title: Prefrontal involvement related to cognitive impairment in progressive muscular atrophy.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: From the Departments of Neurology (J.R., A.J.v.d.K., B.S., M.d.V.) and Radiology (P.F.C.G., C.B.M.), Academic Medical Center, University of Amsterdam; Departments of Psychiatry (D.J.V.) and Anatomy and Neurosciences (Y.D.v.d.W.), VU University Medical Centre, Amsterdam; Department of Psychology (B.S.), University of Amsterdam; Neuroimaging Center (M.-J.v.T.), University Medical Center Groningen, University of Groningen; Brain Center Rudolf Magnus Institute of Neuroscience (L.H.v.d.B), Department of Neurology, University Medical Center Utrecht; Netherlands Institute for Neuroscience (E.A., Y.D.v.d.W.), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam; Department of Neurology (J.R.), Radboud University Medical Center Nijmegen, the Netherlands; and Department of Clinical Neurosciences (E.A.), University of Cambridge, UK. joost.raaphorst@radboudumc.nl.
authors: Joost
authors: J
authors: Raaphorst
authors: From the Departments of Neurology (J.R., A.J.v.d.K., B.S., M.d.V.) and Radiology (P.F.C.G., C.B.M.), Academic Medical Center, University of Amsterdam; Departments of Psychiatry (D.J.V.) and Anatomy and Neurosciences (Y.D.v.d.W.), VU University Medical Centre, Amsterdam; Department of Psychology (B.S.), University of Amsterdam; Neuroimaging Center (M.-J.v.T.), University Medical Center Groningen, University of Groningen; Brain Center Rudolf Magnus Institute of Neuroscience (L.H.v.d.B), Department of Neurology, University Medical Center Utrecht; Netherlands Institute for Neuroscience (E.A., Y.D.v.d.W.), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam; Department of Neurology (J.R.), Radboud University Medical Center Nijmegen, the Netherlands; and Department of Clinical Neurosciences (E.A.), University of Cambridge, UK.
authors: Marie-José
authors: MJ
authors: van Tol
authors: From the Departments of Neurology (J.R., A.J.v.d.K., B.S., M.d.V.) and Radiology (P.F.C.G., C.B.M.), Academic Medical Center, University of Amsterdam; Departments of Psychiatry (D.J.V.) and Anatomy and Neurosciences (Y.D.v.d.W.), VU University Medical Centre, Amsterdam; Department of Psychology (B.S.), University of Amsterdam; Neuroimaging Center (M.-J.v.T.), University Medical Center Groningen, University of Groningen; Brain Center Rudolf Magnus Institute of Neuroscience (L.H.v.d.B), Department of Neurology, University Medical Center Utrecht; Netherlands Institute for Neuroscience (E.A., Y.D.v.d.W.), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam; Department of Neurology (J.R.), Radboud University Medical Center Nijmegen, the Netherlands; and Department of Clinical Neurosciences (E.A.), University of Cambridge, UK.
authors: Paul F C
authors: PF
authors: Groot
authors: From the Departments of Neurology (J.R., A.J.v.d.K., B.S., M.d.V.) and Radiology (P.F.C.G., C.B.M.), Academic Medical Center, University of Amsterdam; Departments of Psychiatry (D.J.V.) and Anatomy and Neurosciences (Y.D.v.d.W.), VU University Medical Centre, Amsterdam; Department of Psychology (B.S.), University of Amsterdam; Neuroimaging Center (M.-J.v.T.), University Medical Center Groningen, University of Groningen; Brain Center Rudolf Magnus Institute of Neuroscience (L.H.v.d.B), Department of Neurology, University Medical Center Utrecht; Netherlands Institute for Neuroscience (E.A., Y.D.v.d.W.), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam; Department of Neurology (J.R.), Radboud University Medical Center Nijmegen, the Netherlands; and Department of Clinical Neurosciences (E.A.), University of Cambridge, UK.
authors: Ellemarije
authors: E
authors: Altena
authors: From the Departments of Neurology (J.R., A.J.v.d.K., B.S., M.d.V.) and Radiology (P.F.C.G., C.B.M.), Academic Medical Center, University of Amsterdam; Departments of Psychiatry (D.J.V.) and Anatomy and Neurosciences (Y.D.v.d.W.), VU University Medical Centre, Amsterdam; Department of Psychology (B.S.), University of Amsterdam; Neuroimaging Center (M.-J.v.T.), University Medical Center Groningen, University of Groningen; Brain Center Rudolf Magnus Institute of Neuroscience (L.H.v.d.B), Department of Neurology, University Medical Center Utrecht; Netherlands Institute for Neuroscience (E.A., Y.D.v.d.W.), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam; Department of Neurology (J.R.), Radboud University Medical Center Nijmegen, the Netherlands; and Department of Clinical Neurosciences (E.A.), University of Cambridge, UK.
authors: Ysbrand D
authors: YD
authors: van der Werf
authors: From the Departments of Neurology (J.R., A.J.v.d.K., B.S., M.d.V.) and Radiology (P.F.C.G., C.B.M.), Academic Medical Center, University of Amsterdam; Departments of Psychiatry (D.J.V.) and Anatomy and Neurosciences (Y.D.v.d.W.), VU University Medical Centre, Amsterdam; Department of Psychology (B.S.), University of Amsterdam; Neuroimaging Center (M.-J.v.T.), University Medical Center Groningen, University of Groningen; Brain Center Rudolf Magnus Institute of Neuroscience (L.H.v.d.B), Department of Neurology, University Medical Center Utrecht; Netherlands Institute for Neuroscience (E.A., Y.D.v.d.W.), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam; Department of Neurology (J.R.), Radboud University Medical Center Nijmegen, the Netherlands; and Department of Clinical Neurosciences (E.A.), University of Cambridge, UK.
