Altered effective connectivity of posterior thalamus in migraine with cutaneous allodynia: a resting-state fMRI study with granger causality analysis

Background: Most migraineurs develop cutaneous allodynia (CA) during migraine, and the underlying mechanism of CA in migraine is thought to be sensitization of the third-order trigeminovascular neurons in the posterior thalamic nuclei. This study aimed to investigate whether the ascending/descending pathway associated with the thalamus is disturbed in migraineurs with CA (MWCA) using effective connectivity analysis of resting-state functional magnetic resonance imaging. Methods:Thirty four migraineurs without aura (14 MWCA and 20 migraineurs without CA (MWoCA)) and 25 matched healthy controls (HC) were recruited in the study. The effective connectivity pathways associated with the posterior thalamus (PTH) were investigated using the Granger causality analysis. We chose bilateral PTH as two individual seeds, and compared MWCA with MWoCA and HC, respectively. Spearman correlation analysis was performed to test the correlation between the abnormal effective connectivity and the allodynia severity of MWCA. Results: Compared with MWoCA, MWCA showed decreased inflows from the left limbic regions and dorsal medial prefrontal cortex (dmPFC) to the ipsilateral PTH, as well as increased inflow from the right ventral medial prefrontal cortex (vmPFC) to the ipsilateral PTH; no significantly different outflows from the bilateral PTH to other regions were found. Compared with HC, MWCA showed increased outflows from the left PTH to the bilateral vmPFC, decreased outflows from the right PTH to the bilateral temporoparietal areas, decreased inflow from the left parietooccipital area to the ipsilateral PTH, and increased inflows from the right dorsolateral prefrontal cortex and the bilateral temporoparietal areas to the right PTH. Correlation analyses revealed that the disturbed connectivities between PTH and cuneus, as well as PTH and middle frontal gyrus were associated with the allodynia severity of MWCA. Conclusions: MWCA demonstrated disrupted effective connection pathways between the PTH and other cortical or subcortical regions that participated in multi-dimentional pain processing. Our findings highlight the dysfunctional ascending and descending pain network at the thalamic-level and may help to illuminate the possible pathophysiologic mechanisms of CA.