Multiple sclerosis patients lacking oligoclonal bands in the cerebrospinal fluid have less global and regional brain atrophy.

PubMed

Ferreira, Daniel; Voevodskaya, Olga; Imrell, Kerstin; Stawiarz, Leszek; Spulber, Gabriela; Wahlund, Lars-Olof; Hillert, Jan; Westman, Eric; Karrenbauer, Virginija Danylaité

2014-09-15

To investigate whether multiple sclerosis (MS) patients with and without cerebrospinal fluid (CSF) oligoclonal immunoglobulin G bands (OCB) differ in brain atrophy. Twenty-eight OCB-negative and thirty-five OCB-positive patients were included. Larger volumes of total CSF and white matter (WM) lesions; smaller gray matter (GM) volume in the basal ganglia, diencephalon, cerebellum, and hippocampus; and smaller WM volume in corpus callosum, periventricular-deep WM, brainstem, and cerebellum, were observed in OCB-positives. OCB-negative patients, known to differ genetically from OCB-positives, are characterized by less global and regional brain atrophy. This finding supports the notion that OCB-negative MS patients may represent a clinically relevant MS subgroup. Copyright © 2014 Elsevier B.V. All rights reserved.

Gender dimorphism of brain reward system volumes in alcoholism.

PubMed

Sawyer, Kayle S; Oscar-Berman, Marlene; Barthelemy, Olivier J; Papadimitriou, George M; Harris, Gordon J; Makris, Nikos

2017-05-30

The brain's reward network has been reported to be smaller in alcoholic men compared to nonalcoholic men, but little is known about the volumes of reward regions in alcoholic women. Morphometric analyses were performed on magnetic resonance brain scans of 60 long-term chronic alcoholics (ALC; 30 men) and 60 nonalcoholic controls (NC; 29 men). We derived volumes of total brain, and cortical and subcortical reward-related structures including the dorsolateral prefrontal (DLPFC), orbitofrontal, and cingulate cortices, and the temporal pole, insula, amygdala, hippocampus, nucleus accumbens septi (NAc), and ventral diencephalon (VDC). We examined the relationships of the volumetric findings to drinking history. Analyses revealed a significant gender interaction for the association between alcoholism and total reward network volumes, with ALC men having smaller reward volumes than NC men and ALC women having larger reward volumes than NC women. Analyses of a priori subregions revealed a similar pattern of reward volume differences with significant gender interactions for DLPFC and VDC. Overall, the volume of the cerebral ventricles in ALC participants was negatively associated with duration of abstinence, suggesting decline in atrophy with greater length of sobriety. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Prognostic Factors for Survival in Patients Treated With Stereotactic Radiosurgery for Recurrent Brain Metastases After Prior Whole Brain Radiotherapy

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

Caballero, Jorge A.; Sneed, Penny K., E-mail: psneed@radonc.ucsf.edu; Lamborn, Kathleen R.

2012-05-01

Purpose: To evaluate prognostic factors for survival after stereotactic radiosurgery (SRS) for new, progressive, or recurrent brain metastases (BM) after prior whole brain radiotherapy (WBRT). Methods and Materials: Patients treated between 1991 and 2007 with Gamma Knife SRS for BM after prior WBRT were retrospectively reviewed. Potential prognostic factors were analyzed overall and by primary site using univariate and stepwise multivariate analyses and recursive partitioning analysis, including age, Karnofsky performance status (KPS), primary tumor control, extracranial metastases, number of BM treated, total SRS target volume, and interval from WBRT to SRS. Results: A total of 310 patients were analyzed, includingmore » 90 breast, 113 non-small-cell lung, 31 small-cell lung, 42 melanoma, and 34 miscellaneous patients. The median age was 56, KPS 80, number of BM treated 3, and interval from WBRT to SRS 8.1 months; 76% had controlled primary tumor and 60% had extracranial metastases. The median survival was 8.4 months overall and 12.0 vs. 7.9 months for single vs. multiple BM treated (p = 0.001). There was no relationship between number of BM and survival after excluding single-BM patients. On multivariate analysis, favorable prognostic factors included age <50, smaller total target volume, and longer interval from WBRT to SRS in breast cancer patients; smaller number of BM, KPS >60, and controlled primary in non-small-cell lung cancer patients; and smaller total target volume in melanoma patients. Conclusions: Among patients treated with salvage SRS for BM after prior WBRT, prognostic factors appeared to vary by primary site. Although survival time was significantly longer for patients with a single BM, the median survival time of 7.9 months for patients with multiple BM seems sufficiently long for salvage SRS to appear to be worthwhile, and no evidence was found to support the use of a cutoff for number of BM appropriate for salvage SRS.« less

Memory performance, global cerebral volumes and hippocampal subfield volumes in long-term survivors of Out-of-Hospital Cardiac Arrest.

PubMed

Ørbo, Marte C; Vangberg, Torgil R; Tande, Pål M; Anke, Audny; Aslaksen, Per M

2018-05-01

We explored the associations between global brain volumes, hippocampal subfield volumes and verbal memory performance in long-term survivors of out-of-hospital cardiac arrest (OHCA). Three months after OHCA, survivors and healthy, age-matched controls were assessed with cerebral MRI and the California Verbal Learning Test-II (CVLT-II). Volumetric brain segmentation was performed automatically by FreeSurfer. Twenty-six OHCA survivors who were living independently in regular homes at the time of assessment and 19 controls participated in the study. Thirteen of the survivors had been conscious upon arrival to the emergency department. The other 13 survivors had 0.5-7 days of inpatient coma before recovery. Memory was poorer in the OHCA group that had been comatose beyond initial hospital admission compared to both other groups. Total cortical volumes, total hippocampus volumes and several hippocampal subfield volumes were significantly smaller in the OHCA group comatose beyond initial hospital admission compared to controls. No significant differences between the OHCA group conscious upon emergency department arrival and the other two groups were found for brain volumes. No significant differences were observed between any groups for white matter or total subcortical volumes. In OHCA survivors with recovery from inpatient coma, the various CVLT-II trials were significantly, but differentially, correlated to total gray matter volume, cortical volume and the hippocampal subfield subiculum. In this small, single-site study, both hippocampal volume and cortical volume were smaller in good outcome OHCA survivors 3 months after resuscitation in comparison to healthy controls. Smaller cerebral volumes were correlated with poorer memory performance. Copyright © 2018 Elsevier B.V. All rights reserved.

Prenatal Tobacco Exposure and Brain Morphology: A Prospective Study in Young Children

PubMed Central

El Marroun, Hanan; Schmidt, Marcus N; Franken, Ingmar H A; Jaddoe, Vincent W V; Hofman, Albert; van der Lugt, Aad; Verhulst, Frank C; Tiemeier, Henning; White, Tonya

2014-01-01

It is well known that smoking during pregnancy can affect offspring health. Prenatal tobacco exposure has been associated with negative behavioral and cognitive outcomes in childhood, adolescence, and young adulthood. These associations between prenatal tobacco exposure and psychopathology in offspring could possibly be explained by the influence of prenatal tobacco exposure on brain development. In this prospective study, we investigated the association between prenatal tobacco exposure, behavioral and emotional functioning and brain morphology in young children. On the basis of age and gender, we matched 113 children prenatally exposed to tobacco with 113 unexposed controls. These children were part of a population-based study in the Netherlands, the Generation R Study, and were followed from pregnancy onward. Behavioral and emotional functioning was assessed at age 6 with the Child Behavior Checklist. We assessed brain morphology using magnetic resonance imaging techniques in children aged 6–8 years. Children exposed to tobacco throughout pregnancy have smaller total brain volumes and smaller cortical gray matter volumes. Continued prenatal tobacco exposure was associated with cortical thinning, primarily in the superior frontal, superior parietal, and precentral cortices. These children also demonstrated increased scores of affective problems. In addition, thickness of the precentral and superior frontal cortices was associated with affective problems. Importantly, brain development in offspring of mothers who quit smoking during pregnancy resembled that of nonexposed controls (no smaller brain volumes and no thinning of the cortex). Our findings suggest an association between continued prenatal tobacco exposure and brain structure and function in school-aged children. PMID:24096296

Neuroimaging effects of prenatal alcohol exposure on the developing human brain: a magnetic resonance imaging review.

PubMed

Donald, Kirsten Ann; Eastman, Emma; Howells, Fleur Margaret; Adnams, Colleen; Riley, Edward Patrick; Woods, Roger Paul; Narr, Katherine Louise; Stein, Dan Joseph

2015-10-01

This paper reviews the magnetic resonance imaging (MRI) literature on the effects of prenatal alcohol exposure on the developing human brain. A literature search was conducted through the following databases: PubMed, PsycINFO and Google Scholar. Combinations of the following search terms and keywords were used to identify relevant studies: 'alcohol', 'fetal alcohol spectrum disorders', 'fetal alcohol syndrome', 'FAS', 'FASD', 'MRI', 'DTI', 'MRS', 'neuroimaging', 'children' and 'infants'. A total of 64 relevant articles were identified across all modalities. Overall, studies reported smaller total brain volume as well as smaller volume of both the white and grey matter in specific cortical regions. The most consistently reported structural MRI findings were alterations in the shape and volume of the corpus callosum, as well as smaller volume in the basal ganglia and hippocampi. The most consistent finding from diffusion tensor imaging studies was lower fractional anisotropy in the corpus callosum. Proton magnetic resonance spectroscopy studies are few to date, but showed altered neurometabolic profiles in the frontal and parietal cortex, thalamus and dentate nuclei. Resting-state functional MRI studies reported reduced functional connectivity between cortical and deep grey matter structures. Discussion There is a critical gap in the literature of MRI studies in alcohol-exposed children under 5 years of age across all MRI modalities. The dynamic nature of brain maturation and appreciation of the effects of alcohol exposure on the developing trajectory of the structural and functional network argue for the prioritisation of studies that include a longitudinal approach to understanding this spectrum of effects and potential therapeutic time points.

Volumetric MRI study of the intrauterine growth restriction fetal brain.

PubMed

Polat, A; Barlow, S; Ber, R; Achiron, R; Katorza, E

2017-05-01

Intrauterine growth restriction (IUGR) is a pathologic fetal condition known to affect the fetal brain regionally and associated with future neurodevelopmental abnormalities. This study employed MRI to assess in utero regional brain volume changes in IUGR fetuses compared to controls. Retrospectively, using MRI images of fetuses at 30-34 weeks gestational age, a total of 8 brain regions-supratentorial brain and cavity, cerebral hemispheres, temporal lobes and cerebellum-were measured for volume in 13 fetuses with IUGR due to placental insufficiency and in 21 controls. Volumes and their ratios were assessed for difference using regression models. Reliability was assessed by intraclass correlation coefficients (ICC) between two observers. In both groups, all structures increase in absolute volume during that gestation period, and the rate of cerebellar growth is higher compared to that of supratentorial structures. All structures' absolute volumes were significantly smaller for the IUGR group. Cerebellar to supratentorial ratios were found to be significantly smaller (P < 0.05) for IUGR compared to controls. No other significant ratio differences were found. ICC showed excellent agreement. The cerebellar to supratentorial volume ratio is affected in IUGR fetuses. Additional research is needed to assess this as a radiologic marker in relation to long-term outcome. • IUGR is a pathologic fetal condition affecting the brain • IUGR is associated with long-term neurodevelopmental abnormalities; fetal characterization is needed • This study aimed to evaluate regional brain volume differences in IUGR • Cerebellar to supratentorial volume ratios were smaller in IUGR fetuses • This finding may play a role in long-term development of IUGR fetuses.

Age-dependent association of thyroid function with brain morphology and microstructural organization: evidence from brain imaging.

PubMed

Chaker, Layal; Cremers, Lotte G M; Korevaar, Tim I M; de Groot, Marius; Dehghan, Abbas; Franco, Oscar H; Niessen, Wiro J; Ikram, M Arfan; Peeters, Robin P; Vernooij, Meike W

2018-01-01

Thyroid hormone (TH) is crucial during neurodevelopment, but high levels of TH have been linked to neurodegenerative disorders. No data on the association of thyroid function with brain imaging in the general population are available. We therefore investigated the association of thyroid-stimulating hormone and free thyroxine (FT4) with magnetic resonance imaging (MRI)-derived total intracranial volume, brain tissue volumes, and diffusion tensor imaging measures of white matter microstructure in 4683 dementia- and stroke-free participants (mean age 60.2, range 45.6-89.9 years). Higher FT4 levels were associated with larger total intracranial volumes (β = 6.73 mL, 95% confidence interval = 2.94-9.80). Higher FT4 levels were also associated with larger total brain and white matter volumes in younger individuals, but with smaller total brain and white matter volume in older individuals (p-interaction 0.02). There was a similar interaction by age for the association of FT4 with mean diffusivity on diffusion tensor imaging (p-interaction 0.026). These results are in line with differential effects of TH during neurodevelopmental and neurodegenerative processes and can improve the understanding of the role of thyroid function in neurodegenerative disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Large-scale structural alteration of brain in epileptic children with SCN1A mutation.

PubMed

Lee, Yun-Jeong; Yum, Mi-Sun; Kim, Min-Jee; Shim, Woo-Hyun; Yoon, Hee Mang; Yoo, Il Han; Lee, Jiwon; Lim, Byung Chan; Kim, Ki Joong; Ko, Tae-Sung

2017-01-01

Mutations in SCN1A gene encoding the alpha 1 subunit of the voltage gated sodium channel are associated with several epilepsy syndromes including genetic epilepsy with febrile seizures plus (GEFS +) and severe myoclonic epilepsy of infancy (SMEI). However, in most patients with SCN1A mutation, brain imaging has reported normal or non-specific findings including cerebral or cerebellar atrophy. The aim of this study was to investigate differences in brain morphometry in epileptic children with SCN1A mutation compared to healthy control subjects. We obtained cortical morphology (thickness, and surface area) and brain volume (global, subcortical, and regional) measurements using FreeSurfer (version 5.3.0, https://surfer.nmr.mgh.harvard.edu) and compared measurements of children with epilepsy and SCN1A gene mutation ( n  = 21) with those of age and gender matched healthy controls ( n  = 42). Compared to the healthy control group, children with epilepsy and SCN1A gene mutation exhibited smaller total brain, total gray matter and white matter, cerebellar white matter, and subcortical volumes, as well as mean surface area and mean cortical thickness. A regional analysis revealed significantly reduced gray matter volume in the patient group in the bilateral inferior parietal, left lateral orbitofrontal, left precentral, right postcentral, right isthmus cingulate, right middle temporal area with smaller surface area and white matter volume in some of these areas. However, the regional cortical thickness was not significantly different in two groups. This study showed large-scale developmental brain changes in patients with epilepsy and SCN1A gene mutation, which may be associated with the core symptoms of the patients. Further longitudinal MRI studies with larger cohorts are required to confirm the effect of SCN1A gene mutation on structural brain development.

The Developmental Course of Sleep Disturbances Across Childhood Relates to Brain Morphology at Age 7: The Generation R Study.

PubMed

Kocevska, Desana; Muetzel, Ryan L; Luik, Annemarie I; Luijk, Maartje P C M; Jaddoe, Vincent W; Verhulst, Frank C; White, Tonya; Tiemeier, Henning

2017-01-01

Little is known about the impact of sleep disturbances on the structural properties of the developing brain. This study explored associations between childhood sleep disturbances and brain morphology at 7 years. Mothers from the Generation R cohort reported sleep disturbances in 720 children at ages 2 months, 1.5, 2, 3, and 6 years. T1-weighted Magnetic Resonance Imaging (MRI) images were used to assess brain structure at 7 years. Associations of sleep disturbances at each age and of sleep disturbance trajectories with brain volumes (total brain volume, cortical and subcortical grey matter, white matter) were tested with linear regressions. To assess regional differences, sleep disturbance trajectories were tested as determinants for cortical thickness in whole-brain analyses. Sleep disturbances followed a declining trend from toddlerhood onwards. Infant sleep was not associated with brain morphology at age 7. Per SD sleep disturbances (one frequent symptom or two less frequent symptoms) at 2 and 3 years of age, children had -6.3 (-11.7 to -0.8) cm3 and -6.4 (-11.7 to -1.7) cm3 smaller grey matter volumes, respectively. Sleep disturbances at age 6 years were associated with global brain morphology (grey matter: -7.3 (-12.1 to -2.6), p value = .01). Consistently, trajectory analyses showed that more adverse developmental course of childhood sleep disturbances are associated with smaller grey matter volumes and thinner dorsolateral prefrontal cortex. Sleep disturbances from age 2 years onwards are associated with smaller grey matter volumes. Thinner prefrontal cortex in children with adverse sleep disturbance trajectories may reflect effects of sleep disturbances on brain maturation. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat.

PubMed

Casas, Rafael; Muthusamy, Siva; Wakim, Paul G; Sinharay, Sanhita; Lentz, Margaret R; Reid, William C; Hammoud, Dima A

2018-01-01

HIV infection is known to be associated with brain volume loss, even in optimally treated patients. In this study, we assessed whether dynamic brain volume changes over time are predictive of neurobehavorial performance in the HIV-1 transgenic (Tg) rat, a model of treated HIV-positive patients. Cross-sectional brain MRI imaging was first performed comparing Tg and wild type (WT) rats at 3 and 19 months of age. Longitudinal MRI and neurobehavioral testing of another group of Tg and WT rats was then performed from 5 to 23 weeks of age. Whole brain and subregional image segmentation was used to assess the rate of brain growth over time. We used repeated-measures mixed models to assess differences in brain volumes and to establish how predictive the volume differences are of specific neurobehavioral deficits. Cross-sectional imaging showed smaller whole brain volumes in Tg compared to WT rats at 3 and at 19 months of age. Longitudinally, Tg brain volumes were smaller than age-matched WT rats at all time points, starting as early as 5 weeks of age. The Tg striatal growth rate delay between 5 and 9 weeks of age was greater than that of the whole brain. Striatal volume in combination with genotype was the most predictive of rota-rod scores and in combination with genotype and age was the most predictive of total exploratory activity scores in the Tg rats. The disproportionately delayed striatal growth compared to whole brain between 5 and 9 weeks of age and the role of striatal volume in predicting neurobehavioral deficits suggest an important role of the dopaminergic system in HIV associated neuropathology. This might explain problems with motor coordination and executive decisions in this animal model. Smaller brain and subregional volumes and neurobehavioral deficits were seen as early as 5 weeks of age, suggesting an early brain insult in the Tg rat. Neuroprotective therapy testing in this model should thus target this early stage of development, before brain damage becomes irreversible.

An event-related brain potential study of schizotypal personality and associative semantic processing

PubMed Central

Kiang, Michael; Prugh, Jocelyn; Kutas, Marta

2009-01-01

To examine whether schizotypal personality is associated with the degree to which concepts activate each other in semantic memory, event-related brain potentials (ERPs) were recorded during a delayed lexical decision task from healthy volunteers rated for schizotypy. Each target word was directly, indirectly, or not at all related to a prime word preceding it at a 300- or 750-ms stimulus-onset asynchrony (SOA). Overall, N400 amplitudes were largest for unrelated targets, smallest for directly related targets, and intermediate for indirectly related targets. Higher total Schizotypal Personality Questionnaire (SPQ) scores correlated with smaller N400 indirect priming effects (i.e., smaller N400 amplitude differences between unrelated and indirectly related targets) at both SOAs. In addition, schizotypal subscale scores were differentially associated with N400 effects. Higher SPQ Cognitive-Perceptual scores correlated with smaller N400 direct priming effects (smaller N400 amplitude differences between unrelated and directly related targets) at both SOAs, and with smaller N400 indirect priming effects at the shorter SOA. These correlations are consistent with the hypothesis that decreased use of meaningful context to activate related concepts in general, and/or to inhibit unrelated concepts, may play some role in the development of unusual beliefs. PMID:19818815

Brain composition and olfactory learning in honey bees

PubMed Central

Gronenberg, Wulfila; Couvillon, Margaret J.

2015-01-01

Correlations between brain or brain component size and behavioral measures are frequently studied by comparing different animal species, which sometimes introduces variables that complicate interpretation in terms of brain function. Here, we have analyzed the brain composition of honey bees (Apis mellifera) that have been individually tested in an olfactory learning paradigm. We found that the total brain size correlated with the bees’ learning performance. Among different brain components, only the mushroom body, a structure known to be involved in learning and memory, showed a positive correlation with learning performance. In contrast, visual neuropils were relatively smaller in bees that performed better in the olfactory learning task, suggesting modality-specific behavioral specialization of individual bees. This idea is also supported by inter-individual differences in brain composition. Some slight yet statistically significant differences in the brain composition of European and Africanized honey bees are reported. Larger bees had larger brains, and by comparing brains of different sizes, we report isometric correlations for all brain components except for a small structure, the central body. PMID:20060918

Combined effects of marijuana and nicotine on memory performance and hippocampal volume.

PubMed

Filbey, Francesca M; McQueeny, Tim; Kadamangudi, Shrinath; Bice, Collette; Ketcherside, Ariel

2015-10-15

Combined use of marijuana (MJ) and tobacco is highly prevalent in today's population. Individual use of either substance is linked to structural brain changes and altered cognitive function, especially with consistent reports of hippocampal volume deficits and poorer memory performance. However, the combined effects of MJ and tobacco on hippocampal structure and on learning and memory processes remain unknown. In this study, we examined both the individual and combined effects of MJ and tobacco on hippocampal volumes and memory performance in four groups of adults taken from two larger studies: MJ-only users (n=36), nicotine-only (Nic-only, n=19), combined marijuana and nicotine users (MJ+Nic, n=19) and non-using healthy controls (n=16). Total bilateral hippocampal volumes and memory performance (WMS-III logical memory) were compared across groups controlling for total brain size and recent alcohol use. Results found MJ and MJ+Nic groups had smaller total hippocampal volumes compared to Nic-only and controls. No significant difference between groups was found between immediate and delayed story recall. However, the controls showed a trend for larger hippocampal volumes being associated with better memory scores, while MJ+Nic users showed a unique inversion, whereby smaller hippocampal volume was associated with better memory. Overall, results suggest abnormalities in the brain-behavior relationships underlying memory processes with combined use of marijuana and nicotine use. Further research will need to address these complex interactions between MJ and nicotine. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Association of white matter hyperintensities and gray matter volume with cognition in older individuals without cognitive impairment.

PubMed

Arvanitakis, Zoe; Fleischman, Debra A; Arfanakis, Konstantinos; Leurgans, Sue E; Barnes, Lisa L; Bennett, David A

2016-05-01

Both presence of white matter hyperintensities (WMH) and smaller total gray matter volume on brain magnetic resonance imaging (MRI) are common findings in old age, and contribute to impaired cognition. We tested whether total WMH volume and gray matter volume had independent associations with cognition in community-dwelling individuals without dementia or mild cognitive impairment (MCI). We used data from participants of the Rush Memory and Aging Project. Brain MRI was available in 209 subjects without dementia or MCI (mean age 80; education = 15 years; 74 % women). WMH and gray matter were automatically segmented, and the total WMH and gray matter volumes were measured. Both MRI-derived measures were normalized by the intracranial volume. Cognitive data included composite measures of five different cognitive domains, based on 19 individual tests. Linear regression analyses, adjusted for age, sex, and education, were used to examine the relationship of logarithmically-transformed total WMH volume and of total gray matter volume to cognition. Larger total WMH volumes were associated with lower levels of perceptual speed (p < 0.001), but not with episodic memory, semantic memory, working memory, or visuospatial abilities (all p > 0.10). Smaller total gray matter volumes were associated with lower levels of perceptual speed (p = 0.013) and episodic memory (p = 0.001), but not with the other three cognitive domains (all p > 0.14). Larger total WMH volume was correlated with smaller total gray matter volume (p < 0.001). In a model with both MRI-derived measures included, the relation of WMH to perceptual speed remained significant (p < 0.001), while gray matter volumes were no longer related (p = 0.14). This study of older community-dwelling individuals without overt cognitive impairment suggests that the association of larger total WMH volume with lower perceptual speed is independent of total gray matter volume. These results help elucidate the pathological processes leading to lower cognitive function in aging.

Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children.

PubMed

Lind, Annika; Parkkola, Riitta; Lehtonen, Liisa; Munck, Petriina; Maunu, Jonna; Lapinleimu, Helena; Haataja, Leena

2011-08-01

Altered brain volumes and associations between volumes and developmental outcomes have been reported in prematurely born children. To assess which regional brain volumes are different in very low birth weight (VLBW) children without neurodevelopmental impairments ([NDI] cerebral palsy, hearing loss, blindness and significantly delayed cognitive performance) compared with VLBW children with NDI, and to evaluate the association between regional brain volumes at term-equivalent age and cognitive development and neurological performance at a corrected age of 2 years. The study group consisted of a regional cohort of 164 VLBW children, divided into one group of children without NDI (n = 148) and one group of children with NDI (n = 16). Brain (MRI) was performed at term-equivalent age, from which brain volumes were manually analysed. Cognitive development was assessed with the Bayley Scales of Infant Development II (BSID-II), and neurological performance with the Hammersmith Infant Neurological Examination at the corrected age of 2 years. The volumes of total brain tissue, cerebrum, frontal lobes, basal ganglia and thalami, and cerebellum were significantly smaller, and the volume of the ventricles significantly larger, in the children with NDI than in those without NDI. Even in children without NDI, a smaller cerebellar volume was significantly correlated with poor neurological performance at 2 years of corrected age. Volumetric analysis at brain MRI can provide an additional parameter for early prediction of outcome in VLBW children.

Superior Temporal Gyrus Volume Abnormalities and Thought Disorder in Left-Handed Schizophrenic Men

PubMed Central

Holinger, Dorothy P.; Shenton, Martha E.; Wible, Cynthia G.; Donnino, Robert; Kikinis, Ron; Jolesz, Ferenc A.; McCarley, Robert W.

2010-01-01

Objective Studies of schizophrenia have not clearly defined handedness as a differentiating variable. Moreover, the relationship between thought disorder and anatomical anomalies has not been studied extensively in left-handed schizophrenic men. The twofold purpose of this study was to investigate gray matter volumes in the superior temporal gyrus of the temporal lobe (left and right hemispheres) in left-handed schizophrenic men and left-handed comparison men, in order to determine whether thought disorder in the left-handed schizophrenic men correlated with tissue volume abnormalities. Method Left-handed male patients (N=8) with DSM-III-R diagnoses of schizophrenia were compared with left-handed comparison men (N=10) matched for age, socioeconomic status, and IQ. Magnetic resonance imaging (MRI) with a 1.5-T magnet was used to obtain scans, which consisted of contiguous 1.5-mm slices of the whole brain. MRI analyses (as previously defined by the authors) included the anterior, posterior, and total superior temporal gyrus in both the left and right hemispheres. Results There were three significant findings regarding the left-handed schizophrenic men: 1) bilaterally smaller gray matter volumes in the posterior superior temporal gyrus (16% smaller on the right, 15% smaller on the left); 2) a smaller volume on the right side of the total superior temporal gyrus; and 3) a positive correlation between thought disorder and tissue volume in the right anterior superior temporal gyrus. Conclusions These results suggest that expression of brain pathology differs between left-handed and right-handed schizophrenic men and that the pathology is related to cognitive disturbance. PMID:10553736

How Do the Size, Charge and Shape of Nanoparticles Affect Amyloid β Aggregation on Brain Lipid Bilayer?

NASA Astrophysics Data System (ADS)

Kim, Yuna; Park, Ji-Hyun; Lee, Hyojin; Nam, Jwa-Min

2016-01-01

Here, we studied the effect of the size, shape, and surface charge of Au nanoparticles (AuNPs) on amyloid beta (Aβ) aggregation on a total brain lipid-based supported lipid bilayer (brain SLB), a fluid platform that facilitates Aβ-AuNP aggregation process. We found that larger AuNPs induce large and amorphous aggregates on the brain SLB, whereas smaller AuNPs induce protofibrillar Aβ structures. Positively charged AuNPs were more strongly attracted to Aβ than negatively charged AuNPs, and the stronger interactions between AuNPs and Aβ resulted in fewer β-sheets and more random coil structures. We also compared spherical AuNPs, gold nanorods (AuNRs), and gold nanocubes (AuNCs) to study the effect of nanoparticle shape on Aβ aggregation on the brain SLB. Aβ was preferentially bound to the long axis of AuNRs and fewer fibrils were formed whereas all the facets of AuNCs interacted with Aβ to produce the fibril networks. Finally, it was revealed that different nanostructures induce different cytotoxicity on neuroblastoma cells, and, overall, smaller Aβ aggregates induce higher cytotoxicity. The results offer insight into the roles of NPs and brain SLB in Aβ aggregation on the cell membrane and can facilitate the understanding of Aβ-nanostructure co-aggregation mechanism and tuning Aβ aggregate structures.

Cigarette smoking is associated with amplified age-related volume loss in subcortical brain regions.

PubMed

Durazzo, Timothy C; Meyerhoff, Dieter J; Yoder, Karmen K; Murray, Donna E

2017-08-01

Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure have primarily employed voxel-based morphometry, and the most consistently reported finding was smaller volumes or lower density in anterior frontal regions and the insula. Much less is known about the effects of smoking on subcortical regions. We compared smokers and non-smokers on regional subcortical volumes, and predicted that smokers demonstrate greater age-related volume loss across subcortical regions than non-smokers. Non-smokers (n=43) and smokers (n=40), 22-70 years of age, completed a 4T MRI study. Bilateral total subcortical lobar white matter (WM) and subcortical nuclei volumes were quantitated via FreeSurfer. In smokers, associations between smoking severity measures and subcortical volumes were examined. Smokers demonstrated greater age-related volume loss than non-smokers in the bilateral subcortical lobar WM, thalamus, and cerebellar cortex, as well as in the corpus callosum and subdivisions. In smokers, higher pack-years were associated with smaller volumes of the bilateral amygdala, nucleus accumbens, total corpus callosum and subcortical WM. Results provide novel evidence that chronic smoking in adults is associated with accelerated age-related volume loss in subcortical WM and GM nuclei. Greater cigarette quantity/exposure was related to smaller volumes in regions that also showed greater age-related volume loss in smokers. Findings suggest smoking adversely affected the structural integrity of subcortical brain regions with increasing age and exposure. The greater age-related volume loss in smokers may have implications for cortical-subcortical structural and/or functional connectivity, and response to available smoking cessation interventions. Published by Elsevier B.V.

Learning performance and brain structure of artificially-reared honey bees fed with different quantities of food

PubMed Central

Spaethe, Johannes; Steffan-Dewenter, Ingolf; Härtel, Stephan

2017-01-01

Background Artificial rearing of honey bee larvae is an established method which enables to fully standardize the rearing environment and to manipulate the supplied diet to the brood. However, there are no studies which compare learning performance or neuroanatomic differences of artificially-reared (in-lab) bees in comparison with their in-hive reared counterparts. Methods Here we tested how different quantities of food during larval development affect body size, brain morphology and learning ability of adult honey bees. We used in-lab rearing to be able to manipulate the total quantity of food consumed during larval development. After hatching, a subset of the bees was taken for which we made 3D reconstructions of the brains using confocal laser-scanning microscopy. Learning ability and memory formation of the remaining bees was tested in a differential olfactory conditioning experiment. Finally, we evaluated how bees reared with different quantities of artificial diet compared to in-hive reared bees. Results Thorax and head size of in-lab reared honey bees, when fed the standard diet of 160 µl or less, were slightly smaller than hive bees. The brain structure analyses showed that artificially reared bees had smaller mushroom body (MB) lateral calyces than their in-hive counterparts, independently of the quantity of food they received. However, they showed the same total brain size and the same associative learning ability as in-hive reared bees. In terms of mid-term memory, but not early long-term memory, they performed even better than the in-hive control. Discussion We have demonstrated that bees that are reared artificially (according to the Aupinel protocol) and kept in lab-conditions perform the same or even better than their in-hive sisters in an olfactory conditioning experiment even though their lateral calyces were consistently smaller at emergence. The applied combination of experimental manipulation during the larval phase plus subsequent behavioral and neuro-anatomic analyses is a powerful tool for basic and applied honey bee research. PMID:29085743

Structure of the alexithymic brain: A parametric coordinate-based meta-analysis.

PubMed

Xu, Pengfei; Opmeer, Esther M; van Tol, Marie-José; Goerlich, Katharina S; Aleman, André

2018-04-01

Alexithymia refers to deficiencies in identifying and expressing emotions. This might be related to changes in structural brain volumes, but its neuroanatomical basis remains uncertain as studies have shown heterogeneous findings. Therefore, we conducted a parametric coordinate-based meta-analysis. We identified seventeen structural neuroimaging studies (including a total of 2586 individuals with different levels of alexithymia) investigating the association between gray matter volume and alexithymia. Volumes of the left insula, left amygdala, orbital frontal cortex and striatum were consistently smaller in people with high levels of alexithymia. These areas are important for emotion perception and emotional experience. Smaller volumes in these areas might lead to deficiencies in appropriately identifying and expressing emotions. These findings provide the first quantitative integration of results pertaining to the structural neuroanatomical basis of alexithymia. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effects of Early Life Stress on Depression, Cognitive Performance, and Brain Morphology

PubMed Central

Saleh, Ayman; Potter, Guy G.; McQuoid, Douglas R.; Boyd, Brian; Turner, Rachel; MacFall, James R; Taylor, Warren D.

2016-01-01

Background Childhood early life stress (ELS) increases risk of adulthood Major Depressive Disorder (MDD) and is associated with altered brain structure and function. It is unclear whether specific ELSs affect depression risk, cognitive function and brain structure. Methods This cross-sectional study included 64 antidepressant-free depressed and 65 never depressed individuals. Both groups reported a range of ELSs on the Early Life Stress Questionnaire, completed neuropsychological testing and 3T MRI. Neuropsychological testing assessed domains of episodic memory, working memory, processing speed and executive function. MRI measures included cortical thickness and regional gray matter volumes, with a priori focus on cingulate cortex, orbitofrontal cortex (OFC), amygdala, caudate and hippocampus. Results Of 19 ELSs, only emotional abuse, sexual abuse and severe family conflict independently predicted adulthood MDD diagnosis. The effect of total ELS score differed between groups. Greater ELS exposure was associated with slower processing speed and smaller OFC volumes in depressed subjects, but faster speed and larger volumes in nondepressed subjects. In contrast, exposure to ELSs predictive of depression had similar effects in both diagnostic groups. Individuals reporting predictive ELSs exhibited poorer processing speed and working memory performance, smaller volumes of the lateral OFC and caudate, and decreased cortical thickness in multiple areas including the insula bilaterally. Predictive ELS exposure was also associated with smaller left hippocampal volume in depressed subjects. Conclusion Findings suggest an association between childhood trauma exposure and adulthood cognitive function and brain structure. These relationships appear to differ between individuals who do and do not develop depression. PMID:27682320

Physiological and pathological clinical conditions and light scattering in brain

NASA Astrophysics Data System (ADS)

Kurata, Tsuyoshi; Iwata, Sachiko; Tsuda, Kennosuke; Kinoshita, Masahiro; Saikusa, Mamoru; Hara, Naoko; Oda, Motoki; Ohmae, Etsuko; Araki, Yuko; Sugioka, Takashi; Takashima, Sachio; Iwata, Osuke

2016-08-01

MRI of preterm infants at term commonly reveals subtle brain lesions such as diffuse white matter injury, which are linked with later cognitive impairments. The timing and mechanism of such injury remains unclear. The reduced scattering coefficient of near-infrared light (μs’) has been shown to correlate linearly with gestational age in neonates. To identify clinical variables associated with brain μs’, 60 preterm and full-term infants were studied within 7 days of birth. Dependence of μs’ obtained from the frontal head on clinical variables was assessed. In the univariate analysis, smaller μs’ was associated with antenatal glucocorticoid, emergency Caesarean section, requirement for mechanical ventilation, smaller gestational age, smaller body sizes, low 1- and 5-minute Apgar scores, higher cord blood pH and PO2, and higher blood HCO3- at the time of study. Multivariate analysis revealed that smaller gestational age, requirement for mechanical ventilation, and higher HCO3- at the time of study were correlated with smaller μs’. Brain μs’ depended on variables associated with physiological maturation and pathological conditions of the brain. Further longitudinal studies may help identify pathological events and clinical conditions responsible for subtle brain injury and subsequent cognitive impairments following preterm birth.

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.

Cumulative adversity and smaller gray matter volume in medial prefrontal, anterior cingulate, and insula regions.

PubMed

Ansell, Emily B; Rando, Kenneth; Tuit, Keri; Guarnaccia, Joseph; Sinha, Rajita

2012-07-01

Cumulative adversity and stress are associated with risk of psychiatric disorders. While basic science studies show repeated and chronic stress effects on prefrontal and limbic neurons, human studies examining cumulative stress and effects on brain morphology are rare. Thus, we assessed whether cumulative adversity is associated with differences in gray matter volume, particularly in regions regulating emotion, self-control, and top-down processing in a community sample. One hundred three healthy community participants, aged 18 to 48 and 68% male, completed interview assessment of cumulative adversity and a structural magnetic resonance imaging protocol. Whole-brain voxel-based-morphometry analysis was performed adjusting for age, gender, and total intracranial volume. Cumulative adversity was associated with smaller volume in medial prefrontal cortex (PFC), insular cortex, and subgenual anterior cingulate regions (familywise error corrected, p < .001). Recent stressful life events were associated with smaller volume in two clusters: the medial PFC and the right insula. Life trauma was associated with smaller volume in the medial PFC, anterior cingulate, and subgenual regions. The interaction of greater subjective chronic stress and greater cumulative life events was associated with smaller volume in the orbitofrontal cortex, insula, and anterior and subgenual cingulate regions. Current results demonstrate that increasing cumulative exposure to adverse life events is associated with smaller gray matter volume in key prefrontal and limbic regions involved in stress, emotion and reward regulation, and impulse control. These differences found in community participants may serve to mediate vulnerability to depression, addiction, and other stress-related psychopathology. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Cumulative Adversity and Smaller Gray Matter Volume in Medial Prefrontal, Anterior Cingulate, and Insula Regions

PubMed Central

Ansell, Emily B.; Rando, Kenneth; Tuit, Keri; Guarnaccia, Joseph; Sinha, Rajita

2012-01-01

Background Cumulative adversity and stress are associated with risk of psychiatric disorders. While basic science studies show repeated and chronic stress effects on prefrontal and limbic neurons, human studies examining cumulative stress and effects on brain morphology are rare. Thus, we assessed whether cumulative adversity is associated with differences in gray matter volume, particularly in regions regulating emotion, self-control, and top-down processing in a community sample. Methods One hundred three healthy community participants, aged 18 to 48 and 68% male, completed interview assessment of cumulative adversity and a structural magnetic resonance imaging protocol. Whole-brain voxel-based-morphometry analysis was performed adjusting for age, gender, and total intracranial volume. Results Cumulative adversity was associated with smaller volume in medial prefrontal cortex (PFC), insular cortex, and subgenual anterior cingulate regions (familywise error corrected, p <.001). Recent stressful life events were associated with smaller volume in two clusters: the medial PFC and the right insula. Life trauma was associated with smaller volume in the medial PFC, anterior cingulate, and subgenual regions. The interaction of greater subjective chronic stress and greater cumulative life events was associated with smaller volume in the orbitofrontal cortex, insula, and anterior and subgenual cingulate regions. Conclusions Current results demonstrate that increasing cumulative exposure to adverse life events is associated with smaller gray matter volume in key prefrontal and limbic regions involved in stress, emotion and reward regulation, and impulse control. These differences found in community participants may serve to mediate vulnerability to depression, addiction, and other stress-related psychopathology. PMID:22218286

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

Grey matter correlates of susceptibility to scams in community-dwelling older adults.

PubMed

Duke Han, S; Boyle, Patricia A; Yu, Lei; Arfanakis, Konstantinos; James, Bryan D; Fleischman, Debra A; Bennett, David A

2016-06-01

Susceptibility to scams is a significant issue among older adults, even among those with intact cognition. Age-related changes in brain macrostructure may be associated with susceptibility to scams; however, this has yet to be explored. Based on previous work implicating frontal and temporal lobe functioning as important in decision making, we tested the hypothesis that susceptibility to scams is associated with smaller grey matter volume in frontal and temporal lobe regions in a large community-dwelling cohort of non-demented older adults. Participants (N = 327, mean age = 81.55, mean education = 15.30, 78.9 % female) completed a self-report measure used to assess susceptibility to scams and an MRI brain scan. Results indicated an inverse association between overall grey matter and susceptibility to scams in models adjusted for age, education, and sex; and in models further adjusted for cognitive function. No significant associations were observed for white matter, cerebrospinal fluid, or total brain volume. Models adjusted for age, education, and sex revealed seven clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, left middle temporal, left orbitofrontal, right ventromedial prefrontal, right middle temporal, right precuneus, and right dorsolateral prefrontal regions. In models further adjusted for cognitive function, results revealed three significant clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, right hippocampal, and right middle temporal regions. Lower grey matter concentration in specific brain regions may be associated with susceptibility to scams, even after adjusting for cognitive ability. Future research is needed to determine whether grey matter reductions in these regions may be a biomarker for susceptibility to scams in old age.

Interaction of parenting experiences and brain structure in the prediction of depressive symptoms in adolescents.

PubMed

Yap, Marie B H; Whittle, Sarah; Yücel, Murat; Sheeber, Lisa; Pantelis, Christos; Simmons, Julian G; Allen, Nicholas B

2008-12-01

Although some evidence suggests that neuroanatomic abnormalities may confer risk for major depressive disorder, findings are inconsistent. One potential explanation for this is the moderating role of environmental context, with individuals differing in their biological sensitivity to context. To examine the influence of adverse parenting as an environmental moderator of the association between brain structure and depressive symptoms. Cross-sectional measurement of brain structure, adverse parenting, and depressive symptoms in early adolescents. General community. A total of 106 students aged 11 to 13 years (55 males [51%]), recruited from primary schools in Melbourne, Australia, and their mothers. Selection was based on affective temperament, aimed at producing a sample representing a broad range of risk for major depressive disorder. No participant evidenced current or past case-level depressive, substance use, or eating disorder. (1) Volumetric measures of adolescents' amygdala, hippocampus, and anterior cingulate cortex (ACC); (2) frequency of observed maternal aggressive behavior during a mother-adolescent conflict-resolution interaction; and (3) adolescent depressive symptoms. Boys with smaller right amygdalas reported more depressive symptoms. However, neither hippocampal volume nor asymmetry measures of limbic or paralimbic ACC were directly related to level of depressive symptoms. Importantly, frequency of maternal aggressive behaviors moderated the associations between both the amygdala and ACC, and adolescent symptoms. Particularly, in conditions of low levels of maternal aggressiveness, boys with larger right amygdalas, girls with smaller bilateral amygdalas, and both boys and girls with smaller left paralimbic ACC reported fewer symptoms. These findings help elucidate the complex relationships between brain structure, environmental factors, and depressive symptoms. Further longitudinal research is required to examine how these factors contribute to the onset of case-level disorder, but given that family context risk factors are modifiable, our findings do suggest the potential utility of targeted early parenting interventions.

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

Evidence of Hippocampal Structural Alterations in Gulf War Veterans With Predicted Exposure to the Khamisiyah Plume.

PubMed

Chao, Linda L; Raymond, Morgan R; Leo, Cynthia K; Abadjian, Linda R

2017-10-01

To replicate and expand our previous findings of smaller hippocampal volumes in Gulf War (GW) veterans with predicted exposure to the Khamisiyah plume. Total hippocampal and hippocampal subfield volumes were quantified from 3 Tesla magnetic resonance images in 113 GW veterans, 62 of whom had predicted exposure as per the Department of Defense exposure models. Veterans with predicted exposure had smaller total hippocampal and CA3/dentate gyrus volumes compared with unexposed veterans, even after accounting for potentially confounding genetic and clinical variables. Among veterans with predicted exposure, memory performance was positively correlated with hippocampal volume and negatively correlated with estimated exposure levels and self-reported memory difficulties. These results replicate and extend our previous finding that low-level exposure to chemical nerve agents from the Khamisiyah pit demolition has detrimental, lasting effects on brain structure and function.

New insights into differences in brain organization between Neanderthals and anatomically modern humans

PubMed Central

Pearce, Eiluned; Stringer, Chris; Dunbar, R. I. M.

2013-01-01

Previous research has identified morphological differences between the brains of Neanderthals and anatomically modern humans (AMHs). However, studies using endocasts or the cranium itself are limited to investigating external surface features and the overall size and shape of the brain. A complementary approach uses comparative primate data to estimate the size of internal brain areas. Previous attempts to do this have generally assumed that identical total brain volumes imply identical internal organization. Here, we argue that, in the case of Neanderthals and AMHs, differences in the size of the body and visual system imply differences in organization between the same-sized brains of these two taxa. We show that Neanderthals had significantly larger visual systems than contemporary AMHs (indexed by orbital volume) and that when this, along with their greater body mass, is taken into account, Neanderthals have significantly smaller adjusted endocranial capacities than contemporary AMHs. We discuss possible implications of differing brain organization in terms of social cognition, and consider these in the context of differing abilities to cope with fluctuating resources and cultural maintenance. PMID:23486442

Evolutionary Divergence in Brain Size between Migratory and Resident Birds

PubMed Central

Sol, Daniel; Garcia, Núria; Iwaniuk, Andrew; Davis, Katie; Meade, Andrew; Boyle, W. Alice; Székely, Tamás

2010-01-01

Despite important recent progress in our understanding of brain evolution, controversy remains regarding the evolutionary forces that have driven its enormous diversification in size. Here, we report that in passerine birds, migratory species tend to have brains that are substantially smaller (relative to body size) than those of resident species, confirming and generalizing previous studies. Phylogenetic reconstructions based on Bayesian Markov chain methods suggest an evolutionary scenario in which some large brained tropical passerines that invaded more seasonal regions evolved migratory behavior and migration itself selected for smaller brain size. Selection for smaller brains in migratory birds may arise from the energetic and developmental costs associated with a highly mobile life cycle, a possibility that is supported by a path analysis. Nevertheless, an important fraction (over 68%) of the correlation between brain mass and migratory distance comes from a direct effect of migration on brain size, perhaps reflecting costs associated with cognitive functions that have become less necessary in migratory species. Overall, our results highlight the importance of retrospective analyses in identifying selective pressures that have shaped brain evolution, and indicate that when it comes to the brain, larger is not always better. PMID:20224776

Divergent structural brain abnormalities between different genetic subtypes of children with Prader-Willi syndrome.

PubMed

Lukoshe, Akvile; White, Tonya; Schmidt, Marcus N; van der Lugt, Aad; Hokken-Koelega, Anita C

2013-10-22

Prader-Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical focal analyses. High resolution structural magnetic resonance images were acquired in 20 children with genetically confirmed PWS (11 children carrying a deletion (DEL), 9 children with maternal uniparental disomy (mUPD)), and compared with 11 age- and gender-matched typically developing siblings as controls. Brain morphology measures were obtained using the FreeSurfer software suite. Both children with DEL and mUPD showed smaller brainstem volume, and a trend towards smaller cortical surface area and white matter volume. Children with mUPD had enlarged lateral ventricles and larger cortical cerebrospinal fluid (CSF) volume. Further, a trend towards increased cortical thickness was found in children with mUPD. Children with DEL had a smaller cerebellum, and smaller cortical and subcortical grey matter volumes. Focal analyses revealed smaller white matter volumes in left superior and bilateral inferior frontal gyri, right cingulate cortex, and bilateral precuneus areas associated with the default mode network (DMN) in children with mUPD. Children with PWS show signs of impaired brain growth. Those with mUPD show signs of early brain atrophy. In contrast, children with DEL show signs of fundamentally arrested, although not deviant brain development and presented few signs of cortical atrophy. Our results of global brain measurements suggest divergent neurodevelopmental patterns in children with DEL and mUPD.

Divergent structural brain abnormalities between different genetic subtypes of children with Prader–Willi syndrome

PubMed Central

2013-01-01

Background Prader–Willi syndrome (PWS) is a complex neurogenetic disorder with symptoms that indicate not only hypothalamic, but also a global, central nervous system (CNS) dysfunction. However, little is known about developmental differences in brain structure in children with PWS. Thus, our aim was to investigate global brain morphology in children with PWS, including the comparison between different genetic subtypes of PWS. In addition, we performed exploratory cortical and subcortical focal analyses. Methods High resolution structural magnetic resonance images were acquired in 20 children with genetically confirmed PWS (11 children carrying a deletion (DEL), 9 children with maternal uniparental disomy (mUPD)), and compared with 11 age- and gender-matched typically developing siblings as controls. Brain morphology measures were obtained using the FreeSurfer software suite. Results Both children with DEL and mUPD showed smaller brainstem volume, and a trend towards smaller cortical surface area and white matter volume. Children with mUPD had enlarged lateral ventricles and larger cortical cerebrospinal fluid (CSF) volume. Further, a trend towards increased cortical thickness was found in children with mUPD. Children with DEL had a smaller cerebellum, and smaller cortical and subcortical grey matter volumes. Focal analyses revealed smaller white matter volumes in left superior and bilateral inferior frontal gyri, right cingulate cortex, and bilateral precuneus areas associated with the default mode network (DMN) in children with mUPD. Conclusions Children with PWS show signs of impaired brain growth. Those with mUPD show signs of early brain atrophy. In contrast, children with DEL show signs of fundamentally arrested, although not deviant brain development and presented few signs of cortical atrophy. Our results of global brain measurements suggest divergent neurodevelopmental patterns in children with DEL and mUPD. PMID:24144356

Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group.

PubMed

Rentería, M E; Schmaal, L; Hibar, D P; Couvy-Duchesne, B; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Gillespie, N A; Hatton, S N; Lagopoulos, J; Veltman, D J; van der Wee, N; van Erp, T G M; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Godlewska, B R; Cowen, P J; Penninx, B W J H; Jahanshad, N; Thompson, P M; Wright, M J; Martin, N G; Christensen, H; Hickie, I B

2017-05-02

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10 -3 ) or a 2.87% smaller volume compared with controls (Cohen's d=-0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28-0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.

Structural MRI correlates of apathy symptoms in older persons without dementia

PubMed Central

Grool, Anne M.; Geerlings, Mirjam I.; Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Jonsson, Palmi V.; Garcia, Melissa E.; Siggeirsdottir, Kristin; Harris, Tamara B.; Sigmundsson, Thordur; Gudnason, Vilmundur

2014-01-01

Objective: We aimed to investigate the relation between apathy symptoms and structural brain changes on MRI, including white matter lesions (WMLs) and atrophy, in a large cohort of older persons. Methods: Cross-sectional analyses are based on 4,354 persons without dementia (aged 76 ± 5 years) participating in the population-based Age, Gene/Environment Susceptibility–Reykjavik Study. Apathy symptoms were assessed with 3 items from the 15-item Geriatric Depression Scale. Brain volumes and total WML volume were estimated on 1.5-tesla MRI using an automated segmentation program; regional WML load was calculated using a semiquantitative scale. Regression analyses were adjusted for age, sex, education, intracranial volume, vascular risk factors, physical activity, brain infarcts, depressive symptoms, antidepressants, and cognitive status. Results: Compared to those with <2 apathy symptoms, participants with ≥2 apathy symptoms (49% of the cohort) had significantly smaller gray matter volumes (mean adjusted difference −3.6 mL, 95% confidence interval [CI] −6.2 to −1.0), particularly in the frontal and temporal lobes; smaller white matter volumes (mean adjusted difference −1.9 mL, 95% CI −3.6 to −0.3), mainly in the parietal lobe; and smaller thalamus volumes. They were also more likely to have WMLs in the frontal lobe (adjusted odds ratio = 1.08, 95% CI 0.9–1.3). Excluding participants with a depression diagnosis did not change the associations. Conclusions: In this older population without dementia, apathy symptoms are associated with a more diffuse loss of both gray and white matter volumes, independent of depression. PMID:24739783

When larger brains do not have more neurons: increased numbers of cells are compensated by decreased average cell size across mouse individuals

PubMed Central

Herculano-Houzel, Suzana; Messeder, Débora J.; Fonseca-Azevedo, Karina; Pantoja, Nilma A.

2015-01-01

There is a strong trend toward increased brain size in mammalian evolution, with larger brains composed of more and larger neurons than smaller brains across species within each mammalian order. Does the evolution of increased numbers of brain neurons, and thus larger brain size, occur simply through the selection of individuals with more and larger neurons, and thus larger brains, within a population? That is, do individuals with larger brains also have more, and larger, neurons than individuals with smaller brains, such that allometric relationships across species are simply an extension of intraspecific scaling? Here we show that this is not the case across adult male mice of a similar age. Rather, increased numbers of neurons across individuals are accompanied by increased numbers of other cells and smaller average cell size of both types, in a trade-off that explains how increased brain mass does not necessarily ensue. Fundamental regulatory mechanisms thus must exist that tie numbers of neurons to numbers of other cells and to average cell size within individual brains. Finally, our results indicate that changes in brain size in evolution are not an extension of individual variation in numbers of neurons, but rather occur through step changes that must simultaneously increase numbers of neurons and cause cell size to increase, rather than decrease. PMID:26082686

When larger brains do not have more neurons: increased numbers of cells are compensated by decreased average cell size across mouse individuals.

PubMed

Herculano-Houzel, Suzana; Messeder, Débora J; Fonseca-Azevedo, Karina; Pantoja, Nilma A

2015-01-01

There is a strong trend toward increased brain size in mammalian evolution, with larger brains composed of more and larger neurons than smaller brains across species within each mammalian order. Does the evolution of increased numbers of brain neurons, and thus larger brain size, occur simply through the selection of individuals with more and larger neurons, and thus larger brains, within a population? That is, do individuals with larger brains also have more, and larger, neurons than individuals with smaller brains, such that allometric relationships across species are simply an extension of intraspecific scaling? Here we show that this is not the case across adult male mice of a similar age. Rather, increased numbers of neurons across individuals are accompanied by increased numbers of other cells and smaller average cell size of both types, in a trade-off that explains how increased brain mass does not necessarily ensue. Fundamental regulatory mechanisms thus must exist that tie numbers of neurons to numbers of other cells and to average cell size within individual brains. Finally, our results indicate that changes in brain size in evolution are not an extension of individual variation in numbers of neurons, but rather occur through step changes that must simultaneously increase numbers of neurons and cause cell size to increase, rather than decrease.

Reduced Gray Matter Volume Is Associated With Poorer Instrumental Activities of Daily Living Performance in Heart Failure.

PubMed

Alosco, Michael L; Brickman, Adam M; Spitznagel, Mary Beth; Narkhede, Atul; Griffith, Erica Y; Cohen, Ronald; Sweet, Lawrence H; Josephson, Richard; Hughes, Joel; Gunstad, John

2016-01-01

Heart failure patients require assistance with instrumental activities of daily living in part because of the high rates of cognitive impairment in this population. Structural brain insult (eg, reduced gray matter volume) is theorized to underlie cognitive dysfunction in heart failure, although no study has examined the association among gray matter, cognition, and instrumental activities of daily living in heart failure. The aim of this study was to investigate the associations among gray matter volume, cognitive function, and functional ability in heart failure. A total of 81 heart failure patients completed a cognitive test battery and the Lawton-Brody self-report questionnaire to assess instrumental activities of daily living. Participants underwent magnetic resonance imaging to quantify total gray matter and subcortical gray matter volume. Impairments in instrumental activities of daily living were common in this sample of HF patients. Regression analyses controlling for demographic and medical confounders showed that smaller total gray matter volume predicted decreased scores on the instrumental activities of daily living composite, with specific associations noted for medication management and independence in driving. Interaction analyses showed that reduced total gray matter volume interacted with worse attention/executive function and memory to negatively impact instrumental activities of daily living. Smaller gray matter volume is associated with greater impairment in instrumental activities of daily living in persons with heart failure, possibly via cognitive dysfunction. Prospective studies are needed to clarify the utility of clinical correlates of gray matter volume (eg, cognitive dysfunction) in identifying heart failure patients at risk for functional decline and determine whether interventions that target improved brain and cognitive function can preserve functional independence in this high-risk population.

Dermatoglyphics in relation to brain volumes in twins concordant and discordant for bipolar disorder.

PubMed

Vonk, R; van der Schot, A C; van Baal, G C M; van Oel, C J; Nolen, W A; Kahn, R S

2014-12-01

Palmar and finger dermatoglyphics are formed between the 10th and the 17th weeks of gestation and their morphology can be influenced by genetic or environmental factors, interfering with normal intrauterine development. As both the skin and the brain develop from the same embryonal ectoderm, dermatoglyphic alterations may be informative for early abnormal neurodevelopmental processes in the brain. We investigated whether dermatoglyphic alterations are related to structural brain abnormalities in bipolar disorder and to what extent they are of a genetic and of an environmental origin. Dermatoglyphics and volumetric data from structural MRI were obtained in 53 twin pairs concordant or discordant for bipolar disorder and 51 healthy matched control twin pairs. Structural equation modeling was used. Bipolar disorder was significantly positively associated with palmar a-b ridge count (ABRC), indicating higher ABRC in bipolar patients (rph=.17 (CI .04-.30)). Common genes appear to be involved because the genetic correlation with ABRC was significant (rph-A=.21 (CI .05-.36). Irrespective of disease, ABRC showed a genetically mediated association with brain volume, indicated by a significant genetic correlation rph-A of respectively -.36 (CI -.52 to -.22) for total brain, -.34 (CI -.51 to -.16) total cortical volume, -.27 (CI -.43 to -.08) cortical gray matter and -.23 (CI -.41 to -.04) cortical white matter. In conclusion, a genetically determined abnormal development of the foetal ectoderm between the 10th and 15th week of gestation appears related to smaller brain volumes in (subjects at risk for) bipolar disorder. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Post-traumatic stress symptoms correlate with smaller subgenual cingulate, caudate, and insula volumes in unmedicated combat veterans.

PubMed

Herringa, Ryan; Phillips, Mary; Almeida, Jorge; Insana, Salvatore; Germain, Anne

2012-01-01

Prior studies have examined differences in brain volume between patients with post-traumatic stress disorder (PTSD) and control subjects. Convergent findings include smaller hippocampus and medial prefrontal cortex volumes in PTSD. However, post-traumatic stress symptoms (PTSS) exist on a spectrum, and neural changes may occur beyond the diagnostic threshold of PTSD. We examined the relationship between PTSS and gray matter among combat-exposed U.S. military veterans. Structural brain magnetic resonance imaging (MRI) was obtained on 28 combat veterans from Operations Enduring and Iraqi Freedom. PTSS were assessed using the Clinician-Administered PTSD Scale (CAPS). Thirteen subjects met criteria for PTSD. Subjects were unmedicated, and free of major comorbid psychiatric disorders. Images were analyzed using voxel-based morphometry, and regressed against the total CAPS score and trauma load. Images were subsequently analyzed by diagnosis of PTSD vs. non-PTSD. CAPS scores were inversely correlated with volumes of the subgenual cingulate (sgACC), caudate, hypothalamus, insula, and left middle temporal gyrus (MTG). Group contrast revealed smaller sgACC, caudate, hypothalamus, left insula, left MTG, and right MFG in the PTSD group. PTSS are associated with abnormalities in limbic structures that may underlie the pathophysiology of PTSD. These abnormalities exist on a continuum with PTSS, beyond a diagnosis of PTSD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Neuroanatomical correlates of Klinefelter syndrome studied in relation to the neuropsychological profile☆

PubMed Central

Skakkebæk, Anne; Gravholt, Claus Højbjerg; Rasmussen, Peter Mondrup; Bojesen, Anders; Jensen, Jens Søndergaard; Fedder, Jens; Laurberg, Peter; Hertz, Jens Michael; Østergaard, John Rosendahl; Pedersen, Anders Degn; Wallentin, Mikkel

2013-01-01

Brain imaging in Klinefelter syndrome (47, XXY) (KS), a genetic disorder characterized by the presence of an extra X chromosome, may contribute to understanding the relationship between gene expression, brain structure, and subsequent cognitive disabilities and psychiatric disorders. We conducted the largest to date voxel-based morphometry study of 65 KS subjects and 65 controls matched for age and education and correlated these data to neuropsychological test scores. The KS patients had significantly smaller total brain volume (TBV), total gray matter volume (GMV) and total white matter volume (WMV) compared to controls, whereas no volumetric difference in cerebral spinal fluid (CSF) was found. There were no differences in TBV, GMV, WMV or CSF between testosterone treated KS (T-KS) and untreated KS (U-KS) patients. Compared to controls, KS patients had significantly decreased GMV bilaterally in insula, putamen, caudate, hippocampus, amygdala, temporal pole and frontal inferior orbita. Additionally, the right parahippocampal region and cerebellar volumes were reduced in KS patients. KS patients had significantly larger volumes in right postcentral gyrus, precuneus and parietal regions. Multivariate classification analysis discriminated KS patients from controls with 96.9% (p < 0.001) accuracy. Regression analyses, however, revealed no significant association between GMV differences and cognitive and psychological factors within the KS patients and controls or the groups combined. These results show that although gene dosage effect of having and extra X-chromosome may lead to large scale alterations of brain morphometry and extended cognitive disabilities no simple correspondence links these measures. PMID:24266006

Subcellular localization and compartmentation of thiamine derivatives in rat brain.

PubMed

Bettendorff, L; Wins, P; Lesourd, M

1994-05-26

The subcellular distribution of thiamine derivatives in rat brain was studied. Thiamine diphosphate content was highest in the mitochondrial and synaptosomal fractions, and lowest in microsomal, myelin and cytosolic fractions. Only 3-5% of total thiamine diphosphate was bound to transketolase, a cytosolic enzyme. Thiamine triphosphate was barely detectable in the microsomal and cytosolic fraction, but synaptosomes were slightly enriched in this compound compared to the crude homogenate. Both myelin and mitochondrial fractions contained significant amounts of thiamine triphosphate. In order to estimate the relative turnover rates of these compounds, the animals received an intraperitoneal injection of either [14C]thiamine or [14C]sulbutiamine (isobutyrylthiamine disulfide) 1 h before decapitation. The specific radioactivities of thiamine compounds found in the brain decreased in the order: thiamine > thiamine triphosphate > thiamine monophosphate > thiamine diphosphate. Incorporation of radioactivity into thiamine triphosphate was more marked with [14C]sulbutiamine than with [14C]thiamine. The highest specific radioactivity of thiamine diphosphate was found in the cytosolic fraction of the brain, though this pool represents less than 10% of total thiamine diphosphate. Cytosolic thiamine diphosphate had a twice higher specific radioactivity when [14C]sulbutiamine was used as precursor compared with thiamine though no significant differences were found in the other cellular compartments. Our results suggest the existence of two thiamine diphosphate pools: the bound cofactor pool is essentially mitochondrial and has a low turnover; a much smaller cytosolic pool (6-7% of total TDP) of high turnover is the likely precursor of thiamine triphosphate.

Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group

PubMed Central

Rentería, M E; Schmaal, L; Hibar, D P; Couvy-Duchesne, B; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Gillespie, N A; Hatton, S N; Lagopoulos, J; Veltman, D J; van der Wee, N; van Erp, T G M; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Godlewska, B R; Cowen, P J; Penninx, B W J H; Jahanshad, N; Thompson, P M; Wright, M J; Martin, N G; Christensen, H; Hickie, I B

2017-01-01

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10−3) or a 2.87% smaller volume compared with controls (Cohen’s d=−0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28–0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments. PMID:28463239

[The synaptic proteins of the temporal associative area in the neocortex (field Ep) of cats with normal and decreased cognitive capacities].

PubMed

Zakharova (Orlova), E I; Mukhin, E I

1994-01-01

Fractions of light and heavy synaptosomes were prepared from associative temporal area of cat brain, which were previously tested behaviorally for ability to solve the generalization, gnostic and abstraction tasks. The synaptic membrane subfractions and synaptoplasma fractions were isolated and the content of the total protein and of the demasked protein sulfhydryl groups (SH groups) was investigated spectrophotometrically. The maximal content of the demasked SH groups was revealed in the upper subfractions (mainly the membranes of cholinergic synapses) and minimal content--in the lower subfractions (mainly noncholinergic synapses). Significantly smaller total protein content in the upper and middle subfractions of light synaptosomes was found, and more demasked SH groups in the membrane-bound proteins of the upper and middle subfractions of light and heavy synaptosomes was found in the cortex area of the "clever" then "silly" cats. Suggestion concerning characteristic for brains of "clever" cats relatively low total quantity of synapses in the area Ep of the cortex and significantly higher proportion of cholinergic ones is discussed.

Monozygotic Twins with Asperger Syndrome: Differences in Behaviour Reflect Variations in Brain Structure and Function

ERIC Educational Resources Information Center

Belmonte, Matthew K.; Carper, Ruth A.

2006-01-01

A pair of monozygotic twins discordant for symptoms of Asperger syndrome was evaluated at the age of 13.45 years using psychometric, morphometric, behavioural, and functional imaging methods. The lower-functioning twin had a smaller brain overall, a smaller right cerebellum, and a disproportionately large left frontal lobe, and manifested almost…

Language and Brain Volumes in Children with Epilepsy

PubMed Central

Caplan, Rochelle; Levitt, Jennifer; Siddarth, Prabha; Wu, Keng Nei; Gurbani, Suresh; Shields, W. Donald; Sankar, Raman

2010-01-01

This study compared the relationship of language skill with fronto-temporal volumes in 69 medically treated epilepsy subjects and 34 healthy children, aged 6.1-16.6 years. It also determined if the patients with linguistic deficits had abnormal volumes and atypical associations between volumes and language skills in these brain regions. The children underwent language testing and magnetic resonance imaging scans at 1.5 Tesla. Brain tissue was segmented and fronto-temporal volumes were computed. Higher mean language scores were significantly associated with larger inferior frontal gyrus, temporal lobe, and posterior superior temporal gyrus gray matter volumes in the epilepsy group and in the children with epilepsy with average language scores. Increased total brain and dorsolateral prefrontal gray and white matter volumes, however, were associated with higher language scores in the healthy controls. Within the epilepsy group, linguistic deficits were related to smaller anterior superior temporal gyrus gray matter volumes and a negative association between language scores and dorsolateral prefrontal gray matter volumes. These findings demonstrate abnormal development of language related brain regions, and imply differential reorganization of brain regions subserving language in children with epilepsy with normal linguistic skills and in those with impaired language. PMID:20149755

Higher fasting plasma glucose is associated with smaller striatal volume and poorer fine motor skills in a longitudinal cohort.

PubMed

Zhang, Tianqi; Shaw, Marnie E; Walsh, Erin I; Sachdev, Perminder S; Anstey, Kaarin J; Cherbuin, Nicolas

2018-06-07

Previous studies have demonstrated associations between higher blood glucose and brain atrophy and functional deficits, however, little is known about the association between blood glucose, striatal volume and striatal function despite sensori-motor deficits being reported in diabetes. This study investigated the relationship between blood glucose levels, striatal volume and fine motor skills in a longitudinal cohort of cognitively healthy individuals living in the community with normal or impaired fasting glucose or type 2 diabetes. Participants were 271 cognitively healthy individuals (mean age 63 years at inclusion) with normal fasting glucose levels (<5.6 mmol/L) (n=173), impaired fasting glucose (5.6-6.9 mmol/L) (n=57), or with type 2 diabetes (≥7.0 mmol/L) (n=41). Fasting glucose, Purdue Pegboard scores as measurement of fine motor skills, and brain scans were collected at wave 1, 2 and 4, over a total follow-up of twelve years. Striatal volumes were measured using FreeSurfer after controlling for age, sex and intracranial volume. Results showed that type 2 diabetes was associated with smaller right putamen volume and lower Purdue Pegboard scores after controlling for age, sex and intracranial volume. These findings add to the evidence suggesting that higher blood glucose levels, especially type 2 diabetes, may impair brain structure and function. Copyright © 2018. Published by Elsevier B.V.

Preliminary evidence for obesity and elevations in fasting insulin mediating associations between cortisol awakening response and hippocampal volumes and frontal atrophy.

PubMed

Ursache, Alexandra; Wedin, William; Tirsi, Aziz; Convit, Antonio

2012-08-01

Recent studies have demonstrated alterations in the cortisol awakening response (CAR) and brain abnormalities in adults with obesity and type 2 diabetes mellitus (T2DM). While adolescents with T2DM exhibit similar brain abnormalities, less is known about whether brain impairments and hypothalamic-pituitary-adrenal (HPA) axis abnormalities are already present in adolescents with pre-diabetic conditions such as insulin resistance (IR). This study included 33 adolescents with IR and 20 without IR. Adolescents with IR had a blunted CAR, smaller hippocampal volumes, and greater frontal lobe atrophy compared to controls. Mediation analyses indicated pathways whereby a smaller CAR was associated with higher BMI which was in turn associated with fasting insulin levels, which in turn was related to smaller hippocampal volume and greater frontal lobe atrophy. While we had hypothesized that HPA dysregulation may result from brain abnormalities, our findings suggest that HPA dysregulation may also impact brain structures through associations with metabolic abnormalities. Copyright © 2012 Elsevier Ltd. All rights reserved.

Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity.

PubMed

Paul, Robert H; Phillips, Sarah; Hoare, Jacqueline; Laidlaw, David H; Cabeen, Ryan; Olbricht, Gayla R; Su, Yuqing; Stein, Dan J; Engelbrecht, Susan; Seedat, Soraya; Salminen, Lauren E; Baker, Laurie M; Heaps, Jodi; Joska, John

2017-04-01

Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV- controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Volumes were determined for the caudate, putamen, thalamus, corpus callosum, total gray matter, and total white matter. DTI metrics included fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Tracts of interest included the anterior thalamic radiation (ATR), cingulum bundle (CING), uncinate fasciculus (UNC), and corpus callosum (CC). HIV+ individuals exhibited smaller volumes in subcortical gray matter, total gray matter and total white matter compared to HIV- controls. HIV+ individuals also exhibited DTI abnormalities across multiple tracts compared to HIV- controls. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status.

Sex dependence of brain size and shape in bipolar disorder: an exploratory study.

PubMed

Mackay, Clare E; Roddick, Elina; Barrick, Thomas R; Lloyd, Adrian J; Roberts, Neil; Crow, Tim J; Young, Allan H; Ferrier, I Nicol

2010-05-01

Anomalies of asymmetry and sex differences in brain structure have frequently been described in schizophrenic illnesses but have seldom been explored in bipolar disorder. We measured volumes of the left and right frontal, temporal, parietal, and occipital lobes and computed the magnitude of brain torque (i.e., rightward frontal and leftward occipital asymmetry) for 49 patients with bipolar disorder and 47 healthy controls and performed an exploratory analysis of sex differences in patients and controls. Patients had significantly greater cerebrospinal fluid volume than controls, but no difference in total brain volume. There were no main effects of diagnosis in gray matter lobe volume or brain torque, but when analyses were performed separately for male and female subjects, significant sex-by-diagnosis interactions were found in the volume of the left frontal, left temporal, right parietal, and right occipital lobes, such that male patients with bipolar disorder tend toward larger, more symmetric brains than male controls, whereas female patients tend toward smaller, more asymmetric brains than female controls. The lateralised nature of these interactions was such that the normal sex difference in volume was significantly accentuated, whilst the normal sex difference in asymmetry tended to be diminished in patients with bipolar disorder. We conclude that bipolar disorder in part reflects an interaction between brain growth and sex along the anterior-posterior axis of the human brain.

Sexually dimorphic subcortical brain volumes in emerging psychosis.

PubMed

Egloff, Laura; Lenz, Claudia; Studerus, Erich; Harrisberger, Fabienne; Smieskova, Renata; Schmidt, André; Huber, Christian; Simon, Andor; Lang, Undine E; Riecher-Rössler, Anita; Borgwardt, Stefan

2018-03-28

In schizophrenic psychoses, the normal sexual dimorphism of the brain has been shown to be disrupted or even reversed. Little is known, however, at what time point in emerging psychosis this occurs. We have therefore examined, if these alterations are already present in the at-risk mental state (ARMS) for psychosis and in first episode psychosis (FEP) patients. Data from 65 ARMS (48 (73.8%) male; age=25.1±6.32) and 50 FEP (37 (74%) male; age=27±6.56) patients were compared to those of 70 healthy controls (HC; 27 (38.6%) male; age=26±4.97). Structural T1-weighted images were acquired using a 3 Tesla magnetic resonance imaging (MRI) scanner. Linear mixed effects models were used to investigate whether subcortical brain volumes are dependent on sex. We found men to have larger total brain volumes (p<0.001), and smaller bilateral caudate (p=0.008) and hippocampus volume (p<0.001) than women across all three groups. Older subjects had more GM and WM volume than younger subjects. No significant sex×group interaction was found. In emerging psychosis there still seem to exist patterns of normal sexual dimorphism in total brain and caudate volume. The only structure affected by reversed sexual dimorphism was the hippocampus, with women showing larger volumes than men even in HC. Thus, we conclude that subcortical volumes may not be primarily affected by disrupted sexual dimorphism in emerging psychosis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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.

Complex oligosaccharides are N-linked to Kv3 voltage-gated K+ channels in rat brain.

PubMed

Cartwright, Tara A; Corey, Melissa J; Schwalbe, Ruth A

2007-04-01

Neuronal Kv3 voltage-gated K(+) channels have two absolutely conserved N-glycosylation sites. Here, it is shown that Kv3.1, 3.3, and 3.4 channels are N-glycosylated in rat brain. Digestion of total brain membranes with peptide N glycosidase F (PNGase F) produced faster migrating immunobands than those of undigested membranes. Additionally, partial PNGase F digests showed that both sites are occupied by oligosaccharides. Neuraminidase treatment produced a smaller immunoband shift relative to PNGase F treatment. These results indicate that both sites are highly available and occupied by N-linked oligosaccharides for Kv3.1, 3.3, and 3.4 in rat brain, and furthermore that at least one oligosaccharide is of complex type. Additionally, these results point to an extracytoplasmic S1-S2 linker in Kv3 proteins expressed in native membranes. We suggest that N-glycosylation processing of Kv3 channels is critical for the expression of K(+) currents at the surface of neurons, and perhaps contributes to the pathophysiology of congenital disorders of glycosylation.

Region-specific reduction in brain volume in young adults with perinatal hypoxic-ischaemic encephalopathy.

PubMed

Bregant, Tina; Rados, Milan; Vasung, Lana; Derganc, Metka; Evans, Alan C; Neubauer, David; Kostovic, Ivica

2013-11-01

A severe form of perinatal hypoxic-ischaemic encephalopathy (HIE) carries a high risk of perinatal death and severe neurological sequelae while in mild HIE only discrete cognitive disorders may occur. To compare total brain volumes and region-specific cortical measurements between young adults with mild-moderate perinatal HIE and a healthy control group of the same age. MR imaging was performed in a cohort of 14 young adults (9 males, 5 females) with a history of mild or moderate perinatal HIE. The control group consisted of healthy participants, matched with HIE group by age and gender. Volumetric analysis was done after the processing of MR images using a fully automated CIVET pipeline. We measured gyrification indexes, total brain volume, volume of grey and white matter, and of cerebrospinal fluid. We also measured volume, thickness and area of the cerebral cortex in the parietal, occipital, frontal, and temporal lobe, and of the isthmus cinguli, parahippocampal and cingulated gyrus, and insula. The HIE patient group showed smaller absolute volumetric data. Statistically significant (p < 0.05) reductions of gyrification index in the right hemisphere, of cortical areas in the right temporal lobe and parahippocampal gyrus, of cortical volumes in the right temporal lobe and of cortical thickness in the right isthmus of the cingulate gyrus were found. Comparison between the healthy group and the HIE group of the same gender showed statistically significant changes in the male HIE patients, where a significant reduction was found in whole brain volume; left parietal, bilateral temporal, and right parahippocampal gyrus cortical areas; and bilateral temporal lobe cortical volume. Our analysis of total brain volumes and region-specific corticometric parameters suggests that mild-moderate forms of perinatal HIE lead to reductions in whole brain volumes. In the study reductions were most pronounced in temporal lobe and parahippocampal gyrus. Copyright © 2013 European Paediatric Neurology Society. All rights reserved.

Sex differences in metabolic aging of the brain: insights into female susceptibility to Alzheimer's disease.

PubMed

Zhao, Liqin; Mao, Zisu; Woody, Sarah K; Brinton, Roberta D

2016-06-01

Despite recent advances in the understanding of clinical aspects of sex differences in Alzheimer's disease (AD), the underlying mechanisms, for instance, how sex modifies AD risk and why the female brain is more susceptible to AD, are not clear. The purpose of this study is to elucidate sex disparities in brain aging profiles focusing on 2 major areas-energy and amyloid metabolism-that are most significantly affected in preclinical development of AD. Total RNA isolated from hippocampal tissues of both female and male 129/C57BL/6 mice at ages of 6, 9, 12, or 15 months were comparatively analyzed by custom-designed Taqman low-density arrays for quantitative real-time polymerase chain reaction detection of a total of 182 genes involved in a broad spectrum of biological processes modulating energy production and amyloid homeostasis. Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains. In female brains, 44.2% of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation. In contrast, in male brains, only 5.4% of genes were significantly altered at this age transition. Subsequent changes in female brains were at a much smaller magnitude, including 10.9% from 9 months to 12 months and 6.1% from 12 months to 15 months. In male brains, most changes occurred from 12 months to 15 months and the majority were upregulated. Furthermore, gene network analysis revealed that clusterin appeared to serve as a link between the overall decreased bioenergetic metabolism and increased amyloid dyshomeostasis associated with the earliest transition in female brains. Together, results from this study indicate that: (1) female and male brains follow profoundly dissimilar trajectories as they age; (2) female brains undergo age-related changes much earlier than male brains; (3) early changes in female brains signal the onset of a hypometabolic phenotype at risk for AD. These findings provide a mechanistic rationale for female susceptibility to AD and suggest a potential window of opportunity for AD prevention and risk reduction in women. Copyright © 2016 Elsevier Inc. All rights reserved.

Validity and Normative Data for the Biber Figure Learning Test: A Visual Supraspan Memory Measure.

PubMed

Gifford, Katherine A; Liu, Dandan; Neal, Jacquelyn E; Acosta, Lealani Mae Y; Bell, Susan P; Wiggins, Margaret E; Wisniewski, Kristi M; Godfrey, Mary; Logan, Laura A; Hohman, Timothy J; Pechman, Kimberly R; Libon, David J; Blennow, Kaj; Zetterberg, Henrik; Jefferson, Angela L

2018-05-01

The Biber Figure Learning Test (BFLT), a visuospatial serial figure learning test, was evaluated for biological correlates and psychometric properties, and normative data were generated. Nondemented individuals ( n = 332, 73 ± 7, 41% female) from the Vanderbilt Memory & Aging Project completed a comprehensive neuropsychological protocol. Adjusted regression models related BFLT indices to structural brain magnetic resonance imaging and cerebrospinal fluid (CSF) markers of brain health. Regression-based normative data were generated. Lower BFLT performances (Total Learning, Delayed Recall, Recognition) related to smaller medial temporal lobe volumes and higher CSF tau concentrations but not CSF amyloid. BFLT indices were most strongly correlated with other measures of verbal and nonverbal memory and visuospatial skills. The BFLT provides a comprehensive assessment of all aspects of visuospatial learning and memory and is sensitive to biomarkers of unhealthy brain aging. Enhanced normative data enriches the clinical utility of this visual serial figure learning test for use with older adults.

Simulation of hydrocephalus condition in infant head

NASA Astrophysics Data System (ADS)

Wijayanti, Erna; Arif, Idam

2014-03-01

Hydrocephalus is a condition of an excessive of cerebrospinal fluid in brain. In this paper, we try to simulate the behavior of hydrocephalus conditions in infant head by using a hydro-elastic model which is combined with orthotropic elastic skull and with the addition of suture that divide the skull into two lobes. The model then gives predictions for the case of stenosis aqueduct by varying the cerebral aqueduct diameter, time constant and brain elastic modulus. The hydrocephalus condition which is shown by the significant value of ventricle displacement, as the result shows, is occurred when the aqueduct is as resistant as brain parenchyma for the flow of cerebrospinal fluid. The decrement of brain elastic modulus causes brain parenchyma displacement value approach ventricle displacement value. The smaller of time constant value causes the smaller value of ventricle displacement.

High-dose estrogen treatment at reperfusion reduces lesion volume and accelerates recovery of sensorimotor function after experimental ischemic stroke.

PubMed

Carpenter, Randall S; Iwuchukwu, Ifeanyi; Hinkson, Cyrus L; Reitz, Sydney; Lee, Wonhee; Kukino, Ayaka; Zhang, An; Pike, Martin M; Ardelt, Agnieszka A

2016-05-15

Estrogens have previously been shown to protect the brain against acute ischemic insults, by potentially augmenting cerebrovascular function after ischemic stroke. The current study hypothesized that treatment with sustained release of high-dose 17β-estradiol (E2) at the time of reperfusion from middle cerebral artery occlusion (MCAO) in rats would attenuate reperfusion injury, augment post-stroke angiogenesis and cerebral blood flow, and attenuate lesion volume. Female Wistar rats underwent ovariectomy, followed two weeks later by transient, two-hour right MCAO (tMCAO) and treatment with E2 (n=13) or placebo (P; n=12) pellets starting at reperfusion. E2 treatment resulted in significantly smaller total lesion volume, smaller lesions within striatal and cortical brain regions, and less atrophy of the ipsilateral hemisphere after six weeks of recovery. E2-treated animals exhibited accelerated recovery of contralateral forelimb sensorimotor function in the cylinder test. Magnetic resonance imaging (MRI) showed that E2 treatment reduced the formation of lesion cysts, decreased lesion volume, and increased lesional cerebral blood flow (CBF). K(trans), a measure of vascular permeability, was increased in the lesions. This finding, which represents lesion neovascularization, was not altered by E2 treatment. Ischemic stroke-related angiogenesis and vessel formation was confirmed with immunolabeling of brain tissue and was not altered with E2 treatment. In summary, E2 treatment administered immediately following reperfusion significantly reduced lesion size, cyst formation, and brain atrophy while improving lesional CBF and accelerating recovery of functional deficits in a rat model of ischemic stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms

PubMed Central

Rojas, Donald C; Peterson, Eric; Winterrowd, Erin; Reite, Martin L; Rogers, Sally J; Tregellas, Jason R

2006-01-01

Background Although differences in brain anatomy in autism have been difficult to replicate using manual tracing methods, automated whole brain analyses have begun to find consistent differences in regions of the brain associated with the social cognitive processes that are often impaired in autism. We attempted to replicate these whole brain studies and to correlate regional volume changes with several autism symptom measures. Methods We performed MRI scans on 24 individuals diagnosed with DSM-IV autistic disorder and compared those to scans from 23 healthy comparison subjects matched on age. All participants were male. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM). Results Controlling for age and total gray matter volume, the volumes of the medial frontal gyri, left pre-central gyrus, right post-central gyrus, right fusiform gyrus, caudate nuclei and the left hippocampus were larger in the autism group relative to controls. Regions exhibiting smaller volumes in the autism group were observed exclusively in the cerebellum. Significant partial correlations were found between the volumes of the caudate nuclei, multiple frontal and temporal regions, the cerebellum and a measure of repetitive behaviors, controlling for total gray matter volume. Social and communication deficits in autism were also associated with caudate, cerebellar, and precuneus volumes, as well as with frontal and temporal lobe regional volumes. Conclusion Gray matter enlargement was observed in areas that have been functionally identified as important in social-cognitive processes, such as the medial frontal gyri, sensorimotor cortex and middle temporal gyrus. Additionally, we have shown that VBM is sensitive to associations between social and repetitive behaviors and regional brain volumes in autism. PMID:17166273

Trajectories of Early Brain Volume Development in Fragile X and Autism RH: Trajectory of Brain Volume in Fragile X

PubMed Central

Hazlett, Heather Cody; Poe, Michele D.; Lightbody, Amy A.; Styner, Martin; MacFall, James R.; Reiss, Allan L.; Piven, Joseph

2012-01-01

Objective To examine patterns of early brain growth in young children with fragile X syndrome (FXS) compared to a comparison group (controls) and a group with idiopathic autism. Method The study included 53 boys between 18–42 months of age with FXS, 68 boys with idiopathic autism (ASD), and a comparison group of 50 typically-developing and developmentally-delayed controls. We examined structural brain volumes using magnetic resonance imaging (MRI) across two timepoints between ages 2–3 and 4–5 years and examined total brain volumes and regional (lobar) tissue volumes. Additionally, we studied a selected group of subcortical structures implicated in the behavioral features of FXS (e.g., basal ganglia, hippocampus, amygdala). Results Children with FXS had greater global brain volumes compared to controls, but were not different than children with idiopathic autism, and the rate of brain growth between ages 2 and 5 paralleled that seen in controls. In contrast to the children with idiopathic autism who had generalized cortical lobe enlargement, the children with FXS showed a specific enlargement in temporal lobe white matter, cerebellar gray matter, and caudate nucleus, but significantly smaller amygdala. Conclusions This structural longitudinal MRI study of preschoolers with FXS observed generalized brain overgrowth in FXS compared to controls, evident at age 2 and maintained across ages 4–5. We also find different patterns of brain growth that distinguishes boys with FXS from children with idiopathic autism. PMID:22917205

Gray matter maturation and cognition in children with different APOE ε genotypes.

