Regulatory Mechanism for Absence Seizures in Bidirectional Interactive Thalamocortical Model via Different Targeted Therapy Schemes

Recent clinical practice has found that the spike-wave discharge (SWD) scopes of absence seizures change from small cortical region to large thalamocortical networks, which has also been proved by theoretical simulation. The best biophysics explanation is that there are interactions between coupled cortico-thalamic and thalamocortical circuits. To agree with experiment results and describe the phenomena better, we constructed a coupled thalamocortical model with bidirectional channel (CTMBC) to account for the causes of absence seizures which are connected by the principle of two-way communication of neural pathways. By adjusting the coupling strength of bidirectional pathways, the spike-wave discharges are reproduced. Regulatory mechanism for absence seizures is further applied to CTMBC via four different targeted therapy schemes, such as deep brain stimulation (DBS), charge-balanced biphasic pulse (CBBP), coordinated reset stimulation (CRS) 1 : 0, and (CRS) 3 : 2. The new CTMBC model shows that neurodiversity in bidirectional interactive channel could supply theory reference for the bidirectional communication mode of thalamocortical networks and the hypothesis validation of pathogenesis.

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Responsive Neurostimulation of the Thalamus Improves Seizure Control in Idiopathic Generalized Epilepsy: A Case Report

Neurosurgery ◽

10.1093/neuros/nyaa001 ◽

2020 ◽

Vol 87 (5) ◽

pp. E578-E583 ◽

Cited By ~ 4

Author(s):

Vasileios Kokkinos ◽

Alexandra Urban ◽

Nathaniel D Sisterson ◽

Ningfei Li ◽

Danielle Corson ◽

...

Keyword(s):

Case Report ◽

Neural Activity ◽

Seizure Control ◽

Clinical Presentation ◽

Idiopathic Generalized Epilepsy ◽

Absence Seizures ◽

Level Of Consciousness ◽

Spike Wave Discharges ◽

Generalized Epilepsy ◽

Spike Wave

Abstract BACKGROUND AND IMPORTANCE At least 25% of patients with idiopathic generalized epilepsy do not obtain adequate seizure control with medication. This report describes the first use of responsive neurostimulation (RNS), bilaterally targeting the centromedian/ventrolateral (CM/VL) region in a patient with drug-refractory Jeavons syndrome (eyelid myoclonia with absences). CLINICAL PRESENTATION A patient, diagnosed with eyelid myoclonia with absences (EMA) and refractory to medication, was offered RNS treatment in the CM/VL region of the thalamus. Stimulation was triggered by thalamic neural activity having morphological, spectral, and synchronous features that corresponded to 3- to 5-Hz spike-wave discharges recorded on prior scalp electroencephalography. CONCLUSION RNS decreased daily absence seizures from a mean of 60 to ≤10 and maintained the patient's level of consciousness during the occurring episodes. This therapy should be evaluated further for its potential to treat patients with pharmaco-refractory generalized epilepsy.

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The Orcadian Rhythm of Spike-Wave Discharges in Patients with Typical Absence Seizures

Psychiatry and Clinical Neurosciences ◽

10.1111/j.1440-1819.1987.tb01722.x ◽

1987 ◽

Vol 41 (3) ◽

pp. 448-449

Author(s):

Hideo Nagao ◽

Takehiko Morimoto ◽

Mitsugi Takahashi ◽

Shinji Habara ◽

Hironao Nagai ◽

...

Keyword(s):

Absence Seizures ◽

Spike Wave Discharges ◽

Spike Wave

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The effect of sleep on spike-wave discharges in absence seizures

Neurology ◽

10.1212/wnl.23.12.1335 ◽

1973 ◽

Vol 23 (12) ◽

pp. 1335-1335 ◽

Cited By ~ 136

Author(s):

S. Sato ◽

F. E. Dreifuss ◽

J. K. Penry

Keyword(s):

Absence Seizures ◽

Spike Wave Discharges ◽

Spike Wave

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Can absence seizures be predicted by vigilance states?: Advanced analysis of sleep–wake states and spike–wave discharges' occurrence in rats

Epilepsy & Behavior ◽

10.1016/j.yebeh.2019.04.012 ◽

2019 ◽

Vol 96 ◽

pp. 200-209 ◽

Cited By ~ 4

Author(s):

Magdalena K. Smyk ◽

Ilya V. Sysoev ◽

Marina V. Sysoeva ◽

Gilles van Luijtelaar ◽

Wilhelmus H. Drinkenburg

Keyword(s):

Absence Seizures ◽

Spike Wave Discharges ◽

Advanced Analysis ◽

Spike Wave

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Decreased overall neuronal activity in a rodent model of impaired consciousness during absence seizures

10.1101/2021.04.20.440390 ◽

2021 ◽

Author(s):

Cian McCafferty ◽

Benjamin Gruenbaum ◽

Renee Tung ◽

Jing-Jing Li ◽

Peter Salvino ◽

...

