Word retrieval in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study

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Abstract
The cognitive impairment revealed in some non‐ demented amyotrophic lateral sclerosis (ALS) patients is characterized by executive dysfunction with widely repeated deficits on tests of verbal (letter) fluency. However, conflicting evidence exists of an impairment on other word retrieval tasks, such as confrontation naming, which do not place heavy demands on executive processes. Previous research has demonstrated intact confrontation naming in the presence of verbal fluency deficits, although naming deficits have been described in other studies. In this investigation, functional MRI (fMRI) techniques were employed to explore whether word retrieval deficits and underlying cerebral abnormalities were specific to letter fluency, which are more likely to indicate executive dysfunction, or were also present in confrontation naming, indicating language dysfunction. Twenty‐eight non‐demented ALS patients were compared with 18 healthy controls. The two groups were matched for age, intelligence quotient, years of education, and anxiety and depression scores. Two compressed‐sequence overt fMRI activation paradigms were employed, letter fluency and confrontation naming, which were developed for use with an older and potentially impaired population. In ALS patients relative to controls, the letter fluency fMRI task revealed significantly impaired activation in the middle and inferior frontal gyri and anterior cingulate gyrus, in addition to regions of the parietal and temporal lobes. The confrontation naming fMRI task also revealed impaired activation in less extensive prefrontal regions, including the inferior frontal gyrus and regions of the temporal, parietal and occipital lobes. These changes were present despite matched performance between patients and controls during each activation paradigm. The pattern of dysfunction corresponded to the presence of cognitive deficits on both letter fluency and confrontation naming in the ALS group. This study provides evidence of cerebral abnormalities in ALS in the network of regions involved in language and executive functions. Moreover, the findings further illustrate the heterogeneity of cognitive and cerebral change in ALS.