OBJECTIVE:The pathological mechanisms underlying the subtypes of Parkinson's disease (PD) remain unclear. The aim of the study was to explore whether synchronized subthalamic oscillatory neurons are associated with the motor symptoms of PD. METHOD:Thirty patients undergoing subthalamic nucleus (STN) deep brain stimulation were included. They were classified tremor dominant (TD, n = 8), indeterminate type (IT, n = 9), and postural instability and gait disorder (PIGD, n = 13) groups. Microelectrode recordings in the STN and the electromyogram (EMG) were recorded. Neuronal background activity was extracted. Spectral and coherence analysis and correlation analysis was used. The locations of the oscillatory neurons were noted. RESULTS:Of total oscillatory neurons, 95.0% β frequency and 83.3% tremor frequency oscillatory neurons were coherent with their background. Of 76 synchronized β frequency oscillatory neurons, 13.2% were coherent with limb rigidity in PIGD group whereas of 30 synchronized tremor frequency oscillatory neurons, 20% were coherent with tremor in TD group. Tremor frequency and β frequency oscillatory neurons correlated with tremor (r = 0.80 [95% CI 0.23,0.98], P < 0.02) and rigidity/bradykinesia (r = 0.81[95% CI 0.47,0.94], P < 0.0008) sub-scores, respectively. All three subbands of β frequency oscillatory neurons correlated with rigidity/bradykinesia subscores; however, the subband of 13-20 Hz had the strongest correlation (r = 0.64 [95% CI 0.38,0.81], P < 0.0002). The majority of synchronized oscillatory neurons were located in the dorsal STN. CONCLUSION:Synchronized tremor frequency and β frequency oscillatory neurons seem to associate with the TD and PIGD subtypes of PD respectively. The low β frequency of 13-20 Hz oscillatory neurons is more implicated for rigidity/bradykinesia. Synchronized oscillatory neurons in the dorsal STN support the idea that the neurons can be used to guide optimal electrode placement.

Exploration is a fundamental innate behavior essential for securing survival-necessary resources, but it also increases risks. However, the neural mechanisms encoding exploration decisions remain unknown. Here, we show that social companionship motivates both innate-driven and experience-dependent explorations in mice. Dopaminergic neurons in the ventral tegmental area (VTADA neurons) determine exploration decisions by encoding risky vigilance (via phasic firing) and exploration motivation (via tonic firing). Two subpopulations of VTADA neurons co-innervate the same population of basolateral amygdala neurons via direct and indirect pathways. Tonic firing-biased DA-D2R transmission in the medial prefrontal cortex (indirect pathway) mediates exploratory behaviors, which are reinforced by social interactions, while phasic firing-biased DA-D1R transmission in the direct pathway mediates avoidant behaviors. The dynamic balance between these two competing DA pathways coordinately encodes exploration decisions. These findings establish the VTADA neuron as a central hub and the circuit integration of biased DA transmission as a central mechanism encoding exploration decisions.

Objective:Evaluate safety and analgesic effect of neuronavigation-guided 10 Hz rTMS precisely targeting facial M1 in atypical facial pain (AFP). Methods:Two adults with refractory AFP received 10 daily sessions (2,500 pulses/day) of 10 Hz rTMS at 110 % resting motor threshold. Targeting used MRI/CT-integrated neuronavigation to the facial M1. Pain severity (Barrow Neurological Institute [BNI] scale I-V) and adverse events were recorded through treatment and short follow-up. Results:Both completed treatment without serious adverse events. Case 1 improved from BNI V at baseline to II at end of treatment, persisting BNI III for 15 days. Case 2 improved from BNI IV to I, with BNI III for 2 days after therapy; both reported better sleep and mood. Conclusions:Neuronavigation-guided 10 Hz rTMS of facial M1 was well tolerated and associated with rapid, clinically meaningful analgesia in two AFP cases. Significance:Pilot data support sham-controlled studies to define dose-response and durability, identify responders, and formalize navigated rTMS as a physiological screen to select candidates and targets for implanted brain stimulations.

