During Deep Brain Stimulation Research Articles

Prediction and Modeling of Sensory and Motor Functions Recovery at Damage of Central Tracts and Peripheral Nerve Fibers

The P50, a positive auditory-evoked potential occurring 50 msec after an auditory click, has been characterized extensively with electroencephalography (EEG) to detect aberrant auditory electrophysiology in disorders like schizophrenia (SZ) where 61–74% have an auditory gating deficit. The P50 response occurs in primary auditory cortex and several thalamocortical regions. In rodents, the gated P50 response has been identified in the reticular thalamic nucleus (RT)—a deep brain structure traversed during deep brain stimulation (DBS) targeting of the ventral intermediate nucleus (VIM) of the thalamus to treat essential tremor (ET) allowing for interspecies comparison. The goal was to utilize the unique opportunity provided by DBS surgery for ET to map the P50 response in multiple deep brain structures in order to determine the utility of intraoperative P50 detection for facilitating DBS targeting of auditory responsive subterritories.We developed a method to assess P50 response intraoperatively with local field potentials (LFP) using microelectrode recording during routine clinical electrophysiologic mapping for awake DBS surgery in seven ET patients. Recording sites were mapped into a common stereotactic space.Forty significant P50 responses of 155 recordings mapped to the ventral thalamus, RT and CN head/body interface at similar rates of 22.7–26.7%. P50 response exhibited anatomic specificity based on distinct positions of centroids of positive and negative responses within brain regions and the fact that P50 response was not identified in the recordings from either the internal capsule or the dorsal thalamus.Detection of P50 response intraoperatively may guide DBS targeting RT and subterritories within CN head/body interface—DBS targets with the potential to treat psychosis and shown to modulate schizophrenia-like aberrancies in mouse models.

α and θ oscillations in the subthalamic nucleus are potential biomarkers for Parkinson's disease with depressive symptoms

IntroductionAbnormal α oscillations in the bed nucleus of stria terminalis and subgenual cingulate of patients with depression correlate with symptom severity. Some Parkinson's disease (PD) patients also have abnormal θ-α oscillations in the subthalamic nucleus (STN). However, the relationship between abnormal θ-α oscillations and depressive symptoms in PD patients has not been determined. This study explored the correlation between α and θ oscillations of the STN and depressive symptoms in PD patients. MethodsWe conducted a retrospective case-control study on 36 PD patients with (dPD group) or without depressive symptoms (nPD group), analyzing the difference in the average power spectral density (PSD) of α and θ oscillations of the local field potential (LFP) recorded in the STN during deep brain stimulation (DBS), and their correlation with the Hamilton depression rating scale (HAMD) of PD patients during the same period. ResultsThe dPD group had a higher PSD of α oscillations and a lower PSD of θ oscillations in the left ventral STN. The PSD of α oscillations of the left ventral STN were positively correlated with the severity of depressive symptoms, whereas the PSD of θ oscillations of this location was negatively correlated with severity of depressive symptoms. The PSD of α and θ oscillations did not correlate with motor symptoms, sleep quality, or quality of life score. ConclusionAbnormal α and θ oscillations of the left ventral STN could be used as biomarkers of PD with depressive symptoms, which might guide STN-DBS treatment.

Electrocorticography During Deep Brain Stimulation Surgery: Safety Experience From 4 Centers Within the National Institute of Neurological Disorders and Stroke Research Opportunities in Human Consortium.

Intraoperative research during deep brain stimulation (DBS) surgery has enabled major advances in understanding movement disorders pathophysiology and potential mechanisms for therapeutic benefit. In particular, over the last decade, recording electrocorticography (ECoG) from the cortical surface, simultaneously with subcortical recordings, has become an important research tool for assessing basal ganglia-thalamocortical circuit physiology. To provide confirmation of the safety of performing ECoG during DBS surgery, using data from centers involved in 2 BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative-funded basic human neuroscience projects. Data were collected separately at 4 centers. The primary endpoint was complication rate, defined as any intraoperative event, infection, or postoperative magnetic resonance imaging abnormality requiring clinical follow-up. Complication rates for explanatory variables were compared using point biserial correlations and Fisher exact tests. A total of 367 DBS surgeries involving ECoG were reviewed. No cortical hemorrhages were observed. Seven complications occurred: 4 intraparenchymal hemorrhages and 3 infections (complication rate of 1.91%; CI=0.77%-3.89%). The placement of 2 separate ECoG research electrodes through a single burr hole (84 cases) did not result in a significantly different rate of complications, compared to placement of a single electrode (3.6%vs 1.5%; P=.4). Research data were obtained successfully in 350 surgeries (95.4%). Combined with the single report previously available, which described no ECoG-related complications in a single-center cohort of 200 cases, these findings suggest that research ECOG during DBS surgery did not significantly alter complication rates.

