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The pathogenesis of amyotrophic lateral sclerosis (ALS) remains obscure, but it is now clear that neuronal loss is not confined to the motor cortex, even in cases without dementia. A reliable method of assessing cortical involvement in vivo remains elusive. WAY100635 binds selectively to the 5-hydroxytryptamine (5-HT_1A) receptor, which is expressed on pyramidal neurones present throughout the cortex. [¹¹C]-WAY100635 PET is, therefore, a potential marker of cerebral neuronal loss or dysfunction in ALS. Twenty-one ALS subjects and 19 healthy volunteers underwent [¹¹C]-WAY100635 PET of the brain. A cortical template consisting of multiple volumes of interest (VOI) was applied to each individual's [¹¹C]-WAY100635 binding potential (BP) image to determine the regional reduction in binding in ALS patients compared to controls. There was a marked reduction (21%) in both the global cortical and raphe …