Hemodynamic Correlates of Fluctuations in Neuronal Excitability: A Simultaneous Paired Associative Stimulation (PAS) and functional Near Infra-Red Spectroscopy (fNIRS) Study

Background: The relationship between task-related hemodynamic activity and brain excitability is poorly understood in humans as it is technically challenging to combine simultaneously non-invasive brain stimulation and neuroimaging modalities. Cortical excitability corresponds to the readiness to become active and as such it may be linked to metabolic demand. Hypotheses: Cortical excitability and hemodynamic activity are positively linked so that increases in hemodynamic activity correspond to increases in excitability and vice-versa. Methods: Fluctuations of excitability and hemodynamic activity were investigated via simultaneous Transcranial Magnetic Stimulation (TMS) and functional Near Infrared Spectroscopy (fNIRS). Sixteen healthy subjects participated in a sham-controlled, pseudorandomized, counterbalanced study with PAS (PAS10/PAS25/Sham) on the right primary motor cortex (M1). The relationship between M1 excitability (Motor Evoked Potentials, MEP) and hemodynamic responses to finger tapping reconstructed via personalized fNIRS was assessed. Results: Hemodynamic activity exhibited a significant correlation with cortical excitability: increased HbO and HbR (absolute amplitude) corresponded to increased excitability and vice-versa (r=0.25; p=0.03 and r=0.16; p=0.17, respectively). The effect of PAS on excitability and hemodynamic activity showed a trend of positive correlation: correlation of MEP ratios (post-PAS/pre-PAS) with HbO and HbR ratios (r=0.19, p=0.29; r=0.18, p=0.30, respectively). Conclusions: TMS-fNIRS is a suitable technique for simultaneous investigation of excitability and hemodynamic responses and indicates a relationship between these two cortical properties. PAS effect is not limited to cortical excitability but also impacts hemodynamic processes. These findings have an impact on the application of neuromodulatory interventions in patients with neuropsychiatric disorders.

Abstract WMP70: Increased Left Atrial Appendage Density on Computerized Tomography is Associated With Cardioembolic Stroke

Background and Purpose: While studies have stratified cardioembolic (CE) stroke risk by qualitative left atrial appendage (LAA) morphology and biomarkers of atrial dysfunction, the quantitative properties that underlie these observations are not well established. Accordingly, we hypothesized that LAA volume and contrast density (attenuation) on computerized tomography (CT) may capture the structural and hemodynamic processes that underlie CE stroke risk. Methods: Data were collected from a single center prospective ischemic stroke database over 18 months and included all patients with ischemic stroke who previously underwent routine, non-gated, contrast enhanced thin-slice (≤2.5 mm) chest CT. Stroke subtype was determined based on the inpatient diagnostic evaluation. LAA volume and attenuation were determined from CT studies performed for various clinically appropriate indications. Univariate and multivariable analyses were performed to determine factors associated with ischemic stroke subtype, including known risk factors and biomarkers, as well as LAA density and morphologic measures. Results: We identified 311 patients with a qualifying chest CT (119 CE subtype, 109 ESUS, and 83 non-CE). In unadjusted models, there was an association between CE (vs. non-CE) stroke subtype and LAA volume (OR per mL increase 1.15, 95% CI 1.07-1.24, p<0.001) and LAA density (4 th quartile vs. 1 st quartile; OR 2.95, 95% CI 1.28-6.80, p=0.011), but not with ESUS (vs. non-CE) subtype. In adjusted models, only the association between LAA density and CE stroke subtype persisted (adjusted OR 3.71, 95% CI 1.37-10.08, p=0.010). Conclusion: The LAA volume and density values on chest CT are associated with CE stroke subtype but not ESUS subtype. Patients with ESUS and increased LAA volume or attenuation may be a subgroup where the mechanism is cardioembolic and anticoagulation can be tested for secondary stroke prevention.

Adaptative dynamics of blood rheological properties in the emergency medical aid personnel

Цель исследования: изучить адаптационные механизмы изменения гемодинамических и вегетативных показателей у медицинских работников станции скорой медицинской помощи в ответ на стрессорные факторы. Материалы и методы. Обследовано 35 работников станции скорой медицинской помощи до и после суточного дежурства. Для оценки характеристик микроциркуляторного кровотока применяли метод динамического рассеяния света от эритроцитов с помощью mDLS датчика (miniaturized Dynamic Light Scattering) от ElfiTech (Rehovot, Israel). Сигнал интегрируется в виде 3 гемодинамических индексов (HI Hemodynamic Index). Низкочастотный индекс (HI1) определяется медленным межслоевым взаимодействием, высокочастотная область (HI3) характеризует быстрые процессы сдвига слоев, HI2 занимает промежуточное положение (прекапиллярный и капиллярный кровоток). Колебания RR интервалов оценивали методом вариационной пульсометрии (Heart Rate Variability HRV). Для повышения чувствительности введена дополнительная стрессовая нагрузка тест Струпа. Результаты. В состоянии покоя после дежурства в компоненте НI1 отмечали значимое уменьшение. Под действием Струптеста динамика расширяется и захватывает нормированный индекс RHI2, который уменьшается, а также показатель RHI3, значимо возрастающий. После дежурства выявляли значимо более низкие показатели частоты сердечных сокращений (HR). Одновременно наблюдали увеличенные показатели общей вариабельности сердечного ритма (SDNN, RMSSD). Значительно возрастали частотные компоненты (LF и HF), однако их взаимоотношение не менялось. Повышался нелинейный парасимпатический индекс (CVI). Заключение. Экстренная суточная нагрузка на врача приводит к значимым изменениям в гемодинамических процессах, но выявляются они только при нанесении дополнительной кратковременной нагрузки, что демонстрирует снижение адаптационных запасов. Со стороны вегетативного баланса значимые различия до и после дежурства отмечаются уже в покое. Aim: to investigate the adaptation mechanisms of changes in hemodynamic and autonomic indexes of the medical workers provide urgent medical assistance in response to stress factors. Materials and methods. We examined 35 ambulance station workers before and after daily duty. The characteristics of the microcirculatory blood flow were assessed by the method of dynamic light scattering from red blood cells using ElfiTech (Rehovot, Israel) mDLS sensor (miniaturized Dynamic Light Scattering). The signal is integrated in the form of 3 hemodynamic indices (HI Hemodynamic Index). The lowfrequency index (HI1) is determined by the slow interlayer interaction, the highfrequency region (HI3) characterizes the fast processes of layer shift. HI2 occupies an intermediate position (precapillary and capillary blood flow). Fluctuations RR intervals were estimated by the method of heart rate variability (HRV). To increase the sensitivity, additional stress load was introduced, that was created using the Stroop test. Results. At rest after duty, a significant decrease is noted in the HI1 component. Under the influence of the Strooptest, the dynamics of changes expands and captures the normalized RHI2 index that decreases, and also the RHI3 indicator that significantly increases. After duty, significantly lower heart rate (HR) was detected. At the same time, increased rates of overall heart rate variability (SDNN, RMSSD) were observed. The frequency components (LF, HF) increased significantly, but their ratio did not change. The nonlinear parasympathetic index (CVI) increased. Conclusion. Emergency 24 hour load on the doctor leads to significant changes in hemodynamic processes, but they are detected only when additional shortterm load is applied, that demonstrates a decrease of adaptive reserves. Significant differences in vegetal balance before and after duty are noted already at rest.

Reduced blood oxygenation level dependent connectivity is related to hypoperfusion in Alzheimer’s disease

Functional connectivity of blood oxygenation level dependent signal fluctuations (BOLD-FC) is decreased in Alzheimer’s disease (AD), and suggested to reflect reduced coherence in neural population activity; however, as both neuronal and vascular-hemodynamic processes underlie BOLD signals, impaired perfusion might also contribute to reduced BOLD-FC; 42 AD patients and 27 controls underwent simultaneous PET/MR imaging. Resting-state functional MRI assessed BOLD co-activity to quantify BOLD-FC, pulsed arterial spin labeling (pASL) assessed cerebral blood flow (CBF) as proxy for vascular hemodynamics, and 18F-fluorodeoxyglucose PET assessed glucose metabolism (GluMet) to index neuronal activity. Patients’ BOLD-FC, CBF, and GluMet were reduced within the same precuneal parietal regions. BOLD-FC was positively associated with mean CBF, specifically in patients and controlled for GluMet levels, suggesting that BOLD-FC reductions correlate with pASL-derived hypoperfusion in AD, independently from 18F-fluorodeoxyglucose PET-derived hypometabolism. Data indicate that impaired vascular hemodynamic processes contribute to reduced BOLD connectivity in AD.

Evaluation of reconstruction parameters of electrical impedance tomography on aorta detection during saline bolus injection

An accurate detection of anatomical structures in electrical impedance tomography (EIT) is still at an early stage. Aorta detection in EIT is of special interest, since it would favor non-invasive assessment of hemodynamic processes in the body. Here, diverse EIT reconstruction parameters of the GREIT algorithm were systematically evaluated to detect the aorta after saline bolus injection in apnea. True aorta position and size were taken from computed tomography (CT). A comparison with CT showed that the smallest error for aorta displacement was attained for noise figure nf = 0.7, weighting radius rw = 0.15, and target size ts = 0.01. The spatial extension of the aorta was most precise for nf = 0.7, rw = 0.25, and ts = 0.07. Detection accuracy (F1-score) was highest with nf = 0.6, rw = 0.15, and ts = 0.04. This work provides algorithm-related evidence for potentially accurate aorta detection in EIT after injection of a saline bolus.

Spontaneous EEG-Functional MRI in Mesial Temporal Lobe Epilepsy: Implications for the Neural Correlates of Consciousness

The combination of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has been shown to have great potential for providing a greater understanding of normal and diseased states in both human and animal studies. Simultaneous EEG-fMRI is particularly well suited for the study of epilepsy in that it may reveal the neurobiology of ictal and interictal epileptiform discharges and noninvasively localize epileptogenic foci. Spontaneous, coherent fluctuations of neuronal activity and the coupled hemodynamic responses have also been shown to provide diagnostic markers of disease, extending our understanding of intrinsically structured ongoing brain activity. Following a short summary of the hardware and software development of simultaneous EEG-fMRI, this paper reviews a unified framework of integrating neuronal and hemodynamic processes during epileptic seizures and discusses the role and impact of spontaneous activity in the mesial temporal lobe epilepsies with particular emphasis on the neural and physiological correlates of consciousness.

Impact of Arginase II on CBF in Experimental Cortical Impact Injury in Mice Using MRI

Traumatic brain injury (TBI) results in reduced cerebral blood flow (CBF) and low levels of the vasodilator nitric oxide (NO) may be involved. Arginase II negatively regulates NO production through competition for the substrate L-arginine. We determined whether arginase II-deficient (ArgII−/−) mice would show improved CBF after TBI through arterial spin-labeling magnetic resonance imaging (MRI). The ArgII−/− mice exhibit a significantly improved CBF recovery after trauma in the perilesional brain ( P=0.0015) and in various other brain regions. In conclusion, arginase II deficiency leads to a better CBF recovery after TBI and implicates arginase II in hemodynamic processes.