Amygdala pathology in amyotrophic lateral sclerosis and primary lateral sclerosis

Temporal lobe studies in motor neuron disease overwhelmingly focus on white matter alterations and cortical grey matter atrophy. Reports on amygdala involvement are conflicting and the amygdala is typically evaluated as single structure despite consisting of several functionally and cytologically distinct nuclei. A prospective, single-centre, neuroimaging study was undertaken to comprehensively characterise amygdala pathology in 100 genetically-stratified ALS patients, 33 patients with PLS and 117 healthy controls. The amygdala was segmented into groups of nuclei using a Bayesian parcellation algorithm based on a probabilistic atlas and shape deformations were additionally assessed by vertex analyses. The accessory basal nucleus (p = .021) and the cortical nucleus (p = .022) showed significant volume reductions in C9orf72 negative ALS patients compared to controls. The lateral nucleus (p = .043) and the cortico-amygdaloid transition (p = .024) were preferentially affected in C9orf72 hexanucleotide carriers. A trend of total volume reduction was identified in C9orf72 positive ALS patients (p = .055) which was also captured in inferior-medial shape deformations on vertex analyses. Our findings highlight that the amygdala is affected in ALS and our study demonstrates the selective involvement of specific nuclei as opposed to global atrophy. The genotype-specific patterns of amygdala involvement identified by this study are consistent with the growing literature of extra-motor clinical features. Mesial temporal lobe pathology in ALS is not limited to hippocampal pathology but, as a key hub of the limbic system, the amygdala is also affected in ALS.