The cerebellum promotes sequential foraging strategies and contributes to the directional modulation of hippocampal place cells.

The cerebellum contributes to goal-directed navigation abilities and place coding in the hippocampus. Here we investigated its contribution to foraging strategies. We recorded hippocampal neurons in mice with impaired PKC-dependent cerebellar functions (L7-PKCI) and in their littermate controls while they performed a task where they were rewarded for visiting a subset of hidden locations. We found that L7-PKCI and control mice developed different foraging strategies: while control mice repeated spatial sequences to maximize their rewards, L7-PKCI mice persisted to use a random foraging strategy. Sequential foraging was associated with more place cells exhibiting theta-phase precession and theta rate modulation. Recording in the dark showed that PKC-dependent cerebellar functions controlled how self-motion cues contribute to the selectivity of place cells to both position and direction. Thus, the cerebellum contributes to the development of optimal sequential paths during foraging, possibly by controlling how self-motion and theta signals contribute to place cell coding.

What is the impact on work of osteoporotic fractures in active patients? A retrospective fracture-liaison-service study-Optiwork 1.

PURPOSE: Osteoporotic fractures have economic consequences and can alter the quality of life. Nevertheless, the direct impact on work has been infrequently reported. Our objective was to estimate the proportion of working patients resuming paid employment within the 3 months following an osteoporotic fracture, and to assess the consequences on their productivity and quality of life. METHODS: Patients aged between 45 and 64, screened by the Fracture Liaison Service of Hospital Paris Saint Joseph for a fragility fracture occurring between January 2017 and December 2018, and being paid employees at the time of the fracture, were included retrospectively. Medical data were extracted from electronic medical records. Self-reporting questionnaires concerning work activity and quality of life before and after the fracture were sent by post. RESULTS: Overall, 121 patients were included, with a mean age of 55.8; 82.6% of patients were female. Fracture of the lower extremity of the radius was the most frequent (38.2%), followed by the upper extremity of the humerus (23.1%). After the index fracture, 82.6% of the patients went back to work, including 76.0% within 3 months following the fracture. The median time to return to work was 2.2 months. Moreover, 19.8% of patients required adaptations of their current work. CONCLUSION: Osteoporotic fractures have a direct impact on work activity, causing work stoppages. Productivity at work and quality of life were also impacted. Further studies are needed to confirm these findings.

Mouse Visual Cortex Is Modulated by Distance Traveled and by Theta Oscillations.

The visual responses of neurons in the primary visual cortex (V1) are influenced by the animal's position in the environment [1-5]. V1 responses encode positions that co-fluctuate with those encoded by place cells in hippocampal area CA1 [2, 5]. This correlation might reflect a common influence of non-visual spatial signals on both areas. Place cells in CA1, indeed, do not rely only on vision; their place preference depends on the physical distance traveled [6-11] and on the phase of the 6-9 Hz theta oscillation [12, 13]. Are V1 responses similarly influenced by these non-visual factors? We recorded V1 and CA1 neurons simultaneously while mice performed a spatial task in a virtual corridor by running on a wheel and licking at a reward location. By changing the gain that couples the wheel movement to the virtual environment, we found that ∼20% of V1 neurons were influenced by the physical distance traveled, as were ∼40% of CA1 place cells. Moreover, the firing rate of ∼24% of V1 neurons was modulated by the phase of theta oscillations recorded in CA1 and the response profiles of ∼7% of V1 neurons shifted spatially across the theta cycle, analogous to the phase precession observed in ∼37% of CA1 place cells. The influence of theta oscillations on V1 responses was more prominent in putative layer 6. These results reveal that, in a familiar environment, sensory processing in V1 is modulated by the key non-visual signals that influence spatial coding in the hippocampus.

Computer-based tailored dietary counselling improves the nutrient adequacy of the diet of French pregnant women: a randomised controlled trial.

