FRONTAL-LOBE DYSFUNCTION IN AMYOTROPHIC-LATERAL-SCLEROSIS - A PET STUDY

PET measurements of regional cerebral blood flow (rCBF) were used to e xplore frontal lobe dysfunction in amyotrophic lateral sclerosis (ALS) . An activation paradigm of executive frontal lobe function (verbal fl uency), which contrasted rCBF during word generation and word repetiti on, was used. Two groups of ALS patients, defined by the presence or a bsence of cognitive impairment (ALSi) (impaired, n = 6; ALSu, unimpair ed, n = 6) were compared with healthy age-matched controls (n = 6). Pa tient selection was based on prior performance on a written test of ve rbal fluency. Additional neuropsychological assessment of the patients revealed evidence of executive and memory dysfunction in the ALSi gro up only, with marked deficits in tests of intrinsic generation. The AL Si patients displayed significantly (P < 0.001) impaired activation in cortical and subcortical regions including the dorsolateral prefronta l 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 sc anning paradigm, the ALSu group displayed a relatively unimpaired patt ern of activation. These results support the presence of extra-motor n euronal involvement, particularly along a thalamo-frontal association pathway, in some non-demented ALS patients. In addition, this study su ggests dysfunction of DLPFC in some ALS patients with associated cogni tive impairments.