Brain network hypersensitivity underlies pain crises in sickle cell disease.

Sickle cell disease (SCD) is a genetic disorder causing painful and unpredictable Vaso-occlusive crises (VOCs) through blood vessel blockages. In this study, we propose explosive synchronization (ES) as a novel approach to comprehend the hypersensitivity and occurrence of VOCs in the SCD brain network. We hypothesized that the accumulated disruptions in the brain network induced by SCD might lead to strengthened ES and hypersensitivity. We explored ES's relationship with patient reported outcome measures (PROMs) as well as VOCs by analyzing EEG data from 25 SCD patients and 18 matched controls. SCD patients exhibited lower alpha frequency than controls. SCD patients showed correlation between frequency disassortativity (FDA), an ES condition, and three important PROMs. Furthermore, stronger FDA was observed in SCD patients with a higher frequency of VOCs and EEG recording near VOC. We also conducted computational modeling on SCD brain network to study FDA's role in network sensitivity. Our model demonstrated that a stronger FDA could be linked to increased sensitivity and frequency of VOCs. This study establishes connections between SCD pain and the universal network mechanism, ES, offering a strong theoretical foundation. This understanding will aid predicting VOCs and refining pain management for SCD patients.

Effects of clamping end-tidal CO2 on neurofluidic low-frequency oscillations.

In recent years, low-frequency oscillations (LFOs) (0.01-0.1 Hz) have been a subject of interest in resting-state functional magnetic resonance imaging research. They are believed to have many possible driving mechanisms, from both regional and global sources. Internal fluctuations in the partial pressure of CO2 (PCO2) has long been thought of as one of these major driving forces, but its exact contributions compared with other mechanisms have yet to be fully understood. This study examined the effects of end-tidal PCO2 (PetCO2) oscillations on LF cerebral hemodynamics and cerebrospinal fluid (CSF) dynamics under "clamped PetCO2" and "free-breathing" conditions. Under clamped PetCO2, a participant's PetCO2 levels were fixed to their baseline average, whereas PetCO2 was not controlled in free breathing. Under clamped PetCO2, the fractional amplitude of hemodynamic LFOs in the occipital and sensorimotor cortex and temporal lobes were found to be significantly reduced. Additionally, the fractional amplitude of CSF LFOs, measured at the fourth ventricle, was found to be reduced by almost one-half. However, the spatiotemporal distributions of blood and CSF delay times, as measured by cross-correlation in the LF domain, were not significantly altered between conditions. This study demonstrates that, while PCO2 oscillations significantly mediate LFOs, especially those observed in the CSF, other mechanisms are able to maintain LFOs, with high correlation, even in their absence.

Brain network hypersensitivity underlies pain crises in sickle cell disease.

Sickle cell disease (SCD) is a genetic disorder causing blood vessel blockages and painful Vaso-occlusive crises (VOCs). VOCs, characterized by severe pain due to blocked blood flow, are recurrent and unpredictable, posing challenges for preventive strategies. In this study we propose explosive synchronization (ES), a phenomenon characterized by abrupt brain network phase transitions, as a novel approach to address this challenge. We hypothesized that the accumulated disruptions in the brain network induced by SCD might lead to strengthened ES and hypersensitivity. We explored ES's relationship with patient reported outcome measures (PROMs) and VOCs by analyzing EEG data from 25 SCD patients and 18 matched controls. SCD patients exhibited significantly lower alpha wave frequency than controls. SCD patients under painful pressure stimulation showed correlation between frequency disassortativity (FDA), an ES condition, and three important PROMs. Furthermore, patients who had a higher frequency of VOCs in the preceding 12 months presented with stronger FDA. The timing of VOC occurrence relative to EEG recordings was significantly associated to FDA. We also conducted computational modeling on SCD brain network to study FDA's role in network sensitivity. Stronger FDA correlated with higher responsivity and complexity in our model. Simulation under noisy environment showed that higher FDA could be linked to increased occurrence frequency of crisis. This study establishes connections between SCD pain and the universal network mechanism, ES, offering a strong theoretical foundation. This understanding will aid predicting VOCs and refining pain management for SCD patients.

Neurofluid coupling during sleep and wake states.

