High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

PubMed

Gizewski, Elke R; Maderwald, Stefan; Linn, Jennifer; Dassinger, Benjamin; Bochmann, Katja; Forsting, Michael; Ladd, Mark E

2014-03-01

The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures.

White matter microstructure and cognitive decline in metabolic syndrome: a review of diffusion tensor imaging.

PubMed

Alfaro, Freddy J; Gavrieli, Anna; Saade-Lemus, Patricia; Lioutas, Vasileios-Arsenios; Upadhyay, Jagriti; Novak, Vera

2018-01-01

Metabolic syndrome is a cluster of cardiovascular risk factors defined by the presence of abdominal obesity, glucose intolerance, hypertension and/or dyslipidemia. It is a major public health epidemic worldwide, and a known risk factor for the development of cognitive dysfunction and dementia. Several studies have demonstrated a positive association between the presence of metabolic syndrome and worse cognitive outcomes, however, evidence of brain structure pathology is limited. Diffusion tensor imaging has offered new opportunities to detect microstructural white matter changes in metabolic syndrome, and a possibility to detect associations between functional and structural abnormalities. This review analyzes the impact of metabolic syndrome on white matter microstructural integrity, brain structure abnormalities and their relationship to cognitive function. Each of the metabolic syndrome components exerts a specific signature of white matter microstructural abnormalities. Metabolic syndrome and its components exert both additive/synergistic, as well as, independent effects on brain microstructure thus accelerating brain aging and cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Validation of voxel-based morphometry (VBM) based on MRI

NASA Astrophysics Data System (ADS)

Yang, Xueyu; Chen, Kewei; Guo, Xiaojuan; Yao, Li

2007-03-01

Voxel-based morphometry (VBM) is an automated and objective image analysis technique for detecting differences in regional concentration or volume of brain tissue composition based on structural magnetic resonance (MR) images. VBM has been used widely to evaluate brain morphometric differences between different populations, but there isn't an evaluation system for its validation until now. In this study, a quantitative and objective evaluation system was established in order to assess VBM performance. We recruited twenty normal volunteers (10 males and 10 females, age range 20-26 years, mean age 22.6 years). Firstly, several focal lesions (hippocampus, frontal lobe, anterior cingulate, back of hippocampus, back of anterior cingulate) were simulated in selected brain regions using real MRI data. Secondly, optimized VBM was performed to detect structural differences between groups. Thirdly, one-way ANOVA and post-hoc test were used to assess the accuracy and sensitivity of VBM analysis. The results revealed that VBM was a good detective tool in majority of brain regions, even in controversial brain region such as hippocampus in VBM study. Generally speaking, much more severity of focal lesion was, better VBM performance was. However size of focal lesion had little effects on VBM analysis.

Boosting brain connectome classification accuracy in Alzheimer's disease using higher-order singular value decomposition

PubMed Central

Zhan, Liang; Liu, Yashu; Wang, Yalin; Zhou, Jiayu; Jahanshad, Neda; Ye, Jieping; Thompson, Paul M.

2015-01-01

Alzheimer's disease (AD) is a progressive brain disease. Accurate detection of AD and its prodromal stage, mild cognitive impairment (MCI), are crucial. There is also a growing interest in identifying brain imaging biomarkers that help to automatically differentiate stages of Alzheimer's disease. Here, we focused on brain structural networks computed from diffusion MRI and proposed a new feature extraction and classification framework based on higher order singular value decomposition and sparse logistic regression. In tests on publicly available data from the Alzheimer's Disease Neuroimaging Initiative, our proposed framework showed promise in detecting brain network differences that help in classifying different stages of Alzheimer's disease. PMID:26257601

Calcified parenchymal central nervous system cysticercosis and clinical outcomes in epilepsy.

PubMed

Leon, Amanda; Saito, Erin K; Mehta, Bijal; McMurtray, Aaron M

2015-02-01

This study aimed to compare clinical outcomes including seizure frequency and psychiatric symptoms between patients with epilepsy with neuroimaging evidence of past brain parenchymal neurocysticercosis infection, patients with other structural brain lesions, and patients without structural neuroimaging abnormalities. The study included retrospective cross-sectional analysis of all patients treated for epilepsy in a community-based adult neurology clinic during a three-month period. A total of 160 patients were included in the analysis, including 63 with neuroimaging findings consistent with past parenchymal neurocysticercosis infection, 55 with structurally normal brain neuroimaging studies, and 42 with other structural brain lesions. No significant differences were detected between groups for either seizure freedom (46.03%, 50.91%, and 47.62%, respectively; p=0.944) or mean seizure frequency per month (mean=2.50, S.D.=8.1; mean=4.83, S.D.=17.64; mean=8.55, S.D.=27.31, respectively; p=0.267). Self-reported depressive symptoms were more prevalent in those with parenchymal neurocysticercosis than in the other groups (p=0.003). No significant differences were detected for prevalence of self-reported anxiety or psychotic symptoms. Calcified parenchymal neurocysticercosis results in refractory epilepsy about as often as other structural brain lesions. Depressive symptoms may be more common among those with epilepsy and calcified parenchymal neurocysticercosis; consequently, screening for depression may be indicated in this population. Published by Elsevier Inc.

Structural and Perfusion Abnormalities of Brain on MRI and Technetium-99m-ECD SPECT in Children With Cerebral Palsy: A Comparative Study.

PubMed

Rana, Kamer Singh; Narwal, Varun; Chauhan, Lokesh; Singh, Giriraj; Sharma, Monica; Chauhan, Suneel

2016-04-01

Cerebral palsy has traditionally been associated with hypoxic ischemic brain damage. This study was undertaken to demonstrate structural and perfusion brain abnormalities. Fifty-six children diagnosed clinically as having cerebral palsy were studied between 1 to 14 years of age and were subjected to 3 Tesla magnetic resonance imaging (MRI). Brain and Technetium-99m-ECD brain single-photon emission computed tomography (SPECT) scan. Male to female ratio was 1.8:1 with a mean age of 4.16 ± 2.274 years. Spastic cerebral palsy was the most common type, observed in 91%. Birth asphyxia was the most common etiology (69.6%). White matter changes (73.2%) such as periventricular leukomalacia and corpus callosal thinning were the most common findings on MRI. On SPECT all cases except one revealed perfusion impairments in different regions of brain. MRI is more sensitive in detecting white matter changes, whereas SPECT is better in detecting cortical and subcortical gray matter abnormalities of perfusion. © The Author(s) 2015.

Imaging of Traumatic Brain Injury.

PubMed

Bodanapally, Uttam K; Sours, Chandler; Zhuo, Jiachen; Shanmuganathan, Kathirkamanathan

2015-07-01

Imaging plays an important role in the management of patients with traumatic brain injury (TBI). Computed tomography (CT) is the first-line imaging technique allowing rapid detection of primary structural brain lesions that require surgical intervention. CT also detects various deleterious secondary insults allowing early medical and surgical management. Serial imaging is critical to identifying secondary injuries. MR imaging is indicated in patients with acute TBI when CT fails to explain neurologic findings. However, MR imaging is superior in patients with subacute and chronic TBI and also predicts neurocognitive outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuroanatomical correlates of biological motion detection.

PubMed

Gilaie-Dotan, Sharon; Kanai, Ryota; Bahrami, Bahador; Rees, Geraint; Saygin, Ayse P

2013-02-01

Biological motion detection is both commonplace and important, but there is great inter-individual variability in this ability, the neural basis of which is currently unknown. Here we examined whether the behavioral variability in biological motion detection is reflected in brain anatomy. Perceptual thresholds for detection of biological motion and control conditions (non-biological object motion detection and motion coherence) were determined in a group of healthy human adults (n=31) together with structural magnetic resonance images of the brain. Voxel based morphometry analyzes revealed that gray matter volumes of left posterior superior temporal sulcus (pSTS) and left ventral premotor cortex (vPMC) significantly predicted individual differences in biological motion detection, but showed no significant relationship with performance on the control tasks. Our study reveals a neural basis associated with the inter-individual variability in biological motion detection, reliably linking the neuroanatomical structure of left pSTS and vPMC with biological motion detection performance. Copyright © 2012 Elsevier Ltd. All rights reserved.

Development of antibodies against the rat brain somatostatin receptor.

PubMed

Theveniau, M; Rens-Domiano, S; Law, S F; Rougon, G; Reisine, T

1992-05-15

Somatostatin (SRIF) is a neurotransmitter in the brain involved in the regulation of motor activity and cognition. It induces its physiological actions by interacting with receptors. We have developed antibodies against the receptor to investigate its structural properties. Rabbit polyclonal antibodies were generated against the rat brain SRIF receptor. These antibodies (F4) were able to immunoprecipitate solubilized SRIF receptors from rat brain and the cell line AtT-20. The specificity of the interaction of these antibodies with SRIF receptors was further demonstrated by immunoblotting. F4 detected SRIF receptors of 60 kDa from rat brain and adrenal cortex and the cell lines AtT-20, GH3, and NG-108, which express high densities of SRIF receptors. They did not detect immunoreactive material from rat liver or COS-1, HEPG, or CRL cells, which do not express functional SRIF receptors. In rat brain, 60-kDa immunoreactivity was detected by F4 in the hippocampus, cerebral cortex, and striatum, which have high densities of SRIF receptors. However, F4 did not interact with proteins from cerebellum and brain stem, which express few SRIF receptors. Immunoreactive material cannot be detected in rat pancreas or pituitary, which have been reported to express a 90-kDa SRIF receptor subtype. The selective detection of 60-kDa SRIF receptors by F4 indicates that the 60- and 90-kDa SRIF receptor subtypes are immunologically distinct. The availability of antibodies that selectively detect native and denatured brain SRIF receptors provides us with a feasible approach to clone the brain SRIF receptor gene(s).

MRI as a tool to study brain structure from mouse models for mental retardation

NASA Astrophysics Data System (ADS)

Verhoye, Marleen; Sijbers, Jan; Kooy, R. F.; Reyniers, E.; Fransen, E.; Oostra, B. A.; Willems, Peter; Van der Linden, Anne-Marie

1998-07-01

Nowadays, transgenic mice are a common tool to study brain abnormalities in neurological disorders. These studies usually rely on neuropathological examinations, which have a number of drawbacks, including the risk of artefacts introduced by fixation and dehydration procedures. Here we present 3D Fast Spin Echo Magnetic Resonance Imaging (MRI) in combination with 2D and 3D segmentation techniques as a powerful tool to study brain anatomy. We set up MRI of the brain in mouse models for the fragile X syndrome (FMR1 knockout) and Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus (CRASH) syndrome (L1CAM knockout). Our major goal was to determine qualitative and quantitative differences in specific brain structures. MRI of the brain of fragile X and CRASH patients has revealed alterations in the size of specific brain structures, including the cerebellar vermis and the ventricular system. In the present MRI study of the brain from fragile X knockout mice, we have measured the size of the brain, cerebellum and 4th ventricle, which were reported as abnormal in human fragile X patients, but found no evidence for altered brain regions in the mouse model. In CRASH syndrome, the most specific brain abnormalities are vermis hypoplasia and abnormalities of the ventricular system with some degree of hydrocephalus. With the MRI study of L1CAM knockout mice we found vermis hypoplasia, abnormalities of the ventricular system including dilatation of the lateral and the 4th ventricles. These subtle abnormalities were not detected upon standard neuropathological examination. Here we proved that this sensitive MRI technique allows to measure small differences which can not always be detected by means of pathology.

The glia doctrine: addressing the role of glial cells in healthy brain ageing.

PubMed

Nagelhus, Erlend A; Amiry-Moghaddam, Mahmood; Bergersen, Linda H; Bjaalie, Jan G; Eriksson, Jens; Gundersen, Vidar; Leergaard, Trygve B; Morth, J Preben; Storm-Mathisen, Jon; Torp, Reidun; Walhovd, Kristine B; Tønjum, Tone

2013-10-01

Glial cells in their plurality pervade the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. Astrocyte biology has been examined using molecular, biochemical and structural methods, as well as 3D brain imaging in live animals and humans. Exosomes are extracelluar membrane vesicles that facilitate communication between glia, and have significant potential for biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may indirectly influence the structure and function of membrane proteins expressed in glial cells and predispose specific cell subgroups to degeneration. Physical exercise may reduce or retard age-related brain deterioration by a mechanism involving neuro-glial processes. It is most likely that additional information about the distribution, structure and function of glial cells will yield novel insight into human brain ageing. Systematic studies of glia and their functions are expected to eventually lead to earlier detection of ageing-related brain dysfunction and to interventions that could delay, reduce or prevent brain dysfunction. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Cortical brain connectivity evaluated by graph theory in dementia: a correlation study between functional and structural data.

PubMed

Vecchio, Fabrizio; Miraglia, Francesca; Curcio, Giuseppe; Altavilla, Riccardo; Scrascia, Federica; Giambattistelli, Federica; Quattrocchi, Carlo Cosimo; Bramanti, Placido; Vernieri, Fabrizio; Rossini, Paolo Maria

2015-01-01

A relatively new approach to brain function in neuroscience is the "functional connectivity", namely the synchrony in time of activity in anatomically-distinct but functionally-collaborating brain regions. On the other hand, diffusion tensor imaging (DTI) is a recently developed magnetic resonance imaging (MRI)-based technique with the capability to detect brain structural connection with fractional anisotropy (FA) identification. FA decrease has been observed in the corpus callosum of subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI, an AD prodromal stage). Corpus callosum splenium DTI abnormalities are thought to be associated with functional disconnections among cortical areas. This study aimed to investigate possible correlations between structural damage, measured by MRI-DTI, and functional abnormalities of brain integration, measured by characteristic path length detected in resting state EEG source activity (40 participants: 9 healthy controls, 10 MCI, 10 mild AD, 11 moderate AD). For each subject, undirected and weighted brain network was built to evaluate graph core measures. eLORETA lagged linear connectivity values were used as weight of the edges of the network. Results showed that callosal FA reduction is associated to a loss of brain interhemispheric functional connectivity characterized by increased delta and decreased alpha path length. These findings suggest that "global" (average network shortest path length representing an index of how efficient is the information transfer between two parts of the network) functional measure can reflect the reduction of fiber connecting the two hemispheres as revealed by DTI analysis and also anticipate in time this structural loss.

Disruptions of brain structural network in end-stage renal disease patients with long-term hemodialysis and normal-appearing brain tissues.

PubMed

Chou, Ming-Chung; Ko, Chih-Hung; Chang, Jer-Ming; Hsieh, Tsyh-Jyi

2018-05-04

End-stage renal disease (ESRD) patients on hemodialysis were demonstrated to exhibit silent and invisible white-matter alterations which would likely lead to disruptions of brain structural networks. Therefore, the purpose of this study was to investigate the disruptions of brain structural network in ESRD patients. Thiry-three ESRD patients with normal-appearing brain tissues and 29 age- and gender-matched healthy controls were enrolled in this study and underwent both cognitive ability screening instrument (CASI) assessment and diffusion tensor imaging (DTI) acquisition. Brain structural connectivity network was constructed using probabilistic tractography with automatic anatomical labeling template. Graph-theory analysis was performed to detect the alterations of node-strength, node-degree, node-local efficiency, and node-clustering coefficient in ESRD patients. Correlational analysis was performed to understand the relationship between network measures, CASI score, and dialysis duration. Structural connectivity, node-strength, node-degree, and node-local efficiency were significantly decreased, whereas node-clustering coefficient was significantly increased in ESRD patients as compared with healthy controls. The disrupted local structural networks were generally associated with common neurological complications of ESRD patients, but the correlational analysis did not reveal significant correlation between network measures, CASI score, and dialysis duration. Graph-theory analysis was helpful to investigate disruptions of brain structural network in ESRD patients with normal-appearing brain tissues. Copyright © 2018. Published by Elsevier Masson SAS.

Expression of defective measles virus genes in brain tissues of patients with subacute sclerosing panencephalitis

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

Baczko, K.; Liebert, U.G.; Billeter, M.

1986-08-01

The persistence of measles virus in selected areas of the brains of four patients with subacute sclerosing panencephalitis (SSPE) was characterized by immunohistological and biochemical techniques. The five measles virus structural proteins were never simultaneously detectable in any of the bran sections. Nucleocapsid proteins and phosphoproteins were found in every diseased brain area, whereas hemagglutinin protein was detected in two cases, fusion protein was detected in three cases, and matrix protein was detected in only one case. Also, it could be shown that the amounts of measles virus RNA in the brains differed from patient to patient and in themore » different regions investigated. In all patients, plus-strand RNAs specific for these five viral genes could be detected. However, the amounts of fusion and hemagglutinin mRNAs were low compared with the amounts in lytically infected cells. The presence of particular measles virus RNAs in SSPE-infected brains did not always correlate with mRNA activity. In in vitro translations, the matrix protein was produced in only one case, and the hemagglutinin protein was produced in none. These results indicate that measles virus persistence in SSPE is correlated with different defects of several genes which probably prevent assembly of viral particles in SSPE-infected brain tissue.« less

Neuroimaging of Cerebrovascular Disease in the Aging Brain

PubMed Central

Gupta, Ajay; Nair, Sreejit; Schweitzer, Andrew D.; Kishore, Sirish; Johnson, Carl E.; Comunale, Joseph P.; Tsiouris, Apostolos J.; Sanelli, Pina C.

2012-01-01

Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Structural abnormalities related to vascular disease in the brain and vessels have been well characterized with CT and MRI based techniques. We review some of the pathophysiologic mechanisms in the aging brain and cerebral vasculature and the related structural abnormalities detectable on neuroimaging, including evaluation of age-related white matter changes, atherosclerosis of the cerebral vasculature, and cerebral infarction. In addition, newer neuroimaging techniques, such as diffusion tensor imaging, perfusion techniques, and assessment of cerebrovascular reserve, are also reviewed, as these techniques can detect physiologic alterations which complement the morphologic changes that cause cerebrovascular disease in the aging brain.Further investigation of these advanced imaging techniques has potential application to the understanding and diagnosis of cerebrovascular disease in the elderly. PMID:23185721

To cut or not to cut? Assessing the modular structure of brain networks.

PubMed

Chang, Yu-Teng; Pantazis, Dimitrios; Leahy, Richard M

2014-05-01

A wealth of methods has been developed to identify natural divisions of brain networks into groups or modules, with one of the most prominent being modularity. Compared with the popularity of methods to detect community structure, only a few methods exist to statistically control for spurious modules, relying almost exclusively on resampling techniques. It is well known that even random networks can exhibit high modularity because of incidental concentration of edges, even though they have no underlying organizational structure. Consequently, interpretation of community structure is confounded by the lack of principled and computationally tractable approaches to statistically control for spurious modules. In this paper we show that the modularity of random networks follows a transformed version of the Tracy-Widom distribution, providing for the first time a link between module detection and random matrix theory. We compute parametric formulas for the distribution of modularity for random networks as a function of network size and edge variance, and show that we can efficiently control for false positives in brain and other real-world networks. Copyright © 2014 Elsevier Inc. All rights reserved.

An object-based approach for detecting small brain lesions: application to Virchow-Robin spaces.

PubMed

Descombes, Xavier; Kruggel, Frithjof; Wollny, Gert; Gertz, Hermann Josef

2004-02-01

This paper is concerned with the detection of multiple small brain lesions from magnetic resonance imaging (MRI) data. A model based on the marked point process framework is designed to detect Virchow-Robin spaces (VRSs). These tubular shaped spaces are due to retraction of the brain parenchyma from its supplying arteries. VRS are described by simple geometrical objects that are introduced as small tubular structures. Their radiometric properties are embedded in a data term. A prior model includes interactions describing the clustering property of VRS. A Reversible Jump Markov Chain Monte Carlo algorithm (RJMCMC) optimizes the proposed model, obtained by multiplying the prior and the data model. Example results are shown on T1-weighted MRI datasets of elderly subjects.

A high resolution spatiotemporal atlas of gene expression of the developing mouse brain

PubMed Central

Thompson, Carol L.; Ng, Lydia; Menon, Vilas; Martinez, Salvador; Lee, Chang-Kyu; Glattfelder, Katie; Sunkin, Susan M.; Henry, Alex; Lau, Christopher; Dang, Chinh; Garcia-Lopez, Raquel; Martinez-Ferre, Almudena; Pombero, Ana; Rubenstein, John L.R.; Wakeman, Wayne B.; Hohmann, John; Dee, Nick; Sodt, Andrew J.; Young, Rob; Smith, Kimberly; Nguyen, Thuc-Nghi; Kidney, Jolene; Kuan, Leonard; Jeromin, Andreas; Kaykas, Ajamete; Miller, Jeremy; Page, Damon; Orta, Geri; Bernard, Amy; Riley, Zackery; Smith, Simon; Wohnoutka, Paul; Hawrylycz, Mike; Puelles, Luis; Jones, Allan R.

2015-01-01

SUMMARY To provide a temporal framework for the genoarchitecture of brain development, in situ hybridization data were generated for embryonic and postnatal mouse brain at 7 developmental stages for ~2100 genes, processed with an automated informatics pipeline and manually annotated. This resource comprises 434,946 images, 7 reference atlases, an ontogenetic ontology, and tools to explore co-expression of genes across neurodevelopment. Gene sets coinciding with developmental phenomena were identified. A temporal shift in the principles governing the molecular organization of the brain was detected, with transient neuromeric, plate-based organization of the brain present at E11.5 and E13.5. Finally, these data provided a transcription factor code that discriminates brain structures and identifies the developmental age of a tissue, providing a foundation for eventual genetic manipulation or tracking of specific brain structures over development. The resource is available as the Allen Developing Mouse Brain Atlas (developingmouse.brain-map.org). PMID:24952961

Composite technique for regional neurochemical studies: measurement of energy and neurotransmitter metabolites in single tissue sample.

PubMed

Djuricic, B M; Ueki, Y; Spatz, M

1985-06-01

A combined method is described for the determination of various metabolites from a single tissue sample of the brain. It comprises a quick inactivation of cerebral enzymes by microwave irradiation, easy separation of the desired brain regions, and perchloric acid extraction of tissue substances, which are assayed either by specific enzymatic techniques or by HPLC with electrochemical detection. The obtained values of most energy and neurotransmitter metabolites in the brain are in agreement with those reported using other methods. However, this technique, in contrast to the brain freezing in vitro or freeze-blowing, provides a more efficient procedure for rapid arrest of cerebral metabolism even in the deep brain structures and is therefore suitable for detection of early changes particularly those occurring in experimental pathological conditions such as ischemia.

Brain structure correlates of urban upbringing, an environmental risk factor for schizophrenia.

PubMed

Haddad, Leila; Schäfer, Axel; Streit, Fabian; Lederbogen, Florian; Grimm, Oliver; Wüst, Stefan; Deuschle, Michael; Kirsch, Peter; Tost, Heike; Meyer-Lindenberg, Andreas

2015-01-01

Urban upbringing has consistently been associated with schizophrenia, but which specific environmental exposures are reflected by this epidemiological observation and how they impact the developing brain to increase risk is largely unknown. On the basis of prior observations of abnormal functional brain processing of social stress in urban-born humans and preclinical evidence for enduring structural brain effects of early social stress, we investigated a possible morphological correlate of urban upbringing in human brain. In a sample of 110 healthy subjects studied with voxel-based morphometry, we detected a strong inverse correlation between early-life urbanicity and gray matter (GM) volume in the right dorsolateral prefrontal cortex (DLPFC, Brodmann area 9). Furthermore, we detected a negative correlation of early-life urbanicity and GM volumes in the perigenual anterior cingulate cortex (pACC) in men only. Previous work has linked volume reductions in the DLPFC to the exposure to psychosocial stress, including stressful experiences in early life. Besides, anatomical and functional alterations of this region have been identified in schizophrenic patients and high-risk populations. Previous data linking functional hyperactivation of pACC during social stress to urban upbringing suggest that the present interaction effect in brain structure might contribute to an increased risk for schizophrenia in males brought up in cities. Taken together, our results suggest a neural mechanism by which early-life urbanicity could impact brain architecture to increase the risk for schizophrenia. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Label-Free SERS Selective Detection of Dopamine and Serotonin Using Graphene-Au Nanopyramid Heterostructure.

PubMed

Wang, Pu; Xia, Ming; Liang, Owen; Sun, Ke; Cipriano, Aaron F; Schroeder, Thomas; Liu, Huinan; Xie, Ya-Hong

2015-10-20

Ultrasensitive detection and spatially resolved mapping of neurotransmitters, dopamine and serotonin, are critical to facilitate understanding brain functions and investigate the information processing in neural networks. In this work, we demonstrated single molecule detection of dopamine and serotonin using a graphene-Au nanopyramid heterostructure platform. The quasi-periodic Au structure boosts high-density and high-homogeneity hotspots resulting in ultrahigh sensitivity with a surface enhanced Raman spectroscopic (SERS) enhancement factor ∼10(10). A single layer graphene superimposed on a Au structure not only can locate SERS hot spots but also modify the surface chemistry to realize selective enhancement Raman yield. Dopamine and serotonin could be detected and distinguished from each other at 10(-10) M level in 1 s data acquisition time without any pretreatment and labeling process. Moreover, the heterostructure realized nanomolar detection of neurotransmitters in the presence of simulated body fluids. These findings represent a step forward in enabling in-depth studies of neurological processes including those closely related to brain activity mapping (BAM).

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

PubMed

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

2014-01-01

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

Analysis of brain patterns using temporal measures

DOEpatents

Georgopoulos, Apostolos

2015-08-11

A set of brain data representing a time series of neurophysiologic activity acquired by spatially distributed sensors arranged to detect neural signaling of a brain (such as by the use of magnetoencephalography) is obtained. The set of brain data is processed to obtain a dynamic brain model based on a set of statistically-independent temporal measures, such as partial cross correlations, among groupings of different time series within the set of brain data. The dynamic brain model represents interactions between neural populations of the brain occurring close in time, such as with zero lag, for example. The dynamic brain model can be analyzed to obtain the neurophysiologic assessment of the brain. Data processing techniques may be used to assess structural or neurochemical brain pathologies.

A computational framework for the detection of subcortical brain dysmaturation in neonatal MRI using 3D Convolutional Neural Networks.

PubMed

Ceschin, Rafael; Zahner, Alexandria; Reynolds, William; Gaesser, Jenna; Zuccoli, Giulio; Lo, Cecilia W; Gopalakrishnan, Vanathi; Panigrahy, Ashok

2018-05-21

Deep neural networks are increasingly being used in both supervised learning for classification tasks and unsupervised learning to derive complex patterns from the input data. However, the successful implementation of deep neural networks using neuroimaging datasets requires adequate sample size for training and well-defined signal intensity based structural differentiation. There is a lack of effective automated diagnostic tools for the reliable detection of brain dysmaturation in the neonatal period, related to small sample size and complex undifferentiated brain structures, despite both translational research and clinical importance. Volumetric information alone is insufficient for diagnosis. In this study, we developed a computational framework for the automated classification of brain dysmaturation from neonatal MRI, by combining a specific deep neural network implementation with neonatal structural brain segmentation as a method for both clinical pattern recognition and data-driven inference into the underlying structural morphology. We implemented three-dimensional convolution neural networks (3D-CNNs) to specifically classify dysplastic cerebelli, a subset of surface-based subcortical brain dysmaturation, in term infants born with congenital heart disease. We obtained a 0.985 ± 0. 0241-classification accuracy of subtle cerebellar dysplasia in CHD using 10-fold cross-validation. Furthermore, the hidden layer activations and class activation maps depicted regional vulnerability of the superior surface of the cerebellum, (composed of mostly the posterior lobe and the midline vermis), in regards to differentiating the dysplastic process from normal tissue. The posterior lobe and the midline vermis provide regional differentiation that is relevant to not only to the clinical diagnosis of cerebellar dysplasia, but also genetic mechanisms and neurodevelopmental outcome correlates. These findings not only contribute to the detection and classification of a subset of neonatal brain dysmaturation, but also provide insight to the pathogenesis of cerebellar dysplasia in CHD. In addition, this is one of the first examples of the application of deep learning to a neuroimaging dataset, in which the hidden layer activation revealed diagnostically and biologically relevant features about the clinical pathogenesis. The code developed for this project is open source, published under the BSD License, and designed to be generalizable to applications both within and beyond neonatal brain imaging. Copyright © 2018 Elsevier Inc. All rights reserved.

Resolving anatomical and functional structure in human brain organization: identifying mesoscale organization in weighted network representations.

PubMed

Lohse, Christian; Bassett, Danielle S; Lim, Kelvin O; Carlson, Jean M

2014-10-01

Human brain anatomy and function display a combination of modular and hierarchical organization, suggesting the importance of both cohesive structures and variable resolutions in the facilitation of healthy cognitive processes. However, tools to simultaneously probe these features of brain architecture require further development. We propose and apply a set of methods to extract cohesive structures in network representations of brain connectivity using multi-resolution techniques. We employ a combination of soft thresholding, windowed thresholding, and resolution in community detection, that enable us to identify and isolate structures associated with different weights. One such mesoscale structure is bipartivity, which quantifies the extent to which the brain is divided into two partitions with high connectivity between partitions and low connectivity within partitions. A second, complementary mesoscale structure is modularity, which quantifies the extent to which the brain is divided into multiple communities with strong connectivity within each community and weak connectivity between communities. Our methods lead to multi-resolution curves of these network diagnostics over a range of spatial, geometric, and structural scales. For statistical comparison, we contrast our results with those obtained for several benchmark null models. Our work demonstrates that multi-resolution diagnostic curves capture complex organizational profiles in weighted graphs. We apply these methods to the identification of resolution-specific characteristics of healthy weighted graph architecture and altered connectivity profiles in psychiatric disease.

Structural MRI biomarkers of shared pathogenesis in autism spectrum disorder and epilepsy.

PubMed

Blackmon, Karen

2015-06-01

Etiological factors that contribute to a high comorbidity between autism spectrum disorder (ASD) and epilepsy are the subject of much debate. Does epilepsy cause ASD or are there common underlying brain abnormalities that increase the risk of developing both disorders? This review summarizes evidence from quantitative MRI studies to suggest that abnormalities of brain structure are not necessarily the consequence of ASD and epilepsy but are antecedent to disease expression. Abnormal gray and white matter volumes are present prior to onset of ASD and evident at the time of onset in pediatric epilepsy. Aberrant brain growth trajectories are also common in both disorders, as evidenced by blunted gray matter maturation and white matter maturation. Although the etiological factors that explain these abnormalities are unclear, high heritability estimates for gray matter volume and white matter microstructure demonstrate that genetic factors assert a strong influence on brain structure. In addition, histopathological studies of ASD and epilepsy brain tissue reveal elevated rates of malformations of cortical development (MCDs), such as focal cortical dysplasia and heterotopias, which supports disruption of neuronal migration as a contributing factor. Although MCDs are not always visible on MRI with conventional radiological analysis, quantitative MRI detection methods show high sensitivity to subtle malformations in epilepsy and can be potentially applied to MCD detection in ASD. Such an approach is critical for establishing quantitative neuroanatomic endophenotypes that can be used in genetic research. In the context of emerging drug treatments for seizures and autism symptoms, such as rapamycin and rapalogs, in vivo neuroimaging markers of subtle structural brain abnormalities could improve sample stratification in human clinical trials and potentially extend the range of patients that might benefit from treatment. This article is part of a Special Issue entitled "Autism and Epilepsy". Copyright © 2015 Elsevier Inc. All rights reserved.

Mapping the order and pattern of brain structural MRI changes using change-point analysis in premanifest Huntington's disease.

PubMed

Wu, Dan; Faria, Andreia V; Younes, Laurent; Mori, Susumu; Brown, Timothy; Johnson, Hans; Paulsen, Jane S; Ross, Christopher A; Miller, Michael I

2017-10-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that progressively affects motor, cognitive, and emotional functions. Structural MRI studies have demonstrated brain atrophy beginning many years prior to clinical onset ("premanifest" period), but the order and pattern of brain structural changes have not been fully characterized. In this study, we investigated brain regional volumes and diffusion tensor imaging (DTI) measurements in premanifest HD, and we aim to determine (1) the extent of MRI changes in a large number of structures across the brain by atlas-based analysis, and (2) the initiation points of structural MRI changes in these brain regions. We adopted a novel multivariate linear regression model to detect the inflection points at which the MRI changes begin (namely, "change-points"), with respect to the CAG-age product (CAP, an indicator of extent of exposure to the effects of CAG repeat expansion). We used approximately 300 T1-weighted and DTI data from premanifest HD and control subjects in the PREDICT-HD study, with atlas-based whole brain segmentation and change-point analysis. The results indicated a distinct topology of structural MRI changes: the change-points of the volumetric measurements suggested a central-to-peripheral pattern of atrophy from the striatum to the deep white matter; and the change points of DTI measurements indicated the earliest changes in mean diffusivity in the deep white matter and posterior white matter. While interpretation needs to be cautious given the cross-sectional nature of the data, these findings suggest a spatial and temporal pattern of spread of structural changes within the HD brain. Hum Brain Mapp 38:5035-5050, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Multivariate Classification of Structural MRI Data Detects Chronic Low Back Pain

PubMed Central

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

2014-01-01

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

Comparison of a modified mid-coronal sectioning technique and Wilson's technique when conducting eye and brain examinations in rabbit teratology studies.

PubMed

Ziejewski, Mary K; Solomon, Howard M; Rendemonti, Joyce; Stanislaus, Dinesh

2015-02-01

There are two methods used when examining fetal rabbit eyes and brain in teratology studies. One method employs prior fixation before serial sectioning (Wilson's technique) and the other uses fresh tissue (mid-coronal sectioning). We modified the mid-coronal sectioning technique to include removal of eyes and brain for closer examination and to increase the number of structures that can be evaluated and compared it to the Wilson's technique. We found that external examination of the head, in conjunction with either sectioning method, is equally sensitive in identifying developmental defects. We evaluated 40,401 New Zealand White (NZW) and Dutch-Belted (DB) rabbit fetuses for external head alterations, of which 28,538 fetuses were further examined for eye and brain alterations using the modified mid-coronal sectioning method (16,675 fetuses) or Wilson's technique (11,863 fetuses). The fetuses were from vehicle control or drug-treated pregnant rabbits in embryo-fetal development studies conducted to meet international regulatory requirements for the development of new drugs. Both methods detected the more common alterations (microphthalmia and dilated lateral cerebral ventricles) and other less common findings (changes in size and/or shape of eye and brain structures). While both methods are equally sensitive at detecting common and rare developmental defects, the modified mid-coronal sectioning technique eliminates the use of chemicals and concomitant fixation artifacts that occur with the Wilson's technique and allows for examination of 100% intact fetuses thereby increasing potential for detecting eye and brain alterations as these findings occur infrequently in rabbits. © 2015 Wiley Periodicals, Inc.

Hemodynamic and morphologic responses in mouse brain during acute head injury imaged by multispectral structured illumination

NASA Astrophysics Data System (ADS)

Volkov, Boris; Mathews, Marlon S.; Abookasis, David

2015-03-01

Multispectral imaging has received significant attention over the last decade as it integrates spectroscopy, imaging, tomography analysis concurrently to acquire both spatial and spectral information from biological tissue. In the present study, a multispectral setup based on projection of structured illumination at several near-infrared wavelengths and at different spatial frequencies is applied to quantitatively assess brain function before, during, and after the onset of traumatic brain injury in an intact mouse brain (n=5). For the production of head injury, we used the weight drop method where weight of a cylindrical metallic rod falling along a metal tube strikes the mouse's head. Structured light was projected onto the scalp surface and diffuse reflected light was recorded by a CCD camera positioned perpendicular to the mouse head. Following data analysis, we were able to concurrently show a series of hemodynamic and morphologic changes over time including higher deoxyhemoglobin, reduction in oxygen saturation, cell swelling, etc., in comparison with baseline measurements. Overall, results demonstrates the capability of multispectral imaging based structured illumination to detect and map of brain tissue optical and physiological properties following brain injury in a simple noninvasive and noncontact manner.

Hierarchical organization of functional connectivity in the mouse brain: a complex network approach.

PubMed

Bardella, Giampiero; Bifone, Angelo; Gabrielli, Andrea; Gozzi, Alessandro; Squartini, Tiziano

2016-08-18

This paper represents a contribution to the study of the brain functional connectivity from the perspective of complex networks theory. More specifically, we apply graph theoretical analyses to provide evidence of the modular structure of the mouse brain and to shed light on its hierarchical organization. We propose a novel percolation analysis and we apply our approach to the analysis of a resting-state functional MRI data set from 41 mice. This approach reveals a robust hierarchical structure of modules persistent across different subjects. Importantly, we test this approach against a statistical benchmark (or null model) which constrains only the distributions of empirical correlations. Our results unambiguously show that the hierarchical character of the mouse brain modular structure is not trivially encoded into this lower-order constraint. Finally, we investigate the modular structure of the mouse brain by computing the Minimal Spanning Forest, a technique that identifies subnetworks characterized by the strongest internal correlations. This approach represents a faster alternative to other community detection methods and provides a means to rank modules on the basis of the strength of their internal edges.

Hierarchical organization of functional connectivity in the mouse brain: a complex network approach

NASA Astrophysics Data System (ADS)

Bardella, Giampiero; Bifone, Angelo; Gabrielli, Andrea; Gozzi, Alessandro; Squartini, Tiziano

2016-08-01

This paper represents a contribution to the study of the brain functional connectivity from the perspective of complex networks theory. More specifically, we apply graph theoretical analyses to provide evidence of the modular structure of the mouse brain and to shed light on its hierarchical organization. We propose a novel percolation analysis and we apply our approach to the analysis of a resting-state functional MRI data set from 41 mice. This approach reveals a robust hierarchical structure of modules persistent across different subjects. Importantly, we test this approach against a statistical benchmark (or null model) which constrains only the distributions of empirical correlations. Our results unambiguously show that the hierarchical character of the mouse brain modular structure is not trivially encoded into this lower-order constraint. Finally, we investigate the modular structure of the mouse brain by computing the Minimal Spanning Forest, a technique that identifies subnetworks characterized by the strongest internal correlations. This approach represents a faster alternative to other community detection methods and provides a means to rank modules on the basis of the strength of their internal edges.

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

Abnormal structural connectivity between the basal ganglia, thalamus, and frontal cortex in patients with disorders of consciousness.

PubMed

Weng, Ling; Xie, Qiuyou; Zhao, Ling; Zhang, Ruibin; Ma, Qing; Wang, Junjing; Jiang, Wenjie; He, Yanbin; Chen, Yan; Li, Changhong; Ni, Xiaoxiao; Xu, Qin; Yu, Ronghao; Huang, Ruiwang

2017-05-01

Consciousness loss in patients with severe brain injuries is associated with reduced functional connectivity of the default mode network (DMN), fronto-parietal network, and thalamo-cortical network. However, it is still unclear if the brain white matter connectivity between the above mentioned networks is changed in patients with disorders of consciousness (DOC). In this study, we collected diffusion tensor imaging (DTI) data from 13 patients and 17 healthy controls, constructed whole-brain white matter (WM) structural networks with probabilistic tractography. Afterward, we estimated and compared topological properties, and revealed an altered structural organization in the patients. We found a disturbance in the normal balance between segregation and integration in brain structural networks and detected significantly decreased nodal centralities primarily in the basal ganglia and thalamus in the patients. A network-based statistical analysis detected a subnetwork with uniformly significantly decreased structural connections between the basal ganglia, thalamus, and frontal cortex in the patients. Further analysis indicated that along the WM fiber tracts linking the basal ganglia, thalamus, and frontal cortex, the fractional anisotropy was decreased and the radial diffusivity was increased in the patients compared to the controls. Finally, using the receiver operating characteristic method, we found that the structural connections within the NBS-derived component that showed differences between the groups demonstrated high sensitivity and specificity (>90%). Our results suggested that major consciousness deficits in DOC patients may be related to the altered WM connections between the basal ganglia, thalamus, and frontal cortex. Copyright © 2017 Elsevier Ltd. All rights reserved.

Advances in neuroimaging of traumatic brain injury and posttraumatic stress disorder

PubMed Central

Van Boven, Robert W.; Harrington, Greg S.; Hackney, David B.; Ebel, Andreas; Gauger, Grant; Bremner, J. Douglas; D’Esposito, Mark; Detre, John A.; Haacke, E. Mark; Jack, Clifford R.; Jagust, William J.; Le Bihan, Denis; Mathis, Chester A.; Mueller, Susanne; Mukherjee, Pratik; Schuff, Norbert; Chen, Anthony; Weiner, Michael W.

2011-01-01

Improved diagnosis and treatment of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are needed for our military and veterans, their families, and society at large. Advances in brain imaging offer important biomarkers of structural, functional, and metabolic information concerning the brain. This article reviews the application of various imaging techniques to the clinical problems of TBI and PTSD. For TBI, we focus on findings and advances in neuroimaging that hold promise for better detection, characterization, and monitoring of objective brain changes in symptomatic patients with combat-related, closed-head brain injuries not readily apparent by standard computed tomography or conventional magnetic resonance imaging techniques. PMID:20104401

Gaining Insight of Fetal Brain Development with Diffusion MRI and Histology

PubMed Central

Huang, Hao; Vasung, Lana

2013-01-01

Human brain is extraordinarily complex and yet its origin is a simple tubular structure. Its development during the fetal period is characterized by a series of accurately organized events which underlie the mechanisms of dramatic structural changes during fetal development. Revealing detailed anatomy at different stages of human fetal brain development provides insight on understanding not only this highly ordered process, but also the neurobiological foundations of cognitive brain disorders such as mental retardation, autism, schizophrenia, bipolar and language impairment. Diffusion tensor imaging (DTI) and histology are complementary tools which are capable of delineating the fetal brain structures at both macroscopic and microscopic level. In this review, the structural development of the fetal brains has been characterized with DTI and histology. Major components of the fetal brain, including cortical plate, fetal white matter and cerebral wall layer between the ventricle and subplate, have been delineated with DTI and histology. Anisotropic metrics derived from DTI were used to quantify the microstructural changes during the dynamic process of human fetal cortical development and prenatal development of other animal models. Fetal white matter pathways have been traced with DTI-based tractography to reveal growth patterns of individual white matter tracts and corticocortical connectivity. These detailed anatomical accounts of the structural changes during fetal period may provide the clues of detecting developmental and cognitive brain disorders at their early stages. The anatomical information from DTI and histology may also provide reference standards for diagnostic radiology of premature newborns. PMID:23796901

Roadmap on neurophotonics

NASA Astrophysics Data System (ADS)

Cho, Yong Ku; Zheng, Guoan; Augustine, George J.; Hochbaum, Daniel; Cohen, Adam; Knöpfel, Thomas; Pisanello, Ferruccio; Pavone, Francesco S.; Vellekoop, Ivo M.; Booth, Martin J.; Hu, Song; Zhu, Jiang; Chen, Zhongping; Hoshi, Yoko

2016-09-01

Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science’s grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain’s structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and ‘map’ them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken.

Roadmap on neurophotonics

PubMed Central

Cho, Yong Ku; Zheng, Guoan; Augustine, George J; Hochbaum, Daniel; Cohen, Adam; Knöpfel, Thomas; Pisanello, Ferruccio; Pavone, Francesco S; Vellekoop, Ivo M; Booth, Martin J; Hu, Song; Zhu, Jiang; Chen, Zhongping; Hoshi, Yoko

2017-01-01

Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science’s grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain’s structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and ‘map’ them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken. PMID:28386392

Serum S100B Protein is Specifically Related to White Matter Changes in Schizophrenia

PubMed Central

Milleit, Berko; Smesny, Stefan; Rothermundt, Matthias; Preul, Christoph; Schroeter, Matthias L.; von Eiff, Christof; Ponath, Gerald; Milleit, Christine; Sauer, Heinrich; Gaser, Christian

2016-01-01

Background: Schizophrenia can be conceptualized as a form of dysconnectivity between brain regions.To investigate the neurobiological foundation of dysconnectivity, one approach is to analyze white matter structures, such as the pathology of fiber tracks. S100B is considered a marker protein for glial cells, in particular oligodendrocytes and astroglia, that passes the blood brain barrier and is detectable in peripheral blood. Earlier Studies have consistently reported increased S100B levels in schizophrenia. In this study, we aim to investigate associations between S100B and structural white matter abnormalities. Methods: We analyzed data of 17 unmedicated schizophrenic patients (first and recurrent episode) and 22 controls. We used voxel based morphometry (VBM) to detect group differences of white matter structures as obtained from T1-weighted MR-images and considered S100B serum levels as a regressor in an age-corrected interaction analysis. Results: S100B was increased in both patient subgroups. Using VBM, we found clusters indicating significant differences of the association between S100B concentration and white matter. Involved anatomical structures are the posterior cingulate bundle and temporal white matter structures assigned to the superior longitudinal fasciculus. Conclusions: S100B-associated alterations of white matter are shown to be existent already at time of first manifestation of psychosis and are distinct from findings in recurrent episode patients. This suggests involvement of S100B in an ongoing and dynamic process associated with structural brain changes in schizophrenia. However, it remains elusive whether increased S100B serum concentrations in psychotic patients represent a protective response to a continuous pathogenic process or if elevated S100B levels are actively involved in promoting structural brain damage. PMID:27013967

Analysis and asynchronous detection of gradually unfolding errors during monitoring tasks

NASA Astrophysics Data System (ADS)

Omedes, Jason; Iturrate, Iñaki; Minguez, Javier; Montesano, Luis

2015-10-01

Human studies on cognitive control processes rely on tasks involving sudden-onset stimuli, which allow the analysis of these neural imprints to be time-locked and relative to the stimuli onset. Human perceptual decisions, however, comprise continuous processes where evidence accumulates until reaching a boundary. Surpassing the boundary leads to a decision where measured brain responses are associated to an internal, unknown onset. The lack of this onset for gradual stimuli hinders both the analyses of brain activity and the training of detectors. This paper studies electroencephalographic (EEG)-measurable signatures of human processing for sudden and gradual cognitive processes represented as a trajectory mismatch under a monitoring task. Time-locked potentials and brain-source analysis of the EEG of sudden mismatches revealed the typical components of event-related potentials and the involvement of brain structures related to cognitive control processing. For gradual mismatch events, time-locked analyses did not show any discernible EEG scalp pattern, despite related brain areas being, to a lesser extent, activated. However, and thanks to the use of non-linear pattern recognition algorithms, it is possible to train an asynchronous detector on sudden events and use it to detect gradual mismatches, as well as obtaining an estimate of their unknown onset. Post-hoc time-locked scalp and brain-source analyses revealed that the EEG patterns of detected gradual mismatches originated in brain areas related to cognitive control processing. This indicates that gradual events induce latency in the evaluation process but that similar brain mechanisms are present in sudden and gradual mismatch events. Furthermore, the proposed asynchronous detection model widens the scope of applications of brain-machine interfaces to other gradual processes.

Third Trimester Brain Growth in Preterm Infants Compared With In Utero Healthy Fetuses.

PubMed

Bouyssi-Kobar, Marine; du Plessis, Adré J; McCarter, Robert; Brossard-Racine, Marie; Murnick, Jonathan; Tinkleman, Laura; Robertson, Richard L; Limperopoulos, Catherine

2016-11-01

Compared with term infants, preterm infants have impaired brain development at term-equivalent age, even in the absence of structural brain injury. However, details regarding the onset and progression of impaired preterm brain development over the third trimester are unknown. Our primary objective was to compare third-trimester brain volumes and brain growth trajectories in ex utero preterm infants without structural brain injury and in healthy in utero fetuses. As a secondary objective, we examined risk factors associated with brain volumes in preterm infants over the third-trimester postconception. Preterm infants born before 32 weeks of gestational age (GA) and weighing <1500 g with no evidence of structural brain injury on conventional MRI and healthy pregnant women were prospectively recruited. Anatomic T2-weighted brain images of preterm infants and healthy fetuses were parcellated into the following regions: cerebrum, cerebellum, brainstem, and intracranial cavity. We studied 205 participants (75 preterm infants and 130 healthy control fetuses) between 27 and 39 weeks' GA. Third-trimester brain volumes were reduced and brain growth trajectories were slower in the ex utero preterm group compared with the in utero healthy fetuses in the cerebrum, cerebellum, brainstem, and intracranial cavity. Clinical risk factors associated with reduced brain volumes included dexamethasone treatment, the presence of extra-axial blood on brain MRI, confirmed sepsis, and duration of oxygen support. These preterm infants exhibited impaired third-trimester global and regional brain growth in the absence of cerebral/cerebellar parenchymal injury detected by using conventional MRI. Copyright © 2016 by the American Academy of Pediatrics.

Third Trimester Brain Growth in Preterm Infants Compared With In Utero Healthy Fetuses

PubMed Central

Bouyssi-Kobar, Marine; du Plessis, Adré J.; McCarter, Robert; Brossard-Racine, Marie; Murnick, Jonathan; Tinkleman, Laura; Robertson, Richard L.

2016-01-01

BACKGROUND AND OBJECTIVES: Compared with term infants, preterm infants have impaired brain development at term-equivalent age, even in the absence of structural brain injury. However, details regarding the onset and progression of impaired preterm brain development over the third trimester are unknown. Our primary objective was to compare third-trimester brain volumes and brain growth trajectories in ex utero preterm infants without structural brain injury and in healthy in utero fetuses. As a secondary objective, we examined risk factors associated with brain volumes in preterm infants over the third-trimester postconception. METHODS: Preterm infants born before 32 weeks of gestational age (GA) and weighing <1500 g with no evidence of structural brain injury on conventional MRI and healthy pregnant women were prospectively recruited. Anatomic T2-weighted brain images of preterm infants and healthy fetuses were parcellated into the following regions: cerebrum, cerebellum, brainstem, and intracranial cavity. RESULTS: We studied 205 participants (75 preterm infants and 130 healthy control fetuses) between 27 and 39 weeks’ GA. Third-trimester brain volumes were reduced and brain growth trajectories were slower in the ex utero preterm group compared with the in utero healthy fetuses in the cerebrum, cerebellum, brainstem, and intracranial cavity. Clinical risk factors associated with reduced brain volumes included dexamethasone treatment, the presence of extra-axial blood on brain MRI, confirmed sepsis, and duration of oxygen support. CONCLUSIONS: These preterm infants exhibited impaired third-trimester global and regional brain growth in the absence of cerebral/cerebellar parenchymal injury detected by using conventional MRI. PMID:27940782

Radiation-induced brain structural and functional abnormalities in presymptomatic phase and outcome prediction.

PubMed

Ding, Zhongxiang; Zhang, Han; Lv, Xiao-Fei; Xie, Fei; Liu, Lizhi; Qiu, Shijun; Li, Li; Shen, Dinggang

2018-01-01

Radiation therapy, a major method of treatment for brain cancer, may cause severe brain injuries after many years. We used a rare and unique cohort of nasopharyngeal carcinoma patients with normal-appearing brains to study possible early irradiation injury in its presymptomatic phase before severe, irreversible necrosis happens. The aim is to detect any structural or functional imaging biomarker that is sensitive to early irradiation injury, and to understand the recovery and progression of irradiation injury that can shed light on outcome prediction for early clinical intervention. We found an acute increase in local brain activity that is followed by extensive reductions in such activity in the temporal lobe and significant loss of functional connectivity in a distributed, large-scale, high-level cognitive function-related brain network. Intriguingly, these radiosensitive functional alterations were found to be fully or partially recoverable. In contrast, progressive late disruptions to the integrity of the related far-end white matter structure began to be significant after one year. Importantly, early increased local brain functional activity was predictive of severe later temporal lobe necrosis. Based on these findings, we proposed a dynamic, multifactorial model for radiation injury and another preventive model for timely clinical intervention. Hum Brain Mapp 39:407-427, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Low-Frequency Cortical Oscillations Entrain to Subthreshold Rhythmic Auditory Stimuli

PubMed Central

Schroeder, Charles E.; Poeppel, David; van Atteveldt, Nienke

2017-01-01

Many environmental stimuli contain temporal regularities, a feature that can help predict forthcoming input. Phase locking (entrainment) of ongoing low-frequency neuronal oscillations to rhythmic stimuli is proposed as a potential mechanism for enhancing neuronal responses and perceptual sensitivity, by aligning high-excitability phases to events within a stimulus stream. Previous experiments show that rhythmic structure has a behavioral benefit even when the rhythm itself is below perceptual detection thresholds (ten Oever et al., 2014). It is not known whether this “inaudible” rhythmic sound stream also induces entrainment. Here we tested this hypothesis using magnetoencephalography and electrocorticography in humans to record changes in neuronal activity as subthreshold rhythmic stimuli gradually became audible. We found that significant phase locking to the rhythmic sounds preceded participants' detection of them. Moreover, no significant auditory-evoked responses accompanied this prethreshold entrainment. These auditory-evoked responses, distinguished by robust, broad-band increases in intertrial coherence, only appeared after sounds were reported as audible. Taken together with the reduced perceptual thresholds observed for rhythmic sequences, these findings support the proposition that entrainment of low-frequency oscillations serves a mechanistic role in enhancing perceptual sensitivity for temporally predictive sounds. This framework has broad implications for understanding the neural mechanisms involved in generating temporal predictions and their relevance for perception, attention, and awareness. SIGNIFICANCE STATEMENT The environment is full of rhythmically structured signals that the nervous system can exploit for information processing. Thus, it is important to understand how the brain processes such temporally structured, regular features of external stimuli. Here we report the alignment of slowly fluctuating oscillatory brain activity to external rhythmic structure before its behavioral detection. These results indicate that phase alignment is a general mechanism of the brain to process rhythmic structure and can occur without the perceptual detection of this temporal structure. PMID:28411273

Novel frontiers in ultra-structural and molecular MRI of the brain.

PubMed

Duyn, Jeff H; Koretsky, Alan P

2011-08-01

Recent developments in the MRI of the brain continue to expand its use in basic and clinical neuroscience. This review highlights some areas of recent progress. Higher magnetic field strengths and improved signal detectors have allowed improved visualization of the various properties of the brain, facilitating the anatomical definition of function-specific areas and their connections. For example, by sensitizing the MRI signal to the magnetic susceptibility of tissue, it is starting to become possible to reveal the laminar structure of the cortex and identify millimeter-scale fiber bundles. Using exogenous contrast agents, and innovative ways to manipulate contrast, it is becoming possible to highlight specific fiber tracts and cell populations. These techniques are bringing us closer to understanding the evolutionary blueprint of the brain, improving the detection and characterization of disease, and help to guide treatment. Recent MRI techniques are leading to more detailed and more specific contrast in the study of the brain.

Differential numbers of foci of lymphocytes within the brains of Lewis rats exposed to weak complex nocturnal magnetic fields during development of experimental allergic encephalomyelitis.

PubMed

Persinger, Michael A

2009-01-01

To discern if specific structures of the rat brain contained more foci of lymphocytes following induction of experimental allergic encephalomyelitis and exposures to weak, amplitude-modulated magnetic fields for 6 min once per hour during the scotophase, the residuals between the observed and predicted values for the numbers of foci for 320 structures were obtained. Compared to the brains of sham-field exposed rats, the brains of rats exposed to 7-Hz 50 nT (0.5 mG) amplitude-modulated fields showed more foci within hippocampal structures and the dorsal central grey of the midbrain while those exposed to 7-Hz 500 nT (5 mG) fields showed greater densities within the hypothalamus and optic chiasm. The brains of rats exposed to either the 50 nT or 500 nT amplitude-modulated 40-Hz fields displayed greater densities of foci within the midbrain structures related to rapid eye movement. Most of the enhancements of infiltrations within the magnetic field-exposed rats occurred in structures within periventricular or periaqueductal regions and were both frequency- and intensity-dependent. The specificity and complexity of the configurations of the residuals of the numbers of infiltrated foci following exposures to the different fields suggest that the brain itself may be a "sensory organ" for the detection of these stimuli.

2,3,7,8-TCDD effects on visual structure and function in swim-up rainbow trout

USGS Publications Warehouse

Carvalho, Paulo S. M.

2004-01-01

An understanding of mechanisms of contaminant effects across levels of biological organization is essential in ecotoxicology if we are to generate predictive models for population-level effects. We applied a suite of biochemical, histological, and behavioral end points related to visual structure and function and foraging behavior to evaluate effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on swim-up rainbow trout. We detected a dose-dependent decrease in densities of retinal ganglion cells (RGC), key retinal neurons that link the eye with the brain. These changes resulted in corresponding deficits in visual/motor function including reductions in visual acuity and in scotopic and photopic thresholds due to TCDD. The loss of RGCs suggests an increase in convergence of synapses from photoreceptors to RGCs as a cellular mechanism for the visual deficits. Dose-dependent increases in immunohistochemical detection of CYP1A protein in the vasculature of the brain and eye choroid was proportional with decreased ganglion cell densities in the retina. TCDD-induced AHR-regulated effects on these tissues might be involved in the detected decrease in ganglion cell densities. Prey capture rate decreased after TCDD exposure only at the highest treatment groups evaluated. Collectively, these results show that TCDD causes biochemical and structural changes in the eye and brain of rainbow trout that are associated with behavioral deficits leading to decreased individual fitness.

Gaining insight of fetal brain development with diffusion MRI and histology.

PubMed

Huang, Hao; Vasung, Lana

2014-02-01

Human brain is extraordinarily complex and yet its origin is a simple tubular structure. Its development during the fetal period is characterized by a series of accurately organized events which underlie the mechanisms of dramatic structural changes during fetal development. Revealing detailed anatomy at different stages of human fetal brain development provides insight on understanding not only this highly ordered process, but also the neurobiological foundations of cognitive brain disorders such as mental retardation, autism, schizophrenia, bipolar and language impairment. Diffusion tensor imaging (DTI) and histology are complementary tools which are capable of delineating the fetal brain structures at both macroscopic and microscopic levels. In this review, the structural development of the fetal brains has been characterized with DTI and histology. Major components of the fetal brain, including cortical plate, fetal white matter and cerebral wall layer between the ventricle and subplate, have been delineated with DTI and histology. Anisotropic metrics derived from DTI were used to quantify the microstructural changes during the dynamic process of human fetal cortical development and prenatal development of other animal models. Fetal white matter pathways have been traced with DTI-based tractography to reveal growth patterns of individual white matter tracts and corticocortical connectivity. These detailed anatomical accounts of the structural changes during fetal period may provide the clues of detecting developmental and cognitive brain disorders at their early stages. The anatomical information from DTI and histology may also provide reference standards for diagnostic radiology of premature newborns. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Abdominal fat distribution and its relationship to brain changes: the differential effects of age on cerebellar structure and function: a cross-sectional, exploratory study

PubMed Central

Raschpichler, Matthias; Straatman, Kees; Schroeter, Matthias Leopold; Arelin, Katrin; Schlögl, Haiko; Fritzsch, Dominik; Mende, Meinhard; Pampel, André; Böttcher, Yvonne; Stumvoll, Michael; Villringer, Arno; Mueller, Karsten

2013-01-01

Objectives To investigate whether the metabolically important visceral adipose tissue (VAT) relates differently to structural and functional brain changes in comparison with body weight measured as body mass index (BMI). Moreover, we aimed to investigate whether these effects change with age. Design Cross-sectional, exploratory. Setting University Clinic, Integrative Research and Treatment Centre. Participants We included 100 (mean BMI=26.0 kg/m², 42 women) out of 202 volunteers randomly invited by the city's registration office, subdivided into two age groups: young-to-mid-age (n=51, 20–45 years of age, mean BMI=24.9, 24 women) versus old (n=49, 65–70 years of age, mean BMI=27.0, 18 women). Main outcome measures VAT, BMI, subcutaneous abdominal adipose tissue, brain structure (grey matter density), functional brain architecture (eigenvector centrality, EC). Results We discovered a loss of cerebellar structure with increasing VAT in the younger participants, most significantly in regions involved in motor processing. This negative correlation disappeared in the elderly. Investigating functional brain architecture showed again inverse VAT–cerebellum correlations, whereas now regions involved in cognitive and emotional processing were significant. Although we detected similar results for EC using BMI, significant age interaction for both brain structure and functional architecture was only found using VAT. Conclusions Visceral adiposity is associated with cerebellar changes of both structure and function, whereas the regions involved contribute to motor, cognitive and emotional processes. Furthermore, these associations seem to be age dependent, with younger adults’ brains being adversely affected. PMID:23355665

Automated diagnosis of Alzheimer's disease with multi-atlas based whole brain segmentations

NASA Astrophysics Data System (ADS)

Luo, Yuan; Tang, Xiaoying

2017-03-01

Voxel-based analysis is widely used in quantitative analysis of structural brain magnetic resonance imaging (MRI) and automated disease detection, such as Alzheimer's disease (AD). However, noise at the voxel level may cause low sensitivity to AD-induced structural abnormalities. This can be addressed with the use of a whole brain structural segmentation approach which greatly reduces the dimension of features (the number of voxels). In this paper, we propose an automatic AD diagnosis system that combines such whole brain segmen- tations with advanced machine learning methods. We used a multi-atlas segmentation technique to parcellate T1-weighted images into 54 distinct brain regions and extract their structural volumes to serve as the features for principal-component-analysis-based dimension reduction and support-vector-machine-based classification. The relationship between the number of retained principal components (PCs) and the diagnosis accuracy was systematically evaluated, in a leave-one-out fashion, based on 28 AD subjects and 23 age-matched healthy subjects. Our approach yielded pretty good classification results with 96.08% overall accuracy being achieved using the three foremost PCs. In addition, our approach yielded 96.43% specificity, 100% sensitivity, and 0.9891 area under the receiver operating characteristic curve.

Pathological changes in Alzheimer"s brain evaluated with fluorescence emission analysis (FEA)

NASA Astrophysics Data System (ADS)

Christov, Alexander; Ottman, Todd; Grammas, Paula

2004-07-01

Development of AD is associated with cerebrovascular deposition of amyloid beta (Aβ) as well as a progressive increase in vasular collagen content. Both AΒ and collagen are naturally fluorescent compounds when exposed to UV light. We analyzed autofluorescence emitted from brain tissue samples and isolated brain resistance vessels harvested postmortem from patients with Alzheimer's disease (AD) and age-matched controls. Fluorescence emission, excited at 355 nm with an Nd:YAG laser, was measured using a fiber-optic based fluorescence spectroscopic system for tissue analysis. Significantly higher values of fluorescence emission intensity (P<0.001) in the spectral region from 465 to 490 nm were detected in brain resistance vessel samples from AD patients compared to the normal individuals. Results from western blot analysis showed elevated levels of type I and type III collagen, and reduced levels of type IV collagen in resistance vessels from AD patients, compared to control samples. In addition, using direct scanning of the cortical suface for fluoresxcence emission by the laser-induced fluorescence spectroscopy system we detected a significantly (P<0.05) higher level of apoptosis in AD brain tissue compared to age-matched controls. Fluorescence emission analysis (FEA) appears to be a sensitive technique for detecting structural changes in AD brain tissue.

Comparison of nine tractography algorithms for detecting abnormal structural brain networks in Alzheimer’s disease

PubMed Central

Zhan, Liang; Zhou, Jiayu; Wang, Yalin; Jin, Yan; Jahanshad, Neda; Prasad, Gautam; Nir, Talia M.; Leonardo, Cassandra D.; Ye, Jieping; Thompson, Paul M.; for the Alzheimer’s Disease Neuroimaging Initiative

2015-01-01

Alzheimer’s disease (AD) involves a gradual breakdown of brain connectivity, and network analyses offer a promising new approach to track and understand disease progression. Even so, our ability to detect degenerative changes in brain networks depends on the methods used. Here we compared several tractography and feature extraction methods to see which ones gave best diagnostic classification for 202 people with AD, mild cognitive impairment or normal cognition, scanned with 41-gradient diffusion-weighted magnetic resonance imaging as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) project. We computed brain networks based on whole brain tractography with nine different methods – four of them tensor-based deterministic (FACT, RK2, SL, and TL), two orientation distribution function (ODF)-based deterministic (FACT, RK2), two ODF-based probabilistic approaches (Hough and PICo), and one “ball-and-stick” approach (Probtrackx). Brain networks derived from different tractography algorithms did not differ in terms of classification performance on ADNI, but performing principal components analysis on networks helped classification in some cases. Small differences may still be detectable in a truly vast cohort, but these experiments help assess the relative advantages of different tractography algorithms, and different post-processing choices, when used for classification. PMID:25926791

VP-Nets : Efficient automatic localization of key brain structures in 3D fetal neurosonography.

PubMed

Huang, Ruobing; Xie, Weidi; Alison Noble, J

2018-04-23

Three-dimensional (3D) fetal neurosonography is used clinically to detect cerebral abnormalities and to assess growth in the developing brain. However, manual identification of key brain structures in 3D ultrasound images requires expertise to perform and even then is tedious. Inspired by how sonographers view and interact with volumes during real-time clinical scanning, we propose an efficient automatic method to simultaneously localize multiple brain structures in 3D fetal neurosonography. The proposed View-based Projection Networks (VP-Nets), uses three view-based Convolutional Neural Networks (CNNs), to simplify 3D localizations by directly predicting 2D projections of the key structures onto three anatomical views. While designed for efficient use of data and GPU memory, the proposed VP-Nets allows for full-resolution 3D prediction. We investigated parameters that influence the performance of VP-Nets, e.g. depth and number of feature channels. Moreover, we demonstrate that the model can pinpoint the structure in 3D space by visualizing the trained VP-Nets, despite only 2D supervision being provided for a single stream during training. For comparison, we implemented two other baseline solutions based on Random Forest and 3D U-Nets. In the reported experiments, VP-Nets consistently outperformed other methods on localization. To test the importance of loss function, two identical models are trained with binary corss-entropy and dice coefficient loss respectively. Our best VP-Net model achieved prediction center deviation: 1.8 ± 1.4 mm, size difference: 1.9 ± 1.5 mm, and 3D Intersection Over Union (IOU): 63.2 ± 14.7% when compared to the ground truth. To make the whole pipeline intervention free, we also implement a skull-stripping tool using 3D CNN, which achieves high segmentation accuracy. As a result, the proposed processing pipeline takes a raw ultrasound brain image as input, and output a skull-stripped image with five detected key brain structures. Copyright © 2018 Elsevier B.V. All rights reserved.

A novel fibrous duct structure discovered in the brain meninges by using polarized light microscopy

NASA Astrophysics Data System (ADS)

Nam, Min-Ho; Jung, Sharon Jiyoon; Soh, Kwang-Sup; Lim, Jaekwan; Seo, Eunseok; Lim, Jun; Baek, Miok; Lee, Sang Joon

2016-05-01

We have previously reported the discovery of a novel fibrous structure (NFS) consisting of unidirectionally arranged collagen fibers in the spinal pia mater. Due to its unique structure, it was easily detected using polarized light microscopy. In the current study, we describe the discovery of a similar NFS in the brain meninges of rats by using polarized light microscopy. This NFS is located beneath the superior sagittal sinus. Initially, we systemically analyzed the polarization properties of the NFS. The change in the light intensity of the NFS, with respect to the polarization angle, was eight times greater than that of blood vessels, showing that the collagen fibers are oriented in a particular direction with almost perfect parallelism (0.99). The orientation angle of the polarization ellipse confirmed the orientation of the collagen fibers in the NFS. Histological studies further confirmed that the unidirectionally arranged collagen fibers were responsible for this distinct polarization property. Surprisingly, X-ray microtomography and 3D confocal imaging revealed that the NFS contains within it a duct structure, a putative primo vessel. In conclusion, we report a NFS in the brain meninges, detected by using polarized light microscopy, that provides space for a putative primo vessel, not a blood vessel.

Brain tissues volume measurements from 2D MRI using parametric approach

NASA Astrophysics Data System (ADS)

L'vov, A. A.; Toropova, O. A.; Litovka, Yu. V.

2018-04-01

The purpose of the paper is to propose a fully automated method of volume assessment of structures within human brain. Our statistical approach uses maximum interdependency principle for decision making process of measurements consistency and unequal observations. Detecting outliers performed using maximum normalized residual test. We propose a statistical model which utilizes knowledge of tissues distribution in human brain and applies partial data restoration for precision improvement. The approach proposes completed computationally efficient and independent from segmentation algorithm used in the application.

Robust and fast characterization of OCT-based optical attenuation using a novel frequency-domain algorithm for brain cancer detection

NASA Astrophysics Data System (ADS)

Yuan, Wu; Kut, Carmen; Liang, Wenxuan; Li, Xingde

2017-03-01

Cancer is known to alter the local optical properties of tissues. The detection of OCT-based optical attenuation provides a quantitative method to efficiently differentiate cancer from non-cancer tissues. In particular, the intraoperative use of quantitative OCT is able to provide a direct visual guidance in real time for accurate identification of cancer tissues, especially these without any obvious structural layers, such as brain cancer. However, current methods are suboptimal in providing high-speed and accurate OCT attenuation mapping for intraoperative brain cancer detection. In this paper, we report a novel frequency-domain (FD) algorithm to enable robust and fast characterization of optical attenuation as derived from OCT intensity images. The performance of this FD algorithm was compared with traditional fitting methods by analyzing datasets containing images from freshly resected human brain cancer and from a silica phantom acquired by a 1310 nm swept-source OCT (SS-OCT) system. With graphics processing unit (GPU)-based CUDA C/C++ implementation, this new attenuation mapping algorithm can offer robust and accurate quantitative interpretation of OCT images in real time during brain surgery.

A Cross-Sectional and Follow-Up Functional MRI Study with a Working Memory Task in Adolescent Anorexia Nervosa

ERIC Educational Resources Information Center

Castro-Fornieles, Josefina; Caldu, Xavier; Andres-Perpina, Susana; Lazaro, Luisa; Bargallo, Nuria; Falcon, Carles; Plana, Maria Teresa; Junque, Carme

2010-01-01

Structural and functional brain abnormalities have been described in anorexia nervosa (AN). The objective of this study was to examine whether there is abnormal regional brain activation during a working memory task not associated with any emotional stimuli in adolescent patients with anorexia and to detect possible changes after weight recovery.…

Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

PubMed Central

Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

2016-01-01

Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain. PMID:27057543

Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder.

PubMed

Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

2016-01-01

Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.

In vivo voxel based morphometry: detection of increased hippocampal volume and decreased glutamate levels in exercising mice.

PubMed

Biedermann, Sarah; Fuss, Johannes; Zheng, Lei; Sartorius, Alexander; Falfán-Melgoza, Claudia; Demirakca, Traute; Gass, Peter; Ende, Gabriele; Weber-Fahr, Wolfgang

2012-07-16

Voluntary exercise has tremendous effects on adult hippocampal plasticity and metabolism and thus sculpts the hippocampal structure of mammals. High-field (1)H magnetic resonance (MR) investigations at 9.4 T of metabolic and structural changes can be performed non-invasively in the living rodent brain. Numerous molecular and cellular mechanisms mediating the effects of exercise on brain plasticity and behavior have been detected in vitro. However, in vivo attempts have been rare. In this work a method for voxel based morphometry (VBM) was developed with automatic tissue segmentation in mice using a 9.4 T animal scanner equipped with a (1)H-cryogenic coil. The thus increased signal to noise ratio enabled the acquisition of high resolution T2-weighted images of the mouse brain in vivo and the creation of group specific tissue class maps for the segmentation and normalization with SPM. The method was used together with hippocampal single voxel (1)H MR spectroscopy to assess the structural and metabolic differences in the mouse brain due to voluntary wheel running. A specific increase of hippocampal volume with a concomitant decrease of hippocampal glutamate levels in voluntary running mice was observed. An inverse correlation of hippocampal gray matter volume and glutamate concentration indicates a possible implication of the glutamatergic system for hippocampal volume. Copyright © 2012 Elsevier Inc. All rights reserved.

Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core.

PubMed

Tice, Colin M; Noto, Paul B; Fan, Kristi Yi; Zhao, Wei; Lotesta, Stephen D; Dong, Chengguo; Marcus, Andrew P; Zheng, Ya-Jun; Chen, Guozhou; Wu, Zhongren; Van Orden, Rebecca; Zhou, Jing; Bukhtiyarov, Yuri; Zhao, Yi; Lipinski, Kerri; Howard, Lamont; Guo, Joan; Kandpal, Geeta; Meng, Shi; Hardy, Andrew; Krosky, Paula; Gregg, Richard E; Leftheris, Katerina; McKeever, Brian M; Singh, Suresh B; Lala, Deepak; McGeehan, Gerard M; Zhuang, Linghang; Claremon, David A

2016-10-15

Liver X receptor (LXR) agonists have been reported to lower brain amyloid beta (Aβ) and thus to have potential for the treatment of Alzheimer's disease. Structure and property based design led to the discovery of a series of orally bioavailable, brain penetrant LXR agonists. Oral administration of compound 18 to rats resulted in significant upregulation of the expression of the LXR target gene ABCA1 in brain tissue, but no significant effect on Aβ levels was detected. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structural Abnormalities and Learning Impairments Induced by Low Level Thyroid Hormone Insufficiency: A Cross-Fostering Study

EPA Science Inventory

Severe reductions in thyroid hormones (TH) during development alter brain structure and impair learning. Uncertainty surrounds both the impact oflower levels of TH disruption and the sensitivity of available metrics to detect neurodevelopmental deficits of this disruption. We ha...

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

Improving resolution of dynamic communities in human brain networks through targeted node removal

PubMed Central

Turner, Benjamin O.; Miller, Michael B.; Carlson, Jean M.

2017-01-01

Current approaches to dynamic community detection in complex networks can fail to identify multi-scale community structure, or to resolve key features of community dynamics. We propose a targeted node removal technique to improve the resolution of community detection. Using synthetic oscillator networks with well-defined “ground truth” communities, we quantify the community detection performance of a common modularity maximization algorithm. We show that the performance of the algorithm on communities of a given size deteriorates when these communities are embedded in multi-scale networks with communities of different sizes, compared to the performance in a single-scale network. We demonstrate that targeted node removal during community detection improves performance on multi-scale networks, particularly when removing the most functionally cohesive nodes. Applying this approach to network neuroscience, we compare dynamic functional brain networks derived from fMRI data taken during both repetitive single-task and varied multi-task experiments. After the removal of regions in visual cortex, the most coherent functional brain area during the tasks, community detection is better able to resolve known functional brain systems into communities. In addition, node removal enables the algorithm to distinguish clear differences in brain network dynamics between these experiments, revealing task-switching behavior that was not identified with the visual regions present in the network. These results indicate that targeted node removal can improve spatial and temporal resolution in community detection, and they demonstrate a promising approach for comparison of network dynamics between neuroscientific data sets with different resolution parameters. PMID:29261662

Assessing the effects of common variation in the FOXP2 gene on human brain structure.

PubMed

Hoogman, Martine; Guadalupe, Tulio; Zwiers, Marcel P; Klarenbeek, Patricia; Francks, Clyde; Fisher, Simon E

2014-01-01

The FOXP2 transcription factor is one of the most well-known genes to have been implicated in developmental speech and language disorders. Rare mutations disrupting the function of this gene have been described in different families and cases. In a large three-generation family carrying a missense mutation, neuroimaging studies revealed significant effects on brain structure and function, most notably in the inferior frontal gyrus, caudate nucleus, and cerebellum. After the identification of rare disruptive FOXP2 variants impacting on brain structure, several reports proposed that common variants at this locus may also have detectable effects on the brain, extending beyond disorder into normal phenotypic variation. These neuroimaging genetics studies used groups of between 14 and 96 participants. The current study assessed effects of common FOXP2 variants on neuroanatomy using voxel-based morphometry (VBM) and volumetric techniques in a sample of >1300 people from the general population. In a first targeted stage we analyzed single nucleotide polymorphisms (SNPs) claimed to have effects in prior smaller studies (rs2253478, rs12533005, rs2396753, rs6980093, rs7784315, rs17137124, rs10230558, rs7782412, rs1456031), beginning with regions proposed in the relevant papers, then assessing impact across the entire brain. In the second gene-wide stage, we tested all common FOXP2 variation, focusing on volumetry of those regions most strongly implicated from analyses of rare disruptive mutations. Despite using a sample that is more than 10 times that used for prior studies of common FOXP2 variation, we found no evidence for effects of SNPs on variability in neuroanatomy in the general population. Thus, the impact of this gene on brain structure may be largely limited to extreme cases of rare disruptive alleles. Alternatively, effects of common variants at this gene exist but are too subtle to be detected with standard volumetric techniques.

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex.

PubMed

Guadalupe, Tulio; Mathias, Samuel R; vanErp, Theo G M; Whelan, Christopher D; Zwiers, Marcel P; Abe, Yoshinari; Abramovic, Lucija; Agartz, Ingrid; Andreassen, Ole A; Arias-Vásquez, Alejandro; Aribisala, Benjamin S; Armstrong, Nicola J; Arolt, Volker; Artiges, Eric; Ayesa-Arriola, Rosa; Baboyan, Vatche G; Banaschewski, Tobias; Barker, Gareth; Bastin, Mark E; Baune, Bernhard T; Blangero, John; Bokde, Arun L W; Boedhoe, Premika S W; Bose, Anushree; Brem, Silvia; Brodaty, Henry; Bromberg, Uli; Brooks, Samantha; Büchel, Christian; Buitelaar, Jan; Calhoun, Vince D; Cannon, Dara M; Cattrell, Anna; Cheng, Yuqi; Conrod, Patricia J; Conzelmann, Annette; Corvin, Aiden; Crespo-Facorro, Benedicto; Crivello, Fabrice; Dannlowski, Udo; de Zubicaray, Greig I; de Zwarte, Sonja M C; Deary, Ian J; Desrivières, Sylvane; Doan, Nhat Trung; Donohoe, Gary; Dørum, Erlend S; Ehrlich, Stefan; Espeseth, Thomas; Fernández, Guillén; Flor, Herta; Fouche, Jean-Paul; Frouin, Vincent; Fukunaga, Masaki; Gallinat, Jürgen; Garavan, Hugh; Gill, Michael; Suarez, Andrea Gonzalez; Gowland, Penny; Grabe, Hans J; Grotegerd, Dominik; Gruber, Oliver; Hagenaars, Saskia; Hashimoto, Ryota; Hauser, Tobias U; Heinz, Andreas; Hibar, Derrek P; Hoekstra, Pieter J; Hoogman, Martine; Howells, Fleur M; Hu, Hao; Hulshoff Pol, Hilleke E; Huyser, Chaim; Ittermann, Bernd; Jahanshad, Neda; Jönsson, Erik G; Jurk, Sarah; Kahn, Rene S; Kelly, Sinead; Kraemer, Bernd; Kugel, Harald; Kwon, Jun Soo; Lemaitre, Herve; Lesch, Klaus-Peter; Lochner, Christine; Luciano, Michelle; Marquand, Andre F; Martin, Nicholas G; Martínez-Zalacaín, Ignacio; Martinot, Jean-Luc; Mataix-Cols, David; Mather, Karen; McDonald, Colm; McMahon, Katie L; Medland, Sarah E; Menchón, José M; Morris, Derek W; Mothersill, Omar; Maniega, Susana Munoz; Mwangi, Benson; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswaamy, Janardhanan C; Nees, Frauke; Nordvik, Jan E; Onnink, A Marten H; Opel, Nils; Ophoff, Roel; Paillère Martinot, Marie-Laure; Papadopoulos Orfanos, Dimitri; Pauli, Paul; Paus, Tomáš; Poustka, Luise; Reddy, Janardhan Yc; Renteria, Miguel E; Roiz-Santiáñez, Roberto; Roos, Annerine; Royle, Natalie A; Sachdev, Perminder; Sánchez-Juan, Pascual; Schmaal, Lianne; Schumann, Gunter; Shumskaya, Elena; Smolka, Michael N; Soares, Jair C; Soriano-Mas, Carles; Stein, Dan J; Strike, Lachlan T; Toro, Roberto; Turner, Jessica A; Tzourio-Mazoyer, Nathalie; Uhlmann, Anne; Hernández, Maria Valdés; van den Heuvel, Odile A; van der Meer, Dennis; van Haren, Neeltje E M; Veltman, Dick J; Venkatasubramanian, Ganesan; Vetter, Nora C; Vuletic, Daniella; Walitza, Susanne; Walter, Henrik; Walton, Esther; Wang, Zhen; Wardlaw, Joanna; Wen, Wei; Westlye, Lars T; Whelan, Robert; Wittfeld, Katharina; Wolfers, Thomas; Wright, Margaret J; Xu, Jian; Xu, Xiufeng; Yun, Je-Yeon; Zhao, JingJing; Franke, Barbara; Thompson, Paul M; Glahn, David C; Mazoyer, Bernard; Fisher, Simon E; Francks, Clyde

2017-10-01

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.