Abstract Objectives To explore the efficacy and potential neurophysiological mechanisms of 77.5 Hz transcranial alternating current stimulation (tACS) in the treatment of female adolescent non-suicidal self-injury (NSSI). Methods Six female NSSI patients received 21 days of 77.5 Hz, 15 mA tACS treatments. Neuropsychological scales were assessed at baseline (W0), after treatment (W3), and 4-week (W7) and 8-week (W11) follow-ups. Transcranial magnetic stimulation with EEG evaluated changes in source-level brain activity and phase-synchronous functional connectivity. Mixed repeated-measures ANOVA with Bonferroni correction (p < 0.017) was used for behavioral data analysis to correct for multiple comparisons. Effect sizes (Cohen’s d) was reported for all statistical results. Results Significant improvements were observed in depressive symptoms and self-injury behaviors after treatment (OSIC: W7: P = 0.009, Cohen’s d=-1.682; HAMD-24: W3: P = 0.006, Cohen’s d=-1.892; W7: P = 0.001, Cohen’s d=-2.839; W11: P = 0.001, Cohen’s d=-2.738; all P < 0.017). Electrophysiological analysis revealed that 77.5 Hz tACS might decrease Default network activity, increased Limbic, SalVAttn and Control network activity, and enhanced the functional connectivity in high-gamma band between Control and SalVAttn/Default network. A positive correlation was found between increased C100 activity in the SalVAttn (left frontal-insula) region and reduced HAMD-24 scores (R = 0.826, p = 0.043), this correlation analysis was based on a small sample size (n = 6), and the correlation coefficient was unstable, with results only for preliminary exploratory reference. Conclusion 77.5 Hz tACS may alleviate NSSI symptoms in female adolescents potentially by regulating brain activity and functional connectivity in emotional-control networks.

Neuroinflammation is a key pathological factor of PD, and T cells play a central role in neuroinflammatory progression. However, the causal effect of T cell–related genes on the risk of PD is still unclear. We explored single-cell RNA sequencing (scRNA-Seq) datasets of the peripheral blood T cells of PD patients and healthy controls, and screened the differentially expressed genes (DEGs) in the cytotoxic CD4 + T cells relative to the other T cell subsets. Pseudo-time series analysis, cell–cell communication analysis, and metabolic pathway analysis was performed for the cytotoxic CD4 + T cells. The DEGs were also functionally annotated through GO and KEGG pathway enrichment analyses. The MR approach was used to establish causal effects of the DEGs (exposure) on PD risk (outcome), and explore new drug targets for PD. The findings of MR analysis were further validated by Steiger filtering, bidirectional MR, Bayesian colocalization analysis, and phenotype scanning, and the GWAS data from an independent PD case–control cohort was used for external validation of the results. Finally, differences in gene expression between PD patients and healthy controls were further validated in scRNA-Seq and bulk transcriptome sequencing data. We found that increased expression of IL-32, GNLY, MT2A, and ARPC2 was significantly associated with a higher risk of PD. In contrast, the increase in ARRB2 was closely related to a lower risk of PD. IL32, GNLY, MT2A, ARRB2, and ARPC2 are the causal genes and potential drug targets of PD. Cytotoxic CD4 + T cells are likely the key effectors of PD-related neuroinflammation. These findings provide new insights into the pathogenesis and treatment options for PD, and further research and clinical trials based on the five potential drug targets and neuroinflammation are necessary.

Animal models are crucial for elucidating the pathological mechanisms underlying Parkinson's disease (PD). Unfortunately, most of transgenic mouse models fail to manifest pathological changes observed in PD patients, pending the advancement of PD research. However, the mechanism underlying this discrepancy remains elusive. Here, we provide compelling evidence that the compensatory expression of synaptotagmin-11 (Syt11) plays a key role in concealing PD-associated phenotypes in parkin knockout (KO) mouse models. Unlike the normal dopamine (DA) release and motor behaviors observed in parkin KO mice, parkin knockdown (KD) in the substantia nigra pars compacta (SNpc) in adult mice led to both the impaired DA release and the pronounced motor deficits. Interestingly, Syt11, a well-established parkin substrate involved in PD, was specifically upregulated in parkin KD mice and in parkin KO mice during the suckling stage, but not in adult parkin KO mice. Importantly, the overexpression of Syt11 alone is capable of inducing PD-like motor and non-motor impairments, as well as the impaired DA release and reuptake, which is essential for parkin-associated pathogenesis of PD. Therefore, this work not only elucidate a compensatory mechanism that accounts for the absence of overt PD phenotypes in parkin KO mice, but also contribute to the comprehensive understanding of the progression of PD, opening new avenues for the therapeutic treatment of PD.

