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无监督聚类揭示帕金森病患者丘脑底核中空间变化的单个神经元放电模式。

Unsupervised clustering reveals spatially varying single neuronal firing patterns in the subthalamic nucleus of patients with Parkinson's disease.

作者信息

Kaku Heet, Ozturk Musa, Viswanathan Ashwin, Shahed Joohi, Sheth Sameer A, Kumar Suneel, Ince Nuri F

机构信息

Department of Biomedical Engineering, University of Houston, 3517 Cullen Blvd, Room 2027, Houston, TX 77204-5060, United States of America.

Department of Neurosurgery, Baylor College of Medicine Medical Center - McNair Campus, 7200 Cambridge, Suite 9A, Houston, TX 77030, United States of America.

出版信息

Clin Park Relat Disord. 2019 Dec 27;3:100032. doi: 10.1016/j.prdoa.2019.100032. eCollection 2020.

DOI:10.1016/j.prdoa.2019.100032
PMID:34316618
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8298773/
Abstract

INTRODUCTION

Subthalamic nucleus (STN) is an effective target for deep brain stimulation (DBS) to reduce the motor symptoms of Parkinson's disease (PD). It is important to identify firing patterns within the structure for a better understanding of the electro-pathophysiology of the disease. Using recently established metrics, our study aims to autonomously identify the discharge patterns of individual cells and examine their spatial distribution within the STN.

METHODS

We recorded single unit activity (SUA) from 12 awake PD patients undergoing a standard clinical DBS surgery. Three extracted features from raw SUA (local variation, bursting index and prominence of peak) were used with k-means clustering to achieve the aforementioned unsupervised grouping of firing patterns.

RESULTS

279 neurons were isolated and four distinct firing patterns were identified across patients: tonic (11%), irregular (55%), periodic (9%) and non-periodic bursts (25%). The mean firing rates for irregular discharges were significantly lower ( < 0.05) than the rest. Tonic firings were significantly ventral (p < 0.05) while periodic (p < 0.05) and non-periodic ( < 0.01) bursts were dorsal. The percentage of periodically bursting neurons in dorsal region and entire STN were significantly correlated with off state UPDRS tremor scores ( = 0.51,  = 0.04) and improvement in bradykinesia and rigidity ( = 0.57,  = 0.02) respectively.

CONCLUSION

Strengthening the application of unsupervised clustering for firing patterns of individual cells, this study shows a unique spatial affinity of tonic activity towards the ventral and bursting activity towards the dorsal region of STN in PD patients. This spatial preference, together with the correlation of clinical scores, can provide a clue towards understanding Parkinsonian symptom generation.

摘要

引言

丘脑底核(STN)是深部脑刺激(DBS)治疗帕金森病(PD)运动症状的有效靶点。识别该结构内的放电模式对于更好地理解该疾病的电病理生理学很重要。本研究旨在使用最近建立的指标自主识别单个细胞的放电模式,并检查它们在STN内的空间分布。

方法

我们记录了12名接受标准临床DBS手术的清醒PD患者的单单位活动(SUA)。从原始SUA中提取的三个特征(局部变化、爆发指数和峰值突出度)与k均值聚类一起用于实现上述放电模式的无监督分组。

结果

分离出279个神经元,在患者中识别出四种不同的放电模式:紧张性(11%)、不规则性(55%)、周期性(9%)和非周期性爆发(25%)。不规则放电的平均放电率显著低于其他放电率(<0.05)。紧张性放电显著位于腹侧(p<0.05),而周期性(p<0.05)和非周期性(<0.01)爆发位于背侧。背侧区域和整个STN中周期性爆发神经元的百分比分别与关期统一帕金森病评定量表(UPDRS)震颤评分(=0.51,=0.04)以及运动迟缓与强直的改善(=0.57,=0.02)显著相关。

结论

本研究加强了对单个细胞放电模式的无监督聚类应用,显示了PD患者中紧张性活动对STN腹侧以及爆发活动对STN背侧区域具有独特的空间亲和力。这种空间偏好以及与临床评分的相关性可为理解帕金森症状的产生提供线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2884/8298773/60abfdfb6eee/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2884/8298773/60abfdfb6eee/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2884/8298773/60abfdfb6eee/gr1.jpg

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