Characterization of Nociception Phenotype in Individuals With Intellectual Disability

STUDY DESCRIPTION:

The study aims to evaluate the somatosensory response to innocuous and noxious stimuli in individuals with Intellectual Disability (ID) compared to healthy controls.

OBJECTIVES:

Primary Objective:

To characterize brain activation patterns using electroencephalography (EEG) and cerebral functional-near-infrared spectroscopy (fNIRS) in response to innocuous and noxious stimulation in individuals with ID (ages, 8-30 years), compared with the brain activation pattern observed in healthy controls.

We hypothesize that compared to healthy controls, individuals with ID will present decreases in oxygenated hemoglobin (measured by fNIRS) in pain responsive regions (e.g., secondary somatosensory cortex), in response to standardized noxious stimuli (heat, cold, and electrical). In addition, individuals with ID will also present smaller suppression of oscillation in alpha and beta frequencies (measured by EEG at central sites) in response to these stimuli.

Exploratory Objective:

To determine the relationship between brain activation patterns to innocuous and noxious stimuli with physiological and behavioral responses to the same stimuli, in individuals with ID. We hypothesize that decreased oxygenated hemoglobin in response to noxious stimuli in the secondary somatosensory cortex, as well as smaller suppression of oscillations in alpha and beta frequencies at central sites in individuals with ID will correlate with changes in heart rate, galvanic skin response and pupil dilation. In addition, we hypothesize that decreased oxygenated hemoglobin to noxious thermal and electrical stimuli in the secondary somatosensory cortex, as well as smaller suppression of oscillations in alpha and beta frequencies will also be associated with behavioral observations (e.g. vocal, social and changes in facial, body and extremities activity).

ENDPOINTS:

Primary Endpoints:

• fNIRS response to innocuous and noxious stimuli: oxygenated and deoxygenated hemoglobin concentration measured in the secondary somatosensory cortex.
• EEG response to innocuous and noxious stimuli: Alpha and beta oscillations measured at central sites (C3 and C4).
• Physiological responses to innocuous and noxious stimulation (heart rate, respiratory rate, galvanic skin response, and pupillary changes).
• Behavioral responses to noxious stimulation (e.g. vocal, social and changes in facial, body and extremities activity).

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

For All Participants

• Provision of signed and dated informed consent form by participant or parent / Legally Authorized Representative (LAR) of patient.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, aged 8-30 years of age.
• Agreement to avoid use of analgesics, NSAIDs, caffeine (24 hours before procedures), illicit substances and alcohol within 2 days prior to enrollment and during study participation.

Healthy Adult Controls

• IQ 85 OR General Adaptive Composite ABAS-3 score above 85
• Must be fluent in the English Language.

Healthy Children

• OR ABAS-3 score above 85.
• Must be fluent in the English Language.

Patients

-Diagnosis of Intellectual Disability.

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

All participants

• NIH employees or children of NIH employee who subordinate to an investigator in this study will be excluded. This will ensure that participation or refusal to participate cannot be perceived as having any beneficial or adverse effects on their employment. There will be no direct solicitation of employees or of employees' children by the employee's supervisor.
• Allergic reactions to EEG water based gel.
• History of concussions in individuals with an IQ>85.
• Uncontrolled seizures.
• Pregnancy (verbal confirmation). Pregnant women will be excluded as there is no data on the effects of nociception in pregnancy.
• For healthy volunteers only - known history of neurological, psychiatric or pain disorders.
• History of head injury resulting in prolonged loss of consciousness in individuals with an IQ>85.

Healthy Children

-Children who have been diagnosed with neurodevelopmental disorders or treated in early intervention programs.

Patients

-Subjects who are on opioids, NSAID, gabapentin, or pregabalin chronically.