Getting the beat: entrainment of brain activity by musical rhythm and pleasantness.

PubMed

Trost, Wiebke; Frühholz, Sascha; Schön, Daniele; Labbé, Carolina; Pichon, Swann; Grandjean, Didier; Vuilleumier, Patrik

2014-12-01

Rhythmic entrainment is an important component of emotion induction by music, but brain circuits recruited during spontaneous entrainment of attention by music and the influence of the subjective emotional feelings evoked by music remain still largely unresolved. In this study we used fMRI to test whether the metric structure of music entrains brain activity and how music pleasantness influences such entrainment. Participants listened to piano music while performing a speeded visuomotor detection task in which targets appeared time-locked to either strong or weak beats. Each musical piece was presented in both a consonant/pleasant and dissonant/unpleasant version. Consonant music facilitated target detection and targets presented synchronously with strong beats were detected faster. FMRI showed increased activation of bilateral caudate nucleus when responding on strong beats, whereas consonance enhanced activity in attentional networks. Meter and consonance selectively interacted in the caudate nucleus, with greater meter effects during dissonant than consonant music. These results reveal that the basal ganglia, involved both in emotion and rhythm processing, critically contribute to rhythmic entrainment of subcortical brain circuits by music. Copyright © 2014 Elsevier Inc. All rights reserved.

Alterations in Brain Structure and Functional Connectivity in Alcohol Dependent Patients and Possible Association with Impulsivity.

PubMed

Wang, Junkai; Fan, Yunli; Dong, Yue; Ma, Mengying; Ma, Yi; Dong, Yuru; Niu, Yajuan; Jiang, Yin; Wang, Hong; Wang, Zhiyan; Wu, Liuzhen; Sun, Hongqiang; Cui, Cailian

2016-01-01

Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity.

Immunocytochemical detection of astrocytes in brain slices in combination with Nissl staining.

PubMed

Korzhevskii, D E; Otellin, V A

2005-07-01

The present study was performed to develop a simple and reliable method for the combined staining of specimens to allow the advantages of immunocytochemical detection of astrocytes and assessment of the functional state of neurons by the Nissl method to be assessed simultaneously. The protocol suggested for processing paraffin sections allows preservation of tissue structure at high quality and allows the selective identification of astrocytes with counterstaining of neurons by the Nissl method. The protocol can be used without modification for processing brain specimens from humans and various mammals--except mice and rabbits.

Investigating brain community structure abnormalities in bipolar disorder using path length associated community estimation.

PubMed

Gadelkarim, Johnson J; Ajilore, Olusola; Schonfeld, Dan; Zhan, Liang; Thompson, Paul M; Feusner, Jamie D; Kumar, Anand; Altshuler, Lori L; Leow, Alex D

2014-05-01

In this article, we present path length associated community estimation (PLACE), a comprehensive framework for studying node-level community structure. Instead of the well-known Q modularity metric, PLACE utilizes a novel metric, Ψ(PL), which measures the difference between intercommunity versus intracommunity path lengths. We compared community structures in human healthy brain networks generated using these two metrics and argued that Ψ(PL) may have theoretical advantages. PLACE consists of the following: (1) extracting community structure using top-down hierarchical binary trees, where a branch at each bifurcation denotes a collection of nodes that form a community at that level, (2) constructing and assessing mean group community structure, and (3) detecting node-level changes in community between groups. We applied PLACE and investigated the structural brain networks obtained from a sample of 25 euthymic bipolar I subjects versus 25 gender- and age-matched healthy controls. Results showed community structural differences in posterior default mode network regions, with the bipolar group exhibiting left-right decoupling. Copyright © 2013 Wiley Periodicals, Inc.

Detection of white matter injury in concussion using high-definition fiber tractography.

PubMed

Shin, Samuel S; Pathak, Sudhir; Presson, Nora; Bird, William; Wagener, Lauren; Schneider, Walter; Okonkwo, David O; Fernandez-Miranda, Juan C

2014-01-01

Over the last few decades, structural imaging techniques of the human brain have undergone significant strides. High resolution provided by recent developments in magnetic resonance imaging (MRI) allows improved detection of injured regions in patients with moderate-to-severe traumatic brain injury (TBI). In addition, diffusion imaging techniques such as diffusion tensor imaging (DTI) has gained much interest recently due to its possible utility in detecting structural integrity of white matter pathways in mild TBI (mTBI) cases. However, the results from recent DTI studies in mTBI patients remain equivocal. Also, there are important shortcomings for DTI such as limited resolution in areas of multiple crossings and false tract formation. The detection of white matter damage in concussion remains challenging, and development of imaging biomarkers for mTBI is still in great need. In this chapter, we discuss our experience with high-definition fiber tracking (HDFT), a diffusion spectrum imaging-based technique. We also discuss ongoing developments and specific advantages HDFT may offer concussion patients. © 2014 S. Karger AG, Basel.

Brain tumor locating in 3D MR volume using symmetry

NASA Astrophysics Data System (ADS)

Dvorak, Pavel; Bartusek, Karel

2014-03-01

This work deals with the automatic determination of a brain tumor location in 3D magnetic resonance volumes. The aim of this work is not the precise segmentation of the tumor and its parts but only the detection of its location. This work is the first step in the tumor segmentation process, an important topic in neuro-image processing. The algorithm expects 3D magnetic resonance volumes of brain containing a tumor. The detection is based on locating the area that breaks the left-right symmetry of the brain. This is done by multi-resolution comparing of corresponding regions in left and right hemisphere. The output of the computation is the probabilistic map of the tumor location. The created algorithm was tested on 80 volumes from publicly available BRATS databases containing 3D brain volumes afflicted by a brain tumor. These pathological structures had various sizes and shapes and were located in various parts of the brain. The locating performance of the algorithm was 85% for T1-weighted volumes, 91% for T1-weighted contrast enhanced volumes, 96% for FLAIR and T2-wieghted volumes and 95% for their combinations.

The role of image registration in brain mapping

PubMed Central

Toga, A.W.; Thompson, P.M.

2008-01-01

Image registration is a key step in a great variety of biomedical imaging applications. It provides the ability to geometrically align one dataset with another, and is a prerequisite for all imaging applications that compare datasets across subjects, imaging modalities, or across time. Registration algorithms also enable the pooling and comparison of experimental findings across laboratories, the construction of population-based brain atlases, and the creation of systems to detect group patterns in structural and functional imaging data. We review the major types of registration approaches used in brain imaging today. We focus on their conceptual basis, the underlying mathematics, and their strengths and weaknesses in different contexts. We describe the major goals of registration, including data fusion, quantification of change, automated image segmentation and labeling, shape measurement, and pathology detection. We indicate that registration algorithms have great potential when used in conjunction with a digital brain atlas, which acts as a reference system in which brain images can be compared for statistical analysis. The resulting armory of registration approaches is fundamental to medical image analysis, and in a brain mapping context provides a means to elucidate clinical, demographic, or functional trends in the anatomy or physiology of the brain. PMID:19890483

Individualized Gaussian process-based prediction and detection of local and global gray matter abnormalities in elderly subjects.

PubMed

Ziegler, G; Ridgway, G R; Dahnke, R; Gaser, C

2014-08-15

Structural imaging based on MRI is an integral component of the clinical assessment of patients with potential dementia. We here propose an individualized Gaussian process-based inference scheme for clinical decision support in healthy and pathological aging elderly subjects using MRI. The approach aims at quantitative and transparent support for clinicians who aim to detect structural abnormalities in patients at risk of Alzheimer's disease or other types of dementia. Firstly, we introduce a generative model incorporating our knowledge about normative decline of local and global gray matter volume across the brain in elderly. By supposing smooth structural trajectories the models account for the general course of age-related structural decline as well as late-life accelerated loss. Considering healthy subjects' demography and global brain parameters as informative about normal brain aging variability affords individualized predictions in single cases. Using Gaussian process models as a normative reference, we predict new subjects' brain scans and quantify the local gray matter abnormalities in terms of Normative Probability Maps (NPM) and global z-scores. By integrating the observed expectation error and the predictive uncertainty, the local maps and global scores exploit the advantages of Bayesian inference for clinical decisions and provide a valuable extension of diagnostic information about pathological aging. We validate the approach in simulated data and real MRI data. We train the GP framework using 1238 healthy subjects with ages 18-94 years, and predict in 415 independent test subjects diagnosed as healthy controls, Mild Cognitive Impairment and Alzheimer's disease. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Individualized Gaussian process-based prediction and detection of local and global gray matter abnormalities in elderly subjects

PubMed Central

Ziegler, G.; Ridgway, G.R.; Dahnke, R.; Gaser, C.

2014-01-01

Structural imaging based on MRI is an integral component of the clinical assessment of patients with potential dementia. We here propose an individualized Gaussian process-based inference scheme for clinical decision support in healthy and pathological aging elderly subjects using MRI. The approach aims at quantitative and transparent support for clinicians who aim to detect structural abnormalities in patients at risk of Alzheimer's disease or other types of dementia. Firstly, we introduce a generative model incorporating our knowledge about normative decline of local and global gray matter volume across the brain in elderly. By supposing smooth structural trajectories the models account for the general course of age-related structural decline as well as late-life accelerated loss. Considering healthy subjects' demography and global brain parameters as informative about normal brain aging variability affords individualized predictions in single cases. Using Gaussian process models as a normative reference, we predict new subjects' brain scans and quantify the local gray matter abnormalities in terms of Normative Probability Maps (NPM) and global z-scores. By integrating the observed expectation error and the predictive uncertainty, the local maps and global scores exploit the advantages of Bayesian inference for clinical decisions and provide a valuable extension of diagnostic information about pathological aging. We validate the approach in simulated data and real MRI data. We train the GP framework using 1238 healthy subjects with ages 18–94 years, and predict in 415 independent test subjects diagnosed as healthy controls, Mild Cognitive Impairment and Alzheimer's disease. PMID:24742919

Classifying social anxiety disorder using multivoxel pattern analyses of brain function and structure☆

PubMed Central

Frick, Andreas; Gingnell, Malin; Marquand, Andre F.; Howner, Katarina; Fischer, Håkan; Kristiansson, Marianne; Williams, Steven C.R.; Fredrikson, Mats; Furmark, Tomas

2014-01-01

Functional neuroimaging of social anxiety disorder (SAD) support altered neural activation to threat-provoking stimuli focally in the fear network, while structural differences are distributed over the temporal and frontal cortices as well as limbic structures. Previous neuroimaging studies have investigated the brain at the voxel level using mass-univariate methods which do not enable detection of more complex patterns of activity and structural alterations that may separate SAD from healthy individuals. Support vector machine (SVM) is a supervised machine learning method that capitalizes on brain activation and structural patterns to classify individuals. The aim of this study was to investigate if it is possible to discriminate SAD patients (n = 14) from healthy controls (n = 12) using SVM based on (1) functional magnetic resonance imaging during fearful face processing and (2) regional gray matter volume. Whole brain and region of interest (fear network) SVM analyses were performed for both modalities. For functional scans, significant classifications were obtained both at whole brain level and when restricting the analysis to the fear network while gray matter SVM analyses correctly classified participants only when using the whole brain search volume. These results support that SAD is characterized by aberrant neural activation to affective stimuli in the fear network, while disorder-related alterations in regional gray matter volume are more diffusely distributed over the whole brain. SVM may thus be useful for identifying imaging biomarkers of SAD. PMID:24239689

Structural connectivity in schizophrenia and its impact on the dynamics of spontaneous functional networks

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

Cabral, Joana; Department of Psychiatry, University of Oxford, Oxford OX3 7JX; Fernandes, Henrique M.

The neuropathology of schizophrenia remains unclear. Some insight has come from modern neuroimaging techniques, which offer an unparalleled opportunity to explore in vivo the structure and function of the brain. Using functional magnetic resonance imaging, it has been found that the large-scale resting-state functional connectivity (rsFC) in schizophrenia — measured as the temporal correlations of the blood-oxygen-level-dependent (BOLD) signal — exhibit altered network topology, with lower small-world index. The origin of these rsFC alterations and link with the underlying structural connectivity remain unclear. In this work, we used a computational model of spontaneous large-scale brain activity to explore the rolemore » of the structural connectivity in the large-scale dynamics of the brain in health and schizophrenia. The structural connectomes from 15 adolescent patients with early-onset schizophrenia and 15 age- and gender-matched controls were built from diffusion tensor imaging data to detect the white matter tracts between 90 brain areas. Brain areas, simulated using a reduced dynamic mean-field model, receive excitatory input from other areas in proportion to the number of fibre tracts between them. The simulated mean field activity was transformed into BOLD signal, and the properties of the simulated functional networks were analyzed. Our results suggest that the functional alterations observed in schizophrenia are not directly linked to alterations in the structural topology. Instead, subtly randomized and less small-world functional networks appear when the brain operates with lower global coupling, which shifts the dynamics from the optimal healthy regime.« less

Structural connectivity in schizophrenia and its impact on the dynamics of spontaneous functional networks

NASA Astrophysics Data System (ADS)

Cabral, Joana; Fernandes, Henrique M.; Van Hartevelt, Tim J.; James, Anthony C.; Kringelbach, Morten L.; Deco, Gustavo

2013-12-01

The neuropathology of schizophrenia remains unclear. Some insight has come from modern neuroimaging techniques, which offer an unparalleled opportunity to explore in vivo the structure and function of the brain. Using functional magnetic resonance imaging, it has been found that the large-scale resting-state functional connectivity (rsFC) in schizophrenia — measured as the temporal correlations of the blood-oxygen-level-dependent (BOLD) signal — exhibit altered network topology, with lower small-world index. The origin of these rsFC alterations and link with the underlying structural connectivity remain unclear. In this work, we used a computational model of spontaneous large-scale brain activity to explore the role of the structural connectivity in the large-scale dynamics of the brain in health and schizophrenia. The structural connectomes from 15 adolescent patients with early-onset schizophrenia and 15 age- and gender-matched controls were built from diffusion tensor imaging data to detect the white matter tracts between 90 brain areas. Brain areas, simulated using a reduced dynamic mean-field model, receive excitatory input from other areas in proportion to the number of fibre tracts between them. The simulated mean field activity was transformed into BOLD signal, and the properties of the simulated functional networks were analyzed. Our results suggest that the functional alterations observed in schizophrenia are not directly linked to alterations in the structural topology. Instead, subtly randomized and less small-world functional networks appear when the brain operates with lower global coupling, which shifts the dynamics from the optimal healthy regime.

ErbB4 in Laminated Brain Structures: A Neurodevelopmental Approach to Schizophrenia

PubMed Central

Perez-Garcia, Carlos G.

2015-01-01

The susceptibility genes for schizophrenia Neuregulin-1 (NRG1) and ErbB4 have critical functions during brain development and in the adult. Alterations in the ErbB4 signaling pathway cause a variety of neurodevelopmental defects including deficiencies in neuronal migration, synaptic plasticity, and myelination. I have used the ErbB4-/- HER4heart KO mice to study the neurodevelopmental insults associated to deficiencies in the NRG1-ErbB4 signaling pathway and their potential implication with brain disorders such as schizophrenia, a chronic psychiatric disease affecting 1% of the population worldwide. ErbB4 deletion results in an array of neurodevelopmental deficits that are consistent with a schizophrenic model. First, similar defects appear in multiple brain structures, from the cortex to the cerebellum. Second, these defects affect multiple aspects of brain development, from deficits in neuronal migration to impairments in excitatory/inhibitory systems, including reductions in brain volume, cortical and cerebellar heterotopias, alterations in number and distribution of specific subpopulations of interneurons, deficiencies in the astrocytic and oligodendrocytic lineages, and additional insults in major brain structures. This suggests that alterations in specific neurodevelopmental genes that play similar functions in multiple neuroanatomical structures might account for some of the symptomatology observed in schizophrenic patients, such as defects in cognition. ErbB4 mutation uncovers flaws in brain development that are compatible with a neurodevelopmental model of schizophrenia, and it establishes a comprehensive model to study the basis of the disorder before symptoms are detected in the adult. PMID:26733804

Multilayer motif analysis of brain networks

NASA Astrophysics Data System (ADS)

Battiston, Federico; Nicosia, Vincenzo; Chavez, Mario; Latora, Vito

2017-04-01

In the last decade, network science has shed new light both on the structural (anatomical) and on the functional (correlations in the activity) connectivity among the different areas of the human brain. The analysis of brain networks has made possible to detect the central areas of a neural system and to identify its building blocks by looking at overabundant small subgraphs, known as motifs. However, network analysis of the brain has so far mainly focused on anatomical and functional networks as separate entities. The recently developed mathematical framework of multi-layer networks allows us to perform an analysis of the human brain where the structural and functional layers are considered together. In this work, we describe how to classify the subgraphs of a multiplex network, and we extend the motif analysis to networks with an arbitrary number of layers. We then extract multi-layer motifs in brain networks of healthy subjects by considering networks with two layers, anatomical and functional, respectively, obtained from diffusion and functional magnetic resonance imaging. Results indicate that subgraphs in which the presence of a physical connection between brain areas (links at the structural layer) coexists with a non-trivial positive correlation in their activities are statistically overabundant. Finally, we investigate the existence of a reinforcement mechanism between the two layers by looking at how the probability to find a link in one layer depends on the intensity of the connection in the other one. Showing that functional connectivity is non-trivially constrained by the underlying anatomical network, our work contributes to a better understanding of the interplay between the structure and function in the human brain.

Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical Vision Loss in Glaucoma.

PubMed

Murphy, Matthew C; Conner, Ian P; Teng, Cindy Y; Lawrence, Jesse D; Safiullah, Zaid; Wang, Bo; Bilonick, Richard A; Kim, Seong-Gi; Wollstein, Gadi; Schuman, Joel S; Chan, Kevin C

2016-08-11

Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease.

Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical Vision Loss in Glaucoma

PubMed Central

Murphy, Matthew C.; Conner, Ian P.; Teng, Cindy Y.; Lawrence, Jesse D.; Safiullah, Zaid; Wang, Bo; Bilonick, Richard A.; Kim, Seong-Gi; Wollstein, Gadi; Schuman, Joel S.; Chan, Kevin C.

2016-01-01

Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease. PMID:27510406

Smart near-infrared fluorescence probes with donor-acceptor structure for in vivo detection of β-amyloid deposits.

PubMed

Cui, Mengchao; Ono, Masahiro; Watanabe, Hiroyuki; Kimura, Hiroyuki; Liu, Boli; Saji, Hideo

2014-03-05

The deposition of β-amyloid (Aβ) plaques in the parenchymal and cortical brain is accepted as the main pathological hallmark of Alzheimer's disease (AD); however, early detection of AD still presents a challenge. With the assistance of molecular imaging techniques, imaging agents specifically targeting Aβ plaques in the brain may lead to the early diagnosis of AD. Herein, we report the design, synthesis, and evaluation of a series of smart near-infrared fluorescence (NIRF) imaging probes with donor-acceptor architecture bridged by a conjugated π-electron chain for Aβ plaques. The chemical structure of these NIRF probes is completely different from Congo Red and Thioflavin-T. Probes with a longer conjugated π system (carbon-carbon double bond) displayed maximum emission in PBS (>650 nm), which falls in the best range for NIRF probes. These probes were proved to have affinity to Aβ plaques in fluorescent staining of brain sections from an AD patient and double transgenic mice, as well as in an in vitro binding assay using Aβ(1-42) aggregates. One probe with high affinity (K(i) = 37 nM, K(d) = 27 nM) was selected for in vivo imaging. It can penetrate the blood-brain barrier of nude mice efficiently and is quickly washed out of the normal brain. Moreover, after intravenous injection of this probe, 22-month-old APPswe/PSEN1 mice exhibited a higher relative signal than control mice over the same period of time, and ex vivo fluorescent observations confirmed the existence of Aβ plaques. In summary, this probe meets most of the requirements for a NIRF contrast agent for the detection of Aβ plaques both in vitro and in vivo.

Neural coding of basic reward terms of animal learning theory, game theory, microeconomics and behavioural ecology.

PubMed

Schultz, Wolfram

2004-04-01

Neurons in a small number of brain structures detect rewards and reward-predicting stimuli and are active during the expectation of predictable food and liquid rewards. These neurons code the reward information according to basic terms of various behavioural theories that seek to explain reward-directed learning, approach behaviour and decision-making. The involved brain structures include groups of dopamine neurons, the striatum including the nucleus accumbens, the orbitofrontal cortex and the amygdala. The reward information is fed to brain structures involved in decision-making and organisation of behaviour, such as the dorsolateral prefrontal cortex and possibly the parietal cortex. The neural coding of basic reward terms derived from formal theories puts the neurophysiological investigation of reward mechanisms on firm conceptual grounds and provides neural correlates for the function of rewards in learning, approach behaviour and decision-making.

Neuroimaging parameters in early open spina bifida detection. Further benefit in first trimester screening?

PubMed

Iliescu, D; Comănescu, A; Antsaklis, P; Tudorache, Stefania; Ghiluşi, Mirela; Comănescu, Violeta; Paulescu, Daniela; Ceauşu, Iuliana; Antsaklis, A; Novac, Liliana; Cernea, N

2011-01-01

Morphological investigation of the central nervous system (CNS) in fetuses with positive markers for open spina bifida (OSB) detection, visualized by ultrasound during the first trimester of pregnancy. Data from fetuses that underwent routine first trimester ultrasound scan in our center during September 2007-March 2011 and presented abnormal aspects of the fourth ventricle, also referred as intracranial translucency (IT), provided the morphological support to evaluate CNS features. A neuro-histological study of posterior cerebral fossa illustrated anatomical features of the structures involved in the sonographic first trimester detection of neural tube defects. Abnormal IT aspects were found in OSB cases examined in the first trimester, but also in other severe cerebral abnormalities. Brain stem antero-posterior diameter (BS) and brain stem to occipital bone (BSOB) ratio may be more specific for OSB detection. Correlations between histological aspects of posterior brain fossa and ultrasound standard assessment have been made; highlighting the anatomical features involved by the new techniques developed for OSB early detection. Preliminary results show that modern sonographic protocols are capable to detect abnormalities in the morphometry of the posterior brain. First trimester fourth ventricle abnormalities should be followed by careful CNS evaluation because are likely to appear in OSB affected fetuses, but also in other CNS severe anomalies; in such cases, normal BS and BSOB ratio may serve as indirect argument for spine integrity, if specificity is confirmed in large series of fetuses.

Trace element distribution in the rat cerebellum

NASA Astrophysics Data System (ADS)

Kwiatek, W. M.; Long, G. J.; Pounds, J. G.; Reuhl, K. R.; Hanson, A. L.; Jones, K. W.

1990-04-01

Spatial distributions and concentrations of trace elements (TE) in the brain are important because TE perform catalytic and structural functions in enzymes which regulate brain function and development. We have investigated the distributions of TE in rat cerebellum. Structures were sectioned and analyzed by the Synchrotron Radiation Induced X-ray Emission (SRIXE) method using the NSLS X-26 white-light microprobe facility. Advantages important for TE analysis of biological specimens with X-ray microscopy include short time of measurement, high brightness and flux, good spatial resolution, multielemental detection, good sensitivity, and nondestructive irradiation. Trace elements were measured in thin rat brain sections of 20 μm thickness. The analyses were performed on sample volumes as small as 0.2 nl with Minimum Detectable Limits (MDL) of 50 ppb wet weight for Fe, 100 ppb wet weight for Cu, and Zn, and 1 ppm wet weight for Pb. The distribution of TE in the molecular cell layer, granule cell layer and fiber tract of rat cerebella was investigated. Both point analyses and two-dimensional semiquantitative mapping of the TE distribution in a section were used. All analyzed elements were observed in each structure of the cerebellum except mercury which was not observed in granule cell layer or fiber tract. This approach permits an exacting correlation of the TE distribution in complex structure with the diet, toxic elements, and functional status of the animal.

A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly

PubMed Central

Stein, Jason L.; Hua, Xue; Lee, Suh; Hibar, Derrek P.; Leow, Alex D.; Dinov, Ivo D.; Toga, Arthur W.; Saykin, Andrew J.; Shen, Li; Foroud, Tatiana; Pankratz, Nathan; Huentelman, Matthew J.; Craig, David W.; Gerber, Jill D.; Allen, April N.; Corneveaux, Jason J.; Stephan, Dietrich A.; DeCarli, Charles S.; DeChairo, Bryan M.; Potkin, Steven G.; Jack, Clifford R.; Weiner, Michael W.; Raji, Cyrus A.; Lopez, Oscar L.; Becker, James T.; Carmichael, Owen T.; Thompson, Paul M.; Weiner, Michael; Thal, Leon; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Gamst, Anthony; Potter, William Z.; Montine, Tom; Anders, Dale; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Trojanowki, John; Shaw, Les; Lee, Virginia M.-Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Harvey, Danielle; Gamst, Anthony; Kornak, John; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Vorobik, Remi; Quinn, Joseph; Schneider, Lon; Pawluczyk, Sonia; Spann, Bryan; Fleisher, Adam S.; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Badger, Beverly; Grossman, Hillel; Tang, Cheuk; Stern, Jessica; deToledo-Morrell, Leyla; Shah, Raj C.; Bach, Julie; Duara, Ranjan; Isaacson, Richard; Strauman, Silvia; Albert, Marilyn S.; Pedroso, Julia; Toroney, Jaimie; Rusinek, Henry; de Leon, Mony J; De Santi, Susan M; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Aiello, Marilyn; Clark, Christopher M.; Pham, Cassie; Nunez, Jessica; Smith, Charles D.; Given II, Curtis A.; Hardy, Peter; DeKosky, Steven T.; Oakley, MaryAnn; Simpson, Donna M.; Ismail, M. Saleem; Porsteinsson, Anton; McCallum, Colleen; Cramer, Steven C.; Mulnard, Ruth A.; McAdams-Ortiz, Catherine; Diaz-Arrastia, Ramon; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Laubinger, Mary M.; Bartzokis, George; Silverman, Daniel H.S.; Lu, Po H.; Fletcher, Rita; Parfitt, Francine; Johnson, Heather; Farlow, Martin; Herring, Scott; Hake, Ann M.; van Dyck, Christopher H.; MacAvoy, Martha G.; Bifano, Laurel A.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Graham, Simon; Caldwell, Curtis; Feldman, Howard; Assaly, Michele; Hsiung, Ging-Yuek R.; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Gitelman, Darren; Johnson, Nancy; Mesulam, Marsel; Sadowsky, Carl; Villena, Teresa; Mesner, Scott; Aisen, Paul S.; Johnson, Kathleen B.; Behan, Kelly E.; Sperling, Reisa A.; Rentz, Dorene M.; Johnson, Keith A.; Rosen, Allyson; Tinklenberg, Jared; Ashford, Wes; Sabbagh, Marwan; Connor, Donald; Obradov, Sanja; Killiany, Ron; Norbash, Alex; Obisesan, Thomas O.; Jayam-Trouth, Annapurni; Wang, Paul; Auchus, Alexander P.; Huang, Juebin; Friedland, Robert P.; DeCarli, Charles; Fletcher, Evan; Carmichael, Owen; Kittur, Smita; Mirje, Seema; Johnson, Sterling C.; Borrie, Michael; Lee, T-Y; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Highum, Diane; Preda, Adrian; Nguyen, Dana; Tariot, Pierre N.; Hendin, Barry A.; Scharre, Douglas W.; Kataki, Maria; Beversdorf, David Q.; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Gandy, Sam; Marenberg, Marjorie E.; Rovner, Barry W.; Pearlson, Godfrey; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Pare, Nadia; Williamson, Jeff D.; Sink, Kaycee M.; Potter, Huntington; Ashok Raj, B.; Giordano, Amy; Ott, Brian R.; Wu, Chuang-Kuo; Cohen, Ronald; Wilks, Kerri L.

2010-01-01

A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly. PMID:20404173

A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly.

PubMed

Ho, April J; Stein, Jason L; Hua, Xue; Lee, Suh; Hibar, Derrek P; Leow, Alex D; Dinov, Ivo D; Toga, Arthur W; Saykin, Andrew J; Shen, Li; Foroud, Tatiana; Pankratz, Nathan; Huentelman, Matthew J; Craig, David W; Gerber, Jill D; Allen, April N; Corneveaux, Jason J; Stephan, Dietrich A; DeCarli, Charles S; DeChairo, Bryan M; Potkin, Steven G; Jack, Clifford R; Weiner, Michael W; Raji, Cyrus A; Lopez, Oscar L; Becker, James T; Carmichael, Owen T; Thompson, Paul M

2010-05-04

A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an approximately 1.2 kg higher weight, on average, in adults and an approximately 1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of approximately 8% in the frontal lobes and 12% in the occipital lobes-these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

Brain Imaging and Human Nutrition: Which Measures to Use in Intervention Studies?12

PubMed Central

Sizonenko, Stéphane V.; Babiloni, Claudio; Sijben, John W.; Walhovd, Kristine B.

2013-01-01

Throughout the life span, the brain is a metabolically highly active organ that uses a large proportion of total nutrient and energy intake. Furthermore, the development and repair of neural tissue depend on the proper intake of essential structural nutrients, minerals, and vitamins. Therefore, what we eat, or refrain from eating, may have an important impact on our cognitive ability and mental performance. Two of the key areas in which diet is thought to play an important role are in optimizing neurodevelopment in children and in preventing neurodegeneration and cognitive decline during aging. From early development to aging, brain imaging can detect structural, functional, and metabolic changes in humans and modifications due to altered nutrition or to additional nutritional supplementation. Inclusion of imaging measures in clinical studies can increase understanding with regard to the modification of brain structure, metabolism, and functional endpoints and may provide early sensitive measures of long-term effects. In this symposium, the utility of existing brain imaging technologies to assess the effects of nutritional intervention in humans is described. Examples of current research showing the utility of these markers are reviewed. PMID:24038255

A Statistical Analysis of Brain Morphology Using Wild Bootstrapping

PubMed Central

Ibrahim, Joseph G.; Tang, Niansheng; Rowe, Daniel B.; Hao, Xuejun; Bansal, Ravi; Peterson, Bradley S.

2008-01-01

Methods for the analysis of brain morphology, including voxel-based morphology and surface-based morphometries, have been used to detect associations between brain structure and covariates of interest, such as diagnosis, severity of disease, age, IQ, and genotype. The statistical analysis of morphometric measures usually involves two statistical procedures: 1) invoking a statistical model at each voxel (or point) on the surface of the brain or brain subregion, followed by mapping test statistics (e.g., t test) or their associated p values at each of those voxels; 2) correction for the multiple statistical tests conducted across all voxels on the surface of the brain region under investigation. We propose the use of new statistical methods for each of these procedures. We first use a heteroscedastic linear model to test the associations between the morphological measures at each voxel on the surface of the specified subregion (e.g., cortical or subcortical surfaces) and the covariates of interest. Moreover, we develop a robust test procedure that is based on a resampling method, called wild bootstrapping. This procedure assesses the statistical significance of the associations between a measure of given brain structure and the covariates of interest. The value of this robust test procedure lies in its computationally simplicity and in its applicability to a wide range of imaging data, including data from both anatomical and functional magnetic resonance imaging (fMRI). Simulation studies demonstrate that this robust test procedure can accurately control the family-wise error rate. We demonstrate the application of this robust test procedure to the detection of statistically significant differences in the morphology of the hippocampus over time across gender groups in a large sample of healthy subjects. PMID:17649909

The musical brain: brain waves reveal the neurophysiological basis of musicality in human subjects.

PubMed

Tervaniemi, M; Ilvonen, T; Karma, K; Alho, K; Näätänen, R

1997-04-18

To reveal neurophysiological prerequisites of musicality, auditory event-related potentials (ERPs) were recorded from musical and non-musical subjects, musicality being here defined as the ability to temporally structure auditory information. Instructed to read a book and to ignore sounds, subjects were presented with a repetitive sound pattern with occasional changes in its temporal structure. The mismatch negativity (MMN) component of ERPs, indexing the cortical preattentive detection of change in these stimulus patterns, was larger in amplitude in musical than non-musical subjects. This amplitude enhancement, indicating more accurate sensory memory function in musical subjects, suggests that even the cognitive component of musicality, traditionally regarded as depending on attention-related brain processes, in fact, is based on neural mechanisms present already at the preattentive level.

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.

Longitudinal assessment of chemotherapy-induced changes in brain and cognitive functioning: A systematic review.

PubMed

Li, Mingmei; Caeyenberghs, Karen

2018-05-20

In addition to the burden of a life-threatening diagnosis, cancer patients are struggling with adverse side-effects from cancer treatment. Chemotherapy has been linked to an array of cognitive impairments and alterations in brain structure and function ("chemobrain"). In this review, we summarized the existing evidence that evaluate the changes in cognitive functioning and brain with chemotherapy, as assessed using structural and functional MRI-based techniques in a longitudinal design. This review followed the latest PRISMA guidelines using Embase, Medline, PsychINFO, Scopus, and Web of Science databases with date restrictions from 2012-2017. Fourteen research articles met the key inclusion criteria: (i) the studies involved adult cancer patients (mean age≥18); (ii) the use of chemotherapy in the treatment of cancer; (iii) pre-post assessment of behavioral and brain-based outcomes; and (iv) abstracts written in English. Effect sizes of subjective and objective cognitive impairments from the reviewed studies were estimated using Cohen's d or z-scores. We calculated percentage of mean change or effect sizes for main neuroimaging findings when data were available. Strength of the correlations between brain alterations and cognitive changes was obtained using squared correlation coefficients. We showed small to medium effect sizes on individual tests of attention, processing speed, verbal memory, and executive control; and medium effect sizes on self-report questionnaires. Neuroimaging data showed reduced grey matter density in cancer patients in frontal, parietal, and temporal regions. Changes in brain function (brain activation and cerebral blood flow) were observed with cancer across functional networks involving (pre)frontal, parietal, occipital, temporal, and cerebellar regions. Data from diffusion-weighted MRI suggested reduced white matter integrity involving the superior longitudinal fasciculus, corpus callosum, forceps major, and corona radiate, and altered structural connectivity across the whole brain network. Finally, we observed moderate-to-strong correlations between worsening cognitive function and morphological changes in frontal brain regions. While MRI is a powerful tool for detection of longitudinal brain changes in the 'chemobrain', the underlying biological mechanisms are still unclear. Continued work in this field will hopefully detect MRI metrics to be used as biomarkers to help guide cognitive treatment at the individual cancer patient level. Copyright © 2018. Published by Elsevier Ltd.

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder

PubMed Central

Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

2018-01-01

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC–vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder. PMID:28944772

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder.

PubMed

Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

2018-04-01

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC-vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder.

Automatic MRI 2D brain segmentation using graph searching technique.

PubMed

Pedoia, Valentina; Binaghi, Elisabetta

2013-09-01

Accurate and efficient segmentation of the whole brain in magnetic resonance (MR) images is a key task in many neuroscience and medical studies either because the whole brain is the final anatomical structure of interest or because the automatic extraction facilitates further analysis. The problem of segmenting brain MRI images has been extensively addressed by many researchers. Despite the relevant achievements obtained, automated segmentation of brain MRI imagery is still a challenging problem whose solution has to cope with critical aspects such as anatomical variability and pathological deformation. In the present paper, we describe and experimentally evaluate a method for segmenting brain from MRI images basing on two-dimensional graph searching principles for border detection. The segmentation of the whole brain over the entire volume is accomplished slice by slice, automatically detecting frames including eyes. The method is fully automatic and easily reproducible by computing the internal main parameters directly from the image data. The segmentation procedure is conceived as a tool of general applicability, although design requirements are especially commensurate with the accuracy required in clinical tasks such as surgical planning and post-surgical assessment. Several experiments were performed to assess the performance of the algorithm on a varied set of MRI images obtaining good results in terms of accuracy and stability. Copyright © 2012 John Wiley & Sons, Ltd.

Visual assessment of brain magnetic resonance imaging detects injury to cognitive regulatory sites in patients with heart failure.

PubMed

Pan, Alan; Kumar, Rajesh; Macey, Paul M; Fonarow, Gregg C; Harper, Ronald M; Woo, Mary A

2013-02-01

Heart failure (HF) patients exhibit depression and executive function impairments that contribute to HF mortality. Using specialized magnetic resonance imaging (MRI) analysis procedures, brain changes appear in areas regulating these functions (mammillary bodies, hippocampi, and frontal cortex). However, specialized MRI procedures are not part of standard clinical assessment for HF (which is usually a visual evaluation), and it is unclear whether visual MRI examination can detect changes in these structures. Using brain MRI, we visually examined the mammillary bodies and frontal cortex for global and hippocampi for global and regional tissue changes in 17 HF and 50 control subjects. Significantly global changes emerged in the right mammillary body (HF 1.18 ± 1.13 vs control 0.52 ± 0.74; P = .024), right hippocampus (HF 1.53 ± 0.94 vs control 0.80 ± 0.86; P = .005), and left frontal cortex (HF 1.76 ± 1.03 vs control 1.24 ± 0.77; P = .034). Comparison of the visual method with specialized MRI techniques corroborates right hippocampal and left frontal cortical, but not mammillary body, tissue changes. Visual examination of brain MRI can detect damage in HF in areas regulating depression and executive function, including the right hippocampus and left frontal cortex. Visual MRI assessment in HF may facilitate evaluation of injury to these structures and the assessment of the impact of potential treatments for this damage. Copyright © 2013 Elsevier Inc. All rights reserved.

Detecting determinism from point processes.

PubMed

Andrzejak, Ralph G; Mormann, Florian; Kreuz, Thomas

2014-12-01

The detection of a nonrandom structure from experimental data can be crucial for the classification, understanding, and interpretation of the generating process. We here introduce a rank-based nonlinear predictability score to detect determinism from point process data. Thanks to its modular nature, this approach can be adapted to whatever signature in the data one considers indicative of deterministic structure. After validating our approach using point process signals from deterministic and stochastic model dynamics, we show an application to neuronal spike trains recorded in the brain of an epilepsy patient. While we illustrate our approach in the context of temporal point processes, it can be readily applied to spatial point processes as well.

Brain Modulyzer: Interactive Visual Analysis of Functional Brain Connectivity

DOE PAGES

Murugesan, Sugeerth; Bouchard, Kristopher; Brown, Jesse A.; ...

2016-05-09

Here, we present Brain Modulyzer, an interactive visual exploration tool for functional magnetic resonance imaging (fMRI) brain scans, aimed at analyzing the correlation between different brain regions when resting or when performing mental tasks. Brain Modulyzer combines multiple coordinated views—such as heat maps, node link diagrams, and anatomical views—using brushing and linking to provide an anatomical context for brain connectivity data. Integrating methods from graph theory and analysis, e.g., community detection and derived graph measures, makes it possible to explore the modular and hierarchical organization of functional brain networks. Providing immediate feedback by displaying analysis results instantaneously while changing parametersmore » gives neuroscientists a powerful means to comprehend complex brain structure more effectively and efficiently and supports forming hypotheses that can then be validated via statistical analysis. In order to demonstrate the utility of our tool, we also present two case studies—exploring progressive supranuclear palsy, as well as memory encoding and retrieval« less

Brain Modulyzer: Interactive Visual Analysis of Functional Brain Connectivity

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

Murugesan, Sugeerth; Bouchard, Kristopher; Brown, Jesse A.

Here, we present Brain Modulyzer, an interactive visual exploration tool for functional magnetic resonance imaging (fMRI) brain scans, aimed at analyzing the correlation between different brain regions when resting or when performing mental tasks. Brain Modulyzer combines multiple coordinated views—such as heat maps, node link diagrams, and anatomical views—using brushing and linking to provide an anatomical context for brain connectivity data. Integrating methods from graph theory and analysis, e.g., community detection and derived graph measures, makes it possible to explore the modular and hierarchical organization of functional brain networks. Providing immediate feedback by displaying analysis results instantaneously while changing parametersmore » gives neuroscientists a powerful means to comprehend complex brain structure more effectively and efficiently and supports forming hypotheses that can then be validated via statistical analysis. In order to demonstrate the utility of our tool, we also present two case studies—exploring progressive supranuclear palsy, as well as memory encoding and retrieval« less

Poor Brain Growth in Extremely Preterm Neonates Long Before the Onset of Autism Spectrum Disorder Symptoms.

PubMed

Padilla, Nelly; Eklöf, Eva; Mårtensson, Gustaf E; Bölte, Sven; Lagercrantz, Hugo; Ådén, Ulrika

2017-02-01

Preterm infants face an increased risk of autism spectrum disorder (ASD). The relationship between autism during childhood and early brain development remains unexplored. We studied 84 preterm children born at <27 weeks of gestation, who underwent neonatal magnetic resonance imaging (MRI) at term and were screened for ASD at 6.5 years. Full-scale intelligence quotient was measured and neonatal morbidities were recorded. Structural brain morphometric studies were performed in 33 infants with high-quality MRI and no evidence of focal brain lesions. Twenty-three (27.4%) of the children tested ASD positive and 61 (72.6%) tested ASD negative. The ASD-positive group had a significantly higher frequency of neonatal complications than the ASD-negative group. In the subgroup of 33 children, the ASD infants had reduced volumes in the temporal, occipital, insular, and limbic regions and in the brain areas involved in social/behavior and salience integration. This study shows that the neonatal MRI scans of extremely preterm children, subsequently diagnosed with ASD at 6.5 years, showed brain structural alterations, localized in the regions that play a key role in the core features of autism. Early detection of these structural alterations may allow the early identification and intervention of children at risk of ASD. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Correlations Between Personality and Brain Structure: A Crucial Role of Gender.

PubMed

Nostro, Alessandra D; Müller, Veronika I; Reid, Andrew T; Eickhoff, Simon B

2017-07-01

Previous studies have shown that males and females differ in personality and gender differences have also been reported in brain structure. However, effects of gender on this "personality-brain" relationship are yet unknown. We therefore investigated if the neural correlates of personality differ between males and females. Whole brain voxel-based morphometry was used to investigate the influence of gender on associations between NEO FFI personality traits and gray matter volume (GMV) in a matched sample of 182 males and 182 females. In order to assess associations independent of and dependent on gender, personality-GMV relationships were tested across the entire sample and separately for males and females. There were no significant correlations between any personality scale and GMV in the analyses across the entire sample. In contrast, significant associations with GMV were detected for neuroticism, extraversion, and conscientiousness only in males. Interestingly, GMV in left precuneus/parieto-occipital sulcus correlated with all 3 traits. Thus, our results indicate that brain structure-personality relationships are highly dependent on gender, which might be attributable to hormonal interplays or differences in brain organization between males and females. Our results thus provide possible neural substrates of personality-behavior relationships and underline the important role of gender in these associations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Joint Pairing and Structured Mapping of Convolutional Brain Morphological Multiplexes for Early Dementia Diagnosis.

PubMed

Lisowska, Anna; Rekik, Islem

2018-06-21

Diagnosis of brain dementia, particularly early mild cognitive impairment (eMCI), is critical for early intervention to prevent the onset of Alzheimer's Disease (AD), where cognitive decline is severe and irreversible. There is a large body of machine-learning based research investigating how dementia alters brain connectivity, mainly using structural (derived from diffusion MRI) and functional (derived from resting-state functional MRI) brain connectomic data. However, how early dementia affects cortical brain connections in morphology remains largely unexplored. To fill this gap, we propose a joint morphological brain multiplexes pairing and mapping strategy for early MCI detection, where a brain multiplex not only encodes the similarity in morphology between pairs of brain regions, but also a pair of brain morphological networks. Experimental results confirm that the proposed framework outperforms in classification accuracy several state-of-the-art methods. More importantly, we unprecedentedly identified most discriminative brain morphological networks between eMCI and NC, which included the paired views derived from maximum principal curvature and the sulcal depth for the left hemisphere and sulcal depth and the average curvature for the right hemisphere. We also identified the most highly correlated morphological brain connections in our cohort, which included the (pericalcarine cortex, insula cortex) on the maximum principal curvature view, (entorhinal cortex, insula cortex) on the mean sulcal depth view, and (entorhinal cortex, pericalcarine cortex) on the mean average curvature view, for both hemispheres. These highly correlated morphological connections might serve as biomarkers for early MCI diagnosis.

ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide☆☆☆★

PubMed Central

Thompson, Paul M.; Andreassen, Ole A.; Arias-Vasquez, Alejandro; Bearden, Carrie E.; Boedhoe, Premika S.; Brouwer, Rachel M.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cannon, Dara M.; Cohen, Ronald A.; Conrod, Patricia J.; Dale, Anders M.; Deary, Ian J.; Dennis, Emily L.; de Reus, Marcel A.; Desrivieres, Sylvane; Dima, Danai; Donohoe, Gary; Fisher, Simon E.; Fouche, Jean-Paul; Francks, Clyde; Frangou, Sophia; Franke, Barbara; Ganjgahi, Habib; Garavan, Hugh; Glahn, David C.; Grabe, Hans J.; Guadalupe, Tulio; Gutman, Boris A.; Hashimoto, Ryota; Hibar, Derrek P.; Holland, Dominic; Hoogman, Martine; Pol, Hilleke E. Hulshoff; Hosten, Norbert; Jahanshad, Neda; Kelly, Sinead; Kochunov, Peter; Kremen, William S.; Lee, Phil H.; Mackey, Scott; Martin, Nicholas G.; Mazoyer, Bernard; McDonald, Colm; Medland, Sarah E.; Morey, Rajendra A.; Nichols, Thomas E.; Paus, Tomas; Pausova, Zdenka; Schmaal, Lianne; Schumann, Gunter; Shen, Li; Sisodiya, Sanjay M.; Smit, Dirk J.A.; Smoller, Jordan W.; Stein, Dan J.; Stein, Jason L.; Toro, Roberto; Turner, Jessica A.; van den Heuvel, Martijn P.; van den Heuvel, Odile L.; van Erp, Theo G.M.; van Rooij, Daan; Veltman, Dick J.; Walter, Henrik; Wang, Yalin; Wardlaw, Joanna M.; Whelan, Christopher D.; Wright, Margaret J.; Ye, Jieping

2016-01-01

In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) – a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date – of schizophrenia and major depression – ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others1, ENIGMA's genomic screens – now numbering over 30,000 MRI scans – have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants – and genetic variants in general – may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures – from tens of thousands of people – that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far. PMID:26658930

Imaging Neural Activity Using Thy1-GCaMP Transgenic mice

PubMed Central

Chen, Qian; Cichon, Joseph; Wang, Wenting; Qiu, Li; Lee, Seok-Jin R.; Campbell, Nolan R.; DeStefino, Nicholas; Goard, Michael J.; Fu, Zhanyan; Yasuda, Ryohei; Looger, Loren L.; Arenkiel, Benjamin R.; Gan, Wen-Biao; Feng, Guoping

2014-01-01

Summary The ability to chronically monitor neuronal activity in the living brain is essential for understanding the organization and function of the nervous system. The genetically encoded green fluorescent protein based calcium sensor GCaMP provides a powerful tool for detecting calcium transients in neuronal somata, processes, and synapses that are triggered by neuronal activities. Here we report the generation and characterization of transgenic mice that express improved GCaMPs in various neuronal subpopulations under the control of the Thy1 promoter. In vitro and in vivo studies show that calcium transients induced by spontaneous and stimulus-evoked neuronal activities can be readily detected at the level of individual cells and synapses in acute brain slices, as well as chronically in awake behaving animals. These GCaMP transgenic mice allow investigation of activity patterns in defined neuronal populations in the living brain, and will greatly facilitate dissecting complex structural and functional relationships of neural networks. PMID:23083733

Dynamic Bayesian network modeling for longitudinal brain morphometry

PubMed Central

Chen, Rong; Resnick, Susan M; Davatzikos, Christos; Herskovits, Edward H

2011-01-01

Identifying interactions among brain regions from structural magnetic-resonance images presents one of the major challenges in computational neuroanatomy. We propose a Bayesian data-mining approach to the detection of longitudinal morphological changes in the human brain. Our method uses a dynamic Bayesian network to represent evolving inter-regional dependencies. The major advantage of dynamic Bayesian network modeling is that it can represent complicated interactions among temporal processes. We validated our approach by analyzing a simulated atrophy study, and found that this approach requires only a small number of samples to detect the ground-truth temporal model. We further applied dynamic Bayesian network modeling to a longitudinal study of normal aging and mild cognitive impairment — the Baltimore Longitudinal Study of Aging. We found that interactions among regional volume-change rates for the mild cognitive impairment group are different from those for the normal-aging group. PMID:21963916

Neonatal neuroimaging: going beyond the pictures.

PubMed

Ramenghi, Luca A; Rutherford, Mary; Fumagalli, Monica; Bassi, Laura; Messner, Hubert; Counsell, Serena; Mosca, Fabio

2009-10-01

The cerebral ultrasound has been used many years for the diagnosis of brain lesions in term and preterm newborns. Major improvements were obtained by the combination of different imaging modalities such as Magnetic Resonance Imaging with the Diffusion Weighted Imaging (DWI) and the new quantitative Diffusion Tensor Imaging (DTI). The clinical use of MRI has been validated over some years especially to depict the perinatal asphyxia lesions in term newborns, but its use in order to diagnose the typical diseases of preterm babies is very recent and useful in identifying a marker able to predict neurological outcome. The imaging correlates for motor impairment are well recognized (periventricular white matter cavitations), but no any imaging correlate for cognitive impairment and neurobehavioral disorders. While DWI has been used in term newborns to identify the ischemic areas with restricted diffusion, it may be also used to characterize brain development in preterm infants with the Apparent Diffusion Coefficient (ADC) and may allow us to detect abnormalities responsible for the non-motor impairments. Recent datas showed that in infants without focal lesions higher ADC values in WM were associated with poorer neurodevelopmental assessment at 2 years. The DTI also allows to detect the Fractional Anisotropy (FA) that measures the microstructure. DTI can also be used to map the WM tracts in the immature brain and may be applied to understand the normal development or the response of the brain to injury. Some WM regions in the preterm brain have a lower FA suggesting that widespread WM abnormalities are present in preterms even in the absence of focal lesions. The complexity of the developing brain can be explained by the new tractography that can assess the connectivity of different WM regions and the association between structure and function, such as optic radiations microstructure and visual assessment score. Technological advances in neonatal brain imaging have made a major contribution to understand the neurobehavioral disorders of the developing brain that have the origin in the early structural cerebral organization and maturation.

A Multivariate Granger Causality Concept towards Full Brain Functional Connectivity.

PubMed

Schmidt, Christoph; Pester, Britta; Schmid-Hertel, Nicole; Witte, Herbert; Wismüller, Axel; Leistritz, Lutz

2016-01-01

Detecting changes of spatially high-resolution functional connectivity patterns in the brain is crucial for improving the fundamental understanding of brain function in both health and disease, yet still poses one of the biggest challenges in computational neuroscience. Currently, classical multivariate Granger Causality analyses of directed interactions between single process components in coupled systems are commonly restricted to spatially low- dimensional data, which requires a pre-selection or aggregation of time series as a preprocessing step. In this paper we propose a new fully multivariate Granger Causality approach with embedded dimension reduction that makes it possible to obtain a representation of functional connectivity for spatially high-dimensional data. The resulting functional connectivity networks may consist of several thousand vertices and thus contain more detailed information compared to connectivity networks obtained from approaches based on particular regions of interest. Our large scale Granger Causality approach is applied to synthetic and resting state fMRI data with a focus on how well network community structure, which represents a functional segmentation of the network, is preserved. It is demonstrated that a number of different community detection algorithms, which utilize a variety of algorithmic strategies and exploit topological features differently, reveal meaningful information on the underlying network module structure.

EBG Based Microstrip Patch Antenna for Brain Tumor Detection via Scattering Parameters in Microwave Imaging System.

PubMed

Inum, Reefat; Rana, Md Masud; Shushama, Kamrun Nahar; Quader, Md Anwarul

2018-01-01

A microwave brain imaging system model is envisaged to detect and visualize tumor inside the human brain. A compact and efficient microstrip patch antenna is used in the imaging technique to transmit equivalent signal and receive backscattering signal from the stratified human head model. Electromagnetic band gap (EBG) structure is incorporated on the antenna ground plane to enhance the performance. Rectangular and circular EBG structures are proposed to investigate the antenna performance. Incorporation of circular EBG on the antenna ground plane provides an improvement of 22.77% in return loss, 5.84% in impedance bandwidth, and 16.53% in antenna gain with respect to the patch antenna with rectangular EBG. The simulation results obtained from CST are compared to those obtained from HFSS to validate the design. Specific absorption rate (SAR) of the modeled head tissue for the proposed antenna is determined. Different SAR values are compared with the established standard SAR limit to provide a safety regulation of the imaging system. A monostatic radar-based confocal microwave imaging algorithm is applied to generate the image of tumor inside a six-layer human head phantom model. S -parameter signals obtained from circular EBG loaded patch antenna in different scanning modes are utilized in the imaging algorithm to effectively produce a high-resolution image which reliably indicates the presence of tumor inside human brain.

EBG Based Microstrip Patch Antenna for Brain Tumor Detection via Scattering Parameters in Microwave Imaging System

PubMed Central

Rana, Md. Masud; Shushama, Kamrun Nahar; Quader, Md. Anwarul

2018-01-01

A microwave brain imaging system model is envisaged to detect and visualize tumor inside the human brain. A compact and efficient microstrip patch antenna is used in the imaging technique to transmit equivalent signal and receive backscattering signal from the stratified human head model. Electromagnetic band gap (EBG) structure is incorporated on the antenna ground plane to enhance the performance. Rectangular and circular EBG structures are proposed to investigate the antenna performance. Incorporation of circular EBG on the antenna ground plane provides an improvement of 22.77% in return loss, 5.84% in impedance bandwidth, and 16.53% in antenna gain with respect to the patch antenna with rectangular EBG. The simulation results obtained from CST are compared to those obtained from HFSS to validate the design. Specific absorption rate (SAR) of the modeled head tissue for the proposed antenna is determined. Different SAR values are compared with the established standard SAR limit to provide a safety regulation of the imaging system. A monostatic radar-based confocal microwave imaging algorithm is applied to generate the image of tumor inside a six-layer human head phantom model. S-parameter signals obtained from circular EBG loaded patch antenna in different scanning modes are utilized in the imaging algorithm to effectively produce a high-resolution image which reliably indicates the presence of tumor inside human brain. PMID:29623087

White matter integrity in brain networks relevant to anxiety and depression: evidence from the human connectome project dataset.

PubMed

De Witte, Nele A J; Mueller, Sven C

2017-12-01

Anxiety and depression are associated with altered communication within global brain networks and between these networks and the amygdala. Functional connectivity studies demonstrate an effect of anxiety and depression on four critical brain networks involved in top-down attentional control (fronto-parietal network; FPN), salience detection and error monitoring (cingulo-opercular network; CON), bottom-up stimulus-driven attention (ventral attention network; VAN), and default mode (default mode network; DMN). However, structural evidence on the white matter (WM) connections within these networks and between these networks and the amygdala is lacking. The current study in a large healthy sample (n = 483) observed that higher trait anxiety-depression predicted lower WM integrity in the connections between amygdala and specific regions of the FPN, CON, VAN, and DMN. We discuss the possible consequences of these anatomical alterations for cognitive-affective functioning and underscore the need for further theory-driven research on individual differences in anxiety and depression on brain structure.

Alternations of White Matter Structural Networks in First Episode Untreated Major Depressive Disorder with Short Duration.

PubMed

Lu, Yi; Shen, Zonglin; Cheng, Yuqi; Yang, Hui; He, Bo; Xie, Yue; Wen, Liang; Zhang, Zhenguang; Sun, Xuejin; Zhao, Wei; Xu, Xiufeng; Han, Dan

2017-01-01

It is crucial to explore the pathogenesis of major depressive disorder (MDD) at the early stage for the better diagnostic and treatment strategies. It was suggested that MDD might be involving in functional or structural alternations at the brain network level. However, at the onset of MDD, whether the whole brain white matter (WM) alterations at network level are already evident still remains unclear. In the present study, diffusion MRI scanning was adopt to depict the unique WM structural network topology across the entire brain at the early stage of MDD. Twenty-one first episode, short duration (<1 year) and drug-naïve depression patients, and 25 healthy control (HC) subjects were recruited. To construct the WM structural network, atlas-based brain regions were used for nodes, and the value of multiplying fiber number by the mean fractional anisotropy along the fiber bundles connected a pair of brain regions were used for edges. The structural network was analyzed by graph theoretic and network-based statistic methods. Pearson partial correlation analysis was also performed to evaluate their correlation with the clinical variables. Compared with HCs, the MDD patients had a significant decrease in the small-worldness (σ). Meanwhile, the MDD patients presented a significantly decreased subnetwork, which mainly involved in the frontal-subcortical and limbic regions. Our results suggested that the abnormal structural network of the orbitofrontal cortex and thalamus, involving the imbalance with the limbic system, might be a key pathology in early stage drug-naive depression. And the structural network analysis might be potential in early detection and diagnosis of MDD.

Alternations of White Matter Structural Networks in First Episode Untreated Major Depressive Disorder with Short Duration

PubMed Central

Lu, Yi; Shen, Zonglin; Cheng, Yuqi; Yang, Hui; He, Bo; Xie, Yue; Wen, Liang; Zhang, Zhenguang; Sun, Xuejin; Zhao, Wei; Xu, Xiufeng; Han, Dan

2017-01-01

It is crucial to explore the pathogenesis of major depressive disorder (MDD) at the early stage for the better diagnostic and treatment strategies. It was suggested that MDD might be involving in functional or structural alternations at the brain network level. However, at the onset of MDD, whether the whole brain white matter (WM) alterations at network level are already evident still remains unclear. In the present study, diffusion MRI scanning was adopt to depict the unique WM structural network topology across the entire brain at the early stage of MDD. Twenty-one first episode, short duration (<1 year) and drug-naïve depression patients, and 25 healthy control (HC) subjects were recruited. To construct the WM structural network, atlas-based brain regions were used for nodes, and the value of multiplying fiber number by the mean fractional anisotropy along the fiber bundles connected a pair of brain regions were used for edges. The structural network was analyzed by graph theoretic and network-based statistic methods. Pearson partial correlation analysis was also performed to evaluate their correlation with the clinical variables. Compared with HCs, the MDD patients had a significant decrease in the small-worldness (σ). Meanwhile, the MDD patients presented a significantly decreased subnetwork, which mainly involved in the frontal–subcortical and limbic regions. Our results suggested that the abnormal structural network of the orbitofrontal cortex and thalamus, involving the imbalance with the limbic system, might be a key pathology in early stage drug-naive depression. And the structural network analysis might be potential in early detection and diagnosis of MDD. PMID:29118724

Structural abnormalities and altered regional brain activity in multiple sclerosis with simple spinal cord involvement.

PubMed

Yin, Ping; Liu, Yi; Xiong, Hua; Han, Yongliang; Sah, Shambhu Kumar; Zeng, Chun; Wang, Jingjie; Li, Yongmei

2018-02-01

To assess the changes of the structural and functional abnormalities in multiple sclerosis with simple spinal cord involvement (MS-SSCI) by using resting-state functional MRI (RS-fMRI), voxel based morphology (VBM) and diffusion tensor tractography. The amplitude of low-frequency fluctuation (ALFF) of 22 patients with MS-SSCI and 22 healthy controls (HCs) matched for age, gender and education were compared by using RS-fMRI. We also compared the volume, fractional anisotropy (FA) and apparent diffusion coefficient of the brain regions in baseline brain activity by using VBM and diffusion tensor imaging. The relationships between the expanded disability states scale (EDSS) scores, changed parameters of structure and function were further explored. (1) Compared with HCs, the ALFF of the bilateral hippocampus and right middle temporal gyrus in MS-SSCI decreased significantly. However, patients exhibited increased ALFF in the left middle frontal gyrus, left posterior cingulate gyrus and right middle occipital gyrus ( two-sample t-test, after AlphaSim correction, p < 0.01, voxel size > 40). The volume of right middle frontal gyrus reduced significantly (p < 0.01). The FA and ADC of right hippocampus, the FA of left hippocampus and right middle temporal gyrus were significantly different. (2) A significant correlation between EDSS scores and ALFF was noted only in the left posterior cingulate gyrus. Our results detected structural and functional abnormalities in MS-SSCI and functional parameters were associated with clinical abnormalities. Multimodal imaging plays an important role in detecting structural and functional abnormalities in MS-SSCI. Advances in knowledge: This is the first time to apply RS-fMRI, VBM and diffusion tensor tractography to study the structural and functional abnormalities in MS-SSCI, and to explore its correlation with EDSS score.

How bilingualism protects the brain from aging: Insights from bimodal bilinguals.

PubMed

Li, Le; Abutalebi, Jubin; Emmorey, Karen; Gong, Gaolang; Yan, Xin; Feng, Xiaoxia; Zou, Lijuan; Ding, Guosheng

2017-08-01

Bilingual experience can delay cognitive decline during aging. A general hypothesis is that the executive control system of bilinguals faces an increased load due to controlling two languages, and this increased load results in a more "tuned brain" that eventually creates a neural reserve. Here we explored whether such a neuroprotective effect is independent of language modality, i.e., not limited to bilinguals who speak two languages but also occurs for bilinguals who use a spoken and a signed language. We addressed this issue by comparing bimodal bilinguals to monolinguals in order to detect age-induced structural brain changes and to determine whether we can detect the same beneficial effects on brain structure, in terms of preservation of gray matter volume (GMV), for bimodal bilinguals as has been reported for unimodal bilinguals. Our GMV analyses revealed a significant interaction effect of age × group in the bilateral anterior temporal lobes, left hippocampus/amygdala, and left insula where bimodal bilinguals showed slight GMV increases while monolinguals showed significant age-induced GMV decreases. We further found through cortical surface-based measurements that this effect was present for surface area and not for cortical thickness. Moreover, to further explore the hypothesis that overall bilingualism provides neuroprotection, we carried out a direct comparison of GMV, extracted from the brain regions reported above, between bimodal bilinguals, unimodal bilinguals, and monolinguals. Bilinguals, regardless of language modality, exhibited higher GMV compared to monolinguals. This finding highlights the general beneficial effects provided by experience handling two language systems, whether signed or spoken. Hum Brain Mapp 38:4109-4124, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Interpretation of the Precision Matrix and Its Application in Estimating Sparse Brain Connectivity during Sleep Spindles from Human Electrocorticography Recordings

PubMed Central

Das, Anup; Sampson, Aaron L.; Lainscsek, Claudia; Muller, Lyle; Lin, Wutu; Doyle, John C.; Cash, Sydney S.; Halgren, Eric; Sejnowski, Terrence J.

2017-01-01

The correlation method from brain imaging has been used to estimate functional connectivity in the human brain. However, brain regions might show very high correlation even when the two regions are not directly connected due to the strong interaction of the two regions with common input from a third region. One previously proposed solution to this problem is to use a sparse regularized inverse covariance matrix or precision matrix (SRPM) assuming that the connectivity structure is sparse. This method yields partial correlations to measure strong direct interactions between pairs of regions while simultaneously removing the influence of the rest of the regions, thus identifying regions that are conditionally independent. To test our methods, we first demonstrated conditions under which the SRPM method could indeed find the true physical connection between a pair of nodes for a spring-mass example and an RC circuit example. The recovery of the connectivity structure using the SRPM method can be explained by energy models using the Boltzmann distribution. We then demonstrated the application of the SRPM method for estimating brain connectivity during stage 2 sleep spindles from human electrocorticography (ECoG) recordings using an 8 × 8 electrode array. The ECoG recordings that we analyzed were from a 32-year-old male patient with long-standing pharmaco-resistant left temporal lobe complex partial epilepsy. Sleep spindles were automatically detected using delay differential analysis and then analyzed with SRPM and the Louvain method for community detection. We found spatially localized brain networks within and between neighboring cortical areas during spindles, in contrast to the case when sleep spindles were not present. PMID:28095202

Manifestations of early brain recovery associated with abstinence from alcoholism.

PubMed

Bartsch, Andreas J; Homola, György; Biller, Armin; Smith, Stephen M; Weijers, Heinz-Gerd; Wiesbeck, Gerhard A; Jenkinson, Mark; De Stefano, Nicola; Solymosi, László; Bendszus, Martin

2007-01-01

Chronic alcohol abuse results in morphological, metabolic, and functional brain damage which may, to some extent, be reversible with early effects upon abstinence. Although morphometric, spectroscopic, and neuropsychological indicators of cerebral regeneration have been described previously, the overall amount and spatial preference of early brain recovery attained by abstinence and its associations with other indicators of regeneration are not well established. We investigated global and local brain volume changes in a longitudinal two-timepoint study with T1-weighted MRI at admission and after short-term (6-7 weeks) sobriety follow-up in 15 uncomplicated, recently detoxified alcoholics. Volumetric brain gain was related to metabolic and neuropsychological recovery. On admission and after short-term abstinence, structural image evaluation using normalization of atrophy (SIENA), its voxelwise statistical extension to multiple subjects, proton MR spectroscopy (1H-MRS), and neuropsychological tests were applied. Upon short-term sobriety, 1H-MRS levels of cerebellar choline and frontomesial N-acetylaspartate (NAA) were significantly augmented. Automatically detected global brain volume gain amounted to nearly two per cent on average and was spatially significant around the superior vermis, perimesencephalic, periventricular and frontal brain edges. It correlated positively with the percentages of cerebellar and frontomesial choline increase, as detected by 1H-MRS. Moreover, frontomesial NAA gains were associated with improved performance on the d2-test of attention. In 10 age- and gender-matched healthy control subjects, no significant brain volume or metabolite changes were observed. Although cerebral osmotic regulations may occur initially upon sobriety, significant increases of cerebellar choline and frontomesial NAA levels detected at stable brain water integrals and creatine concentrations, serum electrolytes and red blood cell indices in our patient sample suggest that early brain recovery through abstinence does not simply reflect rehydration. Instead, even the adult human brain and particularly its white matter seems to possess genuine capabilities for regrowth. Our findings emphasize metabolic as well as regionally distinct morphological capacities for partial brain recovery from toxic insults of chronic alcoholism and substantiate early measurable benefits of therapeutic sobriety. Further understanding of the precise mechanisms of this recovery may become a valuable model of brain regeneration with relevance for other disorders.

Robust estimation of fractal measures for characterizing the structural complexity of the human brain: optimization and reproducibility

PubMed Central

Goñi, Joaquín; Sporns, Olaf; Cheng, Hu; Aznárez-Sanado, Maite; Wang, Yang; Josa, Santiago; Arrondo, Gonzalo; Mathews, Vincent P; Hummer, Tom A; Kronenberger, William G; Avena-Koenigsberger, Andrea; Saykin, Andrew J.; Pastor, María A.

2013-01-01

High-resolution isotropic three-dimensional reconstructions of human brain gray and white matter structures can be characterized to quantify aspects of their shape, volume and topological complexity. In particular, methods based on fractal analysis have been applied in neuroimaging studies to quantify the structural complexity of the brain in both healthy and impaired conditions. The usefulness of such measures for characterizing individual differences in brain structure critically depends on their within-subject reproducibility in order to allow the robust detection of between-subject differences. This study analyzes key analytic parameters of three fractal-based methods that rely on the box-counting algorithm with the aim to maximize within-subject reproducibility of the fractal characterizations of different brain objects, including the pial surface, the cortical ribbon volume, the white matter volume and the grey matter/white matter boundary. Two separate datasets originating from different imaging centers were analyzed, comprising, 50 subjects with three and 24 subjects with four successive scanning sessions per subject, respectively. The reproducibility of fractal measures was statistically assessed by computing their intra-class correlations. Results reveal differences between different fractal estimators and allow the identification of several parameters that are critical for high reproducibility. Highest reproducibility with intra-class correlations in the range of 0.9–0.95 is achieved with the correlation dimension. Further analyses of the fractal dimensions of parcellated cortical and subcortical gray matter regions suggest robustly estimated and region-specific patterns of individual variability. These results are valuable for defining appropriate parameter configurations when studying changes in fractal descriptors of human brain structure, for instance in studies of neurological diseases that do not allow repeated measurements or for disease-course longitudinal studies. PMID:23831414

Strong Functional Connectivity among Homotopic Brain Areas Is Vital for Motor Control in Unilateral Limb Movement.

PubMed

Wei, Pengxu; Zhang, Zuting; Lv, Zeping; Jing, Bin

2017-01-01

The mechanism underlying brain region organization for motor control in humans remains poorly understood. In this functional magnetic resonance imaging (fMRI) study, right-handed volunteers were tasked to maintain unilateral foot movements on the right and left sides as consistently as possible. We aimed to identify the similarities and differences between brain motor networks of the two conditions. We recruited 18 right-handed healthy volunteers aged 25 ± 2.3 years and used a whole-body 3T system for magnetic resonance (MR) scanning. Image analysis was performed using SPM8, Conn toolbox and Brain Connectivity Toolbox. We determined a craniocaudally distributed, mirror-symmetrical modular structure. The functional connectivity between homotopic brain areas was generally stronger than the intrahemispheric connections, and such strong connectivity led to the abovementioned modular structure. Our findings indicated that the interhemispheric functional interaction between homotopic brain areas is more intensive than the interaction along the conventional top-down and bottom-up pathways within the brain during unilateral limb movement. The detected strong interhemispheric horizontal functional interaction is an important aspect of motor control but often neglected or underestimated. The strong interhemispheric connectivity may explain the physiological phenomena and effects of promising therapeutic approaches. Further accurate and effective therapeutic methods may be developed on the basis of our findings.

Glycosaminoglycan in cerebrum, cerebellum and brainstem of young sheep brain with particular reference to compositional and structural variations of chondroitin-dermatan sulfate and hyaluronan.

PubMed

Kilia, Virginia; Skandalis, Spyros S; Theocharis, Achilleas D; Theocharis, Dimitrios A; Karamanos, Nikos K; Papageorgakopoulou, Nickoletta

2008-09-01

Recent advances in the structural biology of chondroitin sulfate chains have suggested important biological functions in the development of the brain. Several studies have demonstrated that the composition of chondroitin sulfate chains changes with aging and normal brain maturation. In this study, we determined the concentration of all glycosaminoglycan types, i.e. chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan sulfate, hyaluronan and chondroitin in cerebrum, cerebellum and brainstem of young sheep brain. In all cases, chondroitin sulfate was the predominant glycosaminoglycan type, comprising about 54-58% of total glycosaminoglycans, with hyaluronan being present also in significant amounts of about 19-28%. Of particular interest was the increased presence of the disulfated disaccharides and dermatan sulfate in cerebellum and brainstem, respectively, as well as the detectable and measurable occurrence of chondroitin in young sheep brain. Among the three brain areas, cerebrum was found to be significantly richer in chondroitin sulfate and hyaluronan, two major extracellular matrix components. These findings imply that the extracellular matrix of the cerebrum is different from those of cerebellum and brainstem, and probably this fact is related to the particular histological and functional characteristics of each anatomic area of the brain.

Label-free NIR reflectance imaging as a complimentary tool for two-photon fluorescence microscopy: multimodal investigation of stroke (Conference Presentation)

NASA Astrophysics Data System (ADS)

Allegra Mascaro, Anna Letizia; Costantini, Irene; Margoni, Emilia; Iannello, Giulio; Bria, Alessandro; Sacconi, Leonardo; Pavone, Francesco S.

2016-03-01

Two-photon imaging combined with targeted fluorescent indicators is extensively used for visualizing critical features of brain functionality and structural plasticity. Back-scattered photons from the NIR laser provide complimentary information without introducing any exogenous labelling. Here, we describe a versatile approach that, by collecting the reflected NIR light, provides structural details on the myelinated axons and blood vessels in the brain, both in fixed samples and in live animals. Indeed, by combining NIR reflectance and two-photon imaging of a slice of hippocampus from Thy1-GFPm mice, we show the presence of randomly oriented axons intermingled with sparsely fluorescent neuronal processes. The back-scattered photons guide the contextualization of the fluorescence structure within brain atlas thanks to the recognition of characteristic hippocampal structures. Label-free detection of axonal elongations over the layer 2/3 of mouse cortex under a cranial window was also possible in live brain. Finally, blood flow could be measured in vivo, thus validating label free NIR reflectance as a tool for monitoring hemodynamic fluctuations. The prospective versatility of this label-free technique complimentary to two-photon fluorescence microscopy is demonstrated in a mouse model of photothrombotic stroke in which the axonal degeneration and blood flow remodeling can be investigated simultaneously.

Increased gray matter volume in the right angular and posterior parahippocampal gyri in loving-kindness meditators.

PubMed

Leung, Mei-Kei; Chan, Chetwyn C H; Yin, Jing; Lee, Chack-Fan; So, Kwok-Fai; Lee, Tatia M C

2013-01-01

Previous voxel-based morphometry (VBM) studies have revealed that meditation is associated with structural brain changes in regions underlying cognitive processes that are required for attention or mindfulness during meditation. This VBM study examined brain changes related to the practice of an emotion-oriented meditation: loving-kindness meditation (LKM). A 3 T magnetic resonance imaging (MRI) scanner captured images of the brain structures of 25 men, 10 of whom had practiced LKM in the Theravada tradition for at least 5 years. Compared with novices, more gray matter volume was detected in the right angular and posterior parahippocampal gyri in LKM experts. The right angular gyrus has not been previously reported to have structural differences associated with meditation, and its specific role in mind and cognitive empathy theory suggests the uniqueness of this finding for LKM practice. These regions are important for affective regulation associated with empathic response, anxiety and mood. At the same time, gray matter volume in the left temporal lobe in the LKM experts appeared to be greater, an observation that has also been reported in previous MRI meditation studies on meditation styles other than LKM. Overall, the findings of our study suggest that experience in LKM may influence brain structures associated with affective regulation.

Studying variability in human brain aging in a population-based German cohort-rationale and design of 1000BRAINS.

PubMed

Caspers, Svenja; Moebus, Susanne; Lux, Silke; Pundt, Noreen; Schütz, Holger; Mühleisen, Thomas W; Gras, Vincent; Eickhoff, Simon B; Romanzetti, Sandro; Stöcker, Tony; Stirnberg, Rüdiger; Kirlangic, Mehmet E; Minnerop, Martina; Pieperhoff, Peter; Mödder, Ulrich; Das, Samir; Evans, Alan C; Jöckel, Karl-Heinz; Erbel, Raimund; Cichon, Sven; Nöthen, Markus M; Sturma, Dieter; Bauer, Andreas; Jon Shah, N; Zilles, Karl; Amunts, Katrin

2014-01-01

The ongoing 1000 brains study (1000BRAINS) is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions and language; examination of motor skills; ratings of personality, life quality, mood and daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla) of the brain. The latter includes (i) 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii) three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fiber tracking and for diffusion kurtosis imaging; (iii) resting-state and task-based functional MRI; and (iv) fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i) comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii) identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates.

Freeze-Drying as Sample Preparation for Micellar Electrokinetic Capillary Chromatography – Electrochemical Separations of Neurochemicals in Drosophila Brains

PubMed Central

Berglund, E. Carina; Kuklinski, Nicholas J.; Karagündüz, Ekin; Ucar, Kubra; Hanrieder, Jörg; Ewing, Andrew G.

2013-01-01

Micellar electrokinetic capillary chromatography with electrochemical detection has been used to quantify biogenic amines in freeze-dried Drosophila melanogaster brains. Freeze drying samples offers a way to preserve the biological sample while making dissection of these tiny samples easier and faster. Fly samples were extracted in cold acetone and dried in a rotary evaporator. Extraction and drying times were optimized in order to avoid contamination by red-pigment from the fly eyes and still have intact brain structures. Single freeze-dried fly-brain samples were found to produce representative electropherograms as a single hand-dissected brain sample. Utilizing the faster dissection time that freeze drying affords, the number of brains in a fixed homogenate volume can be increased to concentrate the sample. Thus, concentrated brain samples containing five or fifteen preserved brains were analyzed for their neurotransmitter content, and five analytes; dopamine N-acetyloctopamine, Nacetylserotonin, N-acetyltyramine, N-acetyldopamine were found to correspond well with previously reported values. PMID:23387977

Amyloid-β Deposits Target Efficient Near-Infrared Fluorescent Probes: Synthesis, in Vitro Evaluation, and in Vivo Imaging.

