EPILEPSIA, Issue 7 2007
Giridhar P. Kalamangalam
Summary:,Purpose: We assessed neuroimaging lesion type and distribution in patients with periodic lateralized epileptiform discharges (PLEDs), with a view to identifying electrographic differences between PLEDs associated with differing lesion locations. Our observations led us to consider a conceptual synthesis between PLEDs and periodic complexes (PCs). Methods: Retrospective review of acute neuroimaging results (CT/MRI) on patients identified to have EEG PLEDs, for the period 1999,2003 (n = 106). Blinded classification of original EEG recordings. Results: Neuroimaging abnormalities were classified as acute or chronic cortical, or acute or chronic subcortical. Seven out of 106 scans were classified nonlesional. Overall ,70% of scans had cortical abnormalities, whether acute or chronic; ,23% had subcortical abnormalities. "Cortical" PLEDs were significantly longer in duration (p < 0.05) and more variable in morphology (p < 0.01) than "subcortical" PLEDs. Conclusions: Structural brain disease commonly, but not invariably, underlies PLEDs; lesion type is spatiotemporally variable. Cortical and subcortical PLEDs have distinct EEG signatures. There is evidence that these may relate to mechanisms for other pathological large-scale oscillatory brain synchronies (e.g., PCs). [source]

Redefining epithelial progenitor potential in the developing thymus

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2007
Simona
Abstract Cortical and medullary epithelium represent specialised cell types that play key roles in thymocyte development, including positive and negative selection of the T cell repertoire. While recent evidence shows that these epithelial lineages share a common embryonic origin, the phenotype and possible persistence of such progenitor cells in the thymus at later stages of development remain controversial. Through use of a panel of reagents including the putative progenitor marker Mts24, we set out to redefine the stages in the development of thymic epithelium. In the early embryonic day (E)12 thymus anlagen we find that almost all epithelial cells are uniformly positive for Mts24 expression. In addition, while the thymus at later stages of development was found to contain distinct Mts24+ and Mts24, epithelial subsets, thymus grafting experiments show that both Mts24+ and Mts24, epithelial subsets share the ability to form organised cortical and medullary thymic microenvironments that support T cell development, a function shown previously to be lost in the Mts24, cells by E15 when lower cell doses were used. Our data help to clarify stages in thymic epithelial development and provide important information in relation to currently used markers of epithelial progenitors. See accompanying commentary: http://dx.doi.org/10.1002/eji.200737709 [source]

Cortical and subcortical correlates of functional electrical stimulation of wrist extensor and flexor muscles revealed by fMRI

HUMAN BRAIN MAPPING, Issue 3 2009
Armin Blickenstorfer
Abstract The main scope of this study was to test the feasibility and reliability of FES in a MR-environment. Functional Electrical Stimulation (FES) is used in the rehabilitation therapy of patients after stroke or spinal cord injury to improve their motor abilities. Its principle lies in applying repeated electrical stimulation to the relevant nerves or muscles for eliciting either isometric or concentric contractions of the treated muscles. In this study we report cerebral activation patterns in healthy subjects undergoing fMRI during FES stimulation. We stimulated the wrist extensor and flexor muscles in an alternating pattern while BOLD-fMRI was recorded. We used both block and event-related designs to demonstrate their feasibility for recording FES activation in the same cortical and subcortical areas. Six out of fifteen subjects repeated the experiment three times within the same session to control intraindividual variance. In both block and event-related design, the analysis revealed an activation pattern comprising the contralateral primary motor cortex, primary somatosensory cortex and premotor cortex; the ipsilateral cerebellum; bilateral secondary somatosensory cortex, the supplementary motor area and anterior cingulate cortex. Within the same subjects we observed a consistent replication of the activation pattern shown in overlapping regions centered on the peak of activation. Similar time course within these regions were demonstrated in the event-related design. Thus, both techniques demonstrate reliable activation of the sensorimotor network and eventually can be used for assessing plastic changes associated with FES rehabilitation treatment. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [source]

Scanning texture analysis of lamellar bone using microbeam synchrotron X-ray radiation

JOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 1 2007
Wolfgang Wagermaier
Texture analysis with microbeam scanning diffraction enables the local mapping of three-dimensional crystallite orientation in heterogeneous natural and synthetic materials. Cortical (compact) bone is an example of a hierarchically structured biocomposite, which is built mainly of cylindrical osteons, having a lamellar texture at the micrometre level. In this work, a combination of microbeam synchrotron X-ray texture analysis with thin sections of osteonal bone is used to measure the three-dimensional distribution of the c -axis orientation of the mineral apatite in bone with positional resolution of 1,µm. The data reduction procedure needed to go from the stereographic projection of X-ray intensity to the determination of the local orientation of mineralized collagen fibrils is described. The procedure can be applied to other mineralized tissues (such as trabecular bone and chitin) with micrometre scale and biologically controlled fibrillar texture. [source]

