizabeth; Sorbi, Sandro; Castelo Branco, Miguel; Rohrer, Jonathan D; Masellis, Mario; MacIntosh, Bradley J

2018-01-01

To compare registration strategies to align arterial spin labeling (ASL) with 3D T1-weighted (T1w) images, with the goal of reducing the between-subject variability of cerebral blood flow (CBF) images. Multi-center 3T ASL data were collected at eight sites with four different sequences in the multi-center GENetic Frontotemporal dementia Initiative (GENFI) study. In a total of 48 healthy controls, we compared the following image registration options: (I) which images to use for registration (perfusion-weighted images [PWI] to the segmented gray matter (GM) probability map (pGM) (CBF-pGM) or M0 to T1w (M0-T1w); (II) which transformation to use (rigid-body or non-rigid); and (III) whether to mask or not (no masking, M0-based FMRIB software library Brain Extraction Tool [BET] masking). In addition to visual comparison, we quantified image similarity using the Pearson correlation coefficient (CC), and used the Mann-Whitney U rank sum test. CBF-pGM outperformed M0-T1w (CC improvement 47.2% ± 22.0%; P < 0.001), and the non-rigid transformation outperformed rigid-body (20.6% ± 5.3%; P < 0.001). Masking only improved the M0-T1w rigid-body registration (14.5% ± 15.5%; P = 0.007). The choice of image registration strategy impacts ASL group analyses. The non-rigid transformation is promising but requires validation. CBF-pGM rigid-body registration without masking can be used as a default strategy. In patients with expansive perfusion deficits, M0-T1w may outperform CBF-pGM in sequences with high effective spatial resolution. BET-masking only improves M0-T1w registration when the M0 image has sufficient contrast. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:131-140. © 2017 International Society for Magnetic Resonance in Medicine.

Reduced limbic and hypothalamic volumes correlate with bone density in early Alzheimer's disease.

PubMed

Loskutova, Natalia; Honea, Robyn A; Brooks, William M; Burns, Jeffrey M

2010-01-01

Accelerated bone loss is associated with Alzheimer's disease (AD). Although the central nervous system plays a direct role in regulating bone mass, primarily through the actions of the hypothalamus, there is little work investigating the possible role of neurodegeneration in bone loss. In this cross-sectional study, we examined the association between bone mineral density (BMD) and neuroimaging markers of neurodegeneration (i.e., global and regional measures of brain volume) in early AD and non-demented aging. Fifty-five non-demented and 63 early AD participants underwent standard neurological and neuropsychological assessment, structural MRI scanning, and dual energy x-ray absorptiometry. In early AD, voxel-based morphometry analyses demonstrated that low BMD was associated with low volume in limbic grey matter (GM) including the hypothalamus, cingulate, and parahippocampal gyri and in the left superior temporal gyrus and left inferior parietal cortex. No relationship between BMD and regional GM volume was found in non-demented controls. The hypothesis-driven region of interest analysis further isolating the hypothalamus demonstrated a positive relationship between BMD and hypothalamic volume after controlling for age and gender in the early AD group but not in non-demented controls. These results demonstrate that lower BMD is associated with lower hypothalamic volume in early AD, suggesting that central mechanisms of bone remodeling may be disrupted by neurodegeneration.

Cerebellum volume in high-risk offspring from multiplex alcohol dependence families: Association with allelic variation in GABRA2 and BDNF

PubMed Central

Hill, Shirley Y.; Wang, Shuhui; Carter, Howard; Tessner, Kevin; Holmes, Brian; McDermott, Michael; Zezza, Nicholas; Stiffler, Scott

2012-01-01

Offspring from families with multiple cases of alcohol dependence have a greater likelihood of developing alcohol dependence (AD) and related substance use disorders. Greater susceptibility for developing these disorders may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing and AD susceptibility. We examined the cerebellum of 71 adolescent/young adult high-risk (HR) offspring from families with multiple cases of alcohol dependence (multiplex families), and 60 low-risk (LR) controls with no family history of alcohol or drug dependence who were matched for age, gender, socioeconomic status and IQ, with attention given to possible effects of personal use of substances and maternal use during pregnancy. Magnetic resonance images were acquired on a General Electric 1.5-Tesla scanner and manually traced (BRAINS2) blind to clinical information. GABRA2 and BDNF variation were tested for their association with cerebellar volumes. High-risk offspring from multiplex AD families showed greater total volume of the cerebellum and total gray matter (GM), in comparison with LR controls. An interaction between allelic variation in GABRA2 and BDNF genes was associated with GM volumes, suggesting that inherited variation in these genes may promote early developmental differences in neuronal proliferation of the cerebellum. PMID:22047728

Are ambiguity aversion and ambiguity intolerance identical? A neuroeconomics investigation.

