Identify abnormal neurocognitive circuits in temporal lobe epilepsy

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DESCRIPTION (provided by applicant): The goal of the study is to detect Magnetic Resonance Imaging (MRI) evidence of correlated neural signalling in medial temporal lobe epilepsy (mTLE) patients consistent with epiletogenesis and then test for the cognitive effects of this potential brain circuit. The development of epileptiform activity remote from the epileptogenic region may facilitate correlated neural signalling between the affected brain regions. The location of new neural connections built up by epileptogenesis, while not completely random, are not constrained to make neuropsychological sense in terms of laying the neural groundwork for effective cognitive skill. This abnormal, correlated signal should create favored neural pathways that can be recruited by neurocognitive networks to cause maladaptive activation that reduces cognitive performance. When cells of the primary focus fire, activation in the newly built neural circuit should be potentiated. Therefore, it becomes possible to observe these aberrant connections not just during clinically observable seizure activity, but also during cognitive stimulation of the primary epileptogenic zone. MTLE patients with Unilateral (n=15) versus Bilateral (n=15) epileptic activity will be studied along with matched, healthy contols (n=15). The goals of the study are to: (1) test for functional connectivity between gray matter regions consistent with epileptogenesis, (2) provide evidence for the development of epilepsy- driven neural circuits and determine their impact on memory performance, (3) provide evidence that flawed task performance can emerge from the activation of disease-driven neural circuits. Two imaging modalities will be utilized. Functional Connectivity MR Analysis will be used to verify the functional connections, respectively, between the regions of interests (left and right medial temporal lobes in patients with mTLE). Functional MRI will be used to determine the presence of anomalous activation involving these mTL regions during the cognitive tasks that is consistent with epileptogenesis. The project offers the possibility of providing indirect evidence for epileptogenesis, specifying its cognitive effects, and offering a potential model for the development of cognitively ineffective and aberrant neural circuitry in adults as a result of neural disease. The data will have implications for theories of learning by demonstrating how disease-driven correlated neural signals can form maladaptive neurocognitive networks that detrimentally influence performance. Summary Developing multimodal brain imaging methods for confirming the presence or impact of additional epileptiform activity outside the primary seizure focus will help with accurate selection of candidates for focal epilepsy surgery, aid in the planning of potential staged surgeries, and influence informed consent regarding surgical risks such as potential cognitive deficits and the expected degree of seizure control. Evidence suggesting that the lesional epileptic zone initiated a circuit of maladaptive cognitive responses will increase the cognitive "cost" of the epilepsy and likely increase the need for surgical control of the seizures. Multimodal mapping of brain regional connectivity will improve localization of functionally intact cognitive networks, increase our ability to tailor the surgical resection to avoid these areas, and open up the benefits of epilepsy surgery to a wider range of patients who might have been excluded because of concerns over cognitive morbidity.