scholarly journals Local neuronal excitation and global inhibition during epileptic fast ripples in humans

2021 ◽  
Author(s):  
Jonathan Curot ◽  
Emmanuel Barbeau ◽  
Elodie Despouy ◽  
Marie Denuelle ◽  
Jean Christophe Sol ◽  
...  
Keyword(s):  
Large Scale ◽  
Epileptiform Activity ◽  
Field Potential ◽  
Brain Regions ◽  
Epileptogenic Zone ◽  
Neuronal Responses ◽  
Local Networks ◽  
Global Networks ◽  
Epileptiform Discharges ◽  
Local Circuits

AbstractUnderstanding the neuronal basis of epileptiform activity is a major challenge in neurology. Interictal epileptiform discharges are associated with fast ripples (FRs, >200 Hz) in the local field potential (LFP) and are a promising marker of the epileptogenic zone. Here, by using a novel hybrid macro-micro depth electrode, combining classic depth recording of LFP and two or three tetrodes enabling up to 15 neurons in local circuits to be recorded simultaneously, we have characterized neuronal responses to FRs on the same hybrid and other electrodes targeting other brain regions. While FRs were associated with increased neuronal activity in local circuits only, they were followed by inhibition in large-scale networks. Neuronal responses to FRs were homogeneous in local networks but differed across brain areas. Similarly, post-FR inhibition varied across recording locations and subjects and was shorter than typical inter-FR intervals, suggesting that this inhibition is a fundamental refractory process for the networks. These findings demonstrate that FRs engage local and global networks and point to network features that pave the way for new diagnostic and therapeutic strategies.

scholarly journals Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology

2017 ◽  
Vol 114 (47) ◽  
pp. E10046-E10055 ◽  
Author(s):  
Tian-Ming Fu ◽  
Guosong Hong ◽  
Robert D. Viveros ◽  
Tao Zhou ◽  
Charles M. Lieber
Keyword(s):  
Large Scale ◽  
Single Neuron ◽  
Neurological Diseases ◽  
Field Potential ◽  
Brain Regions ◽  
Long Term Stability ◽  
High Density Recording ◽  
Local Circuits ◽  
Key Aspects

Implantable electrical probes have led to advances in neuroscience, brain−machine interfaces, and treatment of neurological diseases, yet they remain limited in several key aspects. Ideally, an electrical probe should be capable of recording from large numbers of neurons across multiple local circuits and, importantly, allow stable tracking of the evolution of these neurons over the entire course of study. Silicon probes based on microfabrication can yield large-scale, high-density recording but face challenges of chronic gliosis and instability due to mechanical and structural mismatch with the brain. Ultraflexible mesh electronics, on the other hand, have demonstrated negligible chronic immune response and stable long-term brain monitoring at single-neuron level, although, to date, it has been limited to 16 channels. Here, we present a scalable scheme for highly multiplexed mesh electronics probes to bridge the gap between scalability and flexibility, where 32 to 128 channels per probe were implemented while the crucial brain-like structure and mechanics were maintained. Combining this mesh design with multisite injection, we demonstrate stable 128-channel local field potential and single-unit recordings from multiple brain regions in awake restrained mice over 4 mo. In addition, the newly integrated mesh is used to validate stable chronic recordings in freely behaving mice. This scalable scheme for mesh electronics together with demonstrated long-term stability represent important progress toward the realization of ideal implantable electrical probes allowing for mapping and tracking single-neuron level circuit changes associated with learning, aging, and neurodegenerative diseases.

Partial Disinhibition Is Required for Transition of Stimulus-Induced Sharp Wave–Ripple Complexes Into Recurrent Epileptiform Discharges in Rat Hippocampal Slices

2011 ◽  
Vol 105 (1) ◽  
pp. 172-187 ◽  
Author(s):  
Agustin Liotta ◽  
Gürsel Çalışkan ◽  
Rizwan ul Haq ◽  
Jan O. Hollnagel ◽  
Anton Rösler ◽  
...  
Keyword(s):  
Hippocampal Slices ◽  
Field Potential ◽  
Long Term Potentiation ◽  
Equilibrium Potential ◽  
High Frequency Stimulation ◽  
Extracellular Potassium ◽  
Epileptogenic Zone ◽  
Sharp Wave ◽  
Epileptiform Discharges ◽  
Inhibitory Conductance