PubMed

Fu, Hualong; Tu, Peiyu; Zhao, Liu; Dai, Jiapei; Liu, Boli; Cui, Mengchao

2016-02-02

The formation of extracellular amyloid-β (Aβ) plaques is a common molecular change that underlies several debilitating human conditions, including Alzheimer's disease (AD); however, the existing near-infrared (NIR) fluorescent probes for the in vivo detection of Aβ plaques are limited by undesirable fluorescent properties and poor brain kinetics. In this work, we designed, synthesized, and evaluated a new family of efficient NIR probes that target Aβ plaques by incorporating hydroxyethyl groups into the ligand structure. Among these probes, DANIR 8c showed excellent fluorescent properties with an emission maximum above 670 nm upon binding to Aβ aggregates and also displayed a high sensitivity (a 629-fold increase in fluorescence intensity) and affinity (Kd = 14.5 nM). Because of the improved hydrophilicity that was induced by hydroxyls, 8c displayed increased initial brain uptake and a fast washout from the brain, as well as an acceptable biostability in the brain. In vivo NIR fluorescent imaging revealed that 8c could efficiently distinguish between AD transgenic model mice and normal controls. Overall, 8c is an efficient and veritable NIR fluorescent probe for the in vivo detection of Aβ plaques in the brain.

Increased frequency of brain pathology in inmates of a high-security forensic institution: a qualitative CT and MRI scan study.

PubMed

Witzel, Joachim G; Bogerts, Bernhard; Schiltz, Kolja

2016-09-01

This study aimed to assess whether brain pathology might be more abundant in forensic inpatients in a high-security setting than in non-criminal individuals. By using a previously used reliable approach, we explored the frequency and extent of brain pathology in a large group of institutionalized offenders who had not previously been considered to be suffering from structural brain damage and compare it to healthy, non-offending subjects. MRI and CT brain scans from 148 male inpatients of a high-security mental health institution (offense type: 51 sex, 80 violent, 9 arson, and 8 nonviolent) that were obtained due to headache, vertigo, or psychological complaints during imprisonment were assessed and compared to 52 non-criminal healthy controls. Brain scans were assessed qualitatively with respect to evidence of structural brain damage. Each case received a semiquantitative rating of "normal" (=0), "questionably abnormal" (=1), or "definitely abnormal" (=2) for the lateral ventricles, frontal/parietal cortex, and medial temporal structures bilaterally as well as third ventricle. Forensic inpatients displayed signs of brain damage to a significantly higher degree than healthy controls (p < 0.001). Even after adjustment for age, in the patients, being younger than the controls (p < 0.05), every offender type group displayed a higher proportion of subjects with brain regions categorized as definitely abnormal than the non-criminal controls. Within the forensic inpatients, offense type groups did not significantly differ in brain pathology. The astonishingly high prevalence of brain pathology in institutionalized inmates of a high-security mental health institution who previously had not been considered to be suffering from an organic brain syndrome raises questions on whether such neuroradiological assessment might be considered as a routine procedure in newly admitted patients. Furthermore, it highlights that organic changes, detectable under clinical routine conditions, may play a role in the development of legally relevant behavioral disturbances which might be underestimated.

Application of spatially modulated near-infrared structured light to study changes in optical properties of mouse brain tissue during heatstress.

PubMed

Shaul, Oren; Fanrazi-Kahana, Michal; Meitav, Omri; Pinhasi, Gad A; Abookasis, David

2017-11-10

Heat stress (HS) is a medical emergency defined by abnormally elevated body temperature that causes biochemical, physiological, and hematological changes. The goal of the present research was to detect variations in optical properties (absorption, reduced scattering, and refractive index coefficients) of mouse brain tissue during HS by using near-infrared (NIR) spatial light modulation. NIR spatial patterns with different spatial phases were used to differentiate the effects of tissue scattering from those of absorption. Decoupling optical scattering from absorption enabled the quantification of a tissue's chemical constituents (related to light absorption) and structural properties (related to light scattering). Technically, structured light patterns at low and high spatial frequencies of six wavelengths ranging between 690 and 970 nm were projected onto the mouse scalp surface while diffuse reflected light was recorded by a CCD camera positioned perpendicular to the mouse scalp. Concurrently to pattern projection, brain temperature was measured with a thermal camera positioned slightly off angle from the mouse head while core body temperature was monitored by thermocouple probe. Data analysis demonstrated variations from baseline measurements in a battery of intrinsic brain properties following HS.

Distinct structure and activity of monoamine oxidase in the brain of zebrafish (Danio rerio).

PubMed

Anichtchik, Oleg; Sallinen, Ville; Peitsaro, Nina; Panula, Pertti

2006-10-10

Monoamine oxidase (MAO) is a mitochondrial flavoprotein involved in the metabolism of, e.g., aminergic neurotransmitters and the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). We have reported earlier MPTP-related alterations of brain catecholaminergic system in zebrafish (Danio rerio) brain. Here we describe the structural and functional properties of zebrafish MAO and the distribution of MAO mRNA and activity in zebrafish brain. The gene is located in chromosome 9 and consists of 15 exons. The amino acid composition of the active center resembles both human MAO-A and MAO-B. The enzyme displayed the highest substrate specificity for tyramine, followed by serotonin, phenylethylamine, MPTP, and dopamine; isoform-specific antagonists blocked the activity of the enzyme with equal potency. Zebrafish MAO mRNA, which was present in several tissues, and enzyme displayed differential distribution in the brain; dopaminergic cell clusters had low to moderate levels of MAO activity, whereas the highest levels of MAO activity were detected in noradrenergic and serotonergic cell groups and the habenulointerpeduncular pathway, including its caudal projection to the medial ventral rhombencephalon. The results of this study confirm the presence of functionally active MAO in zebrafish brain and other tissues and characterize the neural systems that express MAO and areas of intense activity in the brain. They also suggest that MPTP toxicity not related to MAO may affect the zebrafish brain.

Human brain detects short-time nonlinear predictability in the temporal fine structure of deterministic chaotic sounds

NASA Astrophysics Data System (ADS)

Itoh, Kosuke; Nakada, Tsutomu

2013-04-01

Deterministic nonlinear dynamical processes are ubiquitous in nature. Chaotic sounds generated by such processes may appear irregular and random in waveform, but these sounds are mathematically distinguished from random stochastic sounds in that they contain deterministic short-time predictability in their temporal fine structures. We show that the human brain distinguishes deterministic chaotic sounds from spectrally matched stochastic sounds in neural processing and perception. Deterministic chaotic sounds, even without being attended to, elicited greater cerebral cortical responses than the surrogate control sounds after about 150 ms in latency after sound onset. Listeners also clearly discriminated these sounds in perception. The results support the hypothesis that the human auditory system is sensitive to the subtle short-time predictability embedded in the temporal fine structure of sounds.

Photoacoustic Imaging of Epilepsy

DTIC Science & Technology

2013-04-01

mouse brain with the skin and skull intact,” Opt. Lett. 28(19), 1739–1741 (2003). 5. Q. Zhang, Z. Liu, P. R. Carney, Z. Yuan, H. Chen, S. N. Roper, and...imaging at centimeter scale depths. To date PAT has been applied to the detection of breast cancer, skin cancer and osteoarthritis in humans [1–3...the hemodynamic changes and reveal the 3D structures in the rat brain. Two small rats (~40g) were imaged with intact skull and skin but hairs on the

Cerebral perfusion abnormalities in therapy-resistant epilepsy in childhood: comparison between EEG, MRI and 99Tcm-ECD brain SPET.

PubMed

Vattimo, A; Burroni, L; Bertelli, P; Volterrani, D; Vella, A

1996-01-01

We performed 99Tcm-ethyl cysteinate dimer (ECD) interictal single photon emission tomography (SPET) in 26 children with severe therapy-resistant epilepsy. All the children underwent a detailed clinical examination, an electroencephalogram (EEG) investigation and brain magnetic resonance imaging (MRI). In 21 of the 26 children, SPET demonstrated brain blood flow abnormalities, in 13 cases in the same territories that showed EEG alterations. MRI showed structural lesions in 6 of the 26 children, while SPET imaging confirmed these abnormalities in only 5 children. The lesion not detected on SPET was shown to be 3 mm thick on MRI. Five symptomatic patients had normal SPET. In one of these patients, the EEG findings were normal and MRI revealed a small calcific nodule (4 mm thick); in the others, the EEG showed non-focal but diffuse abnormalities. These data confirm that brain SPET is sensitive in detecting and localizing hypoperfused areas that could be associated with epileptic foci in this group of patients, even when the MRI image is normal.

Immunolocalization of choline acetyltransferase of common type in the central brain mass of Octopus vulgaris

PubMed Central

Casini, A.; Vaccaro, R.; D'Este, L.; Sakaue, Y.; Bellier, J.P.; Kimura, H.; Renda, T.G.

2012-01-01

Acetylcholine, the first neurotransmitter to be identified in the vertebrate frog, is widely distributed among the animal kingdom. The presence of a large amount of acetylcholine in the nervous system of cephalopods is well known from several biochemical and physiological studies. However, little is known about the precise distribution of cholinergic structures due to a lack of a suitable histochemical technique for detecting acetylcholine. The most reliable method to visualize the cholinergic neurons is the immunohistochemical localization of the enzyme choline acetyltransferase, the synthetic enzyme of acetylcholine. Following our previous study on the distribution patterns of cholinergic neurons in the Octopus vulgaris visual system, using a novel antibody that recognizes choline acetyltransferase of the common type (cChAT), now we extend our investigation on the octopus central brain mass. When applied on sections of octopus central ganglia, immunoreactivity for cChAT was detected in cell bodies of all central brain mass lobes with the notable exception of the subfrontal and subvertical lobes. Positive varicosed nerves fibers where observed in the neuropil of all central brain mass lobes. PMID:23027350

Immunolocalization of choline acetyltransferase of common type in the central brain mass of Octopus vulgaris.

PubMed

Casini, A; Vaccaro, R; D'Este, L; Sakaue, Y; Bellier, J P; Kimura, H; Renda, T G

2012-07-19

Acetylcholine, the first neurotransmitter to be identified in the vertebrate frog, is widely distributed among the animal kingdom. The presence of a large amount of acetylcholine in the nervous system of cephalopods is well known from several biochemical and physiological studies. However, little is known about the precise distribution of cholinergic structures due to a lack of a suitable histochemical technique for detecting acetylcholine. The most reliable method to visualize the cholinergic neurons is the immunohistochemical localization of the enzyme choline acetyltransferase, the synthetic enzyme of acetylcholine. Following our previous study on the distribution patterns of cholinergic neurons in the Octopus vulgaris visual system, using a novel antibody that recognizes choline acetyltransferase of the common type (cChAT), now we extend our investigation on the octopus central brain mass. When applied on sections of octopus central ganglia, immunoreactivity for cChAT was detected in cell bodies of all central brain mass lobes with the notable exception of the subfrontal and subvertical lobes. Positive varicosed nerves fibers where observed in the neuropil of all central brain mass lobes.

Olfactory systems and neural circuits that modulate predator odor fear

PubMed Central

Takahashi, Lorey K.

2014-01-01

When prey animals detect the odor of a predator a constellation of fear-related autonomic, endocrine, and behavioral responses rapidly occur to facilitate survival. How olfactory sensory systems process predator odor and channel that information to specific brain circuits is a fundamental issue that is not clearly understood. However, research in the last 15 years has begun to identify some of the essential features of the sensory detection systems and brain structures that underlie predator odor fear. For instance, the main (MOS) and accessory olfactory systems (AOS) detect predator odors and different types of predator odors are sensed by specific receptors located in either the MOS or AOS. However, complex predator chemosignals may be processed by both the MOS and AOS, which complicate our understanding of the specific neural circuits connected directly and indirectly from the MOS and AOS to activate the physiological and behavioral components of unconditioned and conditioned fear. Studies indicate that brain structures including the dorsal periaqueductal gray (DPAG), paraventricular nucleus (PVN) of the hypothalamus, and the medial amygdala (MeA) appear to be broadly involved in predator odor induced autonomic activity and hypothalamic-pituitary-adrenal (HPA) stress hormone secretion. The MeA also plays a key role in predator odor unconditioned fear behavior and retrieval of contextual fear memory associated with prior predator odor experiences. Other neural structures including the bed nucleus of the stria terminalis and the ventral hippocampus (VHC) appear prominently involved in predator odor fear behavior. The basolateral amygdala (BLA), medial hypothalamic nuclei, and medial prefrontal cortex (mPFC) are also activated by some but not all predator odors. Future research that characterizes how distinct predator odors are uniquely processed in olfactory systems and neural circuits will provide significant insights into the differences of how diverse predator odors activate fear. PMID:24653685

Olfactory systems and neural circuits that modulate predator odor fear.

PubMed

Takahashi, Lorey K

2014-01-01

When prey animals detect the odor of a predator a constellation of fear-related autonomic, endocrine, and behavioral responses rapidly occur to facilitate survival. How olfactory sensory systems process predator odor and channel that information to specific brain circuits is a fundamental issue that is not clearly understood. However, research in the last 15 years has begun to identify some of the essential features of the sensory detection systems and brain structures that underlie predator odor fear. For instance, the main (MOS) and accessory olfactory systems (AOS) detect predator odors and different types of predator odors are sensed by specific receptors located in either the MOS or AOS. However, complex predator chemosignals may be processed by both the MOS and AOS, which complicate our understanding of the specific neural circuits connected directly and indirectly from the MOS and AOS to activate the physiological and behavioral components of unconditioned and conditioned fear. Studies indicate that brain structures including the dorsal periaqueductal gray (DPAG), paraventricular nucleus (PVN) of the hypothalamus, and the medial amygdala (MeA) appear to be broadly involved in predator odor induced autonomic activity and hypothalamic-pituitary-adrenal (HPA) stress hormone secretion. The MeA also plays a key role in predator odor unconditioned fear behavior and retrieval of contextual fear memory associated with prior predator odor experiences. Other neural structures including the bed nucleus of the stria terminalis and the ventral hippocampus (VHC) appear prominently involved in predator odor fear behavior. The basolateral amygdala (BLA), medial hypothalamic nuclei, and medial prefrontal cortex (mPFC) are also activated by some but not all predator odors. Future research that characterizes how distinct predator odors are uniquely processed in olfactory systems and neural circuits will provide significant insights into the differences of how diverse predator odors activate fear.

Brain Metabolism Correlates of the Free and Cued Selective Reminding Test in Mild Cognitive Impairment.

PubMed

Caffarra, Paolo; Ghetti, Caterina; Ruffini, Livia; Spallazzi, Marco; Spotti, Annamaria; Barocco, Federica; Guzzo, Caterina; Marchi, Massimo; Gardini, Simona

2016-01-01

Free and Cued Selective Reminding Test (FCSRT) measures immediate and delayed episodic memory and cueing sensitivity and is suitable to detect prodromal Alzheimer's disease (AD). The present study aimed at investigating the segregation effect of FCSRT scores on brain metabolism of memory-related structures, usually affected by AD pathology, in the Mild Cognitive Impairment (MCI) stage. A cohort of forty-eight MCI patients underwent FCSRT and 18F-FDG-PET. Multiple regression analysis showed that Immediate Free Recall correlated with brain metabolism in the bilateral anterior cingulate and delayed free recall with the left anterior cingulate and medial frontal gyrus, whereas semantic cueing sensitivity with the left posterior cingulate. FCSRT in MCI is associated with neuro-functional activity of specific regions of memory-related structures connected to hippocampal formation, such as the cingulate cortex, usually damaged in AD.

Structured Illumination Diffuse Optical Tomography for Mouse Brain Imaging

NASA Astrophysics Data System (ADS)

Reisman, Matthew David

As advances in functional magnetic resonance imaging (fMRI) have transformed the study of human brain function, they have also widened the divide between standard research techniques used in humans and those used in mice, where high quality images are difficult to obtain using fMRI given the small volume of the mouse brain. Optical imaging techniques have been developed to study mouse brain networks, which are highly valuable given the ability to study brain disease treatments or development in a controlled environment. A planar imaging technique known as optical intrinsic signal (OIS) imaging has been a powerful tool for capturing functional brain hemodynamics in rodents. Recent wide field-of-view implementations of OIS have provided efficient maps of functional connectivity from spontaneous brain activity in mice. However, OIS requires scalp retraction and is limited to imaging a 2-dimensional view of superficial cortical tissues. Diffuse optical tomography (DOT) is a non-invasive, volumetric neuroimaging technique that has been valuable for bedside imaging of patients in the clinic, but previous DOT systems for rodent neuroimaging have been limited by either sparse spatial sampling or by slow speed. My research has been to develop diffuse optical tomography for whole brain mouse neuroimaging by expanding previous techniques to achieve high spatial sampling using multiple camera views for detection and high speed using structured illumination sources. I have shown the feasibility of this method to perform non-invasive functional neuroimaging in mice and its capabilities of imaging the entire volume of the brain. Additionally, the system has been built with a custom, flexible framework to accommodate the expansion to imaging multiple dynamic contrasts in the brain and populations that were previously difficult or impossible to image, such as infant mice and awake mice. I have contributed to preliminary feasibility studies of these more advanced techniques using OIS, which can now be carried out using the structured illumination diffuse optical tomography technique to perform longitudinal, non-invasive studies of the whole volume of the mouse brain.

Structural-metabolic organization of field 4 of the cat brain in normal conditions and after unilateral enucleation of the eye.

PubMed

Zykin, P A

2005-01-01

Comparative data on the structural-metabolic organization of field 4 of the cat brain in normal conditions and after unilateral enucleation of the eye are presented. Cytochrome oxidase was detected histochemically. Data were processed by a computerized method using an original video capture system. Data were obtained demonstrating the uneven distribution of enzyme along sublayer IlIb of field 4 in animals with unilateral enucleation. A hypothesis based on published data is suggested whereby the alternation of high- and low-reactive areas is evidence for the ordering of the retinal representations of the right and left eyes in the sensorimotor cortex.

Blood pressure, brain structure, and cognition: opposite associations in men and women.

PubMed

Cherbuin, Nicolas; Mortby, Moyra E; Janke, Andrew L; Sachdev, Perminder S; Abhayaratna, Walter P; Anstey, Kaarin J

2015-02-01

Research on associations between blood pressure, brain structure, and cognitive function has produced somewhat inconsistent results. In part, this may be due to differences in age ranges studied and because of sex differences in physiology and/or exposure to risk factors, which may lead to different time course or patterns in cardiovascular disease progression. The aim of this study was to investigate the impact of sex on associations between blood pressure, regional cerebral volumes, and cognitive function in older individuals. In this cohort study, brachial blood pressure was measured twice at rest in 266 community-based individuals free of dementia aged 68-73 years who had also undergone a brain scan and a neuropsychological assessment. Associations between mean blood pressure (MAP), regional brain volumes, and cognition were investigated with voxel-wise regression analyses. Positive associations between MAP and regional volumes were detected in men, whereas negative associations were found in women. Similarly, there were sex differences in the brain-volume cognition relationship, with a positive relationship between regional brain volumes associated with MAP in men and a negative relationship in women. In this cohort of older individuals, higher MAP was associated with larger regional volume and better cognition in men, whereas opposite findings were demonstrated in women. These effects may be due to different lifetime risk exposure or because of physiological differences between men and women. Future studies investigating the relationship between blood pressure and brain structure or cognitive function should evaluate the potential for differential sex effects. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Feasibility of in Vivo SAXS Imaging for Detection of Alzheiemer's Disease

NASA Astrophysics Data System (ADS)

Choi, Mina

Small-angle x-ray scattering (SAXS) imaging has been proposed as a technique to characterize and selectively image structures based on electron density structure which allows for discriminating materials based on their scatter cross sections. This dissertation explores the feasibility of SAXS imaging for the detection of Alzheimer's disease (AD) amyloid plaques. The inherent scatter cross sections of amyloid plaque serve as biomarkers in vivo without the need of injected molecular tags. SAXS imaging can also assist in a better understanding of how these biomarkers play a role in Alzheimer's disease which in turn can lead to the development of more effective disease-modifying therapies. I implement simulations of x-ray transport using Monte Carlo methods for SAXS imaging enabling accurate calculation of radiation dose and image quality in SAXS-computed tomography (CT). I describe SAXS imaging phantoms with tissue-mimicking material and embedded scatter targets as a way of demonstrating the characteristics of SAXS imaging. I also performed a comprehensive study of scattering cross sections of brain tissue from measurements of ex-vivo sections of a wild-type mouse brain and reported generalized cross sections of gray matter, white matter, and corpus callosum obtained and registered by planar SAXS imaging. Finally, I demonstrate the ability of SAXS imaging to locate an amyloid fibril pellet within a brain section. This work contributes to novel application of SAXS imaging for Alzheimer's disease detection and studies its feasibility as an imaging tool for AD biomarkers.

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

Neuropsychology and the neurochemical lesion: evolution, applications and extensions.

PubMed

Hartman, D E

1988-01-01

The evolution of neuropsychology into a method for neurotoxic damage detection is reviewed. When neuropsychology is transformed into "neuropsychological toxicology", fundamental philosophical assumptions of the field are altered; the search for brain-behavior relationships must extend from structural damage into the analysis of neurochemical systems. The complementary relationship of human neuropsychology to basic toxicological and animal research is discussed. The great numbers of human "natural experiments" whose employment, medical history or substance abuse subjects them to contact with neurotoxic substances, suggest that there is a great need for expanded human investigations involving neuropsychological testing procedures in the service of research and clinical identification of neurotoxic syndromes. Further, it is argued that neurobehavioral procedures originally developed to detect industrial neurotoxic exposure will prove additionally useful assessing other brain-behavior disruptions mediated by neurochemistry or neurotoxicity rather than structural lesion. These frontiers include physical or emotional illness, substance abuse, effects of abused or prescription drugs as well as little-researched areas deserving of closer study, e.g., allergens or biotoxic exposure.

Non-coding RNAs in cancer brain metastasis

PubMed Central

Wu, Kerui; Sharma, Sambad; Venkat, Suresh; Liu, Keqin; Zhou, Xiaobo; Watabe, Kounosuke

2017-01-01

More than 90% of cancer death is attributed to metastatic disease, and the brain is one of the major metastatic sites of melanoma, colon, renal, lung and breast cancers. Despite the recent advancement of targeted therapy for cancer, the incidence of brain metastasis is increasing. One reason is that most therapeutic drugs can’t penetrate blood-brain-barrier and tumor cells find the brain as sanctuary site. In this review, we describe the pathophysiology of brain metastases to introduce the latest understandings of metastatic brain malignancies. This review also particularly focuses on non-coding RNAs and their roles in cancer brain metastasis. Furthermore, we discuss the roles of the extracellular vesicles as they are known to transport information between cells to initiate cancer cell-microenvironment communication. The potential clinical translation of non-coding RNAs as a tool for diagnosis and for treatment is also discussed in this review. At the end, the computational aspects of non-coding RNA detection, the sequence and structure calculation and epigenetic regulation of non-coding RNA in brain metastasis are discussed. PMID:26709907

Dynamic functional connectivity using state-based dynamic community structure: method and application to opioid analgesia.

PubMed

Robinson, Lucy F; Atlas, Lauren Y; Wager, Tor D

2015-03-01

We present a new method, State-based Dynamic Community Structure, that detects time-dependent community structure in networks of brain regions. Most analyses of functional connectivity assume that network behavior is static in time, or differs between task conditions with known timing. Our goal is to determine whether brain network topology remains stationary over time, or if changes in network organization occur at unknown time points. Changes in network organization may be related to shifts in neurological state, such as those associated with learning, drug uptake or experimental conditions. Using a hidden Markov stochastic blockmodel, we define a time-dependent community structure. We apply this approach to data from a functional magnetic resonance imaging experiment examining how contextual factors influence drug-induced analgesia. Results reveal that networks involved in pain, working memory, and emotion show distinct profiles of time-varying connectivity. Copyright © 2014 Elsevier Inc. All rights reserved.

Single-subject structural networks with closed-form rotation invariant matching mprove power in developmental studies of the cortex.

PubMed

Kandel, Benjamin M; Wang, Danny J J; Gee, James C; Avants, Brian B

2014-01-01

Although much attention has recently been focused on single-subject functional networks, using methods such as resting-state functional MRI, methods for constructing single-subject structural networks are in their infancy. Single-subject cortical networks aim to describe the self-similarity across the cortical structure, possibly signifying convergent developmental pathways. Previous methods for constructing single-subject cortical networks have used patch-based correlations and distance metrics based on curvature and thickness. We present here a method for constructing similarity-based cortical structural networks that utilizes a rotation-invariant representation of structure. The resulting graph metrics are closely linked to age and indicate an increasing degree of closeness throughout development in nearly all brain regions, perhaps corresponding to a more regular structure as the brain matures. The derived graph metrics demonstrate a four-fold increase in power for detecting age as compared to cortical thickness. This proof of concept study indicates that the proposed metric may be useful in identifying biologically relevant cortical patterns.

Brain structural covariance network centrality in maltreated youth with PTSD and in maltreated youth resilient to PTSD.

PubMed

Sun, Delin; Haswell, Courtney C; Morey, Rajendra A; De Bellis, Michael D

2018-04-10

Child maltreatment is a major cause of pediatric posttraumatic stress disorder (PTSD). Previous studies have not investigated potential differences in network architecture in maltreated youth with PTSD and those resilient to PTSD. High-resolution magnetic resonance imaging brain scans at 3 T were completed in maltreated youth with PTSD (n = 31), without PTSD (n = 32), and nonmaltreated controls (n = 57). Structural covariance network architecture was derived from between-subject intraregional correlations in measures of cortical thickness in 148 cortical regions (nodes). Interregional positive partial correlations controlling for demographic variables were assessed, and those correlations that exceeded specified thresholds constituted connections in cortical brain networks. Four measures of network centrality characterized topology, and the importance of cortical regions (nodes) within the network architecture were calculated for each group. Permutation testing and principle component analysis method were employed to calculate between-group differences. Principle component analysis is a methodological improvement to methods used in previous brain structural covariance network studies. Differences in centrality were observed between groups. Larger centrality was found in maltreated youth with PTSD in the right posterior cingulate cortex; smaller centrality was detected in the right inferior frontal cortex compared to youth resilient to PTSD and controls, demonstrating network characteristics unique to pediatric maltreatment-related PTSD. Larger centrality was detected in right frontal pole in maltreated youth resilient to PTSD compared to youth with PTSD and controls, demonstrating structural covariance network differences in youth resilience to PTSD following maltreatment. Smaller centrality was found in the left posterior cingulate cortex and in the right inferior frontal cortex in maltreated youth compared to controls, demonstrating attributes of structural covariance network topology that is unique to experiencing maltreatment. This work is the first to identify cortical thickness-based structural covariance network differences between maltreated youth with and without PTSD. We demonstrated network differences in both networks unique to maltreated youth with PTSD and those resilient to PTSD. The networks identified are important for the successful attainment of age-appropriate social cognition, attention, emotional processing, and inhibitory control. Our findings in maltreated youth with PTSD versus those without PTSD suggest vulnerability mechanisms for developing PTSD.

Technetium-99m-HMPAO SPECT, CT and MRI in the evaluation of patients with chronic traumatic brain injury: a correlation with neuropsychological performance.

PubMed

Ichise, M; Chung, D G; Wang, P; Wortzman, G; Gray, B G; Franks, W

1994-02-01

The purposes of this study were: (1) to compare 99mTc-hexamethylpropyleneamineoxime (HMPAO) SPECT with CT and MRI in chronic traumatic brain injury (TBI) patients and (2) to correlate both functional and structural neuroimaging measurements of brain damage with neuropsychological (NP) performance. Twenty-nine patients (minor TBI, n = 15 and major TBI, n = 14) and 17 normal controls (NC) underwent HMPAO SPECT, CT, MRI and NP testing. Imaging data were analyzed both visually and quantitatively. Nineteen (66%) patients showed 42 abnormalities on SPECT images, whereas 13 (45%) and 10 (34%) patients showed 29 abnormalities on MRI and 24 abnormalities on CT. SPECT detected relatively more abnormalities than CT or MRI in the minor TBI subgroup. The TBI group showed impairment on 11 tests for memory, attention and executive function. Of these, the anterior-posterior ratio (APR) correlated with six tests, whereas the ventricle-to-brain ratio (VBR), a known structural index of a poor NP outcome, correlated with only two tests. In evaluating chronic TBI patients, HMPAO SPECT, as a complement to CT or MRI, may play a useful role by demonstrating brain dysfunction in morphologically intact brain regions and providing objective evidence for some of the impaired NP performance.

Quantitative phase and texture angularity analysis of brain white matter lesions in multiple sclerosis

NASA Astrophysics Data System (ADS)

Baxandall, Shalese; Sharma, Shrushrita; Zhai, Peng; Pridham, Glen; Zhang, Yunyan

2018-03-01

Structural changes to nerve fiber tracts are extremely common in neurological diseases such as multiple sclerosis (MS). Accurate quantification is vital. However, while nerve fiber damage is often seen as multi-focal lesions in magnetic resonance imaging (MRI), measurement through visual perception is limited. Our goal was to characterize the texture pattern of the lesions in MRI and determine how texture orientation metrics relate to lesion structure using two new methods: phase congruency and multi-resolution spatial-frequency analysis. The former aims to optimize the detection of the `edges and corners' of a structure, and the latter evaluates both the radial and angular distributions of image texture associated with the various forming scales of a structure. The radial texture spectra were previously confirmed to measure the severity of nerve fiber damage, and were thus included for validation. All measures were also done in the control brain white matter for comparison. Using clinical images of MS patients, we found that both phase congruency and weighted mean phase detected invisible lesion patterns and were significantly greater in lesions, suggesting higher structure complexity, than the control tissue. Similarly, multi-angular spatial-frequency analysis detected much higher texture across the whole frequency spectrum in lesions than the control areas. Such angular complexity was consistent with findings from radial texture. Analysis of the phase and texture alignment may prove to be a useful new approach for assessing invisible changes in lesions using clinical MRI and thereby lead to improved management of patients with MS and similar disorders.

Longitudinal Structural and Functional Brain Network Alterations in a Mouse Model of Neuropathic Pain.

PubMed

Bilbao, Ainhoa; Falfán-Melgoza, Claudia; Leixner, Sarah; Becker, Robert; Singaravelu, Sathish Kumar; Sack, Markus; Sartorius, Alexander; Spanagel, Rainer; Weber-Fahr, Wolfgang

2018-04-22

Neuropathic pain affects multiple brain functions, including motivational processing. However, little is known about the structural and functional brain changes involved in the transition from an acute to a chronic pain state. Here we combined behavioral phenotyping of pain thresholds with multimodal neuroimaging to longitudinally monitor changes in brain metabolism, structure and connectivity using the spared nerve injury (SNI) mouse model of chronic neuropathic pain. We investigated stimulus-evoked pain responses prior to SNI surgery, and one and twelve weeks following surgery. A progressive development and potentiation of stimulus-evoked pain responses (cold and mechanical allodynia) were detected during the course of pain chronification. Voxel-based morphometry demonstrated striking decreases in volume following pain induction in all brain sites assessed - an effect that reversed over time. Similarly, all global and local network changes that occurred following pain induction disappeared over time, with two notable exceptions: the nucleus accumbens, which played a more dominant role in the global network in a chronic pain state and the prefrontal cortex and hippocampus, which showed lower connectivity. These changes in connectivity were accompanied by enhanced glutamate levels in the hippocampus, but not in the prefrontal cortex. We suggest that hippocampal hyperexcitability may contribute to alterations in synaptic plasticity within the nucleus accumbens, and to pain chronification. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Investigating Neuroanatomical Features in Top Athletes at the Single Subject Level.

PubMed

Taubert, Marco; Wenzel, Uwe; Draganski, Bogdan; Kiebel, Stefan J; Ragert, Patrick; Krug, Jürgen; Villringer, Arno

2015-01-01

In sport events like Olympic Games or World Championships competitive athletes keep pushing the boundaries of human performance. Compared to team sports, high achievements in many athletic disciplines depend solely on the individual's performance. Contrasting previous research looking for expertise-related differences in brain anatomy at the group level, we aim to demonstrate changes in individual top athlete's brain, which would be averaged out in a group analysis. We compared structural magnetic resonance images (MRI) of three professional track-and-field athletes to age-, gender- and education-matched control subjects. To determine brain features specific to these top athletes, we tested for significant deviations in structural grey matter density between each of the three top athletes and a carefully matched control sample. While total brain volumes were comparable between athletes and controls, we show regional grey matter differences in striatum and thalamus. The demonstrated brain anatomy patterns remained stable and were detected after 2 years with Olympic Games in between. We also found differences in the fusiform gyrus in two top long jumpers. We interpret our findings in reward-related areas as correlates of top athletes' persistency to reach top-level skill performance over years.

Investigating Neuroanatomical Features in Top Athletes at the Single Subject Level

PubMed Central

Taubert, Marco; Wenzel, Uwe; Draganski, Bogdan; Kiebel, Stefan J.; Ragert, Patrick; Krug, Jürgen; Villringer, Arno

2015-01-01

In sport events like Olympic Games or World Championships competitive athletes keep pushing the boundaries of human performance. Compared to team sports, high achievements in many athletic disciplines depend solely on the individual’s performance. Contrasting previous research looking for expertise-related differences in brain anatomy at the group level, we aim to demonstrate changes in individual top athlete’s brain, which would be averaged out in a group analysis. We compared structural magnetic resonance images (MRI) of three professional track-and-field athletes to age-, gender- and education-matched control subjects. To determine brain features specific to these top athletes, we tested for significant deviations in structural grey matter density between each of the three top athletes and a carefully matched control sample. While total brain volumes were comparable between athletes and controls, we show regional grey matter differences in striatum and thalamus. The demonstrated brain anatomy patterns remained stable and were detected after 2 years with Olympic Games in between. We also found differences in the fusiform gyrus in two top long jumpers. We interpret our findings in reward-related areas as correlates of top athletes’ persistency to reach top-level skill performance over years. PMID:26079870

A method based on Monte Carlo simulations and voxelized anatomical atlases to evaluate and correct uncertainties on radiotracer accumulation quantitation in beta microprobe studies in the rat brain

NASA Astrophysics Data System (ADS)

Pain, F.; Dhenain, M.; Gurden, H.; Routier, A. L.; Lefebvre, F.; Mastrippolito, R.; Lanièce, P.

2008-10-01

The β-microprobe is a simple and versatile technique complementary to small animal positron emission tomography (PET). It relies on local measurements of the concentration of positron-labeled molecules. So far, it has been successfully used in anesthetized rats for pharmacokinetics experiments and for the study of brain energetic metabolism. However, the ability of the technique to provide accurate quantitative measurements using 18F, 11C and 15O tracers is likely to suffer from the contribution of 511 keV gamma rays background to the signal and from the contribution of positrons from brain loci surrounding the locus of interest. The aim of the present paper is to provide a method of evaluating several parameters, which are supposed to affect the quantification of recordings performed in vivo with this methodology. We have developed realistic voxelized phantoms of the rat whole body and brain, and used them as input geometries for Monte Carlo simulations of previous β-microprobe reports. In the context of realistic experiments (binding of 11C-Raclopride to D2 dopaminergic receptors in the striatum; local glucose metabolic rate measurement with 18F-FDG and H2O15 blood flow measurements in the somatosensory cortex), we have calculated the detection efficiencies and corresponding contribution of 511 keV gammas from peripheral organs accumulation. We confirmed that the 511 keV gammas background does not impair quantification. To evaluate the contribution of positrons from adjacent structures, we have developed β-Assistant, a program based on a rat brain voxelized atlas and matrices of local detection efficiencies calculated by Monte Carlo simulations for several probe geometries. This program was used to calculate the 'apparent sensitivity' of the probe for each brain structure included in the detection volume. For a given localization of a probe within the brain, this allows us to quantify the different sources of beta signal. Finally, since stereotaxic accuracy is crucial for quantification in most microprobe studies, the influence of stereotaxic positioning error was studied for several realistic experiments in favorable and unfavorable experimental situations (binding of 11C-Raclopride to D2 dopaminergic receptors in the striatum; binding of 18F-MPPF to 5HT1A receptors in the dorsal raphe nucleus).

Immunocytochemical Mapping of an RDL-Like GABA Receptor Subunit and of GABA in Brain Structures Related to Learning and Memory in the Cricket Acheta domesticus

PubMed Central

Strambi, Colette; Cayre, Myriam; Sattelle, David B.; Augier, Roger; Charpin, Pierre; Strambi, Alain

1998-01-01

The distribution of putative RDL-like GABA receptors and of γ-aminobutyric acid (GABA) in the brain of the adult house cricket Acheta domesticus was studied using specific antisera. Special attention was given to brain structures known to be related to learning and memory. The main immunostaining for the RDL-like GABA receptor was observed in mushroom bodies, in particular the upper part of mushroom body peduncle and the two arms of the posterior calyx. Weaker immunostaining was detected in the distal part of the peduncle and in the α and β lobes. The dorso- and ventrolateral protocerebrum neuropils appeared rich in RDL-like GABA receptors. Staining was also detected in the glomeruli of the antennal lobe, as well as in the ellipsoid body of the central complex. Many neurons clustered in groups exhibit GABA-like immunoreactivity. Tracts that were strongly immunostained innervated both the calyces and the lobes of mushroom bodies. The glomeruli of the antennal lobe, the ellipsoid body, as well as neuropils of the dorso- and ventrolateral protocerebrum were also rich in GABA-like immuno- reactivity. The data demonstrated a good correlation between the distribution of the GABA-like and of the RDL-like GABA receptor immunoreactivity. The prominent distribution of RDL-like GABA receptor subunits, in particular areas of mushroom bodies and antennal lobes, underlines the importance of inhibitory signals in information processing in these major integrative centers of the insect brain. PMID:10454373

No differences in brain microstructure between young KIBRA-C carriers and non-carriers.

PubMed

Hu, Li; Xu, Qunxing; Li, Jizhen; Wang, Feifei; Xu, Xinghua; Sun, Zhiyuan; Ma, Xiangxing; Liu, Yong; Wang, Qing; Wang, Dawei

2018-01-02

KIBRA rs17070145 polymorphism is associated with variations in memory function and the microstructure of related brain areas. Diffusion kurtosis imaging (DKI) as an extension of diffusion tensor imaging that can provide more information about changes in microstructure, based on the idea that water diffusion in biological tissues is heterogeneous due to structural hindrance and restriction. We used DKI to explore the relationship between KIBRA gene polymorphism and brain microstructure in young adults. We recruited 100 healthy young volunteers, including 53 TT carriers and 47 C allele carriers. No differences were detected between the TT homozygotes and C-allele carriers for any diffusion and kurtosis parameter. These results indicate KIBRA rs17070145 polymorphism likely has little or no effect on brain microstructure in young adults.

Structural and functional differences in the cingulate cortex relate to disease severity in anorexia nervosa

PubMed Central

Bär, Karl-Jürgen; de la Cruz, Feliberto; Berger, Sandy; Schultz, Carl Christoph; Wagner, Gerd

2015-01-01

Background The dysfunction of specific brain areas might account for the distortion of body image in patients with anorexia nervosa. The present study was designed to reveal brain regions that are abnormal in structure and function in patients with this disorder. We hypothesized, based on brain areas of altered activity in patients with anorexia nervosa and regions involved in pain processing, an interrelation of structural aberrations in the frontoparietal–cingulate network and aberrant functional activation during thermal pain processing in patients with the disorder. Methods We determined pain thresholds outside the MRI scanner in patients with anorexia nervosa and matched healthy controls. Thereafter, thermal pain stimuli were applied during fMRI imaging. Structural analyses with high-resolution structural T1-weighted volumes were performed using voxel-based morphometry and a surface-based approach. Results Twenty-six patients and 26 controls participated in our study, and owing to technical difficulties, 15 participants in each group were included in our fMRI analysis. Structural analyses revealed significantly decreased grey matter volume and cortical thickness in the frontoparietal–cingulate network in patients with anorexia nervosa. We detected an increased blood oxygen level–dependent signal in patients during the painful 45°C condition in the midcingulate and posterior cingulate cortex, which positively correlated with increased pain thresholds. Decreased grey matter and cortical thickness correlated negatively with pain thresholds, symptom severity and illness duration, but not with body mass index. Limitations The lack of a specific quantification of body image distortion is a limitation of our study. Conclusion This study provides further evidence for confined structural and functional brain abnormalities in patients with anorexia nervosa in brain regions that are involved in perception and integration of bodily stimuli. The association of structural and functional deviations with thermal thresholds as well as with clinical characteristics might indicate a common neuronal origin. PMID:25825813

Volumetric abnormalities of the brain in a rat model of recurrent headache.

PubMed

Jia, Zhihua; Tang, Wenjing; Zhao, Dengfa; Hu, Guanqun; Li, Ruisheng; Yu, Shengyuan

2018-01-01

Voxel-based morphometry is used to detect structural brain changes in patients with migraine. However, the relevance of migraine and structural changes is not clear. This study investigated structural brain abnormalities based on voxel-based morphometry using a rat model of recurrent headache. The rat model was established by infusing an inflammatory soup through supradural catheters in conscious male rats. Rats were subgrouped according to the frequency and duration of the inflammatory soup infusion. Tactile sensory testing was conducted prior to infusion of the inflammatory soup or saline. The periorbital tactile thresholds in the high-frequency inflammatory soup stimulation group declined persistently from day 5. Increased white matter volume was observed in the rats three weeks after inflammatory soup stimulation, brainstem in the in the low-frequency inflammatory soup-infusion group and cortex in the high-frequency inflammatory soup-infusion group. After six weeks' stimulation, rats showed gray matter volume changes. The brain structural abnormalities recovered after the stimulation was stopped in the low-frequency inflammatory soup-infused rats and persisted even after the high-frequency inflammatory soup stimulus stopped. The changes of voxel-based morphometry in migraineurs may be the result of recurrent headache. Cognition, memory, and learning may play an important role in the chronification of migraines. Reducing migraine attacks has the promise of preventing chronicity of migraine.

Mixed Effects Models for Resampled Network Statistics Improves Statistical Power to Find Differences in Multi-Subject Functional Connectivity

PubMed Central

Narayan, Manjari; Allen, Genevera I.

2016-01-01

Many complex brain disorders, such as autism spectrum disorders, exhibit a wide range of symptoms and disability. To understand how brain communication is impaired in such conditions, functional connectivity studies seek to understand individual differences in brain network structure in terms of covariates that measure symptom severity. In practice, however, functional connectivity is not observed but estimated from complex and noisy neural activity measurements. Imperfect subject network estimates can compromise subsequent efforts to detect covariate effects on network structure. We address this problem in the case of Gaussian graphical models of functional connectivity, by proposing novel two-level models that treat both subject level networks and population level covariate effects as unknown parameters. To account for imperfectly estimated subject level networks when fitting these models, we propose two related approaches—R2 based on resampling and random effects test statistics, and R3 that additionally employs random adaptive penalization. Simulation studies using realistic graph structures reveal that R2 and R3 have superior statistical power to detect covariate effects compared to existing approaches, particularly when the number of within subject observations is comparable to the size of subject networks. Using our novel models and methods to study parts of the ABIDE dataset, we find evidence of hypoconnectivity associated with symptom severity in autism spectrum disorders, in frontoparietal and limbic systems as well as in anterior and posterior cingulate cortices. PMID:27147940

Divide and Conquer: Sub-Grouping of ASD Improves ASD Detection Based on Brain Morphometry.

PubMed

Katuwal, Gajendra J; Baum, Stefi A; Cahill, Nathan D; Michael, Andrew M

2016-01-01

Low success (<60%) in autism spectrum disorder (ASD) classification using brain morphometry from the large multi-site ABIDE dataset and inconsistent findings on brain morphometric abnormalities in ASD can be attributed to the ASD heterogeneity. In this study, we show that ASD brain morphometry is highly heterogeneous, and demonstrate that the heterogeneity can be mitigated and classification improved if autism severity (AS), verbal IQ (VIQ) and age are used with morphometric features. Morphometric features from structural MRIs (sMRIs) of 734 males (ASD: 361, controls: 373) of ABIDE were derived using FreeSurfer. Applying the Random Forest classifier, an AUC of 0.61 was achieved. Adding VIQ and age to morphometric features, AUC improved to 0.68. Sub-grouping the subjects by AS, VIQ and age improved the classification with the highest AUC of 0.8 in the moderate-AS sub-group (AS = 7-8). Matching subjects on age and/or VIQ in each sub-group further improved the classification with the highest AUC of 0.92 in the low AS sub-group (AS = 4-5). AUC decreased with AS and VIQ, and was the lowest in the mid-age sub-group (13-18 years). The important features were mainly from the frontal, temporal, ventricular, right hippocampal and left amygdala regions. However, they highly varied with AS, VIQ and age. The curvature and folding index features from frontal, temporal, lingual and insular regions were dominant in younger subjects suggesting their importance for early detection. When the experiments were repeated using the Gradient Boosting classifier similar results were obtained. Our findings suggest that identifying brain biomarkers in sub-groups of ASD can yield more robust and insightful results than searching across the whole spectrum. Further, it may allow identification of sub-group specific brain biomarkers that are optimized for early detection and monitoring, increasing the utility of sMRI as an important tool for early detection of ASD.

Divide and Conquer: Sub-Grouping of ASD Improves ASD Detection Based on Brain Morphometry

PubMed Central

Baum, Stefi A.; Cahill, Nathan D.; Michael, Andrew M.

2016-01-01

Low success (<60%) in autism spectrum disorder (ASD) classification using brain morphometry from the large multi-site ABIDE dataset and inconsistent findings on brain morphometric abnormalities in ASD can be attributed to the ASD heterogeneity. In this study, we show that ASD brain morphometry is highly heterogeneous, and demonstrate that the heterogeneity can be mitigated and classification improved if autism severity (AS), verbal IQ (VIQ) and age are used with morphometric features. Morphometric features from structural MRIs (sMRIs) of 734 males (ASD: 361, controls: 373) of ABIDE were derived using FreeSurfer. Applying the Random Forest classifier, an AUC of 0.61 was achieved. Adding VIQ and age to morphometric features, AUC improved to 0.68. Sub-grouping the subjects by AS, VIQ and age improved the classification with the highest AUC of 0.8 in the moderate-AS sub-group (AS = 7–8). Matching subjects on age and/or VIQ in each sub-group further improved the classification with the highest AUC of 0.92 in the low AS sub-group (AS = 4–5). AUC decreased with AS and VIQ, and was the lowest in the mid-age sub-group (13–18 years). The important features were mainly from the frontal, temporal, ventricular, right hippocampal and left amygdala regions. However, they highly varied with AS, VIQ and age. The curvature and folding index features from frontal, temporal, lingual and insular regions were dominant in younger subjects suggesting their importance for early detection. When the experiments were repeated using the Gradient Boosting classifier similar results were obtained. Our findings suggest that identifying brain biomarkers in sub-groups of ASD can yield more robust and insightful results than searching across the whole spectrum. Further, it may allow identification of sub-group specific brain biomarkers that are optimized for early detection and monitoring, increasing the utility of sMRI as an important tool for early detection of ASD. PMID:27065101

Brain anomalies in velo-cardio-facial syndrome

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

Mitnick, R.J.; Bello, J.A.; Shprintzen, R.J.

Magnetic resonance imaging of the brain in 11 consecutively referred patients with velo-cardio-facial syndrome (VCF) showed anomalies in nine cases including small vermis, cysts adjacent to the frontal horns, and small posterior fossa. Focal signal hyperintensities in the white matter on long TR images were also noted. The nine patients showed a variety of behavioral abnormalities including mild development delay, learning disabilities, and characteristic personality traits typical of this common multiple anomaly syndrome which has been related to a microdeletion at 22q11. Analysis of the behavorial findings showed no specific pattern related to the brain anomalies, and the patients withmore » VCF who did not have detectable brain lesions also had behavioral abnormalities consistent with VCF. The significance of the lesions is not yet known, but the high prevalence of anomalies in this sample suggests that structural brain abnormalities are probably common in VCF. 25 refs.« less

Detection of Alzheimer’s disease amyloid-beta plaque deposition by deep brain impedance profiling

NASA Astrophysics Data System (ADS)

Béduer, Amélie; Joris, Pierre; Mosser, Sébastien; Fraering, Patrick C.; Renaud, Philippe

2015-04-01

Objective. Alzheimer disease (AD) is the most common form of neurodegenerative disease in elderly people. Toxic brain amyloid-beta (Aß) aggregates and ensuing cell death are believed to play a central role in the pathogenesis of the disease. In this study, we investigated if we could monitor the presence of these aggregates by performing in situ electrical impedance spectroscopy measurements in AD model mice brains. Approach. In this study, electrical impedance spectroscopy measurements were performed post-mortem in APPPS1 transgenic mice brains. This transgenic model is commonly used to study amyloidogenesis, a pathological hallmark of AD. We used flexible probes with embedded micrometric electrodes array to demonstrate the feasibility of detecting senile plaques composed of Aß peptides by localized impedance measurements. Main results. We particularly focused on deep brain structures, such as the hippocampus. Ex vivo experiments using brains from young and old APPPS1 mice lead us to show that impedance measurements clearly correlate with the percentage of Aβ plaque load in the brain tissues. We could monitor the effects of aging in the AD APPPS1 mice model. Significance. We demonstrated that a localized electrical impedance measurement constitutes a valuable technique to monitor the presence of Aβ-plaques, which is complementary with existing imaging techniques. This method does not require prior Aβ staining, precluding the risk of variations in tissue uptake of dyes or tracers, and consequently ensuring reproducible data collection.

[MRI for brain structure and function in patients with first-episode panic disorder].

PubMed

Zhang, Yan; Duan, Lian; Liao, Mei; Yang, Fan; Liu, Jun; Shan, Baoci; Li, Lingjiang

2011-12-01

To determine the brain function and structure in patinets with first-episode panic disorder (PD). All subjects (24 PD patients and 24 healthy subjects) received MRI scan and emotional counting Stroop task during the functional magnetic resonance imaging. Blood oxygenation level dependent functional magnetic resonance imaging and voxel-based morphometric technology were used to detect the gray matter volume. Compared with the healthy controls, left thalamus, left medial frontal gyrus, left anterior cingulate gyrus, left inferior frontal gyrus, left insula (panic-related words vs. neutral words) lacked activation in PD patients, but the over-activation were found in right brain stem, right occipital lobe/lingual gyrus in PD patients. Compared with the healthy controls, the gray matter volume in the PD patients significantly decreased in the left superior temporal gyrus, right medial frontal gyrus, left medial occipital gyrus, dorsomedial nucleus of left thalamus and right anterior cingulate gyrus. There was no significantly increased gray matter volume in any brain area in PD patients. PD patients have selective attentional bias in processing threatening information due to the depression and weakening of the frontal cingulated gyrus.

Mapping the Critical Gestational Age at Birth that Alters Brain Development in Preterm-born Infants using Multi-Modal MRI

PubMed Central

Wu, Dan; Chang, Linda; Akazawa, Kentaro; Oishi, Kumiko; Skranes, Jon; Ernst, Thomas; Oishi, Kenichi

2017-01-01

Preterm birth adversely affects postnatal brain development. In order to investigate the critical gestational age at birth (GAB) that alters the developmental trajectory of gray and white matter structures in the brain, we investigated diffusion tensor and quantitative T2 mapping data in 43 term-born and 43 preterm-born infants. A novel multivariate linear model—the change point model, was applied to detect change points in fractional anisotropy, mean diffusivity, and T2 relaxation time. Change points captured the “critical” GAB value associated with a change in the linear relation between GAB and MRI measures. The analysis was performed in 126 regions across the whole brain using an atlas-based image quantification approach to investigate the spatial pattern of the critical GAB. Our results demonstrate that the critical GABs are region- and modality-specific, generally following a central-to-peripheral and bottom-to-top order of structural development. This study may offer unique insights into the postnatal neurological development associated with differential degrees of preterm birth. PMID:28111189

Mapping the critical gestational age at birth that alters brain development in preterm-born infants using multi-modal MRI.

PubMed

Wu, Dan; Chang, Linda; Akazawa, Kentaro; Oishi, Kumiko; Skranes, Jon; Ernst, Thomas; Oishi, Kenichi

2017-04-01

Preterm birth adversely affects postnatal brain development. In order to investigate the critical gestational age at birth (GAB) that alters the developmental trajectory of gray and white matter structures in the brain, we investigated diffusion tensor and quantitative T2 mapping data in 43 term-born and 43 preterm-born infants. A novel multivariate linear model-the change point model, was applied to detect change points in fractional anisotropy, mean diffusivity, and T2 relaxation time. Change points captured the "critical" GAB value associated with a change in the linear relation between GAB and MRI measures. The analysis was performed in 126 regions across the whole brain using an atlas-based image quantification approach to investigate the spatial pattern of the critical GAB. Our results demonstrate that the critical GABs are region- and modality-specific, generally following a central-to-peripheral and bottom-to-top order of structural development. This study may offer unique insights into the postnatal neurological development associated with differential degrees of preterm birth. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Harnessing functional segregation across brain rhythms as a means to detect EEG oscillatory multiplexing during music listening

NASA Astrophysics Data System (ADS)

Adamos, Dimitrios A.; Laskaris, Nikolaos A.; Micheloyannis, Sifis

2018-06-01

Objective. Music, being a multifaceted stimulus evolving at multiple timescales, modulates brain function in a manifold way that encompasses not only the distinct stages of auditory perception, but also higher cognitive processes like memory and appraisal. Network theory is apparently a promising approach to describe the functional reorganization of brain oscillatory dynamics during music listening. However, the music induced changes have so far been examined within the functional boundaries of isolated brain rhythms. Approach. Using naturalistic music, we detected the functional segregation patterns associated with different cortical rhythms, as these were reflected in the surface electroencephalography (EEG) measurements. The emerged structure was compared across frequency bands to quantify the interplay among rhythms. It was also contrasted against the structure from the rest and noise listening conditions to reveal the specific components stemming from music listening. Our methodology includes an efficient graph-partitioning algorithm, which is further utilized for mining prototypical modular patterns, and a novel algorithmic procedure for identifying ‘switching nodes’ (i.e. recording sites) that consistently change module during music listening. Main results. Our results suggest the multiplex character of the music-induced functional reorganization and particularly indicate the dependence between the networks reconstructed from the δ and β H rhythms. This dependence is further justified within the framework of nested neural oscillations and fits perfectly within the context of recently introduced cortical entrainment to music. Significance. Complying with the contemporary trends towards a multi-scale examination of the brain network organization, our approach specifies the form of neural coordination among rhythms during music listening. Considering its computational efficiency, and in conjunction with the flexibility of in situ electroencephalography, it may lead to novel assistive tools for real-life applications.

Harnessing functional segregation across brain rhythms as a means to detect EEG oscillatory multiplexing during music listening.

PubMed

Adamos, Dimitrios A; Laskaris, Nikolaos A; Micheloyannis, Sifis

2018-06-01

Music, being a multifaceted stimulus evolving at multiple timescales, modulates brain function in a manifold way that encompasses not only the distinct stages of auditory perception, but also higher cognitive processes like memory and appraisal. Network theory is apparently a promising approach to describe the functional reorganization of brain oscillatory dynamics during music listening. However, the music induced changes have so far been examined within the functional boundaries of isolated brain rhythms. Using naturalistic music, we detected the functional segregation patterns associated with different cortical rhythms, as these were reflected in the surface electroencephalography (EEG) measurements. The emerged structure was compared across frequency bands to quantify the interplay among rhythms. It was also contrasted against the structure from the rest and noise listening conditions to reveal the specific components stemming from music listening. Our methodology includes an efficient graph-partitioning algorithm, which is further utilized for mining prototypical modular patterns, and a novel algorithmic procedure for identifying 'switching nodes' (i.e. recording sites) that consistently change module during music listening. Our results suggest the multiplex character of the music-induced functional reorganization and particularly indicate the dependence between the networks reconstructed from the δ and β H rhythms. This dependence is further justified within the framework of nested neural oscillations and fits perfectly within the context of recently introduced cortical entrainment to music. Complying with the contemporary trends towards a multi-scale examination of the brain network organization, our approach specifies the form of neural coordination among rhythms during music listening. Considering its computational efficiency, and in conjunction with the flexibility of in situ electroencephalography, it may lead to novel assistive tools for real-life applications.

Independent Component Analysis of Resting-State Functional Magnetic Resonance Imaging in Pedophiles.

PubMed

Cantor, J M; Lafaille, S J; Hannah, J; Kucyi, A; Soh, D W; Girard, T A; Mikulis, D J

2016-10-01

Neuroimaging and other studies have changed the common view that pedophilia is a result of childhood sexual abuse and instead is a neurologic phenomenon with prenatal origins. Previous research has identified differences in the structural connectivity of the brain in pedophilia. To identify analogous differences in functional connectivity. Functional magnetic resonance images were recorded from three groups of participants while they were at rest: pedophilic men with a history of sexual offenses against children (n = 37) and two control groups: non-pedophilic men who committed non-sexual offenses (n = 28) and non-pedophilic men with no criminal history (n = 39). Functional magnetic resonance imaging data were subjected to independent component analysis to identify known functional networks of the brain, and groups were compared to identify differences in connectivity with those networks (or "components"). The pedophilic group demonstrated wide-ranging increases in functional connectivity with the default mode network compared with controls and regional differences (increases and decreases) with the frontoparietal network. Of these brain regions (total = 23), 20 have been identified by meta-analytic studies to respond to sexually relevant stimuli. Conversely, of the brain areas known to be those that respond to sexual stimuli, nearly all emerged in the present data as significantly different in pedophiles. This study confirms the presence of significant differences in the functional connectivity of the brain in pedophilia consistent with previously reported differences in structural connectivity. The connectivity differences detected here and elsewhere are opposite in direction from those associated with anti-sociality, arguing against anti-sociality and for pedophilia as the source of the neuroanatomic differences detected. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

The "silent" imprint of musical training.

PubMed

Klein, Carina; Liem, Franziskus; Hänggi, Jürgen; Elmer, Stefan; Jäncke, Lutz

2016-02-01

Playing a musical instrument at a professional level is a complex multimodal task requiring information integration between different brain regions supporting auditory, somatosensory, motor, and cognitive functions. These kinds of task-specific activations are known to have a profound influence on both the functional and structural architecture of the human brain. However, until now, it is widely unknown whether this specific imprint of musical practice can still be detected during rest when no musical instrument is used. Therefore, we applied high-density electroencephalography and evaluated whole-brain functional connectivity as well as small-world topologies (i.e., node degree) during resting state in a sample of 15 professional musicians and 15 nonmusicians. As expected, musicians demonstrate increased intra- and interhemispheric functional connectivity between those brain regions that are typically involved in music perception and production, such as the auditory, the sensorimotor, and prefrontal cortex as well as Broca's area. In addition, mean connectivity within this specific network was positively related to musical skill and the total number of training hours. Thus, we conclude that musical training distinctively shapes intrinsic functional network characteristics in such a manner that its signature can still be detected during a task-free condition. Hum Brain Mapp 37:536-546, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Regulation of Drosophila Brain Wiring by Neuropil Interactions via a Slit-Robo-RPTP Signaling Complex.

PubMed

Oliva, Carlos; Soldano, Alessia; Mora, Natalia; De Geest, Natalie; Claeys, Annelies; Erfurth, Maria-Luise; Sierralta, Jimena; Ramaekers, Ariane; Dascenco, Dan; Ejsmont, Radoslaw K; Schmucker, Dietmar; Sanchez-Soriano, Natalia; Hassan, Bassem A

2016-10-24

The axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo receptors also contribute to wiring brain circuits. Whether molecular mechanisms regulating these signals are modified to fit more complex brain wiring processes is unclear. We investigated the role of Slit and Robo receptors in wiring Drosophila higher-order brain circuits and identified differences in the cellular and molecular mechanisms of Robo/Slit function. First, we find that signaling by Robo receptors in the brain is regulated by the Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane availability of Robo3 without affecting its phosphorylation state. Second, we detect no midline localization of Slit during brain development. Instead, Slit is enriched in the mushroom body, a neuronal structure covering large areas of the brain. Thus, a divergent molecular mechanism regulates neuronal circuit wiring in the Drosophila brain, partly in response to signals from the mushroom body. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Brain Imaging and Neurodevelopment in HIV-uninfected Thai Children Born to HIV-infected Mothers.

PubMed

Jahanshad, Neda; Couture, Marie-Claude; Prasitsuebsai, Wasana; Nir, Talia M; Aurpibul, Linda; Thompson, Paul M; Pruksakaew, Kanchana; Lerdlum, Sukalaya; Visrutaratna, Pannee; Catella, Stephanie; Desai, Akash; Kerr, Stephen J; Puthanakit, Thanyawee; Paul, Robert; Ananworanich, Jintanat; Valcour, Victor G

2015-09-01

Perinatal use of combination antiretroviral therapy dramatically reduces vertical (mother-to-child) transmission of HIV but has led to a growing population of children with perinatal HIV-exposure but uninfected (HEU). HIV can cause neurological injury among children born with infection, but the neuroanatomical and developmental effects in HEU children are poorly understood. We used structural magnetic resonance imaging with diffusion tensor imaging to compare brain anatomy between 30 HEU and 33 age-matched HIV-unexposed and uninfected (HUU) children from Thailand. Maps of brain volume and microstructural anatomy were compared across groups; associations were tested between neuroimaging measures and concurrent neuropsychological test performance. Mean (standard deviation) age of children was 10.3 (2.8) years, and 58% were male. All were enrolled in school and lived with family members. Intelligence quotient (IQ) did not differ between groups. Caretaker education levels did not differ, but income was higher for HUU (P < 0.001). We did not detect group differences in brain volume or diffusion tensor imaging metrics, after controlling for sociodemographic factors. The mean (95% confidence interval) fractional anisotropy in the corpus callosum was 0.375 (0.368-0.381) in HEU compared with 0.370 (0.364-0.375) in HUU. Higher fractional anisotropy and lower mean diffusivity were each associated with higher IQ scores in analyses with both groups combined. No differences in neuroanatomical or brain integrity measures were detectable in HEU children compared with age-matched and sex-matched controls (HUU children). Expected associations between brain integrity measures and IQ scores were identified suggesting sufficient power to detect subtle associations that were present.

Mind-Reading Ability and Structural Connectivity Changes in Aging.

PubMed

Cabinio, Monia; Rossetto, Federica; Blasi, Valeria; Savazzi, Federica; Castelli, Ilaria; Massaro, Davide; Valle, Annalisa; Nemni, Raffaello; Clerici, Mario; Marchetti, Antonella; Baglio, Francesca

2015-01-01

The Mind-Reading ability through the eyes is an important component of the affective Theory of Mind (ToM), which allows people to infer the other's mental state from the eye gaze. The aim of the present study was to investigate to which extent age-associated structural brain changes impact this ability and to determine if this association is related to executive functions in elderly subjects. For this purpose, Magnetic Resonance Imaging was used to determine both gray matter and white matter (WM) areas associated with aging. The resulting areas have been included in a subsequent correlation analysis to detect the brain regions whose structure was associated with the Mind-Reading ability through the eyes, assessed with the Italian version of the "Reading the Mind in the Eyes" (RME) test, in a sample of 36 healthy subjects ranging from 24 to 79 years of age. The analysis resulted in three important findings: (1) the performance to the RME test is relatively stable across the decades 20-70 (despite a slight decrease of this ability with aging) and independent from executive functions; (2) structural brain imaging demonstrated the involvement of a great number of cortical ToM areas for the execution of the RME test: the bilateral precentral gyrus, the bilateral posterior insula, the left superior temporal gyrus and the left inferior frontal gyrus, which also showed a significant volume decrease with age; (3) an age and task-related decline in WM connectivity on left fronto-temporal portion of the brain. Our results confirm the age-related structural modifications of the brain and show that these changes have an influence on the Mind-Reading ability through the eyes.

Effects of Hormone Therapy on Brain Volumes Changes of Postmenopausal Women Revealed by Optimally-Discriminative Voxel-Based Morphometry

PubMed Central

Zhang, Tianhao; Casanova, Ramon; Resnick, Susan M.; Manson, JoAnn E.; Baker, Laura D.; Padual, Claudia B.; Kuller, Lewis H.; Bryan, R. Nick; Espeland, Mark A.; Davatzikos, Christos

2016-01-01

Backgrounds The Women's Health Initiative Memory Study Magnetic Resonance Imaging (WHIMS-MRI) provides an opportunity to evaluate how menopausal hormone therapy (HT) affects the structure of older women’s brains. Our earlier work based on region of interest (ROI) analysis demonstrated potential structural changes underlying adverse effects of HT on cognition. However, the ROI-based analysis is limited in statistical power and precision, and cannot provide fine-grained mapping of whole-brain changes. Methods We aimed to identify local structural differences between HT and placebo groups from WHIMS-MRI in a whole-brain refined level, by using a novel method, named Optimally-Discriminative Voxel-Based Analysis (ODVBA). ODVBA is a recently proposed imaging pattern analysis approach for group comparisons utilizing a spatially adaptive analysis scheme to accurately locate areas of group differences, thereby providing superior sensitivity and specificity to detect the structural brain changes over conventional methods. Results Women assigned to HT treatments had significant Gray Matter (GM) losses compared to the placebo groups in the anterior cingulate and the adjacent medial frontal gyrus, and the orbitofrontal cortex, which persisted after multiple comparison corrections. There were no regions where HT was significantly associated with larger volumes compared to placebo, although a trend of marginal significance was found in the posterior cingulate cortical area. The CEE-Alone and CEE+MPA groups, although compared with different placebo controls, demonstrated similar effects according to the spatial patterns of structural changes. Conclusions HT had adverse effects on GM volumes and risk for cognitive impairment and dementia in older women. These findings advanced our understanding of the neurobiological underpinnings of HT effects. PMID:26974440

Mind-Reading Ability and Structural Connectivity Changes in Aging

PubMed Central

Cabinio, Monia; Rossetto, Federica; Blasi, Valeria; Savazzi, Federica; Castelli, Ilaria; Massaro, Davide; Valle, Annalisa; Nemni, Raffaello; Clerici, Mario; Marchetti, Antonella; Baglio, Francesca

2015-01-01

The Mind-Reading ability through the eyes is an important component of the affective Theory of Mind (ToM), which allows people to infer the other’s mental state from the eye gaze. The aim of the present study was to investigate to which extent age-associated structural brain changes impact this ability and to determine if this association is related to executive functions in elderly subjects. For this purpose, Magnetic Resonance Imaging was used to determine both gray matter and white matter (WM) areas associated with aging. The resulting areas have been included in a subsequent correlation analysis to detect the brain regions whose structure was associated with the Mind-Reading ability through the eyes, assessed with the Italian version of the “Reading the Mind in the Eyes” (RME) test, in a sample of 36 healthy subjects ranging from 24 to 79 years of age. The analysis resulted in three important findings: (1) the performance to the RME test is relatively stable across the decades 20–70 (despite a slight decrease of this ability with aging) and independent from executive functions; (2) structural brain imaging demonstrated the involvement of a great number of cortical ToM areas for the execution of the RME test: the bilateral precentral gyrus, the bilateral posterior insula, the left superior temporal gyrus and the left inferior frontal gyrus, which also showed a significant volume decrease with age; (3) an age and task-related decline in WM connectivity on left fronto-temporal portion of the brain. Our results confirm the age-related structural modifications of the brain and show that these changes have an influence on the Mind-Reading ability through the eyes. PMID:26635702

Structural neural correlates of multitasking: A voxel-based morphometry study.

PubMed

Zhang, Rui-Ting; Yang, Tian-Xiao; Wang, Yi; Sui, Yuxiu; Yao, Jingjing; Zhang, Chen-Yuan; Cheung, Eric F C; Chan, Raymond C K

2016-12-01

Multitasking refers to the ability to organize assorted tasks efficiently in a short period of time, which plays an important role in daily life. However, the structural neural correlates of multitasking performance remain unclear. The present study aimed at exploring the brain regions associated with multitasking performance using global correlation analysis. Twenty-six healthy participants first underwent structural brain scans and then performed the modified Six Element Test, which required participants to attempt six subtasks in 10 min while obeying a specific rule. Voxel-based morphometry of the whole brain was used to detect the structural correlates of multitasking ability. Grey matter volume of the anterior cingulate cortex (ACC) was positively correlated with the overall performance and time monitoring in multitasking. In addition, white matter volume of the anterior thalamic radiation (ATR) was also positively correlated with time monitoring during multitasking. Other related brain regions associated with multitasking included the superior frontal gyrus, the inferior occipital gyrus, the lingual gyrus, and the inferior longitudinal fasciculus. No significant correlation was found between grey matter volume of the prefrontal cortex (Brodmann Area 10) and multitasking performance. Using a global correlation analysis to examine various aspects of multitasking performance, this study provided new insights into the structural neural correlates of multitasking ability. In particular, the ACC was identified as an important brain region that played both a general and a specific time-monitoring role in multitasking, extending the role of the ACC from lesioned populations to healthy populations. The present findings also support the view that the ATR may influence multitasking performance by affecting time-monitoring abilities. © 2016 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Infant brain structures, executive function, and attention deficit/hyperactivity problems at preschool age. A prospective study.

PubMed

Ghassabian, Akhgar; Herba, Catherine M; Roza, Sabine J; Govaert, Paul; Schenk, Jacqueline J; Jaddoe, Vincent W; Hofman, Albert; White, Tonya; Verhulst, Frank C; Tiemeier, Henning

2013-01-01

Neuroimaging findings have provided evidence for a relation between variations in brain structures and attention deficit/hyperactivity disorder (ADHD). However, longitudinal neuroimaging studies are typically confined to children who have already been diagnosed with ADHD. In a population-based study, we aimed to characterize the prospective association between brain structures measured during infancy and executive function and attention deficit/hyperactivity problems assessed at preschool age. In the Generation R Study, the corpus callosum length, the gangliothalamic ovoid diameter (encompassing the basal ganglia and thalamus), and the ventricular volume were measured in 784 6-week-old children using cranial postnatal ultrasounds. Parents rated executive functioning at 4 years using the behavior rating inventory of executive function-preschool version in five dimensions: inhibition, shifting, emotional control, working memory, and planning/organizing. Attention deficit/hyperactivity problems were assessed at ages 3 and 5 years using the child behavior checklist. A smaller corpus callosum length during infancy was associated with greater deficits in executive functioning at 4 years. This was accounted for by higher problem scores on inhibition and emotional control. The corpus callosum length during infancy did not predict attention deficit/hyperactivity problem at 3 and 5 years, when controlling for the confounders. We did not find any relation between gangliothalamic ovoid diameter and executive function or Attention deficit/hyperactivity problem. Variations in brain structures detectible in infants predicted subtle impairments in inhibition and emotional control. However, in this population-based study, we could not demonstrate that early structural brain variations precede symptoms of ADHD. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

Multimodal investigation of epileptic networks: The case of insular cortex epilepsy.

PubMed

Zerouali, Y; Ghaziri, J; Nguyen, D K

2016-01-01

The insula is a deep cortical structure sharing extensive synaptic connections with a variety of brain regions, including several frontal, temporal, and parietal structures. The identification of the insular connectivity network is obviously valuable for understanding a number of cognitive processes, but also for understanding epilepsy since insular seizures involve a number of remote brain regions. Ultimately, knowledge of the structure and causal relationships within the epileptic networks associated with insular cortex epilepsy can offer deeper insights into this relatively neglected type of epilepsy enabling the refining of the clinical approach in managing patients affected by it. In the present chapter, we first review the multimodal noninvasive tests performed during the presurgical evaluation of epileptic patients with drug refractory focal epilepsy, with particular emphasis on their value for the detection of insular cortex epilepsy. Second, we review the emerging multimodal investigation techniques in the field of epilepsy, that aim to (1) enhance the detection of insular cortex epilepsy and (2) unveil the architecture and causal relationships within epileptic networks. We summarize the results of these approaches with emphasis on the specific case of insular cortex epilepsy. © 2016 Elsevier B.V. All rights reserved.

Following Acute Encephalitis, Semliki Forest Virus is Undetectable in the Brain by Infectivity Assays but Functional Virus RNA Capable of Generating Infectious Virus Persists for Life.

PubMed

Fragkoudis, Rennos; Dixon-Ballany, Catherine M; Zagrajek, Adrian K; Kedzierski, Lukasz; Fazakerley, John K

2018-05-18

Alphaviruses are mosquito-transmitted RNA viruses which generally cause acute disease including mild febrile illness, rash, arthralgia, myalgia and more severely, encephalitis. In the mouse, peripheral infection with Semliki Forest virus (SFV) results in encephalitis. With non-virulent strains, infectious virus is detectable in the brain, by standard infectivity assays, for around ten days. As we have shown previously, in severe combined immunodeficient (SCID) mice, infectious virus is detectable for months in the brain. Here we show that in MHC-II -/- mice, with no functional CD4 T-cells, infectious virus is also detectable in the brain for long periods. In contrast, in the brains of CD8 -/- mice, virus RNA persists but infectious virus is not detectable. In SCID mice infected with SFV, repeated intraperitoneal administration of anti-SFV immune serum rapidly reduced the titer of infectious virus in the brain to undetectable, however virus RNA persisted. Repeated intraperitoneal passive transfer of immune serum resulted in maintenance of brain virus RNA, with no detectable infectious virus, for several weeks. When passive antibody transfer was stopped, antibody levels declined and infectious virus was again detectable in the brain. In aged immunocompetent mice, previously infected with SFV, immunosuppression of antibody responses many months after initial infection also resulted in renewed ability to detect infectious virus in the brain. In summary, antiviral antibodies control and determine whether infectious virus is detectable in the brain but immune responses cannot clear this infection from the brain. Functional virus RNA capable of generating infectious virus persists and if antibody levels decline, infectious virus is again detectable.

Changes in Structural Connectivity Following a Cognitive Intervention in Children With Traumatic Brain Injury.

PubMed

Yuan, Weihong; Treble-Barna, Amery; Sohlberg, McKay M; Harn, Beth; Wade, Shari L

2017-02-01

Structural connectivity analysis based on graph theory and diffusion tensor imaging tractography is a novel method that quantifies the topological characteristics in the brain network. This study aimed to examine structural connectivity changes following the Attention Intervention and Management (AIM) program designed to improve attention and executive function (EF) in children with traumatic brain injury (TBI). Seventeen children with complicated mild to severe TBI (13.66 ± 2.68 years; >12 months postinjury) completed magnetic resonance imaging (MRI) and neurobehavioral measures at time 1, 10 of whom completed AIM and assessment at time 2. Eleven matched healthy comparison (HC) children (13.37 ± 2.08 years) completed MRI and neurobehavioral assessment at both time points, but did not complete AIM. Network characteristics were analyzed to quantify the structural connectivity before and after the intervention. Mixed model analyses showed that small-worldness was significantly higher in the TBI group than the HC group at time 1, and both small-worldness and normalized clustering coefficient decreased significantly at time 2 in the TBI group whereas the HC group remained relatively unchanged. Reductions in mean local efficiency were significantly correlated with improvements in verbal inhibition and both parent- and child-reported EF. Increased normalized characteristic path length was significantly correlated with improved sustained attention. The results provide preliminary evidence suggesting that graph theoretical analysis may be a sensitive tool in pediatric TBI for detecting ( a) abnormalities of structural connectivity in brain network and ( b) structural neuroplasticity associated with neurobehavioral improvement following a short-term intervention for attention and EF.

Landmark-based deep multi-instance learning for brain disease diagnosis.

PubMed

Liu, Mingxia; Zhang, Jun; Adeli, Ehsan; Shen, Dinggang

2018-01-01

In conventional Magnetic Resonance (MR) image based methods, two stages are often involved to capture brain structural information for disease diagnosis, i.e., 1) manually partitioning each MR image into a number of regions-of-interest (ROIs), and 2) extracting pre-defined features from each ROI for diagnosis with a certain classifier. However, these pre-defined features often limit the performance of the diagnosis, due to challenges in 1) defining the ROIs and 2) extracting effective disease-related features. In this paper, we propose a landmark-based deep multi-instance learning (LDMIL) framework for brain disease diagnosis. Specifically, we first adopt a data-driven learning approach to discover disease-related anatomical landmarks in the brain MR images, along with their nearby image patches. Then, our LDMIL framework learns an end-to-end MR image classifier for capturing both the local structural information conveyed by image patches located by landmarks and the global structural information derived from all detected landmarks. We have evaluated our proposed framework on 1526 subjects from three public datasets (i.e., ADNI-1, ADNI-2, and MIRIAD), and the experimental results show that our framework can achieve superior performance over state-of-the-art approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural and functional bases of inhibited temperament.

PubMed

Clauss, Jacqueline A; Seay, April L; VanDerKlok, Ross M; Avery, Suzanne N; Cao, Aize; Cowan, Ronald L; Benningfield, Margaret M; Blackford, Jennifer Urbano

2014-12-01

Children born with an inhibited temperament are at heightened risk for developing anxiety, depression and substance use. Inhibited temperament is believed to have a biological basis; however, little is known about the structural brain basis of this vulnerability trait. Structural MRI scans were obtained from 84 (44 inhibited, 40 uninhibited) young adults. Given previous findings of amygdala hyperactivity in inhibited individuals, groups were compared on three measures of amygdala structure. To identify novel substrates of inhibited temperament, a whole brain analysis was performed. Functional activation and connectivity were examined across both groups. Inhibited adults had larger amygdala and caudate volume and larger volume predicted greater activation to neutral faces. In addition, larger amygdala volume predicted greater connectivity with subcortical and higher order visual structures. Larger caudate volume predicted greater connectivity with the basal ganglia, and less connectivity with primary visual and auditory cortex. We propose that larger volume in these salience detection regions may result in increased activation and enhanced connectivity in response to social stimuli. Given the strong link between inhibited temperament and risk for psychiatric illness, novel therapeutics that target these brain regions and related neural circuits have the potential to reduce rates of illness in vulnerable individuals. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Gap junctions mediate large-scale Turing structures in a mean-field cortex driven by subcortical noise

NASA Astrophysics Data System (ADS)

Steyn-Ross, Moira L.; Steyn-Ross, D. A.; Wilson, M. T.; Sleigh, J. W.

