Spatiotemporal features of β-γ phase-amplitude coupling in Parkinson's disease derived from scalp EEG.
头皮EEG衍生的帕金森病 β-γ 相位-振幅耦合的时空特征。
- 作者列表："Gong R","Wegscheider M","Mühlberg C","Gast R","Fricke C","Rumpf JJ","Nikulin VV","Knösche TR","Classen J
:Abnormal phase-amplitude coupling between β and broadband-γ activities has been identified in recordings from the cortex or scalp of patients with Parkinson's disease. While enhanced phase-amplitude coupling has been proposed as a biomarker of Parkinson's disease, the neuronal mechanisms underlying the abnormal coupling and its relationship to motor impairments in Parkinson's disease remain unclear. To address these issues, we performed an in-depth analysis of high-density EEG recordings at rest in 19 patients with Parkinson's disease and 20 age- and sex-matched healthy control subjects. EEG signals were projected onto the individual cortical surfaces using source reconstruction techniques and separated into spatiotemporal components using independent component analysis. Compared to healthy controls, phase-amplitude coupling of Parkinson's disease patients was enhanced in dorsolateral prefrontal cortex, premotor cortex, primary motor cortex and somatosensory cortex, the difference being statistically significant in the hemisphere contralateral to the clinically more affected side. β and γ signals involved in generating abnormal phase-amplitude coupling were not strictly phase-phase coupled, ruling out that phase-amplitude coupling merely reflects the abnormal activity of a single oscillator in a recurrent network. We found important differences for couplings between the β and γ signals from identical components as opposed to those from different components (originating from distinct spatial locations). While both couplings were abnormally enhanced in patients, only the latter were correlated with clinical motor severity as indexed by part III of the Movement Disorder Society Unified Parkinson's Disease Rating Scale. Correlations with parkinsonian motor symptoms of such inter-component couplings were found in premotor, primary motor and somatosensory cortex, but not in dorsolateral prefrontal cortex, suggesting motor domain specificity. The topography of phase-amplitude coupling demonstrated profound differences in patients compared to controls. These findings suggest, first, that enhanced phase-amplitude coupling in Parkinson's disease patients originates from the coupling between distinct neural networks in several brain regions involved in motor control. Because these regions included the somatosensory cortex, abnormal phase-amplitude coupling is not exclusively tied to the hyperdirect tract connecting cortical regions monosynaptically with the subthalamic nucleus. Second, only the coupling between β and γ signals from different components appears to have pathophysiological significance, suggesting that therapeutic approaches breaking the abnormal lateral coupling between neuronal circuits may be more promising than targeting phase-amplitude coupling per se.
: 在来自帕金森病患者的皮层或头皮的记录中发现了 β 和宽带-γ 活动之间的异常相位-振幅耦合。虽然已经提出增强的相位-振幅耦合作为帕金森病的生物标志物，但是异常耦合的神经元机制及其与帕金森病中的运动损伤的关系仍然不清楚。为了解决这些问题，我们对19名帕金森病患者和20名年龄和性别匹配的健康对照受试者的静息高密度脑电图记录进行了深入分析。使用源重建技术将EEG信号投射到单个皮质表面上，并使用独立分量分析将其分离成时空分量。与健康对照相比，帕金森病患者的相位-振幅耦合在背外侧前额叶皮层、前运动皮层、初级运动皮层和躯体感觉皮层中增强，差异在临床上较受影响侧对侧的半球中具有统计学意义。参与产生异常相位-振幅耦合的 β 和 γ 信号没有严格的相位-相位耦合，排除了相位-振幅耦合仅反映了递归网络中单个振荡器的异常活动。我们发现来自相同分量的 β 和 γ 信号之间的耦合与来自不同分量的信号 (源自不同的空间位置) 的耦合有重要差异。虽然两种耦合在患者中异常增强，但只有后者与运动障碍学会统一帕金森病评定量表第三部分所索引的临床运动严重程度相关。在前运动、初级运动和躯体感觉皮层中发现了此类组分间耦合与帕金森病运动症状的相关性，但在背外侧前额叶皮层中没有发现，表明运动域特异性。相位-振幅耦合的形貌显示出患者与对照相比的深刻差异。这些发现表明，首先，帕金森病患者中增强的相位-振幅耦合源于参与运动控制的几个脑区中不同神经网络之间的耦合。因为这些区域包括躯体感觉皮层，所以异常相位-振幅耦合并不完全与单突触连接皮层区域与丘脑底核的超直接束有关。第二，只有来自不同组分的 β 和 γ 信号之间的耦合似乎具有病理生理意义，这表明打破神经元电路之间异常横向耦合的治疗方法可能比靶向相位-振幅耦合本身更有前景。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.