PubMed

Chang, Linda; Douet, Vanessa; Bloss, Cinnamon; Lee, Kristin; Pritchett, Alexandra; Jernigan, Terry L; Akshoomoff, Natacha; Murray, Sarah S; Frazier, Jean; Kennedy, David N; Amaral, David G; Gruen, Jeffrey; Kaufmann, Walter E; Casey, B J; Sowell, Elizabeth; Ernst, Thomas

2016-08-09

The aims of the current study were to determine whether children with the 6 different APOE ε genotypes show differences in gray matter maturation, particularly for those with ε4 and ε2 alleles, which are associated with poorer outcomes in many neurologic disorders. A total of 1,187 healthy children (aged 3-20 years, 52.1% boys, 47.9% girls) with acceptable data from the cross-sectional Pediatric Imaging Neurocognition and Genetics Study were evaluated for the effects of 6 APOE ε genotypes on macroscopic and microscopic cortical and subcortical gray matter structures (measured with 3-tesla MRI and FreeSurfer for automated morphometry) and on cognition (NIH Toolbox). Among APOE ε4 carriers, age-related changes in brain structures and cognition varied depending on genotype, with the smallest hippocampi in ε2ε4 children, the lowest hippocampal fractional anisotropy in younger ε4ε4 children, the largest medial orbitofrontal cortical areas in ε3ε4 children, and age-dependent thinning of the entorhinal cortex in ε4ε4 children. Younger ε4ε4 children had the lowest scores on executive function and working memory, while younger ε2ε4 children performed worse on attention tasks. Larger parietal gyri in the younger ε2ε4 children, and thinner temporal and cingulate isthmus cortices or smaller hippocampi in the younger ε4ε4 children, predicted poorer performance on attention or working memory. Our findings validated and extended prior smaller studies that showed altered brain development in APOE ε4-carrier children. The ε4ε4 and ε2ε4 genotypes may negatively influence brain development and brain aging at the extremes of age. Studying APOE ε polymorphisms in young children may provide the earliest indicators for individuals who might benefit from early interventions or preventive measures for future brain injuries and dementia. © 2016 American Academy of Neurology.

Mosaic evolution and adaptive brain component alteration under domestication seen on the background of evolutionary theory.

PubMed

Rehkämper, Gerd; Frahm, Heiko D; Cnotka, Julia

2008-01-01

Brain sizes and brain component sizes of five domesticated pigeon breeds including homing (racing) pigeons are compared with rock doves (Columba livia) based on an allometric approach to test the influence of domestication on brain and brain component size. Net brain volume, the volumes of cerebellum and telencephalon as a whole are significantly smaller in almost all domestic pigeons. Inside the telencephalon, mesopallium, nidopallium (+ entopallium + arcopallium) and septum are smaller as well. The hippocampus is significantly larger, particularly in homing pigeons. This finding is in contrast to the predictions of the 'regression hypothesis' of brain alteration under domestication. Among the domestic pigeons homing pigeons have significantly larger olfactory bulbs. These data are interpreted as representing a functional adaptation to homing that is based on spatial cognition and sensory integration. We argue that domestication as seen in domestic pigeons is not principally different from evolution in the wild, but represents a heuristic model to understand the evolutionary process in terms of adaptation and optimization. Copyright 2007 S. Karger AG, Basel.

Head circumference, atrophy, and cognition: implications for brain reserve in Alzheimer disease.

PubMed

Perneczky, R; Wagenpfeil, S; Lunetta, K L; Cupples, L A; Green, R C; Decarli, C; Farrer, L A; Kurz, A

2010-07-13

Clinical and epidemiologic studies suggest that patients with Alzheimer disease (AD) with larger head circumference have better cognitive performance at the same level of brain pathology than subjects with smaller head circumference. A total of 270 patients with AD participating in the Multi-Institutional Research in Alzheimer's Genetic Epidemiology (MIRAGE) study underwent cognitive testing, APOE genotyping, and MRI of the brain in a cross-sectional study. Linear regression analysis was used to examine the association between cerebral atrophy, as a proxy for AD pathology, and level of cognitive function, adjusting for age, duration of AD symptoms, gender, head circumference, APOE genotype, diabetes mellitus, hypertension, major depression, and ethnicity. An interaction term between atrophy and head circumference was introduced to explore if head circumference modified the association between cerebral atrophy and cognition. There was a significant inverse association between atrophy and cognitive function, and a significant interaction between atrophy and head circumference. With greater levels of atrophy, cognition was higher for individuals with greater head circumference. This study suggests that larger head circumference is associated with less cognitive impairment in the face of cerebral atrophy. This finding supports the notion that head circumference (and presumably brain size) offers protection against AD symptoms through enhanced brain reserve.

A Simple and Efficient Methodology To Improve Geometric Accuracy in Gamma Knife Radiation Surgery: Implementation in Multiple Brain Metastases

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

Karaiskos, Pantelis, E-mail: pkaraisk@med.uoa.gr; Gamma Knife Department, Hygeia Hospital, Athens; Moutsatsos, Argyris

Purpose: To propose, verify, and implement a simple and efficient methodology for the improvement of total geometric accuracy in multiple brain metastases gamma knife (GK) radiation surgery. Methods and Materials: The proposed methodology exploits the directional dependence of magnetic resonance imaging (MRI)-related spatial distortions stemming from background field inhomogeneities, also known as sequence-dependent distortions, with respect to the read-gradient polarity during MRI acquisition. First, an extra MRI pulse sequence is acquired with the same imaging parameters as those used for routine patient imaging, aside from a reversal in the read-gradient polarity. Then, “average” image data are compounded from data acquiredmore » from the 2 MRI sequences and are used for treatment planning purposes. The method was applied and verified in a polymer gel phantom irradiated with multiple shots in an extended region of the GK stereotactic space. Its clinical impact in dose delivery accuracy was assessed in 15 patients with a total of 96 relatively small (<2 cm) metastases treated with GK radiation surgery. Results: Phantom study results showed that use of average MR images eliminates the effect of sequence-dependent distortions, leading to a total spatial uncertainty of less than 0.3 mm, attributed mainly to gradient nonlinearities. In brain metastases patients, non-eliminated sequence-dependent distortions lead to target localization uncertainties of up to 1.3 mm (mean: 0.51 ± 0.37 mm) with respect to the corresponding target locations in the “average” MRI series. Due to these uncertainties, a considerable underdosage (5%-32% of the prescription dose) was found in 33% of the studied targets. Conclusions: The proposed methodology is simple and straightforward in its implementation. Regarding multiple brain metastases applications, the suggested approach may substantially improve total GK dose delivery accuracy in smaller, outlying targets.« less

Understanding heterogeneity in grey matter research of adults with childhood maltreatment-A meta-analysis and review.

PubMed

Paquola, Casey; Bennett, Maxwell R; Lagopoulos, Jim

2016-10-01

Childhood trauma has been associated with long term effects on prefrontal-limbic grey matter. A literature search was conducted to identify structural magnetic resonance imaging studies of adults with a history of childhood trauma. We performed three meta-analyses. Hedges' g effect sizes were calculated for each study providing hippocampal or amygdala volumes of trauma and non-trauma groups. Seed based differential mapping was utilised to synthesise whole brain voxel based morphometry (VBM) studies. A total of 38 articles (17 hippocampus, 13 amygdala, 19 whole brain VBM) were included in the meta-analyses. Trauma cohorts exhibited smaller hippocampus and amygdala volumes bilaterally. The most robust findings of the whole brain VBM meta-analysis were reduced grey matter in the right dorsolateral prefrontal cortex and right hippocampus amongst adults with a history of childhood trauma. Subgroup analyses and meta-regressions showed results were moderated by age, gender, the cohort's psychiatric health and the study's definition of childhood trauma. We provide evidence of abnormal grey matter in prefrontal-limbic brain regions of adults with a history of childhood maltreatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sex Differences in Intelligence and Brain Size: A Developmental Theory.

ERIC Educational Resources Information Center

Lynn, Richard

1999-01-01

Proposes a developmental theory of sex differences in intelligence that states that the faster maturation and brain size growth in girls up to age 15 compensates for their smaller brain size so that sex differences in intelligence are very small. Discusses evidence that supports this theory. (SLD)

Regional growth and atlasing of the developing human brain

PubMed Central

Makropoulos, Antonios; Aljabar, Paul; Wright, Robert; Hüning, Britta; Merchant, Nazakat; Arichi, Tomoki; Tusor, Nora; Hajnal, Joseph V.; Edwards, A. David; Counsell, Serena J.; Rueckert, Daniel

2016-01-01

Detailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45 weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area. PMID:26499811

Regional growth and atlasing of the developing human brain.

PubMed

Makropoulos, Antonios; Aljabar, Paul; Wright, Robert; Hüning, Britta; Merchant, Nazakat; Arichi, Tomoki; Tusor, Nora; Hajnal, Joseph V; Edwards, A David; Counsell, Serena J; Rueckert, Daniel

2016-01-15

Detailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Estimates of plasma, packed cell and total blood volume in tissues of the rainbow trout (Salmo gairdneri)

USGS Publications Warehouse

Gingerich, W.H.; Pityer, R.A.; Rach, J.J.

1987-01-01

1. Total blood volume and relative blood volumes in selected tissues were determined in non-anesthetized, confined rainbow trout by using 51Cr-labelled trout erythrocytes as a vascular space marker.2. Mean total blood volume was estimated to be 4.09 ± 0.55 ml/100 g, or about 75% of that estimated with the commonly used plasma space marker Evans blue dye.3. Relative tissue blood volumes were greatest in highly perfused tissues such as kidney, gills, brain and liver and least in mosaic muscle.4. Estimates of tissue vascular spaces, made using radiolabelled erythrocytes, were only 25–50% of those based on plasma space markers.5. The consistently smaller vascular volumes obtained with labelled erythrocytes could be explained by assuming that commonly used plasma space markers diffuse from the vascular compartment.

Associations Between Left Ventricular Dysfunction and Brain Structure and Function: Findings From the SABRE (Southall and Brent Revisited) Study.

PubMed

Park, Chloe M; Williams, Emily D; Chaturvedi, Nish; Tillin, Therese; Stewart, Robert J; Richards, Marcus; Shibata, Dean; Mayet, Jamil; Hughes, Alun D

2017-04-18

Subclinical left ventricular (LV) dysfunction has been inconsistently associated with early cognitive impairment, and mechanistic pathways have been poorly considered. We investigated the cross-sectional relationship between LV dysfunction and structural/functional measures of the brain and explored the role of potential mechanisms. A total of 1338 individuals (69±6 years) from the Southall and Brent Revisited study underwent echocardiography for systolic (tissue Doppler imaging peak systolic wave) and diastolic (left atrial diameter) assessment. Cognitive function was assessed and total and hippocampal brain volumes were measured by magnetic resonance imaging. Global LV function was assessed by circulating N-terminal pro-brain natriuretic peptide. The role of potential mechanistic pathways of arterial stiffness, atherosclerosis, microvascular disease, and inflammation were explored. After adjusting for age, sex, and ethnicity, lower systolic function was associated with lower total brain (beta±standard error, 14.9±3.2 cm 3 ; P <0.0001) and hippocampal volumes (0.05±0.02 cm 3 , P =0.01). Reduced diastolic function was associated with poorer working memory (-0.21±0.07, P =0.004) and fluency scores (-0.18±0.08, P =0.02). Reduced global LV function was associated with smaller hippocampal volume (-0.10±0.03 cm 3 , P =0.004) and adverse visual memory (-0.076±0.03, P =0.02) and processing speed (0.063±0.02, P =0.006) scores. Separate adjustment for concomitant cardiovascular risk factors attenuated associations with hippocampal volume and fluency only. Further adjustment for the alternative pathways of microvascular disease or arterial stiffness attenuated the relationship between global LV function and visual memory. In a community-based sample of older people, measures of LV function were associated with structural/functional measures of the brain. These associations were not wholly explained by concomitant risk factors or potential mechanistic pathways. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Predator-driven brain size evolution in natural populations of Trinidadian killifish (Rivulus hartii)

PubMed Central

Walsh, Matthew R.; Broyles, Whitnee; Beston, Shannon M.; Munch, Stephan B.

2016-01-01

Vertebrates exhibit extensive variation in relative brain size. It has long been assumed that this variation is the product of ecologically driven natural selection. Yet, despite more than 100 years of research, the ecological conditions that select for changes in brain size are unclear. Recent laboratory selection experiments showed that selection for larger brains is associated with increased survival in risky environments. Such results lead to the prediction that increased predation should favour increased brain size. Work on natural populations, however, foreshadows the opposite trajectory of evolution; increased predation favours increased boldness, slower learning, and may thereby select for a smaller brain. We tested the influence of predator-induced mortality on brain size evolution by quantifying brain size variation in a Trinidadian killifish, Rivulus hartii, from communities that differ in predation intensity. We observed strong genetic differences in male (but not female) brain size between fish communities; second generation laboratory-reared males from sites with predators exhibited smaller brains than Rivulus from sites in which they are the only fish present. Such trends oppose the results of recent laboratory selection experiments and are not explained by trade-offs with other components of fitness. Our results suggest that increased male brain size is favoured in less risky environments because of the fitness benefits associated with faster rates of learning and problem-solving behaviour. PMID:27412278

Higher Intelligence Is Associated with Less Task-Related Brain Network Reconfiguration

PubMed Central

Cole, Michael W.

2016-01-01

The human brain is able to exceed modern computers on multiple computational demands (e.g., language, planning) using a small fraction of the energy. The mystery of how the brain can be so efficient is compounded by recent evidence that all brain regions are constantly active as they interact in so-called resting-state networks (RSNs). To investigate the brain's ability to process complex cognitive demands efficiently, we compared functional connectivity (FC) during rest and multiple highly distinct tasks. We found previously that RSNs are present during a wide variety of tasks and that tasks only minimally modify FC patterns throughout the brain. Here, we tested the hypothesis that, although subtle, these task-evoked FC updates from rest nonetheless contribute strongly to behavioral performance. One might expect that larger changes in FC reflect optimization of networks for the task at hand, improving behavioral performance. Alternatively, smaller changes in FC could reflect optimization for efficient (i.e., small) network updates, reducing processing demands to improve behavioral performance. We found across three task domains that high-performing individuals exhibited more efficient brain connectivity updates in the form of smaller changes in functional network architecture between rest and task. These smaller changes suggest that individuals with an optimized intrinsic network configuration for domain-general task performance experience more efficient network updates generally. Confirming this, network update efficiency correlated with general intelligence. The brain's reconfiguration efficiency therefore appears to be a key feature contributing to both its network dynamics and general cognitive ability. SIGNIFICANCE STATEMENT The brain's network configuration varies based on current task demands. For example, functional brain connections are organized in one way when one is resting quietly but in another way if one is asked to make a decision. We found that the efficiency of these updates in brain network organization is positively related to general intelligence, the ability to perform a wide variety of cognitively challenging tasks well. Specifically, we found that brain network configuration at rest was already closer to a wide variety of task configurations in intelligent individuals. This suggests that the ability to modify network connectivity efficiently when task demands change is a hallmark of high intelligence. PMID:27535904

Perinatal choline deficiency delays brain development and alters metabolite concentrations in the young pig.

PubMed

Mudd, Austin T; Getty, Caitlyn M; Sutton, Brad P; Dilger, Ryan N

2016-12-01

Adequate choline supply during the perinatal period is critical for proper brain formation, when robust neurogenesis and neuronal maturation occur. Therefore, the objective of this study was to examine the impact of perinatal choline status on neurodevelopment. Sows were fed a choline-deficient (CD) or choline-sufficient (CS) diet during the last half of the gestational period. At 2 days of age, piglets from sows within each prenatal treatment group were further stratified into postnatal treatment groups and provided either a CD or CS milk replacer, resulting in four treatment groups. At 30 days of age, piglets underwent magnetic resonance imaging (MRI) procedures to analyze structural and metabolite differences. Single-voxel spectroscopy (SVS) analysis revealed postnatally CS piglets had higher (P < 0.001) concentrations of glycerophosphocholine-phosphocholine than postnatally CD piglets. Volumetric analysis indicated smaller (P < 0.006) total brain volumes in prenatally CD piglets compared with prenatally CS piglets. Differences (P < 0.05) in the corpus callosum, pons, midbrain, thalamus, and right hippocampus, were observed as larger region-specific volumes proportional to total brain size in prenatally CD piglets compared with CS piglets. Diffusion tensor imaging (DTI) suggested interactions (P < 0.05) between prenatal and postnatal choline status in fractional anisotropy values of the thalamus and right hippocampus. Prenatally CS piglets had lower cerebellar radial diffusivity (P = 0.045) compared with prenatally CD piglets. This study demonstrates that prenatal choline deficiency has profound effects by delaying neurodevelopment as evidenced by structural and metabolic MRI assessments.

Smoking and Cerebral Oxidative Stress and Air Pollution: A Dreadful Equation with Particulate Matter Involved and One More Powerful Reason Not to Smoke Anything!

PubMed

Calderón-Garcidueñas, Lilian

2016-07-22

Smoking has serious health effects. Cigarettes, including tobacco, marijuana, and electronic nicotine delivery systems are very effective ways to inhale harmful amounts of fine and ultrafine particulate matter. Does size matter? Yes, indeed! The smaller the particle you inhale, the higher the ability to produce reactive oxygen species and to readily access the brain. In this issue of the Journal of Alzheimer's Disease, Durazzo provides evidence of an association between active cigarette tobacco smoking in cognitively-normal elders and increased cerebral oxidative stress, while in actively smoking Alzheimer's disease (AD) patients, the association was also seen with smaller left and total hippocampal volumes. This paper has highly relevant results of interest across the US and the world because millions of people are active smokers and they have other genetic and environmental risk factors that could play a key role in the development/worsening of brain oxidative stress and neurodegeneration. Smoking basically anything producing aerosols with particulate matter in the fine and ultrafine size range is detrimental to your brain. Marijuana and e-cigarette use has grown steadily among adolescents and young adults. Smoking-related cerebral oxidative stress is a potential mechanism promoting AD pathology and increased risk for AD. Current knowledge also relates fine and ultrafine particles exposures influencing neurodevelopmental processes in utero. The results from Durazzo et al. should be put in a broader context, a context that includes evaluating the oxidative stress of nano-aerosols associated with cigarette emissions and their synergistic effects with air pollution exposures. AD is expected to increase in the US threefold by the year 2050, and some of these future AD patients are smoking and vaping right now. Understanding the impact of everyday exposures to long-term harmful consequences for brain health is imperative.

Distribution of ciprofloxacin into the central nervous system in rats with acute renal or hepatic failure.

PubMed

Naora, K; Ichikawa, N; Hirano, H; Iwamoto, K

1999-05-01

Pharmacokinetic changes of various drugs have been reported in renal or hepatic failure. The present study employed ciprofloxacin, a quinolone antibiotic having neurotoxic side effects, to assess the influence of these diseases on distribution of ciprofloxacin into the central nervous system (CNS). After intravenous dosing of ciprofloxacin (10-30 mg kg(-1)), ciprofloxacin levels in plasma and brain were measured in normal rats (Wistar, male, 10-week-old) and those with acute renal and hepatic injuries which were induced by uranyl nitrate and carbon tetrachloride (CCl4), respectively. In the uranyl nitrate-treated rats, the plasma elimination half-life of ciprofloxacin was prolonged and the total body clearance was reduced when compared with those in the normal rats. Similar but smaller changes were observed in the CCl4-treated group. Brain levels of ciprofloxacin were significantly increased by both uranyl nitrate and CCl4 treatments. A proportional correlation between serum unbound levels and brain levels of ciprofloxacin was observed in the normal group. However, brain-to-serum unbound concentration ratios of ciprofloxacin were reduced in the rats with renal or hepatic failure. These results suggest that renal failure as well as hepatic failure retards elimination of ciprofloxacin from the blood, leading to elevation of the CNS level, and also that ciprofloxacin distribution in the brain is reduced in these disease states.

Insular dwarfism in hippos and a model for brain size reduction in Homo floresiensis.

PubMed

Weston, Eleanor M; Lister, Adrian M

2009-05-07

Body size reduction in mammals is usually associated with only moderate brain size reduction, because the brain and sensory organs complete their growth before the rest of the body during ontogeny. On this basis, 'phyletic dwarfs' are predicted to have a greater relative brain size than 'phyletic giants'. However, this trend has been questioned in the special case of dwarfism of mammals on islands. Here we show that the endocranial capacities of extinct dwarf species of hippopotamus from Madagascar are up to 30% smaller than those of a mainland African ancestor scaled to equivalent body mass. These results show that brain size reduction is much greater than predicted from an intraspecific 'late ontogenetic' model of dwarfism in which brain size scales to body size with an exponent of 0.35. The nature of the proportional change or grade shift observed here indicates that selective pressures on brain size are potentially independent of those on body size. This study demonstrates empirically that it is mechanistically possible for dwarf mammals on islands to evolve significantly smaller brains than would be predicted from a model of dwarfing based on the intraspecific scaling of the mainland ancestor. Our findings challenge current understanding of brain-body allometric relationships in mammals and suggest that the process of dwarfism could in principle explain small brain size, a factor relevant to the interpretation of the small-brained hominin found on the Island of Flores, Indonesia.

Insular dwarfism in hippos and a model for brain size reduction in Homo floresiensis

PubMed Central

Weston, Eleanor M.; Lister, Adrian M.

2009-01-01

Body size reduction in mammals is usually associated with only moderate brain size reduction as the brain and sensory organs complete their growth before the rest of the body during ontogeny1,2. On this basis “phyletic dwarfs” are predicted to have a higher relative brain size than “phyletic giants”1,3. This trend has been questioned, however, in the special case of dwarfism of mammals on islands4. Here we show that the endocranial capacities of extinct dwarf species of hippopotamus from Madagascar are up to 30% smaller than those of a mainland African ancestor scaled to equivalent body mass. These results show brain size reduction is much greater than predicted from an intraspecific ‘late ontogenetic’ model of dwarfism where brain size scales to body size with an exponent of 0.35. The nature of the proportional change or grade shift2,5 observed here indicates that selective pressures upon brain size are potentially independent from those on body size. This study demonstrates empirically that it is mechanistically possible for dwarf mammals on islands to evolve significantly smaller brains than would be predicted from a model of dwarfing based on the intraspecific scaling of the mainland ancestor. Our findings challenge our understanding of brain-body allometric relationships in mammals and suggest that the process of dwarfism could in principle explain small brain size, a factor relevant to the interpretation of the small-brained hominin found on the Island of Flores, Indonesia6. PMID:19424156

Brain morphology in older African Americans, Caribbean Hispanics, and whites from northern Manhattan.

PubMed

Brickman, Adam M; Schupf, Nicole; Manly, Jennifer J; Luchsinger, José A; Andrews, Howard; Tang, Ming X; Reitz, Christiane; Small, Scott A; Mayeux, Richard; DeCarli, Charles; Brown, Truman R

2008-08-01

Aging is accompanied by a decrease in brain volume and by an increase in cerebrovascular disease. To examine the effects of age, sex, race/ethnicity, and vascular disease history on measures of brain morphology, including relative brain volume, ventricular volume, hippocampus and entorhinal cortex volumes, and white matter hyperintensity (WMH) burden, in a large community-based cohort of racially/ethnically diverse older adults without dementia. The associations of age, sex, race/ethnicity, and self-reported vascular disease history with brain morphology were examined in a cross-sectional study using multiple linear regression analyses. Sex x race/ethnicity interactions were also considered. The Washington Heights-Inwood Columbia Aging Project, a community-based epidemiological study of older adults from 3 racial/ethnic groups (white, Hispanic, and African American) from northern Manhattan. Beginning in 2003, high-resolution quantitative magnetic resonance (MR) images were acquired in 769 participants without dementia. Relative brain volume (total brain volume/intracranial volume), ventricular volume, and hippocampus and entorhinal cortex volumes were derived manually on high-resolution MR images. White matter hyperintensities were quantified semiautomatically on fluid-attenuated inversion recovery-T2-weighted MR images. Older age was associated with decreased relative brain volume and with increased ventricular and WMH volumes. Hispanic and African American participants had larger relative brain volumes and more severe WMH burden than white participants, but the associations of these variables with age were similar across racial/ethnic groups. Compared with men, women had larger relative brain volumes. Vascular disease was associated with smaller relative brain volume and with higher WMH burden, particularly among African Americans. Older age and vascular disease, particularly among African Americans, are associated with increased brain atrophy and WMH burden. African American and Hispanic subjects have larger relative brain volumes and more WMH than white subjects. Racial/ethnic group differences in WMH severity seem to be partially attributable to differences in vascular disease. Future work will focus on the determinants and cognitive correlates of these differences.

Virtual endocasts of Eocene Paramys (Paramyinae): oldest endocranial record for Rodentia and early brain evolution in Euarchontoglires.

PubMed

Bertrand, Ornella C; Amador-Mughal, Farrah; Silcox, Mary T

2016-01-27

Understanding the pattern of brain evolution in early rodents is central to reconstructing the ancestral condition for Glires, and for other members of Euarchontoglires including Primates. We describe the oldest virtual endocasts known for fossil rodents, which pertain to Paramys copei (Early Eocene) and Paramys delicatus (Middle Eocene). Both specimens of Paramys have larger olfactory bulbs and smaller paraflocculi relative to total endocranial volume than later occurring rodents, which may be primitive traits for Rodentia. The encephalization quotients (EQs) of Pa. copei and Pa. delicatus are higher than that of later occurring (Oligocene) Ischyromys typus, which contradicts the hypothesis that EQ increases through time in all mammalian orders. However, both species of Paramys have a lower relative neocortical surface area than later rodents, suggesting neocorticalization occurred through time in this Order, although to a lesser degree than in Primates. Paramys has a higher EQ but a lower neocortical ratio than any stem primate. This result contrasts with the idea that primates were always exceptional in their degree of overall encephalization and shows that relative brain size and neocortical surface area do not necessarily covary through time. As such, these data contradict assumptions made about the pattern of brain evolution in Euarchontoglires. © 2016 The Author(s).

Virtual endocasts of Eocene Paramys (Paramyinae): oldest endocranial record for Rodentia and early brain evolution in Euarchontoglires

PubMed Central

Amador-Mughal, Farrah

2016-01-01

Understanding the pattern of brain evolution in early rodents is central to reconstructing the ancestral condition for Glires, and for other members of Euarchontoglires including Primates. We describe the oldest virtual endocasts known for fossil rodents, which pertain to Paramys copei (Early Eocene) and Paramys delicatus (Middle Eocene). Both specimens of Paramys have larger olfactory bulbs and smaller paraflocculi relative to total endocranial volume than later occurring rodents, which may be primitive traits for Rodentia. The encephalization quotients (EQs) of Pa. copei and Pa. delicatus are higher than that of later occurring (Oligocene) Ischyromys typus, which contradicts the hypothesis that EQ increases through time in all mammalian orders. However, both species of Paramys have a lower relative neocortical surface area than later rodents, suggesting neocorticalization occurred through time in this Order, although to a lesser degree than in Primates. Paramys has a higher EQ but a lower neocortical ratio than any stem primate. This result contrasts with the idea that primates were always exceptional in their degree of overall encephalization and shows that relative brain size and neocortical surface area do not necessarily covary through time. As such, these data contradict assumptions made about the pattern of brain evolution in Euarchontoglires. PMID:26817776

Frontal and temporal volumes in Childhood Absence Epilepsy.

PubMed

Caplan, Rochelle; Levitt, Jennifer; Siddarth, Prabha; Wu, Keng Nei; Gurbani, Suresh; Sankar, Raman; Shields, W Donald

2009-11-01

This study compared frontotemporal brain volumes in children with childhood absence epilepsy (CAE) to age- and gender-matched children without epilepsy. It also examined the association of these volumes with seizure, demographic, perinatal, intelligence quotient (IQ), and psychopathology variables. Twenty-six children with CAE, aged 7.5-11.8 years, and 37 children without epilepsy underwent brain magnetic resonance imaging (MRI) scans at 1.5 Tesla. Tissue was segmented, and total brain, frontal lobe, frontal parcellations, and temporal lobe volumes were computed. All children had IQ testing and structured psychiatric interviews. Parents provided seizure, perinatal, and behavioral information on each child. The CAE group had significantly smaller gray matter volumes of the left orbital frontal gyrus as well as both left and right temporal lobes compared to the age- and gender-matched children without epilepsy. In the CAE group these volumes were related to age, gender, ethnicity, and pregnancy complications but not to seizure, IQ, and psychopathology variables. In the group of children without epilepsy, however, the volumes were related to IQ. These findings suggest that CAE impacts brain development in regions implicated in behavior, cognition, and language. In addition to supporting the cortical focus theory of CAE, these findings also imply that CAE is not a benign disorder.

Association of brain metabolism with sulcation and corpus callosum development assessed by MRI in late-onset small fetuses.

PubMed

Sanz-Cortes, Magdalena; Egaña-Ugrinovic, Gabriela; Simoes, Rui V; Vazquez, Lucia; Bargallo, Nuria; Gratacos, Eduard

2015-06-01

We sought to determine the relationship between fetal brain metabolism and microstructure expressed by brain sulcation, and corpus callosum (CC) development assessed by fetal brain magnetic resonance (MR) imaging and proton MR spectroscopy ((1)H-MRS). A total of 119 fetuses, 64 that were small for gestational age (estimated fetal weight <10th centile and normal umbilical artery Doppler) and 55 controls underwent a 3T MR imaging/(1)H-MRS exam at 37 weeks. Anatomical T2-weighted images were obtained in the 3 orthogonal planes and long echo time (TE) (1)H-MRS acquired from the frontal lobe. Head biometrics, cortical fissure depths (insula, Sylvian, parietooccipital, cingulate, and calcarine), and CC area and biometries were blindly performed by manual and semiautomated delineation using Analyze software and corrected creating ratios for biparietal diameter and frontooccipital diameter, respectively, for group comparison. Spectroscopic data were processed using LCModel software and analyzed as metabolic ratios of N-acetylaspartate (NAA) to choline (Cho), Cho to creatine (Cr), and myo-inositol (Ino) to Cho. Differences between cases and controls were assessed. To test for the association between metabolic ratios and microstructural parameters, bivariate correlation analyses were performed. Spectroscopic findings showed decreased NAA/Cho and increased Cho/Cr ratios in small fetuses. They also presented smaller head biometrics, shorter and smaller CC, and greater insular and cingulate depths. Frontal lobe NAA/Cho significantly correlated with biparietal diameter (r = 0.268; P = .021), head circumference (r = 0.259; P = .026), CC length (r = 0.265; P = .026), CC area (r = 0.317; P = .007), and the area of 6 from the 7 CC subdivisions. It did not correlate with any of the cortical sulcation parameters evaluated. None of the other metabolic ratios presented significant correlations with cortical development or CC parameters. Frontal lobe NAA/Cho levels-which are considered a surrogate marker of neuronal activity-show a strong association with CC development. These results suggest that both metabolic and callosal alterations may be part of the same process of impaired brain development associated with intrauterine growth restriction. Copyright © 2015 Elsevier Inc. All rights reserved.

A decade of changes in brain volume and cognition.

PubMed

Aljondi, Rowa; Szoeke, Cassandra; Steward, Chris; Yates, Paul; Desmond, Patricia

2018-05-09

Brain atrophy can occur several decades prior to onset of cognitive impairments. However, few longitudinal studies have examined the relationship between brain volume changes and cognition over a long follow-up period in healthy elderly women. In the present study we investigate the relationship between whole brain and hippocampal atrophy rates and longitudinal changes in cognition, including verbal episodic memory and executive function, in older women. We also examine whether baseline brain volume predicts subsequent changes in cognitive performance over a 10-year period. A total of 60 individuals from the population-based Women's Healthy Ageing Project with a mean age at baseline of 59 years underwent 3T MRI. Of these, 40 women completed follow-up cognitive assessments, 23 of whom had follow-up MRI scans. Linear regression analysis was used to examine the relationship between brain atrophy and changes in verbal episodic memory and executive function over a 10-year period. The results show that baseline measurements of frontal and temporal grey matter volumes predict changes in verbal episodic memory performance, whereas hippocampal volume at baseline is associated with changes in executive function performance over a 10-year period of follow-ups. In addition, higher whole brain and hippocampal atrophy rates are correlated with a decline in verbal episodic memory. These findings indicate that in addition to atrophy rate, smaller regional grey matter volumes even 10 years prior is associated with increased rates of cognitive decline. This study suggests useful neuroimaging biomarkers for the prediction of cognitive decline in healthy elderly women.

Brain and muscle oxygenation monitoring using near-infrared spectroscopy (NIRS) during all-night sleep

NASA Astrophysics Data System (ADS)

Zhang, Zhongxing; Khatami, Ramin

2013-03-01

The hemodynamic changes during natural human sleep are still not well understood. NIRS is ideally suited for monitoring the hemodynamic changes during sleep due to the properties of local measurement, totally safe application and good tolerance to motion. Several studies have been conducted using NIRS in both normal subjects and patients with various sleep disorders during sleep to characterize the hemodynamic changing patterns during different sleep stages and during different symptoms such as obstructive apneas. Here we assessed brain and muscle oxygenation changes in 7 healthy adults during all-night sleep with combined polysomnography measurement to test the notion if hemodynamic changes in sleep are indeed brain specific. We found that muscle and brain showed similar hemodynamic changes during sleep initiation. A decrease in HbO2 and tissue oxygenation index (TOI) while an increase in HHb was observed immediately after sleep onset, and an opposite trend was found after transition with progression to deeper slow-wave sleep (SWS) stage. Spontaneous low frequency oscillations (LFO) and very low frequency oscillations (VLFO) were smaller (Levene's test, p<0.05) during SWS compared to light sleep (LS) and rapid-eye-movement (REM) sleep in both brain and muscle. Spectral analysis of the NIRS signals measured from brain and muscle also showed reductions in VLFO and LFO powers during SWS with respect to LS and REM sleep. These results indicate a systemic attenuation rather than local cerebral reduction of spontaneous hemodynamic activity in SWS. A systemic physiological mechanism may exist to regulate the hemodynamic changes in brain and muscle during sleep.

Mother-infant interactions and regional brain volumes in infancy: an MRI study.

PubMed

Sethna, Vaheshta; Pote, Inês; Wang, Siying; Gudbrandsen, Maria; Blasi, Anna; McCusker, Caroline; Daly, Eileen; Perry, Emily; Adams, Kerrie P H; Kuklisova-Murgasova, Maria; Busuulwa, Paula; Lloyd-Fox, Sarah; Murray, Lynne; Johnson, Mark H; Williams, Steven C R; Murphy, Declan G M; Craig, Michael C; McAlonan, Grainne M

2017-07-01

It is generally agreed that the human brain is responsive to environmental influences, and that the male brain may be particularly sensitive to early adversity. However, this is largely based on retrospective studies of older children and adolescents exposed to extreme environments in childhood. Less is understood about how normative variations in parent-child interactions are associated with the development of the infant brain in typical settings. To address this, we used magnetic resonance imaging to investigate the relationship between observational measures of mother-infant interactions and regional brain volumes in a community sample of 3- to 6-month-old infants (N = 39). In addition, we examined whether this relationship differed in male and female infants. We found that lower maternal sensitivity was correlated with smaller subcortical grey matter volumes in the whole sample, and that this was similar in both sexes. However, male infants who showed greater levels of positive communication and engagement during early interactions had smaller cerebellar volumes. These preliminary findings suggest that variations in mother-infant interaction dimensions are associated with differences in infant brain development. Although the study is cross-sectional and causation cannot be inferred, the findings reveal a dynamic interaction between brain and environment that may be important when considering interventions to optimize infant outcomes.

Interleukin-6 -174 and -572 genotypes and the volume of deep gray matter in preterm infants.

PubMed

Reiman, Milla; Parkkola, Riitta; Lapinleimu, Helena; Lehtonen, Liisa; Haataja, Leena

2009-01-01

Preterm infants have smaller cerebral and cerebellar volumes at term compared with term born infants. Perinatal factors leading to the reduction in volumes are not well known. IL-6 -174 and -572 genotypes partly regulate individual immunologic responses and have also been connected with deviant neurologic development in preterm infants. Our hypothesis was that IL-6 -174 and -572 genetic polymorphisms are associated with brain lesions and regional brain volumes in very low birth weight or in very preterm infants. DNA was genotyped for IL-6 -174 and -572 polymorphisms (GG/GC/CC). Study infants (n = 175) were categorized into three groups according to the most pathologic brain finding in ultrasound examinations until term. The brain MRI performed at term was analyzed for regional brain volumes. Analyzed IL-6 genotypes did not show statistically significant association with structural brain lesions. However, IL-6 -174 CC and -572 GG genotypes associated with reduced volume of one brain region, the combined volume of basal ganglia and thalami, both in univariate and in multivariate analyses (p = 0.009, 0.009, respectively). The association of IL-6 -174 and -572 genetic polymorphisms with smaller volumes in deep gray matter provides us new ways to understand the processes leading to neurologic impairments in preterm infants.

Altered Associations between Pain Symptoms and Brain Morphometry in the Pain Matrix of HIV-Seropositive Individuals.

PubMed

Castillo, Deborrah; Ernst, Thomas; Cunningham, Eric; Chang, Linda

2018-03-01

Pain remains highly prevalent in HIV-seropositive (HIV+) patients despite their well-suppressed viremia with combined antiretroviral therapy. Investigating brain abnormalities within the pain matrix, and in relation to pain symptoms, in HIV+ participants may provide objective biomarkers and insights regarding their pain symptoms. We used Patient-Reported Outcome Measurement Information System (PROMIS®) pain questionnaire to evaluate pain symptoms (pain intensity, pain interference and pain behavior), and structural MRI to assess brain morphometry using FreeSurfer (cortical area, cortical thickness and subcortical volumes were evaluated in 12 regions within the pain matrix). Compared to seronegative (SN) controls, HIV+ participants had smaller surface areas in prefrontal pars triangularis (right: p = 0.04, left: p = 0.007) and right anterior cingulate cortex (p = 0.03) and smaller subcortical regions (thalamus: p ≤ 0.003 bilaterally; right putamen: p = 0.01), as well as higher pain scores (pain intensity-p = 0.005; pain interference-p = 0.008; pain-behavior-p = 0.04). Furthermore, higher pain scores were associated with larger cortical areas, thinner cortices and larger subcortical volumes in HIV+ participants; but smaller cortical areas, thicker cortices and smaller subcortical volumes in SN controls (interaction-p = 0.009 to p = 0.04). These group differences in the pain-associated brain abnormalities suggest that HIV+ individuals have abnormal pain responses. Since these abnormal pain-associated brain regions belong to the affective component of the pain matrix, affective symptoms may influence pain perception in HIV+ patients and should be treated along with their physical pain symptoms. Lastly, associations of lower pain scores with better physical or mental health scores, regardless of HIV-serostatus (p < 0.001), suggest adequate pain treatment would lead to better quality of life in all participants.

Neuroanatomical Diversity of Corpus Callosum and Brain Volume in Autism: Meta-analysis, Analysis of the Autism Brain Imaging Data Exchange Project, and Simulation.

PubMed

Lefebvre, Aline; Beggiato, Anita; Bourgeron, Thomas; Toro, Roberto

2015-07-15

Patients with autism have been often reported to have a smaller corpus callosum (CC) than control subjects. We conducted a meta-analysis of the literature, analyzed the CC in 694 subjects of the Autism Brain Imaging Data Exchange project, and performed computer simulations to study the effect of different analysis strategies. Our meta-analysis suggested a group difference in CC size; however, the studies were heavily underpowered (20% power to detect Cohen's d = .3). In contrast, we did not observe significant differences in the Autism Brain Imaging Data Exchange cohort, despite having achieved 99% power. However, we observed that CC scaled nonlinearly with brain volume (BV): large brains had a proportionally smaller CC. Our simulations showed that because of this nonlinearity, CC normalization could not control for eventual BV differences, but using BV as a covariate in a linear model would. We also observed a weaker correlation of IQ and BV in cases compared with control subjects. Our simulations showed that matching populations by IQ could then induce artifactual BV differences. The lack of statistical power in the previous literature prevents us from establishing the reality of the claims of a smaller CC in autism, and our own analyses did not find any. However, the nonlinear relationship between CC and BV and the different correlation between BV and IQ in cases and control subjects may induce artifactual differences. Overall, our results highlight the necessity for open data sharing to provide a more solid ground for the discovery of neuroimaging biomarkers within the context of the wide human neuroanatomical diversity. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Molecular weights and metabolism of rat brain proteins

PubMed Central

Vrba, R.; Cannon, Wendy

1970-01-01

1. Rats were injected with [U-14C]glucose and after various intervals extracts of whole brain proteins (and in some cases proteins from liver, blood and heart) were prepared by high-speed centrifugation of homogenates in 0.9% sodium chloride or 0.5% sodium deoxycholate. 2. The extracts were subjected to gel filtration on columns of Sephadex G-200 equilibrated with 0.9% sodium chloride or 0.5% sodium deoxycholate. 3. Extracts prepared with both solvents displayed on gel filtration a continuous range of proteins of approximate molecular weights ranging from less than 2×104 to more than 8×105. 4. The relative amount of the large proteins (mol.wt.>8×105) was conspicuously higher in brain and liver than in blood. 5. At 15min after the injection of [U-14C]glucose the smaller protein molecules (mol.wt.<2×104) were significantly radioactive, whereas no 14C could be detected in the larger (mol.wt.>2×104) protein molecules. The labelling of all protein samples was similar within 4h after injection of [U-14C]glucose. Fractionation of brain proteins into distinctly different groups by the methods used in the present work yielded protein samples with a specific radioactivity comparable with that of total brain protein. 6. No evidence could be obtained by the methods used in the present and previous work to indicate the presence of a significant amount of `metabolically inert protein' in the brain. 7. It is concluded that: (a) most or all of the brain proteins are in a dynamic state of equilibrium between continuous catabolism and anabolism; (b) the continuous conversion of glucose into protein is an important part of the maintenance of this equilibrium and of the homoeostasis of brain proteins in vivo. PMID:5435499

s-SMOOTH: Sparsity and Smoothness Enhanced EEG Brain Tomography

PubMed Central

Li, Ying; Qin, Jing; Hsin, Yue-Loong; Osher, Stanley; Liu, Wentai

2016-01-01

EEG source imaging enables us to reconstruct current density in the brain from the electrical measurements with excellent temporal resolution (~ ms). The corresponding EEG inverse problem is an ill-posed one that has infinitely many solutions. This is due to the fact that the number of EEG sensors is usually much smaller than that of the potential dipole locations, as well as noise contamination in the recorded signals. To obtain a unique solution, regularizations can be incorporated to impose additional constraints on the solution. An appropriate choice of regularization is critically important for the reconstruction accuracy of a brain image. In this paper, we propose a novel Sparsity and SMOOthness enhanced brain TomograpHy (s-SMOOTH) method to improve the reconstruction accuracy by integrating two recently proposed regularization techniques: Total Generalized Variation (TGV) regularization and ℓ1−2 regularization. TGV is able to preserve the source edge and recover the spatial distribution of the source intensity with high accuracy. Compared to the relevant total variation (TV) regularization, TGV enhances the smoothness of the image and reduces staircasing artifacts. The traditional TGV defined on a 2D image has been widely used in the image processing field. In order to handle 3D EEG source images, we propose a voxel-based Total Generalized Variation (vTGV) regularization that extends the definition of second-order TGV from 2D planar images to 3D irregular surfaces such as cortex surface. In addition, the ℓ1−2 regularization is utilized to promote sparsity on the current density itself. We demonstrate that ℓ1−2 regularization is able to enhance sparsity and accelerate computations than ℓ1 regularization. The proposed model is solved by an efficient and robust algorithm based on the difference of convex functions algorithm (DCA) and the alternating direction method of multipliers (ADMM). Numerical experiments using synthetic data demonstrate the advantages of the proposed method over other state-of-the-art methods in terms of total reconstruction accuracy, localization accuracy and focalization degree. The application to the source localization of event-related potential data further demonstrates the performance of the proposed method in real-world scenarios. PMID:27965529

Smaller size of high metabolic rate organs explains lower resting energy expenditure in Asian-Indian Than Chinese men.

PubMed

Song, L L T; Venkataraman, K; Gluckman, P; Chong, Y S; Chee, M-W L; Khoo, C M; Leow, M-Ks; Lee, Y S; Tai, E S; Khoo, E Y H

2016-04-01

In Singapore, the obesity prevalence is disproportionately higher in the Asian-Indians and Malays than the Chinese. Lower resting energy expenditure (REE) may be a contributory factor. We explored the association between ethnicity and REE in Chinese, Asian-Indian and Malay men living in Singapore and determined the influence of body composition, mass/volume of high metabolic rate organs, represented by brain volume and trunk fat-free mass (FFM), and physical activity on ethnic differences. Two hundred and forty-four men from Singapore (n=100 Chinese, 70 Asian-Indians and 74 Malays), aged 21-40 years and body mass index of 18.5-30.0 kg m(-2), were recruited in this cross-sectional study. REE was assessed by indirect calorimetry and body composition by dual-energy X-ray absorptiometry. Brain volume was measured by magnetic resonance imaging. Physical activity was assessed by the Singapore Prospective Study Program Physical Activity Questionnaire. REE was significantly lower in Asian-Indians compared with that in Chinese after adjusting for body weight. FFM (total, trunk and limb) and total fat mass were important predictors of REE across all ethnic groups. Brain volume was positively associated with REE only in Malays. Moderate and vigorous physical activity was positively associated with REE only in Asian-Indians and Malays. The difference in REE between Asian-Indians and Chinese was attenuated but remained statistically significant after adjustment for total FFM (59±20 kcal per day), fat mass (67±20 kcal per day) and brain volume (54±22 kcal per day). The association between REE and ethnicity was no longer statistically significant after total FFM was replaced by trunk FFM (which includes heart, liver, kidney and spleen) but not when it was replaced by limb FFM (skeletal muscle). We have demonstrated a lower REE in Asian-Indians compared with Chinese who may contribute to the higher rates of obesity in the former. This difference could be accounted for by differences in metabolically active organs.

Parvovirus associated cerebellar hypoplasia and hydrocephalus in day-old broiler chickens

USDA-ARS?s Scientific Manuscript database

Cerebellar hypoplasia and hydrocephalus were detected in day-old broiler chickens. Brains of chickens evaluated at necropsy appeared to be abnormal; some were disfigured and cerebellae appeared to be smaller than normal. Histopathologic examination of brains revealed cerebellar folia that were sho...

Carotid Artery Disease

MedlinePlus

... brain (cerebrovascular disease). Like the heart, the brain’s cells need a constant supply of oxygen-rich blood. This blood supply is delivered to the brain by the 2 large carotid arteries in the front of your neck and by 2 smaller vertebral arteries at the back of your ...

Basic helix-loop-helix transcription factor NEUROG1 and schizophrenia: effects on illness susceptibility, MRI brain morphometry and cognitive abilities.

PubMed

Ho, Beng-Choon; Epping, Eric; Wang, Kai; Andreasen, Nancy C; Librant, Amy; Wassink, Thomas H

2008-12-01

Transcription factors, including the basic helix-loop-helix (bHLH) family, regulate numerous genes and play vital roles in controlling gene expression. Consequently, transcription factor mutations can lead to phenotypic pleiotropy, and may be a candidate mechanism underlying the complex genetics and heterogeneous phenotype of schizophrenia. Neurogenin1 (NEUROG1; a.k.a. Ngn1 or Neurod3), a bHLH transcription factor encoded on a known schizophrenia linkage region in 5q31.1, induces glutamatergic and suppresses GABAergic neuronal differentiation during embryonic neurodevelopment. The goal of this study is to investigate NEUROG1 effects on schizophrenia risk and on phenotypic features of schizophrenia. We tested 392 patients with schizophrenia or schizoaffective disorder and 226 healthy normal volunteers for association with NEUROG1. Major alleles on two NEUROG1-associated SNPs (rs2344484-C-allele and rs8192558-G-allele) were significantly more prevalent among patients (p

Life-course blood pressure in relation to brain volumes

PubMed Central

Power, Melinda C.; Schneider, Andrea L. C.; Wruck, Lisa; Griswold, Michael; Coker, Laura H.; Alonso, Alvaro; Jack, Clifford R.; Knopman, David; Mosley, Thomas H.; Gottesman, Rebecca F

2016-01-01

INTRODUCTION The impact of blood pressure on brain volumes may be time- or pattern-dependent. METHODS In 1678 participants from the Atherosclerosis Risk in Communities Neurocognitive Study, we quantified the association between measures and patterns of blood pressure over three time points (~24 or ~15 years prior and concurrent with neuroimaging) with late life brain volumes. RESULTS Higher diastolic blood pressure ~24 years prior, higher systolic and pulse pressure ~15 years prior, and consistently elevated or rising systolic blood pressure from ~15 years prior to concurrent with neuroimaging, but not blood pressures measured concurrent with neuroimaging, were associated with smaller volumes. The pattern of hypertension ~15 years prior and hypotension concurrent with neuroimaging was associated with smaller volumes in regions preferentially affected by Alzheimer’s disease (e.g., hippocampus: −0.27 standard units, 95%CI:−0.51,−0.03). DISCUSSION Hypertension 15 to 24 years prior is relevant to current brain volumes. Hypertension followed by hypotension appears particularly detrimental. PMID:27139841

Postoperative stereotactic radiosurgery for resected brain metastases: A comparison of outcomes for large resection cavities.

PubMed

Zhong, Jim; Ferris, Matthew J; Switchenko, Jeffrey; Press, Robert H; Buchwald, Zachary; Olson, Jeffrey J; Eaton, Bree R; Curran, Walter J; Shu, Hui-Kuo G; Crocker, Ian R; Patel, Kirtesh R

Although historical trials have established the role of surgical resection followed by whole brain irradiation (WBRT) for brain metastases, WBRT has recently been shown to cause significant neurocognitive decline. Many practitioners have employed postoperative stereotactic radiosurgery (SRS) to tumor resection cavities to increase local control without causing significant neurocognitive sequelae. However, studies analyzing outcomes of large brain metastases treated with resection and postoperative SRS are lacking. Here we compare outcomes in patients with large brain metastases >4 cm to those with smaller metastases ≤4 cm treated with surgical resection followed by SRS to the resection cavity. Consecutive patients with brain metastases treated at our institution with surgical resection and postoperative SRS were retrospectively reviewed. Patients were stratified into ≤4 cm and >4 cm cohorts based on preoperative maximal tumor dimension. Cumulative incidence of local failure, radiation necrosis, and death were analyzed for the 2 cohorts using a competing-risk model, defined as the time from SRS treatment date to the measured event, death, or last follow-up. A total of 117 consecutive cases were identified. Of these patients, 90 (77%) had preoperative tumors ≤4 cm, and 27 (23%) >4 cm in greatest dimension. The only significant baseline difference between the 2 groups was a higher proportion of patients who underwent gross total resection in the ≤4 cm compared with the >4 cm cohort, 76% versus 48%, respectively (P <.01). The 1-year rates of local failure, radiation necrosis, and overall survival for the ≤4 cm and >4 cm cohorts were 12.3% and 16.0%, 26.9% and 28.4%, and 80.6% and 67.6%, respectively (all P >.05). The rates of local failure and radiation necrosis were not statistically different on multivariable analysis based on tumor size. Brain metastases >4 cm in largest dimension managed by resection and radiosurgery to the tumor cavity have promising local control rates without a significant increase in radiation necrosis on our retrospective review. Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Big-brained birds survive better in nature

PubMed Central

Sol, Daniel; Székely, Tamás; Liker, András; Lefebvre, Louis

2007-01-01

Big brains are hypothesized to enhance survival of animals by facilitating flexible cognitive responses that buffer individuals against environmental stresses. Although this theory receives partial support from the finding that brain size limits the capacity of animals to behaviourally respond to environmental challenges, the hypothesis that large brains are associated with reduced mortality has never been empirically tested. Using extensive information on avian adult mortality from natural populations, we show here that species with larger brains, relative to their body size, experience lower mortality than species with smaller brains, supporting the general importance of the cognitive buffer hypothesis in the evolution of large brains. PMID:17251112

Reduced amygdalar and hippocampal size in adults with generalized social phobia.

PubMed

Irle, Eva; Ruhleder, Mirjana; Lange, Claudia; Seidler-Brandler, Ulrich; Salzer, Simone; Dechent, Peter; Weniger, Godehard; Leibing, Eric; Leichsenring, Falk

2010-03-01

Structural and functional brain imaging studies suggest abnormalities of the amygdala and hippocampus in posttraumatic stress disorder and major depressive disorder. However, structural brain imaging studies in social phobia are lacking. In total, 24 patients with generalized social phobia (GSP) and 24 healthy controls underwent 3-dimensional structural magnetic resonance imaging of the amygdala and hippocampus and a clinical investigation. Compared with controls, GSP patients had significantly reduced amygdalar (13%) and hippocampal (8%) size. The reduction in the size of the amygdala was statistically significant for men but not women. Smaller right-sided hippocampal volumes of GSP patients were significantly related to stronger disorder severity. Our sample included only patients with the generalized subtype of social phobia. Because we excluded patients with comorbid depression, our sample may not be representative. We report for the first time volumetric results in patients with GSP. Future assessment of these patients will clarify whether these changes are reversed after successful treatment and whether they predict treatment response.

Allocation of systemic glucose output to cerebral utilization as a function of fetal canine growth.

PubMed

Huang, M M; Kliegman, R M; Trindade, C; Kall, D; Voelker, K

1988-05-01

To determine whether the neonatal canine brain consumes a major proportion of the systemic glucose production, we investigated the cerebral glucose requirement and hepatic glucose production in beagle pups. Sixteen pups received D-[6-3H]-glucose to determine systemic glucose production. Cerebral blood flow was measured by [N-methyl-14C]antipyrine, and the brain uptake index (BUI) of glucose was determined using 2-[14C]deoxy-D-glucose. Glucose production was 49.6 +/- 11.0 mumol.kg-1.min-1. Cerebral blood flow was 0.83 ml.g-1.min-1; cerebral uptake of glucose was 0.60 +/- 0.15 mumol.g-1.min-1. Of the total glucose production 36.6 +/- 7.9% was accounted for by the cerebral uptake of glucose. Brain-to-body weight and brain-to-liver weight ratios were the greatest in the smallest pups, suggesting brain sparing. The effect of growth status on cerebral substrate availability could not be correlated with cerebral uptake of glucose or oxygen or with systemic glucose production. However, the percentage of systemic glucose production allotted to the cerebral cortex increased with increasing body weight (r = 0.50, P less than 0.05). Cerebral glucose entry measured by BUI was demonstrated to be 0.108 +/- 0.014; BUI inversely correlated with canine birth weight (r = -0.832, P less than 0.001). We conclude that the percentage of glucose production utilized by the neonatal canine brain is not proportionately larger in the smaller pups despite a proportionately larger brain. Because the absolute cerebral glucose utilization may be static, we speculate that BUI (glucose entry) may be less of a rate-limiting factor for cerebral glucose entry in the smallest pups.

Structural Brain Imaging of Long-Term Anabolic-Androgenic Steroid Users and Nonusing Weightlifters.

PubMed

Bjørnebekk, Astrid; Walhovd, Kristine B; Jørstad, Marie L; Due-Tønnessen, Paulina; Hullstein, Ingunn R; Fjell, Anders M

2017-08-15

Prolonged high-dose anabolic-androgenic steroid (AAS) use has been associated with psychiatric symptoms and cognitive deficits, yet we have almost no knowledge of the long-term consequences of AAS use on the brain. The purpose of this study is to investigate the association between long-term AAS exposure and brain morphometry, including subcortical neuroanatomical volumes and regional cortical thickness. Male AAS users and weightlifters with no experience with AASs or any other equivalent doping substances underwent structural magnetic resonance imaging scans of the brain. The current paper is based upon high-resolution structural T1-weighted images from 82 current or past AAS users exceeding 1 year of cumulative AAS use and 68 non-AAS-using weightlifters. Images were processed with the FreeSurfer software to compare neuroanatomical volumes and cerebral cortical thickness between the groups. Compared to non-AAS-using weightlifters, the AAS group had thinner cortex in widespread regions and significantly smaller neuroanatomical volumes, including total gray matter, cerebral cortex, and putamen. Both volumetric and thickness effects remained relatively stable across different AAS subsamples comprising various degrees of exposure to AASs and also when excluding participants with previous and current non-AAS drug abuse. The effects could not be explained by differences in verbal IQ, intracranial volume, anxiety/depression, or attention or behavioral problems. This large-scale systematic investigation of AAS use on brain structure shows negative correlations between AAS use and brain volume and cortical thickness. Although the findings are correlational, they may serve to raise concern about the long-term consequences of AAS use on structural features of the brain. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Light enough to travel or wise enough to stay? Brain size evolution and migratory behavior in birds.

PubMed

Vincze, Orsolya

2016-09-01

Brain size relative to body size is smaller in migratory than in nonmigratory birds. Two mutually nonexclusive hypotheses had been proposed to explain this association. On the one hand, the "energetic trade-off hypothesis" claims that migratory species were selected to have smaller brains because of the interplay between neural tissue volume and migratory flight. On the other hand, the "behavioral flexibility hypothesis" argues that resident species are selected to have higher cognitive capacities, and therefore larger brains, to enable survival in harsh winters, or to deal with environmental seasonality. Here, I test the validity and setting of these two hypotheses using 1466 globally distributed bird species. First, I show that the negative association between migration distance and relative brain size is very robust across species and phylogeny. Second, I provide strong support for the energetic trade-off hypothesis, by showing the validity of the trade-off among long-distance migratory species alone. Third, using resident and short-distance migratory species, I demonstrate that environmental harshness is associated with enlarged relative brain size, therefore arguably better cognition. My study provides the strongest comparative support to date for both the energetic trade-off and the behavioral flexibility hypotheses, and highlights that both mechanisms contribute to brain size evolution, but on different ends of the migratory spectrum. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Postmortem volumetric analysis of the nucleus accumbens in male heroin addicts: implications for deep brain stimulation.

PubMed

Müller, Ulf J; Truebner, Kurt; Schiltz, Kolja; Kuhn, Jens; Mawrin, Christian; Dobrowolny, Henrik; Bernstein, Hans-Gert; Bogerts, Bernhard; Steiner, Johann

2015-12-01

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is increasingly investigated in neuropsychiatric disorders. DBS requires computer-assisted 3D planning to implant the stimulation electrode precisely. Recently, there has been a debate about the true dimensions of NAc in healthy as well as in mentally ill individuals. Knowing its true dimensions in different neuropsychiatric disorders may improve even more precise targeting of NAc for therapeutic DBS. Volumes of NAc of heroin addicts (n = 14) and healthy controls (n = 12) were calculated by using morphometry of serial whole-brain sections. Total brain volume was larger in the heroin group (mean 1478.85 ± 62.34 vs. mean 1352.38 ± 103.24 cm(3)), as the heroin group was more than 10 years younger (p = 0.001). However, the mean volume of the NAc in heroin addicts was smaller than in controls (0.528 ± 0.166 vs. 0.623 ± 0.196 cm(3); p = 0.019). This group effect did not significantly differ between the hemispheres. When assessed separately, left-hemispheric NAc volume was 15 % lower (p = 0.020), while right-hemispheric NAc volume was 16 % lower (p = 0.047) in the heroin-addicted group compared to controls. Based on these diagnosis-related differences, we believe it is important to further analyze NAc volumes in different psychiatric disorders to further improve precise targeting and electrode placement.

Intrinsic sensory deprivation induced by neonatal capsaicin treatment induces changes in rat brain and behaviour of possible relevance to schizophrenia

PubMed Central

Newson, Penny; Lynch-Frame, Ann; Roach, Rebecca; Bennett, Sarah; Carr, Vaughan; Chahl, Loris A

2005-01-01

Schizophrenia is considered to be a neurodevelopmental disorder with origins in the prenatal or neonatal period. Brains from subjects with schizophrenia have enlarged ventricles, reduced cortical thickness (CT) and increased neuronal density in the prefrontal cortex compared with those from normal subjects. Subjects with schizophrenia have reduced pain sensitivity and niacin skin flare responses, suggesting that capsaicin-sensitive primary afferent neurons might be abnormal in schizophrenia. This study tested the hypothesis that intrinsic somatosensory deprivation, induced by neonatal capsaicin treatment, causes changes in the brains of rats similar to those found in schizophrenia. Wistar rats were treated with capsaicin, 50 mg kg−1 subcutaneously, or vehicle (control) at 24–36 h of life. At 5–7 weeks behavioural observations were made, and brains removed, fixed and sectioned. The mean body weight of capsaicin-treated rats was not significantly different from control, but the mean brain weight of male, but not female, rats, was significantly lower than control. Capsaicin-treated rats were hyperactive compared with controls. The hyperactivity was abolished by haloperidol. Coronal brain sections of capsaicin-treated rats had smaller cross-sectional areas, reduced CT, larger ventricles and aqueduct, smaller hippocampal area and reduced corpus callosum thickness, than brain sections from control rats. Neuronal density was increased in several cortical areas and the caudate putamen, but not in the visual cortex. It is concluded that neonatal capsaicin treatment of rats produces brain changes that are similar to those found in brains of subjects with schizophrenia. PMID:16041396

Naked mole-rat cortical neurons are resistant to acid-induced cell death.

PubMed

Husson, Zoé; Smith, Ewan St John

2018-05-09

Regulation of brain pH is a critical homeostatic process and changes in brain pH modulate various ion channels and receptors and thus neuronal excitability. Tissue acidosis, resulting from hypoxia or hypercapnia, can activate various proteins and ion channels, among which acid-sensing ion channels (ASICs) a family of primarily Na + permeable ion channels, which alongside classical excitotoxicity causes neuronal death. Naked mole-rats (NMRs, Heterocephalus glaber) are long-lived, fossorial, eusocial rodents that display remarkable behavioral/cellular hypoxia and hypercapnia resistance. In the central nervous system, ASIC subunit expression is similar between mouse and NMR with the exception of much lower expression of ASIC4 throughout the NMR brain. However, ASIC function and neuronal sensitivity to sustained acidosis has not been examined in the NMR brain. Here, we show with whole-cell patch-clamp electrophysiology of cultured NMR and mouse cortical and hippocampal neurons that NMR neurons have smaller voltage-gated Na + channel currents and more hyperpolarized resting membrane potentials. We further demonstrate that acid-mediated currents in NMR neurons are of smaller magnitude than in mouse, and that all currents in both species are reversibly blocked by the ASIC antagonist benzamil. We further demonstrate that NMR neurons show greater resistance to acid-induced cell death than mouse neurons. In summary, NMR neurons show significant cellular resistance to acidotoxicity compared to mouse neurons, contributing factors likely to be smaller ASIC-mediated currents and reduced NaV activity.

Sex differences in impulsivity and brain morphometry in methamphetamine users

PubMed Central

Kogachi, Shannon; Chang, Linda; Alicata, Daniel; Cunningham, Eric; Ernst, Thomas

2016-01-01

Methamphetamine (METH) is an addictive stimulant, and METH users have abnormal brain structures and function. The aims of this study were to investigate the relationships between impulsivity, brain structures, and possible sex-specific differences between METH users and non-drug using Controls. Structural MRI and the Barratt Impulsiveness Scale (BIS) questionnaire were completed in 124 subjects: 62 METH (ages 41.2 ± 1.4 years, 34 males) and 62 Controls (ages 43.3 ± 2.3 years, 36 males). Independent and interactive effects of METH use status and sex were evaluated. Relationships between METH usage characteristics, brain morphometry, and impulsivity scores were examined. METH users had higher impulsivity scores, on both the Cognitive and Behavioral Factors from the BIS (p < 0.0001–0.0001). Compared with same-sex Controls, male METH users had larger, while female METH users had smaller, right superior frontal cortex (interaction-p = 0.0005). The male METH users with larger frontal volumes and female METH users with smaller or thinner frontal cortices had greater Cognitive impulsivity (interaction-p ≤ 0.05). Only female METH users showed relatively larger nucleus accumbens (interaction-p = 0.03). Greater impulsivity and thinner frontal cortices in METH users are validated. Larger superior frontal cortex in male METH users with greater cognitive impulsivity suggest decreased dendritic pruning during adolescence might have contributed to their impulsive and drug use behaviors. In the female METH users, smaller frontal cortices and the associated greater impulsivity suggest greater neurotoxicity to these brain regions, while their relatively larger nucleus accumbens suggest an estrogen-mediated neuroprotective glial response. Men and women may be affected differently by METH use. PMID:27095357

Sex differences in impulsivity and brain morphometry in methamphetamine users.

PubMed

Kogachi, Shannon; Chang, Linda; Alicata, Daniel; Cunningham, Eric; Ernst, Thomas

2017-01-01

Methamphetamine (METH) is an addictive stimulant, and METH users have abnormal brain structures and function. The aims of this study were to investigate the relationships between impulsivity, brain structures, and possible sex-specific differences between METH users and non-drug using Controls. Structural MRI and the Barratt Impulsiveness Scale (BIS) questionnaire were completed in 124 subjects: 62 METH (ages 41.2 ± 1.4 years, 34 males) and 62 Controls (ages 43.3 ± 2.3 years, 36 males). Independent and interactive effects of METH use status and sex were evaluated. Relationships between METH usage characteristics, brain morphometry, and impulsivity scores were examined. METH users had higher impulsivity scores, on both the Cognitive and Behavioral Factors from the BIS (p < 0.0001-0.0001). Compared with same-sex Controls, male METH users had larger, while female METH users had smaller, right superior frontal cortex (interaction-p = 0.0005). The male METH users with larger frontal volumes and female METH users with smaller or thinner frontal cortices had greater Cognitive impulsivity (interaction-p ≤ 0.05). Only female METH users showed relatively larger nucleus accumbens (interaction-p = 0.03). Greater impulsivity and thinner frontal cortices in METH users are validated. Larger superior frontal cortex in male METH users with greater cognitive impulsivity suggest decreased dendritic pruning during adolescence might have contributed to their impulsive and drug use behaviors. In the female METH users, smaller frontal cortices and the associated greater impulsivity suggest greater neurotoxicity to these brain regions, while their relatively larger nucleus accumbens suggest an estrogen-mediated neuroprotective glial response. Men and women may be affected differently by METH use.

Antidepressant exposure may protect against decrement in frontal gray matter volumes in geriatric depression.

PubMed

Lavretsky, Helen; Roybal, Donna J; Ballmaier, Martina; Toga, Arthur W; Kumar, Anand

2005-08-01

Depressed elderly patients with and without antidepressant exposure were compared to normal controls to examine the effects of prior antidepressant exposure on regional brain gray matter volumes using magnetic resonance imaging (MRI). The study was conducted from October 1999 to January 2003. Patients and controls were closely matched by age and education. They underwent comprehensive neuropsychiatric and physical examinations. Measures of the total frontal lobe and the frontal gray and white matter volumes corrected by the intracranial volume were obtained using MRI, together with clinical measures of medical burden. Historical information about prior exposure to antidepressant drugs was collected using multiple information sources. The groups were compared using multivariate analyses of covariance, controlling for age, sex, and medical burden. The study sample comprised 41 patients who met the DSM-IV criteria for major depressive disorder (32 women; 11 antidepressant exposure and 30 drug-naive; mean age 70.5 years) and 41 controls (20 women; mean age 72.2 years). In the multivariate analysis, the depressed group had smaller corrected orbitofrontal cortex (OFC) total and gray matter volumes compared to the controls (p < .01). However, depressed patients with prior antidepressant exposure had larger OFC gray matter volumes compared to drug-naive depressed patients, but smaller than those in normal controls (p = .005). This effect was not explained by the group differences in sex ratio, age at onset of depression, or the number or duration of depressive episodes. We observed larger OFC regional volumes in depressed patients exposed to antidepressants compared to the drug-naive depressed subjects, but smaller than those in age-matched controls. Antidepressant exposure may protect against gray matter loss in geriatric depression.

Effect of starvation and exercise on actual and total activity of the branched-chain 2-oxo acid dehydrogenase complex in rat tissues.

PubMed Central

Wagenmakers, A J; Schepens, J T; Veerkamp, J H

1984-01-01

Starvation does not change the actual activity per g of tissue of the branched-chain 2-oxo acid dehydrogenase in skeletal muscles, but affects the total activity to a different extent, depending on the muscle type. The activity state (proportion of the enzyme present in the active state) does not change in diaphragm and decreases in quadriceps muscle. Liver and kidney show an increase of both activities, without a change of the activity state. In heart and brain no changes were observed. Related to organ wet weights, the actual activity present in the whole-body muscle mass decreases on starvation, whereas the activities present in liver and kidney do not change, or increase slightly. Exercise (treadmill-running) of untrained rats for 15 and 60 min causes a small increase of the actual activity and the activity state of the branched-chain 2-oxo acid dehydrogenase complex in heart and skeletal muscle. Exercise for 1 h, furthermore, increased the actual and the total activity in liver and kidney, without a change of the activity state. In brain no changes were observed. The actual activity per g of tissue in skeletal muscle was less than 2% of that in liver and kidney, both before and after exercise and starvation. Our data indicate that the degradation of branched-chain 2-oxo acids predominantly occurs in liver and to a smaller extent in kidney and skeletal muscle in fed, starved and exercised rats. PMID:6508743

Mercury and selenium levels, and selenium:mercury molar ratios of brain, muscle and other tissues in bluefish (Pomatomus saltatrix) from New Jersey, USA

PubMed Central

Burger, Joanna; Jeitner, Christian; Donio, Mark; Pittfield, Taryn; Gochfeld, Michael

2015-01-01

A number of contaminants affect fish health, including mercury and selenium, and the selenium: mercury molar ratio. Recently the protective effects of selenium on methylmercury toxicity have been publicized, particularly for consumption of saltwater fish. Yet the relative ameliorating effects of selenium on toxicity within fish have not been examined, nor has the molar ratio in different tissues, (i.e. brain). We examined mercury and selenium levels in brain, kidney, liver, red and white muscle, and skin and scales in bluefish (Pomatomus saltatrix) from New Jersey to determine whether there were toxic levels of either metal, and we computed the selenium: mercury molar ratios by tissues. Total mercury averaged 0.32 ± 0.02 ppm wet weight in edible muscle and 0.09 ± 0.01 ppm in brain. Selenium concentration averaged 0.37 ± 0.03 in muscle and 0.36 ± 0.03 ppm in brain. There were significant differences in levels of mercury, selenium, and selenium: mercury molar ratios, among tissues. Mercury and selenium levels were correlated in kidney and skin/scales. Mercury levels were highest in kidney, intermediate in muscle and liver, and lowest in brain and skin/scales; selenium levels were also highest in kidney, intermediate in liver, and were an order of magnitude lower in the white muscle and brain. Mercury levels in muscle, kidney and skin/scales were positively correlated with fish size (length). Selenium levels in muscle, kidney and liver were positively correlated with fish length, but in brain; selenium levels were negatively correlated with fish length. The selenium: mercury molar ratio was negatively correlated with fish length for white muscle, liver, kidney, and brain, particularly for fish over 50 cm in length, suggesting that older fish experience less protective advantages of selenium against mercury toxicity than smaller fish, and that consumers of bluefish similarly receive less advantage from eating larger fish. PMID:23202378

Neurosurgical tactile discrimination training with haptic-based virtual reality simulation.

PubMed

Patel, Achal; Koshy, Nick; Ortega-Barnett, Juan; Chan, Hoi C; Kuo, Yong-Fan; Luciano, Cristian; Rizzi, Silvio; Matulyauskas, Martin; Kania, Patrick; Banerjee, Pat; Gasco, Jaime

2014-12-01

To determine if a computer-based simulation with haptic technology can help surgical trainees improve tactile discrimination using surgical instruments. Twenty junior medical students participated in the study and were randomized into two groups. Subjects in Group A participated in virtual simulation training using the ImmersiveTouch simulator (ImmersiveTouch, Inc., Chicago, IL, USA) that required differentiating the firmness of virtual spheres using tactile and kinesthetic sensation via haptic technology. Subjects in Group B did not undergo any training. With their visual fields obscured, subjects in both groups were then evaluated on their ability to use the suction and bipolar instruments to find six elastothane objects with areas ranging from 1.5 to 3.5 cm2 embedded in a urethane foam brain cavity model while relying on tactile and kinesthetic sensation only. A total of 73.3% of the subjects in Group A (simulation training) were able to find the brain cavity objects in comparison to 53.3% of the subjects in Group B (no training) (P  =  0.0183). There was a statistically significant difference in the total number of Group A subjects able to find smaller brain cavity objects (size ≤ 2.5 cm2) compared to that in Group B (72.5 vs. 40%, P  =  0.0032). On the other hand, no significant difference in the number of subjects able to detect larger objects (size ≧ 3 cm2) was found between Groups A and B (75 vs. 80%, P  =  0.7747). Virtual computer-based simulators with integrated haptic technology may improve tactile discrimination required for microsurgical technique.

Corpus callosum differences assessed by fetal MRI in late-onset intrauterine growth restriction and its association with neurobehavior.

PubMed

Egaña-Ugrinovic, Gabriela; Sanz-Cortés, Magdalena; Couve-Pérez, Constanza; Figueras, Francesc; Gratacós, Eduard

2014-09-01

The aim of this study is to evaluate corpus callosum (CC) development by Magnetic Resonance Imaging (MRI) in late-onset intrauterine growth restricted (IUGR) fetuses compared to appropriate for gestational age and its association with neurobehavioral outcome. One hundred and seventeen late-onset IUGR and 73 control fetuses were imaged using a 3T MRI scanner at term, obtaining T2 half-Fourier acquisition single-shot turbo spin-echo anatomical slices. CC length, thickness, total area and the areas after a subdivision in 7 portions were assessed. Neonatal Behavioral Assessment Scale test was performed on IUGR newborns at 42 ± 1 weeks. IUGR fetuses showed significantly smaller CC (Total CC Area IUGR: 1.3996 ± 0.26 vs. AGA: 1.664 ± 0.31; p < 0.01) and smaller subdivision areas as compared with controls. The differences were slightly more pronounced in fetuses with very low birth weight and/or abnormal brain and/or abnormal uterine Doppler. CC measurements were significantly associated with neurobehavioral outcome in IUGR cases. CC development was significantly altered in late-onset IUGR fetuses and correlated with worse neurobehavioral performance. CC could be further explored as a potential imaging biomarker to predict abnormal neurodevelopment in pregnancies at risk. © 2014 John Wiley & Sons, Ltd.

Evolution of the felid brain.

PubMed

Radinsky, L

1975-01-01

Endocranial casts of 15 genera of fossil felids provide a record of felid brain evolution over the past 35 million years. Brains of the earliest felids, known as paleofelids, had coronolateral, suprasylvian and variably developed ectosylvian sulci as their only neocortical sulci. The last paleofelids, which became extinct around 8 million years ago, show little change in external brain morphology except for the addition of a presylvian sulcus. The other group of felids, the neofelids, appears about 25 million years ago, with coronolateral and suprasylvian sulci their main neocortical sulci, plus a discontinuous ectosylvian sulcus and small postlateral, sylvian and presylvian sulci. The posterior cerebellar vermis was straight and unexpanded. Beginnings of expansion of the sigmoid gyri and development of the cruciate sulcus are evident in neofelids 15-20 million years ago, and by 5-9 million years ago neofelids had brains that appear modern in external morphology. Endocasts of four genera of Pleistocene saber-toothed felids are similar in sulcal pattern to those of modern felids, except for Dinobastis, which had a unique expansion of visual cortex. Endocasts of 27 species of modern felids, representing the six commonly recognized genera, are strikingly similar in external morphology, although the brains of a few species, such as cheetahs, lynxes and jagouarundis, display distinguishing features. Modern felid brains average about the same size relative to body weight as do those of viverrids, but are about 25% smaller in relative size than those of canids. Olfactory bulbs are relatively smaller in felids than in canids or viverrids.

Ravens, New Caledonian crows and jackdaws parallel great apes in motor self-regulation despite smaller brains.

PubMed

Kabadayi, Can; Taylor, Lucy A; von Bayern, Auguste M P; Osvath, Mathias

2016-04-01

Overriding motor impulses instigated by salient perceptual stimuli represent a fundamental inhibitory skill. Such motor self-regulation facilitates more rational behaviour, as it brings economy into the bodily interaction with the physical and social world. It also underlies certain complex cognitive processes including decision making. Recently, MacLean et al. (MacLean et al. 2014 Proc. Natl Acad. Sci. USA 111, 2140-2148. (doi:10.1073/pnas.1323533111)) conducted a large-scale study involving 36 species, comparing motor self-regulation across taxa. They concluded that absolute brain size predicts level of performance. The great apes were most successful. Only a few of the species tested were birds. Given birds' small brain size-in absolute terms-yet flexible behaviour, their motor self-regulation calls for closer study. Corvids exhibit some of the largest relative avian brain sizes-although small in absolute measure-as well as the most flexible cognition in the animal kingdom. We therefore tested ravens, New Caledonian crows and jackdaws in the so-called cylinder task. We found performance indistinguishable from that of great apes despite the much smaller brains. We found both absolute and relative brain volume to be a reliable predictor of performance within Aves. The complex cognition of corvids is often likened to that of great apes; our results show further that they share similar fundamental cognitive mechanisms.

HEAVY PRENATAL ALCOHOL EXPOSURE IS RELATED TO SMALLER CORPUS CALLOSUM IN NEWBORN MRI SCANS

PubMed Central

Jacobson, Sandra W.; Jacobson, Joseph L.; Molteno, Christopher D.; Warton, Christopher M. R.; Wintermark, Pia; Hoyme, H Eugene; De Jong, Greetje; Taylor, Paul; Warton, Fleur; Lindinger, Nadine M.; Carter, R. Colin; Dodge, Neil C.; Grant, Ellen; Warfield, Simon K.; Zöllei, Lilla; van der Kouwe, André J. W.; Meintjes, Ernesta M.

2017-01-01

Background MRI studies have consistently demonstrated disproportionately smaller corpus callosa in individuals with a history of prenatal alcohol exposure but have not previously examined the feasibility of detecting this effect in infants. Tissue segmentation of the newborn brain is challenging because analysis techniques developed for the adult brain are not directly transferable, and segmentation for cerebral morphometry is difficult in neonates, due to the latter’s incomplete myelination. This study is the first to use volumetric structural MRI to investigate prenatal alcohol exposure effects in newborns using manual tracing and to examine the cross-sectional area of the corpus callosum (CC). Methods 43 nonsedated infants born to 32 Cape Coloured heavy drinkers and 11 controls recruited prospectively during pregnancy were scanned using a custom-designed birdcage coil for infants, which increases signal-to-noise ratio almost two-fold compared to the standard head coil. Alcohol use was ascertained prospectively during pregnancy, and FASD diagnosis was conducted by expert dysmorphologists. Data were acquired using a multi-echo FLASH protocol adapted for newborns, and a knowledge-based procedure was used to hand-segment the neonatal brains. Results CC was disproportionately smaller in alcohol-exposed neonates than controls after controlling for intracranial volume. By contrast, CC area was unrelated to infant sex, gestational age, age at scan, or maternal smoking, marijuana, or methamphetamine use during pregnancy. Conclusions Given that midline craniofacial anomalies have been recognized as a hallmark of FAS in humans and animal models since this syndrome was first identified, the CC deficit identified here in newborns may support early identification of a range of midline structural impairments. Smaller CC during the newborn period may provide an early indicator of fetal alcohol-related cognitive deficits that have been linked to this critically important brain structure in childhood and adolescence. PMID:28247416

Smaller = Denser, and the Brain Knows It: Natural Statistics of Object Density Shape Weight Expectations

PubMed Central

Peters, Megan A. K.; Balzer, Jonathan; Shams, Ladan

2015-01-01

If one nondescript object’s volume is twice that of another, is it necessarily twice as heavy? As larger objects are typically heavier than smaller ones, one might assume humans use such heuristics in preparing to lift novel objects if other informative cues (e.g., material, previous lifts) are unavailable. However, it is also known that humans are sensitive to statistical properties of our environments, and that such sensitivity can bias perception. Here we asked whether statistical regularities in properties of liftable, everyday objects would bias human observers’ predictions about objects’ weight relationships. We developed state-of-the-art computer vision techniques to precisely measure the volume of everyday objects, and also measured their weight. We discovered that for liftable man-made objects, “twice as large” doesn’t mean “twice as heavy”: Smaller objects are typically denser, following a power function of volume. Interestingly, this “smaller is denser” relationship does not hold for natural or unliftable objects, suggesting some ideal density range for objects designed to be lifted. We then asked human observers to predict weight relationships between novel objects without lifting them; crucially, these weight predictions quantitatively match typical weight relationships shown by similarly-sized objects in everyday environments. These results indicate that the human brain represents the statistics of everyday objects and that this representation can be quantitatively abstracted and applied to novel objects. Finally, that the brain possesses and can use precise knowledge of the nonlinear association between size and weight carries important implications for implementation of forward models of motor control in artificial systems. PMID:25768977

Sex differences in the correlation of emotional control and amygdala volumes in adolescents.

PubMed

Blanton, Rebecca E; Chaplin, Tara M; Sinha, Rajita

2010-10-06

We examined male and female adolescents (8-18 years of age) that were scanned with structural brain MRI and looked for a correlation between volume of the right or the left amygdala and parent-reported ability of emotional control. A sex difference was found in the correlation between emotional control and the corrected volume of the left amygdala (that is the amygdala volume adjusted for total cranial volume). In girls, smaller left amygdala volumes were associated with better emotional control. In boys, larger left amygdala volumes were associated with better emotional control. These findings suggest that healthy girls and boys show a difference in the correlation between parental reports of emotional control and the left amygdala volume.

No significant brain volume decreases or increases in adults with high-functioning autism spectrum disorder and above average intelligence: a voxel-based morphometric study.

PubMed

Riedel, Andreas; Maier, Simon; Ulbrich, Melanie; Biscaldi, Monica; Ebert, Dieter; Fangmeier, Thomas; Perlov, Evgeniy; Tebartz van Elst, Ludger

2014-08-30

Autism spectrum disorder (ASD) is increasingly being recognized as an important issue in adult psychiatry and psychotherapy. High intelligence indicates overall good brain functioning and might thus present a particularly good opportunity to study possible cerebral correlates of core autistic features in terms of impaired social cognition, communication skills, the need for routines, and circumscribed interests. Anatomical MRI data sets for 30 highly intelligent patients with high-functioning autism and 30 pairwise-matched control subjects were acquired and analyzed with voxel-based morphometry. The gray matter volume of the pairwise-matched patients and the controls did not differ significantly. When correcting for total brain volume influences, the patients with ASD exhibited smaller left superior frontal volumes on a trend level. Heterogeneous volumetric findings in earlier studies might partly be explained by study samples biased by a high inclusion rate of secondary forms of ASD, which often go along with neuronal abnormalities. Including only patients with high IQ scores might have decreased the influence of secondary forms of ASD and might explain the absence of significant volumetric differences between the patients and the controls in this study. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Mapping the brain correlates of borderline personality disorder: A functional neuroimaging meta-analysis of resting state studies.