2007-07-01

One of the grand puzzles in neuroscience is establishing the link between cognition and the disparate patterns of spontaneous and task-induced brain activity that can be measured clinically using a wide range of detection modalities such as scalp electrodes and imaging tomography. High-level brain function is not a single-neuron property, yet emerges as a cooperative phenomenon of multiply-interacting populations of neurons. Therefore a fruitful modeling approach is to picture the cerebral cortex as a continuum characterized by parameters that have been averaged over a small volume of cortical tissue. Such mean-field cortical models have been used to investigate gross patterns of brain behavior such as anesthesia, the cycles of natural sleep, memory and erasure in slow-wave sleep, and epilepsy. There is persuasive and accumulating evidence that direct gap-junction connections between inhibitory neurons promote synchronous oscillatory behavior both locally and across distances of some centimeters, but, to date, continuum models have ignored gap-junction connectivity. In this paper we employ simple mean-field arguments to derive an expression for D2 , the diffusive coupling strength arising from gap-junction connections between inhibitory neurons. Using recent neurophysiological measurements reported by Fukuda [J. Neurosci. 26, 3434 (2006)], we estimate an upper limit of D2≈0.6cm2 . We apply a linear stability analysis to a standard mean-field cortical model, augmented with gap-junction diffusion, and find this value for the diffusive coupling strength to be close to the critical value required to destabilize the homogeneous steady state. Computer simulations demonstrate that larger values of D2 cause the noise-driven model cortex to spontaneously crystalize into random mazelike Turing structures: centimeter-scale spatial patterns in which regions of high-firing activity are intermixed with regions of low-firing activity. These structures are consistent with the spatial variations in brain activity patterns detected with the BOLD (blood oxygen-level-dependent) signal detected with magnetic resonance imaging, and may provide a natural substrate for synchronous gamma-band rhythms observed across separated EEG (electroencephalogram) electrodes.

Non-destructive optical clearing technique enhances optical coherence tomography (OCT) for real-time, 3D histomorphometry of brain tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Paul, Akshay; Chang, Theodore H.; Chou, Li-Dek; Ramalingam, Tirunelveli S.

2016-03-01

Evaluation of neurodegenerative disease often requires examination of brain morphology. Volumetric analysis of brain regions and structures can be used to track developmental changes, progression of disease, and the presence of transgenic phenotypes. Current standards for microscopic investigation of brain morphology are limited to detection of superficial structures at a maximum depth of 300μm. While histological techniques can provide detailed cross-sections of brain structures, they require complicated tissue preparation and the ultimate destruction of the sample. A non-invasive, label-free imaging modality known as Optical Coherence Tomography (OCT) can produce 3-dimensional reconstructions through high-speed, cross-sectional scans of biological tissue. Although OCT allows for the preservation of intact samples, the highly scattering and absorbing properties of biological tissue limit imaging depth to 1-2mm. Optical clearing agents have been utilized to increase imaging depth by index matching and lipid digestion, however, these contemporary techniques are expensive and harsh on tissues, often irreversibly denaturing proteins. Here we present an ideal optical clearing agent that offers ease-of-use and reversibility. Similar to how SeeDB has been effective for microscopy, our fructose-based, reversible optical clearing technique provides improved OCT imaging and functional immunohistochemical mapping of disease. Fructose is a natural, non-toxic sugar with excellent water solubility, capable of increasing tissue transparency and reducing light scattering. We will demonstrate the improved depth-resolving performance of OCT for enhanced whole-brain imaging of normal and diseased murine brains following a fructose clearing treatment. This technique potentially enables rapid, 3-dimensional evaluation of biological tissues at axial and lateral resolutions comparable to histopathology.

Reconstructing the anterior part of the nervous system of Gordius aquaticus (Nematomorpha, cycloneuralia) by a multimethodological approach.

PubMed

Henne, Stephan; Friedrich, Frank; Hammel, Jörg U; Sombke, Andy; Schmidt-Rhaesa, Andreas

2017-01-01

The Nematomorpha (horsehair worms) and Nematoda (round worms) are sister taxa (together Nematoida) and closely related to Scalidophora (Priapulida, Kinorhyncha, Loricifera). To date, all species were assumed to possess a specific brain type, i.e., the "cycloneuralian" brain that forms a ring-shaped neuropil around the pharynx and is composed of anteriorly and posteriorly located somata. However, descriptions of the nematomorph nervous system are rare and somewhat variable, calling in to question the validity of the cycloneuralian condition. To clarify whether there is a typical cycloneuralian pattern in the nematomorph brain, we investigated the anterior end of Gordius aquaticus with different methods: histology, immunohistochemistry and micro-CT analysis. Three-dimensional reconstructions were made from histological serial sections. The brain is composed of a central neuropil and a ring-shaped structure with associated somata. The unpaired ventral nerve cord emerges from the posteroventral part of the brain. A pharynx/esophagus is absent. In addition to the brain, a peripheral nerve plexus was detected. In summary, we interpret the architecture of the brain as potentially derived from a cycloneuralian structure, but being highly modified. The central position of the neuropil is possibly a consequence of the reduction of the anterior intestinal system as a result of the parasitic lifestyle. The ring-shaped arrangement of the somata may be a remnant of a cycloneuralian arrangement, after the two rings of somata (= cycloneuralian condition) either fused or one ring was reduced to form one massive ring-shaped structure in G. aquaticus. J. Morphol. 278:106-118, 2017. ©© 2016 Wiley Periodicals,Inc. © 2016 Wiley Periodicals, Inc.

Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI

DTIC Science & Technology

2015-10-01

Page | 2 AWARD NUMBER: W81XWH-13-1-0464 TITLE: Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI...Sep 2014 – 29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional...findings include: 1) detection of brain organization in a cohort of 24 pediatric onset multiple sclerosis patients (POMS) and 25 healthy controls

Copper brain protein protection against free radical-induced neuronal death: Survival ratio in SH-SY5Y neuroblastoma cell cultures.

PubMed

Deloncle, Roger; Fauconneau, Bernard; Guillard, Olivier; Delaval, José; Lesage, Gérard; Pineau, Alain

2017-01-01

In Creutzfeldt Jakob, Alzheimer and Parkinson diseases, copper metalloproteins such as prion, amyloid protein precursor and α-synuclein are able to protect against free radicals by reduction from cupric Cu +2 to cupreous Cu + . In these pathologies, a regional copper (Cu) brain decrease correlated with an iron, zinc or manganese (Mn) increase has previously been observed, leading to local neuronal death and abnormal deposition of these metalloproteins in β-sheet structures. In this study we demonstrate the protective effect of Cu metalloproteins against deleterious free-radical effects. With neuroblastoma SH-SY5Y cell cultures, we show that bovine brain prion protein in Cu but not Mn form prevents free radical-induced neuronal death. The survival ratio of SH-SY5Y cells has been measured after UV irradiation (free radical production), when the incubating medium is supplemented with bovine brain homogenate in native, Cu or Mn forms. This ratio, about 28% without any addition or with bovine brain protein added in Mn form, increases by as much as 54.73% with addition to the culture medium of native bovine brain protein and by as much as 95.95% if the addition is carried out in cupric form. This protective effect of brain copper protein against free radical-induced neuronal death has been confirmed with Inductively Coupled Plasma Mass Spectrometry Mn and Cu measurement in bovine brain homogenates: respectively lower than detection limit and 9.01μg/g dry weight for native form; lower than detection limit and 825.85μg/g dry weight for Cu-supplemented form and 1.75 and 68.1μg/g dry weight in Mn-supplemented brain homogenate. Copyright © 2016 Elsevier GmbH. All rights reserved.

Prevalence and spectrum of in utero structural brain abnormalities in fetuses with complex congenital heart disease.

PubMed

Brossard-Racine, M; du Plessis, A J; Vezina, G; Robertson, R; Bulas, D; Evangelou, I E; Donofrio, M; Freeman, D; Limperopoulos, C

2014-08-01

Brain injury is a major complication in neonates with complex congenital heart disease. Preliminary evidence suggests that fetuses with congenital heart disease are at greater risk for brain abnormalities. However, the nature and frequency of these brain abnormalities detected by conventional fetal MR imaging has not been examined prospectively. Our primary objective was to determine the prevalence and spectrum of brain abnormalities detected on conventional clinical MR imaging in fetuses with complex congenital heart disease and, second, to compare the congenital heart disease cohort with a control group of fetuses from healthy pregnancies. We prospectively recruited pregnant women with a confirmed fetal congenital heart disease diagnosis and healthy volunteers with normal fetal echocardiogram findings who underwent a fetal MR imaging between 18 and 39 weeks gestational age. A total of 338 fetuses (194 controls; 144 with congenital heart disease) were studied at a mean gestational age of 30.61 ± 4.67 weeks. Brain abnormalities were present in 23% of the congenital heart disease group compared with 1.5% in the control group (P < .001). The most common abnormalities in the congenital heart disease group were mild unilateral ventriculomegaly in 12/33 (36.4%) and increased extra-axial spaces in 10/33 (30.3%). Subgroup analyses comparing the type and frequency of brain abnormalities based on cardiac physiology did not reveal significant associations, suggesting that the brain abnormalities were not limited to those with the most severe congenital heart disease. This is the first large prospective study reporting conventional MR imaging findings in fetuses with congenital heart disease. Our results suggest that brain abnormalities are prevalent but relatively mild antenatally in fetuses with congenital heart disease. The long-term predictive value of these findings awaits further study. © 2014 by American Journal of Neuroradiology.

Eye tracking detects disconjugate eye movements associated with structural traumatic brain injury and concussion.

PubMed

Samadani, Uzma; Ritlop, Robert; Reyes, Marleen; Nehrbass, Elena; Li, Meng; Lamm, Elizabeth; Schneider, Julia; Shimunov, David; Sava, Maria; Kolecki, Radek; Burris, Paige; Altomare, Lindsey; Mehmood, Talha; Smith, Theodore; Huang, Jason H; McStay, Christopher; Todd, S Rob; Qian, Meng; Kondziolka, Douglas; Wall, Stephen; Huang, Paul

2015-04-15

Disconjugate eye movements have been associated with traumatic brain injury since ancient times. Ocular motility dysfunction may be present in up to 90% of patients with concussion or blast injury. We developed an algorithm for eye tracking in which the Cartesian coordinates of the right and left pupils are tracked over 200 sec and compared to each other as a subject watches a short film clip moving inside an aperture on a computer screen. We prospectively eye tracked 64 normal healthy noninjured control subjects and compared findings to 75 trauma subjects with either a positive head computed tomography (CT) scan (n=13), negative head CT (n=39), or nonhead injury (n=23) to determine whether eye tracking would reveal the disconjugate gaze associated with both structural brain injury and concussion. Tracking metrics were then correlated to the clinical concussion measure Sport Concussion Assessment Tool 3 (SCAT3) in trauma patients. Five out of five measures of horizontal disconjugacy were increased in positive and negative head CT patients relative to noninjured control subjects. Only one of five vertical disconjugacy measures was significantly increased in brain-injured patients relative to controls. Linear regression analysis of all 75 trauma patients demonstrated that three metrics for horizontal disconjugacy negatively correlated with SCAT3 symptom severity score and positively correlated with total Standardized Assessment of Concussion score. Abnormal eye-tracking metrics improved over time toward baseline in brain-injured subjects observed in follow-up. Eye tracking may help quantify the severity of ocular motility disruption associated with concussion and structural brain injury.

Eye Tracking Detects Disconjugate Eye Movements Associated with Structural Traumatic Brain Injury and Concussion

PubMed Central

Ritlop, Robert; Reyes, Marleen; Nehrbass, Elena; Li, Meng; Lamm, Elizabeth; Schneider, Julia; Shimunov, David; Sava, Maria; Kolecki, Radek; Burris, Paige; Altomare, Lindsey; Mehmood, Talha; Smith, Theodore; Huang, Jason H.; McStay, Christopher; Todd, S. Rob; Qian, Meng; Kondziolka, Douglas; Wall, Stephen; Huang, Paul

2015-01-01

Abstract Disconjugate eye movements have been associated with traumatic brain injury since ancient times. Ocular motility dysfunction may be present in up to 90% of patients with concussion or blast injury. We developed an algorithm for eye tracking in which the Cartesian coordinates of the right and left pupils are tracked over 200 sec and compared to each other as a subject watches a short film clip moving inside an aperture on a computer screen. We prospectively eye tracked 64 normal healthy noninjured control subjects and compared findings to 75 trauma subjects with either a positive head computed tomography (CT) scan (n=13), negative head CT (n=39), or nonhead injury (n=23) to determine whether eye tracking would reveal the disconjugate gaze associated with both structural brain injury and concussion. Tracking metrics were then correlated to the clinical concussion measure Sport Concussion Assessment Tool 3 (SCAT3) in trauma patients. Five out of five measures of horizontal disconjugacy were increased in positive and negative head CT patients relative to noninjured control subjects. Only one of five vertical disconjugacy measures was significantly increased in brain-injured patients relative to controls. Linear regression analysis of all 75 trauma patients demonstrated that three metrics for horizontal disconjugacy negatively correlated with SCAT3 symptom severity score and positively correlated with total Standardized Assessment of Concussion score. Abnormal eye-tracking metrics improved over time toward baseline in brain-injured subjects observed in follow-up. Eye tracking may help quantify the severity of ocular motility disruption associated with concussion and structural brain injury. PMID:25582436

Unifying Inference of Meso-Scale Structures in Networks.

PubMed

Tunç, Birkan; Verma, Ragini

2015-01-01

Networks are among the most prevalent formal representations in scientific studies, employed to depict interactions between objects such as molecules, neuronal clusters, or social groups. Studies performed at meso-scale that involve grouping of objects based on their distinctive interaction patterns form one of the main lines of investigation in network science. In a social network, for instance, meso-scale structures can correspond to isolated social groupings or groups of individuals that serve as a communication core. Currently, the research on different meso-scale structures such as community and core-periphery structures has been conducted via independent approaches, which precludes the possibility of an algorithmic design that can handle multiple meso-scale structures and deciding which structure explains the observed data better. In this study, we propose a unified formulation for the algorithmic detection and analysis of different meso-scale structures. This facilitates the investigation of hybrid structures that capture the interplay between multiple meso-scale structures and statistical comparison of competing structures, all of which have been hitherto unavailable. We demonstrate the applicability of the methodology in analyzing the human brain network, by determining the dominant organizational structure (communities) of the brain, as well as its auxiliary characteristics (core-periphery).

Detection of whole-brain abnormalities in temporal lobe epilepsy using tensor-based morphometry with DARTEL

NASA Astrophysics Data System (ADS)

Li, Wenjing; He, Huiguang; Lu, Jingjing; Lv, Bin; Li, Meng; Jin, Zhengyu

2009-10-01

Tensor-based morphometry (TBM) is an automated technique for detecting the anatomical differences between populations by examining the gradients of the deformation fields used to nonlinearly warp MR images. The purpose of this study was to investigate the whole-brain volume changes between the patients with unilateral temporal lobe epilepsy (TLE) and the controls using TBM with DARTEL, which could achieve more accurate inter-subject registration of brain images. T1-weighted images were acquired from 21 left-TLE patients, 21 right-TLE patients and 21 healthy controls, which were matched in age and gender. The determinants of the gradient of deformation fields at voxel level were obtained to quantify the expansion or contraction for individual images relative to the template, and then logarithmical transformation was applied on it. A whole brain analysis was performed using general lineal model (GLM), and the multiple comparison was corrected by false discovery rate (FDR) with p<0.05. For left-TLE patients, significant volume reductions were found in hippocampus, cingulate gyrus, precentral gyrus, right temporal lobe and cerebellum. These results potentially support the utility of TBM with DARTEL to study the structural changes between groups.

Intraoperative visualisation of functional structures facilitates safe frameless stereotactic biopsy in the motor eloquent regions of the brain.

PubMed

Zhang, Jia-Shu; Qu, Ling; Wang, Qun; Jin, Wei; Hou, Yuan-Zheng; Sun, Guo-Chen; Li, Fang-Ye; Yu, Xin-Guang; Xu, Ban-Nan; Chen, Xiao-Lei

2017-12-20

For stereotactic brain biopsy involving motor eloquent regions, the surgical objective is to enhance diagnostic yield and preserve neurological function. To achieve this aim, we implemented functional neuro-navigation and intraoperative magnetic resonance imaging (iMRI) into the biopsy procedure. The impact of this integrated technique on the surgical outcome and postoperative neurological function was investigated and evaluated. Thirty nine patients with lesions involving motor eloquent structures underwent frameless stereotactic biopsy assisted by functional neuro-navigation and iMRI. Intraoperative visualisation was realised by integrating anatomical and functional information into a navigation framework to improve biopsy trajectories and preserve eloquent structures. iMRI was conducted to guarantee the biopsy accuracy and detect intraoperative complications. The perioperative change of motor function and biopsy error before and after iMRI were recorded, and the role of functional information in trajectory selection and the relationship between the distance from sampling site to nearby eloquent structures and the neurological deterioration were further analyzed. Functional neuro-navigation helped modify the original trajectories and sampling sites in 35.90% (16/39) of cases to avoid the damage of eloquent structures. Even though all the lesions were high-risk of causing neurological deficits, no significant difference was found between preoperative and postoperative muscle strength. After data analysis, 3mm was supposed to be the safe distance for avoiding transient neurological deterioration. During surgery, the use of iMRI significantly reduced the biopsy errors (p = 0.042) and potentially increased the diagnostic yield from 84.62% (33/39) to 94.87% (37/39). Moreover, iMRI detected intraoperative haemorrhage in 5.13% (2/39) of patients, all of them benefited from the intraoperative strategies based on iMRI findings. Intraoperative visualisation of functional structures could be a feasible, safe and effective technique. Combined with intraoperative high-field MRI, it contributed to enhance the biopsy accuracy and lower neurological complications in stereotactic brain biopsy involving motor eloquent areas.

Embedding and Chemical Reactivation of Green Fluorescent Protein in the Whole Mouse Brain for Optical Micro-Imaging

PubMed Central

Gang, Yadong; Zhou, Hongfu; Jia, Yao; Liu, Ling; Liu, Xiuli; Rao, Gong; Li, Longhui; Wang, Xiaojun; Lv, Xiaohua; Xiong, Hanqing; Yang, Zhongqin; Luo, Qingming; Gong, Hui; Zeng, Shaoqun

2017-01-01

Resin embedding has been widely applied to fixing biological tissues for sectioning and imaging, but has long been regarded as incompatible with green fluorescent protein (GFP) labeled sample because it reduces fluorescence. Recently, it has been reported that resin-embedded GFP-labeled brain tissue can be imaged with high resolution. In this protocol, we describe an optimized protocol for resin embedding and chemical reactivation of fluorescent protein labeled mouse brain, we have used mice as experiment model, but the protocol should be applied to other species. This method involves whole brain embedding and chemical reactivation of the fluorescent signal in resin-embedded tissue. The whole brain embedding process takes a total of 7 days. The duration of chemical reactivation is ~2 min for penetrating 4 μm below the surface in the resin-embedded brain. This protocol provides an efficient way to prepare fluorescent protein labeled sample for high-resolution optical imaging. This kind of sample was demonstrated to be imaged by various optical micro-imaging methods. Fine structures labeled with GFP across a whole brain can be detected. PMID:28352214

Connectomic correlates of response to treatment in first-episode psychosis

PubMed Central

Crossley, Nicolas A; Marques, Tiago Reis; Taylor, Heather; Chaddock, Chris; Dell’Acqua, Flavio; Reinders, Antje A T S; Mondelli, Valeria; DiForti, Marta; Simmons, Andrew; David, Anthony S; Kapur, Shitij; Pariante, Carmine M; Murray, Robin M; Dazzan, Paola

2017-01-01

Abstract Connectomic approaches using diffusion tensor imaging have contributed to our understanding of brain changes in psychosis, and could provide further insights into the neural mechanisms underlying response to antipsychotic treatment. We here studied the brain network organization in patients at their first episode of psychosis, evaluating whether connectome-based descriptions of brain networks predict response to treatment, and whether they change after treatment. Seventy-six patients with a first episode of psychosis and 74 healthy controls were included. Thirty-three patients were classified as responders after 12 weeks of antipsychotic treatment. Baseline brain structural networks were built using whole-brain diffusion tensor imaging tractography, and analysed using graph analysis and network-based statistics to explore baseline characteristics of patients who subsequently responded to treatment. A subgroup of 43 patients was rescanned at the 12-week follow-up, to study connectomic changes over time in relation to treatment response. At baseline, those subjects who subsequently responded to treatment, compared to those that did not, showed higher global efficiency in their structural connectomes, a network configuration that theoretically facilitates the flow of information. We did not find specific connectomic changes related to treatment response after 12 weeks of treatment. Our data suggest that patients who have an efficiently-wired connectome at first onset of psychosis show a better subsequent response to antipsychotics. However, response is not accompanied by specific structural changes over time detectable with this method. PMID:28007987

3D pre- versus post-season comparisons of surface and relative pose of the corpus callosum in contact sport athletes

NASA Astrophysics Data System (ADS)

Lao, Yi; Gajawelli, Niharika; Haas, Lauren; Wilkins, Bryce; Hwang, Darryl; Tsao, Sinchai; Wang, Yalin; Law, Meng; Leporé, Natasha

2014-03-01

Mild traumatic brain injury (MTBI) or concussive injury affects 1.7 million Americans annually, of which 300,000 are due to recreational activities and contact sports, such as football, rugby, and boxing[1]. Finding the neuroanatomical correlates of brain TBI non-invasively and precisely is crucial for diagnosis and prognosis. Several studies have shown the in influence of traumatic brain injury (TBI) on the integrity of brain WM [2-4]. The vast majority of these works focus on athletes with diagnosed concussions. However, in contact sports, athletes are subjected to repeated hits to the head throughout the season, and we hypothesize that these have an influence on white matter integrity. In particular, the corpus callosum (CC), as a small structure connecting the brain hemispheres, may be particularly affected by torques generated by collisions, even in the absence of full blown concussions. Here, we use a combined surface-based morphometry and relative pose analyses, applying on the point distribution model (PDM) of the CC, to investigate TBI related brain structural changes between 9 pre-season and 9 post-season contact sport athlete MRIs. All the data are fed into surface based morphometry analysis and relative pose analysis. The former looks at surface area and thickness changes between the two groups, while the latter consists of detecting the relative translation, rotation and scale between them.

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

PubMed

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

2012-01-01

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

Investigating Structural Brain Changes of Dehydration Using Voxel-Based Morphometry

PubMed Central

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

2012-01-01

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

Early Detection of Ventilation-Induced Brain Injury Using Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging: An In Vivo Study in Preterm Lambs

PubMed Central

Skiöld, Béatrice; Wu, Qizhu; Hooper, Stuart B.; Davis, Peter G.; McIntyre, Richard; Tolcos, Mary; Pearson, James; Vreys, Ruth; Egan, Gary F.; Barton, Samantha K.; Cheong, Jeanie L. Y.; Polglase, Graeme R.

2014-01-01

Background and Aim High tidal volume (VT) ventilation during resuscitation of preterm lambs results in brain injury evident histologically within hours after birth. We aimed to investigate whether magnetic resonance spectroscopy (MRS) and/or diffusion tensor imaging (DTI) can be used for early in vivo detection of ventilation-induced brain injury in preterm lambs. Methods Newborn lambs (0.85 gestation) were stabilized with a “protective ventilation” strategy (PROT, n = 7: prophylactic Curosurf, sustained inflation, VT 7 mL/kg, positive end expiratory pressure (PEEP) 5 cmH2O) or an initial 15 minutes of “injurious ventilation” (INJ, n = 10: VT 12 mL/kg, no PEEP, late Curosurf) followed by PROT ventilation for the remainder of the experiment. At 1 hour, lambs underwent structural magnetic resonance imaging (Siemens, 3 Tesla). For measures of mean/axial/radial diffusivity (MD, AD, RD) and fractional anisotropy (FA), 30 direction DTI was performed. Regions of interests encompassed the thalamus, internal capsule, periventricular white matter and the cerebellar vermis. MRS was performed using a localized single-voxel (15×15×20 mm3, echo time 270 ms) encompassing suptratentorial deep nuclear grey matter and central white matter. Peak-area ratios for lactate (Lac) relative to N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were calculated. Groups were compared using 2-way RM-ANOVA, Mann-Whitney U-test and Spearman's correlations. Results No cerebral injury was seen on structural MR images. Lambs in the INJ group had higher mean FA and lower mean RD in the thalamus compared to PROT lambs, but not in the other regions of interest. Peak-area lactate ratios >1.0 was only seen in INJ lambs. A trend of higher mean peak-area ratios for Lac/Cr and Lac/Cho was seen, which correlated with lower pH in both groups. Conclusion Acute changes in brain diffusion measures and metabolite peak-area ratios were observed after injurious ventilation. Early MRS/DTI is able to detect the initiation of ventilation-induced brain injury. PMID:24759765

Analysis of the Metabolic and Structural Brain Changes in Patients With Torture-Related Post-Traumatic Stress Disorder (TR-PTSD) Using 18F-FDG PET and MRI

PubMed Central

Zandieh, Shahin; Bernt, Reinhard; Knoll, Peter; Wenzel, Thomas; Hittmair, Karl; Haller, Joerg; Hergan, Klaus; Mirzaei, Siroos

2016-01-01

Abstract Many people exposed to torture later suffer from torture-related post-traumatic stress disorder (TR-PTSD). The aim of this study was to analyze the morphologic and functional brain changes in patients with TR-PTSD using magnetic resonance imaging (MRI) and positron emission tomography (PET). This study evaluated 19 subjects. Thirteen subcortical brain structures were evaluated using FSL software. On the T1-weighted images, normalized brain volumes were measured using SIENAX software. The study compared the volume of the brain and 13 subcortical structures in 9 patients suffering from TR-PTSD after torture and 10 healthy volunteers (HV). Diffusion-weighted imaging (DWI) was performed in the transverse plane. In addition, the 18F-FDG PET data were evaluated to identify the activity of the elected regions. The mean left hippocampal volume for the TR-PTSD group was significantly lower than in the HV group (post hoc test (Bonferroni) P < 0.001). There was a significant difference between the gray matter volume of the patients with TR-PTSD and the HV group (post hoc test (Bonferroni) P < 0.001). The TR-PTSD group showed low significant expansion of the ventricles in contrast to the HV group (post hoc test (Bonferroni) P < 0.001). Diffusion-weighted imaging revealed significant differences in the right frontal lobe and the left occipital lobe between the TR-PTSD and HV group (post hoc test (Bonferroni) P < 0.001). Moderate hypometabolism was noted in the occipital lobe in 6 of the 9 patients with TR-PTSD, in the temporal lobe in 1 of the 9 patients, and in the caudate nucleus in 5 of the 9 patients. In 2 cases, additional hypometabolism was observed in the posterior cingulate cortex and in the parietal and frontal lobes. The findings from this study show that TR-PTSD might have a deleterious influence on a set of specific brain structures. This study also demonstrated that PET combined with MRI is sensitive in detecting possible metabolic and structural brain changes in TR-PTSD. PMID:27082610

Analysis of the Metabolic and Structural Brain Changes in Patients With Torture-Related Post-Traumatic Stress Disorder (TR-PTSD) Using ¹⁸F-FDG PET and MRI.

PubMed

Zandieh, Shahin; Bernt, Reinhard; Knoll, Peter; Wenzel, Thomas; Hittmair, Karl; Haller, Joerg; Hergan, Klaus; Mirzaei, Siroos

2016-04-01

Many people exposed to torture later suffer from torture-related post-traumatic stress disorder (TR-PTSD). The aim of this study was to analyze the morphologic and functional brain changes in patients with TR-PTSD using magnetic resonance imaging (MRI) and positron emission tomography (PET). This study evaluated 19 subjects. Thirteen subcortical brain structures were evaluated using FSL software. On the T1-weighted images, normalized brain volumes were measured using SIENAX software. The study compared the volume of the brain and 13 subcortical structures in 9 patients suffering from TR-PTSD after torture and 10 healthy volunteers (HV). Diffusion-weighted imaging (DWI) was performed in the transverse plane. In addition, the 18F-FDG PET data were evaluated to identify the activity of the elected regions. The mean left hippocampal volume for the TR-PTSD group was significantly lower than in the HV group (post hoc test (Bonferroni) P < 0.001). There was a significant difference between the gray matter volume of the patients with TR-PTSD and the HV group (post hoc test (Bonferroni) P < 0.001). The TR-PTSD group showed low significant expansion of the ventricles in contrast to the HV group (post hoc test (Bonferroni) P < 0.001). Diffusion-weighted imaging revealed significant differences in the right frontal lobe and the left occipital lobe between the TR-PTSD and HV group (post hoc test (Bonferroni) P < 0.001). Moderate hypometabolism was noted in the occipital lobe in 6 of the 9 patients with TR-PTSD, in the temporal lobe in 1 of the 9 patients, and in the caudate nucleus in 5 of the 9 patients. In 2 cases, additional hypometabolism was observed in the posterior cingulate cortex and in the parietal and frontal lobes. The findings from this study show that TR-PTSD might have a deleterious influence on a set of specific brain structures. This study also demonstrated that PET combined with MRI is sensitive in detecting possible metabolic and structural brain changes in TR-PTSD.

Brain connectome modularity in weight-restored anorexia nervosa and body dysmorphic disorder

PubMed Central

Zhang, A; Leow, A; Zhan, L; GadElkarim, J; Moody, T; Khalsa, S; Strober, M; Feusner, JD

2017-01-01

Background Anorexia nervosa (AN) and body dysmorphic disorder (BDD) frequently co-occur, and have several overlapping phenomenological features. Little is known about their shared neurobiology. Aims To compare modular organization of brain structural connectivity. Methods We acquired diffusion-weighted magnetic resonance imaging data on unmedicated individuals with BDD (n=29), weight-restored AN (n=24), and healthy controls (HC) (n=31). We constructed connectivity matrices using whole-brain white matter tractography, and compared modular structures across groups. Results AN showed abnormal modularity involving frontal, basal ganglia, and posterior cingulate nodes. There was a trend in BDD for similar abnormalities, but no significant differences compared with AN. In AN, poor insight correlated with longer path length in right caudal anterior cingulate and right posterior cingulate. Conclusions Abnormal network organization patterns in AN, partially shared with BDD, may have implications for understanding integration between reward and habit/ritual formation, as well as conflict monitoring/error detection. PMID:27429183

Magnetization Transfer Ratio Relates to Cognitive Impairment in Normal Elderly

PubMed Central

Seiler, Stephan; Pirpamer, Lukas; Hofer, Edith; Duering, Marco; Jouvent, Eric; Fazekas, Franz; Mangin, Jean-Francois; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

2014-01-01

Magnetization transfer imaging (MTI) can detect microstructural brain tissue changes and may be helpful in determining age-related cerebral damage. We investigated the association between the magnetization transfer ratio (MTR) in gray and white matter (WM) and cognitive functioning in 355 participants of the Austrian stroke prevention family study (ASPS-Fam) aged 38–86 years. MTR maps were generated for the neocortex, deep gray matter structures, WM hyperintensities, and normal appearing WM (NAWM). Adjusted mixed models determined whole brain and lobar cortical MTR to be directly and significantly related to performance on tests of memory, executive function, and motor skills. There existed an almost linear dose-effect relationship. MTR of deep gray matter structures and NAWM correlated to executive functioning. All associations were independent of demographics, vascular risk factors, focal brain lesions, and cortex volume. Further research is needed to understand the basis of this association at the tissue level, and to determine the role of MTR in predicting cognitive decline and dementia. PMID:25309438

Soluble Amyloid-beta Aggregates from Human Alzheimer’s Disease Brains

PubMed Central

Esparza, Thomas J.; Wildburger, Norelle C.; Jiang, Hao; Gangolli, Mihika; Cairns, Nigel J.; Bateman, Randall J.; Brody, David L.

2016-01-01

Soluble amyloid-beta (Aβ) aggregates likely contribute substantially to the dementia that characterizes Alzheimer’s disease. However, despite intensive study of in vitro preparations and animal models, little is known about the characteristics of soluble Aβ aggregates in the human Alzheimer’s disease brain. Here we present a new method for extracting soluble Aβ aggregates from human brains, separating them from insoluble aggregates and Aβ monomers using differential ultracentrifugation, and purifying them >6000 fold by dual antibody immunoprecipitation. The method resulted in <40% loss of starting material, no detectible ex vivo aggregation of monomeric Aβ, and no apparent ex vivo alterations in soluble aggregate sizes. By immunoelectron microscopy, soluble Aβ aggregates typically appear as clusters of 10–20 nanometer diameter ovoid structures with 2-3 amino-terminal Aβ antibody binding sites, distinct from previously characterized structures. This approach may facilitate investigation into the characteristics of native soluble Aβ aggregates, and deepen our understanding of Alzheimer’s dementia. PMID:27917876

Extracting morphologies from third harmonic generation images of structurally normal human brain tissue.

PubMed

Zhang, Zhiqing; Kuzmin, Nikolay V; Groot, Marie Louise; de Munck, Jan C

2017-06-01

The morphologies contained in 3D third harmonic generation (THG) images of human brain tissue can report on the pathological state of the tissue. However, the complexity of THG brain images makes the usage of modern image processing tools, especially those of image filtering, segmentation and validation, to extract this information challenging. We developed a salient edge-enhancing model of anisotropic diffusion for image filtering, based on higher order statistics. We split the intrinsic 3-phase segmentation problem into two 2-phase segmentation problems, each of which we solved with a dedicated model, active contour weighted by prior extreme. We applied the novel proposed algorithms to THG images of structurally normal ex-vivo human brain tissue, revealing key tissue components-brain cells, microvessels and neuropil, enabling statistical characterization of these components. Comprehensive comparison to manually delineated ground truth validated the proposed algorithms. Quantitative comparison to second harmonic generation/auto-fluorescence images, acquired simultaneously from the same tissue area, confirmed the correctness of the main THG features detected. The software and test datasets are available from the authors. z.zhang@vu.nl. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

A novel tetrode microdrive for simultaneous multi-neuron recording from different regions of primate brain.

PubMed

Santos, Lucas; Opris, Ioan; Fuqua, Joshua; Hampson, Robert E; Deadwyler, Sam A

2012-04-15

A unique custom-made tetrode microdrive for recording from large numbers of neurons in several areas of primate brain is described as a means for assessing simultaneous neural activity in cortical and subcortical structures in nonhuman primates (NHPs) performing behavioral tasks. The microdrive device utilizes tetrode technology with up to six ultra-thin microprobe guide tubes (0.1mm) that can be independently positioned, each containing reduced diameter tetrode and/or hexatrode microwires (0.02 mm) for recording and isolating single neuron activity. The microdrive device is mounted within the standard NHP cranial well and allows traversal of brain depths up to 40.0 mm. The advantages of this technology are demonstrated via simultaneously recorded large populations of neurons with tetrode type probes during task performance from a) primary motor cortex and deep brain structures (caudate-putamen and hippocampus) and b) multiple layers within the prefrontal cortex. The means to characterize interactions of well-isolated ensembles of neurons recorded simultaneously from different regions, as shown with this device, has not been previously available for application in primate brain. The device has extensive application to primate models for the detection and study of inoperative or maladaptive neural circuits related to human neurological disorders. Published by Elsevier B.V.

Direct electrical stimulation as an input gate into brain functional networks: principles, advantages and limitations.

PubMed

Mandonnet, Emmanuel; Winkler, Peter A; Duffau, Hugues

2010-02-01

While the fundamental and clinical contribution of direct electrical stimulation (DES) of the brain is now well acknowledged, its advantages and limitations have not been re-evaluated for a long time. Here, we critically review exactly what DES can tell us about cerebral function. First, we show that DES is highly sensitive for detecting the cortical and axonal eloquent structures. Moreover, DES also provides a unique opportunity to study brain connectivity, since each area responsive to stimulation is in fact an input gate into a large-scale network rather than an isolated discrete functional site. DES, however, also has a limitation: its specificity is suboptimal. Indeed, DES may lead to interpretations that a structure is crucial because of the induction of a transient functional response when stimulated, whereas (1) this effect is caused by the backward spreading of the electro-stimulation along the network to an essential area and/or (2) the stimulated region can be functionally compensated owing to long-term brain plasticity mechanisms. In brief, although DES is still the gold standard for brain mapping, its combination with new methods such as perioperative neurofunctional imaging and biomathematical modeling is now mandatory, in order to clearly differentiate those networks that are actually indispensable to function from those that can be compensated.

Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy

PubMed Central

Holmes, Holly E.; Powell, Nick M.; Ma, Da; Ismail, Ozama; Harrison, Ian F.; Wells, Jack A.; Colgan, Niall; O'Callaghan, James M.; Johnson, Ross A.; Murray, Tracey K.; Ahmed, Zeshan; Heggenes, Morten; Fisher, Alice; Cardoso, M. Jorge; Modat, Marc; O'Neill, Michael J.; Collins, Emily C.; Fisher, Elizabeth M. C.; Ourselin, Sébastien; Lythgoe, Mark F.

2017-01-01

With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our “in-skull” preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes. PMID:28408879

Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural Abnormalities in a Mouse Model of Tauopathy.

PubMed

Holmes, Holly E; Powell, Nick M; Ma, Da; Ismail, Ozama; Harrison, Ian F; Wells, Jack A; Colgan, Niall; O'Callaghan, James M; Johnson, Ross A; Murray, Tracey K; Ahmed, Zeshan; Heggenes, Morten; Fisher, Alice; Cardoso, M Jorge; Modat, Marc; O'Neill, Michael J; Collins, Emily C; Fisher, Elizabeth M C; Ourselin, Sébastien; Lythgoe, Mark F

2017-01-01

With increasingly large numbers of mouse models of human disease dedicated to MRI studies, compromises between in vivo and ex vivo MRI must be fully understood in order to inform the choice of imaging methodology. We investigate the application of high resolution in vivo and ex vivo MRI, in combination with tensor-based morphometry (TBM), to uncover morphological differences in the rTg4510 mouse model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the overexpression of mutant tau can be regulated by the administration of doxycycline, providing us with a platform on which to investigate more subtle alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse brain relative to wild-type controls. Regions of volume loss aligned with neuronal loss and pathological tau accumulation demonstrated by immunohistochemistry. When we sought to investigate more subtle structural alterations in the rTg4510 mice relative to a subset of doxycycline-treated rTg4510 mice, ex vivo imaging enabled the detection of more regions of morphological brain changes. The disadvantages of ex vivo MRI may however mitigate this increase in sensitivity: we observed a 10% global shrinkage in brain volume of the post-mortem tissues due to formalin fixation, which was most notable in the cerebellum and olfactory bulbs. However, many central brain regions were not adversely affected by the fixation protocol, perhaps due to our "in-skull" preparation. The disparity between our TBM findings from in vivo and ex vivo MRI underlines the importance of appropriate study design, given the trade-off between these two imaging approaches. We support the utility of in vivo MRI for morphological phenotyping of mouse models of disease; however, for subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological changes.

Quantitative complexity analysis in multi-channel intracranial EEG recordings form epilepsy brains

PubMed Central

Liu, Chang-Chia; Pardalos, Panos M.; Chaovalitwongse, W. Art; Shiau, Deng-Shan; Ghacibeh, Georges; Suharitdamrong, Wichai; Sackellares, J. Chris

2008-01-01

Epilepsy is a brain disorder characterized clinically by temporary but recurrent disturbances of brain function that may or may not be associated with destruction or loss of consciousness and abnormal behavior. Human brain is composed of more than 10 to the power 10 neurons, each of which receives electrical impulses known as action potentials from others neurons via synapses and sends electrical impulses via a sing output line to a similar (the axon) number of neurons. When neuronal networks are active, they produced a change in voltage potential, which can be captured by an electroencephalogram (EEG). The EEG recordings represent the time series that match up to neurological activity as a function of time. By analyzing the EEG recordings, we sought to evaluate the degree of underlining dynamical complexity prior to progression of seizure onset. Through the utilization of the dynamical measurements, it is possible to classify the state of the brain according to the underlying dynamical properties of EEG recordings. The results from two patients with temporal lobe epilepsy (TLE), the degree of complexity start converging to lower value prior to the epileptic seizures was observed from epileptic regions as well as non-epileptic regions. The dynamical measurements appear to reflect the changes of EEG’s dynamical structure. We suggest that the nonlinear dynamical analysis can provide a useful information for detecting relative changes in brain dynamics, which cannot be detected by conventional linear analysis. PMID:19079790

Effect of socioeconomic status disparity on child language and neural outcome: how early is early?

PubMed

Hurt, Hallam; Betancourt, Laura M

2016-01-01

It is not news that poverty adversely affects child outcome. The literature is replete with reports of deleterious effects on developmental outcome, cognitive function, and school performance in children and youth. Causative factors include poor nutrition, exposure to toxins, inadequate parenting, lack of cognitive stimulation, unstable social support, genetics, and toxic environments. Less is known regarding how early in life adverse effects may be detected. This review proposes to elucidate "how early is early" through discussion of seminal articles related to the effect of socioeconomic status on language outcome and a discussion of the emerging literature on effects of socioeconomic status disparity on brain structure in very young children. Given the young ages at which such outcomes are detected, the critical need for early targeted interventions for our youngest is underscored. Further, the fiscal reasonableness of initiating quality interventions supports these initiatives. As early life adversity produces lasting and deleterious effects on developmental outcome and brain structure, increased focus on programs and policies directed to reducing the impact of socioeconomic disparities is essential.

Brain Signals of Face Processing as Revealed by Event-Related Potentials

PubMed Central

Olivares, Ela I.; Iglesias, Jaime; Saavedra, Cristina; Trujillo-Barreto, Nelson J.; Valdés-Sosa, Mitchell

2015-01-01

We analyze the functional significance of different event-related potentials (ERPs) as electrophysiological indices of face perception and face recognition, according to cognitive and neurofunctional models of face processing. Initially, the processing of faces seems to be supported by early extrastriate occipital cortices and revealed by modulations of the occipital P1. This early response is thought to reflect the detection of certain primary structural aspects indicating the presence grosso modo of a face within the visual field. The posterior-temporal N170 is more sensitive to the detection of faces as complex-structured stimuli and, therefore, to the presence of its distinctive organizational characteristics prior to within-category identification. In turn, the relatively late and probably more rostrally generated N250r and N400-like responses might respectively indicate processes of access and retrieval of face-related information, which is stored in long-term memory (LTM). New methods of analysis of electrophysiological and neuroanatomical data, namely, dynamic causal modeling, single-trial and time-frequency analyses, are highly recommended to advance in the knowledge of those brain mechanisms concerning face processing. PMID:26160999

Detecting brain tumor in computed tomography images using Markov random fields and fuzzy C-means clustering techniques

NASA Astrophysics Data System (ADS)

Abdulbaqi, Hayder Saad; Jafri, Mohd Zubir Mat; Omar, Ahmad Fairuz; Mustafa, Iskandar Shahrim Bin; Abood, Loay Kadom

2015-04-01

Brain tumors, are an abnormal growth of tissues in the brain. They may arise in people of any age. They must be detected early, diagnosed accurately, monitored carefully, and treated effectively in order to optimize patient outcomes regarding both survival and quality of life. Manual segmentation of brain tumors from CT scan images is a challenging and time consuming task. Size and location accurate detection of brain tumor plays a vital role in the successful diagnosis and treatment of tumors. Brain tumor detection is considered a challenging mission in medical image processing. The aim of this paper is to introduce a scheme for tumor detection in CT scan images using two different techniques Hidden Markov Random Fields (HMRF) and Fuzzy C-means (FCM). The proposed method has been developed in this research in order to construct hybrid method between (HMRF) and threshold. These methods have been applied on 4 different patient data sets. The result of comparison among these methods shows that the proposed method gives good results for brain tissue detection, and is more robust and effective compared with (FCM) techniques.

Comparison of brain volume abnormalities between ADHD and conduct disorder in adolescence

PubMed Central

Stevens, Michael C.; Haney-Caron, Emily

2012-01-01

Background Previous studies of brain structure abnormalities in conduct disorder and attention-deficit/hyperactivity disorder (ADHD) samples have been limited owing to cross-comorbidity, preventing clear understanding of which structural brain abnormalities might be specific to or shared by each disorder. To our knowledge, this study was the first direct comparison of grey and white matter volumes in diagnostically “pure” (i.e., no comorbidities) conduct disorder and ADHD samples. Methods Groups of adolescents with noncormobid conduct disorder and with noncomorbid, combined-subtype ADHD were compared with age- and sex-matched controls using DARTEL voxel-based analysis of T1-weighted brain structure images. Analysis of variance with post hoc analyses compared whole brain grey and white matter volumes among the groups. Results We included 24 adolescents in each study group. There was an overall 13% reduction in grey matter volume in adolescents with conduct disorder, reflecting numerous frontal, temporal, parietal and subcortical deficits. The same grey matter regions typically were not abnormal in those with ADHD. Deficits in frontal lobe regions previously identified in studies of patients with ADHD either were not detected, or group differences from controls were not as strong as those between the conduct disorder and control groups. White matter volume measurements did not differentiate conduct disorder and ADHD. Limitations Our modest sample sizes prevented meaningful examination of individual features of ADHD or conduct disorder, such as aggression, callousness, or hyperactive versus inattentive symptom subtypes. Conclusion The evidence supports theories of frontotemporal abnormalities in adolescents with conduct disorder, but raises questions about the prominence of frontal lobe and striatal structural abnormalities in those with noncomorbid, combined-subtype ADHD. The latter point is clinically important, given the widely held belief that ADHD is associated with numerous frontal lobe structural deficits, a conclusion that is not strongly supported following direct comparison of diagnostically pure groups. The results are important for future etiological studies, particularly those seeking to identify how early expression of specific brain structure abnormalities could potentiate the risk for antisocial behaviour. PMID:22663946

Functional photoacoustic tomography for neonatal brain imaging: developments and challenges

NASA Astrophysics Data System (ADS)

Hariri, Ali; Tavakoli, Emytis; Adabi, Saba; Gelovani, Juri; Avanaki, Mohammad R. N.

2017-03-01

Transfontanelle ultrasound imaging (TFUSI) is a routine diagnostic brain imaging method in infants who are born prematurely, whose skull bones have not completely fused together and have openings between them, so-called fontanelles. Open fontanelles in neonates provide acoustic windows, allowing the ultrasound beam to freely pass through. TFUSI is used to rule out neurological complications of premature birth including subarachnoid hemorrhage (SAH), intraventricular (IVH), subependimal (SEPH), subdural (SDH) or intracerebral (ICH) hemorrhages, as well as hypoxic brain injuries. TFUSI is widely used in the clinic owing to its low cost, safety, accessibility, and noninvasive nature. Nevertheless, the accuracy of TFUSI is limited. To address several limitations of current clinical imaging modalities, we develop a novel transfontanelle photoacoustic imaging (TFPAI) probe, which, for the first time, should allow for non-invasive structural and functional imaging of the infant brain. In this study, we test the feasibility of TFPAI for detection of experimentally-induced intra ventricular and Intraparenchymal hemorrhage phantoms in a sheep model with a surgically-induced cranial window which will serve as a model of neonatal fontanelle. This study is towards using the probe we develop for bedside monitoring of neonates with various disease conditions and complications affecting brain perfusion and oxygenation, including apnea, asphyxia, as well as for detection of various types of intracranial hemorrhages (SAH, IVH, SEPH, SDH, ICH).

Detection of intra-brain cytoplasmic 1 (BC1) long noncoding RNA using graphene oxide-fluorescence beacon detector.

PubMed

Kim, Mee Young; Hwang, Do Won; Li, Fangyuan; Choi, Yoori; Byun, Jung Woo; Kim, Dongho; Kim, Jee-Eun; Char, Kookheon; Lee, Dong Soo

2016-03-21

Detection of cellular expression of long noncoding RNAs (lncRNAs) was elusive due to the ambiguity of exposure of their reactive sequences associated with their secondary/tertiary structures and dynamic binding of proteins around lncRNAs. Herein, we developed graphene-based detection techniques exploiting the quenching capability of graphene oxide (GO) flakes for fluorescent dye (FAM)-labeled single-stranded siRNAs and consequent un-quenching by their detachment from GO by matching lncRNAs. A brain cytoplasmic 1 (BC1) lncRNA expression was significantly decreased by a siRNA, siBC1-1. GO quenched the FAM-labeled siBC1-1 peptide nucleic acid (PNA) probe, and this quenching was recovered by BC1. While FAM-siBC1-1-PNA-GO complex transfected spontaneously mouse or human neural stem cells, fluorescence was recovered only in mouse cells having high BC1 expression. Fluorescent dye-labeled single-stranded RNA-GO probe could detect the reactive exposed nucleic acid sequence of a cytoplasmic lncRNA expressing in the cytoplasm, which strategy can be used as a detection method of lncRNA expression.

Human hippocampus associates information in memory

PubMed Central

Henke, Katharina; Weber, Bruno; Kneifel, Stefan; Wieser, Heinz Gregor; Buck, Alfred

1999-01-01

The hippocampal formation, one of the most complex and vulnerable brain structures, is recognized as a crucial brain area subserving human long-term memory. Yet, its specific functions in memory are controversial. Recent experimental results suggest that the hippocampal contribution to human memory is limited to episodic memory, novelty detection, semantic (deep) processing of information, and spatial memory. We measured the regional cerebral blood flow by positron-emission tomography while healthy volunteers learned pairs of words with different learning strategies. These led to different forms of learning, allowing us to test the degree to which they challenge hippocampal function. Neither novelty detection nor depth of processing activated the hippocampal formation as much as semantically associating the primarily unrelated words in memory. This is compelling evidence for another function of the human hippocampal formation in memory: establishing semantic associations. PMID:10318979

Association between brain structural anomalies, electroencephalogram and history of seizures in Mucopolysaccharidosis type II (Hunter syndrome).

PubMed

Jiménez-Arredondo, Ramón Ernesto; Brambila-Tapia, Aniel Jessica Leticia; Mercado-Silva, Francisco Miguel; Ortiz-Aranda, Martha; Benites-Godinez, Verónica; Olmos-García-de-Alba, Graciela; Figuera, Luis Eduardo

2017-03-01

Mucopolysaccharidosis type II or Hunter syndrome (MPS II) is a genetic disease that can course with intellectual impairment and central nervous system (CNS) alterations. To date, no report has documented electroencephalogram (EEG) measures associated with CNS alterations, detected by imaging studies, and the history of seizures in patients with MPS II. Therefore, we decided to search this association. We included 9 patients with MPS II and performed imaging studies of the brain to detect the presence of cortico-subcortical atrophy, enlarged subarachnoid space and supratentorial ventricular size. Additionally, we performed EEG studies in sleep and awake conditions and a complete clinical description. Five out of the nine patients presented history of seizures and all except one patient (88.9%) presented some CNS structural alteration in the imaging studies, being the most frequent the cortico-subcortical atrophy (77.8%). The EEG results showed low amplitude in all patients and low voltage in sleep condition in eight patients with interhemispheric asymmetry in six patients during awake and sleep conditions. Although the five patients with history of seizures did not present a distinctive EEG anomaly, four of them presented some structural alteration in the imaging studies. In conclusion, most patients presented structural alterations in the CNS; likewise, all of them presented EEG anomalies mainly during sleep conditions. However, a clear association between EEG, CNS and the history of seizures was not established.

Commentary: physical approaches for the treatment of epilepsy: electrical and magnetic stimulation and cooling.

PubMed

Löscher, Wolfgang; Cole, Andrew J; McLean, Michael J

2009-04-01

Physical approaches for the treatment of epilepsy currently under study or development include electrical or magnetic brain stimulators and cooling devices, each of which may be implanted or applied externally. Some devices may stimulate peripheral structures, whereas others may be implanted directly into the brain. Stimulation may be delivered chronically, intermittently, or in response to either manual activation or computer-based detection of events of interest. Physical approaches may therefore ultimately be appropriate for seizure prophylaxis by causing a modification of the underlying substrate, presumably with a reduction in the intrinsic excitability of cerebral structures, or for seizure termination, by interfering with the spontaneous discharge of pathological neuronal networks. Clinical trials of device-based therapies are difficult due to ethical issues surrounding device implantation, problems with blinding, potential carryover effects that may occur in crossover designs if substrate modification occurs, and subject heterogeneity. Unresolved issues in the development of physical treatments include optimization of stimulation parameters, identification of the optimal volume of brain to be stimulated, development of adequate power supplies to stimulate the necessary areas, and a determination that stimulation itself does not promote epileptogenesis or adverse long-term effects on normal brain function.

Development and characterization of non-resonant multiphoton photoacoustic spectroscopy (NMPPAS) for brain tumor margining

NASA Astrophysics Data System (ADS)

Dahal, Sudhir

During tumor removal surgery, due to the problems associated with obtaining high-resolution, real-time chemical images of where exactly the tumor ends and healthy tissue begins (tumor margining), it is often necessary to remove a much larger volume of tissue than the tumor itself. In the case of brain tumor surgery, however, it is extremely unsafe to remove excess tissue. Therefore, without an accurate image of the tumor margins, some of the tumor's finger-like projections are inevitably left behind in the surrounding parenchyma to grow again. For this reason, the development of techniques capable of providing high-resolution real-time images of tumor margins up to centimeters below the surface of a tissue is ideal for the diagnosis and treatment of tumors, as well as surgical guidance during brain tumor excision. A novel spectroscopic technique, non-resonant multiphoton photoacoustic spectroscopy (NMPPAS), is being developed with the capabilities of obtaining high-resolution subsurface chemical-based images of underlying tumors. This novel technique combines the strengths of multiphoton tissue spectroscopy and photoacoustic spectroscopy into a diagnostic methodology that will, ultimately, provide unparalleled chemical information and images to provide the state of sub-surface tissues. The NMPPAS technique employs near-infrared light (in the diagnostic window) to excite ultraviolet and/or visible light absorbing species deep below the tissue's surface. Once a multiphoton absorption event occurs, non-radiative relaxation processes generates a localized thermal expansion and subsequent acoustic wave that can be detected using a piezoelectric transducer. Since NMPPAS employs an acoustic detection modality, much deeper diagnoses can be performed than that is possible using current state of the art high-resolution chemical imaging techniques such as multiphoton fluorescence spectroscopy. NMPPAS was employed to differentiate between excised brain tumors (astrocytoma III) and healthy tissue with over 99% accuracy. NMPPAS spectral features showed evident differences between tumor and healthy tissues, and ratiometric analysis ensured that only a few wavelengths could be used for excitation instead of using numerous wavelength excitations to create spectra. This process would significantly reduce the analysis time while maintaining the same degree of accuracy. Tissue phantoms were fabricated in order to characterize the properties of NMPPAS. Scattering particles were doped into the phantoms to simulate their light scattering properties to real tissues. This allowed for better control over shape, size, reproducibility and doping in the sample while maintaining the light-tissue interaction properties of real tissue. To make NMPPAS viable for clinical applications, the technique was characterized to determine the spatial (lateral and longitudinal) resolution, depth of penetration and its ability to image in three-dimension through layers of tissue. Both resolutions were determined to be near-cellular level resolution (50-70 microm), obtained initially with the aid of the technique of multiphoton fluorescence, and later verified using NMPPAS imaging. Additionally, the maximum depth of penetration and detection was determined to be about 1.4cm, making the technique extremely suitable to margin tumors from underlying tissues in the brain. The capability of NMPPAS to detect and image layers that lie beneath other structures and blood vessels was also investigated. Three-dimensional images were obtained for the first time using NMPPAS. The images were obtained from different depths and structures were imaged through other layers of existing structures in the sample. This verified that NMPPAS was capable of detecting and imaging structures that lie embedded within the tissues. NMPPAS images of embedded structures were also obtained with the presence of hemoglobin, which is potentially the largest source of background in blood-perfused tissues, thus showing that the technique is capable of detecting and differentiating in blood-perfused samples.

Alzheimer disease: focus on computed tomography.

PubMed

Reynolds, April

2013-01-01

Alzheimer disease is the most common type of dementia, affecting approximately 5.3 million Americans. This debilitating disease is marked by memory loss, confusion, and loss of cognitive ability. The exact cause of Alzheimer disease is unknown although research suggests that it might result from a combination of factors. The hallmarks of Alzheimer disease are the presence of beta-amyloid plaques and neurofibrillary tangles in the brain. Radiologic imaging can help physicians detect these structural characteristics and monitor disease progression and brain function. Computed tomography and magnetic resonance imaging are considered first-line imaging modalities for the routine evaluation of Alzheimer disease.

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

PubMed Central

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

2014-01-01

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

Interaction between BDNF rs6265 Met allele and low family cohesion is associated with smaller left hippocampal volume in pediatric bipolar disorder.

PubMed

Zeni, Cristian Patrick; Mwangi, Benson; Cao, Bo; Hasan, Khader M; Walss-Bass, Consuelo; Zunta-Soares, Giovana; Soares, Jair C

2016-01-01

Genetic and environmental factors are implicated in the onset and evolution of pediatric bipolar disorder, and may be associated to structural brain abnormalities. The aim of our study was to assess the impact of the interaction between the Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism and family functioning on hippocampal volumes of children and adolescents with bipolar disorder, and typically-developing controls. We evaluated the family functioning cohesion subscale using the Family Environment Scale-Revised, genotyped the BDNF rs6265 polymorphism, and performed structural brain imaging in 29 children and adolescents with bipolar disorder, and 22 healthy controls. We did not find significant differences between patients with BD or controls in left or right hippocampus volume (p=0.44, and p=0.71, respectively). However, we detected a significant interaction between low scores on the cohesion subscale and the presence of the Met allele at BNDF on left hippocampal volume of patients with bipolar disorder (F=3.4, p=0.043). None of the factors independently (BDNF Val66Met, cohesion scores) was significantly associated with hippocampal volume differences. small sample size, cross-sectional study. These results may lead to a better understanding of the impact of the interaction between genes and environment factors on brain structures associated to bipolar disorder and its manifestations. Copyright © 2015 Elsevier B.V. All rights reserved.

Homological scaffolds of brain functional networks

PubMed Central

Petri, G.; Expert, P.; Turkheimer, F.; Carhart-Harris, R.; Nutt, D.; Hellyer, P. J.; Vaccarino, F.

2014-01-01

Networks, as efficient representations of complex systems, have appealed to scientists for a long time and now permeate many areas of science, including neuroimaging (Bullmore and Sporns 2009 Nat. Rev. Neurosci. 10, 186–198. (doi:10.1038/nrn2618)). Traditionally, the structure of complex networks has been studied through their statistical properties and metrics concerned with node and link properties, e.g. degree-distribution, node centrality and modularity. Here, we study the characteristics of functional brain networks at the mesoscopic level from a novel perspective that highlights the role of inhomogeneities in the fabric of functional connections. This can be done by focusing on the features of a set of topological objects—homological cycles—associated with the weighted functional network. We leverage the detected topological information to define the homological scaffolds, a new set of objects designed to represent compactly the homological features of the correlation network and simultaneously make their homological properties amenable to networks theoretical methods. As a proof of principle, we apply these tools to compare resting-state functional brain activity in 15 healthy volunteers after intravenous infusion of placebo and psilocybin—the main psychoactive component of magic mushrooms. The results show that the homological structure of the brain's functional patterns undergoes a dramatic change post-psilocybin, characterized by the appearance of many transient structures of low stability and of a small number of persistent ones that are not observed in the case of placebo. PMID:25401177

Structural and functional changes during epileptogenesis in the mouse model of medial temporal lobe epilepsy.

PubMed

Dietrich, Yvan; Eliat, Pierre-Antoine; Dieuset, Gabriel; Saint-Jalmes, Herve; Pineau, Charles; Wendling, Fabrice; Martin, Benoit

2016-08-01

An important issue in epilepsy research is to understand the structural and functional modifications leading to chronic epilepsy, characterized by spontaneous recurrent seizures, after initial brain insult. To address this issue, we recorded and analyzed electroencephalography (EEG) and quantitative magnetic resonance imaging (MRI) data during epileptogenesis in the in vivo mouse model of Medial Temporal Lobe Epilepsy (MTLE, kainate). Besides, this model of epilepsy is a particular form of drug-resistant epilepsy. The results indicate that high-field (4.7T) MRI parameters (T2-weighted; T2-quantitative) allow to detect the gradual neuro-anatomical changes that occur during epileptogenesis while electrophysiological parameters (number and duration of Hippocampal Paroxysmal Discharges) allow to assess the dysfunctional changes through the quantification of epileptiform activity. We found a strong correlation between EEG-based markers (invasive recording) and MRI-based parameters (non-invasive) periodically computed over the `latent period' that spans over two weeks, on average. These results indicated that both structural and functional changes occur in the considered epilepsy model and are considered as biomarkers of the installation of epilepsy. Additionally, such structural and functional changes can also be observed in human temporal lobe epilepsy. Interestingly, MRI imaging parameters could be used to track early (day-7) structural changes (gliosis, cell loss) in the lesioned brain and to quantify the evolution of epileptogenesis after traumatic brain injury.

A Novel Method of Building Functional Brain Network Using Deep Learning Algorithm with Application in Proficiency Detection.

PubMed

Hua, Chengcheng; Wang, Hong; Wang, Hong; Lu, Shaowen; Liu, Chong; Khalid, Syed Madiha

2018-04-11

Functional brain network (FBN) has become very popular to analyze the interaction between cortical regions in the last decade. But researchers always spend a long time to search the best way to compute FBN for their specific studies. The purpose of this study is to detect the proficiency of operators during their mineral grinding process controlling based on FBN. To save the search time, a novel semi-data-driven method of computing functional brain connection based on stacked autoencoder (BCSAE) is proposed in this paper. This method uses stacked autoencoder (SAE) to encode the multi-channel EEG data into codes and then computes the dissimilarity between the codes from every pair of electrodes to build FBN. The highlight of this method is that the SAE has a multi-layered structure and is semi-supervised, which means it can dig deeper information and generate better features. Then an experiment was performed, the EEG of the operators were collected while they were operating and analyzed to detect their proficiency. The results show that the BCSAE method generated more number of separable features with less redundancy, and the average accuracy of classification (96.18%) is higher than that of the control methods: PLV (92.19%) and PLI (78.39%).

The Effect of Early Detection of Occult Brain Metastases in HER2-Positive Breast Cancer Patients on Survival and Cause of Death

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

Niwinska, Anna, E-mail: alphaonetau@poczta.onet.p; Tacikowska, Malgorzata; Murawska, Magdalena

2010-07-15

Purpose: The aim of the study is to evaluate disease-free survival, survival from the detection of brain metastases, overall survival, and cause of death in patients with occult brain metastases (Group I) vs. patients with symptomatic brain metastases (Group II). Methods and Materials: In 80 HER2-positive breast cancer patients, treated with trastuzumab and cytostatic agents for metastatic disease, magnetic resonance imaging screening of the brain was performed, and in 29 patients (36%) occult brain metastasis was detected (Group I). Whole-brain radiotherapy was delivered to Group I. This first group was compared with 52 patients who had symptomatic brain metastases (Groupmore » II) and was treated the same way, at the same clinic, during the same time period. Results: Median disease-free survival was 17 months in Group I and 19.9 months in Group II (p = 0.58). The median time interval between the dissemination of the disease and the detection of occult or symptomatic brain metastases was 9 and 15 months, respectively (p = 0.11). When the brain metastases were detected, the median survival was 9 and 8.78 months, respectively (p = 0.80). The median overall survival was 53 and 51 months, respectively (p = 0.94). In the group with occult brain metastases (Group I) 16% of patients died because of progression within the brain. In the group with symptomatic brain metastases (Group II) the rate of cerebral death was 48% (p = 0.009). Conclusions: Whole-brain radiotherapy of occult brain metastases in HER2-positive breast cancer patients with visceral dissemination produces a three-fold decrease in cerebral deaths but does not prolong survival.« less

Detecting brain tumor in computed tomography images using Markov random fields and fuzzy C-means clustering techniques

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

Abdulbaqi, Hayder Saad; Department of Physics, College of Education, University of Al-Qadisiya, Al-Qadisiya; Jafri, Mohd Zubir Mat

Brain tumors, are an abnormal growth of tissues in the brain. They may arise in people of any age. They must be detected early, diagnosed accurately, monitored carefully, and treated effectively in order to optimize patient outcomes regarding both survival and quality of life. Manual segmentation of brain tumors from CT scan images is a challenging and time consuming task. Size and location accurate detection of brain tumor plays a vital role in the successful diagnosis and treatment of tumors. Brain tumor detection is considered a challenging mission in medical image processing. The aim of this paper is to introducemore » a scheme for tumor detection in CT scan images using two different techniques Hidden Markov Random Fields (HMRF) and Fuzzy C-means (FCM). The proposed method has been developed in this research in order to construct hybrid method between (HMRF) and threshold. These methods have been applied on 4 different patient data sets. The result of comparison among these methods shows that the proposed method gives good results for brain tissue detection, and is more robust and effective compared with (FCM) techniques.« less

Research of Hubs Location Method for Weighted Brain Network Based on NoS-FA.

PubMed

Weng, Zhengkui; Wang, Bin; Xue, Jie; Yang, Baojie; Liu, Hui; Xiong, Xin

2017-01-01

As a complex network of many interlinked brain regions, there are some central hub regions which play key roles in the structural human brain network based on T1 and diffusion tensor imaging (DTI) technology. Since most studies about hubs location method in the whole human brain network are mainly concerned with the local properties of each single node but not the global properties of all the directly connected nodes, a novel hubs location method based on global importance contribution evaluation index is proposed in this study. The number of streamlines (NoS) is fused with normalized fractional anisotropy (FA) for more comprehensive brain bioinformation. The brain region importance contribution matrix and information transfer efficiency value are constructed, respectively, and then by combining these two factors together we can calculate the importance value of each node and locate the hubs. Profiting from both local and global features of the nodes and the multi-information fusion of human brain biosignals, the experiment results show that this method can detect the brain hubs more accurately and reasonably compared with other methods. Furthermore, the proposed location method is used in impaired brain hubs connectivity analysis of schizophrenia patients and the results are in agreement with previous studies.

Goldfish spexin: solution structure and novel function as a satiety factor in feeding control.

PubMed

Wong, Matthew K H; Sze, Kong Hung; Chen, Ting; Cho, Chi Kong; Law, Henry C H; Chu, Ivan K; Wong, Anderson O L

2013-08-01

Spexin (SPX) is a neuropeptide identified recently by bioinformatic approach. At present not much is known about its biological actions, and comparative studies of SPX in nonmammalian species are still lacking. To examine the structure and function of SPX in fish model, SPX was cloned in goldfish and found to be highly comparable with its mammalian counterparts. As revealed by NMR spectroscopies, goldfish SPX is composed of an α-helix from Gln(5) to Gln(14) with a flexible NH2 terminus from Asn(1) to Pro(4), and its molecular surface is largely hydrophobic except for Lys(11) as the only charged residue in the helical region. In goldfish, SPX transcripts were found to be widely expressed in various tissues, and protein expression of SPX was also detected in the brain. In vivo feeding studies revealed that SPX mRNA levels in the telencephalon, optic tectum, and hypothalamus of goldfish brain could be elevated by food intake. However, brain injection of goldfish SPX inhibited both basal and NPY- or orexin-induced feeding behavior and food consumption. Similar treatment also reduced transcript expression of NPY, AgRP, and apelin, with concurrent rises in CCK, CART, POMC, MCH, and CRH mRNA levels in different brain areas examined. The differential effects of SPX treatment on NPY, CCK, and MCH transcript expression could also be noted in vitro in goldfish brain cell culture. Our studies for the first time unveil the solution structure of SPX and its novel function as a satiety factor through differential modulation of central orexigenic and anorexigenic signals.

The impact of substance use on brain structure in people at high risk of developing schizophrenia.

PubMed

Welch, Killian A; McIntosh, Andrew M; Job, Dominic E; Whalley, Heather C; Moorhead, Thomas W; Hall, Jeremy; Owens, David G C; Lawrie, Stephen M; Johnstone, Eve C

2011-09-01

Ventricular enlargement and reduced prefrontal volume are consistent findings in schizophrenia. Both are present in first episode subjects and may be detectable before the onset of clinical disorder. Substance misuse is more common in people with schizophrenia and is associated with similar brain abnormalities. We employ a prospective cohort study with nested case control comparison design to investigate the association between substance misuse, brain abnormality, and subsequent schizophrenia. Substance misuse history, imaging data, and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls. Regions exhibiting a significant relationship between level of use of alcohol, cannabis or tobacco, and structure volume were identified. Multivariate regression then elucidated the relationship between level of substance use and structure volumes while accounting for correlations between these variables and correcting for potential confounders. Finally, we established whether substance misuse was associated with later risk of schizophrenia. Increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner. Alcohol consumption was associated with reduced frontal lobe volume. Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model. Alcohol and cannabis misuse were associated with an increased subsequent risk of schizophrenia. We provide prospective evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis. A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances.

Demeclocycline as a contrast agent for detecting brain neoplasms using confocal microscopy

NASA Astrophysics Data System (ADS)

Wirth, Dennis; Smith, Thomas W.; Moser, Richard; Yaroslavsky, Anna N.

2015-04-01

Complete resection of brain tumors improves life expectancy and quality. Thus, there is a strong need for high-resolution detection and microscopically controlled removal of brain neoplasms. The goal of this study was to test demeclocycline as a contrast enhancer for the intraoperative detection of brain tumors. We have imaged benign and cancerous brain tumors using multimodal confocal microscopy. The tumors investigated included pituitary adenoma, meningiomas, glioblastomas, and metastatic brain cancers. Freshly excised brain tissues were stained in 0.75 mg ml-1 aqueous solution of demeclocyline. Reflectance images were acquired at 402 nm. Fluorescence signals were excited at 402 nm and registered between 500 and 540 nm. After imaging, histological sections were processed from the imaged specimens and compared to the optical images. Fluorescence images highlighted normal and cancerous brain cells, while reflectance images emphasized the morphology of connective tissue. The optical and histological images were in accordance with each other for all types of tumors investigated. Demeclocyline shows promise as a contrast agent for intraoperative detection of brain tumors.

Gender and age effects in structural brain asymmetry as measured by MRI texture analysis.

PubMed

Kovalev, Vassili A; Kruggel, Frithjof; von Cramon, D Yves

2003-07-01

Effects of gender and age on structural brain asymmetry were studied by 3D texture analysis in 380 adults. Asymmetry is detected by comparing the complex 3D gray-scale image patterns in the left and right cerebral hemispheres as revealed by anatomical T1-weighted MRI datasets. The Talairach and Tournoux parcellation system was applied to study the asymmetry on five levels: the whole cerebrum, nine coronal sections, 12 axial sections, boxes resulting from both coronal and axial subdivisions, and by a sliding spherical window of 9 mm diameter. The analysis revealed that the brain asymmetry increases in the anterior-posterior direction starting from the central region onward. Male brains were found to be more asymmetric than female. This gender-related effect is noticeable in all brain areas but is most significant in the superior temporal gyrus, Heschl's gyrus, the adjacent white matter regions in the temporal stem and the knee of the optic radiation, the thalamus, and the posterior cingulate. The brain asymmetry increases significantly with age in the inferior frontal gyrus, anterior insula, anterior cingulate, parahippocampal gyrus, retrosplenial cortex, coronal radiata, and knee region of the internal capsule. Asymmetry decreases with age in the optic radiation, precentral gyrus, and angular gyrus. The texture-based method reported here is based on extended multisort cooccurrence matrices that employ intensity, gradient, and anisotropy features in a uniform way. It is sensitive, simple to reproduce, robust, and unbiased in the sense that segmentation of brain compartments and spatial transformations are not necessary. Thus, it should be considered as another tool for digital morphometry in neuroscience.

Brain Microstructural Correlates of Cognitive Dysfunction in Clinically and Biochemically Normal Hepatitis C Virus Infection.

PubMed

Kumar, Ajay; Deep, Amar; Gupta, Rakesh K; Atam, Virendra; Mohindra, Samir

2017-09-01

This study examined correlates of the brain's neurocognitive performance among clinically and biochemically normal adult patient with hepatitis C virus (HCV). We hypothesized that anti-HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using diffusion tensor tractrography (DTT) metrics. Anti-HCV positive patient ( n  = 40), and healthy controls ( n  = 31), fulfilling inclusion criteria (incidentally detected anti-HCV positive) and able to provide informed consent were screened and recruited for the study. All these subjects and controls underwent subjective assessment of their quality of life related symptoms, neuropsychometric tests (NPT) and magnetic resonance imaging. The patients were subjected to neuroimaging as well as psychological testing. There was no significant difference in basic laboratory parameters in these two groups. Independent t -test reveals significantly lower neuropsychological functioning as compared to healthy control. A significantly decreased FA values and myoinsitol were observed in HCV subjects on sensory, inferior longitudinal fascicules, and STR fiber bundles as compared to healthy control. Bivariate correlation analysis reveals that neuropsychological scores are significantly positive. Our result show that HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using DTT metrics.

Imaging of mild traumatic brain injury using 57Co and 99mTc HMPAO SPECT as compared to other diagnostic procedures.

PubMed

Audenaert, Kurt; Jansen, Hugo M L; Otte, Andreas; Peremans, Kathelijne; Vervaet, Myriam; Crombez, Roger; de Ridder, Leo; van Heeringen, Cees; Thirot, Joel; Dierckx, Rudi; Korf, Jaap

2003-10-01

Traumatic brain injury (TBI) is usually assessed with the Glasgow Coma Scale (GCS), CT and EEG. TBI can result from either the primary mechanical impact or secondary (ischemic) brain damage, in which calcium (Ca) plays a pivotal role. This study was undertaken to compare the applicability of SPECT using 57Co as a Ca-tracer in patients with mild traumatic brain injury. 8 patients with mild TBI (GCS 15) were clinically examined and studied with EEG, neuropsychological testing (NPT) and SPECT within 2 days post-TBI. After i.v.-administration of 37 MBq (1 mCi) 57Co (effective radiation dose 0.34 mSv x MBq(-1); 1.24 rem x mCi(-1); physical half-life 270 days, biological half-life 37.6 h), single-headed SPECT (12 h pi) was performed, consecutively followed by standard 925 MBq (25 mCi) Tc-99m HMPAO SPECT. In 6 of the 8 patients, baseline NPT and SPECT showed focal abnormalities in the affected frontal and temporal brain regions, which were in good topographical accordance. CT and EEG did not detect (structural) lesions in any of these cases. Single-headed 57Co-SPECT is able to show the site and extent of brain damage in patients with mild TBI, even in the absence of structural lesions. It may confirm and localize NPT findings. The predictive value of 57Co-SPECT should be assessed in larger patient series.

3D brain MR angiography displayed by a multi-autostereoscopic screen

NASA Astrophysics Data System (ADS)

Magalhães, Daniel S. F.; Ribeiro, Fádua H.; Lima, Fabrício O.; Serra, Rolando L.; Moreno, Alfredo B.; Li, Li M.

2012-02-01

The magnetic resonance angiography (MRA) can be used to examine blood vessels in key areas of the body, including the brain. In the MRA, a powerful magnetic field, radio waves and a computer produce the detailed images. Physicians use the procedure in brain images mainly to detect atherosclerosis disease in the carotid artery of the neck, which may limit blood flow to the brain and cause a stroke and identify a small aneurysm or arteriovenous malformation inside the brain. Multi-autostereoscopic displays provide multiple views of the same scene, rather than just two, as in autostereoscopic systems. Each view is visible from a different range of positions in front of the display. This allows the viewer to move left-right in front of the display and see the correct view from any position. The use of 3D imaging in the medical field has proven to be a benefit to doctors when diagnosing patients. For different medical domains a stereoscopic display could be advantageous in terms of a better spatial understanding of anatomical structures, better perception of ambiguous anatomical structures, better performance of tasks that require high level of dexterity, increased learning performance, and improved communication with patients or between doctors. In this work we describe a multi-autostereoscopic system and how to produce 3D MRA images to be displayed with it. We show results of brain MR angiography images discussing, how a 3D visualization can help physicians to a better diagnosis.

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology.

PubMed

Layé, Sophie; Nadjar, Agnès; Joffre, Corinne; Bazinet, Richard P

2018-01-01

Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior. Several active drugs regulate brain lipid signaling and provide proof of concept for targeting the brain. Because brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, including the liver and blood, which supply the brain with PUFAs that can be altered by genetics, sex, and aging, there are many pathways that can be disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling pathways are altered in neurologic disorders and may be viable targets for the development of novel therapeutics. In this study, we discuss in particular how n-3 PUFAs and their metabolites regulate microglia phenotype and function to exert their anti-inflammatory and proresolving activities in the brain. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Blood-based diagnostics of traumatic brain injuries

PubMed Central

Mondello, Stefania; Muller, Uwe; Jeromin, Andreas; Streeter, Jackson; Hayes, Ronald L; Wang, Kevin KW

2011-01-01

Traumatic brain injury is a major health and socioeconomic problem that affects all societies. However, traditional approaches to the classification of clinical severity are the subject of debate and are being supplemented with structural and functional neuroimaging, as the need for biomarkers that reflect elements of the pathogenetic process is widely recognized. Basic science research and developments in the field of proteomics have greatly advanced our knowledge of the mechanisms involved in damage and have led to the discovery and rapid detection of new biomarkers that were not available previously. However, translating this research for patients' benefits remains a challenge. In this article, we summarize new developments, current knowledge and controversies, focusing on the potential role of these biomarkers as diagnostic, prognostic and monitoring tools of brain-injured patients. PMID:21171922

Nonimpact brain injury: neuropsychological and behavioral correlates with consideration of physiological findings.

PubMed

Henry, G K; Gross, H S; Herndon, C A; Furst, C J

2000-01-01

This retrospective clinical study investigated the neuropsychological, physiological, and behavioral functioning of 32 adult outpatients up to 65 months following nonimpact brain injury (i.e., whiplash). All participants were administered a flexible battery of cognitive tests, and some underwent neurodiagnostic procedures and sleep studies. Compared with published norms, neuropsychological data revealed significant and persistent age-adjusted cognitive deficits, primarily in the area of executive functioning. Participants frequently complained of problems with behavioral control, sleep, and sexuality. Although structural neuroimaging was not sensitive in detecting brain pathology, quantitative electroencephalography was abnormal in all the participants evaluated, showing frontocentral slowing and increased spike wave activity. We propose that whiplash injury can produce wide-ranging circuitry dysfunction and that test selection is critical in identifying cognitive deficits.

