Anesthesia blunts carbon dioxide effects on glymphatic cerebrospinal fluid dynamics in mechanically ventilated rats.

BACKGROUND: Impaired glymphatic clearance of cerebral metabolic products and fluids contribute to traumatic and ischemic brain oedema and neurodegeneration in preclinical models. Glymphatic perivascular cerebrospinal fluid (CSF) flow varies between anesthetics possibly due to changes in vasomotor tone and thereby in the dynamics of the periarterial CSF-containing space. To better understand the influence of anesthetics and carbon dioxide levels on CSF dynamics, we studied the effect of periarterial size modulation on CSF distribution by changing blood carbon dioxide levels and anesthetic regimens with opposing vasomotor influences - vasoconstrictive ketamine-dexmedetomidine (K/DEX) and vasodilatory isoflurane (ISO). METHODS: End-tidal carbon dioxide (EtCO2) was modulated with either supplemental inhaled carbon dioxide to reach hypercapnia (EtCO2 80 mmHg) or hyperventilation (EtCO2 20 mmHg) in tracheostomized and anesthetized female rats. Distribution of intracisternally infused radiolabeled CSF tracer 111In-diethylamine pentaacetate was assessed for 86 minutes in 1) normoventilated (EtCO2 40 mmHg) K/DEX, 2) normoventilated ISO, 3) hypercapnic K/DEX, and 4) hyperventilated ISO groups using dynamic whole-body single-photon emission tomography. CSF volume changes were assessed with magnetic resonance imaging. RESULTS: Under normoventilation, cortical CSF tracer perfusion, perivascular space size around middle cerebral arteries (MCAs), and intracranial CSF volume were higher under K/DEX compared with ISO (cortical Cmax ratio 2.33 [95% CI 1.35 to 4.04], perivascular size ratio 2.20 [95% CI 1.09 to 4.45], and intracranial CSF volume ratio 1.90 [95% CI 1.33 to 2.71]). Under ISO, tracer was directed to systemic circulation. Under K/DEX, the intracranial tracer distribution and CSF volume were uninfluenced by hypercapnia compared with normoventilation. Intracranial CSF tracer distribution was unaffected by hyperventilation under ISO despite a 28% increase in CSF volume around MCAs. CONCLUSIONS: K/DEX and ISO overrode carbon dioxide as a regulator of CSF flow. K/DEX could be used to preserve CSF space and dynamics in hypercapnia whereas hyperventilation was insufficient to increase cerebral CSF perfusion under ISO.

The state of brain activity modulates cerebrospinal fluid transport.

Earlier studies based on 2-photon imaging have shown that glymphatic cerebrospinal fluid (CSF) transport is regulated by the sleep-wake cycle. To examine this association, we used 3DISCO whole-body tissue clearing to map CSF tracer distribution in awake, sleeping and ketamine-xylazine anesthetized mice. The results of our analysis showed that CSF tracers entered the brain to a significantly larger extent in natural sleep or ketamine-xylazine anesthesia than in wakefulness. Furthermore, awake mice showed preferential transport of CSF tracers in the rostro-caudal direction towards the cervical and spinal cord lymphatic vessels, and hence to venous circulation and excretion by the kidneys. The study extends the current literature by showing that CSF dynamics on the whole-body scale is controlled by the state of brain activity.

Intellectually able adults with autism spectrum disorder show typical resting-state EEG activity.

There is broad interest in discovering quantifiable physiological biomarkers for psychiatric disorders to aid diagnostic assessment. However, finding biomarkers for autism spectrum disorder (ASD) has proven particularly difficult, partly due to high heterogeneity. Here, we recorded five minutes eyes-closed rest electroencephalography (EEG) from 186 adults (51% with ASD and 49% without ASD) and investigated the potential of EEG biomarkers to classify ASD using three conventional machine learning models with two-layer cross-validation. Comprehensive characterization of spectral, temporal and spatial dimensions of source-modelled EEG resulted in 3443 biomarkers per recording. We found no significant group-mean or group-variance differences for any of the EEG features. Interestingly, we obtained validation accuracies above 80%; however, the best machine learning model merely distinguished ASD from the non-autistic comparison group with a mean balanced test accuracy of 56% on the entirely unseen test set. The large drop in model performance between validation and testing, stress the importance of rigorous model evaluation, and further highlights the high heterogeneity in ASD. Overall, the lack of significant differences and weak classification indicates that, at the group level, intellectually able adults with ASD show remarkably typical resting-state EEG.

Resting-state EEG functional connectivity predicts post-traumatic stress disorder subtypes in veterans.

