Dissociable effects of dopaminergic therapy on spatial versus non-spatial working memory in Parkinson’s disease

There is now evidence for definite and early cognitive deficits in Parkinson's disease (PD), involving, in particular, executive functions and working memory. However, the distinction between visuo-spatial and non-spatial working memory deficits and the impact of dopamine on these deficits are still open to debate. The aim of this study was therefore to investigate cognitive and motor performance in PD patients in two conditional associative learning tasks requiring either spatial or non-spatial visual working memory. The subject had to point to visual targets according to the visual characteristics of memorised visual cues (colour, position and form). To assess the effect of L-dopa therapy, PD patients were studied over two consecutive days: one ON/OFF group of nine PD patients with treatment (ON condition) on the first day and without treatment (OFF condition) on the second day; and another OFF/ON group of nine PD patients tested on reverse. The PD groups were compared to a control group of nine age-matched healthy subjects. Our main data demonstrate that: (1) in PD patients with OFF treatment, the response time of manual pointing is increased mainly in the non-spatial working memory task; and (2) in PD patients with ON treatment, either the response time is normal (on the first day) or is increased in both visuo-spatial and non-spatial tasks. We suggest that this dissociation between spatial versus non-spatial working memory deficits in non-medicated PD might be related to compensatory mechanisms that occur following fronto-striatal dysfunction.

[1]  U Sabatini,et al.  Normal activation of the supplementary motor area in patients with Parkinson's disease undergoing long-term treatment with levodopa. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[2]  W. Gibb,et al.  The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[3]  C. Marsden,et al.  Cognitive function in Parkinson's disease: From description to theory , 1990, Trends in Neurosciences.

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

[5]  P. Calabresi,et al.  Dopaminergic control of synaptic plasticity in the dorsal striatum , 2001, The European journal of neuroscience.

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

[7]  Mark Hallett,et al.  Learning in Parkinson’s disease: eyeblink conditioning, declarative learning, and procedural learning , 1999, Journal of neurology, neurosurgery, and psychiatry.

[8]  A. F. Sanders,et al.  Dual Task Performance , 2001 .

[9]  P. Goldman-Rakic,et al.  Dissociation of object and spatial processing domains in primate prefrontal cortex. , 1993, Science.

[10]  Leslie Henderson,et al.  Eye movements and spatial working memory inParkinsons disease , 1999, Neuropsychologia.

[11]  A. Cools,et al.  Evidence for lateral premotor and parietal overactivity in Parkinson's disease during sequential and bimanual movements. A PET study. , 1998, Brain : a journal of neurology.

[12]  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.

[13]  H. Heuer Dual-task performance. , 1996 .

[14]  B. Dubois,et al.  Procedural learning and striatofrontal dysfunction in Parkinson's disease , 2002, Movement disorders : official journal of the Movement Disorder Society.

[15]  T. Robbins,et al.  Spatial and non-spatial working memory at different stages of Parkinson's disease , 1997, Neuropsychologia.

[16]  Peter Ford Dominey,et al.  Motor imagery in normal subjects and in asymmetrical Parkinson’s disease , 2000, Neurology.

[17]  B. Postle,et al.  An fMRI Investigation of Cortical Contributions to Spatial and Nonspatial Visual Working Memory , 2000, NeuroImage.

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

[19]  R. W. Watson,et al.  A central executive deficit in patients with Parkinson's disease. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[20]  L. Henderson,et al.  Eye movements and spatial working memory in Parkinson's disease. , 1999, Neuropsychologia.

[21]  C. Marsden,et al.  Dual task performance and processing resources in normal subjects and patients with Parkinson's disease. , 1991, Brain : a journal of neurology.

[22]  V. A. Bradley,et al.  Visuospatial working memory in Parkinson's disease. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[23]  Bruno Dubois,et al.  Memory for spatial location in ‘de novo’ parkinsonian patients , 1997, Neuropsychologia.

[24]  Y. Agid,et al.  Impaired simultaneous cognitive task performance in Parkinson's disease , 1994, Neurology.

[25]  W Fernandez,et al.  Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine , 1992, Annals of neurology.

[26]  B. Postle,et al.  The time course of spatial and object learning in Parkinson's disease , 1997, Neuropsychologia.

[27]  A. Bonnet,et al.  Is impaired memory for spatial location in Parkinson's disease domain specific or dependent on ‘strategic’ processes? , 1998, Neuropsychologia.

[28]  M. Hallett,et al.  A PET study of sequential finger movements of varying length in patients with Parkinson's disease. , 1999, Brain : a journal of neurology.

[29]  F. Chollet,et al.  The ipsilateral cerebellar hemisphere is overactive during hand movements in akinetic parkinsonian patients. , 1997, Brain : a journal of neurology.

[30]  Leslie G. Ungerleider,et al.  Object and spatial visual working memory activate separate neural systems in human cortex. , 1996, Cerebral cortex.

[31]  N. Hogan,et al.  Procedural motor learning in Parkinson's disease , 2001, Experimental Brain Research.

[32]  J. Saint-Cyr,et al.  Memory and learning in early Parkinson's disease: Evidence for a “frontal lobe syndrome” , 1990, Brain and Cognition.