Does Cognitive Impairment Influence Motor Speech Performance in De Novo Parkinson's Disease?

brain diseases (eg, stroke or levodopa-induced dyskinesia). However, it was rarely associated with the short-term effects of magnetic stimulation. In our study, we reported functional and structural changes in response to acute exposure of early symptomatic parkinsonian rats to transcranial magnetic stimulation (TMS) using the intermittent theta-burst stimulation (iTBS) pattern. The letter highlights the importance of providing evidence of structural plasticity changes in response to TMS as a morphological correlate of functional outcomes. In support of this concept, the author cites a recent paper from Jung and Lambon Ralph, who re-analyzed previous data to explore the structural aspects using voxel-based morphometry. The study shows that immediate effects of continuous theta-burst stimulation (cTBS) associated with an adaptive functional reorganization in the semantic representation system are because of changes in grey matter density at the targeted and remoted brain regions in vivo, which may include axon sprouting, dendritic branching, as well as changes in glia number and morphology. By linking our paper to the new interpretation of these critical findings, professor Suppa raises two important points on the dynamic nature of preclinical research in the field of neurodegenerative disorders. The first point concerns the possibility that results obtained using a methodological approach thought to offer a limited vision may actually lend themselves to multiple readings over time and on timely analyses. It is the case of the toxic models of experimental parkinsonism that, although limited in many aspects, can be revisited and modularly adapted to reproduce specific features of the disease at a given time point. Standard electrophysiology techniques combined with immunohistochemical identification of recorded neurons allow to correlate cell physiology to structural modifications that can be studied with morphometric analyses. The second aspect that emerges from highlighting a possible link between our preclinical results and the clinical study of Jung and Lambon Ralph is the translational potential of our findings. In our view, this is a critical point as voxel-based morphometry encompasses morphological rearrangements of non-neuronal elements (ie, glial cells), reconnecting with our previous observations obtained in a similar model, where acute iTBS significantly reduced astrogliosis. In conclusion, we agree that these preclinical results on the dendritic spine reorganization after acute iTBS provide an important frame to identify the mechanisms underlying beneficial compensatory changes in parkinsonism and related disorders. An intriguing, but still unexplored possibility is the combined exploitation of new functional and structural markers into synergistic approaches that would preserve and enhance patients’ brain residual functions, to maximize the responses to neurorehabilitation and pharmacotherapy treatments. If further explored in terms of cell-type specificity, effect duration, and the possibility to take a sustainable advantage of transient effects, these experimental findings may contribute to our understanding of structural plasticity involved in clinical interventions with noninvasive brain stimulation. Data Availability Statement