Low-frequency STN-DBS provides acute gait improvements in Parkinson’s disease: a double-blinded randomised cross-over feasibility trial

Background Some people with Parkinson’s disease (PD) report poorer dynamic postural stability following high-frequency deep brain stimulation of the subthalamic nucleus (STN-DBS), which may contribute to an increased falls risk. However, some studies have shown low-frequency (60 Hz) STN-DBS improves clinical measures of postural stability, potentially providing support for this treatment. This double-blind randomised crossover study aimed to investigate the effects of low-frequency STN-DBS compared to high-frequency stimulation on objective measures of gait rhythmicity in people with PD. Methods During high- and low-frequency STN-DBS and while off-medication, participants completed assessments of symptom severity and walking (e.g., Timed Up-and-Go). During comfortable walking, the harmonic ratio, an objective measures of gait rhythmicity, was derived from head- and trunk-mounted accelerometers to provide insight in dynamic postural stability. Lower harmonic ratios represent less rhythmic walking and have discriminated people with PD who experience falls. Linear mixed model analyses were performed on fourteen participants. Results Low-frequency STN-DBS significantly improved medial–lateral and vertical trunk rhythmicity compared to high-frequency. Improvements were independent of electrode location and total electrical energy delivered. No differences were noted between stimulation conditions for temporal gait measures, clinical mobility measures, motor symptom severity or the presence of gait retropulsion. Conclusions This study provides evidence for the acute benefits of low-frequency stimulation for gait outcomes in STN-DBS PD patients, independent of electrode location. However, the perceived benefits of this therapy may be diminished for people who experienced significant tremor pre-operatively, as lower frequencies may cause these symptoms to re-emerge. Trial registration: This study was prospectively registered with the Australian and New Zealand Clinical Trials Registry on 5 June 2018 (ACTRN12618000944235).

Evoked Potentials During Peripheral Stimulation Confirm Electrode Location in Thalamic Subnuclei in Children With Secondary Dystonia

Deep brain stimulation is an elective surgical intervention that improves the function and quality of life in children with dystonia and other movement disorders. Both basal ganglia and thalamic nuclei have been found to be relevant targets for treatment of dystonia in children, including the ventral intermediate nucleus of the thalamus, in which stimulation can control dystonic spasms. Electrophysiological confirmation of correct electrode location within the ventralis intermediate nucleus is thus important for the success of the surgical outcome. The present work shows the evoked potentials response during contralateral median-nerve stimulation at the wrist at low frequency (9 Hz) provides physiological evidence of the electrode’s localization within the thalamus. We show the correlation between evoked potentials and magnetic resonance imaging (MRI) and computed tomography (CT) in 14 children undergoing implantation of deep brain stimulation electrodes for secondary dystonia. High fidelity and reproducibility of our results provides a new approach to ensure the electrode localization in the thalamic subnuclei.

S6. SLEEP ENDOPHENOTYPES OF SCHIZOPHRENIA: A HIGH-DENSITY EEG STUDY IN DRUG-NAïVE, FIRST EPISODE PSYCHOSIS PATIENTS

Background Slow waves, the hallmark of the deep nonrapid eye movement sleep electroencephalogram (EEG), are critical for restorative sleep and brain plasticity. They arise from the synchronous depolarization and hyperpolarization of millions of cortical neurons and their proper generation and propagation relies upon the integrity of widespread cortico-thalamic networks. Slow wave abnormalities have been reported in patient with Schizophrenia, although with partially contradictory results, probably related to antipsychotic and sedative medications. Recently, their presence and delineation, have been convincingly shown in first-episode psychosis patients (FEP). However, clear evidence of this biomarker at the onset of the disease, prior to any psychopharmacological intervention, remains limited. Moreover, no attempt has been made to elucidate the prognostic meaning of this finding. Methods We collected whole night sleep high–density electroencephalography recordings (64-channel BrainAmp, Brain Products GmbH, Gilching, Germany) in 20 drug-naive FEP patients and 20 healthy control subjects (HC). Several clinical psychometric scales as well as neurocognitive tests were administered to all subjects in order to better define psychopathological status and vulnerability. EEG slow wave activity (SWA, spectral power between 1 and 4 Hz) and several slow wave parameters were computed at each electrode location, including density and amplitude, at each electrode location. Along with a group analysis between FEP and HC, a subgroup analysis was also computed between patients who showed a progression of symptoms to full-blown Schizophrenia (SCZ, n = 10) over the next 12-month follow-up and those who did not (OTH, n = 10). Results Sleep macro-architecture was globally preserved in FEP patients. SWA (1–4 Hz) was lower in FEP compared to HC but this difference didn’t reach statistical significance. Slow wave density was decreased in FEP compared to HC, with a significance that survived multiple comparison correction over a large fronto-central cluster. Mean amplitude was preserved. At the subgroup analysis, these results were largely driven by the subgroup of patients with a confirmed diagnosis of SCZ at a 12-month follow-up. Indeed, no difference could be found between OTH and HC, while a strong significance was still evident between SCZ and HC. Discussion Our data confirm previous findings on reduced slow wave density in FEP, and expand them to acute subjects, before any treatment is prescribed. This is in line with available data on diffuse abnormalities of cortico-cortical and cortico-thalamic networks in these patients. Interestingly, our data also offer preliminary evidence that this deficit is specific for SCZ, as it appears to differentiate patients who developed SCZ from those with other diagnoses at follow-up. Given the traveling properties of slow waves, future research should establish their potential as markers of connectivity in SCZ.

