Modelling large motion events in fMRI studies of patients with epilepsy

EEG-correlated fMRI can provide localisation information on the generators of epileptiform discharges in patients with focal epilepsy. To increase the technique's clinical potential, it is important to consider ways of optimising the yield of each experiment while minimizing the risk of false-positive activation. Head motion can lead to severe image degradation and result in false-positive activation and is usually worse in patients than in healthy subjects. We performed general linear model fMRI data analysis on simultaneous EEG–fMRI data acquired in 34 cases with focal epilepsy. Signal changes associated with large inter-scan motion events (head jerks) were modelled using modified design matrices that include ‘scan nulling’ regressors. We evaluated the efficacy of this approach by mapping the proportion of the brain for which F-tests across the additional regressors were significant. In 95% of cases, there was a significant effect of motion in 50% of the brain or greater; for the scan nulling effect, the proportion was 36%; this effect was predominantly in the neocortex. We conclude that careful consideration of the motion-related effects in fMRI studies of patients with epilepsy is essential and that the proposed approach can be effective

EEG–fMRI of idiopathic and secondarily generalized epilepsies

We used simultaneous EEG and functional MRI (EEG–fMRI) to study generalized spike wave activity (GSW) in idiopathic and secondary generalized epilepsy (SGE). Recent studies have demonstrated thalamic and cortical fMRI signal changes in association with GSW in idiopathic generalized epilepsy (IGE). We report on a large cohort of patients that included both IGE and SGE, and give a functional interpretation of our findings. Forty-six patients with GSW were studied with EEG–fMRI; 30 with IGE and 16 with SGE. GSW-related BOLD signal changes were seen in 25 of 36 individual patients who had GSW during EEG–fMRI. This was seen in thalamus (60%) and symmetrically in frontal cortex (92%), parietal cortex (76%), and posterior cingulate cortex/precuneus (80%). Thalamic BOLD changes were predominantly positive and cortical changes predominantly negative. Group analysis showed a negative BOLD response in the cortex in the IGE group and to a lesser extent a positive response in thalamus. Thalamic activation was consistent with its known role in GSW, and its detection in individual cases with EEG–fMRI may in part be related to the number and duration of GSW epochs recorded. The spatial distribution of the cortical fMRI response to GSW in both IGE and SGE involved areas of association cortex that are most active during conscious rest. Reduction of activity in these regions during GSW is consistent with the clinical manifestation of absence seizures

Imaging haemodynamic changes related to seizures: comparison of EEG-based general linear model, independent component analysis of fMRI and intracranial EEG

Background: Simultaneous EEG-fMRI can reveal haemodynamic changes associated with epileptic activity which may contribute to understanding seizure onset and propagation. Methods: Nine of 83 patients with focal epilepsy undergoing pre-surgical evaluation had seizures during EEG-fMRI and analysed using three approaches, two based on the general linear model (GLM) and one using independent component analysis (ICA): 1. EEGs were divided into up to three phases: early ictal EEG change, clinical seizure onset and late ictal EEG change and convolved with a canonical haemodynamic response function (HRF) (canonical GLM analysis). 2. Seizures lasting three scans or longer were additionally modelled using a Fourier basis set across the entire event (Fourier GLM analysis). 3. Independent component analysis (ICA) was applied to the fMRI data to identify ictal BOLD patterns without EEG. The results were compared with intracranial EEG. Results: The canonical GLM analysis revealed significant BOLD signal changes associated with seizures on EEG in 7/9 patients, concordant with the seizure onset zone in 4/7. The Fourier GLM analysis revealed changes in BOLD signal corresponding with the results of the canonical analysis in two patients. ICA revealed components spatially concordant with the seizure onset zone in all patients (8/9 confirmed by intracranial EEG). Conclusion: Ictal EEG-fMRI visualises plausible seizure related haemodynamic changes. The GLM approach to analysing EEG-fMRI data reveals localised BOLD changes concordant with the ictal onset zone when scalp EEG reflects seizure onset. ICA provides additional information when scalp EEG does not accurately reflect seizures and may give insight into ictal haemodynamics

