Skin Sympathetic Nerve Activity and the Short-Term QT Interval Variability in Patients With Electrical Storm

Background: Skin sympathetic nerve activity (SKNA) and QT interval variability are known to be associated with ventricular arrhythmias. However, the relationship between the two remains unclear.Objective: The aim was to test the hypothesis that SKNA bursts are associated with greater short-term variability of the QT interval (STVQT) in patients with electrical storm (ES) or coronary heart disease without arrhythmias (CHD) than in healthy volunteers (HV).Methods: We simultaneously recorded the ECG and SKNA during sinus rhythm in patients with ES (N = 10) and CHD (N = 8) and during cold-water pressor test in HV (N = 12). The QT and QTc intervals were manually marked and calculated within the ECG. The STVQT was calculated and compared to episodes of SKNA burst and non-bursting activity.Results: The SKNA burst threshold for ES and HV was 1.06 ± 1.07 and 1.88 ± 1.09 μV, respectively (p = 0.011). During SKNA baseline and burst, the QT/QTc intervals and STVQT for ES and CHD were significantly higher than those of the HV. In all subjects, SKNA bursts were associated with an increased STVQT (from 6.43 ± 2.99 to 9.40 ± 5.12 ms, p = 0.002 for ES; from 9.48 ± 4.40 to 12.8 ± 5.26 ms, p = 0.016 for CHD; and from 3.81 ± 0.73 to 4.49 ± 1.24 ms, p = 0.016 for HV). The magnitude of increased STVQT in ES (3.33 ± 3.06 ms) and CHD (3.34 ± 2.34 ms) was both higher than that of the HV (0.68 ± 0.84 ms, p = 0.047 and p = 0.020).Conclusion: Compared to non-bursting activity, SKNA bursts were associated with a larger increase in the QTc interval and STVQT in patients with heart disease than in HV.

Impaired reach-to-grasp kinematics in parkinsonian patients relates to dopamine-dependent, subthalamic beta bursts

Excessive beta-band oscillations in the subthalamic nucleus are key neural features of Parkinson’s disease. Yet the distinctive contributions of beta low and high bands, their dependency on striatal dopamine, and their correlates with movement kinematics are unclear. Here, we show that the movement phases of the reach-to-grasp motor task are coded by the subthalamic bursting activity in a maximally-informative beta high range. A strong, three-fold correlation linked beta high range bursts, imbalanced inter-hemispheric striatal dopaminergic tone, and impaired inter-joint movement coordination. These results provide new insight into the neural correlates of motor control in parkinsonian patients, paving the way for more informative use of beta-band features for adaptive deep brain stimulation devices.

Electroacupuncture Attenuates Anxiety-Like Behaviors in a Rat Model of Post-traumatic Stress Disorder: The Role of the Ventromedial Prefrontal Cortex

Electroacupuncture (EA) is a promising clinical approach to treating posttraumatic stress disorder (PTSD), yet the mechanisms whereby EA can alleviate anxiety and other PTSD symptoms have yet to be clarified. In the present report, rats underwent EA for 14 consecutive days following modified single prolonged stress (MSPS) exposure. These animals were then evaluated in open field and elevated plus maze tests (OFT and EPM), while Fos immunohistochemical staining was performed to assess ventromedial prefrontal cortex (vmPFC) functional activation. In addition, an extracellular recording and stimulation system was used to analyze vmPFC inputs into the ventral tegmental area (VTA) in these rats. Temporary vmPFC inactivation was further performed to assess whether this was sufficient to reverse the anxiolytic effects of EA. Overall, rats that underwent EA treatment spent more time in the central region (OFT) and the open arm (EPM) relative to MSPS model animals (P < 0.05). These MSPS model animals also exhibited significantly fewer activated Fos-positive nuclei in the vmPFC following behavioral testing, while EA was associated with a significant relative increase in c-Fos expression in this region. The transient inactivation of the vmPFC was sufficient to reverse the effects of EA treatment on anxiety-like behaviors in MSPS model rats. MSPS and SEA rats exhibiting no differences in bursting activity between baseline and vmPFC stimulation, whereas bursting activity rose relative to baseline upon ventral mPFC stimulation in EA treated and control rats. Together, these findings indicate that the vmPFC and its inputs into the VTA are functionally linked to the anxiolytic activity of EA, implicating this pathway in the EA-mediated treatment of PTSD.

