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Background: The mechanisms of vagal nerve stimulation (VNS) for the treatment of drug‐resistant epilepsy (DRE) remain unclear. This study aimed to measure spontaneous brain activity changes caused by VNS in DRE patients using resting‐state functional MRI (rs‐fMRI). Methods: The rs‐fMRI scans were performed in 16 DRE patients who underwent VNS surgery. Amplitude of low‐frequency fluctuations (ALFF) and regional homogeneity (ReHo) was generated and examined using paired sample t‐test to compare activity changes at different current intensity stage. The preoperative and postoperative ALFF/ReHo were also compared in eight responders (≥50% reduction of seizure frequency three months after surgery) and eight nonresponders using paired sample t‐test. Results: The significant ALFF and ReHo changes were shown in various cortical/subcortical structures in patients under different current intensity. After three months of stimulation, responders exhibited increased ALFF in the right middle cingulate gyrus, left parahippocampal gyrus, and left cerebellum, and increased ReHo in the right postcentral gyrus, left precuneus, left postcentral gyrus, right superior parietal gyrus, right precentral gyrus, and right superior frontal gyrus. Nonresponders exhibited decreased ALFF in the left temporal lobe and right cerebellum, increased ALFF in bilateral brainstem, decreased ReHo in bilateral lingual gyri, and increased ReHo in the right middle frontal gyrus and right anterior cingulate gyrus. Conclusions: The spontaneous neural activity changes in DRE patients caused by VNS were in an ongoing process. Increased ALFF/ReHo in frontal cortex, cingulate gyri, precentral/postcentral gyri, parahippocampal gyri, precuneus, parietal cortex, and cerebellum may implicate in VNS‐induced improvement in seizure frequency. [ABSTRACT FROM AUTHOR]

• Less than 1.5 mA may not affect hippocampal-thalamic functional connectivity. • Shorter than 3 months may not affect hippocampal-thalamic functional connectivity. • VNS may be suitable for patients with low left hippocampal-left thalamic connections. • VNS may be suitable for patients with low left hippocampal-right thalamic connections. • Current intensity should increase > 1.5 mA to cause functional connectivity changes. Vagal nerve stimulation (VNS) is widely used as an auxiliary treatment for patients with intractable epilepsy. Up to now, the therapeutic mechanisms remain elusive, and no surgical prediction criteria has been proposed. In this study, the resting-state functional magnetic resonance imaging (rs-fMRI) was chosen to explore aberrant intrinsic brain activity and functional connections in 14 epilepsy patients with VNS stimulators between March 2019 and April 2019. Seven patients who ≥ 50 % seizure reduction was defined as responders, and seven non-responders. All patients had got rs-fMRI scan before and after operation. The hippocampal - thalamic connections (hippocampal and thalamus as regions of interest) were detected to evaluate the diversity in all 14 patients and seven responders with stimulation at 0, 0.5, 1.0, and 1.5 mA. The hippocampal-thalamic connections before operation were also examined between responders and non-responders. The preoperative left hippocampal - left thalamic connections and left hippocampal - right thalamic connections in responders were lower than those in non-responders (p < 0.05). While, there was no significant difference in hippocampal - thalamic connections in all epilepsy patients or responders with different current intensities (p > 0.05). VNS may be more suitable for patients with lower left hippocampal - left thalamic connections and/or left hippocampal - right thalamic connections. The current intensity ≤ 1.5 mA and stimulation time ≤ 3 months may not cause significant changes in hippocampal-thalamic functional connectivity. [ABSTRACT FROM AUTHOR]

• VNS may cause thalamus-precentral gyrus FC changes in DRE patients. • Enhanced FC was observed between bilateral thalamus and bilateral precentral gyrus in responders. • Decreased FC was observed between bilateral thalamus and bilateral precentral gyrus in nonresponders. Vagal nerve stimulation (VNS) is an effective treatment for patients with drug-resistant epilepsy who are unsuitable for surgical epilepsy treatment. However, the mechanism of action of VNS remains unclear, and the efficacy of VNS treatment regarding seizure frequency reduction cannot be assessed before surgery. This study measured changes in functional connectivity between thalamus and precentral gyrus which are activated as vital targets of deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS) using resting-state functional MRI to evaluate the effects of VNS. 16 epilepsy patients who underwent VNS were collected and scanned by resting-state functional MRI before and after operation. The functional connections (regions of interest: thalamus, precentral gyrus) were examined. After three months of stimulation, there were eight responders (≥50 % seizure reduction) and eight non-responders to VNS. No significant difference in thalamus-precentral gyrus functional connectivity was found between responders and nonresponders before operation. Enhanced functional connections were observed between bilateral thalamus and bilateral precentral gyrus in responders, which decreased in nonresponders, while functional connections between bilateral thalamus decreased in both responders and nonresponders. Short-term stimulation may cause thalamus-precentral gyrus functional connectivity changes in DRE patients, and control seizures by enhancing functional connections between bilateral thalamus and bilateral precentral gyrus. [ABSTRACT FROM AUTHOR]

To explore the effect of vagal nerve stimulation (VNS) on spontaneous brain activity in patients with drug-resistant epilepsy (DRE). 15 patients and eight healthy controls (HC) were enrolled and scanned by resting-state functional MRI to investigate changes in the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). A two-sample t -test or paired sample t -test was used to compare activity between the HCs, preoperative patients (EP-pre), and postoperative patients (EP-post). We also performed correlation analyses to examine the seizure improvement ratio. The voxel-level analyses indicated that, compared with the HC, the EP-pre group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral/postcentral gyrus, amygdala, insula, cerebellum, and lingual gyrus. Furthermore, compared with the EP-pre group, the EP-post group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral gyrus, insula, anterior/median cingulate gyri, and cerebellum. The regions of interest-level analyses indicated that, compared with HC, the EP-pre group exhibited decreased fALFF or ReHo in the caudate nucleus, supramarginal gyrus, precuneus and middle temporal gyrus. Furthermore, compared with the EP-pre group, the EP-post group exhibited increased fALFF or ReHo in the olfactory cortex, gyrus rectus, and superior temporal gyrus. Increased ReHo in the right superior or middle temporal gyrus was positively correlated with the improvement ratio. Altered regional activity in DRE patients was reorganized after 3 months of stimulation. Increased ReHo in the right superior or middle temporal gyrus was implicated in VNS-induced improvement in seizure frequency. [ABSTRACT FROM AUTHOR]