Efficacy of cEEG and hepatic function to diagnose early acute encephalopathy.

BACKGROUND: Early treatment may improve the prognosis of acute encephalopathy (AE). However, methods for early diagnosis have not yet been established. In this paper, we examined methods for the early diagnosis of AE. METHODS: We extracted data on patients with febrile status epilepticus from the electronic medical records in our department between March 2016 and April 2021. Among these, 79 patients who underwent continuous electroencephalography (cEEG) were included in this study. Patients who exhibited psychomotor retardation or abnormal brain magnetic resonance imaging findings were assigned to Group E (n = 20), and the remaining patients were the control group (Group C, n = 59). The following tests were compared retrospectively between these two groups on admission: cEEG, serum hepatic function tests, and blood coagulation tests. RESULTS: The percentage of patients who exhibited high-amplitude slow waves or flat waves on cEEG at the time of admission was statistically significantly higher in Group E than in Group C (p < 0.01). Moreover, the percentage of patients whose high-amplitude slow waves or flat brain waves on admission disappeared within 6 h after an initial episode of convulsion was statistically significantly lower in Group E than in Group C (p < 0.01). Furthermore, all the items in the coagulation and the hepatic function tests were statistically significantly different in Group E from those in Group C (p < 0.05). CONCLUSION: These results showed that cEEG together with hepatic function and coagulation tests may be useful for the differential diagnosis of AE.

Basilar Artery Dissection Complicated with Infective Endocarditis.

A 14 year-old boy developed infective endocarditis of the mitral valve caused by Methicillin-sensitive Staphylococcus aureus and became comatose. Isolated basilar artery dissection was initially observed on the 3rd day by magnetic resonance imaging (MRI), ie, it did not exist on day 1. He underwent successful urgent mitral valve repair on the 5th day because of highly mobile vegetations and a newly emerged brain infarction under optimal antibiotic administration. Postoperatively, he recovered well and the basilar artery dissection was found to have recovered on an MRI on the 25th day without any specific intervention. This clinical course indicated that intracranial artery dissection may occur as a complication of infective endocarditis and supports the importance of the careful evaluation of brain MRI in patients with infective endocarditis.

Similarity in Neuronal Firing Regimes across Mammalian Species.

UNLABELLED: The architectonic subdivisions of the brain are believed to be functional modules, each processing parts of global functions. Previously, we showed that neurons in different regions operate in different firing regimes in monkeys. It is possible that firing regimes reflect differences in underlying information processing, and consequently the firing regimes in homologous regions across animal species might be similar. We analyzed neuronal spike trains recorded from behaving mice, rats, cats, and monkeys. The firing regularity differed systematically, with differences across regions in one species being greater than the differences in similar areas across species. Neuronal firing was consistently most regular in motor areas, nearly random in visual and prefrontal/medial prefrontal cortical areas, and bursting in the hippocampus in all animals examined. This suggests that firing regularity (or irregularity) plays a key role in neural computation in each functional subdivision, depending on the types of information being carried. SIGNIFICANCE STATEMENT: By analyzing neuronal spike trains recorded from mice, rats, cats, and monkeys, we found that different brain regions have intrinsically different firing regimes that are more similar in homologous areas across species than across areas in one species. Because different regions in the brain are specialized for different functions, the present finding suggests that the different activity regimes of neurons are important for supporting different functions, so that appropriate neuronal codes can be used for different modalities.

Hippocampal-prefrontal theta phase synchrony in planning of multi-step actions based on memory retrieval.

Planning of multi-step actions based on the retrieval of acquired information is essential for efficient foraging. The hippocampus (HPC) and prefrontal cortex (PFC) may play critical roles in this process. However, in rodents, many studies investigating such roles utilized T-maze tasks that only require one-step actions (i.e., selection of one of two alternatives), in which memory retrieval and selection of an action based on the retrieval cannot be clearly differentiated. In monkeys, PFC has been suggested to be involved in planning of multi-step actions; however, the synchrony between HPC and PFC has not been evaluated. To address the combined role of the regions in planning of multi-step actions, we introduced a task in rats that required three successive nose-poke responses to three sequentially illuminated nose-poke holes. During the task, local field potentials (LFP) and spikes from hippocampal CA1 and medial PFC (mPFC) were simultaneously recorded. The position of the first hole indicated whether the following two holes would be presented in a predictable sequence or not. During the first nose-poke period, phase synchrony of LFPs in the theta range (4-10 Hz) between the regions was not different between predictable and unpredictable trials. However, only in trials of predictable sequences, the magnitude of theta phase synchrony during the first nose-poke period was negatively correlated with latency of the two-step ahead nose-poke response. Our findings point to the HPC-mPFC theta phase synchrony as a key mechanism underlying planning of multi-step actions based on memory retrieval rather than the retrieval itself.

