Low frequency oscillations reflect neurovascular coupling and disappear after cerebral death.

Spectrum power analysis in the low frequency oscillations (LFO) region of functional near infrared spectroscopy (fNIRS) is a promising method to deliver information about brain activation and therefore might be used for prognostication in patients with disorders of consciousness in the neurocritical care unit alongside with established methods. In this study, we measure the cortical hemodynamic response measured by fNIRS in the LFO region following auditory and somatosensory stimulation in healthy subjects. The significant hemodynamic reaction in the contralateral hemisphere correlation with the physiologic electric response suggests neurovascular coupling. In addition, we investigate power spectrum changes in steady state measurements of cerebral death patients and healthy subjects in the LFO region, the frequency of the heartbeat and respiration. The spectral power within the LFO region was lower in the patients with cerebral death compared to the healthy subjects, whereas there were no differences in spectral power for physiological activities such as heartbeat and respiration rate. This finding indicates the cerebral origin of our low frequency measurements. Therefore, LFO measurements are a potential method to detect brain activation in patients with disorders of consciousness and cerebral death. However, further studies in patients are needed to investigate its potential clinical use.

Evaluation of machine learning algorithms for noninvasive intracranial pressure estimation using near infrared spectroscopy as a covariate.

BACKGROUND: Intracranial pressure (ICP) is a vital parameter that is continuously monitored in patients with severe brain injury and imminent intracranial hypertension. OBJECTIVE: To estimate intracranial pressure without intracranial probes based on transcutaneous near infrared spectroscopy (NIRS). METHODS: We developed machine learning based approaches for noninvasive intracranial pressure (ICP) estimation using signals from transcutaneous near infrared spectroscopy (NIRS) as well as other cardiovascular and artificial ventilation parameters. RESULTS: In a patient cohort of 25 patients, with 22 used for model development and 3 for model testing, the best performing models were Fourier transform based Transformer ICP waveform estimation which produced a mean absolute error of 4.68 mm Hg (SD = 5.4) in estimation. CONCLUSION: We did not find a significant improvement in ICP estimation accuracy by including signals measured by transcutaneous NIRS. We expect that with higher quality and greater volume of data, noninvasive estimation of ICP will improve.

Functional NIRS to detect covert consciousness in neurocritical patients.

OBJECTIVE: This pilot study assesses the feasibility to detect covert consciousness in clinically unresponsive patients by means of functional near infrared spectroscopy (fNIRS) in a real intensive care unit setting. We aimed to verify if the hemodynamic response to familiar music measured with fNIRS varies according to the level consciousness of the patients. METHODS: 22 neurocritical patients and 6 healthy controls were included. The experiment consisted in 3 subsequent blocks including a first resting state recording, a period of music playback and a second resting state recording. fNIRS measurement were performed on each subject with two optodes on the forehead. Main oscillatory frequencies of oxyhemoglobin signal were analyzed. Spectral changes of low frequency oscillations (LFO) between subsequent experimental blocks were used as a marker of cortical response. Cortical response was compared to the level of consciousness of the patients and their functional outcome, through validated clinical scores. RESULTS: Cortical hemodynamic response to music on the left prefrontal brain was associated with the level of consciousness of the patients and with their clinical outcome after three months. CONCLUSIONS: Variations in LFO spectral power measured with fNIRS may be a new marker of cortical responsiveness to detect covert consciousness in neurocritical patients. Left prefrontal cortex may play an important role in the perception of familiar music. SIGNIFICANCE: We showed the feasibility of a simple fNIRS approach to detect cortical response in the real setting of an intensive care unit.

ICU Cockpit: a platform for collecting multimodal waveform data, AI-based computational disease modeling and real-time decision support in the intensive care unit.

ICU Cockpit: a secure, fast, and scalable platform for collecting multimodal waveform data, online and historical data visualization, and online validation of algorithms in the intensive care unit. We present a network of software services that continuously stream waveforms from ICU beds to databases and a web-based user interface. Machine learning algorithms process the data streams and send outputs to the user interface. The architecture and capabilities of the platform are described. Since 2016, the platform has processed over 89 billion data points (N = 979 patients) from 200 signals (0.5-500 Hz) and laboratory analyses (once a day). We present an infrastructure-based framework for deploying and validating algorithms for critical care. The ICU Cockpit is a Big Data platform for critical care medicine, especially for multimodal waveform data. Uniquely, it allows algorithms to seamlessly integrate into the live data stream to produce clinical decision support and predictions in clinical practice.

Functional relationship of arterial blood pressure, central venous pressure and intracranial pressure in the early phase after subarachnoid hemorrhage.

