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autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 [Lefaucheur et al., Clin Neurophysiol 2014;125:2150-206]. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a H1-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respectively, in Parkinson's disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spasticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recommendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance.

INTRODUCTION: Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE. METHODS: General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes. RESULTS: The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice. CONCLUSION: Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients' follow up are proposed in the guideline.

AIMS: To systematically evaluate the published evidence regarding the effectiveness of disease management programmes (DMPs) reducing hospital re-admissions among elderly patients with heart failure (HF). METHODS AND RESULTS: Computerised search of MEDLINE (1966 to 31 August 2003) and EMBASE (1966 to 31 August 2003). The Cochrane Library was also searched, and reference lists of review articles on the topic, and of all relevant studies identified, were scanned. Search and selection of studies, data-extraction using standardised forms, and assessment of study quality was performed by two reviewers. The end-point was the proportion of persons who underwent hospital re-admission, and pooled relative risks (RR) were used to summarise the effectiveness of DMPs. The meta-analysis included 54 articles, comprising 27 randomised and 27 non-randomised controlled studies. Randomised studies consistently suggested that, in comparison with usual care, DMP reduced the frequency of re-admission for HF or cardiovascular disease by 30% (pooled RR 0.70; confidence interval (CI) 95% 0.62-0.79), all-cause re-admission by 12% (pooled RR 0.88, 95% CI: 0.79-0.97), and the combined event of re-admission or death by 18% (pooled RR 0.82, 95% CI: 0.72-0.94). The results displayed no substantial variation when only DMPs with home visits, out-patient visits to a clinic, or patient follow-up longer than 6 months were included. For DMPs with out-patient clinical visits, however, the reduction in re-admission for HF or cardiovascular disease, and for all causes, did not attain statistical significance. The magnitude of DMP benefits reported by non-randomised studies was more than double that reported by randomised studies. Practically all the non-randomised studies failed to control for confounding factors, such as severity, co-morbidity and drug therapy. CONCLUSION: DMPs are effective at reducing re-admissions among elderly patients with HF. Their effectiveness is close to that observed in clinical trials evaluating drugs for HF, such as angiotensin-converting enzyme inhibitors, beta-blockers or digoxin. However, since none of the DMP studies compared different interventions directly, we do not know the relative effectiveness of types of healthcare delivery within the DMP.

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (TMS). When applied to motor cortex it leads to after-effects on corticospinal and corticocortical excitability that may reflect LTP/LTD-like synaptic effects. An inhibitory form of TBS (continuous, cTBS) suppresses MEPs, and spinal epidural recordings show this is due to suppression of the I1 volley evoked by TMS. Here we investigate whether the excitatory form of TBS (intermittent, iTBS) affects the same I-wave circuitry. We recorded corticospinal volleys evoked by single pulse TMS of the motor cortex before and after iTBS in three conscious patients who had an electrode implanted in the cervical epidural space for the control of pain. As in healthy subjects, iTBS increased MEPs, and this was accompanied by a significant increase in the amplitude of later I-waves, but not the I1 wave. In two of the patients we tested the excitability of the contralateral cortex and found a significant suppression of the late I-waves. The extent of the changes varied between the three patients, as did their age. To investigate whether age might be a significant contributor to the variability we examined the effect of iTBS on MEPs in 18 healthy subjects. iTBS facilitated MEPs evoked by TMS of the conditioned hemisphere and suppressed MEPs evoked by stimulation of the contralateral hemisphere. There was a slight but non-significant decline in MEP facilitation with age, suggesting that interindividual variability was more important than age in explaining our data. In a subgroup of 10 subjects we found that iTBS had no effect on the duration of the ipsilateral silent period suggesting that the reduction in contralateral MEPs was not due to an increase in ongoing transcallosal inhibition. In conclusion, iTBS affects the excitability of excitatory synaptic inputs to pyramidal tract neurones that are recruited by a TMS pulse, both in the stimulated hemisphere and in the contralateral hemisphere. However the circuits affected differ from those influenced by the inhibitory, cTBS, protocol. The implication is that cTBS and iTBS may have different therapeutic targets.