Sharp wave–ripple complexes (SPW-Rs) in the intact rodent hippocampus are characterized by slow field potential transients superimposed by close to 200-Hz ripple oscillations. Similar events have been recorded in hippocampal slices where SPW-Rs occur spontaneously or can be induced by repeated application of high-frequency stimulation, a standard protocol for induction of long-lasting long-term potentiation. Such stimulation is reminiscent of protocols used to induce kindling epilepsy and ripple oscillations may be predictive of the epileptogenic zone in temporal lobe epilepsy. In the present study, we investigated the relation between recurrent epileptiform discharges (REDs) and SPW-Rs by studying effects of partial removal of inhibition. In particular, we compared the effects of nicotine, low-dose bicuculline methiodide (BMI), and elevated extracellular potassium concentration ([K+]o) on induced SPW-Rs. We show that nicotine dose-dependently transformed SPW-Rs into REDs. This transition was associated with reduced inhibitory conductance in CA3 pyramidal cells. Similar results were obtained from slices where the GABAergic conductance was reduced by application of low concentrations of BMI (1–2 μM). In contrast, sharp waves were diminished by phenobarbital. Elevating [K+]o from 3 to 8.5 mM did not transform SPW-Rs into REDs but significantly increased their incidence and amplitude. Under these conditions, the equilibrium potential for inhibition was shifted in depolarizing direction, whereas inhibitory conductance was significantly increased. Interestingly, the propensity of elevated [K+]o to induce seizure-like events was reduced in slices where SPW-Rs had been induced. In conclusion, recruitment of inhibitory cells during SPW-Rs may serve as a mechanism by which hyperexcitation and eventually seizure generation might be prevented.

scholarly journals Large- and multi-scale networks in the rodent brain during novelty exploration

2020 ◽  
Author(s):  
Michael X Cohen ◽  
Bernhard Englitz ◽  
Arthur S C França
Keyword(s):  
Prefrontal Cortex ◽  
Parietal Cortex ◽  
Local Field ◽  
Neural Activity ◽  
Large Scale ◽  
Field Potential ◽  
Brain Regions ◽  
Data Availability ◽  
Data Matrix ◽  
Temporal Scales

AbstractNeural activity is coordinated across multiple spatial and temporal scales, and these patterns of coordination are implicated in both healthy and impaired cognitive operations. However, empirical cross-scale investigations are relatively infrequent, due to limited data availability and to the difficulty of analyzing rich multivariate datasets. Here we applied frequency-resolved multivariate source-separation analyses to characterize a large-scale dataset comprising spiking and local field potential activity recorded simultaneously in three brain regions (prefrontal cortex, parietal cortex, hippocampus) in freely-moving mice. We identified a constellation of multidimensional, inter-regional networks across a range of frequencies (2-200 Hz). These networks were reproducible within animals across different recording sessions, but varied across different animals, suggesting individual variability in network architecture. The theta band (~4-10 Hz) networks had several prominent features, including roughly equal contribution from all regions and strong inter-network synchronization. Overall, these findings demonstrate a multidimensional landscape of large-scale functional activations of cortical networks operating across multiple spatial, spectral, and temporal scales during open-field exploration.Significance statementNeural activity is synchronized over space, time, and frequency. To characterize the dynamics of large-scale networks spanning multiple brain regions, we recorded data from the prefrontal cortex, parietal cortex, and hippocampus in awake behaving mice, and pooled data from spiking activity and local field potentials into one data matrix. Frequency-specific multivariate decomposition methods revealed a cornucopia of neural networks defined by coherent spatiotemporal patterns over time. These findings reveal a rich, dynamic, and multivariate landscape of large-scale neural activity patterns during foraging behavior.

scholarly journals Local propagation dynamics of MEG interictal spikes: source reconstruction with traveling wave priors

2020 ◽  
Author(s):  
Aleksandra Kuznetsova ◽  
Mikhail Lebedev ◽  
Alexei Ossadtchi
Keyword(s):  
Traveling Wave ◽  
Large Scale ◽  
Brain Regions ◽  
Propagation Model ◽  
Sensor Data ◽  
Epileptogenic Zone ◽  
Drug Resistant ◽  
Interictal Spikes ◽  
Propagation Dynamics ◽  
Clinical Records

