Perturbation of rapid eye movement (REM) sleep for seizure control in rodent model of temporal lobe epilepsy
Open Access
- Author:
- Parkar, Anjum
- Graduate Program:
- Bioengineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- June 17, 2015
- Committee Members:
- Bruce Gluckman, Dissertation Advisor/Co-Advisor
Bruce Gluckman, Committee Chair/Co-Chair
Steven Schiff, Committee Member
Thomas Neuberger, Committee Member
Kevin Douglas Alloway, Committee Member - Keywords:
- seizure control
seizure prediction
epilepsy
closed loop stimulation
sleep/wake behaviour
trigeminal nerve stimulation - Abstract:
- Seizures are detrimental to the quality of life. Approximately, 1-2% of the US population suff ers from epileptic disorders characterized by spontaneous recurrent seizures. Of these, 25% are uncontrolled by pharmacological treatments. For such patients, alternative therapeutic approaches rely on using stimulation of certain brain regions that can assist in seizure control. Currently used open loop stimulation techniques, such as vagal nerve stimulation (VNS) and deep brain stimulation (DBS) have been tested in rodents and humans with some success. Continuous stimulation at regular intervals, such as VNS and DBS can lead to cognitive impairment, brain tissue damage as well as seizure induced epileptogenesis. Hence predicting and preventing seizures seems to be a more favorable approach. Decades of studies have shown that sleep or state of vigilance (SOV) can have an e ffect on seizures. It has been demonstrated that there is a strong correlation between rapid eye movement (REM) sleep and seizure occurrence. It's also been shown that be- sides REM state, theta (4-8Hz) associated with Wake state is also epileptic. We use the chronic tetanus toxin (TeTx) rodent model of Temporal Lobe Epilepsy (TLE) to investigate if REM state can be perturbed through sensory stimulation of the Trigeminal Ganglion to control seizures. Our results indicate that REM state can be perturbed to control seizures. Fraction of seizures emerging out of stimulated REM state are far lower than REMs that were not stimulated. Since REM state was perturbed and not interrupted, we led to the conclusion that some other dynamic that co-occurs with REM state, makes REM state seizure permissive. Our results also indicated that upon stimulation of the animal during Wake state, when high theta is present, the fraction of seizures emerging from stimulated wake state are also lower compared to un-stimulated Wake state. Hence, stimulation of Wake state during high theta, can also assist in seizure control. Taking these fi ndings together, from a clinical standpoint, this novel approach of closed-loop stimulation based on SOV detection, can be used to design neuro-modulatory systems to help design better treatment approaches for patients refractory to AEDs for seizure control.