Objective. Post-traumatic stress disorder (PTSD) is highly heterogeneous, and identification of quantifiable biomarkers that could pave the way for targeted treatment remains a challenge. Most previous electroencephalography (EEG) studies on PTSD have been limited to specific handpicked features, and their findings have been highly variable and inconsistent. Therefore, to disentangle the role of promising EEG biomarkers, we developed a machine learning framework to investigate a wide range of commonly used EEG biomarkers in order to identify which features or combinations of features are capable of characterizing PTSD and potential subtypes.Approach. We recorded 5 min of eyes-closed and 5 min of eyes-open resting-state EEG from 202 combat-exposed veterans (53% with probable PTSD and 47% combat-exposed controls). Multiple spectral, temporal, and connectivity features were computed and logistic regression, random forest, and support vector machines with feature selection methods were employed to classify PTSD. To obtain robust results, we performed repeated two-layer cross-validation to test on an entirely unseen test set.Main results. Our classifiers obtained a balanced test accuracy of up to 62.9% for predicting PTSD patients. In addition, we identified two subtypes within PTSD: one where EEG patterns were similar to those of the combat-exposed controls, and another that were characterized by increased global functional connectivity. Our classifier obtained a balanced test accuracy of 79.4% when classifying this PTSD subtype from controls, a clear improvement compared to predicting the whole PTSD group. Interestingly, alpha connectivity in the dorsal and ventral attention network was particularly important for the prediction, and these connections were positively correlated with arousal symptom scores, a central symptom cluster of PTSD.Significance. Taken together, the novel framework presented here demonstrates how unsupervised subtyping can delineate heterogeneity and improve machine learning prediction of PTSD, and may pave the way for better identification of quantifiable biomarkers.

Laser-Material Interactions of High-Quality Ultrashort Pulsed Vector Vortex Beams.

Diffractive multi-beams based on 1 × 5 and 2 × 2 binary Dammann gratings applied to a spatial light modulator (SLM) combined with a nanostructured S-wave plate have been used to generate uniform multiple cylindrical vector beams with radial and azimuthal polarizations. The vector quality factor (concurrence) of the single vector vortex beam was found to be C = 0.95 ± 0.02, hence showing a high degree of vector purity. The multi-beams have been used to ablate polished metal samples (Ti-6Al-4V) with laser-induced periodic surface structures (LIPSS), which confirm the polarization states unambiguously. The measured ablation thresholds of the ring mode radial and azimuthal polarizations are close to those of a Gaussian mode when allowance is made for the expected absolute intensity distribution of a ring beam generated from a Gaussian. In addition, ring mode vortex beams with varying orbital angular momentum (OAM) exhibit the same ablation threshold on titanium alloy. Beam scanning with ring modes for surface LIPSS formation can increase micro-structuring throughput by optimizing fluence over a larger effective beam diameter. The comparison of each machined spot was analysed with a machine learning method-cosine similarity-which confirmed the degree of spatial uniformity achieved, reaching cosθ > 0.96 and 0.92 for the 1 × 5 and 2 × 2 arrays, respectively. Scanning electron microscopy (SEM), optical microscopy and white light surface profiling were used to characterize and quantify the effects of surface modification.

Aquaporin 1 and the Na+/K+/2Cl- cotransporter 1 are present in the leptomeningeal vasculature of the adult rodent central nervous system.

BACKGROUND: The classical view of cerebrospinal fluid (CSF) production posits the choroid plexus as its major source. Although previous studies indicate that part of CSF production occurs in the subarachnoid space (SAS), the mechanisms underlying extra-choroidal CSF production remain elusive. We here investigated the distributions of aquaporin 1 (AQP1) and Na+/K+/2Cl- cotransporter 1 (NKCC1), key proteins for choroidal CSF production, in the adult rodent brain and spinal cord. METHODS: We have accessed AQP1 distribution in the intact brain using uDISCO tissue clearing technique and by Western blot. AQP1 and NKCC1 cellular localization were accessed by immunohistochemistry in brain and spinal cord obtained from adult rodents. Imaging was performed using light-sheet, confocal and bright field light microscopy. RESULTS: We determined that AQP1 is widely distributed in the leptomeningeal vasculature of the intact brain and that its glycosylated isoform is the most prominent in different brain regions. Moreover, AQP1 and NKCC1 show specific distributions in the smooth muscle cell layer of penetrating arterioles and veins in the brain and spinal cord, and in the endothelia of capillaries and venules, restricted to the SAS vasculature. CONCLUSIONS: Our results shed light on the molecular framework that may underlie extra-choroidal CSF production and we propose that AQP1 and NKCC1 within the leptomeningeal vasculature, specifically at the capillary level, are poised to play a role in CSF production throughout the central nervous system.

Cannula Implantation into the Cisterna Magna of Rodents.

Cisterna magna cannulation (CMc) is a straightforward procedure that enables direct access to the cerebrospinal fluid (CSF) without operative damage to the skull or the brain parenchyma. In anesthetized rodents, the exposure of the dura mater by blunt dissection of the neck muscles allows the insertion of a cannula into the cisterna magna (CM). The cannula, composed either by a fine beveled needle or borosilicate capillary, is attached via a polyethylene (PE) tube to a syringe. Using a syringe pump, molecules can then be injected at controlled rates directly into the CM, which is continuous with the subarachnoid space. From the subarachnoid space, we can trace CSF fluxes by convective flow into the perivascular space around penetrating arterioles, where solute exchange with the interstitial fluid (ISF) occurs. CMc can be performed for acute injections immediately following the surgery, or for chronic implantation, with later injection in anesthetized or awake, freely moving rodents. Quantitation of tracer distribution in the brain parenchyma can be performed by epifluorescence, 2-photon microscopy, and magnetic resonance imaging (MRI), depending on the physico-chemical properties of the injected molecules. Thus, CMc in conjunction with various imaging techniques offers a powerful tool for assessment of the glymphatic system and CSF dynamics and function. Furthermore, CMc can be utilized as a conduit for fast, brain-wide delivery of signaling molecules and metabolic substrates that could not otherwise cross the blood brain barrier (BBB).