AbstractEpilepsy is one of the most common neurological disorders, with about 30% of cases being drug-resistant and requiring surgical intervention. To localize the epileptogenic zone (EZ), the pathological area that has to be surgically removed, brain regions are inspected for the presence of spikes during the interictal periods. This procedure maps irritative zones where spikes are present, but it is still challenging to determine which of the irritative zones generate seizures. To localize the source of seizures more precisely, a large-scale approach could be applied where the causal relationship is assessed between the signals recorded in a finite number of irritative zones [27]. This method however, does not reveal the fine-grained spatiotemporal patterns of spikes, which could provide valuable information regarding EZ location and increase the likelihood of surgery success [33].Here we present a framework to noninvasively investigate the fine patterns of interictal spikes present in magnetoencephalographic (MEG) data. We use a traveling wave model, previously employed in the analysis of cortical alpha oscillations [16], to regularize the MEG inverse problem and to determine the cortical paths of spike traveling waves. Our algorithm represents spike propagation patterns as a superposition of local waves traveling along radial paths stemming from a single origin. With the help of the positively constrained LASSO technique we scan over wave onset moment and propagation velocity parameters to determine their combination that yields the best fit to the MEG sensor data of each spike.We first used realistically simulated MEG data to validate the algorithm ability to successfully track interictal activity on a millimeter-millisecond scale. Next, we examined MEG data from three patients with drug-resistant epilepsy. Wave-like spike patterns with clear propagation dynamics were found in a fraction of spikes, whereas the other fraction could not be explained by the wave propagation model with a small number of propagation directions. Moreover, in agreement with the previous work [33], the spike waves with clear propagation dynamics exhibited spatial segregation and matched the clinical records on seizure onset zones (SOZs) available for two patients out of three.

scholarly journals Musical components important for the Mozart K448 effect in epilepsy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert J. Quon ◽  
Michael A. Casey ◽  
Edward J. Camp ◽  
Stephen Meisenhelter ◽  
Sarah A. Steimel ◽  
...  
Keyword(s):  
Refractory Epilepsy ◽  
Focal Epilepsy ◽  
Epileptiform Activity ◽  
Brain Regions ◽  
Original Version ◽  
Pharmacological Intervention ◽  
Theta Power ◽  
Epileptiform Discharges ◽  
Interictal Epileptiform Discharges ◽  
Insight Into

AbstractThere is growing evidence for the efficacy of music, specifically Mozart’s Sonata for Two Pianos in D Major (K448), at reducing ictal and interictal epileptiform activity. Nonetheless, little is known about the mechanism underlying this beneficial “Mozart K448 effect” for persons with epilepsy. Here, we measured the influence that K448 had on intracranial interictal epileptiform discharges (IEDs) in sixteen subjects undergoing intracranial monitoring for refractory focal epilepsy. We found reduced IEDs during the original version of K448 after at least 30-s of exposure. Nonsignificant IED rate reductions were witnessed in all brain regions apart from the bilateral frontal cortices, where we observed increased frontal theta power during transitions from prolonged musical segments. All other presented musical stimuli were associated with nonsignificant IED alterations. These results suggest that the “Mozart K448 effect” is dependent on the duration of exposure and may preferentially modulate activity in frontal emotional networks, providing insight into the mechanism underlying this response. Our findings encourage the continued evaluation of Mozart’s K448 as a noninvasive, non-pharmacological intervention for refractory epilepsy.