PubMed

Tanaka, Yusuke; Fujino, Junya; Ideno, Takashi; Okubo, Shigetaka; Takemura, Kazuhisa; Miyata, Jun; Kawada, Ryosaku; Fujimoto, Shinsuke; Kubota, Manabu; Sasamoto, Akihiko; Hirose, Kimito; Takeuchi, Hideaki; Fukuyama, Hidenao; Murai, Toshiya; Takahashi, Hidehiko

2014-01-01

In recent years, there has been growing interest in understanding a person's reaction to ambiguous situations, and two similar constructs related to ambiguity, "ambiguity aversion" and "ambiguity intolerance," are defined in different disciplines. In the field of economic decision-making research, "ambiguity aversion" represents a preference for known risks relative to unknown risks. On the other hand, in clinical psychology, "ambiguity intolerance" describes the tendency to perceive ambiguous situations as undesirable. However, it remains unclear whether these two notions derived from different disciplines are identical or not. To clarify this issue, we combined an economic task, psychological questionnaires, and voxel-based morphometry (VBM) of structural brain magnetic resonance imaging (MRI) in a sample of healthy volunteers. The individual ambiguity aversion tendency parameter, as measured by our economic task, was negatively correlated with agreeableness scores on the self-reported version of the Revised NEO Personality Inventory. However, it was not correlated with scores of discomfort with ambiguity, one of the subscales of the Need for Closure Scale. Furthermore, the ambiguity aversion tendency parameter was negatively correlated with gray matter (GM) volume of areas in the lateral prefrontal cortex and parietal cortex, whereas ambiguity intolerance was not correlated with GM volume in any region. Our results suggest that ambiguity aversion, described in decision theory, may not necessarily be identical to ambiguity intolerance, referred to in clinical psychology. Cautious applications of decision theory to clinical neuropsychiatry are recommended.

Automatic measurement of prosody in behavioral variant FTD.

PubMed

Nevler, Naomi; Ash, Sharon; Jester, Charles; Irwin, David J; Liberman, Mark; Grossman, Murray

2017-08-15

To help understand speech changes in behavioral variant frontotemporal dementia (bvFTD), we developed and implemented automatic methods of speech analysis for quantification of prosody, and evaluated clinical and anatomical correlations. We analyzed semi-structured, digitized speech samples from 32 patients with bvFTD (21 male, mean age 63 ± 8.5, mean disease duration 4 ± 3.1 years) and 17 matched healthy controls (HC). We automatically extracted fundamental frequency (f0, the physical property of sound most closely correlating with perceived pitch) and computed pitch range on a logarithmic scale (semitone) that controls for individual and sex differences. We correlated f0 range with neuropsychiatric tests, and related f0 range to gray matter (GM) atrophy using 3T T1 MRI. We found significantly reduced f0 range in patients with bvFTD (mean 4.3 ± 1.8 ST) compared to HC (5.8 ± 2.1 ST; p = 0.03). Regression related reduced f0 range in bvFTD to GM atrophy in bilateral inferior and dorsomedial frontal as well as left anterior cingulate and anterior insular regions. Reduced f0 range reflects impaired prosody in bvFTD. This is associated with neuroanatomic networks implicated in language production and social disorders centered in the frontal lobe. These findings support the feasibility of automated speech analysis in frontotemporal dementia and other disorders. © 2017 American Academy of Neurology.

Characterizing Solution Surface Loop Conformational Flexibility of the GM2 Activator Protein

PubMed Central

2015-01-01

GM2AP has a β-cup topology with numerous X-ray structures showing multiple conformations for some of the surface loops, revealing conformational flexibility that may be related to function, where function is defined as either membrane binding associated with ligand binding and extraction or interaction with other proteins. Here, site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy and molecular dynamic (MD) simulations are used to characterize the mobility and conformational flexibility of various structural regions of GM2AP. A series of 10 single cysteine amino acid substitutions were generated, and the constructs were chemically modified with the methanethiosulfonate spin label. Continuous wave (CW) EPR line shapes were obtained and subsequently simulated using the microscopic order macroscopic disorder (MOMD) program. Line shapes for sites that have multiple conformations in the X-ray structures required two spectral components, whereas spectra of the remaining sites were adequately fit with single-component parameters. For spin labeled sites L126C and I66C, spectra were acquired as a function of temperature, and simulations provided for the determination of thermodynamic parameters associated with conformational change. Binding to GM2 ligand did not alter the conformational flexibility of the loops, as evaluated by EPR and NMR spectroscopies. These results confirm that the conformational flexibility observed in the surface loops of GM2AP crystals is present in solution and that the exchange is slow on the EPR time scale (>ns). Furthermore, MD simulation results are presented and agree well with the conformational heterogeneity revealed by SDSL. PMID:25127419

Apparent CBF decrease with normal aging due to partial volume effects: MR-based partial volume correction on CBF SPECT.

PubMed

Inoue, Kentaro; Ito, Hiroshi; Goto, Ryoi; Nakagawa, Manabu; Kinomura, Shigeo; Sato, Tachio; Sato, Kazunori; Fukuda, Hiroshi

2005-06-01

Several studies using single photon emission tomography (SPECT) have shown changes in cerebral blood flow (CBF) with age, which were associated with partial volume effects by some authors. Some studies have also demonstrated gender-related differences in CBF. The present study aimed to examine age and gender effects on CBF SPECT images obtained using the 99mTc-ethyl cysteinate dimer and a SPECT scanner, before and after partial volume correction (PVC) using magnetic resonance (MR) imaging. Forty-four healthy subjects (29 males and 15 females; age range, 27-64 y; mean age, 50.0 +/- 9.8 y) participated. Each MR image was segmented to yield grey and white matter images and coregistered to a corresponding SPECT image, followed by convolution to approximate the SPECT spatial resolution. PVC-SPECT images were produced using the convoluted grey matter MR (GM-MR) and white matter MR images. The age and gender effects were assessed using SPM99. Decreases with age were detected in the anterolateral prefrontal cortex and in areas along the lateral sulcus and the lateral ventricle, bilaterally, in the GM-MR images and the SPECT images. In the PVC-SPECT images, decreases in CBF in the lateral prefrontal cortex lost their statistical significance. Decreases in CBF with age found along the lateral sulcus and the lateral ventricle, on the other hand, remained statistically significant, but observation of the spatially normalized MR images suggests that these findings are associated with the dilatation of the lateral sulcus and lateral ventricle, which was not completely compensated for by the spatial normalization procedure. Our present study demonstrated that age effects on CBF in healthy subjects could reflect morphological differences with age in grey matter.

