Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s disease

Neurovascular coupling is a critical brain mechanism whereby changes to blood flow accompany localised neural activity. The breakdown of neurovascular coupling is linked to the development and progression of several neurological conditions including dementia. In this study, we examined cortical haemodynamics in mouse preparations that modelled Alzheimer’s disease (J20-AD) and atherosclerosis (PCSK9-ATH) between 9 and 12 m of age. We report novel findings with atherosclerosis where neurovascular decline is characterised by significantly reduced blood volume, altered levels of oxyhaemoglobin and deoxyhaemoglobin, in addition to global neuroinflammation. In the comorbid mixed model (J20-PCSK9-MIX), we report a 3 x increase in hippocampal amyloid-beta plaques. A key finding was that cortical spreading depression (CSD) due to electrode insertion into the brain was worse in the diseased animals and led to a prolonged period of hypoxia. These findings suggest that systemic atherosclerosis can be detrimental to neurovascular health and that having cardiovascular comorbidities can exacerbate pre-existing Alzheimer’s-related amyloid-plaques.

Fusion of Technology in Cochlear Implantation Surgery: Investigation of Fluoroscopically Assisted Robotic Electrode Insertion

The HEARO cochlear implantation surgery aims to replace the conventional wide mastoidectomy approach with a minimally invasive direct cochlear access. The main advantage of the HEARO access would be that the trajectory accommodates the optimal and individualized insertion parameters such as type of cochlear access and trajectory angles into the cochlea. To investigate the quality of electrode insertion with the HEARO procedure, the insertion process was inspected under fluoroscopy in 16 human cadaver temporal bones. Prior to the insertion, the robotic middle and inner ear access were performed through the HEARO procedures. The status of the insertion was analyzed on the post-operative image with Siemens Artis Pheno (Siemens AG, Munich, Germany). The completion of the full HEARO procedure, including the robotic inner ear access and fluoroscopy electrode insertion, was possible in all 16 cases. It was possible to insert the electrode in all 16 cases through the drilled tunnel. However, one case in which the full cochlea was not visible on the post-operative image for analysis was excluded. The post-operative analysis of the electrode insertion showed an average insertion angle of 507°, which is equivalent to 1.4 turns of the cochlea, and minimal and maximal insertion angles were recorded as 373° (1 cochlear turn) and 645° (1.8 cochlear turn), respectively. The fluoroscopy inspection indicated no sign of complications during the insertion.

Cochlear Size Assessment Predicts Scala Tympani Volume and Electrode Insertion Force- Implications in Robotic Assisted Cochlear Implant Surgery

Objectives: The primary aim was to measure the volume of the scala tympani (ST) and the length of the straight portion of the cochlear basal turn from micro-computed tomography (μCT) images. The secondary aim was to estimate the electrode insertion force based on cochlear size and insertion speed. Both of these objectives have a direct clinical relevance in robotic assisted cochlear implant (CI) surgery.Methods: The ST was segmented in thirty μCT datasets to create a three-dimensional (3D) model and calculate the ST volume. The diameter (A-value), the width (B-value), and the straight portion of the cochlear basal turn (S-value) were measured from the oblique coronal plane. Electrode insertion force was measured in ST models of two different sizes, by inserting FLEX24 (24 mm) and FLEX28 (28 mm) electrode arrays at five different speeds (0.1, 0.5, 1, 2, and 4 mm/s).Results: The mean A-, B-, and S-values measured from the 30 μCT datasets were 9.0 ± 0.5, 6.7 ± 0.4, and 6.9 mm ± 0.5, respectively. The mean ST volume was 34.2 μl ± 7 (range 23–50 μl). The ST volume increased linearly with an increase in A- and B-values (Pearson's coefficient r = 0.55 and 0.56, respectively). The A-value exhibited linear positive correlation with the B-value and S-value (Pearson's coefficient r = 0.64 and r = 0.66, respectively). In the smaller of the two ST models, insertion forces were higher across the range of insertion speeds during both array insertions, when compared to the upscaled model. Before the maximum electrode insertion depths, a trend toward lower insertion force for lower insertion speed and vice-versa was observed.Conclusion: It is important to determine pre-operative cochlear size as this seems to have an effect upon electrode insertion forces. Higher insertion forces were seen in a smaller sized ST model across two electrode array lengths, as compared to an upscaled larger model. The ST volume, which cannot be visualized on clinical CT, correlates with clinical cochlear parameters. This enabled the creation of an equation capable of predicting ST volume utilizing A- and B-values, thus enabling pre-operative prediction of ST volume.

Cochlear implantation under local anesthesia in 117 cases: patients’ subjective experience and outcomes

Purpose To report the outcomes and the patients’ subjective experience of cochlear implantation (CI) performed under local anesthesia (LA). To describe a new form of intraoperative cochlear monitoring based on the patients subjective sound perception during CI. Methods In this retrospective case–cohort study, 117 patients underwent CI under LA with (n = 58) or without conscious sedation (n = 59). Included were primarily elderly patients with elevated risks for general anesthesia and recently patients with residual hearing eligible for electro-acoustic stimulation (EAS) (n = 27), in whom hearing could be monitored during the electrode insertion. A 500 Hz test tone was presented and the patient reported of subjective changes in loudness, leading to a modification of the insertion. A questionnaire was sent to all patients in which they assessed their subjective experience. Results All patients were successfully operated under LA without the need to intraoperatively convert to general anesthesia. 90% of the patients reported that the surgery was a positive experience. The vast majority, 90% of patients were satisfied with the overall treatment and with intraoperative pain management and 84% of the patients would opt for local anesthesia again. Cochlear monitoring by the patients’ subjective sound perception enabled for atraumatic insertions as all EAS patients could hear the test tone up to the end of the surgery. Conclusions CI under LA was well tolerated and recommended by the vast majority of patients. In addition, it offers the possibility to monitor the patients’ hearing during the electrode insertion, which may help to prevent insertion trauma.

Induced Dipoles and Possible Modulation of Wireless Effects in Implanted Electrodes. Effects of Implanting Insulated Electrodes on an Animal Test to Screen Antidepressant Activity

There is evidence that Deep Brain Stimulation (DBS) produces health benefits in patients even before initiating stimulation. Furthermore, DBS electrode insertion in rat infralimbic cortex (ILC) provokes antidepressant-like effects before stimulation, due to local inflammation and astrogliosis. Consequently, a significant effect of implanting electrodes is suspected. External fields, similar in magnitude to the brain’s endogenous fields, induce electric dipoles in conducting materials, in turn influencing neural cell growth through wireless effects. To elucidate if such dipoles influence depressive-like behavior, without external stimulation, the comparative effect of conducting and insulated electrodes along with the glial response is studied in unstressed rats. Naïve and implanted rats with electrically insulated or uninsulated steel electrodes were evaluated in the modified forced swimming test and expression of ILC-glial markers was assessed. An antidepressant-like effect was observed with conducting but not with insulated electrodes. Gliosis was detected in both groups, but astroglial reactivity was larger near uninsulated electrodes. Thus, induced dipoles and antidepressant-like effects were only observed with conducting implants. Such correlation suggests that dipoles induced in electrodes by endogenous fields in turn induce neuron stimulation in a feedback loop between electrodes and neural system. Further research of the effects of unwired conducting implants could open new approaches to regulating neuronal function, and possibly treat neurological disorders.