Gabriel Widi

Date of Award


Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Idil Cavus


Electrical brain stimulation has been proposed as a promising treatment option for patients with medically resistant epilepsy disorder. Glutamate levels in the epileptogenic human hippocampus are elevated interictally and increase with seizures. Fifty Hz stimulation is a candidate therapeutic stimulation that is also used for clinical cortical mapping. We examined the effects of 50 Hz stimulation on glutamate efflux in the hippocampus of patients with medically refractory epilepsy. Subjects (n = 10) underwent intracranial EEG (icEEG) evaluation for possible therapeutic resection. Electrical stimulation was delivered through implanted hippocampal electrodes (n = 11) and microdialysate samples were collected every 2 mins. Basal interictal glutamate was measured with the zero-flow microdialysis method. Stimulation of the epileptogenic hippocampus induced significant glutamate efflux at the time of stimulation (p = 0.005, n = 10) that was significantly related to the basal glutamate concentration (R2 = 0.81, p = 0.001). During stimulation, four patients experienced seizures and two had auras. No change in glutamate level was observed in the group of patients who experienced a seizure (p = 0.47, n = 4). Conversely, a significant increase in glutamate was observed in the patients that did not experience a seizure (p = 0.005, n = 7). Basal glutamate levels were significantly higher in the no seizure group (p = 0.04, n = 5) than in the stimulated seizure group (n = 4). Fifty Hz stimulation of the epileptogenic hippocampus can cause significant glutamate efflux and may produce seizures or auras. The degree of stimulated glutamate elevation is related to the basal glutamate concentration but not to the induction of seizures. Electrical stimulation at 50 Hz may exacerbate interictal glutamate dysregulation in the epileptiogenic hippocampus and may not be optimal for seizure control.


This is an Open Access Thesis.