Focal Epileptogenesis in a Rat Model of Polymicrogyria

1999 ◽  
Vol 81 (1) ◽  
pp. 159-173 ◽  
Author(s):  
Kimberle M. Jacobs ◽  
Bryan J. Hwang ◽  
David A. Prince
Keyword(s):  
Rat Model ◽  
Epileptiform Activity ◽  
Field Potential ◽  
Excitatory Input ◽  
Synaptic Connectivity ◽  
Epileptogenic Zone ◽  
Cortical Malformation ◽  
Rat Cortex ◽  
Aspartate Receptor ◽  
Focal Zone

Jacobs, Kimberle M., Bryan J. Hwang, and David A. Prince. Focal epileptogenesis in a rat model of polymicrogyria. J. Neurophysiol. 81: 159–173, 1999. Polymicrogyria, a developmental cortical malformation associated with epilepsy, can be modeled in rats with a transcortical freeze lesion on the day of birth (P0) or P1. We have used field potential recordings to characterize the incidence, propagation patterns, and distribution of epileptiform activity in slices from rats with experimental microgyri. Interictal-like epileptiform activity was evoked in slices from 85% of freeze-lesioned rats aged P12–P118. These data show age-specific properties of epileptogenesis, including: a delay in onset, a decrease in the incidence of epileptiform activity in rats >P40 that was specific to those lesioned on P0 as opposed to P1, and a shift in the likely site of initiation to areas further from the microgyrus in mature animals. Several observations suggest that the area adjacent to the microgyrus, which appears histologically normal in Nissl stains, contains the necessary epileptogenic neuronal circuits: 1) in 78% of slices, epileptiform activity could be evoked only from a focal zone adjacent to the microgyrus (paramicrogyral zone) and not within the microgyrus proper; 2) epileptiform activity consistently originated from a particular site within this paramicrogyral zone, independent of the location of the stimulating electrode, suggesting that the generator is outside of the microgyrus; 3) evoked epileptiform activities in the paramicrogyral cortex were unaltered after separation of this zone from the microgyrus with a transcortical cut; and 4) the short-latency graded field potential evoked in the paramicrogyral zone contained an additional negativity not seen in control slices. The epileptiform activity was blocked reversibly by N-methyl-d-aspartate receptor antagonists in slices from mature as well as immature freeze-lesioned rats. These results suggest that aberrant synaptic connectivity develops in rat cortex surrounding the microgyrus and produces a focal epileptogenic zone whose capacity to generate epileptiform activities does not depend on connections with the malformation itself. We hypothesize that afferents, originating from cortical and extracortical sites, lose their targets in the region of the malformation and make appropriate laminar contacts in the cortex adjacent to the malformation, creating an overabundance of excitatory input to this cortical zone. Increased excitatory feedback onto specific cortical elements may be one factor involved in epileptogenesis in this model of a cortical malformation.

Dopamine Enhances Spatiotemporal Spread of Activity in Rat Prefrontal Cortex

2005 ◽  
Vol 93 (2) ◽  
pp. 864-872 ◽  
Author(s):  
Susanta Bandyopadhyay ◽  
Carlos Gonzalez-Islas ◽  
John J. Hablitz
Keyword(s):  
Prefrontal Cortex ◽  
Receptor Antagonist ◽  
Epileptiform Activity ◽  
D1 Receptor ◽  
Synaptic Activity ◽  
Patch Clamp Recording ◽  
Whole Cell ◽  
Epileptiform Discharges ◽  
Skf 81297 ◽  
Local Circuits

Dopaminergic modulation of prefrontal cortex (PFC) is important for neuronal integration in this brain region known to be involved in cognition and working memory. Because of the complexity and heterogeneity of the effect of dopamine on synaptic transmission across layers of the neocortex, dopamine's net effect on local circuits in PFC is difficult to predict. We have combined whole cell patch-clamp recording and voltage-sensitive dye imaging to examine the effect of dopamine on the excitability of local excitatory circuits in rat PFC in vitro. Whole cell voltage-clamp recording from visually identified layer II/III pyramidal neurons in rat brain slices revealed that, in the presence of bicuculline (10 μM), bath-applied dopamine (30–60 μM) increased the amplitude of excitatory postsynaptic currents (EPSCs) evoked by weak intracortical stimulus. The effect was mimicked by the selective D1 receptor agonist SKF 81297 (1 μM). Increasing stimulation resulted in epileptiform discharges. SKF 81297 (1 μM) significantly lowered the threshold stimulus required for generating epileptiform discharges to 83% of control. In the imaging experiments, bath application of dopamine or SKF 81297 enhanced the spatiotemporal spread of activity in response to weak stimulation and previously subthreshold stimulation resulted in epileptiform activity that spread across the whole cortex. These effects could be blocked by the selective D1 receptor antagonist SCH 23390 (10 μM) but not by the D2 receptor antagonist eticlopride (5 μM). These results indicate that dopamine, by a D1 receptor–mediated mechanism, enhances spatiotemporal spread of synaptic activity and lowers the threshold for epileptiform activity in local excitatory circuits within PFC.

