This application is for a Mentored Patient-Oriented RCDA (K23). The candidate is trained in clinical neurology and neurophysiology, and completed a Ph.D. thesis in basic visual neurophysiology. He is a tenure track Assistant Professor of Neurology at UC Irvine, and Associate Director of the UCI comprehensive epilepsy program. The candidate's long-term career goal is to study cortical network function and dysfunction using psychophysical, imaging, and electrophysiologic techniques, initially using temporal lobe epilepsy (TLE) as a model system. This grant application represents the first step in that process, by proposing to characterize psychophysically early or """"""""low-lever' perceptual impairments in three sensory modalities in patients with medically intractable (mi) TLE, and to determine if such impaired cortical processing normalizes after surgical removal of the epileptogenic zone. The training portion of the proposal emphasizes three areas: 1) Network theory and its application to human sensory systems, 2) clinical experimental design and biostatistics, and 3) methodology and application of psychophysical perceptual tasks. UC Irvine has a proven reputation in basic, clinical and cognitive neuroscience. It also has developed a busy surgical clinical epilepsy program, and is thus ideally suited to the candidate's career goals. There is limited but compelling evidence that TLE is a network disease, not isolated pathologicallyto the epileptogenic focus. In this view, interictal cerebral function within the network is affected by the seizure focus, even in the absence of frequent seizures. Clinical implications of this theory are significant, and include the possibility that such cerebral dysfunction may normalize with surgical treatment. Outside the domains of language and memory, little is known of cognitive impairments in TLE. It is hypothesized that multi-modal perceptual dysfunction is present in mi TLE, that it may result from transient disruption of normal cerebral processes by interictal """"""""spiking"""""""" originating in the epileptogenic zone, and that it will normalize after surgical removal of the seizure focus. Forty subjects with mi TLE will undergo a battery of auditory, tactile and visual psychophysical tasks, and their performance compared to normal controls. Tasks were chosen to: 1) Determine the effect of stimulus duration on task performance. This should be a critical factor if interictal spiking is responsible for performance deficits, 2) test two analogous abilities (primary tasks) in all three sensory modalities, and 3) test early cortical sensory processes. Subjects will perform a subset of the tasks after anti-epileptic medication (AED) withdrawal during clinically indicated continuous video-EEG monitoring to assess the effect of AEDs on task performance. Subjects will then be retested on all tasks 6 months after surgery, or 6 months after initial testing for those who do not qualify for surgical treatment. If performance improves after surgery and is unchanged without surgery, as is hypothesized, these results would strongly support the notion of TLE as a network disease whose disruption of cortical processes could be reversed with surgical, but not medical treatment.
| Nakhutina, Luba; Gonzalez, Jeffrey S; Margolis, Seth A et al. (2011) Adherence to antiepileptic drugs and beliefs about medication among predominantly ethnic minority patients with epilepsy. Epilepsy Behav 22:584-6 |
| Prus, Nehama; Grant, Arthur C (2010) Patient beliefs about epilepsy and brain surgery in a multicultural urban population. Epilepsy Behav 17:46-9 |
| Marcuse, L V; Schneider, M; Mortati, K A et al. (2008) Quantitative analysis of the EEG posterior-dominant rhythm in healthy adolescents. Clin Neurophysiol 119:1778-81 |
| Grant, Arthur C; Kim, Richard B (2006) Uncommon, exceptional and atypical: a case of frontal lobe epilepsy due to cortical dysplasia. Epileptic Disord 8:73-6 |
| Grant, Arthur C; Fernandez, Raquel; Shilian, Parastou et al. (2006) Tactile spatial acuity differs between fingers: a study comparing two testing paradigms. Percept Psychophys 68:1359-62 |
| Grant, Arthur C; Henry, Thomas R; Fernandez, Raquel et al. (2005) Somatosensory processing is impaired in temporal lobe epilepsy. Epilepsia 46:534-9 |
| Grant, Arthur C; Vazquez, Blanca (2005) A case of extended spectrum GEFS+. Epilepsia 46 Suppl 10:39-40 |
| Grant, Arthur C (2005) Interictal perceptual function in epilepsy. Epilepsy Behav 6:511-9 |
| Nelson, Linda D; Elder, Joseph T; Groot, Jantje et al. (2004) Personality testing and epilepsy: comparison of two MMPI-2 correction procedures. Epilepsy Behav 5:911-8 |
