Frontal lobe dysfunction in amyotrophic lateral sclerosis. A PET study.

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.

[1]  M M Mesulam,et al.  Large‐scale neurocognitive networks and distributed processing for attention, language, and memory , 1990, Annals of neurology.

[2]  M Mishkin,et al.  The origin, course, and termination of the hippocampothalamic projections in the macaque , 1986, The Journal of comparative neurology.

[3]  H. Nagura,et al.  Signal loss in the motor cortex on magnetic resonance images in amyotrophic lateral sclerosis , 1993, Annals of neurology.

[4]  H. Hayashi,et al.  Involvement of the frontotemporal lobe and limbic system in amyotrophic lateral sclerosis: As assessed by serial computed tomography and magnetic resonance imaging , 1993, Journal of the Neurological Sciences.

[5]  G. Huston.  The Hospital Anxiety and Depression Scale. , 1987, The Journal of rheumatology.

[6]  A. Hudson.  Amyotrophic lateral sclerosis and its association with dementia, parkinsonism and other neurological disorders: a review. , 1981, Brain : a journal of neurology.

[7]  J. Mazziotta,et al.  Rapid Automated Algorithm for Aligning and Reslicing PET Images , 1992, Journal of computer assisted tomography.

[8]  Mortimer Mishkin,et al.  Visual recognition impairment follows ventromedial but not dorsolateral prefrontal lesions in monkeys , 1986, Behavioural Brain Research.

[9]  Michael Swash,et al.  Criteria for Diagnosis of Familial Amyotrophic Lateral Sclerosis , 1992, Neuromuscular Disorders.

[10]  B. Brownell,et al.  The central nervous system in motor neurone disease , 1970, Journal of neurology, neurosurgery, and psychiatry.

[11]  C. Frith,et al.  Stereotyped responding by schizophrenic patients on a two-choice guessing task , 1983, Psychological Medicine.

[12]  Richard S. J. Frackowiak,et al.  Differential activation of right and left posterior sylvian regions by semantic and phonological tasks: a positron-emission tomography study in normal human subjects , 1994, Neuroscience Letters.

[13]  E. Cantor-Graae,et al.  Frontal lobe challenge: a comparison of activation procedures during rCBF Measurements in normal subjects , 1993 .

[14]  Y. Mitsuyama.  Presenile dementia with motor neuron disease in Japan: clinico-pathological review of 26 cases. , 1984, Journal of neurology, neurosurgery, and psychiatry.

[15]  M. Torrens.  Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[16]  P N Leigh,et al.  The relationship between abnormalities of cognitive function and cerebral activation in amyotrophic lateral sclerosis. A neuropsychological and positron emission tomography study. , 1993, Brain : a journal of neurology.

[17]  J A Kiernan,et al.  Frontal lobe atrophy in motor neuron diseases. , 1994, Brain : a journal of neurology.

[18]  D. Pandya,et al.  Architecture and Connections of the Frontal Lobe , 2019, The Frontal Lobes Revisited.

[19]  R. Heaton,et al.  Diagnostic utility of the Thurstone Word Fluency Test in neuropsychological evaluations. , 1982, Journal of clinical neuropsychology.

[20]  P. Talbot.  Frontal lobe dementia and motor neuron disease. , 1996, Journal of neural transmission. Supplementum.

[21]  D. Brooks.  Neuropsychology: A Clinical Approach , 1978 .

[22]  H. Yonas,et al.  Thalamic and subcortical gliosis with dementia. , 1987, Archives of neurology.

[23]  K. Heilman,et al.  Anterograde memory deficits for visuospatial material after infarction of the right thalamus. , 1983, Archives of neurology.

[24]  R A Robb,et al.  A software system for interactive and quantitative visualization of multidimensional biomedical images. , 1991, Australasian physical & engineering sciences in medicine.

[25]  L. Mazzini,et al.  Neuropsychological measures in amyotrophic lateral sclerosis and their relationship with CT scan‐assessed cerebral atrophy , 1986, Acta neurologica Scandinavica.

[26]  K Ugurbil,et al.  Functional magnetic resonance imaging of Broca's area during internal speech. , 1993, Neuroreport.

[27]  J. Mazziotta,et al.  MRI‐PET Registration with Automated Algorithm , 1993, Journal of computer assisted tomography.

[28]  Karl J. Friston,et al.  Willed action and the prefrontal cortex in man: a study with PET , 1991, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[29]  K. Ikeda,et al.  Cognitive impairment in amyotrophic lateral sclerosis and its relation to motor disabilities , 1990, Acta neurologica Scandinavica.

[30]  Karl J. Friston,et al.  Comparing Functional (PET) Images: The Assessment of Significant Change , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[31]  C. Caltagirone,et al.  Neuropsychological correlates of localized cerebral lesions in non-aphasic brain-damaged patients. , 1981, Journal of clinical neuropsychology.

