Accuracy of different three-dimensional subcortical human brain atlases for DBS -lead localisation.

BACKGROUND: Accurate interindividual comparability of deep brain stimulation (DBS) lead locations in relation to the surrounding anatomical structures is of eminent importance to define and understand effective stimulation areas. The objective of the current work is to compare the accuracy of the DBS lead localisation relative to the STN in native space with four recently developed three-dimensional subcortical brain atlases in the MNI template space. Accuracy is reviewed by anatomical and volumetric analysis as well as intraoperative electrophysiological data. METHODS: Postoperative lead localisations of 10 patients (19 hemispheres) were analysed in each individual patient based on Brainlab software (native space) and after normalization into the MNI space and application of 4 different human brain atlases using Lead-DBS toolbox within Matlab (template space). Each patient's STN was manually segmented and the relation between the reconstructed lead and the STN was compared to the 4 atlas-based STN models by applying the Dice coefficient. The length of intraoperative electrophysiological STN activity along different microelectrode recording tracks was measured and compared to reconstructions in native and template space. Descriptive non-parametric statistical tests were used to calculate differences between the 4 different atlases. RESULTS: The mean STN volume of the study cohort was 153.3 ±â€¯40.3 mm3 (n = 19). This is similar to the STN volume of the DISTAL atlas (166 mm3; p = .22), but significantly larger compared to the other atlases tested in this study. The anatomical overlap of the lead-STN-reconstruction was highest for the DISTAL atlas (0.56 ±â€¯0.18) and lowest for the PD25 atlas (0.34 ±â€¯0.17). A total number of 47 MER trajectories through the STN were analysed. There was a statistically significant discrepancy of the electrophysiogical STN activity compared to the reconstructed STN of all four atlases (p < .0001). CONCLUSION: Lead reconstruction after normalization into the MNI template space and application of four different atlases led to different results in terms of the DBS lead position relative to the STN. Based on electrophysiological and imaging data, the DISTAL atlas led to the most accurate display of the reconstructed DBS lead relative to the DISTAL-based STN.

Characterization of Cochlear, Vestibular and Cochlear-Vestibular Electrically Evoked Compound Action Potentials in Patients with a Vestibulo-Cochlear Implant.

The peripheral vestibular system is critical for the execution of activities of daily life as it provides movement and orientation information to motor and sensory systems. Patients with bilateral vestibular hypofunction experience a significant decrease in quality of life and have currently no viable treatment option. Vestibular implants could eventually restore vestibular function. Most vestibular implant prototypes to date are modified cochlear implants to fast-track development. These use various objective measurements, such as the electrically evoked compound action potential (eCAP), to supplement behavioral information. We investigated whether eCAPs could be recorded in patients with a vestibulo-cochlear implant. Specifically, eCAPs were successfully recorded for cochlear and vestibular setups, as well as for mixed cochlear-vestibular setups. Similarities and slight differences were found for the recordings of the three setups. These findings demonstrated the feasibility of eCAP recording with a vestibulo-cochlear implant. They could be used in the short term to reduce current spread and avoid activation of non-targeted neurons. More research is warranted to better understand the neural origin of vestibular eCAPs and to utilize them for clinical applications.

Characterization of pulse amplitude and pulse rate modulation for a human vestibular implant during acute electrical stimulation.

OBJECTIVE: The vestibular system provides essential information about balance and spatial orientation via the brain to other sensory and motor systems. Bilateral vestibular loss significantly reduces quality of life, but vestibular implants (VIs) have demonstrated potential to restore lost function. However, optimal electrical stimulation strategies have not yet been identified in patients. In this study, we compared the two most common strategies, pulse amplitude modulation (PAM) and pulse rate modulation (PRM), in patients. APPROACH: Four subjects with a modified cochlear implant including electrodes targeting the peripheral vestibular nerve branches were tested. Charge-equivalent PAM and PRM were applied after adaptation to baseline stimulation. Vestibulo-ocular reflex eye movement responses were recorded to evaluate stimulation efficacy during acute clinical testing sessions. MAIN RESULTS: PAM evoked larger amplitude eye movement responses than PRM. Eye movement response axes for lateral canal stimulation were marginally better aligned with PRM than with PAM. A neural network model was developed for the tested stimulation strategies to provide insights on possible neural mechanisms. This model suggested that PAM would consistently cause a larger ensemble firing rate of neurons and thus larger responses than PRM. SIGNIFICANCE: Due to the larger magnitude of eye movement responses, our findings strongly suggest PAM as the preferred strategy for initial VI modulation.

Neural Network Model of Vestibular Nuclei Reaction to Onset of Vestibular Prosthetic Stimulation.