Iron biomineralization of brain tissue and neurodegenerative disorders

NASA Astrophysics Data System (ADS)

Mikhaylova (Mikhailova), Albina

The brain is an organ with a high concentration of iron in specific areas, particularly in the globus pallidus, the substantia nigra, and the red nucleus. In certain pathological states, such as iron overload disease and neurodegenerative disorders, a disturbed iron metabolism can lead to increased accumulation of iron not only in these areas, but also in the brain regions that are typically low in iron content. Recent studies of the physical and magnetic properties of metalloproteins, and in particular the discovery of biogenic magnetite in human brain tissue, have raised new questions about the role of biogenic iron formations in living organisms. Further investigations revealed the presence of magnetite-like crystalline structures in human ferritin, and indicated that released ferritin iron might act as promoter of oxidative damage to tissue, therefore contributing to pathogenesis of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. The purpose of this work was to examine the elemental composition and structure of iron deposits in normal brain tissue as well as tissue affected by neurodegenerative disorders. Employing the methods of X-ray microfocus fluorescence mapping, X-ray Absorption Near Edge Structure (XANES), X-ray Absorption Fine Structure spectroscopy (XAFS), and light and electron microscopic examinations allows one to obtain qualitative as well as quantitative data with respect to the cellular distribution and chemical state of iron at levels not detected previously. The described tissue preparation technique allows not only satisfactory XAS iron elemental imaging in situ but also multimodal examination with light and electron microscopes of the same samples. The developed protocol has assured consistent and reproducible results on relatively large sections of flat-embedded tissue. The resulting tissue samples were adequate for XAS examination as well as sufficiently well-preserved for future microscopy studies. The continued development of this technique should lead to major advances in mapping iron anomalies and the related chemical and structural information directly to cells and tissue structures in human brain tissue. At present this is done primarily by iron staining methods and any information on the relationship between iron distribution and cellular structures obtained this way is limited. Iron staining also offers no information on the specific compounds of iron that are present. This can be vitally important as the form of iron [including its oxidation state] in the human body can determine whether it plays a detrimental or beneficial role in neurophysiological processes.

The detectability of brain metastases using contrast-enhanced spin-echo or gradient-echo images: a systematic review and meta-analysis.

PubMed

Suh, Chong Hyun; Jung, Seung Chai; Kim, Kyung Won; Pyo, Junhee

2016-09-01

This study aimed to compare the detectability of brain metastases using contrast-enhanced spin-echo (SE) and gradient-echo (GRE) T1-weighted images. The Ovid-MEDLINE and EMBASE databases were searched for studies on the detectability of brain metastases using contrast-enhanced SE or GRE images. The pooled proportions for the detectability of brain metastases were assessed using random-effects modeling. Heterogeneity among studies was determined using χ (2) statistics for the pooled estimates and the inconsistency index, I (2) . To overcome heterogeneity, subgroup analyses according to slice thickness and lesion size were performed. A total of eight eligible studies, which included a sample size of 252 patients and 1413 brain metastases, were included. The detectability of brain metastases using SE images (89.2 %) was higher than using GRE images (81.6 %; adjusted 84.0 %), but this difference was not statistically significant (p = 0.2385). In subgroup analysis of studies with 1-mm-thick slices and small metastases (<5 mm in diameter), 3-dimensional (3D) SE images demonstrated a higher detectability in comparison to 3D GRE images (93.7 % vs 73.1 % in 1-mm-thick slices; 89.5 % vs 59.4 % for small metastases) (p < 0.0001). Although both SE or GRE images are acceptable for detecting brain metastases, contrast-enhanced 3D SE images using 1-mm-thick slices are preferred for detecting brain metastases, especially small lesions (<5 mm in diameter).

Vestibular receptor cells and signal detection: bioaccelerometers and the hexagonal sampling of two-dimensional signals

NASA Technical Reports Server (NTRS)

Mugler, D. H.; Ross, M. D.

1990-01-01

The inner ear contains sensory organs which signal changes in head movement. The vestibular sacs, in particular, are sensitive to linear accelerations. Electron microscopic images have revealed the structure of tiny sensory hair bundles, whose mechanical deformation results in the initiation of neuronal activity and the transmission of electrical signals to the brain. The structure of the hair bundles is shown in this paper to be that of the most efficient two-dimensional phased-array signal processors.

Periventricular Nodular Heterotopia: Detection of Abnormal Microanatomic Fiber Structures with Whole-Brain Diffusion MR Imaging Tractography.

PubMed

Farquharson, Shawna; Tournier, J-Donald; Calamante, Fernando; Mandelstam, Simone; Burgess, Rosemary; Schneider, Michal E; Berkovic, Samuel F; Scheffer, Ingrid E; Jackson, Graeme D; Connelly, Alan

2016-12-01

Purpose To investigate whether it is possible in patients with periventricular nodular heterotopia (PVNH) to detect abnormal fiber projections that have only previously been reported in the histopathology literature. Materials and Methods Whole-brain diffusion-weighted (DW) imaging data from 14 patients with bilateral PVNH and 14 age- and sex-matched healthy control subjects were prospectively acquired by using 3.0-T magnetic resonance (MR) imaging between August 1, 2008, and December 5, 2012. All participants provided written informed consent. The DW imaging data were processed to generate whole-brain constrained spherical deconvolution (CSD)-based tractography data and super-resolution track-density imaging (TDI) maps. The tractography data were overlaid on coregistered three-dimensional T1-weighted images to visually assess regions of heterotopia. A panel of MR imaging researchers independently assessed each case and indicated numerically (no = 1, yes = 2) as to the presence of abnormal fiber tracks in nodular tissue. The Fleiss κ statistical measure was applied to assess the reader agreement. Results Abnormal fiber tracks emanating from one or more regions of heterotopia were reported by all four readers in all 14 patients with PVNH (Fleiss κ = 1). These abnormal structures were not visible on the tractography data from any of the control subjects and were not discernable on the conventional T1-weighted images of the patients with PVNH. Conclusion Whole-brain CSD-based fiber tractography and super-resolution TDI mapping reveals abnormal fiber projections in nodular tissue suggestive of abnormal organization of white matter (with abnormal fibers both within nodules and projecting to the surrounding white matter) in patients with bilateral PVNH. © RSNA, 2016.

Non-invasive detection and quantification of brain microvascular deficits by near-infrared spectroscopy in a rat model of Vascular Cognitive Impairment

NASA Astrophysics Data System (ADS)

Hallacoglu, Bertan; Sassaroli, Angelo M.; Rosenberg, Irwin H.; Troen, Aron; Fantini, Sergio

2011-02-01

Structural abnormalities in brain microvasculature are commonly associated with Alzheimer's Disease and other dementias. However, the extent to which structural microvascular abnormalities cause functional impairments in brain circulation and thereby to cognitive impairment is unclear. Non-invasive, near-infrared spectroscopy (NIRS) methods can be used to determine the absolute hemoglobin concentration and saturation in brain tissue, from which additional parameters such as cerebral blood volume (a theoretical correlate of brain microvascular density) can be derived. Validating such NIRS parameters in animal models, and understanding their relationship to cognitive function is an important step in the ultimate application of these methods to humans. To this end we applied a non-invasive multidistance NIRS method to determine the absolute concentration and saturation of cerebral hemoglobin in rat, by separately measuring absorption and reduced scattering coefficients without relying on pre- or post-correction factors. We applied this method to study brain circulation in folate deficient rats, which express brain microvascular pathology1 and which we have shown to develop cognitive impairment.2 We found absolute brain hemoglobin concentration ([HbT]) and oxygen saturation (StO2) to be significantly lower in folate deficient rats (n=6) with respect to control rats (n=5) (for [HbT]: 73+/-10 μM vs. 95+/-14 μM for StO2: 55%+/-7% vs. 66% +/-4%), implicating microvascular pathology and diminished oxygen delivery as a mechanism of cognitive impairment. More generally, our study highlights how noninvasive, absolute NIRS measurements can provide unique insight into the pathophysiology of Vascular Cognitive Impairment. Applying this method to this and other rat models of cognitive impairment will help to validate physiologically meaningful NIRS parameters for the ultimate goal of studying cerebral microvascular disease and cognitive decline in humans.

Supervised learning based multimodal MRI brain tumour segmentation using texture features from supervoxels.

PubMed

Soltaninejad, Mohammadreza; Yang, Guang; Lambrou, Tryphon; Allinson, Nigel; Jones, Timothy L; Barrick, Thomas R; Howe, Franklyn A; Ye, Xujiong

2018-04-01

Accurate segmentation of brain tumour in magnetic resonance images (MRI) is a difficult task due to various tumour types. Using information and features from multimodal MRI including structural MRI and isotropic (p) and anisotropic (q) components derived from the diffusion tensor imaging (DTI) may result in a more accurate analysis of brain images. We propose a novel 3D supervoxel based learning method for segmentation of tumour in multimodal MRI brain images (conventional MRI and DTI). Supervoxels are generated using the information across the multimodal MRI dataset. For each supervoxel, a variety of features including histograms of texton descriptor, calculated using a set of Gabor filters with different sizes and orientations, and first order intensity statistical features are extracted. Those features are fed into a random forests (RF) classifier to classify each supervoxel into tumour core, oedema or healthy brain tissue. The method is evaluated on two datasets: 1) Our clinical dataset: 11 multimodal images of patients and 2) BRATS 2013 clinical dataset: 30 multimodal images. For our clinical dataset, the average detection sensitivity of tumour (including tumour core and oedema) using multimodal MRI is 86% with balanced error rate (BER) 7%; while the Dice score for automatic tumour segmentation against ground truth is 0.84. The corresponding results of the BRATS 2013 dataset are 96%, 2% and 0.89, respectively. The method demonstrates promising results in the segmentation of brain tumour. Adding features from multimodal MRI images can largely increase the segmentation accuracy. The method provides a close match to expert delineation across all tumour grades, leading to a faster and more reproducible method of brain tumour detection and delineation to aid patient management. Copyright © 2018 Elsevier B.V. All rights reserved.

Evidence for a membrane defect in Alzheimer disease brain

NASA Technical Reports Server (NTRS)

Nitsch, R. M.; Blusztajn, J. K.; Pittas, A. G.; Slack, B. E.; Growdon, J. H.; Wurtman, R. J.

1992-01-01

To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P less than 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P less than 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine choline-phosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease.

Evaluation of biomolecular distributions in rat brain tissues by means of ToF-SIMS using a continuous beam of Ar clusters.

PubMed

Nakano, Shusuke; Yokoyama, Yuta; Aoyagi, Satoka; Himi, Naoyuki; Fletcher, John S; Lockyer, Nicholas P; Henderson, Alex; Vickerman, John C

2016-06-08

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) provides detailed chemical structure information and high spatial resolution images. Therefore, ToF-SIMS is useful for studying biological phenomena such as ischemia. In this study, in order to evaluate cerebral microinfarction, the distribution of biomolecules generated by ischemia was measured with ToF-SIMS. ToF-SIMS data sets were analyzed by means of multivariate analysis for interpreting complex samples containing unknown information and to obtain biomolecular mapping indicated by fragment ions from the target biomolecules. Using conventional ToF-SIMS (primary ion source: Bi cluster ion), it is difficult to detect secondary ions beyond approximately 1000 u. Moreover, the intensity of secondary ions related to biomolecules is not always high enough for imaging because of low concentration even if the masses are lower than 1000 u. However, for the observation of biomolecular distributions in tissues, it is important to detect low amounts of biological molecules from a particular area of tissue. Rat brain tissue samples were measured with ToF-SIMS (J105, Ionoptika, Ltd., Chandlers Ford, UK), using a continuous beam of Ar clusters as a primary ion source. ToF-SIMS with Ar clusters efficiently detects secondary ions related to biomolecules and larger molecules. Molecules detected by ToF-SIMS were examined by analyzing ToF-SIMS data using multivariate analysis. Microspheres (45 μm diameter) were injected into the rat unilateral internal carotid artery (MS rat) to cause cerebral microinfarction. The rat brain was sliced and then measured with ToF-SIMS. The brain samples of a normal rat and the MS rat were examined to find specific secondary ions related to important biomolecules, and then the difference between them was investigated. Finally, specific secondary ions were found around vessels incorporating microspheres in the MS rat. The results suggest that important biomolecules related to cerebral microinfarction can be detected by ToF-SIMS.

Glyphosate induces neurotoxicity in zebrafish.

PubMed

Roy, Nicole M; Carneiro, Bruno; Ochs, Jeremy

2016-03-01

Glyphosate based herbicides (GBH) like Roundup(®) are used extensively in agriculture as well as in urban and rural settings as a broad spectrum herbicide. Its mechanism of action was thought to be specific only to plants and thus considered safe and non-toxic. However, mounting evidence suggests that GBHs may not be as safe as once thought as initial studies in frogs suggest that GBHs may be teratogenic. Here we utilize the zebrafish vertebrate model system to study early effects of glyphosate exposure using technical grade glyphosate and the Roundup(®) Classic formulation. We find morphological abnormalities including cephalic and eye reductions and a loss of delineated brain ventricles. Concomitant with structural changes in the developing brain, using in situ hybridization analysis, we detect decreases in genes expressed in the eye, fore and midbrain regions of the brain including pax2, pax6, otx2 and ephA4. However, we do not detect changes in hindbrain expression domains of ephA4 nor exclusive hindbrain markers krox-20 and hoxb1a. Additionally, using a Retinoic Acid (RA) mediated reporter transgenic, we detect no alterations in the RA expression domains in the hindbrain and spinal cord, but do detect a loss of expression in the retina. We conclude that glyphosate and the Roundup(®) formulation is developmentally toxic to the forebrain and midbrain but does not affect the hindbrain after 24 h exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

A novel application of the fluorescent dye bis-ANS for labeling neurons in acute brain slices.

PubMed

Mozes, Emese; Hunya, Akos; Toth, Aniko; Ayaydin, Ferhan; Penke, Botond; Datki, Zsolt L

2011-10-10

The cell-impermeant oligomer-(e.g. beta-amyloid-, or tubulin-) specific fluorescent dye, bis-ANS (4,4'-bis-1-anilinonaphtalene-8-sulfonate), was successfully used for labeling mechanically damaged but still viable neuron bodies, neurites and neurite cross sections in acute brain slices. Acute hippocampal brain slices of rats were co-stained with bis-ANS and the cell-impermeant, DNA-specific dye propidium iodide (PI) and were then analyzed using fluorescence and confocal microscopes. Both the neuron bodies and the neurites were found to exhibit increased fluorescence intensities, suggesting that using this method they can be detected more easily. In addition, bis-ANS showed good region - but not cell specific co-localization with the neuron-specific fluorescent dye Dil (1,1'-Dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate). These two dyes label different neuronal structures: Dil binds specifically to intact cell membranes while bis-ANS can enter cells with compromised cell membranes and then stain the microtubules in the cytoplasm. For a quick (10min) staining of acute brain slices with bis-ANS both HEPES and NaHCO(3) were needed in order to achieve high signal intensity. Labeling with bis-ANS fluorescent dye is an easy method for imaging the neuronal structures on the surface of acute brain slices. Copyright © 2011 Elsevier Inc. All rights reserved.

Optical coherence tomography and optical coherence domain reflectometry for deep brain stimulation probe guidance

NASA Astrophysics Data System (ADS)

Jeon, Sung W.; Shure, Mark A.; Baker, Kenneth B.; Chahlavi, Ali; Hatoum, Nagi; Turbay, Massud; Rollins, Andrew M.; Rezai, Ali R.; Huang, David

2005-04-01

Deep Brain Stimulation (DBS) is FDA-approved for the treatment of Parkinson's disease and essential tremor. Currently, placement of DBS leads is guided through a combination of anatomical targeting and intraoperative microelectrode recordings. The physiological mapping process requires several hours, and each pass of the microelectrode into the brain increases the risk of hemorrhage. Optical Coherence Domain Reflectometry (OCDR) in combination with current methodologies could reduce surgical time and increase accuracy and safety by providing data on structures some distance ahead of the probe. For this preliminary study, we scanned a rat brain in vitro using polarization-insensitive Optical Coherence Tomography (OCT). For accurate measurement of intensity and attenuation, polarization effects arising from tissue birefringence are removed by polarization diversity detection. A fresh rat brain was sectioned along the coronal plane and immersed in a 5 mm cuvette with saline solution. OCT images from a 1294 nm light source showed depth profiles up to 2 mm. Light intensity and attenuation rate distinguished various tissue structures such as hippocampus, cortex, external capsule, internal capsule, and optic tract. Attenuation coefficient is determined by linear fitting of the single scattering regime in averaged A-scans where Beer"s law is applicable. Histology showed very good correlation with OCT images. From the preliminary study using OCT, we conclude that OCDR is a promising approach for guiding DBS probe placement.

Nuclear microscopy in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Makjanic, Jagoda; Watt, Frank

1999-04-01

The elemental composition of the two types of brain lesions which characterise Alzheimer's disease (AD) has been the subject of intense scrutiny over the last decade, ever since it was proposed that inorganic trace elements, particularly aluminium, might be implicated in the pathogenesis of the disease. The major evidence for this involvement was the detection of aluminium in the characteristic lesions of the AD brain; neuritic plaques and neurofibrillary tangles (NFTs). Using the powerful combination of Particle-Induced X-ray Emission (PIXE), Rutherford Backscattering Spectrometry (RBS) and Scanning Transmission Ion Microscopy (STIM), it is possible to image and analyse structures in brain sections without recourse to chemical staining. Previous results on elemental composition of senile plaques indicated the absence of aluminium at the 15 parts per million level. We have more recently focused on the analysis of neurofibrillary tangles (NFTs), destructive structural defects within neurons. Imaging and analysis of neurons in brain tissue presented a greater challenge due to the small dimensional size compared with the plaques. We describe the methodology and the results of imaging and analysing neurons in brain tissue sections using Nuclear Microscopy. Our results show that aluminium is not present in either neurons or surrounding tissue in unstained sections at the 20 ppm level, but can be observed in stained sections. We also report elemental concentrations showing significant elevations of phosphorus, sulphur, chlorine, iron and zinc.

A Blood-Brain Barrier (BBB) Disrupter Is Also a Potent α-Synuclein (α-syn) Aggregation Inhibitor

PubMed Central

Shaltiel-Karyo, Ronit; Frenkel-Pinter, Moran; Rockenstein, Edward; Patrick, Christina; Levy-Sakin, Michal; Schiller, Abigail; Egoz-Matia, Nirit; Masliah, Eliezer; Segal, Daniel; Gazit, Ehud

2013-01-01

The development of disease-modifying therapy for Parkinson disease has been a main drug development challenge, including the need to deliver the therapeutic agents to the brain. Here, we examined the ability of mannitol to interfere with the aggregation process of α-synuclein in vitro and in vivo in addition to its blood-brain barrier-disrupting properties. Using in vitro studies, we demonstrated the effect of mannitol on α-synuclein aggregation. Although low concentration of mannitol inhibited the formation of fibrils, high concentration significantly decreased the formation of tetramers and high molecular weight oligomers and shifted the secondary structure of α-synuclein from α-helical to a different structure, suggesting alternative potential pathways for aggregation. When administered to a Parkinson Drosophila model, mannitol dramatically corrected its behavioral defects and reduced the amount of α-synuclein aggregates in the brains of treated flies. In the mThy1-human α-synuclein transgenic mouse model, a decrease in α-synuclein accumulation was detected in several brain regions following treatment, suggesting that mannitol promotes α-synuclein clearance in the cell bodies. It appears that mannitol has a general neuroprotective effect in the transgenic treated mice, which includes the dopaminergic system. We therefore suggest mannitol as a basis for a dual mechanism therapeutic agent for the treatment of Parkinson disease. PMID:23637226

A blood-brain barrier (BBB) disrupter is also a potent α-synuclein (α-syn) aggregation inhibitor: a novel dual mechanism of mannitol for the treatment of Parkinson disease (PD).

PubMed

Shaltiel-Karyo, Ronit; Frenkel-Pinter, Moran; Rockenstein, Edward; Patrick, Christina; Levy-Sakin, Michal; Schiller, Abigail; Egoz-Matia, Nirit; Masliah, Eliezer; Segal, Daniel; Gazit, Ehud

2013-06-14

The development of disease-modifying therapy for Parkinson disease has been a main drug development challenge, including the need to deliver the therapeutic agents to the brain. Here, we examined the ability of mannitol to interfere with the aggregation process of α-synuclein in vitro and in vivo in addition to its blood-brain barrier-disrupting properties. Using in vitro studies, we demonstrated the effect of mannitol on α-synuclein aggregation. Although low concentration of mannitol inhibited the formation of fibrils, high concentration significantly decreased the formation of tetramers and high molecular weight oligomers and shifted the secondary structure of α-synuclein from α-helical to a different structure, suggesting alternative potential pathways for aggregation. When administered to a Parkinson Drosophila model, mannitol dramatically corrected its behavioral defects and reduced the amount of α-synuclein aggregates in the brains of treated flies. In the mThy1-human α-synuclein transgenic mouse model, a decrease in α-synuclein accumulation was detected in several brain regions following treatment, suggesting that mannitol promotes α-synuclein clearance in the cell bodies. It appears that mannitol has a general neuroprotective effect in the transgenic treated mice, which includes the dopaminergic system. We therefore suggest mannitol as a basis for a dual mechanism therapeutic agent for the treatment of Parkinson disease.

Research Review: Neural response to threat in children, adolescents, and adults after child maltreatment - a quantitative meta-analysis.

PubMed

Hein, Tyler C; Monk, Christopher S

2017-03-01

Child maltreatment is common and has long-term consequences for affective function. Investigations of neural consequences of maltreatment have focused on the amygdala. However, developmental neuroscience indicates that other brain regions are also likely to be affected by child maltreatment, particularly in the social information processing network (SIPN). We conducted a quantitative meta-analysis to: confirm that maltreatment is related to greater bilateral amygdala activation in a large sample that was pooled across studies; investigate other SIPN structures that are likely candidates for altered function; and conduct a data-driven examination to identify additional regions that show altered activation in maltreated children, teens, and adults. We conducted an activation likelihood estimation analysis with 1,733 participants across 20 studies of emotion processing in maltreated individuals. Maltreatment is associated with increased bilateral amygdala activation to emotional faces. One SIPN structure is altered: superior temporal gyrus, of the detection node, is hyperactive in maltreated individuals. The results of the whole-brain corrected analysis also show hyperactivation of the parahippocampal gyrus and insula in maltreated individuals. The meta-analysis confirms that maltreatment is related to increased bilateral amygdala reactivity and also shows that maltreatment affects multiple additional structures in the brain that have received little attention in the literature. Thus, although the majority of studies examining maltreatment and brain function have focused on the amygdala, these findings indicate that the neural consequences of child maltreatment involve a broader network of structures. © 2016 Association for Child and Adolescent Mental Health.

Evaluation of Morphological Plasticity in the Cerebella of Basketball Players with MRI

PubMed Central

Park, In Sung; Han, Jong Woo; Lee, Kea Joo; Lee, Nam Joon; Lee, Won Teak; Park, Kyung Ah

2006-01-01

Cerebellum is a key structure involved in motor learning and coordination. In animal models, motor skill learning increased the volume of molecular layer and the number of synapses on Purkinje cells in the cerebellar cortex. The aim of this study is to investigate whether the analogous change of cerebellar volume occurs in human population who learn specialized motor skills and practice them intensively for a long time. Magnetic resonance image (MRI)-based cerebellar volumetry was performed in basketball players and matched controls with V-works image software. Total brain volume, absolute and relative cerebellar volumes were compared between two groups. There was no significant group difference in the total brain volume, the absolute and the relative cerebellar volume. Thus we could not detect structural change in the cerebellum of this athlete group in the macroscopic level. PMID:16614526

Non-invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognitive Functions

DTIC Science & Technology

2017-05-14

AFRL-AFOSR-JP-TR-2017-0052 Non-invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions...invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions 5a.  CONTRACT NUMBER 5b.  GRANT...SUPPLEMENTARY NOTES 14. ABSTRACT Brain stress level measurement (non-invasively) in quantitative term is very helpful to correlate with various

Non invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions

DTIC Science & Technology

2017-05-14

AFRL-AFOSR-JP-TR-2017-0052 Non-invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions...invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions 5a.  CONTRACT NUMBER 5b.  GRANT...SUPPLEMENTARY NOTES 14. ABSTRACT Brain stress level measurement (non-invasively) in quantitative term is very helpful to correlate with various

Abnormal functional connectivity of EEG gamma band in patients with depression during emotional face processing.

PubMed

Li, Yingjie; Cao, Dan; Wei, Ling; Tang, Yingying; Wang, Jijun

2015-11-01

This paper evaluates the large-scale structure of functional brain networks using graph theoretical concepts and investigates the difference in brain functional networks between patients with depression and healthy controls while they were processing emotional stimuli. Electroencephalography (EEG) activities were recorded from 16 patients with depression and 14 healthy controls when they performed a spatial search task for facial expressions. Correlations between all possible pairs of 59 electrodes were determined by coherence, and the coherence matrices were calculated in delta, theta, alpha, beta, and gamma bands (low gamma: 30-50Hz and high gamma: 50-80Hz, respectively). Graph theoretical analysis was applied to these matrices by using two indexes: the clustering coefficient and the characteristic path length. The global EEG coherence of patients with depression was significantly higher than that of healthy controls in both gamma bands, especially in the high gamma band. The global coherence in both gamma bands from healthy controls appeared higher in negative conditions than in positive conditions. All the brain networks were found to hold a regular and ordered topology during emotion processing. However, the brain network of patients with depression appeared randomized compared with the normal one. The abnormal network topology of patients with depression was detected in both the prefrontal and occipital regions. The negative bias from healthy controls occurred in both gamma bands during emotion processing, while it disappeared in patients with depression. The proposed work studied abnormally increased connectivity of brain functional networks in patients with depression. By combing the clustering coefficient and the characteristic path length, we found that the brain networks of patients with depression and healthy controls had regular networks during emotion processing. Yet the brain networks of the depressed group presented randomization trends. Moreover, negative bias was detected in the healthy controls during emotion processing, while it was not detected in patients with depression, which might be related to the types of negative stimuli used in this study. The brain networks from both patients with depression and healthy controls were found to hold a regular and ordered topology. Yet the brain networks of patients with depression had randomization trends. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Structural studies of human glioma pathogenesis-related protein 1

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

Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu; Koski, Raymond A.; Bonafé, Nathalie

2011-10-01

Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structuresmore » of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn{sup 2+} complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn{sup 2+} similarly to snake-venom CRISPs, which are involved in Zn{sup 2+}-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.« less

Independent movement, dimerization and stability of tandem repeats of chicken brain alpha-spectrin

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

Kusunoki, H.; Minasov, G.; Macdonald, R.I.

Previous X-ray crystal structures have shown that linkers of five amino acid residues connecting pairs of chicken brain {alpha}-spectrin and human erythroid {beta}-spectrin repeats can undergo bending without losing their {alpha}-helical structure. To test whether bending at one linker can influence bending at an adjacent linker, the structures of two and three repeat fragments of chicken brain {alpha}-spectrin have been determined by X-ray crystallography. The structure of the three-repeat fragment clearly shows that bending at one linker can occur independently of bending at an adjacent linker. This observation increases the possible trajectories of modeled chains of spectrin repeats. Furthermore, themore » three-repeat molecule crystallized as an antiparallel dimer with a significantly smaller buried interfacial area than that of {alpha}-actinin, a spectrin-related molecule, but large enough and of a type indicating biological specificity. Comparison of the structures of the spectrin and {alpha}-actinin dimers supports weak association of the former, which could not be detected by analytical ultracentrifugation, versus strong association of the latter, which has been observed by others. To correlate features of the structure with solution properties and to test a previous model of stable spectrin and dystrophin repeats, the number of inter-helical interactions in each repeat of several spectrin structures were counted and compared to their thermal stabilities. Inter-helical interactions, but not all interactions, increased in parallel with measured thermal stabilities of each repeat and in agreement with the thermal stabilities of two and three repeats and also partial repeats of spectrin.« less

Quantitative evaluation of brain development using anatomical MRI and diffusion tensor imaging☆

PubMed Central

Oishi, Kenichi; Faria, Andreia V.; Yoshida, Shoko; Chang, Linda; Mori, Susumu

2013-01-01

The development of the brain is structure-specific, and the growth rate of each structure differs depending on the age of the subject. Magnetic resonance imaging (MRI) is often used to evaluate brain development because of the high spatial resolution and contrast that enable the observation of structure-specific developmental status. Currently, most clinical MRIs are evaluated qualitatively to assist in the clinical decision-making and diagnosis. The clinical MRI report usually does not provide quantitative values that can be used to monitor developmental status. Recently, the importance of image quantification to detect and evaluate mild-to-moderate anatomical abnormalities has been emphasized because these alterations are possibly related to several psychiatric disorders and learning disabilities. In the research arena, structural MRI and diffusion tensor imaging (DTI) have been widely applied to quantify brain development of the pediatric population. To interpret the values from these MR modalities, a “growth percentile chart,” which describes the mean and standard deviation of the normal developmental curve for each anatomical structure, is required. Although efforts have been made to create such a growth percentile chart based on MRI and DTI, one of the greatest challenges is to standardize the anatomical boundaries of the measured anatomical structures. To avoid inter- and intra-reader variability about the anatomical boundary definition, and hence, to increase the precision of quantitative measurements, an automated structure parcellation method, customized for the neonatal and pediatric population, has been developed. This method enables quantification of multiple MR modalities using a common analytic framework. In this paper, the attempt to create an MRI- and a DTI-based growth percentile chart, followed by an application to investigate developmental abnormalities related to cerebral palsy, Williams syndrome, and Rett syndrome, have been introduced. Future directions include multimodal image analysis and personalization for clinical application. PMID:23796902

EEG resolutions in detecting and decoding finger movements from spectral analysis

PubMed Central

Xiao, Ran; Ding, Lei

2015-01-01

Mu/beta rhythms are well-studied brain activities that originate from sensorimotor cortices. These rhythms reveal spectral changes in alpha and beta bands induced by movements of different body parts, e.g., hands and limbs, in electroencephalography (EEG) signals. However, less can be revealed in them about movements of different fine body parts that activate adjacent brain regions, such as individual fingers from one hand. Several studies have reported spatial and temporal couplings of rhythmic activities at different frequency bands, suggesting the existence of well-defined spectral structures across multiple frequency bands. In the present study, spectral principal component analysis (PCA) was applied on EEG data, obtained from a finger movement task, to identify cross-frequency spectral structures. Features from identified spectral structures were examined in their spatial patterns, cross-condition pattern changes, detection capability of finger movements from resting, and decoding performance of individual finger movements in comparison to classic mu/beta rhythms. These new features reveal some similar, but more different spatial and spectral patterns as compared with classic mu/beta rhythms. Decoding results further indicate that these new features (91%) can detect finger movements much better than classic mu/beta rhythms (75.6%). More importantly, these new features reveal discriminative information about movements of different fingers (fine body-part movements), which is not available in classic mu/beta rhythms. The capability in decoding fingers (and hand gestures in the future) from EEG will contribute significantly to the development of non-invasive BCI and neuroprosthesis with intuitive and flexible controls. PMID:26388720

[The Application of Magnetic Resonance Imaging in Alzheimer's Disease].

PubMed

Matsuda, Hiroshi

2017-07-01

In Alzheimer's disease (AD), magnetic resonance imaging (MRI) is essential for early diagnosis, differential diagnosis, and evaluation of disease progression. In structural MRI, the automatic diagnosis of atrophy by computers, even when it is not visually noticeable, is possible in daily clinical practice. Furthermore, subfield volumetric measurements of the medial temporal structures, as well as longitudinal volume measurements with high accuracy, have been developed and are useful for calculating the needed sample size in clinical trials. In addition to detecting local atrophy, graph theory has been applied to structural MRI for evaluation of alterations of the brain networks potentially affected in AD.

Subcortical shape and volume abnormalities in an elderly HIV+ cohort

NASA Astrophysics Data System (ADS)

Wade, Benjamin S. C.; Valcour, Victor; Busovaca, Edgar; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H.; Wang, Yalin; Thompson, Paul M.

2015-03-01

Over 50% of HIV+ individuals show significant impairment in psychomotor functioning, processing speed, working memory and attention [1, 2]. Patients receiving combination antiretroviral therapy may still have subcortical atrophy, but the profile of HIV-associated brain changes is poorly understood. With parametric surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV+ subjects (4 female; age=65.35 ± 2.21) and 31 uninfected elderly controls (2 female; age=64.68 ± 4.57) scanned with MRI as part of a San Francisco Bay Area study of elderly people with HIV. We also investigated whether morphometry was associated with nadir CD4+ (T-cell) counts, viral load and illness duration among HIV+ participants. FreeSurfer was used to segment the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, accumbens, brainstem, callosum and ventricles from brain MRI scans. To study subcortical shape, we analyzed: (1) the Jacobian determinant (JD) indexed over structures' surface coordinates and (2) radial distances (RD) of structure surfaces from a medial curve. A JD less than 1 reflects regional tissue atrophy and greater than 1 reflects expansion. The volumes of several subcortical regions were found to be associated with HIV status. No regional volumes showed detectable associations with CD4 counts, viral load or illness duration. The shapes of numerous subcortical regions were significantly linked to HIV status, detectability of viral RNA and illness duration. Our results show subcortical brain differences in HIV+ subjects in both shape and volumetric domains.

Comparison between cerebrospinal fluid and serum lactate concentrations in neurologic dogs with and without structural intracranial disease.

PubMed

Benedicenti, Leontine; Gianotti, Giacomo; Galban, Evelyn M

2018-04-01

The objectives of this study were to investigate the relationship between cerebrospinal fluid lactate and serum concentrations in dogs with clinical signs of central nervous system disease and to establish if cerebrospinal fluid lactate (CSF) concentrations are higher in dogs with structural intracranial disease (Group Pos-MRI) compared to dogs that have clinical signs of intracranial disease but no structural brain disease (Group Neg-MRI) based on magnetic resonance imaging (MRI) findings. Using a prospective study canine blood and cerebrospinal fluid were collected in 24 dogs with neurological signs after undergoing brain MRI. Dogs were divided in 2 groups. No significant difference between serum lactate (1.57 ± 0.9 mmol/L) and CSF lactate concentration (1.34 ± 0.3 mmol/L) was detected. There was a direct correlation between CSF and serum lactate concentration ( R = 0.731; P = 0.01). No significant difference was found in CSF lactate concentration between the 2 groups of dogs ( P = 0.13).

[3D FSPGR (fast spoiled gradient echo) magnetic resonance imaging in the diagnosis of focal cortical dysplasia in children].

PubMed

Alikhanov, A A; Sinitsyn, V E; Perepelova, E M; Mukhin, K Iu; Demushkina, A A; Omarova, M O; Piliia, S V

2001-01-01

Small dysplastic lesions of the cerebral cortex are often missed by conventional MRI methods. The identification of subtle structural abnormalities by traditional multiplanar rectilinear slices is often limited by the complex convolutional pattern of the brain. We used a method of FSPGR (fast spoiled gradient-echo) of three-dimensional MRI data that improves the anatomical display of the sulcal structure of the hemispheric convexities. It also reduces the asymmetric sampling of gray-white matter that may lead to false-positive results. We present 5 from 12 patients with dysplastic cortical lesions in whom conventional two-dimensional and three-dimensional MRI with multiplanar reformatting was initially considered normal. Subsequent studies using 3D FSPGR identified various types of focal cortical dysplasia in all. These results indicate that an increase in the detection of subtle focal dysplastic lesions may be accomplished when one improves the anatomical display of the brain sulcal structure by performing 3D FSPGR.

Discovering Event Structure in Continuous Narrative Perception and Memory.

PubMed

Baldassano, Christopher; Chen, Janice; Zadbood, Asieh; Pillow, Jonathan W; Hasson, Uri; Norman, Kenneth A

2017-08-02

During realistic, continuous perception, humans automatically segment experiences into discrete events. Using a novel model of cortical event dynamics, we investigate how cortical structures generate event representations during narrative perception and how these events are stored to and retrieved from memory. Our data-driven approach allows us to detect event boundaries as shifts between stable patterns of brain activity without relying on stimulus annotations and reveals a nested hierarchy from short events in sensory regions to long events in high-order areas (including angular gyrus and posterior medial cortex), which represent abstract, multimodal situation models. High-order event boundaries are coupled to increases in hippocampal activity, which predict pattern reinstatement during later free recall. These areas also show evidence of anticipatory reinstatement as subjects listen to a familiar narrative. Based on these results, we propose that brain activity is naturally structured into nested events, which form the basis of long-term memory representations. Copyright © 2017 Elsevier Inc. All rights reserved.

Cystatin C takes part in melanoma-microglia cross-talk: possible implications for brain metastasis.

PubMed

Moshe, Adi; Izraely, Sivan; Sagi-Assif, Orit; Prakash, Roshini; Telerman, Alona; Meshel, Tsipi; Carmichael, Thomas; Witz, Isaac P

2018-05-02

The development of melanoma brain metastasis is largely dependent on mutual interactions between the melanoma cells and cells in the brain microenvironment. Here, we report that the extracellular cysteine protease inhibitor cystatin C (CysC) is involved in these interactions. Microglia-derived factors upregulated CysC secretion by melanoma. Similarly, melanoma-derived factors upregulated CysC secretion by microglia. Whereas CysC enhanced melanoma cell migration through a layer of brain endothelial cells, it inhibited the migration of microglia cells toward melanoma cells. CysC was also found to promote the formation of melanoma three-dimensional structures in matrigel. IHC analysis revealed increased expression levels of CysC in the brain of immune-deficient mice bearing xenografted human melanoma brain metastasis compared to the brain of control mice. Based on these in vitro and in vivo experiments we hypothesize that CysC promotes melanoma brain metastasis. Increased expression levels of CysC were detected in the regenerating brain of mice after stroke. Post-stroke brain with melanoma brain metastasis showed an even stronger expression of CysC. The in vitro induction of stroke-like conditions in brain microenvironmental cells increased the levels of CysC in the secretome of microglia cells, but not in the secretome of brain endothelial cells. The similarities between melanoma brain metastasis and stroke with respect to CysC expression by and secretion from microglia cells suggest that CysC may be involved in shared pathways between brain metastasis and post-stroke regeneration. This manifests the tendency of tumor cells to highjack physiological molecular pathways in their progression.

Cloning of the cocaine-sensitive bovine dopamine transporter

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

Usdin, T.B.; Chen, C.; Brownstein, M.J.

1991-12-15

A cDNA encoding the dopamine transporter from bovine brain substantia nigra was identified on the basis of its structural homology to other, recently cloned, neurotransmitter transporters. The sequence of the 693-amino acid protein is quite similar to those of the rat {gamma}-aminobutyric acid, human norepinephrine, and rat serotonin transporters. Dopamine transporter mRNA was detected by in situ hybridization in the substantia nigra but not in the locus coeruleus, raphe, caudate, or other brain areas. ({sup 3}H)Dopamine accumulation in tissue culture cells transfected with the cDNA was inhibited by amphetamine, cocaine, and specific inhibitors of dopamine transports, including GBR12909.

Morphometry Based on Effective and Accurate Correspondences of Localized Patterns (MEACOLP)

PubMed Central

Wang, Hu; Ren, Yanshuang; Bai, Lijun; Zhang, Wensheng; Tian, Jie

2012-01-01

Local features in volumetric images have been used to identify correspondences of localized anatomical structures for brain morphometry. However, the correspondences are often sparse thus ineffective in reflecting the underlying structures, making it unreliable to evaluate specific morphological differences. This paper presents a morphometry method (MEACOLP) based on correspondences with improved effectiveness and accuracy. A novel two-level scale-invariant feature transform is used to enhance the detection repeatability of local features and to recall the correspondences that might be missed in previous studies. Template patterns whose correspondences could be commonly identified in each group are constructed to serve as the basis for morphometric analysis. A matching algorithm is developed to reduce the identification errors by comparing neighboring local features and rejecting unreliable matches. The two-sample t-test is finally adopted to analyze specific properties of the template patterns. Experiments are performed on the public OASIS database to clinically analyze brain images of Alzheimer's disease (AD) and normal controls (NC). MEACOLP automatically identifies known morphological differences between AD and NC brains, and characterizes the differences well as the scaling and translation of underlying structures. Most of the significant differences are identified in only a single hemisphere, indicating that AD-related structures are characterized by strong anatomical asymmetry. In addition, classification trials to differentiate AD subjects from NC confirm that the morphological differences are reliably related to the groups of interest. PMID:22540000

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice.

PubMed

Akers, Katherine G; Kushner, Steven A; Leslie, Ana T; Clarke, Laura; van der Kooy, Derek; Lerch, Jason P; Frankland, Paul W

2011-07-07

Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.

Spatial patterns of brain amyloid-beta burden and atrophy rate associations in mild cognitive impairment.

PubMed

Tosun, Duygu; Schuff, Norbert; Mathis, Chester A; Jagust, William; Weiner, Michael W

2011-04-01

Amyloid-β accumulation in the brain is thought to be one of the earliest events in Alzheimer's disease, possibly leading to synaptic dysfunction, neurodegeneration and cognitive/functional decline. The earliest detectable changes seen with neuroimaging appear to be amyloid-β accumulation detected by (11)C-labelled Pittsburgh compound B positron emission tomography imaging. However, some individuals tolerate high brain amyloid-β loads without developing symptoms, while others progressively decline, suggesting that events in the brain downstream from amyloid-β deposition, such as regional brain atrophy rates, play an important role. The main purpose of this study was to understand the relationship between the regional distributions of increased amyloid-β and the regional distribution of increased brain atrophy rates in patients with mild cognitive impairment. To simultaneously capture the spatial distributions of amyloid-β and brain atrophy rates, we employed the statistical concept of parallel independent component analysis, an effective method for joint analysis of multimodal imaging data. Parallel independent component analysis identified significant relationships between two patterns of amyloid-β deposition and atrophy rates: (i) increased amyloid-β burden in the left precuneus/cuneus and medial-temporal regions was associated with increased brain atrophy rates in the left medial-temporal and parietal regions; and (ii) in contrast, increased amyloid-β burden in bilateral precuneus/cuneus and parietal regions was associated with increased brain atrophy rates in the right medial temporal regions. The spatial distribution of increased amyloid-β and the associated spatial distribution of increased brain atrophy rates embrace a characteristic pattern of brain structures known for a high vulnerability to Alzheimer's disease pathology, encouraging for the use of (11)C-labelled Pittsburgh compound B positron emission tomography measures as early indicators of Alzheimer's disease. These results may begin to shed light on the mechanisms by which amyloid-β deposition leads to neurodegeneration and cognitive decline and the development of a more specific Alzheimer's disease-specific imaging signature for diagnosis and use of this knowledge in the development of new anti-therapies for Alzheimer's disease.

Automatic Brain Tumor Detection in T2-weighted Magnetic Resonance Images

NASA Astrophysics Data System (ADS)

Dvořák, P.; Kropatsch, W. G.; Bartušek, K.

2013-10-01

This work focuses on fully automatic detection of brain tumors. The first aim is to determine, whether the image contains a brain with a tumor, and if it does, localize it. The goal of this work is not the exact segmentation of tumors, but the localization of their approximate position. The test database contains 203 T2-weighted images of which 131 are images of healthy brain and the remaining 72 images contain brain with pathological area. The estimation, whether the image shows an afflicted brain and where a pathological area is, is done by multi resolution symmetry analysis. The first goal was tested by five-fold cross-validation technique with 100 repetitions to avoid the result dependency on sample order. This part of the proposed method reaches the true positive rate of 87.52% and the true negative rate of 93.14% for an afflicted brain detection. The evaluation of the second part of the algorithm was carried out by comparing the estimated location to the true tumor location. The detection of the tumor location reaches the rate of 95.83% of correct anomaly detection and the rate 87.5% of correct tumor location.

MRI assessment of whole-brain structural changes in aging.

PubMed

Guo, Hui; Siu, William; D'Arcy, Ryan Cn; Black, Sandra E; Grajauskas, Lukas A; Singh, Sonia; Zhang, Yunting; Rockwood, Kenneth; Song, Xiaowei

2017-01-01

One of the central features of brain aging is the accumulation of multiple age-related structural changes, which occur heterogeneously in individuals and can have immediate or potential clinical consequences. Each of these deficits can coexist and interact, producing both independent and additive impacts on brain health. Many of the changes can be visualized using MRI. To collectively assess whole-brain structural changes, the MRI-based Brain Atrophy and Lesion Index (BALI) has been developed. In this study, we validate this whole-brain health assessment approach using several clinical MRI examinations. Data came from three independent studies: the Alzheimer's Disease Neuroimaging Initiative Phase II (n=950; women =47.9%; age =72.7±7.4 years); the National Alzheimer's Coordinating Center (n=722; women =55.1%; age =72.7±9.9 years); and the Tianjin Medical University General Hospital Research database on older adults (n=170; women =60.0%; age =62.9±9.3 years). The 3.0-Tesla MRI scans were evaluated using the BALI rating scheme on the basis of T1-weighted (T1WI), T2-weighted (T2WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), and T2*-weighted gradient-recalled echo (T2*GRE) images. Atrophy and lesion changes were commonly seen in each MRI test. The BALI scores based on different sequences were highly correlated (Spearman r 2 >0.69; P <0.00001). They were associated with age ( r 2 >0.29; P <0.00001) and differed by cognitive status ( χ 2 >26.48, P <0.00001). T2-FLAIR revealed a greater level of periventricular ( χ 2 =29.09) and deep white matter ( χ 2 =26.65, P <0.001) lesions than others, but missed revealing certain dilated perivascular spaces that were seen in T2WI ( P <0.001). Microhemorrhages occurred in 15.3% of the sample examined and were detected using only T2*GRE. The T1WI- and T2WI-based BALI evaluations consistently identified the burden of aging and dementia-related decline of structural brain health. Inclusion of additional MRI tests increased lesion differentiation. Further research is to integrate MRI tests for a clinical tool to aid the diagnosis and intervention of brain aging.

Direct mapping of 19F in 19FDG-6P in brain tissue at subcellular resolution using soft X-ray fluorescence

NASA Astrophysics Data System (ADS)

Poitry-Yamate, C.; Gianoncelli, A.; Kourousias, G.; Kaulich, B.; Lepore, M.; Gruetter, R.; Kiskinova, M.

2013-10-01

Low energy x-ray fluorescence (LEXRF) detection was optimized for imaging cerebral glucose metabolism by mapping the fluorine LEXRF signal of 19F in 19FDG, trapped as intracellular 19F-deoxyglucose-6-phosphate (19FDG-6P) at 1μm spatial resolution from 3μm thick brain slices. 19FDG metabolism was evaluated in brain structures closely resembling the general cerebral cytoarchitecture following formalin fixation of brain slices and their inclusion in an epon matrix. 2-dimensional distribution maps of 19FDG-6P were placed in a cytoarchitectural and morphological context by simultaneous LEXRF mapping of N and O, and scanning transmission x-ray (STXM) imaging. A disproportionately high uptake and metabolism of glucose was found in neuropil relative to intracellular domains of the cell body of hypothalamic neurons, showing directly that neurons, like glial cells, also metabolize glucose. As 19F-deoxyglucose-6P is structurally identical to 18F-deoxyglucose-6P, LEXRF of subcellular 19F provides a link to in vivo 18FDG PET, forming a novel basis for understanding the physiological mechanisms underlying the 18FDG PET image, and the contribution of neurons and glia to the PET signal.

High-resolution x-ray absorption spectroscopy studies of metal compounds in neurodegenerative brain tissue

NASA Astrophysics Data System (ADS)

Collingwood, J. F.; Mikhaylova, A.; Davidson, M. R.; Batich, C.; Streit, W. J.; Eskin, T.; Terry, J.; Barrea, R.; Underhill, R. S.; Dobson, J.

2005-01-01

Fluorescence mapping and microfocus X-ray absorption spectroscopy are used to detect, locate and identify iron biominerals and other inorganic metal accumulations in neurodegenerative brain tissue at sub-cellular resolution (<5 microns). Recent progress in developing the technique is reviewed. Synchrotron X-rays are used to map tissue sections for metals of interest, and XANES and XAFS are used to characterise anomalous concentrations of the metals in-situ so that they can be correlated with tissue structures and disease pathology. Iron anomalies associated with biogenic magnetite, ferritin and haemoglobin are located and identified in an avian tissue model with a pixel resolution ~5 microns. Subsequent studies include brain tissue sections from transgenic Huntington's mice, and the first high-resolution mapping and identification of iron biominerals in human Alzheimer's and control autopsy brain tissue. Technical developments include use of microfocus diffraction to obtain structural information about biominerals in-situ, and depositing sample location grids by lithography for the location of anomalies by conventional microscopy. The combined techniques provide a breakthrough in the study of both intra- and extra-cellular iron compounds and related metals in tissue. The information to be gained from this approach has implications for future diagnosis and treatment of neurodegeneration, and for our understanding of the mechanisms involved.

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

PubMed Central

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

2014-01-01

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

Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease.

PubMed

Muñoz-Moreno, Emma; Tudela, Raúl; López-Gil, Xavier; Soria, Guadalupe

2018-02-07

Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain connectivity at an early stage (5 months of age) before a significant concentration of β-amyloid plaques is present. Cognitive abilities were assessed by a delayed nonmatch-to-sample (DNMS) task preceded by a training phase where the animals learned the task. The number of training sessions required to achieve a learning criterion was recorded and evaluated. After DNMS, MRI acquisition was performed, including diffusion-weighted MRI and resting-state functional MRI, which were processed to obtain the structural and functional connectomes, respectively. Global and regional graph metrics were computed to evaluate network organization in both transgenic and control rats. The results pointed to a delay in learning the working memory-related task in the AD rats, which also completed a lower number of trials in the DNMS task. Regarding connectivity properties, less efficient organization of the structural brain networks of the transgenic rats with respect to controls was observed. Specific regional differences in connectivity were identified in both structural and functional networks. In addition, a strong correlation was observed between cognitive performance and brain networks, including whole-brain structural connectivity as well as functional and structural network metrics of regions related to memory and reward processes. In this study, connectivity and neurocognitive impairments were identified in TgF344-AD rats at a very early stage of the disease when most of the pathological hallmarks have not yet been detected. Structural and functional network metrics of regions related to reward, memory, and sensory performance were strongly correlated with the cognitive outcome. The use of animal models is essential for the early identification of these alterations and can contribute to the development of early biomarkers of the disease based on MRI connectomics.

Top-down and bottom-up modulation of brain structures involved in auditory discrimination.

PubMed

Diekhof, Esther K; Biedermann, Franziska; Ruebsamen, Rudolf; Gruber, Oliver

2009-11-10

Auditory deviancy detection comprises both automatic and voluntary processing. Here, we investigated the neural correlates of different components of the sensory discrimination process using functional magnetic resonance imaging. Subliminal auditory processing of deviant events that were not detected led to activation in left superior temporal gyrus. On the other hand, both correct detection of deviancy and false alarms activated a frontoparietal network of attentional processing and response selection, i.e. this network was activated regardless of the physical presence of deviant events. Finally, activation in the putamen, anterior cingulate and middle temporal cortex depended on factual stimulus representations and occurred only during correct deviancy detection. These results indicate that sensory discrimination may rely on dynamic bottom-up and top-down interactions.

Inter-subject phase synchronization for exploratory analysis of task-fMRI.

PubMed

Bolt, Taylor; Nomi, Jason S; Vij, Shruti G; Chang, Catie; Uddin, Lucina Q

2018-08-01

Analysis of task-based fMRI data is conventionally carried out using a hypothesis-driven approach, where blood-oxygen-level dependent (BOLD) time courses are correlated with a hypothesized temporal structure. In some experimental designs, this temporal structure can be difficult to define. In other cases, experimenters may wish to take a more exploratory, data-driven approach to detecting task-driven BOLD activity. In this study, we demonstrate the efficiency and power of an inter-subject synchronization approach for exploratory analysis of task-based fMRI data. Combining the tools of instantaneous phase synchronization and independent component analysis, we characterize whole-brain task-driven responses in terms of group-wise similarity in temporal signal dynamics of brain networks. We applied this framework to fMRI data collected during performance of a simple motor task and a social cognitive task. Analyses using an inter-subject phase synchronization approach revealed a large number of brain networks that dynamically synchronized to various features of the task, often not predicted by the hypothesized temporal structure of the task. We suggest that this methodological framework, along with readily available tools in the fMRI community, provides a powerful exploratory, data-driven approach for analysis of task-driven BOLD activity. Copyright © 2018 Elsevier Inc. All rights reserved.

Alternative path to hearing: photonic sonogram hearing aid

NASA Astrophysics Data System (ADS)

Hara, Elmer H.

2002-05-01

For those with total hearing loss, there are no direct remedies except for electronic (i.e. cochlear) implants. They are invasive and do not always function in a satisfactory manner. Although sign language opens the window to a rich culture but communication with the hearing world is hindered. Lip reading can bridge that gap but communication is not without some stress. Inability to detect possible life threatening situations outside the visual field also affects the quality of life for those without the ability to hear. If the hearing process is viewed from the point of system engineering, there is a sound source and air is the transmission medium to the ear. The hearing structure of the ear converts mechanical vibrations to electrical signals that are then transmitted through nerve paths to the section of the brain where sound signals are processed. In most cases of total hearing loss, the hearing structure of the ear is non-functional. A cochlear implant bypasses this hearing structure. It electronically converts sounds from the air into their frequency components and feeds them into transmission nerve paths to the brain as electrical signals. This system-engineering point of view suggests that other pathways to the brain might be explored. The following section considers the visual pathway.

Brain's tumor image processing using shearlet transform

NASA Astrophysics Data System (ADS)

Cadena, Luis; Espinosa, Nikolai; Cadena, Franklin; Korneeva, Anna; Kruglyakov, Alexey; Legalov, Alexander; Romanenko, Alexey; Zotin, Alexander

2017-09-01

Brain tumor detection is well known research area for medical and computer scientists. In last decades there has been much research done on tumor detection, segmentation, and classification. Medical imaging plays a central role in the diagnosis of brain tumors and nowadays uses methods non-invasive, high-resolution techniques, especially magnetic resonance imaging and computed tomography scans. Edge detection is a fundamental tool in image processing, particularly in the areas of feature detection and feature extraction, which aim at identifying points in a digital image at which the image has discontinuities. Shearlets is the most successful frameworks for the efficient representation of multidimensional data, capturing edges and other anisotropic features which frequently dominate multidimensional phenomena. The paper proposes an improved brain tumor detection method by automatically detecting tumor location in MR images, its features are extracted by new shearlet transform.

Calcium imaging of neural circuits with extended depth-of-field light-sheet microscopy

PubMed Central

Quirin, Sean; Vladimirov, Nikita; Yang, Chao-Tsung; Peterka, Darcy S.; Yuste, Rafael; Ahrens, Misha B.

2016-01-01

Increasing the volumetric imaging speed of light-sheet microscopy will improve its ability to detect fast changes in neural activity. Here, a system is introduced for brain-wide imaging of neural activity in the larval zebrafish by coupling structured illumination with cubic phase extended depth-of-field (EDoF) pupil encoding. This microscope enables faster light-sheet imaging and facilitates arbitrary plane scanning—removing constraints on acquisition speed, alignment tolerances, and physical motion near the sample. The usefulness of this method is demonstrated by performing multi-plane calcium imaging in the fish brain with a 416 × 832 × 160 µm field of view at 33 Hz. The optomotor response behavior of the zebrafish is monitored at high speeds, and time-locked correlations of neuronal activity are resolved across its brain. PMID:26974063

Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets

PubMed Central

Santagata, Sandro; Cahill, Daniel P.; Taylor-Weiner, Amaro; Jones, Robert T.; Van Allen, Eliezer M.; Lawrence, Michael S.; Horowitz, Peleg M.; Cibulskis, Kristian; Ligon, Keith L.; Tabernero, Josep; Seoane, Joan; Martinez-Saez, Elena; Curry, William T.; Dunn, Ian F.; Paek, Sun Ha; Park, Sung-Hye; McKenna, Aaron; Chevalier, Aaron; Rosenberg, Mara; Barker, Frederick G.; Gill, Corey M.; Van Hummelen, Paul; Thorner, Aaron R.; Johnson, Bruce E.; Hoang, Mai P.; Choueiri, Toni K.; Signoretti, Sabina; Sougnez, Carrie; Rabin, Michael S.; Lin, Nancy U.; Winer, Eric P.; Stemmer-Rachamimov, Anat; Meyerson, Matthew; Garraway, Levi; Gabriel, Stacey; Lander, Eric S.; Beroukhim, Rameen; Batchelor, Tracy T.; Baselga, Jose; Louis, David N.

2016-01-01

Brain metastases are associated with a dismal prognosis. Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed whole-exome sequencing of 86 matched brain metastases, primary tumors and normal tissue. In all clonally related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found potentially clinically informative alterations in the brain metastases not detected in the matched primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were genetically homogenous. Distal extracranial and regional lymph node metastases were highly divergent from brain metastases. We detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases. PMID:26410082

A pediatric brain structure atlas from T1-weighted MR images

NASA Astrophysics Data System (ADS)

Shan, Zuyao Y.; Parra, Carlos; Ji, Qing; Ogg, Robert J.; Zhang, Yong; Laningham, Fred H.; Reddick, Wilburn E.

2006-03-01

In this paper, we have developed a digital atlas of the pediatric human brain. Human brain atlases, used to visualize spatially complex structures of the brain, are indispensable tools in model-based segmentation and quantitative analysis of brain structures. However, adult brain atlases do not adequately represent the normal maturational patterns of the pediatric brain, and the use of an adult model in pediatric studies may introduce substantial bias. Therefore, we proposed to develop a digital atlas of the pediatric human brain in this study. The atlas was constructed from T1 weighted MR data set of a 9 year old, right-handed girl. Furthermore, we extracted and simplified boundary surfaces of 25 manually defined brain structures (cortical and subcortical) based on surface curvature. Higher curvature surfaces were simplified with more reference points; lower curvature surfaces, with fewer. We constructed a 3D triangular mesh model for each structure by triangulation of the structure's reference points. Kappa statistics (cortical, 0.97; subcortical, 0.91) indicated substantial similarities between the mesh-defined and the original volumes. Our brain atlas and structural mesh models (www.stjude.org/BrainAtlas) can be used to plan treatment, to conduct knowledge and modeldriven segmentation, and to analyze the shapes of brain structures in pediatric patients.

Aerobic Fitness Linked to Cortical Brain Development in Adolescent Males: Preliminary Findings Suggest a Possible Role of BDNF Genotype.

PubMed

Herting, Megan M; Keenan, Madison F; Nagel, Bonnie J

2016-01-01

Aerobic exercise has been shown to impact brain structure and cognition in children and adults. Exercise-induced activation of a growth protein known as brain derived neurotrophic factor (BDNF) is thought to contribute to such relationships. To date, however, no study has examined how aerobic fitness relates to cortical brain structure during development and if BDNF genotype moderates these relationships. Using structural magnetic resonance imaging (MRI) and FreeSurfer, the current study examined how aerobic fitness relates to volume, thickness, and surface area in 34 male adolescents, 15 to 18 years old. Moreover, we examined if the val66met BDNF genotype moderated these relationships. We hypothesized that aerobic fitness would relate to greater thickness and volumes in frontal, parietal, and motor regions, and that these relationships would be less robust in individuals carrying a Met allele, since this genotype leads to lower BDNF expression. We found that aerobic fitness positively related to right rostral middle frontal cortical volume in all adolescents. However, results also showed BDNF genotype moderated the relationship between aerobic fitness and bilateral medial precuneus surface area, with a positive relationship seen in individuals with the Val/Val allele, but no relationship detected in those adolescents carrying a Met allele. Lastly, using self-reported levels of aerobic activity, we found that higher-fit adolescents showed larger right medial pericalcarine, right cuneus and left precuneus surface areas as compared to their low-fit peers. Our findings suggest that aerobic fitness is linked to cortical brain development in male adolescents, and that more research is warranted to determine how an individual's genes may influence these relationships.

Aerobic Fitness Linked to Cortical Brain Development in Adolescent Males: Preliminary Findings Suggest a Possible Role of BDNF Genotype

PubMed Central

Herting, Megan M.; Keenan, Madison F.; Nagel, Bonnie J.

2016-01-01

Aerobic exercise has been shown to impact brain structure and cognition in children and adults. Exercise-induced activation of a growth protein known as brain derived neurotrophic factor (BDNF) is thought to contribute to such relationships. To date, however, no study has examined how aerobic fitness relates to cortical brain structure during development and if BDNF genotype moderates these relationships. Using structural magnetic resonance imaging (MRI) and FreeSurfer, the current study examined how aerobic fitness relates to volume, thickness, and surface area in 34 male adolescents, 15 to 18 years old. Moreover, we examined if the val66met BDNF genotype moderated these relationships. We hypothesized that aerobic fitness would relate to greater thickness and volumes in frontal, parietal, and motor regions, and that these relationships would be less robust in individuals carrying a Met allele, since this genotype leads to lower BDNF expression. We found that aerobic fitness positively related to right rostral middle frontal cortical volume in all adolescents. However, results also showed BDNF genotype moderated the relationship between aerobic fitness and bilateral medial precuneus surface area, with a positive relationship seen in individuals with the Val/Val allele, but no relationship detected in those adolescents carrying a Met allele. Lastly, using self-reported levels of aerobic activity, we found that higher-fit adolescents showed larger right medial pericalcarine, right cuneus and left precuneus surface areas as compared to their low-fit peers. Our findings suggest that aerobic fitness is linked to cortical brain development in male adolescents, and that more research is warranted to determine how an individual’s genes may influence these relationships. PMID:27445764

The Elsevier trophoblast research award lecture: Impacts of placental growth factor and preeclampsia on brain development, behaviour, and cognition.

PubMed

Rätsep, Matthew T; Hickman, Andrew F; Croy, B Anne

2016-12-01

Preeclampsia (PE) is a significant gestational disorder affecting 3-5% of all human pregnancies. In many PE pregnancies, maternal plasma is deficient in placental growth factor (PGF), a placentally-produced angiokine. Beyond immediate fetal risks associated with acute termination of the pregnancy, offspring of PE pregnancies (PE-F1) have higher long-term risks for hypertension, stroke, and cognitive impairment compared to F1s from uncomplicated pregnancies. At present, mechanisms that explain PE-F1 gains in postpartum risks are poorly understood. Our laboratory found that mice genetically-deleted for Pgf have altered fetal and adult brain vascular development. This is accompanied by sexually dimorphic alterations in anatomic structure in the adult Pgf -/- brain and impaired cognitive functions. We hypothesize that cerebrovascular and neurological aberrations occur in fetuses exposed to the progressive development of PE and that these brain changes impair cognitive functioning, enhance risk for stroke, elevate severity of stroke, and lead to worse stroke outcomes. These brain and placental outcomes may be linked to down-regulated PGF gene expression in early pre-implantation embryos, prior to gastrulation. This review explores our hypothesis that there are mechanistic links between low PGF detection in maternal plasma prodromal to PE, PE, and altered brain vascular, structural, and functional development amongst PE-F1s. We also include a summary of preliminary outcomes from a pilot study of 7-10 year old children that is the first to report magnetic resonance imaging, magnetic resonance angiography, and functional brain region assessment by eye movement control studies in PE-F1s. Copyright © 2016 Elsevier Ltd. All rights reserved.

Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

NASA Astrophysics Data System (ADS)

Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

2010-02-01

Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

Enhancement of brain-targeting delivery of danshensu in rat through conjugation with pyrazine moiety to form danshensu-pyrazine ester.

PubMed

Hui, Ailing; Yin, Huayang; Zhang, Zheng; Zhou, An; Chen, Jingchao; Yang, Li; Wu, Zeyu; Zhang, Wencheng

2018-06-01

Tetramethylpyrazine was introduced to the structure of danshensu (DSS) as P-glycoprotein (P-gp)-inhibiting carrier, designing some novel brain-targeting DSS-pyrazine derivatives via prodrug delivery strategy. Following the virtual screening, three DSS-pyrazine esters (DT1, DT2, DT3) were selected because of their better prediction parameters related to brain-targeting. Among them, DT3 was thought to be a promising candidate due to its appropriate bioreversible property in vitro release assay. Further investigation with regard to DT3's brain-targeting effects in vivo was also reported in this study. High-performance liquid chromatography-diode array detection (HPLC-DAD) method was established for the quantitative determination of DT3 and DSS in rat plasma, brain homogenate after intravenous injection. In vivo metabolism of DT3 indicated that it was first converted into DT1, DT2, then the generation of DSS, which could be the result of carboxylesterase activity in rat blood and brain tissue. Moreover, the brain pharmacokinetics of DT3 was significantly altered with 2.16 times increase in half-life compared with that of DSS, and its drug targeting index (DTI) was up to 16.95. Above these data demonstrated that DT3 had better tendency of brain-targeting delivery, which would be positive for the treatment of brain-related disorders.

A whole brain volumetric approach in overweight/obese children: Examining the association with different physical fitness components and academic performance. The ActiveBrains project.

PubMed

Esteban-Cornejo, Irene; Cadenas-Sanchez, Cristina; Contreras-Rodriguez, Oren; Verdejo-Roman, Juan; Mora-Gonzalez, Jose; Migueles, Jairo H; Henriksson, Pontus; Davis, Catherine L; Verdejo-Garcia, Antonio; Catena, Andrés; Ortega, Francisco B

2017-10-01

Obesity, as compared to normal weight, is associated with detectable structural differences in the brain. To the best of our knowledge, no previous study has examined the association of physical fitness with gray matter volume in overweight/obese children using whole brain analyses. Thus, the aim of this study was to examine the association between the key components of physical fitness (i.e. cardiorespiratory fitness, speed-agility and muscular fitness) and brain structural volume, and to assess whether fitness-related changes in brain volumes are related to academic performance in overweight/obese children. A total of 101 overweight/obese children aged 8-11 years were recruited from Granada, Spain. The physical fitness components were assessed following the ALPHA health-related fitness test battery. T1-weighted images were acquired with a 3.0 T S Magnetom Tim Trio system. Gray matter tissue was calculated using Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra (DARTEL). Academic performance was assessed by the Batería III Woodcock-Muñoz Tests of Achievement. All analyses were controlled for sex, peak high velocity offset, parent education, body mass index and total brain volume. The statistical threshold was calculated with AlphaSim and further Hayasaka adjusted to account for the non-isotropic smoothness of structural images. The main results showed that higher cardiorespiratory fitness was related to greater gray matter volumes (P < 0.001, k = 64) in 7 clusters with β ranging from 0.493 to 0.575; specifically in frontal regions (i.e. premotor cortex and supplementary motor cortex), subcortical regions (i.e. hippocampus and caudate), temporal regions (i.e. inferior temporal gyrus and parahippocampal gyrus) and calcarine cortex. Three of these regions (i.e. premotor cortex, supplementary motor cortex and hippocampus) were related to better academic performance (β ranging from 0.211 to 0.352; all P < 0.05). Higher speed-agility was associated with greater gray matter volumes (P < 0.001, k = 57) in 2 clusters (i.e. the inferior frontal gyrus and the superior temporal gyrus) with β ranging from 0.564 to 0.611. Both clusters were related to better academic performance (β ranging from 0.217 to 0.296; both P < 0.05). Muscular fitness was not independently associated with greater gray matter volume in any brain region. Furthermore, there were no statistically significant negative association between any component of physical fitness and gray matter volume in any region of the brain. In conclusion, cardiorespiratory fitness and speed-agility, but not muscular fitness, may independently be associated with greater volume of numerous cortical and subcortical brain structures; besides, some of these brain structures may be related to better academic performance. Importantly, the identified associations of fitness and gray matter volume were different for each fitness component. These findings suggest that increases in cardiorespiratory fitness and speed-agility may positively influence the development of distinctive brain regions and academic indicators, and thus counteract the harmful effect of overweight and obesity on brain structure during childhood. Copyright © 2017 Elsevier Inc. All rights reserved.

CCL11 promotes migration and proliferation of mouse neural progenitor cells.

PubMed

Wang, Feifei; Baba, Nobuyasu; Shen, Yuan; Yamashita, Tatsuyuki; Tsuru, Emi; Tsuda, Masayuki; Maeda, Nagamasa; Sagara, Yusuke

2017-02-07

Neonatal hypoxia-ischemia induces massive brain damage during the perinatal period, resulting in long-term consequences to central nervous system structural and functional maturation. Although neural progenitor cells (NPCs) migrate through the parenchyma and home in to injury sites in the rodent brain, the molecular mechanisms are unknown. We examined the role of chemokines in mediating NPC migration after neonatal hypoxic-ischemic brain injury. Nine-day-old mice were exposed to a 120-minute hypoxia following unilateral carotid occlusion. Chemokine levels were quantified in mouse brain extract. Migration and proliferation assays were performed using embryonic and infant mouse NPCs. The neonatal hypoxic-ischemic brain injury resulted in an ipsilateral lesion, which was extended to the cortical and striatal areas. NPCs migrated toward an injured area, where a marked increase of CC chemokines was detected. In vitro studies showed that incubation of NPCs with recombinant mouse CCL11 promoted migration and proliferation. These effects were partly inhibited by a CCR3 antagonist, SB297006. Our data implicate an important effect of CCL11 for mouse NPCs. The effective activation of NPCs may offer a promising strategy for neuroregeneration in neonatal hypoxic-ischemic brain injury.

Human brain diffusion tensor imaging at submillimeter isotropic resolution on a 3 Tesla clinical MRI scanner

PubMed Central

Chang, Hing-Chiu; Sundman, Mark; Petit, Laurent; Guhaniyogi, Shayan; Chu, Mei-Lan; Petty, Christopher; Song, Allen W.; Chen, Nan-kuei

2015-01-01

The advantages of high-resolution diffusion tensor imaging (DTI) have been demonstrated in a recent post-mortem human brain study (Miller et al., NeuroImage 2011;57(1):167–181), showing that white matter fiber tracts can be much more accurately detected in data at submillimeter isotropic resolution. To our knowledge, in vivo human brain DTI at submillimeter isotropic resolution has not been routinely achieved yet because of the difficulty in simultaneously achieving high resolution and high signal-to-noise ratio (SNR) in DTI scans. Here we report a 3D multi-slab interleaved EPI acquisition integrated with multiplexed sensitivity encoded (MUSE) reconstruction, to achieve high-quality, high-SNR and submillimeter isotropic resolution (0.85 × 0.85 × 0.85 mm3) in vivo human brain DTI on a 3 Tesla clinical MRI scanner. In agreement with the previously reported post-mortem human brain DTI study, our in vivo data show that the structural connectivity networks of human brains can be mapped more accurately and completely with high-resolution DTI as compared with conventional DTI (e.g., 2 × 2 × 2 mm3). PMID:26072250

The Insula: A ‘Hub of Activity’ in Migraine

PubMed Central

Borsook, David; Veggeberg, Rosanna; Erpelding, Nathalie; Borra, Ronald; Linnman, Clas; Burstein, Rami; Becerra, Lino

2017-01-01

The insula, a ‘cortical hub’ buried within the lateral sulcus, is involved in a number of processes including goal-directed cognition, conscious awareness, autonomic regulation, interoception and somatosensation. While some of these processes are well known in the clinical presentation of migraine (i.e., autonomic and somatosensory alterations), other more complex behaviors in migraine, such as conscious awareness and error detection, are less well described. Since the insula processes and relays afferent inputs from brain areas involved in these functions to areas involved in higher cortical function such as frontal, temporal and parietal regions, it may be implicated as a brain region that translates the signals of altered internal milieu in migraine, along with other chronic pain conditions, through the insula into complex behaviors. Here we review how the insula function and structure is altered in migraine. As a brain region of a number of brain functions, it may serve as a model to study new potential clinical perspectives for migraine treatment. PMID:26290446

Bayesian estimation of optical properties of the human head via 3D structural MRI

NASA Astrophysics Data System (ADS)

Barnett, Alexander H.; Culver, Joseph P.; Sorensen, A. Gregory; Dale, Anders M.; Boas, David A.

2003-10-01

Knowledge of the baseline optical properties of the tissues of the human head is essential for absolute cerebral oximetry, and for quantitative studies of brain activation. In this work we numerically model the utility of signals from a small 6-optode time-resolved diffuse optical tomographic apparatus for inferring baseline scattering and absorption coefficients of the scalp, skull and brain, when complete geometric information is available from magnetic resonance imaging (MRI). We use an optical model where MRI-segmented tissues are assumed homogeneous. We introduce a noise model capturing both photon shot noise and forward model numerical accuracy, and use Bayesian inference to predict errorbars and correlations on the measurments. We also sample from the full posterior distribution using Markov chain Monte Carlo. We conclude that ~ 106 detected photons are sufficient to measure the brain"s scattering and absorption to a few percent. We present preliminary results using a fast multi-layer slab model, comparing the case when layer thicknesses are known versus unknown.

An ANOVA approach for statistical comparisons of brain networks.

PubMed

Fraiman, Daniel; Fraiman, Ricardo

2018-03-16

The study of brain networks has developed extensively over the last couple of decades. By contrast, techniques for the statistical analysis of these networks are less developed. In this paper, we focus on the statistical comparison of brain networks in a nonparametric framework and discuss the associated detection and identification problems. We tested network differences between groups with an analysis of variance (ANOVA) test we developed specifically for networks. We also propose and analyse the behaviour of a new statistical procedure designed to identify different subnetworks. As an example, we show the application of this tool in resting-state fMRI data obtained from the Human Connectome Project. We identify, among other variables, that the amount of sleep the days before the scan is a relevant variable that must be controlled. Finally, we discuss the potential bias in neuroimaging findings that is generated by some behavioural and brain structure variables. Our method can also be applied to other kind of networks such as protein interaction networks, gene networks or social networks.

Neuropathology of alcoholism.

PubMed

Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

2014-01-01

Chronic alcohol consumption results in structural changes to the brain. In alcoholics without coexisting thiamine deficiency or liver disease this is largely restricted to a loss of white-matter volume. When it occurs, neuronal loss is limited in anatomic distribution and only detected with quantitative techniques. This relative paucity of neurodegeneration is reflected in studies of gene and protein expression in postmortem brain where findings are subtle and discordant between studies. In alcoholics with coexisting pathologies, neuronal loss is more marked and affects a wider range of anatomic regions, especially subcortical nuclei. Although this more widespread damage may reflect a more severe drinking history, there is evidence linking thiamine deficiency and the consequences of liver disease to the pathogenesis of alcohol-related brain damage. Furthermore, a range of other factors, such as cigarette smoking and mood disorders, that are common in alcoholics, have the potential to influence studies of brain pathology and should be considered in further studies of the neuropathology of alcoholism. © 2014 Elsevier B.V. All rights reserved.

Optical manipulation for optogenetics: otoliths manipulation in zebrafish (Conference Presentation)

NASA Astrophysics Data System (ADS)

Favre-Bulle, Itia A.; Scott, Ethan; Rubinsztein-Dunlop, Halina

2016-03-01

Otoliths play an important role in Zebrafish in terms of hearing and sense of balance. Many studies have been conducted to understand its structure and function, however the encoding of its movement in the brain remains unknown. Here we developed a noninvasive system capable of manipulating the otolith using optical trapping while we image its behavioral response and brain activity. We'll also present our tools for behavioral response detection and brain activity mapping. Acceleration is sensed through movements of the otoliths in the inner ear. Because experimental manipulations involve movements, electrophysiology and fluorescence microscopy are difficult. As a result, the neural codes underlying acceleration sensation are poorly understood. We have developed a technique for optically trapping otoliths, allowing us to simulate acceleration in stationary larval zebrafish. By applying forces to the otoliths, we can elicit behavioral responses consistent with compensation for perceived acceleration. Since the animal is stationary, we can use calcium imaging in these animals' brains to identify the functional circuits responsible for mediating responses to acceleration in natural settings.

Using stochastic language models (SLM) to map lexical, syntactic, and phonological information processing in the brain.

PubMed

Lopopolo, Alessandro; Frank, Stefan L; van den Bosch, Antal; Willems, Roel M

2017-01-01

Language comprehension involves the simultaneous processing of information at the phonological, syntactic, and lexical level. We track these three distinct streams of information in the brain by using stochastic measures derived from computational language models to detect neural correlates of phoneme, part-of-speech, and word processing in an fMRI experiment. Probabilistic language models have proven to be useful tools for studying how language is processed as a sequence of symbols unfolding in time. Conditional probabilities between sequences of words are at the basis of probabilistic measures such as surprisal and perplexity which have been successfully used as predictors of several behavioural and neural correlates of sentence processing. Here we computed perplexity from sequences of words and their parts of speech, and their phonemic transcriptions. Brain activity time-locked to each word is regressed on the three model-derived measures. We observe that the brain keeps track of the statistical structure of lexical, syntactic and phonological information in distinct areas.

Structure-performance relationships of phenyl cinnamic acid derivatives as MALDI-MS matrices for sulfatide detection.

PubMed

Tambe, Suparna; Blott, Henning; Fülöp, Annabelle; Spang, Nils; Flottmann, Dirk; Bräse, Stefan; Hopf, Carsten; Junker, Hans-Dieter

2017-02-01

A key aspect for the further development of matrix-assisted laser desorption ionization (MALDI)-mass spectrometry (MS) is a better understanding of the working principles of MALDI matrices. To address this issue, a chemical compound library of 59 structurally related cinnamic acid derivatives was synthesized. Potential MALDI matrices were evaluated with sulfatides, a class of anionic lipids which are abundant in complex brain lipid mixtures. For each matrix relative mean S/N ratios of sulfatides were determined against 9-aminoacridine as a reference matrix using negative ion mass spectrometry with 355 and 337 nm laser systems. The comparison of matrix features with their corresponding relative mean S/N ratios for sulfatide detection identified correlations between matrix substitution patterns, their chemical functionality, and their MALDI-MS performance. Crystal structures of six selected matrices provided structural insight in hydrogen bond interactions in the solid state. Principal component analysis allowed the additional identification of correlation trends between structural and physical matrix properties like number of exchangeable protons at the head group, MW, logP, UV-Vis, and sulfatide detection sensitivity. Graphical abstract Design, synthesis and mass spectrometric evaluation of MALDI-MS matrix compound libraries allows the identification of matrix structure - MALDI-MS performance relationships using multivariate statistics as a tool.

Human Tonsil-Derived Follicular Dendritic-Like Cells are Refractory to Human Prion Infection in Vitro and Traffic Disease-Associated Prion Protein to Lysosomes

PubMed Central

Krejciova, Zuzana; De Sousa, Paul; Manson, Jean; Ironside, James W.; Head, Mark W.

