Amygdala Abnormalities Are Related to Anxiety in Patients With Sporadic Amyotrophic Lateral Sclerosis

Abstract

To explore selective atrophy patterns and resting-state functional connection (FC) alterations in the amygdala at different stages of amyotrophic lateral sclerosis (ALS), and to determine any correlations between amygdala abnormalities and neuropsychiatric symptoms. We used the King’s clinical staging system for ALS to divide 83 consecutive patients with ALS into comparable subgroups at different disease stages. We investigated the pattern of selective amygdala subnucleus atrophy and analysed amygdala-based whole-brain FC analysis in the patients and 94 healthy controls (HCs). Cognitive and emotional functions were also evaluated using a neuropsychological test battery. There were no significant differences between King’s stage 1 ALS patients and HCs for any amygdala subnucleus volumes. Compared with HCs, King’s stage 2 patients had significantly lower left accessory basal nucleus and cortico-amygdaloid transition volumes after Bonferroni correction. Furthermore, after Bonferroni correction, King’s stage 3 patients demonstrated significant reductions in most subnucleus volumes as well as global amygdala volume compared with HCs. Notably, amygdala-based resting-state FC was unaltered in ALS patients until King’s stage 3. Specific subnucleus volumes were significantly associated with Mini-Mental State Examination scores and Hamilton Anxiety Rating Scale scores in ALS patients. In conclusions, our study provides a comprehensive profile of amygdala abnormalities in ALS patients. The pattern of amygdala abnormalities in ALS patients differed across King’s clinical disease stages, and our findings suggest that amygdala abnormalities are an important feature of patients with ALS. Moreover, amygdala volume may play an important role in anxiety and cognitive dysfunction in ALS patients.