Characteristics of globus pallidus internus local field potentials in generalized dystonia patients with TWNK mutation

ObjectiveWe focused on a rare gene mutation causing dystonia in two siblings who received globus pallidus internus deep brain stimulation (GPi-DBS). The aim was to characterize the relationship between neuronal activity patterns and clinical syndromes.MethodsWhole exome sequencing was applied to identify the TWNK (previous symbol C10orf2) mutation; Two siblings with TWNK mutation presented as generalized dystonia with rigidity and bradykinesia; four other sporadic generalized dystonia patients underwent GPi-DBS and local field potentials (LFPs) were recorded. Oscillatory activities were illustrated with power spectra and temporal dynamics measured by the Lempel-Ziv complexity (LZC).ResultsNormalized power spectra of GPi LFPs differed between patients with TWNK mutation and dystonia over the low beta bands. Patients with TWNK mutation had higher low beta power (15–27 Hz, unpaired t-test, corrected P < 0.0022) and lower LZC (15–27 Hz, unpaired t-test, P < 0.01) than other patients with generalized dystonia. On the other hand, the TWNK mutation patients showed decreased low frequency and beta oscillation in the GPi after DBS, as well as improved movement performance.ConclusionThe LFPs were different in TWNK mutation dystonia siblings than other patients with generalized dystonia, which indicate the abnormal LFPs were related to symptoms rather than specific disease. In addition, the inhibited effect on oscillations also provided a potential evidence for DBS treatment on rare movement disorders.SignificanceThis study could potentially aid in the future development of adaptive DBS via rare disease LFPs comparison.     

Neurophysiology of motor skill learning in chronic stroke

ObjectiveMotor learning is relevant in chronic stroke for acquiring compensatory strategies to motor control deficits. However, the neurophysiological mechanisms underlying motor skill acquisition with the paretic upper limb have received little systematic investigation. The aim of this study was to assess the modulation of corticomotor excitability and intracortical inhibition within ipsilesional primary motor cortex (M1) during motor skill learning.MethodsTen people at the chronic stage after stroke and twelve healthy controls trained on a sequential visuomotor isometric wrist extension task. Skill was quantified before, immediately after, 24 hours and 7 days post-training. Transcranial magnetic stimulation was used to examine corticomotor excitability and short- and long-interval intracortical inhibition (SICI and LICI) pre- and post-training.ResultsThe patient group exhibited successful skill acquisition and retention, although absolute skill level was lower compared with controls. In contrast to controls, patients’ ipsilesional corticomotor excitability was not modulated during skill acquisition, which may be attributed to excessive ipsilesional LICI relative to controls. SICI decreased after training for both patient and control groups.ConclusionsOur findings indicate distinct inhibitory networks within M1 that may be relevant for motor learning after stroke.SignificanceThese findings have potential clinical relevance for neurorehabilitation adjuvants aimed at augmenting the recovery of motor function.     

Developmental trajectory of the late positive potential: Using temporal-spatial PCA to characterize within-subject developmental changes in emotional processing

The late positive potential (LPP) is characterized by temporal and spatial changes across development—though existing work has primarily relied on visual or statistical comparisons of relatively few electrodes and averaged activity over time. The current study used an empirically based approach to characterize temporal and spatial changes in ERPs over time. Data were utilized from a large longitudinal study (N = 380) in which the LPP was recorded to pleasant, neutral, and unpleasant pictures around age 9 and again around age 12. Age 9 ERPs were subtracted from age 12 ERPs for all three image types; the resulting ERPs for each subject at each electrode site were then submitted to a temporospatial principal component analysis (PCA). A PCA factor was greater in amplitude for emotional pictures compared to neutral pictures between ages 9 and 12, evident as an occipital negativity and frontocentral positivity that peaked approximately 850 ms following picture presentation. Furthermore, the factor scores to emotional pictures for this component increased as a function of age 12 pubertal development, consistent with the notion that the LPP shifts from occipital to more frontocentral sites in relation to developmental changes from childhood to adolescence. A similar factor was observed when PCA was applied to all ERPs from both ages 9 and 12. Using temporospatial PCA on ERPs collected from the same subjects over time—especially within-subject subtraction-based ERPs—provides a concise way of characterizing and quantifying within-subject developmental changes in both the timing and scalp distribution of ERPs.     

Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

A potent antiarrhythmic drug N-methyl berbamine extends the action potential through inhibiting both calcium and potassium currents

N-methyl berbamine (N-MB) is a berberine derivative. Its analogue berbamine has been reported to have remarkable antiarrhythmic and ischemic protective effects. However, the pharmacological effects of N-MB are ill-defined. In this study, molecular docking was used to evaluate the binding of N-MB to Ca_V1.2 Ca²⁺ and K_V11.1 K⁺ channels, and the effects of N-MB on action potential and ionic currents were observed in the ventricular myocytes of rabbits, HEK293 cells stably transfected with the hCa_V1.2 gene and CHO cells stably transfected with hERG (human ether-a-go-go related gene). The results showed that N-MB was able to bind to both Ca_V1.2 and K_V11.1 channels. Following a perfusion with N-MB, the durations of action potentials (APD₂₀, APD₅₀ and APD₉₀) were extended, and the outward tail current, I_tail, as well as the hERG current, I_hERG, were inhibited, while the amplitude of action potential (APA) was only slightly reduced. N-MB also decreased the peak amplitude of the L-type Ca²⁺ channel current, I_CaL, as well as the Ca_V1.2 current, I_CaV1.2; this may limit the prolongation of APD. In conclusion, N-MB is a potent and natural antiarrhythmic multitarget drug that may elicit its antiarrhythmic effect through blocking both Ca²⁺ and K⁺ channel currents.     

生物反馈电刺激联合补中益气汤对产妇产后盆底康复效果的影响

目的探讨生物反馈电刺激联合补中益气汤对产妇产后盆底康复效果的影响。方法将56例初产妇按随机数字表法分成对照组与研究组各28例。对照组给予补中益气汤治疗;研究组在对照组基础上联合生物反馈电刺激治疗,两组均治疗6周。观测盆底肌相关电压、盆底肌力、尿失禁率、性生活质量。结果治疗后,两组盆底电位均值均显著升高,研究组高于对照组(P<0.05);治疗后,研究组尿失禁发生率显著降低,且显著低于对照组(P<0.05);研究组Ⅱ、Ⅲ、IV级肌力显著低于对照组(P<0.05);研究组性生活质量高水平显著高于对照组(P<0.05)。结论生物反馈电刺激联合补中益气汤可有效促进产妇产后盆底康复,效果显著优于单独补中益气汤。