The purpose of the present study was to perform a meta-analysis to compare the efficacy of heavy (∼80% of one repetition maximum, 1RM) vs light-moderate load (∼45% 1RM) resistance training (RT) programs in inducing strength gains and skeletal muscle hypertrophy in elderly people. To assess the role of training volumes, studies in which training protocols were matched for mechanical work were independently analyzed. In all 15 studies included (448 subjects, age 67.8 years), when comparing heavy with light-moderate loads, strength gains tended to be larger following RT with higher intensities of load, with the resulting total population effect being μ = 0.430 (P = 0.060). Effect sizes were substantially smaller in "work-matched" studies (μ = 0.297, P = 0.003). Training with higher loads also provoked marginally larger gains in muscle size, although the degree of training-induced muscle hypertrophy was generally small (0.056 < μ < 0.136). To conclude, provided a sufficient number of repetitions is performed, RT at lower than traditionally recommended intensities of load may suffice to induce substantial gains in muscle strength in elderly cohorts.

Advances in new technologies for complete slide digitization in pathology have allowed the appearance of a wide spectrum of technologic solutions for whole-slide scanning, which have been classified into motorized microscopes and scanners. This article describes technical aspects of 31 different digital microscopy systems. The most relevant characteristics of the scanning devices are described, including the cameras used, the speed of digitization, and the image quality. Other aspects, such as the file format, the compression techniques, and the solutions for visualization of digital slides, (including diagnosis-aided tools) are also considered. Most of the systems evaluated allow a high-resolution digitization of the whole slide within about 1 hour using a x40 objective. The image quality of the current virtual microscopy systems is suitable for clinical, educational, and research purposes. The efficient use of digital microscopy by means of image analysis systems can offer important benefits to pathology departments.

Bile acids are steroid acids found in the bile of mammals. The bile acid conjugate tauroursodeoxycholic acid (TUDCA) is neuroprotective in different animal models of stroke and neurological diseases. We have previously shown that TUDCA has anti-inflammatory effects on glial cell cultures and in a mouse model of acute neuroinflammation. We show now that microglial cells (central nervous system resident macrophages) express the G protein-coupled bile acid receptor 1/Takeda G protein-coupled receptor 5 (GPBAR1/TGR5) in vivo and in vitro. TUDCA binding to GPBAR1/TGR5 caused an increase in intracellular cAMP levels in microglia that induced anti-inflammatory markers, while reducing pro-inflammatory ones. This anti-inflammatory effect of TUDCA was inhibited by small interference RNA for GPBAR1/TGR5 receptor, as well as by treatment with a protein kinase A (PKA) inhibitor. In the mouse model of acute neuroinflammation, treating the animals with TUDCA was clearly anti-inflammatory. TUDCA biased the microglial phenotype in vivo and in vitro toward the anti-inflammatory. The bile acid receptor GPBAR1/TGR5 could be a new therapeutic target for pathologies coursing with neuroinflammation and microglia activation, such as traumatic brain injuries, stroke, or neurodegenerative diseases. TUDCA and other GPBAR1/TGR5 agonists need to be further investigated, to determine their potential in attenuating the neuropathologies associated with microglia activation. J. Cell. Physiol. 232: 2231-2245, 2017. © 2016 Wiley Periodicals, Inc.

OBJECTIVES: To demonstrate the value of three-dimensional (3D) ultrasound in the diagnosis of uterine malformations and its concordance with magnetic resonance imaging (MRI). METHODS: This study included 286 women diagnosed with uterine malformation by 3D ultrasound, having been referred to our clinics on suspicion of uterine malformation following clinical and/or conventional two-dimensional ultrasound examination. With the exception of three with intact hymen, patients underwent both bimanual examination and speculoscopy before and/or after sonography. MRI was performed in 65 cases. We analyzed the diagnostic concordance between the techniques in the study of uterine malformations. RESULTS: Using 3D ultrasound we diagnosed: one case with uterine agenesis; 10 with unicornuate uterus, four of which also underwent MRI; six with didelphic uterus, one of which had MRI; 45 with bicornuate uterus, 12 of which had MRI; 125 with septate uterus (18 with two cervices), 42 of which had MRI (six with two cervices); 96 with arcuate uterus, three of which had MRI; and three with diethylstilbestrol (DES) iatrogenic uterine malformations, all of which had MRI. Among the 65 which underwent MRI, the diagnosis was: four cases with unicornuate uterus, 10 with bicornuate uterus (two with two cervices), 45 with septate uterus (five with two cervices), three with arcuate uterus and three with DES-related uterine malformations. The concordance between 3D ultrasound and MRI was very good (kappa index, 0.880 (95% CI, 0.769-0.993)). Discrepancies in diagnosis between the two techniques occurred in four cases. There was very good concordance in the diagnosis of associated findings (kappa index, 0.878 (95% CI, 0.775-0.980)), this analysis identifying differences in two cases. CONCLUSIONS: There is a high degree of concordance between 3D ultrasound and MRI in the diagnosis of uterine malformations, the relationship between cavity and fundus being visualized equally well with both techniques. 3D ultrasound should be complemented by careful gynecological exploration in order to identify any alterations in the cervix.

