A Three-Dimensional Finger-Tapping Framework for Recognition of Patients With Mild Parkinson’s Disease

The finger tapping test is a widely-used and important examination in the Movement Disorder Society Clinical Diagnosis for Parkinson’s Disease. However, finger tapping motion could be affected by age, medication, and other conditions. As a result, Parkinson’s disease patients with mild sign and healthy people could be rated as similar scores on the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale, making it difficult for community doctors to perform diagnosis. We therefore propose a three-dimensional finger tapping framework to recognize mild PD patients. Specifically, we first derive the three-dimensional finger-tapping motion using a self-designed three-dimensional finger-tapping measurement system. We then propose a three-dimensional finger-tapping segmentation algorithm to segment three-dimensional finger tapping motion. We next extract three-dimensional pattern features of motor coordination, imbalance impairment, and entropy. We finally adopted the support vector machine as the classifier to recognize PD patients. We evaluated the proposed framework on 49 PD patients and 29 healthy controls and reached an accuracy of 94.9% for the right hand and 89.4% for the left hand. Moreover, the proposed framework reached an accuracy of 95.0% for the right hand and 97.8% for the left hand on 17 mild PD patients and 28 healthy controls who were both rated as 0 or 1 on the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale. The results demonstrated that the proposed framework was less sensitive to traditional features and performed well in recognizing mild PD patients by involving three-dimensional patter features

Loss of function of CMPK2 causes mitochondria deficiency and brain calcification

Abstract Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions. Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from these patients showed impaired mitochondria-associated metabolism pathways. In situ hybridization and single-cell RNA sequencing revealed robust Cmpk2 expression in neurons and vascular endothelial cells (vECs), two cell types with high energy expenditure in the brain. The neurons in Cmpk2-knockout (KO) mice have fewer mitochondrial DNA copies, down-regulated mitochondrial proteins, reduced ATP production, and elevated intracellular inorganic phosphate (Pi) level, recapitulating the mitochondrial dysfunction observed in the PBMCs isolated from the FBC patients. Morphologically, the cristae architecture of the Cmpk2-KO murine neurons was also impaired. Notably, calcification developed in a progressive manner in the homozygous Cmpk2-KO mice thalamus region as well as in the Cmpk2-knock-in mice bearing the patient mutation, thus phenocopying the calcification pathology observed in the patients. Together, our study identifies biallelic variants of CMPK2 as novel genetic factors for FBC; and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, thereby highlighting the mitochondria dysregulation as a critical pathogenic mechanism underlying brain calcification