Diagnostic and prognostic factors for acute encephalopathy.

BACKGROUND: Acute encephalopathy has the possibility of sequelae. While early treatment is required to prevent the development of sequelae, differential diagnosis is of the utmost priority. The aim of this study was therefore to identify parameters that can facilitate early diagnosis and prediction of outcome of acute encephalopathy. METHODS: We reviewed the medical charts of inpatients from 2005 to 2011 and identified 33 patients with febrile status epilepticus. Subjects were classified into an acute encephalopathy group (n = 20) and a febrile convulsion group (n = 13), and the parameters serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), ammonia (NH3 ), cerebrospinal fluid (CSF) tau protein, and CSF interleukin-6 compared between them. Furthermore, the relationship between each parameter and prognosis was investigated in the encephalopathy group. RESULTS: Significant differences in serum AST, ALT, and LDH were observed between the febrile convulsion and acute encephalopathy group. Moreover, a significant difference in serum LDH was noted between the patients with and without developmental regression at the time of hospital discharge in the encephalopathy group. In particular, CSF tau protein was found to be highly likely to indicate progress, with CSF tau protein >1000 pg/dL associated with poor prognosis leading to developmental regression. CONCLUSION: Serum AST, ALT and LDH may be related to early diagnosis and prognosis, and should be carefully investigated in patients with encephalopathy. CSF tau protein could also be used as an indicator of poor prognosis in acute encephalopathy.

[Pediatric emergency medicine].

Pediatric advanced life support (PALS) is the global standard of pediatric emergency medicine. It depends on the consensus of ILCOR which has been revised every 5 years by the experts worldwide. The concept of PALS is to treat the sick and injured children based on the systematic approach of the evaluation and classification in terms of the respiratory and circulatory status. On the other hand, point of care ultrasound (POCU) has been getting popular worldwide in the field of the emergency and critical care medicine. The PALS approach mainly depends on the physical examination which isn't enough for the decision making of the treatment. Then, POCU has come out as the adjunctive methods to compensate for the physical examination. This article outlines the concept of PALS and POCU.

Efficacy of the Airway Scope (Pentax-AWS) for training in pediatric intubation.

BACKGROUND: The aim of this study was to evaluate the efficacy of the Airway Scope (AWS) in the training of residents in pediatric intubation using high-performance simulators. METHODS: A total of 51 residents were recruited. Baby SIM is a high-performance simulator with a built-in physiological program that reduces SpO2 if it stops breathing and increases SpO2 if assisted ventilation is provided using a bag mask. Therefore, real-life situations can be simulated with this program. Trial 1: after respiration of Baby SIM was stopped, intubation was initiated. If the intubation time was too long, a built-in physiological program led to desaturation. The intubation time and frequency of SpO2 <90% were compared between the Miller laryngoscope and the AWS. Trial 2: an ALS Baby, which is more difficult to intubate than Baby SIM, was used in comparison of intubation time and frequency of failure to intubate within 60 s between the two laryngoscopes. Mann-Whitney and chi-squared tests were used for statistical analysis. RESULTS: Intubation time was significantly shorter using the AWS than the Miller laryngoscope in both trials. Furthermore, desaturation occurred significantly less frequently with the AWS than the Miller laryngoscope in trial 1. The frequency of intubation failure within 60 s was also significantly lower for the AWS than the Miller laryngoscope in trial 2. CONCLUSION: The inclusion of both direct laryngoscopy and the AWS in pediatric resident programs might give pediatricians the option of using a safer and more reliable intubation method for children.

Spike-coding mechanisms of cerebellar temporal processing in classical conditioning and voluntary movements.

Time is a fundamental and critical factor in daily life. Millisecond timing, which is the underlying temporal processing for speaking, dancing, and other activities, is reported to rely on the cerebellum. In this review, we discuss the cerebellar spike-coding mechanisms for temporal processing. Although the contribution of the cerebellum to both classical conditioning and voluntary movements is well known, the difference of the mechanisms for temporal processing between classical conditioning and voluntary movements is not clear. Therefore, we review the evidence of cerebellar temporal processing in studies of classical conditioning and voluntary movements and report the similarities and differences between them. From some studies, which used tasks that can change some of the temporal properties (e.g., the duration of interstimulus intervals) with keeping identical movements, we concluded that classical conditioning and voluntary movements may share a common spike-coding mechanism because simple spikes in Purkinje cells decrease at predicted times for responses regardless of the intervals between responses or stimulation.