Spatial and Interspecies Patterns of PM2.5 at Three Sites in the Pearl River Delta, China: One-Year Observations

NASA Astrophysics Data System (ADS)

Yu, J.; Lau, A. K.; Wu, C.; Ng, W.; Yuan, Z.; Wu, D.

2009-12-01

The Pearl River Delta (PRD) is among the most economically fast-developing regions in China. The region has been experiencing increasing levels of particulate matter (PM) pollution. In an effort of establishing long-term trend in chemical characteristics of PM2.5 and understanding PM sources important at regional scale, filter-based samples have been collected at three sites in the PRD concurrently in one-in-six-day schedule since August 2007. We here report observation results of PM2.5 over one-year period (August 2007-June 2008). The three sites include an urban downtown location in Guangzhou, Nansha, a rural receptor site at the mouth of the Pearl River, and Tsuen Wan, an urban background site in Hong Kong. Guangzhou recorded the highest annual average PM2.5 concentration of 78.2 μgm-3, followed by Nansha (65.9 μgm-3) and Tsuen Wan (42.8 μgm-3). Organic matter (OM) and sulfate are the top two constituents, accounting for ~70% of PM2.5 mass. The annual average nitrate contributions were similar at GZ and NS (~13%), but lower at TW (~7%). Inter-site correlations of PM2.5 and major constituents indicate that GZ strongly influenced ambient PM2.5 levels at NS, but GZ’s influence on TW was much reduced. Sulfate, ammonium, and OM showed strong regional characteristics. To the contrary, EC at the three sites had no correlations, suggesting a dominating local origin. Examples of high PM2.5 episodes are also analyzed to identify the conditions conducive for high PM.

Supervised classification of brain tissues through local multi-scale texture analysis by coupling DIR and FLAIR MR sequences

NASA Astrophysics Data System (ADS)

Poletti, Enea; Veronese, Elisa; Calabrese, Massimiliano; Bertoldo, Alessandra; Grisan, Enrico

2012-02-01

The automatic segmentation of brain tissues in magnetic resonance (MR) is usually performed on T1-weighted images, due to their high spatial resolution. T1w sequence, however, has some major downsides when brain lesions are present: the altered appearance of diseased tissues causes errors in tissues classification. In order to overcome these drawbacks, we employed two different MR sequences: fluid attenuated inversion recovery (FLAIR) and double inversion recovery (DIR). The former highlights both gray matter (GM) and white matter (WM), the latter highlights GM alone. We propose here a supervised classification scheme that does not require any anatomical a priori information to identify the 3 classes, "GM", "WM", and "background". Features are extracted by means of a local multi-scale texture analysis, computed for each pixel of the DIR and FLAIR sequences. The 9 textures considered are average, standard deviation, kurtosis, entropy, contrast, correlation, energy, homogeneity, and skewness, evaluated on a neighborhood of 3x3, 5x5, and 7x7 pixels. Hence, the total number of features associated to a pixel is 56 (9 textures x3 scales x2 sequences +2 original pixel values). The classifier employed is a Support Vector Machine with Radial Basis Function as kernel. From each of the 4 brain volumes evaluated, a DIR and a FLAIR slice have been selected and manually segmented by 2 expert neurologists, providing 1st and 2nd human reference observations which agree with an average accuracy of 99.03%. SVM performances have been assessed with a 4-fold cross-validation, yielding an average classification accuracy of 98.79%.

Global and regional annual brain volume loss rates in physiological aging.

PubMed

Schippling, Sven; Ostwaldt, Ann-Christin; Suppa, Per; Spies, Lothar; Manogaran, Praveena; Gocke, Carola; Huppertz, Hans-Jürgen; Opfer, Roland

2017-03-01

The objective is to estimate average global and regional percentage brain volume loss per year (BVL/year) of the physiologically ageing brain. Two independent, cross-sectional single scanner cohorts of healthy subjects were included. The first cohort (n = 248) was acquired at the Medical Prevention Center (MPCH) in Hamburg, Germany. The second cohort (n = 316) was taken from the Open Access Series of Imaging Studies (OASIS). Brain parenchyma (BP), grey matter (GM), white matter (WM), corpus callosum (CC), and thalamus volumes were calculated. A non-parametric technique was applied to fit the resulting age-volume data. For each age, the BVL/year was derived from the age-volume curves. The resulting BVL/year curves were compared between the two cohorts. For the MPCH cohort, the BVL/year curve of the BP was an increasing function starting from 0.20% at the age of 35 years increasing to 0.52% at 70 years (corresponding values for GM ranged from 0.32 to 0.55%, WM from 0.02 to 0.47%, CC from 0.07 to 0.48%, and thalamus from 0.25 to 0.54%). Mean absolute difference between BVL/year trajectories across the age range of 35-70 years was 0.02% for BP, 0.04% for GM, 0.04% for WM, 0.11% for CC, and 0.02% for the thalamus. Physiological BVL/year rates were remarkably consistent between the two cohorts and independent from the scanner applied. Average BVL/year was clearly age and compartment dependent. These results need to be taken into account when defining cut-off values for pathological annual brain volume loss in disease models, such as multiple sclerosis.

