Sleep brain networks and sleep depth during somatosensory stimulation

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Magnetoencephalography in Stroke Recovery and Rehabilitation

Magnetoencephalography (MEG) is a non-invasive neurophysiological technique used to study the cerebral cortex. Currently, MEG is mainly used clinically to localize epileptic foci and eloquent brain areas in order to avoid damage during neurosurgery. MEG might, however, also be of help in monitoring stroke recovery and rehabilitation. This review focuses on experimental use of MEG in neurorehabilitation. MEG has been employed to detect early modifications in neuroplasticity and connectivity, but there is insufficient evidence as to whether these methods are sensitive enough to be used as a clinical diagnostic test. MEG has also been exploited to derive the relationship between brain activity and movement kinematics for a motor-based brain-computer interface. In the current body of experimental research, MEG appears to be a powerful tool in neurorehabilitation, but it is necessary to produce new data to confirm its clinical utility

Assessment of Event-Related EEG Power After Single-Pulse TMS in Unresponsive Wakefulness Syndrome and Minimally Conscious State Patients

In patients without a behavioral response, non-invasive techniques and new methods of data analysis can complement existing diagnostic tools by providing a method for detecting covert signs of residual cognitive function and awareness. The aim of this study was to investigate the brain oscillatory activities synchronized by single-pulse transcranial magnetic stimulation (TMS) delivered over the primary motor area in the time\u2013frequency domain in patients with the unresponsive wakefulness syndrome or in a minimally conscious state as compared to healthy controls. A time\u2013frequency analysis based on the wavelet transform was used to characterize rapid modifications of oscillatory EEG rhythms induced by TMS in patients as compared to healthy controls. The pattern of EEG changes in the patients differed from that of healthy controls. In the controls there was an early synchronization of slow waves immediately followed by a desynchronization of alpha and beta frequency bands over the frontal and centro-parietal electrodes, whereas an opposite early synchronization, particularly over motor areas for alpha and beta and over the frontal and parietal electrodes for beta power, was seen in the patients. In addition, no relevant modification in slow rhythms (delta and theta) after TMS was noted in patients. The clinical impact of these findings could be relevant in neurorehabilitation settings for increasing the awareness of these patients and defining new treatment procedures

Exoskeleton Training Modulates Complexity in Movement Patterns and Cortical Activity in Able-Bodied Volunteers

Robot-aided gait training (RAGT) plays a crucial role in providing high-dose and high-intensity task-oriented physical therapy. The human-robot interaction during RAGT remains technically challenging. To achieve this aim, it is necessary to quantify how RAGT impacts brain activity and motor learning. This work quantifies the neuromuscular effect induced by a single RAGT session in healthy middle-aged individuals. Electromyographic (EMG) and motion (IMU) data were recorded and processed during walking trials before and after RAGT. Electroencephalographic (EEG) data were recorded during rest before and after the entire walking session. Linear and nonlinear analyses detected changes in the walking pattern, paralleled by a modulation of cortical activity in the motor, attentive, and visual cortices immediately after RAGT. Increases in alpha and beta EEG spectral power and pattern regularity of the EEG match the increased regularity of body oscillations in the frontal plane, and the loss of alternating muscle activation during the gait cycle, when walking after a RAGT session. These preliminary results improve the understanding of human-machine interaction mechanisms and motor learning and may contribute to more efficient exoskeleton development for assisted walking

Experimental protocol to investigate cortical, muscular and body representation alterations in adolescents with idiopathic scoliosis

Background: Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis. AIS is a three-dimensional morphological spinal deformity that affects approximately 1-3% of adolescents. Not all factors related to the etiology of AIS have yet been identified. Objective: The primary aim of this experimental protocol is to quantitatively investigate alterations in body representation in AIS, and to quantitatively and objectively track the changes in body sensorimotor representation due to treatment. Methods: Adolescent girls with a confirmed diagnosis of mild (Cobb angle: 10°-20°) or moderate (21°-35°) scoliosis as well as age and sex-matched controls will be recruited. Participants will be asked to perform a 6-min upright standing and two tasks-named target reaching and forearm bisection task. Eventually, subjects will fill in a self-report questionnaire and a computer-based test to assess body image. This evaluation will be repeated after 6 and 12 months of treatment (i.e., partial or full-time brace and physiotherapy corrective postural exercises). Results: We expect that theta brain rhythm in the central brain areas, alpha brain rhythm lateralization and body representation will change over time depending on treatment and scoliosis progression as a compensatory strategy to overcome a sensorimotor dysfunction. We also expect asymmetric activation of the trunk muscle during reaching tasks and decreased postural stability in AIS. Conclusions: Quantitatively assess the body representation at different time points during AIS treatment may provide new insights on the pathophysiology and etiology of scoliosis