Keyword(s):

Absence Epilepsy ◽

Neuronal Firing ◽

Initial Increase ◽

Loss Of Consciousness ◽

Absence Seizures ◽

Apparent Loss ◽

Neuronal Mechanisms ◽

Spike Wave Discharges ◽

Initial Peak ◽

Spike Wave

AbstractAbsence seizures are characterized by a brief behavioural impairment including apparent loss of consciousness. Neuronal mechanisms determining the behavioural impairment of absence seizures remain unknown, and their elucidation might highlight therapeutic options for reducing seizure severity. However, recent studies have questioned the similarity of animal spike-wave-discharges (SWD) to human absence seizures both behaviourally and neuronally. Here, we report that Genetic Absence Epilepsy Rats from Strasbourg recapitulate the decreased neuroimaging signals and loss of consciousness characteristic of human absence seizures. Overall neuronal firing is decreased but rhythmic in the somatosensory cortex and thalamus during these seizures. Interestingly, individual neurons in both regions tend to consistently express one of four distinct patterns of seizure-associated activity. These patterns differ in firing rate dynamics and in rhythmicity during seizure. One group of neurons showed a transient initial peak in firing at SWD onset, accounting for the brief initial increase in overall neuronal firing seen in cortex and thalamus. The largest group of neurons in both cortex and thalamus showed sustained decreases in firing during SWD. Other neurons showed either sustained increases or no change in firing. These findings suggest that certain classes of cortical and thalamic neurons may be particularly responsible for the paroxysmal oscillations and consequent loss of consciousness in absence epilepsy.

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The γ-hydroxybutyrate model of absence seizures: correlation of regional brain levels of γ-hydroxybutyric acid and γ-butyrolactone with spike wave discharges

Neuropharmacology ◽

10.1016/0028-3908(91)90199-l ◽

1991 ◽

Vol 30 (2) ◽

pp. 161-167 ◽

Cited By ~ 82

Author(s):

O SNEADIII

Keyword(s):

Hydroxybutyric Acid ◽

Absence Seizures ◽

Regional Brain ◽

Brain Levels ◽

Spike Wave Discharges ◽

Spike Wave

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Circuit mechanisms underlying chronic epilepsy in a mouse model of focal cortical malformation

10.1101/2020.04.21.054148 ◽

2020 ◽

Author(s):

Weiguo Yang ◽

Anthony Williams ◽

Qian-Quan Sun

Keyword(s):

Mouse Model ◽

Closed Loop ◽

Pyramidal Neurons ◽

Cortical Region ◽

Cortical Malformation ◽

Optogenetic Stimulation ◽

Layer 2 ◽

Spike Wave Discharges ◽

Spike Wave

HighlightsEctopic interlaminar excitatory inputs from infragranular layers to layer 2/3 pyramidal neurons is a key component of the hyperexcitable circuitryDisrupted E/I balance was located far away from cortical malformationsDendritic inhibition from somatostatin interneurons play a key role in epileptogenesisClosed-loop optogenetic stimulation to activate remainder somatostatin interneurons irreversibly stops the spontaneous spike-wave discharges in vivo.In BriefYang et al. report abnormal synaptic reorganization in an epileptogenesis zone in a mouse model of cortical malformation. The authors further demonstrate that spontaneous spike-wave discharges can be curbed by selectively activating somatostatin interneurons using close-loop fiber optogenetic stimulation to a small cortical region away from the microgyrus.SummaryHow aberrant neural circuits contribute to chronic epilepsy remains unclear. Using a mouse model of focal cortical malformation with spontaneous seizures, we dissected the circuit mechanisms underlying epileptogenesis. Spontaneous and optogenetically induced hyperexcitable bursts in vivo were present in a cortical region distal to (> 1mm) freeze-lesion induced microgyrus, instead of a region near it. ChR2-assisted circuit mapping revealed ectopic interlaminar excitatory inputs from infragranular layers to layer 2/3 pyramidal neurons as a key component of the hyperexcitable circuitry. This disrupted balance between excitation and inhibition was prominent in the cortical region distal to the microgyrus. Consistently, the synapses of both parvalbumin-positive interneurons (PV) and somatostatin-positive interneurons (SOM) to pyramidal neurons were maladaptive in a layer- and site-specific fashion. Finally, closed-loop optogenetic stimulation of SOM, but not PV, terminated spontaneous spike-wave discharges. Together, these results demonstrate highly site- and cell-type specific synaptic reorganization underlying chronic cortical epilepsy and provide insights into potential treatment strategies for this devastating neurological disorder.

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The zona incerta modulates spontaneous spike-wave discharges in the rat

Journal of Neurophysiology ◽

10.1152/jn.00750.2011 ◽

2013 ◽

Vol 109 (10) ◽

pp. 2505-2516 ◽

Cited By ~ 8

Author(s):

Fu-Zen Shaw ◽

Yi-Fang Liao ◽

Ruei-Feng Chen ◽

Yu-Hsing Huang ◽

Rick C. S. Lin

Keyword(s):

Functional Role ◽

Significant Inhibition ◽

Zona Incerta ◽

Obvious Effect ◽

Spike Wave Discharges ◽

Long Evans ◽

Oscillation Frequencies ◽

Spike Wave ◽

Stimulation Of

The contribution of the zona incerta (ZI) of the thalamus on spike-wave discharges (SWDs) was investigated. Chronic recordings of bilateral cortices, bilateral vibrissa muscle, and unilateral ZI were performed in Long-Evans rats to examine the functional role of SWDs. Rhythmic ZI activity appeared at the beginning of SWD and was accompanied by higher-oscillation frequencies and larger spike magnitudes. Bilateral lidocaine injections into the mystacial pads led to a decreased oscillation frequency of SWDs, but the phenomenon of ZI-related spike magnitude enhancement was preserved. Moreover, 800-Hz ZI microstimulation terminates most of the SWDs and whisker twitching (WT; >80%). In contrast, 200-Hz ZI microstimulation selectively stops WTs but not SWDs. Stimulation of the thalamic ventroposteriomedial nucleus showed no obvious effect on terminating SWDs. A unilateral ZI lesion resulted in a significant reduction of 7- to 12-Hz power of both the ipsilateral cortical and contralateral vibrissae muscle activities during SWDs. Intraincertal microinfusion of muscimol showed a significant inhibition on SWDs. Our present data suggest that the ZI actively modulates the SWD magnitude and WT behavior.

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