scholarly journals Probing cortical excitability under GABAergic modulation

2021 ◽  
Author(s):  
Grégory Lepeu ◽  
Ellen Van Maren ◽  
Kristina Slabeva ◽  
Markus Fuchs ◽  
Juan Anso ◽  
...  
Keyword(s):  
Cortical Excitability ◽  
Epileptic Seizures ◽  
Intracranial Stimulation ◽  
Gamma Aminobutyric Acid ◽  
Variable Response ◽  
Gaba Agonist ◽  
Cortical Input ◽  
Tight Correlation ◽  
Gabaergic Modulation

AbstractCortical excitability, the variable response to a given cortical input, is widely studied in neuroscience, from slice experiments and in silico modeling work to human clinical settings. However, a unifying definition and a translational approach to the phenomenon are currently lacking. For example, at the onset of epileptic seizures, cortical excitability may impair resilience to perturbations (external or endogenous). In this study, we tested in vivo whether changes in cortical excitability quantified as evoked response to small perturbation corresponded to changes in resilience to larger perturbations. To do so, we used both cell-type circuit specific optogenetic stimulation in mice and direct intracranial stimulation in one human subject and quantified 1) evoked cortical responses to single pulses of varying intensity, and 2) evoked cortical facilitation and suppression to paired pulses at varying intervals. In the presence of a gamma-Aminobutyric acid (GABA) agonist or antagonist, we found that 1) cortical response to single pulses and 2) cortical facilitation decreased and increased, respectively. Additionally, using trains of opto-pulses in mice in the presence of a GABA agonist, we found increased resilience to the induction of seizures. With this study, we provide evidence for a tight correlation between cortical excitability and resilience, exploring a range of cortical dynamics, from physiological excitability, to pathological discharges. Our study carried out with two different stimulation methods in two species suggests that varying cortical excitability can be tracked with simple protocols involving minute short-lived perturbative stimuli.

Automated System for Epileptic Seizures Prediction based on Multi-Channel Recordings of Electrical Brain Activity

2018 ◽  
pp. 115-122 ◽  
Author(s):  
V. A. Maksimenko ◽  
A. A. Harchenko ◽  
A. Lüttjohann
Keyword(s):  
Epileptic Seizure ◽  
Brain Activity ◽  
Epileptic Seizures ◽  
Automated System ◽  
Brain Computer Interfaces ◽  
Electrical Brain Activity ◽  
Computer Interfaces ◽  
Prediction And Prevention ◽  
The Brain

Introduction: Now the great interest in studying the brain activity based on detection of oscillatory patterns on the recorded data of electrical neuronal activity (electroencephalograms) is associated with the possibility of developing brain-computer interfaces. Braincomputer interfaces are based on the real-time detection of characteristic patterns on electroencephalograms and their transformation  into commands for controlling external devices. One of the important areas of the brain-computer interfaces application is the control of the pathological activity of the brain. This is in demand for epilepsy patients, who do not respond to drug treatment.Purpose: A technique for detecting the characteristic patterns of neural activity preceding the occurrence of epileptic seizures.Results:Using multi-channel electroencephalograms, we consider the dynamics of thalamo-cortical brain network, preceded the occurrence of an epileptic seizure. We have developed technique which allows to predict the occurrence of an epileptic seizure. The technique has been implemented in a brain-computer interface, which has been tested in-vivo on the animal model of absence epilepsy.Practical relevance:The results of our study demonstrate the possibility of epileptic seizures prediction based on multichannel electroencephalograms. The obtained results can be used in the development of neurointerfaces for the prediction and prevention of seizures of various types of epilepsy in humans. 

scholarly journals In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Do-Wan Lee ◽  
Jae-Im Kwon ◽  
Chul-Woong Woo ◽  
Hwon Heo ◽  
Kyung Won Kim ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Rat Model ◽  
Resonance Spectroscopy ◽  
Chow Diet ◽  
Gamma Aminobutyric Acid ◽  
Sprague Dawley ◽  
In Vivo Measurement ◽  
Hippocampal Lesions ◽  
Total Creatine

