title: Frontal lobe dysfunction in amyotrophic lateral sclerosis. A PET study.
abstract: 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 selection 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.
authors.affiliation: Department of Psychology, Institute of Psychiatry, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Abrahams
authors.forename: L H
authors.initials: LH
authors.lastname: Goldstein
authors.forename: J J
authors.initials: JJ
authors.lastname: Kew
authors.forename: D J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: C M
authors.initials: CM
authors.lastname: Lloyd
authors.forename: C D
authors.initials: CD
authors.lastname: Frith
authors.forename: P N
authors.initials: PN
authors.lastname: Leigh
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology*; D002560:Cerebrovascular Circulation; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D007858:Learning; D008297:Male; D008568:Memory; D008875:Middle Aged; D009483:Neuropsychological Tests; D011597:Psychomotor Performance; D014055:Tomography, Emission-Computed