title: Clues about the functional neuroanatomy of verbal working memory: a study of resting brain glucose metabolism in Parkinson's disease.
abstract: In addition to motor impairment, non-demented patients with Parkinson's disease (PD) exhibit a variable degree of cognitive impairment which could indicate dysfunction in the central executive of working memory. In this study, we have employed positron emission tomography measurements of resting brain glucose metabolism (CMRglc) to investigate the neural substrates underlying this dysfunction, taking PD as a model disease to assess, within the framework of Alexander's striato-pallido-thalamo-cortical cognitive circuits the functional neuroanatomy of the central executive. We studied central executive performance in 17 non-demented, highly selected PD patients, by means of the Brown-Peterson paradigm (BPP), and correlated the BPP performance according to various response delays (from 0 to 18 s) with local cerebral metabolic rates of glucose. We document for the first time that the BPP performance in PD is heterogeneous not only across delays (with PD patients selectively impaired for the 0 and 3 s delays, compatible with impaired attention and central executive, respectively), but also from subject to subject; a multiple correspondence analysis was able to distinguish two patient subgroups according to short delay BPP performance. The correlational analysis with PET data evidenced a limited number of significant correlations, most of which were consistent with our working hypothesis. Notably, a positive correlation between lateral frontal relative metabolism and BPP performance for short delays, and a negative one between these scores and mediodorsal (MD) thalamic nucleus metabolism, would fit the way in which caudate dopamine denervation would alter in opposite directions frontal cortex and MD nucleus synaptic activity and in turn affect central executive function. The results from this study lend further support to the role of altered thalamo-prefrontal interplay as the basis for central executive dysfunction in PD.
authors.affiliation: Cyceron, University of Caen, Caen, FranceInserm Unit 320, University of Caen, Caen, FranceService de Neurologie Dejerine, Centre Hospitalo-Universitaire, University of Caen, Caen, FranceCEA DSV/DRIPP, University of Caen, Caen, France.
authors.forename: R M
authors.initials: RM
authors.lastname: Marié
authors.forename: P
authors.initials: P
authors.lastname: Rioux
authors.forename: F
authors.initials: F
authors.lastname: Eustache
authors.forename: J M
authors.initials: JM
authors.lastname: Travère
authors.forename: B
authors.initials: B
authors.lastname: Lechevalier
authors.forename: J C
authors.initials: JC
authors.lastname: Baron