Lack of Funding

The conditioned expectation of pain is an important aspect of pain-related disability produced by environments and stimuli associated with a painful injury on the job, although the neuroscience of this expectation is unclear. We will develop and use novel objective methods for measurement of expectation and threat related attention. The results of this study may lead to testable hypotheses regarding the psychological basis of the fear of pain, threat and task related attention. We will also use these results, and development of novel autonomic and ratings metrics for state and trait anxiety as well as threat and task related attention which could be used as an instrumented test for diagnosis and management of PTSD and anxiety 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.

Inclusion Criteria:

• Man or woman between 18 and 80 years of age.
• Fluent speaker of English.
• Undergoing seizure monitoring at Hopkins Hospital through intracranial electrodes.
• Possess ability to understand study procedures and comply with them for the entire length of the study;
• Women of childbearing age must use pharmacological contraception (oral or patch) for the duration of the study follow-up.

Exclusion Criteria:

• Inability or unwillingness of individual to give written informed consent. Presence of any neurological disease other than epilepsy which is unstable or is not optimally treated.
• Presence of a significant abnormality on routine neuropsychological testing.
• Presence of any medical or psychiatric disease which is unstable or is not optimally treated.

Presence of an abnormal MRI scan except for Normal variants or Medial Temporal Sclerosis (altered pathology and MRI signal in temporal lobe).

• Women who are pregnant or women of childbearing capacity who may become pregnant (i.e. not using contraception).
• Presence of generalized seizures, or reflex seizures i.e. triggered by a sensory stimulus.
• Presence of a language or hearing impairment.
• Non-English speakers.

The PI and Co-PIs are working with the Johns Hopkins Pain Research Institute to set up a website for the Institute to include the labs carrying out pain research in the Department of neurosurgery. As a part of this effort we will include the Functional Neurosurgery Lab to share the following information in the public domain: 1. Our research focus. 2. Biosketches of the investigators 3. All publications as final manuscripts at the time of acceptance for publication, 4. Funded grant applications 5. Collaborators 6. Contact information.

The website will be complete in 3 years.

Up to 3 days