Human Behaviors Related to the Expectation of Pain

Study Overview
=================
Brief Summary
-----------------
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. .

Detailed Description
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Fear Pain

Intervention / Treatment
-----------------
* Behavioral: Skin conductance levels and slopes over time in conditioned fear as metrics.as metrics for anxiety


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 88 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Analysis of eye position and skin conductance levels will be examined to identify attentional and anxiety related processes for the fear of pain during the conditioned stage. Correlation of skin conductance levels versus slopes during the conditioning stage with state versus trait anxiety will be taken as confirmatory evidence. Power analysis for a two-way ANOVA was conducted to determine a sufficient sample size using an alpha of 0.05, power 0.80, a high effect size (pilot data indicate η2 values for main effects > 0.5). Based on these assumptions, we conservatively use a sample size of 40.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eye position and tense arousal over time a metrics for sustained attention in conditioned fear.<br>After conditioning the conditioned stimulus induces autonomic metrics like skin conductance and cognitive ratings like expectancy of the unconditioned stimulus after conditioning. Activity across blocks in the conditioning stage demonstrates that the skin conductance can produce a progressive decrease in skin conductance over the conditioning stage of our fear conditioning protocol. The decline is not apparently related to habituation or changes in the skin conducting electrodes or recording system. It does correspond to the decrease in performance of a visual fixation task which is part of the fear conditioning during the conditioning stage; and to an increase in the unpleasant psychologic activation termed tense arousal over the same stage. If both these changes are found he then we may conclude that sustained task related attention is produced during fear conditioning | Behavioral: Skin conductance levels and slopes over time in conditioned fear as metrics.as metrics for anxiety<br>* After fear conditioning the cue induces autonomic responses like skin conductance and cognitive ratings like expectancy of the unconditioned stimulus after cueing or conditioning. Activity across blocks in the conditioning stage shows that the skin conductance can be described by levels, and slopes which might be related to state anxiety and trait anxiety (Spielberger trait and state anxiety inventory or questionnaire). These skin conductance measures may be concrete metrics for psychological processes in healthy subjects. We will carry out a partial correlation analysis of levels, state anxiety and trait anxiety, and then a similar analysis of slopes, state anxiety and trait anxiety. These results may show that concrete skin conductance levels and slopes are related to metrics of subjective self report measures of state and trait anxiety.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conditioned fear as assessed by skin conductance | Concrete metric is skin conductance measured in microSiemens. | 5 hours | 
| Anxiety as assessed by the Spielberg Anxiety Inventory | Higher scores on the Spielberg Anxiety Inventory indicates more anxiety. | 5 hours | 
| Experimental Pain as assessed by a pain rating scale | Pain Rating for Unpleasantness on a scale of 0 - 10 where 10 is the worst imaginable. | 5 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
fear, pain, conditioning, skin conductance response, Ratings of Pain and Conditioning, Eye position metrics