While abnormally increased Vigilance to pain is found in both ?idiopathic? and ?nociceptive? pain syndromes, the behavioral and neural characteristics of experimental Vigilance to pain are poorly understood. We propose to adapt a Continuous Performance Task (CPT) from Human Factors Research (e.g. air traffic controllers) to study Experimental Vigilance to pain. In our task, the subject pushes a button to indicate detection of painful target stimuli when they occur in a train of nontarget nonpainful stimuli, i.e. CPTpain. During a CPTpain, we propose to record and analyze local field potentials (LFP) directly from the brain through electrodes placed on the brain for the treatment of intractable epilepsy. This technique has unrivalled resolution but limited scope and so complements fMRI, which has lower resolution but surveys the whole brain. Our Premise is that: Errors and Arousal in a CPT with a painful target (CPTpain) mediate the behavioral and neural elements of Vigilance to pain, and affect Central Post Stroke Pain (CePSP). We propose to test the hypothesis that: Behaviors over time in a CPTpain are related to neural activations and interactions of modules in a network for Vigilance to pain, while changes in a behavior after a stroke identify the modules that are essential for that behavior, and for the development and symptoms of CePSP. Networks like this can be characterized by modules, and connections between modules as identified by their causal interactions. Our Preliminary Data shows that over time in a CPTpain detected nontargets and arousal are often associated with increased pain. These Data also suggest a Parietal EEG Signature for Vigilance to pain that is correlated with errors, suggesting that a Parietal module is involved in a distributed network for Vigilance to pain. Although these analyses of LFPs (or fMRI signals) do not prove that modules are essential for Vigilance to pain, a module can be identified as essential for a behavior if lesions of the module affect that behavior. Therefore, we propose to study stroke anatomy (by structural MRI) and behavioral measures in CPTpain in patients with acute strokes. We will use a software package developed at Hopkins for the analysis of lesions (LDDMM) with our long term collaborator, Dr. Hillis, who has broad experience with this package in studies of attention. Finally, our Preliminary Data demonstrates that Parietal structures are spared in patients with insular strokes who develop CePSP but are involved in patients with insular strokes who do not develop CePSP, which suggests a Parietal, Vigilance related mechanism for CePSP. The results of these proposed studies may frame testable hypotheses for the neuroscience of Vigilance to pain, and anatomically based therapies in the treatment of pain syndromes associated with Hypervigilance, and for an objective instrumented test of Vigilance to pain. The potential of analyses of networks for Vigilance to pain is suggested by the impact of network analyses on the neuroscience of vision, and on the development of novel surgical and stimulation therapies for the treatment of movement and psychiatric disorders.

Public Health Relevance

Attention, vigilance and hypervigilance in humans are related dimensions of pain and components of clinical pain syndromes, but our understanding of their neural basis is limited. We propose a novel study of an experimental protocol for vigilance to define the network for vigilance to pain by measuring of neural activity through electrodes implanted on the brain for the investigation of intractable epilepsy. The modules in this network which have a critical role in vigilance to pain will be determined by behavioral studies of patients with acute strokes, and will be potential targets for surgical or stimulation therapies for pain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS107602-03
Application #
9902559
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mohapatra, Durga Prasanna
Project Start
2018-07-01
Project End
2023-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205