BACKGROUND: Intracranial pressure (ICP) and arterial blood pressure (ABP) are related to each other through cerebral autoregulation. Central venous pressure (CVP) is often measured to estimate cardiac filling pressures as an approximate measure for the volume status of a patient. Prior modelling efforts have formalized the functional relationship between CVP, ICP and ABP. However, these models were used to explain short segments of data during controlled experiments and have not yet been used to explain the slowly evolving ICP increase that occurs typically in patients after aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE: To analyze the functional relationship between ICP, ABP and CVP recorded from SAH patients in the first five days after aneurysm. METHODS: Two methods were used to elucidate this relationship on the running average of the signals: First, using Spearman correlation coefficients calculated over 30 min segments Second, for each patient, linear state space models of ICP as the output and ABP and CVP as inputs were estimated. RESULTS: The mean and variance of the data and the correlation coefficients between ICP-ABP and ICP-CVP vary over time as the patient progresses through their stay in the ICU. On average, after an SAH event, the models show that a) ABP is the bigger driver of changes in ICP than CVP and that increasing ABP leads to reduction in ICP and (b) increasing CVP leads to an increase in ICP. CONCLUSIONS: Finding a) agrees with the hypothesis that patients with subarachnoid hemorrhage have defective autoregulation, and b) agrees with the positive correlation observed between central venous pressure and intracranial pressure in the literature.

The effect of nimodipine on pulmonary function in artificially ventilated patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Nimodipine is routinely administered in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the effect of nimodipine on oxygen exchange in the lungs is insufficiently explored. METHODS: The study explored nimodipine medication in artificially ventilated patients with aSAH. The data collection period was divided into nimodipine-dependent (ND) and nimodipine-independent (NID) periods. Values for arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2) were collected and compared between the periods. Patients were divided in those with lung injury (LI), defined as median Horowitz index (PaO2/FiO2) ≤40 kPa (≤300 mmHg), and without and in those with lower respiratory tract infection (LRTI) and without. RESULTS: A total of 53 out of 150 patients were artificially ventilated, and in 29 patients, the Horowitz index could be compared between ND and NID periods. A linear mixed model showed that during ND period the Horowitz index was 2.3 kPa (95% CI, 1.0-3.5 kPa, P<0.001) lower when compared to NID period. The model suggested that in the presence of LI, ND period is associated with a decrease of the index by 2.8 kPa (95% CI, 1.2-4.3 kPa, P<0.001). The decrease was more pronounced with LRTI than without: 3.4 kPa (95% CI, 0.8-6.1 kPa) vs. 2.1 kPa (95% CI, 0.7-3.4 kPa), P=0.011 and P=0.002, respectively. CONCLUSIONS: In patients with LI or LRTI in the context of aSAH, pulmonary function may worsen with nimodipine treatment. The drop of 2 to 3 kPa of the Horowitz index in patients with no lung pathology may not outweigh the benefits of nimodipine. However, in individuals with concomitant lung injury, the effect may be clinically relevant.

Increase in Low-Frequency Oscillations in fNIRS as Cerebral Response to Auditory Stimulation with Familiar Music.

Recognition of typical patterns of brain response to external stimuli using near-infrared spectroscopy (fNIRS) may become a gateway to detecting covert consciousness in clinically unresponsive patients. This is the first fNIRS study on the cortical hemodynamic response to favorite music using a frequency domain approach. The aim of this study was to identify a possible marker of cognitive response in healthy subjects by investigating variations in the oscillatory signal of fNIRS in the spectral regions of low-frequency (LFO) and very-low-frequency oscillations (VLFO). The experiment consisted of two periods of exposure to preferred music, preceded and followed by a resting phase. Spectral power in the LFO region increased in all the subjects after the first exposure to music and decreased again in the subsequent resting phase. After the second music exposure, the increase in LFO spectral power was less distinct. Changes in LFO spectral power were more after first music exposure and the repetition-related habituation effect strongly suggest a cerebral origin of the fNIRS signal. Recognition of typical patterns of brain response to specific environmental stimulation is a required step for the concrete validation of a fNIRS-based diagnostic tool.

A fluoroscopic assessment of brachial plexus block by the supraclavicular approach: Have we been overmedicating?

