Current flowing across active brain synapses may summate to produce Evoked Potentials (EPs) and magnetic fields which can be recorded at a distance. Thus, cognitive EP components may be used to monitor the activity of brain synapses noninvasively in normal and diseased subjects as they think. Eventually, cognitive EPs may be used to identify the nature, sequence, duration and intensity of the information-processing stages involved in perception, memory, and language. Currently, such applications of cognitive EPs are limited because their synaptic generators are unknown. The only unambiguous method for localizing EP generators is to directly record from within the generating structure. The present grant proposes to perform such recordings in patients with epileptic seizures that remain uncontrolled after years of anticonvulsant treatment. Electrodes are implanted in order to localize the epileptogenic tissue, and thus direct its surgical removal. While awaiting spontaneous seizure onset, the patient may consent to perform cognitive tasks while their intracerebral EEG is monitored. Depth recordings will be obtained from macroelectrodes implanted in the occipital, parietal, temporal, rolandic and frontal cortices, and in the limbic system (amygdala, hippocampal formation and cingulate gyrus), during tasks evoking various cognitive EP components, including: (1) the N1abc/P2/MMN/N2/P3a/P3b/SW evoked by infrequent auditory, visual or somaesthetic stimuli; and (2) the P75/N125/P170/N230/ N310/N460/P620/slow wave evoked by faces and words, and their constituent parts. Task variants will be used to differentially evoke successive stages of face and word recognition for characterization of the associated EP components. For each component, recording sites will be classified into: (1) focal generators, where the component is large relative to adjacent structures, and where its amplitude changes rapidly between successive leads, and may polarity-invert; (2) possible diffuse generators, where the voltage gradient may be small but clearly larger in the grey matter than in immediately subjacent white matter, and (3) distant from the generating structure. Laminar recordings will be used to better define the current sources and sinks within focal generators. The possibility that the locally generated EPs propagate to the scalp will be tested by recording before and after therapeutic cortico-limbic excisions. All recordings will be interpreted using an MRI-based finite difference computational model for EP propagation. Overall, the proposed studies will deepen and broaden our knowledge of cognitive EPs in humans. This will permit: integrated neurocognitive models testable using scalp recordings in normal subjects; precise validation criteria for animal models of cognitive EPs, leading to basic neurophysiological studies; and direct functional tests for specific synaptic systems using scalp EPs in patients with neurological or psychiatric disease.
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