Direct visualization of deep brain stimulation targets in patients with Parkinson's disease via 3-T quantitative susceptibility mapping.

The direct visualization of brain nuclei on magnetic resonance (MR) images is important for target localization during deep brain stimulation (DBS) in patients with Parkinson's disease (PD). We demonstrated the superiority of 3-T high-resolution submillimeter voxel size quantitative susceptibility mapping (QSM) for delineating the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Preoperative 3-T QSM and T2 weighted (T2w) images were obtained from ten patients with PD. Qualitative visualization scores were analyzed by two neurosurgeons on both images using a 4-point and 5-point scale, respectively. Images were also compared with regard to contrast-to-noise ratios (CNRs) and edge detection power for the STN and GPi. The Wilcoxon rank-sum test and the signed-rank test were used to compare measurements between the two images. Visualization scores for the STN and GPi, the mean CNR of the STN relative to the zona incerta (ZI) and the substantia nigra, and the mean CNR of the GPi relative to the internal capsule (IC) and the globus pallidum externum, were significantly higher on QSM images than on T2w images (P< 0.01). The edge detection powers of the STN-ZI and GPi-IC on QSM were significantly larger (by 2.6- and 3.8-fold, respectively) than those on T2w images (P< 0.01). QSM detected asymmetry of the STN in two patients. QSM images provided improved delineation ability for the STN and GPi when compared to T2w images. Our findings are important for patients with PD who undergo DBS surgery, particularly those with asymmetric bilateral nuclei.

Subthalamic deep brain stimulation induces finely-tuned gamma oscillations in the absence of levodopa

Finely-tuned gamma (FTG) oscillations can be recorded from cortex or the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) on dopaminergic medication, and have been associated with dyskinesias. When recorded during deep brain stimulation (DBS) on medication the FTG is entrained to half the stimulation frequency. We investigated whether these characteristics are shared off medication by recording local field potentials (LFP) from the STN from externalised DBS leads in 14 PD patients after overnight withdrawal of medication. FTG was induced de-novo by DBS in the absence of dyskinesias in a third of our cohort. The FTG could outlast stimulation or arise only after DBS ceased. FTG frequencies decreased during and across consecutive DBS blocks, but did not shift with changing stimulation frequency off medication. Together with the sustained after-effects this argues against simple entrainment by DBS in the off medication state. We also found significant coherence between STN-LFP and electroencephalogram (EEG) signals at FTG frequencies. We conclude that FTG is a network phenomenon that behaves differently in the off medication state, when it is neither associated with dyskinesias nor susceptible to entrainment.

CT and MRI Image Fusion Error: An Analysis of Co-Registration Error Using Commercially Available Deep Brain Stimulation Surgical Planning Software

Introduction: During deep brain stimulation (DBS) surgery, computed tomography (CT) and magnetic resonance imaging (MRI) scans need to be co-registered or fused. Image fusion is associated with the error that can distort the location of anatomical structures. Co-registration in DBS surgery is usually performed automatically by proprietary software; the amount of error during this process is not well understood. Here, our goal is to quantify the error during automated image co-registration with FrameLink™, a commonly used software for DBS planning and clinical research. Methods: This is a single-center retrospective study at a quaternary care referral center, comparing CT and MR imaging co-registration for a consecutive series of patients over a 12-month period. We collected CT images and MRI scans for 22 patients with Parkinson’s disease requiring placement of DBS. Anatomical landmarks were located on CT images and MRI scans using a novel image analysis algorithm that included a method for capturing the potential error inherent in the image standardization step of the analysis. The distance between the anatomical landmarks was measured, and the error was found by averaging the distances across all patients. Results: The average error during co-registration was 1.25 mm. This error was significantly larger than the error resulting from image standardization (0.19 mm) and was worse in the anterior-posterior direction. Conclusions: The image fusion errors found in this analysis were nontrivial. Although the estimated error may be inflated, it is sig­nificant enough that users must be aware of this potential inaccuracy, and developers of proprietary software should provide details about the magnitude and direction of co-registration errors.

Impulsivity Markers in Parkinsonian Subthalamic Single-Unit Activity.