OBJECTIVES:Conventional deep brain stimulation (cDBS) is an established treatment for Parkinson's disease (PD), whereas adaptive DBS (aDBS) represents a promising approach with potential advantages in minimizing stimulation-induced side effects and enhancing quality of life. This study evaluated the safety and efficacy of a newly developed aDBS closed-loop neurostimulation (CNS) device for one year across multiple centers, with the primary objective of comparing the outcomes of aDBS and cDBS. MATERIALS AND METHODS:This retrospective study included 62 patients with PD who underwent bilateral subthalamic nucleus (STN) DBS. Outcomes were assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson's Disease Questionnaire-39 (PDQ-39), and Schwab and England Activities Scale, whereas the levodopa-equivalent daily dose (LEDD) and adverse events were monitored. This two-phase trial randomized participants into Stim-on or Stim-off groups for 90-day postoperative comparison followed by nonrandomized evaluation of aDBS vs cDBS at 360 days after surgery. RESULTS:At 90 days postoperatively, the Stim-on group exhibited superior outcomes to those in the Stim-off group except for LEDD and speech in the medication-on state. At the 360-day postoperative assessment, the aDBS group showed significantly greater improvements than did the cDBS group in MDS-UPDRS II (57.29% vs 33.02%, p = 0.022), MDS-UPDRS IV (59.83% vs 36.69%, p = 0.026), PDQ-39 (56.91% vs 27.37%, p = 0.031), and LEDD reduction (53.35% vs 29.16%, p = 0.002). CNS aDBS recorded clear STN-beta signals, which could be adopted as a biomarker. CONCLUSIONS:Both aDBS and cDBS significantly alleviate motor symptoms and enhance quality of life in patients with PD. Although comparable in motor symptom control, aDBS indicated advantages over cDBS across LEDD reduction, MDS-UPDRS II, MDS-UPDRS IV, and PDQ-39 over the long term. Further studies with extended follow-up and larger sample sizes are required to validate these results.

Background:Freezing of gait (FOG) is a major disabling symptom that affects the quality of life of patients with Parkinson's disease (PD). To date, notions regarding the effects of deep brain stimulation of the subthalamic neucleus (STN-DBS) on FOG remain controversial. Therefore, we developed a prediction model based on the influence of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on FOG in patients with PD. Methods:We collected data from 104 PD participants with FOG who underwent STN-DBS at Xuanwu Hospital between September 2017 and June 2022. The patients were divided into a training set (70%; n = 68) and a validation set (30%; n = 36). The selected characteristics in the LASSO regression were used in multivariate logistic regression to build the prediction model. The receiver operating characteristic (ROC) curves were constructed for the training and validation sets to verify the model's efficiency. Results:Independent variables in the prediction model included Unified Parkinson's Disease Rating Scale II (UPDRS II), UPDRS IV, leg rigidity, Montreal Cognitive Assessment (MoCA) score, and Mini-Mental State Examination (MMSE) score. The prediction model formula is as follows: Logit(y) = -1.0043 + 0.159 × UPDRS II + 0.030 × UPDRS IV - 1.726 × leg rigidity + 0.121 × MoCA + 0.036 × MMSE. To validate the model, we analyzed the ROC curves of the training and validation sets. The area under the ROC curve (AUC) of internal validation was 0.869 (95% confidence interval [CI]: 0.771-0.967) and the AUC of external validation was 0.845 (95% CI: 0.6526-1). The calibration plots showed good calibration. Conclusion:The model we developed can effectively assist clinicians in assessing the efficacy of deep brain stimulation of the bilateral subthalamic nucleus for freezing of gait in Parkinson's disease patients. This approach can support the formulation of personalized treatment plans and has the potential to improve patient outcomes.