BACKGROUND: In clinical populations, the movement of cerebrospinal fluid (CSF) during sleep is a growing area of research with potential mechanistic connections in both neurodegenerative (e.g., Alzheimer's Disease) and neurodevelopmental disorders. However, we know relatively little about the processes that influence CSF movement. To inform clinical intervention targets this study assesses the coupling between (a) real-time CSF movement, (b) neuronal-driven movement, and (c) non-neuronal systemic physiology driven movement. METHODS: This study included eight young, healthy volunteers, with concurrently acquired neurofluid dynamics using functional Magnetic Resonance Imaging (MRI), neural activity using Electroencephalography (EEG), and non-neuronal systemic physiology with peripheral functional Near-Infrared Spectroscopy (fNIRS). Neuronal and non-neuronal drivers were assessed temporally; wherein, EEG measured slow wave activity that preceded CSF movement was considered neuronally driven. Similarly, slow wave oscillations (assessed via fNIRS) that coupled with CSF movement were considered non-neuronal systemic physiology driven. RESULTS AND CONCLUSIONS: Our results document neural contributions to CSF movement were only present during light NREM sleep but low-frequency non-neuronal oscillations were strongly coupled with CSF movement in all assessed states - awake, NREM-1, NREM-2. The clinical/research implications of these findings are two-fold. First, neuronal-driven oscillations contribute to CSF movement outside of deep sleep (NREM-3); therefore, interventions aimed at increasing CSF movement may yield meaningful increases with the promotion of NREM sleep more generally - a focus on NREM S3 may not be needed. Second, non-neuronal systemic oscillations contribute across wake and sleep stages; therefore, interventions may increase CSF movement by manipulating systemic physiology.

Whole body measurements using near-infrared spectroscopy in a rat spinal cord contusion injury model.

Background: Spinal cord injuries cause great damage to the central nervous system as well as the peripheral vasculature. While treatments for spinal cord injury typically focus on the spine itself, improvements in the function of the peripheral vasculature after spinal cord injury have shown to improve overall neurological recovery.Objective: This study focused on the use of near-infrared spectroscopy (NIRS) as a mode to monitor cerebral and peripheral vascular condition non-invasively during the recovery process.Design: Animal research study.Methods: Rats underwent spinal contusion or sham injury and relative concentrations of de-/oxyhemoglobin (Δ[HbO]/Δ[Hb]) over time were measured over the cerebral, spinal, and pedal regions via NIRS. Correlational relationships across the body were determined. Rats received 1 NIRS measurement before injury and 3 after injury: 4, 7, and 14 days post.Results: Correlational relationships between signals across the body, between animals with and without spinal cord injury, indicate that NIRS was able to detect patterns of vascular change in the spine and the periphery occurring secondary to spinal cord injury and evolving during subsequent recovery. Additionally, NIRS determined an overall correlational decrease within the central nervous system, between spinal and cerebral measurements.Conclusion: NIRS was able to closely reflect physiologic changes in the rat during recovery, demonstrating a promising method to monitor whole body hemodynamics after spinal cord injury.

Human CSF movement influenced by vascular low frequency oscillations and respiration.

Cerebrospinal fluid (CSF) movement through the pathways within the central nervous system is of high significance for maintaining normal brain health and function. Low frequency hemodynamics and respiration have been shown to drive CSF in humans independently. Here, we hypothesize that CSF movement may be driven simultaneously (and in synchrony) by both mechanisms and study their independent and coupled effects on CSF movement using novel neck fMRI scans. Caudad CSF movement at the fourth ventricle and hemodynamics of the major neck blood vessels (internal carotid arteries and internal jugular veins) was measured from 11 young, healthy volunteers using novel neck fMRI scans with simultaneous measurement of respiration. Two distinct models of CSF movement (1. Low-frequency hemodynamics and 2. Respiration) and possible coupling between them were investigated. We show that the dynamics of brain fluids can be assessed from the neck by studying the interrelationships between major neck blood vessels and the CSF movement in the fourth ventricle. We also demonstrate that there exists a cross-frequency coupling between these two separable mechanisms. The human CSF system can respond to multiple coupled physiological forces at the same time. This information may help inform the pathological mechanisms behind CSF movement-related disorders.

Monitoring anesthesia using simultaneous functional Near Infrared Spectroscopy and Electroencephalography.

OBJECTIVE: This study aims to understand the neural and hemodynamic responses during general anesthesia in order to develop a comprehensive multimodal anesthesia depth monitor using simultaneous functional Near Infrared Spectroscopy (fNIRS) and Electroencephalogram (EEG). METHODS: 37 adults and 17 children were monitored with simultaneous fNIRS and EEG, during the complete general anesthesia process. The coupling of fNIRS signals with neuronal signals (EEG) was calculated. Measures of complexity (sample entropy) and phase difference were also quantified from fNIRS signals to identify unique fNIRS based biomarkers of general anesthesia. RESULTS: A significant decrease in the complexity and power of fNIRS signals characterize the anesthesia maintenance phase. Furthermore, responses to anesthesia vary between adults and children in terms of neurovascular coupling and frontal EEG alpha power. CONCLUSIONS: This study shows that fNIRS signals could reliably quantify the underlying neuronal activity under general anesthesia and clearly distinguish the different phases throughout the procedure in adults and children (with less accuracy). SIGNIFICANCE: A multimodal approach incorporating the specific differences between age groups, provides a reliable measure of anesthesia depth.