2014-01-01

The molecular mechanisms involved in human cellular susceptibility to prion infection remain poorly defined. This is due, in part, to the absence of any well characterized and relevant cultured human cells susceptible to infection with human prions, such as those involved in Creutzfeldt-Jakob disease. In variant Creutzfeldt-Jakob disease, prion replication is thought to occur first in the lymphoreticular system and then spread into the brain. We have, therefore, examined the susceptibility of a human tonsil-derived follicular dendritic cell-like cell line (HK) to prion infection. HK cells were found to display a readily detectable, time-dependent increase in cell-associated abnormal prion protein (PrPTSE) when exposed to medium spiked with Creutzfeldt-Jakob disease brain homogenate, resulting in a coarse granular perinuclear PrPTSE staining pattern. Despite their high level of cellular prion protein expression, HK cells failed to support infection, as judged by longer term maintenance of PrPTSE accumulation. Colocalization studies revealed that exposure of HK cells to brain homogenate resulted in increased numbers of detectable lysosomes and that these structures immunostained intensely for PrPTSE after exposure to Creutzfeldt-Jakob disease brain homogenate. Our data suggest that human follicular dendritic-like cells and perhaps other human cell types are able to avoid prion infection by efficient lysosomal degradation of PrPTSE. PMID:24183781

Altered Markers of Brain Development in Crohn’s Disease with Extraintestinal Manifestations – A Pilot Study

PubMed Central

Thomann, Philipp A.; Wolf, Robert C.; Hirjak, Dusan; Schmahl, Christian; Ebert, Matthias P.; Szabo, Kristina; Reindl, Wolfgang; Griebe, Martin

2016-01-01

Background and Objective Alterations of brain morphology in Crohn’s disease have been reported, but data is scarce and heterogenous and the possible impact of disease predisposition on brain development is unknown. Assuming a systemic course of the disease, brain involvement seems more probable in presence of extraintestinal manifestations, but this question has not yet been addressed. The present study examined the relationship between Crohn’s disease and brain structure and focused on the connection with extraintestinal manifestations and markers of brain development. Methods In a pilot study, brains of 15 patients with Crohn’s disease (of which 9 had a history of extraintestinal manifestations, i.e. arthritis, erythema nodosum and primary sclerosing cholangitis) were compared to matched healthy controls using high resolution magnetic resonance imaging. Patients and controls were tested for depression, fatigue and global cognitive function. Cortical thickness, surface area and folding were determined via cortical surface modeling. Results The overall group comparison (i.e. all patients vs. controls) yielded no significant results. In the patient subgroup with extraintestinal manifestations, changes in cortical area and folding, but not thickness, were identified: Patients showed elevated cortical surface area in the left middle frontal lobe (p<0.05) and hypergyrification in the left lingual gyrus (p<0.001) compared to healthy controls. Hypogyrification of the right insular cortex (p<0.05) and hypergyrification of the right anterior cingulate cortex (p<0.001) were detected in the subgroup comparison of patients with against without extraintestinal manifestations. P-values are corrected for multiple comparisons. Conclusions Our findings lend further support to the hypothesis that Crohn’s disease is associated with aberrant brain structure and preliminary support for the hypothesis that these changes are associated with a systemic course of the disease as indicated by extraintestinal manifestations. Changes in cortical surface area and folding suggest a possible involvement of Crohn’s disease or its predisposition during brain development. PMID:27655165

Sample entropy and regularity dimension in complexity analysis of cortical surface structure in early Alzheimer's disease and aging.

PubMed

Chen, Ying; Pham, Tuan D

2013-05-15

We apply for the first time the sample entropy (SampEn) and regularity dimension model for measuring signal complexity to quantify the structural complexity of the brain on MRI. The concept of the regularity dimension is based on the theory of chaos for studying nonlinear dynamical systems, where power laws and entropy measure are adopted to develop the regularity dimension for modeling a mathematical relationship between the frequencies with which information about signal regularity changes in various scales. The sample entropy and regularity dimension of MRI-based brain structural complexity are computed for early Alzheimer's disease (AD) elder adults and age and gender-matched non-demented controls, as well as for a wide range of ages from young people to elder adults. A significantly higher global cortical structure complexity is detected in AD individuals (p<0.001). The increase of SampEn and the regularity dimension are also found to be accompanied with aging which might indicate an age-related exacerbation of cortical structural irregularity. The provided model can be potentially used as an imaging bio-marker for early prediction of AD and age-related cognitive decline. Copyright © 2013 Elsevier B.V. All rights reserved.

MRI anatomy of schizophrenia.

PubMed

McCarley, R W; Wible, C G; Frumin, M; Hirayasu, Y; Levitt, J J; Fischer, I A; Shenton, M E

1999-05-01

Structural magnetic resonance imaging (MRI) data have provided much evidence in support of our current view that schizophrenia is a brain disorder with altered brain structure, and consequently involving more than a simple disturbance in neurotransmission. This review surveys 118 peer-reviewed studies with control group from 1987 to May 1998. Most studies (81%) do not find abnormalities of whole brain/intracranial contents, while lateral ventricle enlargement is reported in 77%, and third ventricle enlargement in 67%. The temporal lobe was the brain parenchymal region with the most consistently documented abnormalities. Volume decreases were found in 62% of 37 studies of whole temporal lobe, and in 81% of 16 studies of the superior temporal gyrus (and in 100% with gray matter separately evaluated). Fully 77% of the 30 studies of the medial temporal lobe reported volume reduction in one or more of its constituent structures (hippocampus, amygdala, parahippocampal gyrus). Despite evidence for frontal lobe functional abnormalities, structural MRI investigations less consistently found abnormalities, with 55% describing volume reduction. It may be that frontal lobe volume changes are small, and near the threshold for MRI detection. The parietal and occipital lobes were much less studied; about half of the studies showed positive findings. Most studies of cortical gray matter (86%) found volume reductions were not diffuse, but more pronounced in certain areas. About two thirds of the studies of subcortical structures of thalamus, corpus callosum and basal ganglia (which tend to increase volume with typical neuroleptics), show positive findings, as do almost all (91%) studies of cavum septi pellucidi (CSP). Most data were consistent with a developmental model, but growing evidence was compatible also with progressive, neurodegenerative features, suggesting a "two-hit" model of schizophrenia, for which a cellular hypothesis is discussed. The relationship of clinical symptoms to MRI findings is reviewed, as is the growing evidence suggesting structural abnormalities differ in affective (bipolar) psychosis and schizophrenia.

[The comparative pathomorphological evaluation of the mice-recipient's brain cell-tissue reactions by the intracerebral imlantation of syngeneic and allogeneic neural cells].

PubMed

Liubych, L D; Semenova, V M; Lisianyĭ, M I

2013-01-01

The aim of the study was to compare the mice-recipient's brain tissue cell-structural reactions in response to intracerebral implantation of syngeneic and allogeneic cell suspensions of neural progenitor cells (NPC) (E13-15). The NPC suspensions from mice-donors of C57BL/6 and CBA containing 72.7 +/- 9.9% Vimentin+ and 81, 812, 5% GFAP+ cells were inoculated by standard procedure in right temporal segment of cerebral hemisphere of mice-recipients C57BL/6 (1 x 10(6) cells per animal). The certain part of mice-recipients of allogeneic NPC were immunosupressed by Sandimmune (100 mkg per animal) on day 0, 3, 6 after neurotransplantation. The standard histological preparations of mice brains were performed after 24 hours, 6, 12, 18 and 37 days after NPC neurotransplantation, which were investigated by cytoanalyzer "IBAS" (Germany). After intracerebral inoculation of allogeneic foetal NPC the signs of the pericellular edema and lymphocyte infiltration were detected in adjacent brain sections on day 12-18 and decreased on day 37. Allogeneic foetal NPC were reserved till day 18 and revealed the signs of primary differentiation. After immunosupression by "Sandimmune" the foetal NPC underwent the phoenotypic differentiation and infiltration in related brain sections. On the day 37 the implanted NPC were not detected. Focal reaction of the brain glial component to implanted NPC declined faster after syngeneic NPC neuroimplantation (up to day 18) than after allogeneic NPC neuroimplantation (up to day 37). After the syngeneic NPC inoculation on the 37th day at the site of implantation the formation of a small fragment of immature bone was fixed, which may indicate the possibility of NPC transdifferentiation in other cell types.

Brain alcohol detectability in human subjects with and without a paternal history of alcoholism.

PubMed

Chiu, Tak-Ming; Mendelson, Jack H; Sholar, Michelle B; Mutschler, Nicole H; Wines, James D; Hesselbrock, Victor M; Mello, Nancy K

2004-01-01

This study examined the putative effects of a paternal history of alcoholism on the apparent detectability of brain alcohol in human subjects. Brain to blood ethanol ratios in two cohorts of men were determined, using proton magnetic resonance spectroscopic imaging in a brain voxel (2 x 2 x 2 cm) containing the putamen. The men were light drinkers with a positive (n = 8) or a negative (n = 8) paternal history of alcoholism and were given an alcohol dose of 0.8 g/kg body weight. In both groups, brain alcohol detectability was less than 100%. No significant difference (p = .37) was found in the brain/blood ethanol ratios of the two groups. However, subjective assessments of feeling the extreme effects of alcohol and the extent of intoxication ("how drunk") were highly correlated with a paternal history of alcoholism, with the paternal history negative group reporting significantly more intense feelings of intoxication. A review of existing literature evidence and data obtained in this study indicate that brain alcohol detectability via magnetic resonance spectroscopic imaging is less than 100%. There were no significant differences in brain alcohol detectability between paternal history positive and paternal history negative men. Differences in the Subjective High Assessment Scale ratings between the two groups, however, indicate the importance of a genetic influence on the subjective response to alcohol.

Evaluation of a Portable Microchip Electrophoresis Fluorescence Detection System for the Analysis of Amino Acid Neurotransmitters in Brain Dialysis Samples

PubMed Central

OBORNY, Nathan J.; COSTA, Elton E. Melo; SUNTORNSUK, Leena; ABREU, Fabiane C.; LUNTE, Susan M.

2016-01-01

A portable fluorescence detection system for use with microchip electrophoresis was developed and compared to a benchtop system. Using this system, six neuroactive amines commonly found in brain dialysate—arginine, citrulline, taurine, histamine, glutamate, and aspartate—were derivatized offline with naphthalene-2,3-dicarboxaldehyde/cyanide, separated electrophoretically, and detected by fluorescence. Limits of detection for the analytes of interest were 50nM – 250nM for the benchtop system and 250 nM – 1.3 μM for the portable system, both of which were adequate for analyte determination in brain microdialysis samples. The portable system was then demonstrated for the detection of the same six amines in a rat brain microdialysis sample. PMID:26753703

When brain neuroscience meets hydrology: timeseries analysis methods for capturing structural and functional aspects of hydrologic connectivity

NASA Astrophysics Data System (ADS)

Ali, G.; Rinderer, M.

2016-12-01

In hydrology, several connectivity definitions exist that hinder intercomparison between different studies. Yet, consensus exists on the distinction between structural connectivity (i.e., physical adjacency of landscape elements that is thought to influence material transfer) and functional or effective connectivity (i.e., interaction or causality between spatial adjacency characteristics and temporally varying factors, leading to the connected flow of material). While hydrologists have succeeded in deriving measures of structural connectivity (SC), the quantification of functional (FC) or effective connectivity (EC) is elusive. Here we borrowed timeseries analysis methods from brain neuroscience to quantify EC and FC among groundwater (n = 34) and stream discharge (n = 1) monitoring sites in a 20-ha Swiss catchment where topography is assumed to be a major driver of connectivity. Influence maps created from elevation data were used to assess SC. FC was assessed by cross-correlation, total and partial mutual information and EC quantified via total and partial entropy, Granger causality and a phase slope index. Results show that generally, a fair percentage of structural connections were also expressed as functional or effective connections. Some FC and EC measures had clear advantages over others, for instance in terms of making a distinction between Darcian fluxes of water and pressure wave-driven processes. False-positive estimations, i.e., the detection of FC and EC despite the absence of SC, were also encountered and used to invalidate the applicability of some brain-connectivity measures in a hydrological context. While our goal was not to identify the best measure of FC or EC, our study showed that the application of brain neuroscience methods for assessing FC and EC in hydrology was possible as long as SC measures were used as constraints for (or prior beliefs about) the establishment of FC and EC.

Increased subcortical neural activity among HIV+ individuals during a lexical retrieval task.

PubMed

Thames, April D; Sayegh, Philip; Terashima, Kevin; Foley, Jessica M; Cho, Andrew; Arentoft, Alyssa; Hinkin, Charles H; Bookheimer, Susan Y

2016-08-01

Deficits in lexical retrieval, present in approximately 40% of HIV+ patients, are thought to reflect disruptions to frontal-striatal functions and may worsen with immunosuppression. Coupling frontal-striatal tasks such as lexical retrieval with functional neuroimaging may help delineate the pathophysiologic mechanisms underlying HIV-associated neurological dysfunction. We examined whether HIV infection confers brain functional changes during lexical access and retrieval. It was expected that HIV+ individuals would demonstrate greater brain activity in frontal-subcortical regions despite minimal differences between groups on neuropsychological testing. Within the HIV+ sample, we examined associations between indices of immunosuppression (recent and nadir CD4+ count) and task-related signal change in frontostriatal structures. Method16 HIV+ participants and 12 HIV- controls underwent fMRI while engaged in phonemic/letter and semantic fluency tasks. Participants also completed standardized measures of verbal fluency HIV status groups performed similarly on phonemic and semantic fluency tasks prior to being scanned. fMRI results demonstrated activation differences during the phonemic fluency task as a function of HIV status, with HIV+ individuals demonstrating significantly greater activation in BG structures than HIV- individuals. There were no significant differences in frontal brain activation between HIV status groups during the phonemic fluency task, nor were there significant brain activation differences during the semantic fluency task. Within the HIV+ group, current CD4+ count, though not nadir, was positively correlated with increased activity in the inferior frontal gyrus and basal ganglia. During phonemic fluency performance, HIV+ patients recruit subcortical structures to a greater degree than HIV- controls despite similar task performances suggesting that fMRI may be sensitive to neurocompromise before overt cognitive declines can be detected. Among HIV+ individuals, reduced activity in the frontal-subcortical structures was associated with lower CD4+ count. Copyright © 2015 Elsevier Inc. All rights reserved.

Altered brain functional networks in people with Internet gaming disorder: Evidence from resting-state fMRI.

PubMed

Wang, Lingxiao; Wu, Lingdan; Lin, Xiao; Zhang, Yifen; Zhou, Hongli; Du, Xiaoxia; Dong, Guangheng

2016-08-30

Although numerous neuroimaging studies have detected structural and functional abnormality in specific brain regions and connections in subjects with Internet gaming disorder (IGD), the topological organization of the whole-brain network in IGD remain unclear. In this study, we applied graph theoretical analysis to explore the intrinsic topological properties of brain networks in Internet gaming disorder (IGD). 37 IGD subjects and 35 matched healthy control (HC) subjects underwent a resting-state functional magnetic resonance imaging scan. The functional networks were constructed by thresholding partial correlation matrices of 90 brain regions. Then we applied graph-based approaches to analysis their topological attributes, including small-worldness, nodal metrics, and efficiency. Both IGD and HC subjects show efficient and economic brain network, and small-world topology. Although there was no significant group difference in global topology metrics, the IGD subjects showed reduced regional centralities in the prefrontal cortex, left posterior cingulate cortex, right amygdala, and bilateral lingual gyrus, and increased functional connectivity in sensory-motor-related brain networks compared to the HC subjects. These results imply that people with IGD may be associated with functional network dysfunction, including impaired executive control and emotional management, but enhanced coordination among visual, sensorimotor, auditory and visuospatial systems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Detection and mapping of delays in early cortical folding derived from in utero MRI

NASA Astrophysics Data System (ADS)

Habas, Piotr A.; Rajagopalan, Vidya; Scott, Julia A.; Kim, Kio; Roosta, Ahmad; Rousseau, Francois; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

2011-03-01

Understanding human brain development in utero and detecting cortical abnormalities related to specific clinical conditions is an important area of research. In this paper, we describe and evaluate methodology for detection and mapping of delays in early cortical folding from population-based studies of fetal brain anatomies imaged in utero. We use a general linear modeling framework to describe spatiotemporal changes in curvature of the developing brain and explore the ability to detect and localize delays in cortical folding in the presence of uncertainty in estimation of the fetal age. We apply permutation testing to examine which regions of the brain surface provide the most statistical power to detect a given folding delay at a given developmental stage. The presented methodology is evaluated using MR scans of fetuses with normal brain development and gestational ages ranging from 20.57 to 27.86 weeks. This period is critical in early cortical folding and the formation of the primary and secondary sulci. Finally, we demonstrate a clinical application of the framework for detection and localization of folding delays in fetuses with isolated mild ventriculomegaly.

Hybrid Clustering And Boundary Value Refinement for Tumor Segmentation using Brain MRI

NASA Astrophysics Data System (ADS)

Gupta, Anjali; Pahuja, Gunjan

2017-08-01

The method of brain tumor segmentation is the separation of tumor area from Brain Magnetic Resonance (MR) images. There are number of methods already exist for segmentation of brain tumor efficiently. However it’s tedious task to identify the brain tumor from MR images. The segmentation process is extraction of different tumor tissues such as active, tumor, necrosis, and edema from the normal brain tissues such as gray matter (GM), white matter (WM), as well as cerebrospinal fluid (CSF). As per the survey study, most of time the brain tumors are detected easily from brain MR image using region based approach but required level of accuracy, abnormalities classification is not predictable. The segmentation of brain tumor consists of many stages. Manually segmenting the tumor from brain MR images is very time consuming hence there exist many challenges in manual segmentation. In this research paper, our main goal is to present the hybrid clustering which consists of Fuzzy C-Means Clustering (for accurate tumor detection) and level set method(for handling complex shapes) for the detection of exact shape of tumor in minimal computational time. using this approach we observe that for a certain set of images 0.9412 sec of time is taken to detect tumor which is very less in comparison to recent existing algorithm i.e. Hybrid clustering (Fuzzy C-Means and K Means clustering).

Development of an assisting detection system for early infarct diagnosis

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

Sim, K. S.; Nia, M. E.; Ee, C. S.

2015-04-24

In this paper, a detection assisting system for early infarct detection is developed. This new developed method is used to assist the medical practitioners to diagnose infarct from computed tomography images of brain. Using this assisting system, the infarct could be diagnosed at earlier stages. The non-contrast computed tomography (NCCT) brain images are the data set used for this system. Detection module extracts the pixel data from NCCT brain images, and produces the colourized version of images. The proposed method showed great potential in detecting infarct, and helps medical practitioners to make earlier and better diagnoses.

Mobile In Vivo Infrared Data Collection and Diagnoses Comparison System

NASA Technical Reports Server (NTRS)

Mintz, Frederick W. (Inventor); Gunapala, Sarath D. (Inventor); Moynihan, Philip I. (Inventor)

2013-01-01

Described is a mobile in vivo infrared brain scan and analysis system. The system includes a data collection subsystem and a data analysis subsystem. The data collection subsystem is a helmet with a plurality of infrared (IR) thermometer probes. Each of the IR thermometer probes includes an IR photodetector capable of detecting IR radiation generated by evoked potentials within a user's skull. The helmet is formed to collect brain data that is reflective of firing neurons in a mobile subject and transmit the brain data to the data analysis subsystem. The data analysis subsystem is configured to generate and display a three-dimensional image that depicts a location of the firing neurons. The data analysis subsystem is also configured to compare the brain data against a library of brain data to detect an anomaly in the brain data, and notify a user of any detected anomaly in the brain data.

Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment.

PubMed

Ahmed, Mohamed; Cannon, Dara M; Scanlon, Cathy; Holleran, Laurena; Schmidt, Heike; McFarland, John; Langan, Camilla; McCarthy, Peter; Barker, Gareth J; Hallahan, Brian; McDonald, Colm

2015-09-01

Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity.

Enhanced detection of infectious prions by direct ELISA from the brains of asymptomatic animals using DRM2-118 monoclonal antibody and Gdn-HCl.

PubMed

Hnasko, Robert; Lin, Alice; McGarvey, Jeffery; Stanker, Larry

2018-05-01

In this report we describe the use of a novel anti-prion monoclonal antibody (DRM2-118) for the direct detection of infectious prions by ELISA. Epitope mapping using overlapping hamster (SHa) prion peptides indicates DRM2-118 binding occurs between residues 93-100 and at the 3 10 -helix (residues 163-170) between alpha helix-A and -B. This antibody shows broad species binding to endogenous prions from brain homogenates and corresponding recombinant prion proteins. To evaluate the performance of this MAb for the detection of prion proteins we performed an animal time course and evaluated prion detection from both crude brain homogenates and lipid raft fractions (DRM) by direct ELISA. Prion detection was significantly enhanced by the addition of the chaotropic guanidine-HCl (Gdn-HCl) during protein immobilization with detection of PK-resistant prion from asymptomatic animal brains at (45-DPI) and from lipid rafts at (24-DPI). Our data demonstrates enhanced prion detection from brain lipid rafts of asymptomatic animals by a simple direct ELISA using the DRM2-118 MAb combined with Gdn-HCl. Published by Elsevier B.V.

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.

Sensitive and specific detection of classical scrapie prions in the brains of goats by real-time quaking-induced conversion.

PubMed

Dassanayake, Rohana P; Orrú, Christina D; Hughson, Andrew G; Caughey, Byron; Graça, Telmo; Zhuang, Dongyue; Madsen-Bouterse, Sally A; Knowles, Donald P; Schneider, David A

2016-03-01

Real-time quaking-induced conversion (RT-QuIC) is a rapid, specific and highly sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect subinfectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully used to detect PrPSc in various tissues from humans and animals, including sheep, tissues from goats infected with classical scrapie have not yet been tested. Therefore, the aims of the present study were to (1) evaluate whether prion seeding activity could be detected in the brain tissues of goats with scrapie using RT-QuIC, (2) optimize reaction conditions to improve scrapie detection in goats, and (3) compare the performance of RT-QuIC for the detection of PrPSc with the more commonly used ELISA and Western blot assays. We further optimized RT-QuIC conditions for sensitive and specific detection of goat scrapie seeding activity in brain tissue from clinical animals. When used with 200  mM sodium chloride, both full-length sheep rPrPSen substrates (PrP genotypes A136R154Q171 and V136R154Q171) provided good discrimination between scrapie-infected and normal goat brain samples at 10(- )3 dilution within 15  h. Our findings indicate that RT-QuIC was at least 10,000-fold more sensitive than ELISA and Western blot assays for the detection of scrapie seeding activity in goat brain samples. In addition to PRNP WT samples, positive RT-QuIC reactions were also observed with three PRNP polymorphic goat brain samples (G/S127, I/M142 and H/R143) tested. Taken together, these findings demonstrate that RT-QuIC sensitively detects prion seeding activity in classical scrapie-infected goat brain samples.

Sensitive and specific detection of classical scrapie prions in the brains of goats by real-time quaking-induced conversion

PubMed Central

Dassanayake, Rohana P.; Orrú, Christina D.; Hughson, Andrew G.; Caughey, Byron; Graça, Telmo; Zhuang, Dongyue; Madsen-Bouterse, Sally A.; Knowles, Donald P.; Schneider, David A.

2016-01-01

Real-time quaking-induced conversion (RT-QuIC) is a rapid, specific and highly sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect subinfectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully used to detect PrPSc in various tissues from humans and animals, including sheep, tissues from goats infected with classical scrapie have not yet been tested. Therefore, the aims of the present study were to (1) evaluate whether prion seeding activity could be detected in the brain tissues of goats with scrapie using RT-QuIC, (2) optimize reaction conditions to improve scrapie detection in goats, and (3) compare the performance of RT-QuIC for the detection of PrPSc with the more commonly used ELISA and Western blot assays. We further optimized RT-QuIC conditions for sensitive and specific detection of goat scrapie seeding activity in brain tissue from clinical animals. When used with 200 mM sodium chloride, both full-length sheep rPrPSen substrates (PrP genotypes A136R154Q171 and V136R154Q171) provided good discrimination between scrapie-infected and normal goat brain samples at 10− 3 dilution within 15 h. Our findings indicate that RT-QuIC was at least 10 000-fold more sensitive than ELISA and Western blot assays for the detection of scrapie seeding activity in goat brain samples. In addition to PRNP WT samples, positive RT-QuIC reactions were also observed with three PRNP polymorphic goat brain samples (G/S127, I/M142 and H/R143) tested. Taken together, these findings demonstrate that RT-QuIC sensitively detects prion seeding activity in classical scrapie-infected goat brain samples. PMID:26653410

Detection by voxel-wise statistical analysis of significant changes in regional cerebral glucose uptake in an APP/PS1 transgenic mouse model of Alzheimer's disease.

PubMed

Dubois, Albertine; Hérard, Anne-Sophie; Delatour, Benoît; Hantraye, Philippe; Bonvento, Gilles; Dhenain, Marc; Delzescaux, Thierry

2010-06-01

Biomarkers and technologies similar to those used in humans are essential for the follow-up of Alzheimer's disease (AD) animal models, particularly for the clarification of mechanisms and the screening and validation of new candidate treatments. In humans, changes in brain metabolism can be detected by 1-deoxy-2-[(18)F] fluoro-D-glucose PET (FDG-PET) and assessed in a user-independent manner with dedicated software, such as Statistical Parametric Mapping (SPM). FDG-PET can be carried out in small animals, but its resolution is low as compared to the size of rodent brain structures. In mouse models of AD, changes in cerebral glucose utilization are usually detected by [(14)C]-2-deoxyglucose (2DG) autoradiography, but this requires prior manual outlining of regions of interest (ROI) on selected sections. Here, we evaluate the feasibility of applying the SPM method to 3D autoradiographic data sets mapping brain metabolic activity in a transgenic mouse model of AD. We report the preliminary results obtained with 4 APP/PS1 (64+/-1 weeks) and 3 PS1 (65+/-2 weeks) mice. We also describe new procedures for the acquisition and use of "blockface" photographs and provide the first demonstration of their value for the 3D reconstruction and spatial normalization of post mortem mouse brain volumes. Despite this limited sample size, our results appear to be meaningful, consistent, and more comprehensive than findings from previously published studies based on conventional ROI-based methods. The establishment of statistical significance at the voxel level, rather than with a user-defined ROI, makes it possible to detect more reliably subtle differences in geometrically complex regions, such as the hippocampus. Our approach is generic and could be easily applied to other biomarkers and extended to other species and applications. Copyright 2010 Elsevier Inc. All rights reserved.

Dual-echo ASL based assessment of motor networks: a feasibility study

NASA Astrophysics Data System (ADS)

Storti, Silvia Francesca; Boscolo Galazzo, Ilaria; Pizzini, Francesca B.; Menegaz, Gloria

2018-04-01

Objective. Dual-echo arterial spin labeling (DE-ASL) technique has been recently proposed for the simultaneous acquisition of ASL and blood-oxygenation-level-dependent (BOLD)-functional magnetic resonance imaging (fMRI) data. The assessment of this technique in detecting functional connectivity at rest or during motor and motor imagery tasks is still unexplored both per-se and in comparison with conventional methods. The purpose is to quantify the sensitivity of the DE-ASL sequence with respect to the conventional fMRI sequence (cvBOLD) in detecting brain activations, and to assess and compare the relevance of node features in decoding the network structure. Approach. Thirteen volunteers were scanned acquiring a pseudo-continuous DE-ASL sequence from which the concomitant BOLD (ccBOLD) simultaneously to the ASL can be extracted. The approach consists of two steps: (i) model-based analyses for assessing brain activations at individual and group levels, followed by statistical analysis for comparing the activation elicited by the three sequences under two conditions (motor and motor imagery), respectively; (ii) brain connectivity graph-theoretical analysis for assessing and comparing the network models properties. Main results. Our results suggest that cvBOLD and ccBOLD have comparable sensitivity in detecting the regions involved in the active task, whereas ASL offers a higher degree of co-localization with smaller activation volumes. The connectivity results and the comparative analysis of node features across sequences revealed that there are no strong changes between rest and tasks and that the differences between the sequences are limited to few connections. Significance. Considering the comparable sensitivity of the ccBOLD and cvBOLD sequences in detecting activated brain regions, the results demonstrate that DE-ASL can be successfully applied in functional studies allowing to obtain both ASL and BOLD information within a single sequence. Further, DE-ASL is a powerful technique for research and clinical applications allowing to perform quantitative comparisons as well as to characterize functional connectivity.

Automatic brain tumor detection in MRI: methodology and statistical validation

NASA Astrophysics Data System (ADS)

Iftekharuddin, Khan M.; Islam, Mohammad A.; Shaik, Jahangheer; Parra, Carlos; Ogg, Robert

2005-04-01

Automated brain tumor segmentation and detection are immensely important in medical diagnostics because it provides information associated to anatomical structures as well as potential abnormal tissue necessary to delineate appropriate surgical planning. In this work, we propose a novel automated brain tumor segmentation technique based on multiresolution texture information that combines fractal Brownian motion (fBm) and wavelet multiresolution analysis. Our wavelet-fractal technique combines the excellent multiresolution localization property of wavelets to texture extraction of fractal. We prove the efficacy of our technique by successfully segmenting pediatric brain MR images (MRIs) from St. Jude Children"s Research Hospital. We use self-organizing map (SOM) as our clustering tool wherein we exploit both pixel intensity and multiresolution texture features to obtain segmented tumor. Our test results show that our technique successfully segments abnormal brain tissues in a set of T1 images. In the next step, we design a classifier using Feed-Forward (FF) neural network to statistically validate the presence of tumor in MRI using both the multiresolution texture and the pixel intensity features. We estimate the corresponding receiver operating curve (ROC) based on the findings of true positive fractions and false positive fractions estimated from our classifier at different threshold values. An ROC, which can be considered as a gold standard to prove the competence of a classifier, is obtained to ascertain the sensitivity and specificity of our classifier. We observe that at threshold 0.4 we achieve true positive value of 1.0 (100%) sacrificing only 0.16 (16%) false positive value for the set of 50 T1 MRI analyzed in this experiment.

Microstructural white matter alterations in preclinical Alzheimer’s disease detected using free water elimination diffusion tensor imaging

PubMed Central

Ly, Martina; Carlsson, Cynthia M.; Okonkwo, Ozioma C.; Zetterberg, Henrik; Blennow, Kaj; Sager, Mark A.; Asthana, Sanjay; Johnson, Sterling C.; Alexander, Andrew L.; Bendlin, Barbara B.

2017-01-01

Brain changes associated with Alzheimer’s disease (AD) begin decades before disease diagnosis. While β-amyloid plaques and neurofibrillary tangles are defining features of AD, neuronal loss and synaptic pathology are closely related to the cognitive dysfunction. Brain imaging methods that are tuned to assess degeneration of myelinated nerve fibers in the brain (collectively called white matter) include diffusion tensor imaging (DTI) and related techniques, and are expected to shed light on disease-related loss of structural connectivity. Participants (N = 70, ages 47–76 years) from the Wisconsin Registry for Alzheimer’s Prevention study underwent DTI and hybrid diffusion imaging to determine a free-water elimination (FWE-DTI) model. The study assessed the extent to which preclinical AD pathology affects brain white matter. Preclinical AD pathology was determined using cerebrospinal fluid (CSF) biomarkers. The sample was enriched for AD risk (APOE ε4 and parental history of AD). AD pathology assessed by CSF analyses was significantly associated with altered microstructure on both DTI and FWE-DTI. Affected regions included frontal, parietal, and especially temporal white matter. The f-value derived from the FWE-DTI model appeared to be the most sensitive to the relationship between the CSF AD biomarkers and microstructural alterations in white matter. These findings suggest that white matter degeneration is an early pathological feature of AD that may have utility both for early disease detection and as outcome measures for clinical trials. More complex models of microstructural diffusion properties including FWE-DTI may provide increased sensitivity to early brain changes associated with AD over standard DTI. PMID:28291839

Cortisol Excess and the Brain.

PubMed

Resmini, Eugenia; Santos, Alicia; Webb, Susan M

2016-01-01

Until the last decade, little was known about the effects of chronic hypercortisolism on the brain. In the last few years, new data have arisen thanks to advances in imaging techniques; therefore, it is now possible to investigate brain activity in vivo. Memory impairments are present in patients with Cushing's syndrome (CS) and are related to hippocampal damage; functional dysfunctions would precede structural abnormalities as detected by brain imaging. Earlier diagnosis and rapid normalization of hypercortisolism could stop the progression of hippocampal damage and memory impairments. Impairments of executive functions (including decision-making) and other functions such as visuoconstructive skills, language, motor functions and information processing speed are also present in CS patients. There is controversy concerning the reversibility of brain impairment. It seems that longer disease duration and older age are associated with less recovery of brain functioning. Conversely, earlier diagnosis and rapid normalization of hypercortisolism appear to stop progression of brain damage and functional impairments. Moreover, brain tissue functioning and neuroplasticity can be influenced by many factors. Currently available studies appear to be complementary, evaluating the same phenomenon from different points of view, but are often not directly comparable. Finally, CS patients have a high prevalence of psychopathology, such as depression and anxiety which do not completely revert after cure. Thus, psychological or psychiatric evaluation could be recommended in CS patients, so that treatment may be prescribed if required. © 2016 S. Karger AG, Basel.

Magnetic bead-quantum dot assay for detection of a biomarker for traumatic brain injury

NASA Astrophysics Data System (ADS)

Kim, Chloe; Searson, Peter C.

2015-10-01

Current diagnostic methods for traumatic brain injury (TBI), which accounts for 15% of all emergency room visits, are limited to neuroimaging modalities. The challenges of accurate diagnosis and monitoring of TBI have created the need for a simple and sensitive blood test to detect brain-specific biomarkers. Here we report on an assay for detection of S100B, a putative biomarker for TBI, using antibody-conjugated magnetic beads for capture of the protein, and antibody-conjugated quantum dots for optical detection. From Western Blot, we show efficient antigen capture and concentration by the magnetic beads. Using magnetic bead capture and quantum dot detection in serum samples, we show a wide detection range and detection limit below the clinical cut-off level.Current diagnostic methods for traumatic brain injury (TBI), which accounts for 15% of all emergency room visits, are limited to neuroimaging modalities. The challenges of accurate diagnosis and monitoring of TBI have created the need for a simple and sensitive blood test to detect brain-specific biomarkers. Here we report on an assay for detection of S100B, a putative biomarker for TBI, using antibody-conjugated magnetic beads for capture of the protein, and antibody-conjugated quantum dots for optical detection. From Western Blot, we show efficient antigen capture and concentration by the magnetic beads. Using magnetic bead capture and quantum dot detection in serum samples, we show a wide detection range and detection limit below the clinical cut-off level. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr05608j

Oligodendroglial Alterations and the Role of Microglia in White Matter Injury: Relevance to Schizophrenia

PubMed Central

Chew, Li-Jin; Fusar-Poli, Paolo; Schmitz, Thomas

2015-01-01

Schizophrenia is a chronic and debilitating mental illness characterized by a broad range of abnormal behaviors, including delusions and hallucinations, impaired cognitive function, as well as mood disturbances and social withdrawal. Due to the heterogeneous nature of the disease, the causes of schizophrenia are very complex; its etiology is believed to involve multiple brain regions and the connections between them, and includes alterations in both gray and white matter regions. The onset of symptoms varies with age and severity, and there is some debate over a degenerative or developmental etiology. Longitudinal magnetic resonance imaging studies have detected progressive gray matter loss in the first years of disease, suggesting neurodegeneration; but there is also increasing recognition of a temporal association between clinical complications at birth and disease onset that supports a neurodevelopmental origin. Presently, neuronal abnormalities in schizophrenia are better understood than alterations in myelin-producing cells of the brain, the oligodendrocytes, which are the predominant constituents of white matter structures. Proper white matter development and its structural integrity critically impacts brain connectivity, which affects sensorimotor coordination and cognitive ability. Evidence of defective white matter growth and compromised white matter integrity has been found in individuals at high risk of psychosis, and decreased numbers of mature oligodendrocytes are detected in schizophrenia patients. Inflammatory markers, including proinflammatory cytokines and chemokines, are also associated with psychosis. A relationship between risk of psychosis, white matter defects and prenatal inflammation is being established. Animal models of perinatal brain injury are successful in producing white matter damage in the brain, typified by hypomyelination and/or dysmyelination, impaired motor coordination and prepulse inhibition of the acoustic startle reflex, recapitulating structural and functional characteristics observed in schizophrenia. In addition, elevated expression of inflammation-related genes in brain tissue and increased production of cytokines by blood cells from patients with schizophrenia indicate immunological dysfunction and abnormal inflammatory responses, which are also important underlying features in experimental models. Microglia, resident immune defenders of the central nervous system, play important roles in the development and protection of neural cells, but can contribute to injury under pathological conditions. This article discusses oligodendroglial changes in schizophrenia and focuses on microglial activity in the context of the disease, in neonatal brain injury and in various experimental models of white matter damage. These include disorders associated with premature birth, and animal models of perinatal bacterial and viral infection, oxygen deprivation (hypoxia) and excess (hyperoxia), and elevated systemic proinflammatory cytokine levels. We briefly review the effects of treatment with antipsychotic and anti-inflammatory agents in models of perinatal brain injury, and comment on the therapeutic potential of these strategies. By understanding the neurobiological basis of oligodendroglial abnormalities in schizophrenia, it is hoped that patients will benefit from the availability of targeted and more efficacious treatment options. PMID:23446060

Automatic detection and segmentation of brain metastases on multimodal MR images with a deep convolutional neural network.

PubMed

Charron, Odelin; Lallement, Alex; Jarnet, Delphine; Noblet, Vincent; Clavier, Jean-Baptiste; Meyer, Philippe

2018-04-01

Stereotactic treatments are today the reference techniques for the irradiation of brain metastases in radiotherapy. The dose per fraction is very high, and delivered in small volumes (diameter <1 cm). As part of these treatments, effective detection and precise segmentation of lesions are imperative. Many methods based on deep-learning approaches have been developed for the automatic segmentation of gliomas, but very little for that of brain metastases. We adapted an existing 3D convolutional neural network (DeepMedic) to detect and segment brain metastases on MRI. At first, we sought to adapt the network parameters to brain metastases. We then explored the single or combined use of different MRI modalities, by evaluating network performance in terms of detection and segmentation. We also studied the interest of increasing the database with virtual patients or of using an additional database in which the active parts of the metastases are separated from the necrotic parts. Our results indicated that a deep network approach is promising for the detection and the segmentation of brain metastases on multimodal MRI. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of Boric Acid Supplementation on the Expression of BDNF in African Ostrich Chick Brain.

PubMed

Tang, Juan; Zheng, Xing-ting; Xiao, Ke; Wang, Kun-lun; Wang, Jing; Wang, Yun-xiao; Wang, Ke; Wang, Wei; Lu, Shun; Yang, Ke-li; Sun, Peng-Peng; Khaliq, Haseeb; Zhong, Juming; Peng, Ke-Mei

2016-03-01

The degree of brain development can be expressed by the levels of brain brain-derived neurotrophic factor (BDNF). BDNF plays an irreplaceable role in the process of neuronal development, protection, and restoration. The aim of the present study was to evaluate the effects of boric acid supplementation in water on the ostrich chick neuronal development. One-day-old healthy animals were supplemented with boron in drinking water at various concentrations, and the potential effects of boric acid on brain development were tested by a series of experiments. The histological changes in brain were observed by hematoxylin and eosin (HE) staining and Nissl staining. Expression of BDNF was analyzed by immunohistochemistry, quantitative real-time PCR (QRT-PCR), and enzyme linked immunosorbent assay (ELISA). Apoptosis was evaluated with Dutp-biotin nick end labeling (TUNEL) reaction, and caspase-3 was detected with QRT-PCR. The results were as follows: (1) under the light microscope, the neuron structure was well developed with abundance of neurites and intact cell morphology when animals were fed with less than 160 mg/L of boric acid (groups II, III, IV). Adversely, when boric acid doses were higher than 320 mg/L(groups V, VI), the high-dose boric acid neuron structure was damaged with less neurites, particularly at 640 mg/L; (2) the quantity of BDNF expression in groups II, III, and IV was increased while it was decreased in groups V and VI when compared with that in group I; (3) TUNEL reaction and the caspase-3 mRNA level showed that the amount of cell apoptosis in group II, group III, and group IV were decreased, but increased in group V and group VI significantly. These results indicated that appropriate supplementation of boric acid, especially at 160 mg/L, could promote ostrich chicks' brain development by promoting the BDNF expression and reducing cell apoptosis. Conversely, high dose of boric acid particularly in 640 mg/L would damage the neuron structure of ostrich chick brain by inhibiting the BDNF expression and increasing cell apoptosis. Taken together, the 160 mg/L boric acid supplementation may be the optimal dose for the brain development of ostrich chicks.

The effects of musical training on structural brain development: a longitudinal study.

PubMed

Hyde, Krista L; Lerch, Jason; Norton, Andrea; Forgeard, Marie; Winner, Ellen; Evans, Alan C; Schlaug, Gottfried

2009-07-01

Long-term instrumental music training is an intense, multisensory and motor experience that offers an ideal opportunity to study structural brain plasticity in the developing brain in correlation with behavioral changes induced by training. Here, for the first time, we demonstrate structural brain changes after only 15 months of musical training in early childhood, which were correlated with improvements in musically relevant motor and auditory skills. These findings shed light on brain plasticity, and suggest that structural brain differences in adult experts (whether musicians or experts in other areas) are likely due to training-induced brain plasticity.

[An experimental study on the Chinese lung adenocarcinoma cell clone CPA-Yang1-BR with brain metastasis potency in nude mice and in vivo imaging research].

PubMed

Lei, Bei; Cao, Jie; Shen, Jie; Zhao, Lanxiang; Liang, Sheng; Meng, Qinggang; Xie, Wenhui; Yang, Shunfang

2013-08-20

Lung cancer is the leading cause of cancer-related death in men and women. It is also the most common cause of brain metastases. A brain metastasis model is difficult to be established because of the presence of the blood-brain barrier (BBB) and the lack of optimal methods for detecting brain metastasis in nude mice. Thus, the establishment of a Chinese lung adenocarcinoma cell line and its animal model with brain metastasis potency and in vivo research is of great significance. CPA-Yang1 cells were obtained from a patient with human lung adenocarcinoma by lentiviral vector-mediated transfection of green fluorescence protein. Intracardiac inoculation of the cells was performed in nude mice, and brain metastatic lesions were detected using micro ¹⁸F FDG-PET/CT scanners, small animal in vivo imaging system for fluorescence, radionuclide and X ray fused imaging, magnetic resonance imaging (MRI) with sense body detection, and resection. The samples were divided into two parts for cell culture and histological diagnosis. The process was repeated in vivo and in vitro for four cycles to obtain a novel cell clone, CPA-Yang1-BR. A novel cell clone, CPA-Yang1-BR, was obtained with a brain metastatic rate of 50%. The use of MRI for the detection of brain metastases has obvious advantages. An experimental Chinese lung adenocarcinoma cell clone (CPA-Yang1-BR) and its animal model with brain metastasis potency in nude mice were established. MRI with sense body or micro MRI may be used as a sensitive, accurate, and noninvasive method to detect experimental brain metastases in intact live immunodeficient mice. The results of this study may serve as a technical platform for brain metastases from lung adenocarcinoma.

Property of lysosomal storage disease associated with midbrain pathology in the central nervous system of Lamp-2-deficient mice.

PubMed

Furuta, Akiko; Kikuchi, Hisae; Fujita, Hiromi; Yamada, Daisuke; Fujiwara, Yuuki; Kabuta, Tomohiro; Nishino, Ichizo; Wada, Keiji; Uchiyama, Yasuo

2015-06-01

Lysosome-associated membrane protein-2 (LAMP-2) is the gene responsible for Danon disease, which is characterized by cardiomyopathy, autophagic vacuolar myopathy, and variable mental retardation. To elucidate the function of LAMP-2 in the central nervous system, we investigated the neuropathological changes in Lamp-2-deficient mice. Immunohistochemical observations revealed that Lamp-1 and cathepsin D-positive lysosomal structures increased in the large neurons of the mouse brain. Ubiquitin-immunoreactive aggregates and concanavalin A-positive materials were detected in these neurons. By means of ultrastructural studies, we found various-shaped accumulations, including lipofuscin, glycolipid-like materials, and membranous structures, in the neurons and glial cells of Lamp-2-deficient brains. In deficient mice, glycogen granules accumulated in hepatocyte lysosomes but were not observed in neurons. These pathological features indicate lysosomal storage disease; however, the findings are unlikely a consequence of deficiency of a single lysosomal enzyme. Although previous study results have shown a large amount of autophagic vacuoles in parenchymal cells of the visceral organs, these findings were rarely detected in the brain tissue except for some axons in the substantia nigra, in which abundant activated microglial cells with increased lipid peroxidation were observed. Thus, LAMP-2 in the central nervous system has a possible role in the degradation of the various macromolecules in lysosomes and an additional function concerning protection from oxidative stress, especially in the substantia nigra. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Drug-enhanced carbon monoxide production from heme by cytochrome P450 reductase.

PubMed

Vukomanovic, Dragic; Rahman, Mona N; Jia, Zongchao; Nakatsu, Kanji

2017-01-01

Carbon monoxide (CO) formed endogenously is considered to be cytoprotective, and the vast majority of CO formation is attributed to the degradation of heme by heme oxygenases-1 and -2 (HO-1, HO-2). Previously, we observed that brain microsomes containing HO-2 produced many-fold more CO in the presence of menadione and its congeners; herein we explored these observations further. We determined the effects of various drugs on CO production of rat brain microsomes and recombinant human cytochrome P450 reductase (CPR); CO was measured by gas chromatography with reductive detection. Brain microsomes of Sprague-Dawley rats or recombinant human cytochrome P450 reductase (CPR) were incubated with NADPH and various drugs in closed vials in phosphate buffer at pH 7.4 and 37°C. After 15 minutes, the reaction was stopped by cooling in dry ice, and the headspace gas was analyzed for CO production using gas chromatography with reductive (mercuric oxide) detection. We observed drug-enhanced CO production in the presence of both microsomes and recombinant CPR alone; the presence of HO was not required. A range of structurally diverse drugs were capable of amplifying this CO formation; these molecules had structures consistent with redox cycling capability. The addition of catalase to a reaction mixture, that contained activating drugs, inhibited the production of CO. Drug-enhanced CO formation can be catalyzed by CPR. The mechanism of CPR activation was not through classical drug-receptor mediation. Redox cycling may be involved in the drug-induced amplification of CO production by CPR through the production of reactive oxygen species.

Cognitive and connectome properties detectable through individual differences in graphomotor organization.

PubMed

Lamar, Melissa; Ajilore, Olusola; Leow, Alex; Charlton, Rebecca; Cohen, Jamie; GadElkarim, Johnson; Yang, Shaolin; Zhang, Aifeng; Davis, Randall; Penney, Dana; Libon, David J; Kumar, Anand

2016-05-01

We investigated whether graphomotor organization during a digitized Clock Drawing Test (dCDT) would be associated with cognitive and/or brain structural differences detected with a tractography-derived structural connectome of the brain. 72 non-demented/non-depressed adults were categorized based on whether or not they used 'anchor' digits (i.e., 12, 3, 6, 9) before any other digits while completing dCDT instructions to "draw the face of a clock with all the numbers and set the hands to 10 after 11". 'Anchorers' were compared to 'non-anchorers' across dCDT, additional cognitive measures and connectome-based metrics. In the context of grossly intact clock drawings, anchorers required fewer strokes to complete the dCDT and outperformed non-anchorers on executive functioning and learning/memory/recognition tasks. Anchorers had higher local efficiency for the left medial orbitofrontal and transverse temporal cortices as well as the right rostral anterior cingulate and superior frontal gyrus versus non-anchorers suggesting better regional integration within local networks involving these regions; select aspects of which correlated with cognition. Results also revealed that anchorers' exhibited a higher degree of modular integration among heteromodal regions of the ventral visual processing stream versus non-anchorers. Thus, an easily observable graphomotor distinction was associated with 1) better performance in specific cognitive domains, 2) higher local efficiency suggesting better regional integration, and 3) more sophisticated modular integration involving the ventral ('what') visuospatial processing stream. Taken together, these results enhance our knowledge of the brain-behavior relationships underlying unprompted graphomotor organization during dCDT. Copyright © 2016 Elsevier Ltd. All rights reserved.

When structure affects function--the need for partial volume effect correction in functional and resting state magnetic resonance imaging studies.

PubMed

Dukart, Juergen; Bertolino, Alessandro

2014-01-01

Both functional and also more recently resting state magnetic resonance imaging have become established tools to investigate functional brain networks. Most studies use these tools to compare different populations without controlling for potential differences in underlying brain structure which might affect the functional measurements of interest. Here, we adapt a simulation approach combined with evaluation of real resting state magnetic resonance imaging data to investigate the potential impact of partial volume effects on established functional and resting state magnetic resonance imaging analyses. We demonstrate that differences in the underlying structure lead to a significant increase in detected functional differences in both types of analyses. Largest increases in functional differences are observed for highest signal-to-noise ratios and when signal with the lowest amount of partial volume effects is compared to any other partial volume effect constellation. In real data, structural information explains about 25% of within-subject variance observed in degree centrality--an established resting state connectivity measurement. Controlling this measurement for structural information can substantially alter correlational maps obtained in group analyses. Our results question current approaches of evaluating these measurements in diseased population with known structural changes without controlling for potential differences in these measurements.

Medication Overuse Headache: Pathophysiological Insights from Structural and Functional Brain MRI Research.

PubMed

Schwedt, Todd J; Chong, Catherine D

2017-07-01

Research imaging of brain structure and function has helped to elucidate the pathophysiology of medication overuse headache (MOH). This is a narrative review of imaging research studies that have investigated brain structural and functional alterations associated with MOH. Studies included in this review have investigated abnormal structure and function of pain processing regions in people with MOH, functional patterns that might predispose individuals to development of MOH, similarity of brain functional patterns in patients with MOH to those found in people with addiction, brain structure that could predict headache improvement following discontinuation of the overused medication, and changes in brain structure and function after discontinuation of medication overuse. MOH is associated with atypical structure and function of brain regions responsible for pain processing as well as brain regions that are commonly implicated in addiction. Several studies have shown "normalization" of structure and function in pain processing regions following discontinuation of the overused medication and resolution of MOH. However, some of the abnormalities in regions also implicated in addiction tend to persist following discontinuation of the overused medication, suggesting that they are a brain trait that predisposes certain individuals to medication overuse and MOH. © 2017 American Headache Society.

Asymmetry of Hemispheric Network Topology Reveals Dissociable Processes between Functional and Structural Brain Connectome in Community-Living Elders

PubMed Central

Sun, Yu; Li, Junhua; Suckling, John; Feng, Lei

2017-01-01

Human brain is structurally and functionally asymmetrical and the asymmetries of brain phenotypes have been shown to change in normal aging. Recent advances in graph theoretical analysis have showed topological lateralization between hemispheric networks in the human brain throughout the lifespan. Nevertheless, apparent discrepancies of hemispheric asymmetry were reported between the structural and functional brain networks, indicating the potentially complex asymmetry patterns between structural and functional networks in aging population. In this study, using multimodal neuroimaging (resting-state fMRI and structural diffusion tensor imaging), we investigated the characteristics of hemispheric network topology in 76 (male/female = 15/61, age = 70.08 ± 5.30 years) community-dwelling older adults. Hemispheric functional and structural brain networks were obtained for each participant. Graph theoretical approaches were then employed to estimate the hemispheric topological properties. We found that the optimal small-world properties were preserved in both structural and functional hemispheric networks in older adults. Moreover, a leftward asymmetry in both global and local levels were observed in structural brain networks in comparison with a symmetric pattern in functional brain network, suggesting a dissociable process of hemispheric asymmetry between structural and functional connectome in healthy older adults. Finally, the scores of hemispheric asymmetry in both structural and functional networks were associated with behavioral performance in various cognitive domains. Taken together, these findings provide new insights into the lateralized nature of multimodal brain connectivity, highlight the potentially complex relationship between structural and functional brain network alterations, and augment our understanding of asymmetric structural and functional specializations in normal aging. PMID:29209197

Mathematical Logic in the Human Brain: Semantics

PubMed Central

Friedrich, Roland M.; Friederici, Angela D.

2013-01-01

As a higher cognitive function in humans, mathematics is supported by parietal and prefrontal brain regions. Here, we give an integrative account of the role of the different brain systems in processing the semantics of mathematical logic from the perspective of macroscopic polysynaptic networks. By comparing algebraic and arithmetic expressions of identical underlying structure, we show how the different subparts of a fronto-parietal network are modulated by the semantic domain, over which the mathematical formulae are interpreted. Within this network, the prefrontal cortex represents a system that hosts three major components, namely, control, arithmetic-logic, and short-term memory. This prefrontal system operates on data fed to it by two other systems: a premotor-parietal top-down system that updates and transforms (external) data into an internal format, and a hippocampal bottom-up system that either detects novel information or serves as an access device to memory for previously acquired knowledge. PMID:23301101

Highly Crumpled All-Carbon Transistors for Brain Activity Recording.

PubMed

Yang, Long; Zhao, Yan; Xu, Wenjing; Shi, Enzheng; Wei, Wenjing; Li, Xinming; Cao, Anyuan; Cao, Yanping; Fang, Ying

2017-01-11

Neural probes based on graphene field-effect transistors have been demonstrated. Yet, the minimum detectable signal of graphene transistor-based probes is inversely proportional to the square root of the active graphene area. This fundamentally limits the scaling of graphene transistor-based neural probes for improved spatial resolution in brain activity recording. Here, we address this challenge using highly crumpled all-carbon transistors formed by compressing down to 16% of its initial area. All-carbon transistors, chemically synthesized by seamless integration of graphene channels and hybrid graphene/carbon nanotube electrodes, maintained structural integrity and stable electronic properties under large mechanical deformation, whereas stress-induced cracking and junction failure occurred in conventional graphene/metal transistors. Flexible, highly crumpled all-carbon transistors were further verified for in vivo recording of brain activity in rats. These results highlight the importance of advanced material and device design concepts to make improvements in neuroelectronics.

Mathematical logic in the human brain: semantics.

PubMed

Friedrich, Roland M; Friederici, Angela D

2013-01-01

As a higher cognitive function in humans, mathematics is supported by parietal and prefrontal brain regions. Here, we give an integrative account of the role of the different brain systems in processing the semantics of mathematical logic from the perspective of macroscopic polysynaptic networks. By comparing algebraic and arithmetic expressions of identical underlying structure, we show how the different subparts of a fronto-parietal network are modulated by the semantic domain, over which the mathematical formulae are interpreted. Within this network, the prefrontal cortex represents a system that hosts three major components, namely, control, arithmetic-logic, and short-term memory. This prefrontal system operates on data fed to it by two other systems: a premotor-parietal top-down system that updates and transforms (external) data into an internal format, and a hippocampal bottom-up system that either detects novel information or serves as an access device to memory for previously acquired knowledge.

Prediction of activation patterns preceding hallucinations in patients with schizophrenia using machine learning with structured sparsity.

PubMed

de Pierrefeu, Amicie; Fovet, Thomas; Hadj-Selem, Fouad; Löfstedt, Tommy; Ciuciu, Philippe; Lefebvre, Stephanie; Thomas, Pierre; Lopes, Renaud; Jardri, Renaud; Duchesnay, Edouard

2018-04-01

Despite significant progress in the field, the detection of fMRI signal changes during hallucinatory events remains difficult and time-consuming. This article first proposes a machine-learning algorithm to automatically identify resting-state fMRI periods that precede hallucinations versus periods that do not. When applied to whole-brain fMRI data, state-of-the-art classification methods, such as support vector machines (SVM), yield dense solutions that are difficult to interpret. We proposed to extend the existing sparse classification methods by taking the spatial structure of brain images into account with structured sparsity using the total variation penalty. Based on this approach, we obtained reliable classifying performances associated with interpretable predictive patterns, composed of two clearly identifiable clusters in speech-related brain regions. The variation in transition-to-hallucination functional patterns not only from one patient to another but also from one occurrence to the next (e.g., also depending on the sensory modalities involved) appeared to be the major difficulty when developing effective classifiers. Consequently, second, this article aimed to characterize the variability within the prehallucination patterns using an extension of principal component analysis with spatial constraints. The principal components (PCs) and the associated basis patterns shed light on the intrinsic structures of the variability present in the dataset. Such results are promising in the scope of innovative fMRI-guided therapy for drug-resistant hallucinations, such as fMRI-based neurofeedback. © 2018 Wiley Periodicals, Inc.

Proton spectroscopy in the narcoleptic syndrome. Is there evidence of a brainstem lesion?

PubMed

Ellis, C M; Simmons, A; Lemmens, G; Williams, S C; Parkes, J D

1998-02-01

There is controversy regarding the relationship of structural or biochemical brainstem lesions to "idiopathic" narcolepsy. Most cases of the narcoleptic syndrome are considered to be idiopathic because no structural lesion is detectable, although some cases of secondary narcolepsy are known to be associated with no structural brainstem lesions. Using proton spectroscopy, we determined levels of ventral pontine metabolite pools in 12 normal subjects and 12 subjects with idiopathic narcolepsy. REM sleep is generated in ventral pontine areas. Proton spectroscopy was used to study levels of N-acetyl aspartate (NAA) as a marker of cell mass, creatine and phosphocreatine (Cr + PCr), and choline (Cho). The intensity of the peaks, as determined by the area under the peak (AUP), was measured. The AUP correlates with the quantity of chemical present. In this study, the ratios of NAA to Cr + PCr were similar in normal subjects and in narcoleptic subjects with idiopathic narcolepsy. No differences in measured metabolic ratio were observed in subjects who slept during the scan procedure compared with those who remained awake. Subjects with "symptomatic" narcolepsy accompanied by an obvious structural brain lesion were not studied. Proton spectroscopy of the brain initiates a new kind of neurochemistry, allowing the noninvasive study of metabolic pools in the living human brain without the use of any kind of tracer or radioactive molecule. In this study, there was no evidence of cell loss in the ventral pontine areas of subjects with the narcoleptic syndrome.

Brain Surface Conformal Parameterization Using Riemann Surface Structure

PubMed Central

Wang, Yalin; Lui, Lok Ming; Gu, Xianfeng; Hayashi, Kiralee M.; Chan, Tony F.; Toga, Arthur W.; Thompson, Paul M.; Yau, Shing-Tung

2011-01-01

In medical imaging, parameterized 3-D surface models are useful for anatomical modeling and visualization, statistical comparisons of anatomy, and surface-based registration and signal processing. Here we introduce a parameterization method based on Riemann surface structure, which uses a special curvilinear net structure (conformal net) to partition the surface into a set of patches that can each be conformally mapped to a parallelogram. The resulting surface subdivision and the parameterizations of the components are intrinsic and stable (their solutions tend to be smooth functions and the boundary conditions of the Dirichlet problem can be enforced). Conformal parameterization also helps transform partial differential equations (PDEs) that may be defined on 3-D brain surface manifolds to modified PDEs on a two-dimensional parameter domain. Since the Jacobian matrix of a conformal parameterization is diagonal, the modified PDE on the parameter domain is readily solved. To illustrate our techniques, we computed parameterizations for several types of anatomical surfaces in 3-D magnetic resonance imaging scans of the brain, including the cerebral cortex, hippocampi, and lateral ventricles. For surfaces that are topologically homeomorphic to each other and have similar geometrical structures, we show that the parameterization results are consistent and the subdivided surfaces can be matched to each other. Finally, we present an automatic sulcal landmark location algorithm by solving PDEs on cortical surfaces. The landmark detection results are used as constraints for building conformal maps between surfaces that also match explicitly defined landmarks. PMID:17679336

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

PubMed Central

2011-01-01

Background Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Results Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Conclusions Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development. PMID:21736737

Bold-Independent Computational Entropy Assesses Functional Donut-Like Structures in Brain fMRI Images

PubMed Central

Peters, James F.; Ramanna, Sheela; Tozzi, Arturo; İnan, Ebubekir

2017-01-01

We introduce a novel method for the measurement of information level in fMRI (functional Magnetic Resonance Imaging) neural data sets, based on image subdivision in small polygons equipped with different entropic content. We show how this method, called maximal nucleus clustering (MNC), is a novel, fast and inexpensive image-analysis technique, independent from the standard blood-oxygen-level dependent signals. MNC facilitates the objective detection of hidden temporal patterns of entropy/information in zones of fMRI images generally not taken into account by the subjective standpoint of the observer. This approach befits the geometric character of fMRIs. The main purpose of this study is to provide a computable framework for fMRI that not only facilitates analyses, but also provides an easily decipherable visualization of structures. This framework commands attention because it is easily implemented using conventional software systems. In order to evaluate the potential applications of MNC, we looked for the presence of a fourth dimension's distinctive hallmarks in a temporal sequence of 2D images taken during spontaneous brain activity. Indeed, recent findings suggest that several brain activities, such as mind-wandering and memory retrieval, might take place in the functional space of a four dimensional hypersphere, which is a double donut-like structure undetectable in the usual three dimensions. We found that the Rényi entropy is higher in MNC areas than in the surrounding ones, and that these temporal patterns closely resemble the trajectories predicted by the possible presence of a hypersphere in the brain. PMID:28203153

Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users.

PubMed

Gilman, Jodi M; Kuster, John K; Lee, Sang; Lee, Myung Joo; Kim, Byoung Woo; Makris, Nikos; van der Kouwe, Andre; Blood, Anne J; Breiter, Hans C

2014-04-16

Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to Δ9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization.

Fetal functional imaging portrays heterogeneous development of emerging human brain networks

PubMed Central

Jakab, András; Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M.; Prayer, Daniela; Schöpf, Veronika; Langs, Georg

2014-01-01

The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26–29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity. PMID:25374531

Fetal functional imaging portrays heterogeneous development of emerging human brain networks.

PubMed

Jakab, András; Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M; Prayer, Daniela; Schöpf, Veronika; Langs, Georg

2014-01-01

The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26-29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity.

Brain hyperintensity location determines outcome in the triad of impaired cognition, physical health and depressive symptoms: A cohort study in late life.

PubMed

Murray, Alison; McNeil, Chris; Salarirad, Sima; Deary, Ian; Phillips, Louise; Whalley, Lawrence; Staff, Roger

2016-01-01

Brain hyperintensities, detectable with MRI, increase with age. They are associated with a triad of impairment in cognitive ability, depression and physical health. Here we test the hypothesis that the association between hyperintensities and cognitive ability, physical health and depressive symptoms depends on lesion location. 244 members of the Aberdeen 1936 Birth Cohort were recruited to this study. 227 participants completed brain MRI and their hyperintensities were scored using Scheltens's scale. 205 had complete imaging, cognitive, physical health and depressive symptom score data. The relationships between hyperintensity location and depressive symptoms, cognitive ability and physical health were examined by correlation and structural equation analysis. We found that depressive symptoms correlated with hyperintensity burden in the grey matter (r=0.14, p=0.04) and infratentorial regions (r=0.17, p=0.01). Infratentorial hyperintensities correlated with reduced peak expiratory flow rate (r=-0.26, p<0.001) and impaired gait (r=0.13, p=0.05). No relationship was found between white matter and periventricular (supratentoral) hyperintensities and depressive symptoms. Hyperintensities in the supratentorial and infratentorial regions were associated with reduced cognitive performance. Using structural equation modelling we found that the association between hyperintensities and depressive symptoms was mediated by negative effects on physical health and cognitive ability. Hyperintensities in deep brain structures are associated with depressive symptoms, mediated via impaired physical health and cognitive ability. Participants with higher cognitive ability and better physical health are at lower risk of depressive symptoms. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Bold-Independent Computational Entropy Assesses Functional Donut-Like Structures in Brain fMRI Images.

PubMed

Peters, James F; Ramanna, Sheela; Tozzi, Arturo; İnan, Ebubekir

2017-01-01

We introduce a novel method for the measurement of information level in fMRI (functional Magnetic Resonance Imaging) neural data sets, based on image subdivision in small polygons equipped with different entropic content. We show how this method, called maximal nucleus clustering (MNC), is a novel, fast and inexpensive image-analysis technique, independent from the standard blood-oxygen-level dependent signals. MNC facilitates the objective detection of hidden temporal patterns of entropy/information in zones of fMRI images generally not taken into account by the subjective standpoint of the observer. This approach befits the geometric character of fMRIs. The main purpose of this study is to provide a computable framework for fMRI that not only facilitates analyses, but also provides an easily decipherable visualization of structures. This framework commands attention because it is easily implemented using conventional software systems. In order to evaluate the potential applications of MNC, we looked for the presence of a fourth dimension's distinctive hallmarks in a temporal sequence of 2D images taken during spontaneous brain activity. Indeed, recent findings suggest that several brain activities, such as mind-wandering and memory retrieval, might take place in the functional space of a four dimensional hypersphere, which is a double donut-like structure undetectable in the usual three dimensions. We found that the Rényi entropy is higher in MNC areas than in the surrounding ones, and that these temporal patterns closely resemble the trajectories predicted by the possible presence of a hypersphere in the brain.

Latent NOTCH3 epitopes unmasked in CADASIL and regulated by protein redox state.

PubMed

Zhang, Xiaojie; Lee, Soo Jung; Young, Kelly Z; Josephson, David A; Geschwind, Michael D; Wang, Michael M

2014-10-02

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy CADASIL is caused by more than a hundred NOTCH3 mutations. Virtually all encoded mutant proteins contain an odd number of cysteines. As such, structural changes in NOTCH3 may be the primary molecular abnormality in CADASIL. Thus, we sought evidence for structurally altered NOTCH3 protein in CADASIL tissue. Four antibodies were raised in rabbits against two non-overlapping N-terminal NOTCH3 sequences. These reagents were used in immunohistochemical experiments to detect epitopes in post-mortem CADASIL brains (n=8), control brains, and cells overexpressing NOTCH3. To determine the biochemical nature of NOTCH3 epitopes, we used these antibodies to probe pure NOTCH3-Fc fusion proteins treated with acid, urea, guanidinium, ionic detergents, acrylamide, and thiol- and phosphorus-based reductants. All antibodies avidly stained arteries in 8 of 8 CADASIL brain samples. The most prominent staining was in degenerating media of leptomeningeal arteries and sclerotic penetrating vessels. Normal appearing vessels from control brains were not reactive. Antibodies did not react with cultured cells overexpressing NOTCH3 or with purified NOTCH3-Fc protein. Furthermore, treatment of pure protein with acid, chaotropic denaturants, alkylators, and detergents failed to unmask N-terminal NOTCH3 epitopes. Antibodies, however, recognized novel N-terminal epitopes in purified NOTCH3-Fc protein treated with three different reductants (DTT, beta-mercaptoethanol, and TCEP). We conclude that CADASIL arteries feature latent N-terminal NOTCH3 epitopes, suggesting the first evidence in vivo of NOTCH3 structural alterations. Published by Elsevier B.V.

Automatic pose correction for image-guided nonhuman primate brain surgery planning

NASA Astrophysics Data System (ADS)

Ghafurian, Soheil; Chen, Antong; Hines, Catherine; Dogdas, Belma; Bone, Ashleigh; Lodge, Kenneth; O'Malley, Stacey; Winkelmann, Christopher T.; Bagchi, Ansuman; Lubbers, Laura S.; Uslaner, Jason M.; Johnson, Colena; Renger, John; Zariwala, Hatim A.

2016-03-01

Intracranial delivery of recombinant DNA and neurochemical analysis in nonhuman primate (NHP) requires precise targeting of various brain structures via imaging derived coordinates in stereotactic surgeries. To attain targeting precision, the surgical planning needs to be done on preoperative three dimensional (3D) CT and/or MR images, in which the animals head is fixed in a pose identical to the pose during the stereotactic surgery. The matching of the image to the pose in the stereotactic frame can be done manually by detecting key anatomical landmarks on the 3D MR and CT images such as ear canal and ear bar zero position. This is not only time intensive but also prone to error due to the varying initial poses in the images which affects both the landmark detection and rotation estimation. We have introduced a fast, reproducible, and semi-automatic method to detect the stereotactic coordinate system in the image and correct the pose. The method begins with a rigid registration of the subject images to an atlas and proceeds to detect the anatomical landmarks through a sequence of optimization, deformable and multimodal registration algorithms. The results showed similar precision (maximum difference of 1.71 in average in-plane rotation) to a manual pose correction.

Magnetic Resonance Imaging to Detect Early Molecular and Cellular Changes in Alzheimer's Disease.

PubMed

Knight, Michael J; McCann, Bryony; Kauppinen, Risto A; Coulthard, Elizabeth J

2016-01-01

Recent pharmaceutical trials have demonstrated that slowing or reversing pathology in Alzheimer's disease is likely to be possible only in the earliest stages of disease, perhaps even before significant symptoms develop. Pathology in Alzheimer's disease accumulates for well over a decade before symptoms are detected giving a large potential window of opportunity for intervention. It is therefore important that imaging techniques detect subtle changes in brain tissue before significant macroscopic brain atrophy. Current diagnostic techniques often do not permit early diagnosis or are too expensive for routine clinical use. Magnetic Resonance Imaging (MRI) is the most versatile, affordable, and powerful imaging modality currently available, being able to deliver detailed analyses of anatomy, tissue volumes, and tissue state. In this mini-review, we consider how MRI might detect patients at risk of future dementia in the early stages of pathological change when symptoms are mild. We consider the contributions made by the various modalities of MRI (structural, diffusion, perfusion, relaxometry) in identifying not just atrophy (a late-stage AD symptom) but more subtle changes reflective of early dementia pathology. The sensitivity of MRI not just to gross anatomy but to the underlying "health" at the cellular (and even molecular) scales, makes it very well suited to this task.

Signaling pathways of interleukin-1 actions in the brain: anatomical distribution of phospho-ERK1/2 in the brain of rat treated systemically with interleukin-1beta.

PubMed

Nadjar, A; Combe, C; Busquet, P; Dantzer, R; Parnet, P

2005-01-01

Interleukin-1beta is released at the periphery during infection and acts on the nervous system to induce fever, neuroendocrine activation, and behavioral changes. These effects are mediated by brain type I IL-1 receptors. In vitro studies have shown the ability of interleukin-1beta to activate mitogen-activated protein kinase signaling pathways including p38, c-Jun N-terminal kinase and extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). In contrast to other mitogen-activated protein kinases, little is known about ERK1/2 activation in the rat brain in response to interleukin-1beta. The aim of the present study was therefore to investigate spatial and temporal activation of ERK1/2 in the rat brain after peripheral administration of interleukin-1beta using immunohistochemistry to detect the phosphorylated form of the kinase. In non-stimulated conditions, phosphorylated ERK1/2 immunoreactivity was observed in neurons throughout the brain. Administration of interleukin-1beta (60 microg/kg, i.p.) induced the phosphorylation of ERK1/2 in areas at the interface between brain and blood or cerebrospinal fluid: meninges, circumventricular organs, endothelial like cells of the blood vessels, and in brain nuclei involved in behavioral depression, fever and neuroendocrine activation: paraventricular nucleus of the hypothalamus, supraoptic nucleus, central amygdala and arcuate nucleus. Double labeling of phosphorylated ERK1/2 and cell markers revealed the expression of phosphorylated ERK1/2 in neurons, astrocytes and microglia. Since phosphorylated ERK1/2 was found in structures in which type I IL-1 receptor has already been identified as well as in structures lacking this receptor, activation of ERK1/2 is likely to occur in response to both direct and indirect action of interleukin-1beta on its target cells.

Human brain lesion-deficit inference remapped.

PubMed

Mah, Yee-Haur; Husain, Masud; Rees, Geraint; Nachev, Parashkev

2014-09-01

Our knowledge of the anatomical organization of the human brain in health and disease draws heavily on the study of patients with focal brain lesions. Historically the first method of mapping brain function, it is still potentially the most powerful, establishing the necessity of any putative neural substrate for a given function or deficit. Great inferential power, however, carries a crucial vulnerability: without stronger alternatives any consistent error cannot be easily detected. A hitherto unexamined source of such error is the structure of the high-dimensional distribution of patterns of focal damage, especially in ischaemic injury-the commonest aetiology in lesion-deficit studies-where the anatomy is naturally shaped by the architecture of the vascular tree. This distribution is so complex that analysis of lesion data sets of conventional size cannot illuminate its structure, leaving us in the dark about the presence or absence of such error. To examine this crucial question we assembled the largest known set of focal brain lesions (n = 581), derived from unselected patients with acute ischaemic injury (mean age = 62.3 years, standard deviation = 17.8, male:female ratio = 0.547), visualized with diffusion-weighted magnetic resonance imaging, and processed with validated automated lesion segmentation routines. High-dimensional analysis of this data revealed a hidden bias within the multivariate patterns of damage that will consistently distort lesion-deficit maps, displacing inferred critical regions from their true locations, in a manner opaque to replication. Quantifying the size of this mislocalization demonstrates that past lesion-deficit relationships estimated with conventional inferential methodology are likely to be significantly displaced, by a magnitude dependent on the unknown underlying lesion-deficit relationship itself. Past studies therefore cannot be retrospectively corrected, except by new knowledge that would render them redundant. Positively, we show that novel machine learning techniques employing high-dimensional inference can nonetheless accurately converge on the true locus. We conclude that current inferences about human brain function and deficits based on lesion mapping must be re-evaluated with methodology that adequately captures the high-dimensional structure of lesion data. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Association of objectively measured physical activity with brain structure: UK Biobank study.

PubMed

Hamer, Mark; Sharma, Nikhil; Batty, G David

2018-05-18

Physical activity may be beneficial for cognition but mechanisms are unclear. We examined the association between objectively assessed physical activity and brain volume, with a focus on the hippocampus region. We used data from UK Biobank (n=5,272; aged 55.4±7.5 yrs; 45.6% men) collected through 2013-2016. Participants wore the Axivity AX3 wrist-worn triaxial accelerometer for seven days to assess habitual physical activity. Structural magnetic resonance imaging was performed using a standard Siemens Skyra 3T running VD13A SP4 to obtain images of the brain. There was an association between physical activity (per SD increase) and grey matter volume after adjustment for a range of covariates, although this association was only detected in older adults (>60 yrs old). We also observed associations of physical activity with both left (B=0.52, 95% CI, 0.01, 1.03; p=0.046) and right hippocampal volume (B=0.59, 95% CI, 0.08, 1.10; p=0.024) in covariate adjusted models. In summary, physical activity may play a role in the prevention of neurodegenerative diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cerebral oxygenation in traumatic brain injury; Can a non-invasive frequency domain near-infrared spectroscopy device detect changes in brain tissue oxygen tension as well as the established invasive monitor?

PubMed

Davies, David James; Clancy, Michael; Dehghani, Hamid; Lucas, Samuel John Edwin; Forcione, Mario; Yakoub, Kamal Makram; Belli, Antonio

2018-06-07

The cost and highly invasive nature of brain monitoring modality in traumatic brain injury patients currently restrict its utility to specialist neurological intensive care settings. We aim to test the abilities of a frequency domain near-infrared spectroscopy (FD-NIRS) device in predicting changes in invasively measured brain tissue oxygen tension. Individuals admitted to a United Kingdom specialist major trauma centre were contemporaneously monitored with an FD-NIRS device and invasively measured brain tissue oxygen tension probe. Area under the curve receiver operating characteristic (AUROC) statistical analysis was utilised to assess the predictive power of FD-NIRS in detecting both moderate and severe hypoxia (20 and 10 mmHg, respectively), as measured invasively. 16 individuals were prospectively recruited to the investigation. Severe hypoxic episodes were detected in 9 of these individuals, with the NIRS demonstrating a broad range of predictive abilities (AUROC 0.68-0.88) from relatively poor to good. Moderate hypoxic episodes were detected in seven individuals with similar predictive performance (AUROC 0.576 - 0.905). A variable performance in the predictive powers of this FD-NIRS device to detect changes in brain tissue oxygen was demonstrated. Consequently, this enhanced NIRS technology has not demonstrated sufficient ability to replace the established invasive measurement.

Learning Effective Connectivity Network Structure from fMRI Data Based on Artificial Immune Algorithm

PubMed Central

Ji, Junzhong; Liu, Jinduo; Liang, Peipeng; Zhang, Aidong

2016-01-01

Many approaches have been designed to extract brain effective connectivity from functional magnetic resonance imaging (fMRI) data. However, few of them can effectively identify the connectivity network structure due to different defects. In this paper, a new algorithm is developed to infer the effective connectivity between different brain regions by combining artificial immune algorithm (AIA) with the Bayes net method, named as AIAEC. In the proposed algorithm, a brain effective connectivity network is mapped onto an antibody, and four immune operators are employed to perform the optimization process of antibodies, including clonal selection operator, crossover operator, mutation operator and suppression operator, and finally gets an antibody with the highest K2 score as the solution. AIAEC is then tested on Smith’s simulated datasets, and the effect of the different factors on AIAEC is evaluated, including the node number, session length, as well as the other potential confounding factors of the blood oxygen level dependent (BOLD) signal. It was revealed that, as contrast to other existing methods, AIAEC got the best performance on the majority of the datasets. It was also found that AIAEC could attain a relative better solution under the influence of many factors, although AIAEC was differently affected by the aforementioned factors. AIAEC is thus demonstrated to be an effective method for detecting the brain effective connectivity. PMID:27045295

Structure changes of human brain gray matter neurons and astrocytes in acute local ischemic injury.

PubMed

Sergeeva, S P; Shishkina, L V; Litvitskiy, P F; Breslavich, I D; Vinogradov, E V

2016-01-01

The purpose to identify key morphological features of the Astrocytes and Neurons in the acute local cerebral ischemia human cortex. Left middle cerebral artery ischemic stroke died persons (n = 9) brain tissue samples from 3 zones: 1st - contiguous to the tissue necrotic damage site zone, 2nd - 5-10 cm distant from the previous one, 3rd - the damage site symmetrical zone of the contralateral hemisphere. For GFAP, MAP-2, NSE, p53 detection indirect immunoperoxidase immunohistochemical staining method has been used. Also, the samples were Nissl and Hematoxylin-Eosin stained. The most pronounced changes in the quantity and morphological structure of astrocytes and neurons are found in directly adjacent to the necrotic core region of theleft middle cerebral artery ischemic stroke brain. This indicates the prevalence of the inflammation processes around the area of nerve tissueischemic destruction. Morphological changes of neurons and astrocytes, apoptosis, enhanced neuron-astrocyte interaction found in the area bordering on necrotic core (5-10 cm from it), as well as ischemic hearth symmetrical sites of the contralateral hemisphere. This interaction is essential for the neuroplasticityrealization in the local ischemic brain injury. The results obtained were shown the nerve tissue morphological characteristics changes occur in local cerebral cortex ischemic injury not only in the lesion, but also in the contralateral hemisphere. These changes are probably related to the implementation of neuroplasticity.

Three-dimensional imaging of the brain cavities in human embryos.