Objectives: With the development of advanced neuroimaging techniques, including resting-state functional magnetic resonance imaging and diffusion tensor imaging, Parkinson’s disease (PD) has increasingly been recognized as a complex brain network disorder. In this review, we summarized research on brain networks in PD to elucidate the network abnormalities underlying its four major motor symptoms and to identify the networks modulated by deep brain stimulation (DBS). Materials and Methods: We searched PubMed and Web of Science for the most recent literature on brain network alterations in PD. Eligible studies included those investigating the general PD network (n = 10), symptom-specific networks—tremor-dominant (n = 13), postural instability and gait disorder (n = 9), freezing of gait (n = 9), akinetic-rigidity (n = 3)—as well as DBS-modulated networks (n = 14). Based on these studies, we integrated the findings and used BrainNet Viewer to generate schematic network visualizations. Results: The symptom-specific networks exhibited common abnormalities within the sensorimotor network. Evidence from DBS studies suggested that therapeutic effects were associated with modulation of the motor cortex through both functional and structural connectivity. Moreover, the four motor symptoms each demonstrated distinct network features. Specifically, the tremor network was characterized by widespread alterations in the cortico-thalamic-cerebellar circuitry; the postural instability and gait disorder network showed more severe disruptions within the striatum and visual cortex; the freezing of gait network exhibited disruptions in midbrain regions, notably the pedunculopontine nucleus; and the akinetic-rigidity network involved changes in cognition-related networks, particularly the default mode network. Conclusions: PD motor symptoms exhibit both distinct network features and shared alterations within the sensorimotor network. DBS modulates large-scale brain networks, especially motor-related networks, contributing to the alleviation of motor symptoms. Characterizing symptom-specific networks may support precision DBS target selection and parameter optimization.

Background: The pathophysiology underlying subtypes of Parkinson’s disease (PD) remain unclear. The study was to explore whether synchronized subthalamic oscillatory neurons can be a biomarker for parkinsonian subtypes. Methods: Thirty patients undergoing subthalamic nucleus (STN) deep brain stimulation were included and classified as postural instability and gait disorder (PIGD), tremor dominant (TD), or intermediate (IT) subtypes. Microelectrode recordings in STN and EMG were simultaneously recorded. Neuronal background was extracted. Spectral and coherence analysis was performed, Correlation test was used. The locations of the oscillatory neurons were noted. Results: Of 116 oscillatory neurons, 95.0% β frequency and 83.3% tremor frequency oscillatory neurons were coherent with their background activity. Of 76 synchronized β frequency oscillatory neurons, 13.2% were coherent with limb rigidity in PIGD group whereas of 30 synchronized tremor frequency oscillatory neurons, 20% were coherent with tremor in TD group. Tremor and β frequency oscillatory neurons were correlated with tremor and rigidity/bradykinesia subscores, respectively. Particularly, β frequency oscillatory neurons in subbands of 8-13 Hz, 13-20 Hz and 20-35 Hz correlated with rigidity/bradykinesia subscores; the 13-20 Hz had the strongest correlation. The majority of synchronized oscillatory neurons located in dorsal-STN. Conclusion: Different patterns of oscillatory neurons are involved in producing subtypes of TD and PIGD. Tremor and β frequency oscillatory neurons can serve as biomarkers for parkinsonian tremor and rigidity/bradykinesia. The low β frequency subband of 13 ̶ 20 Hz is more implicated for rigidity/bradykinesia. Synchronized oscillatory neurons in the dorsal-STN suggest that the neurons can be used to guide electrode placement.

Background: Excessive iron accumulation in the brain has been implicated in Parkinson's disease (PD). However, the patterns and probable sequences of iron accumulation across the PD brain remain largely unknown. This study aimed to explore the sequence of iron accumulation across the PD brain using R2* mapping and a relaxometry covariance network (RCN) approach. Methods: R2* quantification maps were obtained from PD patients (n = 34) and healthy controls (n = 25). RCN was configured on R2* maps to identify covariance differences in iron levels between the two groups. Regions with excessive iron accumulation and large covariance changes in PD patients compared to controls were defined as propagators of iron. In the PD group, causal RCN analysis was performed on the R2* maps sequenced according to disease duration to investigate the dynamics of iron accumulations from the propagators. The associations between individual connections of the RCN and clinical information were analyzed in PD patients. Results: The left substantia nigra pars reticulata (SNpr), left substantia nigra pars compacta (SNpc), and lobule VII of the vermis (VER7) were identified as primary regions for iron accumulation and propagation (propagator). As the disease duration increased, iron accumulation in these three propagators demonstrated positive causal effects on the bilateral pallidum, bilateral gyrus rectus, right middle frontal gyrus, and medial and anterior orbitofrontal cortex (OFC). Furthermore, individual connections of VER7 with the left gyrus rectus and anterior OFC were positively associated with disease duration. Conclusions: Our results indicate that the aberrant iron accumulation in PD involves several regions, mainly starts from the SN and cerebellum and extends to the pallidum and cortices. These findings provide preliminary information on sequences of iron accumulation in PD, which may advance our understanding of the disease.

