Independent component analysis of interictal fMRI in focal epilepsy: comparison with general linear model-based EEG-correlated fMRI

The general linear model (GLM) has been used to analyze simultaneous EEG–fMRI to reveal BOLD changes linked to interictal epileptic discharges (IED) identified on scalp EEG. This approach is ineffective when IED are not evident in the EEG. Data-driven fMRI analysis techniques that do not require an EEG derived model may offer a solution in these circumstances. We compared the findings of independent components analysis (ICA) and EEG-based GLM analyses of fMRI data from eight patients with focal epilepsy. Spatial ICA was used to extract independent components (IC) which were automatically classified as either BOLD-related, motion artefacts, EPI-susceptibility artefacts, large blood vessels, noise at high spatial or temporal frequency. The classifier reduced the number of candidate IC by 78%, with an average of 16 BOLD-related IC. Concordance between the ICA and GLM-derived results was assessed based on spatio-temporal criteria. In each patient, one of the IC satisfied the criteria to correspond to IED-based GLM result. The remaining IC were consistent with BOLD patterns of spontaneous brain activity and may include epileptic activity that was not evident on the scalp EEG. In conclusion, ICA of fMRI is capable of revealing areas of epileptic activity in patients with focal epilepsy and may be useful for the analysis of EEG–fMRI data in which abnormalities are not apparent on scalp EEG

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

The influence of statins on the free intracellular calcium concentration in human umbilical vein endothelial cells

BACKGROUND: Statins are cholesterol-lowering drugs that are widely used to reduce the risk of cardiac infarction. Their beneficial clinical effects, however, are not restricted to their influence on cholesterol production. As several studies have shown that they have a potency of relaxing blood vessels. METHODS: We measured the effects of statins on the intracellular free calcium concentration ([Ca(2+)](i)) in human umbilical vein endothelial cells (HUVEC) after acute application and 24-h-preincubation of statins. RESULTS: Incubation of the cells for 24 h with cerivastatin or fluvastatin significantly increased the resting [Ca(2+)](i). For cerivastatin this effect manifested at a concentration of 1 μM. Increase of resting [Ca(2+)](i )in the presence of cerivastatin also occurred when the nitric oxide synthase was inhibited. Transient Ca(2+ )release induced by histamine was not affected. CONCLUSIONS: The increase of resting [Ca(2+)](i )after incubation with cerivastatin or fluvastatin may provide an explanation for the direct effects of statins on the endothelial-dependent vasodilatation and restoration of endothelial activity in vivo

Large-scale signatures of unconsciousness are consistent with a departure from critical dynamics

Loss of cortical integration and changes in the dynamics of electrophysiological brain signals characterize the transition from wakefulness towards unconsciousness. The common mechanism underlying these observations remains unknown. In this study we arrive at a basic model, which explains these empirical observations based on the theory of phase transitions in complex systems. We studied the link between spatial and temporal correlations of large-scale brain activity recorded with functional magnetic resonance imaging during wakefulness, propofol-induced sedation and loss of consciousness, as well as during the subsequent recovery. We observed that during unconsciousness activity in frontal and thalamic regions exhibited a reduction of long-range temporal correlations and a departure of functional connectivity from the underlying anatomical constraints. These changes in dynamics and anatomy-function coupling were correlated across participants, suggesting that temporal complexity and an efficient exploration of anatomical connectivity are inter-related phenomena. A model of a system exhibiting a phase transition reproduced our findings, as well as the diminished sensitivity of the cortex to external perturbations during unconsciousness. This theoretical framework unifies different empirical observations about brain activity during unconsciousness and predicts that the principles we identified are universal and independent of the causes behind loss of awareness.Comment: to appear in Journal of the Royal Society Interfac

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

Hidden sodium in effervescent-tablet dietary supplements and over-the-counter drugs: a comparative cross-sectional study