PubMed

Blaas, H G; Eik-Nes, S H; Kiserud, T; Berg, S; Angelsen, B; Olstad, B

1995-04-01

A system for high-resolution three-dimensional imaging of small structures has been developed, based on the Vingmed CFM-800 annular array sector scanner with a 7.5-MHz transducer attached to a PC-based TomTec Echo-Scan unit. A stepper motor rotates the transducer 180 degrees and the complete three-dimensional scan consists of 132 two-dimensional images, video-grabbed and scan-converted into a regular volumetric data set by the TomTec unit. Three normal pregnancies with embryos of gestational age 7, 9 and 10 weeks received a transvaginal examination with special attention to the embryonic/fetal brain. In all three cases, it was possible to obtain high-resolution images of the brain cavities. At 7 weeks, both hemispheres and their connection to the third ventricle were delineated. The isthmus rhombencephali could be visualized. At 9 weeks, the continuous development of the brain cavities could be followed and at 11 weeks the dominating size of the hemispheres could be depicted. It is concluded that present ultrasound technology has reached a stage where structures of only a few millimeters can be imaged in vivo in three-dimensions with a quality that resembles the plaster figures used in embryonic laboratories. The method can become an important tool in future embryological research and also in the detection of early developmental disorders of the embryo.

Uncovering the Social Deficits in the Autistic Brain. A Source-Based Morphometric Study

PubMed Central

Grecucci, Alessandro; Rubicondo, Danilo; Siugzdaite, Roma; Surian, Luca; Job, Remo

2016-01-01

Autism is a neurodevelopmental disorder that mainly affects social interaction and communication. Evidence from behavioral and functional MRI studies supports the hypothesis that dysfunctional mechanisms involving social brain structures play a major role in autistic symptomatology. However, the investigation of anatomical abnormalities in the brain of people with autism has led to inconsistent results. We investigated whether specific brain regions, known to display functional abnormalities in autism, may exhibit mutual and peculiar patterns of covariance in their gray-matter concentrations. We analyzed structural MRI images of 32 young men affected by autistic disorder (AD) and 50 healthy controls. Controls were matched for sex, age, handedness. IQ scores were also monitored to avoid confounding. A multivariate Source-Based Morphometry (SBM) was applied for the first time on AD and controls to detect maximally independent networks of gray matter. Group comparison revealed a gray-matter source that showed differences in AD compared to controls. This network includes broad temporal regions involved in social cognition and high-level visual processing, but also motor and executive areas of the frontal lobe. Notably, we found that gray matter differences, as reflected by SBM, significantly correlated with social and behavioral deficits displayed by AD individuals and encoded via the Autism Diagnostic Observation Schedule scores. These findings provide support for current hypotheses about the neural basis of atypical social and mental states information processing in autism. PMID:27630538

Neonatal Seizures: Advances in Mechanisms and Management

PubMed Central

Glass, Hannah C.

2013-01-01

Synopsis Seizures occur in approximately 1–5 per 1,000 live births, and are among the most common neurologic conditions managed by a neonatal neurocritical care service. There are several, age-specific factors that are particular to the developing brain, which influence excitability and seizure generation, response to medications, and impact of seizures on brain structure and function. Neonatal seizures are often associated with serious underlying brain injury such as hypoxia-ischemia, stroke or hemorrhage. Conventional, prolonged, continuous video-electroencephalogram (cEEG) is the gold standard for detecting seizures, whereas amplitude-integrated EEG (aEEG) is a convenient and useful bedside tool. Evaluation of neonatal seizures involves a thorough search for the etiology of the seizures, and includes detailed clinical history, routine chemistries, neuroimaging (and preferably magnetic resonance imaging, MRI), and specialized testing such as screening for inborn errors of metabolism if no structural cause is identified and seizures persist after correction of transient metabolic deficits. Expert opinion supports rapid medical treatment to abolish electrographic seizures, however the relative risk versus benefit for aggressive medical treatment of neonatal seizures is not known. While there is increasing evidence to support a harmful effect of seizures on the developing brain, there is also evidence that commonly used medications are potentially neurotoxic in animal models. Newer agents appear less harmful, but data are lacking regarding optimal dosing and efficacy. PMID:24524454

The effect of coaching on the simulated malingering of memory impairment.

PubMed

Rüsseler, Jascha; Brett, Alexandra; Klaue, Ulrike; Sailer, Michael; Münte, Thomas F

2008-10-07

Detecting malingering or exaggeration of impairments in brain function after traumatic brain injury is of increasing importance in neuropsychological assessment. Lawyers involved in brain injury litigation cases routinely coach their clients how to approach neuropsychological testing to their advantage. Thus, it is important to know how robust assessment methods are with respect to symptom malingering or exaggeration. The influence of different coaching methods on the simulated malingering of memory impairments is investigated in neurologically healthy participants using the Short-Term-Memory Test from the Bremer Symptom-Validierung (STM-BSV). Cut-offs were derived from patients with mild to severe traumatic brain injury. For comparison purposes, the German adaptation of the Rey Auditory Verbal Learning Test (AVLT), and the Rey 15 Items Test (FIT) were additionally administered. Four groups of neurologically healthy subjects were instructed to (1) perform as best as they can, (2) simulate brain injury, (3) simulate brain injury and received additional information about the sequelae of head trauma, (4) simulate brain injury and received additional information on how to avoid detection. Furthermore, a group of patients with mild to severe closed head injury performed the tests with best effort. The naïve simulator and the symptom coached groups were the easiest to detect, whereas the symptom plus test coached group was the hardest to detect. The AVLT and the FIT were not suited to detect simulators (sensitivities from 0% to 50.8% at 75% specificity) whereas the STM-BSV detected simulators with 67% - 88% sensitivity at a specificity of 73%. However, the STM-BSV was not robust to coaching. The present investigation shows that symptom validity testing as implemented in the BSV-STM is one clinically useful element in the detection of memory malingering. However, clinicians have to be aware that coaching influences performance in the test.

Change detection and classification in brain MR images using change vector analysis.

PubMed

Simões, Rita; Slump, Cornelis

2011-01-01

The automatic detection of longitudinal changes in brain images is valuable in the assessment of disease evolution and treatment efficacy. Most existing change detection methods that are currently used in clinical research to monitor patients suffering from neurodegenerative diseases--such as Alzheimer's--focus on large-scale brain deformations. However, such patients often have other brain impairments, such as infarcts, white matter lesions and hemorrhages, which are typically overlooked by the deformation-based methods. Other unsupervised change detection algorithms have been proposed to detect tissue intensity changes. The outcome of these methods is typically a binary change map, which identifies changed brain regions. However, understanding what types of changes these regions underwent is likely to provide equally important information about lesion evolution. In this paper, we present an unsupervised 3D change detection method based on Change Vector Analysis. We compute and automatically threshold the Generalized Likelihood Ratio map to obtain a binary change map. Subsequently, we perform histogram-based clustering to classify the change vectors. We obtain a Kappa Index of 0.82 using various types of simulated lesions. The classification error is 2%. Finally, we are able to detect and discriminate both small changes and ventricle expansions in datasets from Mild Cognitive Impairment patients.

Classification and localization of early-stage Alzheimer's disease in magnetic resonance images using a patch-based classifier ensemble.

PubMed

Simões, Rita; van Cappellen van Walsum, Anne-Marie; Slump, Cornelis H

2014-09-01

Classification methods have been proposed to detect Alzheimer’s disease (AD) using magnetic resonance images. Most rely on features such as the shape/volume of brain structures that need to be defined a priori. In this work, we propose a method that does not require either the segmentation of specific brain regions or the nonlinear alignment to a template. Besides classification, we also analyze which brain regions are discriminative between a group of normal controls and a group of AD patients. We perform 3D texture analysis using Local Binary Patterns computed at local image patches in the whole brain, combined in a classifier ensemble.We evaluate our method in a publicly available database including very mild-to-mild AD subjects and healthy elderly controls. For the subject cohort including only mild AD subjects, the best results are obtained using a combination of large (30×30×30 and 40×40×40 voxels) patches. A spatial analysis on the best performing patches shows that these are located in the medial-temporal lobe and in the periventricular regions. When very mild AD subjects are included in the dataset, the small (10×10×10 voxels) patches perform best, with the most discriminative ones being located near the left hippocampus. We show that our method is able not only to perform accurate classification, but also to localize dis-criminative brain regions, which are in accordance with the medical literature. This is achieved without the need to segment-specific brain structures and without performing nonlinear registration to a template, indicating that the method may be suitable for a clinical implementation that can help to diagnose AD at an earlier stage.

Apolipoprotein E epsilon4 influences on episodic recall and brain structures in aging pilots.

PubMed

Adamson, Maheen M; Landy, Kelly M; Duong, Susan; Fox-Bosetti, Sabrina; Ashford, J Wesson; Murphy, Greer M; Weiner, Michael; Taylor, Joy L

2010-06-01

The apolipoprotein (APOE) epsilon4 allele is associated with cognitive deficits and hippocampal atrophy in nondemented middle-aged and older adults. It is not known to what extent this genetic risk factor for Alzheimer's disease (AD) impacts performance in late middle-aged and older workers in cognitively demanding occupations. This cross-sectional analysis examines brain-cognitive-genetic relationships in actively flying general aviation pilots, half of whom are APOE epsilon4 carriers. Fifty pilots were studied with structural MRI and memory tasks. Average visual paired associate memory recall performance was lower in APOE epsilon4 carriers than non-carriers. Memory performance correlated positively with hippocampal volume, but no structural differences were found in hippocampal or frontal volumes with respect to APOE epsilon4 allele. These results were evident in healthy professionals without any presenting memory problems and without selection for a family history of AD. These findings point to basic memory testing as a sensitive tool for detecting APOE epsilon4-related influences on memory in aging workers. Published by Elsevier Inc.

Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats.

PubMed

Zhang, Na; Cheng, Gen-Yang; Liu, Xian-Zhi; Zhang, Feng-Jiang

2014-05-01

To investigate the effect of acute renal ischemia reperfusion on brain tissue. Fourty eight rats were randomly divided into four groups (n=12): sham operation group, 30 min ischemia 60 min reperfusion group, 60 min ischemia 60 min reperfusion group, and 120 min ischemia 60 min reperfusion group. The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors. Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time. The detection at the molecular level showed decreased Bcl-2 expression, increased Bax expression, upregulated expression of NF-κB and its downstream factor COX-2/PGE2. Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Letter to Editor. Prerequisites for psychiatric examination detecting the intention to commit suicide.

PubMed

Brodziak, Andrzej

2015-01-01

The recent plane crash caused by the pilot increased the interest in the possibility of medical examination, which would be able to detect the intention of committing suicide. The development of such a diagnostic procedure is not only important for the prevention of events in the civil and military aviation, but also due to increase in the incidence of various suicide terrorist acts. The author expresses his opinion on the nature of such examination, due to his experience of working in Acute Poisoning Treatment Centre. The Centre admits about 1 000 patients per year, who have been rescued after suicide attempts made by the intake of a toxic substance. He discusses the developed scheme of structuralized interview, however, he believes that the ability to detect the existence of suicidal ideation was significantly improved as a result of the formulation of Interpersonal Theory of Suicide, which distinguishes four stages: 1) passive suicidal ideation, 2) suicidal desire, 3) suicidal intent, 4) lethal and near lethal suicide attempts. Next, the author presents his own prediction of the development of methods, enabling the objective detection of "suicidal intent" (plan). In his opinion, such an examination in the future, would be based on brain imaging techniques, which could detect the specific configuration of a person's brain neural circuits representing the existing plan of suicide. The real ability to detect such a configuration of neural circuits can be predicted on the basis of new, quoted results of neurophysiological studies.

3D shape analysis of the brain's third ventricle using a midplane encoded symmetric template model

PubMed Central

Kim, Jaeil; Valdés Hernández, Maria del C.; Royle, Natalie A.; Maniega, Susana Muñoz; Aribisala, Benjamin S.; Gow, Alan J.; Bastin, Mark E.; Deary, Ian J.; Wardlaw, Joanna M.; Park, Jinah

2016-01-01

Background Structural changes of the brain's third ventricle have been acknowledged as an indicative measure of the brain atrophy progression in neurodegenerative and endocrinal diseases. To investigate the ventricular enlargement in relation to the atrophy of the surrounding structures, shape analysis is a promising approach. However, there are hurdles in modeling the third ventricle shape. First, it has topological variations across individuals due to the inter-thalamic adhesion. In addition, as an interhemispheric structure, it needs to be aligned to the midsagittal plane to assess its asymmetric and regional deformation. Method To address these issues, we propose a model-based shape assessment. Our template model of the third ventricle consists of a midplane and a symmetric mesh of generic shape. By mapping the template's midplane to the individuals’ brain midsagittal plane, we align the symmetric mesh on the midline of the brain before quantifying the third ventricle shape. To build the vertex-wise correspondence between the individual third ventricle and the template mesh, we employ a minimal-distortion surface deformation framework. In addition, to account for topological variations, we implement geometric constraints guiding the template mesh to have zero width where the inter-thalamic adhesion passes through, preventing vertices crossing between left and right walls of the third ventricle. The individual shapes are compared using a vertex-wise deformity from the symmetric template. Results Experiments on imaging and demographic data from a study of aging showed that our model was sensitive in assessing morphological differences between individuals in relation to brain volume (i.e. proxy for general brain atrophy), gender and the fluid intelligence at age 72. It also revealed that the proposed method can detect the regional and asymmetrical deformation unlike the conventional measures: volume (median 1.95 ml, IQR 0.96 ml) and width of the third ventricle. Similarity measures between binary masks and the shape model showed that the latter reconstructed shape details with high accuracy (Dice coefficient ≥0.9, mean distance 0.5 mm and Hausdorff distance 2.7 mm). Conclusions We have demonstrated that our approach is suitable to morphometrical analyses of the third ventricle, providing high accuracy and inter-subject consistency in the shape quantification. This shape modeling method with geometric constraints based on anatomical landmarks could be extended to other brain structures which require a consistent measurement basis in the morphometry. PMID:27084320

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

PubMed

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

2018-01-01

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

Distinct sensory representations of wind and near-field sound in the Drosophila brain

PubMed Central

Yorozu, Suzuko; Wong, Allan; Fischer, Brian J.; Dankert, Heiko; Kernan, Maurice J.; Kamikouchi, Azusa; Ito, Kei; Anderson, David J.

2009-01-01

Behavioral responses to wind are thought to play a critical role in controlling the dispersal and population genetics of wild Drosophila species1,2, as well as their navigation in flight3, but their underlying neurobiological basis is unknown. We show that Drosophila melanogaster, like wild-caught Drosophila strains4, exhibits robust wind-induced suppression of locomotion (WISL), in response to air currents delivered at speeds normally encountered in nature1,2. Here we identify wind-sensitive neurons in Johnston’s Organ (JO), an antennal mechanosensory structure previously implicated in near-field sound detection (reviewed in5,6). Using Gal4 lines targeted to different subsets of JO neurons7, and a genetically encoded calcium indicator8, we show that wind and near-field sound (courtship song) activate distinct populations of JO neurons, which project to different regions of the antennal and mechanosensory motor center (AMMC) in the central brain. Selective genetic ablation of wind-sensitive JO neurons in the antenna abolishes WISL behavior, without impairing hearing. Different neuronal subsets within the wind-sensitive population, moreover, respond to different directions of arista deflection caused by airflow and project to different regions of the AMMC, providing a rudimentary map of wind-direction in the brain. Importantly, sound- and wind-sensitive JO neurons exhibit different intrinsic response properties: the former are phasically activated by small, bi-directional, displacements of the aristae, while the latter are tonically activated by unidirectional, static deflections of larger magnitude. These different intrinsic properties are well suited to the detection of oscillatory pulses of near-field sound and laminar airflow, respectively. These data identify wind-sensitive neurons in JO, a structure that has been primarily associated with hearing, and reveal how the brain can distinguish different types of air particle movements, using a common sensory organ. PMID:19279637

Detecting stripe artifacts in ultrasound images.

PubMed

Maciak, Adam; Kier, Christian; Seidel, Günter; Meyer-Wiethe, Karsten; Hofmann, Ulrich G

2009-10-01

Brain perfusion diseases such as acute ischemic stroke are detectable through computed tomography (CT)-/magnetic resonance imaging (MRI)-based methods. An alternative approach makes use of ultrasound imaging. In this low-cost bedside method, noise and artifacts degrade the imaging process. Especially stripe artifacts show a similar signal behavior compared to acute stroke or brain perfusion diseases. This document describes how stripe artifacts can be detected and eliminated in ultrasound images obtained through harmonic imaging (HI). On the basis of this new method, both proper identification of areas with critically reduced brain tissue perfusion and classification between brain perfusion defects and ultrasound stripe artifacts are made possible.

Technical and experimental features of Magnetic Resonance Spectroscopy of brain glycogen metabolism.

PubMed

Soares, Ana Francisca; Gruetter, Rolf; Lei, Hongxia

2017-07-15

In the brain, glycogen is a source of glucose not only in emergency situations but also during normal brain activity. Altered brain glycogen metabolism is associated with energetic dysregulation in pathological conditions, such as diabetes or epilepsy. Both in humans and animals, brain glycogen levels have been assessed non-invasively by Carbon-13 Magnetic Resonance Spectroscopy ( 13 C-MRS) in vivo. With this approach, glycogen synthesis and degradation may be followed in real time, thereby providing valuable insights into brain glycogen dynamics. However, compared to the liver and muscle, where glycogen is abundant, the sensitivity for detection of brain glycogen by 13 C-MRS is inherently low. In this review we focus on strategies used to optimize the sensitivity for 13 C-MRS detection of glycogen. Namely, we explore several technical perspectives, such as magnetic field strength, field homogeneity, coil design, decoupling, and localization methods. Furthermore, we also address basic principles underlying the use of 13 C-labeled precursors to enhance the detectable glycogen signal, emphasizing specific experimental aspects relevant for obtaining kinetic information on brain glycogen. Copyright © 2016 Elsevier Inc. All rights reserved.

The detection of brain oedema with frequency-dependent phase shift electromagnetic induction.

PubMed

González, César A; Rubinsky, Boris

2006-06-01

The spectroscopic distribution of inductive phase shift in the brain as a function of the relative volume of oedema was evaluated with theoretical and experimental methods in the frequency range 1 to 8 MHz. The theoretical study employed a simple mathematical model of electromagnetic induction in tissue and brain tissue data available from the literature to calculate the phase shift as a function of oedema in the bulk of the brain. Experimental data were generated from bulk measurements of ex vivo homogenized pig brain tissue mixed with various volumes of physiological saline in a volume sample typical of the human brain. There is good agreement between the analytical and the experimental results. Detectable changes in phase shift begin from a frequency of about 3 MHz to 4 MHz in the tested compositions and volume. The phase shift increases with frequency and fluid content. The results suggest that measuring phase shift in the bulk of the brain has the potential for becoming a robust means for non-contact detection of oedema in the brain.

Professional fighters brain health study: rationale and methods.

PubMed

Bernick, Charles; Banks, Sarah; Phillips, Michael; Lowe, Mark; Shin, Wanyong; Obuchowski, Nancy; Jones, Stephen; Modic, Michael

2013-07-15

Repetitive head trauma is a risk factor for Alzheimer's disease and is the primary cause of chronic traumatic encephalopathy. However, little is known about the natural history of, and risk factors for, chronic traumatic encephalopathy or about means of early detection and intervention. The Professional Fighters Brain Health Study is a longitudinal study of active professional fighters (boxers and mixed martial artists), retired professional fighters, and controls matched for age and level of education. The main objective of the Professional Fighters Brain Health Study is to determine the relationships between measures of head trauma exposure and other potential modifiers and changes in brain imaging and neurological and behavioral function over time. The study is designed to extend over 5 years, and we anticipate enrollment of more than 400 boxers and mixed martial artists. Participants will undergo annual evaluations that include 3-tesla magnetic resonance imaging scanning, computerized cognitive assessments, speech analysis, surveys of mood and impulsivity, and blood sampling for genotyping and exploratory biomarker studies. Statistical models will be developed and validated to predict early and progressive changes in brain structure and function. A composite fight exposure index, developed as a summary measure of cumulative traumatic exposure, shows promise as a predictor of brain volumes and cognitive function.

Semiautomatic Segmentation of Glioma on Mobile Devices.

PubMed

Wu, Ya-Ping; Lin, Yu-Song; Wu, Wei-Guo; Yang, Cong; Gu, Jian-Qin; Bai, Yan; Wang, Mei-Yun

2017-01-01

Brain tumor segmentation is the first and the most critical step in clinical applications of radiomics. However, segmenting brain images by radiologists is labor intense and prone to inter- and intraobserver variability. Stable and reproducible brain image segmentation algorithms are thus important for successful tumor detection in radiomics. In this paper, we propose a supervised brain image segmentation method, especially for magnetic resonance (MR) brain images with glioma. This paper uses hard edge multiplicative intrinsic component optimization to preprocess glioma medical image on the server side, and then, the doctors could supervise the segmentation process on mobile devices in their convenient time. Since the preprocessed images have the same brightness for the same tissue voxels, they have small data size (typically 1/10 of the original image size) and simple structure of 4 types of intensity value. This observation thus allows follow-up steps to be processed on mobile devices with low bandwidth and limited computing performance. Experiments conducted on 1935 brain slices from 129 patients show that more than 30% of the sample can reach 90% similarity; over 60% of the samples can reach 85% similarity, and more than 80% of the sample could reach 75% similarity. The comparisons with other segmentation methods also demonstrate both efficiency and stability of the proposed approach.

Effects of amyloid and small vessel disease on white matter network disruption.

PubMed

Kim, Hee Jin; Im, Kiho; Kwon, Hunki; Lee, Jong Min; Ye, Byoung Seok; Kim, Yeo Jin; Cho, Hanna; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Kim, Jae Seung; Lee, Jae Hong; Na, Duk L; Seo, Sang Won

2015-01-01

There is growing evidence that the human brain is a large scale complex network. The structural network is reported to be disrupted in cognitively impaired patients. However, there have been few studies evaluating the effects of amyloid and small vessel disease (SVD) markers, the common causes of cognitive impairment, on structural networks. Thus, we evaluated the association between amyloid and SVD burdens and structural networks using diffusion tensor imaging (DTI). Furthermore, we determined if network parameters predict cognitive impairments. Graph theoretical analysis was applied to DTI data from 232 cognitively impaired patients with varying degrees of amyloid and SVD burdens. All patients underwent Pittsburgh compound-B (PiB) PET to detect amyloid burden, MRI to detect markers of SVD, including the volume of white matter hyperintensities and the number of lacunes, and detailed neuropsychological testing. The whole-brain network was assessed by network parameters of integration (shortest path length, global efficiency) and segregation (clustering coefficient, transitivity, modularity). PiB retention ratio was not associated with any white matter network parameters. Greater white matter hyperintensity volumes or lacunae numbers were significantly associated with decreased network integration (increased shortest path length, decreased global efficiency) and increased network segregation (increased clustering coefficient, increased transitivity, increased modularity). Decreased network integration or increased network segregation were associated with poor performances in attention, language, visuospatial, memory, and frontal-executive functions. Our results suggest that SVD alters white matter network integration and segregation, which further predicts cognitive dysfunction.

Disruption of hierarchical predictive coding during sleep

PubMed Central

Strauss, Melanie; Sitt, Jacobo D.; King, Jean-Remi; Elbaz, Maxime; Azizi, Leila; Buiatti, Marco; Naccache, Lionel; van Wassenhove, Virginie; Dehaene, Stanislas

2015-01-01

When presented with an auditory sequence, the brain acts as a predictive-coding device that extracts regularities in the transition probabilities between sounds and detects unexpected deviations from these regularities. Does such prediction require conscious vigilance, or does it continue to unfold automatically in the sleeping brain? The mismatch negativity and P300 components of the auditory event-related potential, reflecting two steps of auditory novelty detection, have been inconsistently observed in the various sleep stages. To clarify whether these steps remain during sleep, we recorded simultaneous electroencephalographic and magnetoencephalographic signals during wakefulness and during sleep in normal subjects listening to a hierarchical auditory paradigm including short-term (local) and long-term (global) regularities. The global response, reflected in the P300, vanished during sleep, in line with the hypothesis that it is a correlate of high-level conscious error detection. The local mismatch response remained across all sleep stages (N1, N2, and REM sleep), but with an incomplete structure; compared with wakefulness, a specific peak reflecting prediction error vanished during sleep. Those results indicate that sleep leaves initial auditory processing and passive sensory response adaptation intact, but specifically disrupts both short-term and long-term auditory predictive coding. PMID:25737555

First and second trimester screening for fetal structural anomalies.

PubMed

Edwards, Lindsay; Hui, Lisa

2018-04-01

Fetal structural anomalies are found in up to 3% of all pregnancies and ultrasound-based screening has been an integral part of routine prenatal care for decades. The prenatal detection of fetal anomalies allows for optimal perinatal management, providing expectant parents with opportunities for additional imaging, genetic testing, and the provision of information regarding prognosis and management options. Approximately one-half of all major structural anomalies can now be detected in the first trimester, including acrania/anencephaly, abdominal wall defects, holoprosencephaly and cystic hygromata. Due to the ongoing development of some organ systems however, some anomalies will not be evident until later in the pregnancy. To this extent, the second trimester anatomy is recommended by professional societies as the standard investigation for the detection of fetal structural anomalies. The reported detection rates of structural anomalies vary according to the organ system being examined, and are also dependent upon factors such as the equipment settings and sonographer experience. Technological advances over the past two decades continue to support the role of ultrasound as the primary imaging modality in pregnancy, and the safety of ultrasound for the developing fetus is well established. With increasing capabilities and experience, detailed examination of the central nervous system and cardiovascular system is possible, with dedicated examinations such as the fetal neurosonogram and the fetal echocardiogram now widely performed in tertiary centers. Magnetic resonance imaging (MRI) is well recognized for its role in the assessment of fetal brain anomalies; other potential indications for fetal MRI include lung volume measurement (in cases of congenital diaphragmatic hernia), and pre-surgical planning prior to fetal spina bifida repair. When a major structural abnormality is detected prenatally, genetic testing with chromosomal microarray is recommended over routine karyotype due to its higher genomic resolution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Co-registration of In-Vivo Human MRI Brain Images to Postmortem Histological Microscopic Images

PubMed Central

Singh, M.; Rajagopalan, A.; Kim, T.-S.; Hwang, D.; Chui, H.; Zhang, X.-L.; Lee, A.-Y.; Zarow, C.

2009-01-01

Certain features such as small vascular lesions seen in human MRI are detected reliably only in postmortem histological samples by microscopic imaging. Co-registration of these microscopically detected features to their corresponding locations in the in-vivo images would be of great benefit to understanding the MRI signatures of specific diseases. Using non-linear Polynomial transformation, we report a method to co-register in-vivo MRIs to microscopic images of histological samples drawn off the postmortem brain. The approach utilizes digital photographs of postmortem slices as an intermediate reference to co-register the MRIs to microscopy. The overall procedure is challenging due to gross structural deformations in the postmortem brain during extraction and subsequent distortions in the histological preparations. Hemispheres of the brain were co-registered separately to mitigate these effects. Approaches relying on matching single-slices, multiple-slices and entire volumes in conjunction with different similarity measures suggested that using four slices at a time in combination with two sequential measures, Pearson correlation coefficient followed by mutual information, produced the best MRI-postmortem co-registration according to a voxel mismatch count. The accuracy of the overall registration was evaluated by measuring the 3D Euclidean distance between the locations of microscopically identified lesions on postmortem slices and their MRI-postmortem co-registered locations. The results show a mean 3D displacement of 5.1 ± 2.0 mm between the in-vivo MRI and microscopically determined locations for 21 vascular lesions in 11 subjects. PMID:19169415

Analysis of structure-function network decoupling in the brain systems of spastic diplegic cerebral palsy.

PubMed

Lee, Dongha; Pae, Chongwon; Lee, Jong Doo; Park, Eun Sook; Cho, Sung-Rae; Um, Min-Hee; Lee, Seung-Koo; Oh, Maeng-Keun; Park, Hae-Jeong

2017-10-01

Manifestation of the functionalities from the structural brain network is becoming increasingly important to understand a brain disease. With the aim of investigating the differential structure-function couplings according to network systems, we investigated the structural and functional brain networks of patients with spastic diplegic cerebral palsy with periventricular leukomalacia compared to healthy controls. The structural and functional networks of the whole brain and motor system, constructed using deterministic and probabilistic tractography of diffusion tensor magnetic resonance images and Pearson and partial correlation analyses of resting-state functional magnetic resonance images, showed differential embedding of functional networks in the structural networks in patients. In the whole-brain network of patients, significantly reduced global network efficiency compared to healthy controls were found in the structural networks but not in the functional networks, resulting in reduced structural-functional coupling. On the contrary, the motor network of patients had a significantly lower functional network efficiency over the intact structural network and a lower structure-function coupling than the control group. This reduced coupling but reverse directionality in the whole-brain and motor networks of patients was prominent particularly between the probabilistic structural and partial correlation-based functional networks. Intact (or less deficient) functional network over impaired structural networks of the whole brain and highly impaired functional network topology over the intact structural motor network might subserve relatively preserved cognitions and impaired motor functions in cerebral palsy. This study suggests that the structure-function relationship, evaluated specifically using sparse functional connectivity, may reveal important clues to functional reorganization in cerebral palsy. Hum Brain Mapp 38:5292-5306, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Structural Image Analysis of the Brain in Neuropsychology Using Magnetic Resonance Imaging (MRI) Techniques.

PubMed

Bigler, Erin D

2015-09-01

Magnetic resonance imaging (MRI) of the brain provides exceptional image quality for visualization and neuroanatomical classification of brain structure. A variety of image analysis techniques provide both qualitative as well as quantitative methods to relate brain structure with neuropsychological outcome and are reviewed herein. Of particular importance are more automated methods that permit analysis of a broad spectrum of anatomical measures including volume, thickness and shape. The challenge for neuropsychology is which metric to use, for which disorder and the timing of when image analysis methods are applied to assess brain structure and pathology. A basic overview is provided as to the anatomical and pathoanatomical relations of different MRI sequences in assessing normal and abnormal findings. Some interpretive guidelines are offered including factors related to similarity and symmetry of typical brain development along with size-normalcy features of brain anatomy related to function. The review concludes with a detailed example of various quantitative techniques applied to analyzing brain structure for neuropsychological outcome studies in traumatic brain injury.

Monitoring of injury induced brain regeneration of the adult zebrafish by using optical coherence tomography

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Zhang, Jian

2018-02-01

The adult zebrafish has pronounced regenerative capacity of the brain, which makes it an ideal model organism of vertebrate biology for the investigation of recovery of central nervous system injuries. The aim of this study was to employ spectral-domain optical coherence tomography (SD-OCT) system for long-term in vivo monitoring of tissue regeneration using an adult zebrafish model of brain injury. Based on a 1325 nm light source and two high-speed galvo mirrors, the SD-OCT system can offer a large field of view of the three-dimensional (3D) brain structures with high imaging resolution (12 μm axial and 13 μm lateral) at video rate. In vivo experiments based on this system were conducted to monitor the regeneration process of zebrafish brain after injury during a period of 43 days. To monitor and detect the process of tissue regeneration, we performed 3D in vivo imaging in a zebrafish model of adult brain injury during a period of 43 days. The coronal and sagittal views of the injured zebrafish brain at each time point (0 days, 10 days, 20 days and 43 days postlesion) were presented to show the changes of the brain lesion in detail. In addition, the 3D SD-OCT images for an injured zebrafish brain were also reconstructed at days 0 and days 43 post-lesion. We found that SD-OCT is able to effectively and noninvasively monitor the regeneration of the adult zebrafish brain after injury in real time with high 3D spatial resolution and good penetration depth. Our findings also suggested that the adult zebrafish has the extraordinary capability of brain regeneration and is able to repair itself after brain injury.

Structural covariance of brain region volumes is associated with both structural connectivity and transcriptomic similarity.

PubMed

Yee, Yohan; Fernandes, Darren J; French, Leon; Ellegood, Jacob; Cahill, Lindsay S; Vousden, Dulcie A; Spencer Noakes, Leigh; Scholz, Jan; van Eede, Matthijs C; Nieman, Brian J; Sled, John G; Lerch, Jason P

2018-05-18

An organizational pattern seen in the brain, termed structural covariance, is the statistical association of pairs of brain regions in their anatomical properties. These associations, measured across a population as covariances or correlations usually in cortical thickness or volume, are thought to reflect genetic and environmental underpinnings. Here, we examine the biological basis of structural volume covariance in the mouse brain. We first examined large scale associations between brain region volumes using an atlas-based approach that parcellated the entire mouse brain into 318 regions over which correlations in volume were assessed, for volumes obtained from 153 mouse brain images via high-resolution MRI. We then used a seed-based approach and determined, for 108 different seed regions across the brain and using mouse gene expression and connectivity data from the Allen Institute for Brain Science, the variation in structural covariance data that could be explained by distance to seed, transcriptomic similarity to seed, and connectivity to seed. We found that overall, correlations in structure volumes hierarchically clustered into distinct anatomical systems, similar to findings from other studies and similar to other types of networks in the brain, including structural connectivity and transcriptomic similarity networks. Across seeds, this structural covariance was significantly explained by distance (17% of the variation, up to a maximum of 49% for structural covariance to the visceral area of the cortex), transcriptomic similarity (13% of the variation, up to maximum of 28% for structural covariance to the primary visual area) and connectivity (15% of the variation, up to a maximum of 36% for structural covariance to the intermediate reticular nucleus in the medulla) of covarying structures. Together, distance, connectivity, and transcriptomic similarity explained 37% of structural covariance, up to a maximum of 63% for structural covariance to the visceral area. Additionally, this pattern of explained variation differed spatially across the brain, with transcriptomic similarity playing a larger role in the cortex than subcortex, while connectivity explains structural covariance best in parts of the cortex, midbrain, and hindbrain. These results suggest that both gene expression and connectivity underlie structural volume covariance, albeit to different extents depending on brain region, and this relationship is modulated by distance. Copyright © 2018. Published by Elsevier Inc.

Graph-theoretic analysis of discrete-phase-space states for condition change detection and quantification of information

DOEpatents

Hively, Lee M.

2014-09-16

Data collected from devices and human condition may be used to forewarn of critical events such as machine/structural failure or events from brain/heart wave data stroke. By monitoring the data, and determining what values are indicative of a failure forewarning, one can provide adequate notice of the impending failure in order to take preventive measures. This disclosure teaches a computer-based method to convert dynamical numeric data representing physical objects (unstructured data) into discrete-phase-space states, and hence into a graph (structured data) for extraction of condition change.

Glucose Metabolism during Resting State Reveals Abnormal Brain Networks Organization in the Alzheimer’s Disease and Mild Cognitive Impairment

PubMed Central

Martínez-Montes, Eduardo

2013-01-01

This paper aims to study the abnormal patterns of brain glucose metabolism co-variations in Alzheimer disease (AD) and Mild Cognitive Impairment (MCI) patients compared to Normal healthy controls (NC) using the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The local cerebral metabolic rate for glucose (CMRgl) in a set of 90 structures belonging to the AAL atlas was obtained from Fluro-Deoxyglucose Positron Emission Tomography data in resting state. It is assumed that brain regions whose CMRgl values are significantly correlated are functionally associated; therefore, when metabolism is altered in a single region, the alteration will affect the metabolism of other brain areas with which it interrelates. The glucose metabolism network (represented by the matrix of the CMRgl co-variations among all pairs of structures) was studied using the graph theory framework. The highest concurrent fluctuations in CMRgl were basically identified between homologous cortical regions in all groups. Significant differences in CMRgl co-variations in AD and MCI groups as compared to NC were found. The AD and MCI patients showed aberrant patterns in comparison to NC subjects, as detected by global and local network properties (global and local efficiency, clustering index, and others). MCI network’s attributes showed an intermediate position between NC and AD, corroborating it as a transitional stage from normal aging to Alzheimer disease. Our study is an attempt at exploring the complex association between glucose metabolism, CMRgl covariations and the attributes of the brain network organization in AD and MCI. PMID:23894356

Brain Abnormalities in Congenital Fibrosis of the Extraocular Muscles Type 1: A Multimodal MRI Imaging Study.

PubMed

Miao, Wen; Man, Fengyuan; Wu, Shaoqin; Lv, Bin; Wang, Zhenchang; Xian, Junfang; Sabel, Bernhard A; He, Huiguang; Jiao, Yonghong

2015-01-01

To explore the possible brain structural and functional alterations in congenital fibrosis of extraocular muscles type 1 (CFEOM1) patients using multimodal MRI imaging. T1-weighted, diffusion tensor images and functional MRI data were obtained from 9 KIF21A positive patients and 19 age- and gender-matched healthy controls. Voxel based morphometry and tract based spatial statistics were applied to the T1-weighted and diffusion tensor images, respectively. Amplitude of low frequency fluctuations and regional homogeneity were used to process the functional MRI data. We then compared these multimodal characteristics between CFEOM1 patients and healthy controls. Compared with healthy controls, CFEOM1 patients demonstrated increased grey matter volume in bilateral frontal orbital cortex and in the right temporal pole. No diffusion indices changes were detected, indicating unaffected white matter microstructure. In addition, from resting state functional MRI data, trend of amplitude of low-frequency fluctuations increases were noted in the right inferior parietal lobe and in the right frontal cortex, and a trend of ReHo increase (p<0.001 uncorrected) in the left precentral gyrus, left orbital frontal cortex, temporal pole and cingulate gyrus. CFEOM1 patients had structural and functional changes in grey matter, but the white matter was unaffected. These alterations in the brain may be due to the abnormality of extraocular muscles and their innervating nerves. Future studies should consider the possible correlations between brain morphological/functional findings and clinical data, especially pertaining to eye movements, to obtain more precise answers about the role of brain area changes and their functional consequence in CFEOM1.

Atlas based brain volumetry: How to distinguish regional volume changes due to biological or physiological effects from inherent noise of the methodology.

PubMed

Opfer, Roland; Suppa, Per; Kepp, Timo; Spies, Lothar; Schippling, Sven; Huppertz, Hans-Jürgen

2016-05-01

Fully-automated regional brain volumetry based on structural magnetic resonance imaging (MRI) plays an important role in quantitative neuroimaging. In clinical trials as well as in clinical routine multiple MRIs of individual patients at different time points need to be assessed longitudinally. Measures of inter- and intrascanner variability are crucial to understand the intrinsic variability of the method and to distinguish volume changes due to biological or physiological effects from inherent noise of the methodology. To measure regional brain volumes an atlas based volumetry (ABV) approach was deployed using a highly elastic registration framework and an anatomical atlas in a well-defined template space. We assessed inter- and intrascanner variability of the method in 51 cognitively normal subjects and 27 Alzheimer dementia (AD) patients from the Alzheimer's Disease Neuroimaging Initiative by studying volumetric results of repeated scans for 17 compartments and brain regions. Median percentage volume differences of scan-rescans from the same scanner ranged from 0.24% (whole brain parenchyma in healthy subjects) to 1.73% (occipital lobe white matter in AD), with generally higher differences in AD patients as compared to normal subjects (e.g., 1.01% vs. 0.78% for the hippocampus). Minimum percentage volume differences detectable with an error probability of 5% were in the one-digit percentage range for almost all structures investigated, with most of them being below 5%. Intrascanner variability was independent of magnetic field strength. The median interscanner variability was up to ten times higher than the intrascanner variability. Copyright © 2016 Elsevier Inc. All rights reserved.

Automatic segmentation of brain hemispheres by midplane detection in class images

NASA Astrophysics Data System (ADS)

Wagenknecht, Gudrun; Kaiser, Hans-Juergen; Sabri, Osama; Buell, Udalrich

2000-06-01

Segmentation of brain hemispheres is necessary to study left- right differences in structure and function. For extraction of a 3D individual region-of-interest atlas of the human brain, detection of the midplane is the sine qua non as it provides the reference plane for determining other anatomical objects. Extraction of the sagittal midplane is done in two main steps. First, a 2D filter is used to give a first approximation of the midplane position. To model symmetry properties of the midplane neighborhood, the different filter columns contain class-dependent weights for cerebrospinal fluid, gray and white matter. The filter can be rotated in a range of angles. In a user-defined range of planes, the global maximum of the filter response is searched for and the resulting position is utilized to restrict the search in the remaining planes. In a second step, midplane extraction is refined by searching for the optimal path of the midplane within the filter mask at optimum position. Symmetry properties are modeled analogous to the first step with class-dependent weights of the filter columns. The extraction of the midplane gives accurate and reliable results in simulated data sets and patient studies even if asymmetric artifacts are simulated.

Elastic scattering spectroscopy of coagulated brain tissues

NASA Astrophysics Data System (ADS)

Ateş, Filiz; Tabakoğlu, Haşim Özgür; Bozkulak, Özgüncem; Canpolat, Murat; Gülsoy, Murat

2006-02-01

The goal of this study was to differentiate the parts of lamb brain according to elastic scattering spectroscopy and detect the optical alterations due to coagulation. Cells and tissues are not uniform and have complex structures and shapes. They can be referred to as scattering particles. The process of scattering depends on the light wavelength and on the scattering medium properties; especially on the size and the density of the medium. When elastic scattering spectroscopy (ESS) is employed, the morphological alterations of tissues can be detected using spectral measurements of the elastic scattered light over a wide range of wavelengths. In this study firstly, the slopes of ESS spectra were used to differentiate the parts of lamb brains (brainstem, cerebellum, gray matter, white matter) in vitro in the range of 450 - 750 nm. Secondly, tissues were coagulated at different temperatures (45, 60, and 80 °C) and ESS spectra were taken from native and coagulated tissues. It was observed that as the coagulation temperature increased, the slope of the elastic scattering spectra decreased. Thus, optical properties of tissues were changed with respect to the change in nuclear to cytoplasmic ratio due to the water loss. Results showed that the slopes of ESS spectra in the visible range revealed valuable information about the morphological changes caused by coagulation.

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

PubMed

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

2017-04-01

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

Method and apparatus for extraction of low-frequency artifacts from brain waves for alertness detection

DOEpatents

Clapp, Ned E.; Hively, Lee M.

1997-01-01

Methods and apparatus automatically detect alertness in humans by monitoring and analyzing brain wave signals. Steps include: acquiring the brain wave (EEG or MEG) data from the subject, digitizing the data, separating artifact data from raw data, and comparing trends in f-data to alertness indicators, providing notification of inadequate alertness.

Structural and Functional Neuroimaging of Visual Hallucinations in Lewy Body Disease: A Systematic Literature Review

PubMed Central

Cagnin, Annachiara; Bandmann, Oliver; Venneri, Annalena

2017-01-01

Patients with Lewy body disease (LBD) frequently experience visual hallucinations (VH), well-formed images perceived without the presence of real stimuli. The structural and functional brain mechanisms underlying VH in LBD are still unclear. The present review summarises the current literature on the neural correlates of VH in LBD, namely Parkinson’s disease (PD), and dementia with Lewy bodies (DLB). Following a systematic literature search, 56 neuroimaging studies of VH in PD and DLB were critically reviewed and evaluated for quality assessment. The main structural neuroimaging results on VH in LBD revealed grey matter loss in frontal areas in patients with dementia, and parietal and occipito-temporal regions in PD without dementia. Parietal and temporal hypometabolism was also reported in hallucinating PD patients. Disrupted functional connectivity was detected especially in the default mode network and fronto-parietal regions. However, evidence on structural and functional connectivity is still limited and requires further investigation. The current literature is in line with integrative models of VH suggesting a role of attention and perception deficits in the development of VH. However, despite the close relationship between VH and cognitive impairment, its associations with brain structure and function have been explored only by a limited number of studies. PMID:28714891

Brain tumor segmentation in MR slices using improved GrowCut algorithm

NASA Astrophysics Data System (ADS)

Ji, Chunhong; Yu, Jinhua; Wang, Yuanyuan; Chen, Liang; Shi, Zhifeng; Mao, Ying

2015-12-01

The detection of brain tumor from MR images is very significant for medical diagnosis and treatment. However, the existing methods are mostly based on manual or semiautomatic segmentation which are awkward when dealing with a large amount of MR slices. In this paper, a new fully automatic method for the segmentation of brain tumors in MR slices is presented. Based on the hypothesis of the symmetric brain structure, the method improves the interactive GrowCut algorithm by further using the bounding box algorithm in the pre-processing step. More importantly, local reflectional symmetry is used to make up the deficiency of the bounding box method. After segmentation, 3D tumor image is reconstructed. We evaluate the accuracy of the proposed method on MR slices with synthetic tumors and actual clinical MR images. Result of the proposed method is compared with the actual position of simulated 3D tumor qualitatively and quantitatively. In addition, our automatic method produces equivalent performance as manual segmentation and the interactive GrowCut with manual interference while providing fully automatic segmentation.

Effects of Adult Female Rat Androgenization on Brain Morphology and Metabolomic Profile.

PubMed

Perez-Laso, Carmen; Cerdan, Sebastián; Junque, Carme; Gómez, Ángel; Ortega, Esperanza; Mora, Mireia; Avendaño, Carlos; Gómez-Gil, Esther; Del Cerro, María Cruz Rodríguez; Guillamon, Antonio

2017-07-06

Androgenization in adult natal women, as in transsexual men (TM), affects brain cortical thickness and the volume of subcortical structures. In order to understand the mechanism underlying these changes we have developed an adult female rat model of androgenization. Magnetic resonance imaging and spectroscopy were used to monitor brain volume changes, white matter microstructure and ex vivo metabolic profiles over 32 days in androgenized and control subjects. Supraphysiological doses of testosterone prevents aging decrease of fractional anisotropy values, decreased general cortical volume and the relative concentrations of glutamine (Gln) and myo-Inositol (mI). An increase in the N-acetylaspartate (NAA)/mI ratio was detected d. Since mI and Gln are astrocyte markers and osmolytes, we suspect that the anabolic effects of testosterone change astrocyte osmolarity so as to extrude Mi and Gln from these cells in order to maintain osmotic homeostasis. This mechanism could explain the brain changes observed in TM and other individuals receiving androgenic anabolic steroids. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Sensing of glucose in the brain.

PubMed

Thorens, Bernard

2012-01-01

The brain, and in particular the hypothalamus and brainstem, have been recognized for decades as important centers for the homeostatic control of feeding, energy expenditure, and glucose homeostasis. These structures contain neurons and neuronal circuits that may be directly or indirectly activated or inhibited by glucose, lipids, or amino acids. The detection by neurons of these nutrient cues may become deregulated, and possibly cause metabolic diseases such as obesity and diabetes. Thus, there is a major interest in identifying these neurons, how they respond to nutrients, the neuronal circuits they form, and the physiological function they control. Here I will review some aspects of glucose sensing by the brain. The brain is responsive to both hyperglycemia and hypoglycemia, and the glucose sensing cells involved are distributed in several anatomical sites that are connected to each other. These eventually control the activity of the sympathetic or parasympathetic nervous system, which regulates the function of peripheral organs such as liver, white and brown fat, muscle, and pancreatic islets alpha and beta cells. There is now evidence for an extreme diversity in the sensing mechanisms used, and these will be reviewed.

Novel Noninvasive Brain Disease Detection System Using a Facial Image Sensor

PubMed Central

Shu, Ting; Zhang, Bob; Tang, Yuan Yan

2017-01-01

Brain disease including any conditions or disabilities that affect the brain is fast becoming a leading cause of death. The traditional diagnostic methods of brain disease are time-consuming, inconvenient and non-patient friendly. As more and more individuals undergo examinations to determine if they suffer from any form of brain disease, developing noninvasive, efficient, and patient friendly detection systems will be beneficial. Therefore, in this paper, we propose a novel noninvasive brain disease detection system based on the analysis of facial colors. The system consists of four components. A facial image is first captured through a specialized sensor, where four facial key blocks are next located automatically from the various facial regions. Color features are extracted from each block to form a feature vector for classification via the Probabilistic Collaborative based Classifier. To thoroughly test the system and its performance, seven facial key block combinations were experimented. The best result was achieved using the second facial key block, where it showed that the Probabilistic Collaborative based Classifier is the most suitable. The overall performance of the proposed system achieves an accuracy −95%, a sensitivity −94.33%, a specificity −95.67%, and an average processing time (for one sample) of <1 min at brain disease detection. PMID:29292716

Differential display detects host nucleic acid motifs altered in scrapie-infected brain.

PubMed

Lathe, Richard; Harris, Alyson

2009-09-25

The transmissible spongiform encephalopathies (TSEs) including scrapie have been attributed to an infectious protein or prion. Infectivity is allied to conversion of the endogenous nucleic-acid-binding protein PrP to an infectious modified form known as PrP(sc). The protein-only theory does not easily explain the enigmatic properties of the agent including strain variation. It was previously suggested that a short nucleic acid, perhaps host-encoded, might contribute to the pathoetiology of the TSEs. No candidate host molecules that might explain transmission of strain differences have yet been put forward. Differential display is a robust technique for detecting nucleic acid differences between two populations. We applied this technique to total nucleic acid preparations from scrapie-infected and control brain. Independent RNA preparations from eight normal and eight scrapie-infected (strain 263K) hamster brains were randomly amplified and visualized in parallel. Though the nucleic acid patterns were generally identical in scrapie-infected versus control brain, some rare bands were differentially displayed. Molecular species consistently overrepresented (or underrepresented) in all eight infected brain samples versus all eight controls were excised from the display, sequenced, and assembled into contigs. Only seven ros contigs (RNAs over- or underrepresented in scrapie) emerged, representing <4 kb from the transcriptome. All contained highly stable regions of secondary structure. The most abundant scrapie-only ros sequence was homologous to a repetitive transposable element (LINE; long interspersed nuclear element). Other ros sequences identified cellular RNA 7SL, clathrin heavy chain, visinin-like protein-1, and three highly specific subregions of ribosomal RNA (ros1-3). The ribosomal ros sequences accurately corresponded to LINE; retrotransposon insertion sites in ribosomal DNA (p<0.01). These differential motifs implicate specific host RNAs in the pathoetiology of the TSEs.

Insights into Brain Glycogen Metabolism: THE STRUCTURE OF HUMAN BRAIN GLYCOGEN PHOSPHORYLASE.

PubMed

Mathieu, Cécile; Li de la Sierra-Gallay, Ines; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

2016-08-26

Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Expression of the plasminogen activator system and the inhibitors PAI-1 and PAI-2 in posttraumatic lesions of the CNS and brain injuries following dramatic circulatory arrests: an immunohistochemical study.

PubMed

Dietzmann, K; von Bossanyi, P; Krause, D; Wittig, H; Mawrin, C; Kirches, E

2000-01-01

Plasminogen activators as inducible extracellular serine proteases are involved in a variety of processes, such as the degradation of brain structures. In regions of brain degradation, an increase in the expression of genes encoding cytokines and proteinases has recently been demonstrated. We tested the hypothesis, whether the plasminogen activator system as well as the plasminogen activator inhibitors are expressed and possibly involved in a proteolytic cascade that breaks down the extracellular matrix as a result of ischemic or posttraumatic brain destructions. To study this supposition, we investigated immunohistochemically the expression of tPA, uPA and its receptor, the plasminogen activator inhibitors PAI-1 and PAI-2, tetranectin as well as the laminin breakdown as an event of secondary brain injury. Brain tissue from 21 autopsy cases with severe brain injuries, material from 14 ischemic infarcts and 11 controls with acute hypoxia were used. All components of the plasminogen activator system studied were over-expressed immunohistochemically in reactive astrocytes, microglia and endothelial cells around the lesion zone. Tetranectin showed an analogous distribution to the plasminogen activator system. A reduced immunoreactivity of laminin within the identical region of destruction was detected concomitant with laminin remnants in perivascular macrophages, so that a remarkable role of the plasmin cascade in the degradation of extracellular matrix proteins in the brain is taken into consideration.

NIH workshop report on the trans-agency blood-brain interface workshop 2016: exploring key challenges and opportunities associated with the blood, brain and their interface.

PubMed

Ochocinska, Margaret J; Zlokovic, Berislav V; Searson, Peter C; Crowder, A Tamara; Kraig, Richard P; Ljubimova, Julia Y; Mainprize, Todd G; Banks, William A; Warren, Ronald Q; Kindzelski, Andrei; Timmer, William; Liu, Christina H

2017-05-01

A trans-agency workshop on the blood-brain interface (BBI), sponsored by the National Heart, Lung and Blood Institute, the National Cancer Institute and the Combat Casualty Care Research Program at the Department of Defense, was conducted in Bethesda MD on June 7-8, 2016. The workshop was structured into four sessions: (1) blood sciences; (2) exosome therapeutics; (3) next generation in vitro blood-brain barrier (BBB) models; and (4) BBB delivery and targeting. The first day of the workshop focused on the physiology of the blood and neuro-vascular unit, blood or biofluid-based molecular markers, extracellular vesicles associated with brain injury, and how these entities can be employed to better evaluate injury states and/or deliver therapeutics. The second day of the workshop focused on technical advances in in vitro models, BBB manipulations and nanoparticle-based drug carrier designs, with the goal of improving drug delivery to the central nervous system. The presentations and discussions underscored the role of the BBI in brain injury, as well as the role of the BBB as both a limiting factor and a potential conduit for drug delivery to the brain. At the conclusion of the meeting, the participants discussed challenges and opportunities confronting BBI translational researchers. In particular, the participants recommended using BBI translational research to stimulate advances in diagnostics, as well as targeted delivery approaches for detection and therapy of both brain injury and disease.

Human Brain Modeling with Its Anatomical Structure and Realistic Material Properties for Brain Injury Prediction.

PubMed

Atsumi, Noritoshi; Nakahira, Yuko; Tanaka, Eiichi; Iwamoto, Masami

2018-05-01

Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.

Pharmacologic and therapeutic features of sulbutiamine.

PubMed

Van Reeth, O

1999-03-01

Asthenia is the most frequent medical reason for people seeking help from their physician. In 75% of cases, the cause is functional (either reactive or psychiatric) and in 25% it is organic. In order to provide patients with rapid relief of symptoms, appropriate antiasthenic treatment should be initiated immediately, while at the same time, adequate clinical and laboratory assessments should be performed to detect the underlying cause of asthenia. Sulbutiamine, a highly lipophilic thiamine derivative, is the only antiasthenic compound known to cross the blood-brain barrier and to be selectively active on specific brain structures directly involved in asthenia. This article reviews the current knowledge on the effects of sulbutiamine in animal models and in various forms of human asthenia. (c) 1999 Prous Science. All rights reserved.

Implantable self-reset CMOS image sensor and its application to hemodynamic response detection in living mouse brain

NASA Astrophysics Data System (ADS)

Yamaguchi, Takahiro; Takehara, Hiroaki; Sunaga, Yoshinori; Haruta, Makito; Motoyama, Mayumi; Ohta, Yasumi; Noda, Toshihiko; Sasagawa, Kiyotaka; Tokuda, Takashi; Ohta, Jun

2016-04-01

A self-reset pixel of 15 × 15 µm2 with high signal-to-noise ratio (effective peak SNR ≃64 dB) for an implantable image sensor has been developed for intrinsic signal detection arising from hemodynamic responses in a living mouse brain. For detecting local conversion between oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) in brain tissues, an implantable imaging device was fabricated with our newly designed self-reset image sensor and orange light-emitting diodes (LEDs; λ = 605 nm). We demonstrated imaging of hemodynamic responses in the sensory cortical area accompanied by forelimb stimulation of a living mouse. The implantable imaging device for intrinsic signal detection is expected to be a powerful tool to measure brain activities in living animals used in behavioral analysis.

Neural networks improve brain cancer detection with Raman spectroscopy in the presence of light artifacts

NASA Astrophysics Data System (ADS)

Jermyn, Michael; Desroches, Joannie; Mercier, Jeanne; St-Arnaud, Karl; Guiot, Marie-Christine; Petrecca, Kevin; Leblond, Frederic

2016-03-01

It is often difficult to identify cancer tissue during brain cancer (glioma) surgery. Gliomas invade into areas of normal brain, and this cancer invasion is frequently not detected using standard preoperative magnetic resonance imaging (MRI). This results in enduring invasive cancer following surgery and leads to recurrence. A hand-held Raman spectroscopy is able to rapidly detect cancer invasion in patients with grade 2-4 gliomas. However, ambient light sources can produce spectral artifacts which inhibit the ability to distinguish between cancer and normal tissue using the spectral information available. To address this issue, we have demonstrated that artificial neural networks (ANN) can accurately classify invasive cancer versus normal brain tissue, even when including measurements with significant spectral artifacts from external light sources. The non-parametric and adaptive model used by ANN makes it suitable for detecting complex non-linear spectral characteristics associated with different tissues and the confounding presence of light artifacts. The use of ANN for brain cancer detection with Raman spectroscopy, in the presence of light artifacts, improves the robustness and clinical translation potential for intraoperative use. Integration with the neurosurgical workflow is facilitated by accounting for the effect of light artifacts which may occur, due to operating room lights, neuronavigation systems, windows, or other light sources. The ability to rapidly detect invasive brain cancer under these conditions may reduce residual cancer remaining after surgery, and thereby improve patient survival.

Brain-mapping projects using the common marmoset.

PubMed

Okano, Hideyuki; Mitra, Partha

2015-04-01

Globally, there is an increasing interest in brain-mapping projects, including the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative project in the USA, the Human Brain Project (HBP) in Europe, and the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) project in Japan. These projects aim to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain. Brain/MINDS is focused on structural and functional mapping of the common marmoset (Callithrix jacchus) brain. This non-human primate has numerous advantages for brain mapping, including a well-developed frontal cortex and a compact brain size, as well as the availability of transgenic technologies. In the present review article, we discuss strategies for structural and functional mapping of the marmoset brain and the relation of the common marmoset to other animals models. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Over-hydration detection in brain by magnetic induction spectroscopy

NASA Astrophysics Data System (ADS)

González, César A.; Pérez, María; Hevia, Nidiyare; Arámbula, Fernándo; Flores, Omar; Aguilar, Eliot; Hinojosa, Ivonne; Joskowicz, Leo; Rubinsky, Boris

2010-04-01

Detection and continuous monitoring of edema in the brain in early stages is useful for assessment of medical condition and treatment. We have proposed a solution in which the bulk measurements of the tissue electrical properties to detect edema or in general accumulation of fluids are made through measurement of the magnetic induction phase shift between applied and measured currents at different frequencies (Magnetic Induction Spectroscopy; MIS). Magnetic Resonant Imaging (MRI) has been characterized because its capability to detect different levels of brain tissue hydration by differences in diffusion-weighted (DW) sequences and it's involve apparent diffusion coefficient (ADC). The objective of this study was to explore the viability to use measurements of the bulk tissue electrical properties to detect edema or in general accumulation of fluids by MIS. We have induced a transitory and generalized tissue over-hydration condition in ten volunteers ingesting 1.5 to 2 liters of water in ten minutes. Basal and over-hydration conditions were monitored by MIS and MRI. Changes in the inductive phase shift at certain frequencies were consistent with changes in the brain tissue hydration level observed by DW-ADC. The results suggest that MIS has the potential to detect pathologies associated to changes in the content of fluids in brain tissue such as edema and hematomas.

Detection of experimental brain tumors using time-resolved laser-induced fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Thompson, Reid C.; Black, Keith L.; Kateb, Babak; Marcu, Laura

2002-05-01

Time-Resolved Laser-Induced Fluorescence Spectroscopy (TR-LIFS) has the potential to provide a non- invasive characterization and detection of tumors. We utilized TR-LIFS to detect gliomas in-vivo in the rat C6 glioma model. Time-resolved emission spectra of both normal brain and tumor were analyzed to determine if unique fluorescence signatures could be used to distinguish the two. Fluorescence parameters derived from both spectral and time domain were used for tissue characterization. Our results show that in the rat C6 glioma model, TR-LIFS can be used to differentiate brain tumors from normal tissue (gray and white mater) based upon time- resolved fluorescence signatures seen in brain tumors.

Incorporating virtual reality graphics with brain imaging for assessment of sport-related concussions.

PubMed

Slobounov, Semyon; Sebastianelli, Wayne; Newell, Karl M

2011-01-01

There is a growing concern that traditional neuropsychological (NP) testing tools are not sensitive to detecting residual brain dysfunctions in subjects suffering from mild traumatic brain injuries (MTBI). Moreover, most MTBI patients are asymptomatic based on anatomical brain imaging (CT, MRI), neurological examinations and patients' subjective reports within 10 days post-injury. Our ongoing research has documented that residual balance and visual-kinesthetic dysfunctions along with its underlying alterations of neural substrates may be detected in "asymptomatic subjects" by means of Virtual Reality (VR) graphics incorporated with brain imaging (EEG) techniques.

Blockade of Nociceptin Signaling Reduces Biochemical, Structural and Cognitive Deficits after Traumatic Brain Injury

DTIC Science & Technology

2010-07-01

also will determine if ORL1 antagonists block downstream gene transcription subsequent to enzyme activation. BODY: Task 1a was to optimize blast...value between 60 and 80 psi at which defects in vestibulomotor function can be detected. These findings could potentially become a clinical...nociceptin-mediated desensitization of opioid receptor-like 1 receptor and mu opioid receptors involves protein kinase C: a molecular mechanism for

Automated detection of extradural and subdural hematoma for contrast-enhanced CT images in emergency medical care

NASA Astrophysics Data System (ADS)

Hara, Takeshi; Matoba, Naoto; Zhou, Xiangrong; Yokoi, Shinya; Aizawa, Hiroaki; Fujita, Hiroshi; Sakashita, Keiji; Matsuoka, Tetsuya

2007-03-01

We have been developing the CAD scheme for head and abdominal injuries for emergency medical care. In this work, we have developed an automated method to detect typical head injuries, rupture or strokes of brain. Extradural and subdural hematoma region were detected by comparing technique after the brain areas were registered using warping. We employ 5 normal and 15 stroke cases to estimate the performance after creating the brain model with 50 normal cases. Some of the hematoma regions were detected correctly in all of the stroke cases with no false positive findings on normal cases.

Earlier Detection of Tumor Treatment Response Using Magnetic Resonance Diffusion Imaging with Oscillating Gradients

PubMed Central

Colvin, Daniel C.; Loveless, Mary E.; Does, Mark D.; Yue, Zou; Yankeelov, Thomas E.; Gore, John C.

2011-01-01

An improved method for detecting early changes in tumors in response to treatment, based on a modification of diffusion-weighted magnetic resonance imaging, has been demonstrated in an animal model. Early detection of therapeutic response in tumors is important both clinically and in pre-clinical assessments of novel treatments. Non-invasive imaging methods that can detect and assess tumor response early in the course of treatment, and before frank changes in tumor morphology are evident, are of considerable interest as potential biomarkers of treatment efficacy. Diffusion-weighted magnetic resonance imaging is sensitive to changes in water diffusion rates in tissues that result from structural variations in the local cellular environment, but conventional methods mainly reflect changes in tissue cellularity and do not convey information specific to micro-structural variations at sub-cellular scales. We implemented a modified imaging technique using oscillating gradients of the magnetic field for evaluating water diffusion rates over very short spatial scales that are more specific for detecting changes in intracellular structure that may precede changes in cellularity. Results from a study of orthotopic 9L gliomas in rat brains indicate that this method can detect changes as early as 24 hours following treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), when conventional approaches do not find significant effects. These studies suggest that diffusion imaging using oscillating gradients may be used to obtain an earlier indication of treatment efficacy than previous magnetic resonance imaging methods. PMID:21190804

EXPRESSION OF REELIN, ITS RECEPTORS AND ITS INTRACELLULAR SIGNALING PROTEIN, DISABLED-1 (DAB-1) IN THE CANARY BRAIN: RELATIONSHIPS WITH THE SONG CONTROL SYSTEM

PubMed Central

BALTHAZART, JACQUES; VOIGT, CORNELIA; BOSERET, GÉRALDINE; BALL, GREGORY F

2008-01-01

Songbirds produce learned vocalizations that are controlled by a specialized network of neural structures, the song control system. Several nuclei in this song control system demonstrate a marked degree of adult seasonal plasticity. Nucleus volume varies seasonally based on changes in cell size or spacing, and in the case of nucleus HVC and area X on the incorporation of new neurons. Reelin, a large glycoprotein defective in reeler mice, is assumed to determine the final location of migrating neurons in the developing brain. In mammals, reelin is also expressed in the adult brain but its functions are less well characterized. We investigated the relationships between the expression of reelin and/or its receptors and the dramatic seasonal plasticity in the canary (Serinus canaria) brain. We detected a broad distribution of the reelin protein, its messenger RNA and the mRNAs encoding for the reelin receptors (VLDLR and ApoER2) as well as for its intracellular signaling protein, Dab1. These different mRNAs and proteins did not display the same neuroanatomical distribution and were not clearly associated, in an exclusive manner, with telencephalic brain areas that incorporate new neurons in adulthood. Song control nuclei were associated with a particular specialized expression of reelin and its mRNA, with the reelin signal being either denser or lighter in the song nucleus than in the surrounding tissue. The density of reelin-ir structures did not seem to be affected by four weeks of treatment with exogenous testosterone. These observations do not provide conclusive evidence that reelin plays a prominent role in the positioning of new neurons in the adult canary brain but call for additional work on this protein analyzing its expression comparatively during development and in adulthood with a better temporal resolution at critical points in the reproductive cycle when brain plasticity is known to occur. PMID:18448255

Immunocytochemical Studies of Neurofibrillary Tangles

PubMed Central

Yen, Shu-Hui C.; Gaskin, Felicia; Terry, Robert D.

1981-01-01

The molecular nature of neurofibrillary tangles of senile dementia of the Alzheimer type (SDAT) was studied by immunoperoxidase and immunofluorescence techniques. Five antiserums, including anti-humanbrain-2-cycle-purified-microtubule-fractions (2 × MT), anti-calf-brain-2 × MT, anti-sea-urchin-egg-tubulin, antibeef-brain-tubulin, and anti-human-brain-neurofilament(NF)-210-kilodalton(kd)-protein were tested for their binding to neurofibrillary tangles. The antihuman-2 × MT serum stained structures resembling neurofibrillary tangles, neurites of neuritic plaques, and microglialike cells in SDAT brains, but no such staining pattern was detected in normal brain sections. In neurons isolated from SDAT brains, about 40% of the tangles were labeled by the anti-human-2×MT serum with an identical pattern. Other antiserums tested did not preferentially bind tanglelike structures in tissue sections and bound to less than 5% of the tangles in isolated neurons. These results suggest that the antigenic sites of tubulin and NF proteins are not shared by neurofibrillary tangles. Different from the calf preparation, the human-2 × MT fractions contained a prominent protein band that was identical to ferritin in molecular weight and cross-reacted with anti-human-2 × MT and anti-human-ferritin serums. However, antiserums to this ferritinlike protein, or anti-ferritin, did not stain neurofibrillary tangles. Although neither the calf 2 × MT nor two other human MT fractions failed to elicit an antiserum that stained tangles, these fractions were able to remove the antihuman-2 × MT serum activity that binds to tangles. The data suggest that the protein (or proteins) that makes up neurofibrillary tangles of SDAT is present in various quantities in microtubule fractions of normal brain. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9Figure 10Figure 11Figure 12Figure 13Figure 14Figure 15Figure 16 PMID:7020426

Method and apparatus for extraction of low-frequency artifacts from brain waves for alertness detection

DOEpatents

Clapp, N.E.; Hively, L.M.

1997-05-06

Methods and apparatus automatically detect alertness in humans by monitoring and analyzing brain wave signals. Steps include: acquiring the brain wave (EEG or MEG) data from the subject, digitizing the data, separating artifact data from raw data, and comparing trends in f-data to alertness indicators, providing notification of inadequate alertness. 4 figs.

Brain tumour classification and abnormality detection using neuro-fuzzy technique and Otsu thresholding.

PubMed

Renjith, Arokia; Manjula, P; Mohan Kumar, P

2015-01-01

Brain tumour is one of the main causes for an increase in transience among children and adults. This paper proposes an improved method based on Magnetic Resonance Imaging (MRI) brain image classification and image segmentation approach. Automated classification is encouraged by the need of high accuracy when dealing with a human life. The detection of the brain tumour is a challenging problem, due to high diversity in tumour appearance and ambiguous tumour boundaries. MRI images are chosen for detection of brain tumours, as they are used in soft tissue determinations. First of all, image pre-processing is used to enhance the image quality. Second, dual-tree complex wavelet transform multi-scale decomposition is used to analyse texture of an image. Feature extraction extracts features from an image using gray-level co-occurrence matrix (GLCM). Then, the Neuro-Fuzzy technique is used to classify the stages of brain tumour as benign, malignant or normal based on texture features. Finally, tumour location is detected using Otsu thresholding. The classifier performance is evaluated based on classification accuracies. The simulated results show that the proposed classifier provides better accuracy than previous method.

Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons.

PubMed

Jo, Junghyun; Xiao, Yixin; Sun, Alfred Xuyang; Cukuroglu, Engin; Tran, Hoang-Dai; Göke, Jonathan; Tan, Zi Ying; Saw, Tzuen Yih; Tan, Cheng-Peow; Lokman, Hidayat; Lee, Younghwan; Kim, Donghoon; Ko, Han Seok; Kim, Seong-Oh; Park, Jae Hyeon; Cho, Nam-Joon; Hyde, Thomas M; Kleinman, Joel E; Shin, Joo Heon; Weinberger, Daniel R; Tan, Eng King; Je, Hyunsoo Shawn; Ng, Huck-Hui

2016-08-04

Recent advances in 3D culture systems have led to the generation of brain organoids that resemble different human brain regions; however, a 3D organoid model of the midbrain containing functional midbrain dopaminergic (mDA) neurons has not been reported. We developed a method to differentiate human pluripotent stem cells into a large multicellular organoid-like structure that contains distinct layers of neuronal cells expressing characteristic markers of human midbrain. Importantly, we detected electrically active and functionally mature mDA neurons and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using 2D methods or MLOs generated from mouse embryonic stem cells, our human MLOs produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a tractable in vitro system to study the human midbrain and its related diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

SPED light sheet microscopy: fast mapping of biological system structure and function

PubMed Central

Tomer, Raju; Lovett-Barron, Matthew; Kauvar, Isaac; Andalman, Aaron; Burns, Vanessa M.; Sankaran, Sethuraman; Grosenick, Logan; Broxton, Michael; Yang, Samuel; Deisseroth, Karl

2016-01-01

The goal of understanding living nervous systems has driven interest in high-speed and large field-of-view volumetric imaging at cellular resolution. Light-sheet microscopy approaches have emerged for cellular-resolution functional brain imaging in small organisms such as larval zebrafish, but remain fundamentally limited in speed. Here we have developed SPED light sheet microscopy, which combines large volumetric field-of-view via an extended depth of field with the optical sectioning of light sheet microscopy, thereby eliminating the need to physically scan detection objectives for volumetric imaging. SPED enables scanning of thousands of volumes-per-second, limited only by camera acquisition rate, through the harnessing of optical mechanisms that normally result in unwanted spherical aberrations. We demonstrate capabilities of SPED microscopy by performing fast sub-cellular resolution imaging of CLARITY mouse brains and cellular-resolution volumetric Ca2+ imaging of entire zebrafish nervous systems. Together, SPED light sheet methods enable high-speed cellular-resolution volumetric mapping of biological system structure and function. PMID:26687363

Brain Network Analysis from High-Resolution EEG Signals

NASA Astrophysics Data System (ADS)

de Vico Fallani, Fabrizio; Babiloni, Fabio

Over the last decade, there has been a growing interest in the detection of the functional connectivity in the brain from different neuroelectromagnetic and hemodynamic signals recorded by several neuro-imaging devices such as the functional Magnetic Resonance Imaging (fMRI) scanner, electroencephalography (EEG) and magnetoencephalography (MEG) apparatus. Many methods have been proposed and discussed in the literature with the aim of estimating the functional relationships among different cerebral structures. However, the necessity of an objective comprehension of the network composed by the functional links of different brain regions is assuming an essential role in the Neuroscience. Consequently, there is a wide interest in the development and validation of mathematical tools that are appropriate to spot significant features that could describe concisely the structure of the estimated cerebral networks. The extraction of salient characteristics from brain connectivity patterns is an open challenging topic, since often the estimated cerebral networks have a relative large size and complex structure. Recently, it was realized that the functional connectivity networks estimated from actual brain-imaging technologies (MEG, fMRI and EEG) can be analyzed by means of the graph theory. Since a graph is a mathematical representation of a network, which is essentially reduced to nodes and connections between them, the use of a theoretical graph approach seems relevant and useful as firstly demonstrated on a set of anatomical brain networks. In those studies, the authors have employed two characteristic measures, the average shortest path L and the clustering index C, to extract respectively the global and local properties of the network structure. They have found that anatomical brain networks exhibit many local connections (i.e. a high C) and few random long distance connections (i.e. a low L). These values identify a particular model that interpolate between a regular lattice and a random structure. Such a model has been designated as "small-world" network in analogy with the concept of the small-world phenomenon observed more than 30 years ago in social systems. In a similar way, many types of functional brain networks have been analyzed according to this mathematical approach. In particular, several studies based on different imaging techniques (fMRI, MEG and EEG) have found that the estimated functional networks showed small-world characteristics. In the functional brain connectivity context, these properties have been demonstrated to reflect an optimal architecture for the information processing and propagation among the involved cerebral structures. However, the performance of cognitive and motor tasks as well as the presence of neural diseases has been demonstrated to affect such a small-world topology, as revealed by the significant changes of L and C. Moreover, some functional brain networks have been mostly found to be very unlike the random graphs in their degree-distribution, which gives information about the allocation of the functional links within the connectivity pattern. It was demonstrated that the degree distributions of these networks follow a power-law trend. For this reason those networks are called "scale-free". They still exhibit the small-world phenomenon but tend to contain few nodes that act as highly connected "hubs". Scale-free networks are known to show resistance to failure, facility of synchronization and fast signal processing. Hence, it would be important to see whether the scaling properties of the functional brain networks are altered under various pathologies or experimental tasks. The present Chapter proposes a theoretical graph approach in order to evaluate the functional connectivity patterns obtained from high-resolution EEG signals. In this way, the "Brain Network Analysis" (in analogy with the Social Network Analysis that has emerged as a key technique in modern sociology) represents an effective methodology improving the comprehension of the complex interactions in the brain.

Cognitive Reserve and Brain Maintenance: Orthogonal Concepts in Theory and Practice.

PubMed

Habeck, C; Razlighi, Q; Gazes, Y; Barulli, D; Steffener, J; Stern, Y

2017-08-01

Cognitive Reserve and Brain Maintenance have traditionally been understood as complementary concepts: Brain Maintenance captures the processes underlying the structural preservation of the brain with age, and might be assessed relative to age-matched peers. Cognitive Reserve, on the other hand, refers to how cognitive processing can be performed regardless of how well brain structure has been maintained. Thus, Brain Maintenance concerns the "hardware," whereas Cognitive Reserve concerns "software," that is, brain functioning explained by factors beyond mere brain structure. We used structural brain data from 368 community-dwelling adults, age 20-80, to derive measures of Brain Maintenance and Cognitive Reserve. We found that Brain Maintenance and Cognitive were uncorrelated such that values on one measure did not imply anything about the other measure. Further, both measures were positively correlated with verbal intelligence and education, hinting at formative influences of the latter to both measures. We performed extensive split-half simulations to check our derived measures' statistical robustness. Our approach enables the out-of-sample quantification of Brain Maintenance and Cognitive Reserve for single subjects on the basis of chronological age, neuropsychological performance and structural brain measures. Future work will investigate the prognostic power of these measures with regard to future cognitive status. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Development of stereotactic mass spectrometry for brain tumor surgery.

PubMed

Agar, Nathalie Y R; Golby, Alexandra J; Ligon, Keith L; Norton, Isaiah; Mohan, Vandana; Wiseman, Justin M; Tannenbaum, Allen; Jolesz, Ferenc A

2011-02-01

Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue. To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents. Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity. Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence. The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of any organ and with a rapidity that allows real-time analysis.

Skull metastases detecting on arterial spin labeling perfusion: Three case reports and review of literature.

PubMed

Ryu, Kyeong H; Baek, Hye J; Cho, Soo B; Moon, Jin I; Choi, Bo H; Park, Sung E; An, Hyo J

2017-11-01

Detection of skull metastases is as important as detection of brain metastases because early diagnosis of skull metastases is a crucial determinant of treatment. However, the skull can be a blind spot for assessing metastases on routine brain magnetic resonance imaging (MRI). To the best of our knowledge, the finding of skull metastases on arterial spin labeling (ASL) has not been reported. ASL is a specific MRI sequence for evaluating cerebral blood flow using magnetized endogenous inflow blood. This study uses ASL as a routine sequence of brain MRI protocol and describes 3 clinical cases of skull metastases identified by ASL. The study also highlights the clinical usefulness of ASL in detecting skull metastases. Three patients with known malignancy underwent brain MRI to evaluate for brain metastases. All of the skull metastases were conspicuously depicted on routine ASL images, and the lesions correlated well with other MRI sequences. Three patients received palliative chemotherapy. Three patients are being followed up regularly at the outpatient department. The routine use of ASL may help to detect lesions in blind spots, such as skull metastases, and to facilitate the evaluation of intracranial pathologies without the use of contrast materials in exceptional situations.

Structure Shapes Dynamics and Directionality in Diverse Brain Networks: Mathematical Principles and Empirical Confirmation in Three Species

NASA Astrophysics Data System (ADS)

Moon, Joon-Young; Kim, Junhyeok; Ko, Tae-Wook; Kim, Minkyung; Iturria-Medina, Yasser; Choi, Jee-Hyun; Lee, Joseph; Mashour, George A.; Lee, Uncheol

2017-04-01

Identifying how spatially distributed information becomes integrated in the brain is essential to understanding higher cognitive functions. Previous computational and empirical studies suggest a significant influence of brain network structure on brain network function. However, there have been few analytical approaches to explain the role of network structure in shaping regional activities and directionality patterns. In this study, analytical methods are applied to a coupled oscillator model implemented in inhomogeneous networks. We first derive a mathematical principle that explains the emergence of directionality from the underlying brain network structure. We then apply the analytical methods to the anatomical brain networks of human, macaque, and mouse, successfully predicting simulation and empirical electroencephalographic data. The results demonstrate that the global directionality patterns in resting state brain networks can be predicted solely by their unique network structures. This study forms a foundation for a more comprehensive understanding of how neural information is directed and integrated in complex brain networks.