CATEGORY-SPECIFIC SEMANTIC MEMORY: CONVERGING EVIDENCE FROM BOLD fMRI AND ALZHEIMER’S DISEASE

PubMed Central

Grossman, Murray; Peelle, Jonathan E.; Smith, Edward E.; McMillan, Corey T.; Cook, Philip; Powers, John; Dreyfuss, Michael; Bonner, Michael F.; Richmond, Lauren; Boller, Ashley; Camp, Emily; Burkholder, Lisa

2012-01-01

Patients with Alzheimer’s disease have category-specific semantic memory difficulty for natural relative to manufactured objects. We assessed the basis for this deficit by asking healthy adults and patients to judge whether pairs of words share a feature (e.g. “banana:lemon – COLOR”). In an fMRI study, healthy adults showed gray matter (GM) activation of temporal-occipital cortex (TOC) where visual-perceptual features may be represented, and prefrontal cortex (PFC) which may contribute to feature selection. Tractography revealed dorsal and ventral stream white matter (WM) projections between PFC and TOC. Patients had greater difficulty with natural than manufactured objects. This was associated with greater overlap between diseased GM areas correlated with natural kinds in patients and fMRI activation in healthy adults for natural than manufactured artifacts, and the dorsal WM projection between PFC and TOC in patients correlated only with judgments of natural kinds. Patients thus remained dependent on the same neural network as controls during judgments of natural kinds, despite disease in these areas. For manufactured objects, patients’ judgments showed limited correlations with PFC and TOC GM areas activated by controls, and did not correlate with the PFC-TOC dorsal WM tract. Regions outside of the PFC–TOC network thus may help support patients’ judgments of manufactured objects. We conclude that a large-scale neural network for semantic memory implicates both feature knowledge representations in modality-specific association cortex and heteromodal regions important for accessing this knowledge, and that patients’ relative deficit for natural kinds is due in part to their dependence on this network despite disease in these areas. PMID:23220494

Category-specific semantic memory: converging evidence from bold fMRI and Alzheimer's disease.

PubMed

Grossman, Murray; Peelle, Jonathan E; Smith, Edward E; McMillan, Corey T; Cook, Philip; Powers, John; Dreyfuss, Michael; Bonner, Michael F; Richmond, Lauren; Boller, Ashley; Camp, Emily; Burkholder, Lisa

2013-03-01

Patients with Alzheimer's disease have category-specific semantic memory difficulty for natural relative to manufactured objects. We assessed the basis for this deficit by asking healthy adults and patients to judge whether pairs of words share a feature (e.g. "banana:lemon-COLOR"). In an fMRI study, healthy adults showed gray matter (GM) activation of temporal-occipital cortex (TOC) where visual-perceptual features may be represented, and prefrontal cortex (PFC) which may contribute to feature selection. Tractography revealed dorsal and ventral stream white matter (WM) projections between PFC and TOC. Patients had greater difficulty with natural than manufactured objects. This was associated with greater overlap between diseased GM areas correlated with natural kinds in patients and fMRI activation in healthy adults for natural kinds. The dorsal WM projection between PFC and TOC in patients correlated only with judgments of natural kinds. Patients thus remained dependent on the same neural network as controls during judgments of natural kinds, despite disease in these areas. For manufactured objects, patients' judgments showed limited correlations with PFC and TOC GM areas activated by controls, and did not correlate with the PFC-TOC dorsal WM tract. Regions outside of the PFC-TOC network thus may help support patients' judgments of manufactured objects. We conclude that a large-scale neural network for semantic memory implicates both feature knowledge representations in modality-specific association cortex and heteromodal regions important for accessing this knowledge, and that patients' relative deficit for natural kinds is due in part to their dependence on this network despite disease in these areas. Copyright © 2012 Elsevier Inc. All rights reserved.

Changes in cognitive functions and cerebral grey matter and their associations with inflammatory markers, endocrine markers, and APOE genotypes in testicular cancer patients undergoing treatment.

PubMed

Amidi, Ali; Agerbæk, Mads; Wu, Lisa M; Pedersen, Anders D; Mehlsen, Mimi; Clausen, Cecilie R; Demontis, Ditte; Børglum, Anders D; Harbøll, Anja; Zachariae, Robert

2017-06-01

Evidence suggests that testicular cancer (TC) and its treatment are associated with cognitive impairment. However, the underlying neural substrate and biological mechanisms are poorly understood. This study aimed to investigate changes in cognition and brain grey matter (GM) morphology in TC patients undergoing treatment, and to explore associations with immune markers, endocrine markers, and genotype. Sixty-five patients with stage I-III TC underwent assessment after surgery but prior to further treatment and again 6 months after. Twenty-two patients received chemotherapy (+CT), while 43 did not (-CT). Assessments included neuropsychological testing, whole-brain magnetic resonance imaging, and blood samples. Twenty-five healthy controls (HCs) underwent neuropsychological testing with a matching time interval. A regression-based approach was used to determine cognitive changes and longitudinal voxel-based morphometry (VBM) was performed to investigate changes in GM density in the TC groups. Compared with the HCs, both TC groups showed higher rates of cognitive decline (p < 0.05). A trend towards greater decline was observed in + CT (63.6 %) compared with -CT patients (39.5 %) (p = 0.07). VBM revealed widespread GM reductions in both TC groups, but a group-by-time interaction analysis revealed prefrontal reductions specific to the + CT group (p = 0.02), which were associated with poorer cognitive performance. Poorer cognitive performance was also associated with an increase in tumor necrosis factor alpha in + CT patients. Furthermore, an interaction effect was found between the APOE ε4 genotype and chemotherapy on cognitive performance with ε4 carriers performing significantly worse. These findings provide novel evidence of changes in cognition and brain morphology in TC patients undergoing treatment.

