Pain & Reward Neuromodulation of CNS Circuits

Change in Pain Intensity

PROMIS Short Form - Pain Intensity (3a) is a 3-item measure which includes questions of pain at its worst (past 7 days), average pain (past 7 days), and pain right now (at time of survey). Each item is rated from No Pain (1) to Very Severe (5).

Change in Fatigue

The PROMIS Fatigue Computer Adaptive Test (CAT) is a dynamic, patient-reported outcome tool that measures fatigue severity (intensity, frequency, and impact) over the past seven days. Using item response theory (IRT), it selects the next best question based on previous answers, typically requiring only 4-6 items to produce highly precise, reliable scores while minimizing patient burden. Scoring: Results are reported as T-scores, where 50 is the general population mean and 10 is the standard deviation. A T-score of 60 or higher is one standard deviation worse than average.

Change in FMS-related brain/fibro fog as measured by the Montreal Cognitive Assessment (MoCA)

The Montreal Cognitive Assessment (MoCA) is a valid, 30-point screening tool used to assess "fibro fog"-the cognitive dysfunction, memory loss, and attention difficulties associated with fibromyalgia. Scoring: The test is scored out of 30 points. A score of 26-30 is considered normal, while scores below 26 may indicate mild cognitive impairment (19-25) or more advanced impairment (below 21). One point is added for individuals with 12 years or fewer of formal education.

Change in the brain's response to task stimuli

Functional Magnetic Resonance Imaging (fMRI) will be used to track blood-oxygen-level-dependent (BOLD) signals during reward anticipation and feedback. BOLD signal change identifies neural activity in the brain which will be reported as normalized to percent signal change (Avg%Δ) relative to the mean image intensity to allow for cross-subject comparison (i.e., arbitrary units scale).

Change in the brain's cortico-striatal circuit functional connectivity

Functional connectivity in fMRI measures the statistical dependencies (similarities) between blood oxygen level-dependent (BOLD) signal time series from different brain regions. Typically quantified using Pearson's correlation or covariance in either resting-state or task-based studies, it identifies synchronized activity indicating functionally linked regions/networks.

Ventral-dorsal spinal cord fMRI-indicated activity

Amplitude of Low-Frequency Fluctuations (ALFF) in fMRI measures the intensity of spontaneous brain activity by calculating the square root of the power spectrum (via Fast Fourier Transform) within a specific low-frequency range. It quantifies the amplitude of resting-state BOLD signal oscillations, typically after voxel-wise standardization (i.e., arbitrary units scale).

Blood cytokine levels

Cytokines in blood, when measured using Meso Scale Discovery (MSD) multiplex immunoassay kits, are typically reported in picograms per milliliter (pg/mL). MSD assays are known for their high sensitivity, capable of detecting analytes in the low pg/mL to sub-pg/mL range.

PEG Scale Change

The PEG scale (Pain, Enjoyment, General Activity) is a 3-item, patient-reported tool that measures chronic pain intensity and its interference with daily life. It uses a 0-10 numerical rating scale (NRS) for each item, where 0 represents "no pain/no interference" and 10 represents "worst pain/complete interference," averaging the three to produce a final score.

Fibromyalgia Impact Questionnaire (FIQ-R) Change

The Fibromyalgia Impact Questionnaire (FIQ) and its revision (FIQR) measure the overall impact of fibromyalgia on a patient's life, including physical function, work difficulty, pain, fatigue, sleep quality, and psychological symptoms over the past 7 days. Total scores range from 0 to 100, with higher scores indicating greater severity.