PubMed

Visintin, Eleonora; De Panfilis, Chiara; Amore, Mario; Balestrieri, Matteo; Wolf, Robert Christian; Sambataro, Fabio

2016-11-01

Altered intrinsic function of the brain has been implicated in Borderline Personality Disorder (BPD). Nonetheless, imaging studies have yielded inconsistent alterations of brain function. To investigate the neural activity at rest in BPD, we conducted a set of meta-analyses of brain imaging studies performed at rest. A total of seven functional imaging studies (152 patients with BPD and 147 control subjects) were combined using whole-brain Signed Differential Mapping meta-analyses. Furthermore, two conjunction meta-analyses of neural activity at rest were also performed: with neural activity changes during emotional processing, and with structural differences, respectively. We found altered neural activity in the regions of the default mode network (DMN) in BPD. Within the regions of the midline core DMN, patients with BPD showed greater activity in the anterior as well as in the posterior midline hubs relative to controls. Conversely, in the regions of the dorsal DMN they showed reduced activity compared to controls in the right lateral temporal complex and bilaterally in the orbitofrontal cortex. Increased activity in the precuneus was observed both at rest and during emotional processing. Reduced neural activity at rest in lateral temporal complex was associated with smaller volume of this area. Heterogeneity across imaging studies. Altered activity in the regions of the midline core as well as of the dorsal subsystem of the DMN may reflect difficulties with interpersonal and affective regulation in BPD. These findings suggest that changes in spontaneous neural activity could underlie core symptoms in BPD. Copyright © 2016 Elsevier B.V. All rights reserved.

A Systematic and Meta-analytic Review of Neural Correlates of Functional Outcome in Schizophrenia.

PubMed

Wojtalik, Jessica A; Smith, Matthew J; Keshavan, Matcheri S; Eack, Shaun M

2017-10-21

Individuals with schizophrenia are burdened with impairments in functional outcome, despite existing interventions. The lack of understanding of the neurobiological correlates supporting adaptive function in the disorder is a significant barrier to developing more effective treatments. This research conducted a systematic and meta-analytic review of all peer-reviewed studies examining brain-functional outcome relationships in schizophrenia. A total of 53 (37 structural and 16 functional) brain imaging studies examining the neural correlates of functional outcome across 1631 individuals with schizophrenia were identified from literature searches in relevant databases occurring between January, 1968 and December, 2016. Study characteristics and results representing brain-functional outcome relationships were systematically extracted, reviewed, and meta-analyzed. Results indicated that better functional outcome was associated with greater fronto-limbic and whole brain volumes, smaller ventricles, and greater activation, especially during social cognitive processing. Thematic observations revealed that the dorsolateral prefrontal cortex, anterior cingulate, posterior cingulate, parahippocampal gyrus, superior temporal sulcus, and cerebellum may have role in functioning. The neural basis of functional outcome and disability is infrequently studied in schizophrenia. While existing evidence is limited and heterogeneous, these findings suggest that the structural and functional integrity of fronto-limbic brain regions is consistently related to functional outcome in individuals with schizophrenia. Further research is needed to understand the mechanisms and directionality of these relationships, and the potential for identifying neural targets to support functional improvement. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Reduced White Matter Connectivity in the Corpus Callosum of Children with Tourette Syndrome

ERIC Educational Resources Information Center

Plessen, Kerstin J.; Gruner, Renate; Lundervold, Arvid; Hirsch, Jochen G.; Xu, Dongrong; Bansal, Ravi; Hammar, Asa; Lundervold, Astri J.; Wentzel-Larsen, Tore; Lie, Stein Atle; Gass, Achim; Peterson, Bradley S.; Hugdahl, Kenneth

2006-01-01

Background: Brain imaging studies have revealed anatomical anomalies in the brains of individuals with Tourette syndrome (TS). Prefrontal regions have been found to be larger and the corpus callosum (CC) area smaller in children and young adults with TS compared with healthy control subjects, and these anatomical features have been understood to…

Increased Testosterone Decreases Medial Cortical Volume and Neurogenesis in Territorial Side-Blotched Lizards (Uta stansburiana)

PubMed Central

LaDage, Lara D.; Roth, Timothy C.; Downs, Cynthia J.; Sinervo, Barry; Pravosudov, Vladimir V.

2017-01-01

Variation in an animal's spatial environment can induce variation in the hippocampus, an area of the brain involved in spatial cognitive processing. Specifically, increased spatial area use is correlated with increased hippocampal attributes, such as volume and neurogenesis. In the side-blotched lizard (Uta stansburiana), males demonstrate alternative reproductive tactics and are either territorial—defending large, clearly defined spatial boundaries—or non-territorial—traversing home ranges that are smaller than the territorial males' territories. Our previous work demonstrated cortical volume (reptilian hippocampal homolog) correlates with these spatial niches. We found that territorial holders have larger medial cortices than non-territory holders, yet these differences in the neural architecture demonstrated some degree of plasticity as well. Although we have demonstrated a link among territoriality, spatial use, and brain plasticity, the mechanisms that underlie this relationship are unclear. Previous studies found that higher testosterone levels can induce increased use of the spatial area and can cause an upregulation in hippocampal attributes. Thus, testosterone may be the mechanistic link between spatial area use and the brain. What remains unclear, however, is if testosterone can affect the cortices independent of spatial experiences and whether testosterone differentially interacts with territorial status to produce the resultant cortical phenotype. In this study, we compared neurogenesis as measured by the total number of doublecortin-positive cells and cortical volume between territorial and non-territorial males supplemented with testosterone. We found no significant differences in the number of doublecortin-positive cells or cortical volume among control territorial, control non-territorial, and testosterone-supplemented non-territorial males, while testosterone-supplemented territorial males had smaller medial cortices containing fewer doublecortin-positive cells. These results demonstrate that testosterone can modulate medial cortical attributes outside of differential spatial processing experiences but that territorial males appear to be more sensitive to alterations in testosterone levels compared with non-territorial males. PMID:28298883

Cloning and expression of hepatic synaptotagmin 1 in mouse.

PubMed

Sancho-Knapik, Sara; Guillén, Natalia; Osada, Jesús

2015-05-15

Mouse hepatic synaptotagmin 1 (SYT1) cDNA was cloned, characterized and compared to the brain one. The hepatic transcript was 1807 bp in length, smaller than the brain, and only encoded by 9 of 11 gene exons. In this regard, 5'-and 3'-untranslated regions were 66 and 476 bp, respectively; the open reading frame of 1266 bp codified for a protein of 421 amino acids, identical to the brain, with a predicted molecular mass of 47.4 kDa and highly conserved across different species. Immunoblotting of protein showed two isoforms of higher molecular masses than the theoretical prediction based on amino acid sequence suggesting posttranslational modifications. Subcellular distribution of protein isoforms corresponded to plasma membrane, lysosomes and microsomes and was identical between the brain and liver. Nonetheless, the highest molecular weight isoform was smaller in the liver, irrespective of subcellular location. Quantitative mRNA tissue distribution showed that it was widely expressed and that the highest values corresponded to the brain, followed by the liver, spleen, abdominal fat, intestine and skeletal muscle. These findings indicate tissue-specific splicing of the gene and posttranslational modification and the variation in expression in the different tissues might suggest a different requirement of SYT1 for the specific function in each organ. Copyright © 2015 Elsevier B.V. All rights reserved.

Individual differences in the dominance of interhemispheric connections predict cognitive ability beyond sex and brain size.

PubMed

Martínez, Kenia; Janssen, Joost; Pineda-Pardo, José Ángel; Carmona, Susanna; Román, Francisco Javier; Alemán-Gómez, Yasser; Garcia-Garcia, David; Escorial, Sergio; Quiroga, María Ángeles; Santarnecchi, Emiliano; Navas-Sánchez, Francisco Javier; Desco, Manuel; Arango, Celso; Colom, Roberto

2017-07-15

Global structural brain connectivity has been reported to be sex-dependent with women having increased interhemispheric connectivity (InterHc) and men having greater intrahemispheric connectivity (IntraHc). However, (a) smaller brains show greater InterHc, (b) larger brains show greater IntraHc, and (c) women have, on average, smaller brains than men. Therefore, sex differences in brain size may modulate sex differences in global brain connectivity. At the behavioural level, sex-dependent differences in connectivity are thought to contribute to men-women differences in spatial and verbal abilities. But this has never been tested at the individual level. The current study assessed whether individual differences in global structural connectome measures (InterHc, IntraHc and the ratio of InterHc relative to IntraHc) predict spatial and verbal ability while accounting for the effect of sex and brain size. The sample included forty men and forty women, who did neither differ in age nor in verbal and spatial latent components defined by a broad battery of tests and tasks. High-resolution T 1 -weighted and diffusion-weighted images were obtained for computing brain size and reconstructing the structural connectome. Results showed that men had higher IntraHc than women, while women had an increased ratio InterHc/IntraHc. However, these sex differences were modulated by brain size. Increased InterHc relative to IntraHc predicted higher spatial and verbal ability irrespective of sex and brain size. The positive correlations between the ratio InterHc/IntraHc and the spatial and verbal abilities were confirmed in 1000 random samples generated by bootstrapping. Therefore, sex differences in global structural connectome connectivity were modulated by brain size and did not underlie sex differences in verbal and spatial abilities. Rather, the level of dominance of InterHc over IntraHc may be associated with individual differences in verbal and spatial abilities in both men and women. Copyright © 2017 Elsevier Inc. All rights reserved.

Inter-Relations of Orthostatic Blood Pressure Change, Aortic Stiffness, and Brain Structure and Function in Young Adults.

PubMed

Cooper, Leroy L; Himali, Jayandra J; Torjesen, Alyssa; Tsao, Connie W; Beiser, Alexa; Hamburg, Naomi M; DeCarli, Charles; Vasan, Ramachandran S; Seshadri, Sudha; Pase, Matthew P; Mitchell, Gary F

2017-08-17

Relations of orthostatic change in blood pressure with brain structure and function have not been studied thoroughly, particularly in younger, healthier individuals. Elucidation of factors that contribute to early changes in brain integrity may lead to development of interventions that delay or prevent cognitive impairment. In a sample of the Framingham Heart Study Third Generation (N=2119; 53% women; mean age±SD, 47±8 years), we assessed orthostatic change in mean arterial pressure (MAP), aortic stiffness (carotid-femoral pulse wave velocity), neuropsychological function, and markers of subclinical brain injury on magnetic resonance imaging. Multivariable regression analyses were used to assess relations between orthostatic change in MAP and brain structural and neuropsychological outcomes. Greater orthostatic increase in MAP on standing was related to better Trails B-A performance among participants aged <49 years (β±SE, 0.062±0.029; P =0.031) and among participants with carotid-femoral pulse wave velocity <6.9 m/s (β±SE, 0.063±0.026; P =0.016). This relation was not significant among participants who were older or had stiffer aortas. Conversely, greater orthostatic increase in MAP was related to larger total brain volume among older participants (β±SE, 0.065±0.029; P =0.023) and among participants with carotid-femoral pulse wave velocity ≥6.9 m/s (β±SE, 0.078±0.031; P =0.011). Blunted orthostatic increase in MAP was associated with smaller brain volume among participants who were older or had stiffer aortas and with poorer executive function among persons who were younger or who had more-elastic aortas. Our findings suggest that the brain is sensitive to orthostatic change in MAP, with results dependent on age and aortic stiffness. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

2017 Military Supplement: Dodecafluoropentane Emulsion (Ddfpe) as a Resuscitation Fluid for Treatment of Hemorrhagic Shock and Traumatic Brain Injury: A Review.

PubMed

Graham, Kaitlin; Moon-Massat, Paula F; Unger, Evan C

2017-11-15

Dodecafluoropentane emulsion (DDFPe) is a novel nanotechnology for oxygen delivery with therapeutic potential for hemorrhagic shock and/or traumatic brain injury (TBI). DDFPe demonstrates efficacy at smaller doses than previously tested perfluorocarbon oxygen therapeutics. This smaller dose potentially eliminates toxicities exhibited by previous oxygen therapeutics, while anti-inflammatory properties of DDFPe may alleviate damage from ischemia reperfusion injury. This mini-review summarizes our progress in developing a battle-field ready product to prevent combat death due to hemorrhagic shock and/or TBI. Preclinical studies, for both indications, show promising effects of DDFPe as a resuscitation fluid. DDFPe may become a part of the toolkit for tactical healthcare professionals in battlefield and domestic emergency medicine.

The arteries of the base of the brain in the N. American mink (Mustela vison (Brisson, 1756)).

PubMed

Gościcka, D; Stankiewicz, W; Szpinda, M

1995-01-01

110 brains of the N. American mink were studied for the arteries of the base of the brain, using the anatomical method and Digital Imaging Analysis. Two arterial circles were isolated: the larger cerebral circle (CC) and the smaller medullar circle (MC). These were connected by the basal artery of the brain. We found that in CC, its left part was larger, whereas in MC, it was the right part that was larger. Also, the capacity was larger in the caudal part of MC than in its rostral part.

Subclinical cerebrovascular disease inversely associates with learning ability

PubMed Central

Glazer, Hilary; Dong, Chuanhui; Yoshita, Mitsuhiro; Rundek, Tatjana; Elkind, Mitchell S.V.; Sacco, Ralph L.; DeCarli, Charles; Stern, Yaakov

2015-01-01

Objective: Memory has been examined in subjects with imaging markers of cerebrovascular disease, but learning has been less well studied. We examined the relationship among subclinical cerebrovascular disease, cerebral volumes, and verbal learning in an ethnically and racially diverse community sample. Methods: A clinically stroke-free subset of Northern Manhattan Study participants underwent cognitive testing and brain MRI with quantification of white matter hyperintensity volume (WMHV) and total cerebral volume (TCV) using semiautomated segmentation. We used generalized linear regression and mixed models to examine the association between imaging findings and verbal learning. Results: There were 1,272 participants (61% women, mean age 70 ± 9 years). Participants with greater WMHV and smaller TCV remembered fewer total words on a list-learning task (β = −0.83 per SD change in WMHV, 95% confidence interval [CI] = −1.22 to −0.45, p < 0.0001; and β = 0.48 per SD change in TCV, 95% CI = 0.05 to 0.90, p = 0.03, respectively). Subclinical brain infarction (SBI) was not associated with total words learned (β = −0.04, 95% CI = −1.08 to 1.00, p = 0.94). Those with greater WMHV had increased odds of a flatter learning slope. After excluding participants with SBI, the association between total words learned and WMHV remained significant. All measurements were adjusted for age, education, race/ethnicity, medical insurance status, and the presence of SBI. Conclusions: White matter hyperintensities, a marker of cerebral small vessel disease, may have an impact on learning slope. This suggests that verbal learning performance can be incorporated into neuropsychological measures for vascular cognitive impairment and that cerebrovascular disease discovered on imaging affects the ability to learn new information. PMID:26002489

Cerebral tuberculomas – A clinical challenge

PubMed Central

Monteiro, Regina; Carneiro, José Carlos; Costa, Claúdia; Duarte, Raquel

2013-01-01

Cerebral tuberculomas are a rare and serious form of tuberculosis (TB) due to the haematogenous spread of Mycobacterium Tuberculosis (MT). Symptoms and radiologic features are nonspecific, leading sometimes to misdiagnosis. Anti-TB drugs are essential for the successful treatment of cerebral tuberculomas but there is no agreement regarding the duration of therapy. The authors present a case of a 55 years old male, presented to the emergency room with sudden onset of diplopia. Cerebral computerized tomography revealed multiple brain lesions, with contrast enhancement and peri-lesional oedema. The patient was HIV negative and because of previous malignancy the first suspicion was metastatic disease. Cultural exam of the bronchial wash showed MT sensitive to all first-line drugs. The patient started antituberculosis treatment with 4 drugs (HRZE) for 2 months, followed by maintenance therapy (HR). Treatment was prolonged for 24 months because at 12th and 18th months of treatment one of the brain lesions, although significantly smaller, still showed contrast enhancement. Even though it is not clear if contrast enhancement lesions represent active lesions or just inflammation, continuing treatment until total resolution of the tuberculomas is probably prudent. PMID:26029627

Sex differences in the relationship between planum temporale asymmetry and corpus callosum morphology in chimpanzees (Pan troglodytes): A combined MRI and DTI analysis.

PubMed

Hopkins, William D; Hopkins, Anna M; Misiura, Maria; Latash, Elitaveta M; Mareno, Mary Catherine; Schapiro, Steven J; Phillips, Kimberley A

2016-12-01

Increases brain size has been hypothesized to be inversely associated with the expression of behavioral and brain asymmetries within and between species. We tested this hypothesis by analyzing the relation between asymmetries in the planum temporale (PT) and different measures of the corpus callosum (CC) including surface area, streamline count as measured from diffusion tensor imaging, fractional anisotropy values and the ratio in the number of fibers to surface area in a sample of chimpanzees. We found that chimpanzees with larger PT asymmetries in absolute terms had smaller CC surface areas, fewer streamlines and a smaller ratio of fibers to surface area. These results were largely specific to male but not female chimpanzees. Our results partially support the hypothesis that brain asymmetries are linked to variation in corpus callosum morphology, although these associations may be sex-dependent. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tracking Brain Development and Dimensional Psychiatric Symptoms in Children: A Longitudinal Population-Based Neuroimaging Study.

PubMed

Muetzel, Ryan L; Blanken, Laura M E; van der Ende, Jan; El Marroun, Hanan; Shaw, Philip; Sudre, Gustavo; van der Lugt, Aad; Jaddoe, Vincent W V; Verhulst, Frank C; Tiemeier, Henning; White, Tonya

2018-01-01

Psychiatric symptomatology during childhood predicts persistent mental illness later in life. While neuroimaging methodologies are routinely applied cross-sectionally to the study of child and adolescent psychopathology, the nature of the relationship between childhood symptoms and the underlying neurodevelopmental processes remains unclear. The authors used a prospective population-based cohort to delineate the longitudinal relationship between childhood psychiatric problems and brain development. A total of 845 children participated in the study. Psychiatric symptoms were measured with the parent-rated Child Behavior Checklist at ages 6 and 10. MRI data were collected at ages 8 and 10. Cross-lagged panel models and linear mixed-effects models were used to determine the associations between psychiatric symptom ratings and quantitative anatomic and white matter microstructural measures over time. Higher ratings for externalizing and internalizing symptoms at baseline predicted smaller increases in both subcortical gray matter volume and global fractional anisotropy over time. The reverse relationship did not hold; thus, baseline measures of gray matter and white matter were not significantly related to changes in symptom ratings over time. Children presenting with behavioral problems at an early age show differential subcortical and white matter development. Most neuroimaging models tend to explain brain differences observed in psychopathology as an underlying (causal) neurobiological substrate. However, the present work suggests that future neuroimaging studies showing effects that are pathogenic in nature should additionally explore the possibility of the downstream effects of psychopathology on the brain.

Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder.

PubMed

Henje Blom, E; Han, L K M; Connolly, C G; Ho, T C; Lin, J; LeWinn, K Z; Simmons, A N; Sacchet, M D; Mobayed, N; Luna, M E; Paulus, M; Epel, E S; Blackburn, E H; Wolkowitz, O M; Yang, T T

2015-11-10

Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.

Hippocampus and amygdala volumes in parents of children with autistic disorder.

PubMed

Rojas, Donald C; Smith, J Allegra; Benkers, Tara L; Camou, Suzanne L; Reite, Martin L; Rogers, Sally J

2004-11-01

Structural and functional abnormalities in the medial temporal lobe, particularly the hippocampus and amygdala, have been described in people with autism. The authors hypothesized that parents of children with a diagnosis of autistic disorder would show similar changes in these structures. Magnetic resonance imaging scans were performed in 17 biological parents of children with a diagnosis of DSM-IV autistic disorder. The scans were compared with scans from 15 adults with autistic disorder and 17 age-matched comparison subjects with no personal or familial history of autism. The volumes of the hippocampus, amygdala, and total brain were measured in all participants. The volume of the left hippocampus was larger in both the parents of children with autistic disorder and the adults with autistic disorder, relative to the comparison subjects. The hippocampus was significantly larger in the adults with autistic disorder than in the parents of children with autistic disorder. The left amygdala was smaller in the adults with autistic disorder, relative to the other two groups. No differences in total brain volume were observed between the three groups. The finding of larger hippocampal volume in autism is suggestive of abnormal early neurodevelopmental processes but is partly consistent with only one prior study and contradicts the findings of several others. The finding of larger hippocampal volume for the parental group suggests a potential genetic basis for hippocampal abnormalities in autism.

Total Brain Death and the Integration of the Body Required of a Human Being

PubMed Central

Lee, Patrick

2016-01-01

I develop and refine an argument for the total brain death criterion of death previously advanced by Germain Grisez and me: A human being is essentially a rational animal, and so must have a radical capacity for rational operations. For rational animals, conscious sensation is a pre-requisite for rational operation. But total brain death results in the loss of the radical capacity for conscious sensation, and so also for rational operations. Hence, total brain death constitutes a substantial change—the ceasing to be of the human being. Objections are considered, including the objection that total brain death need not result in the loss of capacity for sensation, and that damage to the brain less than total brain death can result in loss of capacity for rational operations. PMID:27097647

Visceral fat is associated with brain structure independent of human immunodeficiency virus infection status.

PubMed

Lake, Jordan E; Popov, Mikhail; Post, Wendy S; Palella, Frank J; Sacktor, Ned; Miller, Eric N; Brown, Todd T; Becker, James T

2017-06-01

The combined effects of human immunodeficiency virus (HIV), obesity, and elevated visceral adipose tissue (VAT) on brain structure are unknown. In a cross-sectional analysis of Multicenter AIDS Cohort Study (MACS) participants, we determined associations between HIV serostatus, adiposity, and brain structure. Men (133 HIV+, 84 HIV-) in the MACS Cardiovascular 2 and magnetic resonance imaging (MRI) sub-studies with CT-quantified VAT and whole brain MRI measured within 1 year were assessed. Voxel-based morphometry analyzed brain volumes. Men were stratified by elevated (eVAT, ≥100cm 2 ) or "normal" (nVAT, <100cm 2 ) VAT. Forward stepwise modeling determined associations between clinical and demographic variables and regional brain volumes. eVAT was present in 67% of men. Groups were similar in age and education, but eVAT men were more likely to be HIV+ and have hypertension, diabetes mellitus, body mass index >25 kg/m 2 , smaller gray and white matter volumes, and larger cerebrospinal fluid volume than nVAT men. In multivariate analysis, hypertension, higher adiponectin, higher interleukin-6, age, diabetes mellitus, higher body mass index, and eVAT were associated with brain atrophy (p < 0.05, ordered by increasing strength of association), but HIV serostatus and related factors were generally not. No interactions were observed. Greater VAT was associated with smaller bilateral posterior hippocampus and left mesial temporal lobe and temporal stem white matter volume. Traditional risk factors are more strongly associated with brain atrophy than HIV serostatus, with VAT having the strongest association. However, HIV+ MACS men had disproportionately greater VAT, suggesting the risk for central nervous system effects may be amplified in this population.

Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings.

PubMed

Bralten, Janita; Greven, Corina U; Franke, Barbara; Mennes, Maarten; Zwiers, Marcel P; Rommelse, Nanda N J; Hartman, Catharina; van der Meer, Dennis; O'Dwyer, Laurence; Oosterlaan, Jaap; Hoekstra, Pieter J; Heslenfeld, Dirk; Arias-Vasquez, Alejandro; Buitelaar, Jan K

2016-06-01

Data on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to detect structural brain alterations in adolescents and young adults with ADHD compared with healthy controls. We examined whether these alterations were also found in their unaffected siblings, using a uniquely large sample. We performed voxel-based morphometry analyses on MRI scans of patients with ADHD, their unaffected siblings and typically developing controls. We identified brain areas that differed between participants with ADHD and controls and investigated whether these areas were different in unaffected siblings. Influences of medication use, age, sex and IQ were considered. Our sample included 307 patients with ADHD, 169 unaffected siblings and 196 typically developing controls (mean age 17.2 [range 8-30] yr). Compared with controls, participants with ADHD had significantly smaller grey matter volume in 5 clusters located in the precentral gyrus, medial and orbitofrontal cortex, and (para)cingulate cortices. Unaffected siblings showed intermediate volumes significantly different from controls in 4 of these clusters (all except the precentral gyrus). Medication use, age, sex and IQ did not have an undue influence on the results. Our sample was heterogeneous, most participants with ADHD were taking medication, and the comparison was cross-sectional. Brain areas involved in decision making, motivation, cognitive control and motor functioning were smaller in participants with ADHD than in controls. Investigation of unaffected siblings indicated familiality of 4 of the structural brain differences, supporting their potential in molecular genetic analyses in ADHD research.

Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings

PubMed Central

Bralten, Janita; Greven, Corina U.; Franke, Barbara; Mennes, Maarten; Zwiers, Marcel P.; Rommelse, Nanda N.J.; Hartman, Catharina; van der Meer, Dennis; O’Dwyer, Laurence; Oosterlaan, Jaap; Hoekstra, Pieter J.; Heslenfeld, Dirk; Arias-Vasquez, Alejandro; Buitelaar, Jan K.

2016-01-01

Background Data on structural brain alterations in patients with attention-deficit/hyperactivity disorder (ADHD) have been inconsistent. Both ADHD and brain volumes have a strong genetic loading, but whether brain alterations in patients with ADHD are familial has been underexplored. We aimed to detect structural brain alterations in adolescents and young adults with ADHD compared with healthy controls. We examined whether these alterations were also found in their unaffected siblings, using a uniquely large sample. Methods We performed voxel-based morphometry analyses on MRI scans of patients with ADHD, their unaffected siblings and typically developing controls. We identified brain areas that differed between participants with ADHD and controls and investigated whether these areas were different in unaffected siblings. Influences of medication use, age, sex and IQ were considered. Results Our sample included 307 patients with ADHD, 169 unaffected siblings and 196 typically developing controls (mean age 17.2 [range 8–30] yr). Compared with controls, participants with ADHD had significantly smaller grey matter volume in 5 clusters located in the precentral gyrus, medial and orbitofrontal cortex, and (para)cingulate cortices. Unaffected siblings showed intermediate volumes significantly different from controls in 4 of these clusters (all except the precentral gyrus). Medication use, age, sex and IQ did not have an undue influence on the results. Limitations Our sample was heterogeneous, most participants with ADHD were taking medication, and the comparison was cross-sectional. Conclusion Brain areas involved in decision making, motivation, cognitive control and motor functioning were smaller in participants with ADHD than in controls. Investigation of unaffected siblings indicated familiality of 4 of the structural brain differences, supporting their potential in molecular genetic analyses in ADHD research. PMID:26679925

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.

Construction of brain atlases based on a multi-center MRI dataset of 2020 Chinese adults

PubMed Central

Liang, Peipeng; Shi, Lin; Chen, Nan; Luo, Yishan; Wang, Xing; Liu, Kai; Mok, Vincent CT; Chu, Winnie CW; Wang, Defeng; Li, Kuncheng

2015-01-01

Despite the known morphological differences (e.g., brain shape and size) in the brains of populations of different origins (e.g., age and race), the Chinese brain atlas is less studied. In the current study, we developed a statistical brain atlas based on a multi-center high quality magnetic resonance imaging (MRI) dataset of 2020 Chinese adults (18–76 years old). We constructed 12 Chinese brain atlas from the age 20 year to the age 75 at a 5 years interval. New Chinese brain standard space, coordinates, and brain area labels were further defined. The new Chinese brain atlas was validated in brain registration and segmentation. It was found that, as contrast to the MNI152 template, the proposed Chinese atlas showed higher accuracy in hippocampus segmentation and relatively smaller shape deformations during registration. These results indicate that a population-specific time varying brain atlas may be more appropriate for studies involving Chinese populations. PMID:26678304

A Multiscale Parallel Computing Architecture for Automated Segmentation of the Brain Connectome

PubMed Central

Knobe, Kathleen; Newton, Ryan R.; Schlimbach, Frank; Blower, Melanie; Reid, R. Clay

2015-01-01

Several groups in neurobiology have embarked into deciphering the brain circuitry using large-scale imaging of a mouse brain and manual tracing of the connections between neurons. Creating a graph of the brain circuitry, also called a connectome, could have a huge impact on the understanding of neurodegenerative diseases such as Alzheimer’s disease. Although considerably smaller than a human brain, a mouse brain already exhibits one billion connections and manually tracing the connectome of a mouse brain can only be achieved partially. This paper proposes to scale up the tracing by using automated image segmentation and a parallel computing approach designed for domain experts. We explain the design decisions behind our parallel approach and we present our results for the segmentation of the vasculature and the cell nuclei, which have been obtained without any manual intervention. PMID:21926011

Cortical thinness and volume differences associated with marijuana abuse in emerging adults.

PubMed

Mashhoon, Y; Sava, S; Sneider, J T; Nickerson, L D; Silveri, M M

2015-10-01

The prevalence of marijuana (MJ) use among youth and its legalization for medical or recreational use has intensified public health endeavors of understanding MJ effects on brain structure and function. Studies indicate that MJ use is related to impaired cognitive performance, and altered functional brain activation and chemistry in adolescents and adults, but MJ effects on brain morphology in emerging adults are less understood. Fifteen MJ users (age 21.8±3.6, 2 females) and 15 non-user (NU) participants (age 22.3±3.5, 2 females) were included, demographically matched on age, education and alcohol use. High-resolution structural MR images were acquired at 3Tesla. Cortical thickness (CT) and volumetric analyses were performed using Freesurfer. A priori regions of interest (ROI) included orbitofrontal and cingulate cortices, amygdala, hippocampus and thalamus. Whole brain CT analysis did not result in significant group differences in a priori ROIs but revealed MJ users had significantly less CT (i.e., thinness) in right fusiform gyrus (rFG) compared to NU (p<0.05). Thalamic volume was significantly smaller in MJ users compared to NU (right, p=0.05; left, p=0.01) and associated with greater non-planning (p<0.01) and overall impulsivity (p=0.04). There were no other group differences. RFG cortical thinness and smaller thalamic volume in emerging adults is associated with MJ abuse. Furthermore, smaller thalamic volume associated with greater impulsivity contributes to growing evidence that the thalamus is neurobiologically perturbed by MJ use. Collectively, altered thalamic and rFG structural integrity may interfere with their known roles in regulating visuoperceptual and object information processing. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Smaller Cerebellar Growth and Poorer Neurodevelopmental Outcomes in Very Preterm Infants Exposed to Neonatal Morphine.

PubMed

Zwicker, Jill G; Miller, Steven P; Grunau, Ruth E; Chau, Vann; Brant, Rollin; Studholme, Colin; Liu, Mengyuan; Synnes, Anne; Poskitt, Kenneth J; Stiver, Mikaela L; Tam, Emily W Y

2016-05-01

To examine the relationship between morphine exposure and growth of the cerebellum and cerebrum in very preterm neonates from early in life to term-equivalent age, as well as to examine morphine exposure and brain volumes in relation to neurodevelopmental outcomes at 18 months corrected age (CA). A prospective cohort of 136 very preterm neonates (24-32 weeks gestational age) was serially scanned with magnetic resonance imaging near birth and at term-equivalent age for volumetric measurements of the cerebellum and cerebrum. Motor outcomes were assessed with the Peabody Developmental Motor Scales, Second Edition and cognitive outcomes with the Bayley Scales of Infant and Toddler Development, Third Edition at 18 months CA. Generalized least squares models and linear regression models were used to assess relationships between morphine exposure, brain volumes, and neurodevelopmental outcomes. A 10-fold increase in morphine exposure was associated with a 5.5% decrease in cerebellar volume, after adjustment for multiple clinical confounders and total brain volume (P = .04). When infants exposed to glucocorticoids were excluded, the association of morphine was more pronounced, with an 8.1% decrease in cerebellar volume. Morphine exposure was not associated with cerebral volume (P = .30). Greater morphine exposure also predicted poorer motor (P < .001) and cognitive outcomes (P = .006) at 18 months CA, an association mediated, in part, by slower brain growth. Morphine exposure in very preterm neonates is independently associated with impaired cerebellar growth in the neonatal period and poorer neurodevelopmental outcomes in early childhood. Alternatives to better manage pain in preterm neonates that optimize brain development and functional outcomes are urgently needed. Copyright © 2016 Elsevier Inc. All rights reserved.

Amnestic MCI Patients' Perspectives toward Disclosure of Amyloid PET Results in a Research Context.

PubMed

Vanderschaeghe, Gwendolien; Schaeverbeke, Jolien; Vandenberghe, Rik; Dierickx, Kris

2017-01-01

Researchers currently are not obligated to share individual research results (IRR) with participants. This non-disclosure policy has been challenged on the basis of participants' rights to be aware and in control of their personal medical information. Here, we determined how patients view disclosure of research PET results of brain amyloid and why they believe it is advantageous or disadvantageous to disclose. As a part of a larger diagnostic trial, we conducted semi-structured interviews with patients with amnestic Mild Cognitive Impairment (aMCI). Participants had the option to receive their brain amyloid PET scan result (i.e., their IRR). Interviews were conducted before they received their IRR. A total of 38 aMCI patients (100% of study participants) wanted to know their IRR. The two most frequently mentioned reasons for choosing IRR disclosure were to better understand their brain health status and to be better able to make informed decisions about future personal arrangements (e.g., inheritance tax, moving into a smaller house, end-of-life decisions, etc.). Emotional risk was mentioned as the primary disadvantage of knowing one's IRR. On the other hand, non-disclosure was considered to be emotionally difficult also, as patients would be uncertain about their future health condition. Many patients diagnosed clinically with aMCI want to know their brain amyloid test results, even though this knowledge may be disadvantageous to them. Knowing what is going on with their health and the ability to make informed decisions about their future were the two principal advantages mentioned for obtaining their amyloid PET results. Because of the overwhelming consensus of aMCI patients was to disclose their brain amyloid PET scan results, researchers should strongly consider releasing this information to research subjects.

The impact of ADHD persistence, recent cannabis use, and age of regular cannabis use onset on subcortical volume and cortical thickness in young adults.

PubMed

Lisdahl, Krista M; Tamm, Leanne; Epstein, Jeffery N; Jernigan, Terry; Molina, Brooke S G; Hinshaw, Stephen P; Swanson, James M; Newman, Erik; Kelly, Clare; Bjork, James M

2016-04-01

Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Association of Serum Vitamin D with the Risk of Incident Dementia and Subclinical Indices of Brain Aging: The Framingham Heart Study.

PubMed

Karakis, Ioannis; Pase, Matthew P; Beiser, Alexa; Booth, Sarah L; Jacques, Paul F; Rogers, Gail; DeCarli, Charles; Vasan, Ramachandran S; Wang, Thomas J; Himali, Jayandra J; Annweiler, Cedric; Seshadri, Sudha

2016-01-01

Identifying nutrition- and lifestyle-based risk factors for cognitive impairment and dementia may aid future primary prevention efforts. We aimed to examine the association of serum vitamin D levels with incident all-cause dementia, clinically characterized Alzheimer's disease (AD), MRI markers of brain aging, and neuropsychological function. Framingham Heart Study participants had baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations measured between 1986 and 2001. Vitamin D status was considered both as a continuous variable and dichotomized as deficient (<10 ng/mL), or at the cohort-specific 20th and 80th percentiles. Vitamin D was related to the 9-year risk of incident dementia (n = 1663), multiple neuropsychological tests (n = 1291) and MRI markers of brain volume, white matter hyperintensities and silent cerebral infarcts (n = 1139). In adjusted models, participants with vitamin D deficiency (n = 104, 8% of the cognitive sample) displayed poorer performance on Trail Making B-A (β= -0.03 to -0.05±0.02) and the Hooper Visual Organization Test (β= -0.09 to -0.12±0.05), indicating poorer executive function, processing speed, and visuo-perceptual skills. These associations remained when vitamin D was examined as a continuous variable or dichotomized at the cohort specific 20th percentile. Vitamin D deficiency was also associated with lower hippocampal volumes (β= -0.01±0.01) but not total brain volume, white matter hyperintensities, or silent brain infarcts. No association was found between vitamin D deficiency and incident all-cause dementia or clinically characterized AD. In this large community-based sample, low 25(OH)D concentrations were associated with smaller hippocampal volume and poorer neuropsychological function.

The Impact of ADHD Persistence, Recent Cannabis Use, and Age of Regular Cannabis Use Onset on Subcortical Volume and Cortical Thickness in Young Adults

PubMed Central

Lisdahl, Krista M.; Tamm, Leanne; Epstein, Jeffery N.; Jernigan, Terry; Molina, Brooke S.G.; Hinshaw, Stephen P.; Swanson, James M.; Newman, Erik; Kelly, Clare; Bjork, James M.

2017-01-01

Background Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Methods Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. Results After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Discussion Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. PMID:26897585

Fetal growth, cognitive function, and brain volumes in childhood and adolescence.

PubMed

Rogne, Tormod; Engstrøm, Andreas Aass; Jacobsen, Geir Wenberg; Skranes, Jon; Østgård, Heidi Furre; Martinussen, Marit

2015-03-01

To evaluate the association between fetal growth pattern and cognitive function at 5 and 9 years and regional brain volumes at 15 years. Eighty-three term-born small-for-gestational-age (SGA) neonates and 105 non-SGA neonates in a control group were available for follow-up. Based on serial fetal ultrasound measurements from gestational weeks 25-37, SGA neonates were classified with fetal growth restriction (n=13) or non-fetal growth restriction (n=36). Cognitive function was assessed at 5 and 9 years, and brain volumes were estimated with cerebral magnetic resonance imaging at 15 years. Small-for-gestational-age children had lower performance intelligence quotient at 5 years compared with those in a control group (107.3 compared with 112.5, P<.05). Although there were no differences between the SGA non-fetal growth restriction and control groups, the SGA fetal growth restriction group had significantly lower performance intelligence quotient at 5 years (103.5 compared with 112.5, P<.05) and 9 years (96.2 compared with 107.5, P<.05) compared with those in the control group. There were some brain volume differences at 15 years between SGA children and those in the control group, but after adjustment for total intracranial volume, age at examination, and sex, there were only significant differences between the SGA fetal growth restriction and control groups for thalamic (17.4 compared with 18.6 cm, P<.01) and cerebellar white matter volumes (21.5 compared with 24.3 cm, P<.01). Small-for-gestational-age children had lower intelligence quotient scores at 5 and 9 years and smaller brain volumes at 15 years compared with those in the control group, but these findings were only found in those with fetal growth restriction, indicating a possible relationship to decelerated fetal growth. II.

Smaller Cerebellar Growth and Poorer Neurodevelopmental Outcomes in Very Preterm Infants exposed to morphine

PubMed Central

Zwicker, Jill G; Miller, Steven P; Grunau, Ruth E; Chau, Vann; Brant, Rollin; Studholme, Colin; Liu, Mengyuan; Synnes, Anne; Poskitt, Kenneth J; Stiver, Mikaela L; Tam, Emily WY

2017-01-01

Objective To examine the relationship between morphine exposure and growth of the cerebellum and cerebrum in very preterm neonates from early in life to term-equivalent age, as well as to examine morphine exposure and brain volumes in relation to neurodevelopmental outcomes at 18 months corrected age (CA). Study design A prospective cohort of 136 very preterm neonates (24–32 weeks gestational age) was serially scanned with MRI near birth and at term-equivalent age for volumetric measurements of the cerebellum and cerebrum. Motor outcomes were assessed with the Peabody Scales of Motor Development-2 and cognitive outcomes with the Bayley-III at 18 months CA. Generalized least squares models and linear regression models were used to assess relationships between morphine exposure, brain volumes, and neurodevelopmental outcomes. Results A 10-fold increase in morphine exposure was associated with a 5.5% decrease in cerebellar volume, after adjustment for multiple clinical confounders and total brain volume (P=0.04). When infants exposed to glucocorticoids were excluded, the association of morphine was more pronounced, with an 8.2% decrease in cerebellar volume. Morphine exposure was not associated with cerebral volume (P=0.30). Greater morphine exposure also predicted poorer motor (P<0.001) and cognitive outcomes (P=0.006) at 18 months CA, an association mediated, in part, by slower brain growth. Conclusions Morphine exposure in very preterm neonates is independently associated with impaired cerebellar growth in the neonatal period and poorer neurodevelopmental outcomes in early childhood. Alternatives to better manage pain in preterm neonates that optimize brain development and functional outcomes are urgently needed. PMID:26763312

Abnormal left superior temporal gyrus volumes in children and adolescents with bipolar disorder: a magnetic resonance imaging study.

PubMed

Chen, Hua Hsua; Nicoletti, Mark A; Hatch, John P; Sassi, Roberto B; Axelson, David; Brambilla, Paolo; Monkul, E Serap; Keshavan, Matcheri S; Ryan, Neal D; Birmaher, Boris; Soares, Jair C

2004-06-03

Abnormalities in left superior temporal gyrus (STG) have been reported in adult bipolar patients. However, it is not known whether such abnormalities are already present early in the course of this illness. Magnetic resonance imaging (MRI) morphometric analysis of STG was performed in 16 DSM-IV children and adolescents with bipolar disorder (mean age+/-SD 15.5+/-3.4 years) and 21 healthy controls (mean age+/-SD 16.9+/-3.8 years). Subjects underwent a 3D spoiled gradient recalled acquisition MRI examination. Using analysis of covariance with age, gender and intra-cranial brain volume as covariates, we found significantly smaller left total STG volumes in bipolar patients (12.5+/-1.5 cm(3)) compared with healthy controls (13.6+/-2.5 cm(3)) (F=4.45, d.f.=1, 32, P=0.04). This difference was accounted for by significantly smaller left and right STG white matter volumes in bipolar patients. Decreased white matter connections may be the core of abnormalities in STG, which is an important region for speech, language and communication, and could possibly underlie neurocognitive deficits present in bipolar patients.

Age and Sex Related Differences in Subcortical Brain Iron Concentrations among Healthy Adults

PubMed Central

Persson, Ninni; Wu, Jianlin; Zhang, Qing; Liu, Ting; Shen, Jing; Bao, Ruyi; Ni, Mingfei; Liu, Tian; Wang, Yi; Spincemaille, Pascal

2015-01-01

Age and sex can influence brain iron levels. We studied the influence of these variables on deep gray matter magnetic susceptibilities. In 183 healthy volunteers (44.7 ± 14.2 years, range 20-69, ♀ 49%), in vivo Quantitative Susceptibility Mapping (QSM) at 1.5T was performed to estimate brain iron accumulation in the following regions of interest (ROIs): caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), thalamus (Th), pulvinar (Pul), red nucleus (Rn), substantia nigra (Sn) and the cerebellar dentate nuclei (Dn). We gauged the influence of age and sex on magnetic susceptibility by specifying a series of Structural Equation Models. The distributions of susceptibility varied in degree across the structures, conforming to histologic findings (Hallgren & Sourander, 1958), with the highest degree of susceptibility in the Gp and the lowest in the Th. Iron increase correlated across several ROIs, which may reflect an underlying age-related process. Advanced age was associated with a particularly strong linear rise of susceptibility in the striatum. Nonlinear age trends were found in the Rn, where they were the most pronounced, followed by the Pul and Sn, while minimal nonlinear trends were observed for the Pt, Th, and Dn. Moreover, sex related variations were observed, so that women showed lower levels of susceptibility in the Sn after accounting for age. Regional susceptibility of the Pul increased linearly with age in men but exhibited a nonlinear association with age in women with a leveling off starting from midlife. Women expected to be post menopause (+51 years) showed lower total magnetic susceptibility in the subcortical gray matter. The current report is consistent with previous reports of age related variations of brain iron, but also adds to the current knowledge by reporting age-related changes in less studied, smaller subcortical nuclei. This is the first in-vivo report to show lower total subcortical brain iron levels selectively in women from midlife, compared to men and younger women. These results encourage further assessment of sex differences in brain iron. We anticipate that age and sex are important co-factors to take into account when establishing a baseline level for differentiating pathologic neurodegeneration from healthy aging. The variations in regional susceptibility reported herein should be evaluated further using a longitudinal study design to determine within-person age related changes. PMID:26216277

Age and sex related differences in subcortical brain iron concentrations among healthy adults.

PubMed

Persson, Ninni; Wu, Jianlin; Zhang, Qing; Liu, Ting; Shen, Jing; Bao, Ruyi; Ni, Mingfei; Liu, Tian; Wang, Yi; Spincemaille, Pascal

2015-11-15

Age and sex can influence brain iron levels. We studied the influence of these variables on deep gray matter magnetic susceptibilities. In 183 healthy volunteers (44.7 ± 14.2 years, range 20-69, ♀ 49%), in vivo quantitative susceptibility mapping (QSM) at 1.5T was performed to estimate brain iron accumulation in the following regions of interest (ROIs): caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), thalamus (Th), pulvinar (Pul), red nucleus (Rn), substantia nigra (Sn) and the cerebellar dentate nuclei (Dn). We gauged the influence of age and sex on magnetic susceptibility by specifying a series of structural equation models. The distributions of susceptibility varied in degree across the structures, conforming to histologic findings (Hallgren and Sourander, 1958), with the highest degree of susceptibility in the Gp and the lowest in the Th. Iron increase correlated across several ROIs, which may reflect an underlying age-related process. Advanced age was associated with a particularly strong linear rise of susceptibility in the striatum. Nonlinear age trends were found in the Rn, where they were the most pronounced, followed by the Pul and Sn, while minimal nonlinear trends were observed for the Pt, Th, and Dn. Moreover, sex related variations were observed, so that women showed lower levels of susceptibility in the Sn after accounting for age. Regional susceptibility of the Pul increased linearly with age in men but exhibited a nonlinear association with age in women with a leveling off starting from midlife. Women expected to be post menopause (+51 years) showed lower total magnetic susceptibility in the subcortical gray matter. The current report not only is consistent with previous reports of age related variations of brain iron, but also adds to the current knowledge by reporting age-related changes in less studied, smaller subcortical nuclei. This is the first in-vivo report to show lower total subcortical brain iron levels selectively in women from midlife, compared to men and younger women. These results encourage further assessment of sex differences in brain iron. We anticipate that age and sex are important co-factors to take into account when establishing a baseline level for differentiating pathologic neurodegeneration from healthy aging. The variations in regional susceptibility reported herein should be evaluated further using a longitudinal study design to determine within-person changes in aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Mercury and selenium levels, and selenium:mercury molar ratios of brain, muscle and other tissues in bluefish (Pomatomus saltatrix) from New Jersey, USA.

PubMed

Burger, Joanna; Jeitner, Christian; Donio, Mark; Pittfield, Taryn; Gochfeld, Michael

2013-01-15

A number of contaminants affect fish health, including mercury and selenium, and the selenium:mercury molar ratio. Recently the protective effects of selenium on methylmercury toxicity have been publicized, particularly for consumption of saltwater fish. Yet the relative ameliorating effects of selenium on toxicity within fish have not been examined, nor has the molar ratio in different tissues, (i.e. brain). We examined mercury and selenium levels in brain, kidney, liver, red and white muscle, and skin and scales in bluefish (Pomatomus saltatrix) (n=40) from New Jersey to determine whether there were toxic levels of either metal, and we computed the selenium:mercury molar ratios by tissues. Total mercury averaged 0.32±0.02 ppm wet weight in edible muscle and 0.09±0.01 ppm in brain. Selenium concentration averaged 0.37±0.03 in muscle and 0.36±0.03 ppm in brain. There were significant differences in levels of mercury, selenium, and selenium:mercury molar ratios, among tissues. Mercury and selenium levels were correlated in kidney and skin/scales. Mercury levels were highest in kidney, intermediate in muscle and liver, and lowest in brain and skin/scales; selenium levels were also highest in kidney, intermediate in liver, and were an order of magnitude lower in the white muscle and brain. Mercury levels in muscle, kidney and skin/scales were positively correlated with fish size (length). Selenium levels in muscle, kidney and liver were positively correlated with fish length, but in brain; selenium levels were negatively correlated with fish length. The selenium:mercury molar ratio was negatively correlated with fish length for white muscle, liver, kidney, and brain, particularly for fish over 50 cm in length, suggesting that older fish experience less protective advantages of selenium against mercury toxicity than smaller fish, and that consumers of bluefish similarly receive less advantage from eating larger fish. Copyright © 2012 Elsevier B.V. All rights reserved.

Traumatic brain injury and hemorrhagic shock: evaluation of different resuscitation strategies in a large animal model of combined insults.

PubMed

Jin, Guang; DeMoya, Marc A; Duggan, Michael; Knightly, Thomas; Mejaddam, Ali Y; Hwabejire, John; Lu, Jennifer; Smith, William Michael; Kasotakis, Georgios; Velmahos, George C; Socrate, Simona; Alam, Hasan B

2012-07-01

Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related mortality and morbidity. Combination of TBI and HS (TBI + HS) is highly lethal, and the optimal resuscitation strategy for this combined insult remains unclear. A critical limitation is the lack of suitable large animal models to test different treatment strategies. We have developed a clinically relevant large animal model of TBI + HS, which was used to evaluate the impact of different treatments on brain lesion size and associated edema. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters and intracranial pressure. A computer-controlled cortical impact device was used to create a TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-ms dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was started (40% blood volume) concurrent with the TBI. After 2 h of shock, animals were randomized to one of three resuscitation groups (n = 5/group): (a) normal saline (NS); (b) 6% hetastarch, Hextend (Hex); and (c) fresh frozen plasma (FFP). Volumes of Hex and FFP matched the shed blood, whereas NS was three times the volume. After 6 h of postresuscitation monitoring, brains were sectioned into 5-mm slices and stained with TTC (2,3,5-triphenyltetrazolium chloride) to quantify the lesion size and brain swelling. Combination of 40% blood loss with cortical impact and a period of shock (2 h) resulted in a highly reproducible brain injury. Total fluid requirements were lower in the Hex and FFP groups. Lesion size and brain swelling in the FFP group (2,160 ± 202.63 mm and 22% ± 1.0%, respectively) were significantly smaller than those in the NS group (3,285 ± 130.8 mm3 and 37% ± 1.6%, respectively) (P < 0.05). Hex treatment decreased the swelling (29% ± 1.6%) without reducing the lesion size. Early administration of FFP reduces the size of brain lesion and associated swelling in a large animal model of TBI + HS. In contrast, artificial colloid (Hex) decreases swelling without reducing the actual size of the brain lesion.

Birds have primate-like numbers of neurons in the forebrain

PubMed Central

Olkowicz, Seweryn; Kocourek, Martin; Lučan, Radek K.; Porteš, Michal; Fitch, W. Tecumseh; Herculano-Houzel, Suzana; Němec, Pavel

2016-01-01

Some birds achieve primate-like levels of cognition, even though their brains tend to be much smaller in absolute size. This poses a fundamental problem in comparative and computational neuroscience, because small brains are expected to have a lower information-processing capacity. Using the isotropic fractionator to determine numbers of neurons in specific brain regions, here we show that the brains of parrots and songbirds contain on average twice as many neurons as primate brains of the same mass, indicating that avian brains have higher neuron packing densities than mammalian brains. Additionally, corvids and parrots have much higher proportions of brain neurons located in the pallial telencephalon compared with primates or other mammals and birds. Thus, large-brained parrots and corvids have forebrain neuron counts equal to or greater than primates with much larger brains. We suggest that the large numbers of neurons concentrated in high densities in the telencephalon substantially contribute to the neural basis of avian intelligence. PMID:27298365

Neuroanatomy of the killer whale (Orcinus orca) from magnetic resonance images.

PubMed

Marino, Lori; Sherwood, Chet C; Delman, Bradley N; Tang, Cheuk Y; Naidich, Thomas P; Hof, Patrick R

2004-12-01

This article presents the first series of MRI-based anatomically labeled sectioned images of the brain of the killer whale (Orcinus orca). Magnetic resonance images of the brain of an adult killer whale were acquired in the coronal and axial planes. The gross morphology of the killer whale brain is comparable in some respects to that of other odontocete brains, including the unusual spatial arrangement of midbrain structures. There are also intriguing differences. Cerebral hemispheres appear extremely convoluted and, in contrast to smaller cetacean species, the killer whale brain possesses an exceptional degree of cortical elaboration in the insular cortex, temporal operculum, and the cortical limbic lobe. The functional and evolutionary implications of these features are discussed. (c) 2004 Wiley-Liss, Inc.

Quantification of metabotropic glutamate subtype 5 receptors in the brain by an equilibrium method using 18F-SP203.

PubMed

Kimura, Yasuyuki; Siméon, Fabrice G; Zoghbi, Sami S; Zhang, Yi; Hatazawa, Jun; Pike, Victor W; Innis, Robert B; Fujita, Masahiro

2012-02-01

A new PET ligand, 3-fluoro-5-(2-(2-(18)F-(fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile (18F-SP203) can quantify metabotropic glutamate subtype 5 receptors (mGluR5) in human brain by a bolus injection and kinetic modeling. As an alternative approach to a bolus injection, binding can simply be measured as a ratio of tissue to metabolite-corrected plasma at a single time point under equilibrium conditions achieved by administering the radioligand with a bolus injection followed by a constant infusion. The purpose of this study was to validate the equilibrium method as an alternative to the standard kinetic method for measuring 18F-SP203 binding in the brain. Nine healthy subjects were injected with 18F-SP203 using a bolus plus constant infusion for 300 min. A single ratio of bolus-to-constant infusion (the activity of bolus equaled to that of infusion over 219 min) was applied to all subjects to achieve equilibrium in approximately 120 min. As a measure of ligand binding, we compared total distribution volume (VT) calculated by the equilibrium and kinetic methods in each scan. The equilibrium method calculated VT by the ratio of radioactivity in the brain to the concentration of 18F-SP203 in arterial plasma at 120 min, and the kinetic method calculated VT by a two-tissue compartment model using brain and plasma dynamic data from 0 to 120 min. VT obtained via the equilibrium method was highly correlated with VT obtained via kinetic modeling. Inter-subject variability of VT obtained via the equilibrium method was slightly smaller than VT obtained via the kinetic method. VT obtained via the equilibrium method was ~10% higher than VT obtained via the kinetic method, indicating a small difference between the measurements. Taken together, the results of this study show that using the equilibrium method is an acceptable alternative to the standard kinetic method when using 18F-SP203 to measure mGluR5. Although small differences in the measurements obtained via the equilibrium and kinetic methods exist, both methods consistently measured mGluR5 as indicated by the highly correlated VT values; the equilibrium method was slightly more precise, as indirectly measured by the smaller coefficient of variability across subjects. In addition, when using 18F-SP203, the equilibrium method is more efficient because it requires much less data. Copyright © 2011. Published by Elsevier Inc.

Volumetric differences suggest involvement of cerebellum and brainstem in chronic migraine.

PubMed

Bilgiç, Başar; Kocaman, Gülşen; Arslan, Ali Bilgin; Noyan, Handan; Sherifov, Resul; Alkan, Alpay; Asil, Talip; Parman, Yeşim; Baykan, Betül

2016-04-01

Chronic migraine (CM) is a disabling neurologic condition that often evolves from episodic migraine. There has been mounting evidence on the volumetric changes detected by magnetic resonance imaging (MRI) technique in migraineurs. These studies mainly focused on episodic migraine patients and less is known about the differences in CM patients. A total of 24 CM patients and 24 healthy control individuals (all females) were included in this study. All participants underwent neurological examination and MRI. High-resolution anatomical MRI images were processed with an automated segmentation method (FreeSurfer). White-matter abnormalities of the brain were also evaluated with the Age-Related White-Matter-Changes Scale. The volumes of the cerebellum and brainstem were found to be smaller in CM patients compared to healthy controls. White-matter abnormalities were also found in CM patients, specifically in the bilateral parieto-occipital areas. There was no correlation between the clinical variables and volume decrease in these regions. CM patients showed significant volume differences in infratentorial areas and white-matter abnormalities in the posterior part of the brain. It is currently unclear whether the structural brain changes seen in migraine patients are the cause or the result of headaches. Longitudinal volumetric neuroimaging studies with larger groups, especially on the chronification of migraine, are needed to shed light on this topic. © International Headache Society 2015.

Quantifying Differences and Similarities in Whole-Brain White Matter Architecture Using Local Connectome Fingerprints

PubMed Central

Singh, Aarti; Poczos, Barnabas; Erickson, Kirk I.; Tseng, Wen-Yih I.; Verstynen, Timothy D.

2016-01-01

Quantifying differences or similarities in connectomes has been a challenge due to the immense complexity of global brain networks. Here we introduce a noninvasive method that uses diffusion MRI to characterize whole-brain white matter architecture as a single local connectome fingerprint that allows for a direct comparison between structural connectomes. In four independently acquired data sets with repeated scans (total N = 213), we show that the local connectome fingerprint is highly specific to an individual, allowing for an accurate self-versus-others classification that achieved 100% accuracy across 17,398 identification tests. The estimated classification error was approximately one thousand times smaller than fingerprints derived from diffusivity-based measures or region-to-region connectivity patterns for repeat scans acquired within 3 months. The local connectome fingerprint also revealed neuroplasticity within an individual reflected as a decreasing trend in self-similarity across time, whereas this change was not observed in the diffusivity measures. Moreover, the local connectome fingerprint can be used as a phenotypic marker, revealing 12.51% similarity between monozygotic twins, 5.14% between dizygotic twins, and 4.51% between none-twin siblings, relative to differences between unrelated subjects. This novel approach opens a new door for probing the influence of pathological, genetic, social, or environmental factors on the unique configuration of the human connectome. PMID:27846212

Early Brain Vulnerability in Wolfram Syndrome

PubMed Central

Hershey, Tamara; Lugar, Heather M.; Shimony, Joshua S.; Rutlin, Jerrel; Koller, Jonathan M.; Perantie, Dana C.; Paciorkowski, Alex R.; Eisenstein, Sarah A.; Permutt, M. Alan

2012-01-01

Wolfram Syndrome (WFS) is a rare autosomal recessive disease characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, deafness, and neurological dysfunction leading to death in mid-adulthood. WFS is caused by mutations in the WFS1 gene, which lead to endoplasmic reticulum (ER) stress-mediated cell death. Case studies have found widespread brain atrophy in late stage WFS. However, it is not known when in the disease course these brain abnormalities arise, and whether there is differential vulnerability across brain regions and tissue classes. To address this limitation, we quantified regional brain abnormalities across multiple imaging modalities in a cohort of young patients in relatively early stages of WFS. Children and young adults with WFS were evaluated with neurological, cognitive and structural magnetic resonance imaging measures. Compared to normative data, the WFS group had intact cognition, significant anxiety and depression, and gait abnormalities. Compared to healthy and type 1 diabetic control groups, the WFS group had smaller intracranial volume and preferentially affected gray matter volume and white matter microstructural integrity in the brainstem, cerebellum and optic radiations. Abnormalities were detected in even the youngest patients with mildest symptoms, and some measures did not follow the typical age-dependent developmental trajectory. These results establish that WFS is associated with smaller intracranial volume with specific abnormalities in the brainstem and cerebellum, even at the earliest stage of clinical symptoms. This pattern of abnormalities suggests that WFS has a pronounced impact on early brain development in addition to later neurodegenerative effects, representing a significant new insight into the WFS disease process. Longitudinal studies will be critical for confirming and expanding our understanding of the impact of ER stress dysregulation on brain development. PMID:22792385

Association of the Fractal Dimension of Retinal Arteries and Veins with Quantitative Brain MRI Measures in HIV-Infected and Uninfected Women

PubMed Central

Crystal, Howard A.; Holman, Susan; Lui, Yvonne W.; Baird, Alison E.; Yu, Hua; Klein, Ronald; Rojas-Soto, Diana Marcella; Gustafson, Deborah R.; Stebbins, Glenn T.

2016-01-01

Objective The fractal dimension of retinal arteries and veins is a measure of the complexity of the vascular tree. We hypothesized that retinal fractal dimension would be associated with brain volume and white matter integrity in HIV-infected women. Design Nested case-control within longitudinal cohort study. Methods Women were recruited from the Brooklyn site of the Women’s Interagency HIV study (WIHS); 34 HIV-infected and 21 HIV-uninfected women with analyzable MRIs and retinal photographs were included. Fractal dimension was determined using the SIVA software program on skeletonized retinal images. The relationship between predictors (retinal vascular measures) and outcomes (quantitative MRI measures) were analyzed with linear regression models. All models included age, intracranial volume, and both arterial and venous fractal dimension. Some models were adjusted for blood pressure, race/ethnicity, and HIV-infection. Results The women were 45.6 ± 7.3 years of age. Higher arterial dimension was associated with larger cortical volumes, but higher venous dimension was associated with smaller cortical volumes. In fully adjusted models, venous dimension was significantly associated with fractional anisotropy (standardized β = -0.41, p = 0.009) and total gray matter volume (β = -0.24, p = 0.03), and arterial dimension with mean diffusivity (β = -0.33,.p = 0.04) and fractional anisotropy (β = 0.34, p = 0.03). HIV-infection was not associated with any retinal or MRI measure. Conclusions Higher venous fractal dimension was associated with smaller cortical volumes and lower fractional anisotropy, whereas higher arterial fractal dimension was associated with the opposite patterns. Longitudinal studies are needed to validate this finding. PMID:27158911

Total Brain Death and the Integration of the Body Required of a Human Being.

PubMed

Lee, Patrick

2016-06-01

I develop and refine an argument for the total brain death criterion of death previously advanced by Germain Grisez and me: A human being is essentially a rational animal, and so must have a radical capacity for rational operations. For rational animals, conscious sensation is a pre-requisite for rational operation. But total brain death results in the loss of the radical capacity for conscious sensation, and so also for rational operations. Hence, total brain death constitutes a substantial change-the ceasing to be of the human being. Objections are considered, including the objection that total brain death need not result in the loss of capacity for sensation, and that damage to the brain less than total brain death can result in loss of capacity for rational operations. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of Breast Cancer Chemotherapy Agents on Brain Activity in Rats: Functional Imaging Studies

DTIC Science & Technology

2011-04-29

and in a small region of the striatum. Visual stimulation produced bilateral activation of the superior colliculus, lateral geniculate and a small...pattern was seen in the lateral geniculate . These results demonstrate the feasibility of using brain activation by parametric sensory stimulation as...both the right and left lateral geniculate functional ROIs (25% and 29%, respectively). There were smaller but not statistically significant decreases

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.

T cell–derived interleukin (IL)-21 promotes brain injury following stroke in mice

PubMed Central

Clarkson, Benjamin D.S.; Ling, Changying; Shi, Yejie; Harris, Melissa G.; Rayasam, Aditya; Sun, Dandan; Salamat, M. Shahriar; Kuchroo, Vijay; Lambris, John D.; Sandor, Matyas

2014-01-01

T lymphocytes are key contributors to the acute phase of cerebral ischemia reperfusion injury, but the relevant T cell–derived mediators of tissue injury remain unknown. Using a mouse model of transient focal brain ischemia, we report that IL-21 is highly up-regulated in the injured mouse brain after cerebral ischemia. IL-21–deficient mice have smaller infarcts, improved neurological function, and reduced lymphocyte accumulation in the brain within 24 h of reperfusion. Intracellular cytokine staining and adoptive transfer experiments revealed that brain-infiltrating CD4+ T cells are the predominant IL-21 source. Mice treated with decoy IL-21 receptor Fc fusion protein are protected from reperfusion injury. In postmortem human brain tissue, IL-21 localized to perivascular CD4+ T cells in the area surrounding acute stroke lesions, suggesting that IL-21–mediated brain injury may be relevant to human stroke. PMID:24616379

Enhanced neuroinvasion by smaller, soluble prions.

PubMed

Bett, Cyrus; Lawrence, Jessica; Kurt, Timothy D; Orru, Christina; Aguilar-Calvo, Patricia; Kincaid, Anthony E; Surewicz, Witold K; Caughey, Byron; Wu, Chengbiao; Sigurdson, Christina J

2017-04-21

Infectious prion aggregates can propagate from extraneural sites into the brain with remarkable efficiency, likely transported via peripheral nerves. Yet not all prions spread into the brain, and the physical properties of a prion that is capable of transit within neurons remain unclear. We hypothesized that small, diffusible aggregates spread into the CNS via peripheral nerves. Here we used a structurally diverse panel of prion strains to analyze how the prion conformation impacts transit into the brain. Two prion strains form fibrils visible ultrastructurally in the brain in situ, whereas three strains form diffuse, subfibrillar prion deposits and no visible fibrils. The subfibrillar strains had significantly higher levels of soluble prion aggregates than the fibrillar strains. Primary neurons internalized both the subfibrillar and fibril-forming prion strains by macropinocytosis, and both strain types were transported from the axon terminal to the cell body in vitro. However in mice, only the predominantly soluble, subfibrillar prions, and not the fibrillar prions, were efficiently transported from the tongue to the brain. Sonicating a fibrillar prion strain increased the solubility and enabled prions to spread into the brain in mice, as evident by a 40% increase in the attack rate, indicating that an increase in smaller particles enhances prion neuroinvasion. Our data suggest that the small, highly soluble prion particles have a higher capacity for transport via nerves. These findings help explain how prions that predominantly assemble into subfibrillar states can more effectively traverse into and out of the CNS, and suggest that promoting fibril assembly may slow the neuron-to-neuron spread of protein aggregates.

Brain-region–specific alterations of the trajectories of neuronal volume growth throughout the lifespan in autism

PubMed Central

2014-01-01

Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon’s horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits. PMID:24612906

Correlates of head circumference growth in infants later diagnosed with autism spectrum disorders.

PubMed

Mraz, Krista D; Green, James; Dumont-Mathieu, Thyde; Makin, Sarah; Fein, Deborah

2007-06-01

Previous research has demonstrated that children diagnosed with autism spectrum disorder show an abnormal acceleration of head growth during the first year of life. This study attempts to replicate these findings and to determine whether overgrowth is associated with clinical outcome. Measurements of head circumference, body length, and body weight taken during the first 2 years of life were obtained from a sample of 35 children diagnosed with autism spectrum disorder and compared to both national normative data (Centers for Disease Control and Prevention) and a control group of 37 healthy infants. Results demonstrated that compared to national averages, infants who were later diagnosed with autism spectrum disorder had a significantly smaller head circumference at birth to 2 weeks and a significantly larger head circumference by 10 to 14 months. Children with autism spectrum disorder were also significantly longer and heavier beginning at 1 to 2 months. However, when overall length and weight were controlled, head circumference was not bigger in the autistic spectrum disorder group compared to local controls. Correlations between head circumference and clinical outcome were significant for 5 of the 30 clinical variables that were run, suggesting that there appears to be no simple or straightforward relationship between head circumference and clinical outcome. Smaller head circumference at birth to 2 weeks was associated with a greater number of symptoms related to social impairment and a greater total number of autism spectrum disorder symptoms based on the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria. Larger head circumference at 15 to 25 months was also associated with a greater number of symptoms of social impairment. In addition, greater head circumference change during the first 2 years was associated with poorer performance on the visual reception subtest of the Mullen Scales of Early Learning and a smaller number of stereotyped and repetitive behaviors and interests based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. These findings support previous findings of accelerated brain growth during the first year of life in autism spectrum disorder and question whether growth factors might contribute to both accelerated brain growth and overall body growth.

Evolution of brain region volumes during artificial selection for relative brain size.

PubMed

Kotrschal, Alexander; Zeng, Hong-Li; van der Bijl, Wouter; Öhman-Mägi, Caroline; Kotrschal, Kurt; Pelckmans, Kristiaan; Kolm, Niclas

2017-12-01

The vertebrate brain shows an extremely conserved layout across taxa. Still, the relative sizes of separate brain regions vary markedly between species. One interesting pattern is that larger brains seem associated with increased relative sizes only of certain brain regions, for instance telencephalon and cerebellum. Till now, the evolutionary association between separate brain regions and overall brain size is based on comparative evidence and remains experimentally untested. Here, we test the evolutionary response of brain regions to directional selection on brain size in guppies (Poecilia reticulata) selected for large and small relative brain size. In these animals, artificial selection led to a fast response in relative brain size, while body size remained unchanged. We use microcomputer tomography to investigate how the volumes of 11 main brain regions respond to selection for larger versus smaller brains. We found no differences in relative brain region volumes between large- and small-brained animals and only minor sex-specific variation. Also, selection did not change allometric scaling between brain and brain region sizes. Our results suggest that brain regions respond similarly to strong directional selection on relative brain size, which indicates that brain anatomy variation in contemporary species most likely stem from direct selection on key regions. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Self-efficacy is independently associated with brain volume in older women.

PubMed

Davis, Jennifer C; Nagamatsu, Lindsay S; Hsu, Chun Liang; Beattie, B Lynn; Liu-Ambrose, Teresa

2012-07-01

ageing is highly associated with neurodegeneration and atrophy of the brain. Evidence suggests that personality variables are risk factors for reduced brain volume. We examine whether falls-related self-efficacy is independently associated with brain volume. a cross-sectional analysis of whether falls-related self-efficacy is independently associated with brain volumes (total, grey and white matter). Three multivariate regression models were constructed. Covariates included in the models were age, global cognition, systolic blood pressure, functional comorbidity index and current physical activity level. MRI scans were acquired from 79 community-dwelling senior women aged 65-75 years old. Falls-related self-efficacy was assessed by the activities-specific balance confidence (ABC) scale. after accounting for covariates, falls-related self-efficacy was independently associated with both total brain volume and total grey matter volume. The final model for total brain volume accounted for 17% of the variance, with the ABC score accounting for 8%. For total grey matter volume, the final model accounted for 24% of the variance, with the ABC score accounting for 10%. we provide novel evidence that falls-related self-efficacy, a modifiable risk factor for healthy ageing, is positively associated with total brain volume and total grey matter volume. ClinicalTrials.gov Identifier: NCT00426881.

Self-efficacy is independently associated with brain volume in older women

PubMed Central

Davis, Jennifer C.; Nagamatsu, Lindsay S.; Hsu, Chun Liang; Beattie, B. Lynn; Liu-Ambrose, Teresa

2015-01-01

Background Aging is highly associated with neurodegeneration and atrophy of the brain. Evidence suggests that personality variables are risk factors for reduced brain volume. We examine whether falls-related self-efficacy is independently associated with brain volume. Method A cross-sectional analysis of whether falls-related self-efficacy is independently associated with brain volumes (total, grey, and white matter). Three multivariate regression models were constructed. Covariates included in the models were age, global cognition, systolic blood pressure, functional comorbidity index, and current physical activity level. MRI scans were acquired from 79 community-dwelling senior women aged 65 to 75 years old. Falls-related self-efficacy was assessed by the Activities Specific Balance Confidence (ABC) Scale. Results After accounting for covariates, falls-related self-efficacy was independently associated with both total brain volume and total grey matter volume. The final model for total brain volume accounted for 17% of the variance, with the ABC score accounting for 8%. For total grey matter volume, the final model accounted for 24% of the variance, with the ABC score accounting for 10%. Conclusion We provide novel evidence that falls-related self-efficacy, a modifiable risk factor for healthy aging, is positively associated with total brain volume and total grey matter volume. Trial Registration ClinicalTrials.gov Identifier: NCT00426881. PMID:22436405

Handedness- and brain size-related efficiency differences in small-world brain networks: a resting-state functional magnetic resonance imaging study.

PubMed

Li, Meiling; Wang, Junping; Liu, Feng; Chen, Heng; Lu, Fengmei; Wu, Guorong; Yu, Chunshui; Chen, Huafu

2015-05-01

The human brain has been described as a complex network, which integrates information with high efficiency. However, the relationships between the efficiency of human brain functional networks and handedness and brain size remain unclear. Twenty-one left-handed and 32 right-handed healthy subjects underwent a resting-state functional magnetic resonance imaging scan. The whole brain functional networks were constructed by thresholding Pearson correlation matrices of 90 cortical and subcortical regions. Graph theory-based methods were employed to further analyze their topological properties. As expected, all participants demonstrated small-world topology, suggesting a highly efficient topological structure. Furthermore, we found that smaller brains showed higher local efficiency, whereas larger brains showed higher global efficiency, reflecting a suitable efficiency balance between local specialization and global integration of brain functional activity. Compared with right-handers, significant alterations in nodal efficiency were revealed in left-handers, involving the anterior and median cingulate gyrus, middle temporal gyrus, angular gyrus, and amygdala. Our findings indicated that the functional network organization in the human brain was associated with handedness and brain size.

Military deployment correlates with smaller prefrontal gray matter volume and psychological symptoms in a subclinical population.

PubMed

Butler, O; Adolf, J; Gleich, T; Willmund, G; Zimmermann, P; Lindenberger, U; Gallinat, J; Kühn, S

2017-02-14

Research investigating the effects of trauma exposure on brain structure and function in adults has mainly focused on post-traumatic stress disorder (PTSD), whereas trauma-exposed individuals without a clinical diagnoses often serve as controls. However, this assumes a dichotomy between clinical and subclinical populations that may not be supported at the neural level. In the current study we investigate whether the effects of repeated or long-term stress exposure on brain structure in a subclinical sample are similar to previous PTSD neuroimaging findings. We assessed 27 combat trauma-exposed individuals by means of whole-brain voxel-based morphometry on 3 T magnetic resonance imaging scans and identified a negative association between duration of military deployment and gray matter volumes in ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (ACC). We also found a negative relationship between deployment-related gray matter volumes and psychological symptoms, but not between military deployment and psychological symptoms. To our knowledge, this is the first whole-brain analysis showing that longer military deployment is associated with smaller regional brain volumes in combat-exposed individuals without PTSD. Notably, the observed gray matter associations resemble those previously identified in PTSD populations, and concern regions involved in emotional regulation and fear extinction. These findings question the current dichotomy between clinical and subclinical populations in PTSD neuroimaging research. Instead, neural correlates of both stress exposure and PTSD symptomatology may be more meaningfully investigated at a continuous level.

Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease

PubMed Central

Chen, Meng-Hsiang; Lu, Cheng-Hsien; Chen, Pei-Chin; Tsai, Nai-Wen; Huang, Chih-Cheng; Chen, Hsiu-Ling; Yang, I-Hsiao; Yu, Chiun-Chieh; Lin, Wei-Che

2016-01-01

Abstract Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex. Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation. In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD. PMID:26986144

Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease.

PubMed

Chen, Meng-Hsiang; Lu, Cheng-Hsien; Chen, Pei-Chin; Tsai, Nai-Wen; Huang, Chih-Cheng; Chen, Hsiu-Ling; Yang, I-Hsiao; Yu, Chiun-Chieh; Lin, Wei-Che

2016-03-01

Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex. Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation. In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD.

Military deployment correlates with smaller prefrontal gray matter volume and psychological symptoms in a subclinical population

PubMed Central

Butler, O; Adolf, J; Gleich, T; Willmund, G; Zimmermann, P; Lindenberger, U; Gallinat, J; Kühn, S

2017-01-01

Research investigating the effects of trauma exposure on brain structure and function in adults has mainly focused on post-traumatic stress disorder (PTSD), whereas trauma-exposed individuals without a clinical diagnoses often serve as controls. However, this assumes a dichotomy between clinical and subclinical populations that may not be supported at the neural level. In the current study we investigate whether the effects of repeated or long-term stress exposure on brain structure in a subclinical sample are similar to previous PTSD neuroimaging findings. We assessed 27 combat trauma-exposed individuals by means of whole-brain voxel-based morphometry on 3 T magnetic resonance imaging scans and identified a negative association between duration of military deployment and gray matter volumes in ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (ACC). We also found a negative relationship between deployment-related gray matter volumes and psychological symptoms, but not between military deployment and psychological symptoms. To our knowledge, this is the first whole-brain analysis showing that longer military deployment is associated with smaller regional brain volumes in combat-exposed individuals without PTSD. Notably, the observed gray matter associations resemble those previously identified in PTSD populations, and concern regions involved in emotional regulation and fear extinction. These findings question the current dichotomy between clinical and subclinical populations in PTSD neuroimaging research. Instead, neural correlates of both stress exposure and PTSD symptomatology may be more meaningfully investigated at a continuous level. PMID:28195568

Risk of brain tumours in relation to estimated RF dose from mobile phones: results from five Interphone countries.

PubMed

Cardis, E; Armstrong, B K; Bowman, J D; Giles, G G; Hours, M; Krewski, D; McBride, M; Parent, M E; Sadetzki, S; Woodward, A; Brown, J; Chetrit, A; Figuerola, J; Hoffmann, C; Jarus-Hakak, A; Montestruq, L; Nadon, L; Richardson, L; Villegas, R; Vrijheid, M

2011-09-01

The objective of this study was to examine the associations of brain tumours with radio frequency (RF) fields from mobile phones. Patients with brain tumour from the Australian, Canadian, French, Israeli and New Zealand components of the Interphone Study, whose tumours were localised by neuroradiologists, were analysed. Controls were matched on age, sex and region and allocated the 'tumour location' of their matched case. Analyses included 553 glioma and 676 meningioma cases and 1762 and 1911 controls, respectively. RF dose was estimated as total cumulative specific energy (TCSE; J/kg) absorbed at the tumour's estimated centre taking into account multiple RF exposure determinants. ORs with ever having been a regular mobile phone user were 0.93 (95% CI 0.73 to 1.18) for glioma and 0.80 (95% CI 0.66 to 0.96) for meningioma. ORs for glioma were below 1 in the first four quintiles of TCSE but above 1 in the highest quintile, 1.35 (95% CI 0.96 to 1.90). The OR increased with increasing TCSE 7+ years before diagnosis (p-trend 0.01; OR 1.91, 95% CI 1.05 to 3.47 in the highest quintile). A complementary analysis in which 44 glioma and 135 meningioma cases in the most exposed area of the brain were compared with gliomas and meningiomas located elsewhere in the brain showed increased ORs for tumours in the most exposed part of the brain in those with 10+ years of mobile phone use (OR 2.80, 95% CI 1.13 to 6.94 for glioma). Patterns for meningioma were similar, but ORs were lower, many below 1.0. There were suggestions of an increased risk of glioma in long-term mobile phone users with high RF exposure and of similar, but apparently much smaller, increases in meningioma risk. The uncertainty of these results requires that they be replicated before a causal interpretation can be made.

Risk of brain tumours in relation to estimated RF dose from mobile phones: results from five Interphone countries

PubMed Central

Armstrong, B K; Bowman, J D; Giles, G G; Hours, M; Krewski, D; McBride, M; Parent, M E; Sadetzki, S; Woodward, A; Brown, J; Chetrit, A; Figuerola, J; Hoffmann, C; Jarus-Hakak, A; Montestruq, L; Nadon, L; Richardson, L; Villegas, R; Vrijheid, M

2011-01-01

Objectives The objective of this study was to examine the associations of brain tumours with radio frequency (RF) fields from mobile phones. Methods Patients with brain tumour from the Australian, Canadian, French, Israeli and New Zealand components of the Interphone Study, whose tumours were localised by neuroradiologists, were analysed. Controls were matched on age, sex and region and allocated the ‘tumour location’ of their matched case. Analyses included 553 glioma and 676 meningioma cases and 1762 and 1911 controls, respectively. RF dose was estimated as total cumulative specific energy (TCSE; J/kg) absorbed at the tumour's estimated centre taking into account multiple RF exposure determinants. Results ORs with ever having been a regular mobile phone user were 0.93 (95% CI 0.73 to 1.18) for glioma and 0.80 (95% CI 0.66 to 0.96) for meningioma. ORs for glioma were below 1 in the first four quintiles of TCSE but above 1 in the highest quintile, 1.35 (95% CI 0.96 to 1.90). The OR increased with increasing TCSE 7+ years before diagnosis (p-trend 0.01; OR 1.91, 95% CI 1.05 to 3.47 in the highest quintile). A complementary analysis in which 44 glioma and 135 meningioma cases in the most exposed area of the brain were compared with gliomas and meningiomas located elsewhere in the brain showed increased ORs for tumours in the most exposed part of the brain in those with 10+ years of mobile phone use (OR 2.80, 95% CI 1.13 to 6.94 for glioma). Patterns for meningioma were similar, but ORs were lower, many below 1.0. Conclusions There were suggestions of an increased risk of glioma in long-term mobile phone users with high RF exposure and of similar, but apparently much smaller, increases in meningioma risk. The uncertainty of these results requires that they be replicated before a causal interpretation can be made. PMID:21659469

Impact of cardiosynchronous brain pulsations on Monte Carlo calculated doses for synchrotron micro- and minibeam radiation therapy.

PubMed

Manchado de Sola, Francisco; Vilches, Manuel; Prezado, Yolanda; Lallena, Antonio M

2018-05-15

The purpose of this study was to assess the effects of brain movements induced by heartbeat on dose distributions in synchrotron micro- and minibeam radiation therapy and to develop a model to help guide decisions and planning for future clinical trials. The Monte Carlo code PENELOPE was used to simulate the irradiation of a human head phantom with a variety of micro- and minibeam arrays, with beams narrower than 100 μm and above 500 μm, respectively, and with radiation fields of 1 × 2 cm and 2 × 2 cm. The dose in the phantom due to these beams was calculated by superposing the dose profiles obtained for a single beam of 1 μm × 2 cm. A parameter δ, accounting for the total displacement of the brain during the irradiation and due to the cardiosynchronous pulsation, was used to quantify the impact on peak-to-valley dose ratios and the full width at half maximum. The difference between the maximum (at the phantom entrance) and the minimum (at the phantom exit) values of the peak-to-valley dose ratio reduces when the parameter δ increases. The full width at half maximum remains almost constant with depth for any δ value. Sudden changes in the two quantities are observed at the interfaces between the various tissues (brain, skull, and skin) present in the head phantom. The peak-to-valley dose ratio at the center of the head phantom reduces when δ increases, remaining above 70% of the static value only for minibeams and δ smaller than ∼200 μm. Optimal setups for brain treatments with synchrotron radiation micro- and minibeam combs depend on the brain displacement due to cardiosynchronous pulsation. Peak-to-valley dose ratios larger than 90% of the maximum values obtained in the static case occur only for minibeams and relatively large dose rates. © 2018 American Association of Physicists in Medicine.

Smaller Brains and Optic Lobes in Reproductive Workers of the Ant Harpegnathos

NASA Astrophysics Data System (ADS)

Gronenberg, Wulfila; Liebig, Jürgen

Most animals show long-term modifications of their behavior which often reflect an adaptation to seasonal variations (e.g., hibernation) or result from changes in the animal's internal state (e.g., estrous cycle or sexual maturity). Such modifications may substantially affect the nervous system [1, 2]. A particularly striking behavioral change can occur in workers of the ant Harpegnathos. A few young workers in the colony may become reproductives and are thus confined to their dark nest chambers, whereas most workers spend their lives as foragers, employing acute vision when hunting prey. This behavioral difference coincides with a marked decrease in brain volume and with an even stronger reduction in the large visual brain centers. Instead of maintaining superfluous brain functions, these ants reduce brain matter which is expensive to support.

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.

Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils.

PubMed

Holguin, Sarah; Martinez, Joseph; Chow, Camille; Wurtman, Richard

2008-11-01

This study examined the effects on cognitive behaviors of giving normal adult gerbils three compounds, normally in the circulation, which interact to increase brain phosphatides, synaptic proteins, dendritic spines, and neurotransmitter release. Animals received supplemental uridine (as its monophosphate, UMP; 0.5%) and choline (0.1%) via the diet, and docosahexaenoic acid (DHA; 300 mg/kg/day) by gavage, for 4 wk, and then throughout the subsequent period of behavioral training and testing. As shown previously, giving all three compounds caused highly significant (P<0.001) increases in total brain phospholipids and in each major phosphatide; giving DHA or UMP (plus choline) produced smaller increases in some of the phosphatides. DHA plus choline improved performance on the four-arm radial maze, T-maze, and Y-maze tests; coadministering UMP further enhanced these increases. (Uridine probably acts by generating both CTP, which can be limiting in phosphatide synthesis, and UTP, which activates P2Y receptors coupled to neurite outgrowth and protein synthesis. All three compounds also act by enhancing the substrate-saturation of phosphatide-synthesizing enzymes.) These findings demonstrate that a treatment that increases synaptic membrane content can enhance cognitive functions in normal animals.