A simple optical model to estimate suspended particulate matter in Yellow River Estuary.

PubMed

Qiu, Zhongfeng

2013-11-18

Distribution of the suspended particulate matter (SPM) concentration is a key issue for analyzing the deposition and erosion variety of the estuary and evaluating the material fluxes from river to sea. Satellite remote sensing is a useful tool to investigate the spatial variation of SPM concentration in estuarial zones. However, algorithm developments and validations of the SPM concentrations in Yellow River Estuary (YRE) have been seldom performed before and therefore our knowledge on the quality of retrieval of SPM concentration is poor. In this study, we developed a new simple optical model to estimate SPM concentration in YRE by specifying the optimal wavelength ratios (600-710 nm)/ (530-590 nm) based on observations of 5 cruises during 2004 and 2011. The simple optical model was attentively calibrated and the optimal band ratios were selected for application to multiple sensors, 678/551 for the Moderate Resolution Imaging Spectroradiometer (MODIS), 705/560 for the Medium Resolution Imaging Spectrometer (MERIS) and 680/555 for the Geostationary Ocean Color Imager (GOCI). With the simple optical model, the relative percentage difference and the mean absolute error were 35.4% and 15.6 gm(-3) respectively for MODIS, 42.2% and 16.3 gm(-3) for MERIS, and 34.2% and 14.7 gm(-3) for GOCI, based on an independent validation data set. Our results showed a good precision of estimation for SPM concentration using the new simple optical model, contrasting with the poor estimations derived from existing empirical models. Providing an available atmospheric correction scheme for satellite imagery, our simple model could be used for quantitative monitoring of SPM concentrations in YRE.

Sequential stages and distribution patterns of aging-related tau astrogliopathy (ARTAG) in the human brain.

PubMed

Kovacs, Gabor G; Xie, Sharon X; Robinson, John L; Lee, Edward B; Smith, Douglas H; Schuck, Theresa; Lee, Virginia M-Y; Trojanowski, John Q

2018-06-11

Aging-related tau astrogliopathy (ARTAG) describes tau pathology in astrocytes in different locations and anatomical regions. In the present study we addressed the question of whether sequential distribution patterns can be recognized for ARTAG or astroglial tau pathologies in both primary FTLD-tauopathies and non-FTLD-tauopathy cases. By evaluating 687 postmortem brains with diverse disorders we identified ARTAG in 455. We evaluated frequencies and hierarchical clustering of anatomical involvement and used conditional probability and logistic regression to model the sequential distribution of ARTAG and astroglial tau pathologies across different brain regions. For subpial and white matter ARTAG we recognize three and two patterns, respectively, each with three stages initiated or ending in the amygdala. Subependymal ARTAG does not show a clear sequential pattern. For grey matter (GM) ARTAG we recognize four stages including a striatal pathway of spreading towards the cortex and/or amygdala, and the brainstem, and an amygdala pathway, which precedes the involvement of the striatum and/or cortex and proceeds towards the brainstem. GM ARTAG and astrocytic plaque pathology in corticobasal degeneration follows a predominantly frontal-parietal cortical to temporal-occipital cortical, to subcortical, to brainstem pathway (four stages). GM ARTAG and tufted astrocyte pathology in progressive supranuclear palsy shows a striatum to frontal-parietal cortical to temporal to occipital, to amygdala, and to brainstem sequence (four stages). In Pick's disease cases with astroglial tau pathology an overlapping pattern with PSP can be appreciated. We conclude that tau-astrogliopathy type-specific sequential patterns cannot be simplified as neuron-based staging systems. The proposed cytopathological and hierarchical stages provide a conceptual approach to identify the initial steps of the pathogenesis of tau pathologies in ARTAG and primary FTLD-tauopathies.

Corpus callosum damage predicts disability progression and cognitive dysfunction in primary-progressive MS after five years.