RANKL Inhibition with Osteoprotegerin Increases Bone Strength by Improving Cortical and Trabecular bone Architecture in Ovariectomized Rats,,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008
Michael S Ominsky
Abstract Introduction: Ovariectomy (OVX) results in bone loss caused by increased bone resorption. RANKL is an essential mediator of bone resorption. We examined whether the RANKL inhibitor osteoprotegerin (OPG) would preserve bone volume, density, and strength in OVX rats. Materials and Methods: Rats were OVX or sham-operated at 3 mo of age. Sham controls were treated for 6 wk with vehicle (Veh, PBS). OVX rats were treated with Veh or human OPG-Fc (10 mg/kg, 2/wk). Serum RANKL and TRACP5b was measured by ELISA. BMD of lumbar vertebrae (L1,L5) and distal femur was measured by DXA. Right distal femurs were processed for bone histomorphometry. Left femurs and the fifth lumbar vertebra (L5) were analyzed by ,CT and biomechanical testing, and L6 was analyzed for ash weight. Results: OVX was associated with significantly greater serum RANKL and osteoclast surface and with reduced areal and volumetric BMD. OPG markedly reduced osteoclast surface and serum TRACP5b while completely preventing OVX-associated bone loss in the lumbar vertebrae, distal femur, and femur neck. Vertebrae from OPG-treated rats had increased dry and ash weight, with no significant differences in tissue mineralization versus OVX controls. ,CT showed that trabecular compartments in OVX-OPG rats had significantly greater bone volume fraction, vBMD, bone area, trabecular thickness, and number, whereas their cortical compartments had significantly greater bone area (p < 0.05 versus OVX-Veh). OPG improved cortical area in L5 and the femur neck to levels that were significantly greater than OVX or sham controls (p < 0.05). Biomechanical testing of L5 and femur necks showed significantly greater maximum load values in the OVX-OPG group (p < 0.05 versus OVX-Veh). Bone strength at both sites was linearly correlated with total bone area (r2 = 0.54,0.74, p < 0.0001), which was also significantly increased by OPG (p < 0.05 versus OVX). Conclusions: OPG treatment prevented bone loss, preserved trabecular architecture, and increased cortical area and bone strength in OVX rats. [source]

,-Arrestin2 Regulates the Differential Response of Cortical and Trabecular Bone to Intermittent PTH in Female Mice,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2005
Mary L Bouxsein PhD
Abstract Cytoplasmic arrestins regulate PTH signaling in vitro. We show that female ,-arrestin2,/, mice have decreased bone mass and altered bone architecture. The effects of intermittent PTH administration on bone microarchitecture differed in ,-arrestin2,/, and wildtype mice. These data indicate that arrestin-mediated regulation of intracellular signaling contributes to the differential effects of PTH at endosteal and periosteal bone surfaces. Introduction: The effects of PTH differ at endosteal and periosteal surfaces, suggesting that PTH activity in these compartments may depend on some yet unidentified mechanism(s) of regulation. The action of PTH in bone is mediated primarily by intracellular cAMP, and the cytoplasmic molecule ,-arrestin2 plays a central role in this signaling regulation. Thus, we hypothesized that arrestins would modulate the effects of PTH on bone in vivo. Materials and Methods: We used pDXA, ,CT, histomorphometry, and serum markers of bone turnover to assess the skeletal response to intermittent PTH (0, 20, 40, or 80 ,g/kg/day) in adult female mice null for ,-arrestin2 (,-arr2,/,) and wildtype (WT) littermates (7-11/group). Results and Conclusions: ,-arr2,/, mice had significantly lower total body BMD, trabecular bone volume fraction (BV/TV), and femoral cross-sectional area compared with WT. In WT females, PTH increased total body BMD, trabecular bone parameters, and cortical thickness, with a trend toward decreased midfemoral medullary area. In ,-arr2,/, mice, PTH not only improved total body BMD, trabecular bone architecture, and cortical thickness, but also dose-dependently increased femoral cross-sectional area and medullary area. Histomorphometry showed that PTH-stimulated periosteal bone formation was 2-fold higher in ,-arr2,/, compared with WT. Osteocalcin levels were significantly lower in ,-arr2,/, mice, but increased dose-dependently with PTH in both ,-arr2,/, and WT. In contrast, whereas the resorption marker TRACP5B increased dose-dependently in WT, 20-80 ,g/kg/day of PTH was equipotent with regard to stimulation of TRACP5B in ,-arr2,/,. In summary, ,-arrestin2 plays an important role in bone mass acquisition and remodeling. In estrogen-replete female mice, the ability of intermittent PTH to stimulate periosteal bone apposition and endosteal resorption is inhibited by arrestins. We therefore infer that arrestin-mediated regulation of intracellular signaling contributes to the differential effects of PTH on cancellous and cortical bone. [source]