BACKGROUND: Nonadherence and medication errors are common among patients with complex drug regimens. Apps for smartphones and tablets are effective for improving adherence, but they have not been tested in elderly patients with complex chronic conditions and who typically have less experience with this type of technology. OBJECTIVE: The objective of this study was to design, implement, and evaluate a medication self-management app (called ALICE) for elderly patients taking multiple medications with the intention of improving adherence and safe medication use. METHODS: A single-blind randomized controlled trial was conducted with a control and an experimental group (N=99) in Spain in 2013. The characteristics of ALICE were specified based on the suggestions of 3 nominal groups with a total of 23 patients and a focus group with 7 professionals. ALICE was designed for Android and iOS to allow for the personalization of prescriptions and medical advice, showing images of each of the medications (the packaging and the medication itself) together with alerts and multiple reminders for each alert. The randomly assigned patients in the control group received oral and written information on the safe use of their medications and the patients in the experimental group used ALICE for 3 months. Pre and post measures included rate of missed doses and medication errors reported by patients, scores from the 4-item Morisky Medication Adherence Scale (MMAS-4), level of independence, self-perceived health status, and biochemical test results. In the experimental group, data were collected on their previous experience with information and communication technologies, their rating of ALICE, and their perception of the level of independence they had achieved. The intergroup intervention effects were calculated by univariate linear models and ANOVA, with the pre to post intervention differences as the dependent variables. RESULTS: Data were obtained from 99 patients (48 and 51 in the control and experimental groups, respectively). Patients in the experimental group obtained better MMAS-4 scores (P<.001) and reported fewer missed doses of medication (P=.02). ALICE only helped to significantly reduce medication errors in patients with an initially higher rate of errors (P<.001). Patients with no experience with information and communication technologies reported better adherence (P<.001), fewer missed doses (P<.001), and fewer medication errors (P=.02). The mean satisfaction score for ALICE was 8.5 out of 10. In all, 45 of 51 patients (88%) felt that ALICE improved their independence in managing their medications. CONCLUSIONS: The ALICE app improves adherence, helps reduce rates of forgetting and of medication errors, and increases perceived independence in managing medication. Elderly patients with no previous experience with information and communication technologies are capable of effectively using an app designed to help them take their medicine more safely. TRIAL REGISTRATION: Clinicaltrials.gov NCT02071498; http://clinicaltrials.gov/ct2/show/NCT02071498.

Fast ripples are a type of transient high-frequency oscillations recorded from the epileptogenic regions of the hippocampus and the temporal cortex of epileptic humans and rodents. These events presumably reflect hypersynchronous bursting of pyramidal cells. However, the oscillatory spectral content of fast ripples varies from 250 to 800 Hz, well above the maximal firing frequency of most hippocampal pyramidal neurons. How such high-frequency oscillations are generated is therefore unclear. Here, we combine computational simulations of fast ripples with multisite and juxtacellular recordings in vivo to examine the underlying mechanisms in the hippocampus of epileptic rats. We show that populations of bursting cells firing individually at 100-400 Hz can create fast ripples according to two main firing regimes: (1) in-phase synchronous firing resulting in "pure" fast ripples characterized by single spectral peaks that reflect single-cell behavior and (2) out-of-phase firing that results in "emergent" fast ripples. Using simulations, we found that fast ripples generated under these two different regimes can be quantitatively separated by their spectral characteristics, and we took advantage of this separability to examine their dynamics in vivo. We found that in-phase firing can reach frequencies up to 300 Hz in the CA1 and up to 400 Hz in the dentate gyrus. The organization of out-of-phase firing is determined by firing delays between cells discharging at low frequencies. The two firing regimes compete dynamically, alternating randomly from one fast ripple event to the next, and they reflect the functional dynamic organization of the different regions of the hippocampus.

