The long-term goal of these studies is to understand human cortical mechanisms of the sensory and affective dimensions of acute pain. Little is known about the specific functions of the human cortical structures receiving nociceptive input, their relationship to various dimensions of pain, the modulation of these inputs by attention, or the interactions which may connect these structures. In preliminary studies, we have used a cutaneous laser stimulus to produce a pure pain sensation by selective activation of cutaneous nociceptors, and to evoke subdural potentials (LEPs). These LEPs were localized over human anterior cingulate (ACC), somatosensory (SI) and parasylvian (PS) cortices. The distribution of LEPs in our preliminary data, the effect of lesions, and primate electrophysiological studies suggest that there may be functional elements within each of these cortical areas. We propose to define the elements within each of these structures by source analysis of LEPs and of nearby, well-characterized, generators for vibratory, or auditory stimuli and for electric nerve stimuli. A two-modality, simultaneous presentation paradigm will be employed to assess the effect of directed attention and attention evoked by novel stimuli on LEPs, subdural EEG activation and synchrony between structures. Our preliminary analysis of synchrony demonstrates significant functional connectivity between SI and PS prior to the stimulus, as the patient anticipates the stimulus in an attention task. After the stimulus occurs, the patient counts it and synchrony develops between both SI-ACC and PS-ACC. We now propose to characterize this rapidly switching, task-dependent functional connectivity between pain-related cortical areas. Many of these studies are performed by recording directly from the surface of the human brain during extra-operative seizure monitoring, a technique which has tremendous clarity and resolution. Therefore, this proposal represents a unique opportunity to study the functional anatomy and connectivity of forebrain pain-related structures.
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