APOE Polymorphism Affects Brain Default Mode Network in Healthy Young Adults

PubMed Central

Su, Yun Yan; Liang, Xue; Schoepf, U. Joseph; Varga-Szemes, Akos; West, Henry C.; Qi, Rongfeng; Kong, Xiang; Chen, Hui Juan; Lu, Guang Ming; Zhang, Long Jiang

2015-01-01

Abstract To investigate the effect of apolipoprotein E (APOE) gene polymorphism on the resting-state brain function, structure, and blood flow in healthy adults younger than 35 years, using multimodality magnetic resonance (MR) imaging. Seventy-six healthy adults (34 men, 23.7 ± 2.8 y; 31 APOE ε4/ε3 carriers, 31 ε3/ε3 carriers, and 14 ε2/ε3 carriers) were included. For resting-state functional MRI data, default mode network (DMN) and amplitude of low-frequency fluctuation maps were extracted and analyzed. Voxel-based morphometry, diffusion tensor imaging from structural imaging, and cerebral blood flow based on arterial spin labeling MR imaging were also analyzed. Correlation analysis was performed between the above mentioned brain parameters and neuropsychological tests. There were no differences in neuropsychological performances, amplitude of low-frequency fluctuation, gray/white matter volumes, fractional anisotropy, mean diffusivity, or whole brain cerebral blood flow among the 3 groups. As for DMN, the ε4/ε3 group showed increased functional connectivities (FCs) in the left medial prefrontal cortex and bilateral posterior cingulate cortices/precuneus compared with the ε3/ε3 group, and increased FCs in the left medial prefrontal cortex and right temporal lobe compared with the ε2/ε3 group (P < 0.05, Alphasim corrected). No differences of DMN FCs were found between the ε2/ε3 and ε3/ε3 groups. FCs in the right temporal lobe positively correlated with the performances of vocabulary learning, delayed recall, and graph recall in all participants (P < 0.05). APOE ε4 carriers exhibited significantly increased DMN FCs when compared with ε3 and ε2 carriers. The ε4 affects DMN FCs before brain structure and blood flow in cognitively intact young patients, suggesting DMN FC may serve as a potential biomarker for the detection of early manifestations of genetic effect. PMID:26717353

Impact of time-of-day on diffusivity measures of brain tissue derived from diffusion tensor imaging.

PubMed

Thomas, Cibu; Sadeghi, Neda; Nayak, Amrita; Trefler, Aaron; Sarlls, Joelle; Baker, Chris I; Pierpaoli, Carlo

2018-06-01

Diurnal fluctuations in MRI measures of structural and functional properties of the brain have been reported recently. These fluctuations may have a physiological origin, since they have been detected using different MRI modalities, and cannot be explained by factors that are typically known to confound MRI measures. While preliminary evidence suggests that measures of structural properties of the brain based on diffusion tensor imaging (DTI) fluctuate as a function of time-of-day (TOD), the underlying mechanism has not been investigated. Here, we used a longitudinal within-subjects design to investigate the impact of time-of-day on DTI measures. In addition to using the conventional monoexponential tensor model to assess TOD-related fluctuations, we used a dual compartment tensor model that allowed us to directly assess if any change in DTI measures is due to an increase in CSF/free-water volume fraction or due to an increase in water diffusivity within the parenchyma. Our results show that Trace or mean diffusivity, as measured using the conventional monoexponential tensor model tends to increase systematically from morning to afternoon scans at the interface of grey matter/CSF, most prominently in the major fissures and the sulci of the brain. Interestingly, in a recent study of the glymphatic system, these same regions were found to show late enhancement after intrathecal injection of a CSF contrast agent. The increase in Trace also impacts DTI measures of diffusivity such as radial and axial diffusivity, but does not affect fractional anisotropy. The dual compartment analysis revealed that the increase in diffusivity measures from PM to AM was driven by an increase in the volume fraction of CSF-like free-water. Taken together, our findings provide important insight into the likely physiological origins of diurnal fluctuations in MRI measurements of structural properties of the brain. Published by Elsevier Inc.

Epigenetics in Developmental Disorder: ADHD and Endophenotypes

PubMed Central

Archer, Trevor; Oscar-Berman, Marlene; Blum, Kenneth

2011-01-01

Heterogeneity in attention-deficit/hyperactivity disorder (ADHD), with complex interactive operations of genetic and environmental factors, is expressed in a variety of disorder manifestations: severity, co-morbidities of symptoms, and the effects of genes on phenotypes. Neurodevelopmental influences of genomic imprinting have set the stage for the structural-physiological variations that modulate the cognitive, affective, and pathophysiological domains of ADHD. The relative contributions of genetic and environmental factors provide rapidly proliferating insights into the developmental trajectory of the condition, both structurally and functionally. Parent-of-origin effects seem to support the notion that genetic risks for disease process debut often interact with the social environment, i.e., the parental environment in infants and young children. The notion of endophenotypes, markers of an underlying liability to the disorder, may facilitate detection of genetic risks relative to a complex clinical disorder. Simple genetic association has proven insufficient to explain the spectrum of ADHD. At a primary level of analysis, the consideration of epigenetic regulation of brain signalling mechanisms, dopamine, serotonin, and noradrenaline is examined. Neurotrophic factors that participate in the neurogenesis, survival, and functional maintenance of brain systems, are involved in neuroplasticity alterations underlying brain disorders, and are implicated in the genetic predisposition to ADHD, but not obviously, nor in a simple or straightforward fashion. In the context of intervention, genetic linkage studies of ADHD pharmacological intervention have demonstrated that associations have fitted the “drug response phenotype,” rather than the disorder diagnosis. Despite conflicting evidence for the existence, or not, of genetic associations between disorder diagnosis and genes regulating the structure and function of neurotransmitters and brain-derived neurotrophic factor (BDNF), associations between symptoms-profiles endophenotypes and single nucleotide polymorphisms appear reassuring. PMID:22224195

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group

PubMed Central

Schmaal, L; Hibar, D P; Sämann, P G; Hall, G B; Baune, B T; Jahanshad, N; Cheung, J W; van Erp, T G M; Bos, D; Ikram, M A; Vernooij, M W; Niessen, W J; Tiemeier, H; Hofman, A; Wittfeld, K; Grabe, H J; Janowitz, D; Bülow, R; Selonke, M; Völzke, H; Grotegerd, D; Dannlowski, U; Arolt, V; Opel, N; Heindel, W; Kugel, H; Hoehn, D; Czisch, M; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Wright, M J; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Goya-Maldonado, R; Gruber, O; Krämer, B; Hatton, S N; Lagopoulos, J; Hickie, I B; Frodl, T; Carballedo, A; Frey, E M; van Velzen, L S; Penninx, B W J H; van Tol, M-J; van der Wee, N J; Davey, C G; Harrison, B J; Mwangi, B; Cao, B; Soares, J C; Veer, I M; Walter, H; Schoepf, D; Zurowski, B; Konrad, C; Schramm, E; Normann, C; Schnell, K; Sacchet, M D; Gotlib, I H; MacQueen, G M; Godlewska, B R; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Hall, J; Sussmann, J E; Li, M; Walter, M; Aftanas, L; Brack, I; Bokhan, N A; Thompson, P M; Veltman, D J

2017-01-01

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: −0.10 to −0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: −0.26 to −0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life. PMID:27137745

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

PubMed Central

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

2014-01-01

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

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.

PubMed

Schmaal, L; Hibar, D P; Sämann, P G; Hall, G B; Baune, B T; Jahanshad, N; Cheung, J W; van Erp, T G M; Bos, D; Ikram, M A; Vernooij, M W; Niessen, W J; Tiemeier, H; Hofman, A; Wittfeld, K; Grabe, H J; Janowitz, D; Bülow, R; Selonke, M; Völzke, H; Grotegerd, D; Dannlowski, U; Arolt, V; Opel, N; Heindel, W; Kugel, H; Hoehn, D; Czisch, M; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Wright, M J; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Goya-Maldonado, R; Gruber, O; Krämer, B; Hatton, S N; Lagopoulos, J; Hickie, I B; Frodl, T; Carballedo, A; Frey, E M; van Velzen, L S; Penninx, B W J H; van Tol, M-J; van der Wee, N J; Davey, C G; Harrison, B J; Mwangi, B; Cao, B; Soares, J C; Veer, I M; Walter, H; Schoepf, D; Zurowski, B; Konrad, C; Schramm, E; Normann, C; Schnell, K; Sacchet, M D; Gotlib, I H; MacQueen, G M; Godlewska, B R; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Hall, J; Sussmann, J E; Li, M; Walter, M; Aftanas, L; Brack, I; Bokhan, N A; Thompson, P M; Veltman, D J

2017-06-01

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Schizophrenia‐like topological changes in the structural connectome of individuals with subclinical psychotic experiences

PubMed Central

Caeyenberghs, Karen; Dutt, Anirban; Zammit, Stanley; Evans, C. John; Reichenberg, Abraham; Lewis, Glyn; David, Anthony S.; Jones, Derek K.

2015-01-01

Abstract Schizophrenia is often regarded as a “dysconnectivity” disorder and recent work using graph theory has been used to better characterize dysconnectivity of the structural connectome in schizophrenia. However, there are still little data on the topology of connectomes in less severe forms of the condition. Such analysis will identify topological markers of less severe disease states and provide potential predictors of further disease development. Individuals with psychotic experiences (PEs) were identified from a population‐based cohort without relying on participants presenting to clinical services. Such individuals have an increased risk of developing clinically significant psychosis. 123 individuals with PEs and 125 controls were scanned with diffusion‐weighted MRI. Whole‐brain structural connectomes were derived and a range of global and local GT‐metrics were computed. Global efficiency and density were significantly reduced in individuals with PEs. Local efficiency was reduced in a number of regions, including critical network hubs. Further analysis of functional subnetworks showed differential impairment of the default mode network. An additional analysis of pair‐wise connections showed no evidence of differences in individuals with PEs. These results are consistent with previous findings in schizophrenia. Reduced efficiency in critical core hubs suggests the brains of individuals with PEs may be particularly predisposed to dysfunction. The absence of any detectable effects in pair‐wise connections illustrates that, at less severe stages of psychosis, white‐matter alterations are subtle and only manifest when examining network topology. This study indicates that topology could be a sensitive biomarker for early stages of psychotic illness. Hum Brain Mapp 36:2629–2643, 2015.© 2015 TheAuthors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:25832856

A Pathological Brain Detection System based on Extreme Learning Machine Optimized by Bat Algorithm.

PubMed

Lu, Siyuan; Qiu, Xin; Shi, Jianping; Li, Na; Lu, Zhi-Hai; Chen, Peng; Yang, Meng-Meng; Liu, Fang-Yuan; Jia, Wen-Juan; Zhang, Yudong

2017-01-01

It is beneficial to classify brain images as healthy or pathological automatically, because 3D brain images can generate so much information which is time consuming and tedious for manual analysis. Among various 3D brain imaging techniques, magnetic resonance (MR) imaging is the most suitable for brain, and it is now widely applied in hospitals, because it is helpful in the four ways of diagnosis, prognosis, pre-surgical, and postsurgical procedures. There are automatic detection methods; however they suffer from low accuracy. Therefore, we proposed a novel approach which employed 2D discrete wavelet transform (DWT), and calculated the entropies of the subbands as features. Then, a bat algorithm optimized extreme learning machine (BA-ELM) was trained to identify pathological brains from healthy controls. A 10x10-fold cross validation was performed to evaluate the out-of-sample performance. The method achieved a sensitivity of 99.04%, a specificity of 93.89%, and an overall accuracy of 98.33% over 132 MR brain images. The experimental results suggest that the proposed approach is accurate and robust in pathological brain detection. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Human Brain Activity Patterns beyond the Isoelectric Line of Extreme Deep Coma

PubMed Central

Kroeger, Daniel; Florea, Bogdan; Amzica, Florin

2013-01-01

The electroencephalogram (EEG) reflects brain electrical activity. A flat (isoelectric) EEG, which is usually recorded during very deep coma, is considered to be a turning point between a living brain and a deceased brain. Therefore the isoelectric EEG constitutes, together with evidence of irreversible structural brain damage, one of the criteria for the assessment of brain death. In this study we use EEG recordings for humans on the one hand, and on the other hand double simultaneous intracellular recordings in the cortex and hippocampus, combined with EEG, in cats. They serve to demonstrate that a novel brain phenomenon is observable in both humans and animals during coma that is deeper than the one reflected by the isoelectric EEG, and that this state is characterized by brain activity generated within the hippocampal formation. This new state was induced either by medication applied to postanoxic coma (in human) or by application of high doses of anesthesia (isoflurane in animals) leading to an EEG activity of quasi-rhythmic sharp waves which henceforth we propose to call ν-complexes (Nu-complexes). Using simultaneous intracellular recordings in vivo in the cortex and hippocampus (especially in the CA3 region) we demonstrate that ν-complexes arise in the hippocampus and are subsequently transmitted to the cortex. The genesis of a hippocampal ν-complex depends upon another hippocampal activity, known as ripple activity, which is not overtly detectable at the cortical level. Based on our observations, we propose a scenario of how self-oscillations in hippocampal neurons can lead to a whole brain phenomenon during coma. PMID:24058669

Wavelet analysis of head acceleration response under dirac excitation for early oedema detection.

PubMed

Kostopoulos, V; Loutas, T H; Derdas, C; Douzinas, E

2008-04-01

The present work deals with the application of an innovative in-house developed wavelet-based methodology for the analysis of the acceleration responses of a human head complex model as a simulated diffused oedema progresses. The human head complex has been modeled as a structure consisting of three confocal prolate spheroids, whereas the three defined regions by the system of spheroids, from the outside to the inside, represent the scull, the region of cerebrospinal fluid, and the brain tissue. A Dirac-like pulse has been used to excite the human head complex model and the acceleration response of the system has been calculated and analyzed via the wavelet-based methodology. For the purpose of the present analysis, a wave propagation commercial finite element code, LS-DYNA 3D, has been used. The progressive diffused oedema was modeled via consecutive increases in brain volume accompanied by a decrease in brain density. It was shown that even a small increase in brain volume (at the level of 0.5%) can be identified by the effect it has on the vibration characteristics of the human head complex. More precisely, it was found that for some of the wavelet decomposition levels, the energy content changes monotonically as the brain volume increases, thus providing a useful index of monitoring an oncoming brain oedema before any brain damage appears due to uncontrolled intracranial hypertension. For the purpose of the present work and for the levels of brain volume increase considered in the present analysis, no pressure increase was assumed into the cranial vault and, associatively, no brain compliance variation.

TSPO Expression and Brain Structure in the Psychosis Spectrum.

PubMed

Hafizi, Sina; Guma, Elisa; Koppel, Alex; Da Silva, Tania; Kiang, Michael; Houle, Sylvain; Wilson, Alan A; Rusjan, Pablo M; Chakravarty, M Mallar; Mizrahi, Romina

2018-06-12

Psychosis is associated with abnormal structural changes in the brain including decreased regional brain volumes and abnormal brain morphology. However, the underlying causes of these structural abnormalities are less understood. The immune system, including microglial activation, has been implicated in the pathophysiology of psychosis. Although previous studies have suggested a connection between peripheral proinflammatory cytokines and structural brain abnormalities in schizophrenia, no in-vivo studies have investigated whether microglial activation is also linked to brain structure alterations previously observed in schizophrenia and its putative prodrome. In this study, we investigated the link between mitochondrial 18kDa translocator protein (TSPO) and structural brain characteristics (i.e. regional brain volume, cortical thickness, and hippocampal shape) in key brain regions such as dorsolateral prefrontal cortex and hippocampus of a large group of participants (N = 90) including individuals at clinical high risk (CHR) for psychosis, first-episode psychosis (mostly antipsychotic naïve) patients, and healthy volunteers. The participants underwent structural brain MRI scan and [ 18 F]FEPPA positron emission tomography (PET) targeting TSPO. A significant [ 18 F]FEPPA binding-by-group interaction was observed in morphological measures across the left hippocampus. In first-episode psychosis, we observed associations between [ 18 F]FEPPA V T (total volume of distribution) and outward and inward morphological alterations, respectively, in the dorsal and ventro-medial portions of the left hippocampus. These associations were not significant in CHR or healthy volunteers. There was no association between [ 18 F]FEPPA V T and other structural brain characteristics. Our findings suggest a link between TSPO expression and alterations in hippocampal morphology in first-episode psychosis. Copyright © 2018. Published by Elsevier Inc.

[Initial diagnosis of Parkinson's disease - neuroradiological diagnosis].

PubMed

Orimo, Satoshi

2013-01-01

Brain MRI is essential for differentiating Parkinson's disease (PD) from other parkinsonian syndromes. The purpose of performing brain MRI is not to make a diagnosis of PD but is to exclude other parkinsonian syndromes. Recently, several new MRI techniques such as voxel based morphometry, relaxometry, magnetization transfer, spectroscopy, tractography, and functional MRI have been introduced in the diagnosis of PD. Neuromelanin imaging is one of the new techniques and can be useful to make an initial diagnosis of PD. MIBG myocardial scintigraphy is a sensitive imaging tool to differentiate PD from other parkinsonian syndromes and is one of the good tools to make an initial diagnosis of PD. Brain perfusion imaging is sometimes useful to make an initial diagnosis of PD, because reduced brain perfusion area can be detected before brain MRI detects morphological changes of the brain. Dopamine transporter imaging, not available in Japan, is a sensitive tool to detect very early parkinsonism and is useful to make an initial diagnosis of PD. However, it is difficult to differentiate PD from other parkinsonian syndromes.

Matched signal detection on graphs: Theory and application to brain imaging data classification.

PubMed

Hu, Chenhui; Sepulcre, Jorge; Johnson, Keith A; Fakhri, Georges E; Lu, Yue M; Li, Quanzheng

2016-01-15

Motivated by recent progress in signal processing on graphs, we have developed a matched signal detection (MSD) theory for signals with intrinsic structures described by weighted graphs. First, we regard graph Laplacian eigenvalues as frequencies of graph-signals and assume that the signal is in a subspace spanned by the first few graph Laplacian eigenvectors associated with lower eigenvalues. The conventional matched subspace detector can be applied to this case. Furthermore, we study signals that may not merely live in a subspace. Concretely, we consider signals with bounded variation on graphs and more general signals that are randomly drawn from a prior distribution. For bounded variation signals, the test is a weighted energy detector. For the random signals, the test statistic is the difference of signal variations on associated graphs, if a degenerate Gaussian distribution specified by the graph Laplacian is adopted. We evaluate the effectiveness of the MSD on graphs both with simulated and real data sets. Specifically, we apply MSD to the brain imaging data classification problem of Alzheimer's disease (AD) based on two independent data sets: 1) positron emission tomography data with Pittsburgh compound-B tracer of 30 AD and 40 normal control (NC) subjects, and 2) resting-state functional magnetic resonance imaging (R-fMRI) data of 30 early mild cognitive impairment and 20 NC subjects. Our results demonstrate that the MSD approach is able to outperform the traditional methods and help detect AD at an early stage, probably due to the success of exploiting the manifold structure of the data. Copyright © 2015. Published by Elsevier Inc.

Transcripts with in silico predicted RNA structure are enriched everywhere in the mouse brain

PubMed Central

2012-01-01

Background Post-transcriptional control of gene expression is mostly conducted by specific elements in untranslated regions (UTRs) of mRNAs, in collaboration with specific binding proteins and RNAs. In several well characterized cases, these RNA elements are known to form stable secondary structures. RNA secondary structures also may have major functional implications for long noncoding RNAs (lncRNAs). Recent transcriptional data has indicated the importance of lncRNAs in brain development and function. However, no methodical efforts to investigate this have been undertaken. Here, we aim to systematically analyze the potential for RNA structure in brain-expressed transcripts. Results By comprehensive spatial expression analysis of the adult mouse in situ hybridization data of the Allen Mouse Brain Atlas, we show that transcripts (coding as well as non-coding) associated with in silico predicted structured probes are highly and significantly enriched in almost all analyzed brain regions. Functional implications of these RNA structures and their role in the brain are discussed in detail along with specific examples. We observe that mRNAs with a structure prediction in their UTRs are enriched for binding, transport and localization gene ontology categories. In addition, after manual examination we observe agreement between RNA binding protein interaction sites near the 3’ UTR structures and correlated expression patterns. Conclusions Our results show a potential use for RNA structures in expressed coding as well as noncoding transcripts in the adult mouse brain, and describe the role of structured RNAs in the context of intracellular signaling pathways and regulatory networks. Based on this data we hypothesize that RNA structure is widely involved in transcriptional and translational regulatory mechanisms in the brain and ultimately plays a role in brain function. PMID:22651826

Detecting large-scale networks in the human brain using high-density electroencephalography.

PubMed

Liu, Quanying; Farahibozorg, Seyedehrezvan; Porcaro, Camillo; Wenderoth, Nicole; Mantini, Dante

2017-09-01

High-density electroencephalography (hdEEG) is an emerging brain imaging technique that can be used to investigate fast dynamics of electrical activity in the healthy and the diseased human brain. Its applications are however currently limited by a number of methodological issues, among which the difficulty in obtaining accurate source localizations. In particular, these issues have so far prevented EEG studies from reporting brain networks similar to those previously detected by functional magnetic resonance imaging (fMRI). Here, we report for the first time a robust detection of brain networks from resting state (256-channel) hdEEG recordings. Specifically, we obtained 14 networks previously described in fMRI studies by means of realistic 12-layer head models and exact low-resolution brain electromagnetic tomography (eLORETA) source localization, together with independent component analysis (ICA) for functional connectivity analysis. Our analyses revealed three important methodological aspects. First, brain network reconstruction can be improved by performing source localization using the gray matter as source space, instead of the whole brain. Second, conducting EEG connectivity analyses in individual space rather than on concatenated datasets may be preferable, as it permits to incorporate realistic information on head modeling and electrode positioning. Third, the use of a wide frequency band leads to an unbiased and generally accurate reconstruction of several network maps, whereas filtering data in a narrow frequency band may enhance the detection of specific networks and penalize that of others. We hope that our methodological work will contribute to rise of hdEEG as a powerful tool for brain research. Hum Brain Mapp 38:4631-4643, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Neuroimaging of the Wernicke–Korsakoff Syndrome

PubMed Central

Sullivan, Edith V.; Pfefferbaum, Adolf

2009-01-01

Aim: Presented is the neuroradiological signature of acute Wernicke's encephalopathy (WE), derived from different types of magnetic resonance imaging (MRI) sequences. WE results from thiamine depletion, and its most typical antecedent is chronic alcohol dependence. Brain regions observed with in vivo MRI affected in acute WE include the mammillary bodies, periaqueductal and periventricular gray matter, collicular bodies and thalamus. These affected areas are usually edematous and are best visualized and quantified with MRI sequences that highlight such tissue. Following the acute WE phase and resolution of edema and inflammation of affected brain tissue, WE, if not adequately treated with thiamine repletion, can herald Korsakoff's syndrome (KS), with its symptomatic hallmark of global amnesia, that is, the inability to commit newly encountered (episodic) information to memory for later recall or recognition. Methods: Neuropathology of KS detectable with MRI has a different neuroradiological signature from the acute stage and can be observed as tissue shrinkage or atrophy of selective brain structures, including the mammillary bodies and thalamus and ventricular expansion, probably indicative of atrophy of surrounding gray matter nuclei. Quantification of these and additional gray matter structures known to underlie global amnesia reveal substantial bilateral volume deficits in the hippocampus, in addition to the mammillary bodies and thalamus, and modest deficits in the medial septum/diagonal band of Broca. The infratentorium is also affected, exhibiting volume deficits in cerebellar hemispheres, anterior superior vermis and pons, contributing to ataxia of gait and stance. Results: Consideration of WKS structural brain changes in the context of the neuropathology of non-WKS alcoholism revealed a graded pattern of volume deficits, from mild in non-WKS alcoholics to moderate or severe in WKS, in the mammillary bodies, hippocampus, thalamus, cerebellum and pons. The development and resolution of brain structures affected in acute, chronic and treated WE was verified in longitudinal MRI study of rats that modeled of the interaction of extensive alcohol consumption and thiamine depletion and repletion. Conclusions: Thus, neuroradiological examination with MRI is valuable in the diagnosis of acute WE and enables in vivo tracking of the progression of the brain pathology of WE from the acute pathological phase to resolution with thiamine treatment or to progression to KS without treatment. Further, in vivo MRI facilitates translational studies to model antecedent conditions contributing to the development, sequelae and treatment of WE. PMID:19066199

Neuroimaging of the Wernicke-Korsakoff syndrome.

PubMed

Sullivan, Edith V; Pfefferbaum, Adolf

2009-01-01

Presented is the neuroradiological signature of acute Wernicke's encephalopathy (WE), derived from different types of magnetic resonance imaging (MRI) sequences. WE results from thiamine depletion, and its most typical antecedent is chronic alcohol dependence. Brain regions observed with in vivo MRI affected in acute WE include the mammillary bodies, periaqueductal and periventricular gray matter, collicular bodies and thalamus. These affected areas are usually edematous and are best visualized and quantified with MRI sequences that highlight such tissue. Following the acute WE phase and resolution of edema and inflammation of affected brain tissue, WE, if not adequately treated with thiamine repletion, can herald Korsakoff's syndrome (KS), with its symptomatic hallmark of global amnesia, that is, the inability to commit newly encountered (episodic) information to memory for later recall or recognition. Neuropathology of KS detectable with MRI has a different neuroradiological signature from the acute stage and can be observed as tissue shrinkage or atrophy of selective brain structures, including the mammillary bodies and thalamus and ventricular expansion, probably indicative of atrophy of surrounding gray matter nuclei. Quantification of these and additional gray matter structures known to underlie global amnesia reveal substantial bilateral volume deficits in the hippocampus, in addition to the mammillary bodies and thalamus, and modest deficits in the medial septum/diagonal band of Broca. The infratentorium is also affected, exhibiting volume deficits in cerebellar hemispheres, anterior superior vermis and pons, contributing to ataxia of gait and stance. Consideration of WKS structural brain changes in the context of the neuropathology of non-WKS alcoholism revealed a graded pattern of volume deficits, from mild in non-WKS alcoholics to moderate or severe in WKS, in the mammillary bodies, hippocampus, thalamus, cerebellum and pons. The development and resolution of brain structures affected in acute, chronic and treated WE was verified in longitudinal MRI study of rats that modeled of the interaction of extensive alcohol consumption and thiamine depletion and repletion. Thus, neuroradiological examination with MRI is valuable in the diagnosis of acute WE and enables in vivo tracking of the progression of the brain pathology of WE from the acute pathological phase to resolution with thiamine treatment or to progression to KS without treatment. Further, in vivo MRI facilitates translational studies to model antecedent conditions contributing to the development, sequelae and treatment of WE.

Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model

PubMed Central

Tagge, Chad A; Fisher, Andrew M; Minaeva, Olga V; Gaudreau-Balderrama, Amanda; Moncaster, Juliet A; Zhang, Xiao-Lei; Wojnarowicz, Mark W; Casey, Noel; Lu, Haiyan; Kokiko-Cochran, Olga N; Saman, Sudad; Ericsson, Maria; Onos, Kristen D; Veksler, Ronel; Senatorov, Vladimir V; Kondo, Asami; Zhou, Xiao Z; Miry, Omid; Vose, Linnea R; Gopaul, Katisha R; Upreti, Chirag; Nowinski, Christopher J; Cantu, Robert C; Alvarez, Victor E; Hildebrandt, Audrey M; Franz, Erich S; Konrad, Janusz; Hamilton, James A; Hua, Ning; Tripodis, Yorghos; Anderson, Andrew T; Howell, Gareth R; Kaufer, Daniela; Hall, Garth F; Lu, Kun P; Ransohoff, Richard M; Cleveland, Robin O; Kowall, Neil W; Stein, Thor D; Lamb, Bruce T; Huber, Bertrand R; Moss, William C; Friedman, Alon; Stanton, Patric K; McKee, Ann C; Goldstein, Lee E

2018-01-01

Abstract The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood–brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood–brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath. PMID:29360998

Brain Structure and Executive Functions in Children with Cerebral Palsy: A Systematic Review

ERIC Educational Resources Information Center

Weierink, Lonneke; Vermeulen, R. Jeroen; Boyd, Roslyn N.

2013-01-01

This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using…

Growth of melanoma brain tumors monitored by photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

2010-07-01

Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

Neuroimaging, Pain Sensitivity, and Neuropsychological Functioning in School-Age Neonatal Extracorporeal Membrane Oxygenation Survivors Exposed to Opioids and Sedatives.

PubMed

van den Bosch, Gerbrich E; IJsselstijn, Hanneke; van der Lugt, Aad; Tibboel, Dick; van Dijk, Monique; White, Tonya

2015-09-01

Animal studies found negative long-term effects of exposure to sedatives and opioids in early life, especially when administered in the absence of pain. Around the world, children who require extracorporeal membrane oxygenation receive opioids and sedatives for extended periods, generally in the absence of major pain as extracorporeal membrane oxygenation cannulation is considered minor surgery. Therefore, our objective was to determine the long-term effects of extracorporeal membrane oxygenation treatment with respect to pain sensitivity, brain functioning during pain, brain morphology, and neuropsychological functioning in humans. Prospective follow-up study. Level III university hospital. Thirty-six extracorporeal membrane oxygenation survivors (8.1-15.5 yr) and 64 healthy controls (8.2-15.3 yr). We measured detection and pain thresholds, brain activity during pain (functional MRI), brain morphology (high-resolution structural MRI), and neuropsychological functioning and collected information regarding the subject's experience of chronic pain. We found a significant difference in the detection threshold for cold measured in a reaction time-dependent fashion (extracorporeal membrane oxygenation group, 29.9°C [SD, 1.4]; control group, 30.6°C [SD, 0.8]; p < 0.01), but no differences in other modalities or in pain sensitivity between groups. Furthermore, no differences in brain activation during pain, brain morphology, or in the occurrence of chronic pain were observed. However, extracorporeal membrane oxygenation survivors performed significantly worse on a verbal memory test compared with controls (p = 0.001). While the most critically ill newborns receive extracorporeal membrane oxygenation and, relatedly, large doses of opioids and sedatives for extended periods, global measures of pain sensitivity and neurobiological and neuropsychological development appear to have minor long-term consequences. Possible memory deficits in extracorporeal membrane oxygenation survivors require additional study, but neonatal extracorporeal membrane oxygenation treatment and associated exposure to opioids and sedatives seem less harmful to humans than expected from animal studies.

Changes of Visual Pathway and Brain Connectivity in Glaucoma: A Systematic Review

PubMed Central

Nuzzi, Raffaele; Dallorto, Laura; Rolle, Teresa

2018-01-01

Background: Glaucoma is a leading cause of irreversible blindness worldwide. The increasing interest in the involvement of the cortical visual pathway in glaucomatous patients is due to the implications in recent therapies, such as neuroprotection and neuroregeneration. Objective: In this review, we outline the current understanding of brain structural, functional, and metabolic changes detected with the modern techniques of neuroimaging in glaucomatous subjects. Methods: We screened MEDLINE, EMBASE, CINAHL, CENTRAL, LILACS, Trip Database, and NICE for original contributions published until 31 October 2017. Studies with at least six patients affected by any type of glaucoma were considered. We included studies using the following neuroimaging techniques: functional Magnetic Resonance Imaging (fMRI), resting-state fMRI (rs-fMRI), magnetic resonance spectroscopy (MRS), voxel- based Morphometry (VBM), surface-based Morphometry (SBM), diffusion tensor MRI (DTI). Results: Over a total of 1,901 studies, 56 case series with a total of 2,381 patients were included. Evidence of neurodegenerative process in glaucomatous patients was found both within and beyond the visual system. Structural alterations in visual cortex (mainly reduced cortex thickness and volume) have been demonstrated with SBM and VBM; these changes were not limited to primary visual cortex but also involved association visual areas. Other brain regions, associated with visual function, demonstrated a certain grade of increased or decreased gray matter volume. Functional and metabolic abnormalities resulted within primary visual cortex in all studies with fMRI and MRS. Studies with rs-fMRI found disrupted connectivity between the primary and higher visual cortex and between visual cortex and associative visual areas in the task-free state of glaucomatous patients. Conclusions: This review contributes to the better understanding of brain abnormalities in glaucoma. It may stimulate further speculation about brain plasticity at a later age and therapeutic strategies, such as the prevention of cortical degeneration in patients with glaucoma. Structural, functional, and metabolic neuroimaging methods provided evidence of changes throughout the visual pathway in glaucomatous patients. Other brain areas, not directly involved in the processing of visual information, also showed alterations. PMID:29896087

Rapid and Sensitive Detection of Brain-Derived Neurotrophic Factor with a Plasmonic Chip

NASA Astrophysics Data System (ADS)

Tawa, Keiko; Satoh, Mari; Uegaki, Koichi; Hara, Tomoko; Kojima, Masami; Kumanogoh, Haruko; Aota, Hiroyuki; Yokota, Yoshiki; Nakaoki, Takahiko; Umetsu, Mitsuo; Nakazawa, Hikaru; Kumagai, Izumi

2013-06-01

Plasmonic chips, which are grating replicas coated with thin metal layers and overlayers such as ZnO, were applied in immunosensors to improve their detection sensitivity. Fluorescence from labeled antibodies bound to plasmonic chips can be enhanced on the basis of a grating-coupled surface plasmon resonance (GC-SPR) field. In this study, as one of the representative candidate protein markers for brain disorders, the brain-derived neurotrophic factor (BDNF) was quantitatively measured by sandwich assay on a plasmonic chip and detected on our plasmonic chip in the concentration of 5-7 ng/mL within 40 min. Furthermore, BDNF was detected in the blood sera from three types of mice: wild-type mice and two types of mutant mice. This technique is promising as a new clinical diagnosis tool for brain disorders based on scientific evidence such as blood test results.

Insights into Brain Glycogen Metabolism

PubMed Central

Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

2016-01-01

Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID:27402852

A comparative study of theoretical graph models for characterizing structural networks of human brain.

PubMed

Li, Xiaojin; Hu, Xintao; Jin, Changfeng; Han, Junwei; Liu, Tianming; Guo, Lei; Hao, Wei; Li, Lingjiang

2013-01-01

Previous studies have investigated both structural and functional brain networks via graph-theoretical methods. However, there is an important issue that has not been adequately discussed before: what is the optimal theoretical graph model for describing the structural networks of human brain? In this paper, we perform a comparative study to address this problem. Firstly, large-scale cortical regions of interest (ROIs) are localized by recently developed and validated brain reference system named Dense Individualized Common Connectivity-based Cortical Landmarks (DICCCOL) to address the limitations in the identification of the brain network ROIs in previous studies. Then, we construct structural brain networks based on diffusion tensor imaging (DTI) data. Afterwards, the global and local graph properties of the constructed structural brain networks are measured using the state-of-the-art graph analysis algorithms and tools and are further compared with seven popular theoretical graph models. In addition, we compare the topological properties between two graph models, namely, stickiness-index-based model (STICKY) and scale-free gene duplication model (SF-GD), that have higher similarity with the real structural brain networks in terms of global and local graph properties. Our experimental results suggest that among the seven theoretical graph models compared in this study, STICKY and SF-GD models have better performances in characterizing the structural human brain network.

Segmentation of brain structures in presence of a space-occupying lesion.

PubMed

Pollo, Claudio; Cuadra, Meritxell Bach; Cuisenaire, Olivier; Villemure, Jean-Guy; Thiran, Jean-Philippe

2005-02-15

Brain deformations induced by space-occupying lesions may result in unpredictable position and shape of functionally important brain structures. The aim of this study is to propose a method for segmentation of brain structures by deformation of a segmented brain atlas in presence of a space-occupying lesion. Our approach is based on an a priori model of lesion growth (MLG) that assumes radial expansion from a seeding point and involves three steps: first, an affine registration bringing the atlas and the patient into global correspondence; then, the seeding of a synthetic tumor into the brain atlas providing a template for the lesion; finally, the deformation of the seeded atlas, combining a method derived from optical flow principles and a model of lesion growth. The method was applied on two meningiomas inducing a pure displacement of the underlying brain structures, and segmentation accuracy of ventricles and basal ganglia was assessed. Results show that the segmented structures were consistent with the patient's anatomy and that the deformation accuracy of surrounding brain structures was highly dependent on the accurate placement of the tumor seeding point. Further improvements of the method will optimize the segmentation accuracy. Visualization of brain structures provides useful information for therapeutic consideration of space-occupying lesions, including surgical, radiosurgical, and radiotherapeutic planning, in order to increase treatment efficiency and prevent neurological damage.

Critical perspectives on causality and inference in brain networks: Allusions, illusions, solutions?. Comment on: "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

NASA Astrophysics Data System (ADS)

Diwadkar, Vaibhav A.

2015-12-01

The human brain is an impossibly difficult cartographic landscape to map out. Within it's convoluted and labyrinthine structure is folded a million years of phylogeny, somehow expressed in the ontogeny of the specific organism; an ontogeny that conceals idiosyncratic effects of countless genes, and then the (perhaps) countably infinite effects of processes of the organism's lifespan subsequently resulting in remarkable heterogeneity [1,2]. The physical brain itself is therefore a nearly un-decodable ;time machine; motivating more questions than frameworks for answering those questions: Why has evolution endowed it with the general structure that is possesses [3]; Is there regularity in macroscopic metrics of structure across species [4]; What are the most meaningful structural units in the brain: molecules, neurons, cortical columns or cortical maps [5]? Remarkably, understanding the intricacies of structure is perhaps not even the most difficult aspect of understanding the human brain. In fact, and as recently argued, a central issue lies in resolving the dialectic between structure and function: how does dynamic function arises from static (at least at the time scales at which human brain function is experimentally studied) brain structures [6]? In other words, if the mind is the brain ;in action;, how does it arise?

Detection of small human cerebral cortical lesions with MRI under different levels of Gaussian smoothing: applications in epilepsy

NASA Astrophysics Data System (ADS)

Cantor-Rivera, Diego; Goubran, Maged; Kraguljac, Alan; Bartha, Robert; Peters, Terry

2010-03-01

The main objective of this study was to assess the effect of smoothing filter selection in Voxel-Based Morphometry studies on structural T1-weighted magnetic resonance images. Gaussian filters of 4 mm, 8 mm or 10 mm Full Width at High Maximum are commonly used, based on the assumption that the filter size should be at least twice the voxel size to obtain robust statistical results. The hypothesis of the presented work was that the selection of the smoothing filter influenced the detectability of small lesions in the brain. Mesial Temporal Sclerosis associated to Epilepsy was used as the case to demonstrate this effect. Twenty T1-weighted MRIs from the BrainWeb database were selected. A small phantom lesion was placed in the amygdala, hippocampus, or parahippocampal gyrus of ten of the images. Subsequently the images were registered to the ICBM/MNI space. After grey matter segmentation, a T-test was carried out to compare each image containing a phantom lesion with the rest of the images in the set. For each lesion the T-test was repeated with different Gaussian filter sizes. Voxel-Based Morphometry detected some of the phantom lesions. Of the three parameters considered: location,size, and intensity; it was shown that location is the dominant factor for the detection of the lesions.

Unification of automatic target tracking and automatic target recognition

NASA Astrophysics Data System (ADS)

Schachter, Bruce J.

2014-06-01

The subject being addressed is how an automatic target tracker (ATT) and an automatic target recognizer (ATR) can be fused together so tightly and so well that their distinctiveness becomes lost in the merger. This has historically not been the case outside of biology and a few academic papers. The biological model of ATT∪ATR arises from dynamic patterns of activity distributed across many neural circuits and structures (including retina). The information that the brain receives from the eyes is "old news" at the time that it receives it. The eyes and brain forecast a tracked object's future position, rather than relying on received retinal position. Anticipation of the next moment - building up a consistent perception - is accomplished under difficult conditions: motion (eyes, head, body, scene background, target) and processing limitations (neural noise, delays, eye jitter, distractions). Not only does the human vision system surmount these problems, but it has innate mechanisms to exploit motion in support of target detection and classification. Biological vision doesn't normally operate on snapshots. Feature extraction, detection and recognition are spatiotemporal. When vision is viewed as a spatiotemporal process, target detection, recognition, tracking, event detection and activity recognition, do not seem as distinct as they are in current ATT and ATR designs. They appear as similar mechanism taking place at varying time scales. A framework is provided for unifying ATT and ATR.

Multivariate statistics of the Jacobian matrices in tensor based morphometry and their application to HIV/AIDS.

PubMed

Lepore, Natasha; Brun, Caroline A; Chiang, Ming-Chang; Chou, Yi-Yu; Dutton, Rebecca A; Hayashi, Kiralee M; Lopez, Oscar L; Aizenstein, Howard J; Toga, Arthur W; Becker, James T; Thompson, Paul M

2006-01-01

Tensor-based morphometry (TBM) is widely used in computational anatomy as a means to understand shape variation between structural brain images. A 3D nonlinear registration technique is typically used to align all brain images to a common neuroanatomical template, and the deformation fields are analyzed statistically to identify group differences in anatomy. However, the differences are usually computed solely from the determinants of the Jacobian matrices that are associated with the deformation fields computed by the registration procedure. Thus, much of the information contained within those matrices gets thrown out in the process. Only the magnitude of the expansions or contractions is examined, while the anisotropy and directional components of the changes are ignored. Here we remedy this problem by computing multivariate shape change statistics using the strain matrices. As the latter do not form a vector space, means and covariances are computed on the manifold of positive-definite matrices to which they belong. We study the brain morphology of 26 HIV/AIDS patients and 14 matched healthy control subjects using our method. The images are registered using a high-dimensional 3D fluid registration algorithm, which optimizes the Jensen-Rényi divergence, an information-theoretic measure of image correspondence. The anisotropy of the deformation is then computed. We apply a manifold version of Hotelling's T2 test to the strain matrices. Our results complement those found from the determinants of the Jacobians alone and provide greater power in detecting group differences in brain structure.

Alexithymia is related to differences in gray matter volume: a voxel-based morphometry study.

PubMed

Ihme, Klas; Dannlowski, Udo; Lichev, Vladimir; Stuhrmann, Anja; Grotegerd, Dominik; Rosenberg, Nicole; Kugel, Harald; Heindel, Walter; Arolt, Volker; Kersting, Anette; Suslow, Thomas

2013-01-23

Alexithymia has been characterized as the inability to identify and describe feelings. Functional imaging studies have revealed that alexithymia is linked to reactivity changes in emotion- and face-processing-relevant brain areas. In this respect, anterior cingulate cortex (ACC), amygdala, anterior insula and fusiform gyrus (FFG) have been consistently reported. However, it remains to be clarified whether alexithymia is also associated with structural differences. Voxel-based morphometry on T1-weighted magnetic resonance images was used to investigate gray matter volume in 17 high alexithymics (HA) and 17 gender-matched low alexithymics (LA), which were selected from a sample of 161 healthy volunteers on basis of the 20-item Toronto Alexithymia Scale. Data were analyzed as statistic parametric maps for the comparisons LA>HA and HA>LA in a priori determined regions of interests (ROIs), i.e., ACC, amygdala, anterior insula and FFG. Moreover, an exploratory whole brain analysis was accomplished. For the contrast LA>HA, significant clusters were detected in the ACC, left amygdala and left anterior insula. Additionally, the whole brain analysis revealed volume differences in the left middle temporal gyrus. No significant differences were found for the comparison HA>LA. Our findings suggest that high compared to low alexithymics show less gray matter volume in several emotion-relevant brain areas. These structural differences might contribute to the functional alterations found in previous imaging studies in alexithymia. Copyright © 2012 Elsevier B.V. All rights reserved.

Glial architecture of the ghost shark (Callorhinchus milii, Holocephali, Chondrichthyes) as revealed by different immunohistochemical markers.

PubMed

Ari, Csilla; Kálmán, Mihály

2008-09-15

This article presents the first study on the glial architecture of a representative species of Holocephali, Callorhinchus milii (ghost shark). Holocephali are a small subclass of Chondrichthyes, with only a few extant genera, and those are considered to have a brain organization more similar to squalomorph sharks than to galeomorph sharks, skates, and rays. Three different astroglial markers--glial fibrillary acidic protein, S-100 protein, and glutamine synthetase (GS)--were investigated by immunohistochemical methods, applying both diaminobenzidine (DAB) and fluorescent techniques. They revealed similar glial structures, although most of them were detected by immunohistochemical reaction against GS and visualized by DAB. The predominant elements were radial ependymoglia spanning the area between the ventricular and meningeal surfaces, as in squalomorph sharks. Other similar features were the light appearance of myelinated neural tracts devoid of immunoreactivity, and the glial architecture of the reticular formation of the brain stem, cerebellum, and tectum, the latter with recognizable layers. The immunoreactivity of the vascular walls was similar; however, it is believed that different cell types form the blood-brain barrier in chimeras and in elasmobranchs. Some glial structures, however, resembled those of skates, rays, and galeomorph sharks. In C. milii astrocyte-like elements were observed in the telencephalon, using GS and S-100, although typical astrocyte-rich regions were not found. In some areas, especially the telencephalon, not only endfeet but also cell bodies were observed to be attached to the meningeal surface, with processes extending into the brain substance.

Dynamic change in cerebral microcirculation and focal cerebral metabolism in experimental subarachnoid hemorrhage in rabbits.

PubMed

Song, Jin-Ning; Chen, Hu; Zhang, Ming; Zhao, Yong-Lin; Ma, Xu-Dong

2013-03-01

Regional cerebral blood flow (rCBF) in the cerebral metabolism and energy metabolism measurements can be used to assess blood flow of brain cells and to detect cell activity. Changes of rCBF in the cerebral microcirculation and energy metabolism were determined in an experimental model of subarachnoid hemorrhage (SAH) model in 56 large-eared Japanese rabbits about 12 to 16-month old. Laser Doppler flowmetry was used to detect the blood supply to brain cells. Internal carotid artery and vein blood samples were used for duplicate blood gas analysis to assess the energy metabolism of brain cells. Cerebral blood flow (CBF) was detected by single photon emission computed tomography (SPECT) perfusion imaging using Tc-99m ethyl cysteinate dimer (Tc-99m ECD) as an imaging reagent. The percentage of injected dose per gram of brain tissue was calculated and analyzed. There were positive correlations between the percentage of radionuclide injected per gram of brain tissue and rCBF supply and cerebral metabolic rate for oxygen (P < 0.05). However, there was a negative correlation between radioactivity counts per unit volume detected on the SPECT rheoencephalogram and lactic acid concentration in the homolateral internal carotid artery and vein. In summary, this study found abnormal CBF in metabolism and utilization of brain cells after SAH, and also found that deterioration of energy metabolism of brain cells played a significant role in the development of SAH. There are matched reductions in CBF and metabolism. Thus, SPECT imaging could be used as a noninvasive method to detect CBF.

Good outcome of brain stem progressive multifocal leukoencephalopathy in an immunosuppressed renal transplant patient: Importance of early detection and rapid immune reconstitution.

PubMed

Sauer, Roland; Gölitz, Philipp; Jacobi, Johannes; Schwab, Stefan; Linker, Ralf A; Lee, De-Hyung

2017-04-15

Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic and often fatal disease of the CNS which may occur under immunosuppression in transplant patients. Brain stem PML is associated with a particularly bad prognosis. Here, we present a case of a renal transplant patient treated with mycophenolate mofetil (MMF) and tacrolimus who developed brain stem PML with limb ataxia, dysarthria and dysphagia. Diagnosis was established by typical MRI features and detection of JCV-DNA in the CSF. Immune reconstitution after stopping MMF and tacrolimus led to a complete and sustained remission of symptoms with improvement of the brain stem lesion over a follow-up over 20months. In summary, early detection of PML and consequent treatment may improve neurological outcomes even in brain stem disease with a notorious bad prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantitative assessment of Cerenkov luminescence for radioguided brain tumor resection surgery

NASA Astrophysics Data System (ADS)

Klein, Justin S.; Mitchell, Gregory S.; Cherry, Simon R.

2017-05-01

Cerenkov luminescence imaging (CLI) is a developing imaging modality that detects radiolabeled molecules via visible light emitted during the radioactive decay process. We used a Monte Carlo based computer simulation to quantitatively investigate CLI compared to direct detection of the ionizing radiation itself as an intraoperative imaging tool for assessment of brain tumor margins. Our brain tumor model consisted of a 1 mm spherical tumor remnant embedded up to 5 mm in depth below the surface of normal brain tissue. Tumor to background contrast ranging from 2:1 to 10:1 were considered. We quantified all decay signals (e±, gamma photon, Cerenkov photons) reaching the brain volume surface. CLI proved to be the most sensitive method for detecting the tumor volume in both imaging and non-imaging strategies as assessed by contrast-to-noise ratio and by receiver operating characteristic output of a channelized Hotelling observer.

Functional brain networks reconstruction using group sparsity-regularized learning.

PubMed

Zhao, Qinghua; Li, Will X Y; Jiang, Xi; Lv, Jinglei; Lu, Jianfeng; Liu, Tianming

2018-06-01

Investigating functional brain networks and patterns using sparse representation of fMRI data has received significant interests in the neuroimaging community. It has been reported that sparse representation is effective in reconstructing concurrent and interactive functional brain networks. To date, most of data-driven network reconstruction approaches rarely take consideration of anatomical structures, which are the substrate of brain function. Furthermore, it has been rarely explored whether structured sparse representation with anatomical guidance could facilitate functional networks reconstruction. To address this problem, in this paper, we propose to reconstruct brain networks utilizing the structure guided group sparse regression (S2GSR) in which 116 anatomical regions from the AAL template, as prior knowledge, are employed to guide the network reconstruction when performing sparse representation of whole-brain fMRI data. Specifically, we extract fMRI signals from standard space aligned with the AAL template. Then by learning a global over-complete dictionary, with the learned dictionary as a set of features (regressors), the group structured regression employs anatomical structures as group information to regress whole brain signals. Finally, the decomposition coefficients matrix is mapped back to the brain volume to represent functional brain networks and patterns. We use the publicly available Human Connectome Project (HCP) Q1 dataset as the test bed, and the experimental results indicate that the proposed anatomically guided structure sparse representation is effective in reconstructing concurrent functional brain networks.

Beyond sex differences: new approaches for thinking about variation in brain structure and function

PubMed Central

Joel, Daphna; Fausto-Sterling, Anne

2016-01-01

In the study of variation in brain structure and function that might relate to sex and gender, language matters because it frames our research questions and methods. In this article, we offer an approach to thinking about variation in brain structure and function that pulls us outside the sex differences formulation. We argue that the existence of differences between the brains of males and females does not unravel the relations between sex and the brain nor is it sufficient to characterize a population of brains. Such characterization is necessary for studying sex effects on the brain as well as for studying brain structure and function in general. Animal studies show that sex interacts with environmental, developmental and genetic factors to affect the brain. Studies of humans further suggest that human brains are better described as belonging to a single heterogeneous population rather than two distinct populations. We discuss the implications of these observations for studies of brain and behaviour in humans and in laboratory animals. We believe that studying sex effects in context and developing or adopting analytical methods that take into account the heterogeneity of the brain are crucial for the advancement of human health and well-being. PMID:26833844

MR Anatomy of Deep Brain Nuclei with Special Reference to Specific Diseases and Deep Brain Stimulation Localization

PubMed Central

Telford, Ryan; Vattoth, Surjith

2014-01-01

Summary Diseases affecting the basal ganglia and deep brain structures vary widely in etiology and include metabolic, infectious, ischemic, and neurodegenerative conditions. Some neurologic diseases, such as Wernicke encephalopathy or pseudohypoparathyroidism, require specific treatments, which if unrecognized could lead to further complications. Other pathologies, such as hypertrophic olivary degeneration, if not properly diagnosed may be mistaken for a primary medullary neoplasm and create unnecessary concern. The deep brain structures are complex and can be difficult to distinguish on routine imaging. It is imperative that radiologists first understand the intrinsic anatomic relationships between the different basal ganglia nuclei and deep brain structures with magnetic resonance (MR) imaging. It is important to understand the "normal" MR signal characteristics, locations, and appearances of these structures. This is essential to recognizing diseases affecting the basal ganglia and deep brain structures, especially since most of these diseases result in symmetrical, and therefore less noticeable, abnormalities. It is also crucial that neurosurgeons correctly identify the deep brain nuclei presurgically for positioning deep brain stimulator leads, the most important being the subthalamic nucleus for Parkinson syndromes and the thalamic ventral intermediate nucleus for essential tremor. Radiologists will be able to better assist clinicians in diagnosis and treatment once they are able to accurately localize specific deep brain structures. PMID:24571832

Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging.

PubMed

Jin, Ping; Pan, Yongming; Pan, Zhiyong; Xu, Jianqin; Lin, Min; Sun, Zhichao; Chen, Minli; Xu, Maosheng

2018-03-27

Hypercholesterolemia is known to increase the risk of AD in later life, the purpose of this study is to illustrate brain metabolic and structural changes in a cholesterol-fed rabbit model of Alzheimer's Disease (AD) by using clinical 3 T Magnetic Resonance Imaging (MRI). The Institutional Animal Care and Use Committee of Zhejiang Chinese Medical University approved the study. Totally 16 Japanese White Rabbits (JWR) were randomly divided into 2 groups including normal control group fed with routine diet (group NC) and high cholesterol diet group (group CD) fed a 2% cholesterol diet with 0.24 ppm copper in the drinking water for 12 weeks. Magnetic resonance spectroscopy (MRS) and structural image of rabbit brain were performed by using a 3 Tesla (T) MRI scanner with an 8 channel Rabbit coil. The chemical metabolites were identified by LC Model including N-acetylaspartate (NAA), creatine (Cr), glutamate (Glu), glutamine (Gln), Glycerophosphatidylcholine (GPC), phosphorylcholine (PCH), and myoinositol (MI). The relative concentrations (/Cr) were analyzed. Additionally, Amyloid-β (Aβ) accumulation in the brain was measured postmortem. For comparisons of MR and Aβ data between groups, two-tailed t-tests were performed. The ratio of NAA/Cr (0.76 ± 0.10) and Glu/Cr (0.90 ± 0.14) in group CD were lower than those in the group NC (0.87 ± 0.06, 1.13 ± 0.22, respectively, P <  0.05). Compared to the group NC (2.88 ± 0.09 cm 3 , 0.63 ± 0.08 cm 3 , respectively), the cortical and hippocampal volumes (2.60 ± 0.14 cm 3 and 0.47 ± 0.07 cm 3 , respectively) of rabbits brain decreased in the group CD while the third and lateral ventricular volumes enlarged (44.56 ± 6.01 mm 3 vs 31.40 ± 6.14 mm 3 , 261.40 ± 30.98 mm 3 vs 153.81 ± 30.08 mm 3 , P <  0.05). These metabolic and structural changes were additionally accompanied by the significant increase of Aβ1-42 in the cortex and hippocampus (163.60 ± 16.26 pg/mg and 215.20 ± 69.86 pg/mg, respectively, P <  0.05). High cholesterol diet can induce the brain metabolic and structural changes of the rabbit including lowered level of NAA and Glu and the atrophy of the brain which were similar to those of human AD.

Role of More Active Identification of Brain-Dead Cases in Increasing Organ Donation.

PubMed

Sadegh Beigee, Farahnaz; Mohsenzadeh, Mojtaba; Shahryari, Shagin; Mojtabaee, Meysam

2017-02-01

Organ donor shortage is a worldwide problem, resulting in 10% to 30% mortality rates for patients on wait lists for organ transplant. For brain-dead patients in Iran, it is mandatory for intensive care unit patients with Glasgow Coma Scale below 5/15 to be reported to an organ procurement unit. However, this process has not been functioning effectively. Here, we present the effects of changing the strategies on detecting brain-dead cases on the organ donor pool. From March 2015 to March 2016, we changed our strategy in active detection of brain-dead cases. Since March 2015, our newly established protocol for active detection of brain-dead cases includes the following changes: (1) instead of calling high-volume intensive care units 3 times per week, we switched to calling every day in the morning; (2) instead of calling low-volume intensive care units 1 time per week, we switched to calling 3 times per week; (3) we included intensive care units (cardiac and general), neurosurgery, and emergency departments, as well as nursing supervisor offices, in our call and visit lists; and (4) we increased visits to wards by our trained staff as inspectors. From March 2015 to March 2016, the number of reported suspected brain-dead cases has increased from 224 to 460 per year, with proven brain death increasing from 180 to 306 cases. The actual number of donors has also increased, from 116 to 165 donations (53% increase) over 1 year. More proactive strategies have had significant effects on brain-dead detection, resulting in significantly increased donor pools and organ donations. In countries with low cooperation of hospital staff, more proactive engagement in detecting brain-dead cases is a good solution to prevent loss of potential organ donors, with a final result of decreasing wait list mortality.

Advancing multiscale structural mapping of the brain through fluorescence imaging and analysis across length scales

PubMed Central

Hogstrom, L. J.; Guo, S. M.; Murugadoss, K.; Bathe, M.

2016-01-01

Brain function emerges from hierarchical neuronal structure that spans orders of magnitude in length scale, from the nanometre-scale organization of synaptic proteins to the macroscopic wiring of neuronal circuits. Because the synaptic electrochemical signal transmission that drives brain function ultimately relies on the organization of neuronal circuits, understanding brain function requires an understanding of the principles that determine hierarchical neuronal structure in living or intact organisms. Recent advances in fluorescence imaging now enable quantitative characterization of neuronal structure across length scales, ranging from single-molecule localization using super-resolution imaging to whole-brain imaging using light-sheet microscopy on cleared samples. These tools, together with correlative electron microscopy and magnetic resonance imaging at the nanoscopic and macroscopic scales, respectively, now facilitate our ability to probe brain structure across its full range of length scales with cellular and molecular specificity. As these imaging datasets become increasingly accessible to researchers, novel statistical and computational frameworks will play an increasing role in efforts to relate hierarchical brain structure to its function. In this perspective, we discuss several prominent experimental advances that are ushering in a new era of quantitative fluorescence-based imaging in neuroscience along with novel computational and statistical strategies that are helping to distil our understanding of complex brain structure. PMID:26855758

Detection of tyrosine hydroxylase in dopaminergic neuron cell using gold nanoparticles-based barcode DNA.

PubMed

An, Jeung Hee; Oh, Byung-Keun; Choi, Jeong Woo

2013-04-01

Tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosysthesis, is predominantly expressed in several cell groups within the brain, including the dopaminergic neurons of the substantia nigra and ventral tegmental area. We evaluated the efficacy of this protein-detection method in detecting tyrosine hydroxylase in normal and oxidative stress damaged dopaminergic cells. In this study, a coupling of DNA barcode and bead-based immnunoassay for detecting tyrosine hydroxylaser with PCR-like sensitivity is reported. The method relies on magnetic nanoparticles with antibodies and nanoparticles that are encoded with DNA and antibodies that can sandwich the target protein captured by the nanoparticle-bound antibodies. The aggregate sandwich structures are magnetically separated from solution, and treated to remove the conjugated barcode DNA. The DNA barcodes were identified by PCR analysis. The concentration of tyrosine hydroxylase in dopaminergic cell can be easily and rapidly detected using bio-barcode assay. The bio-barcode assay is a rapid and high-throughput screening tool to detect of neurotransmitter such as dopamine.

SERS-active ZnO/Ag hybrid WGM microcavity for ultrasensitive dopamine detection

NASA Astrophysics Data System (ADS)

Lu, Junfeng; Xu, Chunxiang; Nan, Haiyan; Zhu, Qiuxiang; Qin, Feifei; Manohari, A. Gowri; Wei, Ming; Zhu, Zhu; Shi, Zengliang; Ni, Zhenhua

2016-08-01

Dopamine (DA) is a potential neuro modulator in the brain which influences a variety of motivated behaviors and plays a key role in life science. A hybrid ZnO/Ag microcavity based on Whispering Gallery Mode (WGM) effect has been developed for ultrasensitive detection of dopamine. Utilizing this effect of structural cavity mode, a Raman signal of R6G (5 × 10-3 M) detected by this designed surface-enhanced Raman spectroscopy (SERS)-active substrate was enhanced more than 10-fold compared with that of ZnO film/Ag substrate. Also, this hybrid microcavity substrate manifests high SERS sensitivity to rhodamine 6 G and detection limit as low as 10-12 M to DA. The Localized Surface Plasmons of Ag nanoparticles and WGM-enhanced light-matter interaction mainly contribute to the high SERS sensitivity and help to achieve a lower detection limit. This designed SERS-active substrate based on the WGM effect has the potential for detecting neurotransmitters in life science.

Commonalities in the central nervous system's involvement with complementary medical therapies: limbic morphinergic processes.

PubMed

Esch, Tobias; Guarna, Massimo; Bianchi, Enrica; Zhu, Wei; Stefano, George B

2004-06-01

Currently, complementary and alternative medicine (CAM) are experiencing growing popularity, especially in former industrialized countries. However, most of the underlying physiological and molecular mechanisms as well as participating biological structures are still speculative. Specific and non-specific effects may play a role in CAM. Moreover, trust, belief, and expectation may be of importance, pointing towards common central nervous system (CNS) pathways involved in CAM. Four CAM approaches (acupuncture, meditation, music therapy, and massage therapy) were examined with regard to the CNS activity pattern involved. CNS commonalities between different approaches were investigated. Frontal/prefrontal and limbic brain structures play a role in CAM. Particularly, left-anterior regions of the brain and reward or motivation circuitry constituents are involved, indicating positive affect and emotion-related memory processing--accompanied by endocrinologic and autonomic functions--as crucial components of CAM effects. Thus, trust and belief in a therapist or positive therapy expectations seem to be important. However, besides common non-specific or subjective effects, specific (objective) physiological components also exist. Non-specific CNS commonalities are involved in various CAM therapies. Different therapeutic approaches physiologically overlap in the brain. However, molecular correspondents of the detected CNS analogies still have to be specified. In particular, fast acting autoregulatory signaling molecules presumably play a role. These may also be involved in the placebo response.

Brain metastasis detection by resonant Raman optical biopsy method

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Cheng, Gangge; Zhou, Lixin; Zhang, Chunyuan; Pu, Yang; Li, Zhongwu; Liu, Yulong; Li, Qingbo; Wang, Wei; Alfano, Robert R.

2014-03-01

Resonant Raman (RR) spectroscopy provides an effective way to enhance Raman signal from particular bonds associated with key molecules due to changes on a molecular level. In this study, RR is used for detection of human brain metastases of five kinds of primary organs of lung, breast, kidney, rectal and orbital in ex-vivo. The RR spectra of brain metastases cancerous tissues were measured and compared with those of normal brain tissues and the corresponding primary cancer tissues. The differences of five types of brain metastases tissues in key bio-components of carotene, tryptophan, lactate, alanine and methyl/methylene group were investigated. The SVM-KNN classifier was used to categorize a set of RR spectra data of brain metastasis of lung cancerous tissues from normal brain tissue, yielding diagnostic sensitivity and specificity at 100% and 75%, respectively. The RR spectroscopy may provide new moleculebased optical probe tools for diagnosis and classification of brain metastatic of cancers.

Surface-based brain morphometry and diffusion tensor imaging in schizoaffective disorder.

PubMed

Landin-Romero, Ramón; Canales-Rodríguez, Erick J; Kumfor, Fiona; Moreno-Alcázar, Ana; Madre, Mercè; Maristany, Teresa; Pomarol-Clotet, Edith; Amann, Benedikt L

2017-01-01

The profile of grey matter abnormalities and related white-matter pathology in schizoaffective disorder has only been studied to a limited extent. The aim of this study was to identify grey- and white-matter abnormalities in patients with schizoaffective disorder using complementary structural imaging techniques. Forty-five patients meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria and Research Diagnostic Criteria for schizoaffective disorder and 45 matched healthy controls underwent structural-T1 and diffusion magnetic resonance imaging to enable surface-based brain morphometry and diffusion tensor imaging analyses. Analyses were conducted to determine group differences in cortical volume, cortical thickness and surface area, as well as in fractional anisotropy and mean diffusivity. At a threshold of p = 0.05 corrected, all measures revealed significant differences between patients and controls at the group level. Spatial overlap of abnormalities was observed across the various structural neuroimaging measures. In grey matter, patients with schizoaffective disorder showed abnormalities in the frontal and temporal lobes, striatum, fusiform, cuneus, precuneus, lingual and limbic regions. White-matter abnormalities were identified in tracts connecting these areas, including the corpus callosum, superior and inferior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus and cingulum bundle. The spatial overlap of abnormalities across the different imaging techniques suggests widespread and consistent brain pathology in schizoaffective disorder. The abnormalities were mainly detected in areas that have commonly been reported to be abnormal in schizophrenia, and to some extent in bipolar disorder, which may explain the clinical and aetiological overlap in these disorders.

Differences in Supratentorial Damage of White Matter in Pediatric Survivors of Posterior Fossa Tumors With and Without Adjuvant Treatment as Detected by Magnetic Resonance Diffusion Tensor Imaging

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

Rueckriegel, Stefan Mark, E-mail: stefan.rueckriegel@charite.d; Driever, Pablo Hernaiz; Blankenburg, Friederike

2010-03-01

Purpose: To elucidate morphologic correlates of brain dysfunction in pediatric survivors of posterior fossa tumors by using magnetic resonance diffusion tensor imaging (DTI) to examine neuroaxonal integrity in white matter. Patients and Methods: Seventeen medulloblastoma (MB) patients who had received surgery and adjuvant treatment, 13 pilocytic astrocytoma (PA) patients who had been treated only with surgery, and age-matched healthy control subjects underwent magnetic resonance imaging on a 3-Tesla system. High-resolution conventional T1- and T2-weighted magnetic resonance imaging and DTI data sets were obtained. Fractional anisotropy (FA) maps were analyzed using tract-based spatial statistics, a part of the Functional MRI ofmore » the Brain Software Library. Results: Compared with control subjects, FA values of MB patients were significantly decreased in the cerebellar midline structures, in the frontal lobes, and in the callosal body. Fractional anisotropy values of the PA patients were not only decreased in cerebellar hemispheric structures as expected, but also in supratentorial parts of the brain, with a distribution similar to that in MB patients. However, the amount of significantly decreased FA was greater in MB than in PA patients, underscoring the aggravating neurotoxic effect of the adjuvant treatment. Conclusions: Neurotoxic mechanisms that are present in PA patients (e.g., internal hydrocephalus and damaged cerebellar structures affecting neuronal circuits) contribute significantly to the alteration of supratentorial white matter in pediatric posterior fossa tumor patients.« less

Fronto-Parietal Subnetworks Flexibility Compensates For Cognitive Decline Due To Mental Fatigue.

PubMed

Taya, Fumihiko; Dimitriadis, Stavros I; Dragomir, Andrei; Lim, Julian; Sun, Yu; Wong, Kian Foong; Thakor, Nitish V; Bezerianos, Anastasios

2018-04-24

Fronto-parietal subnetworks were revealed to compensate for cognitive decline due to mental fatigue by community structure analysis. Here, we investigate changes in topology of subnetworks of resting-state fMRI networks due to mental fatigue induced by prolonged performance of a cognitively demanding task, and their associations with cognitive decline. As it is well established that brain networks have modular organization, community structure analyses can provide valuable information about mesoscale network organization and serve as a bridge between standard fMRI approaches and brain connectomics that quantify the topology of whole brain networks. We developed inter- and intramodule network metrics to quantify topological characteristics of subnetworks, based on our hypothesis that mental fatigue would impact on functional relationships of subnetworks. Functional networks were constructed with wavelet correlation and a data-driven thresholding scheme based on orthogonal minimum spanning trees, which allowed detection of communities with weak connections. A change from pre- to posttask runs was found for the intermodule density between the frontal and the temporal subnetworks. Seven inter- or intramodule network metrics, mostly at the frontal or the parietal subnetworks, showed significant predictive power of individual cognitive decline, while the network metrics for the whole network were less effective in the predictions. Our results suggest that the control-type fronto-parietal networks have a flexible topological architecture to compensate for declining cognitive ability due to mental fatigue. This community structure analysis provides valuable insight into connectivity dynamics under different cognitive states including mental fatigue. © 2018 Wiley Periodicals, Inc.

Alterations of Brain Structural Network in Parkinson's Disease With and Without Rapid Eye Movement Sleep Behavior Disorder.

PubMed

Guo, Tao; Guan, Xiaojun; Zeng, Qiaoling; Xuan, Min; Gu, Quanquan; Huang, Peiyu; Xu, Xiaojun; Zhang, Minming

2018-01-01

Rapid eye movement sleep behavior disorder (RBD) has a strong association with alpha synucleinpathies such as Parkinson's disease (PD) and PD patients with RBD tend to have a poorer prognosis. However, we still know little about the pathogenesis of RBD in PD. Therefore, we aim to detect the alterations of structural correlation network (SCN) in PD patients with and without RBD. A total of 191 PD patients, including 51 patients with possible RBD (pRBD) and 140 patients with non-possible RBD, and 76 normal controls were included in the present study. Structural brain networks were constructed by thresholding gray matter volume correlation matrices of 116 regions and analyzed using graph theoretical approaches. There was no difference in global properties among the three groups. Significant enhanced regional nodal measures in limbic system, frontal-temporal regions, and occipital regions and decreased nodal measures in cerebellum were found in PD patients with pRBD (PD-pRBD) compared with PD patients without pRBD. Besides, nodes in frontal lobe, temporal lobe, and limbic system were served as hubs in both two PD groups, and PD-pRBD exhibited additionally recruited hubs in limbic regions. Based on the SCN analysis, we found PD-pRBD exhibited a reorganization of nodal properties as well as the remapping of the hub distribution in whole brain especially in limbic system, which may shed light to the pathophysiology of PD with RBD.

Ontogenesis of the angiotensin II (ANGII) receptor system in the duck brain.

PubMed

Müller, A R; Gerstberger, R

1994-03-18

The ontogenetic development of the central nervous angiotensin II (ANGII) receptor system in the duck was studied at embryonic days E20 and E27 and at postnatal days P3 and P14 by computerized semiquantitative autoradiography employing the receptor antagonist 125I[1Sar,8Ile]ANGII as radioligand. For circumventricular structures involved in the sensing of brain-intrinsic (AV3V region) or blood-borne (subfornical organ, SFO) ANGII, binding sites for 125I[1Sar,8Ile]ANGII were first detectable at E27, with a steady rise in binding density up to P14. The choroid plexus of the lateral (PCVL) and third (PCVIII) cerebral ventricles responsible for cerebrospinal fluid (CSF) production were endowed with maximal ANGII receptor densities at E20 with subsequent reduction to constant medium (PCVIII) or low (PCVL) values. Besides the choroid plexus, the magnocellular paraventricular nucleus (PVN) was the only structure presenting ANGII specific binding sites at E20, although at low density. As for the SFO and AV3V region, labelling of ANGII binding sites in the PVN increased continuously during development to high values at P14. Nuclear components of the limbic system (archistriatum, amygdala and habenular complex) did not reveal specific labelling by the radioligand at E20 with constant, moderate binding densities evaluated for E27, P3 and P14. In the duck brain, functionally related structures exhibited a homogeneous ontogenetic development of their ANGII receptor system.

A convergent functional architecture of the insula emerges across imaging modalities.

PubMed

Kelly, Clare; Toro, Roberto; Di Martino, Adriana; Cox, Christine L; Bellec, Pierre; Castellanos, F Xavier; Milham, Michael P

2012-07-16

Empirical evidence increasingly supports the hypothesis that patterns of intrinsic functional connectivity (iFC) are sculpted by a history of evoked coactivation within distinct neuronal networks. This, together with evidence of strong correspondence among the networks defined by iFC and those delineated using a variety of other neuroimaging techniques, suggests a fundamental brain architecture detectable across multiple functional and structural imaging modalities. Here, we leverage this insight to examine the functional organization of the human insula. We parcellated the insula on the basis of three distinct neuroimaging modalities - task-evoked coactivation, intrinsic (i.e., task-independent) functional connectivity, and gray matter structural covariance. Clustering of these three different covariance-based measures revealed a convergent elemental organization of the insula that likely reflects a fundamental brain architecture governing both brain structure and function at multiple spatial scales. While not constrained to be hierarchical, our parcellation revealed a pseudo-hierarchical, multiscale organization that was consistent with previous clustering and meta-analytic studies of the insula. Finally, meta-analytic examination of the cognitive and behavioral domains associated with each of the insular clusters obtained elucidated the broad functional dissociations likely underlying the topography observed. To facilitate future investigations of insula function across healthy and pathological states, the insular parcels have been made freely available for download via http://fcon_1000.projects.nitrc.org, along with the analytic scripts used to perform the parcellations. Copyright © 2012 Elsevier Inc. All rights reserved.

Cerebral cortex three-dimensional profiling in human fetuses by magnetic resonance imaging

PubMed Central

Sbarbati, Andrea; Pizzini, Francesca; Fabene, Paolo F; Nicolato, Elena; Marzola, Pasquina; Calderan, Laura; Simonati, Alessandro; Longo, Laura; Osculati, Antonio; Beltramello, Alberto

2004-01-01

Seven human fetuses of crown/rump length corresponding to gestational ages ranging from the 12th to the 16th week were studied using a paradigm based on three-dimensional reconstruction of the brain obtained by magnetic resonance imaging (MRI). The aim of the study was to evaluate brain morphology in situ and to describe developmental dynamics during an important period of fetal morphogenesis. Three-dimensional MRI showed the increasing degree of maturation of the brains; fronto-occipital distance, bitemporal distance and occipital angle were examined in all the fetuses. The data were interpreted by correlation with the internal structure as visualized using high-spatial-resolution MRI, acquired using a 4.7-T field intensity magnet with a gradient power of 20 G cm−1. The spatial resolution was sufficient for a detailed detection of five layers, and the contrast was optimized using sequences with different degrees of T1 and T2 weighting. Using the latter, it was possible to visualize the subplate and marginal zones. The cortical thickness was mapped on to the hemispheric surface, describing the thickness gradient from the insular cortex to the periphery of the hemispheres. The study demonstrates the utility of MRI for studying brain development. The method provides a quantitative profiling of the brain, which allows the calculation of important morphological parameters, and it provides informative regarding transient features of the developing brain. PMID:15198688

Psychogenic amnesia--a malady of the constricted self.

PubMed

Staniloiu, Angelica; Markowitsch, Hans J; Brand, Matthias

2010-09-01

Autobiographical-episodic memory is the conjunction of subjective time, autonoetic consciousness and the experiencing self. Understanding the neural correlates of autobiographical-episodic memory might therefore be essential for shedding light on the neurobiology underlying the experience of being an autonoetic self. In this contribution we illustrate the intimate relationship between autobiographical-episodic memory and self by reviewing the clinical and neuropsychological features and brain functional imaging correlates of psychogenic amnesia - a condition that is usually characterized by severely impaired retrograde memory functioning, in absence of structural brain damage as detected by standard imaging. We demonstrate that in this disorder the autobiographical-episodic memory deficits do not exist in isolation, but occur with impairments of the autonoetic self-consciousness, emotional processing, and theory of mind or executive functions. Furthermore functional and metabolic brain alterations involving regions that are agreed upon to exert crucial roles in memory processes were frequently found to accompany the psychogenic memory "loss". Copyright © 2010 Elsevier Inc. All rights reserved.

Random Feedback Makes Listeners Tone-Deaf.

PubMed

Vuvan, Dominique T; Zendel, Benjamin Rich; Peretz, Isabelle

2018-05-08

The mental representation of pitch structure (tonal knowledge) is a core component of musical experience and is learned implicitly through exposure to music. One theory of congenital amusia (tone deafness) posits that conscious access to tonal knowledge is disrupted, leading to a severe deficit of music cognition. We tested this idea by providing random performance feedback to neurotypical listeners while they listened to melodies for tonal incongruities and had their electrical brain activity monitored. The introduction of random feedback was associated with a reduction of accuracy and confidence, and a suppression of the late positive brain response usually elicited by conscious detection of a tonal violation. These effects mirror the behavioural and neurophysiological profile of amusia. In contrast, random feedback was associated with an increase in the amplitude of the early right anterior negativity, possibly due to heightened attention to the experimental task. This successful simulation of amusia in a normal brain highlights the key role of feedback in learning, and thereby provides a new avenue for the rehabilitation of learning disorders.

Structural characterization of osmoregulator peptides from the brain of the leech Theromyzon tessulatum: IPEPYVWD and IPEPYVWD-amide.

PubMed

Salzet, M; Vandenbulcke, F; Verger-Bocquet, M

1996-12-31

Neurons immunoreactive to an antiserum (a-OT) directed specifically against the C-terminal part (prolyl-leucyl-glycinamide) of vertebrate oxytocin (OT) were detected in the brain of the leech Theromyzon tessulatum. With high pressure gel permeation chromatography followed by reversed-phase HPLC on brain extracts, evidence was given of the presence of three peptides (P1, P2, P3) immunoreactive to a-OT. Results of injection experiments in T. tessulatum and of titrations of each peptide at the different physiological stages of the animals which showed a peak in peptide P1 amount at stage 3B, indicated that P1 is the active OT-like peptide. Using three steps of reversed-phase HPLC, Edman degradation and electrospray mass spectrometry, two sequences for P1 (IPEPYVWD and IPEPYVWD-amide) were found. These peptides differ from peptides to the oxytocin/vasopressin family and are unique in the animal kingdom. Confirmation of their action on the hydric balance and their distribution in the CNS were presented.

Neurodegenerative dementias: From MR Physics lab to assessment room

NASA Astrophysics Data System (ADS)

Bruno, S. D.; Cercignani, M.; Wheeler-Kingshott, C. A. M.

2012-11-01

Theimpact of neuroimaging on the study and understanding of dementing illnesses has been enormous. Here we review the main MR structural technical developments applied to Alzheimer's disease and fronto-temporal dementia, two forms of neurodegenerative disorders that have a number of similarities but also several differences. The possibility of detecting increasingly subtle brain changes, together with the need of handling larger and larger data sets, keeping up with the ever expanding aging population, are perhaps the main driving forces behind recent MR technique developments in the field of dementia. The measurement of atrophy is now integrated by more advanced approaches, investigating the alterations of the architecture of brain tissues beyond pure volumetric loss. Brain connectivity is now studied in vivo with techniques such as diffusion tensor imaging and tractography. Also, automated methods of subject classification open up new possibilities of rapid and cost-effective diagnosis. The inter-disciplinary efforts are changing the clinical scenario of dementia care from one of helpless defeat to one of promising innovation.

A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment.

PubMed

Xie, Long; Dolui, Sudipto; Das, Sandhitsu R; Stockbower, Grace E; Daffner, Molly; Rao, Hengyi; Yushkevich, Paul A; Detre, John A; Wolk, David A

2016-01-01

Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or "stress test", may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease.