Abstract
BackgroundThe moment-to-moment variability of resting-state brain activity has been suggested to play an active role in chronic pain. Here, we investigated the regional blood-oxygen-level-dependent signal variability (BOLDSV) and inter-regional dynamic functional connectivity (dFC) in the interictal phase of migraine and its relationship with the attack severity.MethodsWe acquired resting-state functional magnetic resonance imaging from 20 migraine patients and 26 healthy controls (HC). We calculated the standard deviation (SD) of the BOLD time-series at each voxel as a measure of the BOLD signal variability (BOLDSV) and performed a whole-brain voxel-wise group comparison. The brain regions showing significant group differences in BOLDSV were used to define the regions of interest (ROIs). The SD and mean of the dynamic conditional correlation between those ROIs were calculated to measure the variability and strength of the dFC. Furthermore, patients’ experimental pain thresholds and headache pain area/intensity levels during the migraine ictal-phase were assessed for clinical correlations.ResultsWe found that migraineurs, compared to HCs, displayed greater BOLDSV in the ascending trigeminal spinal-thalamo-cortical pathways, including the spinal trigeminal nucleus, pulvinar/ventral posteromedial (VPM) nuclei of the thalamus, primary somatosensory cortex (S1), and posterior insula. Conversely, migraine patients exhibited lower BOLDSV in the top-down modulatory pathways, including the dorsolateral prefrontal (dlPFC) and inferior parietal (IPC) cortices compared to HCs. Importantly, abnormal interictal BOLDSV in the ascending trigeminal spinal-thalamo-cortical and frontoparietal pathways were associated with the patient’s headache severity and thermal pain sensitivity during the migraine attack. Migraineurs also had significantly lower variability and greater strength of dFC within the thalamo-cortical pathway (VPM-S1) than HCs. In contrast, migraine patients showed greater variability and lower strength of dFC within the frontoparietal pathway (dlPFC-IPC).ConclusionsMigraine is associated with alterations in temporal signal variability in the ascending trigeminal somatosensory and top-down modulatory pathways, which may explain migraine-related pain and allodynia. Contrasting patterns of time-varying connectivity within the thalamo-cortical and frontoparietal pathways could be linked to abnormal network integrity and instability for pain transmission and modulation.
Highlights
The moment-to-moment variability of resting-state brain activity has been suggested to play an active role in chronic pain
Migraine is associated with alterations in temporal signal variability in the ascending trigeminal somatosensory and top-down modulatory pathways, which may explain migraine-related pain and allodynia
blood-oxygen-level-dependent signal variability (BOLDSV) We found that patients with migraine exhibited greater BOLDSV in the left thalamus encompassing the Medial pulvinar nucleus (PuM) and VPM, right thalamus (VPM), left dorsal posterior insula (dpINS), superior/ middle temporal gyrus, right hippocampus, and left cerebellar vermis compared with healthy controls (HC) subjects within the entire frequency range from 0.01 to 0.198 Hz (p < 0.05, Family-wise error (FWE)-corrected) (Fig. 1A, Table 2)
Summary
The moment-to-moment variability of resting-state brain activity has been suggested to play an active role in chronic pain. Moment-to-moment brain signal variability in fMRI resting-state, once regarded as just a noise and ignored in the neuroimaging field, has recently been proposed as an indicator of the brain function and its response to an environmental challenge [12,13,14]. It might be an important index for brain function related to pain perception and modulation. In a resting-state fMRI study, healthy subjects with high blood-oxygen-level-dependent signal variability (BOLDSV) had low pain sensitivity and better coping ability [15]. Few studies measuring regional brain activity with the ALFF method reported that interictal migraine patients had increased ALFF in the thalamus [8, 10] and decreased in the rostral anterior cingulate cortex and medial prefrontal cortex [10], indicating a disrupted low-frequency oscillation in spontaneous brain activity
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