Objective Dietary sodium intake represents a risk factor for cardiovascular disease and mortality. The study sought to analyse the sodium content of effervescent dietary supplements and drugs in Germany and the USA. Design Comparative cross-sectional study. Setting and methods The sodium content of 39 dietary supplement effervescent tablets available in Germany was measured in May and June 2022 using optical emission spectrometry with inductively coupled argon plasma. The sodium content of 33 common pharmacyonly effervescent tablets (over-the-counter (OTC) drugs) in Germany was obtained from the summary of product characteristics. We compared the sodium content of the measured German dietary supplement effervescent tablets to that of 51 dietary supplement effervescent tablets available in the USA (data: National Institutes of Health’s Dietary Supplement Label Database). Results The measured sodium content in the German dietary supplements was 283.9±122.6 mg sodium/tablet, equivalent to 14±6% of the maximum recommended daily sodium intake (MRDSI). Vitamin products had the highest (378.3±112.8 mg, 19±6% of MRDSI), and calcium products had the lowest mean sodium content (170.4±113.2 mg, 9±6% of MRDSI). Vitamin products contained significantly more sodium than magnesium (378.3 mg vs 232.7 mg; p=0.004), calcium (378.3 mg vs 170.4 mg; p=0.006) and mineral products (378.3 mg vs 191.6 mg; p=0.048). The sodium content measured in products available in Germany was higher when compared with the declared sodium content on the label of the products sold in the USA (283.9 mg vs 190.0 mg; p<0.001). The median summary of product characteristics-declared sodium content of a single dose of the German OTC drugs was 157.0 mg (IQR: 98.9–417.3 mg); pain/common cold drugs contained the most sodium (median: 452.1 mg; IQR: 351.3–474.0 mg). Conclusion Effervescent tablets of nutritional supplements and OTC drugs contain high amounts of sodium, which often is not disclosed

Epileptic networks in focal cortical dysplasia revealed using electroencephalography-functional magnetic resonance imaging.

Surgical treatment of focal epilepsy in patients with focal cortical dysplasia (FCD) is most successful if all epileptogenic tissue is resected. This may not be evident on structural magnetic resonance imaging (MRI), so intracranial electroencephalography (icEEG) is needed to delineate the seizure onset zone (SOZ). EEG-functional MRI (fMRI) can reveal interictal discharge (IED)-related hemodynamic changes in the irritative zone (IZ). We assessed the value of EEG-fMRI in patients with FCD-associated focal epilepsy by examining the relationship between IED-related hemodynamic changes, icEEG findings, and postoperative outcome

Heart failure is independently associated with white matter lesions: Insights from the population-based LIFE-Adult Study

Aims: White matter lesions (WML) are common structural alterations in the white matter of the brain and their prevalence increases with age. They are associated with cerebral ischaemia and cognitive dysfunction. Patients with heart failure (HF) are at risk for cognitive decline. We hypothesized that the presence and duration of HF are associated with WML. Methods and results: The LIFE-Adult Study is a population-based study of 10 000 residents of Leipzig, Germany. WML were quantitated in 2490 participants who additionally underwent cerebral MRI using the Fazekas score. Mean age was 64 years, and 46% were female; 2156 (86.6%) subjects had Fazekas score of 0-1, and 334 (13.4%) had Fazekas score of 2-3. Thirty participants had a medical history of HF, 1019 had hypertension, and 51 had a history of stroke. Median left ventricular ejection fraction of the participants with HF was 57% (interquartile ranges 54-62). Age, troponin T, NT-proBNP, body mass index, history of acute myocardial infarction, stroke, HF, and diabetes were positively associated with WML in univariate analysis. On multivariate analysis, age, hypertension, stroke, and HF were independently associated with WML. The odd's ratio for the association of WML (Fazekas 2-3) with HF was 2.8 (95% CI 1.2-6.5; P = 0.019). WML increased with longer duration of HF (P = 0.036 for trend). Conclusions: In addition to age, hypertension, and stroke, the prevalence and duration of HF are independently associated with WML. This observation sets the stage to investigate the prognostic value of WML in HF and the impact of HF therapies on WML