[32]  D. Neary,et al.  Hippocampal and neocortical ubiquitin-immunoreactive inclusions in amyotrophic lateral sclerosis with dementia , 1992, Neuroscience Letters.

[33]  P. Leigh,et al.  Unusual Forms of Dementia , 1994 .

[34]  H. Kaiya,et al.  Presenile dementia combined with amyotrophy: a review of 34 Japanese cases. , 1987, Archives of gerontology and geriatrics.

[35]  M. Mesulam,et al.  The Insula of Reil in Man and Monkey , 1985 .

[36]  Brenda Milner,et al.  Design fluency: The invention of nonsense drawings after focal cortical lesions , 1977, Neuropsychologia.

[37]  M. Gilardi,et al.  Physical performance of the latest generation of commercial positron scanner , 1988 .

[38]  Tim Shallice,et al.  Neuropsychological impairments of short-term memory , 1992 .

[39]  C. Adcock,et al.  Primary Mental Abilities. , 1971, The Journal of general psychology.

[40]  B. Milner.  Effects of Different Brain Lesions on Card Sorting: The Role of the Frontal Lobes , 1963 .

[41]  Richard S. J. Frackowiak,et al.  The neural correlates of the verbal component of working memory , 1993, Nature.

[42]  Toshio Shimizu,et al.  Participation of the limbic system and its associated areas in the dementia of amyotrophic lateral sclerosis , 1994, Journal of the Neurological Sciences.

[43]  Yoichi Nakazato,et al.  New ubiquitin-positive intraneuronal inclusions in the extra-motor cortices in patients with amyotrophic lateral sclerosis , 1991, Neuroscience Letters.

[44]  Alan C. Evans,et al.  Lateralization of phonetic and pitch discrimination in speech processing. , 1992, Science.

[45]  A. David,et al.  Neuropsychological study of motor neuron disease. , 1986, Psychosomatics.

[46]  Karl J. Friston,et al.  A PET study of word finding , 1991, Neuropsychologia.

[47]  R. Bornstein,et al.  Contribution of various neuropsychological measures to detection of frontal lobe impairment , 1986 .

[48]  K. Yorkston,et al.  Amyotrophic lateral sclerosis severity scale. , 1989, Neuroepidemiology.

[49]  A. Stracciari,et al.  Cognitive impairment in motor neuron disease , 1985, Acta neurologica Scandinavica.

[50]  Karl J. Friston,et al.  The Relationship between Global and Local Changes in PET Scans , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[51]  Marion C. Smith.  NERVE FIBRE DEGENERATION IN THE BRAIN IN AMYOTROPHIC LATERAL SCLEROSIS , 1960, Journal of neurology, neurosurgery, and psychiatry.

[52]  B. Milner,et al.  Interhemispheric differences in the localization of psychological processes in man. , 1971, British medical bulletin.

[53]  D. Neary,et al.  Inter-relation between "classic" motor neuron disease and frontotemporal dementia: neuropsychological and single photon emission computed tomography study. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[54]  K. Heilman,et al.  Amnestic disturbance following infarction of the left dorsomedial nucleus of the thalamus , 1982, Neuropsychologia.

[55]  P N Leigh,et al.  Cortical function in amyotrophic lateral sclerosis. A positron emission tomography study. , 1993, Brain : a journal of neurology.

[56]  Richard S. J. Frackowiak,et al.  The anatomy of phonological and semantic processing in normal subjects. , 1992, Brain : a journal of neurology.

[57]  M. Mesulam,et al.  Neuropsychological aspects of dementia of motor neuron disease , 1992, Neurology.

[58]  Richard S. J. Frackowiak,et al.  Area V5 of the human brain: evidence from a combined study using positron emission tomography and magnetic resonance imaging. , 1993, Cerebral cortex.

[59]  A. Paetau,et al.  Classic amyotrophic lateral sclerosis with dementia. , 1982, Archives of neurology.

[60]  E. Miller,et al.  Verbal fluency as a function of a measure of verbal intelligence and in relation to different types of cerebral pathology. , 1984, The British journal of clinical psychology.

[61]  Arthur L. Benton,et al.  Differential behavioral effects in frontal lobe disease , 1968 .

[62]  Karl J. Friston,et al.  Distribution of cortical neural networks involved in word comprehension and word retrieval. , 1991, Brain : a journal of neurology.

[63]  Karl J. Friston,et al.  Localisation in PET Images: Direct Fitting of the Intercommissural (AC—PC) Line , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[64]  P. Montagna,et al.  Neuropsychological, electroencephalogram and brain computed tomography findings in motor neuron disease. , 1989, European neurology.