fMRI and DTI of Cerebellar Responses to Pain in the Human Trigeminal System
This K01 application is designed to prepare the applicant with the skills necessary to establish an independent research program on pain--related processing in the cerebellum. Although pain studies using functional imaging in humans consistently find cerebellar activation, the role of this structure during pain is unknown. In such studies, speculation regarding the cerebellum's function during a painful event is often influenced by its reputation as a coordinator of motor function, though animal studies have indicated that it may also modulate the neural encoding of noxious stimuli. The candidate has published work that indicates a functional dichotomy in the way the cerebellum responds to experimental pain in healthy subjects and neuropathic pain patients. This suggests that the cerebellum has been overlooked as a potential pain processing area, and research into this area could lend invaluable insight into the basic physiological circuitry involved with pain and its modulation.
The hypothesis of this project is that the cerebellum serves as an integrator of aversive stimuli and adaptive motor behavior, and may modulate the emotional and cognitive experience that distinguishes the perception of pain from the appreciation of innocuous sensory stimulation. A human trigeminal model of experimental pain will be used, as all the pain--‐related circuitry involved can be imaged along with the cerebellum at the same time. The specific aims are (1) to map cerebellar activations related to sensory coding of noxious stimuli and to correlate functional activity with anatomical connectivity using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI); (2) to distinguish between pain and its anticipation based on cerebellar responses and connectivity; and (3) to determine whether physical pain and aversive images engage similar circuitry in the cerebellum. To accomplish these aims, the candidate will need to expand his background in fMRI of cortical and brainstem pain processing to encompass cerebellar physiology, become proficient in DTI analysis, and learn the white matter connectivity to and from the cerebellum. The research environment at McLean Hospital and the other affiliates of the Harvard Medical School system will provide the candidate with the resources to reach his aims within 4 years.
Cerebellum and Pain in Healthy Volunteers.
|Study Design:||Observational Model: Cohort|
- Whole brain functional magnetic resonance imaging (fMRI) data [ Time Frame: 1 year ] [ Designated as safety issue: No ]fMRI data is used to indirectly measure neurophysiological responses in the brain using the blood oxygen level dependent (BOLD) signal.
- Pain ratings [ Time Frame: 1 year ] [ Designated as safety issue: No ]Subjective pain ratings elicited by experimental stimuli.
- Whole-brain diffusion tensor imaging (DTI) data [ Time Frame: 1 year ] [ Designated as safety issue: No ]DTI data measures the integrity of white matter tracts in the brain, based on principles of water diffusion.
|Study Start Date:||May 2009|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
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