The aim of the present study was to investigate the cognitive, neuropsychiatric, and quality-of-life profiles of patients with PD 12 months after STN DBS as a function of motor symptom asymmetry. According to recent research 15, motor symptom asymmetry could be a meaningful predictor of non-motor performance following surgery. The present results seem to indicate that, at 12 months, DBS does not have a detrimental effect on cognitive measures for RPD patients (with inferred left cerebral pathology), whereas we did observe a harmful effect for LPD patients compared with HCs. In addition, whereas apathy seemed to be reduced for RPD patients, there were no changes in the severity of neuropsychiatric symptoms (i.e., apathy and depression scores) for LPD patients. As a consequence, DBS primarily had a beneficial effect on quality of life for RPD patients. These findings indicate that PD motor symptom asymmetry is a risk factor in the non-motor impact of STN DBS.
Before taking the interpretation any further, several main limitations need to be considered. First, the retrospective nature of the study, as well as the small size of the sample, represent limitations to the inferences that can be made from the present results. Second, the contacts used for chronic stimulation, according to the coordinates X, Y, Z, which were calculated with respect to the inter-commissural (anterior commissure-posterior commissure) line, did not allow precise localization of the stimulation contacts within the STN. Even if it does not reach statistical significance, a mean difference in laterality greater than 1 mm is relevant in the context of the STN and may help explain part of the present results. However, the unavailability of contact coordinates for 21 subjects did not allow specific speculation about the direct effects of stimulation as a function of laterality of motor symptoms, and so these effects remain to be explored in future studies. Third and finally, one can argue that dopaminergic treatment may underlie the post-DBS effects, notably on apathy found in RPD patients. That being said, we failed to observe a significant difference between RPD and LPD patients for LEDD in both the pre- and postoperative conditions, or to find a significant correlation between LEDD and AES in the multiple regression analyses.
Analysis of cognitive measures revealed differential effects of DBS as a function of motor symptom asymmetry. As predicted, cognitive performances were mostly preserved in RPD patients compared with those in HCs at 12 months post-DBS, the exception being scores on the executive verbal task, where performance worsened post-DBS. In contrast, at 12 months, the performances of LPD patients worsened on nonverbal executive functions compared with those in HCs. This pattern of results corroborates the post-DBS results reported by Hershey, et al. 35, as well as those observed by Voruz, et al. 36. A first interpretation of these results may be that they represent an overload effect of the DBS in the cerebral hemisphere ipsilateral to motor symptoms. Indeed, as postulated by Péron, et al. 37, DBS would induce a desynchronizing effect on this ipsilateral associative loop through possible interconnectivity between the motor and associative areas of the STN 38, or by an direct effect of the DBS on the associative loop 39, while restoring the synchronization of the contralateral loops. That said, how can we explain that this effect would be more prominent for LPD than for RPD patients? A more critical and complex role of the left STN may be suspected, despite interhemispheric interaction between the large-scale networks involving the two STNs 17. In the case of LPD patients, as suggested by our results, dynamics and connectivity between the basal ganglia and other cortical regions involving fine executive processing would be altered. The LPD subgroup’s poorer performance on the TMT B-A, the number of categories on the MCST, and verbal fluency could be explained by an alteration of processes of connectivity involving the prefrontal, frontal, and basal ganglia regions of the left hemisphere 40–42. A similar phenomenon could be hypothesized for the RPD subgroup, with a potential overload effect of the DBS on the right STN, but because tasks that investigate visuo-spatial performance are lacking, these phenomena could not be observed during our study. In the future, it would be interesting to perform wider neuropsychological testing (including exhaustive memory and visuo-spatial tests) post-DBS. Finally, in the very long term, we predict that LPD patients would be able to compensate for the detrimental effect of DBS and would stabilize cognitively. RPD patients, on the other hand, would remain stable in the first month post-DBS (except for visuo-spatial performances for the reasons evoked earlier), but are expected to exhibit major cognitive impairment in the very long term because of the well-known vulnerability of the left hemisphere to neurodegeneration, which was illustrated in our results by the worsening of verbal executive tasks in these patients 43–45.
Analysis of neuropsychiatric measures revealed no significant differences between the PD subgroups for depression symptoms. However, there were significant differences between LPD and RPD patients on the AES-E and AES-O subscores. At the pre-DBS assessment, RPD patients scored higher than LPD patients on these two subscales, indicating greater apathy in RPD than in LPD patients. Interestingly, at 12 months post-DBS, LPD and RPD patients no longer differed significantly on the AES-O and AES-E subscales. Although we failed to observe intragroup effects, intergroup effects suggest a differential modification in post-DBS apathy as a function of motor asymmetry. These findings may suggest greater vulnerability of RPD patients for developing neuropsychiatric symptoms in the natural evolution of the disease and that DBS has the potential to restore mood disorders in this patient subtype. Previous results that showed an increase in apathy may have been biased by the presence of unequal proportions of LPD and RPD patients 46. Future empirical and meta-analytic studies are needed, considering the motor symptom asymmetry.
Finally, in line with our predictions, results for quality of life also differed according to motor symptom asymmetry. Notably, RPD patients exhibited post-DBS improvement in their quality of life across all domains (overall, global health, social function, physical role, and physical function scores) at 12 months post-DBS, whereas LPD patients did not display an improvement in the overall and physical scores or in the social function score. These results are in line with the literature suggesting an improvement in quality of life post-DBS 6; in addition, they demonstrate a weaker effect in LPD patients. Moreover, as expected, motor scores significantly predicted improvement in global health but, interestingly, the neuropsychiatric (AES-E) and cognitive (TMT) scores were also significant predictors and may explain why quality of life is significantly less increased for the LPD subgroup, in whom cognitive performances decrease in postoperative conditions.