Robotic and functional electrical stimulation (FES) approaches are used for rehabilitation of walking impairment of spinal cord injured individuals. Although devices are commercially available, there are still issues that remain to be solved. Control of hybrid exoskeletons aims at blending robotic exoskeletons and electrical stimulation to overcome the drawbacks of each approach while preserving their advantages. Hybrid actuation and control have a considerable potential for walking rehabilitation but there is a need of novel control strategies of hybrid systems that adequately manage the balance between FES and robotic controllers. Combination of FES and robotic control is a challenging issue, due to the non-linear behavior of muscle under stimulation and the lack of developments in the field of hybrid control. In this article, a cooperative control strategy of a hybrid exoskeleton is presented. This strategy is designed to overcome the main disadvantages of muscular stimulation: electromechanical delay and change in muscle performance over time, and to balance muscular and robotic actuation during walking.Experimental results in healthy subjects show the ability of the hybrid FES-robot cooperative control to balance power contribution between exoskeleton and muscle stimulation. The robotic exoskeleton decreases assistance while adequate knee kinematics are guaranteed. A new technique to monitor muscle performance is employed, which allows to estimate muscle fatigue and implement muscle fatigue management strategies. Kinesis is therefore the first ambulatory hybrid exoskeleton that can effectively balance robotic and FES actuation during walking. This represents a new opportunity to implement new rehabilitation interventions to induce locomotor activity in patients with paraplegia.Acronym list: 10 mWT: ten meters walking test; 6 MWT: six minutes walking test; FSM: finite-state machine; t-FSM: time-domain FSM; c-FSM: cycle-domain FSM; FES: functional electrical stimulation; HKAFO: hip-knee-ankle-foot orthosis; ILC: iterative error-based learning control; MFE: muscle fatigue estimator; NILC: Normalized stimulation output from ILC controller; PID: Proportional-Integral-derivative Control; PW: Stimulation pulse width; QUEST: Quebec User Evaluation of Satisfaction with assistive Technology; SCI: Spinal cord injury; TTI: torque-time integral; VAS: Visual Analog Scale.

BACKGROUND: It is commonly accepted that pregnancy-related physiological changes (circulatory, respiratory, and locomotor) negatively influence the daily physical activity of pregnant women. OBJECTIVES: The aim of this study is to conduct a meta-analysis of randomised controlled trials (RCTs) for assessing the effectiveness of physical exercise interventions during pregnancy to prevent gestational diabetes mellitus and excessive maternal weight gain. SEARCH STRATEGY: Keywords were used to conduct a computerised search in six databases: Cochrane Library Plus, Science Direct, EMBASE, PubMed, Web of Science, and ClinicalTrials.gov. SELECTION CRITERIA: Healthy pregnant women who were sedentary or had low levels of physical activity were selected for RCTs that included an exercise programme. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and assessed the quality of the included studies. Of 4225 articles retrieved, 13 RCTs (2873 pregnant women) met the inclusion criteria. Pooled relative risk (RR) or weighted mean differences (WMDs) (depending on the outcome measure) were calculated using a random-effects model. MAIN RESULTS: Overall, physical exercise programmes during pregnancy decreased the risk of gestational diabetes mellitus (RR = 0.69; P = 0.009), particularly when the exercise programme was performed throughout pregnancy (RR = 0.64; P = 0.038). Furthermore, decreases were also observed in maternal weight (WMD = -1.14 kg; 95% CI -1.50 to -0.78; P < 0.001). No serious adverse effects were reported. CONCLUSION: Structured moderate physical exercise programmes during pregnancy decrease the risk of gestational diabetes mellitus and diminish maternal weight gain, and seem to be safe for the mother and the neonate; however, further studies are needed to establish recommendations.

