Timescales of Multineuronal Activity Patterns Reflect Temporal Structure of Visual Stimuli

The investigation of distributed coding across multiple neurons in the cortex remains to this date a challenge. Our current understanding of collective encoding of information and the relevant timescales is still limited. Most results are restricted to disparate timescales, focused on either very fast, e.g., spike-synchrony, or slow timescales, e.g., firing rate. Here, we investigated systematically multineuronal activity patterns evolving on different timescales, spanning the whole range from spike-synchrony to mean firing rate. Using multi-electrode recordings from cat visual cortex, we show that cortical responses can be described as trajectories in a high-dimensional pattern space. Patterns evolve on a continuum of coexisting timescales that strongly relate to the temporal properties of stimuli. Timescales consistent with the time constants of neuronal membranes and fast synaptic transmission (5–20 ms) play a particularly salient role in encoding a large amount of stimulus-related information. Thus, to faithfully encode the properties of visual stimuli the brain engages multiple neurons into activity patterns evolving on multiple timescales

Changing eating behaviours to treat childhood obesity in the community using Mandolean: the Community Mandolean randomised controlled trial (ComMando) – a pilot study

Background Around one in five children in England is obese when they leave primary school. Thus far, it has not been demonstrated that primary care interventions to manage childhood obesity can achieve significant weight reduction. Training obese children to eat more slowly as an adjunct to other healthy lifestyle behaviour change has been shown to increase weight reduction in a hospital setting. Objectives This pilot study aimed to test recruitment strategies, treatment adherence, clinic attendance and participants’ experiences of using a device [Mandolean® (previously Mandometer®, Mikrodidakt AB, Lund, Sweden)] to slow down speed of eating as an adjunct to dietary and activity advice in treating obesity in primary school-aged children. Design A two-arm, parallel, randomised controlled trial with a qualitative study embedded within the pilot. Randomisation occurred after informed consent and baseline measures were collected. Participants were randomised by the Bristol Randomised Trials Collaboration randomisation service with allocation stratified by hub and minimised by age of the child, gender, and baseline body mass index (BMI) standard deviation score (BMI z-value) of the child, and by BMI of the study parent (obese/not obese). Setting General practices across Bristol, North Somerset and South Gloucestershire primary care trusts. Participants Children (BMI ≥ 95th percentile) aged 5–11 years and their families. Intervention Standard care comprised dietary and activity advice by trained practice nurses. Adjunctive Mandolean training (the intervention) educated participants to eat meals more slowly and to rate levels of fullness (satiety). Mandolean is a small computer device attached to a weighing scale that provides visual and oral feedback during meals while generating a visual representation of levels of satiety during the meal. Participants were encouraged to eat their main meal each day from the Mandolean. One parent was also given a Mandolean to use when eating with the child. Outcome measures Outcomes for the pilot were recruitment of 36 families to the trial in the 9-month pilot phase, that meals would be eaten at least five times a week off a Mandolean by 90% of patients randomised to the intervention arm, that 80% of patients in both arms would attend the weight management clinic appointment 3 months post randomisation and that > 60% of children using Mandolean would demonstrate a reduction in speed of eating from baseline within 3 months of randomisation. Results None of the criteria for progression to the main trial were reached. Despite numerous pathways being available for referral, only 21 (13 to standard care, eight to intervention arm; 58%) of the target 36 families were recruited in the pilot phase. Less than 20% of those randomised to Mandolean used the device at least five times a week. The > 60% target for slowing down of eating speed by 3 months was unmet. Attendance at the weight management clinic in general practice hubs for both arms of the study at 3 months was 44% against a target of 80%. Conclusions This pilot trial failed to meet its objectives in terms of recruitment, treatment adherence, demonstration of a reduction in speed of eating in sufficient numbers of children, and attendance at follow–up appointments. Despite a high prevalence of childhood obesity in the geographical area and practices signing up for the trial, this study, like many others, demonstrates a failure of families to engage with and respond to primary care weight management interventions. We need to understand why the target population seems inured to the health message that childhood obesity is a significant health-care issue and identify the barriers to seeking help and then acting on positive health behaviour retraining. Only when we have fully understood the general public’s perceptions of childhood obesity and have identified ways of engaging target populations can we hope to develop interventions that can work in a primary or community-based setting