[Learning and Neural Activity: Beyond Localization].

Learning is classified into two types: "classical conditioning," which modifies simple reflexes, and "operant conditioning," which modifies complex voluntary behaviors. The neural circuits underlying these two types differ significantly. During the learning process of operant conditioning tasks, various changes in firing rate and firing synchrony of neurons can be observed across multiple brain regions. Additionally, neuronal firing rate and synchrony in several brain regions can be voluntarily controlled through operant conditioning. Consequently, it is evident that neurons in widespread brain regions have the potential for plastic changes to facilitate learning. It may be suggested that the learning of complex voluntary behaviors is underlined by widespread dynamic changes in neural activity and is not restricted to only a few brain regions.

An intra-oral flavor detection task in freely moving mice.

Flavor plays a critical role in the pleasure of food. Flavor research has mainly focused on human subjects and revealed that many brain regions are involved in flavor perception. However, animal models for elucidating the mechanisms of neural circuits are lacking. Herein, we demonstrate the use of a novel behavioral task in which mice are capable of flavor detection. When the olfactory pathways of the mice were blocked, they could not perform the task. However, behavioral accuracy was not affected when the gustatory pathway was blocked by benzocaine. These results indicate that the mice performed this detection task mainly based on the olfaction. We conclude that this novel task can contribute to research on the neural mechanisms of flavor perception.

Conditioned enhancement of firing rates and synchrony of hippocampal neurons and firing rates of motor cortical neurons in rats.

The aim of this study was to examine the potential ability of neuronal groups to enhance their activities by conditioning without behaviors. We employed a method of neuronal operant conditioning in which increments in the firing rates and synchrony of closely neighboring neurons in the motor cortex and hippocampus were rewarded in the absence of behaviors. Rats were trained to engage in a free-operant task in which nose-poke behaviors were rewarded in session 1, and firing rates and synchrony above preset criteria were rewarded in sessions 2 and 3, respectively. The firing rates of motor cortical and hippocampal neuron groups were found to increase rapidly in session 2 similarly to the nose-poke behavior in session 1. Placing contingency of reward on firing synchrony resulted in selective enhancement of firing synchrony of only hippocampal neurons in session 3. Control experiments revealed that the enhancement of neuronal firing was not attributable to increments of superstitious behaviors or excitation caused by reward delivery. Analysis of the firing rates and synchrony of individual neurons and neuron pairs in each group revealed that the firing rates and synchrony of some but not all neurons and neuron pairs increased in each group. No enhancement was observed in any neurons and neuron pairs recorded by neighboring electrodes not used for conditioning. These results suggest that neuronal operant conditioning enhances the firing rates and synchrony of only some neurons in small restricted areas. The present findings are expected to contribute to further research into neurorehabilitation and neuroprosthesis.

Rats adaptively seek information to accommodate a lack of information.

Metacognition is the ability to adaptively control one's behavior by referring to one's own cognitive processes. It is thought to contribute to learning in situations where there is insufficient information available from the environment. Information-seeking behavior is a type of metacognition in which one confirms the necessary information only when one does not have the necessary and sufficient information to accomplish a task. The rats were required to respond to a nose poke hole on one wall of the experimental box for a certain period of time and then move to the opposite side at a specific time. Unfortunately, they were unable to match the timing when responding to the hole on one side. Therefore, they had to look back and confirm that now was the right time. The results obtained by analyzing these looking-back movements using a motion capture system showed that this behavior occurred frequently and rapidly in situations of insufficient information, such as in the early stages of learning, but was hardly observed and became slower as learning progressed. These results suggest that rats can adjust their behavior in response to a lack of information more flexibly than previously assumed.

Mechanically ventilated children with 2009 pandemic influenza A/H1N1: results from the National Pediatric Intensive Care Registry in Japan.