Changes in brain amino acid content induced by hyposmolar stress and energy deprivation.

PubMed

Haugstad, T S; Valø, E T; Langmoen, I A

1995-12-01

The changes in endogenous amino acids in brain extracellular and intracellular compartments evoked by hyposmotic stress and energy deprivation were compared. Tissue content and release of ten amino acids were measured simultaneously in rat hippocampal slices by means of high performance liquid chromatography. Hyposmotic stress induced a large release of taurine (25568 pmol mg-1 protein), and a smaller release of glutamate, accompanied by an inverse change in tissue content. Adding mannitol to correct osmolarity, blocked these changes. Energy deprivation caused an increase in the release of all amino acids except glutamine. The release was particularly large for glutamate and GABA (31141 and 13282 pmol mg-1, respectively). The intracellular concentrations were generally reduced, but the total amount of the released amino acids increased In contrast to the effect seen during hyposmolar stress, mannitol enhanced the changes due to energy deprivation. The results show that hyposmolar stress and energy deprivation cause different content and release profiles, suggesting that the mechanisms involved in the two situations are either different or modulated in different ways. The intracellular amino acid depletion seen during energy deprivation shows that increased outward transport is probably a primary event, and increased amino acid formation likely secondary to this release.

Retinal thinning is uniquely associated with medial temporal lobe atrophy in neurologically normal older adults

PubMed Central

Casaletto, Kaitlin B.; Ward, Michael E.; Baker, Nicholas S.; Bettcher, Brianne M.; Gelfand, Jeffrey M.; Li, Yaqiao; Chen, Robert; Dutt, Shubir; Miller, Bruce; Kramer, Joel H.; Green, Ari J.

2017-01-01

Given the converging pathologic and epidemiologic data indicating a relationship between retinal integrity and neurodegeneration, including Alzheimer’s disease (AD), we aimed to determine if retinal structure correlates with medial temporal lobe (MTL) structure and function in neurologically normal older adults. Spectral-domain optical coherence tomography, verbal and visual memory testing, and 3T-magnetic resonance imaging of the brain were performed in 79 neurologically normal adults enrolled in a healthy aging cohort study. Retinal nerve fiber thinning and reduced total macular and macular ganglion cell volumes were each associated with smaller MTL volumes (ps < 0.04). Notably, these markers of retinal structure were not associated with primary motor cortex or basal ganglia volumes (regions relatively unaffected in AD) (ps > 0.70), or frontal, precuneus, or temporoparietal volumes (regions affected in later AD Braak staging ps > 0.20). Retinal structure was not significantly associated with verbal or visual memory consolidation performances (ps > 0.14). Retinal structure was associated with MTL volumes, but not memory performances, in otherwise neurologically normal older adults. Given that MTL atrophy is a neuropathological hallmark of AD, retinal integrity may be an early marker of ongoing AD-related brain health. PMID:28068565

Neural predictors of substance use disorders in Young adulthood.

PubMed

O'Brien, Jessica W; Hill, Shirley Y

2017-10-30

Offspring from multiplex, alcohol-dependent families are at heightened risk for substance use disorders (SUDs) in adolescence and young adulthood. These high-risk offspring have also been shown to have atypical structure and function of brain regions implicated in emotion regulation, social cognition, and reward processing. This study assessed the relationship between amygdala and orbitofrontal cortex (OFC) volumes obtained in adolescence and SUD outcomes in young adulthood among high-risk offspring and low-risk controls. A total of 78 participants (40 high-risk; 38 low-risk) from a longitudinal family study, ages 8-19, underwent magnetic resonance imaging; volumes of the amygdala and OFC were obtained with manual tracing. SUD outcomes were assessed at approximately yearly intervals. Cox regression survival analyses were used to assess the effect of regional brain volumes on SUD outcomes. The ratio of OFC to amygdala volume significantly predicted SUD survival time across the sample; reduction in survival time was seen in those with smaller ratios for both high-risk and low-risk groups. Morphology of prefrontal relative to limbic regions in adolescence prospectively predicts age of onset for substance use disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Total brain death: a reply to Alan Shewmon.

PubMed

Lee, Patrick; GriseZ, Germain

2012-06-01

D. Alan Shewmon has advanced a well-documented challenge to the widely accepted total brain death criterion for death of the human being. We show that Shewmon’s argument against this criterion is unsound, though he does refute the standard argument for that criterion. We advance a distinct argument for the total brain death criterion and answer likely objections. Since human beings are rational animals--sentient organisms of a specific type--the loss of the radical capacity for sentience (the capacity to sense or to develop the capacity to sense) involves a substantial change, the passing away of the human organism. In human beings total brain death involves the complete loss of the radical capacity for sentience, and so in human beings total brain death is death.

Stress predicts brain changes in children: a pilot longitudinal study on youth stress, posttraumatic stress disorder, and the hippocampus.

PubMed

Carrion, Victor G; Weems, Carl F; Reiss, Allan L

2007-03-01

Does stress damage the brain? Studies of adults with posttraumatic stress disorder have demonstrated smaller hippocampal volumes when compared with the volumes of adults with no posttraumatic stress disorder. Studies of children with posttraumatic stress disorder have not replicated the smaller hippocampal findings in adults, which suggests that smaller hippocampal volume may be caused by neurodevelopmental experiences with stress. Animal research has demonstrated that the glucocorticoids secreted during stress can be neurotoxic to the hippocampus, but this has not been empirically demonstrated in human samples. We hypothesized that cortisol volumes would predict hippocampal volume reduction in patients with posttraumatic symptoms. We report data from a pilot longitudinal study of children (n = 15) with history of maltreatment who underwent clinical evaluation for posttraumatic stress disorder, cortisol, and neuroimaging. Posttraumatic stress disorder symptoms and cortisol at baseline predicted hippocampal reduction over an ensuing 12- to 18-month interval. Results from this pilot study suggest that stress is associated with hippocampal reduction in children with posttraumatic stress disorder symptoms and provide preliminary human evidence that stress may indeed damage the hippocampus. Additional studies seem to be warranted.

MRI-Based Measurement of Hippocampal Volume in Patients With Combat-Related Posttraumatic Stress Disorder

PubMed Central

Bremner, J. Douglas; Randall, Penny; Scott, Tammy M.; Bronen, Richard A.; Seibyl, John P.; Southwick, Steven M.; Delaney, Richard C.; McCarthy, Gregory; Charney, Dennis S.; Innis, Robert B.

2011-01-01

Objective Studies in nonhuman primates suggest that high levels of cortisol associated with stress have neurotoxic effects on the hippocampus, a brain structure involved in memory. The authors previously showed that patients with combat-related posttraumatic stress disorder (PTSD) had deficits in short-term memory. The purpose of this study was to compare the hippocampal volume of patients with PTSD to that of subjects without psychiatric disorder. Method Magnetic resonance imaging was used to measure the volume of the hippocampus in 26 Vietnam combat veterans with PTSD and 22 comparison subjects selected to be similar to the patients in age, sex, race, years of education, socioeconomic status, body size, and years of alcohol abuse. Results The PTSD patients had a statistically significant 8% smaller right hippocampal volume relative to that of the comparison subjects, but there was no difference in the volume of other brain regions (caudate and temporal lobe). Deficits in short-term verbal memory as measured with the Wechsler Memory Scale were associated with smaller right hippocampal volume in the PTSD patients only. Conclusions These findings are consistent with a smaller right hippocampal volume in PTSD that is associated with functional deficits in verbal memory. PMID:7793467

S-values calculated from a tomographic head/brain model for brain imaging

NASA Astrophysics Data System (ADS)

Chao, Tsi-chian; Xu, X. George

2004-11-01

A tomographic head/brain model was developed from the Visible Human images and used to calculate S-values for brain imaging procedures. This model contains 15 segmented sub-regions including caudate nucleus, cerebellum, cerebral cortex, cerebral white matter, corpus callosum, eyes, lateral ventricles, lenses, lentiform nucleus, optic chiasma, optic nerve, pons and middle cerebellar peduncle, skull CSF, thalamus and thyroid. S-values for C-11, O-15, F-18, Tc-99m and I-123 have been calculated using this model and a Monte Carlo code, EGS4. Comparison of the calculated S-values with those calculated from the MIRD (1999) stylized head/brain model shows significant differences. In many cases, the stylized head/brain model resulted in smaller S-values (as much as 88%), suggesting that the doses to a specific patient similar to the Visible Man could have been underestimated using the existing clinical dosimetry.

Poly(3,4-ethylenedioxythiophene) (PEDOT) polymer coatings facilitate smaller neural recording electrodes

NASA Astrophysics Data System (ADS)

Ludwig, Kip A.; Langhals, Nicholas B.; Joseph, Mike D.; Richardson-Burns, Sarah M.; Hendricks, Jeffrey L.; Kipke, Daryl R.

2011-02-01

We investigated using poly(3,4-ethylenedioxythiophene) (PEDOT) to lower the impedance of small, gold recording electrodes with initial impedances outside of the effective recording range. Smaller electrode sites enable more densely packed arrays, increasing the number of input and output channels to and from the brain. Moreover, smaller electrode sizes promote smaller probe designs; decreasing the dimensions of the implanted probe has been demonstrated to decrease the inherent immune response, a known contributor to the failure of long-term implants. As expected, chronically implanted control electrodes were unable to record well-isolated unit activity, primarily as a result of a dramatically increased noise floor. Conversely, electrodes coated with PEDOT consistently recorded high-quality neural activity, and exhibited a much lower noise floor than controls. These results demonstrate that PEDOT coatings enable electrode designs 15 µm in diameter.

DNA methylation signatures of educational attainment

NASA Astrophysics Data System (ADS)

van Dongen, Jenny; Bonder, Marc Jan; Dekkers, Koen F.; Nivard, Michel G.; van Iterson, Maarten; Willemsen, Gonneke; Beekman, Marian; van der Spek, Ashley; van Meurs, Joyce B. J.; Franke, Lude; Heijmans, Bastiaan T.; van Duijn, Cornelia M.; Slagboom, P. Eline; Boomsma, Dorret I.; BIOS consortium

2018-03-01

Educational attainment is a key behavioural measure in studies of cognitive and physical health, and socioeconomic status. We measured DNA methylation at 410,746 CpGs (N = 4152) and identified 58 CpGs associated with educational attainment at loci characterized by pleiotropic functions shared with neuronal, immune and developmental processes. Associations overlapped with those for smoking behaviour, but remained after accounting for smoking at many CpGs: Effect sizes were on average 28% smaller and genome-wide significant at 11 CpGs after adjusting for smoking and were 62% smaller in never smokers. We examined sources and biological implications of education-related methylation differences, demonstrating correlations with maternal prenatal folate, smoking and air pollution signatures, and associations with gene expression in cis, dynamic methylation in foetal brain, and correlations between blood and brain. Our findings show that the methylome of lower-educated people resembles that of smokers beyond effects of their own smoking behaviour and shows traces of various other exposures.

Head circumference, education and risk of dementia: findings from the Nun Study.

PubMed

Mortimer, James A; Snowdon, David A; Markesbery, William R

2003-08-01

To examine the prevalence of dementia associated with having a smaller brain, lower education or both of these characteristics, 294 Catholic sisters were assessed annually for dementia. Sixty participants died and their brains were evaluated to determine fulfillment of neuropathological criteria for Alzheimer's disease (AD). Lower educational attainment and the interaction of smaller head circumference with lower education were associated with the presence of dementia, controlling for age and the presence of one or more apolipoprotein E-epsilon 4 alleles. By contrast, neither low educational attainment nor head circumference was significantly associated with fulfillment of neuropathological criteria for AD. Individuals having both low education and small head circumference were four times as likely to be demented as the rest of the sample. The findings suggest that higher education and larger head size, alone or in combination, may reduce the risk of expressing dementia in late life.

Feasibility of studying brain morphology in major depressive disorder with structural magnetic resonance imaging and clinical data from the electronic medical record: A pilot study

PubMed Central

Hoogenboom, Wouter S.; Perlis, Roy H.; Smoller, Jordan W.; Zeng-Treitler, Qing; Gainer, Vivian S.; Murphy, Shawn N.; Churchill, Susanne E.; Kohane, Isaac S.; Shenton, Martha E.; Iosifescu, Dan V.

2012-01-01

For certain research questions related to long-term outcomes or to rare disorders, designing prospective studies is impractical or prohibitively expensive. Such studies could instead utilize clinical and magnetic resonance imaging data (MRI) collected as part of routine clinical care, stored in the electronic medical record (EMR). Using major depressive disorder (MDD) as a disease model, we examined the feasibility of studying brain morphology and associations with remission using clinical and MRI data exclusively drawn from the EMR. Advanced automated tools were used to select MDD patients and controls from the EMR who had brain MRI data, but no diagnosed brain pathology. MDD patients were further assessed for remission status by review of clinical charts. Twenty MDD patients (eight full-remitters, six partial-remitters, and six non-remitters), and fifteen healthy control subjects met all study criteria for advanced morphometric analyses. Compared to controls, MDD patients had significantly smaller right rostral-anterior cingulate volume, and level of non-remission was associated with smaller left hippocampus and left rostral-middle frontal gyrus volume. The use of EMR data for psychiatric research may provide a timely and cost-effective approach with the potential to generate large study samples reflective of the real population with the illness studied. PMID:23149041

Eating disorder psychopathology, brain structure, neuropsychological correlates and risk mechanisms in very preterm young adults.

PubMed

Micali, Nadia; Kothari, Radha; Nam, Kie Woo; Gioroukou, Elena; Walshe, Muriel; Allin, Matthew; Rifkin, Larry; Murray, Robin M; Nosarti, Chiara

2015-03-01

This study investigates the prevalence of eating disorder (ED) psychopathology, neuropsychological function, structural brain correlates and risk mechanisms in a prospective cohort of very preterm (VPT) young adults. We assessed ED psychopathology and neuropsychological correlates in 143 cohort individuals born at <33 weeks of gestation. Structural brain correlates and risk factors at birth, in childhood and adolescence, were investigated using prospectively collected data throughout childhood/adolescence. VPT-born individuals had high levels of ED psychopathology at age 21 years. Executive function did not correlate with ED symptomatology. VPT adults presenting with ED psychopathology had smaller grey matter volume at age 14/15 years in the left posterior cerebellum and smaller white matter volume in the fusiform gyrus bilaterally, compared with VPT adults with no ED psychopathology. Caesarean delivery predicted engaging in compensatory behaviours, and severe eating difficulty at age 14 years predicted ED symptomatology in young adulthood. VPT individuals are at risk for ED symptomatology, with evidence of associated structural alterations in posterior brain regions. Further prospective studies are needed to clarify the pathways that lead from perinatal/obstetric complications to ED and relevant neurobiological mechanisms. © 2015 The Authors. European Eating Disorders Review published by John Wiley &Sons, Ltd. © 2015 The Authors. European Eating Disorders Review published by John Wiley & Sons, Ltd.

Family income, parental education and brain structure in children and adolescents.

PubMed

Noble, Kimberly G; Houston, Suzanne M; Brito, Natalie H; Bartsch, Hauke; Kan, Eric; Kuperman, Joshua M; Akshoomoff, Natacha; Amaral, David G; Bloss, Cinnamon S; Libiger, Ondrej; Schork, Nicholas J; Murray, Sarah S; Casey, B J; Chang, Linda; Ernst, Thomas M; Frazier, Jean A; Gruen, Jeffrey R; Kennedy, David N; Van Zijl, Peter; Mostofsky, Stewart; Kaufmann, Walter E; Kenet, Tal; Dale, Anders M; Jernigan, Terry L; Sowell, Elizabeth R

2015-05-01

Socioeconomic disparities are associated with differences in cognitive development. The extent to which this translates to disparities in brain structure is unclear. We investigated relationships between socioeconomic factors and brain morphometry, independently of genetic ancestry, among a cohort of 1,099 typically developing individuals between 3 and 20 years of age. Income was logarithmically associated with brain surface area. Among children from lower income families, small differences in income were associated with relatively large differences in surface area, whereas, among children from higher income families, similar income increments were associated with smaller differences in surface area. These relationships were most prominent in regions supporting language, reading, executive functions and spatial skills; surface area mediated socioeconomic differences in certain neurocognitive abilities. These data imply that income relates most strongly to brain structure among the most disadvantaged children.

Gender effects on age-related changes in brain structure.

PubMed

Xu, J; Kobayashi, S; Yamaguchi, S; Iijima, K; Okada, K; Yamashita, K

2000-01-01

Previous reports have suggested that brain atrophy is associated with aging and that there are gender differences in brain atrophy with aging. These reports, however, neither exclude silent brain lesions in "healthy subjects" nor divide the brain into subregions. The aim of this study is to clarify the effect of gender on age-related changes in brain subregions by MR imaging. A computer-assisted system was used to calculate the brain matter area index (BMAI) of various regions of the brain from MR imaging of 331 subjects without brain lesions. There was significantly more brain atrophy with aging in the posterior parts of the right frontal lobe in male subjects than there was in female subjects. Age-related atrophy in the middle part of the right temporal lobe, the left basal ganglia, the parietal lobe, and the cerebellum also was found in male subjects, but not in female subjects. In the temporal lobe, thalamus, parieto-occipital lobe, and cerebellum, brain volume in the left hemisphere is significantly smaller than in the right hemisphere; sex and age did not affect the hemisphere differences of brain volume in these regions. The effect of gender on brain atrophy with aging varied in different subregions of the brain. There was more brain atrophy with aging in male subjects than in female subjects.

Population differences in brain morphology: Need for population specific brain template.

PubMed

Rao, Naren P; Jeelani, Haris; Achalia, Rashmin; Achalia, Garima; Jacob, Arpitha; Bharath, Rose Dawn; Varambally, Shivarama; Venkatasubramanian, Ganesan; K Yalavarthy, Phaneendra

2017-07-30

Brain templates provide a standard anatomical platform for population based morphometric assessments. Typically, standard brain templates for such assessments are created using Caucasian brains, which may not be ideal to analyze brains from other ethnicities. To effectively demonstrate this, we compared brain morphometric differences between T1 weighted structural MRI images of 27 healthy Indian and Caucasian subjects of similar age and same sex ratio. Furthermore, a population specific brain template was created from MRI images of healthy Indian subjects and compared with standard Montreal Neurological Institute (MNI-152) template. We also examined the accuracy of registration of by acquiring a different T1 weighted MRI data set and registering them to newly created Indian template and MNI-152 template. The statistical analysis indicates significant difference in global brain measures and regional brain structures of Indian and Caucasian subjects. Specifically, the global brain measurements of the Indian brain template were smaller than that of the MNI template. Also, Indian brain images were better realigned to the newly created template than to the MNI-152 template. The notable variations in Indian and Caucasian brains convey the need to build a population specific Indian brain template and atlas. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Nanoparticle Formulation Derived from Carboxymethyl Cellulose, Polyethylene Glycol, and Cabazitaxel for Chemotherapy Delivery to the Brain.

PubMed

Bteich, Joseph; Ernsting, Mark J; Mohammed, Mohammed; Kiyota, Taira; McKee, Trevor D; Trikha, Mohit; Lowman, Henry B; Sokoll, Kenneth K

2018-05-23

Nanoparticles provide a unique opportunity to explore the benefits of selective distribution and release of cancer therapeutics at sites of disease through varying particle sizes and compositions that exploit the enhanced permeability of tumor-associated blood vessels. Though delivery of larger as opposed to smaller and/or actively transported molecules to the brain is prima facie a challenging endeavor, we wondered whether nanoparticles could improve the therapeutic index of existing drugs for use in treating brain tumors via these vascular effects. We therefore selected a family of nanoparticles composed of cabazitaxel-carboxymethyl cellulose amphiphilic polymers to investigate the potential for delivering a brain-penetrant taxane to intracranial brain tumors in mice. Among a small set of nanoparticle formulations, we found evidence for nanoparticle accumulation in the brain, and one such formulation demonstrated activity in an orthotopic model of glioma, suggesting that such nanoparticles could be useful for the treatment of glioma and brain metastases of other tumor types.

Cerebellar Volume in Children With Attention-Deficit Hyperactivity Disorder (ADHD).

PubMed

Wyciszkiewicz, Aleksandra; Pawlak, Mikolaj A; Krawiec, Krzysztof

2017-02-01

Attention Deficit Hyperactivity Disorder (ADHD) is associated with altered cerebellar volume and cerebellum is associated with cognitive performance. However there are mixed results regarding the cerebellar volume in young patients with ADHD. To clarify the size and direction of this effect, we conducted the analysis on the large public database of brain images. The aim of this study was to confirm that cerebellar volume in ADHD is smaller than in control subjects in currently the largest publicly available cohort of ADHD subjects.We applied cross-sectional case control study design by comparing 286 ADHD patients (61 female) with age and gender matched control subjects. Volumetric measurements of cerebellum were obtained using automated segmentation with FreeSurfer 5.1. Statistical analysis was performed in R-CRAN statistical environment. Patients with ADHD had significantly smaller total cerebellar volumes (134.5±17.11cm 3 vs.138.90±15.32 cm 3 ). The effect was present in both females and males (males 136.9±14.37 cm 3 vs. 141.20±14.75 cm 3 ; females 125.7±12.34 cm 3 vs. 131.20±15.03 cm 3 ). Age was positively and significantly associated with the cerebellar volumes. These results indicate either delayed or disrupted cerebellar development possibly contributing to ADHD pathophysiology.

The Effects of Prediction on the Perception for Own-Race and Other-Race Faces

PubMed Central

Ran, Guangming; Zhang, Qi; Chen, Xu; Pan, Yangu

2014-01-01

Human beings do not passively perceive important social features about others such as race and age in social interactions. Instead, it is proposed that humans might continuously generate predictions about these social features based on prior similar experiences. Pre-awareness of racial information conveyed by others' faces enables individuals to act in “culturally appropriate” ways, which is useful for interpersonal relations in different ethnicity groups. However, little is known about the effects of prediction on the perception for own-race and other-race faces. Here, we addressed this issue using high temporal resolution event-related potential techniques. In total, data from 24 participants (13 women and 11 men) were analyzed. It was found that the N170 amplitudes elicited by other-race faces, but not own-race faces, were significantly smaller in the predictable condition compared to the unpredictable condition, reflecting a switch to holistic processing of other-race faces when those faces were predictable. In this respect, top-down prediction about face race might contribute to the elimination of the other-race effect (one face recognition impairment). Furthermore, smaller P300 amplitudes were observed for the predictable than for unpredictable conditions, which suggested that the prediction of race reduced the neural responses of human brains. PMID:25422892

Large Soluble Oligomers of Amyloid β-Protein from Alzheimer Brain Are Far Less Neuroactive Than the Smaller Oligomers to Which They Dissociate

PubMed Central

Yang, Ting; Li, Shaomin; Xu, Huixin

2017-01-01

Soluble oligomers of amyloid β-protein (oAβ) isolated from the brains of Alzheimer's disease (AD) patients have been shown experimentally (in the absence of amyloid plaques) to impair hippocampal synaptic plasticity, decrease synapses, induce tau hyperphosphorylation and neuritic dystrophy, activate microglial inflammation, and impair memory in normal adult rodents. Nevertheless, there has been controversy about what types of oligomers actually confer these AD-like phenotypes. Here, we show that the vast majority of soluble Aβ species obtained from brains of humans who died with confirmed AD elute at high molecular weight (HMW) on nondenaturing size-exclusion chromatography. These species have little or no cytotoxic activity in several bioassays. However, incubation of HMW oAβ in mildly alkaline buffer led to their quantitative dissociation into low molecular weight oligomers (∼8–70 kDa), and these were now far more bioactive: they impaired hippocampal LTP, decreased neuronal levels of β2-adrenergic receptors, and activated microglia in wt mice in vivo. Thus, most soluble Aβ assemblies in AD cortex are large and inactive but under certain circumstances can dissociate into smaller, highly bioactive species. Insoluble amyloid plaques likely sequester soluble HMW oligomers, limiting their potential to dissociate. We conclude that conditions that destabilize HMW oligomers or retard the sequestration of their smaller, more bioactive components are important drivers of Aβ toxicity. Selectively targeting these small, cytotoxic forms should be therapeutically beneficial. SIGNIFICANCE STATEMENT Oligomers of amyloid β-protein (oAβ) are tought to play an important role in Alzheimer's disease (AD), but there is confusion and controversy about what types and sizes of oligomers have disease-relevant activity. Using size-exclusion chromatography and three distinct measures of bioactivity, we show that the predominant forms of Aβ in aqueous extracts of AD brain are high molecular weight (HMW) and relatively inactive. Importantly, under certain conditions, the abundant HMW oAβ can dissociate into low molecular weight species, and these low molecular weight oligomers are significantly more bioactive on synapses and microglia than the HMW species from which they are derived. We conclude that conditions that destabilize HMW oAβ or retard the sequestration of smaller, more bioactive components are important drivers of Aβ toxicity. PMID:28053038

Orbitofrontal and caudate volumes in cannabis users: a multi-site mega-analysis comparing dependent versus non-dependent users.

PubMed

Chye, Yann; Solowij, Nadia; Suo, Chao; Batalla, Albert; Cousijn, Janna; Goudriaan, Anna E; Martin-Santos, Rocio; Whittle, Sarah; Lorenzetti, Valentina; Yücel, Murat

2017-07-01

Cannabis (CB) use and dependence are associated with regionally specific alterations to brain circuitry and substantial psychosocial impairment. The objective of this study was to investigate the association between CB use and dependence, and the volumes of brain regions critically involved in goal-directed learning and behaviour-the orbitofrontal cortex (OFC) and caudate. In the largest multi-site structural imaging study of CB users vs healthy controls (HC), 140 CB users and 121 HC were recruited from four research sites. Group differences in OFC and caudate volumes were investigated between HC and CB users and between 70 dependent (CB-dep) and 50 non-dependent (CB-nondep) users. The relationship between quantity of CB use and age of onset of use and caudate and OFC volumes was explored. CB users (consisting of CB-dep and CB-nondep) did not significantly differ from HC in OFC or caudate volume. CB-dep compared to CB-nondep users exhibited significantly smaller volume in the medial and the lateral OFC. Lateral OFC volume was particularly smaller in CB-dep females, and reduced volume in the CB-dep group was associated with higher monthly cannabis dosage. Smaller medial OFC volume may be driven by CB dependence-related mechanisms, while smaller lateral OFC volume may be due to ongoing exposure to cannabinoid compounds. The results highlight a distinction between cannabis use and dependence and warrant examination of gender-specific effects in studies of CB dependence.

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.

The effect of brain size evolution on feeding propensity, digestive efficiency, and juvenile growth

PubMed Central

Kotrschal, Alexander; Corral‐Lopez, Alberto; Szidat, Sönke; Kolm, Niclas

2015-01-01

One key hypothesis in the study of brain size evolution is the expensive tissue hypothesis; the idea that increased investment into the brain should be compensated by decreased investment into other costly organs, for instance the gut. Although the hypothesis is supported by both comparative and experimental evidence, little is known about the potential changes in energetic requirements or digestive traits following such evolutionary shifts in brain and gut size. Organisms may meet the greater metabolic requirements of larger brains despite smaller guts via increased food intake or better digestion. But increased investment in the brain may also hamper somatic growth. To test these hypotheses we here used guppy (Poecilia reticulata) brain size selection lines with a pronounced negative association between brain and gut size and investigated feeding propensity, digestive efficiency (DE), and juvenile growth rate. We did not find any difference in feeding propensity or DE between large‐ and small‐brained individuals. Instead, we found that large‐brained females had slower growth during the first 10 weeks after birth. Our study provides experimental support that investment into larger brains at the expense of gut tissue carries costs that are not necessarily compensated by a more efficient digestive system. PMID:26420573

Marijuana effects on changes in brain structure and cognitive function among HIV+ and HIV- adults.

PubMed

Thames, April D; Kuhn, Taylor P; Williamson, Timothy J; Jones, Jacob D; Mahmood, Zanjbeel; Hammond, Andrea

2017-01-01

The current study examined the independent and interactive effects of HIV and marijuana (MJ) use on brain structure and cognitive function among a sample of HIV-positive (HIV+) and HIV-negative (HIV-) individuals. Participants (HIV+, n=48; HIV-, n=29) individuals underwent cognitive testing, questionnaires about substance use, and brain MRI. The HIV+ group was clinically stable based upon current plasma CD4 count, 50% had undetectable viral load (i.e.,<20 copies/mL), and all were on a stable regimen of cART. For HIV+ and HIV- participants, higher levels of MJ use were associated with smaller volumes in the entorhinal cortex and fusiform gyrus. HIV status (but not MJ use) was associated with cingulate thickness, such that HIV+ participants evidenced smaller thickness of the cingulate, as compared to HIV- controls. Regarding neurocognitive functioning, there was a HIV*MJ interactive effect on global cognition, such that when the amount of MJ use was less than 1.43g per week, the HIV- group displayed significantly better neurocognitive performance than the HIV+ group (t=3.14, p=0.002). However, when MJ use reached 1.43g per week, there were no significant HIV group differences in global cognitive performance (t=1.39, p=0.168). Our results show independent and interactive effects of HIV and MJ on brain structure and cognition. However, our results do not support that HIV+ MJ users are at greater risk for adverse brain or cognitive outcomes compared to HIV- MJ users. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Acute Ischemic Stroke Infarct Topology: Association with Lesion Volume and Severity of Symptoms at Admission and Discharge.

PubMed

Payabvash, S; Taleb, S; Benson, J C; McKinney, A M

2017-01-01

Acute stroke presentation and outcome depend on both ischemic infarct volume and location. We aimed to determine the association between acute ischemic infarct topology and lesion volume and stroke severity at presentation and discharge. Patients with acute ischemic stroke who underwent MR imaging within 24 hours of symptom onset or last seen well were included. Infarcts were segmented and coregistered on the Montreal Neurological Institute-152 brain map. Voxel-based analyses were performed to determine the distribution of infarct lesions associated with larger volumes, higher NIHSS scores at admission and discharge, and greater NIHSS/volume ratios. A total of 238 patients were included. Ischemic infarcts involving the bilateral lentiform nuclei, insular ribbons, middle corona radiata, and right precentral gyrus were associated with larger infarct volumes (average, 76.7 ± 125.6 mL versus 16.4 ± 24.0 mL, P < .001) and higher admission NIHSS scores. Meanwhile, brain stem and thalami infarctions were associated with higher admission NIHSS/volume ratios. The discharge NIHSS scores were available in 218 patients, in whom voxel-based analysis demonstrated that ischemic infarcts of the bilateral posterior insular ribbons, middle corona radiata, and right precentral gyrus were associated with more severe symptoms at discharge, whereas ischemic lesions of the brain stem, bilateral thalami, and, to a lesser extent, the middle corona radiata were associated with higher ratios of discharge NIHSS score/infarct volume. Acute ischemic infarcts of the insulae, lentiform nuclei, and middle corona radiata tend to have larger volumes, more severe presentations, and worse outcomes, whereas brain stem and thalamic infarcts have greater symptom severity relative to smaller lesion volumes. © 2017 by American Journal of Neuroradiology.

Reproducibility of Brain Morphometry from Short-Term Repeat Clinical MRI Examinations: A Retrospective Study

PubMed Central

Liu, Hon-Man; Chen, Shan-Kai; Chen, Ya-Fang; Lee, Chung-Wei; Yeh, Lee-Ren

2016-01-01

Purpose To assess the inter session reproducibility of automatic segmented MRI-derived measures by FreeSurfer in a group of subjects with normal-appearing MR images. Materials and Methods After retrospectively reviewing a brain MRI database from our institute consisting of 14,758 adults, those subjects who had repeat scans and had no history of neurodegenerative disorders were selected for morphometry analysis using FreeSurfer. A total of 34 subjects were grouped by MRI scanner model. After automatic segmentation using FreeSurfer, label-wise comparison (involving area, thickness, and volume) was performed on all segmented results. An intraclass correlation coefficient was used to estimate the agreement between sessions. Wilcoxon signed rank test was used to assess the population mean rank differences across sessions. Mean-difference analysis was used to evaluate the difference intervals across scanners. Absolute percent difference was used to estimate the reproducibility errors across the MRI models. Kruskal-Wallis test was used to determine the across-scanner effect. Results The agreement in segmentation results for area, volume, and thickness measurements of all segmented anatomical labels was generally higher in Signa Excite and Verio models when compared with Sonata and TrioTim models. There were significant rank differences found across sessions in some labels of different measures. Smaller difference intervals in global volume measurements were noted on images acquired by Signa Excite and Verio models. For some brain regions, significant MRI model effects were observed on certain segmentation results. Conclusions Short-term scan-rescan reliability of automatic brain MRI morphometry is feasible in the clinical setting. However, since repeatability of software performance is contingent on the reproducibility of the scanner performance, the scanner performance must be calibrated before conducting such studies or before using such software for retrospective reviewing. PMID:26812647

Perifocal and remote blood-brain barrier disruption in cortical photothrombotic ischemic lesion and its modulation by the choice of anesthesia.

PubMed

Krysl, D; Deykun, K; Lambert, L; Pokorny, J; Mares, J

2012-04-01

We assessed blood-brain barrier (BBB) disruption in early stage of photothrombotic focal cerebral ischemia in the rat. We specifically looked for contralateral changes in BBB permeability and tested the influence of two anesthetics on the results. Adult Wistar rats were randomly anesthetized with pentobarbital (PB) or ketamine-xylazine (KX). Rats received intravenously (i.v.) Rose Bengal followed by Evans Blue (EB). Stereotactically defined spots on denuded skull were irradiated by laser (532 nm) for 18 min. Twenty four hours later, rats were killed, brains perfused, fixated, sectioned and slices analyzed by fluorescence microscopy. Volume of necrosis and volume of EB-albumin extravasation were calculated. Evidence of BBB breakdown in remote brain areas was sought and compared to sham handled controls. BBB disruption was consistently present, frequently with EB-albumin accumulating cells. Total lesion volume did not significantly differ among groups (TLVPB=9.4±1.3 mm³ vs. TLVKX=8.3±2.1 mm³); same was true for the volume of necrosis (NVPB=5.1±0.7 mm³ vs. NVKX=6.3±1.9 mm³). However, volume of EB-albumin extravasation area was significantly smaller in KX group (EBEVPB=4.3±0.8 mm³ vs. EBEVKX=2.0±0.5 mm³; p=0.0293). Median background EB-fluorescence signal density was higher in PB group (p<0.0001). Furthermore, regional increase in EB-fluorescence was found in two animals in PB group. Our study shows that anesthesia with NMDA-antagonist ketamine and α2-adrenergic agonist xylazine may reduce BBB breakdown in photothrombosis. Pentobarbital anesthesia lead to increased BBB permeability in the contralateral hemisphere.

Functional mapping of language networks in the normal brain using a word-association task.

PubMed

Ghosh, Shantanu; Basu, Amrita; Kumaran, Senthil S; Khushu, Subash

2010-08-01

Language functions are known to be affected in diverse neurological conditions, including ischemic stroke, traumatic brain injury, and brain tumors. Because language networks are extensive, interpretation of functional data depends on the task completed during evaluation. The aim was to map the hemodynamic consequences of word association using functional magnetic resonance imaging (fMRI) in normal human subjects. Ten healthy subjects underwent fMRI scanning with a postlexical access semantic association task vs lexical processing task. The fMRI protocol involved a T2*-weighted gradient-echo echo-planar imaging (GE-EPI) sequence (TR 4523 ms, TE 64 ms, flip angle 90°) with alternate baseline and activation blocks. A total of 78 scans were taken (interscan interval = 3 s) with a total imaging time of 587 s. Functional data were processed in Statistical Parametric Mapping software (SPM2) with 8-mm Gaussian kernel by convolving the blood oxygenation level-dependent (BOLD) signal with an hemodynamic response function estimated by general linear method to generate SPM{t} and SPM{F} maps. Single subject analysis of the functional data (FWE-corrected, P≤0.001) revealed extensive activation in the frontal lobes, with overlaps among middle frontal gyrus (MFG), superior, and inferior frontal gyri. BOLD activity was also found in the medial frontal gyrus, middle occipital gyrus (MOG), anterior fusiform gyrus, superior and inferior parietal lobules, and to a smaller extent, the thalamus and right anterior cerebellum. Group analysis (FWE-corrected, P≤0.001) revealed neural recruitment of bilateral lingual gyri, left MFG, bilateral MOG, left superior occipital gyrus, left fusiform gyrus, bilateral thalami, and right cerebellar areas. Group data analysis revealed a cerebellar-occipital-fusiform-thalamic network centered around bilateral lingual gyri for word association, thereby indicating how these areas facilitate language comprehension by activating a semantic association network of words processed postlexical access. This finding is important when assessing the extent of cognitive damage and/or recovery and can be used for presurgical planning after optimization.

Artificial selection on relative brain size in the guppy reveals costs and benefits of evolving a larger brain.

PubMed

Kotrschal, Alexander; Rogell, Björn; Bundsen, Andreas; Svensson, Beatrice; Zajitschek, Susanne; Brännström, Ioana; Immler, Simone; Maklakov, Alexei A; Kolm, Niclas

2013-01-21

The large variation in brain size that exists in the animal kingdom has been suggested to have evolved through the balance between selective advantages of greater cognitive ability and the prohibitively high energy demands of a larger brain (the "expensive-tissue hypothesis"). Despite over a century of research on the evolution of brain size, empirical support for the trade-off between cognitive ability and energetic costs is based exclusively on correlative evidence, and the theory remains controversial. Here we provide experimental evidence for costs and benefits of increased brain size. We used artificial selection for large and small brain size relative to body size in a live-bearing fish, the guppy (Poecilia reticulata), and found that relative brain size evolved rapidly in response to divergent selection in both sexes. Large-brained females outperformed small-brained females in a numerical learning assay designed to test cognitive ability. Moreover, large-brained lines, especially males, developed smaller guts, as predicted by the expensive-tissue hypothesis, and produced fewer offspring. We propose that the evolution of brain size is mediated by a functional trade-off between increased cognitive ability and reproductive performance and discuss the implications of these findings for vertebrate brain evolution. Copyright © 2013 Elsevier Ltd. All rights reserved.

Artistic creativity and dementia.

PubMed

Miller, Zachary A; Miller, Bruce L

2013-01-01

Artistic ability and creativity are defining characteristics of human behavior. Behavioral neurology, as a specialty, believes that even the most complex behaviors can be modeled and understood as the summation of smaller cognitive functions. Literature from individuals with specific brain lesions has helped to map out these smaller regions of cognitive abilities. More recently, models based on neurodegenerative conditions, especially from the frontotemporal dementias, have allowed for greater nuanced investigations into the various functional anatomies necessary for artistic behavior and possibly the underlying networks that promote creativity. © 2013 Elsevier B.V. All rights reserved.

Family Income, Parental Education and Brain Structure in Children and Adolescents

PubMed Central

Noble, Kimberly G.; Houston, Suzanne M.; Brito, Natalie H.; Bartsch, Hauke; Kan, Eric; Kuperman, Joshua M.; Akshoomoff, Natacha; Amaral, David G.; Bloss, Cinnamon S.; Libiger, Ondrej; Schork, Nicholas J.; Murray, Sarah S.; Casey, B. J.; Chang, Linda; Ernst, Thomas M.; Frazier, Jean A.; Gruen, Jeffrey R.; Kennedy, David N.; Zijl, Peter Van; Mostofsky, Stewart; Kaufmann, Walter E.; Kenet, Tal; Dale, Anders M.; Jernigan, Terry L.; Sowell, Elizabeth R.

2015-01-01

Socioeconomic disparities are associated with differences in cognitive development. The extent to which this translates to disparities in brain structure is unclear. Here, we investigated relationships between socioeconomic factors and brain morphometry, independently of genetic ancestry, among a cohort of 1099 typically developing individuals between 3 and 20 years. Income was logarithmically associated with brain surface area. Specifically, among children from lower income families, small differences in income were associated with relatively large differences in surface area, whereas, among children from higher income families, similar income increments were associated with smaller differences in surface area. These relationships were most prominent in regions supporting language, reading, executive functions and spatial skills; surface area mediated socioeconomic differences in certain neurocognitive abilities. These data indicate that income relates most strongly to brain structure among the most disadvantaged children. Potential implications are discussed. PMID:25821911

Visuospatial asymmetries and interocular transfer in the split-brain rat.

PubMed

Adelstein, A; Crowne, D P

1991-06-01

Interocular transfer (IOT), hemispheric superiority, and cerebral dominance were examined in split-brain female albino rats. Callosum-sectioned and intact animals were monocularly trained in the Morris water maze and tested in IOT and reversal phases. In the IOT phase, split-brain rats entered more nontarget quadrants and headed less accurately toward the platform than did controls. For both split-brain animals and controls, right-eye training resulted in shorter latencies and fewer nontarget entries than did left-eye training. Analyses of cerebral dominance showed shorter latencies and smaller heading errors over all 3 phases in rats that were trained with the nondominant eye. Right-eye dominant controls were less affected by platform reversal. Split-brain rats were inferior to controls in latency to find the platform and in target quadrant entries. This finding establishes a spatial cognitive deficit from callosum section.

Variations and asymmetries in regional brain surface in the genus Homo.

PubMed

Balzeau, Antoine; Holloway, Ralph L; Grimaud-Hervé, Dominique

2012-06-01

Paleoneurology is an important field of research within human evolution studies. Variations in size and shape of an endocast help to differentiate among fossil hominin species whereas endocranial asymmetries are related to behavior and cognitive function. Here we analyse variations of the surface of the frontal, parieto-temporal and occipital lobes among different species of Homo, including 39 fossil hominins, ten fossil anatomically modern Homo sapiens and 100 endocasts of extant modern humans. We also test for the possible asymmetries of these features in a large sample of modern humans and observe individual particularities in the fossil specimens. This study contributes important new information about the brain evolution in the genus Homo. Our results show that the general pattern of surface asymmetry for the different regional brain surfaces in fossil species of Homo does not seem to be different from the pattern described in a large sample of anatomically modern H. sapiens, i.e., the right hemisphere has a larger surface than the left, as do the right frontal, the right parieto-temporal and the left occipital lobes compared with the contra-lateral side. It also appears that Asian Homo erectus specimens are discriminated from all other samples of Homo, including African and Georgian specimens that are also sometimes included in that taxon. The Asian fossils show a significantly smaller relative size of the parietal and temporal lobes. Neandertals and anatomically modern H. sapiens, who share the largest endocranial volume of all hominins, show differences when considering the relative contribution of the frontal, parieto-temporal and occipital lobes. These results illustrate an original variation in the pattern of brain organization in hominins independent of variations in total size. The globularization of the brain and the enlargement of the parietal lobes could be considered derived features observed uniquely in anatomically modern H. sapiens. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hemodynamic measurements in rat brain and human muscle using diffuse near-infrared absorption and correlation spectroscopies

NASA Astrophysics Data System (ADS)

Yu, Guoqiang; Durduran, Turgut; Furuya, D.; Lech, G.; Zhou, Chao; Chance, Britten; Greenberg, J. H.; Yodh, Arjun G.

2003-07-01

Measurement of concentration, oxygenation, and flow characteristics of blood cells can reveal information about tissue metabolism and functional heterogeneity. An improved multifunctional hybrid system has been built on the basis of our previous hybrid instrument that combines two near-infrared diffuse optical techniques to simultaneously monitor the changes of blood flow, total hemoglobin concentration (THC) and blood oxygen saturation (StO2). Diffuse correlation spectroscopy (DCS) monitors blood flow (BF) by measuring the optical phase shifts caused by moving blood cells, while diffuse photon density wave spectroscopy (DPDW) measures tissue absorption and scattering. Higher spatial resolution, higher data acquisition rate and higher dynamic range of the improved system allow us to monitor rapid hemodynamic changes in rat brain and human muscles. We have designed two probes with different source-detector pairs and different separations for the two types of experiments. A unique non-contact probe mounted on the back of a camera, which allows continuous measurements without altering the blood flow, was employed to in vivo monitor the metabolic responses in rat brain during KCl induced cortical spreading depression (CSD). A contact probe was used to measure changes of blood flow and oxygenation in human muscle during and after cuff occlusion or exercise, where the non-contact probe is not appropriate for monitoring the moving target. The experimental results indicate that our multifunctional hybrid system is capable of in vivo and non-invasive monitoring of the hemodynamic changes in different tissues (smaller tissues in rat brain, larger tissues in human muscle) under different conditions (static versus moving). The time series images of flow during CSD obtained by our technique revealed spatial and temporal hemodynamic changes in rat brain. Two to three fold longer recovery times of flow and oxygenation after cuff occlusion or exercise from calf flexors in a patient with peripheral vascular disease (PVD) were found.

Combat-acquired traumatic brain injury, posttraumatic stress disorder, and their relative associations with postdeployment binge drinking

PubMed Central

Adams, Rachel Sayko; Larson, Mary Jo; Corrigan, John D.; Ritter, Grant A.; Horgan, Constance M.; Bray, Robert M.; Williams, Thomas V.

2014-01-01

Objective To examine whether experiencing a traumatic brain injury (TBI) on a recent combat deployment was associated with postdeployment binge drinking, independent of posttraumatic stress disorder (PTSD). Methods Using the 2008 Department of Defense Survey of Health Related Behaviors among Active Duty Military Personnel, an anonymous survey completed by 28,546 personnel, the study sample included 6,824 personnel who had a combat deployment in the past year. Path analysis was used to examine whether PTSD accounted for the total association between TBI and binge drinking. Main Measures The dependent variable, binge drinking days, was an ordinal measure capturing the number of times personnel drank 5+ drinks on one occasion (4+ for women) in the past month. TBI-level captured the severity of TBI after a combat injury event exposure: TBI-AC (altered consciousness only), TBI-LOC≤20 (loss of consciousness up to 20 minutes), and TBI-LOC>20 (loss of consciousness greater than 20 minutes). APTSD positive screen relied on the standard diagnostic cutoff of 50+ on the PCL-C. Results The final path model found that while the direct effect of TBI (0.097) on binge drinking was smaller than that of PTSD (0.156), both were significant. Almost 70% of the total effect of TBI on binge drinking was from the direct effect; only 30% represented the indirect effect through PTSD. Conclusion Further research is needed to replicate these findings and to understand the underlying mechanisms that explain the relationship between TBI and increased postdeployment drinking. PMID:25310293

Gray Matter Alterations in Adults with Attention-Deficit/Hyperactivity Disorder Identified by Voxel Based Morphometry

PubMed Central

Seidman, Larry J.; Biederman, Joseph; Liang, Lichen; Valera, Eve M.; Monuteaux, Michael C.; Brown, Ariel; Kaiser, Jonathan; Spencer, Thomas; Faraone, Stephen V.; Makris, Nikos

2014-01-01

Background Gray and white matter volume deficits have been reported in many structural magnetic resonance imaging (MRI) studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural MRI studies of adults with ADHD. This study used voxel based morphometry and applied an a priori region of interest approach based on our previous work, as well as from well-developed neuroanatomical theories of ADHD. Methods Seventy-four adults with DSM-IV ADHD and 54 healthy control subjects comparable on age, sex, race, handedness, IQ, reading achievement, frequency of learning disabilities, and whole brain volume had an MRI on a 1.5T Siemens scanner. A priori region of interest hypotheses focused on reduced volumes in ADHD in dorsolateral prefrontal cortex, anterior cingulate cortex, caudate, putamen, inferior parietal lobule, and cerebellum. Analyses were carried out by FSL-VBM 1.1. Results Relative to control subjects, ADHD adults had significantly smaller gray matter volumes in parts of six of these regions at p ≤ .01, whereas parts of the dorsolateral prefrontal cortex and inferior parietal lobule were significantly larger in ADHD at this threshold. However, a number of other regions were smaller and larger in ADHD (especially fronto-orbital cortex) at this threshold. Only the caudate remained significantly smaller at the family-wise error rate. Conclusions Adults with ADHD have subtle volume reductions in the caudate and possibly other brain regions involved in attention and executive control supporting frontostriatal models of ADHD. Modest group brain volume differences are discussed in the context of the nature of the samples studied and voxel based morphometry methodology. PMID:21183160

Cannabis, Cigarettes, and Their Co-Occurring Use: Disentangling Differences in Gray Matter Volume

PubMed Central

Jagannathan, Kanchana; Hager, Nathan; Childress, Anna Rose; Rao, Hengyi; Franklin, Teresa R.

2015-01-01

Background: Structural magnetic resonance imaging techniques are powerful tools for examining the effects of drug use on the brain. The nicotine and cannabis literature has demonstrated differences between nicotine cigarette smokers and cannabis users compared to controls in brain structure; however, less is known about the effects of co-occurring cannabis and tobacco use. Methods: We used voxel-based morphometry to examine gray matter volume differences between four groups: (1) cannabis-dependent individuals who do not smoke tobacco (Cs); (2) cannabis-dependent individuals who smoke tobacco (CTs); (3) cannabis-naïve, nicotine-dependent individuals who smoke tobacco (Ts); and (4) healthy controls (HCs). We also explored associations between gray matter volume and measures of cannabis and tobacco use. Results: A significant group effect was observed in the left putamen, thalamus, right precentral gyrus, and left cerebellum. Compared to HCs, the Cs, CTs, and Ts exhibited larger gray matter volumes in the left putamen. Cs also had larger gray matter volume than HCs in the right precentral gyrus. Cs and CTs exhibited smaller gray matter volume than HCs in the thalamus, and CTs and Ts had smaller left cerebellar gray matter volume than HCs. Conclusions: This study extends previous research that independently examined the effects of cannabis or tobacco use on brain structure by including an examination of co-occurring cannabis and tobacco use, and provides evidence that cannabis and tobacco exposure are associated with alterations in brain regions associated with addiction. PMID:26045474

Application of machine learning methods to describe the effects of conjugated equine estrogens therapy on region-specific brain volumes.

PubMed

Casanova, Ramon; Espeland, Mark A; Goveas, Joseph S; Davatzikos, Christos; Gaussoin, Sarah A; Maldjian, Joseph A; Brunner, Robert L; Kuller, Lewis H; Johnson, Karen C; Mysiw, W Jerry; Wagner, Benjamin; Resnick, Susan M

2011-05-01

Use of conjugated equine estrogens (CEE) has been linked to smaller regional brain volumes in women aged ≥65 years; however, it is unknown whether this results in a broad-based characteristic pattern of effects. Structural magnetic resonance imaging was used to assess regional volumes of normal tissue and ischemic lesions among 513 women who had been enrolled in a randomized clinical trial of CEE therapy for an average of 6.6 years, beginning at ages 65-80 years. A multivariate pattern analysis, based on a machine learning technique that combined Random Forest and logistic regression with L(1) penalty, was applied to identify patterns among regional volumes associated with therapy and whether patterns discriminate between treatment groups. The multivariate pattern analysis detected smaller regional volumes of normal tissue within the limbic and temporal lobes among women that had been assigned to CEE therapy. Mean decrements ranged as high as 7% in the left entorhinal cortex and 5% in the left perirhinal cortex, which exceeded the effect sizes reported previously in frontal lobe and hippocampus. Overall accuracy of classification based on these patterns, however, was projected to be only 54.5%. Prescription of CEE therapy for an average of 6.6 years is associated with lower regional brain volumes, but it does not induce a characteristic spatial pattern of changes in brain volumes of sufficient magnitude to discriminate users and nonusers. Copyright © 2011 Elsevier Inc. All rights reserved.

Application of machine learning methods to describe the effects of conjugated equine estrogens therapy on region-specific brain volumes

PubMed Central

Casanova, Ramon; Espeland, Mark A.; Goveas, Joseph S.; Davatzikos, Christos; Gaussoin, Sarah A.; Maldjian, Joseph A.; Brunner, Robert L.; Kuller, Lewis H.; Johnson, Karen C.; Mysiw, W. Jerry; Wagner, Benjamin; Resnick, Susan M.

2011-01-01

Use of conjugated equine estrogens (CEE) has been linked to smaller regional brain volumes in women aged ≥65 years, however it is unknown whether this results in a broad-based characteristic pattern of effects. Structural MRI was used to assess regional volumes of normal tissue and ischemic lesions among 513 women who had been enrolled in a randomized clinical trial of CEE therapy for an average of 6.6 years, beginning at ages 65-80 years. A multivariate pattern analysis, based on a machine learning technique that combined Random Forest and logistic regression with L1 penalty, was applied to identify patterns among regional volumes associated with therapy and whether patterns discriminate between treatment groups. The multivariate pattern analysis detected smaller regional volumes of normal tissue within the limbic and temporal lobes among women that had been assigned to CEE therapy. Mean decrements ranged as high as 7% in the left entorhinal cortex and 5% in the left perirhinal cortex, which exceeded the effect sizes reported previously in frontal lobe and hippocampus. Overall accuracy of classification based on these patterns, however, was projected to be only 54.5%. Prescription of CEE therapy for an average of 6.6 years is associated with lower regional brain volumes, but it does not induce a characteristic spatial pattern of changes in brain volumes of sufficient magnitude to discriminate users and non-users. PMID:21292420

Moderate and late preterm birth: effect on brain size and maturation at term-equivalent age.

PubMed

Walsh, Jennifer M; Doyle, Lex W; Anderson, Peter J; Lee, Katherine J; Cheong, Jeanie L Y

2014-10-01

To compare the size of multiple brain structures, maturation in terms of both brain myelination and gyral development, and evidence of brain injury between moderate and late preterm (MLPT) and term-born infants at term-equivalent age. The study was approved by the human research ethics committees of the participating hospitals, and informed parental consent was obtained for all infants. One hundred ninety-nine MLPT and 50 term-born infants underwent 3-T magnetic resonance (MR) imaging brain examinations at 38-44 weeks of corrected gestational age. T1- and T2-weighted MR images were compared between groups for size of multiple cerebral structures, degree of myelination in the posterior limb of the internal capsule, gyral maturation, signal intensity abnormalities, and presence of cysts by a single assessor who was blinded to the gestational group and perinatal course of the infants. Group differences were compared by using linear regression for continuous variables and logistic regression for categorical variables, and interrater and intrarater reliability was assessed by using intraclass correlation coefficients. Compared with those in the term-born control group, measurements of brain biparietal diameter, corpus callosum, basal ganglia and thalami, and cerebellum were smaller in infants in the MLPT group (all P ≤ .01), while extracerebral space was larger (P < .0001). Myelination of the posterior limb of the internal capsule was less developed, and gyral maturation was delayed in the MLPT group (both P < .001). Signal intensity abnormalities and cysts were uncommon in both groups, with 13 (6.5%) MLPT infants and one (2%) term infant having abnormalities. Inter- and intrarater reliability was good for most measures, with intraclass correlation coefficients generally greater than 0.68. MLPT birth is associated with smaller brain size, less-developed myelination of the posterior limb of the internal capsule, and more immature gyral folding than those associated with full-term birth. These brain changes may form the basis of some of the long-term neurodevelopmental deficits observed in MLPT children. Online supplemental material is available for this article. © RSNA, 2014.

Congenital heart disease affects cerebral size but not brain growth.

PubMed

Ortinau, Cynthia; Inder, Terrie; Lambeth, Jennifer; Wallendorf, Michael; Finucane, Kirsten; Beca, John

2012-10-01

Infants with congenital heart disease (CHD) have delayed brain maturation and alterations in brain volume. Brain metrics is a simple measurement technique that can be used to evaluate brain growth. This study used brain metrics to test the hypothesis that alterations in brain size persist at 3 months of age and that infants with CHD have slower rates of brain growth than control infants. Fifty-seven infants with CHD underwent serial brain magnetic resonance imaging (MRI). To evaluate brain growth across the first 3 months of life, brain metrics were undertaken using 19 tissue and fluid spaces shown on MRIs performed before surgery and again at 3 months of age. Before surgery, infants with CHD have smaller frontal, parietal, cerebellar, and brain stem measures (p < 0.001). At 3 months of age, alterations persisted in all measures except the cerebellum. There was no difference between control and CHD infants in brain growth. However, the cerebellum trended toward greater growth in infants with CHD. Somatic growth was the primary factor that related to brain growth. Presence of focal white matter lesions before and after surgery did not relate to alterations in brain size or growth. Although infants with CHD have persistent alterations in brain size at 3 months of age, rates of brain growth are similar to that of healthy term infants. Somatic growth was the primary predictor of brain growth, emphasizing the importance of optimal weight gain in this population.

Large-brained frogs mature later and live longer.

PubMed

Yu, Xin; Zhong, Mao Jun; Li, Da Yong; Jin, Long; Liao, Wen Bo; Kotrschal, Alexander

2018-05-01

Brain sizes vary substantially across vertebrate taxa, yet, the evolution of brain size appears tightly linked to the evolution of life histories. For example, larger brained species generally live longer than smaller brained species. A larger brain requires more time to grow and develop at a cost of exceeded gestation period and delayed weaning age. The cost of slower development may be compensated by better homeostasis control and increased cognitive abilities, both of which should increase survival probabilities and hence life span. To date, this relationship between life span and brain size seems well established in homoeothermic animals, especially in mammals. Whether this pattern occurs also in other clades of vertebrates remains enigmatic. Here, we undertake the first comparative test of the relationship between life span and brain size in an ectothermic vertebrate group, the anuran amphibians. After controlling for the effects of shared ancestry and body size, we find a positive correlation between brain size, age at sexual maturation, and life span across 40 species of frogs. Moreover, we also find that the ventral brain regions, including the olfactory bulbs, are larger in long-lived species. Our results indicate that the relationship between life history and brain evolution follows a general pattern across vertebrate clades. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Effects of marijuana use on prefrontal and parietal volumes and cognition in emerging adults.

PubMed

Price, Jenessa S; McQueeny, Tim; Shollenbarger, Skyler; Browning, Erin L; Wieser, Jon; Lisdahl, Krista M

2015-08-01

Chronic marijuana (MJ) use among adolescents has been associated with structural and functional abnormalities, particularly in developing regions responsible for higher order cognition. This study investigated prefrontal (PFC) and parietal volumes and executive function in emerging adult MJ users and explored potential gender differences. Participants (ages 18-25) were 27 MJ users and 32 controls without neurologic or psychiatric disorders or heavy other drug use. A series of multiple regressions examined whether group status, past year MJ use, and their interactions with gender predicted ROI volumes. Post hoc analyses consisted of brain-behavior correlations between volumes and cognitive variables and Fisher's z tests to assess group differences. MJ users demonstrated significantly smaller medial orbitofrontal (mOFC; p = 0.004, FDR p = 0.024) and inferior parietal volumes (p = 0.04, FDR p = 0.12); follow-up regressions found that increased past year MJ use did not significantly dose-dependently predict smaller mOFC volume in a sub-sample of individuals with at least one past year MJ use. There were no significant gender interactions. There was a significant brain-behavior difference by group, such that smaller mOFC volumes were associated with poorer complex attention for MJ users (p < 0.05). Smaller mOFC volumes among MJ users suggest disruption of typical neurodevelopmental processes associated with regular MJ use for both genders. These results highlight the need for longitudinal, multi-modal imaging studies providing clearer information on timing of neurodevelopmental processes and neurocognitive impacts of youth MJ initiation.

Higher Media Multi-Tasking Activity Is Associated with Smaller Gray-Matter Density in the Anterior Cingulate Cortex

PubMed Central

Loh, Kep Kee; Kanai, Ryota

2014-01-01

Media multitasking, or the concurrent consumption of multiple media forms, is increasingly prevalent in today’s society and has been associated with negative psychosocial and cognitive impacts. Individuals who engage in heavier media-multitasking are found to perform worse on cognitive control tasks and exhibit more socio-emotional difficulties. However, the neural processes associated with media multi-tasking remain unexplored. The present study investigated relationships between media multitasking activity and brain structure. Research has demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. Thus, we expected differential engagements in media multitasking to correlate with brain structure variability. This was confirmed via Voxel-Based Morphometry (VBM) analyses: Individuals with higher Media Multitasking Index (MMI) scores had smaller gray matter density in the anterior cingulate cortex (ACC). Functional connectivity between this ACC region and the precuneus was negatively associated with MMI. Our findings suggest a possible structural correlate for the observed decreased cognitive control performance and socio-emotional regulation in heavy media-multitaskers. While the cross-sectional nature of our study does not allow us to specify the direction of causality, our results brought to light novel associations between individual media multitasking behaviors and ACC structure differences. PMID:25250778

Internet Communication Disorder and the structure of the human brain: initial insights on WeChat addiction.

PubMed

Montag, Christian; Zhao, Zhiying; Sindermann, Cornelia; Xu, Lei; Fu, Meina; Li, Jialin; Zheng, Xiaoxiao; Li, Keshuang; Kendrick, Keith M; Dai, Jing; Becker, Benjamin

2018-02-01

WeChat represents one of the most popular smartphone-based applications for communication. Although the application provides several useful features that simplify daily life, a growing number of users spend excessive amounts of time on the application. This may lead to interferences with everyday life and even to addictive patterns of use. In the context of the ongoing discussion on Internet Communication Disorder (ICD), the present study aimed to better characterize the addictive potential of communication applications, using WeChat as an example, by examining associations between individual variations in tendencies towards WeChat addiction and brain structural variations in fronto-striatal-limbic brain regions. To this end levels of addictive tendencies, frequency of use and structural MRI data were assessed in n = 61 healthy participants. Higher tendencies towards WeChat addiction were associated with smaller gray matter volumes of the subgenual anterior cingulate cortex, a key region for monitoring and regulatory control in neural networks underlying addictive behaviors. Moreover, a higher frequency of the paying function was associated with smaller nucleus accumbens volumes. Findings were robust after controlling for levels of anxiety and depression. The present results are in line with previous findings in substance and behavioral addictions, and suggest a similar neurobiological basis in ICD.

Preliminary Evidence for the Impact of Combat Experiences on Gray Matter Volume of the Posterior Insula

PubMed Central

Clausen, Ashley N.; Billinger, Sandra A.; Sisante, Jason-Flor V.; Suzuki, Hideo; Aupperle, Robin L.

2017-01-01

Background: Combat-exposed veteran populations are at an increased risk for developing cardiovascular disease. The anterior cingulate cortex (ACC) and insula have been implicated in both autonomic arousal to emotional stressors and homeostatic processes, which may contribute to cardiovascular dysfunction in combat veteran populations. The aim of the present study was to explore the intersecting relationships of combat experiences, rostral ACC and posterior insula volume, and cardiovascular health in a sample of combat veterans. Method: Twenty-four male combat veterans completed clinical assessment of combat experiences and posttraumatic stress symptoms. Subjects completed a magnetic resonance imaging scan and autosegmentation using FreeSurfer was used to estimate regional gray matter volume (controlling for total gray matter volume) of the rostral ACC and posterior insula. Flow-mediated dilation (FMD) was conducted to assess cardiovascular health. Theil-sen robust regressions and Welch's analysis of variance were used to examine relationships of combat experiences and PTSD symptomology with (1) FMD and (2) regional gray matter volume. Results: Increased combat experiences, deployment duration, and multiple deployments were related to smaller posterior insula volume. Combat experiences were marginally associated with poorer cardiovascular health. However, cardiovascular health was not related to rostral ACC or posterior insula volume. Conclusion: The present study provides initial evidence for the relationships of combat experiences, deployment duration, and multiple deployments with smaller posterior insula volume. Results may suggest that veterans with increased combat experiences may exhibit more dysfunction regulating the autonomic nervous system, a key function of the posterior insula. However, the relationship between combat and cardiovascular health was not mediated by regional brain volume. Future research is warranted to further clarify the cardiovascular or functional impact of smaller posterior insula volume in combat veterans. PMID:29312038

Designing a compact high performance brain PET scanner—simulation study

NASA Astrophysics Data System (ADS)

Gong, Kuang; Majewski, Stan; Kinahan, Paul E.; Harrison, Robert L.; Elston, Brian F.; Manjeshwar, Ravindra; Dolinsky, Sergei; Stolin, Alexander V.; Brefczynski-Lewis, Julie A.; Qi, Jinyi

2016-05-01

The desire to understand normal and disordered human brain function of upright, moving persons in natural environments motivates the development of the ambulatory micro-dose brain PET imager (AMPET). An ideal system would be light weight but with high sensitivity and spatial resolution, although these requirements are often in conflict with each other. One potential approach to meet the design goals is a compact brain-only imaging device with a head-sized aperture. However, a compact geometry increases parallax error in peripheral lines of response, which increases bias and variance in region of interest (ROI) quantification. Therefore, we performed simulation studies to search for the optimal system configuration and to evaluate the potential improvement in quantification performance over existing scanners. We used the Cramér-Rao variance bound to compare the performance for ROI quantification using different scanner geometries. The results show that while a smaller ring diameter can increase photon detection sensitivity and hence reduce the variance at the center of the field of view, it can also result in higher variance in peripheral regions when the length of detector crystal is 15 mm or more. This variance can be substantially reduced by adding depth-of-interaction (DOI) measurement capability to the detector modules. Our simulation study also shows that the relative performance depends on the size of the ROI, and a large ROI favors a compact geometry even without DOI information. Based on these results, we propose a compact ‘helmet’ design using detectors with DOI capability. Monte Carlo simulations show the helmet design can achieve four-fold higher sensitivity and resolve smaller features than existing cylindrical brain PET scanners. The simulations also suggest that improving TOF timing resolution from 400 ps to 200 ps also results in noticeable improvement in image quality, indicating better timing resolution is desirable for brain imaging.

Designing a compact high performance brain PET scanner—simulation study

PubMed Central

Gong, Kuang; Majewski, Stan; Kinahan, Paul E; Harrison, Robert L; Elston, Brian F; Manjeshwar, Ravindra; Dolinsky, Sergei; Stolin, Alexander V; Brefczynski-Lewis, Julie A; Qi, Jinyi

2016-01-01

The desire to understand normal and disordered human brain function of upright, moving persons in natural environments motivates the development of the ambulatory micro-dose brain PET imager (AMPET). An ideal system would be light weight but with high sensitivity and spatial resolution, although these requirements are often in conflict with each other. One potential approach to meet the design goals is a compact brain-only imaging device with a head-sized aperture. However, a compact geometry increases parallax error in peripheral lines of response, which increases bias and variance in region of interest (ROI) quantification. Therefore, we performed simulation studies to search for the optimal system configuration and to evaluate the potential improvement in quantification performance over existing scanners. We used the Cramér–Rao variance bound to compare the performance for ROI quantification using different scanner geometries. The results show that while a smaller ring diameter can increase photon detection sensitivity and hence reduce the variance at the center of the field of view, it can also result in higher variance in peripheral regions when the length of detector crystal is 15 mm or more. This variance can be substantially reduced by adding depth-of- interaction (DOI) measurement capability to the detector modules. Our simulation study also shows that the relative performance depends on the size of the ROI, and a large ROI favors a compact geometry even without DOI information. Based on these results, we propose a compact ‘helmet’ design using detectors with DOI capability. Monte Carlo simulations show the helmet design can achieve four-fold higher sensitivity and resolve smaller features than existing cylindrical brain PET scanners. The simulations also suggest that improving TOF timing resolution from 400 ps to 200 ps also results in noticeable improvement in image quality, indicating better timing resolution is desirable for brain imaging. PMID:27081753

Face-name association learning and brain structural substrates in alcoholism.

PubMed

Pitel, Anne-Lise; Chanraud, Sandra; Rohlfing, Torsten; Pfefferbaum, Adolf; Sullivan, Edith V

2012-07-01

Associative learning is required for face-name association and is impaired in alcoholism, but the cognitive processes and brain structural components underlying this deficit remain unclear. It is also unknown whether prompting alcoholics to implement a deep level of processing during face-name encoding would enhance performance. Abstinent alcoholics and controls performed a levels-of-processing face-name learning task. Participants indicated whether the face was that of an honest person (deep encoding) or that of a man (shallow encoding). Retrieval was examined using an associative (face-name) recognition task and a single-item (face or name only) recognition task. Participants also underwent 3T structural MRI. Compared with controls, alcoholics had poorer associative and single-item learning and performed at similar levels. Level of processing at encoding had little effect on recognition performance but affected reaction time (RT). Correlations with brain volumes were generally modest and based primarily on RT in alcoholics, where the deeper the processing at encoding, the more restricted the correlations with brain volumes. In alcoholics, longer control task RTs correlated modestly with smaller tissue volumes across several anterior to posterior brain regions; shallow encoding correlated with calcarine and striatal volumes; deep encoding correlated with precuneus and parietal volumes; and associative recognition RT correlated with cerebellar volumes. In controls, poorer associative recognition with deep encoding correlated significantly with smaller volumes of frontal and striatal structures. Despite prompting, alcoholics did not take advantage of encoding memoranda at a deep level to enhance face-name recognition accuracy. Nonetheless, conditions of deeper encoding resulted in faster RTs and more specific relations with regional brain volumes than did shallow encoding. The normal relation between associative recognition and corticostriatal volumes was not present in alcoholics. Rather, their speeded RTs occurred at the expense of accuracy and were related most robustly to cerebellar volumes. Copyright © 2012 by the Research Society on Alcoholism.

Efficiency of weak brain connections support general cognitive functioning.

PubMed

Santarnecchi, Emiliano; Galli, Giulia; Polizzotto, Nicola Riccardo; Rossi, Alessandro; Rossi, Simone

2014-09-01

Brain network topology provides valuable information on healthy and pathological brain functioning. Novel approaches for brain network analysis have shown an association between topological properties and cognitive functioning. Under the assumption that "stronger is better", the exploration of brain properties has generally focused on the connectivity patterns of the most strongly correlated regions, whereas the role of weaker brain connections has remained obscure for years. Here, we assessed whether the different strength of connections between brain regions may explain individual differences in intelligence. We analyzed-functional connectivity at rest in ninety-eight healthy individuals of different age, and correlated several connectivity measures with full scale, verbal, and performance Intelligent Quotients (IQs). Our results showed that the variance in IQ levels was mostly explained by the distributed communication efficiency of brain networks built using moderately weak, long-distance connections, with only a smaller contribution of stronger connections. The variability in individual IQs was associated with the global efficiency of a pool of regions in the prefrontal lobes, hippocampus, temporal pole, and postcentral gyrus. These findings challenge the traditional view of a prominent role of strong functional brain connections in brain topology, and highlight the importance of both strong and weak connections in determining the functional architecture responsible for human intelligence variability. Copyright © 2014 Wiley Periodicals, Inc.

Role of stereotactic radiosurgery in patients with more than four brain metastases

PubMed Central

Jairam, Vikram; Chiang, Veronica LS; Yu, James B; Knisely, Jonathan PS

2013-01-01

SUMMARY For patients presenting with brain metastases, two methods of radiation treatment currently exist: stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT). SRS is a minimally invasive to noninvasive technique that delivers a high dose of ionizing radiation to a precisely defined focal target volume, whereas WBRT involves multiple smaller doses of radiation delivered to the whole brain. Evidence exists from randomized controlled trials for SRS in the treatment of patients with one to four brain metastases. Patients with more than four brain metastases generally receive WBRT, which can effectively treat undetected metastases and protect against intracranial relapse. However, WBRT has been associated with an increased potential for toxic neurocognitive side effects, including memory loss and early dementia, and does not provide 100% protection against relapse. For this reason, physicians at many medical centers are opting to use SRS as first-line treatment for patients with more than four brain metastases, despite evidence showing an increased rate of intracranial relapse compared with WBRT. In light of the evolving use of SRS, this review will examine the available reports on institutional trials and outcomes for patients with more than four brain metastases treated with SRS alone as first-line therapy. PMID:24273642

Early parental care is important for hippocampal maturation: evidence from brain morphology in humans.

PubMed

Rao, Hengyi; Betancourt, Laura; Giannetta, Joan M; Brodsky, Nancy L; Korczykowski, Marc; Avants, Brian B; Gee, James C; Wang, Jiongjiong; Hurt, Hallam; Detre, John A; Farah, Martha J

2010-01-01

The effects of early life experience on later brain structure and function have been studied extensively in animals, yet the relationship between childhood experience and normal brain development in humans remains largely unknown. Using a unique longitudinal data set including ecologically valid in-home measures of early experience during childhood (at age 4 and 8 years) and high-resolution structural brain imaging during adolescence (mean age 14 years), we examined the effects on later brain morphology of two dimensions of early experience: parental nurturance and environmental stimulation. Parental nurturance at age 4 predicts the volume of the left hippocampus in adolescence, with better nurturance associated with smaller hippocampal volume. In contrast, environmental stimulation did not correlate with hippocampal volume. Moreover, the association between hippocampal volume and parental nurturance disappears at age 8, supporting the existence of a sensitive developmental period for brain maturation. These findings indicate that variation in normal childhood experience is associated with differences in brain morphology, and hippocampal volume is specifically associated with early parental nurturance. Our results provide neuroimaging evidence supporting the important role of warm parental care during early childhood for brain maturation.

Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis.

PubMed

Sacco, Roberto; Gabriele, Stefano; Persico, Antonio M

2015-11-30

Macrocephaly and brain overgrowth have been associated with autism spectrum disorder. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and statistical significance for both head circumference and total brain volume in autism. Our literature search strategy identified 261 and 391 records, respectively; 27 studies defining percentages of macrocephalic patients and 44 structural brain imaging studies providing total brain volumes for patients and controls were included in our meta-analyses. Head circumference was significantly larger in autistic compared to control individuals, with 822/5225 (15.7%) autistic individuals displaying macrocephaly. Structural brain imaging studies measuring brain volume estimated effect size. The effect size is higher in low functioning autistics compared to high functioning and ASD individuals. Brain overgrowth was recorded in 142/1558 (9.1%) autistic patients. Finally, we found a significant interaction between age and total brain volume, resulting in larger head circumference and brain size during early childhood. Our results provide conclusive effect sizes and prevalence rates for macrocephaly and brain overgrowth in autism, confirm the variation of abnormal brain growth with age, and support the inclusion of this endophenotype in multi-biomarker diagnostic panels for clinical use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Uptake of selenium and mercury by captive mink: Results of a controlled feeding experiment.

PubMed

Evans, R D; Grochowina, N M; Basu, N; O'Connor, E M; Hickie, B E; Rouvinen-Watt, K; Evans, H E; Chan, H M

2016-02-01

Captive, juvenile, ranch-bred, male mink (Neovison vison) were fed diets containing various concentrations of methyl-mercury (MeHg) and selenium (Se) for a period of 13 weeks and then sacrificed to determine total Hg levels in fur, blood, brain, liver and kidneys and total Se concentrations in brain tissue. As MeHg concentrations in the diet increased, concentrations of total Hg in the tissues also increased with the highest level occurring in the fur > liver = kidney > brain > blood. Concentrations of Hg in the fur were correlated (r(2) > 0.97) with liver, kidney, blood and brain concentrations. The addition of Se to the mink diet did not appear to affect most tissue concentrations of total Hg nor did it affect the partitioning of Hg between the liver:blood, kidney:blood and brain:blood; however, partitioning of Hg between fur and blood was apparently affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anomalous Putamen Volume in Children with Complex Motor Stereotypies

PubMed Central

Mahone, E. Mark; Crocetti, Deana; Tochen, Laura; Kline, Tina; Mostofsky, Stewart H.; Singer, Harvey S.

2016-01-01

Introduction Complex motor stereotypies in children are repetitive, rhythmic movements that have a predictable pattern and location, seem purposeful, but serve no obvious function, tend to be prolonged, and stop with distraction, e.g., arm/hand flapping, waving. They occur in both “primary” (otherwise typically developing) and secondary conditions. These movements are best defined as habitual behaviors and therefore pathophysiologically hypothesized to reside in premotor to posterior putamen circuits. This study sought to clarify the underlying neurobiological abnormality in children with primary complex motor stereotypies using structural neuroimaging, emphasizing brain regions hypothesized to underlie these atypical behaviors. Methods High-resolution anatomical MRI images, acquired at 3.0T, were analyzed in children ages 8–12 years (20 with primary complex motor stereotypies, 20 typically developing). Frontal lobe sub-regions and striatal structures were delineated for analysis. Results Significant reductions (p=0.045) in the stereotypies group were identified in total putamen volume, but not caudate, nucleus accumbens or frontal sub-regions. There were no group differences in total cerebral volume. Conclusion Findings of a smaller putamen provide preliminary evidence suggesting the potential involvement of the habitual pathway as the underlying anatomical site in primary complex motor stereotypies. PMID:27751663

Small Brain Lesions and Incident Stroke and Mortality: A Cohort Study.

PubMed

Windham, B Gwen; Deere, Bradley; Griswold, Michael E; Wang, Wanmei; Bezerra, Daniel C; Shibata, Dean; Butler, Kenneth; Knopman, David; Gottesman, Rebecca F; Heiss, Gerardo; Mosley, Thomas H

2015-07-07

Although cerebral lesions 3 mm or larger on imaging are associated with incident stroke, lesions smaller than 3 mm are typically ignored. To examine stroke risks associated with subclinical brain lesions (<3 mm only, ≥3 mm only, and both sizes) and white matter hyperintensities (WMHs). Community cohort from the ARIC (Atherosclerosis Risk in Communities) Study. Two ARIC sites with magnetic resonance imaging (MRI) data from 1993 to 1995. 1884 adults aged 50 to 73 years with MRI, no prior stroke, and average follow-up of 14.5 years. Lesions on MRI (by size), WMH score (scale of 0 to 9), incident stroke, all-cause mortality, and stroke-related mortality. Hazard ratios (HRs) were estimated with proportional hazards models. Compared with no lesions, stroke risk tripled with lesions smaller than 3 mm only (HR, 3.47 [95% CI, 1.86 to 6.49]), doubled with lesions 3 mm or larger only (HR, 1.94 [CI, 1.22 to 3.07]), was 8-fold higher with lesions of both sizes (HR, 8.59 [CI, 4.69 to 15.73]), and doubled with a WMH score of at least 3 (HR, 2.14 [CI, 1.45 to 3.16]). Risk for stroke-related death tripled with lesions smaller than 3 mm only (HR, 3.05 [CI, 1.04 to 8.94]) and was 7 times higher with lesions of both sizes (HR, 6.97 [CI, 2.03 to 23.93]). Few strokes (especially hemorrhagic) and few participants with lesions smaller than 3 mm only or lesions of both sizes. Very small cerebrovascular lesions may be associated with increased risks for stroke and death; presence of lesions smaller than 3 mm and 3 mm or larger may result in a particularly striking risk increase. Larger studies are needed to confirm findings and provide more precise estimates. National Heart, Lung, and Blood Institute.

Sample size requirements for one-year treatment effects using deep gray matter volume from 3T MRI in progressive forms of multiple sclerosis.

PubMed

Kim, Gloria; Chu, Renxin; Yousuf, Fawad; Tauhid, Shahamat; Stazzone, Lynn; Houtchens, Maria K; Stankiewicz, James M; Severson, Christopher; Kimbrough, Dorlan; Quintana, Francisco J; Chitnis, Tanuja; Weiner, Howard L; Healy, Brian C; Bakshi, Rohit

2017-11-01

The subcortical deep gray matter (DGM) develops selective, progressive, and clinically relevant atrophy in progressive forms of multiple sclerosis (PMS). This patient population is the target of active neurotherapeutic development, requiring the availability of outcome measures. We tested a fully automated MRI analysis pipeline to assess DGM atrophy in PMS. Consistent 3D T1-weighted high-resolution 3T brain MRI was obtained over one year in 19 consecutive patients with PMS [15 secondary progressive, 4 primary progressive, 53% women, age (mean±SD) 50.8±8.0 years, Expanded Disability Status Scale (median, range) 5.0, 2.0-6.5)]. DGM segmentation applied the fully automated FSL-FIRST pipeline ( http://fsl.fmrib.ox.ac.uk ). Total DGM volume was the sum of the caudate, putamen, globus pallidus, and thalamus. On-study change was calculated using a random-effects linear regression model. We detected one-year decreases in raw [mean (95% confidence interval): -0.749 ml (-1.455, -0.043), p = 0.039] and annualized [-0.754 ml/year (-1.492, -0.016), p = 0.046] total DGM volumes. A treatment trial for an intervention that would show a 50% reduction in DGM brain atrophy would require a sample size of 123 patients for a single-arm study (one-year run-in followed by one-year on-treatment). For a two-arm placebo-controlled one-year study, 242 patients would be required per arm. The use of DGM fraction required more patients. The thalamus, putamen, and globus pallidus, showed smaller effect sizes in their on-study changes than the total DGM; however, for the caudate, the effect sizes were somewhat larger. DGM atrophy may prove efficient as a short-term outcome for proof-of-concept neurotherapeutic trials in PMS.

Traumatic stress: effects on the brain

PubMed Central

Bremner, J. Douglas

2006-01-01

Brain areas implicated in the stress response include the amygdala, hippocampus, and prefrontal cortex. Traumatic stress can be associated with lasting changes in these brain areas. Traumatic stress is associated with increased cortisol and norepinephrine responses to subsequent stressors. Antidepressants have effets on the hippocampus that counteract the effects of stress. Findings from animal studies have been extended to patients with post-traumatic stress disorder (PTSD) showing smaller hippocampal and anterior cingulate volumes, increased amygdala function, and decreased medial prefrontal/anterior cingulate function. In addition, patients with PTSD show increased cortisol and norepinephrine responses to stress. Treatments that are efficacious for PTSD show a promotion of neurogenesis in animal studies, as well as promotion of memory and increased hippocampal volume in PTSD. PMID:17290802

Comparison of Infant and Adult P300 from Auditory Stimuli.

ERIC Educational Resources Information Center

McIsaac, Heather; Polich, John

1992-01-01

Recorded electroencephalographic activity of infants and adults who heard 1 unique tone in a series of 10 tones. The amplitude of event-related brain potentials in response to the unique tone was smaller, and its latency longer, for infants than for adults. Evoked potentials remained stable across trials. (BC)

Motor-Perceptual Function in Children with Developmental Reading Disorders: Neuropsychophysiological Analysis.

ERIC Educational Resources Information Center

Chiarenza, Giuseppe Augusto

1990-01-01

Eight reading-disordered and 9 nondisabled males (age 10) performed a skilled motor-perceptual task. The children with reading disorders were slower, less accurate, and achieved a smaller number of target performances. Their brain macropotentials associated with motor programing, processing of sensory information, and evaluation of the results…

Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury.

PubMed

Wurzelmann, Mary; Romeika, Jennifer; Sun, Dong

2017-01-01

Traumatic brain injury (TBI) is a major health problem worldwide. Following primary mechanical insults, a cascade of secondary injuries often leads to further neural tissue loss. Thus far there is no cure to rescue the damaged neural tissue. Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration. The neurotrophin brain-derived neurotrophic factor (BDNF) has significant effect in both aspects, promoting neuronal survival, synaptic plasticity and neurogenesis. Recently, the flavonoid 7,8-dihydroxyflavone (7,8-DHF), a small TrkB agonist that mimics BDNF function, has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI. Compared to BDNF, 7,8-DHF has a longer half-life and much smaller molecular size, capable of penetrating the blood-brain barrier, which makes it possible for non-invasive clinical application. In this review, we summarize functions of the BDNF/TrkB signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.

Lack of Influence of Apolipoprotein E Status on Cognition or Brain Structure in Professional Fighters

PubMed Central

Miller, Justin B.; Rissman, Robert A.; Bernick, Charles B.

2017-01-01

Abstract The role of the apolipoprotein e4 allele in moderating cognitive and neuroanatomical degeneration following repeated traumatic brain injury is controversial. Here we sought to establish the presence or absence of such a moderating relationship in a prospective study of active and retired boxers and mixed martial arts fighters. Fighters (n = 193) underwent cognitive evaluations, interviews regarding fight history, MRI of the brain, and genetic testing. We used a series of moderator analyses to test for any relationship of apolipoprotein genotype on structural volumes of brain regions previously established to be smaller in those with the most fight exposure, and on cognitive abilities also established to be sensitive to fight exposure. No moderating relationship was detected in any of the analyses. The results of this study suggest that there is no impact of apolipoprotein genotype on the apparent negative association between exposure to professional fighting and brain structure volume or aspects of cognition. PMID:27245878

The temporal structures and functional significance of scale-free brain activity

PubMed Central

He, Biyu J.; Zempel, John M.; Snyder, Abraham Z.; Raichle, Marcus E.

