Pain from Parkinson's disease (PD) is a non-motor symptom affecting the quality of life and has prevalence of 20–80%. However, it is unclear whether subthalamic nucleus deep brain stimulation (STN–DBS), a well-established treatment for PD, is effective forPD-related pain. Thus, the objective of this meta-analysis was to investigate the efficacy of STN-DBS on PD-related pain and explore how its duration affects the efficacy of STN-DBS. A systematic search was performed using PubMed, Embase, and the Cochrane Library. Nine studies included numerical rating scale (NRS), visual analog scale (VAS), or non-motor symptom scale (NMSS) scores at baseline and at the last follow-up visit and therefore met the inclusion criteria of the authors. These studies exhibited moderate- to high-quality evidence. Two reviewers conducted assessments for study eligibility, risk of bias, data extraction, and quality of evidence rating. Random effect meta-analysis revealed a significant change in PD-related pain as assessed by NMSS, NRS, and VAS (P <0.01). Analysis of the short and long follow-up subgroups indicated delayed improvement in PD-related pain. These findings (a) show the efficacy of STN-DBS on PD-related pain and provide higher-level evidence, and (b) implicate delayed improvement in PD-related pain, which may help programming doctors with supplement selecting target and programming.Systematic Review Registration: This study is registered in Open Science Framework (DOI: 10.17605/OSF.IO/DNM6K).

BackgroundDeep brain stimulation (DBS) improves motor and non-motor symptoms in patients with Parkinson’s disease (PD). Researchers mainly investigated the motor networks to reveal DBS mechanisms, with few studies extending to other networks. This study aimed to investigate multi-network modulation patterns using DBS in patients with PD.MethodsTwenty-four patients with PD underwent 1.5 T functional MRI (fMRI) scans in both DBS-on and DBS-off states, with twenty-seven age-matched healthy controls (HCs). Default mode, sensorimotor, salience, and left and right frontoparietal networks were identified by using the independent component analysis. Power spectra and functional connectivity of these networks were calculated. In addition, multiregional connectivity was established from 15 selected regions extracted from the abovementioned networks. Comparisons were made among groups. Finally, correlation analyses were performed between the connectivity changes and symptom improvements.ResultsCompared with HCs, PD-off showed abnormal power spectra and functional connectivity both within and among these networks. Some of the abovementioned abnormalities could be corrected by DBS, including increasing the power spectra in the sensorimotor network and modulating the parts of the ipsilateral functional connectivity in different regions centered in the frontoparietal network. Moreover, the DBS-induced functional connectivity changes were correlated with motor and depression improvements in patients with PD.ConclusionDBS modulated the abnormalities in multi-networks. The functional connectivity alterations were associated with motor and psychiatric improvements in PD. This study lays the foundation for large-scale brain network research on multi-network DBS modulation.

Objective: In this study, we aimed to investigate the effects of STN-DBS on PD patients with different levels of depression and to identify predictors of the effects of STN-DBS on PD depression. Methods: We retrospectively collected data for 118 patients with PD depression who underwent STN-DBS at Beijing Tiantan Hospital. Neuropsychological, motor, and quality of life assessments were applied preoperatively and postoperatively. All patients were divided into two groups according to their HAM-D24 total scores (group Ⅰ: mild depression; group Ⅱ: moderate depression). A mixed repeated-measure analysis of variance (ANOVA) was performed to investigate whether there were differences in depression scores before and after STN-DBS between the two groups. The changes in depression scores were also compared between groups using ANCOVA, adjusting for gender and preoperative HAMA scores. Logistic regression was performed to identify predictors of STN-DBS’s effects on PD depression. Results: Both groups showed significant improvement in depression symptoms after STN-DBS. Compared with patients in group Ⅰ, patients in group Ⅱ showed greater reductions in their HAM-D24 total scores (p = 0.002) and in HAM-D24 subitems including cognitive disturbances (p = 0.026) and hopelessness symptoms (p = 0.018). Logistic regression indicated that gender (female) (p = 0.014) and preoperative moderate depression (p < 0.001) patients had greater improvements in depression after STN-DBS. Conclusions: Patients with moderate depression showed better improvement than patients with mild depression. Gender (female) and preoperative HAMA scores are predictors of STN-DBS’s effects on PD depression.