The COMT val158met Polymorphism Is Associated With Peak BMD in Men,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2004
Mattias Lorentzon
Abstract The associations between the functional val158met polymorphism of the estrogen-degrading COMT enzyme and skeletal properties in young men were investigated. BMD was associated with COMT genotype. Introduction: Peak BMD is an important predictor of future risk of osteoporosis, and it is to a large extent determined by genetic factors. Estrogens are involved in the accretion of bone mass during puberty. Catechol- O -methyltransferase (COMT) is involved in the degradation of estrogens. There is a functional polymorphism in the COMT gene (val158met), resulting in a 60,75% difference in enzyme activity between the val (high activity [H]) and met (low activity [L]) variants. The aim of this cross-sectional study was to investigate the associations between this polymorphism and peak BMD in young men. Materials and Methods: A total of 458 healthy men (mean age, 19 ± 0.6 years) were genotyped and classified as COMTLL, COMTHL, or COMTHH. Areal BMD (aBMD) was measured by DXA. Cortical and trabecular volumetric BMD (vBMD) were measured by pQCT. The associations between COMT genotype and skeletal phenotypes were determined. Results and Conclusions: Regression models using physical activity, height, weight, age, and COMT genotype as covariates showed that COMT genotype was an independent predictor of aBMD in the total body and in all femur locations investigated, but not in the spine. The values for COMTHL and COMTHH were very similar, and therefore, they were pooled into one group. aBMD at Ward's triangle, trochanter, and total femur were 4.9%, 4.5%, and 3.7% lower, respectively, in the COMTLL than in the COMTHL/HH group (p < 0.01). pQCT analyses showed that COMT genotype was an independent predictor of trabecular vBMD of the tibia, radius, and fibula. Trabecular vBMD of the radius and fibula in COMTLL was 5.3% and 7.4% lower, respectively, than that of the combined COMTHL/HH group. COMT genotype was associated with cortical vBMD but not with cortical cross-sectional area in the tibia. These findings show that the COMT polymorphism is associated with BMD in young adult men. [source]

Recombinant Human Parathyroid Hormone (1,34) [Teriparatide] Improves Both Cortical and Cancellous Bone Structure

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2003
Yebin Jiang MD
Abstract Histomorphometry and ,CT of 51 paired iliac crest biopsy specimens from women treated with teriparatide revealed significant increases in cancellous bone volume, cancellous bone connectivity density, cancellous bone plate-like structure, and cortical thickness, and a reduction in marrow star volume. Introduction: We studied the ability of teriparatide (rDNA origin) injection [rhPTH(1,34), TPTD] to improve both cancellous and cortical bone in a subset of women enrolled in the Fracture Prevention Trial of postmenopausal women with osteoporosis after a mean treatment time of 19 months. This is the first report of a biopsy study after treatment with teriparatide having a sufficient number of paired biopsy samples to provide quantitative structural data. Methods: Fifty-one paired iliac crest bone biopsy specimens (placebo [n = 19], 20 ,g teriparatide [n = 18], and 40 ,g teriparatide [n = 14]) were analyzed using both two-dimensional (2D) histomorphometry and three-dimensional (3D) microcomputed tomography (,CT). Data for both teriparatide treatment groups were pooled for analysis. Results and Conclusions: By 2D histomorphometric analyses, teriparatide significantly increased cancellous bone volume (median percent change: teriparatide, 14%; placebo, ,24%; p = 0.001) and reduced marrow star volume (teriparatide, ,16%; placebo, 112%; p = 0.004). Teriparatide administration was not associated with osteomalacia or woven bone, and there were no significant changes in mineral appositional rate or wall thickness. By 3D cancellous and cortical bone structural analyses, teriparatide significantly decreased the cancellous structure model index (teriparatide, ,12%; placebo, 7%; p = 0.025), increased cancellous connectivity density (teriparatide, 19%; placebo, ,14%; p = 0.034), and increased cortical thickness (teriparatide, 22%; placebo, 3%; p = 0.012). These data show that teriparatide treatment of postmenopausal women with osteoporosis significantly increased cancellous bone volume and connectivity, improved trabecular morphology with a shift toward a more plate-like structure, and increased cortical bone thickness. These changes in cancellous and cortical bone morphology should improve biomechanical competence and are consistent with the substantially reduced incidences of vertebral and nonvertebral fractures during administration of teriparatide. [source]