OBJECTIVE: To outline the characteristics, clinical course, and outcome of pediatric patients requiring mechanical ventilation with influenza A/H1N1 infection in Japan. DESIGN: Prospective case registry analysis. SETTING: Eleven pediatric or general intensive care units in Japan. PATIENTS: Consecutive patients infected with A/H1N1, aged from 1 month to 16 yrs old admitted to the intensive care unit for mechanical ventilation between July 2009 and March 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-one children, aged 6.3 [0.8-13.6] (median [interquartile range]) years, were enrolled. Seventy-four (91%) had mechanical ventilation with tracheal intubation. Median duration of mechanical ventilation was 4 days (range 0.04-87) and 18 patients (23%) required mechanical ventilation >7 days. Two patients (2%) required extracorporeal membrane oxygenation. The in-hospital mortality was 1%. Forty-one patients (50%) had at least one underlying chronic condition, including 31 with asthma. Associated clinical symptoms and diagnosis were as follows: acute respiratory distress syndrome (9%), asthma or bronchitis (37%), pneumonia (68%) with 8 (14%) having bacterial pneumonia, neurological symptoms (32%), myocarditis (2%), and rhabdomyolysis (1%). Therapeutic interventions include inotropic support (21%), methylprednisolone therapy (33%), and antimicrobial therapy (88%). Multivariate analysis revealed that inotropic support was the only statistically significant factor associated with mechanical ventilation for more than a week (odds ratio 5.5, 95% confidence interval 1.5-20.5, p = .005). CONCLUSIONS: The clinical presentations of pediatric patients requiring mechanical ventilation for A/H1N1 in Japan were diverse. In-hospital mortality of this population was remarkably low. Rapid access to medical facilities in combination with early administration of antiviral agents may have contributed to the low mortality in this population.

Medial prefrontal cortex stimulation disrupts observational learning in Barnes maze in rats.

Observational learning, which improves one's own behavior by observing the adaptive behavior of others, has been experimentally demonstrated in primates and rodents in several behavioral studies, including our previous study. However, its neural mechanisms remain unclear. We electrically stimulated the brain regions of rats and disturbed their neural activities during observation periods in the observational learning task using Barnes maze. According to comparison of escaping latencies of the observer and model rats, the observer rats with stimulation of the medial prefrontal cortex (mPFC) showed no observational learning, whereas both of the observer rats with stimulation of the dorsal hippocampus and with no stimulation (control) showed observational learning. These results suggest that mPFC stimulation disrupts observational learning and confirms that the mPFC is an important brain region for it in rats.

Imaging of extrapontine myelinolysis preceding central pontine myelinolysis in a case of ornithine transcarbamylase deficiency with hyperammonaemia and hypokalaemia.

Background: Patients with ornithine transcarbamylase deficiency (OTCD) often present with severe hyperammonaemia. We report a case of osmotic demyelination syndrome (ODS) secondary to the treatment of hyperammonaemia due to OTCD, a disease requiring early diagnosis, as it can have a severe prognosis. Case: A girl toddler was brought to the hospital with a complaint of somnolence, presenting with hyperammonaemia and liver failure, and was diagnosed with OTCD. Treatment was started immediately, and the ammonia level returned to the normal range within 24 hours. On days 13-20, another treatment was commenced for re-elevated ammonia levels, which subsequently returned to within the reference range; however, mildly impaired consciousness persisted. Hypokalaemia coincided with temporary intravenous treatment and continuous haemodialysis. T2-weighted magnetic resonance images revealed lesions as high-signal areas in the bilateral putamen on day 11 (extrapontine myelinolysis (EPM)) and in the pons on day 51 (central pontine myelinolysis (CPM)). Consequently, ODS was diagnosed. Conclusion: When interpreting magnetic resonance images of patients under acute treatment for hyperammonaemia due to OTCD, a condition that may be complicated by hypokalaemia, paying attention to findings suggesting EPM may help detect ODS before CPM appears and may improve patient prognosis.

Auditory Cortex Neurons Show Task-Related and Learning-Dependent Selectivity toward Sensory Input and Reward during the Learning Process of an Associative Memory Task.

The activity of primary auditory cortex (A1) neurons is modulated not only by sensory inputs but also by other task-related variables in associative learning. However, it is unclear how A1 neural activity changes dynamically in response to these variables during the learning process of associative memory tasks. Therefore, we developed an associative memory task using auditory stimuli in rats. In this task, rats were required to associate tone frequencies (high and low) with a choice of ports (right or left) to obtain a reward. The activity of A1 neurons in the rats during the learning process of the task was recorded. A1 neurons increased their firing rates either when the rats were presented with a high or low tone (frequency-selective cells) before they chose either the left or right port (choice-direction cells), or when they received a reward after choosing either the left or right port (reward-direction cells). Furthermore, the proportion of frequency-selective cells and reward-direction cells increased with task acquisition and reached the maximum level in the last stage of learning. These results suggest that A1 neurons have task- and learning-dependent selectivity toward sensory input and reward when auditory tones and behavioral responses are gradually associated during task training. This selective activity of A1 neurons may facilitate the formation of associations, leading to the consolidation of associative memory.