BACKGROUND: Ultrasonography-guided supraclavicular brachial plexus block has demonstrated safety as compared with landmark or nerve stimulation techniques. However, the minimum effective analgesic volume (MEAV) necessary for adequate blockade has not been determined. This study was undertaken to assess under fluoroscopy the postinjection spread of different drug volumes with clinical correlation. Secondary outcome measures included correlation of onset of block, block quality, and incidence of side effects. METHODS: This randomized, multiarm, cross-sectional, observational study was conducted at a single tertiary care center. A total of 549 patients were randomly allocated to 3 groups (20 ml, 30 ml, and 40 ml of drug mixture). A local anesthetic drug mixture with a radiopaque dye was administered under ultrasonographic guidance, and postinjection fluoroscopic drug spread was studied. RESULTS: Surgical anesthesia was achieved in 494 (89.98%) patients with 85.25%, 92.97%, and 91.71% in 20-, 30-, and 40-ml groups, respectively, being significantly low (p = 0.0317) in the 20-mL group. Cephalad and infraclavicular spread was higher in the 40-mL group than in other two groups (p = 0.103). Horner syndrome (HS) was seen in 51.18% of patients. First, ipsilateral superficial cervical plexus block was also observed in 40.22% of patients. Among patients who developed both, ∼60% of patients (99/167) belonged to the 40-mL group. CONCLUSIONS: Optimal MEAV appears between 20 and 30 mL. Higher drug volumes are associated with more cephalad spread and side effects. Drug spread can predict block efficacy as well. It is postulated that loss of sensation in the ipsilateral neck can be used to predict development of hemidiaphragmatic paresis similar to HS.

Learning auditory discriminations from observation is efficient but less robust than learning from experience.

Social learning enables complex societies. However, it is largely unknown how insights obtained from observation compare with insights gained from trial-and-error, in particular in terms of their robustness. Here, we use aversive reinforcement to train "experimenter" zebra finches to discriminate between auditory stimuli in the presence of an "observer" finch. We show that experimenters are slow to successfully discriminate the stimuli, but immediately generalize their ability to a new set of similar stimuli. By contrast, observers subjected to the same task are able to discriminate the initial stimulus set, but require more time for successful generalization. Drawing on concepts from machine learning, we suggest that observer learning has evolved to rapidly absorb sensory statistics without pressure to minimize neural resources, whereas learning from experience is endowed with a form of regularization that enables robust inference.

A Bayesian Account of Vocal Adaptation to Pitch-Shifted Auditory Feedback.

Motor systems are highly adaptive. Both birds and humans compensate for synthetically induced shifts in the pitch (fundamental frequency) of auditory feedback stemming from their vocalizations. Pitch-shift compensation is partial in the sense that large shifts lead to smaller relative compensatory adjustments of vocal pitch than small shifts. Also, compensation is larger in subjects with high motor variability. To formulate a mechanistic description of these findings, we adapt a Bayesian model of error relevance. We assume that vocal-auditory feedback loops in the brain cope optimally with known sensory and motor variability. Based on measurements of motor variability, optimal compensatory responses in our model provide accurate fits to published experimental data. Optimal compensation correctly predicts sensory acuity, which has been estimated in psychophysical experiments as just-noticeable pitch differences. Our model extends the utility of Bayesian approaches to adaptive vocal behaviors.

Effects of combined administration of captopril and DMSA on arsenite induced oxidative stress and blood and tissue arsenic concentration in rats.

We compared the therapeutic efficacy of captopril and a thiol chelating agent, meso 2,3-dimercaptosuccinic acid (DMSA) either individually or in combination against arsenite induced oxidative stress and mobilization of metal in rats. Animals were exposed to 100 ppm arsenite as sodium arsenite in drinking water for six weeks followed by treatment with DMSA (50 mg/kg, orally), captopril (50 mg/kg, intraperitoneally) either alone or in combination, once daily for 5 consecutive days. Arsenite exposure led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity, glutathione and platelet levels while significantly increased the level of reactive oxygen species (in RBCs). Hepatic reduced glutathione (GSH) level showed a significant decrease while, thiobarbituric acid reactive substances (TBARS) levels increased on arsenite exposure indicating arsenite induced hepatic oxidative stress. Kidney GSH, GSSG, catalase and TBARS remained unchanged on arsenite exposure. Treatment with DMSA was effective in increasing ALAD activity while, captopril was ineffective when given alone. Captopril when co-administered with DMSA also provided no additional beneficial effect on blood ALAD activity but significant brought altered platelet counts back to the normal value. In contrast, administration of captopril alone provided significant beneficial effects on hepatic oxidative stress, and in combination with DMSA provided a more pronounced recovery in the TBARS level compared to the individual effect of DMSA and captopril. Renal biochemical variables remained insensitive to arsenite and any of the treatments. Interestingly, combined administration of captopril with DMSA had a remarkable effect in depleting total arsenic concentration from blood and soft tissues. These results lead us to conclude that captopril administration during chelation treatment had some beneficial effects particularly on the protection of inhibited blood ALAD activity, and depletion of arsenic level. The study supports our earlier conclusion that a co-administration of an antioxidant is more beneficial than monotherapy with the chelating agents, in order to achieve optimal effects of chelation in arsenite toxicity.