Cortical versus spinal dysfunction in amyotrophic lateral sclerosis

MUSCLE AND NERVE, Issue 5 2006
Shahram Attarian MD
Abstract Little is known about the possible link between cortical and spinal motor neuron dysfunction in amyotrophic lateral sclerosis (ALS). We correlated the characteristics of the responses to transcranial magnetic stimulation (TMS) with the electromechanical properties and firing pattern of single motor units (MUs) tested in nine ALS patients, three patients with Kennedy's disease, and 15 healthy subjects. In Kennedy's disease, 19 of 22 MUs were markedly enlarged with good electromechanical coupling and discharged with great variability. Their excitatory responses increased with MU size. In ALS, 17 of 34 MUs with excitatory responses behaved as in Kennedy's disease. By contrast, 28 MUs with nonsignificant responses showed poor electromechanical coupling and high firing rates, whereas 28 MUs with inhibitory responses showed moderate functional alterations. This result indicates that in ALS as in Kennedy's disease, sprouting of corticospinal axons may occur on surviving motoneurons. A clear relationship exists between the responsiveness of MUs to TMS and their functional state. Muscle Nerve, 2006 [source]

Proteomic and functional alterations in brain mitochondria from Tg2576 mice occur before amyloid plaque deposition

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2007
Frank Gillardon Dr.
Abstract Synaptic dysfunction is an early event in Alzheimer's disease patients and has also been detected in transgenic mouse models. In the present study, we analyzed proteomic changes in synaptosomal fractions from Tg2576 mice that overexpress mutant human amyloid precursor protein (K670N, M671L) and from their nontransgenic littermates. Cortical and hippocampal tissue was microdissected at the onset of cognitive impairment, but before deposition of amyloid plaques. Crude synaptosomal fractions were prepared by differential centrifugation, proteins were separated by 2-D DIGE and identified by MS/MS. Significant alterations were detected in mitochondrial heat shock protein 70 pointing to a mitochondrial stress response. Subsequently, synaptosomal versus nonsynaptic mitochondria were purified from Tg2576 mice brains by density gradient centrifugation. Mitochondrial proteins were separated by IEF or Blue-native gel electrophoresis in the first dimension and SDS-PAGE in the second dimension. Numerous changes in the protein subunit composition of the respiratory chain complexes I and III were identified. Levels of corresponding mRNAs remain unchanged as shown by Affymetrix oligonucleotide array analysis. Functional examination revealed impaired state 3 respiration and uncoupled respiration in brain mitochondria from young Tg2576 mice. By immunoblotting, amyloid-beta oligomers were detected in synaptosomal fractions from Tg2576 mice and reduced glucose metabolism was observed in Tg2576 mice brains by [14C]-2-deoxyglucose infusion. Taken together, we demonstrate alterations in the mitochondrial proteome and function that occur in Tg2576 mice brains before amyloid plaque deposition suggesting that mitochondria are early targets of amyloid-beta aggregates. [source]

Morphological changes induced in the pig kidney by extracorporeal shock wave lithotripsy: Nephron injury

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 1 2003
Youzhi Shao
Abstract While shock wave lithotripsy (SWL) is known to cause significant damage to the kidney, little is known about the initial injury to cells along the nephron. In this study, one kidney in each of six juvenile pigs (6,7 weeks old) was treated with 1,000 shock waves (at 24 kV) directed at a lower pole calyx with an unmodified HM-3 lithotripter. Three pigs were utilized as sham-controls. Kidneys were fixed by vascular perfusion immediately after SWL or sham-SWL. Three of the treated kidneys were used to quantitate lesion size. Cortical and medullary samples for light (LM) and transmission electron microscopy (TEM) were taken from the focal zone for the shock waves (F2), the contralateral kidney, and the kidneys of sham-SWL pigs. Because preservation of the tissue occurred within minutes of SWL, the initial injury caused by the shock waves could be separated from secondary changes. No tissue damage was observed in contralateral sham-SWL kidneys, but treated kidneys showed signs of injury, with a lesion of 0.2% ± 0.1% of renal volume. Intraparenchymal hemorrhage and injury to tubules was found at F2 in both the cortex and medulla of SWL-treated kidneys. Tubular injury was always associated with intraparenchymal bleeding, and the range of tissue injury included total destruction of tubules, focal cellular fragmentation, necrosis, cell vacuolization, and membrane blebbing. The initial injury caused by SWL was cellular fragmentation and necrosis. Cellular vacuolization, membrane blebbing, and disorganization of apical brush borders appear to be secondary changes related to hypoxia. Anat Rec Part A 275A:979,989, 2003. © 2003 Wiley-Liss, Inc. [source]

Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis

ARTHRITIS & RHEUMATISM, Issue 10 2009
Timothy M. Griffin
Objective To test the hypothesis that obesity resulting from deletion of the leptin gene or the leptin receptor gene results in increased knee osteoarthritis (OA), systemic inflammation, and altered subchondral bone morphology. Methods Leptin-deficient (ob/ob) and leptin receptor,deficient (db/db) female mice compared with wild-type mice were studied, to document knee OA via histopathology. The levels of serum proinflammatory and antiinflammatory cytokines were measured using a multiplex bead immunoassay. Cortical and trabecular subchondral bone changes were documented by microfocal computed tomography, and body composition was quantified by dual x-ray absorptiometry. Results Adiposity was increased by ,10-fold in ob/ob and db/db mice compared with controls, but it was not associated with an increased incidence of knee OA. Serum cytokine levels were unchanged in ob/ob and db/db mice relative to controls, except for the level of cytokine-induced neutrophil chemoattractant (keratinocyte chemoattractant; murine analog of interleukin-8), which was elevated. Leptin impairment was associated with reduced subchondral bone thickness and increased relative trabecular bone volume in the tibial epiphysis. Conclusion Extreme obesity due to impaired leptin signaling induced alterations in subchondral bone morphology without increasing the incidence of knee OA. Systemic inflammatory cytokine levels remained largely unchanged in ob/ob and db/db mice. These findings suggest that body fat, in and of itself, may not be a risk factor for joint degeneration, because adiposity in the absence of leptin signaling is insufficient to induce systemic inflammation and knee OA in female C57BL/6J mice. These results imply a pleiotropic role of leptin in the development of OA by regulating both the skeletal and immune systems. [source]

Changes in presumed motor cortical activity during fatiguing muscle contraction in humans

ACTA PHYSIOLOGICA, Issue 3 2010
T. Seifert
Abstract Aim:, Changes in sensory information from active muscles accompany fatiguing exercise and the force-generating capacity deteriorates. The central motor commands therefore must adjust depending on the task performed. Muscle potentials evoked by transcranial magnetic stimulation (TMS) change during the course of fatiguing muscle activity, which demonstrates activity changes in cortical or spinal networks during fatiguing exercise. Here, we investigate cortical mechanisms that are actively involved in driving the contracting muscles. Methods:, During a sustained submaximal contraction (30% of maximal voluntary contraction) of the elbow flexor muscles we applied TMS over the motor cortex. At an intensity below motor threshold, TMS reduced the ongoing muscle activity in biceps brachii. This reduction appears as a suppression at short latency of the stimulus-triggered average of rectified electromyographic (EMG) activity. The magnitude of the suppression was evaluated relative to the mean EMG activity during the 50 ms prior to the cortical stimulus. Results:, During the first 2 min of the fatiguing muscle contraction the suppression was 10 ± 0.9% of the ongoing EMG activity. At 2 min prior to task failure the suppression had reached 16 ± 2.1%. In control experiments without fatigue we did not find a similar increase in suppression with increasing levels of ongoing EMG activity. Conclusion:, Using a form of TMS which reduces cortical output to motor neurones (and disfacilitates them), this study suggests that neuromuscular fatigue increases this disfacilitatory effect. This finding is consistent with an increase in the excitability of inhibitory circuits controlling corticospinal output. [source]

Environmental complexity and central nervous system development and function

DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2004
Mark H. Lewis
Abstract Environmental restriction or deprivation early in development can induce social, cognitive, affective, and motor abnormalities similar to those associated with autism. Conversely, rearing animals in larger, more complex environments results in enhanced brain structure and function, including increased brain weight, dendritic branching, neurogenesis, gene expression, and improved learning and memory. Moreover, in animal models of CNS insult (e.g., gene deletion), a more complex environment has attenuated or prevented the sequelae of the insult. Of relevance is the prevention of seizures and attenuation of their neuropathological sequelae as a consequence of exposure to a more complex environment. Relatively little attention, however, has been given to the issue of sensitive periods associated with such effects, the relative importance of social versus inanimate stimulation, or the unique contribution of exercise. Our studies have examined the effects of environmental complexity on the development of the restricted, repetitive behavior commonly observed in individuals with autism. In this model, a more complex environment substantially attenuates the development of the spontaneous and persistent stereotypies observed in deer mice reared in standard laboratory cages. Our findings support a sensitive period for such effects and suggest that early enrichment may have persistent neuroprotective effects after the animal is returned to a standard cage environment. Attenuation or prevention of repetitive behavior by environmental complexity was associated with increased neuronal metabolic activity, increased dendritic spine density, and elevated neurotrophin (BDNF) levels in brain regions that are part of cortical,basal ganglia circuitry. These effects were not observed in limbic areas such as the hippocampus. MRDD Research Reviews 2004;10:91,95. © 2004 Wiley-Liss, Inc. [source]

Effect of canonical Wnt inhibition in the neurogenic cortex, hippocampus, and premigratory dentate gyrus progenitor pool

DEVELOPMENTAL DYNAMICS, Issue 7 2008
Nina Solberg
Abstract Canonical Wnt signaling is crucial for the correct development of both cortical and hippocampal structures in the dorsal telencephalon. In this study, we examined the role of the canonical Wnt signaling in the dorsal telencephalon of mouse embryos at defined time periods by inhibition of the pathway with ectopic expression of Dkk1. Transgenic mice with the D6-driven Dkk1 gene exhibited reduced canonical Wnt signaling in the cortex and hippocampus. As a result, all hippocampal fields were reduced in size. Neurogenesis in the dentate gyrus was severely reduced both in the premigratory and migratory progenitor pool. The lower number of progenitors in the dentate gyrus was not rescued after migration to the subgranular zone and thus the dentate gyrus lacked the entire internal blade and a part of the external blade from postnatal to adult stages. Developmental Dynamics 237:1799,1811, 2008. © 2008 Wiley-Liss, Inc. [source]

