Both children and adults with epilepsy, particularly left temporal lobe foci, may have diminished language functioning. Specific naming difficulties have been reported in pediatric, and adult studies of patients with temporal lobe epilepsy. A significantly larger percentage of epilepsy patients have right or bilateral hemispheric dominance for language than normal healthy volunteers. Epilepsy offers the opportunity to examine the effects of pathological processes on language processing. The ability of language reorganization tends to diminish after language networks areas are established between ages 4-7. A large proportion of patients with left mesial temporal sclerosis (MTS) and seizure onset before five show atypical language. A dysfunctional left hippocampus can alter the development of cerebral language ability. A recent study found that atypical handedness, specific structural lesions, and age at onset were the most important factors leading to atypical language representation in patients with left hemispheric epileptic foci. It remains uncertain whether the reduced AI in patients with left TLE is due to permanent functional reorganization or temporary compensation. Advances in neuroimaging, including fMRI and MEG, provide noninvasive alternatives for language mapping in patients with uncontrolled epilepsy being considered for surgery. Functional MRI has become an established technique in the evaluation of epilepsy, with accuracy comparable to the Wada test. MEG is less well-developed, due in part to lack of clearly established methods, uncertainty over the best frequency bands to evaluate, and failure to perform careful clinical correlation. Some studies suggest that synthetic aperture magnetometry (SAM) may be superior to dipole analysis for language lateralization. One small study suggested that combined MEG and fMRI might provide more accurate language localization than either procedure alone. Surprisingly few studies have examined the effect of epilepsy surgery on the functional anatomy of language. Our study will test several hypotheses: 1: After successful (>90% seizure frequency reduction) but not unsuccessful resection of a left hemisphere epileptic focus, the L/R activation asymmetry index (AI) will increase, reflecting normalization of left hemisphere dominance for language. 2: The increase in asymmetry index will not be seen in right-handed patients after right hemispheric epileptic focus resection. 3: The increase in asymmetry index will not be seen in patients whose seizures began before age 6, because these patients will be more likely to have had definitive language reorganization 4: MEG and fMRI will demonstrate congruent language lateralization. The study will be a collaboration with CNMC. It will include children and adults between the ages of 7-55 years with localization-related epilepsy who are surgical candidates. Each subject will have formal neuropsychological assessment using age-appropriate panels. We will use a series of fMRI activation tasks. The Word Definition task (Auditory) will be used as probe for Wernicke's area , and the Category Decision task (Auditory) will be the probe for Broca's area. Functional MRI images will be reconstructed and corrected for motion. Studies with significant motion artifact will be discarded, and the study repeated. The MEG tasks are event-related adaptations of our fMRI paradigms. EEG electrodes will be placed as part of the EEG procedure, in order to allow analysis of MEG events that occur during EEG spikes. Synthetic aperture magnetometry (SAM) will be used to localize event-related differences in oscillatory power between the experimental and control conditions. SAM, is an example of minimum-variance beamformer. SAM-estimated source activation within user-defined voxel consists of time series dipole moments with no loss of MEGs millisecond temporal resolution. The power of this activity can be computed for specified frequency which can be compared between the experimental and control conditions. Thus, the resulting SAM volumes are maps of the ratio between the power in the experimental and control conditions within a specified time/frequency window. Our preliminary data suggest that SAM may be an accurate language mapping procedure. Several approaches will be used to obviate potential confounding factors. The order of fMRI and MEG will be counterbalanced. Age-appropriate neuropsychological test results, particularly the Boston naming will be used as an explanatory variable for interpretation of changes in fMRI and MEG AI. In order to examine the effect of performance variables on fMRI and MEG activation, we will compare the relative change in AI to relative changes in neuropsychological test scores after surgery. The healthy controls will provide a measure of baseline scan to scan variability, and practice effects. They are also necessary to help establish normal MEG language measures. The primary outcome measure will be change in fMRI laterality index post-surgery in Brocas and Wernickes areas. The secondary outcome measure will be changes in MEG laterality index post-surgery in Brocas and Wernickes areas. Based on our preliminary data, we predict that the mean change in asymmetry index (AI) for the left hemisphere patients with successful surgery is 0.2, and for the right temporal and unsuccessful left temporal patients is 0.0 with a common within cell standard deviation of 0.2.Using a one way three group ANOVA to calculate sample size, 16 patients per cell would have 80% power with an alpha of 0.05 to detect a significant difference. We plan to perform separate analyses for children and adults. Thus, we would need 48 children (16 in each of the three patient groups) and 48 adults in the study. In order to account for dropouts, subjects lost to follow-up, or technical difficulties, approximately 150 patients may be needed. A comparison of the successful left temporal patients with the control group will provide an added test of the hypothesis. Using a two-group Student's T-Test, with the same assumptions, 17 subjects per group (children and adults) would show a significant difference between successful left lobectomy patients and controls. We will perform separate analyses for adults and children. In order to obtain 35 evaluable controls, we may need to recruit up to 50. In addition to the main analysis, we will perform subanalysis for both fMRI and MEG data across two regions (IFG and STS) and 2 time points for patients (baseline, 12 months after surgery). For MEG. we will examine the time course of activation in fMRI-identified regions activated by the Auditory Description Decision Task, including primary auditory cortex, auditory association cortex, posterior temporal-occipital cortex, inferior frontal gyrus, and motor cortex. Normal volunteers will be very important in selecting the best time bins for analysis. The control group will enable us to confirm our assumptions of the scan to scan variability.
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