We thank Laura CIF and her colleagues very much for their comments on our published paper [[1]Wang K.-L. Li J.-P. Shan Y.-Z. Zhao G.-G. Ma J.-H. Ramirez-Zamora A. et al.Centromedian-parafascicular complex deep brain stimulation improves motor symptoms in rapid onset Dystonia-Parkinsonism (DYT12-ATP1A3).Brain Stimul. 2023; 16: 1310-1312https://doi.org/10.1016/j.brs.2023.08.021Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar], and they comment on three key aspects of our report: i) the history and phenomenology of the movement disorder/clinical presentation; ii) the choice of the DBS target; iii) DBS settings programming. Firstly, as to the history and phenomenology of the movement disorder/clinical presentation, I'd like to add more details of this case. In fact, the patient suddenly developed difficult walking on 4th June 2022. Only five days later, he also had difficult in speech and barely talking with others. Twelve days after disease onset, he couldn't walk independently and couldn't say any words. He also developed severe dysphagia and could only swallow liquid food when he was lying down. Within twelve days, his symptoms had reached the peak, so he has the typical abrupt onset commonly seen in DYT-PARK-ATP1A3. The speech and swallowing problems occurred only several days after disease onset, not three months later (About the mentioned three-month mark, it mainly refers to the overall duration from the onset of the disease to when the patient seeks medical care at our hospital.). At the same time, the patient developed paroxysmal dystonia episodes presenting with blepharospasm or opening the mouth or rigidity in limbs especially the left side with abnormal posture, sometimes all these symptoms occurred simultaneously. The episodes could be triggered by stress, actions, or occurred spontaneously, lasting for a few minutes with dozens of episodes every day (as shown in the attached Supplementary Video 1 of our paper [[1]Wang K.-L. Li J.-P. Shan Y.-Z. Zhao G.-G. Ma J.-H. Ramirez-Zamora A. et al.Centromedian-parafascicular complex deep brain stimulation improves motor symptoms in rapid onset Dystonia-Parkinsonism (DYT12-ATP1A3).Brain Stimul. 2023; 16: 1310-1312https://doi.org/10.1016/j.brs.2023.08.021Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar]: When the patient move his limbs or raises a cup, the patient's left upper limb and bilateral lower limbs will induce dystonia episodes, especially more pronounced on the left side.). Occasionally, neuroleptics are needed to stop the episode. All of these symptoms could disappear during sleep. The following is/are the supplementary data related to this article.eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJkMWFlOTYyZjEwMGJlMTZjMDhkMjRkYWNmYmNhMDZkYiIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNzE0MjkyMzY5fQ.H_34ajCF9BoGS0AuGQEjAC4HNlb1fgc57l2VhgYqDQbT8-pW0M4y-G_urv24hE62LNuhOXirpzk6LMWWqa2A2V8XmhQGTMaiDt83pTPIqvewP5M9A59qip25ZgM24fcEFXXLmEbtjC-4t12VBIksG0TV9RfAKWVHoyLbbbDf17aE-ysIGPQANU8ohIt4hsU0oz13c_qdZWmI9nGfc2fCvSbHeX-BJBgDO4Mh6Rp_FQI4qX6gvokaXYJvXi9ylI3jFjr0REZi6v_YYX90fC2zwBtZ9tASFVPGiaFn6UPDH1YKWisQyMgRSrydxUUQcHUhBva2g9L-yyEgJOMFTXbNMw(mp4, (1.27 MB) Download video eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJkMWFlOTYyZjEwMGJlMTZjMDhkMjRkYWNmYmNhMDZkYiIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNzE0MjkyMzY5fQ.H_34ajCF9BoGS0AuGQEjAC4HNlb1fgc57l2VhgYqDQbT8-pW0M4y-G_urv24hE62LNuhOXirpzk6LMWWqa2A2V8XmhQGTMaiDt83pTPIqvewP5M9A59qip25ZgM24fcEFXXLmEbtjC-4t12VBIksG0TV9RfAKWVHoyLbbbDf17aE-ysIGPQANU8ohIt4hsU0oz13c_qdZWmI9nGfc2fCvSbHeX-BJBgDO4Mh6Rp_FQI4qX6gvokaXYJvXi9ylI3jFjr0REZi6v_YYX90fC2zwBtZ9tASFVPGiaFn6UPDH1YKWisQyMgRSrydxUUQcHUhBva2g9L-yyEgJOMFTXbNMw(mp4, (1.27 MB) Download video In this case, the pregnancy was full term and delivered by caesarean section. Compared to his peers, the patient only showed mental retardation and performed poor academic scores since childhood without walking problems. Cognitive testing was not available due to severe speech problems during the hospital stay. Because of short stature, he received growth hormone injection since the age of thirteen-years-old, until one month before the onset of the disease. His family members didn't complain his psychiatric symptoms in childhood but really not excluding any sign of attention deficit and hyperactivity disorder and other psychiatric symptoms due to without particular concerns. Overall, this patient appears to be normal, except for height and intellectual development (as shown in the Supplementary Video-the patient's condition before the onset of the disease). Family history was unremarkable with healthy parents and an older brother. Molecular testing indicated a de novo mutation c.2401G > T (p.Asp801Tyr), as attached in our published paper. This variant commonly presents with alternating hemiplegia of childhood (AHC) phenotype [[2]Vezyroglou A. Akilapa R. Barwick K. Koene S. Brownstein C.A. Holder-Espinasse M. et al.The phenotypic continuum of ATP1A3-related disorders.Neurology. 2022; 99: e1511-e1526https://doi.org/10.1212/wnl.0000000000200927Crossref PubMed Scopus (0) Google Scholar]. While in our case the patient showed abrupt onset of the disease at fourteen years old, asymmetric symptoms and prominent dystonia more consistent with the diagnostic criteria of rapid-onset dystonia-parkinsonism (RDP) except the paroxysmal episodes which is more common in AHC [[3]Rosewich H. Sweney M.T. DeBrosse S. Ess K. Ozelius L. Andermann E. et al.Research conference summary from the 2014 international task force on ATP1A3 -related disorders.Neurol Genet. 2017; 3 (NA)https://doi.org/10.1212/nxg.0000000000000139Crossref PubMed Google Scholar]. While the clinical symptom overlaps between the distinct syndromes is common in ATP1A3-related disorders [[4]Salles P. Fernandez H.H. Untangling the complicated web of ATP1A3 mutations.Park Relat Disord. 2020; 78: 186-188https://doi.org/10.1016/j.parkreldis.2020.09.010Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar]. We really agree that ATP1A3-related disorders with paroxysmal dystonia maybe responsive to DBS, because in our case the paroxysmal episodes greatly improved immediately after the surgery. The early intervention with DBS maybe a key point for positive result, but the optimal timing of DBS treatment remains underexplored, and all these need to be retested in more similar cases. We are also planning to implement the DBS in patients with ATP1A3-related disorders and paroxysmal episodes in the future. Secondly, about the choice of the DBS target, As reviewed in Supplementary Table 1 with our paper [[1]Wang K.-L. Li J.-P. Shan Y.-Z. Zhao G.-G. Ma J.-H. Ramirez-Zamora A. et al.Centromedian-parafascicular complex deep brain stimulation improves motor symptoms in rapid onset Dystonia-Parkinsonism (DYT12-ATP1A3).Brain Stimul. 2023; 16: 1310-1312https://doi.org/10.1016/j.brs.2023.08.021Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar], more GPi target previously was tried for the DYT12 patients with frustrating results, compared to the STN target (only 1 report). So, we tried the STN target firstly and STN is also the most common used target in our center. Unfortunately, the DBS treatment effect of STN is unsatisfactory. Since the CM-Pf receives strong projections from the GPi and sends a strong (glutamatergic) output to the STN, and also within the striatum, CM preferentially targets the dorsolateral caudate and putamen, while the Pf mainly projects to cognitive and limbic areas [[5]Sherman S.M. Thalamus plays a central role in ongoing cortical functioning.Nat Neurosci. 2016; 19: 533-541https://doi.org/10.1038/nn.4269Crossref PubMed Scopus (469) Google Scholar]. The CM-Pf has been suggested as an alternative target to study in patients with PD [[6]Smith Y. Galvan A. Ellender T.J. Doig N. Villalba R.M. Huerta-Ocampo I. et al.The thalamostriatal system in normal and diseased states.Front Syst Neurosci. 2014; 8: 5https://doi.org/10.3389/fnsys.2014.00005Crossref PubMed Scopus (179) Google Scholar]. In clinical practice, DBS of the CM-Pf might be a possible 'add-on' in the treatment of specific symptoms that are resistant to DBS of more established targets, including the STN and GPi [[7]Arnts H. Coolen S.E. Fernandes F.W. Schuurman R. Krauss J.K. Groenewegen H.J. et al.The intralaminar thalamus: a review of its role as a target in functional neurosurgery.Brain Commun. 2023; 5fcad003https://doi.org/10.1093/braincomms/fcad003Crossref PubMed Scopus (4) Google Scholar]. What's more, CM-Pf DBS showed a promising effect in the treatment for other hyperkinetic movement disorders (not PD) like Tourette syndrome, cervical dystonia [[8]Semenova U. Raeva S. Sedov A. Participation of the thalamic CM‐Pf complex in movement performance in patients with dystonia.Movement Disord. 2016; 31: 1398-1404https://doi.org/10.1002/mds.26653Crossref PubMed Scopus (4) Google Scholar] and pain with movement disorders [[7]Arnts H. Coolen S.E. Fernandes F.W. Schuurman R. Krauss J.K. Groenewegen H.J. et al.The intralaminar thalamus: a review of its role as a target in functional neurosurgery.Brain Commun. 2023; 5fcad003https://doi.org/10.1093/braincomms/fcad003Crossref PubMed Scopus (4) Google Scholar].Many electrostimulation studies suggested that stimulation of the CM-Pf is associated with relief in muscle stiffness [[7]Arnts H. Coolen S.E. Fernandes F.W. Schuurman R. Krauss J.K. Groenewegen H.J. et al.The intralaminar thalamus: a review of its role as a target in functional neurosurgery.Brain Commun. 2023; 5fcad003https://doi.org/10.1093/braincomms/fcad003Crossref PubMed Scopus (4) Google Scholar]. Therefore, in the current case, we chose the CM-Pf target. In addition, when we adjusted the stimulation targets from STN to CM-Pf, the two STN leads were removed simultaneously and only the two CM-Pf electrodes were kept. As the author suggested, as attached, we provided the postoperative CT images (Fig. 1) to show the leads localization. Thirdly, we should clarify that during the testing period why we adopted the bipolar programing strategy for both STN and CM-Pf is because we cannot apply the cathodal monopolar or the double-monopolar stimulation programming settings which can only be available after the implantation of IPG. And the temporary Medtronic testing stimulator in our country can only support the bipolar programing setting. In conclusion, according to the theory of brain networks, various movement disorders that share some common clinical manifestations might have their-specific circuit fingerprints [[9]Hollunder B. Rajamani N. Siddiqi S.H. Finke C. Kühn A.A. Mayberg H.S. et al.Toward personalized medicine in connectomic deep brain stimulation.Prog Neurobiol. 2022; 210102211https://doi.org/10.1016/j.pneurobio.2021.102211Crossref PubMed Scopus (24) Google Scholar]. Our future work will focus on the personalized stimulation strategy through identifying the aberrant individualized brain networks. The current report showed that the CM-PF may be a more promising target for DYT12 cases, but more sample studies are needed. None.