2010-01-01

SUMMARY Scale-free dynamics, with a power spectrum following P ∝ f-β, are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is often neglected in electrophysiological research. Here, we investigate scale-free dynamics in human brain and show that it contains extensive nested frequencies, with the phase of lower frequencies modulating the amplitude of higher frequencies in an upward progression across the frequency spectrum. The functional significance of scale-free brain activity is indicated by task performance modulation and regional variation, with β being larger in default network and visual cortex and smaller in hippocampus and cerebellum. The precise patterns of nested frequencies in the brain differ from other scale-free dynamics in nature, such as earth seismic waves and stock market fluctuations, suggesting system-specific generative mechanisms. Our findings reveal robust temporal structures and behavioral significance of scale-free brain activity and should motivate future study on its physiological mechanisms and cognitive implications. PMID:20471349

Comparative support for the expensive tissue hypothesis: Big brains are correlated with smaller gut and greater parental investment in Lake Tanganyika cichlids.

PubMed

Tsuboi, Masahito; Husby, Arild; Kotrschal, Alexander; Hayward, Alexander; Buechel, Séverine D; Zidar, Josefina; Løvlie, Hanne; Kolm, Niclas

2015-01-01

The brain is one of the most energetically expensive organs in the vertebrate body. Consequently, the energetic requirements of encephalization are suggested to impose considerable constraints on brain size evolution. Three main hypotheses concerning how energetic constraints might affect brain evolution predict covariation between brain investment and (1) investment into other costly tissues, (2) overall metabolic rate, and (3) reproductive investment. To date, these hypotheses have mainly been tested in homeothermic animals and the existing data are inconclusive. However, there are good reasons to believe that energetic limitations might play a role in large-scale patterns of brain size evolution also in ectothermic vertebrates. Here, we test these hypotheses in a group of ectothermic vertebrates, the Lake Tanganyika cichlid fishes. After controlling for the effect of shared ancestry and confounding ecological variables, we find a negative association between brain size and gut size. Furthermore, we find that the evolution of a larger brain is accompanied by increased reproductive investment into egg size and parental care. Our results indicate that the energetic costs of encephalization may be an important general factor involved in the evolution of brain size also in ectothermic vertebrates. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Oxytocin enhances inter-brain synchrony during social coordination in male adults

PubMed Central

Mu, Yan; Guo, Chunyan

2016-01-01

Recent brain imaging research has revealed oxytocin (OT) effects on an individual's brain activity during social interaction but tells little about whether and how OT modulates the coherence of inter-brain activity related to two individuals' coordination behavior. We developed a new real-time coordination game that required two individuals of a dyad to synchronize with a partner (coordination task) or with a computer (control task) by counting in mind rhythmically. Electroencephalography (EEG) was recorded simultaneously from a dyad to examine OT effects on inter-brain synchrony of neural activity during interpersonal coordination. Experiment 1 found that dyads showed smaller interpersonal time lags of counting and greater inter-brain synchrony of alpha-band neural oscillations during the coordination (vs control) task and these effects were reliably observed in female but not male dyads. Moreover, the increased alpha-band inter-brain synchrony predicted better interpersonal behavioral synchrony across all participants. Experiment 2, using a double blind, placebo-controlled between-subjects design, revealed that intranasal OT vs placebo administration in male dyads improved interpersonal behavioral synchrony in both the coordination and control tasks but specifically enhanced alpha-band inter-brain neural oscillations during the coordination task. Our findings provide first evidence that OT enhances inter-brain synchrony in male adults to facilitate social coordination. PMID:27510498

Acetate transport and utilization in the rat brain.

PubMed

Deelchand, Dinesh K; Shestov, Alexander A; Koski, Dee M; Uğurbil, Kâmil; Henry, Pierre-Gilles

2009-05-01

Acetate, a glial-specific substrate, is an attractive alternative to glucose for the study of neuronal-glial interactions. The present study investigates the kinetics of acetate uptake and utilization in the rat brain in vivo during infusion of [2-13C]acetate using NMR spectroscopy. When plasma acetate concentration was increased, the rate of brain acetate utilization (CMR(ace)) increased progressively and reached close to saturation for plasma acetate concentration > 2-3 mM, whereas brain acetate concentration continued to increase. The Michaelis-Menten constant for brain acetate utilization (K(M)(util) = 0.01 +/- 0.14 mM) was much smaller than for acetate transport through the blood-brain barrier (BBB) (K(M)(t) = 4.18 +/- 0.83 mM). The maximum transport capacity of acetate through the BBB (V(max)(t) = 0.96 +/- 0.18 micromol/g/min) was nearly twofold higher than the maximum rate of brain acetate utilization (V(max)(util) = 0.50 +/- 0.08 micromol/g/min). We conclude that, under our experimental conditions, brain acetate utilization is saturated when plasma acetate concentrations increase above 2-3 mM. At such high plasma acetate concentration, the rate-limiting step for glial acetate metabolism is not the BBB, but occurs after entry of acetate into the brain.

Influence of irradiation on development of Caribbean fruit fly (diptera: tephritidae) larvae

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

Nation, J.L.; Milne, K.; Dykstra, T.M.

1995-05-01

Larvae of the Caribbean fruit fly, Anastrepha suspensa (Loew), were irradiated at hatching with 0, 5, 10, 20, 50, 75, 100 and 150 Gy doses from a Cesium-137 source and dissected for measurements of the supraesophageal ganglion (brain) and proventriculus (B/Prv) as mature third instars. Cross-sectional area of a plane through the brain and proventriculus, and simple dorsal width measurements of the two organs were evaluated as indicators of radiation exposure. Brain area, brain width, and brain/proventriculus (B/Prv) ratios were significantly different from controls in insects treated with a dose {ge}20 Gy. Detailed dissections of hatching larvae exposed to 50more » Gy revealed reductions in brain growth, small and misshapen compound eye and leg imaginal disks, and a ventral nerve cord that was elongated and sinuous. Larvae irradiated on the 1st d of each of the three instars had smaller brains, with the percentage of reduction in brain size being greater the younger the larvae were at the time of exposure. Brain and proventriculus measurements and calculated B/Prv values are indicative of irradiation in Caribbean fruit fly larvae, but the procedure may not be adaptable for routine use by quarantine inspectors. 14 refs., 4 figs., 2 tabs.« less

Relative brain displacement and deformation during constrained mild frontal head impact.

PubMed

Feng, Y; Abney, T M; Okamoto, R J; Pless, R B; Genin, G M; Bayly, P V

2010-12-06

This study describes the measurement of fields of relative displacement between the brain and the skull in vivo by tagged magnetic resonance imaging and digital image analysis. Motion of the brain relative to the skull occurs during normal activity, but if the head undergoes high accelerations, the resulting large and rapid deformation of neuronal and axonal tissue can lead to long-term disability or death. Mathematical modelling and computer simulation of acceleration-induced traumatic brain injury promise to illuminate the mechanisms of axonal and neuronal pathology, but numerical studies require knowledge of boundary conditions at the brain-skull interface, material properties and experimental data for validation. The current study provides a dense set of displacement measurements in the human brain during mild frontal skull impact constrained to the sagittal plane. Although head motion is dominated by translation, these data show that the brain rotates relative to the skull. For these mild events, characterized by linear decelerations near 1.5g (g = 9.81 m s⁻²) and angular accelerations of 120-140 rad s⁻², relative brain-skull displacements of 2-3 mm are typical; regions of smaller displacements reflect the tethering effects of brain-skull connections. Strain fields exhibit significant areas with maximal principal strains of 5 per cent or greater. These displacement and strain fields illuminate the skull-brain boundary conditions, and can be used to validate simulations of brain biomechanics.

The effect of brain size evolution on feeding propensity, digestive efficiency, and juvenile growth.

PubMed

Kotrschal, Alexander; Corral-Lopez, Alberto; Szidat, Sönke; Kolm, Niclas

2015-11-01

One key hypothesis in the study of brain size evolution is the expensive tissue hypothesis; the idea that increased investment into the brain should be compensated by decreased investment into other costly organs, for instance the gut. Although the hypothesis is supported by both comparative and experimental evidence, little is known about the potential changes in energetic requirements or digestive traits following such evolutionary shifts in brain and gut size. Organisms may meet the greater metabolic requirements of larger brains despite smaller guts via increased food intake or better digestion. But increased investment in the brain may also hamper somatic growth. To test these hypotheses we here used guppy (Poecilia reticulata) brain size selection lines with a pronounced negative association between brain and gut size and investigated feeding propensity, digestive efficiency (DE), and juvenile growth rate. We did not find any difference in feeding propensity or DE between large- and small-brained individuals. Instead, we found that large-brained females had slower growth during the first 10 weeks after birth. Our study provides experimental support that investment into larger brains at the expense of gut tissue carries costs that are not necessarily compensated by a more efficient digestive system. © 2015 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

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.

Hippocampal volume and memory performance in children with perinatal stroke.

PubMed

Gold, Jeffrey J; Trauner, Doris A

2014-01-01

Pediatric neurologists and neonatologists often are asked to predict cognitive outcome after perinatal brain injury (including likely memory and learning outcomes). However, relatively few data exist on how accurate predictions can be made. Furthermore, although the consequences of brain injury on hippocampal volume and memory performance have been studied extensively in adults, little work has been done in children. We measured the volume of the hippocampus in 27 children with perinatal stroke and 19 controls, and measured their performance on standardized verbal and non-verbal memory tests. We discovered the following: (1) As a group, children with perinatal stroke had smaller left and right hippocampi compared with control children. (2) Individually, children with perinatal stroke demonstrated 1 of 3 findings: no hippocampal loss, unilateral hippocampal loss, or bilateral hippocampal volume loss compared with control children. (3) Hippocampal volume inversely correlated with memory test performance in the perinatal stroke group, with smaller left and right hippocampal volumes related to poorer verbal and non-verbal memory test performance, respectively. (4) Seizures played a significant role in determining memory deficit and extent of hippocampal volume reduction in patients with perinatal stroke. These findings support the view that, in the developing brain, the left and right hippocampi preferentially support verbal and nonverbal memory respectively, a consistent finding in the adult literature but a subject of debate in the pediatric literature. This is the first work to report that children with focal brain injury incurred from perinatal stroke have volume reduction in the hippocampus and impairments in certain aspects of declarative memory. Copyright © 2014 Elsevier Inc. All rights reserved.

Chronic Alcohol Consumption and its Effect on Nodes of Frontocerebellar and Limbic Circuitry: Comparison of Effects in France and the United States

PubMed Central

Le Berre, Anne-Pascale; Pitel, Anne-Lise; Chanraud, Sandra; Beaunieux, Hélène; Eustache, Francis; Martinot, Jean-Luc; Reynaud, Michel; Martelli, Catherine; Rohlfing, Torsten; Sullivan, Edith V.; Pfefferbaum, Adolf

2016-01-01

Alcohol Use Disorders present a significant public health problem in France and the United States (U.S.), but whether the untoward effect of alcohol on the brain results in similar damage in both countries remains unknown. Accordingly, we conducted a retrospective collaborative investigation between two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) with T1-weighted, structural MRI data collected on a common imaging platform (1.5T, General Electric) on 288 normal controls (NC), 165 uncomplicated alcoholics (ALC), and 26 patients with alcoholic Korsakoff’s syndrome (KS) diagnosed at all sites with a common interview instrument. Data from the two countries were pooled, then preprocessed and analyzed together at the U.S. site using atlas-based parcellation. National differences indicated that thalamic volumes were smaller in ALC in France than the U.S. despite similar alcohol consumption levels in both countries. By contrast, volumes of the hippocampus, amygdala, and cerebellar vermis were smaller in KS in the U.S. than France. Estimated amount of alcohol consumed over a lifetime, duration of alcoholism, and length of sobriety were significant predictors of selective regional brain volumes in France and in the U.S. The common analysis of MRI data enabled identification of discrepancies in brain volume deficits in France and the U.S. that may reflect fundamental differences in the consequences of alcoholism on brain structure between the two countries, possibly related to genetic or environmental differences. PMID:24639416

Cannabis, Cigarettes, and Their Co-Occurring Use: Disentangling Differences in Gray Matter Volume.

PubMed

Wetherill, Reagan R; Jagannathan, Kanchana; Hager, Nathan; Childress, Anna Rose; Rao, Hengyi; Franklin, Teresa R

2015-06-04

Structural magnetic resonance imaging techniques are powerful tools for examining the effects of drug use on the brain. The nicotine and cannabis literature has demonstrated differences between nicotine cigarette smokers and cannabis users compared to controls in brain structure; however, less is known about the effects of co-occurring cannabis and tobacco use. We used voxel-based morphometry to examine gray matter volume differences between four groups: (1) cannabis-dependent individuals who do not smoke tobacco (Cs); (2) cannabis-dependent individuals who smoke tobacco (CTs); (3) cannabis-naïve, nicotine-dependent individuals who smoke tobacco (Ts); and (4) healthy controls (HCs). We also explored associations between gray matter volume and measures of cannabis and tobacco use. A significant group effect was observed in the left putamen, thalamus, right precentral gyrus, and left cerebellum. Compared to HCs, the Cs, CTs, and Ts exhibited larger gray matter volumes in the left putamen. Cs also had larger gray matter volume than HCs in the right precentral gyrus. Cs and CTs exhibited smaller gray matter volume than HCs in the thalamus, and CTs and Ts had smaller left cerebellar gray matter volume than HCs. This study extends previous research that independently examined the effects of cannabis or tobacco use on brain structure by including an examination of co-occurring cannabis and tobacco use, and provides evidence that cannabis and tobacco exposure are associated with alterations in brain regions associated with addiction. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Brain reserve against physical disability progression over 5 years in multiple sclerosis.

PubMed

Sumowski, James F; Rocca, Maria A; Leavitt, Victoria M; Meani, Alessandro; Mesaros, Sarlota; Drulovic, Jelena; Preziosa, Paolo; Habeck, Christian G; Filippi, Massimo

2016-05-24

The brain reserve hypothesis links larger maximal lifetime brain growth (MLBG, estimated with intracranial volume [ICV]) with lower risk for cognitive decline/dementia. We examined whether larger MLBG is also linked to less physical disability progression over 5 years in a prospective sample of treatment-naive patients with multiple sclerosis (MS). Physical disability was measured with the Expanded Disability Status Scale (EDSS) at baseline and 5-year follow-up in 52 treatment-naive Serbian patients with MS. MRI measured disease burden (cerebral atrophy, T2 lesion volume) and MLBG: a genetically determined, premorbid (established during adolescence, stable thereafter) patient characteristic estimated with ICV (adjusted for sex). Logistic regression tested whether MLBG (smaller vs larger) predicts disability progression (stable vs worsened) independently of disease burden. Disability progression was observed in 29 (55.8%) patients. Larger MLBG predicted lower risk for progression (odds ratio 0.13, 95% confidence interval 0.02-0.78), independently of disease burden. We also calculated absolute change in EDSS scores, and observed that patients with smaller MLBG showed worse EDSS change (0.91 ± 0.71) than patients with larger MLBG (0.42 ± 0.87). Larger MLBG was linked to lower risk for disability progression in patients with MS over 5 years, which is the first extension of the brain reserve hypothesis to physical disability. MLBG (ICV) represents a clinically available metric that may help gauge risk for future disability in patients with MS, which may advance the science and practice of early intervention. Potential avenues for future research are discussed. © 2016 American Academy of Neurology.

Pilot study of brain morphometry in a sample of Brazilian children with attention deficit hyperactivity disorder: influence of clinical presentation.

PubMed

Pastura, Giuseppe; Kubo, Tadeu Takao Almodovar; Gasparetto, Emerson Leandro; Figueiredo, Otavio; Mattos, Paulo; Prüfer Araújo, Alexandra

2017-12-01

Currently, the diagnosis of attention deficit hyperactivity disorder (ADHD) rests on clinical criteria. Nonetheless, neuroimaging studies have demonstrated that children with ADHD have different cortical thickness and volume measures to typically developing children (TDC). In general, studies do not evaluate the influence of clinical presentation in the brain morphometry of ADHD children. Our objective was to perform a pilot study in order to evaluate cortical thickness and brain volume in a sample of Brazilian ADHD children and compare these to those of TDC, taking into account the influence of clinical presentation. We performed an analytic study comparing 17 drug-naïve ADHD children of both genders, aged between 7 and 10, and 16 TDC. ADHD subjects were first considered as one group and further separated based on clinical presentation. The brain volume did not differ between patients and TDC. Smaller cortical thicknesses were identified on the left superior, medium and inferior temporal cortex, as well as in the left inferior parietal cortex. When compared to TDC, combined and inattentive ADHD presentations depicted smaller cortical thickness with high significance and power. The same magnitude of results was not observed when comparing inattentive ADHD and TDC. In this pilot study, ADHD is associated with abnormalities involving the cortical thickness of the posterior attentional system. The cortical thickness in the left superior, medium and inferior temporal cortex, as well as in the left inferior parietal cortex may differ according to ADHD presentations.

Associations between biomarkers and age in the presenilin 1 E280A autosomal dominant Alzheimer disease kindred: a cross-sectional study.

PubMed

Fleisher, Adam S; Chen, Kewei; Quiroz, Yakeel T; Jakimovich, Laura J; Gutierrez Gomez, Madelyn; Langois, Carolyn M; Langbaum, Jessica B S; Roontiva, Auttawut; Thiyyagura, Pradeep; Lee, Wendy; Ayutyanont, Napatkamon; Lopez, Liliana; Moreno, Sonia; Muñoz, Claudia; Tirado, Victoria; Acosta-Baena, Natalia; Fagan, Anne M; Giraldo, Margarita; Garcia, Gloria; Huentelman, Matthew J; Tariot, Pierre N; Lopera, Francisco; Reiman, Eric M

2015-03-01

Age-associated changes in brain imaging and fluid biomarkers are characterized and compared in presenilin 1 (PSEN1)E280A mutation carriers and noncarriers from the world's largest known autosomal dominant Alzheimer disease (AD) kindred. To characterize and compare age-associated changes in brain imaging and fluid biomarkers in PSEN1 E280A mutation carriers and noncarriers. Cross-sectional measures of 18F-florbetapir positron emission tomography, 18F-fludeoxyglucose positron emission tomography, structural magnetic resonance imaging, cerebrospinal fluid (CSF), and plasma biomarkers of AD were assessed from 54 PSEN1 E280A kindred members (age range, 20-59 years). We used brain mapping algorithms to compare regional cerebral metabolic rates for glucose and gray matter volumes in cognitively unimpaired mutation carriers and noncarriers. We used regression analyses to characterize associations between age and the mean cortical to pontine 18F-florbetapir standard uptake value ratios, precuneus cerebral metabolic rates for glucose, hippocampal gray matter volume, CSF Aβ1-42, total tau and phosphorylated tau181, and plasma Aβ measurements. Age at onset of progressive biomarker changes that distinguish carriers from noncarriers was estimated using best-fitting regression models. Compared with noncarriers, cognitively unimpaired mutation carriers had significantly lower precuneus cerebral metabolic rates for glucose, smaller hippocampal volume, lower CSF Aβ1-42, higher CSF total tau and phosphorylated tau181, and higher plasma Aβ1-42 measurements. Sequential changes in biomarkers were seen at age 20 years (95% CI, 14-24 years) for CSF Aβ1-42, age 16 years (95% CI, 11-24 years) for the mean cortical 18F-florbetapir standard uptake value ratio, age 15 years (95% CI, 10-24 years) for precuneus cerebral metabolic rate for glucose, age 15 years (95% CI, 7-20 years) for CSF total tau, age 13 years (95% CI, 8-19 years) for phosphorylated tau181, and age 6 years (95% CI, 1-10 years) for hippocampal volume, with cognitive decline up to 6 years before the kindred's estimated median age of 44 years (95% CI, 43-45 years) at mild cognitive impairment diagnosis. No age-associated findings were seen in plasma Aβ1-42 or Aβ1-40. This cross-sectional study provides additional information about the course of different AD biomarkers in the preclinical and clinical stages of autosomal dominant AD.

Education amplifies brain atrophy effect on cognitive decline: implications for cognitive reserve.

PubMed

Mungas, Dan; Gavett, Brandon; Fletcher, Evan; Farias, Sarah Tomaszewski; DeCarli, Charles; Reed, Bruce

2018-08-01

Level of education is often regarded as a proxy for cognitive reserve in older adults. This implies that brain degeneration has a smaller effect on cognitive decline in those with more education, but this has not been directly tested in previous research. We examined how education, quantitative magnetic resonance imaging-based measurement of brain degeneration, and their interaction affect cognitive decline in diverse older adults spanning the spectrum from normal cognition to dementia. Gray matter atrophy was strongly related to cognitive decline. While education was not related to cognitive decline, brain atrophy had a stronger effect on cognitive decline in those with more education. Importantly, high education was associated with slower decline in individuals with lesser atrophy but with faster decline in those with greater atrophy. This moderation effect was observed in Hispanics (who had high heterogeneity of education) but not in African-Americans or Caucasians. These results suggest that education is an indicator of cognitive reserve in individuals with low levels of brain degeneration, but the protective effect of higher education is rapidly depleted as brain degeneration progresses. Copyright © 2018 Elsevier Inc. All rights reserved.

Ultrasound evaluation of cortical brain development in fetuses with intrauterine growth restriction.

PubMed

Businelli, Caterina; de Wit, Charlotte; Visser, Gerard H A; Pistorius, Lourens R

2014-09-10

Abstract Objective: We evaluated the ultrasound appearance of brain volume and cortical development in fetuses with early growth restriction and placental insufficiency. Methods: We examined a cohort of 20 fetuses with severe intrauterine growth restriction (IUGR) and evidence of placental insufficiency by three-dimensional (3D) ultrasound between 24 and 34 weeks. We graded cortical development and measured the supratentorial intracranial volume. The cortical grading and volume were compared to data obtained from a reference population of 28 adequate for gestational age (AGA) fetuses. Results: Ultrasound examinations were performed in 20 fetuses with IUGR. The biometry and brain volume were significantly reduced in IUGR fetuses. There was evidence of accelerated cortical development in IUGR fetuses. Conclusion: This study confirms that the smaller brain volume in IUGR fetuses, with normal or accelerated cortical maturation as previously depicted with postnatal MRI examination, can be demonstrated by prenatal 3D ultrasound.

Brain Mass and Encephalization Quotients in the Domestic Industrial Pig (Sus scrofa)

PubMed Central

Minervini, Serena; Accogli, Gianluca; Pirone, Andrea; Graïc, Jean-Marie; Cozzi, Bruno; Desantis, Salvatore

2016-01-01

In the present study we examined the brain of fetal, newborn, and adult pigs raised for meat production. The fresh and formalin-fixed weights of the brain have been recorded and used, together with body weight, to calculate the Encephalization Quotient (EQ). The weight of the cerebellum has been used to calculate the Cerebellar Quotient (CQ). The results have been discussed together with analogue data obtained in other terrestrial Cetartiodactyla (including the domestic bovine, sheep, goat, and camel), domesticated Carnivora, Proboscidata, and Primates. Our study, based on a relatively large experimental series, corrects former observations present in the literature based on smaller samples, and emphasizes that the domestic pig has a small brain relative to its body size (EQ = 0.38 for adults), possibly due to factors linked to the necessity of meat production and improved body weight. Comparison with other terrestrial Cetartiodactyla indicates a similar trend for all domesticated species. PMID:27351807

Physical activity level and medial temporal health in youth at ultra high-risk for psychosis.

PubMed

Mittal, Vijay A; Gupta, Tina; Orr, Joseph M; Pelletier-Baldelli, Andrea; Dean, Derek J; Lunsford-Avery, Jessica R; Smith, Ashley K; Robustelli, Briana L; Leopold, Daniel R; Millman, Zachary B

2013-11-01

A growing body of evidence suggests that moderate to vigorous activity levels can affect quality of life, cognition, and brain structure in patients diagnosed with schizophrenia. However, physical activity has not been systematically studied during the period immediately preceding the onset of psychosis. Given reports of exercise-based neurogenesis in schizophrenia, understanding naturalistic physical activity levels in the prodrome may provide valuable information for early intervention efforts. The present study examined 29 ultra high-risk (UHR) and 27 matched controls to determine relationships between physical activity level, brain structure (hippocampus and parahippocampal gyrus), and symptoms. Participants were assessed with actigraphy for a 5-day period, MRI, and structured clinical interviews. UHR participants showed a greater percentage of time in sedentary behavior while healthy controls spent more time engaged in light to vigorous activity. There was a strong trend to suggest the UHR group showed less total physical activity. The UHR group exhibited smaller medial temporal volumes when compared with healthy controls. Total level of physical activity in the UHR group was moderately correlated with parahippocampal gyri bilaterally (right: r = .44, left: r = .55) and with occupational functioning (r = -.36; of negative symptom domain), but not positive symptomatology. Results suggest that inactivity is associated with medial temporal lobe health. Future studies are needed to determine if symptoms are driving inactivity, which in turn may be affecting the health of the parahippocampal structure and progression of illness. Although causality cannot be determined from the present design, these findings hold important implications for etiological conceptions and suggest promise for an experimental trial. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Neuroanatomical Abnormalities in Violent Individuals with and without a Diagnosis of Schizophrenia.

PubMed

Del Bene, Victor A; Foxe, John J; Ross, Lars A; Krakowski, Menahem I; Czobor, Pal; De Sanctis, Pierfilippo

2016-01-01

Several structural brain abnormalities have been associated with aggression in patients with schizophrenia. However, little is known about shared and distinct abnormalities underlying aggression in these subjects and non-psychotic violent individuals. We applied a region-of-interest volumetric analysis of the amygdala, hippocampus, and thalamus bilaterally, as well as whole brain and ventricular volumes to investigate violent (n = 37) and non-violent chronic patients (n = 26) with schizophrenia, non-psychotic violent (n = 24) as well as healthy control subjects (n = 24). Shared and distinct volumetric abnormalities were probed by analysis of variance with the factors violence (non-violent versus violent) and diagnosis (non-psychotic versus psychotic), adjusted for substance abuse, age, academic achievement and negative psychotic symptoms. Patients showed elevated vCSF volume, smaller left hippocampus and smaller left thalamus volumes. This was particularly the case for non-violent individuals diagnosed with schizophrenia. Furthermore, patients had reduction in right thalamus size. With regard to left amygdala, we found an interaction between violence and diagnosis. More specifically, we report a double dissociation with smaller amygdala size linked to violence in non-psychotic individuals, while for psychotic patients smaller size was linked to non-violence. Importantly, the double dissociation appeared to be mostly driven by substance abuse. Overall, we found widespread morphometric abnormalities in subcortical regions in schizophrenia. No evidence for shared volumetric abnormalities in individuals with a history of violence was found. Finally, left amygdala abnormalities in non-psychotic violent individuals were largely accounted for by substance abuse. This might be an indication that the association between amygdala reduction and violence is mediated by substance abuse. Our results indicate the importance of structural abnormalities in aggressive individuals.

Metopic synostosis: Measuring intracranial volume change following fronto-orbital advancement using three-dimensional photogrammetry.

PubMed

Freudlsperger, Christian; Steinmacher, Sahra; Bächli, Heidi; Somlo, Elek; Hoffmann, Jürgen; Engel, Michael

2015-06-01

There is still disagreement regarding the intracranial volumes of patients with metopic synostosis compared with healthy patients. This study aimed to compare the intracranial volume of children with metopic synostosis before and after surgery to an age- and sex-matched control cohort using three-dimensional (3D) photogrammetry. Eighteen boys with metopic synostosis were operated on using standardized fronto-orbital advancement. Frontal, posterior and total intracranial volumes were measured exactly 1 day pre-operatively and 10 days post-operatively, using 3D photogrammetry. To establish an age- and sex-matched control group, the 3D photogrammetric data of 634 healthy boys between the ages of 3 and 13 months were analyzed. Mean age at surgery was 9 months (SD 1.7). Prior to surgery, boys with metopic synostosis showed significantly reduced frontal and total intracranial volumes compared with the reference group, but similar posterior volumes. After surgery, frontal and total intracranial volumes did not differ statistically from the control group. As children with metopic synostosis showed significantly smaller frontal and total intracranial volumes compared with an age- and sex-matched control group, corrective surgery should aim to achieve volume expansion. Furthermore, 3D photogrammetry provides a valuable alternative to CT scans in the measurement of intracranial volume in children with metopic synostosis, which significantly reduces the amount of radiation exposure to the growing brain. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Real-time imaging of trapping and urease-dependent transmigration of Cryptococcus neoformans in mouse brain

PubMed Central

Shi, Meiqing; Li, Shu Shun; Zheng, Chunfu; Jones, Gareth J.; Kim, Kwang Sik; Zhou, Hong; Kubes, Paul; Mody, Christopher H.

2010-01-01

Infectious meningitis and encephalitis is caused by invasion of circulating pathogens into the brain. It is unknown how the circulating pathogens dynamically interact with brain endothelium under shear stress, leading to invasion into the brain. Here, using intravital microscopy, we have shown that Cryptococcus neoformans, a yeast pathogen that causes meningoencephalitis, stops suddenly in mouse brain capillaries of a similar or smaller diameter than the organism, in the same manner and with the same kinetics as polystyrene microspheres, without rolling and tethering to the endothelial surface. Trapping of the yeast pathogen in the mouse brain was not affected by viability or known virulence factors. After stopping in the brain, C. neoformans was seen to cross the capillary wall in real time. In contrast to trapping, viability, but not replication, was essential for the organism to cross the brain microvasculature. Using a knockout strain of C. neoformans, we demonstrated that transmigration into the mouse brain is urease dependent. To determine whether this could be amenable to therapy, we used the urease inhibitor flurofamide. Flurofamide ameliorated infection of the mouse brain by reducing transmigration into the brain. Together, these results suggest that C. neoformans is mechanically trapped in the brain capillary, which may not be amenable to pharmacotherapy, but actively transmigrates to the brain parenchyma with contributions from urease, suggesting that a therapeutic strategy aimed at inhibiting this enzyme could help prevent meningitis and encephalitis caused by C. neoformans infection. PMID:20424328

Performance modeling of a wearable brain PET (BET) camera

NASA Astrophysics Data System (ADS)

Schmidtlein, C. R.; Turner, J. N.; Thompson, M. O.; Mandal, K. C.; Häggström, I.; Zhang, J.; Humm, J. L.; Feiglin, D. H.; Krol, A.

2016-03-01

Purpose: To explore, by means of analytical and Monte Carlo modeling, performance of a novel lightweight and low-cost wearable helmet-shaped Brain PET (BET) camera based on thin-film digital Geiger Avalanche Photo Diode (dGAPD) with LSO and LaBr3 scintillators for imaging in vivo human brain processes for freely moving and acting subjects responding to various stimuli in any environment. Methods: We performed analytical and Monte Carlo modeling PET performance of a spherical cap BET device and cylindrical brain PET (CYL) device, both with 25 cm diameter and the same total mass of LSO scintillator. Total mass of LSO in both the BET and CYL systems is about 32 kg for a 25 mm thick scintillator, and 13 kg for 10 mm thick scintillator (assuming an LSO density of 7.3 g/ml). We also investigated a similar system using an LaBr3 scintillator corresponding to 22 kg and 9 kg for the 25 mm and 10 mm thick systems (assuming an LaBr3 density of 5.08 g/ml). In addition, we considered a clinical whole body (WB) LSO PET/CT scanner with 82 cm ring diameter and 15.8 cm axial length to represent a reference system. BET consisted of distributed Autonomous Detector Arrays (ADAs) integrated into Intelligent Autonomous Detector Blocks (IADBs). The ADA comprised of an array of small LYSO scintillator volumes (voxels with base a×a: 1.0 <= a <= 2.0 mm and length c: 3.0 <= c <= 6.0 mm) with 5-65 μm thick reflective layers on its five sides and sixth side optically coupled to the matching array of dGAPDs and processing electronics with total thickness of 50 μm. Simulated energy resolution was 10.8% and 3.3% for LSO and LaBr3 respectively and the coincidence window was set at 2 ns. The brain was simulated as a sphere of uniform F-18 activity with diameter of 10 cm embedded in a center of water sphere with diameter of 10 cm. Results: Analytical and Monte Carlo models showed similar results for lower energy window values (458 keV versus 445 keV for LSO, and 492 keV versus 485 keV for LaBr3), and for the relative performance of system sensitivity. Monte Carlo results further showed that the BET geometry had >50% better noise equivalent count (NEC) performance relative to the CYL geometry, and >1100% better performance than a WB geometry for 25 mm thick LSO and LaBr3. For 10 mm thick LaBr3 equivalent mass systems LSO (7 mm thick) performed ~40% higher NEC than LaBr3. Analytic and Monte Carlo simulations also showed that 1×1×3 mm scintillator crystals can achieve ~1.2 mm FWHM spatial resolution. Conclusions: This study shows that a spherical cap brain PET system can provide improved NEC while preserving spatial resolution when compared to an equivalent dedicated cylindrical PET brain camera and shows greatly improved PET performance relative to a conventional whole body PET/CT. In addition, our simulations show that LSO will generally outperform LaBr3 for NEC unless the timing resolution for LaBr3 is considerably smaller than presently used for LSO, i.e. well below 300 ps.

Brain enlargement and dental reduction were not linked in hominin evolution

PubMed Central

Smaers, Jeroen B.; Holloway, Ralph L.

2017-01-01

The large brain and small postcanine teeth of modern humans are among our most distinctive features, and trends in their evolution are well studied within the hominin clade. Classic accounts hypothesize that larger brains and smaller teeth coevolved because behavioral changes associated with increased brain size allowed a subsequent dental reduction. However, recent studies have found mismatches between trends in brain enlargement and posterior tooth size reduction in some hominin species. We use a multiple-variance Brownian motion approach in association with evolutionary simulations to measure the tempo and mode of the evolution of endocranial and dental size and shape within the hominin clade. We show that hominin postcanine teeth have evolved at a relatively consistent neutral rate, whereas brain size evolved at comparatively more heterogeneous rates that cannot be explained by a neutral model, with rapid pulses in the branches leading to later Homo species. Brain reorganization shows evidence of elevated rates only much later in hominin evolution, suggesting that fast-evolving traits such as the acquisition of a globular shape may be the result of direct or indirect selection for functional or structural traits typical of modern humans. PMID:28049819

Structural imaging of the brain reveals decreased total brain and total gray matter volumes in obese but not in lean women with polycystic ovary syndrome compared to body mass index-matched counterparts.

PubMed

Ozgen Saydam, Basak; Has, Arzu Ceylan; Bozdag, Gurkan; Oguz, Kader Karli; Yildiz, Bulent Okan

2017-07-01

To detect differences in global brain volumes and identify relations between brain volume and appetite-related hormones in women with polycystic ovary syndrome (PCOS) compared to body mass index-matched controls. Forty subjects participated in this study. Cranial magnetic resonance imaging and measurements of fasting ghrelin, leptin and glucagon-like peptide 1 (GLP-1), as well as GLP-1 levels during mixed-meal tolerance test (MTT), were performed. Total brain volume and total gray matter volume (GMV) were decreased in obese PCOS compared to obese controls (p < 0.05 for both) whereas lean PCOS and controls did not show a significant difference. Secondary analyses of regional brain volumes showed decreases in GMV of the caudate nucleus, ventral diencephalon and hippocampus in obese PCOS compared to obese controls (p < 0.05 for all), whereas lean patients with PCOS had lower GMV in the amygdala than lean controls (p < 0.05). No significant relations were detected between structural differences and measured hormone levels at baseline or during MTT. This study, investigating structural brain alterations in PCOS, suggests volumetric reductions in global brain areas in obese women with PCOS. Functional studies with larger sample size are needed to determine physiopathological roles of these changes and potential effects of long-term medical management on brain structure of PCOS.

Interaction between physostigmine and soman on brain regional cholinesterase activity and /sup 3/H-physostigmine distribution

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

Hallak, M.E.; Woodruff, E.; Giacobini, E.

1986-03-05

Physostigmine (Phy) concentrations (as radioactivity) were studied in various brain areas after /sup 3/H-Phy administration as a function of time. Five min after 500 ..mu..g/kg i.m., cortex (CX) and total brain showed similar concentrations (370 ng/g) which were 50-90% higher than those of other brain regions (striatum, hippocampus, and medulla oblongata). Soman did not affect Phy levels in whole brain after pretreatment with Phy (100 or 500 ..mu..g/kg), however, the regional distribution of Phy was altered by soman as was ChE inhibition. A significant increase in Phy concentration was seen in HC (22 and 45% at 5 and 30 min,more » respectively) and CX (21% at 30 min). ChE activity in total brain was 12, 30, and 24% (5, 15 and 30 min after soman administration) lower than after Phy alone. If the pretreatment dose of Phy was increased to 500 ..mu..g/kg /sup 3/H-Phy, ChE activity was further reduced to 4, 13 and 19%. This might indicate that higher doses of Phy provide more protection of the enzyme from soman than lower doses. The protective role of Phy seen in total brain was not consistent for all brain regions. Soman alone produced a 95% ChE inhibition and there were no differences in its effect between total brain or brain areas. Pretreatment of the rat with Phy produced a protective effect upon ChE activity up to 30 min. However, no protective effect on survival was observed.« less

Structural growth trajectories and rates of change in the first 3 months of infant brain development.

PubMed

Holland, Dominic; Chang, Linda; Ernst, Thomas M; Curran, Megan; Buchthal, Steven D; Alicata, Daniel; Skranes, Jon; Johansen, Heather; Hernandez, Antonette; Yamakawa, Robyn; Kuperman, Joshua M; Dale, Anders M

2014-10-01

The very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders. To assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth. Serial structural T1-weighted and/or T2-weighted magnetic resonance images were obtained for 211 time points from 87 healthy term-born or term-equivalent preterm-born infants, aged 2 to 90 days, between October 5, 2007, and June 12, 2013. We segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods. We modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms. Whole-brain volume at birth was approximately one-third of healthy elderly brain volume, and did not differ significantly between male and female infants (347 388 mm3 and 335 509 mm3, respectively, P = .12). The growth rate was approximately 1%/d, slowing to 0.4%/d by the end of the first 3 months, when the brain reached just more than half of elderly adult brain volume. Overall growth in the first 90 days was 64%. There was a significant age-by-sex effect leading to widening separation in brain sizes with age between male and female infants (with male infants growing faster than females by 200.4 mm3/d, SE = 67.2, P = .003). Longer gestation was associated with larger brain size (2215 mm3/d, SE = 284, P = 4×10-13). The expected brain size of an infant born one week earlier than average was 5% smaller than average; at 90 days it will not have caught up, being 2% smaller than average. The cerebellum grew at the highest rate, more than doubling in 90 days, and the hippocampus grew at the slowest rate, increasing by 47% in 90 days. There was left-right asymmetry in multiple regions of interest, particularly the lateral ventricles where the left was larger than the right by 462 mm3 on average (approximately 5% of lateral ventricular volume at 2 months). We calculated volume-by-age percentile plots for assessing individual development. Normative trajectories for early postnatal brain structural development can be determined from magnetic resonance imaging and could be used to improve the detection of deviant maturational patterns indicative of neurodevelopmental disorders.

Structural Growth Trajectories and Rates of Change in the First 3 Months of Infant Brain Development

PubMed Central

Holland, Dominic; Chang, Linda; Ernst, Thomas M.; Curran, Megan; Buchthal, Steven D.; Alicata, Daniel; Skranes, Jon; Johansen, Heather; Hernandez, Antonette; Yamakawa, Robyn; Kuperman, Joshua M.; Dale, Anders M.

2016-01-01

IMPORTANCE The very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders. OBJECTIVE To assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth. DESIGN, SETTING, AND PARTICIPANTS Serial structural T1-weighted and/or T2-weighted magnetic resonance images were obtained for 211 time points from 87 healthy term-born or term-equivalent preterm-born infants, aged 2 to 90 days, between October 5, 2007, and June 12, 2013. MAIN OUTCOMES AND MEASURES We segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods. We modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms. RESULTS Whole-brain volume at birth was approximately one-third of healthy elderly brain volume, and did not differ significantly between male and female infants (347 388 mm3 and 335 509 mm3, respectively, P = .12). The growth rate was approximately 1%/d, slowing to 0.4%/d by the end of the first 3 months, when the brain reached just more than half of elderly adult brain volume. Overall growth in the first 90 days was 64%. There was a significant age-by-sex effect leading to widening separation in brain sizes with age between male and female infants (with male infants growing faster than females by 200.4 mm3/d, SE = 67.2, P = .003). Longer gestation was associated with larger brain size (2215 mm3/d, SE = 284, P = 4×10−13). The expected brain size of an infant born one week earlier than average was 5% smaller than average; at 90 days it will not have caught up, being 2% smaller than average. The cerebellum grew at the highest rate, more than doubling in 90 days, and the hippocampus grew at the slowest rate, increasing by 47% in 90 days. There was left-right asymmetry in multiple regions of interest, particularly the lateral ventricles where the left was larger than the right by 462 mm3 on average (approximately 5% of lateral ventricular volume at 2 months). We calculated volume-by-age percentile plots for assessing individual development. CONCLUSIONS AND RELEVANCE Normative trajectories for early postnatal brain structural development can be determined from magnetic resonance imaging and could be used to improve the detection of deviant maturational patterns indicative of neurodevelopmental disorders. PMID:25111045

Assessment of the computational uncertainty of temperature rise and SAR in the eyes and brain under far-field exposure from 1 to 10 GHz

NASA Astrophysics Data System (ADS)

Laakso, Ilkka

2009-06-01

This paper presents finite-difference time-domain (FDTD) calculations of specific absorption rate (SAR) values in the head under plane-wave exposure from 1 to 10 GHz using a resolution of 0.5 mm in adult male and female voxel models. Temperature rise due to the power absorption is calculated by the bioheat equation using a multigrid method solver. The computational accuracy is investigated by repeating the calculations with resolutions of 1 mm and 2 mm and comparing the results. Cubically averaged 10 g SAR in the eyes and brain and eye-averaged SAR are calculated and compared to the corresponding temperature rise as well as the recommended limits for exposure. The results suggest that 2 mm resolution should only be used for frequencies smaller than 2.5 GHz, and 1 mm resolution only under 5 GHz. Morphological differences in models seemed to be an important cause of variation: differences in results between the two different models were usually larger than the computational error due to the grid resolution, and larger than the difference between the results for open and closed eyes. Limiting the incident plane-wave power density to smaller than 100 W m-2 was sufficient for ensuring that the temperature rise in the eyes and brain were less than 1 °C in the whole frequency range.

Heterogeneity of anatomic regions by MR volumetry in juvenile myoclonic epilepsy.

PubMed

Swartz, B E; Spitz, J; Vu, A L; Mandelkern, M; Su, M L

2016-10-01

To investigate brain volumes in patients with well-characterized juvenile myoclonic epilepsy (JME). We studied the MRI images of seventeen subjects with EEG and clinically defined JME and seventeen age- and sex-matched controls using voxel-based morphometry (VBM) and automated and manual volumetry. We found no significant group differences in the cortical volumes by automated techniques for all regions or for the whole brain. However, we found a larger pulvinar nucleus in JME using VBM with small volume correction and a larger thalamus with manual volumetry (P = 0.001; corrected two-tailed t-test). By analysing the individual subjects, we determined that considerable heterogeneity exists even in this highly selected group. Histograms of all JME and matched control regions' volumes showed more subjects with JME had smaller hippocampi and larger thalami (P < 0.05; chi-square). Subjects in whom the first seizure was absence were more likely to have smaller hippocampi than their matched control, while those without absences showed no differences (P < 0.05, chi-square). There is ample evidence for frontal cortical thalamic network changes in JME, but subcortical structural differences were more distinct in this group. Given the heterogeneity of brain volumes in the clinical population, further advancement in the field will require the examination of stringent genetically controlled populations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains.

PubMed Central

Pulliam, L; Herndier, B G; Tang, N M; McGrath, M S

1991-01-01

We wanted to establish an in vitro human model for AIDS-associated dementia and pursue the hypothesis that this disease process may be a result of soluble factors produced by HIV-infected macrophages. Human brain aggregates were prepared from nine different brain specimens, and were treated with supernatants from in vitro HIV-infected macrophages (SI), uninfected macrophages (SU), infected T cells, or macrophage-conditioned media from four AIDS patients. Seven of nine treated brains exposed to SI showed peripheral rarefaction after 1 wk of incubation that by ultrastructural analysis showed cytoplasmic vacuolation. Aggregates from two of three brain cultures treated with SI for 3 wk became smaller, an approximately 50% decrease in size. The degree of apparent toxicity in brains exposed to patient-derived macrophage supernatants paralleled the proportion of macrophages found to be expressing HIV p24. Ultrastructural abnormalities were not observed in brains treated with supernatants from HIV-infected T cells, uninfected macrophages, or LPS-activated macrophages. Levels of five neurotransmitter amino acids were decreased in comparison to the structural amino acid leucine. These findings suggest that HIV-infected macrophages, infected both in vitro as well as derived from AIDS patients' peripheral blood, produce factors that cause reproducible histochemical, ultrastructural, and functional abnormalities in human brain aggregates. Images PMID:1671392

Cortical Gray Matter in Attention-Deficit/Hyperactivity Disorder: A Structural Magnetic Resonance Imaging Study

ERIC Educational Resources Information Center

Batty, Martin J.; Liddle, Elizabeth B.; Pitiot, Alain; Toro, Roberto; Groom, Madeleine J.; Scerif, Gaia; Liotti, Mario; Liddle, Peter F.; Paus, Tomas; Hollis, Chris

2010-01-01

Objective: Previous studies have shown smaller brain volume and less gray matter in children with attention-deficit/hyperactivity disorder (ADHD). Relatively few morphological studies have examined structures thought to subserve inhibitory control, one of the diagnostic features of ADHD. We examined one such region, the pars opercularis,…

Structural Neuroimaging in Adolescents with a First Psychotic Episode

ERIC Educational Resources Information Center

Moreno, Dolores; Burdalo, Maite; Reig, Santiago; Parellada, Mara; Zabala, Arantzazu; Desco, Manuel; Baca-Baldomero, Enrique; Arango, Celso

2005-01-01

Objective: The objective of the present study is to replicate findings in first-episode psychosis reporting a smaller volume in brain structures in a population with adolescent onset. Method: Magnetic resonance imaging studies were performed on 23 psychotic adolescents (12-18 years old, 17 males, 6 females) consecutively admitted to an adolescent…

Infant Brain Development and Vulnerability to Later Internalizing Difficulties: The Generation R Study

ERIC Educational Resources Information Center

Herba, Catherine M.; Roza, Sabine J.; Govaert, Paul; van Rossum, Joram; Hofman, Albert; Jaddoe, Vincent; Verhulst, Frank C.; Tiemeier, Henning

2010-01-01

Objective: Although clinical studies have demonstrated smaller subcortical volumes in structures such as the amygdala, hippocampus, caudate nucleus, and thalamus in adults and adolescents with depressive disorders and anxiety, no study has assessed such structures in babies, long before the development of the disorders. This study examined whether…

A Blast Model of Traumatic Brain Injury in Swine

DTIC Science & Technology

2011-02-01

the smaller gun had a slower recovery, was extubated 14 minutes post injury, was given 100 mg carprofen IM one hour post injury because of the slow...at 80 psi was extubated 12 minutes post injury, showed signs of pain by excessively grinding teeth and was given 100 mg carprofen one hour post

Ventral striatal volume is associated with cognitive decline in older people: a population based MR-study

PubMed Central

de Jong, L.W.; Wang, Y.; White, L.R.; Yu, B.; van Buchem, M.A.; Launer, L.J.

2012-01-01

Striatal degeneration may contribute to cognitive impairment in older people. Here, we examine the relation of degeneration of the striatum and substructures to cognitive decline and dementia in subjects with a wide range of cognitive function. Data are from the prospective community-based Honolulu Asia Aging Study of Japanese American men born 1900–1919. Brain MRI (1.5T) was acquired on a stratified sub-sample (n=477) that included four groups defined by cognitive status relative to the scan date: subjects without dementia (n=347), subjects identified as demented 2–3 years prior to brain scanning (n=30), at the time of scanning (n=58), and 3–5 years after scanning (n=42). Volumes of the striatum, including the accumbens, putamen, and caudate nucleus were automatically estimated from T1 MR images. Global cognitive function was measured with the CASI, at four exams spanning an 8 year interval. Trajectories of cognitive decline were estimated for each quartile of striatal volume using mixed models, controlling for demographic variables, measures of cerebro-vascular damage, global brain atrophy, and hippocampal volume. Diagnosis of dementia before, during, and after brain scanning was associated with smaller volumes of n. accumbens and putamen, but not with caudate nucleus volume. Subjects in the lowest quartile of n. accumbens, both in the total sample and in the subjects not diagnosed with dementia during the study, had a significantly (p < 0.0001) steeper decline in cognitive performance compared to those in the highest quartile. In conclusion, volumes of the n. accumbens and putamen are closely associated with the occurrence of dementia and n. accumbens volume predicts cognitive decline in older people. These associations were found independent of the magnitude of other pivotal markers of cognitive decline, i.e. cerebro-vascular damage and hippocampal volume. The present study suggests a role for the ventral striatum in the development of clinical dementia. PMID:21075480

Using the Optical Fractionator to Estimate Total Cell Numbers in the Normal and Abnormal Developing Human Forebrain.

PubMed

Larsen, Karen B

2017-01-01

Human fetal brain development is a complex process which is vulnerable to disruption at many stages. Although histogenesis is well-documented, only a few studies have quantified cell numbers across normal human fetal brain growth. Due to the present lack of normative data it is difficult to gauge abnormal development. Furthermore, many studies of brain cell numbers have employed biased counting methods, whereas innovations in stereology during the past 20-30 years enable reliable and efficient estimates of cell numbers. However, estimates of cell volumes and densities in fetal brain samples are unreliable due to unpredictable shrinking artifacts, and the fragility of the fetal brain requires particular care in handling and processing. The optical fractionator design offers a direct and robust estimate of total cell numbers in the fetal brain with a minimum of handling of the tissue. Bearing this in mind, we have used the optical fractionator to quantify the growth of total cell numbers as a function of fetal age. We discovered a two-phased development in total cell numbers in the human fetal forebrain consisting of an initial steep rise in total cell numbers between 13 and 20 weeks of gestation, followed by a slower linear phase extending from mid-gestation to 40 weeks of gestation. Furthermore, we have demonstrated a reduced total cell number in the forebrain in fetuses with Down syndome at midgestation and in intrauterine growth-restricted fetuses during the third trimester.

Factors affecting the internal brain drain of Saudi healthcare professionals.

PubMed

Bakhsh, Zuhair T; Mansour, Ameerah Y; Mensah, Edward K; Croke, Kevin G; Drummond, James L; Koerber, Anne

2012-12-01

To investigate factors affecting the internal brain drain of healthcare professionals in the Kingdom of Saudi Arabia. A cross-sectional study was conducted using an anonymous self-administered online questionnaire sent to all Saudi students enrolled in healthcare profession programs in North America. The data was collected between January and March 2008 at the University of Illinois at Chicago, Chicago, Illinois, United States of America. Results were analyzed using logistic regression analyses. A total of 377 completed questionnaires were returned. Results revealed that 71% of respondents intended to return to work within the 2 major urban cities Riyadh and Jeddah. Respondents who completed their undergraduate studies in a large city were more likely to work in the same city (odds ratio [OR]=3.2; p=0.000; 95% confidence interval [CI] = 2.0-5.2). Furthermore, 51% of the students were willing to work in a rural area for a 50% or more increase in their salary. Finally, men were more willing to work in a rural area for a financial incentive (OR=2.3; p=0.006, 95% CI = 1.3-4.3). This study suggests that realistic financial incentives would probably not suffice to attract Saudi healthcare providers to rural areas. The provision of medical schools in smaller cities and rural areas is predicted to be a more effective method for improving the current maldistribution of healthcare providers.

Selective Serotonin Reuptake Inhibitors for Treating Neurocognitive and Neuropsychiatric Disorders Following Traumatic Brain Injury: An Evaluation of Current Evidence

PubMed Central

Yue, John K.; Burke, John F.; Upadhyayula, Pavan S.; Winkler, Ethan A.; Deng, Hansen; Robinson, Caitlin K.; Pirracchio, Romain; Suen, Catherine G.; Sharma, Sourabh; Ferguson, Adam R.; Ngwenya, Laura B.; Stein, Murray B.; Manley, Geoffrey T.; Tarapore, Phiroz E.

2017-01-01

The prevalence of neuropsychiatric disorders following traumatic brain injury (TBI) is 20%–50%, and disorders of mood and cognition may remain even after recovery of neurologic function is achieved. Selective serotonin reuptake inhibitors (SSRI) block the reuptake of serotonin in presynaptic cells to lead to increased serotonergic activity in the synaptic cleft, constituting first-line treatment for a variety of neurocognitive and neuropsychiatric disorders. This review investigates the utility of SSRIs in treating post-TBI disorders. In total, 37 unique reports were consolidated from the Cochrane Central Register and PubMed (eight randomized-controlled trials (RCTs), nine open-label studies, 11 case reports, nine review articles). SSRIs are associated with improvement of depressive but not cognitive symptoms. Pooled analysis using the Hamilton Depression Rating Scale demonstrate a significant mean decrease of depression severity following sertraline compared to placebo—a result supported by several other RCTs with similar endpoints. Evidence from smaller studies demonstrates mood improvement following SSRI administration with absent or negative effects on cognitive and functional recovery. Notably, studies on SSRI treatment effects for post-traumatic stress disorder after TBI remain absent, and this represents an important direction of future research. Furthermore, placebo-controlled studies with extended follow-up periods and concurrent biomarker, neuroimaging and behavioral data are necessary to delineate the attributable pharmacological effects of SSRIs in the TBI population. PMID:28757598

Selective Serotonin Reuptake Inhibitors for Treating Neurocognitive and Neuropsychiatric Disorders Following Traumatic Brain Injury: An Evaluation of Current Evidence.

PubMed

Yue, John K; Burke, John F; Upadhyayula, Pavan S; Winkler, Ethan A; Deng, Hansen; Robinson, Caitlin K; Pirracchio, Romain; Suen, Catherine G; Sharma, Sourabh; Ferguson, Adam R; Ngwenya, Laura B; Stein, Murray B; Manley, Geoffrey T; Tarapore, Phiroz E

2017-07-25

The prevalence of neuropsychiatric disorders following traumatic brain injury (TBI) is 20%-50%, and disorders of mood and cognition may remain even after recovery of neurologic function is achieved. Selective serotonin reuptake inhibitors (SSRI) block the reuptake of serotonin in presynaptic cells to lead to increased serotonergic activity in the synaptic cleft, constituting first-line treatment for a variety of neurocognitive and neuropsychiatric disorders. This review investigates the utility of SSRIs in treating post-TBI disorders. In total, 37 unique reports were consolidated from the Cochrane Central Register and PubMed (eight randomized-controlled trials (RCTs), nine open-label studies, 11 case reports, nine review articles). SSRIs are associated with improvement of depressive but not cognitive symptoms. Pooled analysis using the Hamilton Depression Rating Scale demonstrate a significant mean decrease of depression severity following sertraline compared to placebo-a result supported by several other RCTs with similar endpoints. Evidence from smaller studies demonstrates mood improvement following SSRI administration with absent or negative effects on cognitive and functional recovery. Notably, studies on SSRI treatment effects for post-traumatic stress disorder after TBI remain absent, and this represents an important direction of future research. Furthermore, placebo-controlled studies with extended follow-up periods and concurrent biomarker, neuroimaging and behavioral data are necessary to delineate the attributable pharmacological effects of SSRIs in the TBI population.

Effect of enriched environment on angiogenesis and neurological functions in rats with focal cerebral ischemia.

PubMed

Zhang, Xin; Chen, Xiu-Ping; Lin, Jun-Bin; Xiong, Yu; Liao, Wei-Jing; Wan, Qi

2017-01-15

The purpose of this study was to investigate the effect of enriched environment (EE) on cerebral angiogenesis after ischemia-reperfusion injury. Middle cerebral artery occlusion (MCAO) followed by reperfusion was performed in rats to set up an animal model of ischemia-reperfusion injury. In a set of behavioral tests, we demonstrated that the animals in the IEE (ischemia + enriched environment) group exhibited significantly improved neurological functions compared to those in the standard housing condition group. In consistent with the functional tests, smaller infarction volumes were observed in the animals of IEE group. Laser scanning confocal microscopy and 3D quantitative analysis of cerebral microvessels revealed that EE treatment increased the total vessel surface area and number of branch point in the ischemic boundary zone. IgG extraction assay showed that the blood brain barrier (BBB) leakage in the ischemic brain was attenuated after EE treatment. EE treatment also enhanced endothelial cells (ECs) proliferation and increased the expression levels of VEGF and its receptor Flk-1 after ischemia-reperfusion injury. Analyses of Spearman's correlation coefficients indicated a correlation of mNSS scores with enhanced cerebral angiogenesis. Together, the results suggest that EE treatment-induced cerebral angiogenesis may contribute to the improved neurological outcome of stroke animals after ischemia-reperfusion injury. Copyright © 2016 Elsevier B.V. All rights reserved.

SU-F-T-613: Multi-Lesion Cranial SRS VMAT Plan Quality

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

Ballangrud, A; Kuo, L; Happersett, L

Purpose: Cranial SRS VMAT plans must have steep dose gradient around each target to reduce dose to normal brain. This study reports on the correlation between gradient index (GI=V50%/V100%), target size and target dose heterogeneity index (HI=PTV Dmax/prescription dose) for multi-lesion cranial SRS VMAT plans. Methods: VMAT plans for 10 cranial cases with 3 to 6 lesions (total 39 lesions) generated in Varian Eclipse V11.0.47 with a fine-tuned AAA beam model and 0.125 cm dose grid were analyzed. One or two iso centers were used depending on the spatial distribution of lesions. Two to nine coplanar and non-coplanar arcs weremore » used per isocenter. Conformity index (CI= V100%/VPTV), HI, and GI were determined for each lesion. Dose to critical structures were recorded. Results: Lesion size ranged from 0.05–11.00 cm3. HI ranged from 1.2–1.4, CI ranged from 1.0–2.8 and GI from 3.1–8.4. Maximum dose to brainstem, chiasm, lenses, optic nerves and eyes ranged from 120–1946 cGy, 47–463 cGy, 9–121 cGy, 14–512 cGy, and 17–294 cGy, respectively. Brain minus PTV (Brain-PTV) V7Gy was in the range 1.1–6.5%, and Brain-PTV Dmean was in the range 94–324 cGy. Conclusion: This work shows that a GI < 5 can be achieved for lesions > 0.4cc. For smaller lesions, GI increases rapidly. GI is lower when HI is increased. Based on this study, recommend HI is 1.4, and recommended GI is for volumes <0.1cc GI<9, 0.1–0.4cc GI<6, 0.4–0.1.0cc GI<5, and for volumes >1.0cc GI<4. CI is < 1.3 for all lesions except for targets < 0.1cc. Cranial SRS VMAT plans must be optimized to lower the GI to reduce the dose to normal brain tissue.« less

Development of the Korean Academy of Medical Sciences Guideline for Rating the Impairment in the Brain Injured and Brain Diseased Persons with Motor Dysfunction

PubMed Central

Baik, Jong Sam; Jang, Seong Ho; Park, Dong Sik

2009-01-01

To develop an objective and scientific method to evaluate the brain injured and brain diseased persons with motor dysfunction, American Medical Association's Guides to the Evaluation of Permanent Impairment was used as an exemplar. After the motor dysfunction due to brain injury or brain disease was confirmed, active range of motion and muscle strength of affected extremities were measured. Also, the total function of extremities was evaluated through the assessment of activities of daily living, fine coordination of hand, balance and gait. Then, the total score of manual muscle test and functional assessment of impaired upper and lower extremity were added, respectively. Spasticity of upper and lower extremity was used as minus factors. Patients with movement disorder such as Parkinson's disease were assessed based on the degree of dysfunction in response to medication. We develop a new rating system based on the concept of total score. PMID:19503680

Familial and environmental influences on brain volumes in twins with schizophrenia.

PubMed

Picchioni, Marco M; Rijsdijk, Fruhling; Toulopoulou, Timothea; Chaddock, Christopher; Cole, James H; Ettinger, Ulrich; Oses, Ana; Metcalfe, Hugo; Murray, Robin M; McGuire, Philip

2017-03-01

Reductions in whole brain and grey matter volumes are robust features of schizophrenia, yet their etiological influences are unclear. We investigated the association between the genetic and environmental risk for schizophrenia and brain volumes. Whole brain, grey matter and white matter volumes were established from structural MRIs from twins varying in their zygosity and concordance for schizophrenia. Hippocampal volumes were measured manually. We conducted between-group testing and full genetic modelling. We included 168 twins in our study. Whole brain, grey matter, white matter and right hippocampal volumes were smaller in twins with schizophrenia. Twin correlations were larger for whole brain, grey matter and white matter volumes in monozygotic than dizygotic twins and were significantly heritable, whereas hippocampal volume was the most environmentally sensitive. There was a significant phenotypic correlation between schizophrenia and reductions in all the brain volumes except for that of the left hippocampus. For whole brain, grey matter and the right hippocampus the etiological links with schizophrenia were principally associated with the shared familial environment. Lower birth weight and perinatal hypoxia were both associated with lower whole brain volume and with lower white matter and grey matter volumes, respectively. Scan data were collected across 2 sites, and some groups were modest in size. Whole brain, grey matter and right hippocampal volume reductions are linked to schizophrenia through correlated familial risk (i.e., the shared familial environment). The degree of influence of etiological factors varies between brain structures, leading to the possibility of a neuroanatomically specific etiological imprint.

Brain volume reduction after whole-brain radiotherapy: quantification and prognostic relevance.

PubMed

Hoffmann, Christian; Distel, Luitpold; Knippen, Stefan; Gryc, Thomas; Schmidt, Manuel Alexander; Fietkau, Rainer; Putz, Florian

2018-01-22

Recent studies have questioned the value of adding whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) for brain metastasis treatment. Neurotoxicity, including radiation-induced brain volume reduction, could be one reason why not all patients benefit from the addition of WBRT. In this study, we quantified brain volume reduction after WBRT and assessed its prognostic significance. Brain volumes of 91 patients with cerebral metastases were measured during a 150-day period after commencing WBRT and were compared with their pretreatment volumes. The average daily relative change in brain volume of each patient, referred to as the "brain volume reduction rate," was calculated. Univariate and multivariate Cox regression analyses were performed to assess the prognostic significance of the brain volume reduction rate, as well as of 3 treatment-related and 9 pretreatment factors. A one-way analysis of variance was used to compare the brain volume reduction rate across recursive partitioning analysis (RPA) classes. On multivariate Cox regression analysis, the brain volume reduction rate was a significant predictor of overall survival after WBRT (P < 0.001), as well as the number of brain metastases (P = 0.002) and age (P = 0.008). Patients with a relatively favorable prognosis (RPA classes 1 and 2) experienced significantly less brain volume decrease after WBRT than patients with a poor prognosis (RPA class 3) (P = 0.001). There was no significant correlation between delivered radiation dose and brain volume reduction rate (P = 0.147). In this retrospective study, a smaller decrease in brain volume after WBRT was an independent predictor of longer overall survival. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Auditory brainstem evoked responses and temperature monitoring during pediatric cardiopulmonary bypass.

PubMed

Rodriguez, R A; Edmonds, H L; Auden, S M; Austin, E H

1999-09-01

To examine the effects of temperature on auditory brainstem responses (ABRs) in infants during hypothermic cardiopulmonary bypass for total circulatory arrest (TCA). The relationship between ABRs (as a surrogate measure of core-brain temperature) and body temperature as measured at several temperature monitoring sites was determined. In a prospective, observational study, ABRs were recorded non-invasively at normothermia and at every 1 or 2 degrees C change in ear-canal temperature during cooling and rewarming in 15 infants (ages: 2 days to 14 months) that required TCA. The ABR latencies and amplitudes and the lowest temperatures at which an ABR was identified (the threshold) were measured during both cooling and rewarming. Temperatures from four standard temperature monitoring sites were simultaneously recorded. The latencies of ABRs increased and amplitudes decreased with cooling (P < 0.01), but rewarming reversed these effects. The ABR threshold temperature as related to each monitoring site (ear-canal, nasopharynx, esophagus and bladder) was respectively determined as 23 +/- 2.2 degrees C, 20.8 +/- 1.7 degrees C, 14.6 +/- 3.4 degrees C, and 21.5 +/- 3.8 degrees C during cooling and 21.8 +/- 1.6 degrees C, 22.4 +/- 2.0 degrees C, 27.6 +/- 3.6 degrees C, and 23.0 +/- 2.4 degrees C during rewarming. The rewarming latencies were shorter and Q10 latencies smaller than the corresponding cooling values (P < 0.01). Esophageal and bladder sites were more susceptible to temperature variations as compared with the ear-canal and nasopharynx. No temperature site reliably predicted an electrophysiological threshold. A faster latency recovery during rewarming suggests that body temperature monitoring underestimates the effects of rewarming in the core-brain. ABRs may be helpful to monitor the effects of cooling and rewarming on the core-brain during pediatric cardiopulmonary bypass.

Postconcussive symptoms (PCS) following combat-related traumatic brain injury (TBI) in Veterans with posttraumatic stress disorder (PTSD): Influence of TBI, PTSD, and depression on symptoms measured by the Neurobehavioral Symptom Inventory (NSI).

PubMed

Porter, Katherine E; Stein, Murray B; Martis, Brian; Avallone, Kimberly M; McSweeney, Lauren B; Smith, Erin R; Simon, Naomi M; Gargan, Sean; Liberzon, Israel; Hoge, Charles W; Rauch, Sheila A M

2018-07-01

Mild traumatic brain injury (mTBI) is commonly reported in recent combat Veterans. While the majority resolve, some Veterans develop postconcussive symptoms (PCS). Previous research suggests these symptoms are not specific to head injury and are often associated with psychiatric symptoms. The current study examines the relative contributions of posttraumatic stress, depressive symptoms, and TBI on postconcussive symptoms, and explores whether the relationship remains after controlling for symptom overlap. Two hundred eighteen combat Veterans from Operation Iraqi Freedom (OIF), Operation Enduring Freedom (OEF), and Operation New Dawn (OND) provided the data for this study as part of a baseline evaluation for inclusion into larger treatment study for posttraumatic stress disorder (PTSD). Participants completed the Brief Traumatic Brain Injury Screen (BTBIS), Neurobehavioral Symptom Inventory (NSI), PTSD Checklist-Stressor Version (PCL-S), Beck Depression Inventory-II (BDI-II). Significant differences in NSI total score between individuals with and without history of TBI were not found. A series of regression analyses demonstrated that Depression and PTSD were significant predictors of NSI score even after removal of NSI symptoms that overlap with PTSD or depression. TBI status was also a significant predictor of PCS in most models, but its relative contribution was much smaller than that of depression and PTSD. Within PTSD symptoms, hyperarousal cluster was a significant predictor of NSI scores. Findings demonstrate that depression and PTSD are related to PCS beyond similarities in construct. Further, within a primarily PTSD treatment-seeking population, these psychiatric symptoms appear to be a stronger contributor than TBI. Copyright © 2018. Published by Elsevier Ltd.

[Computer tomography of the brain in children. I. 1. Perinatal encephalopathy of vascular origin. 2. Congenital brain malformations].

PubMed

Cernoch, Z; Sercl, M; Parízek, J; Lichý, J

1990-01-01

CT findings are evaluated in 103 children with vascular lesions (aged up to 15 years), and in 59 children with congenital cerebral and cerebellar malformations. Their maximum has been stated to occur perinatally due to hypoxic and ischemic brain affections. Therefore most of diagnostical problems were related to the differentiation of hypodense immature brain from ischemic changes. Mentioned findings were always correlated with clinical course. Similar confrontations along with earlier CT control examination may be helpful in distinguishing milder transitory postischemic oedema from serious necrotic and malatic changes. In more aged children, vascular lesions are of rare occurrence being different in etiology. More unambiguous CT patterns are obtained in vascular changes with hemorrhagies. Of special importance in their onset is a hypoxic attack with subsequent venous bleeding mainly into the germinative matrix. While well tolerated in premature newborns, the extensive hemorrhagies in on-term ones have worser prognosis, resulting in significant changes on control examination, predominantly hydrocephalus and porencephalia. Atrophies of various extent were the most common consequence of all encephalopathies of vascular origine. In almost a half of congenital brain and cerebellar anomalies, unsignificant findings of smaller middle line cavities were obtained predominantly in pellucide septum. From the serious findings, most frequent were different varieties of dysgenesis, hypogenesis up to agenesis of corpus callosum combined sometimes with either the lipomas or cysts. Another findings consisted in Dandy-Walker's cerebellar malformation, holoprosencephalia and only two patients manifested hydrencephalia and basal meningoencephalocele. Most of diagnostical effort has been made in mainly anomalies associated with ventriculomegalia and/or cystic formations in order to elucidate the eventual communication between the structures mentioned. In addition, CT ventriculo-cysto-orcisternography has also been performed using smaller amount of nonionic contrast. At present, an important portion of CT examinations may be replaced with sonography which is more simple as used in both newborns and toddlers.

Oxytocin enhances inter-brain synchrony during social coordination in male adults.

PubMed

Mu, Yan; Guo, Chunyan; Han, Shihui

2016-12-01

Recent brain imaging research has revealed oxytocin (OT) effects on an individual's brain activity during social interaction but tells little about whether and how OT modulates the coherence of inter-brain activity related to two individuals' coordination behavior. We developed a new real-time coordination game that required two individuals of a dyad to synchronize with a partner (coordination task) or with a computer (control task) by counting in mind rhythmically. Electroencephalography (EEG) was recorded simultaneously from a dyad to examine OT effects on inter-brain synchrony of neural activity during interpersonal coordination. Experiment 1 found that dyads showed smaller interpersonal time lags of counting and greater inter-brain synchrony of alpha-band neural oscillations during the coordination (vs control) task and these effects were reliably observed in female but not male dyads. Moreover, the increased alpha-band inter-brain synchrony predicted better interpersonal behavioral synchrony across all participants. Experiment 2, using a double blind, placebo-controlled between-subjects design, revealed that intranasal OT vs placebo administration in male dyads improved interpersonal behavioral synchrony in both the coordination and control tasks but specifically enhanced alpha-band inter-brain neural oscillations during the coordination task. Our findings provide first evidence that OT enhances inter-brain synchrony in male adults to facilitate social coordination. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

A Systematic Review and Meta-analysis of Neuroimaging in Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) Taking Attention-Deficit Hyperactivity Disorder (ADHD) Into Account.

PubMed

Noordermeer, Siri D S; Luman, Marjolein; Oosterlaan, Jaap

2016-03-01

Oppositional defiant disorder (ODD) and conduct disorder (CD) are common behavioural disorders in childhood and adolescence and are associated with brain abnormalities. This systematic review and meta-analysis investigates structural (sMRI) and functional MRI (fMRI) findings in individuals with ODD/CD with and without attention-deficit hyperactivity disorder (ADHD). Online databases were searched for controlled studies, resulting in 12 sMRI and 17 fMRI studies. In line with current models on ODD/CD, studies were classified in hot and cool executive functioning (EF). Both the meta-analytic and narrative reviews showed evidence of smaller brain structures and lower brain activity in individuals with ODD/CD in mainly hot EF-related areas: bilateral amygdala, bilateral insula, right striatum, left medial/superior frontal gyrus, and left precuneus. Evidence was present in both structural and functional studies, and irrespective of the presence of ADHD comorbidity. There is strong evidence that abnormalities in the amygdala are specific for ODD/CD as compared to ADHD, and correlational studies further support the association between abnormalities in the amygdala and ODD/CD symptoms. Besides the left precuneus, there was no evidence for abnormalities in typical cool EF related structures, such as the cerebellum and dorsolateral prefrontal cortex. Resulting areas are associated with emotion-processing, error-monitoring, problem-solving and self-control; areas associated with neurocognitive and behavioural deficits implicated in ODD/CD. Our findings confirm the involvement of hot, and to a smaller extent cool, EF associated brain areas in ODD/CD, and support an integrated model for ODD/CD (e.g. Blair, Development and Psychopathology, 17(3), 865-891, 2005).

Endoplasmic reticulum stress in the brain subfornical organ contributes to sex differences in angiotensin-dependent hypertension in rats.

PubMed

Dai, S-Y; Fan, J; Shen, Y; He, J-J; Peng, W

2016-05-01

Endoplasmic reticulum (ER) stress in the brain subfornical organ (SFO), a key cardiovascular regulatory centre, has been implicated in angiotensin (ANG) II-induced hypertension in males; however, the contribution of ER stress to ANG II-induced hypertension in females is unknown. Female hormones have been shown to prevent ER stress in the periphery. We tested the hypothesis that females are less susceptible to ANG II-induced SFO ER stress than males, leading to sex differences in hypertension. Male, intact and ovariectomized (OVX) female rats received a continuous 2-week subcutaneous infusion of ANG II or saline. Additional male, intact and OVX female rats received intracerebroventricular (ICV) injection of ER stress inducer tunicamycin. ANG II, but not saline, increased blood pressure (BP) in both males and females, but intact females exhibited smaller increase in BP and less depressor response to ganglionic blockade compared with males or OVX females. Molecular studies revealed that ANG II elevated expression of ER stress biomarkers and Fra-like activity in the SFO in both males and females; however, elevations in these parameters were less in intact females than in males or OVX females. Moreover, ICV tunicamycin induced smaller elevation in BP and less increase in expression of ER stress biomarkers in the SFO in intact females compared with males or OVX females. The results suggest that differences in ANG II-induced brain ER stress between males and females contribute to sex differences in ANG II-mediated hypertension and that oestrogen protects females against ANG II-induced brain ER stress. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Duration and numerical estimation in right brain-damaged patients with and without neglect: Lack of support for a mental time line.

PubMed

Masson, Nicolas; Pesenti, Mauro; Dormal, Valérie

2016-08-01

Previous studies have shown that left neglect patients are impaired when they have to orient their attention leftward relative to a standard in numerical comparison tasks. This finding has been accounted for by the idea that numerical magnitudes are represented along a spatial continuum oriented from left to right with small magnitudes on the left and large magnitudes on the right. Similarly, it has been proposed that duration could be represented along a mental time line that shares the properties of the number continuum. By comparing directly duration and numerosity processing, this study investigates whether or not the performance of neglect patients supports the hypothesis of a mental time line. Twenty-two right brain-damaged patients (11 with and 11 without left neglect), as well as 11 age-matched healthy controls, had to judge whether a single dot presented visually lasted shorter or longer than 500 ms and whether a sequence of flashed dots was smaller or larger than 5. Digit spans were also assessed to measure verbal working memory capacities. In duration comparison, no spatial-duration bias was found in neglect patients. Moreover, a significant correlation between verbal working memory and duration performance was observed in right brain-damaged patients, irrespective of the presence or absence of neglect. In numerical comparison, only neglect patients showed an enhanced distance effect for numerical magnitude smaller than the standard. These results do not support the hypothesis of the existence of a mental continuum oriented from left to right for duration. We discuss an alternative account to explain the duration impairment observed in right brain-damaged patients. © 2015 The British Psychological Society.

Entorhinal Cortex Volume Is Associated With Dual-Task Gait Cost Among Older Adults With MCI: Results From the Gait and Brain Study.

PubMed

Sakurai, Ryota; Bartha, Robert; Montero-Odasso, Manuel

2018-05-15

Low dual-task gait performance (the slowing of gait speed while performing a demanding cognitive task) is associated with low cognitive performance and an increased risk of progression to dementia in older adults with mild cognitive impairment. However, the reason for this remains unclear. This study aimed to examine the relationship between dual-task cost and regional brain volume, focusing on the hippocampus, parahippocampal gyrus, entorhinal cortex, and motor and lateral frontal cortices in older adults with mild cognitive impairment. Forty older adults with mild cognitive impairment from the "Gait and Brain Study" were included in this study. Gait velocity was measured during single-task (ie, walking alone) and dual-task (ie, counting backwards, subtracting serial sevens, and naming animals, in addition to walking) conditions, using an electronic walkway. Regional brain volumes were derived by automated segmentation, using 3T magnetic resonance imaging. Partial rank correlation analyses demonstrated that a smaller volume of the left entorhinal cortex was associated with higher dual-task costs in counting backwards and subtracting serial sevens conditions. Subsequent logistic regression analyses demonstrated that a smaller volume of the left entorhinal cortex was independently associated with higher dual-task cost (slowing down >20% when performing cognitive task) in these two conditions. There were no other significant associations. Our results show that lower dual-task gait performance is associated with volume reduction in the entorhinal cortex. Cognitive and motor dysfunction in older adults with mild cognitive impairment may reflect a shared pathogenic mechanism, and dual-task-related gait changes might be a surrogate motor marker for Alzheimer's disease pathology.

Ganoderma lucidum total triterpenes prevent γ-radiation induced oxidative stress in Swiss albino mice in vivo.

PubMed

Smina, T P; Joseph, Jini; Janardhanan, K K

2016-11-01

The in vivo radio-protective effect of total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst was evaluated using Swiss albino mice, by pre-treatment with total triterpenes for 14 days, followed by a whole body exposure to γ-radiation. The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) were analysed in liver and brain homogenates. The extent of lipid and protein peroxidation was also estimated in liver and brain homogenates after irradiation. Protection of radiation-induced DNA strand breaks in peripheral blood lymphocytes and bone marrow cells was assessed using the comet assay. Total triterpenes were highly effective in reducing the levels of lipid peroxidation and protein oxidation to near normal values in both liver and brain tissues. Total triterpenes, when administered in vivo, were also found to be successful in restoring the antioxidant enzyme activities and GSH level in liver and brain of irradiated mice. Administration of total triterpenes, prior to radiation exposure, significantly decreased the DNA strand breaks. The results of the present study thus revealed the potential therapeutic use of Ganoderma total triterpenes as an adjuvant in radiation therapy.

Physiological Fluctuations in Brain Temperature as a Factor Affecting Electrochemical Evaluations of Extracellular Glutamate and Glucose in Behavioral Experiments

PubMed Central

2013-01-01

The rate of any chemical reaction or process occurring in the brain depends on temperature. While it is commonly believed that brain temperature is a stable, tightly regulated homeostatic parameter, it fluctuates within 1–4 °C following exposure to salient arousing stimuli and neuroactive drugs, and during different behaviors. These temperature fluctuations should affect neural activity and neural functions, but the extent of this influence on neurochemical measurements in brain tissue of freely moving animals remains unclear. In this Review, we present the results of amperometric evaluations of extracellular glutamate and glucose in awake, behaving rats and discuss how naturally occurring fluctuations in brain temperature affect these measurements. While this temperature contribution appears to be insignificant for glucose because its extracellular concentrations are large, it is a serious factor for electrochemical evaluations of glutamate, which is present in brain tissue at much lower levels, showing smaller phasic fluctuations. We further discuss experimental strategies for controlling the nonspecific chemical and physical contributions to electrochemical currents detected by enzyme-based biosensors to provide greater selectivity and reliability of neurochemical measurements in behaving animals. PMID:23448428

Predisposition to and effects of methamphetamine use on the adolescent brain

PubMed Central

Lyoo, IK; Yoon, S; Kim, TS; Lim, SM; Choi, Y; Kim, JE; Hwang, J; Jeong, HS; Cho, HB; Chung, YA; Renshaw, PF

2017-01-01

Adolescence is a period of heightened vulnerability both to addictive behaviors and drug-induced brain damage. Yet, only limited information exists on the brain mechanisms underlying these adolescent-specific characteristics. Moreover, distinctions in brain correlates between predisposition to drug use and effects of drugs in adolescents are unclear. Using cortical thickness and diffusion tensor image analyses, we found greater and more widespread gray and white matter alterations, particularly affecting the frontostriatal system, in adolescent methamphetamine (MA) users compared with adult users. Among adolescent-specific gray matter alterations related to MA use, smaller cortical thickness in the orbitofrontal cortex was associated with family history of drug use. Our findings highlight that the adolescent brain, which undergoes active myelination and maturation, is more vulnerable to MA-related alterations than the adult brain. Furthermore, MA-use-related executive dysfunction was greater in adolescent MA users than in adult users. These findings may provide explanation for the severe behavioral complications and relapses that are common in adolescent-onset drug addiction. Additionally, these results may provide insights into distinguishing the neural mechanisms that underlie the predisposition to drug addiction from effects of drugs in adolescents. PMID:25666756

Predisposition to and effects of methamphetamine use on the adolescent brain.

PubMed

Lyoo, I K; Yoon, S; Kim, T S; Lim, S M; Choi, Y; Kim, J E; Hwang, J; Jeong, H S; Cho, H B; Chung, Y A; Renshaw, P F

2015-12-01

Adolescence is a period of heightened vulnerability both to addictive behaviors and drug-induced brain damage. Yet, only limited information exists on the brain mechanisms underlying these adolescent-specific characteristics. Moreover, distinctions in brain correlates between predisposition to drug use and effects of drugs in adolescents are unclear. Using cortical thickness and diffusion tensor image analyses, we found greater and more widespread gray and white matter alterations, particularly affecting the frontostriatal system, in adolescent methamphetamine (MA) users compared with adult users. Among adolescent-specific gray matter alterations related to MA use, smaller cortical thickness in the orbitofrontal cortex was associated with family history of drug use. Our findings highlight that the adolescent brain, which undergoes active myelination and maturation, is more vulnerable to MA-related alterations than the adult brain. Furthermore, MA-use-related executive dysfunction was greater in adolescent MA users than in adult users. These findings may provide explanation for the severe behavioral complications and relapses that are common in adolescent-onset drug addiction. Additionally, these results may provide insights into distinguishing the neural mechanisms that underlie the predisposition to drug addiction from effects of drugs in adolescents.

Task vs. rest-different network configurations between the coactivation and the resting-state brain networks.

PubMed

Di, Xin; Gohel, Suril; Kim, Eun H; Biswal, Bharat B

2013-01-01

There is a growing interest in studies of human brain networks using resting-state functional magnetic resonance imaging (fMRI). However, it is unclear whether and how brain networks measured during the resting-state exhibit comparable properties to brain networks during task performance. In the present study, we investigated meta-analytic coactivation patterns among brain regions based upon published neuroimaging studies, and compared the coactivation network configurations with those in the resting-state network. The strength of resting-state functional connectivity between two regions were strongly correlated with the coactivation strength. However, the coactivation network showed greater global efficiency, smaller mean clustering coefficient, and lower modularity compared with the resting-state network, which suggest a more efficient global information transmission and between system integrations during task performing. Hub shifts were also observed within the thalamus and the left inferior temporal cortex. The thalamus and the left inferior temporal cortex exhibited higher and lower degrees, respectively in the coactivation network compared with the resting-state network. These results shed light regarding the reconfiguration of the brain networks between task and resting-state conditions, and highlight the role of the thalamus in change of network configurations in task vs. rest.

Task vs. rest—different network configurations between the coactivation and the resting-state brain networks

PubMed Central

Di, Xin; Gohel, Suril; Kim, Eun H.; Biswal, Bharat B.

2013-01-01

There is a growing interest in studies of human brain networks using resting-state functional magnetic resonance imaging (fMRI). However, it is unclear whether and how brain networks measured during the resting-state exhibit comparable properties to brain networks during task performance. In the present study, we investigated meta-analytic coactivation patterns among brain regions based upon published neuroimaging studies, and compared the coactivation network configurations with those in the resting-state network. The strength of resting-state functional connectivity between two regions were strongly correlated with the coactivation strength. However, the coactivation network showed greater global efficiency, smaller mean clustering coefficient, and lower modularity compared with the resting-state network, which suggest a more efficient global information transmission and between system integrations during task performing. Hub shifts were also observed within the thalamus and the left inferior temporal cortex. The thalamus and the left inferior temporal cortex exhibited higher and lower degrees, respectively in the coactivation network compared with the resting-state network. These results shed light regarding the reconfiguration of the brain networks between task and resting-state conditions, and highlight the role of the thalamus in change of network configurations in task vs. rest. PMID:24062654

Evidence for a Heritable Brain Basis to Deviance-Promoting Deficits in Self-Control.

