scholarly journals Local sleep-like cortical reactivity in the awake brain after focal injury

Brain ◽  
2020 ◽  
Author(s):  
Simone Sarasso ◽  
Sasha D’Ambrosio ◽  
Matteo Fecchio ◽  
Silvia Casarotto ◽  
Alessandro Viganò ◽  
...  
Keyword(s):  
Structural Damage ◽  
Brain Injuries ◽  
Network Activity ◽  
Cortical Dynamics ◽  
Electrophysiological Properties ◽  
Focal Brain Injury ◽  
Functional Consequences ◽  
Neurophysiological Assessment ◽  
Brain States ◽  
Focal Injury

Abstract The functional consequences of focal brain injury are thought to be contingent on neuronal alterations extending beyond the area of structural damage. This phenomenon, also known as diaschisis, has clinical and metabolic correlates but lacks a clear electrophysiological counterpart, except for the long-standing evidence of a relative EEG slowing over the injured hemisphere. Here, we aim at testing whether this EEG slowing is linked to the pathological intrusion of sleep-like cortical dynamics within an awake brain. We used a combination of transcranial magnetic stimulation and electroencephalography (TMS/EEG) to study cortical reactivity in a cohort of 30 conscious awake patients with chronic focal and multifocal brain injuries of ischaemic, haemorrhagic and traumatic aetiology. We found that different patterns of cortical reactivity typically associated with different brain states (coma, sleep, wakefulness) can coexist within the same brain. Specifically, we detected the occurrence of prominent sleep-like TMS-evoked slow waves and off-periods—reflecting transient suppressions of neuronal activity—in the area surrounding focal cortical injuries. These perilesional sleep-like responses were associated with a local disruption of signal complexity whereas complex responses typical of the awake brain were present when stimulating the contralesional hemisphere. These results shed light on the electrophysiological properties of the tissue surrounding focal brain injuries in humans. Perilesional sleep-like off-periods can disrupt network activity but are potentially reversible, thus representing a principled read-out for the neurophysiological assessment of stroke patients, as well as an interesting target for rehabilitation.

scholarly journals Local sleep-like cortical reactivity in the awake brain after focal injury

2019 ◽  
Author(s):  
Simone Sarasso ◽  
Sasha D’Ambrosio ◽  
Matteo Fecchio ◽  
Silvia Casarotto ◽  
Alessandro Viganò ◽  
...  
Keyword(s):  
Brain Injury ◽  
Structural Damage ◽  
Brain Injuries ◽  
Neuronal Firing ◽  
Slow Waves ◽  
Cortical Circuits ◽  
Signal Complexity ◽  
Focal Injury ◽  
Intact Cortex ◽  
Local Sleep

AbstractThe functional consequences of brain injury are known to depend on neuronal alterations extending beyond the area of structural damage. Although a lateralized EEG slowing over the injured hemisphere was known since the early days of clinical neurophysiology, its electrophysiological mechanisms were not systematically investigated. In parallel, basic sleep research has thoroughly characterized the neuronal events underlying EEG slow waves in physiological conditions. These EEG events reflect brief interruptions of neuronal firing (OFF-periods) that can occur locally and have prominent consequences on network and behavioral functions. Notably, the EEG slow waves observed following focal brain injury have been never explicitly connected to local sleep-like neuronal events. In previous works, probing cortical circuits with transcranial magnetic stimulation coupled with EEG (TMS/EEG) proved as an effective way to reveal the tendency of cortical circuits to transiently plunge into silent OFF-periods. Here, using this approach, we show that the intact cortex surrounding focal brain injuries engages locally in pathological sleep-like dynamics. Specifically, we employed TMS/EEG in a cohort of thirty conscious awake patients with chronic focal and multifocal brain injuries of various etiologies. TMS systematically evoked prominent slow waves associated with sleep-like OFF-periods in the area surrounding focal cortico-subcortical lesions. These events were associated with a local disruption of signal complexity and were absent when stimulating the contralateral hemisphere. Perilesional sleep-like OFF-periods may represent a valid read-out of the electrophysiological state of discrete cortical circuits following brain injury as well as a potential target of interventions aimed at fostering functional recovery.One Sentence SummaryFocal cortical injuries are associated with local intrusion of sleep-like dynamics over the perilesional areas which disrupt local signal complexity and coexist with typical wakefulness cortical reactivity patterns within the same brain.

scholarly journals Novel Assessment for Interpreting and Documenting an Absence of Suspicion of Injury Including Protocols based on Recognizable Clinically-Relevant Neurophysiological Methods