EEG correlated functional MRI and postoperative outcome in focal epilepsy

Background: The main challenge in assessing patients with epilepsy for resective surgery is localising seizure onset. Frequently, identification of the irritative and seizure onset zones requires invasive EEG. EEG correlated functional MRI (EEG-fMRI) is a novel imaging technique which may provide localising information with regard to these regions. In patients with focal epilepsy, interictal epileptiform discharge (IED) correlated blood oxygen dependent level (BOLD) signal changes were observed in approximately 50% of patients in whom IEDs are recorded. In 70%, these are concordant with expected seizure onset defined by non-invasive electroclinical information. Assessment of clinical validity requires post-surgical outcome studies which have, to date, been limited to case reports of correlation with intracranial EEG. The value of EEG-fMRI was assessed in patients with focal epilepsy who subsequently underwent epilepsy surgery, and IED correlated fMRI signal changes were related to the resection area and clinical outcome. Methods: Simultaneous EEG-fMRI was recorded in 76 patients undergoing presurgical evaluation and the locations of IED correlated preoperative BOLD signal change were compared with the resected area and postoperative outcome. Results: 21 patients had activations with epileptic activity on EEG-fMRI and 10 underwent surgical resection. Seven of 10 patients were seizure free following surgery and the area of maximal BOLD signal change was concordant with resection in six of seven patients. In the remaining three patients, with reduced seizure frequency post-surgically, areas of significant IED correlated BOLD signal change lay outside the resection. 42 of 55 patients who had no IED related activation underwent resection. Conclusion: These results show the potential value of EEG-fMRI in presurgical evaluation

Morphogenesis at the inflorescence shoot apex of Anagallis arvensis: surface geometry and growth in comparison with the vegetative shoot

Quantitative analysis of geometry and surface growth based on the sequential replica method is used to compare morphogenesis at the shoot apex of Anagallis arvensis in the reproductive and vegetative phases of development. Formation of three types of lateral organs takes place at the Anagallis shoot apical meristem (SAM): vegetative leaf primordia are formed during the vegetative phase and leaf-like bracts and flower primordia during the reproductive phase. Although the shapes of all the three types of primordia are very similar during their early developmental stages, areal growth rates and anisotropy of apex surface growth accompanying formation of leaf or bract primordia are profoundly different from those during formation of flower primordia. This provides an example of different modes of de novo formation of a given shape. Moreover, growth accompanying the formation of the boundary between the SAM and flower primordium is entirely different from growth at the adaxial leaf or bract primordium boundary. In the latter, areal growth rates at the future boundary are the lowest of all the apex surface, while in the former they are relatively very high. The direction of maximal growth rate is latitudinal (along the future boundary) in the case of leaf or bract primordium but meridional (across the boundary) in the case of flower. The replica method does not enable direct analysis of growth in the direction perpendicular to the apex surface (anticlinal direction). Nevertheless, the reconstructed surfaces of consecutive replicas taken from an individual apex allow general directions of SAM surface bulging accompanying primordium formation to be recognized. Precise alignment of consecutive reconstructions shows that the direction of initial bulging during the leaf or bract formation is nearly parallel to the shoot axis (upward bulging), while in the case of flower it is perpendicular to the axis (lateral bulging). In future, such 3D reconstructions can be used to assess displacement velocity fields so that growth in the anticlinal direction can be assessed. In terms of self-perpetuation, the inflorescence SAM of Anagallis differs from the SAM in the vegetative phase in that the centrally located region of slow growth is less distinct in the inflorescence SAM. Moreover, the position of this slowly growing zone with respect to cells is not stable in the course of the meristem ontogeny

Causal hierarchy within the thalamo-cortical network in spike and wave discharges

Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al

“Pure” severe aortic stenosis without concomitant valvular heart diseases:echocardiographic and pathophysiological features

Purpose!#!In echocardiography the severity of aortic stenosis (AS) is defined by effective orifice area (EOA), mean pressure gradient (mPG!##!Methods and results!#!Patients (n = 306) with asymptomatic (n = 133) and symptomatic (n = 173) 'pure' severe AS (mean age 78 ± 9.5 years) defined by indexed EOA < 0.6 cm!##!Conclusion!#!In patients with 'pure' AS according to current guidelines the presence of combined LVH, DD and PAH as accepted pathophysiological sequelae of severe AS cannot be confirmed. Probably, the detection of these secondary cardiac alterations might improve the diagnostic algorithm to avoid overestimation of AS severity

Effects of oxidized low density lipoprotein, lipid mediators and statins on vascular cell interactions

The integrin heterodimer CD11b/CD18 (alpha M beta 2, Mac-1, CR3) expressed on monocytes or polymorphonuclear leukocytes (PMN) is a receptor for iC3b, fibrinogen, heparin, and for intercellular adhesion molecule (ICAM)-1 on endothelium, crucially contributing to vascular cell interactions in inflammation and atherosclerosis. In this report, we summarize our findings on the effects of lipid mediators and lipid-lowering drugs. Exposure of endothelial cells to oxidized low density lipoprotein (oxLDL) induces upregulation of ICAM-1 and increases adhesion of monocytic cells expressing Mac-1. Inhibition experiments show that monocytes use distinct ligands, i.e. ICAM-1 and heparan sulfate proteoglycans for adhesion to oxLDL-treated endothelium. An albumin-transferable oxLDL activity is inhibited by the antioxidant pyrrolidine dithiocarbamate (PDTC), while 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) or lysophosphatidylcholine had no effect, implicating yet unidentified radicals. Sequential adhesive! and signaling events lead to the firm adhesion of rolling PMN on activated and adherent platelets, which may occupy areas of endothelial denudation. Shear resistant arrest of PMN on thrombin-stimulated platelets in flow conditions requires distinct regions of Mac-1, involving its interactions with fibrinogen bound to platelet alpha llb beta 3, and with other platelet ligands. Both arrest and adhesion strengthening under flow are stimulated by platelet-activating factor and leukotriene B4, but not by the chemokine receptor CXCR2. We tested whether Mac-1-dependent monocyte adhesiveness is affected by inhibitors of hydroxy-methylglutaryl-Coenzyme A reductase (statins) which improve morbidity and survival of patients with coronary heart disease. As compared to controls, adhesion of isolated monocytes to endothelium ex vivo was increased in patients with hypercholesterolemia. Treatment with statins decreased total and low density lipoprotein (LDL) cholesterol plasma levels, surface expression of Mac-1, and resulted in a dramatic reduction of Mac,mediated monocyte adhesion to endothelium. The inhibition of monocyte adhesion was reversed by mevalonate but not LDL in vitro,indicating that isoprenoid precursors are crucial for adhesiveness of Mac-1. Such effects may crucially contribute to the clinical benefit of statins, independent of cholesterol-lowering, and may represent a paradigm for novel, anti-inflammatory mechanisms of action by this class of drugs

Making Gestural Interaction Accessible to Visually Impaired People

International audienceAs touch screens become widely spread, making them more accessible to visually impaired people is an important task. Touch displays possess a poor accessibility for visually impaired people. One possibility to make them more accessible without sight is through gestural interaction. Yet, there are still few studies on using gestural interaction for visually impaired people. In this paper we present a comprehensive summary of existing projects investigating accessible gestural interaction. We also highlight the limits of current approaches and propose future working directions. Then, we present the design of an interactive map prototype that includes both a raised-line map overlay and gestural interaction for accessing different types of information (e.g., opening hours, distances). Preliminary results of our project show that basic gestural interaction techniques can be successfully used in interactive maps for visually impaired people