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Brain, Vol. 119, No. 6, 2105-2120, 1996
© 1996 Guarantors of Brain

research-article

Frontal lobe dysfunction in amyotrophic lateral sclerosis

A PET study

S. Abrahams1,, L. H. Goldstein1, J. J. M. Kew3, D. J. Brooks3, C. M. Lloyd2, C. D. Frith3,4 and P. N. Leigh2

1Department of Psychology, Institute of Psychiatry, Institute of Psychiatry and King's College Hospital Medical School London, UK 2Department of Clinical Neurosciences, Institute of Psychiatry and King's College Hospital Medical School London, UK 3MRC Cyclotron Unit, Hammersmith Hospital, Institute of Neurology London, UK 4Wellcome Department of Cognitive Neurology, Institute of Neurology London, UK

Correspondence to: Correspondence to: Dr Sharon Abrahams, Department of Psychology, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK

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.

frontal lobes; cognitive impairment; ALS; PET; verbal fluency

Received August 14, 1996. Revised June 24, 1996. Accepted July 24, 1996.


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