Dopamine-Dependent Frontostriatal Planning Deficits in Early Parkinson's Disease

Three groups of medicated and nonmedicated patients at different stages of Parkinson's disease and a group of neurosurgical patients with localized frontal lobe excisions were assessed on 2 novel tests of planning and spatial working memory. Results demonstrate that, like other tests of frontal lobe dysfunction, planning and spatial working memory are vulnerable in nonmedicated patients with mild Parkinson's disease and suggest that certain aspects of the planning impairment in these patients may be ameliorated by dopaminergic therapy. Specifically, with medication there was an improvement in accuracy of planning, but not in latency, in a series of problems based on the Tower of London test of planning. The results in terms of the frontostriatal, dopamine-dependent nature of some of the cognitive deficits found in early Parkinson's disease versus the apparent dopamine-independent nature of deficits in other cognitive processes are discussed. As may be expected from the intimate relation that exists between the basal ganglia and the frontal cortex (Alexander, Delong, & Strick, 1986), recent neuropsychological evidence suggests a substantial role for frontal lobe dysfunction in the cognitive profile of patients with Parkinson's disease (Bowen, Kamienny, Burns, & Yahr, 1975; Canavan et al., 1989; Downes et al., 1989; Lees & Smith, 1983; Owen et al., 1992; Scatton, Javoy-Agid, Rouquier, Dubois, & Agid, 1983; Taylor, SaintCyr, & Lang, 1986). Although few direct comparisons have been made between patients with frontal lobe damage and patients with Parkinson's disease, similar patterns of cognitive impairment have been observed in the two groups in many studies. For example, deficits on the Wisconsin Card Sorting Task, a commonly used clinical index of frontal lobe damage

[1]  M. M. Burns,et al.  Parkinsonism , 1975, Neurology.

[2]  R. Godwin-Austen,et al.  Diffuse Lewy body disease: clinical features in 15 cases. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[3]  B. J. Winer Statistical Principles in Experimental Design , 1992 .

[4]  C. Marsden,et al.  The performance on learning tasks of patients in the early stages of Parkinson's disease , 1989, Neuropsychologia.

[5]  M. Hoehn,et al.  Parkinsonism , 1967, Neurology.

[6]  A. MacLeod,et al.  Associations between phenomenal and objective aspects of concentration problems in depressed patients. , 1988, British journal of psychology.

[7]  A. C. Roberts,et al.  Impaired extra-dimensional shift performance in medicated and unmedicated Parkinson's disease: Evidence for a specific attentional dysfunction , 1989, Neuropsychologia.

[8]  P. Lantos,et al.  Cortical Lewy body dementia: clinical features and classification. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[9]  F Lhermitte,et al.  Heterogeneity of cognitive impairment in progressive supranuclear palsy, Parkinson's disease, and Alzheimer's disease , 1986, Neurology.

[10]  P. Goldman-Rakic Cellular and circuit basis of working memory in prefrontal cortex of nonhuman primates. , 1990, Progress in brain research.

[11]  J. Saint-Cyr,et al.  Procedural learning and neostriatal dysfunction in man. , 1988, Brain : a journal of neurology.

[12]  C. Marsden,et al.  'Subcortical dementia': the neuropsychological evidence. , 1988, Neuroscience.

[13]  HighWire Press Philosophical Transactions of the Royal Society of London , 1781, The London Medical Journal.

[14]  T. Robbins,et al.  Planning and spatial working memory in Parkinson's disease. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[15]  H. E. Rosvold,et al.  Localization of function within the dorsolateral prefrontal cortex of the rhesus monkey. , 1970, Experimental neurology.

[16]  F Lhermitte,et al.  Cholinergic‐dependent cognitive deficits in Parkinson's disease , 1987, Annals of neurology.

[17]  D. Rogers Bradyphrenia in parkinsonism: a historical review , 1986, Psychological Medicine.

[18]  A J Lees,et al.  Bradyphrenia in Parkinson's disease and psychomotor retardation in depressive illness. An experimental study. , 1987, Brain : a journal of neurology.

