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Prefrontal involvement related to cognitive impairment in progressive muscular atrophy

Publicatiejaar 2014
Gepubliceerd in Neurology
Auteur(s) Joost Raaphorst, Marie-José van Tol, Paul F C Groot, Ellemarije Altena, Y.D. van der Werf, Charles B Majoie, Anneke J van der Kooi, Leonard H van den Berg, Ben Schmand, Marianne de Visser, Dick J Veltman

OBJECTIVE: To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS).

METHODS: fMRI was used to examine the blood oxygen level-dependent response during letter and category fluency performance in 18 patients with PMA, 21 patients with ALS, and 17 healthy control subjects, matched for age and education. fMRI results are reported at p<0.05, family-wise error (FWE)-corrected for multiple comparisons. We analyzed effects of performance, age-related white matter changes (ARWMC), and regional brain volumes; all participants underwent neuropsychological investigation.

RESULTS: Disease duration of patients with PMA (mean 26.0 months, SD 13.6) and ALS (22.2 months, SD 11.4) was comparable. Patients with PMA and ALS had mild to moderate disease severity and showed impaired letter fluency compared with controls. Between-group analysis showed a main effect of group in the left inferior frontal gyrus (IFG, Brodmann area 45) during letter fluency, which was unaffected by performance, ARWMC, and IFG volume: patients with PMA showed lower activation than controls but higher than that of patients with ALS (ALS<PMA<healthy controls; pFWE=0.035; z score 4.11; cluster size=11). A more caudal region in the IFG showed lower activation in patients with PMA than controls during letter fluency performance (post hoc test; pFWE=0.026). No activation differences were observed during the category fluency task.

CONCLUSION: Prefrontal activation abnormalities are related to an important clinical measure of executive dysfunction in patients with motor neuron disease with and without upper motor neuron signs.

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