Patients with uncontrolled epilepsy may have impairment of language and memory associated with their seizures. In addition, it is critical to map these functions when surgery is being considered. We are using imaging methods in an effort to replace more invasive approaches to detecting the effects of epilepsy on language and memory, and for preoperative mapping. Methods: We use positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to map language and memory in patients with temporal lobe epilepsy to perform non-invasive evaluation of functional cortex, and study the effect of epilepsy on cognitive anatomy in children and adults with seizures. Our studies in both normal volunteers and patients with uncontrolled seizures have shown that imaging evaluation compares well with more invasive procdures such as electrostimulation mapping and the intracarotid sodium amytal test. We also evaluate the effect of seizures on the development of functional cognitive anatomy. fMRI language tasks readily identify frontal language areas; temporal activation has been less consistent. No studies have compared clinical visual judgment to quantitative region of interest (ROI) analysis. We identified temporal language areas in patients with partial epilepsy using a reading paradigm with clinical and ROI interpretation. Thirty patients with temporal lobe epilepsy, aged 8 to 56 years, had 1.5-T fMRI. Patients silently named an object described by a sentence compared to a visual control. Data were analyzed with ROI analysis from t-maps. t-Maps were visually rated by three readers at three t thresholds. Twenty-one patients had intracarotid amobarbital test (IAT). The fMRI reading task provided evidence of language lateralization in 27 of 30 patients with ROI analysis. Twenty-five were left dominant, two right, one bilateral, and two were nondiagnostic; IAT and fMRI agreed in most patients, three had partial agreement, none overtly disagreed. Interrater agreement ranged between 0.77 to 0.82 agreement between visual and ROI reading with IAT was 0.71 to 0.77. Viewing data at lower thresholds added interpretation to 12 patients on visual analysis and 8 with ROI analysis. Conclusions: An fMRI reading paradigm can identify language dominance in frontal and temporal areas. Clinical visual interpretation is comparable to quantitative ROI analysis. The extent to which visual word perception engages speech codes (i.e., phonological recoding) remains a crucial question in understanding mechanisms of reading. In this study, we used functional magnetic resonance imaging (fMRI) techniques combined with behavioral response measures to examine neural responses to focused versus incidental phonological and semantic processing of written words. Three groups of subjects made simple button-pressing responses in either phonologically (rhyming-judgment) or semantically (category-judgment) focused tasks or both tasks with identical sets of visual stimuli. In the phonological tasks, subjects were given both words and pseudowords separated in different scan runs. The baseline task required feature search of scrambled letter strings created from the stimuli for the experimental conditions. The results showed that cortical regions associated with both semantic and phonological processes were strongly activated when the task required active processing of word meaning. However, when subjects were actively processing the speech sounds of the same set of written words, brain areas typically engaged in semantic processing became silent. In addition, subjects performed both the rhyming- and semantic tasks showed diverse and significant bilateral activation in the prefrontal, temporal, and other brain regions. Taken together, the pattern of brain activity provides evidence of a neural basis supporting the theory that in normal word reading, phonological recoding is automatic and facilitates semantic processing of written words, while rapid comprehension of word meaning requires devoted attention. These results also raise questions about including multiple cognitive tasks in the same neuroimaging sessions. fMRI language tasks reliably identify language areas but activation using single paradigms occasionally disagrees with IAT. To determine whether a panel of fMRI tasks targeting different aspects of language processing increases yield in determining hemisphere dominance for language, we studied 26 patients aged 12-56 years, with temporal lobe epilepsy using whole brain 1.5T fMRI (EPI BOLD) with three task categories using a block design: Verbal Fluency; Reading Comprehension, and Auditory Comprehension. fMRI t maps were visually rated at three thresholds. All patients had confirmation of language lateralization by intra-carotid amobarbital test (IAT) or surgery. fMRI showed left dominance in 23 patients, right dominance in two, and symmetric activation in one. There was agreement between IAT and fMRI in 24 of 26 patients. IAT was left and fMRI bilateral in one patient; and, in the other, IAT bilateral and fMRI left dominant. In both instances the fMRI panel showed consistent findings. Agreement between raters was excellent (Cramer's V 0.75-0.93). A panel of fMRI language paradigms is more useful for evaluating partial epilepsy patients than a single task. A panel of tasks reduces the likelihood of non-diagnostic findings and helps confirmlanguage laterality. Current Studies: we are developing new paradigms, particularly using event-related strategies, appropriate for various age groups and developmental levels (with an emphasis on younger age groups, particularly children younger than 7 years old). These studies will primarily use the 3T magnet. We will also design fMRI activation studies using arterial spin tagging at 3T that will examine developmental differences in cerebral blood flow and BOLD signal response. We also plan to study the effects of temporal lobectomy on the functional anatomy of language and working memory.
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