Periaqueductal gray functional connectivity abnormalities associated with acute post-traumatic headache.

Area of Science:

• Neuroimaging
• Neurology
• Pain Medicine

Background:

• Post-traumatic headache (PTH) is a common complication following mild traumatic brain injury (mTBI).
• Understanding the neural mechanisms of acute PTH is crucial for predicting its chronicity.
• Functional connectivity (FC) alterations in pain networks may underlie PTH development.

Purpose of the Study:

• To investigate functional connectivity (FC) within pain networks and the periaqueductal gray matter (PAG) in acute post-traumatic headache (PTH) patients.
• To compare PAG FC in individuals with acute PTH due to mild traumatic brain injury (mTBI) versus healthy controls (HC).
• To explore the association between PAG FC and clinical parameters, including headache outcomes.

Main Methods:

• Utilized 3 Tesla magnetic resonance imaging (MRI) on 98 participants with acute PTH and 85 HC.
• Examined static FC within pain matrix regions and between the PAG and the rest of the brain.
• Employed linear regression to correlate FC with clinical parameters and assessed PTH outcomes at 3 months.

Main Results:

• The PTH group exhibited altered FC, including stronger PAG connectivity with somatosensory and lingual areas, and weaker thalamus-caudate connectivity.
• Whole-brain analysis revealed increased PAG FC with somatosensory, motor, and occipital regions in PTH patients.
• PAG FC patterns were associated with headache frequency, anxiety, time since mTBI, and predicted 3-month PTH improvement with high accuracy (82% sensitivity, 100% specificity).

Conclusions:

• Periaqueductal gray matter (PAG) functional connectivity (FC) patterns are distinct in acute post-traumatic headache (PTH) following mild traumatic brain injury (mTBI).
• PAG FC alterations are linked to clinical features of PTH and can predict headache persistence.
• PAG FC shows potential as an early biomarker for identifying individuals at risk of developing chronic PTH.