177 research outputs found
Morphometric analysis of subcortical structures in progressive supranuclear palsy: In vivo evidence of neostriatal and mesencephalic atrophy
Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by gait and postural disturbance, gaze palsy, apathy, decreased verbal fluency and dysexecutive symptoms, with some of these clinical features potentially having origins in degeneration of frontostriatal circuits and the mesencephalon. This hypothesis was investigated by manual segmentation of the caudate and putamen on MRI scans, using previously published protocols, in 15 subjects with PSP and 15 healthy age-matched controls. Midbrain atrophy was assessed by measurement of mid-sagittal area of the midbrain and pons. Shape analysis of the caudate and putamen was performed using spherical harmonics (SPHARM-PDM, University of North Carolina). The sagittal pons area/midbrain area ratio (P/M ratio) was significantly higher in the PSP group, consistent with previous findings. Significantly smaller striatal volumes were found in the PSP group - putamina were 10% smaller and caudate volumes were 17% smaller than in controls after controlling for age and intracranial volume. Shape analysis revealed significant shape deflation in PSP in the striatum, compared to controls; with regionally significant change relevant to frontostriatal and corticostriatal circuits in the caudate. Thus, in a clinically diagnosed and biomarker-confirmed cohort with early PSP, we demonstrate that neostriatal volume and shape are significantly reduced in vivo. The findings suggest a neostriatal and mesencephalic structural basis for the clinical features of PSP leading to frontostriatal and mesocortical-striatal circuit disruption. (C) 2011 Elsevier Ireland Ltd. All rights reserved
Regional structural hypo- and hyperconnectivity of frontal-striatal and frontal-thalamic pathways in behavioral variant frontotemporal dementia
Behavioral variant frontotemporal dementia (bvFTD) has been predominantly considered as a frontotemporal cortical disease, with limited direct investigation of frontalâsubcortical connections. We aim to characterize the grey and white matter components of frontalâthalamic and frontalâstriatal circuits in bvFTD. Twentyâfour patients with bvFTD and 24 healthy controls underwent morphological and diffusion imaging. Subcortical structures were manually segmented according to published protocols. Probabilistic pathways were reconstructed separately from the dorsolateral, orbitofrontal and medial prefrontal cortex to the striatum and thalamus. Patients with bvFTD had smaller cortical and subcortical volumes, lower fractional anisotropy, and higher mean diffusivity metrics, which is consistent with disruptions in frontalâstriatalâthalamic pathways. Unexpectedly, regional volumes of the striatum and thalamus connected to the medial prefrontal cortex were significantly larger in bvFTD (by 135% in the striatum, pâ=â.032, and 217% in the thalamus, pâ=â.004), despite smaller dorsolateral prefrontal cortex connected regional volumes (by 67% in the striatum, pâ=â.002, and 65% in the thalamus, pâ=â.020), and inconsistent changes in orbitofrontal cortex connected regions. These unanticipated findings may represent compensatory or maladaptive remodeling in bvFTD networks. Comparisons are made to other neuropsychiatric disorders suggesting a common mechanism of changes in frontalâsubcortical networks; however, longitudinal studies are necessary to test this hypothesis.Miller Family Bridgewater Illawarra Health
and Medical Research Initiative Summer
Scholarship; The Swedish Alzheimer
foundation; Thureus foundation; The
Swedish Society for Medical Research; The
Bente Rexed Gersteds Foundation for Brain
Researc
Ionic and electronic properties of the topological insulator BiTeSe investigated using -detected nuclear magnetic relaxation and resonance of Li
We report measurements on the high temperature ionic and low temperature
electronic properties of the 3D topological insulator BiTeSe using
ion-implanted Li -detected nuclear magnetic relaxation and
resonance. With implantation energies in the range 5-28 keV, the probes
penetrate beyond the expected range of the topological surface state, but are
still within 250 nm of the surface. At temperatures above ~150 K, spin-lattice
relaxation measurements reveal isolated Li diffusion with an
activation energy eV and attempt frequency s for atomic site-to-site hopping. At lower
temperature, we find a linear Korringa-like relaxation mechanism with a field
dependent slope and intercept, which is accompanied by an anomalous field
dependence to the resonance shift. We suggest that these may be related to a
strong contribution from orbital currents or the magnetic freezeout of charge
carriers in this heavily compensated semiconductor, but that conventional
theories are unable to account for the extent of the field dependence.
Conventional NMR of the stable host nuclei may help elucidate their origin.Comment: 17 pages, 12 figures, submitted to Phys. Rev.
Saccadic Eye Movement Characteristics in Adult Niemann-Pick Type C Disease: Relationships with Disease Severity and Brain Structural Measures
Niemann-Pick Type C disease (NPC) is a rare genetic disorder of lipid metabolism. A parameter related to horizontal saccadic peak velocity was one of the primary outcome measures in the clinical trial assessing miglustat as a treatment for NPC. Neuropathology is widespread in NPC, however, and could be expected to affect other saccadic parameters. We compared horizontal saccadic velocity, latency, gain, antisaccade error percentage and self-paced saccade generation in 9 adult NPC patients to data from 10 age-matched controls. These saccadic measures were correlated with appropriate MRI-derived brain structural measures (e.g., dorsolateral prefrontal cortex, frontal eye fields, supplemental eye fields, parietal eye fields, pons, midbrain and cerebellar vermis) and with measures of disease severity and duration. The best discriminators between groups were reflexive saccade gain and the two volitional saccade measures. Gain was also the strongest correlate with disease severity and duration. Most of the saccadic measures showed strongly significant correlations with neurophysiologically appropriate brain regions. While our patient sample is small, the apparent specificity of these relationships suggests that as new diagnostic methods and treatments become available for NPC, a broader range of saccadic measures may be useful tools for the assessment of disease progression and treatment efficacy.No external funding was received for this study. JCLL self-funded computational, travel and accommodation costs to conduct his component of this
research in Melbourne
Left Ventricular Noncompaction:Anatomical Phenotype or Distinct Cardiomyopathy?