Optimization of interneuron function by direct coupling of cell migration and axonal targeting

Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Altering the normal migratory route of Martinotti cells by conditional deletion of Mafb—a gene that is preferentially expressed by these cells—cell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex

Hyperexcitability of the local cortical circuit in mouse models of tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is a neurogenetic disorder associated with epilepsy, intellectual disabilities, and autistic behaviors. These neurological symptoms result from synaptic dysregulations, which shift a balance between excitation and inhibition. To decipher the synaptic substrate of hyperexcitability, we examined pan-neuronal Tsc1 knockout mouse and found a reduction in surface expression of a GABA receptor (GABAR) subunit but not AMPA receptor (AMPAR) subunit. Using electrophysiological recordings, we found a significant reduction in the frequency of GABAR-mediated miniature inhibitory postsynaptic currents (GABAR-mIPSCs) but not AMPAR-mediated miniature excitatory postsynaptic currents (AMPAR-mEPSCs) in layer 2/3 pyramidal neurons. To determine a subpopulation of interneurons that are especially vulnerable to the absence of TSC1 function, we also analyzed two strains of conditional knockout mice targeting two of the prominent interneuron subtypes that express parvalbumin (PV) or somatostatin (SST). Unlike pan-neuronal knockout mice, both interneuron-specific Tsc-1 knockout mice did not develop spontaneous seizures and grew into adults. Further, the properties of AMPAR-mEPSCs and GABAR-mIPSCs were normal in both Pv-Cre and Sst-Cre x Tsc1fl/fl knockout mice. These results indicate that removal of TSC1 from all neurons in a local cortical circuit results in hyperexcitability while connections between pyramidal neurons and interneurons expressing PV and SST are preserved in the layer 2/3 visual cortex. Our study suggests that another inhibitory cell type or a combination of multiple subtypes may be accountable for hyperexcitability in TSC. Keywords: Tuberous sclerosis complex; E/I balance; AMPA receptor; GABA receptor; Autism; Epilepsy; mTOR pathwa

Noise Suppression and Surplus Synchrony by Coincidence Detection

The functional significance of correlations between action potentials of neurons is still a matter of vivid debates. In particular it is presently unclear how much synchrony is caused by afferent synchronized events and how much is intrinsic due to the connectivity structure of cortex. The available analytical approaches based on the diffusion approximation do not allow to model spike synchrony, preventing a thorough analysis. Here we theoretically investigate to what extent common synaptic afferents and synchronized inputs each contribute to closely time-locked spiking activity of pairs of neurons. We employ direct simulation and extend earlier analytical methods based on the diffusion approximation to pulse-coupling, allowing us to introduce precisely timed correlations in the spiking activity of the synaptic afferents. We investigate the transmission of correlated synaptic input currents by pairs of integrate-and-fire model neurons, so that the same input covariance can be realized by common inputs or by spiking synchrony. We identify two distinct regimes: In the limit of low correlation linear perturbation theory accurately determines the correlation transmission coefficient, which is typically smaller than unity, but increases sensitively even for weakly synchronous inputs. In the limit of high afferent correlation, in the presence of synchrony a qualitatively new picture arises. As the non-linear neuronal response becomes dominant, the output correlation becomes higher than the total correlation in the input. This transmission coefficient larger unity is a direct consequence of non-linear neural processing in the presence of noise, elucidating how synchrony-coded signals benefit from these generic properties present in cortical networks

To Each According to His Need? Variability in the Responses to Inequity in Nonhuman Primates

While it is well established that humans respond to inequity, it remains unclear the extent to which this behavior occurs in our nonhuman primate relatives. By comparing a variety of species, spanning from New World and Old World monkeys to great apes, scientists can begin to answer questions about how the response to inequity evolved, what the function of this response is, and why and how different contexts shape it. In particular, research across nonhuman primate species suggests that the response is quite variable across species, contexts and individuals. In this paper, we aim to review these differences in an attempt to identify and better understand the patterns that emerge from the existing data with the goal of developing directions for future research. To begin, we address the importance of considering socio-ecological factors in nonhuman primates in order to better understand and predict expected patterns of cooperation and aversion to inequity in different species, following which we provide a detailed analysis of the patterns uncovered by these comparisons. Ultimately, we use this synthesis to propose new ideas for research to better understand this response and, hence, the evolution of our own responses to inequity

Spike-Based Bayesian-Hebbian Learning of Temporal Sequences

Many cognitive and motor functions are enabled by the temporal representation and processing of stimuli, but it remains an open issue how neocortical microcircuits can reliably encode and replay such sequences of information. To better understand this, a modular attractor memory network is proposed in which meta-stable sequential attractor transitions are learned through changes to synaptic weights and intrinsic excitabilities via the spike-based Bayesian Confidence Propagation Neural Network (BCPNN) learning rule. We find that the formation of distributed memories, embodied by increased periods of firing in pools of excitatory neurons, together with asymmetrical associations between these distinct network states, can be acquired through plasticity. The model's feasibility is demonstrated using simulations of adaptive exponential integrate-and-fire model neurons (AdEx). We show that the learning and speed of sequence replay depends on a confluence of biophysically relevant parameters including stimulus duration, level of background noise, ratio of synaptic currents, and strengths of short-term depression and adaptation. Moreover, sequence elements are shown to flexibly participate multiple times in the sequence, suggesting that spiking attractor networks of this type can support an efficient combinatorial code. The model provides a principled approach towards understanding how multiple interacting plasticity mechanisms can coordinate hetero-associative learning in unison

Nivel de conocimientos de estudiantes de medicina sobre diagnóstico y manejo del infarto agudo del miocardio

Introduction: acute myocardial infarction is a disease with high morbidity and mortality.Objective: to determine the knowledge level of medical students about the diagnosis and management of acute myocardial infarction.Method: an observational, descriptive and cross-sectional study was carried out between January and February 2022 in medical students from the University of Medical Sciences of Pinar del Río who participated in the provincial update workshop on acute myocardial infarction. Through intentional sampling, a sample of 92 students was selected. To collect the information, a survey was used using Google Forms.Results: the female sex (65,21%), the age group from 21 to 22 years (65,21%) and the fourth-year students (50%) prevailed. Hypertension was the most identified risk factor (97,98%). 97,82% of the students identified precordial pain as the main clinical manifestation. 100% identified the presentation with complications, where sudden death was the most identified (81,52%). 100% point to the electrocardiogram as the main complementary, where ST alterations were the most identified (84,78%). 95,65% of the students indicated constant monitoring of vital parameters and cardiovascular function as the management measure.Conclusions: Medicine students belonging to the clinical area at the University of Medical Sciences of Pinar del Río have an adequate level of knowledge about the diagnosis and management of acute myocardial infarction.Introducción: el infarto agudo del miocardio constituye una enfermedad con elevada morbilidad y mortalidad.Objetivo: determinar el nivel de conocimientos de estudiantes de medicina sobre el diagnóstico y manejo del infarto agudo del miocardioMétodo: se realizó un estudio observacional, descriptivo y transversal entre enero y febrero de 2022 en estudiantes de Medicina de la Universidad de Ciencias Médicas de Pinar del Río del ciclo clínico que participaron en el Taller provincial de actualización sobre infarto agudo de miocardio. Mediante un muestreo intencional se seleccionó una muestra de 92 estudiantes. Para la recolección de la información se empleó una encuesta mediante Google Forms.Resultados: predominó el sexo femenino (65,21 %), el grupo etario de 21 a 22 años (65,21 %) y los estudiantes de cuarto año (50 %). La hipertensión fue el factor de riesgo más identificado (97,98 %). El 97,82 % de los estudiantes identificó el dolor precordial como principal manifestación clínica. El 100 % identificó la presentación con complicaciones, donde la muerte súbita fue la más identificada (81,52 %). El 100 % señala al electrocardiograma como principal complementario, donde las alteraciones del ST fueron las más identificada (84,78 %). El 95,65 % de los estudiantes indicaron la monitorización constante de los parámetros vitales y función cardiovascular como la medida de manejo.Conclusiones: los estudiantes de Medicina pertenecientes al área clínica en la Universidad de Ciencias Médicas de Pinar del Río poseen un adecuado nivel de conocimientos sobre el diagnóstico y manejo del infarto agudo del miocardio.