Neurology ◽  
2019 ◽  
Vol 93 (14 Supplement 1) ◽  
pp. S31.1-S31
Author(s):  
Jonathan Vincent ◽  
Joseph Clark ◽  
Robert Mangine ◽  
Aaron Keuhn-Himmler ◽  
Kimberly Hasselfeld ◽  
...  
Keyword(s):  
Brain Injuries ◽  
Athletic Trainers ◽  
Return To Play ◽  
Valuable Insight ◽  
Sports Teams ◽  
Objective Evidence ◽  
Increased Sensitivity ◽  
Neurophysiological Assessment ◽  
University Of Cincinnati ◽  
The University

ObjectiveOur goal was to develop and validate a neurophysiological assessment that provides objective evidence useful for interpreting and documenting an absence of suspicious injury by the sports-neuro community.BackgroundAs concussion awareness gains public notoriety, the pressure on athletic organizations for timely diagnosis has risen, leading to an increase in assessments detecting brain injuries. Furthermore, legislation has mandated evaluations of suspicious injuries before returning athletes to play. However, validation and standardization of these current tests have been remiss, and their data is often not familiar to athletic trainers.Design/MethodsWe conducted exams on 18 University of Cincinnati athletes from various sports teams. The 18 athletes were assessed after being pulled-from-play, sometimes including failed pulled-from-play, to document the athlete’s return-to-play. All 18 athletes were referrals sent by athletic trainers unsure of the presence of neurotrauma. The list of assessments includes: stereopsis measurements, phoria, oculomotor performance, near-point of convergence, pupil responses, visual suppression, and balance.ResultsAfter examination of the 18 participants, 4 were diagnosed having high suspicion of concussion while the other 14 were cleared to return-to-play. Of the 14 cleared athletes, 0 were found to exhibit any persistent or newly developed symptoms. These results suggest that this assessment can provide useful data for clinical concussive injury evaluation. These demographics can also be examined for developing normative data and increased sensitivity with baselines.ConclusionsWe feel that current concussion assessments for athletic organizations are inadequate. We identified a series of neurophysiological tests that are more clinically-relevant, easy to perform, and document as evidenced from the evaluations used on the University of Cincinnati athletes for diagnostic and return-to-play decisions. This assessment’s functionality goes beyond the sideline, providing valuable insight for documenting presence or absence of suspicious injury post-competition. We feel this model has enhanced clinical utility compared to the current widespread concussion sideline assessments.

scholarly journals Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment

Science ◽  
2021 ◽  
Vol 371 (6530) ◽  
pp. eaax2537 ◽  
Author(s):  
Cleber A. Trujillo ◽  
Edward S. Rice ◽  
Nathan K. Schaefer ◽  
Isaac A. Chaim ◽  
Emily C. Wheeler ◽  
...  
Keyword(s):  
Neural Development ◽  
Modern Human ◽  
Protein Coding ◽  
Electrophysiological Properties ◽  
Induced Pluripotent Cells ◽  
Synaptic Markers ◽  
Functional Consequences ◽  
Induced Pluripotent ◽  
Human Induced Pluripotent Cells ◽  
And Function

The evolutionarily conserved splicing regulator neuro-oncological ventral antigen 1 (NOVA1) plays a key role in neural development and function. NOVA1 also includes a protein-coding difference between the modern human genome and Neanderthal and Denisovan genomes. To investigate the functional importance of an amino acid change in humans, we reintroduced the archaic allele into human induced pluripotent cells using genome editing and then followed their neural development through cortical organoids. This modification promoted slower development and higher surface complexity in cortical organoids with the archaic version of NOVA1. Moreover, levels of synaptic markers and synaptic protein coassociations correlated with altered electrophysiological properties in organoids expressing the archaic variant. Our results suggest that the human-specific substitution in NOVA1, which is exclusive to modern humans since divergence from Neanderthals, may have had functional consequences for our species’ evolution.

scholarly journals Borna Disease Virus Infection Impairs Synaptic Plasticity

2007 ◽  
Vol 81 (16) ◽  
pp. 8833-8837 ◽  
Author(s):  
Romain Volmer ◽  
Christine M. A. Prat ◽  
Gwendal Le Masson ◽  
André Garenne ◽  
Daniel Gonzalez-Dunia
Keyword(s):  
Synaptic Plasticity ◽  
Disease Virus ◽  
Network Activity ◽  
Multielectrode Arrays ◽  
Neuronal Function ◽  
Borna Disease Virus ◽  
Electrophysiological Properties ◽  
Neuronal Network Activity ◽  
Activity Dependent ◽  
Borna Disease

ABSTRACT The mechanisms whereby Borna disease virus (BDV) can impair neuronal function and lead to neurobehavioral disease are not well understood. To analyze the electrophysiological properties of neurons infected with BDV, we used cultures of neurons grown on multielectrode arrays, allowing a real-time monitoring of the electrical activity across the network shaped by synaptic transmission. Although infection did not affect spontaneous neuronal activity, it selectively blocked activity-dependent enhancement of neuronal network activity, one form of synaptic plasticity thought to be important for learning and memory. These findings highlight the original mechanism of the neuronal dysfunction caused by noncytolytic infection with BDV.