BACKGROUND:Deep brain stimulation (DBS) is a well-established treatment for Parkinson's disease (PD). However, infection following DBS surgery is a serious complication that can lead to the recurrence and worsening of Parkinson's symptoms or related hardware reimplantation, causing considerable patient suffering and financial burden. OBJECTIVE:This study aims to compare the therapeutic efficiency of different treatment approaches for scalp incision infections after DBS surgery in PD patients. METHODS:We conducted a retrospective review of patients with PD who experienced scalp infections following DBS at our hospital between January 2017 and December 2021. The patients were divided into 2 groups based on whether affected implants were removed or not. Fisher's exact test was applied to compare the reinfection rates between groups A and B. RESULTS:In group A, 4 patients underwent debridement only, and all of them experienced reinfection between 2 and 25 months after the initial treatment. In group B, 9 patients underwent debridement and removal of potentially affected implants. Among them, 8 patients underwent reimplantation of the DBS device within 3-6 months after the initial treatment, and no cases of reinfection occurred. However, 1 patient experienced reinfection in the postauricular incision and percutaneous tunnel 5 months after the initial treatment, resulting in the complete removal of the entire DBS system. The reinfection rate in group B (11.11%) was significantly lower than that in group A (100%, P = 0.007). CONCLUSIONS:Scalp incision infections following DBS surgery can affect deep tissues, and the implementation of a comprehensive treatment strategy involving local debridement and removal of potentially affected implants can significantly reduce the risk of infection recurrence and its spread.