Brain oscillatory activity in adolescent idiopathic scoliosis

Pathophysiology of Adolescent Idiopathic Scoliosis (AIS) is not yet completely understood. This exploratory study aims to investigate two aspects neglected in clinical practice: a defective postural central nervous system control in AIS, and alterations of body schema due to scoliosis spinal deformities. We recorded EEG data and balance data in four different standing positions in 14 adolescents with AIS and in 14 controls. A re-adaptation of the Image Marking Procedure (IMP) assessed body schema alterations on the horizontal (Body Perception Indices (BPIs)) and vertical direction (interacromial and bisiliac axes inclinations). Our results revealed no differences in balance control between groups; higher EEG alpha relative power over sensorimotor areas ipsilateral to the side of the curve and a significant increase of theta relative power localized over the central areas in adolescents with AIS. The difference in BPI shoulder and BPI waist significantly differed between the two groups. The inclinations of the perceived interacromial axes in adolescents with AIS was opposite to the real inclination. Increased theta activity and alpha lateralization observed may be a compensatory strategy to overcome sensorimotor dysfunction mirrored by altered body schema. Scoliosis onset might be preceded by sensorimotor control impairments that last during curve progression

Neurophysiological and BOLD signal uncoupling of giant somatosensory evoked potentials in progressive myoclonic epilepsy: a case-series study

In progressive myoclonic epilepsy (PME), a rare epileptic syndrome caused by a variety of genetic disorders, the combination of peripheral stimulation and functional magnetic resonance imaging (fMRI) can shed light on the mechanisms underlying cortical dysfunction. The aim of the study is to investigate sensorimotor network modifications in PME by assessing the relationship between neurophysiological findings and blood oxygen level dependent (BOLD) activation. Somatosensory-evoked potential (SSEP) obtained briefly before fMRI and BOLD activation during median-nerve electrical stimulation were recorded in four subjects with typical PME phenotype and compared with normative data. Giant scalp SSEPs with enlarger N20-P25 complex compared to normal data (mean amplitude of 26.2\u2009\ub1\u20098.2\u2009\u3bcV after right stimulation and 27.9\u2009\ub1\u20093.7\u2009\u3bcV after left stimulation) were detected. Statistical group analysis showed a reduced BOLD activation in response to median nerve stimulation in PMEs compared to controls over the sensorimotor (SM) areas and an increased response over subcortical regions (p\u2009\u20092.3, corrected). PMEs show dissociation between neurophysiological and BOLD findings of SSEPs (giant SSEP with reduced BOLD activation over SM). A direct pathway connecting a highly restricted area of the somatosensory cortex with the thalamus can be hypothesized to support the higher excitability of these areas

Patient-specific detection of cerebral blood flow alterations as assessed by arterial spin labeling in drug-resistant epileptic patients

Electrophysiological and hemodynamic data can be integrated to accurately and precisely identify the generators of abnormal electrical activity in drug-resistant focal epilepsy. Arterial Spin Labeling (ASL), a magnetic resonance imaging (MRI) technique for quantitative noninvasive measurement of cerebral blood flow (CBF), can provide a direct measure of variations in cerebral perfusion associated with the epileptic focus. In this study, we aimed to confirm the ASL diagnostic value in the identification of the epileptogenic zone, as compared to electrical source imaging (ESI) results, and to apply a template-based approach to depict statistically significant CBF alterations. Standard video-electroencephalography (EEG), high-density EEG, and ASL were performed to identify clinical seizure semiology and noninvasively localize the epileptic focus in 12 drug-resistant focal epilepsy patients. The same ASL protocol was applied to a control group of 17 healthy volunteers from which a normal perfusion template was constructed using a mixed-effect approach. CBF maps of each patient were then statistically compared to the reference template to identify perfusion alterations. Significant hypo- and hyperperfused areas were identified in all cases, showing good agreement between ASL and ESI results. Interictal hypoperfusion was observed at the site of the seizure in 10/12 patients and early postictal hyperperfusion in 2/12. The epileptic focus was correctly identified within the surgical resection margins in the 5 patients who underwent lobectomy, all of which had good postsurgical outcomes. The combined use of ESI and ASL can aid in the noninvasive evaluation of drug-resistant epileptic patients