scholarly journals Unaltered Network Activity and Interneuronal Firing During Spontaneous Cortical Dynamics In Vivo in a Mouse Model of Severe Myoclonic Epilepsy of Infancy

2016 ◽  
Vol 26 (4) ◽  
pp. 1778-1794 ◽  
Author(s):  
Angela Michela De Stasi ◽  
Pasqualina Farisello ◽  
Iacopo Marcon ◽  
Stefano Cavallari ◽  
Angelo Forli ◽  
...  
Keyword(s):  
Mouse Model ◽  
Myoclonic Epilepsy ◽  
Network Activity ◽  
Cortical Dynamics ◽  
Severe Myoclonic Epilepsy ◽  
Myoclonic Epilepsy Of Infancy

scholarly journals Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting

2021 ◽  
Author(s):  
Nasim Biglari ◽  
Isabella Gaziano ◽  
Jonas Schumacher ◽  
Jan Radermacher ◽  
Lars Paeger ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Energy State ◽  
Functional Characterization ◽  
Anatomical Distribution ◽  
Electrophysiological Properties ◽  
Functional Consequences ◽  
Glucagon Like Peptide 1 ◽  
Differential Ability

AbstractPro-opiomelanocortin (POMC)-expressing neurons in the arcuate nucleus of the hypothalamus represent key regulators of metabolic homeostasis. Electrophysiological and single-cell sequencing experiments have revealed a remarkable degree of heterogeneity of these neurons. However, the exact molecular basis and functional consequences of this heterogeneity have not yet been addressed. Here, we have developed new mouse models in which intersectional Cre/Dre-dependent recombination allowed for successful labeling, translational profiling and functional characterization of distinct POMC neurons expressing the leptin receptor (Lepr) and glucagon like peptide 1 receptor (Glp1r). Our experiments reveal that POMCLepr+ and POMCGlp1r+ neurons represent largely nonoverlapping subpopulations with distinct basic electrophysiological properties. They exhibit a specific anatomical distribution within the arcuate nucleus and differentially express receptors for energy-state communicating hormones and neurotransmitters. Finally, we identify a differential ability of these subpopulations to suppress feeding. Collectively, we reveal a notably distinct functional microarchitecture of critical metabolism-regulatory neurons.

scholarly journals Robust switches in thalamic network activity require a timescale separation between sodium and T-type calcium channel activations

2020 ◽  
Author(s):  
Kathleen Jacquerie ◽  
Guillaume Drion
Keyword(s):  
Synaptic Plasticity ◽  
Calcium Channel ◽  
Network Activity ◽  
Channel Activation ◽  
Channel Inactivation ◽  
Calcium Channel Inactivation ◽  
Target Neuron ◽  
Sodium Channel Activation ◽  
Brain States

AbstractSwitches in brain states, synaptic plasticity and neuromodulation are fundamental processes in our brain that take place concomitantly across several spatial and timescales. All these processes target neuron intrinsic properties and connectivity to achieve specific physiological goals, raising the question of how they can operate without interfering with each other. Here, we highlight the central importance of a timescale separation in the activation of sodium and T-type calcium channels to sustain robust switches in brain states in thalamic neurons that are compatible with synaptic plasticity and neuromodulation. We quantify the role of this timescale separation by comparing the robustness of rhythms of six published conductance-based models at the cellular, circuit and network levels. We show that robust rhythm generation requires a T-type calcium channel activation whose kinetics are situated between sodium channel activation and T-type calcium channel inactivation in all models despite their quantitative differences.

scholarly journals Maturation-dependent response of the piglet brain to scaled cortical impact

2000 ◽  
Vol 93 (3) ◽  
pp. 455-462 ◽  
Author(s):  
Ann-Christine Duhaime ◽  
Susan S. Margulies ◽  
Susan R. Durham ◽  
Maureen M. O'Rourke ◽  
Jeffrey A. Golden ◽  
...  
Keyword(s):  
Mechanical Trauma ◽  
Content Type ◽  
Clinical Syndromes ◽  
Contusion Injury ◽  
Different Ages ◽  
Focal Brain Injury ◽  
Maturational Stage ◽  
Cortical Impact ◽  
Focal Injury ◽  
Fine Print