Intraoperative Electrically Evoked Compound Action Potential (ECAP) Measurements in Traditional and Hearing Preservation Cochlear Implantation

In current practice, the status of residual low-frequency acoustic hearing in hearing preservation cochlear implantation (CI) is unknown until activation two to three weeks postoperatively. The intraoperatively measured electrically evoked compound action potential (ECAP), a synchronous response from electrically stimulated auditory nerve fibers, is one of the first markers of auditory nerve function after cochlear implant surgery and such may provide information regarding the status of residual low-frequency acoustic hearing.This study aimed to evaluate the relationship between intraoperative ECAP at the time of CI and presence of preoperative and postoperative low-frequency acoustic hearing.A retrospective case review.Two hundred seventeen adult ears receiving CI (42 Advanced Bionics, 82 Cochlear, and 93 MED-EL implants).Intraoperative ECAP and CI.ECAP measurements were obtained intraoperatively, whereas residual hearing data were obtained from postoperative CI activation audiogram. A linear mixed model test revealed no interaction effects for the following variables: manufacturer, electrode location (basal, middle, and apical), preoperative low-frequency pure-tone average (LFPTA), and postoperative LFPTA. The postoperative residual low-frequency hearing status was defined as preservation of unaided air conduction thresholds ≤90 dB at 250 Hz. Electrode location and hearing preservation data were analyzed individually for both the ECAP threshold and ECAP maximum amplitude using multiple t-tests, without assuming a consistent standard deviation between the groups, and with alpha correction.The maximum amplitude, in microvolts, was significantly higher throughout apical and middle regions of the cochlea in patients who had preserved low-frequency acoustic hearing as compared with those who did not have preserved hearing (p = 0.0001 and p = 0.0088, respectively). ECAP threshold, in microamperes, was significantly lower throughout the apical region of the cochlea in patients with preserved low-frequency acoustic hearing as compared with those without preserved hearing (p = 0.0099). Basal electrode maximum amplitudes and middle and basal electrode thresholds were not significantly correlated with postoperative low-frequency hearing.Apical and middle electrode maximum amplitudes and apical electrode thresholds detected through intraoperative ECAP measurements are significantly correlated with preservation of low-frequency acoustic hearing. This association may represent a potential immediate feedback mechanism for postoperative outcomes that can be applied to all CIs.

Optimized Electrode Locations for Wearable Single-Lead ECG Monitoring Devices: A Case Study Using WFEES Modules based on the LANS Method

Body surface potential mapping (BSPM) is a valuable tool for research regarding electrocardiograms (ECG). However, the BSPM system is limited by its large number of electrodes and wires, long installation time, and high computational complexity. In this paper, we designed a wearable four-electrode electrocardiogram-sensor (WFEES) module that measures six-channel ECGs simultaneously for ECG investigation. To reduce the testing lead number and the measurement complexity, we further proposed a method, the layered (A, N) square-based (LANS) method, to optimize the ECG acquisition and analysis process using WFEES modules for different applications. Moreover, we presented a case study of electrode location optimization for wearable single-lead ECG monitoring devices using WFEES modules with the LANS method. In this study, 102 sets of single-lead ECG data from 19 healthy subjects were analyzed. The signal-to-noise ratio of ECG, as well as the mean and coefficient of variation of QRS amplitude, was derived among different channels to determine the optimal electrode locations. The results showed that a single-lead electrode pair should be placed on the left chest above the electrode location of standard precordial leads V1 to V4. Additionally, the best orientation was the principal diagonal as the direction of the heart’s electrical axis.

Impulse Breakdown Characteristics of Main Gap in the Presence of a Local Discharge

The characteristics of impulse breakdown voltages and the influence of the position of third electrode in air gap are investigated experimentally to study the parameters influencing the breakdown voltage in the presence of metallic objects around the high voltage power apparatus with air insulation. Experimental results show that the factors affecting the breakdown voltage are the shape and the size of the grounded electrode, the third metallic electrode location and the gap length. A comparison between negative and positive polarities of the applied voltages indicates an important influence of the polarity in the dielectric breakdown mechanism. The possible mechanism by which the local electric discharge initiates the main dielectric breakdown seems to be the high electric field around the local discharge channel and the streamers protruding from its surface.