Aberrant functional and causal connectivity of the amygdala in herpes zoster and post-herpetic neuralgia patients

Resting-state functional magnetic resonance imaging (rs-fMRI) and Granger causality analysis (GCA) were used to observe the characteristics of amygdala and whole-brain effect connections in patients with herpes zoster (HZ) and post-herpetic neuralgia (PHN) and to determine their relationship with clinical features.Rs-fMRI scans were performed on 50 HZ; 50 PHN; and 50 age-, sex- and education-year-matched healthy controls (HCs). Bilateral amygdala subregions were used as seeds for functional connectivity (FC). GCA was used to analyze the effective connection of brain regions that were significantly different among groups. Then, the correlation between FC, and GCA values and clinical indices was investigated.PHN had impaired FC between the amygdala subregion with the putamen, cortex, anterior cingulate cortex (ACC) to HCs and reduced FC of medial amygdala (MeA) with the parieto-occipital lobe and motor cortex to HZ; HZ had reduced FC of the lateral amygdala (LA) with the insula to HCs. GCA values from the bilateral LA to the bilateral ACC, left MeA to the bilateral ACC and left putamen, and right ACC to the bilateral MeA were reduced in PHN patients compared to HCs. Compared with HCs, the GCA values from the left MeA to the left ACC and right putamen were reduced in HZ. The GCA values from the amygdala subregion to the ACC were positively correlated with HAMA or HAMD scores in PHN.PHN showed reduced FC between the amygdala subregions and cortico-putamen and decreased effective connectivity from the amygdala subregion to the ACC and putamen.HZ and PHN patients had significant changes in effective connectivity in brain regions, including diverse functional areas emanating from and projecting to the amygdala. The current findings will provide a new perspective for understanding the neuropathophysiological mechanism HZ and PHN.