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (p = 0.001), gamma-aminobutyric acid (p = 0.019), and glutamate + glutamine (p = 0.001); however, creatine + phosphocreatine (p = 0.006) and myo-inositol (p = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (p < 0.001), glutamate/total creatine (p < 0.001), and GABA/total creatine (p = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.

scholarly journals Cortical Excitability across the ALS Clinical Motor Phenotypes

2021 ◽  
Vol 11 (6) ◽  
pp. 715
Author(s):  
Thanuja Dharmadasa
Keyword(s):  
Motor Cortex ◽  
Cortical Excitability ◽  
Phenotypic Variability ◽  
Specific Treatment ◽  
Underlying Disease ◽  
Selective Vulnerability ◽  
Clinical Feature ◽  
Cortical Hyperexcitability ◽  
Wide Range

Amyotrophic lateral sclerosis (ALS) is characterized by its marked clinical heterogeneity. Although the coexistence of upper and lower motor neuron signs is a common clinical feature for most patients, there is a wide range of atypical motor presentations and clinical trajectories, implying a heterogeneity of underlying pathogenic mechanisms. Corticomotoneuronal dysfunction is increasingly postulated as the harbinger of clinical disease, and neurophysiological exploration of the motor cortex in vivo using transcranial magnetic stimulation (TMS) has suggested that motor cortical hyperexcitability may be a critical pathogenic factor linked to clinical features and survival. Region-specific selective vulnerability at the level of the motor cortex may drive the observed differences of clinical presentation across the ALS motor phenotypes, and thus, further understanding of phenotypic variability in relation to cortical dysfunction may serve as an important guide to underlying disease mechanisms. This review article analyses the cortical excitability profiles across the clinical motor phenotypes, as assessed using TMS, and explores this relationship to clinical patterns and survival. This understanding will remain essential to unravelling central disease pathophysiology and for the development of specific treatment targets across the ALS clinical motor phenotypes.

scholarly journals Multimodal in vivo recording using transparent graphene microelectrodes illuminates spatiotemporal seizure dynamics at the microscale

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nicolette Driscoll ◽  
Richard E. Rosch ◽  
Brendan B. Murphy ◽  
Arian Ashourvan ◽  
Ramya Vishnubhotla ◽  
...  
Keyword(s):  
Temporal Resolution ◽  
Spatial Scales ◽  
Epileptic Seizures ◽  
Therapeutic Interventions ◽  
State Transitions ◽  
Integrated Analysis ◽  
High Temporal Resolution ◽  
Seizure Onset ◽  
Acute Seizures

AbstractNeurological disorders such as epilepsy arise from disrupted brain networks. Our capacity to treat these disorders is limited by our inability to map these networks at sufficient temporal and spatial scales to target interventions. Current best techniques either sample broad areas at low temporal resolution (e.g. calcium imaging) or record from discrete regions at high temporal resolution (e.g. electrophysiology). This limitation hampers our ability to understand and intervene in aberrations of network dynamics. Here we present a technique to map the onset and spatiotemporal spread of acute epileptic seizures in vivo by simultaneously recording high bandwidth microelectrocorticography and calcium fluorescence using transparent graphene microelectrode arrays. We integrate dynamic data features from both modalities using non-negative matrix factorization to identify sequential spatiotemporal patterns of seizure onset and evolution, revealing how the temporal progression of ictal electrophysiology is linked to the spatial evolution of the recruited seizure core. This integrated analysis of multimodal data reveals otherwise hidden state transitions in the spatial and temporal progression of acute seizures. The techniques demonstrated here may enable future targeted therapeutic interventions and novel spatially embedded models of local circuit dynamics during seizure onset and evolution.