PubMed

Yancey, James R; Venables, Noah C; Hicks, Brian M; Patrick, Christopher J

2013-01-01

Classic criminological theories emphasize the role of impaired self-control in behavioral deviancy. Reduced amplitude of the P300 brain response is reliably observed in individuals with antisocial and substance-related problems, suggesting it may serve as a neurophysiological indicator of deficiencies in self-control that confer liability to deviancy. The current study evaluated the role of self-control capacity - operationalized by scores on a scale measure of trait disinhibition - in mediating the relationship between P300 brain response and behavioral deviancy in a sample of adult twins ( N =419) assessed for symptoms of antisocial/addictive disorders and P300 brain response. As predicted, greater disorder symptoms and higher trait disinhibition scores each predicted smaller P300 amplitude, and trait disinhibition mediated observed relations between antisocial/addictive disorders and P300 response. Further, twin modeling analyses revealed that trait disinhibition scores and disorder symptoms reflected a common genetic liability, and this genetic liability largely accounted for the observed phenotypic relationship between antisocial-addictive problems and P300 brain response. These results provide further evidence that heritable weaknesses in self-control capacity confer liability to antisocial/addictive outcomes and that P300 brain response indexes this dispositional liability.

Value of brain scanning in the management of strokes

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

Antunes, J.L.; Schlesinger, E.B.; Michelsen, W.J.

1975-01-01

The usefulness of brain scanning in the diagnosis and management of strokes was evaluated in 313 serial cases. Of 38 patients with transient ischemic attacks (TIAs), only one had a positive test. The optimal time for scanning completed strokes was between seven and 14 days after onset. The pattern of uptake was characteristic of a vascular lesion in 76.8 percent. When uptake was indistinguishable from tumor, follow-up scans were useful. Patients with negative scans in the second week have a significantly better prognosis than the ones with a positive study. Cerebral angiography and brain scan correlated well in 56 patientsmore » who had both tests performed. The postmortem findings in 12 cases again emphasize the importance of the correct timing of the study, and the fact that a brain scan does not usually demonstrate lesions smaller than 2 cm in diameter. It is concluded that the brain scan represents a useful tool in the diagnosis of strokes and helps in predicting the degree of recovery following a vascular insult.« less

The influence of negative life events on hippocampal and amygdala volumes in old age: a life-course perspective.

PubMed

Gerritsen, L; Kalpouzos, G; Westman, E; Simmons, A; Wahlund, L O; Bäckman, L; Fratiglioni, L; Wang, H X

2015-04-01

Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older adults. In 466 non-demented old adults (age range 60-96 years, 58% female), hippocampal and amygdala volumes were segmented using Freesurfer. Negative life events and the age at which these events occurred were assessed by means of a structured questionnaire. Using generalized linear models, hippocampal and amygdala volumes were estimated with life events as independent variables. The statistical analyses were adjusted for age, gender, intracranial volume, lifestyle factors, cardiovascular risk factors, depressive symptoms, and cognitive functioning. Total number of negative life events and of late-life events, but not of early-life, early-adulthood, or middle-adulthood events, was related to larger amygdala volume. There were interactions of early-life events with age and gender. Participants who reported two or more early-life events had significantly smaller amygdala and hippocampal volumes with increasing age. Furthermore, smaller hippocampal volume was found in men who reported two or more early-life events, but not in women. These results suggest that the effect of negative life events on the brain depends on the time when the events occurred, with the strongest effects observed during the critical time periods of early and late life.

Corpus Callosum Size is Linked to Dichotic Deafness and Hemisphericity, Not Sex or Handedness

ERIC Educational Resources Information Center

Morton, Bruce E.; Rafto, Stein E.

2006-01-01

Individuals differ in the number of corpus callosum (CC) nerve fibers interconnecting their cerebral hemispheres by about threefold. Early reports suggested that males had smaller CCs than females. This was often interpreted to support the concept that the male brain is more "lateralized" or "specialized," thus accounting for presumed male…

Internalization of targeted quantum dots by brain capillary endothelial cells in vivo.

PubMed

Paris-Robidas, Sarah; Brouard, Danny; Emond, Vincent; Parent, Martin; Calon, Frédéric

2016-04-01

Receptors located on brain capillary endothelial cells forming the blood-brain barrier are the target of most brain drug delivery approaches. Yet, direct subcellular evidence of vectorized transport of nanoformulations into the brain is lacking. To resolve this question, quantum dots were conjugated to monoclonal antibodies (Ri7) targeting the murine transferrin receptor. Specific transferrin receptor-mediated endocytosis of Ri7-quantum dots was first confirmed in N2A and bEnd5 cells. After intravenous injection in mice, Ri7-quantum dots exhibited a fourfold higher volume of distribution in brain tissues, compared to controls. Immunofluorescence analysis showed that Ri7-quantum dots were sequestered throughout the cerebral vasculature 30 min, 1 h, and 4 h post injection, with a decline of signal intensity after 24 h. Transmission electron microscopic studies confirmed that Ri7-quantum dots were massively internalized by brain capillary endothelial cells, averaging 37 ± 4 Ri7-quantum dots/cell 1 h after injection. Most quantum dots within brain capillary endothelial cells were observed in small vesicles (58%), with a smaller proportion detected in tubular structures or in multivesicular bodies. Parenchymal penetration of Ri7-quantum dots was extremely low and comparable to control IgG. Our results show that systemically administered Ri7-quantum dots complexes undergo extensive endocytosis by brain capillary endothelial cells and open the door for novel therapeutic approaches based on brain endothelial cell drug delivery. © The Author(s) 2015.

Brain volume reductions in adolescent heavy drinkers.

PubMed

Squeglia, Lindsay M; Rinker, Daniel A; Bartsch, Hauke; Castro, Norma; Chung, Yoonho; Dale, Anders M; Jernigan, Terry L; Tapert, Susan F

2014-07-01

Brain abnormalities in adolescent heavy drinkers may result from alcohol exposure, or stem from pre-existing neural features. This longitudinal morphometric study investigated 40 healthy adolescents, ages 12-17 at study entry, half of whom (n=20) initiated heavy drinking over the 3-year follow-up. Both assessments included high-resolution magnetic resonance imaging. FreeSurfer was used to segment brain volumes, which were measured longitudinally using the newly developed quantitative anatomic regional change analysis (QUARC) tool. At baseline, participants who later transitioned into heavy drinking showed smaller left cingulate, pars triangularis, and rostral anterior cingulate volume, and less right cerebellar white matter volumes (p<.05), compared to continuous non-using teens. Over time, participants who initiated heavy drinking showed significantly greater volume reduction in the left ventral diencephalon, left inferior and middle temporal gyrus, and left caudate and brain stem, compared to substance-naïve youth (p<.05). Findings suggest pre-existing volume differences in frontal brain regions in future drinkers and greater brain volume reduction in subcortical and temporal regions after alcohol use was initiated. This is consistent with literature showing pre-existing cognitive deficits on tasks recruited by frontal regions, as well as post-drinking consequences on brain regions involved in language and spatial tasks. Published by Elsevier Ltd.

[Disturbances of cerebral perfusion in patients with bacterial meningoencephalitis].

PubMed

Garlicki, Aleksander; Podsiadło-Kleinrok, Beata; Bociaga-Jasik, Monika; Kleinrok, Krzysztof; Tomik, Barbara

2003-01-01

The investigations were done in acute and reconvalescent phase in 34 patients with bacterial meningoencephalitis. Neurologic condition, degree of the brain injury on the basis of Glasgow Coma Scale (GCS), protein level and pleocytosis in cerebrospinal fluid (CSF), and regional cerebral blood flow on dynamic computed tomography (CT) were assessed. The brain blood flow was measured in the white matter of the frontal and occipital horns of lateral ventricles, symmetrically in both hemispheres. Statistically significant reduction of the brain perfusion in acute phase of illness was improved. In reconvalescent phase normalisation of the brain blood supply was observed. 56% of patients had changes of consciousness. There was no significant correlation between these symptoms and parameters describing blood supply. The rest of patients had neurologic abnormalities: seizure, pyramidal syndrome, injury of the central nerves due to the reduction of blood flow in selected regions of the brain. Patients who aggregated low GCS score had high inflow of the blood. In patients who were in better condition, inflow was smaller. High pleocytosis in CSF was associated with small blood inflow and perfusion in investigated regions of the brain. Whereas high protein concentration correlated with higher inflow and increase in regional perfusion. We consider, that the brain blood supply correlate with intensification of inflammatory response in CSF.

Revisiting atenolol as a low passive permeability marker.

PubMed

Chen, Xiaomei; Slättengren, Tim; de Lange, Elizabeth C M; Smith, David E; Hammarlund-Udenaes, Margareta

2017-10-31

Atenolol, a hydrophilic beta blocker, has been used as a model drug for studying passive permeability of biological membranes such as the blood-brain barrier (BBB) and the intestinal epithelium. However, the extent of S-atenolol (the active enantiomer) distribution in brain has never been evaluated, at equilibrium, to confirm that no transporters are involved in its transport at the BBB. To assess whether S-atenolol, in fact, depicts the characteristics of a low passive permeable drug at the BBB, a microdialysis study was performed in rats to monitor the unbound concentrations of S-atenolol in brain extracellular fluid (ECF) and plasma during and after intravenous infusion. A pharmacokinetic model was developed, based on the microdialysis data, to estimate the permeability clearance of S-atenolol into and out of brain. In addition, the nonspecific binding of S-atenolol in brain homogenate was evaluated using equilibrium dialysis. The steady-state ratio of unbound S-atenolol concentrations in brain ECF to that in plasma (i.e., K p,uu,brain ) was 3.5% ± 0.4%, a value much less than unity. The unbound volume of distribution in brain (V u, brain ) of S-atenolol was also calculated as 0.69 ± 0.10 mL/g brain, indicating that S-atenolol is evenly distributed within brain parenchyma. Lastly, equilibrium dialysis showed limited nonspecific binding of S-atenolol in brain homogenate with an unbound fraction (f u,brain ) of 0.88 ± 0.07. It is concluded, based on K p,uu,brain being much smaller than unity, that S-atenolol is actively effluxed at the BBB, indicating the need to re-consider S-atenolol as a model drug for passive permeability studies of BBB transport or intestinal absorption.

Effects of severity of traumatic brain injury and brain reserve on cognitive-control related brain activation.

PubMed

Scheibel, Randall S; Newsome, Mary R; Troyanskaya, Maya; Steinberg, Joel L; Goldstein, Felicia C; Mao, Hui; Levin, Harvey S

2009-09-01

Functional magnetic resonance imaging (fMRI) has revealed more extensive cognitive-control related brain activation following traumatic brain injury (TBI), but little is known about how activation varies with TBI severity. Thirty patients with moderate to severe TBI and 10 with orthopedic injury (OI) underwent fMRI at 3 months post-injury using a stimulus response compatibility task. Regression analyses indicated that lower total Glasgow Coma Scale (GCS) and GCS verbal component scores were associated with higher levels of brain activation. Brain-injured patients were also divided into three groups based upon their total GCS score (3-4, 5-8, or 9-15), and patients with a total GCS score of 8 or less produced increased, diffuse activation that included structures thought to mediate visual attention and cognitive control. The cingulate gyrus and thalamus were among the areas showing greatest increases, and this is consistent with vulnerability of these midline structures in severe, diffuse TBI. Better task performance was associated with higher activation, and there were differences in the over-activation pattern that varied with TBI severity, including greater reliance upon left-lateralized brain structures in patients with the most severe injuries. These findings suggest that over-activation is at least partially effective for improving performance and may be compensatory.

Bivariate Heritability of Total and Regional Brain Volumes: the Framingham Study

PubMed Central

DeStefano, Anita L.; Seshadri, Sudha; Beiser, Alexa; Atwood, Larry D.; Massaro, Joe M.; Au, Rhoda; Wolf, Philip A.; DeCarli, Charles

2009-01-01

Heritability and genetic and environmental correlations of total and regional brain volumes were estimated from a large, generally healthy, community-based sample, to determine if there are common elements to the genetic influence of brain volumes and white matter hyperintensity volume. There were 1538 Framingham Heart Study participants with brain volume measures from quantitative magnetic resonance imaging (MRI) who were free of stroke and other neurological disorders that might influence brain volumes and who were members of families with at least two Framingham Heart Study participants. Heritability was estimated using variance component methodology and adjusting for the components of the Framingham stroke risk profile. Genetic and environmental correlations between traits were obtained from bivariate analysis. Heritability estimates ranging from 0.46 to 0.60, were observed for total brain, white matter hyperintensity, hippocampal, temporal lobe, and lateral ventricular volumes. Moderate, yet significant, heritability was observed for the other measures. Bivariate analyses demonstrated that relationships between brain volume measures, except for white matter hyperintensity, reflected both moderate to strong shared genetic and shared environmental influences. This study confirms strong genetic effects on brain and white matter hyperintensity volumes. These data extend current knowledge by showing that these two different types of MRI measures do not share underlying genetic or environmental influences. PMID:19812462

Anomalous Putamen Volume in Children With Complex Motor Stereotypies.

PubMed

Mahone, E Mark; Crocetti, Deana; Tochen, Laura; Kline, Tina; Mostofsky, Stewart H; Singer, Harvey S

2016-12-01

Complex motor stereotypies in children are repetitive rhythmic movements that have a predictable pattern and location, seem purposeful, but serve no obvious function, tend to be prolonged, and stop with distraction, e.g., arm or hand flapping, waving. They occur in both "primary" (otherwise typically developing) and secondary conditions. These movements are best defined as habitual behaviors and therefore pathophysiologically hypothesized to reside in premotor to posterior putamen circuits. This study sought to clarify the underlying neurobiologic abnormality in children with primary complex motor stereotypies using structural neuroimaging, emphasizing brain regions hypothesized to underlie these atypical behaviors. High-resolution anatomic magnetic resonance images, acquired at 3.0 T, were analyzed in children aged eight to twelve years (20 with primary complex motor stereotypies and 20 typically developing). Frontal lobe subregions and striatal structures were delineated for analysis. Significant reductions (P = 0.045) in the stereotypies group were identified in total putamen volume but not in caudate, nucleus accumbens, or frontal subregions. There were no group differences in total cerebral volume. Findings of a smaller putamen provide preliminary evidence suggesting the potential involvement of the habitual pathway as the underlying anatomic site in primary complex motor stereotypies. Copyright © 2016 Elsevier Inc. All rights reserved.

Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage

PubMed Central

Wang, Jian; Doré, Sylvain

2008-01-01

Because heme oxygenase (HO) is the rate limiting enzyme in the degradation of the pro-oxidant hemin/heme from blood, here we investigated the contribution of the inducible HO-1 to early brain injury produced by intracerebral haemorrhage (ICH). We found that after induction of ICH, HO-1 proteins were highly detectable in the peri-ICH region predominantly in microglia/macrophages and endothelial cells. Remarkably, the injury volume was significantly smaller in HO-1 knockout (HO-1−/−) mice than in wild-type controls 24 and 72 h after ICH. Although the brain water content did not appear to be significantly different, the protection in HO-1−/− mice was associated with a marked reduction in ICH-induced leucocyte infiltration, microglia/macrophage activation and free radical levels. These data reveal a previously unrecognized role of HO-1 in early brain injury after ICH. Thus, modulation of HO-1 signalling should be assessed further in clinical settings, especially for haemorrhagic states. PMID:17525142

Problem-solving by traumatically brain injured and neurologically intact subjects on an adaptation of the twenty questions test.

PubMed

Marshall, Robert C; Karow, Colleen M; Morelli, Claudia A; Iden, Kristin K; Dixon, Judith

2003-07-01

RAPS (Rapid Assessment of Problem-Solving) is a clinical measure for assessing verbal problem-solving in hard-to-test patients or those that may not be able to tolerate a longer, more detailed assessment. The design of the test is based on Mosher and Hornsby's Twenty Question test, but RAPS contains several modifications to facilitate its use with brain-injured individuals. This study used RAPS to compare the verbal problem-solving ability of subjects that were neurologically intact and subjects that had chronic traumatic brain injuries. Twenty-one adults that were neurologically intact (NI) and 21 adults that had incurred a traumatic brain injury (TBI) matched for age, gender and education took part in the study. Before being tested with RAPS, participants signed an IRB-approved consent form and completed a battery of neurocognitive measures. RAPS entailed the solving of three verbal problems. Each problem involved an array of 32 pictures of common objects (e.g. football) arranged in a 4x 8 grid. The subjects were instructed to ask yes/no questions to determine which picture the examiner was 'thinking of '. Three scores were computed for each problem solved: number of questions asked, percentage of constraint-seeking questions, and question-asking efficiency scores for the first four questions. No learning effects across the problems were found for any of the RAPS measures. Scores were averaged across the three problems to determine group effects. Groups of TBI and NI subjects did not differ significantly in the number of questions asked in solving RAPS problems. Members of the NI group asked significantly more constraint-seeking questions (e.g. Is it an animal?) than those in the TBI group, and the subjects that had incurred brain injuries did more guessing than the NI group. Over 70% of the time, guessing took place after the semantic category containing the target picture was known to the subject. Guesses took the form of pseudo-constraint questions (e.g. Is it the animal with a long neck?) rather than frank guesses (e.g. Is it the giraffe?). These trends were seen for both groups. Question-asking efficiency scores, computed for the first four questions of each problem, reflected the amount of information gained by the subjects' questions. It was anticipated that subjects' questioning strategies would target larger rather than smaller number of pictures and systematically reduce the number of total pictures under consideration. Question-asking efficiency scores were significantly higher for the group of NI subjects. Both groups increased question-asking efficiency scores across the first four questions, and there was no significant group x question interaction. Further analysis of the question-asking efficiency scores revealed that questions from the group of NI subjects tended to target multiple categories of pictures and larger single semantic categories of pictures on the 32-item problem-solving board, whereas those from the group of TBI subjects often targeted smaller categories or portions of categories. Two meta-cognitive functions, planning and strategy shifting, appeared to explain most of the differences in the verbal problem-solving performance between the groups. Both groups, however, demonstrated a range of abilities on RAPS. Until a larger normative database for RAPS is available, it behooves clinicians using the test to analyse results on an individual basis, to consider the subject's pre-morbid problem-solving ability and to weigh those factors associated with brain injury that could affect RAPS performance.

Application and validation of the barrow neurological institute screen for higher cerebral functions in a control population and in patient groups commonly seen in neurorehabilitation.

PubMed

Hofgren, Caisa; Esbjörnsson, Eva; Aniansson, Hans; Sunnerhagen, Katharina Stibrant

2007-09-01

To determine whether the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) can differentiate brain-dysfunctional patients from controls. A case-control study. A total of 92 controls and 120 patients from a neuro-rehabilitation clinic with a diagnosis of: right and left hemisphere stroke, traumatic brain injury, Parkinson's disease or anoxic brain damage. The BNIS has a maximum total score of 50 points, < 47 indicates cognitive dysfunction. Group comparisons and exploration of variables influencing the BNIS total score were made. A significant difference was found between the control group and the total patient group for the BNIS total score and for the subscales (p < 0.0005). Sensitivity was 88% and specificity 78%. Presence of disease and educational level had the greatest influence on the results of the BNIS. Patients with Parkinson's disease were shown to be the least cognitively affected and those with anoxic brain damage the most affected. The BNIS has potential value as a screening instrument for cognitive functions and is sufficiently sensitive to differentiate brain-dysfunctional patients from a control population. It appears to be applicable in a neurological rehabilitation setting, and can be used early in the process, giving a baseline cognitive functional level.

On the relationship between head circumference, brain size, prenatal long-chain PUFA/5-methyltetrahydrofolate supplementation and cognitive abilities during childhood.

PubMed

Catena, Andrés; Martínez-Zaldívar, Cristina; Diaz-Piedra, Carolina; Torres-Espínola, Francisco J; Brandi, Pilar; Pérez-García, Miguel; Decsi, Tamás; Koletzko, Berthold; Campoy, Cristina

2017-03-29

Head circumference in infants has been reported to predict brain size, total grey matter volume (GMV) and neurocognitive development. However, it is unknown whether it has predictive value on regional and subcortical brain volumes. We aimed to explore the relationship between several head circumference measurements since birth and distributions of GMV and subcortical volumes at later childhood. We examined seventy-four, Caucasian, singleton, term-born infants born to mothers randomised to receive fish oil and/or 5-methyltetrahydrofolate or placebo prenatal supplementation. We assessed head circumference at birth and at 4 and 10 years of age and cognitive abilities at 7 years of age. We obtained brain MRI at 10 years of age, on which we performed voxel-based morphometry, cortical surface extraction and subcortical segmentation. Analyses were controlled for sex, age, height, weight, family status, laterality and total intracranial volume. Prenatal supplementation did not affect head circumference at any age, cognitive abilities or total brain volumes. Head circumference at 4 years presented the highest correlation with total GMV, white matter volume and brain surface area, and was also strongly associated with GMV of frontal, temporal and occipital areas, as well as with caudate nucleus, globus pallidus, putamen and thalamus volumes. As relationships between brain volumes in childhood and several outcomes extend into adulthood, we have found that ages between 0 and 4 years as the optimal time for brain growth; postnatal factors might have the most relevant impact on structural maturation of certain cortical areas and subcortical nuclei, independent of prenatal supplementation.

Repeated head trauma is associated with smaller thalamic volumes and slower processing speed: the Professional Fighters’ Brain Health Study

PubMed Central

Bernick, Charles; Banks, Sarah J; Shin, Wanyong; Obuchowski, Nancy; Butler, Sam; Noback, Michael; Phillips, Michael; Lowe, Mark; Jones, Stephen; Modic, Michael

2015-01-01

Objectives Cumulative head trauma may alter brain structure and function. We explored the relationship between exposure variables, cognition and MRI brain structural measures in a cohort of professional combatants. Methods 224 fighters (131 mixed martial arts fighters and 93 boxers) participating in the Professional Fighters Brain Health Study, a longitudinal cohort study of licensed professional combatants, were recruited, as were 22 controls. Each participant underwent computerised cognitive testing and volumetric brain MRI. Fighting history including years of fighting and fights per year was obtained from self-report and published records. Statistical analyses of the baseline evaluations were applied cross-sectionally to determine the relationship between fight exposure variables and volumes of the hippocampus, amygdala, thalamus, caudate, putamen. Moreover, the relationship between exposure and brain volumes with cognitive function was assessed. Results Increasing exposure to repetitive head trauma measured by number of professional fights, years of fighting, or a Fight Exposure Score (FES) was associated with lower brain volumes, particularly the thalamus and caudate. In addition, speed of processing decreased with decreased thalamic volumes and with increasing fight exposure. Higher scores on a FES used to reflect exposure to repetitive head trauma were associated with greater likelihood of having cognitive impairment. Conclusions Greater exposure to repetitive head trauma is associated with lower brain volumes and lower processing speed in active professional fighters. PMID:25633832

BEaST: brain extraction based on nonlocal segmentation technique.

PubMed

Eskildsen, Simon F; Coupé, Pierrick; Fonov, Vladimir; Manjón, José V; Leung, Kelvin K; Guizard, Nicolas; Wassef, Shafik N; Østergaard, Lasse Riis; Collins, D Louis

2012-02-01

Brain extraction is an important step in the analysis of brain images. The variability in brain morphology and the difference in intensity characteristics due to imaging sequences make the development of a general purpose brain extraction algorithm challenging. To address this issue, we propose a new robust method (BEaST) dedicated to produce consistent and accurate brain extraction. This method is based on nonlocal segmentation embedded in a multi-resolution framework. A library of 80 priors is semi-automatically constructed from the NIH-sponsored MRI study of normal brain development, the International Consortium for Brain Mapping, and the Alzheimer's Disease Neuroimaging Initiative databases. In testing, a mean Dice similarity coefficient of 0.9834±0.0053 was obtained when performing leave-one-out cross validation selecting only 20 priors from the library. Validation using the online Segmentation Validation Engine resulted in a top ranking position with a mean Dice coefficient of 0.9781±0.0047. Robustness of BEaST is demonstrated on all baseline ADNI data, resulting in a very low failure rate. The segmentation accuracy of the method is better than two widely used publicly available methods and recent state-of-the-art hybrid approaches. BEaST provides results comparable to a recent label fusion approach, while being 40 times faster and requiring a much smaller library of priors. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of head circumference and metabolic syndrome on cognitive decline.

PubMed

Lee, Kang Soo; Eom, Jin-Sup; Cheong, Hae-Kwan; Oh, Byoung Hoon; Hong, Chang Hyung

2010-01-01

Brain volume progressively decreases with an increase in atrophy, and the brain becomes more susceptible to degenerative brain diseases such as Alzheimer's disease. Metabolic syndrome has also been associated with an increased risk of cognitive decline in the elderly. In this study, we aimed to examine the effects of head circumference and metabolic syndrome on cognitive decline. This study was part of a longitudinal study conducted on Koreans aged 60 years or older. We analyzed a final sample of 596 Korean participants with complete baseline and 2-year follow-up data. The cognitive function of the subjects was assessed using the Korean version of the Mini Mental State Examination (MMSE). Head circumference was measured from the glabella to the occipital protuberance using a measuring tape. Metabolic syndrome was defined according to the NCEP-ATP III standards. Central obesity was assessed on the basis of waist-circumference values, in accordance with the World Health Organization Western Pacific Region report on Asians. We used a longitudinal factorial design in which the MMSE score was the dependent variable, and head circumference and metabolic syndrome were considered as factors. After adjusting the results for age, gender, education, height, weight, baseline MMSE, and number of follow-up years, we observed that smaller head circumference and the presence of metabolic syndrome were independently associated with rapid cognitive decline. All these findings suggest that smaller head circumference and the presence of metabolic syndrome have additive effects on cognitive decline. Copyright 2009 S. Karger AG, Basel.

Physical activity and inflammation: effects on gray-matter volume and cognitive decline in aging.

PubMed

Papenberg, Goran; Ferencz, Beata; Mangialasche, Francesca; Mecocci, Patrizia; Cecchetti, Roberta; Kalpouzos, Grégoria; Fratiglioni, Laura; Bäckman, Lars

2016-10-01

Physical activity has been positively associated with gray-matter integrity. In contrast, pro-inflammatory cytokines seem to have negative effects on the aging brain and have been related to dementia. It was investigated whether an inactive lifestyle and high levels of inflammation resulted in smaller gray-matter volumes and predicted cognitive decline across 6 years in a population-based study of older adults (n = 414). Self-reported physical activity (fitness-enhancing, health-enhancing, inadequate) was linked to gray-matter volume, such that individuals with inadequate physical activity had the least gray matter. There were no overall associations between different pro-and anti-inflammatory markers (IL-1β, IL-6, IL-10, IL-12p40, IL-12p70, G-CSF, and TNF-α) and gray-matter integrity. However, persons with inadequate activity and high levels of the pro-inflammatory marker IL-12p40 had smaller volumes of lateral prefrontal cortex and hippocampus and declined more on the Mini-Mental State Examination test over 6 years compared with physically inactive individuals with low levels of IL-12p40 and to more physically active persons, irrespective of their levels of IL-12p40. These patterns of data suggested that inflammation was particularly detrimental in inactive older adults and may exacerbate the negative effects of physical inactivity on brain and cognition in old age. Hum Brain Mapp 37:3462-3473, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fabp1 gene ablation inhibits high-fat diet-induced increase in brain endocannabinoids.

PubMed

Martin, Gregory G; Landrock, Danilo; Chung, Sarah; Dangott, Lawrence J; Seeger, Drew R; Murphy, Eric J; Golovko, Mikhail Y; Kier, Ann B; Schroeder, Friedhelm

2017-01-01

The endocannabinoid system shifts energy balance toward storage and fat accumulation, especially in the context of diet-induced obesity. Relatively little is known about factors outside the central nervous system that may mediate the effect of high-fat diet (HFD) on brain endocannabinoid levels. One candidate is the liver fatty acid binding protein (FABP1), a cytosolic protein highly prevalent in liver, but not detected in brain, which facilitates hepatic clearance of fatty acids. The impact of Fabp1 gene ablation (LKO) on the effect of high-fat diet (HFD) on brain and plasma endocannabinoid levels was examined and data expressed for each parameter as the ratio of high-fat diet/control diet. In male wild-type mice, HFD markedly increased brain N-acylethanolamides, but not 2-monoacylglycerols. LKO blocked these effects of HFD in male mice. In female wild-type mice, HFD slightly decreased or did not alter these endocannabinoids as compared with male wild type. LKO did not block the HFD effects in female mice. The HFD-induced increase in brain arachidonic acid-derived arachidonoylethanolamide in males correlated with increased brain-free and total arachidonic acid. The ability of LKO to block the HFD-induced increase in brain arachidonoylethanolamide correlated with reduced ability of HFD to increase brain-free and total arachidonic acid in males. In females, brain-free and total arachidonic acid levels were much less affected by either HFD or LKO in the context of HFD. These data showed that LKO markedly diminished the impact of HFD on brain endocannabinoid levels, especially in male mice. © 2016 International Society for Neurochemistry.

How Acute Total Sleep Loss Affects the Attending Brain: A Meta-Analysis of Neuroimaging Studies

PubMed Central

Ma, Ning; Dinges, David F.; Basner, Mathias; Rao, Hengyi

2015-01-01

Study Objectives: Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Design: Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. Methods: The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. Results: The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Conclusion: Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. Citation: Ma N, Dinges DF, Basner M, Rao H. How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies. SLEEP 2015;38(2):233–240. PMID:25409102

Injured Brain Regions Associated with Anxiety in Vietnam Veterans

PubMed Central

Knutson, Kristine M.; Rakowsky, Shana T.; Solomon, Jeffrey; Krueger, Frank; Raymont, Vanessa; Tierney, Michael C.; Wassermann, Eric M.; Grafman, Jordan

2013-01-01

Anxiety negatively affects quality of life and psychosocial functioning. Previous research has shown that anxiety symptoms in healthy individuals are associated with variations in the volume of brain regions, such as the amygdala, hippocampus, and the bed nucleus of the stria terminalis. Brain lesion data also suggests the hemisphere damaged may affect levels of anxiety. We studied a sample of 182 male Vietnam War veterans with penetrating brain injuries, using a semi-automated voxel-based lesion-symptom mapping (VLSM) approach. VLSM reveals significant associations between a symptom such as anxiety and the location of brain lesions, and does not require a broad, subjective assignment of patients into categories based on lesion location. We found that lesioned brain regions in cortical and limbic areas of the left hemisphere, including middle, inferior and superior temporal lobe, hippocampus, and fusiform regions, along with smaller areas in the inferior occipital lobe, parahippocampus, amygdala, and insula, were associated with increased anxiety symptoms as measured by the Neurobehavioral Rating Scale (NRS). These results were corroborated by similar findings using Neuropsychiatric Inventory (NPI) anxiety scores, which supports these regions’ role in regulating anxiety. In summary, using a semi-automated analysis tool, we detected an effect of focal brain damage on the presentation of anxiety. We also separated the effects of brain injury and war experience by including a control group of combat veterans without brain injury. We compared this control group against veterans with brain lesions in areas associated with anxiety, and against veterans with lesions only in other brain areas. PMID:23328629

Pharmacokinetics of pericyte involvement in small-molecular drug transport across the blood-brain barrier.

PubMed

Mihajlica, Nebojsa; Betsholtz, Christer; Hammarlund-Udenaes, Margareta

2018-06-19

Pericytes are perivascular cells that play important roles in the regulation of the blood-brain barrier (BBB) properties. Pericyte-deficiency causes compromised BBB integrity and increase in permeability to different macromolecules mainly by upregulated transcytosis. The aim of the present study was to investigate pericyte involvement in the extent of small-molecular drug transport across the BBB. This was performed with five compounds: diazepam, digoxin, levofloxacin, oxycodone and paliperidone. Compounds were administered at low doses via subcutaneous injections as a cassette (simultaneously) to pericyte-deficient Pdgfb ret/ret mice and corresponding WT controls. Total drug partitioning across the BBB was calculated as the ratio of total drug exposures in brain tissue and plasma (K p,brain ). In addition, equilibrium dialysis experiments were performed to estimate unbound drug fractions in brain (f u,brain ) and plasma (f u,plasma ). This enabled estimation of unbound drug partitioning coefficients (K p,uu,brain ). The results indicated slight tendencies towards increase of total brain exposures in Pdgfb ret/ret mice as reflected in K p,brain values, which were within the 2-fold limit. Part of these differences could be explained by differences in plasma protein binding. No difference was found in brain tissue binding. The combined in vivo and in vitro data resulted in no differences in BBB transport in pericyte-deficiency, as described by similar K p,uu,brain values in Pdgfb ret/ret and control mice. In conclusion, these findings imply no influence of pericytes on the extent of BBB transport of small-molecular drugs, and suggest preserved BBB features relevant for handling of this type of molecules irrespective of pericyte presence at the brain endothelium. Copyright © 2018. Published by Elsevier B.V.

Anti-cancer Antibody Trastuzumab-Melanotransferrin Conjugate (BT2111) for the Treatment of Metastatic HER2+ Breast Cancer Tumors in the Brain: an In-Vivo Study.

PubMed

Nounou, Mohamed Ismail; Adkins, Chris E; Rubinchik, Evelina; Terrell-Hall, Tori B; Afroz, Mohamed; Vitalis, Tim; Gabathuler, Reinhard; Tian, Mei Mei; Lockman, Paul R

2016-12-01

The ability of human melanotransferrin (hMTf) to carry a therapeutic concentration of trastuzumab (BTA) in the brain after conjugation (in the form of trastuzumab-melanotransferrin conjugate, BT2111 conjugate) was investigated by measuring the reduction of the number and size of metastatic human HER 2+ breast cancer tumors in a preclinical model of brain metastases of breast cancer. Human metastatic brain seeking breast cancer cells were injected in NuNu mice (n = 6-12 per group) which then developed experimental brain metastases. Drug uptake was analyzed in relation to metastasis size and blood-tumor barrier permeability. To investigate in-vivo activity against brain metastases, equimolar doses of the conjugate, and relevant controls (hMTf and BTA) in separate groups were administered biweekly after intracardiac injection of the metastatic cancer cells. The trastuzumab-melanotransferrin conjugate (BT2111) reduced the number of preclinical human HER 2+ breast cancer metastases in the brain by 68% compared to control groups. Tumors which remained after treatment were 46% smaller than the control groups. In contrast, BTA alone had no effect on reducing number of metastases, and was associated with only a minimal reduction in metastasis size. The results suggest the novel trastuzumab-melanotransferrin conjugate (BT2111) may have utility in treating brain metastasis and validate hMTf as a potential vector for antibody transport across the Blood Brain Barrier (BBB).

Selective Activation of Resting-State Networks following Focal Stimulation in a Connectome-Based Network Model of the Human Brain

PubMed Central

2016-01-01

Abstract When the brain is stimulated, for example, by sensory inputs or goal-oriented tasks, the brain initially responds with activities in specific areas. The subsequent pattern formation of functional networks is constrained by the structural connectivity (SC) of the brain. The extent to which information is processed over short- or long-range SC is unclear. Whole-brain models based on long-range axonal connections, for example, can partly describe measured functional connectivity dynamics at rest. Here, we study the effect of SC on the network response to stimulation. We use a human whole-brain network model comprising long- and short-range connections. We systematically activate each cortical or thalamic area, and investigate the network response as a function of its short- and long-range SC. We show that when the brain is operating at the edge of criticality, stimulation causes a cascade of network recruitments, collapsing onto a smaller space that is partly constrained by SC. We found both short- and long-range SC essential to reproduce experimental results. In particular, the stimulation of specific areas results in the activation of one or more resting-state networks. We suggest that the stimulus-induced brain activity, which may indicate information and cognitive processing, follows specific routes imposed by structural networks explaining the emergence of functional networks. We provide a lookup table linking stimulation targets and functional network activations, which potentially can be useful in diagnostics and treatments with brain stimulation. PMID:27752540

Volumetric evaluation of the relations among the cerebrum, cerebellum and brain stem in young subjects: a combination of stereology and magnetic resonance imaging.

PubMed

Ekinci, Nihat; Acer, Niyazi; Akkaya, Akcan; Sankur, Seref; Kabadayi, Taner; Sahin, Bünyamin

2008-08-01

The Cavalieri estimator using a point grid is used to estimate the volume of three-dimensional structures based on two-dimensional slices of the object. The size of the components of intracranial neural structures should have proportional relations among them. The volume fraction approach of stereological methods provides information about volumetric relations of the components of structures. The purpose of our study is to estimate the volume and volume fraction data related to the cerebrum, cerebellum and brain stem. In this study, volume of the total brain, cerebrum, cerebellum and brain stem were estimated in 24 young Turkish volunteers (12 males and 12 females) who are free of any neurological symptoms and signs. The volume and volume fraction of the total brain, cerebrum, cerebellum and brain stem were determined on magnetic resonance (MR) images using the point-counting approach of stereological methods. The mean (+/-SD) total brain, cerebrum and cerebellum volumes were 1,202.05 +/- 103.51, 1,143.65 +/- 106.25 cm3 in males and females, 1,060.0 +/- 94.6, 1,008.9 +/- 104.3 cm3 in males and females, 117.75 +/- 10.7, 111.83 +/- 8.0 cm3 in males and females, respectively. The mean brain stem volumes were 24.3 +/- 2.89, 22.9 +/- 4.49 cm3 in males and females, respectively. Our results revealed that female subjects have less cerebral, cerebellar and brain stem volumes compared to males, although there was no statistically significant difference between genders (P > 0.05). The volume ratio of the cerebrum to total brain volume (TBV), cerebellum to TBV and brain stem to TBV were 88.16 and 88.13% in males and females, 9.8 and 9.8% in males and females, 2.03 and 2.03% in males and females, respectively. The volume ratio of the cerebellum to cerebrum, brain stem to cerebrum and brain stem to cerebellum were 11.12 and 11.16% in males and females, 2.30 and 2.31% in males and females, 20.7 and 20.6% in males and females, respectively. The difference between the genders was not statistically significant (P > 0.05). Our results revealed that the volumetric composition of the cerebrum, cerebellum and brain stem does not show sexual dimorphism.

Effect of fish oils containing different amounts of EPA, DHA, and antioxidants on plasma and brain fatty acids and brain nitric oxide synthase activity in rats

PubMed Central

Engström, Karin; Saldeen, Ann-Sofie; Yang, Baichun; Mehta, Jawahar L.

2009-01-01

Background The interest in n-3 polyunsaturated fatty acids (PUFAs) has expanded significantly in the last few years, due to their many positive effects described. Consequently, the interest in fish oil supplementation has also increased, and many different types of fish oil supplements can be found on the market. Also, it is well known that these types of fatty acids are very easily oxidized, and that stability among supplements varies greatly. Aims of the study In this pilot study we investigated the effects of two different types of natural fish oils containing different amounts of the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and antioxidants on plasma and brain fatty acids, blood lipids, vitamin E, and in vivo lipid peroxidation, as well as brain nitric oxide synthase (NOS) activity, an enzyme which has been shown to be important for memory and learning ability. Methods Sprague-Dawley rats were divided into four groups and fed regular rat chow pellets enriched with 5% (w/w) of butter (control group), a natural fish oil (17.4% EPA and 11.7% DHA, referred to as EPA-rich), and a natural fish oil rich in DHA (7.7% EPA and 28.0% DHA, referred to as DHA-rich). Both of the fish oils were stabilized by a commercial antioxidant protection system (Pufanox®) at production. The fourth group received the same DHA-rich oil, but without Pufanox® stabilization (referred to as unstable). As an index of stability of the oils, their peroxide values were repeatedly measured during 9 weeks. The dietary treatments continued until sacrifice, after 10 days. Results Stability of the oils varied greatly. It took the two stabilized oils 9 weeks to reach the same peroxide value as the unstable oil reached after only a few days. Both the stabilized EPA- and DHA-rich diets lowered the triacylglycerols and total cholesterol compared to control (-45%, P < 0.05 and -54%, P < 0.001; -31%, P < 0.05 and -25%, P < 0.01) and so did the unstable oil, but less efficiently. Only the unstable oil increased in vivo lipid peroxidation significantly compared to control (+40%, P < 0.001). Most of the fatty acids in the plasma phospholipids were significantly affected by both the EPA- and DHA-rich diets compared to control, reflecting their specific fatty acid pattern. The unstable oil diet resulted in smaller changes, especially in n-3 PUFAs. In the brain phospholipids the changes were less pronounced, and only the diet enriched with the stabilized DHA-rich oil resulted in a significantly greater incorporation of DHA (+13%, P < 0.01), as well as total n-3 PUFAs (+13%, P < 0.01) compared to control. Only the stabilized DHA-rich oil increased the brain NOS activity (+33%, P < 0.01). Conclusions Both the EPA- and DHA-rich diets affected the blood lipids in a similarly positive manner, and they both had a large impact on plasma phospholipid fatty acids. It was only the unstable oil that increased in vivo lipid peroxidation. However, the intake of DHA was more important than that of EPA for brain phospholipid DHA enrichment and brain NOS activity, and the stability of the fish oil was also important for these effects. PMID:19961266

Effect of fish oils containing different amounts of EPA, DHA, and antioxidants on plasma and brain fatty acids and brain nitric oxide synthase activity in rats.

PubMed

Engström, Karin; Saldeen, Ann-Sofie; Yang, Baichun; Mehta, Jawahar L; Saldeen, Tom

2009-01-01

The interest in n-3 polyunsaturated fatty acids (PUFAs) has expanded significantly in the last few years, due to their many positive effects described. Consequently, the interest in fish oil supplementation has also increased, and many different types of fish oil supplements can be found on the market. Also, it is well known that these types of fatty acids are very easily oxidized, and that stability among supplements varies greatly. In this pilot study we investigated the effects of two different types of natural fish oils containing different amounts of the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and antioxidants on plasma and brain fatty acids, blood lipids, vitamin E, and in vivo lipid peroxidation, as well as brain nitric oxide synthase (NOS) activity, an enzyme which has been shown to be important for memory and learning ability. Sprague-Dawley rats were divided into four groups and fed regular rat chow pellets enriched with 5% (w/w) of butter (control group), a natural fish oil (17.4% EPA and 11.7% DHA, referred to as EPA-rich), and a natural fish oil rich in DHA (7.7% EPA and 28.0% DHA, referred to as DHA-rich). Both of the fish oils were stabilized by a commercial antioxidant protection system (Pufanox) at production. The fourth group received the same DHA-rich oil, but without Pufanox stabilization (referred to as unstable). As an index of stability of the oils, their peroxide values were repeatedly measured during 9 weeks. The dietary treatments continued until sacrifice, after 10 days. Stability of the oils varied greatly. It took the two stabilized oils 9 weeks to reach the same peroxide value as the unstable oil reached after only a few days. Both the stabilized EPA- and DHA-rich diets lowered the triacylglycerols and total cholesterol compared to control (-45%, P < 0.05 and -54%, P < 0.001; -31%, P < 0.05 and -25%, P < 0.01) and so did the unstable oil, but less efficiently. Only the unstable oil increased in vivo lipid peroxidation significantly compared to control (+40%, P < 0.001). Most of the fatty acids in the plasma phospholipids were significantly affected by both the EPA- and DHA-rich diets compared to control, reflecting their specific fatty acid pattern. The unstable oil diet resulted in smaller changes, especially in n-3 PUFAs. In the brain phospholipids the changes were less pronounced, and only the diet enriched with the stabilized DHA-rich oil resulted in a significantly greater incorporation of DHA (+13%, P < 0.01), as well as total n-3 PUFAs (+13%, P < 0.01) compared to control. Only the stabilized DHA-rich oil increased the brain NOS activity (+33%, P < 0.01). Both the EPA- and DHA-rich diets affected the blood lipids in a similarly positive manner, and they both had a large impact on plasma phospholipid fatty acids. It was only the unstable oil that increased in vivo lipid peroxidation. However, the intake of DHA was more important than that of EPA for brain phospholipid DHA enrichment and brain NOS activity, and the stability of the fish oil was also important for these effects.

LORETA current source density for duration mismatch negativity and neuropsychological assessment in early schizophrenia.

PubMed

Miyanishi, Tomohiro; Sumiyoshi, Tomiki; Higuchi, Yuko; Seo, Tomonori; Suzuki, Michio

2013-01-01

Patients with schizophrenia elicit cognitive decline from the early phase of the illness. Mismatch negativity (MMN) has been shown to be associated with cognitive function. We investigated the current source density of duration mismatch negativity (dMMN), by using low-resolution brain electromagnetic tomography (LORETA), and neuropsychological performance in subjects with early schizophrenia. Data were obtained from 20 patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder, and 20 healthy control (HC) subjects. An auditory odd-ball paradigm was used to measure dMMN. Neuropsychological performance was evaluated by the brief assessment of cognition in schizophrenia Japanese version (BACS-J). Patients showed smaller dMMN amplitudes than those in the HC subjects. LORETA current density for dMMN was significantly lower in patients compared to HC subjects, especially in the temporal lobes. dMMN current density in the frontal lobe was positively correlated with working memory performance in patients. This is the first study to identify brain regions showing smaller dMMN current density in early schizophrenia. Further, poor working memory was associated with decreased dMMN current density in patients. These results are likely to help understand the neural basis for cognitive impairment of schizophrenia.

Amino acid sequence of the smaller basic protein from rat brain myelin

PubMed Central

Dunkley, Peter R.; Carnegie, Patrick R.

1974-01-01

1. The complete amino acid sequence of the smaller basic protein from rat brain myelin was determined. This protein differs from myelin basic proteins of other species in having a deletion of a polypeptide of 40 amino acid residues from the centre of the molecule. 2. A detailed comparison is made of the constant and variable regions in a group of myelin basic proteins from six species. 3. An arginine residue in the rat protein was found to be partially methylated. The ratio of methylated to unmethylated arginine at this position differed from that found for the human basic protein. 4. Three tryptic peptides were isolated in more than one form. The differences between the two forms of each peptide are discussed in relation to the electrophoretic heterogeneity of myelin basic proteins, which is known to occur at alkaline pH values. 5. Detailed evidence for the amino acid sequence of the protein has been deposited as Supplementary Publication SUP 50029 at the British Library (Lending Division) (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies may be obtained on the terms given in Biochem. J. (1973) 131, 5. PMID:4141893

Brain structure correlates of emotion-based rash impulsivity

PubMed Central

Muhlert, N.; Lawrence, A.D.

2015-01-01

Negative urgency (the tendency to engage in rash, ill-considered action in response to intense negative emotions), is a personality trait that has been linked to problematic involvement in several risky and impulsive behaviours, and to various forms of disinhibitory psychopathology, but its neurobiological correlates are poorly understood. Here, we explored whether inter-individual variation in levels of trait negative urgency was associated with inter-individual variation in regional grey matter volumes. Using voxel-based morphometry (VBM) in a sample (n = 152) of healthy participants, we found that smaller volumes of the dorsomedial prefrontal cortex and right temporal pole, regions previously linked to emotion appraisal, emotion regulation and emotion-based decision-making, were associated with higher levels of trait negative urgency. When controlling for other impulsivity linked personality traits (sensation seeking, lack of planning/perseverance) and negative emotionality per se (neuroticism), these associations remained, and an additional relationship was found between higher levels of trait negative urgency and smaller volumes of the left ventral striatum. This latter finding mirrors recent VBM findings in an animal model of impulsivity. Our findings offer novel insight into the brain structure correlates of one key source of inter-individual differences in impulsivity. PMID:25957991

A Wireless Fully Passive Neural Recording Device for Unobtrusive Neuropotential Monitoring.

PubMed

Kiourti, Asimina; Lee, Cedric W L; Chae, Junseok; Volakis, John L

2016-01-01

We propose a novel wireless fully passive neural recording device for unobtrusive neuropotential monitoring. Previous work demonstrated the feasibility of monitoring emulated brain signals in a wireless fully passive manner. In this paper, we propose a novel realistic recorder that is significantly smaller and much more sensitive. The proposed recorder utilizes a highly efficient microwave backscattering method and operates without any formal power supply or regulating elements. Also, no intracranial wires or cables are required. In-vitro testing is performed inside a four-layer head phantom (skin, bone, gray matter, and white matter). Compared to our former implementation, the neural recorder proposed in this study has the following improved features: 1) 59% smaller footprint, 2) up to 20-dB improvement in neuropotential detection sensitivity, and 3) encapsulation in biocompatible polymer. For the first time, temporal emulated neuropotentials as low as 63 μVpp can be detected in a wireless fully passive manner. Remarkably, the high-sensitivity achieved in this study implies reading of most neural signals generated by the human brain. The proposed recorder brings forward transformational possibilities in wireless fully passive neural detection for a very wide range of applications (e.g., epilepsy, Alzheimer's, mental disorders, etc.).

Associations Between Biomarkers and Age in the Presenilin 1 E280A Autosomal Dominant Alzheimer Disease Kindred A Cross-sectional Study

PubMed Central

Fleisher, Adam S.; Chen, Kewei; Quiroz, Yakeel T.; Jakimovich, Laura J.; Gomez, Madelyn Gutierrez; Langois, Carolyn M.; Langbaum, Jessica B. S.; Roontiva, Auttawut; Thiyyagura, Pradeep; Lee, Wendy; Ayutyanont, Napatkamon; Lopez, Liliana; Moreno, Sonia; Muñoz, Claudia; Tirado, Victoria; Acosta-Baena, Natalia; Fagan, Anne M.; Giraldo, Margarita; Garcia, Gloria; Huentelman, Matthew J.; Tariot, Pierre N.; Lopera, Francisco; Reiman, Eric M.

2015-01-01

IMPORTANCE Age-associated changes in brain imaging and fluid biomarkers are characterized and compared in presenilin 1 (PSEN1) E280A mutation carriers and noncarriers from the world’s largest known autosomal dominant Alzheimer disease (AD) kindred. OBJECTIVE To characterize and compare age-associated changes in brain imaging and fluid biomarkers in PSEN1 E280A mutation carriers and noncarriers. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional measures of 18F-florbetapir positron emission tomography, 18F-fludeoxyglucose positron emission tomography, structural magnetic resonance imaging, cerebrospinal fluid (CSF), and plasma biomarkers of AD were assessed from 54 PSEN1 E280A kindred members (age range, 20-59 years). MAIN OUTCOMES AND MEASURES We used brain mapping algorithms to compare regional cerebral metabolic rates for glucose and gray matter volumes in cognitively unimpaired mutation carriers and noncarriers. We used regression analyses to characterize associations between age and the mean cortical to pontine 18F-florbetapir standard uptake value ratios, precuneus cerebral metabolic rates for glucose, hippocampal gray matter volume, CSF Aβ1-42, total tau and phosphorylated tau181, and plasma Aβ measurements. Age at onset of progressive biomarker changes that distinguish carriers from noncarriers was estimated using best-fitting regression models. RESULTS Compared with noncarriers, cognitively unimpaired mutation carriers had significantly lower precuneus cerebral metabolic rates for glucose, smaller hippocampal volume, lower CSF Aβ1-42, higher CSF total tau and phosphorylated tau181, and higher plasma Aβ1-42 measurements. Sequential changes in biomarkers were seen at age 20 years (95% CI, 14-24 years) for CSF Aβ1-42, age 16 years (95% CI, 11-24 years) for the mean cortical 18F-florbetapir standard uptake value ratio, age 15 years (95% CI, 10-24 years) for precuneus cerebral metabolic rate for glucose, age 15 years (95% CI, 7-20 years) for CSF total tau, age 13 years (95% CI, 8-19 years) for phosphorylated tau181, and age 6 years (95% CI, 1-10 years) for hippocampal volume, with cognitive decline up to 6 years before the kindred’s estimated median age of 44 years (95% CI, 43-45 years) at mild cognitive impairment diagnosis. No age-associated findings were seen in plasma Aβ1-42 or Aβ1-40. CONCLUSIONS AND RELEVANCE This cross-sectional study provides additional information about the course of different AD biomarkers in the preclinical and clinical stages of autosomal dominant AD. PMID:25580592

Density of mushroom body synaptic complexes limits intraspecies brain miniaturization in highly polymorphic leaf-cutting ant workers

PubMed Central

Groh, Claudia; Kelber, Christina; Grübel, Kornelia; Rössler, Wolfgang

2014-01-01

Hymenoptera possess voluminous mushroom bodies (MBs), brain centres associated with sensory integration, learning and memory. The mushroom body input region (calyx) is organized in distinct synaptic complexes (microglomeruli, MG) that can be quantified to analyse body size-related phenotypic plasticity of synaptic microcircuits in these small brains. Leaf-cutting ant workers (Atta vollenweideri) exhibit an enormous size polymorphism, which makes them outstanding to investigate neuronal adaptations underlying division of labour and brain miniaturization. We particularly asked how size-related division of labour in polymorphic workers is reflected in volume and total numbers of MG in olfactory calyx subregions. Whole brains of mini, media and large workers were immunolabelled with anti-synapsin antibodies, and mushroom body volumes as well as densities and absolute numbers of MG were determined by confocal imaging and three-dimensional analyses. The total brain volume and absolute volumes of olfactory mushroom body subdivisions were positively correlated with head widths, but mini workers had significantly larger MB to total brain ratios. Interestingly, the density of olfactory MG was remarkably independent from worker size. Consequently, absolute numbers of olfactory MG still were approximately three times higher in large compared with mini workers. The results show that the maximum packing density of synaptic microcircuits may represent a species-specific limit to brain miniaturization. PMID:24807257

Hepatoprotective activity of Annona muricata Linn. and Polyalthia cerasoides bedd.

PubMed Central

Padma, P.; Chansouria, J.P.N.; Khosa, R.L.

1999-01-01

The hepatoprotective effect of Annona muricata and Polyalthia cerasoides (Annonaceae) were monitored by estimating the serum transaminases (SGOT and SGPT), serum alkaline phosphatase (SALP), liver and brain lipid peroxidation (LOP) and their total protein content. Both drugs at a dose of 100 μg/kg significantly prevented the increase in serum transaminases, SALP, liver and brain LOP and decrease in liver and brain total protein content following carbontetrachloride (CCl) induced hepatoxicity in albino rats. PMID:22556909

Postmenopausal hormone therapy, type 2 diabetes mellitus, and brain volumes.

PubMed

Espeland, Mark A; Brinton, Roberta Diaz; Manson, JoAnn E; Yaffe, Kristine; Hugenschmidt, Christina; Vaughan, Leslie; Craft, Suzanne; Edwards, Beatrice J; Casanova, Ramon; Masaki, Kamal; Resnick, Susan M

2015-09-29

To examine whether the effect of postmenopausal hormone therapy (HT) on brain volumes in women aged 65-79 years differs depending on type 2 diabetes status during postintervention follow-up of a randomized controlled clinical trial. The Women's Health Initiative randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without 2.5 mg/day medroxyprogesterone acetate) or placebo for an average of 5.6 years. A total of 1,402 trial participants underwent brain MRI 2.4 years after the trials; these were repeated in 699 women 4.7 years later. General linear models were used to assess the interaction between diabetes status and HT assignment on brain volumes. Women with diabetes at baseline or during follow-up who had been assigned to HT compared to placebo had mean decrement in total brain volume of -18.6 mL (95% confidence interval [CI] -29.6, -7.6). For women without diabetes, this mean decrement was -0.4 (95% CI -3.8, 3.0) (interaction p=0.002). This interaction was evident for total gray matter (p<0.001) and hippocampal (p=0.006) volumes. It was not evident for changes in brain volumes over follow-up or for ischemic lesion volumes and was not influenced by diabetes duration or oral medications. For women aged 65 years or older who are at increased risk for brain atrophy due to type 2 diabetes, prescription of postmenopausal HT is associated with lower gray matter (total and hippocampal) volumes. Interactions with diabetes and insulin resistance may explain divergent findings on how estrogen influences brain volume among older women. © 2015 American Academy of Neurology.

Postmenopausal hormone therapy, type 2 diabetes mellitus, and brain volumes

PubMed Central

Brinton, Roberta Diaz; Manson, JoAnn E.; Yaffe, Kristine; Hugenschmidt, Christina; Vaughan, Leslie; Craft, Suzanne; Edwards, Beatrice J.; Casanova, Ramon; Masaki, Kamal; Resnick, Susan M.

2015-01-01

Objective: To examine whether the effect of postmenopausal hormone therapy (HT) on brain volumes in women aged 65–79 years differs depending on type 2 diabetes status during postintervention follow-up of a randomized controlled clinical trial. Methods: The Women's Health Initiative randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without 2.5 mg/day medroxyprogesterone acetate) or placebo for an average of 5.6 years. A total of 1,402 trial participants underwent brain MRI 2.4 years after the trials; these were repeated in 699 women 4.7 years later. General linear models were used to assess the interaction between diabetes status and HT assignment on brain volumes. Results: Women with diabetes at baseline or during follow-up who had been assigned to HT compared to placebo had mean decrement in total brain volume of −18.6 mL (95% confidence interval [CI] −29.6, −7.6). For women without diabetes, this mean decrement was −0.4 (95% CI −3.8, 3.0) (interaction p = 0.002). This interaction was evident for total gray matter (p < 0.001) and hippocampal (p = 0.006) volumes. It was not evident for changes in brain volumes over follow-up or for ischemic lesion volumes and was not influenced by diabetes duration or oral medications. Conclusions: For women aged 65 years or older who are at increased risk for brain atrophy due to type 2 diabetes, prescription of postmenopausal HT is associated with lower gray matter (total and hippocampal) volumes. Interactions with diabetes and insulin resistance may explain divergent findings on how estrogen influences brain volume among older women. PMID:26163429

Accelerated echo-planar J-resolved spectroscopic imaging in the human brain using compressed sensing: a pilot validation in obstructive sleep apnea.

PubMed

Sarma, M K; Nagarajan, R; Macey, P M; Kumar, R; Villablanca, J P; Furuyama, J; Thomas, M A

2014-06-01

Echo-planar J-resolved spectroscopic imaging is a fast spectroscopic technique to record the biochemical information in multiple regions of the brain, but for clinical applications, time is still a constraint. Investigations of neural injury in obstructive sleep apnea have revealed structural changes in the brain, but determining the neurochemical changes requires more detailed measurements across multiple brain regions, demonstrating a need for faster echo-planar J-resolved spectroscopic imaging. Hence, we have extended the compressed sensing reconstruction of prospectively undersampled 4D echo-planar J-resolved spectroscopic imaging to investigate metabolic changes in multiple brain locations of patients with obstructive sleep apnea and healthy controls. Nonuniform undersampling was imposed along 1 spatial and 1 spectral dimension of 4D echo-planar J-resolved spectroscopic imaging, and test-retest reliability of the compressed sensing reconstruction of the nonuniform undersampling data was tested by using a brain phantom. In addition, 9 patients with obstructive sleep apnea and 11 healthy controls were investigated by using a 3T MR imaging/MR spectroscopy scanner. Significantly reduced metabolite differences were observed between patients with obstructive sleep apnea and healthy controls in multiple brain regions: NAA/Cr in the left hippocampus; total Cho/Cr and Glx/Cr in the right hippocampus; total NAA/Cr, taurine/Cr, scyllo-Inositol/Cr, phosphocholine/Cr, and total Cho/Cr in the occipital gray matter; total NAA/Cr and NAA/Cr in the medial frontal white matter; and taurine/Cr and total Cho/Cr in the left frontal white matter regions. The 4D echo-planar J-resolved spectroscopic imaging technique using the nonuniform undersampling-based acquisition and compressed sensing reconstruction in patients with obstructive sleep apnea and healthy brain is feasible in a clinically suitable time. In addition to brain metabolite changes previously reported by 1D MR spectroscopy, our results show changes of additional metabolites in patients with obstructive sleep apnea compared with healthy controls. © 2014 by American Journal of Neuroradiology.

Behavioral problems after early life stress: contributions of the hippocampus and amygdala.

PubMed

Hanson, Jamie L; Nacewicz, Brendon M; Sutterer, Matthew J; Cayo, Amelia A; Schaefer, Stacey M; Rudolph, Karen D; Shirtcliff, Elizabeth A; Pollak, Seth D; Davidson, Richard J

2015-02-15

Early life stress (ELS) can compromise development, with higher amounts of adversity linked to behavioral problems. To understand this linkage, a growing body of research has examined two brain regions involved with socioemotional functioning-amygdala and hippocampus. Yet empirical studies have reported increases, decreases, and no differences within human and nonhuman animal samples exposed to different forms of ELS. This divergence in findings may stem from methodological factors, nonlinear effects of ELS, or both. We completed rigorous hand-tracing of the amygdala and hippocampus in three samples of children who experienced different forms of ELS (i.e., physical abuse, early neglect, or low socioeconomic status). Interviews were also conducted with children and their parents or guardians to collect data about cumulative life stress. The same data were also collected in a fourth sample of comparison children who had not experienced any of these forms of ELS. Smaller amygdala volumes were found for children exposed to these different forms of ELS. Smaller hippocampal volumes were also noted for children who were physically abused or from low socioeconomic status households. Smaller amygdala and hippocampal volumes were also associated with greater cumulative stress exposure and behavioral problems. Hippocampal volumes partially mediated the relationship between ELS and greater behavioral problems. This study suggests ELS may shape the development of brain areas involved with emotion processing and regulation in similar ways. Differences in the amygdala and hippocampus may be a shared diathesis for later negative outcomes related to ELS. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Ethanol Withdrawal Drives Anxiety-Related Behaviors by Reducing M-type Potassium Channel Activity in the Lateral Habenula.

PubMed

Kang, Seungwoo; Li, Jing; Zuo, Wanhong; Fu, Rao; Gregor, Danielle; Krnjevic, Kresimir; Bekker, Alex; Ye, Jiang-Hong

2017-08-01

Alcohol use disorders (AUDs) and anxiety disorders (ADs) are often seen concurrently, but their underlying cellular basis is unclear. For unclear reasons, the lateral habenula (LHb), a key brain region involved in the pathophysiology of ADs, becomes hyperactive after ethanol withdrawal. M-type K + channels (M-channels), important regulators of neuronal activity, are abundant in the LHb, yet little is known about their role in AUDs and associated ADs. We report here that in rats at 24 h withdrawal from systemic ethanol administration (either by intraperitoneal injection, 2 g/kg, twice/day, for 7 days; or intermittent drinking 20% ethanol in a two-bottle free choice protocol for 8 weeks), the basal firing rate and the excitability of LHb neurons in brain slices was higher, whereas the amplitude of medium afterhyperpolarization and M-type K + currents were smaller, when compared to ethanol naive rats. Concordantly, M-channel blocker (XE991)-induced increase in the spontaneous firing rate in LHb neurons was smaller. The protein expression of M-channel subunits, KCNQ2/3 in the LHb was also smaller. Moreover, anxiety levels (tested in open field, marble burying, and elevated plus maze) were higher, which were alleviated by LHb inhibition either chemogenetically or by local infusion of the M-channel opener, retigabine. Intra-LHb infusion of retigabine also reduced ethanol consumption and preference. These findings reveal an important role of LHb M-channels in the expression of AUDs and ADs, and suggest that the M-channels could be a potential therapeutic target for alcoholics.

Mediterranean-type diet and brain structural change from 73 to 76 years in a Scottish cohort

PubMed Central

Corley, Janie; Cox, Simon R.; Valdés Hernández, Maria C.; Craig, Leone C.A.; Dickie, David Alexander; Karama, Sherif; McNeill, Geraldine M.; Bastin, Mark E.; Wardlaw, Joanna M.; Deary, Ian J.

2017-01-01

Objective: To assess the association between Mediterranean-type diet (MeDi) and change in brain MRI volumetric measures and mean cortical thickness across a 3-year period in older age (73–76 years). Methods: We focused on 2 longitudinal brain volumes (total and gray matter; n = 401 and 398, respectively) plus a longitudinal measurement of cortical thickness (n = 323), for which the previous cross-sectional evidence of an association with the MeDi was strongest. Adherence to the MeDi was calculated from data gathered from a food frequency questionnaire at age 70, 3 years prior to the baseline imaging data collection. Results: In regression models adjusting for relevant demographic and physical health indicators, we found that lower adherence to the MeDi was associated with greater 3-year reduction in total brain volume (explaining 0.5% of variance, p < 0.05). This effect was half the size of the largest covariate effect (i.e., age). Cross-sectional associations between MeDi and baseline MRI measures in 562 participants were not significant. Targeted analyses of meat and fish consumption did not replicate previous associations with total brain volume or total gray matter volume. Conclusions: Lower adherence to the MeDi in an older Scottish cohort is predictive of total brain atrophy over a 3-year interval. Fish and meat consumption does not drive this change, suggesting that other components of the MeDi or, possibly, all of its components in combination are responsible for the association. PMID:28053008

Postmortem changes in the neuroanatomical characteristics of the primate brain: the hippocampal formation

PubMed Central

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L.; Amaral, David G.

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused, or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger, as compared to perfusion-fixed tissue. Non-phosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well-stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences. PMID:18972553

Postmortem changes in the neuroanatomical characteristics of the primate brain: hippocampal formation.

PubMed

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L; Amaral, David G

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger as compared to perfusion-fixed tissue. Nonphosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells, and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences.

Early-onset behavioral and neurochemical deficits in the genetic mouse model of phenylketonuria

PubMed Central

Fiori, Elena; Oddi, Diego; Ventura, Rossella; Colamartino, Marco; Valzania, Alessandro; D’Amato, Francesca Romana; Bruinenberg, Vibeke; van der Zee, Eddy; Puglisi-Allegra, Stefano

2017-01-01

Phenylketonuria (PKU) is one of the most common human inborn errors of metabolism, caused by phenylalanine hydroxylase deficiency, leading to high phenylalanine and low tyrosine levels in blood and brain causing profound cognitive disability, if untreated. Since 1960, population is screened for hyperphenylalaninemia shortly after birth and submitted to early treatment in order to prevent the major manifestations of the disease. However, the dietetic regimen (phenylalanine free diet) is difficult to maintain, and despite the recommendation to a strict and lifelong compliance, up to 60% of adolescents partially or totally abandons the treatment. The development and the study of new treatments continue to be sought, taking advantage of preclinical models, the most used of which is the PAHenu2 (BTBR ENU2), the genetic murine model of PKU. To date, adult behavioral and neurochemical alterations have been mainly investigated in ENU2 mice, whereas there are no clear indications about the onset of these deficiencies. Here we investigated and report, for the first time, a comprehensive behavioral and neurochemical assay of the developing ENU2 mice. Overall, our findings demonstrate that ENU2 mice are significantly smaller than WT until pnd 24, present a significant delay in the acquisition of tested developmental reflexes, impaired communicative, motor and social skills, and have early reduced biogenic amine levels in several brain areas. Our results extend the understanding of behavioral and cerebral abnormalities in PKU mice, providing instruments to an early preclinical evaluation of the effects of new treatments. PMID:28850618

Neonatal morphine exposure in very preterm infants-cerebral development and outcomes.

PubMed

Steinhorn, Rachel; McPherson, Christopher; Anderson, Peter J; Neil, Jeffrey; Doyle, Lex W; Inder, Terrie

2015-05-01

To investigate the association of morphine exposure in very preterm infants with cerebral volumes and neurodevelopmental outcome from birth through middle childhood. Observational study of very preterm infants in the Victorian Infant Brain Study cohort. A total of 230 infants born <30 weeks' gestational age or <1250 g were recruited from all admissions to the neonatal intensive care unit of the Royal Women's Hospital. Fifty-seven (25%) infants received morphine analgesia during their neonatal intensive care unit stay at the attending physician's discretion. Primary outcomes were regional brain volumes at term and 7 years; neurobehavioral performance at term; and cognitive, motor, emotional, behavioral, communication, and executive function scores at age 2 and 7 years. Linear regressions were used to compare outcomes between participants who did and did not receive morphine. At term, preterm infants who received morphine had similar rates of gray matter injury to no-morphine infants, but a trend toward smaller cortical volumes in the orbitofrontal (Pleft=.002, Pright=.01) and subgenual (Pleft=.01) regions. At 7 years, cortical volumes did not differ between groups. At 2 years, morphine-exposed children were more likely to show behavioral dysregulation (P=.007) than no-morphine children, but at 7 years no detrimental impacts of morphine on neurobehavioral outcome were observed. Low-dose morphine analgesia received during neonatal intensive care was associated with early alterations in cerebral structure and short-term neurobehavioral problems that did not persist into childhood. Copyright © 2015 Elsevier Inc. All rights reserved.

3D morphological analysis of the mouse cerebral vasculature: Comparison of in vivo and ex vivo methods

PubMed Central

Steinman, Joe; Koletar, Margaret M.; Stefanovic, Bojana; Sled, John G.

2017-01-01

Ex vivo 2-photon fluorescence microscopy (2PFM) with optical clearing enables vascular imaging deep into tissue. However, optical clearing may also produce spherical aberrations if the objective lens is not index-matched to the clearing material, while the perfusion, clearing, and fixation procedure may alter vascular morphology. We compared in vivo and ex vivo 2PFM in mice, focusing on apparent differences in microvascular signal and morphology. Following in vivo imaging, the mice (four total) were perfused with a fluorescent gel and their brains fructose-cleared. The brain regions imaged in vivo were imaged ex vivo. Vessels were segmented in both images using an automated tracing algorithm that accounts for the spatially varying PSF in the ex vivo images. This spatial variance is induced by spherical aberrations caused by imaging fructose-cleared tissue with a water-immersion objective. Alignment of the ex vivo image to the in vivo image through a non-linear warping algorithm enabled comparison of apparent vessel diameter, as well as differences in signal. Shrinkage varied as a function of diameter, with capillaries rendered smaller ex vivo by 13%, while penetrating vessels shrunk by 34%. The pial vasculature attenuated in vivo microvascular signal by 40% 300 μm below the tissue surface, but this effect was absent ex vivo. On the whole, ex vivo imaging was found to be valuable for studying deep cortical vasculature. PMID:29053753

Quantitative comparison of 3D third harmonic generation and fluorescence microscopy images.

PubMed

Zhang, Zhiqing; Kuzmin, Nikolay V; Groot, Marie Louise; de Munck, Jan C

2018-01-01

Third harmonic generation (THG) microscopy is a label-free imaging technique that shows great potential for rapid pathology of brain tissue during brain tumor surgery. However, the interpretation of THG brain images should be quantitatively linked to images of more standard imaging techniques, which so far has been done qualitatively only. We establish here such a quantitative link between THG images of mouse brain tissue and all-nuclei-highlighted fluorescence images, acquired simultaneously from the same tissue area. For quantitative comparison of a substantial pair of images, we present here a segmentation workflow that is applicable for both THG and fluorescence images, with a precision of 91.3 % and 95.8 % achieved respectively. We find that the correspondence between the main features of the two imaging modalities amounts to 88.9 %, providing quantitative evidence of the interpretation of dark holes as brain cells. Moreover, 80 % bright objects in THG images overlap with nuclei highlighted in the fluorescence images, and they are 2 times smaller than the dark holes, showing that cells of different morphologies can be recognized in THG images. We expect that the described quantitative comparison is applicable to other types of brain tissue and with more specific staining experiments for cell type identification. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Alterations in blood-brain barrier function following acute hypertension: comparison of the blood-to-brain transfer of horseradish peroxidase with that of alpha-aminisobutyric acid

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

Ellison, M.D.B.

The blood-brain barrier (BBB) selectively restricts the blood-to-brain passage of many solutes owing to unique properties of cerebrovascular endothelial cell membranes. To date, experimental study of the BBB has been accomplished primarily through the use of two different methodological approaches. Morphological studies have mostly employed large molecular weight (MW) tracers to detect morphological alterations underlying increased permeability. Physiological studies, employing smaller, more physiologic tracers have successfully described, quantitatively, certain functional aspects of blood-to-brain transfer. The current work attempts to merge these two approaches and to consider barrier function/dysfunction from both a morphological and a functional perspective. Specifically, the study comparesmore » in rats, following acute hypertension, the cerebrovascular passage of /sup 14/C-alpha-aminoisobutyric acid (AIB) and that of horseradish peroxidase (HRP). The blood-to-brain passage of AIB and HRP were compared following acute hypertension, with regard to both the distributions of the tracer extravasation patterns and the magnitude of tracer extravasation. The results of this study suggest that traditional morphological barrier studies alone do not reveal all aspects of altered barrier status and that multiple mechanisms underlying increased BBB permeability may operate simultaneously during BBB dysfunction.« less

Numerical study of the impact response of woodpecker's head

NASA Astrophysics Data System (ADS)

Zhu, Zhao Dan; Ma, Guo Jun; Wu, Cheng Wei; Chen, Zhen

2012-12-01

Woodpecker can beat trees 20-25 times per second and lasts for several seconds, with a 1200 g deceleration, but it appears that they never get brain concussion. How does the stress wave propagate from the beak tip to brain and how does a woodpecker protect itself from brain damage? In this paper, we establish a finite element model of typical woodpecker head based on its X-ray tomography images and conduct the numerical analysis of the impact response of the woodpecker's head by using a viscoelasticity material model. Especially, the woodpecker head response to an impact speed of 7 m/s is investigated to explore the stress concentration zone and how the stress wave propagates in its head. The numerical results show that the stress wave in the head propagates from the upper beak to back skull and is reduced by the specific structure of hyoid and viscoelasticity of biomaterials. The maximum stresses in skull and brain are both below the safe level. The stress in skull almost disappears before the next impact. The stress in brain lasts for a little longer but shows smaller value with little variation. The stress is impossible to accumulate in the limited pecking time, so the brain damage can be avoided.

Greater impulsivity is associated with decreased brain activation in obese women during a delay discounting task.

PubMed

Stoeckel, Luke E; Murdaugh, Donna L; Cox, James E; Cook, Edwin W; Weller, Rosalyn E

2013-06-01

Impulsivity and poor inhibitory control are associated with higher rates of delay discounting (DD), or a greater preference for smaller, more immediate rewards at the expense of larger, but delayed rewards. Of the many functional magnetic resonance imaging (fMRI) studies of DD, few have investigated the correlation between individual differences in DD rate and brain activation related to DD trial difficulty, with difficult DD trials expected to activate putative executive function brain areas involved in impulse control. In the current study, we correlated patterns of brain activation as measured by fMRI during difficult vs. easy trials of a DD task with DD rate (k) in obese women. Difficulty was defined by how much a reward choice deviated from an individual's 'indifference point', or the point where the subjective preference for an immediate and a delayed reward was approximately equivalent. We found that greater delay discounting was correlated with less modulation of activation in putative executive function brain areas, such as the middle and superior frontal gyri and inferior parietal lobule, in response to difficult compared to easy DD trials. These results support the suggestion that increased impulsivity is associated with deficient functioning of executive function areas of the brain.

The role of mechanics during brain development

NASA Astrophysics Data System (ADS)

Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

2014-12-01

Convolutions are a classical hallmark of most mammalian brains. Brain surface morphology is often associated with intelligence and closely correlated with neurological dysfunction. Yet, we know surprisingly little about the underlying mechanisms of cortical folding. Here we identify the role of the key anatomic players during the folding process: cortical thickness, stiffness, and growth. To establish estimates for the critical time, pressure, and the wavelength at the onset of folding, we derive an analytical model using the Föppl-von Kármán theory. Analytical modeling provides a quick first insight into the critical conditions at the onset of folding, yet it fails to predict the evolution of complex instability patterns in the post-critical regime. To predict realistic surface morphologies, we establish a computational model using the continuum theory of finite growth. Computational modeling not only confirms our analytical estimates, but is also capable of predicting the formation of complex surface morphologies with asymmetric patterns and secondary folds. Taken together, our analytical and computational models explain why larger mammalian brains tend to be more convoluted than smaller brains. Both models provide mechanistic interpretations of the classical malformations of lissencephaly and polymicrogyria. Understanding the process of cortical folding in the mammalian brain has direct implications on the diagnostics of neurological disorders including severe retardation, epilepsy, schizophrenia, and autism.

The role of mechanics during brain development

PubMed Central

Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

2014-01-01

Convolutions are a classical hallmark of most mammalian brains. Brain surface morphology is often associated with intelligence and closely correlated to neurological dysfunction. Yet, we know surprisingly little about the underlying mechanisms of cortical folding. Here we identify the role of the key anatomic players during the folding process: cortical thickness, stiffness, and growth. To establish estimates for the critical time, pressure, and the wavelength at the onset of folding, we derive an analytical model using the Föppl-von-Kármán theory. Analytical modeling provides a quick first insight into the critical conditions at the onset of folding, yet it fails to predict the evolution of complex instability patterns in the post-critical regime. To predict realistic surface morphologies, we establish a computational model using the continuum theory of finite growth. Computational modeling not only confirms our analytical estimates, but is also capable of predicting the formation of complex surface morphologies with asymmetric patterns and secondary folds. Taken together, our analytical and computational models explain why larger mammalian brains tend to be more convoluted than smaller brains. Both models provide mechanistic interpretations of the classical malformations of lissencephaly and polymicrogyria. Understanding the process of cortical folding in the mammalian brain has direct implications on the diagnostics of neurological disorders including severe retardation, epilepsy, schizophrenia, and autism. PMID:25202162

Evidence for a Heritable Brain Basis to Deviance-Promoting Deficits in Self-Control

PubMed Central

Yancey, James R.; Venables, Noah C.; Hicks, Brian M.; Patrick, Christopher J.

2013-01-01

Purpose Classic criminological theories emphasize the role of impaired self-control in behavioral deviancy. Reduced amplitude of the P300 brain response is reliably observed in individuals with antisocial and substance-related problems, suggesting it may serve as a neurophysiological indicator of deficiencies in self-control that confer liability to deviancy. Methods The current study evaluated the role of self-control capacity — operationalized by scores on a scale measure of trait disinhibition — in mediating the relationship between P300 brain response and behavioral deviancy in a sample of adult twins (N=419) assessed for symptoms of antisocial/addictive disorders and P300 brain response. Results As predicted, greater disorder symptoms and higher trait disinhibition scores each predicted smaller P300 amplitude, and trait disinhibition mediated observed relations between antisocial/addictive disorders and P300 response. Further, twin modeling analyses revealed that trait disinhibition scores and disorder symptoms reflected a common genetic liability, and this genetic liability largely accounted for the observed phenotypic relationship between antisocial-addictive problems and P300 brain response. Conclusions These results provide further evidence that heritable weaknesses in self-control capacity confer liability to antisocial/addictive outcomes and that P300 brain response indexes this dispositional liability. PMID:24187392

Ex vivo MR volumetry of human brain hemispheres.

PubMed

Kotrotsou, Aikaterini; Bennett, David A; Schneider, Julie A; Dawe, Robert J; Golak, Tom; Leurgans, Sue E; Yu, Lei; Arfanakis, Konstantinos

2014-01-01

The aims of this work were to (a) develop an approach for ex vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, (b) longitudinally assess regional brain volumes postmortem, and (c) investigate the relationship between MR volumetric measurements performed in vivo and ex vivo. An approach for ex vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex vivo was assessed. The relationship between in vivo and ex vivo volumetric measurements was investigated in seven elderly subjects imaged both antemortem and postmortem. This approach for ex vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than intersubject volume variation. A close linear correspondence was detected between in vivo and ex vivo volumetric measurements. Regional brain volumes measured with this approach for ex vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in vivo and ex vivo MR volumetric measurements suggests that this approach captures information linked to antemortem macrostructural brain characteristics. Copyright © 2013 Wiley Periodicals, Inc.

Ex-vivo MR Volumetry of Human Brain Hemispheres

PubMed Central

Kotrotsou, Aikaterini; Bennett, David A.; Schneider, Julie A.; Dawe, Robert J.; Golak, Tom; Leurgans, Sue E.; Yu, Lei; Arfanakis, Konstantinos

2013-01-01

Purpose The aims of this work were to: a) develop an approach for ex-vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, b) longitudinally assess regional brain volumes postmortem, and c) investigate the relationship between MR volumetric measurements performed in-vivo and ex-vivo. Methods An approach for ex-vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex-vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex-vivo was assessed. The relationship between in-vivo and ex-vivo volumetric measurements was investigated in seven elderly subjects imaged both ante-mortem and postmortem. Results The presented approach for ex-vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than inter-subject volume variation. A close linear correspondence was detected between in-vivo and ex-vivo volumetric measurements. Conclusion Regional brain volumes measured with the presented approach for ex-vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in-vivo and ex-vivo MR volumetric measurements suggests that the presented approach captures information linked to ante-mortem macrostructural brain characteristics. PMID:23440751

Corticolimbic anatomical characteristics predetermine risk for chronic pain

PubMed Central

Vachon-Presseau, Etienne; Tétreault, Pascal; Petre, Bogdan; Huang, Lejian; Berger, Sara E.; Torbey, Souraya; Baria, Alexis T.; Mansour, Ali R.; Hashmi, Javeria A.; Griffith, James W.; Comasco, Erika; Schnitzer, Thomas J.

2016-01-01

See Tracey (doi:10.1093/brain/aww147) for a scientific commentary on this article. Mechanisms of chronic pain remain poorly understood. We tracked brain properties in subacute back pain patients longitudinally for 3 years as they either recovered from or transitioned to chronic pain. Whole-brain comparisons indicated corticolimbic, but not pain-related circuitry, white matter connections predisposed patients to chronic pain. Intra-corticolimbic white matter connectivity analysis identified three segregated communities: dorsal medial prefrontal cortex–amygdala–accumbens, ventral medial prefrontal cortex–amygdala, and orbitofrontal cortex–amygdala–hippocampus. Higher incidence of white matter and functional connections within the dorsal medial prefrontal cortex–amygdala–accumbens circuit, as well as smaller amygdala volume, represented independent risk factors, together accounting for 60% of the variance for pain persistence. Opioid gene polymorphisms and negative mood contributed indirectly through corticolimbic anatomical factors, to risk for chronic pain. Our results imply that persistence of chronic pain is predetermined by corticolimbic neuroanatomical factors. PMID:27190016

Conjugating time and frequency: hemispheric specialization, acoustic uncertainty, and the mustached bat

PubMed Central

Washington, Stuart D.; Tillinghast, John S.

2015-01-01

A prominent hypothesis of hemispheric specialization for human speech and music states that the left and right auditory cortices (ACs) are respectively specialized for precise calculation of two canonically-conjugate variables: time and frequency. This spectral-temporal asymmetry does not account for sex, brain-volume, or handedness, and is in opposition to closed-system hypotheses that restrict this asymmetry to humans. Mustached bats have smaller brains, but greater ethological pressures to develop such a spectral-temporal asymmetry, than humans. Using the Heisenberg-Gabor Limit (i.e., the mathematical basis of the spectral-temporal asymmetry) to frame mustached bat literature, we show that recent findings in bat AC (1) support the notion that hemispheric specialization for speech and music is based on hemispheric differences in temporal and spectral resolution, (2) discredit closed-system, handedness, and brain-volume theories, (3) underscore the importance of sex differences, and (4) provide new avenues for phonological research. PMID:25926767

Conjugating time and frequency: hemispheric specialization, acoustic uncertainty, and the mustached bat.

PubMed

Washington, Stuart D; Tillinghast, John S

2015-01-01

A prominent hypothesis of hemispheric specialization for human speech and music states that the left and right auditory cortices (ACs) are respectively specialized for precise calculation of two canonically-conjugate variables: time and frequency. This spectral-temporal asymmetry does not account for sex, brain-volume, or handedness, and is in opposition to closed-system hypotheses that restrict this asymmetry to humans. Mustached bats have smaller brains, but greater ethological pressures to develop such a spectral-temporal asymmetry, than humans. Using the Heisenberg-Gabor Limit (i.e., the mathematical basis of the spectral-temporal asymmetry) to frame mustached bat literature, we show that recent findings in bat AC (1) support the notion that hemispheric specialization for speech and music is based on hemispheric differences in temporal and spectral resolution, (2) discredit closed-system, handedness, and brain-volume theories, (3) underscore the importance of sex differences, and (4) provide new avenues for phonological research.

Pleasure systems in the brain

PubMed Central

Berridge, Kent C.; Kringelbach, Morten L.