Microtubule-dependent organization of subcortical microfilaments in the early Drosophila embryo

DEVELOPMENTAL DYNAMICS, Issue 3 2007
Maria Giovanna Riparbelli
Abstract Dynamic alterations in the spatial organization of cytoskeletal elements constitute a prominent morphological feature of the early, syncytial stages of embryogenesis in Drosophila. Here, we describe and characterize the dynamic behavior of cytoplasmic, subcortical microfilaments, which form a series of nucleus-associated structures, at different phases of the simultaneous nuclear division cycles characteristic of early Drosophila embryos. Remodeling of the cytoplasmic microfilament arrays takes place in parallel to the established cyclic reorganization of cortical microfilament structures. We provide evidence that the cortical and subcortical microfilament populations organize independently of each other, and in response to distinct instructive cues. Specifically, formation of subcortical microfilament structures appears to rely on, and spatially mirror, the organization of polarized microtubule arrays, while cortical microfilament restructuring constitutes a centrosome-dependent process. Genetic analysis identifies a requirement for SCAR, a key mediator of Arp2/3-based microfilament dynamics, in organization of subcortical microfilament structures. Developmental Dynamics 236:662,670, 2007. © 2007 Wiley-Liss, Inc. [source]

Toward a better understanding of the pathophysiology of OCD SSRI responders: QEEG source localization

ACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2007
T. G. Bolwig
Objective:, To demonstrate the utility of three-dimensional source localization of the scalp-recorded electroencephalogram (EEG) for the identification of the most probable underlying brain dysfunction in patients with obsessive,compulsive disorder (OCD). Method:, Eyes-closed resting EEG data was recorded from the scalp locations of the International 10/20 System. Variable resolution electromagnetic tomography (VARETA) was applied to artifact-free EEG data. This mathematical algorithm estimates the source generators of EEG recorded from the scalp. Results:, An excess in the alpha range was found with sources in the corpus striatum, in the orbito-frontal and temporo-frontal regions in untreated OCD patients. This abnormality was seen to decrease following successful treatment with paroxetine. Conclusion:, The VARETA findings of an activation/deactivation pattern in cortical and subcortical structures in paroxetine-responsive patients are in good accordance with data obtained in previously published positron emission tomography studies related to current hypotheses of a thalamo-striatal-frontal feedback loop being relevant for understanding the pathophysiology of OCD. [source]

Development of cortical and subcortical brain structures in childhood and adolescence: a structural MRI study

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 1 2002
Elizabeth R Sowell PhD
The purpose of the present study was to describe in greater anatomical detail the changes in brain structure that occur during maturation between childhood and adolescence. High-resolution MRI, tissue classification, and anatomical segmentation of cortical and subcortical regions were used in a sample of 35 normally developing children and adolescents between 7 and 16 years of age (mean age 11 years; 20 males, 15 females). Each cortical and subcortical measure was examined for age and sex effects on raw volumes and on the measures as proportions of total supratentorial cranial volume. Results indicate age-related increases in total supratentorial cranial volume and raw and proportional increases in total cerebral white matter. Gray-matter volume reductions were only observed once variance in total brain size was proportionally controlled. The change in total cerebral white-matter proportion was significantly greater than the change in total cerebral gray-matter proportion over this age range, suggesting that the relative gray-matter reduction is probably due to significant increases in white matter. Total raw cerebral CSF volume increases were also observed. Within the cerebrum, regional patterns varied depending on the tissue (or CSF) assessed. Only frontal and parietal cortices showed changes in gray matter, white matter, and CSF measures. Once the approximately 7% larger brain volume in males was controlled, only mesial temporal cortex, caudate, thalamus, and basomesial diencephalic structures showed sex effects with the females having greater relative volumes in these regions than the males. Overall, these results are consistent with earlier reports and describe in greater detail the regional pattern of age-related differences in gray and white matter in normally developing children and adolescents. [source]

Development of the corticospinal system and hand motor function: central conduction times and motor performance tests

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2000
U M Fietzek
Maturation of the corticospinal (CS) tract and hand motor function provide paradigms for central nervous system development. In this study, involving 112 participants (aged from 0.2 to 30 years), we evaluated central motor conduction times (CMCT) obtained with transcranial magnetic stimulation (TMS) during preinnervation conditions of facilitation and relaxation. Auditory reaction time, velocity of a ballistic movement of the arm, finger tapping, diadochokinesis, and fine motor visuomanual tracking were also examined. The maturation profiles for every parameter were calculated. CMCTs for the different preinnervation conditions reached adult values at different times and this could be explained by maturation of excitability at the cortical and spinal level. A stable phase for CMCTs and reaction time was reached during childhood. Parameters which measured motor speed and skill indicated that the development of these continued into adulthood. The maturation of the fast CS tract seems to be completed before the acquisition of the related motor performance has been accomplished. In conclusion, we could demonstrate that data from several neurophysiological methods can be combined and used to study the maturation of the function of the nervous system. This approach could allow appraisal of pathological conditions that show parallels with omissions or lack of developmental progress. [source]