Brain glutamate metabolism during hypoxia and peripheral chemodenervation

1990 ◽  
Vol 69 (1) ◽  
pp. 147-154 ◽  
Author(s):  
B. Hoop ◽  
M. R. Masjedi ◽  
V. E. Shih ◽  
H. Kazemi
Keyword(s):  
Brain Tissue ◽  
Gamma Aminobutyric Acid ◽  
Glutamate Metabolism ◽  
Peripheral Chemoreceptor ◽  
Transfer Rates ◽  
Neural Excitability ◽  
Glutamate Concentration ◽  
Ventilatory Drive ◽  
Anesthetized Dogs

Glutamate stimulates resting ventilation by altering neural excitability centrally. Hypoxia increases central ventilatory drive through peripheral chemoreceptor stimulation and may also alter cerebral perfusion and glutamate metabolism locally. Therefore the effect of hypoxia and peripheral chemodenervation on cerebrospinal fluid (CSF) transfer rate of in vivo tracer amidated central nervous system glutamate was studied in intact and chemodenervated pentobarbital-anesthetized dogs during normoxia and after 1 h of hypoxia induced with 10 or 12% O2 in N2 breathing at constant expired ventilation and arterial CO2 tension. Chemodenervation was performed by bilateral sectioning of the carotid body nerves and cervical vagi. CSF transfer rates of radiotracer 13NH4+ and [13N]glutamine synthesized via the reaction, glutamate + NH4(+)----glutamine, in brain glia were measured during normoxia and after 1 h of hypoxia. At normoxia, maximal glial glutamine efflux rate jm = 103.3 +/- 11.2 (SE) mumol.l-1.min-1 in all animals. After 1 h of hypoxia in intact animals, jm = 78.4 +/- 10.0 mumol.l-1.min-1. In denervated animals, jm was decreased to 46.3 +/- 4.3 mumol.l-1.min-1. During hypoxia, mean cerebral cortical glutamate concentration was higher in denervated animals (9.98 +/- 1.43 mumol/g brain tissue) than in intact animals (7.63 +/- 1.82 mumol/g brain tissue) and corresponding medullary glutamate concentration tended to be higher in denervated animals. There were no differences between mean glutamine and gamma-aminobutyric acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Interrogation of SLFN11 in pediatric sarcomas uncovers an unexpected biological role and a novel therapeutic approach to overcoming resistance to replicative stress

2020 ◽  
Author(s):  
Jessica Gartrell ◽  
Marcia Mellado-Largarde ◽  
Nancy E. Martinez ◽  
Michael R. Clay ◽  
Armita Bahrami ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Topoisomerase I ◽  
Parp Inhibitor ◽  
Selective Inhibition ◽  
Common Mechanism ◽  
Variable Response ◽  
Replicative Stress ◽  
Pediatric Sarcomas

AbstractPediatric sarcomas represent a heterogeneous group of malignancies that exhibit variable response to DNA damaging chemotherapy. Schlafen family member 11 protein (SLFN11) increases sensitivity to replicative stress, and SLFN11 gene silencing has been implicated as a common mechanism of drug resistance in tumors in adults. We found SLFN11 to be widely expressed in our cohort of pediatric sarcomas. In sarcoma cell lines, protein expression strongly correlated with response to the PARP inhibitor talazoparib (TAL) and the topoisomerase I inhibitor irinotecan (IRN), with SLFN11 knockout resulting in significant loss of sensitivity in vitro and in vivo. However, SLFN11 expression was not associated with favorable outcomes in a retrospective analysis of our patient cohort; instead, the protein was retained and promoted tumor growth and evasion. Furthermore, we show that pediatric sarcomas develop resistance to TAL and IRN through impaired intrinsic apoptosis, and that resistance can be reversed by selective inhibition of BCL-XL.Statement of SignificanceThe role of SLFN11 in pediatric sarcomas has not been thoroughly explored. In contrast to its activity in adult tumors, SLFN11 did not predict favorable outcomes in pediatric patients, was not silenced, and promoted tumor growth. Resistance to replicative stress in SLFN11-expressing sarcomas was reversed by selective inhibition of BCL-XL.

scholarly journals Functional topography of auditory areas derived from the combination of electrophysiological recordings and cortical electrical stimulation.