PubMed

Bodini, Benedetta; Cercignani, Mara; Khaleeli, Zhaleh; Miller, David H; Ron, Maria; Penny, Sophie; Thompson, Alan J; Ciccarelli, Olga

2013-05-01

We aim to identify specific areas of white matter (WM) and grey matter (GM), which predict disability progression and cognitive dysfunction after five years in patients with primary-progressive multiple sclerosis (PPMS). Thirty-two patients with early PPMS were assessed at baseline and after five years on the Expanded Disability Status Scale (EDSS), and EDSS step-changes were calculated. At year five, a subgroup of 25 patients and 31 healthy controls underwent a neuropsychological assessment. Baseline imaging consisted of dual-echo (proton density and T2-weighted), T1-weighted volumetric, and diffusion tensor imaging. Fractional anisotropy (FA) maps were created, and fed into tract-based spatial statistics. To compensate for the potential bias introduced by WM lesions, the T1 volumes underwent a lesion-filling procedure before entering a voxel-based morphometry protocol. To investigate whether FA and GM volume predicted EDSS step-changes over five years and neuropsychological tests scores at five years, voxelwise linear regression analyses were performed. Lower FA in the splenium of the corpus callosum (CC) predicted a greater progression of disability over the follow-up. Lower FA along the entire CC predicted worse verbal memory, attention and speed of information processing, and executive function at five years. GM baseline volume did not predict any clinical variable. Our findings highlight the importance of damage to the interhemispheric callosal pathways in determining physical and cognitive disability in PPMS. Disruption of these pathways, which interconnect motor and cognitive networks between the two hemispheres, may result in a disconnection syndrome that contributes to long-term physical and cognitive disability. Copyright © 2011 Wiley Periodicals, Inc.

Characteristics of sediment resuspension in Lake Taihu, China: A wave flume study

NASA Astrophysics Data System (ADS)

Ding, Yanqing; Sun, Limin; Qin, Boqiang; Wu, Tingfeng; Shen, Xia; Wang, Yongping

2018-06-01

Lake Taihu is a typical shallow lake which frequently happens sediment resuspension induced by wind-induced waves. The experiments are carried on to simulate the wave disturbance processes in wave flume by setting a series of wave periods (1.2 s, 1.5 s, 1.8 s) and wave heights (2 cm, 10 cm). It aims to analyze the characteristics of sediment resuspension and the mechanisms of nutrients release and to evaluate the effects of sediment dredging on sediment resuspension and nutrients release in Lake Taihu. The results show that wave shear stress during 2 cm and 10 cm wave height processes ranges 0.018-0.023 N/m2 and 0.221-0.307 N/m2, respectively. Wave shear stress has no significant differences between wave periods. Wave height has much more effects on sediment resuspension. Wave height of 2 cm could induce total suspended solids (TSS) reaching up to 5.21 g/m2 and resuspension flux of sediment (M) up to 1.74 g/m2. TSS sharply increases to 30.33-52.41 g/m2 and M reached up to 48.94 g/m2 when wave height reaches to 10 cm. The disturbance depth under different sediment bulk weights ranges from 0.089 to 0.161 mm. Variation of suspended solids in 3 layers (1 cm, 5 cm, 20 cm above sediment interface) has no significant differences. Organic matter, TN and TP have positive relationship with SS. Organic matter is only accounted for 5.7%-7.3% of SS. The experiments under different sediment bulk densities (1.34 g/cm3, 1.47 g/cm3 and 1.59 g/cm3) find that TSS and M fall by 44.2% and 39.8% with sediment bulk density increasing, respectively. Total TN, DTN, TP and DTP decrease by 24.3%-33.6%. It indicates that sediment dredging could effectively reduce SS concentration and nutrient levels in water column. The researches provide a theoretical basis for sediment dredging to control the shore zone of Lake Taihu for lake management.

A Theory of Gravity and General Relativity based on Quantum Electromagnetism

NASA Astrophysics Data System (ADS)

Zheng-Johansson, J. X.

2018-02-01

Based on first principles solutions in a unified framework of quantum mechanics and electromagnetism we predict the presence of a universal attractive depolarisation radiation (DR) Lorentz force (F) between quantum entities, each being either an IED matter particle or light quantum, in a polarisable dielectric vacuum. Given two quantum entities i = 1, 2 of either kind, of characteristic frequencies ν _i^0, masses m_i0 = hν _i^0/{c^2} and separated at a distance r 0, the solution for F is F = - G}m_1^0m_2^0/{≤ft( {{r^2}} \\right)^2}, where G} = χ _0^2{e^4}/12{π ^2} \\in _0^2{ρ _λ };{χ _0} is the susceptibility and π λ is the reduced linear mass density of the vacuum. This force F resembles in all respects Newton’s gravity and is accurate at the weak F limit; hence ℊ equals the gravitational constant G. The DR wave fields and hence the gravity are each propagated in the dielectric vacuum at the speed of light c; these can not be shielded by matter. A test particle µ of mass m 0 therefore interacts gravitationally with all of the building particles of a given large mass M at r 0 apart, by a total gravitational force F = -GMm 0/(r 0)2 and potential V = -∂F/∂r 0. For a finite V and hence a total Hamiltonian H = m 0 c 2 + V, solution for the eigenvalue equation of µ presents a red-shift in the eigen frequency ν = ν 0(1 - GM/r 0 c 2) and hence in other wave variables. The quantum solutions combined with the wave nature of the gravity further lead to dilated gravito optical distance r = r 0/(1 - GM/r 0 c 2) and time t = t 0/(1 - GM/r 0 c 2), and modified Newton’s gravity and Einstein’s mass energy relation. Applications of these give predictions of the general relativistic effects manifested in the four classical test experiments of Einstein’s general relativity (GR), in direct agreement with the experiments and the predictions given based on GR.

Resting-State Hyperperfusion of the Supplementary Motor Area in Catatonia.