Effects of early weaning on anxiety and prefrontal cortical and hippocampal myelination in male and female wistar rats

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2008
Yuka Kodama
Abstract We investigated developmental changes in myelin formation in the prefrontal cortex and the hippocampus, and behavioral effects of early weaning in Wistar rats. Early-weaned rats showed decreased numbers of open-arm entries in an elevated plus-maze in both sexes at 4 weeks old; this effect persisted in males, but ceased in females after this age. Expression of myelin basic protein (MBP) showed both age-dependent increases and sex differences; 4-week-old males exhibited higher MBP levels in the hippocampus, whereas 7-week-old males showed lower MBP levels in the prefrontal cortex compared to females of the same age. There was a tendency for group differences from weaning for the 21.5-kDa isoform in the prefrontal cortex. Although these results suggest that male rats are more vulnerable than females to early-weaning effects on anxiety-related behaviors, further detailed analysis is needed to clarify the functional relationship between myelination and anxiety-related behaviors. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 332,342, 2008. [source]

The cortex in multidimensional space: where do cortical areas come from?

DEVELOPMENTAL SCIENCE, Issue 2 2001
Marcy A. Kingsbury
The concept of a cortical ,area' as a discrete phylogenetic, developmental and computational unit is evaluated. Evidence including the comparative organization of the forebrain in vertebrates, the organization of cortex in different mammals, the scaling of the areas of the isocortex in mammals, and the early molecular differentiation of the cortex all suggest a special status for the primary sensory cortical areas, particularly the visual cortex. Furthermore, the overlapping gradients of early molecular expression and the patterning of cortical structure and connectivity by thalamic input suggest a new view of cortical organization that is different from the traditional view of a developmentally mosaic cortex; this view proposes that distinct cortical areas arise combinatorily from the multiple overlapping processes imposed upon the developing cortex. [source]

Corticolimbic dysregulation and chronic methamphetamine abuse

ADDICTION, Issue 2007
Kate Baicy
ABSTRACT Aims This review aims to present and interpret evidence that methamphetamine dependence is associated with disorder of brain function that is required for top-down control of behavior. Approach Presented here are findings from brain imaging studies of human research participants with histories of chronic methamphetamine abuse in the context of functional consequences and implications for treatment of their dependence on methamphetamine. Findings Brain imaging studies have revealed differences in the brains of research participants who have used methamphetamine chronically and then abstained from taking the drug, compared with healthy control subjects. These abnormalities are prominent in cortical and limbic systems, and include deficits in markers of dopaminergic and serotonergic neurotransmitter systems, differences in glucose metabolism and deficits in gray matter. These abnormalities accompany cognitive deficits, including evidence of impaired inhibitory control. Conclusion Cortical deficits in abstinent methamphetamine abusers can affect a wide range of functions that can be important for success in maintaining drug abstinence. These include but are not limited to modulation of responses to environmental stimuli as well as internal triggers that can lead to craving and relapse. Potential therapies may combine behavioral approaches with medications that can improve cognitive control. [source]

Sublobar dysplasia,A clinicopathologic report after successful epilepsy surgery

EPILEPSIA, Issue 12 2009
Ingrid Tuxhorn
Summary We report the clinical presentation, neuroradiologic characteristics, and detailed histopathologic findings in a unique case of drug-resistant focal epilepsy due to sublobar dysplasia (SLD), treated successfully by resection of the malformed cortex. Histopathology with leptomeningeal and subcortical heterotopia, disturbance of cortical lamination and marked cortical and subcortical astrocytosis, but absence of balloon cells, points to a disorder of neuronal migration and organization rather than proliferation in SLD. The additional presence of a lateral proboscis and meningocele in our case as well as further associated callosal and cerebellar anomalies may suggest an etiologic unknown damage of pathways controlling the embryogenesis of craniofacial field processes. [source]

Coexistence of symptomatic focal and absence seizures: Video-EEG and EEG-fMRI evidence of overlapping but independent epileptogenic networks

