Microglial TDP-43 mediates myelin refinement and represses Tyrobp cryptic exon inclusion in mice.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms such as bradykinesia, rigidity, and tremor However, most patients also experience non-motor symptoms (NMS), including cognitive impairment, mood disturbances, sleep-wake disorders, and autonomic dysfunction. NMS are often not reported to healthcare providers and have a high impact on the quality of life of patients. While specific treatments are available for some NMS, high-quality evidence is limited, and their effectiveness remains suboptimal. This underscores the need for more targeted therapies addressing non-motor symptoms in patients with PD. Deep brain stimulation (DBS) is an effective treatment for medication-refractory motor symptoms in PD. DBS has been associated with both improvements (e.g., depression and autonomic dysfunction) and deteriorations (e.g., verbal fluency and apathy) of several NMS. However, some of these changes may result from postoperative reductions in dopaminergic medications or from the surgery itself. DBS has advanced our understanding of the neurophysiology underlying PD by enabling subcortical local field potential (LFP) recordings from the target nuclei using the implanted DBS electrodes. These LFP signals represent the summed and synchronized activity of surrounding neural tissue and have been shown to harbor neurophysiological markers, or physiomarkers, indexing the severity of motor symptoms such as bradykinesia, rigidity, and dyskinesia. These physiomarkers hold promise for optimizing DBS programming and have led to the development of closed-loop or adaptive DBS. Physiomarkers indexing NMS would provide objective measures of symptom presence and severity and could guide DBS stimulation paradigms to improve the effectiveness of DBS. However, research in this area remains limited, and a comprehensive overview of existing studies is lacking. A recent study reviewed the literature on neurophysiology underlying mood, motivation, and behavioral symptoms in PD However, they did not systematically address the full spectrum of NMS. Instead, it primarily explored non-motor aspects through behavioral paradigms, regardless of whether NMS were present. To address these gaps, we aimed to systematically review the literature examining the relationship between basal ganglia LFPs and both the presence and severity of NMS in patients with PD.