Working memory in strategic verbal task: study in patients with mDLPFC dysfunction

During word lists learning tasks, PD patients are not significantly impaired in encoding items compared to normal controls, but they don’t benefit from semantic cues. In similar tasks, Frontal Patients (FP) show an overall deficit in list learning, but patients with lesions involving Area 9 (A9) result significantly more impaired when compared to other groups with lesions in mDLPFC (Fn), due to poor semantic strategy use. Based on the evidence of an associative fronto-striatal circuit involving A9, we aimed at evaluating the causal relation linking the impairment of the aforementioned neural circuit and the neuropsychological similarities between these two patients’ groups. After excluding aphasia and dementia with a preliminary neuropsychological battery, 30 PD patients, 10 FP and Normal Controls (NC) matched for age, sex and education were recruited and tested with a two-part verbal learning test: multi-trial repetition in free recall and multi-trial repetition preceded by an explicit semantical strategy cue. FP were divided into two groups: patients with frontal lesions involving (F9) or sparing (Fn) A9. Bivariate between-group comparisons were performed by covarying age, sex and education in order to evaluate the performance of the four groups (NC, PD, F9, Fn) using the number of items recalled and the effective use of learning strategies (suggested or not). PD patients learned fewer words and found difficulties in using semantic strategies compared to NC. When the strategy was suggested by the examiner, PD patients improved their performance, but not as much as NC. F9 showed similar results to PD patients. Fn showed similar results to the NC. These results are in line with previous studies and show that the similarity between groups may be due to the degeneration of specific connections between Caudate Nuclei and A9. This is particularly evident in the comparison between PD and F9 as the impaired results in the learning task in PD is due to subcortical degeneration that arise from the basal ganglia. These findings support the idea that A9 and its connections with Caudate Nuclei have a prominent role in strategy implementation. These results show that A9, and not surrounding areas, is the responsible for the effective use of semantic strategies in learning tasks. The similarities between PD and F9 suggest that the connection between Caudate Nuclei and A9 is an integrant part of the dorsolateral cognitive circuit of the extrapyramidal system.