BACKGROUND: There is inconsistent evidence about the effect of physical activity on the prevention and treatment of depression during the postnatal period. The aim of this meta-analysis was to determine the effect of physical activity interventions during pregnancy and the postpartum period for controlling postpartum depressive symptoms. METHODS: We systematically searched Cochrane Library Plus, Science Direct, EMBASE, CINAHL, PubMed, Web of Science, and Scopus, from January 1990 to May 2016, for randomized or nonrandomized controlled trials addressing the effect of physical activity on postpartum depression. The inverse variance-weighted method was used to compute pooled estimates of effect size and respective 95% confidence intervals (95% CI) for physical activity intervention on postpartum depression. Subgroup analyses were performed comparing women with and without postpartum depressive symptoms according to specific scales measuring this construct. Meta-regression and sensitivity analysis were computed to evaluate heterogeneity. RESULTS: = 33.1% (P = .117). When subgroup analyses were done, pooled effect sizes were 0.67 (95% CI 0.44-0.90) for mothers who met postpartum depressive symptoms criteria at baseline based on specific scales, and 0.29 (95% CI 0.14-0.45) for mothers who did not meet those depressive symptoms criteria at baseline. CONCLUSION: Physical exercise during pregnancy and the postpartum period is a safe strategy to achieve better psychological well-being and to reduce postpartum depressive symptoms.

The motor system may rely on a modular organization (muscle synergies activated in time) to execute different tasks. We investigated the common control features of walking and cycling in healthy humans from the perspective of muscle synergies. Three hypotheses were tested: 1) muscle synergies extracted from walking trials are similar to those extracted during cycling; 2) muscle synergies extracted from one of these motor tasks can be used to mathematically reconstruct the electromyographic (EMG) patterns of the other task; 3) muscle synergies of cycling can result from merging synergies of walking. A secondary objective was to identify the speed (and cadence) at which higher similarities emerged. EMG activity from eight muscles of the dominant leg was recorded in eight healthy subjects during walking and cycling at four matched cadences. A factorization technique [nonnegative matrix factorization (NNMF)] was applied to extract individual muscle synergy vectors and the respective activation coefficients behind the global muscular activity of each condition. Results corroborated hypotheses 2 and 3, showing that 1) four synergies from walking and cycling can successfully explain most of the EMG variability of cycling and walking, respectively, and 2) two of four synergies from walking appear to merge together to reconstruct one individual synergy of cycling, with best reconstruction values found for higher speeds. Direct comparison of the muscle synergy vectors of walking and the muscle synergy vectors of cycling (hypothesis 1) produced moderated values of similarity. This study provides supporting evidence for the hypothesis that cycling and walking share common neuromuscular mechanisms.

The aim of the present study was to investigate in healthy humans the possibility of a non-invasive modulation of motor cortex excitability by the application of static magnetic fields through the scalp. Static magnetic fields were obtained by using cylindrical NdFeB magnets. We performed four sets of experiments. In Experiment 1, we recorded motor potentials evoked by single-pulse transcranial magnetic stimulation (TMS) of the motor cortex before and after 10 min of transcranial static magnetic field stimulation (tSMS) in conscious subjects. We observed an average reduction of motor cortex excitability of up to 25%, as revealed by TMS, which lasted for several minutes after the end of tSMS, and was dose dependent (intensity of the magnetic field) but not polarity dependent. In Experiment 2, we confirmed the reduction of motor cortex excitability induced by tSMS using a double-blind sham-controlled design. In Experiment 3, we investigated the duration of tSMS that was necessary to modulate motor cortex excitability. We found that 10 min of tSMS (compared to 1 min and 5 min) were necessary to induce significant effects. In Experiment 4, we used transcranial electric stimulation (TES) to establish that the tSMS-induced reduction of motor cortex excitability was not due to corticospinal axon and/or spinal excitability, but specifically involved intracortical networks. These results suggest that tSMS using small static magnets may be a promising tool to modulate cerebral excitability in a non-invasive, painless, and reversible way.