2015-01-01

Pleasure is mediated by well-developed mesocorticolimbic circuitry, and serves adaptive functions. In affective disorders anhedonia (lack of pleasure) or dysphoria (negative affect) can result from breakdowns of that hedonic system. Human neuroimaging studies indicate that surprisingly similar circuitry is activated by quite diverse pleasures, suggesting a common neural currency shared by all. Wanting for rewards is generated by a large and distributed brain system. Liking, or pleasure itself, is generated by a smaller set of hedonic hotspots within limbic circuitry. Those hotspots also can be embedded in broader anatomical patterns of valence organization, such as in a keyboard pattern of nucleus accumbens generators for desire versus dread. In contrast, some of the best known textbook candidates for pleasure generators, including classic pleasure electrodes and the mesolimbic dopamine system, may not generate pleasure after all. These emerging insights into brain pleasure mechanisms may eventually facilitate better treatments for affective disorders. PMID:25950633

Structural magnetic resonance imaging in patients with first-episode schizophrenia, psychotic and severe non-psychotic depression and healthy controls. Results of the schizophrenia and affective psychoses (SAP) project.

PubMed

Salokangas, R K R; Cannon, T; Van Erp, T; Ilonen, T; Taiminen, T; Karlsson, H; Lauerma, H; Leinonen, K M; Wallenius, E; Kaljonen, A; Syvälahti, E; Vilkman, H; Alanen, A; Hietala, J

2002-09-01

Structural brain abnormalities are prevalent in patients with schizophrenia and affective disorders. To study how regional brain volumes and their ratios differ between patients with schizophrenia, psychotic depression, severe non-psychotic depression and healthy controls. Magnetic resonance imaging scans of the brain on first-episode patients and on healthy controls. Patients with schizophrenia had a smaller left frontal grey matter volume than the other three groups. Patients with psychotic depression had larger ventricular and posterior sulcal cerebrospinal fluid (CSF) volumes than controls. Patients with depression had larger white matter volumes than the other patients. Left frontal lobe, especially its grey matter volume, seems to be specifically reduced in first-episode schizophrenia. Enlarged cerebral ventricles and sulcal CSF volumes are prevalent in psychotic depression. Preserved or expanded white matter is typical of non-psychotic depression.

The braingraph.org database of high resolution structural connectomes and the brain graph tools.

PubMed

Kerepesi, Csaba; Szalkai, Balázs; Varga, Bálint; Grolmusz, Vince

2017-10-01

Based on the data of the NIH-funded Human Connectome Project, we have computed structural connectomes of 426 human subjects in five different resolutions of 83, 129, 234, 463 and 1015 nodes and several edge weights. The graphs are given in anatomically annotated GraphML format that facilitates better further processing and visualization. For 96 subjects, the anatomically classified sub-graphs can also be accessed, formed from the vertices corresponding to distinct lobes or even smaller regions of interests of the brain. For example, one can easily download and study the connectomes, restricted to the frontal lobes or just to the left precuneus of 96 subjects using the data. Partially directed connectomes of 423 subjects are also available for download. We also present a GitHub-deposited set of tools, called the Brain Graph Tools, for several processing tasks of the connectomes on the site http://braingraph.org.

On the possibility of using multi-element phased arrays for shock-wave action on deep brain structures

NASA Astrophysics Data System (ADS)

Rosnitskiy, P. B.; Gavrilov, L. R.; Yuldashev, P. V.; Sapozhnikov, O. A.; Khokhlova, V. A.

2017-09-01

A noninvasive ultrasound surgery method that relies on using multi-element focused phased arrays is being successfully used to destroy tumors and perform neurosurgical operations in deep structures of the human brain. However, several drawbacks that limit the possibilities of the existing systems in their clinical use have been revealed: a large size of the hemispherical array, impossibility of its mechanical movement relative to the patient's head, limited volume of dynamic focusing around the center of curvature of the array, and side effect of overheating skull. Here we evaluate the possibility of using arrays of smaller size and aperture angles to achieve shock-wave formation at the focus for thermal and mechanical ablation (histotripsy) of brain tissue taking into account current intensity limitations at the array elements. The proposed approach has potential advantages to mitigate the existing limitations and expand the possibilities of transcranial ultrasound surgery.

On how whales avoid decompression sickness and why they sometimes strand.

PubMed

Blix, Arnoldus Schytte; Walløe, Lars; Messelt, Edward B

2013-09-15

Whales are unique in that the supply of blood to the brain is not by the internal carotid arteries, but by way of thoracic and intra-vertebral arterial retia. We found in the harbor porpoise (Phocoena phocoena) that these retia split up into smaller anastomosing vessels and thin-walled sinusoid structures that are embedded in fat. The solubility of nitrogen is at least six times larger in fat than in water, and we suggest that nitrogen in supersaturated blood will be absorbed in the fat, by diffusion, during the very slow passage of the blood through the arterial retia. Formation of nitrogen bubbles that may reach the brain is thereby avoided. We also suggest that mass stranding of whales may be due to disturbances to their normal dive profiles, resulting in extra release of nitrogen that may overburden the nitrogen 'trap' and allow bubbles to reach the brain and cause abnormal behavior.

Brain metabolite alterations in infants born preterm with intrauterine growth restriction: association with structural changes and neurodevelopmental outcome.

PubMed

Simões, Rui V; Muñoz-Moreno, Emma; Cruz-Lemini, Mónica; Eixarch, Elisenda; Bargalló, Núria; Sanz-Cortés, Magdalena; Gratacós, Eduard

2017-01-01

Intrauterine growth restriction and premature birth represent 2 independent problems that may occur simultaneously and contribute to impaired neurodevelopment. The objective of the study was to assess changes in the frontal lobe metabolic profiles of 1 year old intrauterine growth restriction infants born prematurely and adequate-for-gestational-age controls, both premature and term adequate for gestational age and their association with brain structural and biophysical parameters and neurodevelopmental outcome at 2 years. A total of 26 prematurely born intrauterine growth restriction infants (birthweight <10th centile for gestational age), 22 prematurely born but adequate for gestational age controls, and 26 term adequate-for-gestational-age infants underwent brain magnetic resonance imaging and magnetic resonance spectroscopy at 1 year of age during natural sleep, on a 3 Tesla scanner. All brain T1-weighted and diffusion-weighted images were acquired along with short echo time single-voxel proton spectra from the frontal lobe. Magnetic resonance imaging/magnetic resonance spectroscopy data were processed to derive structural, biophysical, and metabolic information, respectively. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales 3rd edition, assessing cognitive, language, motor, socioemotional, and adaptive behavior. Prematurely born intrauterine growth restriction infants had slightly smaller brain volumes and increased frontal lobe white matter mean diffusivity compared with both prematurely born but adequate for gestational age and term adequate for gestational age controls. Frontal lobe N-acetylaspartate levels were significantly lower in prematurely born intrauterine growth restriction than in prematurely born but adequate for gestational age infants but increased in prematurely born but adequate for gestational age compared with term adequate-for-gestational-age infants. The prematurely born intrauterine growth restriction group also showed slightly lower choline compounds, borderline decrements of estimated glutathione levels, and increased myoinositol to choline ratios, compared with prematurely born but adequate for gestational age controls. These specific metabolite changes were locally correlated to lower gray matter content and increased mean diffusivity and reduced white matter fraction and fractional anisotropy. Prematurely born intrauterine growth restriction infants also showed a tendency for poorer neurodevelopmental outcome at 2 years, associated with lower levels of frontal lobe N-acetylaspartate at 1 year within the preterm subset. Preterm intrauterine growth restriction infants showed altered brain metabolite profiles during a critical stage of brain maturation, which correlate with brain structural and biophysical parameters and neurodevelopmental outcome. Our results suggest altered neurodevelopmental trajectories in preterm intrauterine growth restriction and adequate-for-gestational-age infants, compared with term adequate-for-gestational-age infants, which require further characterization. Copyright © 2016 Elsevier Inc. All rights reserved.

Childhood adversity impacts on brain subcortical structures relevant to depression.

PubMed

Frodl, Thomas; Janowitz, Deborah; Schmaal, Lianne; Tozzi, Leonardo; Dobrowolny, Henrik; Stein, Dan J; Veltman, Dick J; Wittfeld, Katharina; van Erp, Theo G M; Jahanshad, Neda; Block, Andrea; Hegenscheid, Katrin; Völzke, Henry; Lagopoulos, Jim; Hatton, Sean N; Hickie, Ian B; Frey, Eva Maria; Carballedo, Angela; Brooks, Samantha J; Vuletic, Daniella; Uhlmann, Anne; Veer, Ilya M; Walter, Henrik; Schnell, Knut; Grotegerd, Dominik; Arolt, Volker; Kugel, Harald; Schramm, Elisabeth; Konrad, Carsten; Zurowski, Bartosz; Baune, Bernhard T; van der Wee, Nic J A; van Tol, Marie-Jose; Penninx, Brenda W J H; Thompson, Paul M; Hibar, Derrek P; Dannlowski, Udo; Grabe, Hans J

2017-03-01

Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression. Copyright © 2016. Published by Elsevier Ltd.

Mycobacteria employ two different mechanisms to cross the blood-brain barrier.

PubMed

van Leeuwen, Lisanne M; Boot, Maikel; Kuijl, Coen; Picavet, Daisy I; van Stempvoort, Gunny; van der Pol, Susanne M A; de Vries, Helga E; van der Wel, Nicole N; van der Kuip, Martijn; van Furth, A Marceline; van der Sar, Astrid M; Bitter, Wilbert

2018-05-10

Central nervous system (CNS) infection by Mycobacterium tuberculosis is one of the most devastating complications of tuberculosis, in particular in early childhood. In order to induce CNS infection, M. tuberculosis needs to cross specialised barriers protecting the brain. How M. tuberculosis crosses the blood-brain barrier (BBB) and enters the CNS is not well understood. Here, we use transparent zebrafish larvae and the closely related pathogen Mycobacterium marinum to answer this question. We show that in the early stages of development, mycobacteria rapidly infect brain tissue, either as free mycobacteria or within circulating macrophages. After the formation of a functionally intact BBB, the infiltration of brain tissue by infected macrophages is delayed, but not blocked, suggesting that crossing the BBB via phagocytic cells is one of the mechanisms used by mycobacteria to invade the CNS. Interestingly, depletion of phagocytic cells did not prevent M. marinum from infecting the brain tissue, indicating that free mycobacteria can independently cause brain infection. Detailed analysis showed that mycobacteria are able to cause vasculitis by extracellular outgrowth in the smaller blood vessels and by infecting endothelial cells. Importantly, we could show that this second mechanism is an active process that depends on an intact ESX-1 secretion system, which extends the role of ESX-1 secretion beyond the macrophage infection cycle. © 2018 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.

What kind of noise is brain noise: anomalous scaling behavior of the resting brain activity fluctuations

PubMed Central

Fraiman, Daniel; Chialvo, Dante R.

2012-01-01

The study of spontaneous fluctuations of brain activity, often referred as brain noise, is getting increasing attention in functional magnetic resonance imaging (fMRI) studies. Despite important efforts, much of the statistical properties of such fluctuations remain largely unknown. This work scrutinizes these fluctuations looking at specific statistical properties which are relevant to clarify its dynamical origins. Here, three statistical features which clearly differentiate brain data from naive expectations for random processes are uncovered: First, the variance of the fMRI mean signal as a function of the number of averaged voxels remains constant across a wide range of observed clusters sizes. Second, the anomalous behavior of the variance is originated by bursts of synchronized activity across regions, regardless of their widely different sizes. Finally, the correlation length (i.e., the length at which the correlation strength between two regions vanishes) as well as mutual information diverges with the cluster's size considered, such that arbitrarily large clusters exhibit the same collective dynamics than smaller ones. These three properties are known to be exclusive of complex systems exhibiting critical dynamics, where the spatio-temporal dynamics show these peculiar type of fluctuations. Thus, these findings are fully consistent with previous reports of brain critical dynamics, and are relevant for the interpretation of the role of fluctuations and variability in brain function in health and disease. PMID:22934058

[Effect of aminothiol anthihypoxants on hydration and peroxidation processes in traumatic brain injury].

PubMed

Novikov, V E; Ponamareva, N S

2007-01-01

The hydration (content of total, bound, and free water) and the activity of lipid peroxidation (LPO) processes in the brain have been studied in rats on the background of traumatic brain injury (TBI) dynamics. It is established that aminothiol-based anthihypoxants such as bemithyl and amthizol in a dose of 25 mg/kg alleviate changes induced by TBI. In particular, the drugs decrease the content of total and free water, increase the level of bound water, and inhibit the LPO intensity in the brain. The effect of drugs is more pronounced on the 4th and 7th day after TBI model induction.

Investigation of brain structure in the 1-month infant.

PubMed

Dean, Douglas C; Planalp, E M; Wooten, W; Schmidt, C K; Kecskemeti, S R; Frye, C; Schmidt, N L; Goldsmith, H H; Alexander, A L; Davidson, R J

2018-05-01

The developing brain undergoes systematic changes that occur at successive stages of maturation. Deviations from the typical neurodevelopmental trajectory are hypothesized to underlie many early childhood disorders; thus, characterizing the earliest patterns of normative brain development is essential. Recent neuroimaging research provides insight into brain structure during late childhood and adolescence; however, few studies have examined the infant brain, particularly in infants under 3 months of age. Using high-resolution structural MRI, we measured subcortical gray and white matter brain volumes in a cohort (N = 143) of 1-month infants and examined characteristics of these volumetric measures throughout this early period of neurodevelopment. We show that brain volumes undergo age-related changes during the first month of life, with the corresponding patterns of regional asymmetry and sexual dimorphism. Specifically, males have larger total brain volume and volumes differ by sex in regionally specific brain regions, after correcting for total brain volume. Consistent with findings from studies of later childhood and adolescence, subcortical regions appear more rightward asymmetric. Neither sex differences nor regional asymmetries changed with gestation-corrected age. Our results complement a growing body of work investigating the earliest neurobiological changes associated with development and suggest that asymmetry and sexual dimorphism are present at birth.

Opioid Abuse after Traumatic Brain Injury: Evaluation Using Rodent Models

DTIC Science & Technology

2015-09-01

depending on the aspect of SA being assessed. This includes time for acclimation to the laboratory and handling, catheterization surgery and recovery, brain...across the three years / total number to be completed by project end. Total # subjects entered into protocol =50 Total number catheterized = 0...and acclimation before intravenous catheterization or pump implantation was performed (see below). Subjects to be used in the warm water tail

Automatic Segmentation of Drosophila Neural Compartments Using GAL4 Expression Data Reveals Novel Visual Pathways.

PubMed

Panser, Karin; Tirian, Laszlo; Schulze, Florian; Villalba, Santiago; Jefferis, Gregory S X E; Bühler, Katja; Straw, Andrew D

2016-08-08

Identifying distinct anatomical structures within the brain and developing genetic tools to target them are fundamental steps for understanding brain function. We hypothesize that enhancer expression patterns can be used to automatically identify functional units such as neuropils and fiber tracts. We used two recent, genome-scale Drosophila GAL4 libraries and associated confocal image datasets to segment large brain regions into smaller subvolumes. Our results (available at https://strawlab.org/braincode) support this hypothesis because regions with well-known anatomy, namely the antennal lobes and central complex, were automatically segmented into familiar compartments. The basis for the structural assignment is clustering of voxels based on patterns of enhancer expression. These initial clusters are agglomerated to make hierarchical predictions of structure. We applied the algorithm to central brain regions receiving input from the optic lobes. Based on the automated segmentation and manual validation, we can identify and provide promising driver lines for 11 previously identified and 14 novel types of visual projection neurons and their associated optic glomeruli. The same strategy can be used in other brain regions and likely other species, including vertebrates. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Structural and metabolic relationships between goldfish brain glycoproteins participating in functional plasticity of the central nervous system.

PubMed

Schmidt, R; Shashoua, V E

1983-03-01

Ependymins beta and gamma (MW 32,000 and 26,000 daltons) are two secreted goldfish brain glycoproteins that exhibit a specifically enhanced turnover rate when the animals successfully acquire a new pattern of swimming behaviour. Both proteins are bound identically to concanavalin A and can be isolated from brain extracellular fluid and from brain cytoplasm by lectin affinity chromatography. Radioimmunoassay data, using purified 125I-labeled ependymins and antisera directed against ependymin beta or ependymin gamma, show complete cross-reactivity between the two proteins. It is demonstrated by Scatchard-plot analysis that the antisera recognize identical immunological determinants in both proteins. The amino acid composition of the ependymins is similar, and several identical polypeptide fragments are obtained after limited proteolysis with Staphylococcus aureus protease. The proteins are capable of forming complexes of the compositions gamma 2, beta gamma, and beta 2. A protease present in the extracellular fluid of goldfish brain promotes proteolysis of ependymin beta to ependymin gamma. The finding that ependymin gamma is physiologically derived from ependymin beta suggests the possibility that ependymin beta might exert its biological function during consolidation of new behavioural patterns via smaller polypeptide fragments.

Caffeine and human cerebral blood flow: A positron emission tomography study

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

Cameron, O.G.; Modell, J.G.; Hariharan, M.

1990-01-01

Positron emission tomography (PET) was used to quantify the effect of caffeine on whole brain and regional cerebral blood flow (CBF) in humans. A mean dose of 250 mg of caffeine produced approximately a 30% decrease in whole brain CBF; regional differences in caffeine effect were not observed. Pre-caffeine CBF strongly influenced the magnitude of the caffeine-induced decrease. Caffeine decreased p{sub a}CO{sub 2} and increased systolic blood pressure significantly; the change in p{sub a}CO{sub 2} did not account for the change in CBF. Smaller increases in diastolic blood pressure, heart rate, plasma epinephrine and norepinephrine, and subjectively reported anxiety weremore » also observed.« less

Evidence for a "metabolically inactive" inorganic phosphate pool in adenosine triphosphate synthase reaction using localized 31P saturation transfer magnetic resonance spectroscopy in the rat brain at 11.7 T.

PubMed

Tiret, Brice; Brouillet, Emmanuel; Valette, Julien

2016-09-01

With the increased spectral resolution made possible at high fields, a second, smaller inorganic phosphate resonance can be resolved on (31)P magnetic resonance spectra in the rat brain. Saturation transfer was used to estimate de novo adenosine triphosphate synthesis reaction rate. While the main inorganic phosphate pool is used by adenosine triphosphate synthase, the second pool is inactive for this reaction. Accounting for this new pool may not only help us understand (31)P magnetic resonance spectroscopy metabolic profiles better but also better quantify adenosine triphosphate synthesis. © The Author(s) 2016.

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.

Random-Walk Model of Diffusion in Three Dimensions in Brain Extracellular Space: Comparison with Microfiberoptic Photobleaching Measurements

PubMed Central

Jin, Songwan; Zador, Zsolt; Verkman, A. S.

2008-01-01

Diffusion through the extracellular space (ECS) in brain is important in drug delivery, intercellular communication, and extracellular ionic buffering. The ECS comprises ∼20% of brain parenchymal volume and contains cell-cell gaps ∼50 nm. We developed a random-walk model to simulate macromolecule diffusion in brain ECS in three dimensions using realistic ECS dimensions. Model inputs included ECS volume fraction (α), cell size, cell-cell gap geometry, intercellular lake (expanded regions of brain ECS) dimensions, and molecular size of the diffusing solute. Model output was relative solute diffusion in water versus brain ECS (Do/D). Experimental Do/D for comparison with model predictions was measured using a microfiberoptic fluorescence photobleaching method involving stereotaxic insertion of a micron-size optical fiber into mouse brain. Do/D for the small solute calcein in different regions of brain was in the range 3.0–4.1, and increased with brain cell swelling after water intoxication. Do/D also increased with increasing size of the diffusing solute, particularly in deep brain nuclei. Simulations of measured Do/D using realistic α, cell size and cell-cell gap required the presence of intercellular lakes at multicell contact points, and the contact length of cell-cell gaps to be least 50-fold smaller than cell size. The model accurately predicted Do/D for different solute sizes. Also, the modeling showed unanticipated effects on Do/D of changing ECS and cell dimensions that implicated solute trapping by lakes. Our model establishes the geometric constraints to account quantitatively for the relatively modest slowing of solute and macromolecule diffusion in brain ECS. PMID:18469079

Random-walk model of diffusion in three dimensions in brain extracellular space: comparison with microfiberoptic photobleaching measurements.

PubMed

Jin, Songwan; Zador, Zsolt; Verkman, A S

2008-08-01

Diffusion through the extracellular space (ECS) in brain is important in drug delivery, intercellular communication, and extracellular ionic buffering. The ECS comprises approximately 20% of brain parenchymal volume and contains cell-cell gaps approximately 50 nm. We developed a random-walk model to simulate macromolecule diffusion in brain ECS in three dimensions using realistic ECS dimensions. Model inputs included ECS volume fraction (alpha), cell size, cell-cell gap geometry, intercellular lake (expanded regions of brain ECS) dimensions, and molecular size of the diffusing solute. Model output was relative solute diffusion in water versus brain ECS (D(o)/D). Experimental D(o)/D for comparison with model predictions was measured using a microfiberoptic fluorescence photobleaching method involving stereotaxic insertion of a micron-size optical fiber into mouse brain. D(o)/D for the small solute calcein in different regions of brain was in the range 3.0-4.1, and increased with brain cell swelling after water intoxication. D(o)/D also increased with increasing size of the diffusing solute, particularly in deep brain nuclei. Simulations of measured D(o)/D using realistic alpha, cell size and cell-cell gap required the presence of intercellular lakes at multicell contact points, and the contact length of cell-cell gaps to be least 50-fold smaller than cell size. The model accurately predicted D(o)/D for different solute sizes. Also, the modeling showed unanticipated effects on D(o)/D of changing ECS and cell dimensions that implicated solute trapping by lakes. Our model establishes the geometric constraints to account quantitatively for the relatively modest slowing of solute and macromolecule diffusion in brain ECS.

Tensor-Based Morphometry Reveals Volumetric Deficits in Moderate=Severe Pediatric Traumatic Brain Injury.

PubMed

Dennis, Emily L; Hua, Xue; Villalon-Reina, Julio; Moran, Lisa M; Kernan, Claudia; Babikian, Talin; Mink, Richard; Babbitt, Christopher; Johnson, Jeffrey; Giza, Christopher C; Thompson, Paul M; Asarnow, Robert F

2016-05-01

Traumatic brain injury (TBI) can cause widespread and prolonged brain degeneration. TBI can affect cognitive function and brain integrity for many years after injury, often with lasting effects in children, whose brains are still immature. Although TBI varies in how it affects different individuals, image analysis methods such as tensor-based morphometry (TBM) can reveal common areas of brain atrophy on magnetic resonance imaging (MRI), secondary effects of the initial injury, which will differ between subjects. Here we studied 36 pediatric moderate to severe TBI (msTBI) participants in the post-acute phase (1-6 months post-injury) and 18 msTBI participants who returned for their chronic assessment, along with well-matched controls at both time-points. Participants completed a battery of cognitive tests that we used to create a global cognitive performance score. Using TBM, we created three-dimensional (3D) maps of individual and group differences in regional brain volumes. At both the post-acute and chronic time-points, the greatest group differences were expansion of the lateral ventricles and reduction of the lingual gyrus in the TBI group. We found a number of smaller clusters of volume reduction in the cingulate gyrus, thalamus, and fusiform gyrus, and throughout the frontal, temporal, and parietal cortices. Additionally, we found extensive associations between our cognitive performance measure and regional brain volume. Our results indicate a pattern of atrophy still detectable 1-year post-injury, which may partially underlie the cognitive deficits frequently found in TBI.

Compensatory Motor Network Connectivity is Associated with Motor Sequence Learning after Subcortical Stroke

PubMed Central

Wadden, Katie P.; Woodward, Todd S.; Metzak, Paul D.; Lavigne, Katie M.; Lakhani, Bimal; Auriat, Angela M.; Boyd, Lara A.

2015-01-01

Following stroke, functional networks reorganize and the brain demonstrates widespread alterations in cortical activity. Implicit motor learning is preserved after stroke. However the manner in which brain reorganization occurs, and how it supports behaviour within the damaged brain remains unclear. In this functional magnetic resonance imaging (fMRI) study, we evaluated whole brain patterns of functional connectivity during the performance of an implicit tracking task at baseline and retention, following 5 days of practice. Following motor practice, a significant difference in connectivity within a motor network, consisting of bihemispheric activation of the sensory and motor cortices, parietal lobules, cerebellar and occipital lobules, was observed at retention. Healthy subjects demonstrated greater activity within this motor network during sequence learning compared to random practice. The stroke group did not show the same level of functional network integration, presumably due to the heterogeneity of functional reorganization following stroke. In a secondary analysis, a binary mask of the functional network activated from the aforementioned whole brain analyses was created to assess within-network connectivity, decreasing the spatial distribution and large variability of activation that exists within the lesioned brain. The stroke group demonstrated reduced clusters of connectivity within the masked brain regions as compared to the whole brain approach. Connectivity within this smaller motor network correlated with repeated sequence performance on the retention test. Increased functional integration within the motor network may be an important neurophysiological predictor of motor learning-related change in individuals with stroke. PMID:25757996

Measurement and Finite Element Model Validation of Immature Porcine Brain-Skull Displacement during Rapid Sagittal Head Rotations.

PubMed

Pasquesi, Stephanie A; Margulies, Susan S

2018-01-01

Computational models are valuable tools for studying tissue-level mechanisms of traumatic brain injury, but to produce more accurate estimates of tissue deformation, these models must be validated against experimental data. In this study, we present in situ measurements of brain-skull displacement in the neonatal piglet head ( n  = 3) at the sagittal midline during six rapid non-impact rotations (two rotations per specimen) with peak angular velocities averaging 51.7 ± 1.4 rad/s. Marks on the sagittally cut brain and skull/rigid potting surfaces were tracked, and peak values of relative brain-skull displacement were extracted and found to be significantly less than values extracted from a previous axial plane model. In a finite element model of the sagittally transected neonatal porcine head, the brain-skull boundary condition was matched to the measured physical experiment data. Despite smaller sagittal plane displacements at the brain-skull boundary, the corresponding finite element boundary condition optimized for sagittal plane rotations is far less stiff than its axial counterpart, likely due to the prominent role of the boundary geometry in restricting interface movement. Finally, bridging veins were included in the finite element model. Varying the bridging vein mechanical behavior over a previously reported range had no influence on the brain-skull boundary displacements. This direction-specific sagittal plane boundary condition can be employed in finite element models of rapid sagittal head rotations.

Body and brain temperature coupling: the critical role of cerebral blood flow

PubMed Central

Ackerman, Joseph J. H.; Yablonskiy, Dmitriy A.

2010-01-01

Direct measurements of deep-brain and body-core temperature were performed on rats to determine the influence of cerebral blood flow (CBF) on brain temperature regulation under static and dynamic conditions. Static changes of CBF were achieved using different anesthetics (chloral hydrate, CH; α-chloralose, αCS; and isoflurane, IF) with αCS causing larger decreases in CBF than CH and IF; dynamic changes were achieved by inducing transient hypercapnia (5% CO2 in 40% O2 and 55% N2). Initial deep-brain/body-core temperature differentials were anesthetic-type dependent with the largest differential observed with rats under αCS anesthesia (ca. 2°C). Hypercapnia induction raised rat brain temperature under all three anesthesia regimes, but by different anesthetic-dependent amounts correlated with the initial differentials—αCS anesthesia resulted in the largest brain temperature increase (0.32 ± 0.08°C), while CH and IF anesthesia lead to smaller increases (0.12 ± 0.03 and 0.16 ± 0.05°C, respectively). The characteristic temperature transition time for the hypercapnia-induced temperature increase was 2–3 min under CH and IF anesthesia and ~4 min under αCS anesthesia. We conclude that both, the deep-brain/body-core temperature differential and the characteristic temperature transition time correlate with CBF: a lower CBF promotes higher deep-brain/body-core temperature differentials and, upon hypercapnia challenge, longer characteristic transition times to increased temperatures. PMID:19277681

Body and brain temperature coupling: the critical role of cerebral blood flow.

PubMed

Zhu, Mingming; Ackerman, Joseph J H; Yablonskiy, Dmitriy A

2009-08-01

Direct measurements of deep-brain and body-core temperature were performed on rats to determine the influence of cerebral blood flow (CBF) on brain temperature regulation under static and dynamic conditions. Static changes of CBF were achieved using different anesthetics (chloral hydrate, CH; alpha-chloralose, alphaCS; and isoflurane, IF) with alphaCS causing larger decreases in CBF than CH and IF; dynamic changes were achieved by inducing transient hypercapnia (5% CO(2) in 40% O(2) and 55% N(2)). Initial deep-brain/body-core temperature differentials were anesthetic-type dependent with the largest differential observed with rats under alphaCS anesthesia (ca. 2 degrees C). Hypercapnia induction raised rat brain temperature under all three anesthesia regimes, but by different anesthetic-dependent amounts correlated with the initial differentials--alphaCS anesthesia resulted in the largest brain temperature increase (0.32 +/- 0.08 degrees C), while CH and IF anesthesia lead to smaller increases (0.12 +/- 0.03 and 0.16 +/- 0.05 degrees C, respectively). The characteristic temperature transition time for the hypercapnia-induced temperature increase was 2-3 min under CH and IF anesthesia and approximately 4 min under alphaCS anesthesia. We conclude that both, the deep-brain/body-core temperature differential and the characteristic temperature transition time correlate with CBF: a lower CBF promotes higher deep-brain/body-core temperature differentials and, upon hypercapnia challenge, longer characteristic transition times to increased temperatures.

Abnormal Hippocampal Morphology in Dissociative Identity Disorder and Posttraumatic Stress Disorder Correlates with Childhood Trauma and Dissociative Symptoms

PubMed Central

Chalavi, Sima; Vissia, Eline M.; Giesen, Mechteld E.; Nijenhuis, Ellert R.S.; Draijer, Nel; Cole, James H.; Dazzan, Paola; Pariante, Carmine M.; Madsen, Sarah K.; Rajagopalan, Priya; Thompson, Paul M.; Toga, Arthur W.; Veltman, Dick J.; Reinders, Antje A.T.S.

2015-01-01

Smaller hippocampal volume has been reported in individuals with posttraumatic stress disorder (PTSD) and dissociative identity disorder (DID), but the regional specificity of hippocampal volume reductions and the association with severity of dissociative symptoms and/or childhood traumatization are still unclear. Brain structural MRI scans were analyzed for 33 outpatients (17 with DID and 16 with PTSD only) and 28 healthy controls (HC), all matched for age, sex, and education. DID patients met criteria for PTSD (PTSD-DID). Hippocampal global and subfield volumes and shape measurements were extracted. We found that global hippocampal volume was significantly smaller in all 33 patients (left: 6.75%; right: 8.33%) compared to HC. PTSD-DID (left: 10.19%; right: 11.37%) and PTSD-only with a history of childhood traumatization (left: 7.11%; right: 7.31%) had significantly smaller global hippocampal volume relative to HC. PTSD-DID had abnormal shape and significantly smaller volume in the CA2-3, CA4-DG and (pre)subiculum compared to HC. In the patient groups, smaller global and subfield hippocampal volumes significantly correlated with higher severity of childhood traumatization and dissociative symptoms. These findings support a childhood trauma-related etiology for abnormal hippocampal morphology in both PTSD and DID and can further the understanding of neurobiological mechanisms involved in these disorders. PMID:25545784

Abnormal hippocampal morphology in dissociative identity disorder and post-traumatic stress disorder correlates with childhood trauma and dissociative symptoms.

PubMed

Chalavi, Sima; Vissia, Eline M; Giesen, Mechteld E; Nijenhuis, Ellert R S; Draijer, Nel; Cole, James H; Dazzan, Paola; Pariante, Carmine M; Madsen, Sarah K; Rajagopalan, Priya; Thompson, Paul M; Toga, Arthur W; Veltman, Dick J; Reinders, Antje A T S

2015-05-01

Smaller hippocampal volume has been reported in individuals with post-traumatic stress disorder (PTSD) and dissociative identity disorder (DID), but the regional specificity of hippocampal volume reductions and the association with severity of dissociative symptoms and/or childhood traumatization are still unclear. Brain structural magnetic resonance imaging scans were analyzed for 33 outpatients (17 with DID and 16 with PTSD only) and 28 healthy controls (HC), all matched for age, sex, and education. DID patients met criteria for PTSD (PTSD-DID). Hippocampal global and subfield volumes and shape measurements were extracted. We found that global hippocampal volume was significantly smaller in all 33 patients (left: 6.75%; right: 8.33%) compared with HC. PTSD-DID (left: 10.19%; right: 11.37%) and PTSD-only with a history of childhood traumatization (left: 7.11%; right: 7.31%) had significantly smaller global hippocampal volume relative to HC. PTSD-DID had abnormal shape and significantly smaller volume in the CA2-3, CA4-DG and (pre)subiculum compared with HC. In the patient groups, smaller global and subfield hippocampal volumes significantly correlated with higher severity of childhood traumatization and dissociative symptoms. These findings support a childhood trauma-related etiology for abnormal hippocampal morphology in both PTSD and DID and can further the understanding of neurobiological mechanisms involved in these disorders. © 2014 Wiley Periodicals, Inc.

Effects of different components of Mao Dongqing's total flavonoids and total saponins on transient ischemic attack (TIA) model of rats.

PubMed

Miao, Ming-San; Peng, Meng-Fan; Ma, Rui-Juan; Bai, Ming; Liu, Bao-Song

2018-03-01

Objective: To study the effects of the different components of the total flavonoids and total saponins from Mao Dongqing's active site on the rats of TIA model, determine the optimal reactive components ratio of Mao Dongqing on the rats of TIA. Methods: TIA rat model was induced by tail vein injection of tert butyl alcohol, the blank group was injected with the same amount of physiological saline, then behavioral score wasevaluated. Determination the level of glutamic acid in serum, the activity of Na+-K+-ATP enzyme, CA ++ -ATP enzyme and Mg ++ -ATP enzyme in Brain tissue, observe the changes of hippocampus in brain tissue, the comprehensive weight method was used to evaluate the efficacy of each component finally. Results: The contents of total flavonoids and total saponins in the active part of Mao Dongqing can significantly improve the pathological changes of brain tissue in rats, improve the activity of Na + -K + -ATP enzyme, Ca ++ -ATP enzyme and Mg ++ -ATP enzyme in the brain of rats, and reduce the level of glutamic acid in serum. The most significant of the contents was the ratio of 10:6. The different proportions of total flavonoids and total saponins in the active part of Mao Dongqing all has a better effect on the rats with TIA, and the ratio of 10:6 is the best active component for preventing and controlling TIA.

[Effect of centrophenoxine, piracetam and aniracetam on the monoamine oxidase activity in different brain structures of rats].

PubMed

Stancheva, S L; Alova, L G

1988-01-01

In vitro studies of effects of some nootropic drugs (centrophenoxine, piracetam and aniracetam) on monoamine oxidase (MAO) activity in the rat striatum and hypothalamus, using tyramine, serotonin and beta-phenylethylamine as substrates, were carried out. At all concentrations used (5.10(-5)-1.10(-3) M) centrophenoxine inhibited total MAO, MAO A and MAO B in both brain structures. Piracetam activated striatal and hypothalamic total MAO, hypothalamic MAO A and MAO B but exerted a pronounced inhibitory effect on MAO A and MAO B activity in the striatum. Aniracetam inhibited total MAO and MAO A in both brain structures but activated striatal and hypothalamic MAO B. The different effects of centrophenoxine, piracetam and aniracetam on MAO activity in the brain structures support the view for the independent mode of action of nootropic drugs in spite of their similar molecular and metabolic activity.

Iris melanocyte numbers in Asian, African American, and Caucasian irides.

PubMed Central

Albert, Daniel M; Green, W Richard; Zimbric, Michele L; Lo, Cecilia; Gangnon, Ronald E; Hope, Kirsten L; Gleiser, Joel

2003-01-01

PURPOSE: The anatomical basis for iris color has long been a controversial issue in ophthalmology. Recent studies demonstrated that in Caucasians, blue-eyed, gray-eyed, and hazel-eyed individuals have comparable numbers of iris melanocytes. The present investigation was carried out to compare melanocyte numbers in the irides of Asian, African American, and Caucasian brown-eyed individuals. METHODS: Paraffin-embedded sections from 71 brown-colored irides were incubated with rabbit anti-cow antibody against S100a, linked with an FITC conjugate antibody, and counterstained with Evans blue. Cells were counted under a fluorescence microscope and scored as melanocytes or other cells. Cell number, density, and iris area were calculated for each specimen. RESULTS: Caucasian and African American irides had comparable mean total melanocyte numbers. Asian irides had fewer total melanocytes than African American (P = .042) and Caucasian (P = .001) irides and smaller total number of cells (ie, melanocytes plus other cells) than African American (P = .054) or Caucasian (P = .009) irides. CONCLUSIONS: There is a statistically significant smaller mean total melanocyte number and mean total cellularity in Asian irides as compared to Caucasian and African American irides. This difference appears to be due to the combination of smaller iris area and lower melanocyte density in the Asian irides. The possibility exists that this may be a factor in ethnic variations in certain ocular diseases. PMID:14971580

Stress and inflammation reduce brain-derived neurotrophic factor expression in first-episode psychosis: a pathway to smaller hippocampal volume.

PubMed

Mondelli, Valeria; Cattaneo, Annamaria; Murri, Martino Belvederi; Di Forti, Marta; Handley, Rowena; Hepgul, Nilay; Miorelli, Ana; Navari, Serena; Papadopoulos, Andrew S; Aitchison, Katherine J; Morgan, Craig; Murray, Robin M; Dazzan, Paola; Pariante, Carmine M

2011-12-01

Reduced brain-derived neurotrophic factor (BDNF) levels have been reported in the serum and plasma of patients with psychosis. The aim of this cross-sectional case-control study was to investigate potential causes and consequences of reduced BDNF expression in these patients by examining the association between BDNF levels and measures of stress, inflammation, and hippocampal volume in first-episode psychosis. Brain-derived neurotrophic factor, interleukin (IL)-6, and tumor necrosis factor (TNF)-α messenger RNA levels were measured in the leukocytes of 49 first-episode psychosis patients (DSM-IV criteria) and 30 healthy controls, all aged 18 to 65 years, recruited between January 2006 and December 2008. Patients were recruited from inpatient and outpatient units of the South London and Maudsley National Health Service Foundation Trust in London, United Kingdom, and the healthy controls were recruited from the same catchment area via advertisement and volunteer databases. In these same subjects, we measured salivary cortisol levels and collected information about psychosocial stressors (number of childhood traumas, number of recent stressors, and perceived stress). Finally, hippocampal volume was measured using brain magnetic resonance imaging in a subsample of 19 patients. Patients had reduced BDNF (effect size, d = 1.3; P < .001) and increased IL-6 (effect size, d = 1.1; P < .001) and TNF-α (effect size, d = 1.7; P < .001) gene expression levels when compared with controls, as well as higher levels of psychosocial stressors. A linear regression analysis in patients showed that a history of childhood trauma and high levels of recent stressors predicted lower BDNF expression through an inflammation-mediated pathway (adjusted R(2) = 0.23, P = .009). In turn, lower BDNF expression, increased IL-6 expression, and increased cortisol levels all significantly and independently predicted a smaller left hippocampal volume (adjusted R(2) = 0.71, P < .001). Biological changes activated by stress represent a significant factor influencing brain structure and function in first-episode psychosis through an effect on BDNF. © Copyright 2011 Physicians Postgraduate Press, Inc.

Volumetric Magnetic Resonance Imaging Study of Brain and Cerebellum in Children with Cerebral Palsy

PubMed Central

Maciorkowska, Elżbieta; Gościk, Elżbieta

2016-01-01

Introduction. Quantitative magnetic resonance imaging (MRI) studies are rarely used in the diagnosis of patients with cerebral palsy. The aim of present study was to assess the relationships between the volumetric MRI and clinical findings in children with cerebral palsy compared to control subjects. Materials and Methods. Eighty-two children with cerebral palsy and 90 age- and sex-matched healthy controls were collected. Results. The dominant changes identified on MRI scans in children with cerebral palsy were periventricular leukomalacia (42%) and posthemorrhagic hydrocephalus (21%). The total brain and cerebellum volumes in children with cerebral palsy were significantly reduced in comparison to controls. Significant grey matter volume reduction was found in the total brain in children with cerebral palsy compared with the control subjects. Positive correlations between the age of the children of both groups and the grey matter volumes in the total brain were found. Negative relationship between width of third ventricle and speech development was found in the patients. Positive correlations were noted between the ventricles enlargement and motor dysfunction and mental retardation in children with cerebral palsy. Conclusions. By using the voxel-based morphometry, the total brain, cerebellum, and grey matter volumes were significantly reduced in children with cerebral palsy. PMID:27579318

Volumetric Magnetic Resonance Imaging Study of Brain and Cerebellum in Children with Cerebral Palsy.

PubMed

Kułak, Piotr; Maciorkowska, Elżbieta; Gościk, Elżbieta

2016-01-01

Introduction. Quantitative magnetic resonance imaging (MRI) studies are rarely used in the diagnosis of patients with cerebral palsy. The aim of present study was to assess the relationships between the volumetric MRI and clinical findings in children with cerebral palsy compared to control subjects. Materials and Methods. Eighty-two children with cerebral palsy and 90 age- and sex-matched healthy controls were collected. Results. The dominant changes identified on MRI scans in children with cerebral palsy were periventricular leukomalacia (42%) and posthemorrhagic hydrocephalus (21%). The total brain and cerebellum volumes in children with cerebral palsy were significantly reduced in comparison to controls. Significant grey matter volume reduction was found in the total brain in children with cerebral palsy compared with the control subjects. Positive correlations between the age of the children of both groups and the grey matter volumes in the total brain were found. Negative relationship between width of third ventricle and speech development was found in the patients. Positive correlations were noted between the ventricles enlargement and motor dysfunction and mental retardation in children with cerebral palsy. Conclusions. By using the voxel-based morphometry, the total brain, cerebellum, and grey matter volumes were significantly reduced in children with cerebral palsy.

[Personality Change due to Brain Trauma Caused by Traffic Accidents and Its Assessment of Psychiatric Impairment].

PubMed

Fan, Hui-yu; Zhang, Qin-ting; Tang, Tao; Cai, Wei-xiong

2016-04-01

To explore the main performance of personality change in people with mild psychiatric impairments which due to the brain trauma caused by traffic accidents and its value in assessment of psychiatric impairment. The condition of personality change of patients with traumatic brain injury caused by traffic accident was evaluated by the Scale of Personality Change Post-traumatic Brain Injury (SPCPTBI). Furthermore, the correlation between the personality change and the degrees of traumatic brain injury and psychiatric impairment were explored. Results In 271 samples, 239 (88.2%) with personality changes. Among these 239 samples, 178 (65.7%), 46 (17.0%), 15 (5.5%) with mild, moderate and severe personality changes, respectively. The ratio based on the extent of personality changes to the degree of brain trauma was not significant (P > 0.05), but the total score difference between the groups was significant (P < 0.05). There was no statistical significance between the medium and high severity brain trauma groups. The higher degree of personality changes, the higher rank of mental disabilities. The total score difference of the scale of personality change among the different mild psychiatric impairment group was significant (P<0.05). The difference between other psychiatric impairment levels had statistical significance (P < 0.05) except level 7 and 8. The occurrence of personality change due to traumatic brain injury caused by traffic accident was high. Correlations exist between the personality change and the degree of psychiatric impairment. Personality change due to brain trauma caused by traffic accident can be assessed effectively by means of SPCPTBI, and the correlation between the total score and the extent of traumatic brain injury can be found.

Nonlinear analysis of saccade speed fluctuations during combined action and perception tasks

PubMed Central

Stan, C.; Astefanoaei, C.; Pretegiani, E.; Optican, L.; Creanga, D.; Rufa, A.; Cristescu, C.P.

2014-01-01

Background: Saccades are rapid eye movements used to gather information about a scene which requires both action and perception. These are usually studied separately, so that how perception influences action is not well understood. In a dual task, where the subject looks at a target and reports a decision, subtle changes in the saccades might be caused by action-perception interactions. Studying saccades might provide insight into how brain pathways for action and for perception interact. New method: We applied two complementary methods, multifractal detrended fluctuation analysis and Lempel-Ziv complexity index to eye peak speed recorded in two experiments, a pure action task and a combined action-perception task. Results: Multifractality strength is significantly different in the two experiments, showing smaller values for dual decision task saccades compared to simple-task saccades. The normalized Lempel-Ziv complexity index behaves similarly i.e. is significantly smaller in the decision saccade task than in the simple task. Comparison with existing methods: Compared to the usual statistical and linear approaches, these analyses emphasize the character of the dynamics involved in the fluctuations and offer a sensitive tool for quantitative evaluation of the multifractal features and of the complexity measure in the saccades peak speeds when different brain circuits are involved. Conclusion: Our results prove that the peak speed fluctuations have multifractal characteristics with lower magnitude for the multifractality strength and for the complexity index when two neural pathways are simultaneously activated, demonstrating the nonlinear interaction in the brain pathways for action and perception. PMID:24854830

Differences in Brain Adaptive Functional Reorganization in Right and Left Total Brachial Plexus Injury Patients.

PubMed

Feng, Jun-Tao; Liu, Han-Qiu; Xu, Jian-Guang; Gu, Yu-Dong; Shen, Yun-Dong

2015-09-01

Total brachial plexus avulsion injury (BPAI) results in the total functional loss of the affected limb and induces extensive brain functional reorganization. However, because the dominant hand is responsible for more cognitive-related tasks, injuries on this side induce more adaptive changes in brain function. In this article, we explored the differences in brain functional reorganization after injuries in unilateral BPAI patients. We applied resting-state functional magnetic resonance imaging scanning to 10 left and 10 right BPAI patients and 20 healthy control subjects. The amplitude of low-frequency fluctuation (ALFF), which is a resting-state index, was calculated for all patients as an indication of the functional activity level of the brain. Two-sample t-tests were performed between left BPAI patients and controls, right BPAI patients and controls, and between left and right BPAI patients. Two-sample t-tests of the ALFF values revealed that right BPAIs induced larger scale brain reorganization than did left BPAIs. Both left and right BPAIs elicited a decreased ALFF value in the right precuneus (P < 0.05, Alphasim corrected). In addition, right BPAI patients exhibited increased ALFF values in a greater number of brain regions than left BPAI patients, including the inferior temporal gyrus, lingual gyrus, calcarine sulcus, and fusiform gyrus. Our results revealed that right BPAIs induced greater extents of brain functional reorganization than left BPAIs, which reflected the relatively more extensive adaptive process that followed injuries of the dominant hand. Copyright © 2015 Elsevier Inc. All rights reserved.

Readmission to an Acute Care Hospital During Inpatient Rehabilitation for Traumatic Brain Injury.

PubMed

Hammond, Flora M; Horn, Susan D; Smout, Randall J; Beaulieu, Cynthia L; Barrett, Ryan S; Ryser, David K; Sommerfeld, Teri

2015-08-01

To assess the incidence of, causes for, and factors associated with readmission to an acute care hospital (RTAC) during inpatient rehabilitation for traumatic brain injury (TBI). Prospective observational cohort. Inpatient rehabilitation. Individuals with TBI admitted consecutively for inpatient rehabilitation (N=2130). Not applicable. RTAC incidence, RTAC causes, rehabilitation length of stay (RLOS), and rehabilitation discharge location. A total of 183 participants (9%) experienced RTAC for a total of 210 episodes. Of 183 participants, 161 patients experienced 1 RTAC episode, 17 had 2, and 5 had 3. The mean time from rehabilitation admission to first RTAC was 22±22 days. The mean duration in acute care during RTAC was 7±8 days. Eighty-four participants (46%) had ≥1 RTAC episodes for medical reasons, 102 (56%) had ≥1 RTAC episodes for surgical reasons, and 6 (3%) participants had RTAC episodes for unknown reasons. Most common surgical RTAC reasons were neurosurgical (65%), pulmonary (9%), infection (5%), and orthopedic (5%); most common medical reasons were infection (26%), neurological (23%), and cardiac (12%). Any RTAC was predicted as more likely for patients with older age, history of coronary artery disease, history of congestive heart failure, acute care diagnosis of depression, craniotomy or craniectomy during acute care, and presence of dysphagia at rehabilitation admission. RTAC was less likely for patients with higher admission FIM motor scores and education less than high school diploma. RTAC occurrence during rehabilitation was significantly associated with longer RLOS and smaller likelihood of discharge home. Approximately 9% of patients with TBI experienced RTAC episodes during inpatient rehabilitation for various medical and surgical reasons. This information may help inform interventions aimed at reducing interruptions in rehabilitation for RTAC. RTACs were associated with longer RLOS and discharge to an institutional setting. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The anti-oxidant and anti-apoptotic effects of nebivolol and zofenopril in a model of cerebral ischemia/reperfusion in rats.

PubMed

Uzar, Ertuğrul; Acar, Abdullah; Evliyaoğlu, Osman; Fırat, Uğur; Kamasak, Kağan; Göçmez, Cüneyt; Alp, Harun; Tüfek, Adnan; Taşdemir, Nebahat; Ilhan, Atilla

2012-01-10

The aim of this experiment was to investigate whether nebivolol and zofenopril have protective effects against oxidative damage and apoptosis induced by cerebral ischemia/reperfusion (I/R). There were seven groups of rats, with each containing eight rats. The groups were: the control group, I/R group, I/R plus zofenopril, I/R plus nebivolol, I/R plus nebivolol and zofenopril, zofenopril only and nebivolol only. Cerebral I/R was induced by clamping the bilateral common carotid artery and through hypotension. The rats were sacrificed 1h after ischemia, and histopathological and biochemical analyses were carried out on their brains. The total antioxidant capacity was evaluated by using an automated and colorimetric measurement method developed by Erel. I/R produced a significant increase in the levels of total oxidant status and malondialdehyde levels, the number of caspase-3 immunopositive cells and activities of prolidase and paraoxonase in brain when compared with the control group (p<0.05). A significant decrease in brain total antioxidant capacity and nitric oxide levels were found in I/R group when compared with the control group (p<0.05). Both nebivolol and zofenopril treatment prevented decreasing of the total antioxidant capacity and nitric oxide levels, produced by I/R in the brain (p<0.05). Both nebivolol and zofenopril treatment prevented the total oxidant status, malondialdehyde levels, activities of paraoxonase and prolidase from increasing in brains of rats exposed to I/R (p<0.05). In conclusion, both nebivolol and zofenopril protected rats from ischemia-induced brain injury. The protection may be due to the indirect prevention of oxidative stress and apoptosis. Copyright © 2011 Elsevier Inc. All rights reserved.

Macro- and Microstructural Magnetic Resonance Imaging Indices Associated With Diabetes Among Community-Dwelling Older Adults

PubMed Central

Falvey, Cherie M.; Rosano, Caterina; Simonsick, Eleanor M.; Harris, Tamara; Strotmeyer, Elsa S.; Satterfield, Suzanne; Yaffe, Kristine

2013-01-01

OBJECTIVE To better understand the association between diabetes and cognitive impairment, we evaluated macro- and microstructural brain MRI measures for the total brain and regions of interest (ROIs) in a group of community-dwelling elders with and without diabetes. RESEARCH DESIGN AND METHODS MRI measures were obtained on 308 elders (mean age 83.3 years; n = 85 with diabetes) from the Health ABC Healthy Brain Substudy. We performed a series of linear regressions and used standardized β values to estimate the cross-sectional association between diabetes and macrostructural (gray matter volume [GMV] and white matter hyperintensities [WMHs]) and microstructural (mean diffusivity [MD] and fractional anisotropy [FA]) measures for the total brain and ROIs. Models were adjusted for age, race, and sex; GMV values for ROIs were also adjusted for total brain volume (TBV). RESULTS In multivariate-adjusted models, diabetes was associated with lower total GMV (P = 0.0006), GMV in the putamen (P = 0.02 for left and right), and TBV (P = 0.04) and greater cerebral atrophy (P = 0.02). There was no association with WMHs. On microstructural measures, diabetes was associated with reduced FA for total white matter (P = 0.006) and greater MD for the hippocampus (P = 0.006 left; P = 0.01 right), dorsolateral prefrontal cortex (P = 0.0007, left; P = 0.002, right), left posterior cingulate (P = 0.02), and right putamen (P = 0.02). Further adjustment for stroke, hypertension, and myocardial infarction produced similar results. CONCLUSIONS In this cross-sectional study, elders with diabetes compared with those without had greater brain atrophy and early signs of neurodegeneration. Further studies are needed to determine whether these structural changes associated with diabetes predict risk of cognitive decline. PMID:23160721

Prefoldin and Pins synergistically regulate asymmetric division and suppress dedifferentiation

PubMed Central

Zhang, Yingjie; Rai, Madhulika; Wang, Cheng; Gonzalez, Cayetano; Wang, Hongyan

2016-01-01

Prefoldin is a molecular chaperone complex that regulates tubulin function in mitosis. Here, we show that Prefoldin depletion results in disruption of neuroblast polarity, leading to neuroblast overgrowth in Drosophila larval brains. Interestingly, co-depletion of Prefoldin and Partner of Inscuteable (Pins) leads to the formation of gigantic brains with severe neuroblast overgrowth, despite that Pins depletion alone results in smaller brains with partially disrupted neuroblast polarity. We show that Prefoldin acts synergistically with Pins to regulate asymmetric division of both neuroblasts and Intermediate Neural Progenitors (INPs). Surprisingly, co-depletion of Prefoldin and Pins also induces dedifferentiation of INPs back into neuroblasts, while depletion either Prefoldin or Pins alone is insufficient to do so. Furthermore, knocking down either α-tubulin or β-tubulin in pins- mutant background results in INP dedifferentiation back into neuroblasts, leading to the formation of ectopic neuroblasts. Overexpression of α-tubulin suppresses neuroblast overgrowth observed in prefoldin pins double mutant brains. Our data elucidate an unexpected function of Prefoldin and Pins in synergistically suppressing dedifferentiation of INPs back into neural stem cells. PMID:27025979

Altered resting brain function and structure in professional badminton players.

PubMed

Di, Xin; Zhu, Senhua; Jin, Hua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan; Rao, Hengyi

2012-01-01

Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills.

Overexpression of Thioredoxin in Transgenic Mice Attenuates Focal Ischemic Brain Damage

NASA Astrophysics Data System (ADS)

Takagi, Yasushi; Mitsui, Akira; Nishiyama, Akira; Nozaki, Kazuhiko; Sono, Hiroshi; Gon, Yasuhiro; Hashimoto, Nobuo; Yodoi, Junji

1999-03-01

Thioredoxin (TRX) plays important biological roles both in intra- and extracellular compartments, including in regulation of various intracellular molecules via thiol redox control. We produced TRX overexpressing mice and confirmed that there were no anatomical and physiological differences between wild-type (WT) mice and TRX transgenic (Tg) mice. In the present study we subjected mice to focal brain ischemia to shed light on the role of TRX in brain ischemic injury. At 24 hr after middle cerebral artery occlusion, infarct areas and volume were significantly smaller in Tg mice than in WT mice. Moreover neurological deficit was ameliorated in Tg mice compared with WT mice. Protein carbonyl content, a marker of cellular protein oxidation, in Tg mice showed less increase than did that of WT mice after the ischemic insult. Furthermore, c-fos expression in Tg mice was stronger than in WT mice 1 hr after ischemia. Our results suggest that transgene expression of TRX decreased ischemic neuronal injury and that TRX and the redox state modified by TRX play a crucial role in brain damage during stroke.

Earliest Cranio-Encephalic Trauma from the Levantine Middle Palaeolithic: 3D Reappraisal of the Qafzeh 11 Skull, Consequences of Pediatric Brain Damage on Individual Life Condition and Social Care

PubMed Central

Coqueugniot, Hélène; Dutour, Olivier; Arensburg, Baruch; Duday, Henri; Vandermeersch, Bernard; Tillier, Anne-marie

2014-01-01

The Qafzeh site (Lower Galilee, Israel) has yielded the largest Levantine hominin collection from Middle Palaeolithic layers which were dated to circa 90–100 kyrs BP or to marine isotope stage 5b–c. Within the hominin sample, Qafzeh 11, circa 12–13 yrs old at death, presents a skull lesion previously attributed to a healed trauma. Three dimensional imaging methods allowed us to better explore this lesion which appeared as being a frontal bone depressed fracture, associated with brain damage. Furthermore the endocranial volume, smaller than expected for dental age, supports the hypothesis of a growth delay due to traumatic brain injury. This trauma did not affect the typical human brain morphology pattern of the right frontal and left occipital petalia. It is highly probable that this young individual suffered from personality and neurological troubles directly related to focal cerebral damage. Interestingly this young individual benefited of a unique funerary practice among the south-western Asian burials dated to Middle Palaeolithic. PMID:25054798

Correlation analysis for the incubation period of prion disease.

PubMed

Bae, Se-Eun; Jung, Sunghoon; Kim, Ha-Yeon; Son, Hyeon S

2012-07-01

Previous studies have shown that genetic quantitative trait loci (QTL), strain barriers, inoculation dose and inoculation method modulate the incubation period of prion diseases. We examined the relationship between a diverse set of physical, genetic and immunological characteristics and the incubation period of prion disease using correlation analyses. We found that incubation period was highly correlated with brain weight. In addition, mean corpuscular volume and cell size were strongly correlated with incubation period, indicating that the physical magnitude of prion-infected organs or individual cells may be important in determining the incubation period. Given the same prion inoculation dose, animals with a lower brain weight, mean corpuscular volume or cell size may experience more virulent disease, as the effective concentration of abnormal prion, which might regulate the attachment rate of prions to aggregates, is increased with smaller capacity of brains and cells. This is partly consistent with previous theoretical modeling. The strong correlations between incubation period and physical properties of the brain and cells in this study suggest that the mechanism underlying prion disease pathology may be physical, indicating that the incubation process is governed by simple chemical stoichiometry.

High brain distribution of a new central nervous system drug candidate despite its P-glycoprotein-mediated efflux at the mouse blood-brain barrier.

PubMed

Taccola, Camille; Cartot-Cotton, Sylvaine; Valente, Delphine; Barneoud, Pascal; Aubert, Catherine; Boutet, Valérie; Gallen, Fabienne; Lochus, Murielle; Nicolic, Sophie; Dodacki, Agnès; Smirnova, Maria; Cisternino, Salvatore; Declèves, Xavier; Bourasset, Fanchon

2018-05-30

Efficacy of drugs aimed at treating central nervous system (CNS) disorders rely partly on their ability to cross the cerebral endothelium, also called the blood-brain barrier (BBB), which constitutes the main interface modulating exchanges of compounds between the brain and blood. In this work, we used both, conventional pharmacokinetics (PK) approach and in situ brain perfusion technique to study the blood and brain PK of PKRinh, an inhibitor of the double-stranded RNA-dependent protein kinase (PKR) activation, in mice. PKRinh showed a supra dose-proportional blood exposure that was not observed in the brain, and a brain to blood AUC ratio of unbound drug smaller than 1 at all tested doses. These data suggested the implication of an active efflux at the BBB. Using in situ brain perfusion technique, we showed that PKRinh has a very high brain uptake clearance which saturates with increasing concentrations. Fitting the data to a Michaelis-Menten equation revealed that PKRinh transport through the BBB is composed of a passive unsaturable flux and an active saturable protein-mediated efflux with a k m of ≅ 3 μM. We were able to show that the ATP-binding cassette (ABC) transporter P-gp (Abcb1), but not Bcrp (Abcg2), was involved in the brain to blood efflux of PKRinh. At the circulating PKRinh concentrations of this study, the P-gp was not saturated, in accordance with the linear brain PKRinh PK. Finally, PKRinh had high brain uptake clearance (14 μl/g/s) despite it is a good P-gp substrate (P-gp Efflux ratio ≅ 3.6), and reached similar values than the cerebral blood flow reference, diazepam, in P-gp saturation conditions. With its very unique brain transport properties, PKRinh improves our knowledge about P-gp-mediated efflux across the BBB for the development of new CNS directed drugs. Copyright © 2018. Published by Elsevier B.V.

Effect of growth hormone deficiency on brain structure, motor function and cognition.

PubMed

Webb, Emma A; O'Reilly, Michelle A; Clayden, Jonathan D; Seunarine, Kiran K; Chong, Wui K; Dale, Naomi; Salt, Alison; Clark, Chris A; Dattani, Mehul T

2012-01-01

The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone <6.7 µg/l) and idiopathic short stature (peak growth hormone >10 µg/l) underwent cognitive assessment, diffusion tensor imaging and volumetric magnetic resonance imaging prior to commencing growth hormone treatment. Total brain, corpus callosal, hippocampal, thalamic and basal ganglia volumes were determined using Freesurfer. Fractional anisotropy (a marker of white matter structural integrity) images were aligned and tract-based spatial statistics performed. Fifteen children (mean 8.8 years of age) with isolated growth hormone deficiency [peak growth hormone <6.7 µg/l (mean 3.5 µg/l)] and 14 controls (mean 8.4 years of age) with idiopathic short stature [peak growth hormone >10 µg/l (mean 15 µg/l) and normal growth rate] were recruited. Compared with controls, children with isolated growth hormone deficiency had lower Full-Scale IQ (P < 0.01), Verbal Comprehension Index (P < 0.01), Processing Speed Index (P < 0.05) and Movement-Assessment Battery for Children (P < 0.008) scores. Verbal Comprehension Index scores correlated significantly with insulin-like growth factor-1 (P < 0.03) and insulin-like growth factor binding protein-3 (P < 0.02) standard deviation scores in isolated growth hormone deficiency. The splenium of the corpus callosum, left globus pallidum, thalamus and hippocampus (P < 0.01) were significantly smaller; and corticospinal tract (bilaterally; P < 0.045, P < 0.05) and corpus callosum (P < 0.05) fractional anisotropy were significantly lower in the isolated growth hormone deficiency group. Basal ganglia volumes and bilateral corticospinal tract fractional anisotropy correlated significantly with Movement-Assessment Battery for Children scores, and corpus callosum fractional anisotropy with Full-Scale IQ and Processing Speed Index. In patients with isolated growth hormone deficiency, white matter abnormalities in the corpus callosum and corticospinal tract, and reduced thalamic and globus pallidum volumes relate to deficits in cognitive function and motor performance. Follow-up studies that investigate the course of the structural and cognitive deficits on growth hormone treatment are now required to confirm that growth hormone deficiency impacts significantly on brain structure, cognitive function and motor performance.

N-Terminal Pro-B-Type Natriuretic Peptide and Subclinical Brain Damage in the General Population.

PubMed

Zonneveld, Hazel I; Ikram, M Arfan; Hofman, Albert; Niessen, Wiro J; van der Lugt, Aad; Krestin, Gabriel P; Franco, Oscar H; Vernooij, Meike W

2017-04-01

Purpose To investigate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP), which is a marker of heart disease, and markers of subclinical brain damage on magnetic resonance (MR) images in community-dwelling middle-aged and elderly subjects without dementia and without a clinical diagnosis of heart disease. Materials and Methods This prospective population-based cohort study was approved by a medical ethics committee overseen by the national government, and all participants gave written informed consent. Serum levels of NT-proBNP were measured in 2397 participants without dementia or stroke (mean age, 56.6 years; age range, 45.7-87.3 years) and without clinical diagnosis of heart disease who were drawn from the population-based Rotterdam Study. All participants were examined with a 1.5-T MR imager. Multivariable linear and logistic regression analyses were used to investigate the association between NT-proBNP level and MR imaging markers of subclinical brain damage, including volumetric, focal, and microstructural markers. Results A higher NT-proBNP level was associated with smaller total brain volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.021; 95% confidence interval [CI]: -0.034, -0.007; P = .003) and was predominantly driven by gray matter volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.037; 95% CI: -0.057, -0.017; P < .001). Higher NT-proBNP level was associated with larger white matter lesion volume (mean difference in z score per standard deviation increase in NT-proBNP level, 0.090; 95% CI: 0.051, 0.129; P < .001), with lower fractional anisotropy (mean difference in z score per standard deviation increase in NT-proBNP level, -0.048; 95% CI: -0.088, -0.008; P = .019) and higher mean diffusivity (mean difference in z score per standard deviation increase in NT-proBNP level, 0.054; 95% CI: 0.018, 0.091; P = .004) of normal-appearing white matter. Conclusion In community-dwelling persons, higher serum NT-proBNP levels are associated with volumetric and microstructural MR imaging markers of subclinical brain damage. © RSNA, 2016 Online supplemental material is available for this article.

Chronic sucrose intake decreases concentrations of n6 fatty acids, but not docosahexaenoic acid in the rat brain phospholipids.

PubMed

Mašek, Tomislav; Starčević, Kristina

2017-07-13

We investigated the influence of high sucrose intake, administered in drinking water, on the lipid profile of the brain and on the expression of SREBP1c and Δ-desaturase genes. Adult male rats received 30% sucrose solution for 20 weeks (Sucrose group), or plain water (Control group). After the 20th week of sucrose treatment, the Sucrose group showed permanent hyperglycemia. Sucrose treatment also increased the amount of total lipids and fatty acids in the brain. The brain fatty acid profile of total lipids as well as phosphatidylethanolamine, phosphatidylcholine and cardiolipin of the Sucrose group was extensively changed. The most interesting change was a significant decrease in n6 fatty acids, including the important arachidonic acid, whereas the content of oleic and docosahexaenoic acid remained unchanged. RT-qPCR revealed an increase in Δ-5-desaturase and SREBP1c gene expression. In conclusion, high sucrose intake via drinking water extensively changes rat brain fatty acid profile by decreasing n6 fatty acids, including arachidonic acid. In contrast, the content of docosahexaenoic acid remains constant in the brain total lipids as well as in phospholipids. Changes in the brain fatty acid profile reflect changes in the lipid metabolism of the rat lipogenic tissues and concentrations in the circulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Tau Processing by Mural Cells in Traumatic Brain Injury and Alzheimer’s Disease

DTIC Science & Technology

2017-10-01

Cerebrovessels were treated with recombinant human tau (5ng/ml) for 1 hour at 37oC and total tau uptake was assessed in the lysates via ELISA . We observed a...to 5ng/ml recombinant human tau (rhtau-441) for 1 hour at 37oC. Lysates were analyzed for total tau content by ELISA and normalized to total protein...and 6 months post-last injury). Brain vessels were analyzed for PDGFRβ and α-SMC-actin content by ELISA and normalized to total protein using the

Semi-automated brain tumor and edema segmentation using MRI.

PubMed

Xie, Kai; Yang, Jie; Zhang, Z G; Zhu, Y M

2005-10-01

Manual segmentation of brain tumors from magnetic resonance images is a challenging and time-consuming task. A semi-automated method has been developed for brain tumor and edema segmentation that will provide objective, reproducible segmentations that are close to the manual results. Additionally, the method segments non-enhancing brain tumor and edema from healthy tissues in magnetic resonance images. In this study, a semi-automated method was developed for brain tumor and edema segmentation and volume measurement using magnetic resonance imaging (MRI). Some novel algorithms for tumor segmentation from MRI were integrated in this medical diagnosis system. We exploit a hybrid level set (HLS) segmentation method driven by region and boundary information simultaneously, region information serves as a propagation force which is robust and boundary information serves as a stopping functional which is accurate. Ten different patients with brain tumors of different size, shape and location were selected, a total of 246 axial tumor-containing slices obtained from 10 patients were used to evaluate the effectiveness of segmentation methods. This method was applied to 10 non-enhancing brain tumors and satisfactory results were achieved. Two quantitative measures for tumor segmentation quality estimation, namely, correspondence ratio (CR) and percent matching (PM), were performed. For the segmentation of brain tumor, the volume total PM varies from 79.12 to 93.25% with the mean of 85.67+/-4.38% while the volume total CR varies from 0.74 to 0.91 with the mean of 0.84+/-0.07. For the segmentation of edema, the volume total PM varies from 72.86 to 87.29% with the mean of 79.54+/-4.18% while the volume total CR varies from 0.69 to 0.85 with the mean of 0.79+/-0.08. The HLS segmentation method perform better than the classical level sets (LS) segmentation method in PM and CR. The results of this research may have potential applications, both as a staging procedure and a method of evaluating tumor response during treatment, this method can be used as a clinical image analysis tool for doctors or radiologists.

Evidence of second-trimester changes in head biometry and brain perfusion in fetuses with congenital heart disease.

PubMed

Masoller, N; Martínez, J M; Gómez, O; Bennasar, M; Crispi, F; Sanz-Cortés, M; Egaña-Ugrinovic, G; Bartrons, J; Puerto, B; Gratacós, E

2014-08-01

To evaluate the associations between congenital heart disease (CHD) and head biometry and cerebrovascular blood flow dynamics at the time of diagnosis of CHD in the second trimester of pregnancy. This was a study of 95 consecutive fetuses diagnosed with CHD. At the time of diagnosis, fetal biometry was performed and brain perfusion was assessed by middle cerebral artery pulsatility index (MCA-PI), cerebroplacental ratio (CPR) and fractional moving blood volume (FMBV). The results were compared with those of 95 normal fetuses matched for gestational age. Median gestational age at diagnosis was 22 + 3 (range, 20 + 0 to 23 + 5) weeks. Fetuses with CHD showed significantly lower MCA-PI and CPR Z-scores (-0.23 vs 0.34 and -0.37 vs 0.30, respectively; both P < 0.001) and higher FMBV Z-scores (2.35 vs 0.15; P < 0.001). FMBV > 95(th) percentile was observed in 81.1% of cases as compared with 10.5% in controls (P < 0.001). Moreover, cases showed significantly smaller biparietal diameter (BPD) and head circumference (HC) Z-scores (-1.61 vs -0.43 and -0.89 vs 0.09, respectively; both P < 0.001), with a higher proportion of BPD and HC measurements below the 5(th) percentile compared with controls (51.6% vs 13.7% and 26.3% vs 4.2%, respectively; both P < 0.001). These findings were more pronounced in those cases with types of CHD associated with compromised oxygenated blood delivery to the brain, such as left outflow tract obstruction and transposition of the great arteries. A high proportion of fetuses with CHD have a smaller head and increased brain perfusion already in the second trimester, suggesting an early onset of the mechanisms leading to poorer neurodevelopment later in life. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Optimizing the learning rate for adaptive estimation of neural encoding models

PubMed Central

2018-01-01

Closed-loop neurotechnologies often need to adaptively learn an encoding model that relates the neural activity to the brain state, and is used for brain state decoding. The speed and accuracy of adaptive learning algorithms are critically affected by the learning rate, which dictates how fast model parameters are updated based on new observations. Despite the importance of the learning rate, currently an analytical approach for its selection is largely lacking and existing signal processing methods vastly tune it empirically or heuristically. Here, we develop a novel analytical calibration algorithm for optimal selection of the learning rate in adaptive Bayesian filters. We formulate the problem through a fundamental trade-off that learning rate introduces between the steady-state error and the convergence time of the estimated model parameters. We derive explicit functions that predict the effect of learning rate on error and convergence time. Using these functions, our calibration algorithm can keep the steady-state parameter error covariance smaller than a desired upper-bound while minimizing the convergence time, or keep the convergence time faster than a desired value while minimizing the error. We derive the algorithm both for discrete-valued spikes modeled as point processes nonlinearly dependent on the brain state, and for continuous-valued neural recordings modeled as Gaussian processes linearly dependent on the brain state. Using extensive closed-loop simulations, we show that the analytical solution of the calibration algorithm accurately predicts the effect of learning rate on parameter error and convergence time. Moreover, the calibration algorithm allows for fast and accurate learning of the encoding model and for fast convergence of decoding to accurate performance. Finally, larger learning rates result in inaccurate encoding models and decoders, and smaller learning rates delay their convergence. The calibration algorithm provides a novel analytical approach to predictably achieve a desired level of error and convergence time in adaptive learning, with application to closed-loop neurotechnologies and other signal processing domains. PMID:29813069

Optimizing the learning rate for adaptive estimation of neural encoding models.

PubMed

Hsieh, Han-Lin; Shanechi, Maryam M

2018-05-01

Closed-loop neurotechnologies often need to adaptively learn an encoding model that relates the neural activity to the brain state, and is used for brain state decoding. The speed and accuracy of adaptive learning algorithms are critically affected by the learning rate, which dictates how fast model parameters are updated based on new observations. Despite the importance of the learning rate, currently an analytical approach for its selection is largely lacking and existing signal processing methods vastly tune it empirically or heuristically. Here, we develop a novel analytical calibration algorithm for optimal selection of the learning rate in adaptive Bayesian filters. We formulate the problem through a fundamental trade-off that learning rate introduces between the steady-state error and the convergence time of the estimated model parameters. We derive explicit functions that predict the effect of learning rate on error and convergence time. Using these functions, our calibration algorithm can keep the steady-state parameter error covariance smaller than a desired upper-bound while minimizing the convergence time, or keep the convergence time faster than a desired value while minimizing the error. We derive the algorithm both for discrete-valued spikes modeled as point processes nonlinearly dependent on the brain state, and for continuous-valued neural recordings modeled as Gaussian processes linearly dependent on the brain state. Using extensive closed-loop simulations, we show that the analytical solution of the calibration algorithm accurately predicts the effect of learning rate on parameter error and convergence time. Moreover, the calibration algorithm allows for fast and accurate learning of the encoding model and for fast convergence of decoding to accurate performance. Finally, larger learning rates result in inaccurate encoding models and decoders, and smaller learning rates delay their convergence. The calibration algorithm provides a novel analytical approach to predictably achieve a desired level of error and convergence time in adaptive learning, with application to closed-loop neurotechnologies and other signal processing domains.

Brain Pressure Monitoring

NASA Technical Reports Server (NTRS)

1977-01-01

A transducer originally used to measure air pressure in aircraft wind tunnel tests is the basis for a development important in diagnosis and treatment of certain types of brain damage. A totally implantable device, tbe intracranial pressure monitor measures and reports brain pressure by telemetry.

Effects of peripubertal gonadotropin-releasing hormone agonist on brain development in sheep--a magnetic resonance imaging study.

PubMed

Nuruddin, Syed; Bruchhage, Muriel; Ropstad, Erik; Krogenæs, Anette; Evans, Neil P; Robinson, Jane E; Endestad, Tor; Westlye, Lars T; Madison, Cindee; Haraldsen, Ira Ronit Hebold

2013-10-01

In many species sexual dimorphisms in brain structures and functions have been documented. In ovine model, we have previously demonstrated that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) action increased sex-differences of executive emotional behavior. The structural substrate of this behavioral alteration however is unknown. In this magnetic resonance image (MRI) study on the same animals, we investigated the effects of GnRH agonist (GnRHa) treatment on the volume of total brain, hippocampus and amygdala. In total 41 brains (17 treated; 10 females and 7 males, and 24 controls; 11 females and 13 males) were included in the MRI study. Image acquisition was performed with 3-T MRI scanner. Segmentation of the amygdala and the hippocampus was done by manual tracing and total gray and white matter volumes were estimated by means of automated brain volume segmentation of the individual T2-weighted MRI volumes. Statistical comparisons were performed with general linear models. Highly significant GnRHa treatment effects were found on the volume of left and right amygdala, indicating larger amygdalae in treated animals. Significant sex differences were found for total gray matter and right amygdala, indicating larger volumes in male compared to female animals. Additionally, we observed a significant interaction between sex and treatment on left amygdala volume, indicating stronger effects of treatment in female compared to male animals. The effects of GnRHa treatment on amygdala volumes indicate that increasing GnRH concentration during puberty may have an important impact on normal brain development in mammals. These novel findings substantiate the need for further studies investigating potential neurobiological side effects of GnRHa treatment on the brains of young animals and humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats.

PubMed

Kopjar, Nevenka; Žunec, Suzana; Mendaš, Gordana; Micek, Vedran; Kašuba, Vilena; Mikolić, Anja; Lovaković, Blanka Tariba; Milić, Mirta; Pavičić, Ivan; Čermak, Ana Marija Marjanović; Pizent, Alica; Lucić Vrdoljak, Ana; Želježić, Davor

2018-01-05

In this 28 day-study, we evaluated the effects of the insecticide chlorpyrifos orally administered to Wistar rats at doses 0.160, 0.015, and 0.010 mg/kg b. w./day. Following treatment, total cholinesterase activity and activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were measured. Oxidative stress responses were evaluated using a battery of endpoints to establish lipid peroxidation, changes in total antioxidant capacity, level of reactive oxygen species (ROS), glutathione (GSH) level and activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase. Using HPLC-UV DAD analysis, levels of the parent compound and its main metabolite 3,5,6-trichloro-2-pyridinol in plasma and brain tissue were measured. The genotoxic effect was estimated using alkaline comet assay in leukocytes and brain tissue. The exposure did not result in significant effects on total cholinesterase, AChE and BChE activity in plasma and brain tissue. Lipid peroxidation slightly increased both in plasma and brain tissue. Total antioxidant capacity, ROS and GSH levels were marginally influenced by the exposure. Treatment led to significant increases of GSH-Px activity in blood, SOD activity in erythrocytes and a slight increase of catalase activity in plasma. HPLC-UV DAD analysis revealed the presence of both the parent compound and its main metabolite in the plasma of all of the experimental animals and brain tissue of the animals treated at the two higher doses. All of the tested doses of chlorpyrifos were slightly genotoxic, both to leukocytes and brain tissue. Our results call for further research using other sensitive biomarkers of effect, along with different exposure scenarios. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of passive permeability at the blood-tumor barrier in five preclinical models of brain metastases of breast cancer

PubMed Central

Adkins, Chris E.; Mohammad, Afroz S.; Terrell-Hall, Tori; Dolan, Emma L.; Shah, Neal; Sechrest, Emily; Griffith, Jessica; Lockman, Paul R.

2016-01-01

The blood brain barrier (BBB) is compromised in brain metastases, allowing for enhanced drug permeation into brain. The extent and heterogeneity of BBB permeability in metastatic lesions is important when considering the administration of chemotherapeutics. Since permeability characteristics have been described in limited experimental models of brain metastases, we sought to define these changes in five brain-tropic breast cancer cell lines: MDA-MB-231BR (triple negative), MDA-MB-231BR-HER2, JIMT-1-BR3, 4T1-BR5 (murine), and SUM190 (inflammatory HER2 expressing). Permeability was assessed using quantitative autoradiography and fluorescence microscopy by co-administration of the tracers 14C-aminoisobutyric acid (AIB) and Texas Red conjugated dextran (TRD) prior to euthanasia. Each experimental brain metastases model produced variably increased permeability to both tracers; additionally, the magnitude of heterogeneity was different among each model with the highest ranges observed in the SUM190 (up to 45-fold increase in AIB) and MDA-MB-231BR-HER2 (up to 33-fold in AIB) models while the lowest range was observed in the JIMT-1-BR3 (up to 5.5-fold in AIB) model. There was no strong correlation observed between lesion size and permeability in any of these preclinical models of brain metastases. Interestingly, the experimental models resulting in smaller mean metastases size resulted in shorter median survival while models producing larger lesions had longer median survival. These findings strengthen the evidence of heterogeneity in brain metastases of breast cancer by utilizing five unique experimental models and simultaneously emphasize the challenges of chemotherapeutic approaches to treat brain metastases. PMID:26944053

Variability of the cranial and dental phenotype in Williams syndrome.

PubMed

Axelsson, Stefan

2005-01-01

Williams syndrome (WS) is a rare congenital disorder involving the cardiovascular system, connective tissue, and the central nervous system, resulting in mild to moderate mental retardation, a specific cognitive profile, unique personality characteristics, distinctive facial features, and cardiovascular disease. The majority of individuals with a clinical diagnosis of WS have a contiguous gene deletion at chromosome 7 (7q11.23). Physical features include characteristic facial features with full prominent cheeks, wide mouth, long philtrum, small nose with depressed nasal bridge, heavy orbital ridges, medial eyebrow flare, dental abnormalities, hoarse voice, growth retardation, and cardiovascular abnormalities (most commonly supravalvular aortic stenosis and/or peripheral pulmonary artery stenosis). The cognitive profile is distinctive, consisting of strengths in auditory memory, language, and face-processing, but extreme weakness in visuospatial, numerical and problem-solving abilities. Neurological studies have identified a significantly decreased brain volume in adult individuals with WS with relatively normal development of the limbic, frontal and cerebellar structures. The aims were to analyse the neurocranium, the craniofacial region, and the dentition in a well defined Norwegian group of individuals with WS. In order to accomplish this, normative cephalometric standards for the neurocranium, including the cranial base and the sella turcica, were established for Norwegian males and females from 6 to 21 years of age, using lateral radiographic cephalograms from the Oslo University Craniofacial Growth Archive. The study material comprised radiographic lateral cephalograms, orthopantomograms and dental casts from 62 individuals with WS ranging from 4 to 44 years. The lateral cephalograms, orthopantomograms and dental casts were analysed using standard methods reported in the literature. Neurocranium: The results from the cephalometric analyses showed that the size and shape of the neurocranium in WS differed from normal controls. A flattening of the superior aspect of the parietal bone was found and the posterior prominence of the occipital bone was larger. These findings were in concordance with published neuroanatomical/neuropathological studies on WS and fit well with the reported anatomical aberrations in the WS brain, e.g. a smaller brain volume where some parts are of relatively normal size while others are decreased. The anterior and posterior cranial base was shorter in WS, but with a normal cranial base angle. The thickness of the calvarian bones, especially the frontal and occipital bones, was greater in WS than in normal controls. Sella turcica: The size of the sella turcica was somewhat smaller in WS compared with normal controls, though not significant. Aberrant types of shape of the sella turcica in WS are demonstrated. The correlation between prenatal malformation in the pituitary gland/sella turcica and the postnatal morphology of the sella turcica is discussed. The craniofacial skeleton: Two areas, in addition to the cranial base, have been identified to contribute to the characteristic facial appearance in WS; the anterior inclination of the maxilla, and the shape of the mandible. The severely deficient bony chin in combination with the high mandibular plane angle can explain earlier clinical descriptions of a retrusive mandible in WS. Frequent mouth breathing during childhood and the smaller cranial base may be associated with the characteristic craniofacial pattern. Dentition: In individuals with WS over 10 years of age 40.5 per cent had agenesis of one or more permanent teeth and 11.9 percent had agenesis of 6 teeth or more. The missing permanent teeth in the maxilla most commonly included 2nd premolars, 1st premolars, and lateral incisors. In the mandible most commonly 2nd premolars, 1st premolars, and central incisors were absent. The tooth crowns of permanent teeth were smaller, both in the mesio-distal and labio-lingual dimension. The permanent tooth crowns have several characteristic deviations from normal shape; especially incisors in both jaws were tapered or screwdriver-shaped. An evaluation of taurodontism on permanent molars was performed. However, most of the molars rated as being taurodontic had short total tooth lengths and could thus be rated taurodontic without meeting the classical definition. These studies have shown aberrations in the neurocranium including the sella turcica in WS not previously reported. In the craniofacial skeleton specific traits have been identified to contribute to the characteristic facial appearance in WS. Dental aberrations in the permanent dentition including agenesis, smaller size, and aberrant shape of teeth, are common in WS.

A Score to Identify Patients with Brain Metastases from Colorectal Cancer Who May Benefit from Whole-brain Radiotherapy in Addition to Stereotactic Radiosurgery/Radiotherapy.

PubMed

Rades, Dirk; Dziggel, Liesa; Blanck, Oliver; Gebauer, Niklas; Bartscht, Tobias; Schild, Steven E

2018-05-01

To design a tool to predict the probability of new cerebral lesions after stereotactic radiosurgery/radiotherapy for patients with 1-3 brain metastases from colorectal cancer. In 21 patients, nine factors were evaluated for freedom from new brain metastases, namely age, gender, Karnofsky performance score (KPS), tumor type, number, maximum total diameter of all lesions and sites of cerebral lesions, extra-cranial metastases, and time from cancer diagnosis to irradiation. Freedom from new lesions was positively associated with KPS of 90-100 (p=0.013); maximum total diameter ≤15 mm showed a trend for positive association (p=0.09). Points were assigned as: KPS 70-80=1 point, KPS 90-100=2 points, maximum diameter ≤15 mm=2 points and maximum diameter >15 mm=1 point. Six-month rates of freedom from new lesions were 29%, 45% and 100% for those with total scores of 2, 3 and 4 points, respectively, with corresponding 12-month rates of 0%, 45% and 100% (p=0.027). This study identified three risk groups regarding new brain metastases after stereotactic irradiation. Patients with 2 points could benefit from additional whole-brain radiotherapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Where's Waldo? The 'decapitation gambit' and the definition of death.

