About 35% of epileptic patients do not respond to antiepileptic drugs. Of these, only a quarter of them can be treated by resective surgery. Patients who have seizures arising from eloquent cortex, or which are multi-focal, bilateral or generalized are not candidates for resective surgery. For these patients, one currently available therapy is neurostimulation via electrodes. Neurostimulation reduces the probability of seizure occurrence and propagation either by manipulating remote control systems or by interfering with the epileptogenic zone itself. Recent evidence suggests that epileptic seizures in humans may be better controlled with adaptive (closed-loop), i.e. seizure-triggered stimulation. This requires a complex setup that integrates an implanted stimulation device coupled with real-time analysis techniques. Indeed, recent studies demonstrate that closed-loop stimulation in patients effectively decrease seizure frequency and severity. However, this invasive approach suffers from the need to implant complex, large and expansive electronic devices which depend on an external power supply, the need for major and sometimes repetitive brain surgeries and the unexpected and undesirable side effects that the actual placement of the neurostimulation electrodes often produces.
We aim to develop an alternative, minimally-invasive, neuronal specific therapeutic strategy to adaptively control neuronal firing rates in the epileptic brain. o test the efficacy of this new technology, we will use the kainate acid model of experimental epilepsy in rats that has been demonstrated to produce an epilepsy syndrome similar to human temporal lobe epilepsy. At the end of the funding period we anticipate the development of a novel technology that could revolutionize therapeutic strategies of epilepsy management as well as introduce a new neuroscientific tool for studying the activity of neuronal networks associated with normal brain functions, other brain disorders and neuroplasticity.

Public Health Relevance

Epilepsy is a common chronic neurological disorder that affects 0.5-1% of the population. We aim to develop a novel, minimally-invasive, neuronal specific therapeutic strategy to adaptively control neuronal firing rates in the epileptic brain. T test the efficacy of this new technology, we will use an animal model of experimental epilepsy that has been demonstrated to produce an epilepsy syndrome similar to human temporal lobe epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS079288-01
Application #
8333669
Study Section
Special Emphasis Panel (ZNS1-SRB-B (32))
Program Officer
Fureman, Brandy E
Project Start
2012-04-01
Project End
2015-12-31
Budget Start
2012-04-01
Budget End
2012-12-31
Support Year
1
Fiscal Year
2012
Total Cost
$323,297
Indirect Cost
$108,256
Name
Hugo W. Moser Research Institute Kennedy Krieger
Department
Type
DUNS #
155342439
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Shin, Samuel S; Krishnan, Vijai; Stokes, William et al. (2018) Transcranial magnetic stimulation and environmental enrichment enhances cortical excitability and functional outcomes after traumatic brain injury. Brain Stimul 11:1306-1313
Krishnan, Vijai; Park, Sarah A; Shin, Samuel S et al. (2018) Wireless control of cellular function by activation of a novel protein responsive to electromagnetic fields. Sci Rep 8:8764
Bar-Shir, Amnon; Alon, Lina; Korrer, Michael J et al. (2018) Quantification and tracking of genetically engineered dendritic cells for studying immunotherapy. Magn Reson Med 79:1010-1019
Gilad, Assaf A; Pelled, Galit (2015) New approaches for the neuroimaging of gene expression. Front Integr Neurosci 9:5
Bar-Shir, Amnon; Bulte, Jeff W M; Gilad, Assaf A (2015) Molecular engineering of nonmetallic biosensors for CEST MRI. ACS Chem Biol 10:1160-70
Jouroukhin, Yan; Nonyane, Bareng A S; Gilad, Assaf A et al. (2014) Molecular neuroimaging of post-injury plasticity. J Mol Neurosci 54:630-8