Nitric oxide (NO) is a relatively short-lived inorganic free radical, which can be produced by different types of cells in multi-cellular organisms. This diffusible messenger functions as either an effector or a second messenger in many intercellular communications or intracellular signaling pathways. NO becomes noxious if it is produced in excess. These effects are mainly mediated by the reactivity of NO with various reactive oxygen species, which can be countered by antioxidant enzymes. In addition, NO can directly modify biological molecules via S-nitrosylation and lead to altered signaling responses. Accumulating evidence suggests that NO has a double-edged role in a dose-dependent, cell-type specific, and biological milieu-dependent way. In the present review, we summarized the synthesis and signaling pathway of NO, and especially focused on its involvement in biological processes, such as endoplasmic reticulum stress, apoptosis and autophagy. Besides, we discussed the functions of NO in the nervous system and its potential role in neurodegenerative diseases. We proposed the target on NO may shed light on the treatment of the related diseases.

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KCNQ/M potassium channels play a vital role in neuronal excitability; however, it is required to explore their pharmacological modulation on N‐Methyl‐ d‐aspartic acid receptors (NMDARs)‐mediated glutamatergic transmission of neurons upon ischemic insults. In the current study, both presynaptic glutamatergic release and activities of NMDARs were measured by NMDAR‐induced miniature excitatory postsynaptic currents (mEPSCs) in cultured cortical neurons of C57 mice undergoing oxygen and glucose deprivation (OGD) or OGD/reperfusion (OGD/R). The KCNQ/M‐channel opener, retigabine (RTG), suppressed the overactivation of postsynaptic NMDARs induced by OGD and then NO transient; RTG also decreased OGD‐induced neuronal death measured with MTT assay, suggesting the beneficial role of KCNQ/M‐channels for the neurons exposed to ischemic insults. However, when the neurons exposed to the subsequent reperfusion, KCNQ/M‐channels played a differential role from its protective effect. OGD/R increased presynaptic glutamatergic release, which was further augmented by RTG or decreased by KCNQ/M‐channel blocker, XE991. Reactive oxygen species (ROS) were produced partly in a NO‐dependent manner. In addition, XE991 decreased neuronal injuries upon reperfusion measured with DCF and PI staining. Meanwhile, the addition of RTG upon OGD or XE991 upon reperfusion can reverse OGD or OGD/R‐reduced mitochondrial membrane potential. Our present study indicates the dual role of KCNQ/M‐channels in OGD and OGD/R, which will decide the fate of neurons. Provided that activation of KCNQ/M‐channels has differential effects on neuronal injuries during OGD or OGD/R, we propose that therapy targeting KCNQ/M‐channels may be effective for ischemic injuries but the proper timing is so crucial for the corresponding treatment.

Background: The successful application of subthalamic nucleus (STN) deep brain stimulation (DBS) surgery relies mostly on optimal lead placement, whereas the major challenge is how to precisely localize STN. Microstimulation, which can induce differentiating inhibitory responses between STN and substantia nigra pars reticulata (SNr) near the ventral border of STN, has indicated a great potential of breaking through this barrier.Objective: This study aims to investigate the feasibility of localizing the boundary between STN and SNr (SSB) using microstimulation and promote better lead placement.Methods: We recorded neurophysiological data from 41 patients undergoing STN-DBS surgery with microstimulation in our hospital. Trajectories with typical STN signal were included. Microstimulation was applied near the bottom of STN to determine SSB, which was validated by the imaging reconstruction of DBS leads.Results: In most trajectories with microstimulation (84.4%), neuronal firing in STN could not be inhibited by microstimulation, whereas in SNr long inhibition was observed following microstimulation. The success rate of localizing SSB was significantly higher in trajectories with microstimulation than those without. Moreover, results from imaging reconstruction and intraoperative neurological assessments demonstrated better lead location and higher therapeutic effectiveness in trajectories with microstimulation and accurately identified SSB.Conclusion: Microstimulation on microelectrode recording is an effective approach to localize the SSB. Our data provide clinical evidence that microstimulation can be routinely employed to achieve better lead placement.

Kv channels, the voltage-gated potassium channels, are encoded by KCN gene family. Kv channels are important in maintaining the resting membrane potential and spiking threshold, deciding the firing frequency and nerve hyperexcitability, and inducing after hyperpolarization after burst firing. In this family, Kv7 is a special one for it is activated at subthreshold potentials. Because of its specific characteristics, Kv7 channels show pronounced control over the excitability of neurons and often inhibit neuronal excitability. Moreover, it is also documented that mutations of Kv7 channels are associated with the occurrence of epilepsy, deafness and cardiac arrhythmia. In this review, we discussed the characteristics and functions of Kv channels especially the Kv7 channels, which determined their targeting role in treatment against epilepsy.