2021 ◽  
Author(s):  
Agnès Trébuchon ◽  
F.-Xavier Alario ◽  
Catherine Liégeois-Chauvel
Keyword(s):  
Language Processing ◽  
Hemispheric Specialization ◽  
Functional Characterization ◽  
Posterior Part ◽  
Epileptic Seizures ◽  
Superior Temporal Gyrus ◽  
Time Frequency ◽  
Depth Electrodes ◽  
Electrophysiological Recordings

The posterior part of the superior temporal gyrus (STG) has long been known to be a crucial hub for auditory and language processing, at the crossroad of the functionally defined ventral and dorsal pathways. Anatomical studies have shown that this “auditory cortex” is composed of several cytoarchitectonic areas whose limits do not consistently match macro-anatomic landmarks like gyral and sulcal borders. The functional characterization of these areas derived from brain imaging studies has some limitations, even when high field functional magnetic resonance imaging (fMRI) is used, because of the variability observed in the extension of these areas between hemispheres and individuals. In patients implanted with depth electrodes, in vivo recordings and direct electrical stimulations of the different sub-parts of the posterior STG allow to delineate different auditory sub-fields in Heschl’s gyrus (HG), Planum Temporale (PT), the posterior part of the superior temporal gyrus anterior to HG, the posterior superior temporal sulcus (STS), and the region at the parietal-temporal boundary commonly labelled “Spt”. We describe how this delineation can be achieved using data from electrical cortical stimulation combined with local field potentials and time frequency analysis recorded as responses to pure tones and syllables. We show the differences in functional roles between the primary and non-primary auditory areas, in the left and the right hemispheres. We discuss how these findings help understanding the auditory semiology of certain epileptic seizures and, more generally, the neural substrate of hemispheric specialization for language.

scholarly journals Opposing Influence of Sensory and Motor Cortical Input on Striatal Circuitry and Choice Behavior

2018 ◽  
Author(s):  
Christian R. Lee ◽  
Alex J. Yonk ◽  
Joost Wiskerke ◽  
Kenneth G. Paradiso ◽  
James M. Tepper ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Dorsal Striatum ◽  
Behavioral Effect ◽  
Projection Neurons ◽  
Cortical Input ◽  
Optogenetic Stimulation ◽  
Main Input ◽  
Opposing Effects ◽  
Stimulation Of

SummaryThe striatum is the main input nucleus of the basal ganglia and is a key site of sensorimotor integration. While the striatum receives extensive excitatory afferents from the cerebral cortex, the influence of different cortical areas on striatal circuitry and behavior is unknown. Here we find that corticostriatal inputs from whisker-related primary somatosensory (S1) and motor (M1) cortex differentially innervate projection neurons and interneurons in the dorsal striatum, and exert opposing effects on sensory-guided behavior. Optogenetic stimulation of S1-corticostriatal afferents in ex vivo recordings produced larger postsynaptic potentials in striatal parvalbumin (PV)-expressing interneurons than D1- or D2-expressing spiny projection neurons (SPNs), an effect not observed for M1-corticostriatal afferents. Critically, in vivo optogenetic stimulation of S1-corticostriatal afferents produced task-specific behavioral inhibition, which was bidirectionally modulated by striatal PV interneurons. Optogenetic stimulation of M1 afferents produced the opposite behavioral effect. Thus, our results suggest opposing roles for sensory and motor cortex in behavioral choice via distinct influences on striatal circuitry.