Intracellular Na+ Modulates Pacemaking Activity in Murine Sinoatrial Node Myocytes: An In Silico Analysis

Background: The mechanisms underlying dysfunction in the sinoatrial node (SAN), the heart’s primary pacemaker, are incompletely understood. Electrical and Ca2+-handling remodeling have been implicated in SAN dysfunction associated with heart failure, aging, and diabetes. Cardiomyocyte [Na+]i is also elevated in these diseases, where it contributes to arrhythmogenesis. Here, we sought to investigate the largely unexplored role of Na+ homeostasis in SAN pacemaking and test whether [Na+]i dysregulation may contribute to SAN dysfunction. Methods: We developed a dataset-specific computational model of the murine SAN myocyte and simulated alterations in the major processes of Na+ entry (Na+/Ca2+ exchanger, NCX) and removal (Na+/K+ ATPase, NKA). Results: We found that changes in intracellular Na+ homeostatic processes dynamically regulate SAN electrophysiology. Mild reductions in NKA and NCX function increase myocyte firing rate, whereas a stronger reduction causes bursting activity and loss of automaticity. These pathologic phenotypes mimic those observed experimentally in NCX- and ankyrin-B-deficient mice due to altered feedback between the Ca2+ and membrane potential clocks underlying SAN firing. Conclusions: Our study generates new testable predictions and insight linking Na+ homeostasis to Ca2+ handling and membrane potential dynamics in SAN myocytes that may advance our understanding of SAN (dys)function.

Sex-Specific Cannabidiol- and Iloperidone-Induced Neuronal Activity Changes in an In Vitro MAM Model System of Schizophrenia

Cortical circuit dysfunction is thought to be an underlying mechanism of schizophrenia (SZ) pathophysiology with normalization of aberrant circuit activity proposed as a biomarker for antipsychotic efficacy. Cannabidiol (CBD) shows potential as an adjunctive antipsychotic therapy; however, potential sex effects in these drug interactions remain unknown. In the present study, we sought to elucidate sex effects of CBD coadministration with the atypical antipsychotic iloperidone (ILO) on the activity of primary cortical neuron cultures derived from the rat methylazoxymethanol acetate (MAM) model used for the study of SZ. Spontaneous network activity measurements were obtained using a multielectrode array at baseline and following administration of CBD or ILO alone, or combined. At baseline, MAM male neurons displayed increased bursting activity whereas MAM female neurons exhibited no difference in bursting activity compared to sex-matched controls. CBD administered alone showed a rapid but transient increase in neuronal activity in the MAM networks, an effect more pronounced in females. Furthermore, ILO had an additive effect on CBD-induced elevations in activity in the MAM male neurons. In the MAM female neurons, CBD or ILO administration resulted in time-dependent elevations in neuronal activity, but the short-term CBD-induced increases in activity were lost when CBD and ILO were combined. Our findings indicate that CBD induces rapid increases in cortical neuronal activity, with sex-specific drug interactions upon ILO coadministration. This suggests that sex should be a consideration when implementing adjunct therapy for treatment of SZ.

Testing models of periodically modulated FRB activity

The activity of the repeating FRB 20180916B is periodically modulated with a period of 16.3 days, and FRB 121102 may be similarly modulated with a period of about 160 days. In some models of this modulation the period derivative is insensitive to the uncertain parameters; these models can be tested by measurement of or bounds on the derivative. In other models values of the uncertain parameters can be constrained. Periodic modulation of aperiodic bursting activity may result from emission by a narrow beam wandering within a cone or funnel along the axis of a precessing disc, such as the accretion discs in X-ray binaries. The production of FRB 200428 by a neutron star that is neither accreting nor in a binary then shows universality: coherent emission occurring in a wide range of circumstances.