PubMed

Lizza, John P

2011-12-01

The 'decapitation gambit' holds that, if physical decapitation normally entails the death of the human being, then physiological decapitation, evident in cases of total brain failure, entails the death of the human being. This argument has been challenged by Franklin Miller and Robert Truog, who argue that physical decapitation does not necessarily entail the death of human beings and that therefore, by analogy, artificially sustained human bodies with total brain failure are living human beings. They thus challenge the current neurological criterion for determining death and argue for a return to the traditional criterion of the irreversible loss of circulation and respiration. In this paper, I defend the decapitation gambit and total brain failure as a criterion for determining death against Miller and Truog's criticism.

Smaller Dentate Gyrus and CA2 and CA3 Volumes Are Associated with Kynurenine Metabolites in Collegiate Football Athletes.

PubMed

Meier, Timothy B; Savitz, Jonathan; Singh, Rashmi; Teague, T Kent; Bellgowan, Patrick S F

2016-07-15

An imbalance in kynurenine pathway metabolism is hypothesized to be associated with dysregulated glutamatergic neurotransmission, which has been proposed as a mechanism underlying the hippocampal volume loss observed in a variety of neurological disorders. Pre-clinical models suggest that the CA2-3 and dentate gyrus hippocampal subfields are particularly susceptible to excitotoxicity after experimental traumatic brain injury. We tested the hypothesis that smaller hippocampal volumes in collegiate football athletes with (n = 25) and without (n = 24) a concussion history would be most evident in the dentate gyrus and CA2-3 subfields relative to nonfootball healthy controls (n = 27). Further, we investigated whether the concentration of peripheral levels of kynurenine metabolites are altered in football athletes. Football athletes with and without a self-reported concussion history had smaller dentate gyrus (p < 0.05, p < 0.10) and CA2-3 volumes (p's < 0.05) relative to healthy controls. Football athletes with and without a concussion history had a trend toward lower (p < 0.10) and significantly lower (p < 0.05) kynurenine levels compared with healthy controls, while athletes with a concussion history had greater levels of quinolinic acid compared with athletes without a concussion history (p < 0.05). Finally, plasma levels of 3-hydroxykynurenine inversely correlated with bilateral hippocampal volumes in football athletes with a concussion history (p < 0.01), and left hippocampal volume was correlated with the ratio of kynurenic acid to quinolinic acid in football athletes without a concussion history (p < 0.05). Our results raise the possibility that abnormalities of the kynurenine metabolic pathway constitute a mechanism for hippocampal volume differences in the context of sports-related brain injury.

Progression of cognitive impairment in stroke/TIA patients over 3 years.

PubMed

Sachdev, Perminder S; Lipnicki, Darren M; Crawford, John D; Wen, Wei; Brodaty, Henry

2014-12-01

To examine how cognitive deficits progress in the years following a stroke or transient ischaemic attack (TIA). A follow-up study, with neuropsychological and MRI assessments undertaken 3 years after baseline assessments made 3-6 months poststroke in 183 stroke/TIA patients and 97 healthy controls participating in the Sydney Stroke Study. Additional measures included cardiovascular risk factors and apolipoprotein E (APOE) genotype. Stroke/TIA patients had poorer cognitive function and more vascular risk factors than controls at baseline, but did not show greater decline in cognitive function over 3 years except for verbal memory. Patients with a subsequent stroke/TIA showed greater decline in global cognitive function and a number of domains. Rates of incident dementia were 5.9% per year in patients and 0.4% in controls. Both groups showed increased atrophy of the hippocampus, amygdala and whole brain, and an increase in white matter hyperintensities over 3 years; whole brain atrophy was greater in patients. Cognitive decline was greater in women and in those with smaller hippocampi at baseline. For patients without a subsequent stroke/TIA, those with smaller hippocampi or the APOE ε4 allele had greater global cognitive and verbal memory decline. In poststroke patients, cognitive decline was not greater than in comparison subjects, except for verbal memory, unless they had another stroke/TIA. However, dementia incidence was higher in patients, as might be expected from their poorer baseline cognitive functioning. Smaller hippocampi were associated with an increased risk of decline in memory, and APOE ε4 was a risk factor in those without a subsequent stroke/TIA. 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.

Smaller Dentate Gyrus and CA2 and CA3 Volumes Are Associated with Kynurenine Metabolites in Collegiate Football Athletes

PubMed Central

Savitz, Jonathan; Singh, Rashmi; Teague, T. Kent; Bellgowan, Patrick S.F.

2016-01-01

Abstract An imbalance in kynurenine pathway metabolism is hypothesized to be associated with dysregulated glutamatergic neurotransmission, which has been proposed as a mechanism underlying the hippocampal volume loss observed in a variety of neurological disorders. Pre-clinical models suggest that the CA2-3 and dentate gyrus hippocampal subfields are particularly susceptible to excitotoxicity after experimental traumatic brain injury. We tested the hypothesis that smaller hippocampal volumes in collegiate football athletes with (n = 25) and without (n = 24) a concussion history would be most evident in the dentate gyrus and CA2-3 subfields relative to nonfootball healthy controls (n = 27). Further, we investigated whether the concentration of peripheral levels of kynurenine metabolites are altered in football athletes. Football athletes with and without a self-reported concussion history had smaller dentate gyrus (p < 0.05, p < 0.10) and CA2-3 volumes (p's < 0.05) relative to healthy controls. Football athletes with and without a concussion history had a trend toward lower (p < 0.10) and significantly lower (p < 0.05) kynurenine levels compared with healthy controls, while athletes with a concussion history had greater levels of quinolinic acid compared with athletes without a concussion history (p < 0.05). Finally, plasma levels of 3-hydroxykynurenine inversely correlated with bilateral hippocampal volumes in football athletes with a concussion history (p < 0.01), and left hippocampal volume was correlated with the ratio of kynurenic acid to quinolinic acid in football athletes without a concussion history (p < 0.05). Our results raise the possibility that abnormalities of the kynurenine metabolic pathway constitute a mechanism for hippocampal volume differences in the context of sports-related brain injury. PMID:26493952

Physiological roles of trehalose in Leptinotarsa larvae revealed by RNA interference of trehalose-6-phosphate synthase and trehalase genes.

PubMed

Shi, Ji-Feng; Xu, Qing-Yu; Sun, Qiang-Kun; Meng, Qing-Wei; Mu, Li-Li; Guo, Wen-Chao; Li, Guo-Qing

2016-10-01

Trehalose is proposed to serve multiple physiological roles in insects. However, its importance remains largely unconfirmed. In the present paper, we knocked down either a trehalose biosynthesis gene (trehalose-6-phosphate synthase, LdTPS) or each of three degradation genes (soluble trehalases LdTRE1a, LdTRE1b or membrane-bound LdTRE2) in Leptinotarsa decemlineata by RNA interference (RNAi). Knockdown of LdTPS decreased trehalose content and caused larval and pupal lethality. The LdTPS RNAi survivors consumed a greater amount of foliage, obtained a heavier body mass, accumulated more glycogen, lipid and proline, and had a smaller amount of chitin compared with the controls. Ingestion of trehalose but not glucose rescued the food consumption increase and larval mass rise, increased survivorship, and recovered glycogen, lipid and chitin to the normal levels. In contrast, silencing of LdTRE1a increased trehalose content and resulted in larval and pupal lethality. The surviving LdTRE1a RNAi hypomorphs fed a smaller quantity of food, had a lighter body weight, depleted lipid and several glucogenic amino acids, and contained a smaller amount of chitin. Neither trehalose nor glucose ingestion rescued these LdTRE1a RNAi defects. Silencing of LdTRE1b caused little effects. Knockdown of LdTRE2 caused larval death, increased trehalose contents in several tissues and diminished glycogen in the brain-corpora cardiaca-corpora allata complex (BCC). Feeding glucose but not trehalose partially rescued the high mortality rate and recovered glycogen content in the BCC. It seems that trehalose is involved in feeding regulation, sugar absorption, brain energy supply and chitin biosynthesis in L. decemlineata larvae. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Antiepileptic Drug Levetiracetam Suppresses Non-Convulsive Seizure Activity and Reduces Ischemic Brain Damage in Rats Subjected to Permanent Middle Cerebral Artery Occlusion

PubMed Central

Cuomo, Ornella; Rispoli, Vincenzo; Leo, Antonio; Politi, Giovanni Bosco; Vinciguerra, Antonio; di Renzo, Gianfranco; Cataldi, Mauro

2013-01-01

The antiepileptic drug Levetiracetam (Lev) has neuroprotective properties in experimental stroke, cerebral hemorrhage and neurotrauma. In these conditions, non-convulsive seizures (NCSs) propagate from the core of the focal lesion into perilesional tissue, enlarging the damaged area and promoting epileptogenesis. Here, we explore whether Lev neuroprotective effect is accompanied by changes in NCS generation or propagation. In particular, we performed continuous EEG recordings before and after the permanent occlusion of the middle cerebral artery (pMCAO) in rats that received Lev (100 mg/kg) or its vehicle immediately before surgery. Both in Lev-treated and in control rats, EEG activity was suppressed after pMCAO. In control but not in Lev-treated rats, EEG activity reappeared approximately 30-45 min after pMCAO. It initially consisted in single spikes and, then, evolved into spike-and-wave and polyspike-and-wave discharges. In Lev-treated rats, only rare spike events were observed and the EEG power was significantly smaller than in controls. Approximately 24 hours after pMCAO, EEG activity increased in Lev-treated rats because of the appearance of polyspike events whose power was, however, significantly smaller than in controls. In rats sacrificed 24 hours after pMCAO, the ischemic lesion was approximately 50% smaller in Lev-treated than in control rats. A similar neuroprotection was observed in rats sacrificed 72 hours after pMCAO. In conclusion, in rats subjected to pMCAO, a single Lev injection suppresses NCS occurrence for at least 24 hours. This electrophysiological effect could explain the long lasting reduction of ischemic brain damage caused by this drug. PMID:24236205

Dysarthria associated with traumatic brain injury: speaking rate and emphatic stress.

PubMed

Wang, Yu-Tsai; Kent, Ray D; Duffy, Joseph R; Thomas, Jack E

2005-01-01

Prosodic abnormality is common in the dysarthria associated with traumatic brain injury (TBI), and adjustments of speaking rate and emphatic stress are often used as steps in treating the speech disorder in patients with TBI-induced dysarthria. However, studies to date do not present a clear and detailed picture of how speaking rate and emphatic stress are affected in this speech disorder. This study, based on the acoustic analyses of syllable repetitions and sentence speech samples, reports on speaking rate and emphatic stress for 12 subjects with TBI and 8 healthy controls. For speaking rate, the subjects with TBI had (1) both slow speaking and articulation rates, (2) smaller phonation proportion and larger pause proportion, and (3) larger percentage change in speaking rate and smaller percentage change in articulation rate. For emphatic stress, the subjects with TBI had (1) significant increases in the difference and percentage change between pre-stressed and pre-unstressed pause durations, (2) significantly smaller difference between stressed and unstressed word durations, but not the percentage change between stressed and unstressed word durations, and (3) significantly reduced differences in f(0) movement and f(0) slope between stressed and unstressed words, but not in RMS range. This study demonstrates the multidimensional nature of prosodic deficits in the dysarthria related to TBI and illustrates the ability of acoustic measures to give a picture of the dysprosody related to TBI-induced dysarthria. As a result of this activity, the participant will be able to (1) describe the prosodic disturbances that have been reported in studies of dysarthria associated with TBI; (2) define acoustic measures appropriate to the analysis of changes in speaking rate and emphatic stress; and (3) discuss the importance of prosody to spoken communication.

Potential effect of skull thickening on the associations between cognition and brain atrophy in ageing.

PubMed

Aribisala, Benjamin Segun; Royle, Natalie A; Valdés Hernández, Maria C; Murray, Catherine; Penke, Lars; Gow, Alan; Maniega, Susana Muñoz; Starr, John M; Bastin, Mark; Deary, Ian; Wardlaw, Joanna

2014-09-01

intracranial volume (ICV) is commonly used as a marker of premorbid brain size in neuroimaging studies as it is thought to remain fixed throughout adulthood. However, inner skull table thickening would encroach on ICV and could mask actual brain atrophy. we investigated the effect that thickening might have on the associations between brain atrophy and cognition. the sample comprised 57 non-demented older adults who underwent structural brain MRI at mean age 72.7 ± 0.7 years and were assessed on cognitive ability at mean age 11 and 73 years. Principal component analysis was used to derive factors of general cognitive ability (g), information processing speed and memory from the recorded cognitive ability data. The total brain tissue volume and ICV with (estimated original ICV) and without (current ICV) adjusting for the effects of inner table skull thickening were measured. General linear modelling was used to test for associations. all cognitive ability variables were significantly (P < 0.01) associated with percentage total brain volume in ICV measured without adjusting for skull thickening (g: η(2) = 0.177, speed: η(2) = 0.264 and memory: η(2) = 0.132). After accounting for skull thickening, only speed was significantly associated with percentage total brain volume in ICV (η(2) = 0.085, P = 0.034), not g or memory. not accounting for skull thickening when computing ICV can distort the association between brain atrophy and cognitive ability in old age. Larger samples are required to determine the true effect. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Socialization of prosocial behavior: Gender differences in the mediating role of child brain volume.

PubMed

Kok, Rianne; Prinzie, Peter; Bakermans-Kranenburg, Marian J; Verhulst, Frank C; White, Tonya; Tiemeier, Henning; van IJzendoorn, Marinus H

2018-08-01

Evidence has been accumulating for the impact of normal variation in caregiving quality on brain morphology in children, but the question remains whether differences in brain volume related to early caregiving translate to behavioral implications. In this longitudinal population-based study (N = 162), moderated mediation was tested for the relation between parental sensitivity and child prosocial behavior via brain volume, in boys and girls. Both maternal and paternal sensitivity were repeatedly observed between 1 and 4 years of age. Brain volume was assessed using magnetic resonance imaging measurements at age 8, and self-reported prosocial behavior of children was assessed at 9 years of age. Parental sensitivity was positively related to child brain volume, and to child prosocial behavior at trend level. Child brain volume was negatively related to child prosocial behavior. A significant gender-by-brain interaction was found, illustrating that daughters of sensitive parents were more prosocial and that less prosocial behavior was reported for girls with a larger total brain volume. Child gender significantly moderated the indirect effect of parental sensitivity on prosocial behavior via total brain volume. A significant indirect pathway was found only in girls. The results warrant replication but indicate the importance of considering gender when studying the behavioral implications of differences in brain volume related to early caregiving experiences.

[Levels of unified metabolites and thyroid hormones in blood and oral fluid of children with minimal brain dysfunction].

PubMed

Gil'miiarova, F N; Pervova, Iu V; Radomskaia, V M; Gergel', N I; Tarasova, S V

2004-01-01

Minimal brain dysfunctions in children with various perinatal complications are accompanied by metabolic imbalance manifested by decreased total protein content, the tendency to reduced triglycerides, increased cholesterol concentrations in the oral fluid, the trend to hypoproteinaemia, hypoglycaemia, hypotriglyceridaemia. The most significant changes in the redox systems alpha-ketoglutarate-glutamate, oxaloacetate-malate, pyruvate-lactate, dioxyacetone phosphate-alpha-glycerophosphate in biological fluids were revealed in cases of antenatal alcoholisation. A certain correlation was found between anemia in pregnant women and hypothyroidal background in children. In addition, a high level of free and total thyroxine, that of total triiodthyronine were found in the oral fluid. Hypophysis--thyroid dysregulation in children with minimal brain dysfunction associated with gestosis in their mothers during pregnancy, was manifested by decreased content of total and free T4 and T3 in blood serum and increased level of the thyroid-stimulating hormone.

Expression and characterization of a brain-specific protein kinase BSK146 from zebrafish.

PubMed

Chou, Chih-Ming; Chen, Yi-Chung; Lee, Ming-Ting; Chen, Gen-Der; Lu, I-Ching; Chen, Shui-Tsung; Huang, Chang-Jen

2006-02-17

We have previously identified a novel protein kinase, pk146, in the brain of Tetraodon. In the present study, we cloned the homologous protein kinase gene encoding a protein of 385 amino acid residues from zebrafish. The overall amino acid sequence and the kinase domain of zebrafish BSK146 shows 48% and 69% identity to that of rat sbk, a SH3-containing serine/threonine protein kinase. By whole-mount in situ hybridization and RT-PCR, the expression of bsk146 mRNA was mainly in the brain. To explore the in vivo function of BSK146 during zebrafish development, we used morpholino knockdown approach and found that BSK146 morphants displayed enlarged hindbrain ventricle and smaller eyes. Whole-mount in situ hybridization was further performed to analyze the brain defects in BSK146-MO-injected embryos. The expression of brain-specific markers, such as otx2, pax2.1, and krox20, was found normal in morphant embryos at 24hpf, while expression of pax2.1 exerted changes in midbrain-hindbrain boundary and hindbrain in morphant embryos at 48hpf. These data suggest that BSK146 may play an important role in later ventricle expansion in zebrafish brain development. Although the recombinant BSK146 protein produced in insect cells was active and could phosphorylate both histone H1 and histone 2B, the endogenous substrate of BSK146 in the embryonic brain of zebrafish is not clear at the present time and needs further investigation.

Metastatic brain cancer: prediction of response to whole-brain helical tomotherapy with simultaneous intralesional boost for metastatic disease using quantitative MR imaging features

NASA Astrophysics Data System (ADS)

Sharma, Harish; Bauman, Glenn; Rodrigues, George; Bartha, Robert; Ward, Aaron

2014-03-01

The sequential application of whole brain radiotherapy (WBRT) and more targeted stereotactic radiosurgery (SRS) is frequently used to treat metastatic brain tumors. However, SRS has side effects related to necrosis and edema, and requires separate and relatively invasive localization procedures. Helical tomotherapy (HT) allows for a SRS-type simultaneous infield boost (SIB) of multiple brain metastases, synchronously with WBRT and without separate stereotactic procedures. However, some patients' tumors may not respond to HT+SIB, and would be more appropriately treated with radiosurgery or conventional surgery despite the additional risks and side effects. As a first step toward a broader objective of developing a means for response prediction to HT+SIB, the goal of this study was to investigate whether quantitative measurements of tumor size and appearance (including first- and second-order texture features) on a magnetic resonance imaging (MRI) scan acquired prior to treatment could be used to differentiate responder and nonresponder patient groups after HT+SIB treatment of metastatic disease of the brain. Our results demonstrated that smaller lesions may respond better to this form of therapy; measures of appearance provided limited added value over measures of size for response prediction. With further validation on a larger data set, this approach may lead to a means for prediction of individual patient response based on pre-treatment MRI, supporting appropriate therapy selection for patients with metastatic brain cancer.

LORETA Current Source Density for Duration Mismatch Negativity and Neuropsychological Assessment in Early Schizophrenia

PubMed Central

Miyanishi, Tomohiro; Sumiyoshi, Tomiki; Higuchi, Yuko; Seo, Tomonori; Suzuki, Michio

2013-01-01

Introduction Patients with schizophrenia elicit cognitive decline from the early phase of the illness. Mismatch negativity (MMN) has been shown to be associated with cognitive function. We investigated the current source density of duration mismatch negativity (dMMN), by using low-resolution brain electromagnetic tomography (LORETA), and neuropsychological performance in subjects with early schizophrenia. Methods Data were obtained from 20 patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder, and 20 healthy control (HC) subjects. An auditory odd-ball paradigm was used to measure dMMN. Neuropsychological performance was evaluated by the brief assessment of cognition in schizophrenia Japanese version (BACS-J). Results Patients showed smaller dMMN amplitudes than those in the HC subjects. LORETA current density for dMMN was significantly lower in patients compared to HC subjects, especially in the temporal lobes. dMMN current density in the frontal lobe was positively correlated with working memory performance in patients. Conclusions This is the first study to identify brain regions showing smaller dMMN current density in early schizophrenia. Further, poor working memory was associated with decreased dMMN current density in patients. These results are likely to help understand the neural basis for cognitive impairment of schizophrenia. PMID:23577204

Dynamics of a neural system with a multiscale architecture

PubMed Central

Breakspear, Michael; Stam, Cornelis J

2005-01-01

The architecture of the brain is characterized by a modular organization repeated across a hierarchy of spatial scales—neurons, minicolumns, cortical columns, functional brain regions, and so on. It is important to consider that the processes governing neural dynamics at any given scale are not only determined by the behaviour of other neural structures at that scale, but also by the emergent behaviour of smaller scales, and the constraining influence of activity at larger scales. In this paper, we introduce a theoretical framework for neural systems in which the dynamics are nested within a multiscale architecture. In essence, the dynamics at each scale are determined by a coupled ensemble of nonlinear oscillators, which embody the principle scale-specific neurobiological processes. The dynamics at larger scales are ‘slaved’ to the emergent behaviour of smaller scales through a coupling function that depends on a multiscale wavelet decomposition. The approach is first explicated mathematically. Numerical examples are then given to illustrate phenomena such as between-scale bifurcations, and how synchronization in small-scale structures influences the dynamics in larger structures in an intuitive manner that cannot be captured by existing modelling approaches. A framework for relating the dynamical behaviour of the system to measured observables is presented and further extensions to capture wave phenomena and mode coupling are suggested. PMID:16087448

Preschool Externalizing Behavior Predicts Gender-Specific Variation in Adolescent Neural Structure

PubMed Central

Caldwell, Jessica Z. K.; Armstrong, Jeffrey M.; Hanson, Jamie L.; Sutterer, Matthew J.; Stodola, Diane E.; Koenigs, Michael; Kalin, Ned H.

2015-01-01

Dysfunction in the prefrontal cortex, amygdala, and hippocampus is believed to underlie the development of much psychopathology. However, to date only limited longitudinal data relate early behavior with neural structure later in life. Our objective was to examine the relationship of early life externalizing behavior with adolescent brain structure. We report here the first longitudinal study linking externalizing behavior during preschool to brain structure during adolescence. We examined the relationship of preschool externalizing behavior with amygdala, hippocampus, and prefrontal cortex volumes at age 15 years in a community sample of 76 adolescents followed longitudinally since their mothers’ pregnancy. A significant gender by externalizing behavior interaction revealed that males—but not females—with greater early childhood externalizing behavior had smaller amygdala volumes at adolescence (t = 2.33, p = .023). No significant results were found for the hippocampus or the prefrontal cortex. Greater early externalizing behavior also related to smaller volume of a cluster including the angular gyrus and tempoparietal junction across genders. Results were not attributable to the impact of preschool anxiety, preschool maternal stress, school-age internalizing or externalizing behaviors, or adolescent substance use. These findings demonstrate a novel, gender-specific relationship between early-childhood externalizing behavior and adolescent amygdala volume, as well as a cross-gender result for the angular gyrus and tempoparietal junction. PMID:25658357

Red and NIR light dosimetry in the human deep brain

NASA Astrophysics Data System (ADS)

Pitzschke, A.; Lovisa, B.; Seydoux, O.; Zellweger, M.; Pfleiderer, M.; Tardy, Y.; Wagnières, G.

2015-04-01

Photobiomodulation (PBM) appears promising to treat the hallmarks of Parkinson’s Disease (PD) in cellular or animal models. We measured light propagation in different areas of PD-relevant deep brain tissue during transcranial, transsphenoidal illumination (at 671 and 808 nm) of a cadaver head and modeled optical parameters of human brain tissue using Monte-Carlo simulations. Gray matter, white matter, cerebrospinal fluid, ventricles, thalamus, pons, cerebellum and skull bone were processed into a mesh of the skull (158 × 201 × 211 voxels; voxel side length: 1 mm). Optical parameters were optimized from simulated and measured fluence rate distributions. The estimated μeff for the different tissues was in all cases larger at 671 than at 808 nm, making latter a better choice for light delivery in the deep brain. Absolute values were comparable to those found in the literature or slightly smaller. The effective attenuation in the ventricles was considerably larger than literature values. Optimization yields a new set of optical parameters better reproducing the experimental data. A combination of PBM via the sphenoid sinus and oral cavity could be beneficial. A 20-fold higher efficiency of light delivery to the deep brain was achieved with ventricular instead of transcranial illumination. Our study demonstrates that it is possible to illuminate deep brain tissues transcranially, transsphenoidally and via different application routes. This opens therapeutic options for sufferers of PD or other cerebral diseases necessitating light therapy.

Applications of Ultrasound in the Resection of Brain Tumors

PubMed Central

Sastry, Rahul; Bi, Wenya Linda; Pieper, Steve; Frisken, Sarah; Kapur, Tina; Wells, William; Golby, Alexandra J.

2016-01-01

Neurosurgery makes use of pre-operative imaging to visualize pathology, inform surgical planning, and evaluate the safety of selected approaches. The utility of pre-operative imaging for neuronavigation, however, is diminished by the well characterized phenomenon of brain shift, in which the brain deforms intraoperatively as a result of craniotomy, swelling, gravity, tumor resection, cerebrospinal fluid (CSF) drainage, and many other factors. As such, there is a need for updated intraoperative information that accurately reflects intraoperative conditions. Since 1982, intraoperative ultrasound has allowed neurosurgeons to craft and update operative plans without ionizing radiation exposure or major workflow interruption. Continued evolution of ultrasound technology since its introduction has resulted in superior imaging quality, smaller probes, and more seamless integration with neuronavigation systems. Furthermore, the introduction of related imaging modalities, such as 3-dimensional ultrasound, contrast-enhanced ultrasound, high-frequency ultrasound, and ultrasound elastography have dramatically expanded the options available to the neurosurgeon intraoperatively. In the context of these advances, we review the current state, potential, and challenges of intraoperative ultrasound for brain tumor resection. We begin by evaluating these ultrasound technologies and their relative advantages and disadvantages. We then review three specific applications of these ultrasound technologies to brain tumor resection: (1) intraoperative navigation, (2) assessment of extent of resection, and (3) brain shift monitoring and compensation. We conclude by identifying opportunities for future directions in the development of ultrasound technologies. PMID:27541694

A meta-analysis of sex differences in human brain structure☆

PubMed Central

Ruigrok, Amber N.V.; Salimi-Khorshidi, Gholamreza; Lai, Meng-Chuan; Baron-Cohen, Simon; Lombardo, Michael V.; Tait, Roger J.; Suckling, John

2014-01-01

The prevalence, age of onset, and symptomatology of many neuropsychiatric conditions differ between males and females. To understand the causes and consequences of sex differences it is important to establish where they occur in the human brain. We report the first meta-analysis of typical sex differences on global brain volume, a descriptive account of the breakdown of studies of each compartmental volume by six age categories, and whole-brain voxel-wise meta-analyses on brain volume and density. Gaussian-process regression coordinate-based meta-analysis was used to examine sex differences in voxel-based regional volume and density. On average, males have larger total brain volumes than females. Examination of the breakdown of studies providing total volumes by age categories indicated a bias towards the 18–59 year-old category. Regional sex differences in volume and tissue density include the amygdala, hippocampus and insula, areas known to be implicated in sex-biased neuropsychiatric conditions. Together, these results suggest candidate regions for investigating the asymmetric effect that sex has on the developing brain, and for understanding sex-biased neurological and psychiatric conditions. PMID:24374381

Relating Brain Damage to Brain Plasticity in Patients With Multiple Sclerosis

PubMed Central

Tomassini, Valentina; Johansen-Berg, Heidi; Jbabdi, Saad; Wise, Richard G.; Pozzilli, Carlo; Palace, Jacqueline; Matthews, Paul M.

2013-01-01

Background Failure of adaptive plasticity with increasing pathology is suggested to contribute to progression of disability in multiple sclerosis (MS). However, functional impairments can be reduced with practice, suggesting that brain plasticity is preserved even in patients with substantial damage. Objective Here, functional magnetic resonance imaging (fMRI) was used to probe systems-level mechanisms of brain plasticity associated with improvements in visuomotor performance in MS patients and related to measures of microstructural damage. Methods 23 MS patients and 12 healthy controls underwent brain fMRI during the first practice session of a visuomotor task (short-term practice) and after 2 weeks of daily practice with the same task (longer-term practice). Participants also underwent a structural brain MRI scan. Results Patients performed more poorly than controls at baseline. Nonetheless, with practice, patients showed performance improvements similar to controls and independent of the extent of MRI measures of brain pathology. Different relationships between performance improvements and activations were found between groups: greater short-term improvements were associated with lower activation in the sensorimotor, posterior cingulate, and parahippocampal cortices for patients, whereas greater long-term improvements correlated with smaller activation reductions in the visual cortex of controls. Conclusions Brain plasticity for visuomotor practice is preserved in MS patients despite a high burden of cerebral pathology. Cognitive systems different from those acting in controls contribute to this plasticity in patients. These findings challenge the notion that increasing pathology is accompanied by an outright failure of adaptive plasticity, supporting a neuroscientific rationale for recovery-oriented strategies even in chronically disabled patients. PMID:22328685

Brain structure differences between Chinese and Caucasian cohorts: A comprehensive morphometry study.

PubMed

Tang, Yuchun; Zhao, Lu; Lou, Yunxia; Shi, Yonggang; Fang, Rui; Lin, Xiangtao; Liu, Shuwei; Toga, Arthur

2018-05-01

Numerous behavioral observations and brain function studies have demonstrated that neurological differences exist between East Asians and Westerners. However, the extent to which these factors relate to differences in brain structure is still not clear. As the basis of brain functions, the anatomical differences in brain structure play a primary and critical role in the origination of functional and behavior differences. To investigate the underlying differences in brain structure between the two cultural/ethnic groups, we conducted a comparative study on education-matched right-handed young male adults (age = 22-29 years) from two cohorts, Han Chinese (n = 45) and Caucasians (n = 45), using high-dimensional structural magnetic resonance imaging (MRI) data. Using two well-validated imaging analysis techniques, surface-based morphometry (SBM) and voxel-based morphometry (VBM), we performed a comprehensive vertex-wise morphometric analysis of the brain structures between Chinese and Caucasian cohorts. We identified consistent significant between-group differences in cortical thickness, volume, and surface area in the frontal, temporal, parietal, occipital, and insular lobes as well as the cingulate cortices. The SBM analyses revealed that compared with Caucasians, the Chinese population showed larger cortical structures in the temporal and cingulate regions, and smaller structural measures in the frontal and parietal cortices. The VBM data of the same sample was well-aligned with the SBM findings. Our findings systematically revealed comprehensive brain structural differences between young male Chinese and Caucasians, and provided new neuroanatomical insights to the behavioral and functional distinctions in the two cultural/ethnic populations. © 2018 Wiley Periodicals, Inc.

Atlas-Guided Segmentation of Vervet Monkey Brain MRI

PubMed Central

Fedorov, Andriy; Li, Xiaoxing; Pohl, Kilian M; Bouix, Sylvain; Styner, Martin; Addicott, Merideth; Wyatt, Chris; Daunais, James B; Wells, William M; Kikinis, Ron

2011-01-01

The vervet monkey is an important nonhuman primate model that allows the study of isolated environmental factors in a controlled environment. Analysis of monkey MRI often suffers from lower quality images compared with human MRI because clinical equipment is typically used to image the smaller monkey brain and higher spatial resolution is required. This, together with the anatomical differences of the monkey brains, complicates the use of neuroimage analysis pipelines tuned for human MRI analysis. In this paper we developed an open source image analysis framework based on the tools available within the 3D Slicer software to support a biological study that investigates the effect of chronic ethanol exposure on brain morphometry in a longitudinally followed population of male vervets. We first developed a computerized atlas of vervet monkey brain MRI, which was used to encode the typical appearance of the individual brain structures in MRI and their spatial distribution. The atlas was then used as a spatial prior during automatic segmentation to process two longitudinal scans per subject. Our evaluation confirms the consistency and reliability of the automatic segmentation. The comparison of atlas construction strategies reveals that the use of a population-specific atlas leads to improved accuracy of the segmentation for subcortical brain structures. The contribution of this work is twofold. First, we describe an image processing workflow specifically tuned towards the analysis of vervet MRI that consists solely of the open source software tools. Second, we develop a digital atlas of vervet monkey brain MRIs to enable similar studies that rely on the vervet model. PMID:22253661

Fronto-Parietal gray matter and white matter efficiency differentially predict intelligence in males and females.

PubMed

Ryman, Sephira G; Yeo, Ronald A; Witkiewitz, Katie; Vakhtin, Andrei A; van den Heuvel, Martijn; de Reus, Marcel; Flores, Ranee A; Wertz, Christopher R; Jung, Rex E

2016-11-01

While there are minimal sex differences in overall intelligence, males, on average, have larger total brain volume and corresponding regional brain volumes compared to females, measures that are consistently related to intelligence. Limited research has examined which other brain characteristics may differentially contribute to intelligence in females to facilitate equal performance on intelligence measures. Recent reports of sex differences in the neural characteristics of the brain further highlight the need to differentiate how the structural neural characteristics relate to intellectual ability in males and females. The current study utilized a graph network approach in conjunction with structural equation modeling to examine potential sex differences in the relationship between white matter efficiency, fronto-parietal gray matter volume, and general cognitive ability (GCA). Participants were healthy adults (n = 244) who completed a battery of cognitive testing and underwent structural neuroimaging. Results indicated that in males, a latent factor of fronto-parietal gray matter was significantly related to GCA when controlling for total gray matter volume. In females, white matter efficiency and total gray matter volume were significantly related to GCA, with no specificity of the fronto-parietal gray matter factor over and above total gray matter volume. This work highlights that different neural characteristics across males and females may contribute to performance on intelligence measures. Hum Brain Mapp 37:4006-4016, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Total numbers of neurons and glial cells in cortex and basal ganglia of aged brains with Down syndrome--a stereological study.

PubMed

Karlsen, Anna Schou; Pakkenberg, Bente

2011-11-01

The total numbers of neurons and glial cells in the neocortex and basal ganglia in adults with Down syndrome (DS) were estimated with design-based stereological methods, providing quantitative data on brains affected by delayed development and accelerated aging. Cell numbers, volume of regions, and densities of neurons and glial cell subtypes were estimated in brains from 4 female DS subjects (mean age 66 years) and 6 female controls (mean age 70 years). The DS subjects were estimated to have about 40% fewer neocortical neurons in total (11.1 × 10(9) vs. 17.8 × 10(9), 2p ≤ 0.001) and almost 30% fewer neocortical glial cells with no overlap to controls (12.8 × 10(9) vs. 18.2 × 10(9), 2p = 0.004). In contrast, the total number of neurons in the basal ganglia was the same in the 2 groups, whereas the number of oligodendrocytes in the basal ganglia was reduced by almost 50% in DS (405 × 10(6) vs. 816 × 10(6), 2p = 0.01). We conclude that trisomy 21 affects cortical structures more than central gray matter emphasizing the differential impairment of brain development. Despite concomitant Alzheimer-like pathology, the neurodegenerative outcome in a DS brain deviates from common Alzheimer disease.

Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis.

PubMed

Yan, Kun; Fu, Zongming; Yang, Chen; Zhang, Kai; Jiang, Shanshan; Lee, Dong-Hoon; Heo, Hye-Young; Zhang, Yi; Cole, Robert N; Van Eyk, Jennifer E; Zhou, Jinyuan

2015-08-01

To investigate the biochemical origin of the amide photon transfer (APT)-weighted hyperintensity in brain tumors. Seven 9 L gliosarcoma-bearing rats were imaged at 4.7 T. Tumor and normal brain tissue samples of equal volumes were prepared with a coronal rat brain matrix and a tissue biopsy punch. The total tissue protein and the cytosolic subproteome were extracted from both samples. Protein samples were analyzed using two-dimensional gel electrophoresis, and the proteins with significant abundance changes were identified by mass spectrometry. There was a significant increase in the cytosolic protein concentration in the tumor, compared to normal brain regions, but the total protein concentrations were comparable. The protein profiles of the tumor and normal brain tissue differed significantly. Six cytosolic proteins, four endoplasmic reticulum proteins, and five secreted proteins were considerably upregulated in the tumor. Our experiments confirmed an increase in the cytosolic protein concentration in tumors and identified several key proteins that may cause APT-weighted hyperintensity.

How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies.

PubMed

Ma, Ning; Dinges, David F; Basner, Mathias; Rao, Hengyi

2015-02-01

Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. © 2015 Associated Professional Sleep Societies, LLC.

Surface-based morphometry reveals the neuroanatomical basis of the five-factor model of personality

PubMed Central

Riccelli, Roberta; Toschi, Nicola; Nigro, Salvatore; Terracciano, Antonio

2017-01-01

Abstract The five-factor model (FFM) is a widely used taxonomy of human personality; yet its neuro anatomical basis remains unclear. This is partly because past associations between gray-matter volume and FFM were driven by different surface-based morphometry (SBM) indices (i.e. cortical thickness, surface area, cortical folding or any combination of them). To overcome this limitation, we used Free-Surfer to study how variability in SBM measures was related to the FFM in n = 507 participants from the Human Connectome Project. Neuroticism was associated with thicker cortex and smaller area and folding in prefrontal–temporal regions. Extraversion was linked to thicker pre-cuneus and smaller superior temporal cortex area. Openness was linked to thinner cortex and greater area and folding in prefrontal–parietal regions. Agreeableness was correlated to thinner prefrontal cortex and smaller fusiform gyrus area. Conscientiousness was associated with thicker cortex and smaller area and folding in prefrontal regions. These findings demonstrate that anatomical variability in prefrontal cortices is linked to individual differences in the socio-cognitive dispositions described by the FFM. Cortical thickness and surface area/folding were inversely related each others as a function of different FFM traits (neuroticism, extraversion and consciousness vs openness), which may reflect brain maturational effects that predispose or protect against psychiatric disorders. PMID:28122961

UMTS base station-like exposure, well-being, and cognitive performance.

PubMed

Regel, Sabine J; Negovetic, Sonja; Röösli, Martin; Berdiñas, Veronica; Schuderer, Jürgen; Huss, Anke; Lott, Urs; Kuster, Niels; Achermann, Peter

2006-08-01

Radio-frequency electromagnetic fields (RF EMF) of mobile communication systems are widespread in the living environment, yet their effects on humans are uncertain despite a growing body of literature. We investigated the influence of a Universal Mobile Telecommunications System (UMTS) base station-like signal on well-being and cognitive performance in subjects with and without self-reported sensitivity to RF EMF. We performed a controlled exposure experiment (45 min at an electric field strength of 0, 1, or 10 V/m, incident with a polarization of 45 degrees from the left back side of the subject, weekly intervals) in a randomized, double-blind crossover design. A total of 117 healthy subjects (33 self-reported sensitive, 84 nonsensitive subjects) participated in the study. We assessed well-being, perceived field strength, and cognitive performance with questionnaires and cognitive tasks and conducted statistical analyses using linear mixed models. Organ-specific and brain tissue-specific dosimetry including uncertainty and variation analysis was performed. In both groups, well-being and perceived field strength were not associated with actual exposure levels. We observed no consistent condition-induced changes in cognitive performance except for two marginal effects. At 10 V/m we observed a slight effect on speed in one of six tasks in the sensitive subjects and an effect on accuracy in another task in nonsensitive subjects. Both effects disappeared after multiple end point adjustment. In contrast to a recent Dutch study, we could not confirm a short-term effect of UMTS base station-like exposure on well-being. The reported effects on brain functioning were marginal and may have occurred by chance. Peak spatial absorption in brain tissue was considerably smaller than during use of a mobile phone. No conclusions can be drawn regarding short-term effects of cell phone exposure or the effects of long-term base station-like exposure on human health.

Treatment of rats with a self-selected hyperlipidic diet, increases the lipid content of the main adipose tissue sites in a proportion similar to that of the lipids in the rest of organs and tissues.

PubMed

Romero, María Del Mar; Roy, Stéphanie; Pouillot, Karl; Feito, Marisol; Esteve, Montserrat; Grasa, María Del Mar; Fernández-López, José-Antonio; Alemany, Marià; Remesar, Xavier

2014-01-01

Adipose tissue (AT) is distributed as large differentiated masses, and smaller depots covering vessels, and organs, as well as interspersed within them. The differences between types and size of cells makes AT one of the most disperse and complex organs. Lipid storage is partly shared by other tissues such as muscle and liver. We intended to obtain an approximate estimation of the size of lipid reserves stored outside the main fat depots. Both male and female rats were made overweight by 4-weeks feeding of a cafeteria diet. Total lipid content was analyzed in brain, liver, gastrocnemius muscle, four white AT sites: subcutaneous, perigonadal, retroperitoneal and mesenteric, two brown AT sites (interscapular and perirenal) and in a pool of the rest of organs and tissues (after discarding gut contents). Organ lipid content was estimated and tabulated for each individual rat. Food intake was measured daily. There was a surprisingly high proportion of lipid not accounted for by the main macroscopic AT sites, even when brain, liver and BAT main sites were discounted. Muscle contained about 8% of body lipids, liver 1-1.4%, four white AT sites lipid 28-63% of body lipid, and the rest of the body (including muscle) 38-44%. There was a good correlation between AT lipid and body lipid, but lipid in "other organs" was highly correlated too with body lipid. Brain lipid was not. Irrespective of dietary intake, accumulation of body fat was uniform both for the main lipid storage and handling organs: large masses of AT (but also liver, muscle), as well as in the "rest" of tissues. These storage sites, in specialized (adipose) or not-specialized (liver, muscle) tissues reacted in parallel against a hyperlipidic diet challenge. We postulate that body lipid stores are handled and regulated coordinately, with a more centralized and overall mechanisms than usually assumed.

UMTS Base Station-like Exposure, Well-Being, and Cognitive Performance

PubMed Central

Regel, Sabine J.; Negovetic, Sonja; Röösli, Martin; Berdiñas, Veronica; Schuderer, Jürgen; Huss, Anke; Lott, Urs; Kuster, Niels; Achermann, Peter

2006-01-01

Background Radio-frequency electromagnetic fields (RF EMF) of mobile communication systems are widespread in the living environment, yet their effects on humans are uncertain despite a growing body of literature. Objectives We investigated the influence of a Universal Mobile Telecommunications System (UMTS) base station-like signal on well-being and cognitive performance in subjects with and without self-reported sensitivity to RF EMF. Methods We performed a controlled exposure experiment (45 min at an electric field strength of 0, 1, or 10 V/m, incident with a polarization of 45° from the left back side of the subject, weekly intervals) in a randomized, double-blind crossover design. A total of 117 healthy subjects (33 self-reported sensitive, 84 nonsensitive subjects) participated in the study. We assessed well-being, perceived field strength, and cognitive performance with questionnaires and cognitive tasks and conducted statistical analyses using linear mixed models. Organ-specific and brain tissue–specific dosimetry including uncertainty and variation analysis was performed. Results In both groups, well-being and perceived field strength were not associated with actual exposure levels. We observed no consistent condition-induced changes in cognitive performance except for two marginal effects. At 10 V/m we observed a slight effect on speed in one of six tasks in the sensitive subjects and an effect on accuracy in another task in nonsensitive subjects. Both effects disappeared after multiple end point adjustment. Conclusions In contrast to a recent Dutch study, we could not confirm a short-term effect of UMTS base station-like exposure on well-being. The reported effects on brain functioning were marginal and may have occurred by chance. Peak spatial absorption in brain tissue was considerably smaller than during use of a mobile phone. No conclusions can be drawn regarding short-term effects of cell phone exposure or the effects of long-term base station-like exposure on human health. PMID:16882538

Post-Inpatient Brain Injury Rehabilitation Outcomes: Report from the National OutcomeInfo Database.

PubMed

Malec, James F; Kean, Jacob

2016-07-15

This study examined outcomes for intensive residential and outpatient/community-based post-inpatient brain injury rehabilitation (PBIR) programs compared with supported living programs. The goal of supported living programs was stable functioning (no change). Data were obtained for a large cohort of adults with acquired brain injury (ABI) from the OutcomeInfo national database, a web-based database system developed through National Institutes of Health (NIH) Small Business Technology Transfer (STTR) funding for monitoring progress and outcomes in PBIR programs primarily with the Mayo-Portland Adaptability Inventory (MPAI-4). Rasch-derived MPAI-4 measures for cases from 2008 to 2014 from 9 provider organizations offering programs in 23 facilities throughout the United States were examined. Controlling for age at injury, time in program, and time since injury on admission (chronicity), both intensive residential (n = 205) and outpatient/community-based (n = 2781) programs resulted in significant (approximately 1 standard deviation [SD]) functional improvement on the MPAI-4 Total Score compared with supported living (n = 101) programs (F = 18.184, p < 0.001). Intensive outpatient/community-based programs showed greater improvements on MPAI-4 Ability (F = 14.135, p < 0.001), Adjustment (F = 12.939, p < 0.001), and Participation (F = 16.679, p < 0.001) indices than supported living programs; whereas, intensive residential programs showed improvement primarily in Adjustment and Participation. Age at injury and time in program had small effects on outcome; the effect of chronicity was small to moderate. Examination of more chronic cases (>1 year post-injury) showed significant, but smaller (approximately 0.5 SD) change on the MPAI-4 relative to supported living programs (F = 17.562, p < 0.001). Results indicate that intensive residential and outpatient/community-based PIBR programs result in substantial positive functional changes moderated by chronicity.

Impact of 36 h of total sleep deprivation on resting-state dynamic functional connectivity.

PubMed

Xu, Huaze; Shen, Hui; Wang, Lubin; Zhong, Qi; Lei, Yu; Yang, Liu; Zeng, Ling-Li; Zhou, Zongtan; Hu, Dewen; Yang, Zheng

2018-06-01

Resting-state functional magnetic resonance imaging (fMRI) studies using static functional connectivity (sFC) measures have shown that the brain function is severely disrupted after long-term sleep deprivation (SD). However, increasing evidence has suggested that resting-state functional connectivity (FC) is dynamic and exhibits spontaneous fluctuation on a smaller timescale. The process by which long-term SD can influence dynamic functional connectivity (dFC) remains unclear. In this study, 37 healthy subjects participated in the SD experiment, and they were scanned both during rested wakefulness (RW) and after 36 h of SD. A sliding-window based approach and a spectral clustering algorithm were used to evaluate the effects of SD on dFC based on the 26 qualified subjects' data. The outcomes showed that time-averaging FC across specific regions as well as temporal properties of the FC states, such as the dwell time and transition probability, was strongly influenced after SD in contrast to the RW condition. Based on the occurrences of FC states, we further identified some RW-dominant states characterized by anti-correlation between the default mode network (DMN) and other cortices, and some SD-dominant states marked by significantly decreased thalamocortical connectivity. In particular, the temporal features of these FC states were negatively correlated with the correlation coefficients between the DMN and dorsal attention network (dATN) and demonstrated high potential in classification of sleep state (with 10-fold cross-validation accuracy of 88.6% for dwell time and 88.1% for transition probability). Collectively, our results suggested that the temporal properties of the FC states greatly account for changes in the resting-state brain networks following SD, which provides new insights into the impact of SD on the resting-state functional organization in the human brain. Copyright © 2017. Published by Elsevier B.V.

Post-Inpatient Brain Injury Rehabilitation Outcomes: Report from the National OutcomeInfo Database

PubMed Central

Kean, Jacob

2016-01-01

Abstract This study examined outcomes for intensive residential and outpatient/community-based post-inpatient brain injury rehabilitation (PBIR) programs compared with supported living programs. The goal of supported living programs was stable functioning (no change). Data were obtained for a large cohort of adults with acquired brain injury (ABI) from the OutcomeInfo national database, a web-based database system developed through National Institutes of Health (NIH) Small Business Technology Transfer (STTR) funding for monitoring progress and outcomes in PBIR programs primarily with the Mayo-Portland Adaptability Inventory (MPAI-4). Rasch-derived MPAI-4 measures for cases from 2008 to 2014 from 9 provider organizations offering programs in 23 facilities throughout the United States were examined. Controlling for age at injury, time in program, and time since injury on admission (chronicity), both intensive residential (n = 205) and outpatient/community-based (n = 2781) programs resulted in significant (approximately 1 standard deviation [SD]) functional improvement on the MPAI-4 Total Score compared with supported living (n = 101) programs (F = 18.184, p < 0.001). Intensive outpatient/community-based programs showed greater improvements on MPAI-4 Ability (F = 14.135, p < 0.001), Adjustment (F = 12.939, p < 0.001), and Participation (F = 16.679, p < 0.001) indices than supported living programs; whereas, intensive residential programs showed improvement primarily in Adjustment and Participation. Age at injury and time in program had small effects on outcome; the effect of chronicity was small to moderate. Examination of more chronic cases (>1 year post-injury) showed significant, but smaller (approximately 0.5 SD) change on the MPAI-4 relative to supported living programs (F = 17.562, p < 0.001). Results indicate that intensive residential and outpatient/community-based PIBR programs result in substantial positive functional changes moderated by chronicity. PMID:26414433

Morphological brain measures of cortico-limbic inhibition related to resilience.

PubMed

Gupta, Arpana; Love, Aubrey; Kilpatrick, Lisa A; Labus, Jennifer S; Bhatt, Ravi; Chang, Lin; Tillisch, Kirsten; Naliboff, Bruce; Mayer, Emeran A

2017-09-01

Resilience is the ability to adequately adapt and respond to homeostatic perturbations. Although resilience has been associated with positive health outcomes, the neuro-biological basis of resilience is poorly understood. The aim of the study was to identify associations between regional brain morphology and trait resilience with a focus on resilience-related morphological differences in brain regions involved in cortico-limbic inhibition. The relationship between resilience and measures of affect were also investigated. Forty-eight healthy subjects completed structural MRI scans. Self-reported resilience was measured using the Connor and Davidson Resilience Scale. Segmentation and regional parcellation of images was performed to yield a total of 165 regions. Gray matter volume (GMV), cortical thickness, surface area, and mean curvature were calculated for each region. Regression models were used to identify associations between morphology of regions belonging to executive control and emotional arousal brain networks and trait resilience (total and subscales) while controlling for age, sex, and total GMV. Correlations were also conducted between resilience scores and affect scores. Significant associations were found between GM changes in hypothesized brain regions (subparietal sulcus, intraparietal sulcus, amygdala, anterior mid cingulate cortex, and subgenual cingulate cortex) and resilience scores. There were significant positive correlations between resilience and positive affect and negative correlations with negative affect. Resilience was associated with brain morphology of regions involved in cognitive and affective processes related to cortico-limbic inhibition. Brain signatures associated with resilience may be a biomarker of vulnerability to disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Global and Regional Differences in Brain Anatomy of Young Children Born Small for Gestational Age

PubMed Central

De Bie, Henrica M. A.; Oostrom, Kim J.; Boersma, Maria; Veltman, Dick J.; Barkhof, Frederik

2011-01-01

In children who are born small for gestational age (SGA), an adverse intrauterine environment has led to underdevelopment of both the body and the brain. The delay in body growth is (partially) restored during the first two years in a majority of these children. In addition to a negative influence on these physical parameters, decreased levels of intelligence and cognitive impairments have been described in children born SGA. In this study, we used magnetic resonance imaging to examine brain anatomy in 4- to 7-year-old SGA children with and without complete bodily catch-up growth and compared them to healthy children born appropriate for gestational age. Our findings demonstrate that these children strongly differ on brain organisation when compared with healthy controls relating to both global and regional anatomical differences. Children born SGA displayed reduced cerebral and cerebellar grey and white matter volumes, smaller volumes of subcortical structures and reduced cortical surface area. Regional differences in prefrontal cortical thickness suggest a different development of the cerebral cortex. SGA children with bodily catch-up growth constitute an intermediate between those children without catch-up growth and healthy controls. Therefore, bodily catch-up growth in children born SGA does not implicate full catch-up growth of the brain. PMID:21931650

Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium.

PubMed

Kong, Xiang-Zhen; Mathias, Samuel R; Guadalupe, Tulio; Glahn, David C; Franke, Barbara; Crivello, Fabrice; Tzourio-Mazoyer, Nathalie; Fisher, Simon E; Thompson, Paul M; Francks, Clyde

2018-05-29

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets ( n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.

Morphometric brain abnormalities in boys with conduct disorder.

PubMed

Huebner, Thomas; Vloet, Timo D; Marx, Ivo; Konrad, Kerstin; Fink, Gereon R; Herpertz, Sabine C; Herpertz-Dahlmann, Beate

2008-05-01

Children with the early-onset type of conduct disorder (CD) are at high risk for developing an antisocial personality disorder. Although there have been several neuroimaging studies on morphometric differences in adults with antisocial personality disorder, little is known about structural brain aberrations in boys with CD. Magnetic resonance imaging and voxel-based morphometry were used to assess abnormalities in gray matter volumes in 23 boys ages 12 to 17 years with CD (17 comorbid for attention-deficit/hyperactivity disorder) in comparison with age- and IQ-matched controls. Compared with healthy controls, mean gray matter volume was 6% smaller in the clinical group. Compared with controls, reduced gray matter volumes were found in the left orbitofrontal region and bilaterally in the temporal lobes, including the amygdala and hippocampus on the left side in the CD group. Regression analyses in the clinical group indicated an inverse association of hyperactive/impulsive symptoms and widespread gray matter abnormalities in the frontoparietal and temporal cortices. By contrast, CD symptoms correlated primarily with gray matter reductions in limbic brain structures. The data suggest that boys with CD and comorbid attention-deficit/hyperactivity disorder show brain abnormalities in frontolimbic areas that resemble structural brain deficits, which are typically observed in adults with antisocial behavior.

Brain tissue deforms similarly to filled elastomers and follows consolidation theory

NASA Astrophysics Data System (ADS)

Franceschini, G.; Bigoni, D.; Regitnig, P.; Holzapfel, G. A.

2006-12-01

Slow, large deformations of human brain tissue—accompanying cranial vault deformation induced by positional plagiocephaly, occurring during hydrocephalus, and in the convolutional development—has surprisingly received scarce mechanical investigation. Since the effects of these deformations may be important, we performed a systematic series of in vitro experiments on human brain tissue, revealing the following features. (i) Under uniaxial (quasi-static), cyclic loading, brain tissue exhibits a peculiar nonlinear mechanical behaviour, exhibiting hysteresis, Mullins effect and residual strain, qualitatively similar to that observed in filled elastomers. As a consequence, the loading and unloading uniaxial curves have been found to follow the Ogden nonlinear elastic theory of rubber (and its variants to include Mullins effect and permanent strain). (ii) Loaded up to failure, the "shape" of the stress/strain curve qualitatively changes, evidencing softening related to local failure. (iii) Uniaxial (quasi-static) strain experiments under controlled drainage conditions provide the first direct evidence that the tissue obeys consolidation theory involving fluid migration, with properties similar to fine soils, but having much smaller volumetric compressibility. (iv) Our experimental findings also support the existence of a viscous component of the solid phase deformation. Brain tissue should, therefore, be modelled as a porous, fluid-saturated, nonlinear solid with very small volumetric (drained) compressibility.

Sexual selection predicts brain structure in dragon lizards.

PubMed

Hoops, D; Ullmann, J F P; Janke, A L; Vidal-Garcia, M; Stait-Gardner, T; Dwihapsari, Y; Merkling, T; Price, W S; Endler, J A; Whiting, M J; Keogh, J S

2017-02-01

Phenotypic traits such as ornaments and armaments are generally shaped by sexual selection, which often favours larger and more elaborate males compared to females. But can sexual selection also influence the brain? Previous studies in vertebrates report contradictory results with no consistent pattern between variation in brain structure and the strength of sexual selection. We hypothesize that sexual selection will act in a consistent way on two vertebrate brain regions that directly regulate sexual behaviour: the medial preoptic nucleus (MPON) and the ventromedial hypothalamic nucleus (VMN). The MPON regulates male reproductive behaviour whereas the VMN regulates female reproductive behaviour and is also involved in male aggression. To test our hypothesis, we used high-resolution magnetic resonance imaging combined with traditional histology of brains in 14 dragon lizard species of the genus Ctenophorus that vary in the strength of precopulatory sexual selection. Males belonging to species that experience greater sexual selection had a larger MPON and a smaller VMN. Conversely, females did not show any patterns of variation in these brain regions. As the volumes of both these regions also correlated with brain volume (BV) in our models, we tested whether they show the same pattern of evolution in response to changes in BV and found that the do. Therefore, we show that the primary brain nuclei underlying reproductive behaviour in vertebrates can evolve in a mosaic fashion, differently between males and females, likely in response to sexual selection, and that these same regions are simultaneously evolving in concert in relation to overall brain size. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Brain Volume Estimation Enhancement by Morphological Image Processing Tools.

PubMed

Zeinali, R; Keshtkar, A; Zamani, A; Gharehaghaji, N

2017-12-01

Volume estimation of brain is important for many neurological applications. It is necessary in measuring brain growth and changes in brain in normal/abnormal patients. Thus, accurate brain volume measurement is very important. Magnetic resonance imaging (MRI) is the method of choice for volume quantification due to excellent levels of image resolution and between-tissue contrast. Stereology method is a good method for estimating volume but it requires to segment enough MRI slices and have a good resolution. In this study, it is desired to enhance stereology method for volume estimation of brain using less MRI slices with less resolution. In this study, a program for calculating volume using stereology method has been introduced. After morphologic method, dilation was applied and the stereology method enhanced. For the evaluation of this method, we used T1-wighted MR images from digital phantom in BrainWeb which had ground truth. The volume of 20 normal brain extracted from BrainWeb, was calculated. The volumes of white matter, gray matter and cerebrospinal fluid with given dimension were estimated correctly. Volume calculation from Stereology method in different cases was made. In three cases, Root Mean Square Error (RMSE) was measured. Case I with T=5, d=5, Case II with T=10, D=10 and Case III with T=20, d=20 (T=slice thickness, d=resolution as stereology parameters). By comparing these results of two methods, it is obvious that RMSE values for our proposed method are smaller than Stereology method. Using morphological operation, dilation allows to enhance the estimation volume method, Stereology. In the case with less MRI slices and less test points, this method works much better compared to Stereology method.

Sex on the brain: Are gender-dependent structural and functional differences associated with behavior?

PubMed

Grabowska, Anna

2017-01-02

A substantial number of studies provide evidence documenting a variety of sex differences in the brain. It remains unclear whether sexual differentiation at the neural level is related to that observed in daily behavior, cognitive function, and the risk of developing certain psychiatric and neurological disorders. Some investigators have questioned whether the brain is truly sexually differentiated and support this view with several arguments including the following: (1) brain structural or functional differences are not necessarily reflected in appropriate differences at the behavioral level, which might suggest that these two phenomena are not linked to each other; and (2) sex-related differences in the brain are rather small and concern features that significantly overlap between males and females. This review polemicizes with those opinions and presents examples of sex-related local neural differences underpinning a variety of sex differences in behaviors, skills, and cognitive/emotional abilities. Although male/female brain differentiation may vary in pattern and scale, nonetheless, in some respects (e.g., relative local gray matter volumes) it can be substantial, taking the form of sexual dimorphism and involving large areas of the brain (the cortex in particular). A significant part of this review is devoted to arguing that some sex differences in the brain may serve to prevent (in the case where they are maladaptive), rather than to produce, differences at the behavioral/skill level. Specifically, some differences might result from compensatory mechanisms aimed at maintaining similar intellectual capacities across the sexes, despite the smaller average volume of the brain in females compared with males. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

512-Channel and 13-Region Simultaneous Recordings Coupled with Optogenetic Manipulation in Freely Behaving Mice

PubMed Central

Xie, Kun; Fox, Grace E.; Liu, Jun; Tsien, Joe Z.

2016-01-01

The development of technologies capable of recording both single-unit activity and local field potentials (LFPs) over a wide range of brain circuits in freely behaving animals is the key to constructing brain activity maps. Although mice are the most popular mammalian genetic model, in vivo neural recording has been traditionally limited to smaller channel count and fewer brain structures because of the mouse’s small size and thin skull. Here, we describe a 512-channel tetrode system that allows us to record simultaneously over a dozen cortical and subcortical structures in behaving mice. This new technique offers two major advantages – namely, the ultra-low cost and the do-it-yourself flexibility for targeting any combination of many brain areas. We show the successful recordings of both single units and LFPs from 13 distinct neural circuits of the mouse brain, including subregions of the anterior cingulate cortices, retrosplenial cortices, somatosensory cortices, secondary auditory cortex, hippocampal CA1, dentate gyrus, subiculum, lateral entorhinal cortex, perirhinal cortex, and prelimbic cortex. This 512-channel system can also be combined with Cre-lox neurogenetics and optogenetics to further examine interactions between genes, cell types, and circuit dynamics across a wide range of brain structures. Finally, we demonstrate that complex stimuli – such as an earthquake and fear-inducing foot-shock – trigger firing changes in all of the 13 brain regions recorded, supporting the notion that neural code is highly distributed. In addition, we show that localized optogenetic manipulation in any given brain region could disrupt network oscillations and caused changes in single-unit firing patterns in a brain-wide manner, thereby raising the cautionary note of the interpretation of optogenetically manipulated behaviors. PMID:27378865

Measuring iron in the brain using quantitative susceptibility mapping and X-ray fluorescence imaging

PubMed Central

Zheng, Weili; Nichol, Helen; Liu, Saifeng; Cheng, Yu-Chung N.; Haacke, E. Mark

2013-01-01

Measuring iron content in the brain has important implications for a number of neurodegenerative diseases. Quantitative susceptibility mapping (QSM), derived from magnetic resonance images, has been used to measure total iron content in vivo and in post mortem brain. In this paper, we show how magnetic susceptibility from QSM correlates with total iron content measured by X-ray fluorescence (XRF) imaging and by inductively coupled plasma mass spectrometry (ICPMS). The relationship between susceptibility and ferritin iron was estimated at 1.10 ± 0.08 ppb susceptibility per μg iron/g wet tissue, similar to that of iron in fixed (frozen/thawed) cadaveric brain and previously published data from unfixed brains. We conclude that magnetic susceptibility can provide a direct and reliable quantitative measurement of iron content and that it can be used clinically at least in regions with high iron content. PMID:23591072

Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography.

PubMed

Mielke, Michelle M; Hagen, Clinton E; Xu, Jing; Chai, Xiyun; Vemuri, Prashanthi; Lowe, Val J; Airey, David C; Knopman, David S; Roberts, Rosebud O; Machulda, Mary M; Jack, Clifford R; Petersen, Ronald C; Dage, Jeffrey L

2018-04-04

We examined and compared plasma phospho-tau181 (pTau181) and total tau: (1) across the Alzheimer's disease (AD) clinical spectrum; (2) in relation to brain amyloid β (Aβ) positron emission tomography (PET), tau PET, and cortical thickness; and (3) as a screening tool for elevated brain Aβ. Participants included 172 cognitively unimpaired, 57 mild cognitively impaired, and 40 AD dementia patients with concurrent Aβ PET (Pittsburgh compound B), tau PET (AV1451), magnetic resonance imaging, plasma total tau, and pTau181. Plasma total tau and pTau181 levels were higher in AD dementia patients than those in cognitively unimpaired. Plasma pTau181 was more strongly associated with both Aβ and tau PET. Plasma pTau181 was a more sensitive and specific predictor of elevated brain Aβ than total tau and was as good as, or better than, the combination of age and apolipoprotein E (APOE). Plasma pTau181 may have utility as a biomarker of AD pathophysiology and as a noninvasive screener for elevated brain Aβ. Copyright © 2018. Published by Elsevier Inc.

FABP-1 gene ablation impacts brain endocannabinoid system in male mice.

PubMed

Martin, Gregory G; Chung, Sarah; Landrock, Danilo; Landrock, Kerstin K; Huang, Huan; Dangott, Lawrence J; Peng, Xiaoxue; Kaczocha, Martin; Seeger, Drew R; Murphy, Eric J; Golovko, Mikhail Y; Kier, Ann B; Schroeder, Friedhelm

2016-08-01

Liver fatty acid-binding protein (FABP1, L-FABP) has high affinity for and enhances uptake of arachidonic acid (ARA, C20:4, n-6) which, when esterified to phospholipids, is the requisite precursor for synthesis of endocannabinoids (EC) such as arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). The brain derives most of its ARA from plasma, taking up ARA and transporting it intracellularly via cytosolic fatty acid-binding proteins (FABPs 3,5, and 7) localized within the brain. In contrast, the much more prevalent cytosolic FABP1 is not detectable in the brain but is instead highly expressed in the liver. Therefore, the possibility that FABP1 outside the central nervous system may regulate brain AEA and 2-AG was examined in wild-type (WT) and FABP1 null (LKO) male mice. LKO increased brain levels of AA-containing EC (AEA, 2-AG), correlating with increased free and total ARA in brain and serum. LKO also increased brain levels of non-ARA that contain potentiating endocannabinoids (EC*) such as oleoyl ethanolamide (OEA), PEA, 2-OG, and 2-PG. Concomitantly, LKO decreased serum total ARA-containing EC, but not non-ARA endocannabinoids. LKO did not elicit these changes in the brain EC and EC* as a result of compensatory up-regulation of brain protein levels of enzymes in EC synthesis (NAPEPLD, DAGLα) or cytosolic EC chaperone proteins (FABPs 3, 5, 7, SCP-2, HSP70), or cannabinoid receptors (CB1, TRVP1). These data show for the first time that the non-CNS fatty acid-binding protein FABP1 markedly affected brain levels of both ARA-containing endocannabinoids (AEA, 2-AG) as well as their non-ARA potentiating endocannabinoids. Fatty acid-binding protein-1 (FABP-1) is not detectable in brain but instead is highly expressed in liver. The possibility that FABP1 outside the central nervous system may regulate brain endocannabinoids arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) was examined in wild-type (WT) and FABP-1 null (LKO) male mice. LKO increased brain levels of arachidonic acid-containing endocannabinoids (AEA, 2-AG), correlating with increased free and total arachidonic acid in brain and serum. Read the Editorial Highlight for this article on page 371. © 2016 International Society for Neurochemistry.

Serotonin has opposite effects on the aggressiveness of crayfish, facing either a smaller or a larger rival: alteration of size perception.

PubMed

Bacqué-Cazenave, Julien; Cattaert, Daniel; Delbecque, Jean Paul; Fossat, Pascal

2018-04-26

We injected serotonin (5-HT) in adult male crayfish before pairing them with size-matched non-injected competitors, and we observed dyadic agonistic interactions. Paradoxically, 5-HT elicited opposite behavioral responses if the injected animal was opposed by a smaller or larger rival: the level of aggressiveness of the injected crayfish was higher in front of a larger rival but lower in front of a smaller rival. Our results indicate that the effects of 5-HT on aggressiveness are dependent on the perception of the relative size difference of the opponent. In both cases, however, 5-HT significantly delayed the decision to retreat. We conclude that 5-HT does not primarily act on aggressiveness but rather on the brain centers that integrate risk assessment and/or decision-making, which then modulate the aggressive response. Our study supports a reinterpretation of the role of 5-HT in crustacean agonistic behavior that may be of interest for other animals. © 2018. Published by The Company of Biologists Ltd.

Trait positive affect is associated with hippocampal volume and change in caudate volume across adolescence.

PubMed

Dennison, Meg; Whittle, Sarah; Yücel, Murat; Byrne, Michelle L; Schwartz, Orli; Simmons, Julian G; Allen, Nicholas B

2015-03-01

Trait positive affect (PA) in childhood confers both risk and resilience to psychological and behavioral difficulties in adolescence, although explanations for this association are lacking. Neurodevelopment in key areas associated with positive affect is ongoing throughout adolescence, and is likely to be related to the increased incidence of disorders of positive affect during this period of development. The aim of this study was to prospectively explore the relationship between trait indices of PA and brain development in subcortical reward regions during early to mid-adolescence in a community sample of adolescents. A total of 89 (46 male, 43 female) adolescents participated in magnetic resonance imaging assessments during both early and mid-adolescence (mean age at baseline = 12.6 years, SD = 0.45; mean follow-up period = 3.78 years, SD = 0.21) and also completed self-report measures of trait positive and negative affect (at baseline). To examine the specificity of these effects, the relation between negative affect and brain development was also examined. The degree of volume reduction in the right caudate over time was predicted by PA. Independent of time, larger hippocampal volumes were associated with higher PA, and negative affect was associated with smaller left amygdala volume. The moderating effect of negative affect on the development of the left caudate varied as a function of lifetime psychiatric history. These findings suggest that early to mid-adolescence is an important period whereby neurodevelopmental processes may underlie key phenotypes conferring both risk and resilience for emotional and behavioral difficulties later in life.

Region specific regulation of glutamic acid decarboxylase mRNA expression by dopamine neurons in rat brain.

PubMed

Lindefors, N; Brene, S; Herrera-Marschitz, M; Persson, H

1989-01-01

In situ hybridization histochemistry and RNA blots were used to study the expression of glutamic acid decarboxylase (GAD) mRNA in rats with or without a unilateral lesion of midbrain dopamine neurons. Two populations of GAD mRNA positive neurons were found in the intact caudate-putamen, substantia nigra and fronto-parietal cortex. In caudate-putamen, only one out of ten of the GAD mRNA positive neurons expressed high levels, while in substantia nigra every second of the positive neurons expressed high levels of GAD mRNA. Relatively few, but intensively labelled neurons were found in the intact fronto-parietal cerebral cortex. In addition, one out of six of the GAD mRNA positive neurons in the fronto-parietal cortex showed a low labeling. On the ipsilateral side, the forebrain dopamine deafferentation induced an increase in the number of neurons expressing high levels of GAD mRNA in caudate-putamen, and a decrease in fronto-parietal cortex. A smaller decrease was also seen in substantia nigra. However, the total number of GAD mRNA positive neurons were not significantly changed in any of these brain regions. The changes in the levels of GAD mRNA after the dopamine lesion were confirmed by RNA blot analysis. Hence, midbrain dopamine neurons appear to control neuronal expression of GAD mRNA by a tonic down-regulation in a fraction of GAD mRNA positive neurons in caudate-putamen, and a tonic up-regulation in a fraction of GAD mRNA positive neurons in fronto-parietal cortex and substantia nigra.

Comparative study of tissue deposition of omega-3 fatty acids from polar-lipid rich oil of the microalgae Nannochloropsis oculata with krill oil in rats.

PubMed

Kagan, Michael L; Levy, Aharon; Leikin-Frenkel, Alicia

2015-01-01

Long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) exert health benefits which are dependent upon their incorporation into blood, cells and tissues. Plasma and tissue deposition of LC n-3 PUFA from oils extracted from the micro-algae Nannochloropsis oculata and from krill were compared in rats. The algal oil provides eicosapentaenoic acid (EPA) partly conjugated (15%) to phospholipids and glycolipids but no docosahexaenoic acid (DHA), whereas krill oil provides both EPA and DHA conjugated in part (40%) to phospholipids. Rats fed a standard diet received either krill oil or polar-lipid rich algal oil by gavage daily for 7 days (5 ml oil per kg body weight each day). Fatty acid concentrations were analyzed in plasma, brain and liver, and two adipose depots since these represent transport, functional and storage pools of fatty acids, respectively. When measuring total LC n-3 PUFA (sum of EPA, docosapentaenoic acid (DPA) and DHA), there was no statistically significant difference between the algal oil and krill oil for plasma, brain, liver and gonadal adipose tissue. Concentrations of LC n-3 PUFA were higher in the retroperitoneal adipose tissue from the algal oil group. Tissue uptake of LC n-3 PUFA from an algal oil containing 15% polar lipids (glycolipids and phospholipids) was found to be equivalent to krill oil containing 40% phospholipids. This may be due to glycolipids forming smaller micelles during ingestive hydrolysis than phospholipids. Ingestion of fatty acids with glycolipids may improve bioavailability, but this needs to be further explored.

Practical design of a 4 Tesla double-tuned RF surface coil for interleaved 1H and 23Na MRI of rat brain.

PubMed

Alecci, M; Romanzetti, S; Kaffanke, J; Celik, A; Wegener, H P; Shah, N J

2006-08-01

MRI is proving to be a very useful tool for sodium quantification in animal models of stroke, ischemia, and cancer. In this work, we present the practical design of a dual-frequency RF surface coil that provides (1)H and (23)Na images of the rat head at 4 T. The dual-frequency RF surface coil comprised of a large loop tuned to the (1)H frequency and a smaller co-planar loop tuned to the (23)Na frequency. The mutual coupling between the two loops was eliminated by the use of a trap circuit inserted in the smaller coil. This independent-loop design was versatile since it enabled a separate optimisation of the sensitivity and RF field distributions of the two coils. To allow for an easy extension of this simple double-tuned coil design to other frequencies (nuclei) and dimensions, we describe in detail the practical aspects of the workbench design and MRI testing using a phantom that mimics in vivo conditions. A comparison between our independent-loop, double-tuned coil and a single-tuned (23)Na coil of equal size obtained with a phantom matching in vivo conditions, showed a reduction of the (23)Na sensitivity (about 28 %) because of signal losses in the trap inductance. Typical congruent (1)H and (23)Na rat brain images showing good SNR ((23)Na: brain 7, ventricular cerebrospinal fluid 11) and spatial resolution ((23)Na: 1.25 x 1.25 x 5mm(3)) are also reported. The in vivo SNR values obtained with this coil were comparable to, if not better than, other contemporary designs in the literature.

Preliminary evidence of altered gray matter volume in subjects with internet gaming disorder: associations with history of childhood attention-deficit/hyperactivity disorder symptoms.

PubMed

Lee, Deokjong; Namkoong, Kee; Lee, Junghan; Jung, Young-Chul

2018-05-11

Attention-deficit/hyperactivity disorder (ADHD) is commonly comorbid with Internet gaming disorder (IGD). Although childhood ADHD symptoms may decline during late brain maturation, structural alterations in some brain areas may persist into adulthood. This study investigated whether young adults with IGD and a history of childhood ADHD symptoms had gray matter volume (GMV) alterations that were distinct from subjects without a history of childhood ADHD. As an exploratory investigation, we conducted a whole-brain voxel-based morphometry with the diffeomorphic anatomical registration using an exponentiated Lie algebra algorithm and applied an uncorrected threshold at the voxel level for multiple comparisons. GMVs of IGD subjects with a history of childhood ADHD (IGD ADHD+ group; n = 20; 24.5 ± 2.5 years) were compared to those of subjects without a history of childhood ADHD (IGD ADHD- group; n = 20; 23.9 ± 2.5 years) and controls (n = 20; 22.7 ± 2.4 years). Compared with controls, both IGD groups had a smaller GMV in the right anterior cingulate cortex, the left inferior frontal gyrus, and the left insula, yet had a larger GMV in the right angular gyrus. The IGD ADHD+ group had a larger GMV in the right precuneus than the IGD ADHD- group and controls. When controlling for other comorbid psychiatric symptoms, the IGD ADHD+ group also had a smaller GMV in the right inferior frontal gyrus. In conclusion, we found that young adults with IGD and a history of childhood ADHD symptoms had characteristic GMV alterations, which may be linked with their manifestation of childhood ADHD.

Practical design of a 4 Tesla double-tuned RF surface coil for interleaved 1H and 23Na MRI of rat brain

NASA Astrophysics Data System (ADS)

Alecci, M.; Romanzetti, S.; Kaffanke, J.; Celik, A.; Wegener, H. P.; Shah, N. J.

2006-08-01

MRI is proving to be a very useful tool for sodium quantification in animal models of stroke, ischemia, and cancer. In this work, we present the practical design of a dual-frequency RF surface coil that provides 1H and 23Na images of the rat head at 4 T. The dual-frequency RF surface coil comprised of a large loop tuned to the 1H frequency and a smaller co-planar loop tuned to the 23Na frequency. The mutual coupling between the two loops was eliminated by the use of a trap circuit inserted in the smaller coil. This independent-loop design was versatile since it enabled a separate optimisation of the sensitivity and RF field distributions of the two coils. To allow for an easy extension of this simple double-tuned coil design to other frequencies (nuclei) and dimensions, we describe in detail the practical aspects of the workbench design and MRI testing using a phantom that mimics in vivo conditions. A comparison between our independent-loop, double-tuned coil and a single-tuned 23Na coil of equal size obtained with a phantom matching in vivo conditions, showed a reduction of the 23Na sensitivity (about 28 %) because of signal losses in the trap inductance. Typical congruent 1H and 23Na rat brain images showing good SNR ( 23Na: brain 7, ventricular cerebrospinal fluid 11) and spatial resolution ( 23Na: 1.25 × 1.25 × 5 mm 3) are also reported. The in vivo SNR values obtained with this coil were comparable to, if not better than, other contemporary designs in the literature.

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

A finite element analysis of the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in tDCS

NASA Astrophysics Data System (ADS)

Faria, Paula; Hallett, Mark; Cavaleiro Miranda, Pedro

2011-12-01

We investigated the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in transcranial direct current stimulation (tDCS). For this purpose, we used the finite element method to compute the distribution of the current density in a four-layered spherical head model using various electrode montages, corresponding to a range of electrode sizes and inter-electrode distances. We found that smaller electrodes required slightly less current to achieve a constant value of the current density at a reference point on the brain surface located directly under the electrode center. Under these conditions, smaller electrodes also produced a more focal current density distribution in the brain, i.e. the magnitude of the current density fell more rapidly with distance from the reference point. The combination of two electrodes with different areas produced an asymmetric current distribution that could lead to more effective and localized neural modulation under the smaller electrode than under the larger one. Focality improved rapidly with decreasing electrode size when the larger electrode sizes were considered but the improvement was less marked for the smaller electrode sizes. Also, focality was not affected significantly by inter-electrode distance unless two large electrodes were placed close together. Increasing the inter-electrode distance resulted in decreased shunting of the current through the scalp and the cerebrospinal fluid, and decreasing electrode area resulted in increased current density on the scalp under the edges of the electrode. Our calculations suggest that when working with conventional electrodes (25-35 cm2), one of the electrodes should be placed just 'behind' the target relative to the other electrode, for maximum current density on the target. Also electrodes with areas in the range 3.5-12 cm2 may provide a better compromise between focality and current density in the scalp than the traditional electrodes. Finally, the use of multiple small return electrodes may be more efficient than the use of a single large return electrode.

Structural variations in prefrontal cortex mediate the relationship between early childhood stress and spatial working memory

PubMed Central

Hanson, Jamie L.; Chung, Moo K.; Avants, Brian B.; Rudolph, Karen D.; Shirtcliff, Elizabeth A.; Gee, James C.; Davidson, Richard J.; Pollak, Seth D.

2012-01-01

A large corpus of research indicates exposure to stress impairs cognitive abilities, specifically executive functioning dependent on the prefrontal cortex (PFC). We collected structural MRI scans (n=61), well-validated assessments of executive functioning, and detailed interviews assessing stress exposure in humans, to examine whether cumulative life stress affected brain morphometry and one type of executive functioning, spatial working memory, during adolescence—a critical time of brain development and reorganization. Analysis of variations in brain structure revealed that cumulative life stress and spatial working memory were related to smaller volumes in the PFC, specifically prefrontal gray and white matter between the anterior cingulate and the frontal poles. Mediation analyses revealed that individual differences in prefrontal volumes accounted for the association between cumulative life stress and spatial working memory. These results suggest that structural changes in the PFC may serve as a mediating mechanism through which greater cumulative life stress engenders decrements in cognitive functioning. PMID:22674267

Porphyrin-laser photodynamic induction of focal brain necrosis

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

Stroop, W.G.; Battles, E.J.; Townsend, J.J.

A noninvasive photodynamic method has been developed to produce focal brain necrosis using porphyrin activated in vivo with laser light. After peripheral injection of the photosensitive porphyrin derivative, Photofrin I, mice were irradiated on the posterior lateral aspect of the head through the intact depilated scalp with 632 nm argon-dye laser light. Animals were studied at one, two and seven days after irradiation. Blood-brain barrier damage was detected by the intravenous injection of Evans blue, horseradish peroxidase and heterologous immunoglobulins. At one and two days after irradiation, the lesions were characterized by extravasation of immunoglobulin and Evans blue, and bymore » edema, ischemia and infiltration by monocytes. On the seventh day after irradiation, the lesion was smaller than it had been two days after irradiation, and had reactive changes at its edges and coagulative necrosis at its center. Extravasation of Evans blue and immunoglobulin was markedly reduced by the seventh day after irradiation, but uptake of horseradish peroxidase by macrophages located at the periphery of the lesion was evident.« less

SPECT study of low intensity He-Ne laser intravascular irradiation therapy for brain infarction

NASA Astrophysics Data System (ADS)

Xiao, Xue-Chang; Dong, Jia-Zheng; Chu, Xiao-Fan; Jia, Shao-Wei; Liu, Timon C.; Jiao, Jian-Ling; Zheng, Xi-Yuan; Zhou, Ci-Xiong

2003-12-01

We used single photon emission computed tomography (SPECT) in brain perfusion imaging to study the changes of regional cerebral blood flow (rCBF) and cerebral function in brain infarction patients treated with intravascular laser irradiation of blood (ILIB). 17 of 35 patients with brain infarction were admitted to be treated by ILIB on the base of standard drug therapy, and SPECT brain perfusion imaging was performed before and after ILIB therapy with self-comparison. The results were analyzed in quantity with brain blood flow function change rate (BFCR%) model. Effect of ILIB during the therapy process in the other 18 patients were also observed. In the 18 patients, SPECT indicated an improvement of rCBF (both in focus and in total brain) and cerebral function after a 30 min-ILIB therapy. And the 17 patients showed an enhancement of total brain rCBF and cerebral function after ILIB therapy in comparison with that before, especially for the focus side of the brain. The enhancement for focus itself was extremely obvious with a higher significant difference (P<0.0001). The mirror regions had no significant change (P>0.05). BFCR% of foci was prominently higher than that of mirror regions (P<0.0001). In conclusion, the ILIB therapy can improve rCBF and cerebral function and activate brain cells of patients with brain infarction. The results denote new evidence of ILIB therapy for those patients with cerebral ischemia.

Opioid Abuse after Traumatic Brain Injury: Evaluation Using Rodent Models

DTIC Science & Technology

2013-07-01

acclimation to the laboratory and handling, catheterization surgery and recovery, brain injury and evaluation of acquisition, reinforcing efficacy or...subjects entered into protocol =112 (10+10+20+22+ 24+26) Total number catheterized =62 Total number undergoing sham injury =33...did not enter into the experimental protocol until after VCU IACUC and ACURO approval in July 2013. Twenty-two subjects have been catheterized and

Teaching English through Action: Total Physical Response (T.P.R.). A Right-Brain/Left-Brain Approach to Language Acquisition. A Workshop.

ERIC Educational Resources Information Center

Segal, Bertha E.

Materials from a teacher workshop on the Total Physical Response method for teaching English as a second language are presented. The technique describes the process of first language acquisition, uses physical activities in the classroom to reinforce learning, and allows a long period of receptive language learning before requiring production. The…

Direct Global Measurements of Tropspheric Winds Employing a Simplified Coherent Laser Radar using Fully Scalable Technology and Technique

NASA Technical Reports Server (NTRS)

Kavaya, Michael J.; Spiers, Gary D.; Lobl, Elena S.; Rothermel, Jeff; Keller, Vernon W.

1996-01-01

Innovative designs of a space-based laser remote sensing 'wind machine' are presented. These designs seek compatibility with the traditionally conflicting constraints of high scientific value and low total mission cost. Mission cost is reduced by moving to smaller, lighter, more off-the-shelf instrument designs which can be accommodated on smaller launch vehicles.

Preliminary study of brain glucose metabolism changes in patients with lung cancer of different histological types.

PubMed

Li, Wei-Ling; Fu, Chang; Xuan, Ang; Shi, Da-Peng; Gao, Yong-Ju; Zhang, Jie; Xu, Jun-Ling

2015-02-05

Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. One hundred and twenty patients with primary untreated lung cancer, who visited People's Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases), squamous cell carcinoma (43 cases), and small-cell carcinoma (25 cases). The whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software, with 50 age-matched and gender-matched healthy controls for comparison. The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292). The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.