Hemodynamic correlates of spontaneous neural activity measured by human whole-head resting state EEG + fNIRS

The brains of awake, resting human subjects display spontaneously occurring neural activity patterns whose magnitude is typically many times greater than those triggered by cognitive or perceptual performance. Such resting state (RS) activity is thought to reflect the functional organization of the brain. In addition, both evoked and RS activation affect local cerebral hemodynamic properties through processes collectively referred to as neurovascular coupling. This is a major topic of interest due to its relationship with pathological conditions that include hypertension, stroke, subarachnoid hemorrhage, and traumatic brain injury. Its investigation calls for an ability to track both the neural and vascular aspects of brain function. We used scalp electroenc ephalography (EEG) which provided a measure of the electrical potentials generated by cortical postsynaptic currents. Simultaneously we utilized functional near-infrared spectroscopy (NIRS) to continuously monitor hemoglobin concentration changes in superficial cortical layers. The multi-modal signal from 18 healthy adult subjects allowed us to investigate the association of neural activity in a range of frequencies over the whole-head to local changes in hemoglobin concentrations. Our results verified the delayed alpha (8-16 Hz) modulation of hemodynamics in posterior areas known from the literature. They also indicated strong beta (16-32 Hz) modulation of hemodynamics. Analysis revealed, however, that beta modulation was likely generated by the alpha-beta coupling in EEG. Signals from the inferior electrode sites were dominated by scalp muscle related activity. Our study aimed to characterize the phenomena related to neurovascular coupling observable by practical, cost-effective, and non-invasive multi-modal techniques

Due to intravascular multiple sequential scattering, Diffuse Correlation Spectroscopy of tissue primarily measures relative red blood cell motion within vessels

We suggest that Diffuse Correlation Spectroscopy (DCS) measurements of tissue blood flow primarily probe relative red blood cell (RBC) motion, due to the occurrence of multiple sequential scattering events within blood vessels. The magnitude of RBC shear-induced diffusion is known to correlate with flow velocity, explaining previous reports of linear scaling of the DCS “blood flow index” with tissue perfusion despite the observed diffusion-like auto-correlation decay. Further, by modeling RBC mean square displacement using a formulation that captures the transition from ballistic to diffusive motion, we improve the fit to experimental data and recover effective diffusion coefficients and velocity de-correlation time scales in the range expected from previous blood rheology studies

Simulation of Preterm Neonatal Brain Metabolism During Functional Neuronal Activation Using a Computational Model

We present a computational model of metabolism in the preterm neonatal brain. The model has the capacity to mimic haemodynamic and metabolic changes during functional activation and simulate functional near-infrared spectroscopy (fNIRS) data. As an initial test of the model's efficacy, we simulate data obtained from published studies investigating functional activity in preterm neonates. In addition we simulated recently collected data from preterm neonates during visual activation. The model is well able to predict the haemodynamic and metabolic changes from these observations. In particular, we found that changes in cerebral blood flow and blood pressure may account for the observed variability of the magnitude and sign of stimulus-evoked haemodynamic changes reported in preterm infants

Assessment of the frequency-domain multi-distance method to evaluate the brain optical properties: Monte Carlo simulations from neonate to adult

The near infrared spectroscopy (NIRS) frequency-domain multi-distance (FD-MD) method allows for the estimation of optical properties in biological tissue using the phase and intensity of radiofrequency modulated light at different source-detector separations. In this study, we evaluated the accuracy of this method to retrieve the absorption coefficient of the brain at different ages. Synthetic measurements were generated with Monte Carlo simulations in magnetic resonance imaging (MRI)-based heterogeneous head models for four ages: newborn, 6 and 12 month old infants, and adult. For each age, we determined the optimal set of source-detector separations and estimated the corresponding errors. Errors arise from different origins: methodological (FD-MD) and anatomical (curvature, head size and contamination by extra-cerebral tissues). We found that the brain optical absorption could be retrieved with an error between 8–24% in neonates and infants, while the error increased to 19–44% in adults over all source-detector distances. The dominant contribution to the error was found to be the head curvature in neonates and infants, and the extra-cerebral tissues in adults

Calibration of diffuse correlation spectroscopy with a time-resolved near-infrared technique to yield absolute cerebral blood flow measurements

A primary focus of neurointensive care is the prevention of secondary brain injury, mainly caused by ischemia. A noninvasive bedside technique for continuous monitoring of cerebral blood flow (CBF) could improve patient management by detecting ischemia before brain injury occurs. A promising technique for this purpose is diffuse correlation spectroscopy (DCS) since it can continuously monitor relative perfusion changes in deep tissue. In this study, DCS was combined with a time-resolved near-infrared technique (TR-NIR) that can directly measure CBF using indocyanine green as a flow tracer. With this combination, the TR-NIR technique can be used to convert DCS data into absolute CBF measurements. The agreement between the two techniques was assessed by concurrent measurements of CBF changes in piglets. A strong correlation between CBF changes measured by TR-NIR and changes in the scaled diffusion coefficient measured by DCS was observed (R2 = 0.93) with a slope of 1.05 ± 0.06 and an intercept of 6.4 ± 4.3% (mean ± standard error)

Brain Cortical Mapping by Simultaneous Recording of Functional Near Infrared Spectroscopy and Electroencephalograms from the Whole Brain During Right Median Nerve Stimulation

To investigate relationships between hemodynamic responses and neural activities in the somatosensory cortices, hemodynamic responses by near infrared spectroscopy (NIRS) and electroencephalograms (EEGs) were recorded simultaneously while subjects received electrical stimulation in the right median nerve. The statistical significance of the hemodynamic responses was evaluated by a general linear model (GLM) with the boxcar design matrix convoluted with Gaussian function. The resulting NIRS and EEGs data were stereotaxically superimposed on the reconstructed brain of each subject. The NIRS data indicated that changes in oxy-hemoglobin concentration increased at the contralateral primary somatosensory (SI) area; responses then spread to the more posterior and ipsilateral somatosensory areas. The EEG data indicated that positive somatosensory evoked potentials peaking at 22 ms latency (P22) were recorded from the contralateral SI area. Comparison of these two sets of data indicated that the distance between the dipoles of P22 and NIRS channels with maximum hemodynamic responses was less than 10 mm, and that the two topographical maps of hemodynamic responses and current source density of P22 were significantly correlated. Furthermore, when onset of the boxcar function was delayed 5–15 s (onset delay), hemodynamic responses in the bilateral parietal association cortices posterior to the SI were more strongly correlated to electrical stimulation. This suggests that GLM analysis with onset delay could reveal the temporal ordering of neural activation in the hierarchical somatosensory pathway, consistent with the neurophysiological data. The present results suggest that simultaneous NIRS and EEG recording is useful for correlating hemodynamic responses to neural activity

Optical imaging in vivo with a focus on paediatric disease: technical progress, current preclinical and clinical applications and future perspectives

To obtain information on the occurrence and location of molecular events as well as to track target-specific probes such as antibodies or peptides, drugs or even cells non-invasively over time, optical imaging (OI) technologies are increasingly applied. Although OI strongly contributes to the advances made in preclinical research, it is so far, with the exception of optical coherence tomography (OCT), only very sparingly applied in clinical settings. Nevertheless, as OI technologies evolve and improve continuously and represent relatively inexpensive and harmful methods, their implementation as clinical tools for the assessment of children disease is increasing. This review focuses on the current preclinical and clinical applications as well as on the future potential of OI in the clinical routine. Herein, we summarize the development of different fluorescence and bioluminescence imaging techniques for microscopic and macroscopic visualization of microstructures and biological processes. In addition, we discuss advantages and limitations of optical probes with distinct mechanisms of target-detection as well as of different bioluminescent reporter systems. Particular attention has been given to the use of near-infrared (NIR) fluorescent probes enabling observation of molecular events in deeper tissue

Être touché : une action immobile, fondation de notre développement

National audienceAt the start of my research, touch was not yet my object of study. It was a means of eliciting neuronal activity in babies' brains, the characteristics of which I could then study. As my work on brain development progressed, it became clear to me that this sense, neglected by neuroscientists, held untapped potential, not only for understanding how the newborn brain makes sense of its environment, but also for elucidating the pathological mechanisms of neurodevelopmental disorders (which include autism spectrum disorders, attention deficit disorders with or without hyperactivity, and dys learning disorders). In this chapter, through my scientific journey, I set out to develop this potential of the tactile sense to understand how our brain functions or dysfunctions at the beginning of life.Au début de mes travaux de Recherche, le toucher n’était pas encore mon objet d’étude. Il était un moyen de susciter dans le cerveau des bébés une activité neuronale dont je pourrais ensuite étudier les caractéristiques. Au fur et à mesure de la progression de mes travaux sur le développement cérébral, il m’apparut que ce sens négligé des neuroscientifiques recelait un potentiel inexploité, non seulement pour comprendre comment le cerveau du nouveau-né donne du sens à son environnement, mais aussi pour élucider les mécanismes pathologiques des troubles du neurodéveloppement (qui comprennent notamment les troubles du spectre de l’autisme, les troubles de l’attention avec ou sans hyperactivité, ou les troubles des apprentissages dits « dys »). Dans ce chapitre, à travers mon cheminement scientifique, j’entreprends de développer ce potentiel du sens tactile pour comprendre comment notre cerveau fonctionne ou dysfonctionne au début de la vie