Different approaches are available to compensate gait in persons with spinal cord injury, including passive orthoses, functional electrical stimulation (FES), and robotic exoskeletons. However, several drawbacks arise from each specific approach. Orthotic gait is energy-demanding for the user and functionally ineffective. FES uses the muscles as natural actuators to generate gait, providing not only functional but also psychological benefits to the users. However, disadvantages are also related to the early appearance of muscle fatigue and the control of joint trajectories. Robotic exoskeletons that provide joint moment compensation or substitution to the body during walking have been developed in recent years. Significant advances have been achieved, but the technology itself is not mature yet because of many limitations related to both physical and cognitive interaction as well as portability and energy-management issues. Meanwhile, the combination of FES technology and exoskeletons has emerged as a promising approach to both gait compensation and rehabilitation, bringing together technologies, methods, and rehabilitation principles that can overcome the drawbacks of each individual approach. This article presents an overview of hybrid lower-limb exoskeletons, related technologies, and advances in actuation and control systems. Also, we highlight the functional assessment of individuals with spinal cord injury.

While neurons principally mediate brain function, astrocytes are emerging as cells with important neuromodulatory actions in brain physiology. In addition to homeostatic roles, astrocytes respond to neurotransmitters with calcium transients stimulating the release of gliotransmitters that regulate synaptic and neuronal functions. We investigated astrocyte-neuronal network interactions in vivo by combining two-photon microscopy to monitor astrocyte calcium and electrocorticogram to record neuronal network activity in the somatosensory cortex during sensory stimulation. We found astrocytes respond to sensory stimuli in a stimulus-dependent manner. Sensory stimuli elicit a surge of neuronal network activity in the gamma range (30-50 Hz) followed by a delayed astrocyte activity that dampens the steady-state gamma activity. This sensory-evoked gamma activity increase is enhanced in transgenic mice with impaired astrocyte calcium signaling and is decreased by pharmacogenetic stimulation of astrocytes. Therefore, cortical astrocytes respond to sensory inputs and regulate sensory-evoked neuronal network activity maximizing its dynamic range.

The basic information architecture in the basal ganglia circuit is under debate. Whereas anatomical studies quantify extensive convergence/divergence patterns in the circuit, suggesting an information sharing scheme, neurophysiological studies report an absence of linear correlation between single neurones in normal animals, suggesting a segregated parallel processing scheme. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and in parkinsonian patients single neurones become linearly correlated, thus leading to a loss of segregation between neurones. Here we propose a possible integrative solution to this debate, by extending the concept of functional segregation from the cellular level to the network level. To this end, we recorded local field potentials (LFPs) from electrodes implanted for deep brain stimulation (DBS) in the subthalamic nucleus (STN) of parkinsonian patients. By applying bispectral analysis, we found that in the absence of dopamine stimulation STN LFP rhythms became non-linearly correlated, thus leading to a loss of segregation between rhythms. Non-linear correlation was particularly consistent between the low-beta rhythm (13-20 Hz) and the high-beta rhythm (20-35 Hz). Levodopa administration significantly decreased these non-linear correlations, therefore increasing segregation between rhythms. These results suggest that the extensive convergence/divergence in the basal ganglia circuit is physiologically necessary to sustain LFP rhythms distributed in large ensembles of neurones, but is not sufficient to induce correlated firing between neurone pairs. Conversely, loss of dopamine generates pathological linear correlation between neurone pairs, alters the patterns within LFP rhythms, and induces non-linear correlation between LFP rhythms operating at different frequencies. The pathophysiology of information processing in the human basal ganglia therefore involves not only activities of individual rhythms, but also interactions between rhythms.

Spinal cord injury can produce extensive long-term reorganization of the cerebral cortex. Little is known, however, about the sequence of cortical events starting immediately after the lesion. Here we show that a complete thoracic transection of the spinal cord produces immediate functional reorganization in the primary somatosensory cortex of anesthetized rats. Besides the obvious loss of cortical responses to hindpaw stimuli (below the level of the lesion), cortical responses evoked by forepaw stimuli (above the level of the lesion) markedly increase. Importantly, these increased responses correlate with a slower and overall more silent cortical spontaneous activity, representing a switch to a network state of slow-wave activity similar to that observed during slow-wave sleep. The same immediate cortical changes are observed after reversible pharmacological block of spinal cord conduction, but not after sham. We conclude that the deafferentation due to spinal cord injury can immediately (within minutes) change the state of large cortical networks, and that this state change plays a critical role in the early cortical reorganization after spinal cord injury.