Metabolic network analysis in Parkinson's disease (PD) based on 18F-FDG PET has revealed PD-related metabolic patterns. However, alterations at the systemic metabolic network level and at the connection level between different brain regions still remain unknown. This study aimed to explore metabolic network alterations at multiple network levels among PD patients using an individual-specific metabolic network (ISMN) approach. 18F-FDG-PET images of patients with PD (n = 34) and healthy subjects (n = 47) were collected. Healthy subjects were further separated into reference group (n = 28) and control group (n = 19) randomly. Standardized uptake value normalized by lean body mass ratio (SULr) maps was calculated from the PET images. ISMNs were constructed based on SULr maps for PD patients and controls with reference to the reference group. Comparisons of nodal and edge features were performed between PD and control groups. Correlation analysis was conducted between multilevel network properties and clinical scales in PD group. A linear classifier was trained based on nodal or edge features to distinguish PD from controls. The distance from each patient's ISMN to the group-level difference network showed a negative correlation with Hoehn and Yahr stage (r = -0.390, p = .023). Eight nodes from ISMN were identified which exhibited significantly increased nodal degree in PD patients compared to controls (p < .05). Eleven edges were observed which demonstrated significant distinctions in Z-score values in comparisons to the control group (p < .05). Furthermore, the nodal and edge features showed comparable performances in PD diagnosis compared to the traditional SULr values, with area under the receiver operating characteristic curve larger than 0.91. The proposed ISMN approach revealed systemic metabolic deviations, as well as nodal and edge distinctions in PD, which might be supplementary to the existing findings on PD-related metabolic patterns.

