Dataset Information

Asynchronous Distributed Multielectrode Microstimulation Reduces Seizures in the Dorsal Tetanus Toxin Model of Temporal Lobe Epilepsy.

ABSTRACT:

Background

Electrical brain stimulation has shown promise for reducing seizures in drug-resistant epilepsy, but the electrical stimulation parameter space remains largely unexplored. New stimulation parameters, electrode types, and stimulation targets may be more effective in controlling seizures compared to currently available options.

Hypothesis

We hypothesized that a novel electrical stimulation approach involving distributed multielectrode microstimulation at the epileptic focus would reduce seizure frequency in the tetanus toxin model of temporal lobe epilepsy.

Methods

We explored a distributed multielectrode microstimulation (DMM) approach in which electrical stimulation was delivered through 15 33-µm-diameter electrodes implanted at the epileptic focus (dorsal hippocampus) in the rat tetanus toxin model of temporal lobe epilepsy.

Results

We show that hippocampal theta (6-12 Hz brain oscillations) is decreased in this animal model during awake behaving conditions compared to control animals (p < 10(-4)). DMM with biphasic, theta-range (6-12 Hz/electrode) pulses delivered asynchronously on the 15 microelectrodes was effective in reducing seizures by 46% (p < 0.05). When theta pulses or sinusoidal stimulation was delivered synchronously and continuously on the 15 microelectrodes, or through a single macroelectrode, no effects on seizure frequency were observed. High frequency stimulation (>16.66 Hz/per electrode), in contrast, had a tendency to increase seizure frequency.

Conclusions

These results indicate that DMM could be a new effective approach to therapeutic brain stimulation for reducing seizures in epilepsy.

SUBMITTER: Desai SA

PROVIDER: S-EPMC4724241 | biostudies-literature | 2016 Jan-Feb

REPOSITORIES: biostudies-literature

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Publications

Asynchronous Distributed Multielectrode Microstimulation Reduces Seizures in the Dorsal Tetanus Toxin Model of Temporal Lobe Epilepsy.

Desai Sharanya Arcot SA Rolston John D JD McCracken Courtney E CE Potter Steve M SM Gross Robert E RE

Brain stimulation 20150820 1

<h4>Background</h4>Electrical brain stimulation has shown promise for reducing seizures in drug-resistant epilepsy, but the electrical stimulation parameter space remains largely unexplored. New stimulation parameters, electrode types, and stimulation targets may be more effective in controlling seizures compared to currently available options.<h4>Hypothesis</h4>We hypothesized that a novel electrical stimulation approach involving distributed multielectrode microstimulation at the epileptic foc ...[more]

PMID: 26607483

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Project description:BackgroundMedial temporal lobe epilepsy (MTLE) is associated with limbic atrophy involving the hippocampus, peri-hippocampal and extra-temporal structures. While MTLE is related to static structural limbic compromise, it is unknown whether the limbic system undergoes dynamic regional perfusion network alterations during seizures. In this study, we aimed to investigate state specific (i.e. ictal versus interictal) perfusional limbic networks in patients with MTLE.MethodsWe studied clinical information and single photon emission computed tomography (SPECT) images obtained with intravenous infusion of the radioactive tracer Technetium- Tc 99 m Hexamethylpropyleneamine Oxime (Tc-99 m HMPAO) during ictal and interictal state confirmed by video-electroencephalography (VEEG) in 20 patients with unilateral MTLE (12 left and 8 right MTLE). Pair-wise voxel-based analyses were used to define global changes in tracer between states. Regional tracer uptake was calculated and state specific adjacency matrices were constructed based on regional correlation of uptake across subjects. Graph theoretical measures were applied to investigate global and regional state specific network reconfigurations.ResultsA significant increase in tracer uptake was observed during the ictal state in the medial temporal region, cerebellum, thalamus, insula and putamen. From network analyses, we observed a relative decreased correlation between the epileptogenic temporal region and remaining cortex during the interictal state, followed by a surge of cross-correlated perfusion in epileptogenic temporal-limbic structures during a seizure, corresponding to local network integration.ConclusionsThese results suggest that MTLE is associated with a state specific perfusion and possibly functional organization consisting of a surge of limbic cross-correlated tracer uptake during a seizure, with a relative disconnection of the epileptogenic temporal lobe in the interictal period. This pattern of state specific shift in metabolic networks in MTLE may improve the understanding of epileptogenesis and neuropsychological impairments associated with MTLE.

Project description:ObjectiveThe features of cerebral metabolism associated with loss of consciousness in patients with temporal lobe epilepsy (TLE) have not been fully elucidated. We aim to investigate the alterations in cortical-subcortical metabolism in temporal lobe epilepsy with impaired awareness seizures (IAS).MethodsRegional cerebral metabolism was measured using fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with TLE-IAS and healthy controls. All patients had a comprehensive evaluation to confirm their seizure origin and lateralization. Videos of all seizures were viewed and rated by at least two epileptologists to identify the state of consciousness when a seizure occurred. By synthesizing the seizure history, semeiology, and video EEG of all patients, as long as the patients had one seizure with impaired awareness, she/he will be included. 76 patients with TLE-IAS and 60 age-matched healthy controls were enrolled in this study. Regional cerebral metabolic patterns were analyzed for TLE-IAS and healthy control groups using statistical parametric mapping. Besides, we compared the MRI-negative patients and MRI-positive patients with healthy controls, respectively.ResultsThere were no significant differences in the age and sex of TLE-IAS patients and healthy control. TLE-IAS patients showed extensive bilateral hypermetabolism in the frontoparietal regions, cingulate gyrus, corpus callosum, occipital lobes, basal ganglia, thalamus, brainstem, and cerebellum. The region of metabolic change was more extensive in right TLE-IAS than that of the left, including extensive hypometabolism in the ipsilateral temporal, frontal, parietal, and insular lobes. And contralateral temporal lobe, bilateral frontoparietal regions, occipital lobes, the anterior and posterior regions of the cingulate gyrus, bilateral thalamus, bilateral basal ganglia, brainstem, and bilateral cerebellum showed hypermetabolism. The TLE patients with impaired awareness seizure showed hypermetabolism in the cortical-subcortical network including the arousal system. Additionally, 48 MRI-positive and 28 MRI-negative TLE-IAS patients were included in our study. TLE-IAS patients with MRI-negative and MRI-positive were both showed hypermetabolism in the cingulate gyrus. Hypometabolism in the bilateral temporal lobe was showed in the TLE-IAS with MRI-positive.ConclusionThese findings suggested that the repetitive consciousness impairing ictal events may have an accumulative effect on brain metabolism, resulting in abnormal interictal cortical-subcortical metabolic disturbance in TLE patients with impaired awareness seizure. Understanding these metabolic mechanisms may guide future clinical treatments to prevent seizure-related awareness deficits and improve quality of life in people with TLE.

Dataset Information

Asynchronous Distributed Multielectrode Microstimulation Reduces Seizures in the Dorsal Tetanus Toxin Model of Temporal Lobe Epilepsy.

Background

Hypothesis

Methods

Results

Conclusions

Publications

Asynchronous Distributed Multielectrode Microstimulation Reduces Seizures in the Dorsal Tetanus Toxin Model of Temporal Lobe Epilepsy.

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