Aplicant's Abstract): Human cognition proceeds by a series of steps that can be measured with millisecond accuracy as endogenous electroencephalographic (EEG) and magnetoencephalographic (MEG) fields. MEG/EEG are complementary to functional magnetic resonance imaging (fMRI), in that fMRI provides direct localization of brain activation during cognition, but with poor temporal resolution. Only intracerebral EEG (iEEG) recordings can prove local generation with high spatiotemporal accuracy. However, iEEG is limited by possible pathological contamination and incomplete sampling. The proposed studies seek to localize with high temporal and spatial accuracy by combining the above techniques within an accurate computational biophysical model of the brain and its surroundings. First, activation will be localized in the entire brain of normal subjects using fMRI during orienting, face, object and word perception, remote semantic memory, syntactic analysis, recent declarative memory, and primary memory. Second, whole-head MEG/EEG will be recorded from the same subjects during the same tasks, evoking the N2, P3a, P3b, and SW in simple tasks, and additionally the P170, N310, N400, and CNV in tasks using semantic stimuli. Third, the time-course of activation of the cortical dipoles lying in the areas identified by fMRI, that best fits the EEG/MEG data, will be found. Finally, these hypothesized time-courses will be tested with iEEG recordings directly from the sites that have been found in the studies above to be activated with fMRI, during the tasks that activate each site, using intracerebral electrodes in patients with epilepsy. Hypothesized time-courses of activation in specific brain regions related to visual motion and attention obtained in previous fMRI/MEG studies will also be tested. Across-subjects, cortical and limbic areas in all lobes will be sampled. Within-subject validation will be possible in limited number of patients with fMRI/MEG/iEEG/EEG recordings during the same cognitive tasks. fMRI/EEG will be recorded from these same patients before and after surgical excision of generator areas, in order to test if the altered propagation to the scalp predicted by the model is observed, and for the possible loss of modulatory effects. The proposed studies will allow the different views on brain activity from fMRI, EEG, MEG, and iEEG to be compared, singly and together, leading possibly to better understanding of their relative strengths, and the refinement of techniques for their integration. In addition, the proposed studies will deepen our knowledge of brain activity patterns during perception, memory and language, an essential step toward the eventual construction of functional neural models for cognition. Finally, more complete knowledge regarding the generators of cognitive potentials should greatly increase their value as functional tests for specific brain systems in patients with neurological or psychiatric disease.
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