Cardiac sensing at a spinal cord stimulation lead: a promising on-device potential biomarker for pain and wellbeing.

Introduction: In the search for objective measures of therapeutic outcomes for patients with spinal cord stimulation (SCS) devices, various metrics of cardiac performance have been linked to pain as well as overall health. To track such measures at home, recent studies have incorporated wearables to monitor cardiac activity over months or years. The drawbacks to wearables, such as patient compliance, would be obviated by on-device sensing that incorporates the SCS lead. This study sought to evaluate the feasibility of using SCS leads to record cardiac electrograms. Methods: The quality of signals sensed by externalized, percutaneous leads in the thoracic spine of 10 subjects at the end of their SCS trial were characterized across various electrode configurations and postures by detecting R-peaks and calculating signal-to-noise ratio (SNR). In a subset of 5 subjects, cardiac metrics were then compared to those measured simultaneously with a wearable. Results: The average signal quality was acceptable for R-peak detection (i.e., SNR > 5) for all configurations and positions across all 10 subjects, with higher signal quality achieved when recording in resting positions. Notably, the spinal lead recordings enabled more reliable beat detection compared to the wearable (n = 29 recording pairs; p < 0.001). When excluding wearable recordings with over 35% missed beats, the inter-beat intervals across devices were highly correlated (n = 22 recording pairs; Pearson correlation: R = 0.99, p < 0.001). Further comparisons in these aligned wearable and corresponding spinal-lead recordings revealed significant differences in the frequency domain metrics (i.e., absolute and normalized high and low frequency HRV power, p < 0.05), but not in time domain HRV parameters. Discussion: The ability of an implanted SCS system to record electrocardiograms, as demonstrated here, could provide the basis of automated SCS therapy by tracking potential biomarkers of the patient's overall health state without the need for additional external devices.

Active contact proximity to the cerebellothalamic tract predicts initial therapeutic current requirement with DBS for ET: an application of 7T MRI.

Objective: To characterize how the proximity of deep brain stimulation (DBS) active contact locations relative to the cerebellothalamic tract (CTT) affect clinical outcomes in patients with essential tremor (ET). Background: DBS is an effective treatment for refractory ET. However, the role of the CTT in mediating the effect of DBS for ET is not well characterized. 7-Tesla (T) MRI-derived tractography provides a means to measure the distance between the active contact and the CTT more precisely. Methods: A retrospective review was conducted of 12 brain hemispheres in 7 patients at a single center who underwent 7T MRI prior to ventral intermediate nucleus (VIM) DBS lead placement for ET following failed medical management. 7T-derived diffusion tractography imaging was used to identify the CTT and was merged with the post-operative CT to calculate the Euclidean distance from the active contact to the CTT. We collected optimized stimulation parameters at initial programing, 1- and 2-year follow up, as well as a baseline and postoperative Fahn-Tolosa-Marin (FTM) scores. Results: The therapeutic DBS current mean (SD) across implants was 1.8 mA (1.8) at initial programming, 2.5 mA (0.6) at 1 year, and 2.9 mA (1.1) at 2-year follow up. Proximity of the clinically-optimized active contact to the CTT was 3.1 mm (1.2), which correlated with lower current requirements at the time of initial programming (R2 = 0.458, p = 0.009), but not at the 1- and 2-year follow up visits. Subjects achieved mean (SD) improvement in tremor control of 77.9% (14.5) at mean follow-up time of 22.2 (18.9) months. Active contact distance to the CTT did not predict post-operative tremor control at the time of the longer term clinical follow up (R2 = -0.073, p = 0.58). Conclusion: Active DBS contact proximity to the CTT was associated with lower therapeutic current requirement following DBS surgery for ET, but therapeutic current was increased over time. Distance to CTT did not predict the need for increased current over time, or longer term post-operative tremor control in this cohort. Further study is needed to characterize the role of the CTT in long-term DBS outcomes.

Longitudinal analysis of local field potentials recorded from directional deep brain stimulation lead implants in the subthalamic nucleus.

Objective.The electrode-tissue interface surrounding a deep brain stimulation (DBS) lead is known to be highly dynamic following implantation, which may have implications on the interpretation of intraoperatively recorded local field potentials (LFPs). We characterized beta-band LFP dynamics following implantation of a directional DBS lead in the sensorimotor subthalamic nucleus (STN), which is a primary target for treating Parkinson's disease.Approach.Directional STN-DBS leads were implanted in four healthy, non-human primates. LFPs were recorded over two weeks and again 1-4 months after implantation. Impedance was measured for two weeks post-implant without stimulation to compare the reactive tissue response to changes in LFP oscillations. Beta-band (12-30 Hz) peak power was calculated from the LFP power spectra using both common average referencing (CAR) and intra-row bipolar referencing (IRBR).Results.Resting-state LFPs in two of four subjects revealed a steady increase of beta power over the initial two weeks post-implant whereas the other two subjects showed variable changes over time. Beta power variance across days was significantly larger in the first two weeks compared to 1-4 months post-implant in all three long-term subjects. Further, spatial maps of beta power several hours after implantation did not correlate with those measured two weeks or 1-4 months post-implant. CAR and IRBR beta power correlated across short- and long-term time points. However, depending on the time period, subjects showed a significant bias towards larger beta power using one referencing scheme over the other. Lastly, electrode-tissue impedance increased over the two weeks post-implant but showed no significant correlation to beta power.Significance.These results suggest that beta power in the STN may undergo significant changes following DBS lead implantation. DBS lead diameter and electrode recording configurations can affect the post-implant interpretation of oscillatory features. Such insights will be important for extrapolating results from intraoperative and externalized LFP recordings.

Microstructure and nanomechanical properties of the exoskeleton of an ironclad beetle (Zopherus haldemani).

This study examined natural composite structures within the remarkably strong exoskeleton of the southwestern ironclad beetle (Z. haldemani). Structural and nanomechanical analyses revealed that the exoskeleton's extraordinary resistance to external forces is provided by its exceptional thickness and multi-layered structure, in which each layer performed a distinct function. In detail, the epicuticle, the outmost layer, comprised 3%-5% of the overall thickness with reduced Young's moduli of 2.2-3.2 GPa, in which polygonal-shaped walls (2-3µm in diameter) were observed on the surface. The next layer, the exocuticle, consisted of 17%-20% of the total thickness and exhibited the greatest Young's moduli (∼15 GPa) and hardness (∼800 MPa) values. As such, this layer provided the bulk of the mechanical strength for the exoskeleton. While the endocuticle spanned 70%-75% of the total thickness, it contained lower moduli (∼8-10 GPa) and hardness (∼400 MPa) values than the exocuticle. Instead, this layer may provide flexibility through its specifically organized chitin fiber layers, known as Bouligand structures. Nanoindentation testing further reiterated that the various fibrous layer orientations resulted in different elastic moduli throughout the endocuticle's cross-section. Additionally, this exoskeleton prevented delamination within the composite materials by overlapping approximately 5%-19% of each fibrous stack with neighboring layers. Finally, the innermost layer, the epidermis contributing 5%-7 % of the total thickness, contains attachment sites for muscle and soft tissue that connect the exoskeleton to the beetle. As such, it is the softest region with reduced Young's modulus of ∼2-3 GPa and hardness values of ∼290 MPa. These findings can be applied to the development of innovative, fiber-reinforced composite materials.