PubMed

Walther, Sebastian; Schäppi, Lea; Federspiel, Andrea; Bohlhalter, Stephan; Wiest, Roland; Strik, Werner; Stegmayer, Katharina

2017-09-01

Catatonia is a psychomotor syndrome that not only frequently occurs in the context of schizophrenia but also in other conditions. The neural correlates of catatonia remain unclear due to small-sized studies. We therefore compared resting-state cerebral blood flow (rCBF) and gray matter (GM) density between schizophrenia patients with current catatonia and without catatonia and healthy controls. We included 42 schizophrenia patients and 41 controls. Catatonia was currently present in 15 patients (scoring >2 items on the Bush Francis Catatonia Rating Scale screening). Patients did not differ in antipsychotic medication or positive symptoms. We acquired whole-brain rCBF using arterial spin labeling and GM density. We compared whole-brain perfusion and GM density over all and between the groups using 1-way ANCOVAs (F and T tests). We found a group effect (F test) of rCBF within bilateral supplementary motor area (SMA), anterior cingulate cortex, dorsolateral prefrontal cortex, left interior parietal lobe, and cerebellum. T tests indicated 1 cluster (SMA) to be specific to catatonia. Moreover, catatonia of excited and retarded types differed in SMA perfusion. Furthermore, increased catatonia severity was associated with higher perfusion in SMA. Finally, catatonia patients had a distinct pattern of GM density reduction compared to controls with prominent GM loss in frontal and insular cortices. SMA resting-state hyperperfusion is a marker of current catatonia in schizophrenia. This is highly compatible with a dysregulated motor system in catatonia, particularly affecting premotor areas. Moreover, SMA perfusion was differentially altered in retarded and excited catatonia subtypes, arguing for distinct pathobiology. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Automatical and accurate segmentation of cerebral tissues in fMRI dataset with combination of image processing and deep learning

NASA Astrophysics Data System (ADS)

Kong, Zhenglun; Luo, Junyi; Xu, Shengpu; Li, Ting

2018-02-01

Image segmentation plays an important role in medical science. One application is multimodality imaging, especially the fusion of structural imaging with functional imaging, which includes CT, MRI and new types of imaging technology such as optical imaging to obtain functional images. The fusion process require precisely extracted structural information, in order to register the image to it. Here we used image enhancement, morphometry methods to extract the accurate contours of different tissues such as skull, cerebrospinal fluid (CSF), grey matter (GM) and white matter (WM) on 5 fMRI head image datasets. Then we utilized convolutional neural network to realize automatic segmentation of images in deep learning way. Such approach greatly reduced the processing time compared to manual and semi-automatic segmentation and is of great importance in improving speed and accuracy as more and more samples being learned. The contours of the borders of different tissues on all images were accurately extracted and 3D visualized. This can be used in low-level light therapy and optical simulation software such as MCVM. We obtained a precise three-dimensional distribution of brain, which offered doctors and researchers quantitative volume data and detailed morphological characterization for personal precise medicine of Cerebral atrophy/expansion. We hope this technique can bring convenience to visualization medical and personalized medicine.

Evidence of neurodegeneration in brains of older adults who do not yet fulfill MCI criteria

PubMed Central

Chao, L.L.; Mueller, S.G.; Buckley, S.T.; Peek, K.; Raptentsetseng, S.; Elman, J.; Yaffe, K.; Miller, B.L.; Kramer, J.H.; Madison, C.; Mungas, D.; Schuff, N.; Weiner, M.W.

2008-01-01

We sought to determine whether there are structural and metabolic changes in the brains of older adults with cognitive complaints yet who do not meet MCI criteria (i.e., preMCI). We compared the volumes of regional lobar gray matter (GM) and medial temporal lobe structures, including the hippocampus, entorhinal cortex (ERC), fusiform and parahippocampal gyri, and metabolite ratios from the posterior cingulate in individuals who had a Clinical Demetia Rating (CDR) of 0.5, but who did not meet MCI criteria (preMCI, N = 17), patients with mild cognitive impairment (MCI, N = 13), and cognitively normal controls (N = 18). Controls had more ERC, fusiform, and frontal gray matter volume than preMCI and MCI subjects and greater parahippocampal volume and more posterior cingulate N-acetylaspartate (NAA)/myoinosotil (mI) than MCI. There were no significant differences between MCI and preMCI subjects on any of these measures. These findings suggest there are neurodegenerative changes in the brains of older adults who have cognitive complaints severe enough to qualify for CDR = 0.5 yet show no deficits on formal neuropsychological testing. The results further support the hypothesis that detection of individuals with very mild forms of Alzheimer's disease (AD) may be facilitated by use of the CDR, which emphasizes changes in cognition over time within individuals rather than comparison with group norms. PMID:18550226

Comprehensive Analysis of the Soybean (Glycine max) GmLAX Auxin Transporter Gene Family

PubMed Central

Chai, Chenglin; Wang, Yongqin; Valliyodan, Babu; Nguyen, Henry T.