GABAA-mediated inhibition and in vitro epileptogenesis in the human neocortex

1995 ◽  
Vol 73 (2) ◽  
pp. 468-484 ◽  
Author(s):  
M. Avoli ◽  
J. Louvel ◽  
C. Drapeau ◽  
R. Pumain ◽  
I. Kurcewicz
Keyword(s):  
Epileptiform Activity ◽  
Field Potential ◽  
High Strength ◽  
Epileptiform Discharge ◽  
Gamma Aminobutyric Acid ◽  
Epileptiform Discharges ◽  
Bath Application ◽  
Gabaa Receptor Antagonist ◽  
K Concentration

1. We made intracellular and extracellular field potential recordings and ion-selective measurements of extracellular Ca2+ concentration ([Ca2+]o) and extracellular K+ concentration ([K+]o) in human neocortical slices that were obtained in the course of epilepsy surgery. Slices were maintained in vitro at 34-35 degrees C and were perfused with Mg(2+)-free artificial cerebrospinal fluid (ACSF). 2. Spontaneous field potential epileptiform discharges (duration = 2.5-80 s) occurred in most of the slices studied (approximately 60%) after 1.5-2 h of perfusion with Mg(2+)-free ACSF. Intracellular recordings from regular-spiking neocortical neurons showed that epileptiform events consisted of large-amplitude (15-30 mV) depolarizing shifts that were capped by bursts of fast action potentials. A decrease in [Ca2+]o (change in [Ca2+]o = 0.02-0.17 mM, 0.07 +/- 0.046 mM, mean +/- SD, from a baseline of 1.8 mM, n = 10 slices) and an increase in [K+]o (change in [K+]o = 0.5-3.8 mM, 1.6 +/- 1.24 mM, from a baseline of 3.25 mM, n = 10) were associated with each epileptiform discharge. 3. The epileptiform activity induced by Mg(2+)-free ACSF was abolished by bath application of antagonists of the N-methyl-D-aspartate (NMDA) receptor. This procedure also blocked the appearance of spreading depression-like episodes. By contrast, the rate of occurrence of epileptiform discharges was not significantly modified by antagonizing non-NMDA receptors. 4. We also observed spontaneous, rhythmic potentials of positive polarity during perfusion of Mg(2+)-free ACSF; the potentials became hyperpolarizing when the neuron membrane was made less negative than -75 mV with intracellular injection of depolarizing current, and they were decreased or abolished during application of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline methiodide (BMI). The rate of occurrence and/or the amplitude of these presumably GABAA-mediated events decreased approximately 2 s before the onset of each epileptiform discharge. 5. Application of BMI prolonged the epileptiform discharges while decreasing their rate of occurrence. These changes were also accompanied by an increase in the amplitude of the epileptiform field potential DC shift, whereas the concomitant decreases in [Ca2+]o and increases in [K+]o became more pronounced than in control Mg(2+)-free medium (31.2% and 42.8%, respectively, n = 10 slices). 6. Intracellular analysis of regular-spiking neurons in slices that did not generate spontaneous epileptiform discharges after > 2 h of perfusion with Mg2+-free ACSF showed all-or none, variable-latency epileptiform bursts that were induced by high-strength focal extracellular stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Interictal Epileptiform Discharges are Task Dependent and are Associated with Lasting Electrocorticographic Changes

2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Stephen Meisenhelter ◽  
Robert J Quon ◽  
Sarah A Steimel ◽  
Markus E Testorf ◽  
Edward J Camp ◽  
...  
Keyword(s):  
Epileptiform Activity ◽  
Memory Task ◽  
Low Frequency ◽  
Brain Regions ◽  
Blank Screen ◽  
High Frequency Oscillations ◽  
Epileptiform Discharges ◽  
Interictal Epileptiform Discharges ◽  
Task Dependence ◽  
Low Frequency Power

