Frontal lobe dysfunction in amyotrophic lateral sclerosis

S. Abrahams, L. H. Goldstein, J. J. M. Kew, D. J. Brooks, C. M. Lloyd, C. D. Frith, P. N. Leigh
1996 Brain  
PET measurements of regional cerebral blood flow (rCBF) were used to explore frontal lobe dysfunction in amyotrophic lateral sclerosis (ALS). An activation paradigm of executive frontal lobe function (verbal fluency), which contrasted rCBF during word generation and word repetition, was used. Two groups of ALS patients, defined by the presence or absence of cognitive impairment (ALSi) (impaired, n = 6; ALSu, unimpaired, n = 6) were compared with healthy age-matched controls (n = 6). Patient
more » ... ction was based on prior performance on a written test of verbal fluency. Additional neuropsychological assessment of the patients revealed evidence of executive and memory dysfunction in the ALSi group only, with marked deficits in tests of intrinsic generation. The ALSi patients displayed significantly (P < 0.001) impaired activation in cortical and subcortical regions including the dorsolateral prefrontal cortex (DLPFC; areas 46 and 9), lateral premotor cortex (areas 8 and 6), medial prefrontal and premotor cortices (areas 8 and 9), insular cortex bilaterally and the anterior thalamic nuclear complex. Although the three groups showed matched word generation performance on the scanning paradigm, the ALSu group displayed a relatively unimpaired pattern of activation. These results support the presence of extra-motor neuronal involvement, particularly along a thalamo-frontal association pathway, in some non-demented ALS patients. In addition, this study suggests dysfunction of DLPFC in some ALS patients with associated cognitive impairments. Abbreviations: ALS = amyotrophic lateral sclerosis; ALSi = cognitively impaired ALS patients; ALSu, = cognitively unimpaired ALS patients; DLPFC = dorsolateral prefrontal cortex; rCBF = regional cerebral blood flow; RMJT = random movement joystick task; SPM = statistical parametric mapping; VFI = Verbal Fluency Index; WCST = Wisconsin Card Sorting Test
doi:10.1093/brain/119.6.2105 pmid:9010014 fatcat:n2uehqikn5ck7bvaxla7mtucsy