2016-01-01

The phytohormone auxin plays a critical role in regulation of plant growth and development as well as plant responses to abiotic stresses. This is mainly achieved through its uneven distribution in plant via a polar auxin transport process. Auxin transporters are major players in polar auxin transport. The AUXIN RESISTENT 1/LIKE AUX1 (AUX/LAX) auxin influx carriers belong to the amino acid permease family of proton-driven transporters and function in the uptake of indole-3-acetic acid (IAA). In this study, genome-wide comprehensive analysis of the soybean AUX/LAX (GmLAX) gene family, including phylogenic relationships, chromosome localization, and gene structure, was carried out. A total of 15 GmLAX genes, including seven duplicated gene pairs, were identified in the soybean genome. They were distributed on 10 chromosomes. Despite their higher percentage identities at the protein level, GmLAXs exhibited versatile tissue-specific expression patterns, indicating coordinated functioning during plant growth and development. Most GmLAXs were responsive to drought and dehydration stresses and auxin and abscisic acid (ABA) stimuli, in a tissue- and/or time point- sensitive mode. Several GmLAX members were involved in responding to salt stress. Sequence analysis revealed that promoters of GmLAXs contained different combinations of stress-related cis-regulatory elements. These studies suggest that the soybean GmLAXs were under control of a very complex regulatory network, responding to various internal and external signals. This study helps to identity candidate GmLAXs for further analysis of their roles in soybean development and adaption to adverse environments. PMID:27014306

In search of a solution to the sphinx-like riddle of GM1.

PubMed

Ledeen, Robert W; Wu, Gusheng

2010-12-01

Among the many glycoconjugates contributing to the sugar code, gangliosides have drawn special attention owing to their predominance as the major sialoglycoconjugate category within the nervous system. However, their occurrence, albeit at lower levels, appears ubiquitous in vertebrate cells and even some invertebrate tissues. Now that over 100 gangliosides have been structurally characterized, their diverse physiological functions constitute a remaining enigma. This has been especially true of GM1, for which a surprising array of functions has already been revealed. Our current research has focused on two areas of GM1 function: (a) signaling induced in neural and immune cells by cross-linking of GM1 in the plasma membrane that leads to activation of TRPC5 (transient receptor potiential, canonical form 5) channels, a process important in neuritogenesis and autoimmune suppression; (b) activation by GM1 of a sodium-calcium exchanger (NCX) in the inner membrane of the nuclear envelope (NE) with resulting modulation of nuclear and cellular calcium. The latter has a role in maintaining neuronal viability, loss of which renders neurons vulnerable to Ca(2+) overload. Pathological manifestations in mutant mice and their cultured neurons lacking GM1 have shown dramatic rescue with a membrane permeable derivative of GM1 that enters the nucleus and restores NCX activity. Nuclear function of GM1 is related to the presence of neuraminidase in the NE, an enzyme that generates GM1 through hydrolysis of GD1a. A different isoform of this enzyme was found in each of the two membranes of the NE.

Structural basis of GM-CSF and IL-2 sequestration by the viral decoy receptor GIF

PubMed Central

Felix, Jan; Kandiah, Eaazhisai; De Munck, Steven; Bloch, Yehudi; van Zundert, Gydo C.P.; Pauwels, Kris; Dansercoer, Ann; Novanska, Katka; Read, Randy J.; Bonvin, Alexandre M.J.J.; Vergauwen, Bjorn; Verstraete, Kenneth; Gutsche, Irina; Savvides, Savvas N.

2016-01-01

Subversion of the host immune system by viruses is often mediated by molecular decoys that sequester host proteins pivotal to mounting effective immune responses. The widespread mammalian pathogen parapox Orf virus deploys GIF, a member of the poxvirus immune evasion superfamily, to antagonize GM-CSF (granulocyte macrophage colony-stimulating factor) and IL-2 (interleukin-2), two pleiotropic cytokines of the mammalian immune system. However, structural and mechanistic insights into the unprecedented functional duality of GIF have remained elusive. Here we reveal that GIF employs a dimeric binding platform that sequesters two copies of its target cytokines with high affinity and slow dissociation kinetics to yield distinct complexes featuring mutually exclusive interaction footprints. We illustrate how GIF serves as a competitive decoy receptor by leveraging binding hotspots underlying the cognate receptor interactions of GM-CSF and IL-2, without sharing any structural similarity with the cytokine receptors. Our findings contribute to the tracing of novel molecular mimicry mechanisms employed by pathogenic viruses. PMID:27819269

Impact of climatic extremity upon human health

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miah, M.A.; Samad, M.A.

The extreme climate generated in the wake of the shortage of the supply of natural water in the lower Ganges basin has triggered a number of environmental diseases in the lower Ganges basin. In the wake of improper sanitation conditions for the scarcity of water, water-borne diseases like cholera, diarrhea, hepatitis, etc., break out and take out the lives of victims. Further, the development of the dry climate has favored an increased amount of suspended particulate matter in the air. The result is the prevalent problem of asthma which is even worse than the water-borne diseases. Almost one in everymore » four families living in this city has an asthma patient. The worst is that more than 10% of the families have three asthma patients. And, most of the elderly asthma patients suffer from diabetes and high blood pressure at the same time. The wide spread of asthma is thought to be related to the triggering allergic action suffered by patients due to the presence of excess particulate matter in the air. More than 50% of the population suffer from nasal allergy, sinusitis, and chronic bronchitis. The suspended particles are mostly fine grains of sands and carbon. The cleanest air (usually, after a heavy rainfall) contains at least one gm of particulate matter in every 2,039 cubic meter of air. An average man will inhale about 1.11 million gallons of air per year which amounts to about 2 gm of particulate matter per year. Additionally, during the dry months, major duststorms appear a couple of times with an uplift of half a million kg of dust in air over about 810 square km each time. The paper will focus on water scarcity, the climatic extremity, suspended particulate matter, the outbreaks of water-borne and the prevalent respiratory diseases, and suggestions to mitigate human sufferings.« less