Object. The goal of this study was to investigate the relationship between maturational stage and the brain's response to mechanical trauma in a gyrencephalic model of focal brain injury. Age-dependent differences in injury response might explain certain unique clinical syndromes seen in infants and young children and would determine whether specific therapies might be particularly effective or even counterproductive at different ages.Methods. To deliver proportionally identical injury inputs to animals of different ages, the authors have developed a piglet model of focal contusion injury by using specific volumes of rapid cortical displacement that are precisely scaled to changes in size and dimensions of the growing brain. Using this model, the histological response to a scaled focal cortical impact was compared at 7 days after injury in piglets that were 5 days, 1 month, and 4 months of age at the time of trauma. Despite comparable injury inputs and stable physiological parameters, the percentage of hemisphere injured differed significantly among ages, with the youngest animals sustaining the smallest lesions (0.8%, 8.4%, and 21.5%, for 5-day-, 1-month-, and 4-month-old animals, respectively, p = 0.0018).Conclusions. These results demonstrate that, for this particular focal injury type and severity, vulnerability to mechanical trauma increases progressively during maturation. Because of its developmental and morphological similarity to the human brain, the piglet brain provides distinct advantages in modeling age-specific responses to mechanical trauma. Differences in pathways leading to cell death or repair may be relevant to designing therapies appropriate for patients of different ages.

scholarly journals The asynchronous state's relation to large-scale potentials in cortex

2019 ◽  
Vol 122 (6) ◽  
pp. 2206-2219 ◽  
Author(s):  
A. Alishbayli ◽  
J. G. Tichelaar ◽  
U. Gorska ◽  
M. X. Cohen ◽  
B. Englitz
Keyword(s):  
Firing Rate ◽  
Clinical Diagnosis ◽  
Neural Activity ◽  
Large Scale ◽  
Cortical Activity ◽  
Spike Count ◽  
Cortical Dynamics ◽  
Brain States ◽  
Asynchronous State ◽  
Cortical Regions

Understanding the relation between large-scale potentials (M/EEG) and their underlying neural activity can improve the precision of research and clinical diagnosis. Recent insights into cortical dynamics highlighted a state of strongly reduced spike count correlations, termed the asynchronous state (AS). The AS has received considerable attention from experimenters and theorists alike, regarding its implications for cortical dynamics and coding of information. However, how reconcilable are these vanishing correlations in the AS with large-scale potentials such as M/EEG observed in most experiments? Typically the latter are assumed to be based on underlying correlations in activity, in particular between subthreshold potentials. We survey the occurrence of the AS across brain states, regions, and layers and argue for a reconciliation of this seeming disparity: large-scale potentials are either observed, first, at transitions between cortical activity states, which entail transient changes in population firing rate, as well as during the AS, and, second, on the basis of sufficiently large, asynchronous populations that only need to exhibit weak correlations in activity. Cells with no or little spiking activity can contribute to large-scale potentials via their subthreshold currents, while they do not contribute to the estimation of spiking correlations, defining the AS. Furthermore, third, the AS occurs only within particular cortical regions and layers associated with the currently selected modality, allowing for correlations at other times and between other areas and layers.

scholarly journals GABA-mediated tonic inhibition differentially modulates gain in functional subtypes of cortical interneurons

2020 ◽  
Vol 117 (6) ◽  
pp. 3192-3202 ◽  
Author(s):  
Alexander Bryson ◽  
Robert John Hatch ◽  
Bas-Jan Zandt ◽  
Christian Rossert ◽  
Samuel F. Berkovic ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Action Potential ◽  
In Silico ◽  
In Silico Analysis ◽  
Tonic Inhibition ◽  
Network Activity ◽  
Gain Modulation ◽  
Neuron Models ◽  
Electrophysiological Properties ◽  
Cortical Interneurons

The binding of GABA (γ-aminobutyric acid) to extrasynaptic GABAA receptors generates tonic inhibition that acts as a powerful modulator of cortical network activity. Despite GABA being present throughout the extracellular space of the brain, previous work has shown that GABA may differentially modulate the excitability of neuron subtypes according to variation in chloride gradient. Here, using biophysically detailed neuron models, we predict that tonic inhibition can differentially modulate the excitability of neuron subtypes according to variation in electrophysiological properties. Surprisingly, tonic inhibition increased the responsiveness (or gain) in models with features typical for somatostatin interneurons but decreased gain in models with features typical for parvalbumin interneurons. Patch-clamp recordings from cortical interneurons supported these predictions, and further in silico analysis was then performed to seek a putative mechanism underlying gain modulation. We found that gain modulation in models was dependent upon the magnitude of tonic current generated at depolarized membrane potential—a property associated with outward rectifying GABAA receptors. Furthermore, tonic inhibition produced two biophysical changes in models of relevance to neuronal excitability: 1) enhanced action potential repolarization via increased current flow into the dendritic compartment, and 2) reduced activation of voltage-dependent potassium channels. Finally, we show theoretically that reduced potassium channel activation selectively increases gain in models possessing action potential dynamics typical for somatostatin interneurons. Potassium channels in parvalbumin-type models deactivate rapidly and are unavailable for further modulation. These findings show that GABA can differentially modulate interneuron excitability and suggest a mechanism through which this occurs in silico via differences of intrinsic electrophysiological properties.

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