[19]  M Petrides,et al.  Monitoring of selections of visual stimuli and the primate frontal cortex , 1991, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[20]  Edward E. Smith,et al.  Spatial working memory in humans as revealed by PET , 1993, Nature.

[21]  D. Stuss,et al.  Neuropsychological studies of the frontal lobes. , 1984, Psychological bulletin.

[22]  E. Sullivan,et al.  Cognitive impairment in early, untreated Parkinson's disease and its relationship to motor disability. , 1991, Brain : a journal of neurology.

[23]  C. Marsden,et al.  Fronto-striatal cognitive deficits at different stages of Parkinson's disease. , 1992, Brain : a journal of neurology.

[24]  R. Heaton,et al.  The utility of the Wisconsin Card Sorting Test in detecting and localizing frontal lobe lesions. , 1980, Journal of consulting and clinical psychology.

[25]  T. Robbins,et al.  Planning and spatial working memory following frontal lobe lesions in man , 1990, Neuropsychologia.

[26]  H. Nelson A Modified Card Sorting Test Sensitive to Frontal Lobe Defects , 1976, Cortex.

[27]  R E Passingham Memory of monkeys (Macaca mulatta) with lesions in prefrontal cortex. , 1985, Behavioral neuroscience.

[28]  J. Saint-Cyr,et al.  Frontal lobe dysfunction in Parkinson's disease. The cortical focus of neostriatal outflow. , 1986, Brain : a journal of neurology.

[29]  P. Rabbitt,et al.  Cambridge Neuropsychological Test Automated Battery (CANTAB): a factor analytic study of a large sample of normal elderly volunteers. , 1994, Dementia.

[30]  M. Albert,et al.  Perseveration in behavioral neurology , 1987, Neurology.

[31]  H J Sagar,et al.  Temporal ordering and short-term memory deficits in Parkinson's disease. , 1988, Brain : a journal of neurology.

[32]  P N Leigh,et al.  Cognitive deficits in progressive supranuclear palsy, Parkinson's disease, and multiple system atrophy in tests sensitive to frontal lobe dysfunction. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[33]  C. Marsden,et al.  'Frontal' cognitive function in patients with Parkinson's disease 'on' and 'off' levodopa. , 1988, Brain : a journal of neurology.

[34]  T. Robbins,et al.  Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man , 1991, Neuropsychologia.

[35]  Adrian M. Owen,et al.  Visuo-spatial short-term recognition memory and learning after temporal lobe excisions, frontal lobe excisions or amygdalo-hippocampectomy in man , 1995, Neuropsychologia.

[36]  N C Andreasen,et al.  The neuropsychology of the prefrontal cortex. , 1993, Archives of neurology.

[37]  A. M. Owen,et al.  Visuospatial memory deficits at different stages of Parkinson's disease , 1993, Neuropsychologia.

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

[39]  T. Robbins,et al.  Contrasting mechanisms of impaired attentional set-shifting in patients with frontal lobe damage or Parkinson's disease. , 1993, Brain : a journal of neurology.

[40]  A. Lees,et al.  Cognitive deficits in the early stages of Parkinson's disease. , 1983, Brain : a journal of neurology.

[41]  H. E. Rosvold,et al.  Analysis of the delayed-alternation deficit produced by dorsolateral prefrontal lesions in the rhesus monkey. , 1971, Journal of comparative and physiological psychology.

[42]  V. Leirer,et al.  Development and validation of a geriatric depression screening scale: a preliminary report. , 1982, Journal of psychiatric research.

[43]  Y. Agid,et al.  Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson's disease , 1983, Brain Research.

[44]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[45]  E. Drewe,et al.  The effect of type and area of brain lesion on Wisconsin card sorting test performance. , 1974, Cortex; a journal devoted to the study of the nervous system and behavior.

[46]  P. Goldman-Rakic,et al.  Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. , 1989, Journal of neurophysiology.

[47]  T. Robbins,et al.  A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease. , 1988, Brain : a journal of neurology.

[48]  G. E. Alexander,et al.  Parallel organization of functionally segregated circuits linking basal ganglia and cortex. , 1986, Annual review of neuroscience.

[49]  T. Shallice Specific impairments of planning. , 1982, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.