Altered effective connectivity in leucine-rich glioma-inactivated 1 antibody encephalitis: a spectral dynamic causal modeling study

Background Despite advances in understanding the effective connectivity (EC) of brain networks in leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis, the specific cause and underlying mechanisms of LGI1 remain unclear. Materials and Methods The study included 27 patients with anti-LGI1 encephalitis and 28 age- and sex-matched normal controls. Low-frequency fluctuation amplitude analysis (ALFF) was performed to identify significant brain regions. Subsequently, spectral dynamic causal modeling (spDCM) was employed to assess effective connectivity between these brain regions. Finally, we investigated the relationship between the strength of effective connections and both symptom severity and cognitive function in anti-LGI1 patients. Results We found distinct patterns of effective connectivity in anti-LGI1 patients compared to normal controls. Specifically, we observed inhibitory effective connectivity from the hippocampus to the superior temporal gyrus in LGI1 patients. In contrast, excitatory effective connectivity was observed from the superior temporal gyrus to the hippocampus. Furthermore, anti-LGI1 patients exhibited reduced inhibitory self-connections within the posterior cingulate cortex. Correlation analyses showed that inhibitory effective connectivity from the right hippocampus to the left superior temporal gyrus was inversely correlated with symptom severity and positively associated with cognitive performance in LGI1 patients. In contrast, the reduced inhibitory self-connections in the posterior cingulate cortex were positively correlated with symptom severity and negatively correlated with cognitive function in anti-LGI1 encephalitis patients. Conclusions Our findings suggested that changes in the causal connections between specific brain regions contribute significantly to the neurological functional deficits observed in anti-LGI1 encephalitis patients. Furthermore, the inhibitory connectivity from the hippocampus to the superior temporal gyrus may serve as a potential biomarker for personalized diagnosis, providing insights into the underlying pathological mechanisms of this disorder.