The vestibular system incorporates multiple sensory pathways to provide crucial information about head and body motion. Damage to the semicircular canals, the peripheral vestibular organs that sense rotational velocities of the head, can severely degrade the ability to perform activities of daily life. Vestibular prosthetics address this problem by using stimulating electrodes that can trigger primary vestibular afferents to modulate their firing rates, thus encoding head movement. These prostheses have been demonstrated chronically in multiple animal models and acutely tested in short-duration trials within the clinic in humans. However, mainly, due to limited opportunities to fully characterize stimulation parameters, there is a lack of understanding of "optimal" stimulation configurations for humans. Here, we model possible adaptive plasticity in the vestibular pathway. Specifically, this model highlights the influence of adaptation of synaptic strengths and offsets in the vestibular nuclei to compensate for the initial activation of the prosthetic. By changing the synaptic strengths, the model is able to replicate the clinical observation that erroneous eye movements are attenuated within 30 minutes without any change to the prosthetic stimulation rate. Although our model was only built to match this time point, we further examined how it affected subsequent pulse rate modulation (PRM) and pulse amplitude modulation (PAM). PAM was more effective than PRM for nearly all stimulation configurations during these acute tests. Two non-intuitive relationships highlighted by our model explain this performance discrepancy. Specifically, the attenuation of synaptic strengths for afferents stimulated during baseline adaptation and the discontinuity between baseline and residual firing rates both disproportionally boost PAM. Comodulation of pulse rate and amplitude has been experimentally shown to induce both excitatory and inhibitory eye movements even at high baseline stimulation rates. We also modeled comodulation and found synergistic combinations of stimulation parameters to achieve equivalent output to only amplitude modulation. This may be an important strategy to reduce current spread and misalignment. The model outputs reflected observed trends in clinical testing and aspects of existing vestibular prosthetic literature. Importantly, the model provided insight to efficiently explore the stimulation parameter space, which was helpful, given limited available patient time.

Vestibular implants: Hope for improving the quality of life of patients with bilateral vestibular loss.

The vestibular system plays an essential role in crucial tasks such as postural control, gaze stabilization, and spatial orientation. Currently, there is no effective treatment for a bilateral loss of the vestibular function (BVL). The quality of life of affected patients is significantly impaired. During the last decade, our group has explored the potential of using electrical stimulation to artificially restore the vestibular function. Our vestibular implant prototype consists of a custom modified cochlear implant featuring one to three vestibular electrodes implanted in the proximity of the ampullary branches of the vestibular nerve; in addition to the main cochlear array. Special surgical techniques for safe implantation of these devices have been developed. In addition, we have developed stimulation strategies to generate bidirectional eye movements as well as the necessary interfaces to capture the signal from a motion sensor (e.g., gyroscope) and use it to modulate the stimulation signals delivered to the vestibular nerves. To date, 24 vestibular electrodes have been implanted in 11 BVL patients. Using a virtual motion profile to modulate the "baseline" electrical stimulation, vestibular responses could be evoked with 21 electrodes. Eye movements with mean peak eye velocities of 32°/s and predominantly in the plane of the stimulated canal were successfully generated. These are within the range of normal compensatory eye movements during walking and were large enough to have a significant effect on the patients' visual acuity. These results indicate that electrical stimulation of the vestibular nerve has a significant functional impact; eye movements generated this way could be sufficient to restore gaze stabilization during essential everyday tasks such as walking. The innovative concept of the vestibular implant has the potential to restore the vestibular function and have a central role in improving the quality of life of BVL patients in the near future.

Finding physiological responses in vestibular evoked potentials.

Vestibular prostheses are regarded as a promising tool to restore lost sensation in patients with vestibular disorders. These prostheses often electrically stimulate the vestibular nerve and stimulation efficacy is evaluated by measuring the vestibulo-ocular reflex (VOR). However, eye movement recording as intuitive metric of vestibular functionality is difficult to obtain outside the laboratory environment, and hence not available as an error signal in a closed-loop prosthesis. Recently we investigated vestibular evoked potentials (VEPs) by stimulating and recording in the same semicircular canal of a guinea pig. Here we studied the correlation between VOR and one region of VEP. We further analyzed a second portion of VEP, where vestibular nerve activity should occur using rectified bin integration (RBI). To this end, stimulation artifact was significantly reduced by hardware and software approaches. We found a high VEP-VOR correlation (R-squared=0.86), suggesting that VEP could substitute VOR as metric of vestibular function. Differences between below and above vestibular threshold stimulation were seen for the second portion of VEP. Further investigations are required to determine the specific parts of VEP that accurately represents vestibular function(s).