The present study was funded by the Souter Charitable Foundation and the Chest, Heart and Stroke Scotland Charity. Dr. Weir-McCall is supported by the Wellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative (Grant no. WT 085664) in the form of a Clinical Research Fellowship.Background: There is considerable overlap between left ventricular noncompaction (LVNC) and other cardiomyopathies. LVNC has been reported in up to 40% of the general population, raising questions about whether it is a distinct pathological entity, a remodeling epiphenomenon, or merely an anatomical phenotype. Objectives:  The authors determined the prevalence and predictors of LVNC in a healthy population using 4 cardiac magnetic resonance imaging diagnostic criteria. Methods:  Volunteers >40 years of age (N = 1,651) with no history of cardiovascular disease (CVD), a 10-year risk of CVD < 20%, and a B-type natriuretic peptide level greater than their gender-specific median underwent magnetic resonance imaging scan as part of the TASCFORCE (Tayside Screening for Cardiac Events) study. LVNC ratios were measured on the horizontal and vertical long axis cine sequences. All individuals with a noncompaction ratio of â„2 underwent short axis systolic and diastolic LVNC ratio measurements, and quantification of noncompacted and compacted myocardial mass ratios. Those who met all 4 criteria were considered to have LVNC. Results: Of 1,480 participants analyzed, 219 (14.8%) met â„1 diagnostic criterion for LVNC, 117 (7.9%) met 2 criteria, 63 (4.3%) met 3 criteria, and 19 (1.3%) met all 4 diagnostic criteria. There was no difference in demographic or allometric measures between those with and without LVNC. Long axis noncompaction ratios were the least specific, with current diagnostic criteria positive in 219 (14.8%), whereas the noncompacted to compacted myocardial mass ratio was the most specific, only being met in 61 (4.4%). Conclusions:  A significant proportion of an asymptomatic population free from CVD satisfy all currently used cardiac magnetic resonance imaging diagnostic criteria for LVNC, suggesting that those criteria have poor specificity for LVNC, or that LVNC is an anatomical phenotype rather than a distinct cardiomyopathy.Publisher PDFPeer reviewe
Depth-resolved measurement of the Meissner screening profile in a niobium thin film from spin-lattice relaxation of the implanted -emitter Li
We report measurements of the Meissner screening profile in a Nb(300
nm)/AlO thin film using Li -detected nuclear magnetic
resonance (-NMR). The NMR probe Li was ion-implanted into the Nb
film at energies 20 keV, corresponding to mean stopping depths
comparable to Nb's magnetic penetration depth . Li's strong
dipole-dipole coupling with the host Nb nuclei provided a
"cross-relaxation" channel that dominated in low magnetic fields, which
conferred indirect sensitivity to the local magnetic field via the spin-lattice
relaxation (SLR) rate . From a fit of the data to a model
accounting for its dependence on temperature, magnetic field, and
Li implantation energy, we obtained a magnetic penetration depth
= 51.5(22) nm, consistent with a relatively short carrier
mean-free-path = 18.7(29) nm typical of similarly prepared Nb films. The
results presented here constitute an important step towards using Li
-NMR to characterize bulk Nb samples with engineered surfaces, which are
often used in the fabrication of particle accelerators.Comment: 16 pages, 4 figure
Nuclear magnetic resonance of ion implanted Li in ZnO
We report on the stability and magnetic state of ion implanted Li in
single crystals of the semiconductor ZnO using -detected nuclear
magnetic resonance. At ultradilute concentrations, the spectra reveal distinct
Li sites from 7.6 to 400 K. Ionized shallow donor interstitial Li is stable
across the entire temperature range, confirming its ability to self-compensate
the acceptor character of its (Zn) substitutional counterpart. Above 300 K,
spin-lattice relaxation indicates the onset of correlated local motion of
interacting defects, and the spectra show a site change transition from
disordered configurations to substitutional. Like the interstitial, the
substitutional shows no resolved hyperfine splitting, indicating it is also
fully ionized above 210 K. The electric field gradient at the interstitial
Li exhibits substantial temperature dependence with a power law typical of
non-cubic metals.Comment: 15 pages and 11 figure
Genetic risk prediction of atrial fibrillation
BackgroundâAtrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke.
MethodsâTo determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3,028 referents. Scores were based on 11 to 719 common variants (â„5%) associated with AF at P-values ranging from <1x10-3 to <1x10-8 in a prior independent genetic association study.
ResultsâIncident AF occurred in 1,032 (5.5%) individuals. AF genetic risk scores were associated with new-onset AF after adjusting for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95%CI, 1.13-1.46; P=1.5x10-4) to 1.67 (25 variants; 95%CI, 1.47-1.90; P=9.3x10-15). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629-0.811; maximum ÎC statistic from clinical score alone, 0.009-0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest versus lowest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke (95%CI, 1.39-4.58; P=2.7x10-3). The effect persisted after excluding individuals (n=70) with known AF (odds ratio, 2.25; 95%CI, 1.20-4.40; P=0.01).
ConclusionsâComprehensive AF genetic risk scores were associated with incident AF beyond associations for clinical AF risk factors, though offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts are warranted to determine whether AF genetic risk may improve identification of subclinical AF or help distinguish between stroke mechanisms
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