During pregnancy, mothers-to-be should adapt their diet to meet increases in nutrient requirements. Pregnant women appear to be keener to adopt healthier diets, but are not always successful. The objective of the present study was to determine whether a guided, stepwise and tailored dietary counselling programme, designed using an optimisation algorithm, could improve the nutrient adequacy of the diet of pregnant women, beyond generic guidelines. Pregnant women (n 80) who attended Notre-Dame-de-Bon-Secours Maternity Clinic were randomly allocated to the control or intervention arm. Dietary data were obtained twice from an online 3-d dietary record. The nutrient adequacy of the diet was calculated using the PANDiet score, a 100-point diet quality index adapted to the specific nutrient requirements for pregnancy. Women were supplied with generic dietary guidelines in a reference booklet. In the intervention arm, they also received nine sets of tailored dietary advice identified by an optimisation algorithm as best improving their PANDiet score. Pregnant women (n 78) completed the 12-week dietary follow-up. Initial PANDiet scores were similar in the control and intervention arms (60·4 (sd 7·3) v. 60·3 (sd 7·3), P = 0·92). The PANDiet score increased in the intervention arm (+3·6 (sd 9·3), P = 0·02) but not in the control arm (-0·3 (sd 7·3), P = 0·77), and these changes differed between arms (P = 0·04). In the intervention arm, there were improvements in the probabilities of adequacy for α-linolenic acid, thiamin, folate and cholesterol intakes (P < 0·05). Tailored dietary counselling using a computer-based algorithm is more effective than generic dietary counselling alone in improving the nutrient adequacy of the diet of French women in mid-pregnancy.

Accuracy of the sleep-related breathing disorder scale to diagnose obstructive sleep apnea in children: a meta-analysis.

OBJECTIVES: The main objective of this meta-analysis was to assess the accuracy of the Sleep-Related Breathing Disorder (SRBD) Scale in the diagnosis of obstructive sleep apnea syndrome (OSAS) in children. PATIENTS/METHODS: A literature search of studies comparing SRBD to polysomnography for the diagnosis of OSAS in children was performed. Risks of biases were quantified using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Analyses determined the summary receiver operator characteristic area under the curve (SROC), the pooled sensitivity (Se), the specificity (Sp), and the positive and negative likelihood ratios (LR+ and LR-). Results were graded and are expressed as means [95% confidence interval]. Post-test probabilities were computed for various populations. RESULTS: Eleven studies were included; and two were considered to have high risk of bias. The SROC was 0.73 [CI: 0.63; 0.82]. The combined Se, Sp, LR+ and LR- were: 0.72 [CI: 0.68; 0.77], 0.59 [CI: 0.56; 0.63], 1.74 [CI: 1.32; 2.30], 0.53 [CI: 0.39; 0.71], respectively. Sub-group analyses displayed similar results in comparison to overall results. GRADE evidence for the overall analysis was low to moderate. Finally, pre-test to post-test probabilities were estimated to be: 3.5%-1%, 50%-30% and 75%-30%, for the general population, the obese patients and the patients assigned for surgical treatment of OSAS, respectively. CONCLUSIONS: The current meta-analysis indicates that the SRBD scale has acceptable accuracy in detecting patients with OSAS. It may be useful when evaluating patients with suspected OSAS before surgery. STUDY REGISTRATION: PROSPERO database (CRD42018088216).

Coherent encoding of subjective spatial position in visual cortex and hippocampus.

A major role of vision is to guide navigation, and navigation is strongly driven by vision1-4. Indeed, the brain's visual and navigational systems are known to interact5,6, and signals related to position in the environment have been suggested to appear as early as in the visual cortex6,7. Here, to establish the nature of these signals, we recorded in the primary visual cortex (V1) and hippocampal area CA1 while mice traversed a corridor in virtual reality. The corridor contained identical visual landmarks in two positions, so that a purely visual neuron would respond similarly at those positions. Most V1 neurons, however, responded solely or more strongly to the landmarks in one position rather than the other. This modulation of visual responses by spatial location was not explained by factors such as running speed. To assess whether the modulation is related to navigational signals and to the animal's subjective estimate of position, we trained the mice to lick for a water reward upon reaching a reward zone in the corridor. Neuronal populations in both CA1 and V1 encoded the animal's position along the corridor, and the errors in their representations were correlated. Moreover, both representations reflected the animal's subjective estimate of position, inferred from the animal's licks, better than its actual position. When animals licked in a given location-whether correctly or incorrectly-neural populations in both V1 and CA1 placed the animal in the reward zone. We conclude that visual responses in V1 are controlled by navigational signals, which are coherent with those encoded in hippocampus and reflect the animal's subjective position. The presence of such navigational signals as early as a primary sensory area suggests that they permeate sensory processing in the cortex.

Spatial Information in a Non-retinotopic Visual Cortex.

Turtle dorsal cortex (dCx), a three-layered cortical area of the reptilian telencephalon, receives inputs from the retina via the thalamic lateral geniculate nucleus and constitutes the first cortical stage of visual processing. The receptive fields of dCx neurons usually occupy the entire contralateral visual field. Electrophysiological recordings in awake and anesthetized animals reveal that dCx is sensitive to the spatial structure of natural images, that dCx receptive fields are not entirely uniform across space, and that adaptation to repeated stimulation is position specific. Hence, spatial information can be found both at the single-neuron and population scales. Anatomical data are consistent with the absence of a clear retinotopic mapping of thalamocortical projections. The mapping and representation of visual space in this three-layered cortex thus differ from those found in mammalian primary visual cortex. Our results support the notion that dCx performs a global, rather than local, analysis of the visual scene.

Consensus-Based Sorting of Neuronal Spike Waveforms.

Optimizing spike-sorting algorithms is difficult because sorted clusters can rarely be checked against independently obtained "ground truth" data. In most spike-sorting algorithms in use today, the optimality of a clustering solution is assessed relative to some assumption on the distribution of the spike shapes associated with a particular single unit (e.g., Gaussianity) and by visual inspection of the clustering solution followed by manual validation. When the spatiotemporal waveforms of spikes from different cells overlap, the decision as to whether two spikes should be assigned to the same source can be quite subjective, if it is not based on reliable quantitative measures. We propose a new approach, whereby spike clusters are identified from the most consensual partition across an ensemble of clustering solutions. Using the variability of the clustering solutions across successive iterations of the same clustering algorithm (template matching based on K-means clusters), we estimate the probability of spikes being clustered together and identify groups of spikes that are not statistically distinguishable from one another. Thus, we identify spikes that are most likely to be clustered together and therefore correspond to consistent spike clusters. This method has the potential advantage that it does not rely on any model of the spike shapes. It also provides estimates of the proportion of misclassified spikes for each of the identified clusters. We tested our algorithm on several datasets for which there exists a ground truth (simultaneous intracellular data), and show that it performs close to the optimum reached by a support vector machine trained on the ground truth. We also show that the estimated rate of misclassification matches the proportion of misclassified spikes measured from the ground truth data.

Impact of Proactive Nurse Participation in ICU Family Conferences: A Mixed-Method Study.

OBJECTIVES: To investigate family perceptions of having a nurse participating in family conferences and to assess the psychologic well being of the same families after ICU discharge. DESIGN: Mixed-method design with a qualitative study embedded in a single-center randomized study. SETTING: Twelve-bed medical-surgical ICU in a 460-bed tertiary hospital. SUBJECTS: One family member for each consecutive patient who received more than 48 hours of mechanical ventilation in the ICU. INTERVENTION: Planned proactive participation of a nurse in family conferences led by a physician. In the control group, conferences were led by a physician without a nurse. MEASUREMENTS AND MAIN RESULTS: Of the 172 eligible family members, 100 (60.2%) were randomized; among them, 88 underwent semistructured interviews at ICU discharge and 86 completed the Peritraumatic Dissociative Experiences Questionnaire at ICU discharge and then the Hospital Anxiety Depression Questionnaire and the Impact of Event Scale (for posttraumatic stress-related symptoms) 3 months later. The intervention and control groups were not significantly different regarding the prevalence of posttraumatic stress-related symptoms (52.3 vs 50%, respectively; p = 0.83). Anxiety and depression subscale scores were significantly lower in the intervention group. The qualitative data indicated that the families valued the principle of the conference itself. Perceptions of nurse participation clustered into four main themes: trust that ICU teamwork was effective (50/88; 56.8%), trust that care was centered on the patient (33/88; 37.5%), trust in effective dissemination of information (15/88; 17%), and trust that every effort was made to relieve anxiety in family members (12/88; 13.6%). CONCLUSIONS: Families valued the conferences themselves and valued the proactive participation of a nurse. These positive perceptions were associated with significant anxiety or depression subscale scores but not with changes in posttraumatic stress-related symptoms.

Looking for the roots of cortical sensory computation in three-layered cortices.

Despite considerable effort over a century and the benefit of remarkable technical advances in the past few decades, we are still far from understanding mammalian cerebral neocortex. With its six layers, modular architecture, canonical circuits, innumerable cell types, and computational complexity, isocortex remains a challenging mystery. In this review, we argue that identifying the structural and functional similarities between mammalian piriform cortex and reptilian dorsal cortex could help reveal common organizational and computational principles and by extension, some of the most primordial computations carried out in cortical networks.

Hidden complexity of synaptic receptive fields in cat V1.

In the primary visual cortex (V1), Simple and Complex receptive fields (RFs) are usually characterized on the basis of the linearity of the cell spiking response to stimuli of opposite contrast. Whether or not this classification reflects a functional dichotomy in the synaptic inputs to Simple and Complex cells is still an open issue. Here we combined intracellular membrane potential recordings in cat V1 with 2D dense noise stimulation to decompose the Simple-like and Complex-like components of the subthreshold RF into a parallel set of functionally distinct subunits. Results show that both Simple and Complex RFs exhibit a remarkable diversity of excitatory and inhibitory Complex-like contributions, which differ in orientation and spatial frequency selectivity from the linear RF, even in layer 4 and layer 6 Simple cells. We further show that the diversity of Complex-like contributions recovered at the subthreshold level is expressed in the cell spiking output. These results demonstrate that the Simple or Complex nature of V1 RFs does not rely on the diversity of Complex-like components received by the cell from its synaptic afferents but on the imbalance between the weights of the Simple-like and Complex-like synaptic contributions.

The role of delayed suppression in slow and fast contrast adaptation in V1 simple cells.

The sensitivity and rate of neural coding along the early visual pathways adapt to changes in contrast of the retinal image caused by external motion or self-generated eye movements. To identify the functional mechanisms of fast and slow contrast adaptation at the level of the visual cortex, we randomly varied, over both short and long timescales, the contrast of optimal sinusoidal gratings flashed in the receptive field of simple cells. We found that fast contrast-dependent suppression lagged excitation by ~11 ms and controlled the spike's temporal precision. During slow adaptation to low contrasts, the gain and latency of excitation increased whereas suppression became less visible, resulting in more sensitive but slower and more variable responses. We conclude that delayed suppression controls the response dynamics during both fast and slow contrast adaptation. More generally, we propose that sensory adaptation trades neuronal sensitivity for processing speed by changing the balance between excitation and delayed inhibition.

Virological response and resistance profiles after 18 to 30 months of first- or second-/third-line antiretroviral treatment: a cross-sectional evaluation in HIV type 1-infected children living in the Central African Republic.

A total of 242 HIV-1-infected children were followed up at the Complexe Pédiatrique of Bangui, Central African Republic, including 165 receiving antiretroviral treatment in first- (n=150) or second-/third-line (n=15) regimens. They were prospectively included in a study, in 2009, to assess their virological status and prevalence of antiretroviral drug-resistance mutations in cases of virological failure, according to revised 2010 WHO criteria (e.g., HIV-1 RNA >3.7 log(10) copies/ml). Detectable plasma HIV-1 RNA was observed in 53% of children under first-line treatment, and virological failure was diagnosed in 40%, which was associated in 85% of cases with viruses harboring at least one drug-resistance mutation to nucleoside reverse transcriptase inhibitors (NRTI) or nonnucleoside reverse transcriptase inhibitors (NNRTI), and in 36% of cases with at least one major drug-resistance mutation to NRTI or NNRTI when excluding the M184V mutation. Overall, the proportion of children receiving a first-line regimen for a median of 18 months with virological failure associated with drug-resistance mutations, and thus eligible for a second-line treatment, was estimated at 34% of the whole cohort. In children under second-/third-line therapy, virological failure occurred in 47%, plus at least one major drug-resistance mutation to NRTI or NNRTI, though less commonly to protease inhibitors. Taken together, these findings argue in favor of the urgent need to improve distribution of pediatric antiretroviral drugs in the Central African Republic, to increase adherence by treated children, and to offer adequate HIV biological monitoring.

Surveillance of antiretroviral drug resistance mutations in untreated young children living in the Central African Republic.

BACKGROUND: A survey of drug resistance-associated mutations (DRMs) was conducted in 2009 among 77 vertically HIV-infected children not treated by antiretroviral drugs, followed up at the Complexe Pédiatrique of Bangui, (Bangui, Central African Republic), a country where HIV mother-to-child transmission is prevented by the wide use of single-dose nevirapine in delivering mother and neonate. METHODS: Protease and reverse transcriptase sequencing was performed using the ViroSeq HIV-1 genotyping system, and DRMs were identified according to the 2009 update surveillance of transmitted HIV-1 drug resistance. RESULTS: DRMs were detected in 6 out of 43 samples with interpretable genotypic resistance tests, leading to a 'moderate' DRM prevalence of 13.9% (95% CI 3.5-24.3). DRM to non-nucleoside reverse transcriptase inhibitors were found in 5 samples (11.6% [95% CI, 2.0-21.2]) involving K103N, Y181C and G190A mutations. DRMs to nucleoside reverse transcriptase inhibitors was found in 1 sample (2.3% [95% CI 0.0-6.8]), with the K219Q mutation. No DRMs to protease inhibitors was detected. CONCLUSIONS: This survey predicts a moderate (between 5% and 15%) prevalence of DRMs in the Central African HIV-infected paediatric population of Bangui. These observations highlight the need to make an early diagnosis of the possibility of virological failure in Central African children receiving their first-line antiretroviral regimen.

Adaptation of the simple or complex nature of V1 receptive fields to visual statistics.

Receptive fields in primary visual cortex (V1) are categorized as simple or complex, depending on their spatial selectivity to stimulus contrast polarity. We studied the dependence of this classification on visual context by comparing, in the same cell, the synaptic responses to three classical receptive field mapping protocols: sparse noise, ternary dense noise and flashed Gabor noise. Intracellular recordings revealed that the relative weights of simple-like and complex-like receptive field components were scaled so as to make the same receptive field more simple-like with dense noise stimulation and more complex-like with sparse or Gabor noise stimulations. However, once these context-dependent receptive fields were convolved with the corresponding stimulus, the balance between simple-like and complex-like contributions to the synaptic responses appeared to be invariant across input statistics. This normalization of the linear/nonlinear input ratio suggests a previously unknown form of homeostatic control of V1 functional properties, optimizing the network nonlinearities to the statistical structure of the visual input.

Usefulness of a genotypic resistance test using dried blood spot specimens in African HIV-infected children with virological failure according to the 2010-revised WHO criteria.

We compared paired plasma and dried blood spot (DBS) samples from 54 HIV-1-treated children living in Bangui, Central African Republic, for antiretroviral-resistance-associated mutations. All children displayed virological failure (HIV-1 RNA >3.70 log(10)copies/ml). Testing for resistance genotype was carried out in a reference laboratory in Paris, France. A successful test result was obtained in 54 (100%) plasmas and 25 DBSs (46%). Among the 732 resistance-associated mutations analyzed, 718 were identical, leading to a high concordance rate of 98.1%. Genotypic resistance tests on DBS samples were found to be highly feasible and accurate in a foreign reference laboratory, but with additional costs for shipping and decreased sensitivity.

High-resolution intracellular recordings using a real-time computational model of the electrode.

Intracellular recordings of neuronal membrane potential are a central tool in neurophysiology. In many situations, especially in vivo, the traditional limitation of such recordings is the high electrode resistance and capacitance, which may cause significant measurement errors during current injection. We introduce a computer-aided technique, Active Electrode Compensation (AEC), based on a digital model of the electrode interfaced in real time with the electrophysiological setup. The characteristics of this model are first estimated using white noise current injection. The electrode and membrane contribution are digitally separated, and the recording is then made by online subtraction of the electrode contribution. Tests performed in vitro and in vivo demonstrate that AEC enables high-frequency recordings in demanding conditions, such as injection of conductance noise in dynamic-clamp mode, not feasible with a single high-resistance electrode until now. AEC should be particularly useful to characterize fast neuronal phenomena intracellularly in vivo.