Bi-directional encoding of context-based odors and behavioral states by the nucleus of the lateral olfactory tract.

The nucleus of the lateral olfactory tract (NLOT) is not only a part of the olfactory cortex that receives olfactory sensory inputs but also a part of the cortical amygdala, which regulates motivational behaviors. To examine how neural activity of the NLOT is modulated by decision-making processes that occur during various states of learned goal-directed behaviors, we recorded NLOT spike activities of mice performing odor-guided go/no-go tasks to obtain a water reward. We observed that several NLOT neurons exhibited sharp go-cue excitation and persistent no-go-cue suppression responses triggered by an odor onset. The bidirectional cue encoding introduced NLOT population response dynamics and provided a high odor decoding accuracy before executing cue-odor-evoked behaviors. The go-cue responsive neurons were also activated in the reward drinking state, indicating context-based odor-outcome associations. These findings suggest that NLOT neurons play an important role in the translation from context-based odor information to appropriate behavior.

Over-representation of fundamental decision variables in the prefrontal cortex underlies decision bias.

The brain is organized into anatomically distinct structures consisting of a variety of projection neurons. While such evolutionarily conserved neural circuit organization underlies the innate ability of animals to swiftly adapt to environments, they can cause biased cognition and behavior. Although recent studies have begun to address the causal importance of projection-neuron types as distinct computational units, it remains unclear how projection types are functionally organized in encoding variables during cognitive tasks. This review focuses on the neural computation of decision making in the prefrontal cortex and discusses what decision variables are encoded by single neurons, neuronal populations, and projection type, alongside how specific projection types constrain decision making. We focus particularly on "over-representations" of distinct decision variables in the prefrontal cortex that reflect the biological and subjective significance of the variables for the decision makers. We suggest that task-specific over-representation in the prefrontal cortex involves the refinement of the given decision making, while generalized over-representation of fundamental decision variables is associated with suboptimal decision biases, including pathological ones such as those in patients with psychiatric disorders. Such over-representation of the fundamental decision variables in the prefrontal cortex appear to be tightly constrained by afferent and efferent connections that can be optogenetically intervened on. These ideas may provide critical insights into potential therapeutic targets for psychiatric disorders, including addiction and depression.

Contribution of non-sensory neurons in visual cortical areas to visually guided decisions in the rat.

It is widely assumed that trial-by-trial variability in visual detection performance is explained by the fidelity of visual responses in visual cortical areas influenced by fluctuations of internal states, such as vigilance and behavioral history. However, it is not clear which neuronal ensembles represent such different internal states. Here, we utilized a visual detection task, which distinguishes internal states in response to identical stimuli, while recording neurons simultaneously from the primary visual cortex (V1) and the posterior parietal cortex (PPC). We found that rats sometimes withheld their responses to visual stimuli despite the robust presence of visual responses in V1. Our unsupervised analysis revealed distinct population dynamics segregating hit responses from misses, orthogonally embedded to visual response dynamics in both V1 and PPC. Heterogeneous non-sensory neurons in V1 and PPC significantly contributed to population-level encoding accompanied with the modulation of noise correlation only in V1. These results highlight the non-trivial contributions of non-sensory neurons in V1 and PPC for population-level computations that reflect the animals' internal states to drive behavioral responses to visual stimuli.

Markedly long pause due to sinus arrest during dexmedetomidine use and nasal continuous positive airway pressure in two infants with respiratory syncytial virus infection.

Nasal respiratory support for infants with respiratory distress caused by respiratory syncytial (RS) virus infection sometimes requires appropriate sedation. Dexmedetomidine can be an alternative sedative because of its advantage of less frequent respiratory suppression. We report the cases of twin infants with RS virus infection who showed unreported long pauses (4 and 10 s) due to sinus arrest while receiving dexmedetomidine. After termination of dexmedetomidine administration, the long pause of >2 s was no longer observed in both cases. RS virus infection may inhibit the conduction system and sometimes induce bradyarrhythmia. Cardiac and sinus arrests are reported as complications of dexmedetomidine administration. Thus, because dexmedetomidine administration and RS virus infection may additively or synergistically inhibit the conduction system, the use of dexmedetomidine in infantile RS infection should be carefully considered. If sedation is unavoidable, other drugs should be used first. An evidence-based safe regimen for sedation in infants with RS infection should be established in the near future. .