Incremental Mutual Information: A New Method for Characterizing the Strength and Dynamics of Connections in Neuronal Circuits

Understanding the computations performed by neuronal circuits requires characterizing the strength and dynamics of the connections between individual neurons. This characterization is typically achieved by measuring the correlation in the activity of two neurons. We have developed a new measure for studying connectivity in neuronal circuits based on information theory, the incremental mutual information (IMI). By conditioning out the temporal dependencies in the responses of individual neurons before measuring the dependency between them, IMI improves on standard correlation-based measures in several important ways: 1) it has the potential to disambiguate statistical dependencies that reflect the connection between neurons from those caused by other sources (e. g. shared inputs or intrinsic cellular or network mechanisms) provided that the dependencies have appropriate timescales, 2) for the study of early sensory systems, it does not require responses to repeated trials of identical stimulation, and 3) it does not assume that the connection between neurons is linear. We describe the theory and implementation of IMI in detail and demonstrate its utility on experimental recordings from the primate visual system

Dual Requirement for Yeast hnRNP Nab2p in mRNA poly(A) Tail Length Control and Nuclear Export

Recent studies of mRNA export factors have provided additional evidence for a mechanistic link between mRNA 3′‐end formation and nuclear export. Here, we identify Nab2p as a nuclear poly(A)‐binding protein required for both poly(A) tail length control and nuclear export of mRNA. Loss of NAB2 expression leads to hyperadenylation and nuclear accumulation of poly(A)+ RNA but, in contrast to mRNA export mutants, these defects can be uncoupled in a nab2 mutant strain. Previous studies have implicated the cytoplasmic poly(A) tail‐binding protein Pab1p in poly(A) tail length control during polyadenylation. Although cells are viable in the absence of NAB2 expression when PAB1 is overexpressed, Pab1p fails to resolve the nab2Δ hyperadenylation defect even when Pab1p is tagged with a nuclear localization sequence and targeted to the nucleus. These results indicate that Nab2p is essential for poly(A) tail length control in vivo, and we demonstrate that Nab2p activates polyadenylation, while inhibiting hyperadenylation, in the absence of Pab1p in vitro. We propose that Nab2p provides an important link between the termination of mRNA polyadenylation and nuclear export

Electroconvulsive Therapy Practice Changes in Older Individuals Due to COVID-19: Expert Consensus Statement

© 2020 American Association for Geriatric Psychiatry The ubiquitous coronavirus 2019 (COVID-19) pandemic has required healthcare providers across all disciplines to rapidly adapt to public health guidelines to reduce risk while maintaining quality of care. Electroconvulsive therapy (ECT), which involves an aerosol-generating procedure from manual ventilation with a bag mask valve while under anesthesia, has undergone drastic practice changes in order to minimize disruption of treatment in the midst of COVID-19. In this paper, we provide a consensus statement on the clinical practice changes in ECT specific to older adults based on expert group discussions of ECT practitioners across the country and a systematic review of the literature. There is a universal consensus that ECT is an essential treatment of severe mental illness. In addition, there is a clear consensus on what modifications are imperative to ensure continued delivery of ECT in a manner that is safe for patients and Northwell Health, while maintaining the viability of ECT services. Approaches to modifications in ECT to address infection control, altered ECT procedures, and adjusting ECT operations are almost uniform across the globe. With modified ECT procedures, it is possible to continue to meet the needs of older patients while mitigating risk of transmission to this vulnerable population

Population coding by globally coupled phase oscillators

A system of globally coupled phase oscillators subject to an external input is considered as a simple model of neural circuits coding external stimulus. The information coding efficiency of the system in its asynchronous state is quantified using Fisher information. The effect of coupling and noise on the information coding efficiency in the stationary state is analyzed. The relaxation process of the system after the presentation of an external input is also studied. It is found that the information coding efficiency exhibits a large transient increase before the system relaxes to the final stationary state.Comment: 7 pages, 9 figures, revised version, new figures added, to appear in JPSJ Vol 75, No.

Seizure frequency discrepancy between subjective and objective ictal electroencephalography data in dogs

Background Many studies of epilepsy in veterinary medicine use subjective data (eg, caregiver-derived histories) to determine seizure frequency. Conversely, in people, objective data from electroencephalography (EEG) are mainly used to diagnose epilepsy, measure seizure frequency and evaluate efficacy of antiseizure drugs. These EEG data minimize the possibility of the underreporting of seizures, a known phenomenon in human epileptology. Objective To evaluate the correlation between reported seizure frequency and EEG frequency of ictal paroxysmal discharges (PDs) and to determine whether seizure underreporting phenomenon exists in veterinary epileptology. Animals Thirty-three ambulatory video-EEG recordings in dogs showing >= 1 ictal PD, excluding dogs with status epilepticus. Methods Retrospective observational study. Ictal PDs were counted manually over the entire recording to obtain the frequency of EEG seizures. Caregiver-reported seizure frequency from the medical record was categorized into weekly, daily, hourly, and per minute seizure groupings. The Spearman rank test was used for correlation analysis. Results The coefficient value (r(s)) comparing reported seizure to EEG-confirmed ictal PD frequencies was 0.39 (95% confidence interval [CI] = 0.048-0.64, P = .03). Other r(s) values comparing history against various seizure types were: 0.36 for motor seizures and 0.37 for nonmotor (absence) seizures. Conclusions and Clinical Importance A weak correlation was found between the frequency of reported seizures from caregivers (subjective data) and ictal PDs on EEG (objective data). Subjective data may not be reliable enough to determine true seizure frequency given the discrepancy with EEG-confirmed seizure frequency. Confirmation of the seizure underreporting phenomenon in dogs by prospective study should be carried out.Peer reviewe

