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.

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Key information

Conditions

Cerebellum and Pain in Healthy Volunteers. Neurologic Manifestations Pain Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Observational

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Right-handed subjects
Good physical health
No history of claustrophobia
English speaking and reading ability sufficient to comprehend consent without assistance

Exclusion criteria

History of drug abuse or positive drug screen
Magnetic Implants of any type (including dental bridges, crowns, retainers, orthodontic devices, etc)
Weight > 285 pounds (weight limit of the fMRI table)
Positive pregnancy screen
Beck Depression Inventory II (BDI-II) score > 25 (moderate to severe depression)
History of primary depression, anxiety disorders, or mood disorders
Prolonged use of antidepressants or anticonvulsants
Evidence of local pathology; e.g. cancer affecting the face
History of systemic disorders, e.g. multiple sclerosis
History of chronic pain, e.g. back pain
History of primary headache, e.g. migraine, tension-type headache
Recent orofacial surgery or trauma
History of central origin disorders, eg. stroke
History of dermatological hypersensitivity in the facial area
History of Eczema
Significant medical history of seizure disorder, diabetes, cardiac disease including coronary artery disease, psychiatric problems; respiratory problems, liver disease, etc.
Significant alcohol history (ingestion of 5 or more glasses (>40 oz) of alcohol per week)
Claustrophobia
Pregnancy
Smokers
Tattoos containing metallic ink on the neck, shoulders, upper arm and head (which could become heated up in the scanner, and potentially cause blistering or burning)
Cardiac pacemakers
Aneurysm clips and other vascular stents, filters, clips or other devices
Prosthetic heart valves
Other prostheses
Neuro-stimulator devices
Implanted infusion pumps
Cochlear (ear) implants
Ocular (eye) implants or known metal fragments in eyes
Exposure to shrapnel or metal filings (sheet metal workers, welders, and others)
Other metallic surgical hardware in vital areas
Repeated monthly usage of the ovulation test kit fails to detect a luteinizing hormone surge (for females not on contraception only)

Treatment and study plan

Primary outcomes

Whole brain functional magnetic resonance imaging (fMRI) data

Time frame: 1 year

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

Subjective pain ratings elicited by experimental stimuli.
Whole-brain diffusion tensor imaging (DTI) data

Time frame: 1 year

DTI data measures the integrity of white matter tracts in the brain, based on principles of water diffusion.

Sponsors and collaborators

Lead sponsor

Mclean Hospital

Other

Registry information

Important dates

Study start: 2009
Primary completion: 2014
Study completion: 2014
First posted: Nov 30, 2012
Registry last updated: Sep 15, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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