Mechanisms involved in neuroprotective effects of transcranial magnetic stimulation

2021 ◽  
Vol 20 ◽  
Author(s):  
Javier Caballero-Villarraso ◽  
Francisco Javier Medina ◽  
Begoña M. Escribano ◽  
Eduardo Agüera ◽  
Abel Santamaría ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Cortical Excitability ◽  
Therapeutic Effects ◽  
Special Role ◽  
Gamma Aminobutyric Acid ◽  
Neuroprotective Effects ◽  
Paradoxical Response ◽  
Molecular Events

: Transcranial magnetic stimulation (TMS) is widely used in neurophysiology to study cortical excitability. Research over the last few decades has highlighted its additional value as a potential therapeutic tool in the treatment of a broad range of psychiatric disorders. More recently, a number of studies have reported beneficial and therapeutic effects for TMS in neurodegenerative conditions and strokes. Yet despite its recognised clinical applications and despite considerable research using animal models, the molecular and physiological mechanisms through which TMS exerts its beneficial and therapeutic effects remain unclear. They are thought to involve biochemical-molecular events affecting membrane potential and gene expression. In this aspect, the dopaminergic system plays a special role. This is the most directly and selectively modulated neurotransmitter system, producing an increase in the flux of dopamine (DA) in various areas of the brain after the application of repetitive TMS (rTMS). Other neurotransmitters, such as glutamate and gamma-aminobutyric acid (GABA) have shown a paradoxical response to rTMS. In this way, their levels increased in the hippocampus and striatum but decreased in the hypothalamus and remained unchanged in the mesencephalon. Similarly, there are sufficient evidences that TMS up-regulates the gene expression of BDNF (one of the main brain neurotrophins). Something similar occurs with the expression of genes such as c-Fos and zif268 that encode trophic and regenerative action neuropeptides. Consequently, the application of TMS can promote the release of molecules involved in neuronal genesis and maintenance. This capacity may mean that TMS becomes a useful therapeutic resource to antagonize processes that underlie the previously mentioned neurodegenerative conditions.

A target-derived chemoattractant controls the development of the corticopontine projection by a novel mechanism of axon targeting

Development ◽  
1991 ◽  
Vol 113 (Supplement_2) ◽  
pp. 123-130
Author(s):  
D. D. M. O'Leary ◽  
C. D. Heffner ◽  
L. Kutka ◽  
L. López-Mascaraque ◽  
A. Missias ◽  
...  
Keyword(s):  
De Novo ◽  
Target Recognition ◽  
Collagen Matrices ◽  
Axon Targeting ◽  
Cortical Input ◽  
3 Dimensional ◽  
In Vivo Experiments ◽  
X Irradiation ◽  
Series Of Experiments

Here, we review our studies in rats of target recognition by developing cortical axons focusing on their innervation of the basilar pons, a major hindbrain target. The corticopontine projection develops by a ‘delayed interstitial budding’ of collaterals from layer 5 corticospinal axons, rather than by a direct ingrowth of primary axons or by bifurcation of the growth cone. Branches form de novo from the axon cylinder in the pathway overlying the basilar pons and extend directly into it. Cocultures of cortex and basilar pons in 3-dimensional collagen matrices show that a diffusible chemotropic signal released by the basilar pons directs the growth of collateral branches from layer 5 axons in a target and neuron specific manner. ‘Delayed’ co-cultures suggest that a diffusible, pontine-derived signal also initiates the selective branching of layer 5 axons. In vivo experiments support this chemotropic mechanism. First, corticospinal axons form collateral branches at novel locations directly over ectopic aggregations of basilar pontine neurons induced by X-irradiation; no branches form at positions that would normally overlie the appropriate region of basilar pons which is absent because of the X-irradiation. Thus, the basilar pons, rather than local cues in the axon pathway, appears to control the location of corticospinal axon branching. Second, in a series of experiments in which different subsets of corticospinal axons are prevented from innervating the basilar pons, remaining corticospinal axons extend collaterals in a directed manner to regions of the basilar pons deprived of cortical input, a behavior consistent with a response to a diffusible chemoattractant emanating from these regions. In conclusion, our findings suggest that a diffusible, target-derived chemotropic molecule(s) underlies target recognition in this developing system by initiating the formation and directing the growth of pontine collateral branches of primary layer 5 corticospinal axons.

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