authors: Charles B
authors: CB
authors: Majoie
authors: From the Departments of Neurology (J.R., A.J.v.d.K., B.S., M.d.V.) and Radiology (P.F.C.G., C.B.M.), Academic Medical Center, University of Amsterdam; Departments of Psychiatry (D.J.V.) and Anatomy and Neurosciences (Y.D.v.d.W.), VU University Medical Centre, Amsterdam; Department of Psychology (B.S.), University of Amsterdam; Neuroimaging Center (M.-J.v.T.), University Medical Center Groningen, University of Groningen; Brain Center Rudolf Magnus Institute of Neuroscience (L.H.v.d.B), Department of Neurology, University Medical Center Utrecht; Netherlands Institute for Neuroscience (E.A., Y.D.v.d.W.), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam; Department of Neurology (J.R.), Radboud University Medical Center Nijmegen, the Netherlands; and Department of Clinical Neurosciences (E.A.), University of Cambridge, UK.
authors: Anneke J
authors: AJ
authors: van der Kooi
authors: From the Departments of Neurology (J.R., A.J.v.d.K., B.S., M.d.V.) and Radiology (P.F.C.G., C.B.M.), Academic Medical Center, University of Amsterdam; Departments of Psychiatry (D.J.V.) and Anatomy and Neurosciences (Y.D.v.d.W.), VU University Medical Centre, Amsterdam; Department of Psychology (B.S.), University of Amsterdam; Neuroimaging Center (M.-J.v.T.), University Medical Center Groningen, University of Groningen; Brain Center Rudolf Magnus Institute of Neuroscience (L.H.v.d.B), Department of Neurology, University Medical Center Utrecht; Netherlands Institute for Neuroscience (E.A., Y.D.v.d.W.), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam; Department of Neurology (J.R.), Radboud University Medical Center Nijmegen, the Netherlands; and Department of Clinical Neurosciences (E.A.), University of Cambridge, UK.
authors: Leonard H
authors: LH
authors: van den Berg
authors: From the Departments of Neurology (J.R., A.J.v.d.K., B.S., M.d.V.) and Radiology (P.F.C.G., C.B.M.), Academic Medical Center, University of Amsterdam; Departments of Psychiatry (D.J.V.) and Anatomy and Neurosciences (Y.D.v.d.W.), VU University Medical Centre, Amsterdam; Department of Psychology (B.S.), University of Amsterdam; Neuroimaging Center (M.-J.v.T.), University Medical Center Groningen, University of Groningen; Brain Center Rudolf Magnus Institute of Neuroscience (L.H.v.d.B), Department of Neurology, University Medical Center Utrecht; Netherlands Institute for Neuroscience (E.A., Y.D.v.d.W.), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam; Department of Neurology (J.R.), Radboud University Medical Center Nijmegen, the Netherlands; and Department of Clinical Neurosciences (E.A.), University of Cambridge, UK.
authors: Ben
authors: B
authors: Schmand
authors: From the Departments of Neurology (J.R., A.J.v.d.K., B.S., M.d.V.) and Radiology (P.F.C.G., C.B.M.), Academic Medical Center, University of Amsterdam; Departments of Psychiatry (D.J.V.) and Anatomy and Neurosciences (Y.D.v.d.W.), VU University Medical Centre, Amsterdam; Department of Psychology (B.S.), University of Amsterdam; Neuroimaging Center (M.-J.v.T.), University Medical Center Groningen, University of Groningen; Brain Center Rudolf Magnus Institute of Neuroscience (L.H.v.d.B), Department of Neurology, University Medical Center Utrecht; Netherlands Institute for Neuroscience (E.A., Y.D.v.d.W.), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam; Department of Neurology (J.R.), Radboud University Medical Center Nijmegen, the Netherlands; and Department of Clinical Neurosciences (E.A.), University of Cambridge, UK.
authors: Marianne
authors: M
authors: de Visser
authors: From the Departments of Neurology (J.R., A.J.v.d.K., B.S., M.d.V.) and Radiology (P.F.C.G., C.B.M.), Academic Medical Center, University of Amsterdam; Departments of Psychiatry (D.J.V.) and Anatomy and Neurosciences (Y.D.v.d.W.), VU University Medical Centre, Amsterdam; Department of Psychology (B.S.), University of Amsterdam; Neuroimaging Center (M.-J.v.T.), University Medical Center Groningen, University of Groningen; Brain Center Rudolf Magnus Institute of Neuroscience (L.H.v.d.B), Department of Neurology, University Medical Center Utrecht; Netherlands Institute for Neuroscience (E.A., Y.D.v.d.W.), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam; Department of Neurology (J.R.), Radboud University Medical Center Nijmegen, the Netherlands; and Department of Clinical Neurosciences (E.A.), University of Cambridge, UK.
authors: Dick J
authors: DJ
authors: Veltman
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009134:Muscular Atrophy, Spinal / Q000150:complications* / Q000503:physiopathology*; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000473:pathology / Q000503:physiopathology*