Mechanisms explaining transitions between tonic and phasic firing in neuronal populations as predicted by a low dimensional firing rate model

Several firing patterns experimentally observed in neural populations have been successfully correlated to animal behavior. Population bursting, hereby regarded as a period of high firing rate followed by a period of quiescence, is typically observed in groups of neurons during behavior. Biophysical membrane-potential models of single cell bursting involve at least three equations. Extending such models to study the collective behavior of neural populations involves thousands of equations and can be very expensive computationally. For this reason, low dimensional population models that capture biophysical aspects of networks are needed. \noindent The present paper uses a firing-rate model to study mechanisms that trigger and stop transitions between tonic and phasic population firing. These mechanisms are captured through a two-dimensional system, which can potentially be extended to include interactions between different areas of the nervous system with a small number of equations. The typical behavior of midbrain dopaminergic neurons in the rodent is used as an example to illustrate and interpret our results. \noindent The model presented here can be used as a building block to study interactions between networks of neurons. This theoretical approach may help contextualize and understand the factors involved in regulating burst firing in populations and how it may modulate distinct aspects of behavior.Comment: 25 pages (including references and appendices); 12 figures uploaded as separate file

Recurring large deletion in DRC1 (CCDC164) identified as causing primary ciliary dyskinesia in two Asian patients

Background: Primary ciliary dyskinesia (PCD) is a relatively rare autosomal recessive or X-linked disorder affecting ciliary function. In the set of causative genes, however, predominant pathogenic variants remain unknown in Asia. Method: A diagnosis of PCD was made following a modern comprehensive testing including genetic analysis; targeted resequencing for screening variants, and Sanger sequencing for determination of the breakpoints, with an additional review of databases to calculate the deletion frequency. A multiplexed PCR-based detection method has also been developed. Results: We ascertained a 50-year-old Japanese male who had been diagnosed with diffuse panbronchiolitis (DPB), but refractory to macrolide therapy. We reevaluated the case and identified a large homozygous deletion spanning exons 1 to 4 of the DRC1 and determined the breakpoints (NM_145038.4: c.1-3952_540 + 1331del27748-bp). In the PCD cohort at the University of North Carolina, we found a female PCD patient of Korean descent harboring the same homozygous deletion. From the Invitae testing cohort, we extracted four carriers of the same deletion among 965 Asian individuals, whereas no deletion was found in the 23,951 non-Asians. Conclusion: We speculate that the DRC1 deletion is a recurrent or perhaps founder mutation in Asians. The simple PCR method could be a useful screening tool

Primary ciliary dyskinesia: Longitudinal study of lung disease by ultrastructure defect and genotype

Rationale: In primary ciliary dyskinesia, factors leading to disease heterogeneity are poorly understood. Objectives: To describe early lung disease progression in primary ciliary dyskinesia and identify associations between ultrastructural defects and genotypes with clinical phenotype. Methods: This was a prospective, longitudinal (5 yr), multicenter, observational study. Inclusion criteria were less than 19 years at enrollment and greater than or equal to two annual study visits. Linear mixed effects models including random slope and random intercept were used to evaluate longitudinal associations between the ciliary defect group (or genotype group) and clinical features (percent predicted FEV 1 and weight and height z-scores). Measurements and Main Results: A total of 137 participants completed 732 visits. The group with absent inner dynein arm, central apparatus defects, and microtubular disorganization (IDA/CA/MTD) (n = 41) were significantly younger at diagnosis and in mixed effects models had significantly lower percent predicted FEV 1 and weight and height z-scores than the isolated outer dynein arm defect (n = 55) group. Participants with CCDC39 or CCDC40 mutations (n = 34) had lower percent predicted FEV 1 and weight and height z-scores than those with DNAH5 mutations (n = 36). For the entire cohort, percent predicted FEV 1 decline was heterogeneous with a mean (SE) decline of 0.57 (0.25) percent predicted/yr. Rate of decline was different from zero only in the IDA/MTD/CA group (mean [SE], 21.11 [0.48] percent predicted/yr; P = 0.02). Conclusions: Participants with IDA/MTD/CA defects, which included individuals with CCDC39 or CCDC40 mutations, had worse lung function and growth indices compared with those with outer dynein arm defects and DNAH5 mutations, respectively. The only group with a significant lung function decline over time were participants with IDA/MTD/CA defects

Divisive Gain Modulation with Dynamic Stimuli in Integrate-and-Fire Neurons

The modulation of the sensitivity, or gain, of neural responses to input is an important component of neural computation. It has been shown that divisive gain modulation of neural responses can result from a stochastic shunting from balanced (mixed excitation and inhibition) background activity. This gain control scheme was developed and explored with static inputs, where the membrane and spike train statistics were stationary in time. However, input statistics, such as the firing rates of pre-synaptic neurons, are often dynamic, varying on timescales comparable to typical membrane time constants. Using a population density approach for integrate-and-fire neurons with dynamic and temporally rich inputs, we find that the same fluctuation-induced divisive gain modulation is operative for dynamic inputs driving nonequilibrium responses. Moreover, the degree of divisive scaling of the dynamic response is quantitatively the same as the steady-state responses—thus, gain modulation via balanced conductance fluctuations generalizes in a straight-forward way to a dynamic setting