Abstract The factors that control the occurrence of interictal epileptiform discharges (IEDs) are not well understood. We suspected that this phenomenon reflects an attention-dependent suppression of interictal epileptiform activity. We hypothesized that IEDs would occur less frequently when a subject viewed a task-relevant stimulus compared with viewing a blank screen. Furthermore, IEDs have been shown to impair memory when they occur in certain regions during the encoding or recall phases of a memory task. Although these discharges have a short duration, their impact on memory suggests that they have longer lasting electrophysiological effects. We found that IEDs were associated with an increase in low-frequency power and a change in the balance between low- and high-frequency oscillations for several seconds. We found that the occurrence of IEDs is modified by whether a subject is attending to a word displayed on screen or is observing a blank screen. In addition, we found that discharges in brain regions in every lobe impair memory. These findings elucidate the relationship between IEDs and memory impairment and reveal the task dependence of the occurrence of IEDs.

Local Circuit Abnormalities in Chronically Epileptic Rats After Intrahippocampal Tetanus Toxin Injection in Infancy

1998 ◽  
Vol 79 (1) ◽  
pp. 106-116 ◽  
Author(s):  
Karen L. Smith ◽  
Chong L. Lee ◽  
John W. Swann
Keyword(s):  
Tetanus Toxin ◽  
Hippocampal Slices ◽  
Field Potential ◽  
Pyramidal Cells ◽  
Membrane Properties ◽  
Small Subset ◽  
Local Circuit ◽  
Epileptiform Discharges ◽  
Network Bursts ◽  
Local Circuits

Smith, Karen L. Chong L. Lee, and John W. Swann. Local circuit abnormalities in chronically epileptic rats after intrahippocampal tetanus toxin injection in infancy. J. Neurophysiol. 79: 106–116, 1998. In vitro slice experiments were undertaken in adult rats to investigate the physiological origins of a chronic epileptic condition that was initiated in infancy. A unilateral injection of a minute quantity of tetanus toxin into hippocampus on postnatal day 10 produced a severe convulsive syndrome characterized by brief but repeated seizures that lasted for 5–7 days. Hippocampal slices were then taken from these rats in adulthood because at this time previous studies have shown the occurrence of electrographic and behavioral seizures. Dramatic alterations in local circuit functioning were observed. In normal artificial cerebrospinal fluid (ACSF), spontaneous epileptiform network bursts were recorded in a majority (73%) of experimental rats. Network bursts occurred in area CA3of both the injected and contralateral hippocampus. These consisted of intracellular depolarization shifts that were coincident with extracellularly recorded network bursts. Often they occurred at frequencies of 0.05–0.1 Hz and although variable in amplitude and duration, had all-or-none-like qualities. These events appeared to arise largely from local circuits in the CA3Csubfield. Network bursts were rarely recorded in area CA1and were never observed in the dentate gyrus. However in 31% of rats, a novel, higher frequency (2–8 Hz) field potential was recorded in area CA1. This was coincident with rhythmic, intracellularly recorded, inhibitory postsynaptic potentials (IPSPs). These summated IPSPs blocked action potential firing and reversed polarity near −75 mV. To understand the origins of network bursting in area CA3C, comparisons were made of the fundamental neurophysiological properties of pyramidal cells in epileptic and control rats. Of the passive and active membrane properties examined, all appeared normal. Unusually prolonged bursts of action potentials were observed in a small subset of pyramidal cells. However on average the duration of intrinsic bursts were unaltered in the CA3 neurons analyzed from experimental rats. To explore the role that alterations in CA3recurrent excitatory network excitability may play in epileptiform discharges, picrotoxin was bath applied. On blockade of γ-aminobutyric acid (GABAA) receptors, slices from experimental rats underwent prolonged electrographic seizures that were up to 10 s in duration. In contrast, slices from control rats produced only brief 100-ms network bursts. These results suggest that a change in excitability within CA3Crecurrent excitatory networks likely contributes to seizures in chronically epileptic rats. However, at the same time, this hyperexcitability is controlled to an important degree by functional GABAA-mediated synaptic inhibition.

Sign in / Sign up

Export Citation Format

Share Document