Physiological Studies in Healthy Subjects, Chronic Pain Patients and in Patients Undergoing Neurosurgical Procedures of Human Forebrain Mechanisms Mediating Somatic Sensation, Motor Control and Neurological Disorders

The conditioned expectation or fear of pain often results in disability produced by stimuli related to a painful injury on the job, although there are questions about attentional and anxiety related expectation. Conditioned expectation in humans can be produced by a protocol that consists of a train of two visual conditioning stimuli, one of which is paired (CS+) with a painful laser pulse unconditioned stimulus (US), while the other is not. This protocol will be used to study the expectation of pain in this study, and its relationship to task and threat related attention measured by eye position and to anxiety, task directed sustained attention, and scalp EEG metrics. These results may also be used in an instrumented test for the diagnosis and management of PTSD and anxiety disorders.

EEG studies may clarify the relationship of unpleasantness (valence) and the ability of stimuli to command attention (salience) of the conditioned and unconditioned stimuli which which are significant but under studied aspects of the fear of the pain. Studies of scalp EEG activation and functional connectivity will be used to estimate global properties of the forebrain networks involved in the fear of pain, as well as the valence and the salience) of the conditioned and unconditioned stimuli.

Activations are measured by the proportion of electrodes over a quadrant or lobe of the scalp a significant ratio of electrical power following an event over baseline (event related spectral perturbation, ERSP). Functional connectivity will be measured by causal interactions following an event over baseline. The approach of this protocol is that causal interactions are based upon causal influences by an approach based upon the concept of linear predictability. Briefly, a signal Y is said to exert an influence upon signal X when the predication error of the X is reduced by adding the past information of Y (causal interaction). The signals from any two quadrants or lobes will be analyzed by event related causality to determine the magnitude and direction of causal interactions between the two to determine fear and pain related directed interactions related to aversive conditioning.

Our Preliminary Data shows EEG activations in global distributed forebrain networks for the expectation of pain are consistent with the evidence of studies of anatomic projections and functional MRI (fMRI) signals. These models including our Preliminary Data from intracranial recordings identify structures in the medial temporal lobe (amygdala and hippocampus) which are involved in expectation of pain, while EEG suggests global activations related to valence and salience of conditioned and unconditioned stimuli. The premise of this study is that novel autonomic and eye position metrics will measure state and trait anxiety as well as threat and task related attention to parse out the experience and anticipation of pain.