LRRC8A is essential for swelling-activated chloride current and for regulatory volume decrease in astrocytes

Consolidated evidence indicates that astroglial cells are critical in the homeostatic regulation of cellular volume by means of ion channels and aquaporin-4. Volume-regulated anion channel (VRAC) is the chloride channel that is activated upon cell swelling and critically contributes to cell volume regulation in astrocytes. The molecular identity of VRAC has been recently defined, revealing that it belongs to the leucine-rich repeat-containing 8 (LRRC8) protein family. However, there is a lack of evidence demonstrating that LRRC8A underpins VRAC currents in astrocyte. Nonetheless, direct evidence of the role of LRRC8A in astrocytic regulatory volume decrease remains to be proved. Here, we aim to bridge this gap in knowledge by combining RNA interference specific for LRRC8A with patch-clamp analyses and a water-permeability assay. We demonstrated that LRRC8A molecular expression is essential for swelling-activated chloride current via VRAC in primary-cultured cortical astrocytes. The knockdown of LRRC8A with a specific short interference RNA abolished the recovery of the cell volume after swelling induced by hypotonic challenge. In addition, immunoblotting, immunofluorescence, confocal imaging, and immunogold electron microscopy demonstrated that LRRC8A is expressed in the plasma membrane of primary cortical astrocytes and in situ in astrocytes at the perivascular interface with endothelial cells. Collectively, our results suggest that LRRC8A is an essential subunit of VRAC and a key factor for astroglial volume homeostasis.-Formaggio, F., Saracino, E., Mola, M. G., Rao, S. B., Amiry-Moghaddam, M., Muccini, M., Zamboni, R., Nicchia, G. P., Caprini, M., Benfenati, V. LRRC8A is essential for swelling-activated chloride current and for regulatory volume decrease in astrocytes

AQP4-independent TRPV4 modulation of plasma membrane water permeability

: Despite of the major role of aquaporin (AQP) water channels in controlling transmembrane water fluxes, alternative ways for modulating water permeation have been proposed. In the Central Nervous System (CNS), Aquaporin-4 (AQP4) is reported to be functionally coupled with the calcium-channel Transient-Receptor Potential Vanilloid member-4 (TRPV4), which is controversially involved in cell volume regulation mechanisms and water transport dynamics. The present work aims to investigate the selective role of TRPV4 in regulating plasma membrane water permeability in an AQP4-independent way. Fluorescence-quenching water transport experiments in Aqp4-/- astrocytes revealed that cell swelling rate is significantly increased upon TRPV4 activation and in the absence of AQP4. The biophysical properties of TRPV4-dependent water transport were therefore assessed using the HEK-293 cell model. Calcein quenching experiments showed that chemical and thermal activation of TRPV4 overexpressed in HEK-293 cells leads to faster swelling kinetics. Stopped-flow light scattering water transport assay was used to measure the osmotic permeability coefficient (Pf, cm/s) and activation energy (Ea, kcal/mol) conferred by TRPV4. Results provided evidence that although the Pf measured upon TRPV4 activation is lower than the one obtained in AQP4-overexpressing cells (Pf of AQP4 = 0.01667 ± 0.0007; Pf of TRPV4 = 0.002261 ± 0.0004; Pf of TRPV4 + 4αPDD = 0.007985 ± 0.0006; Pf of WT = 0.002249 ± 0.0002), along with activation energy values (Ea of AQP4 = 0.86 ± 0.0006; Ea of TRPV4 + 4αPDD = 2.73 ± 1.9; Ea of WT = 8.532 ± 0.4), these parameters were compatible with a facilitated pathway for water movement rather than simple diffusion. The possibility to tune plasma membrane water permeability more finely through TRPV4 might represent a protective mechanism in cells constantly facing severe osmotic challenges to avoid the potential deleterious effects of the rapid cell swelling occurring via AQP channels