EDITORIAL article Front. Aging Neurosci., 10 April 2024Sec. Parkinson's Disease and Aging-related Movement Disorders Volume 16 - 2024 | https://doi.org/10.3389/fnagi.2024.1407216

左旋多巴反应试验是一项临床常用的简便有效的评价帕金森病患者多巴反应性的方法,对于帕金森病的诊断和指导药物治疗具有重要意义,也是外科脑深部电刺激手术(DBS)的患者筛选指标及术后疗效的预测因素之一.目前普遍认为左旋多巴反应试验的改善率大于30％适合DBS手术,然而关于改善率临界值尚存在争议.左旋多巴反应试验与手术患者筛选及术后疗效预测之间的关系也没有定论.了解左旋多巴反应试验的发展历史可以更科学地指导外科手术患者的筛选及个体化治疗.

Functional MRI studies have achieved promising outcomes in revealing abnormal functional connectivity in Parkinson's disease (PD). The primary sensorimotor area (PSMA) received a large amount of attention because it closely correlates with motor deficits. While functional connectivity represents signaling between PSMA and other brain regions, the metabolic mechanism behind PSMA connectivity has rarely been well established. By introducing hybrid PET/MRI scanning, the current study enrolled 33 advanced PD patients during medication-off condition and 25 age-and-sex-matched healthy controls (HCs), aiming to not only identify the abnormal functional connectome pattern of the PSMA, but also to simultaneously investigate how PSMA functional connectome correlates with glucose metabolism. We calculated degree centrality (DC) and the ratio of standard uptake value (SUVr) using resting state fMRI and 18F-FDG-PET data. A two-sample t-test revealed significantly decreased PSMA DC (PFWE < 0.014) in PD patients. The PSMA DC also correlated negatively with H-Y stage (P = 0.031). We found a widespread reduction of H-Y stage associated (P-values < 0.041) functional connectivity between PSMA and the visual network, attention network, somatomotor network, limbic network, frontoparietal network as well as the default mode network. The PSMA DC correlated positively with FDG-uptake in the HCs (P = 0.039) but not in the PD patients (P > 0.44). In summary, we identified disease severity-dependent PSMA functional connectome which in addition uncoupled with glucose metabolism in PD patients. The current study highlighted the critical role of simultaneous PET/fMRI in revealing the functional-metabolic mechanism in the PSMA of PD patients.