The overall goal of this project is to elucidate the kind and degree of transient brain dysfunction induced by single focal interictal spikes. Specific hypotheses to be tested are that: (1) spikes temporarily disrupt the ongoing physiologic functioning of the cortical area of the focus as well as contralateral homotopic cortex and closely related subcortical nuclei; (2) this dysfunction is measurable and of a magnitude that could be clinically relevant; (3) the after-coming slow wave is an important contributor to the dysfunction, the duration of which corresponds to the duration of the entire spike-wave complex. The methodology involves two basic types of paradigms: subject- interactive tasks, and evoked potentials (EPs). In the former, the subject responds to brief computer-generated stimuli in whatever functional modality is to be tested. Some of the stimulus presentations are triggered by spikes, and others are given at random intervals between spikes. Spike-locked versus control performances are then compared within the same subject. The EP paradigms also cover various modalities. The phase of stimulus presentation is reset at each spike, so that an intraspike EP can be calculated at a given latency from the spike (after having subtracted the average waveform of the spike itself). This is then compared with the interspike EP in terms of both waveform components and spatial characteristics, providing a further measure of spike-induced dysfunction in specific brain regions. The phenomenon of focal spike-induced dysfunction has a number of important ramifications for both clinical neurology and basic neuroscience. Definitions of """"""""ictal"""""""" and """"""""interictal"""""""" will need to be refined with greater precision. Frequent interictal spikes may impair activities requiring accurate perception and/or fast reaction, and they may interfere with brain development. Elimination of such spikes may therefore have a therapeutic importance of its own, independent of seizure control. Transient spike-induced dysfunction also provides a noninvasive means to investigate in the human certain pathophysiologic mechanisms related to the regulation of seizures, particularly local and projected inhibition.