EPILEPSIA, Issue 7 2009
Serge Chassagnon
Summary The distinction between typical absences and hypomotor seizures in patients having frontal lesions is difficult. In focal epilepsy, generalized-like interictal discharges can reflect either a coexistent generalized epileptic trait or a secondary bilateral synchrony. Using combined measures of the EEG and blood oxygenation level dependent (BOLD) activity, we studied a 50-year-old patient with both absence-like and symptomatic focal motor seizures. Focal activity induced activation in the lesional area and deactivation in the contralateral central cortex. Generalized spike-and-wave discharges (GSWDs) resulted also in perilesional activation, and multifocal symmetrical cortical and thalamic activations, and deactivation in associative cortical areas. Although the central cortex was involved during both types of epileptic activity, electroencephalography (EEG),functional magnetic resonance imaging (fMRI) revealed distinct neuronal networks at the time of the focal or generalized discharges, allowing a clear-cut differentiation of the generators. Whether the patient had distinct epileptic syndromes or distinct electrographic patterns from the lesional trigger remains debatable. [source]

Molecular and diffusion tensor imaging of epileptic networks

EPILEPSIA, Issue 2008
Aimee F. Luat
Summary Several studies have shown that seizure-induced cellular and molecular changes associated with chronic epilepsy can lead to functional and structural alterations in the brain. Chronic epilepsy, when medically refractory, may be associated with an expansion of the epileptic circuitry to involve complex interactions between cortical and subcortical neuroanatomical substrates. Progress in neuroimaging has led not only to successful identification of epileptic foci for surgical resection, but also to an improved understanding of the functional and microstructural changes in long-standing epilepsy. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are all promising tools that can assist in elucidating the underlying pathophysiology in chronic epilepsy. Studies using PET scanning have demonstrated dynamic changes associated with the evolution from acute to chronic intractable epilepsy. Among these changes are data to support the existence of secondary epileptogenesis in humans. MRI with DTI is a powerful tool which has the ability to characterize microstructural abnormalities in epileptic foci, and to demonstrate the white matter fibers and tracts participating in the epileptic network. In this review, we illustrate how PET and DTI can be applied to depict the functional and microstructural alterations associated with chronic epilepsy. [source]

Neuroimaging and Neurophysiology of Periodic Lateralized Epileptiform Discharges: Observations and Hypotheses

fMRI of Brain Activation in a Genetic Rat Model of Absence Seizures

EPILEPSIA, Issue 6 2004
Jeffrey R. Tenney
Summary: Purpose: EEG-triggered functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during spontaneous spike-and-wave discharges (SWDs) in an epileptic rat strain under awake conditions. Methods: Spontaneous absence seizures from 10 WAG/Rij rats were imaged by using T2*-weighted echo planar imaging at 4.7 Tesla. fMRI of the blood-oxygenation-level,dependent (BOLD) signal was triggered based on EEG recordings during imaging. Images obtained during spontaneous SWDs were compared with baseline images. Results: Significant positive BOLD signal changes were apparent in several areas of the cortex and several important nuclei of the thalamus. In addition, no negative BOLD signal was found in any brain area. Conclusions: We have shown that EEG-triggered BOLD fMRI can be used to detect cortical and thalamic activation related to the spontaneous SWDs that characterize absence seizures in awake WAG/Rij rats. These results draw an anatomic correlation between areas in which increased BOLD signal is found and those in which SWDs have been recorded. In addition, no negative BOLD signal was found to be associated with these spontaneous SWDs. We also demonstrated the technical feasibility of using EEG-triggered fMRI in a genetic rat model of absence seizure. [source]

Ictal Pattern of EEG and Muscular Activation in Symptomatic Infantile Spasms: A Videopolygraphic and Computer Analysis

EPILEPSIA, Issue 12 2002
Francesca Bisulli
Summary: ,Purpose: To investigate ictal muscular phenomena characterizing symptomatic infantile spasms (ISs) and their relation to ictal EEG. Methods: Four children with severe encephalopathy, neurologic impairment, and refractory ISs related to different dysplastic lesions, underwent videopolygraphic recordings collecting surface electromyogram (EMG) activity from several cranial and limb muscles to evaluate the pattern of muscular recruitment, duration, and side-to-side asymmetry of ISs. Acquired data were stored for off-line analysis by a computerized polygraphic system. Results: Spasms were characterized by a complex pattern of muscular activation. A constant or rostrocaudal propagation pattern was lacking in all patients. Intervals between the onset of EMG activity in different muscles in each spasm were very long: ,100,200 ms. Two patients, with hemispheric cortical dysplasia and agenesis of the corpus callosum, had asymmetric and asynchronous spasms in which the EMG onset of the muscles contralateral to the affected hemisphere constantly anticipated that of the ipsilateral ones. Backaveraging of EEG activity disclosed a high-amplitude EEG complex on the same side as the dysplastic lesion, preceding or succeeding the contralateral muscle activity onset. In the other two patients with diffuse cortical dysplasia, no EEG transient was related to EMG activity onset. Conclusions: Despite clinical similarity between spasms in the same patient, our data demonstrate the complexity and heterogeneity of these motor phenomena. Our findings cannot be explained simply in terms of cortical or reticular generators like other motor phenomena such as cortical myoclonus or startle reflex. [source]