Impulsive-compulsive behaviors are common in Parkinson's disease (PD) patients. However, the basal ganglia dysfunctions associated with high impulsivity have not been fully characterized. The objective of this study was to identify the features associated with impulsive-compulsive behaviors in single neurons of the subthalamic nucleus (STN). We compared temporal and spectral features of 412 subthalamic neurons from 12 PD patients with impulsive-compulsive behaviors and 330 neurons from 12 PD patients without. Single-unit activities were extracted from exploratory microrecordings performed during deep brain stimulation (DBS) implant surgery in an OFF medication state. Patients with impulsive-compulsive behaviors displayed decreased firing frequency during bursts and a larger fraction of tonic neurons combined with weaker beta coherence. Information carried by these features led to the identification of patients with impulsive-compulsive behaviors with an accuracy greater than 80%. Impulsive-compulsive behaviors in PD patients are associated with decreased bursts in STN neurons in the OFF medication state. © 2021 International Parkinson and Movement Disorder Society.

Implementation of Intraoperative Cone-Beam Computed Tomography (O-arm) for Stereotactic Imaging During Deep Brain Stimulation Procedures.

BACKGROUNDIntraoperative cone-beam computed tomography (iCBCT) allows for rapid 3-dimensional imaging. However, it is currently unknown whether this imaging technique offers sufficient accuracy for stereotactic registration during deep brain stimulation (DBS) procedures.OBJECTIVETo determine the accuracy of iCBCT, with the O-arm O2 (Medtronic), for stereotactic registration by comparing this modality to stereotactic magnetic resonance imaging (MRI).METHODSAll DBS patients underwent a preoperative non-stereotactic 3 Tesla MRI, stereotactic 1.5 Tesla MRI, stereotactic O-arm iCBCT, postimplantation O-arm iCBCT, and postoperative conventional multidetector computed tomography (CT) scan. We compared stereotactic (X, Y, and Z) coordinates of the anterior commissure (AC), the posterior commissure (PC), and midline reference (MR) between stereotactic MRI and iCBCT. For localisation comparison of electrode contacts, stereotactic coordinates of electrode tips were compared between the postoperative multidetector CT and iCBCT.RESULTSA total of 20 patients were evaluated. The average absolute difference in stereotactic coordinates of AC, PC, and MR was 0.4 ± 0.4 mm for X, 0.4 ± 0.4 mm for Y, and 0.7 ± 0.5 mm for Z. The average absolute difference in X-, Y-, and Z-coordinates for electrode localisation (N = 34) was 0.3 ± 0.3 mm, 0.6 ± 0.3 mm, and 0.6 ± 0.6 mm. These differences were small enough not to be considered clinically relevant.CONCLUSIONStereotactic MRI and O-arm iCBCT yield comparable coordinates in pre- and postoperative imaging. Differences found are below the threshold of clinical relevance. Intraoperative O-arm CBCT offers rapid stereotactic registration and evaluation of electrode placement. This increases patient comfort and neurosurgical workflow efficiency.

Defining the Border of the Subthalamic Nucleus for Deep Brain Stimulation: A Proposed Model Using the Symmetrical Sigmoid Curve Function

The subthalamic nucleus (STN) is an important target during deep brain stimulation (DBS). Accurate lead placement is integral to achieving satisfactory clinical outcomes; however, the STN remains a structure whose visualization is highly variable with borders often difficult to define. We aimed to develop an objective method of evaluating the visibility of the STN on preoperative magnetic resonance imaging (MRI) to standardize future comparative assessments between imaging protocols and patient-specific parameters. An imaging study of 64 prospectively collected patients undergoing bilateral DBS of the STN for various movement disorders was performed with institutional approval. MRI scans were acquired using a uniform protocol involving general anesthesia, cranial fixation in a Leksell stereotactic frame, and long acquisition times using a 3T MRI scanner. The images were analyzed using the iPlan Stereotaxy, version 2.6, workstation. High-resolution T2-weighted axial sections were evaluated, and the voxel values in the region of the presumed posterior border of the STN (as defined by the operating neurosurgeon) were obtained. A 4-parameter logistic symmetrical sigmoid curve was used to map the voxel values as they progressed from within to outside the region of the STN border. The inflection point and Hill coefficient of this symmetrical curve was calculated to provide objective information on the location and clarity of the STN border, respectively. These findings were compared with the surgeon's judgment of the STN border. To demonstrate the use of the sigmoid curve, the patients' head volumes were also calculated and evaluated to assess whether larger head volumes adversely affected STN visibility. The symmetrical sigmoid curve model provided objective information on the visibility of the STN on T2-weighted MRI scans and could be generated in 86% of the patients. The other 14% of patients had MRI scans that generated linear graphs, indicating the poorest scoring for STN image quality. No correlation between head volume and STN visibility was identified. Our proposed statistical model allows for standardized examination of the visibility of the STN border for DBS and has potential for both clinical and academic applications.

OSS-DBS: Open-source simulation platform for deep brain stimulation with a comprehensive automated modeling.

In this study, we propose a new open-source simulation platform that comprises computer-aided design and computer-aided engineering tools for highly automated evaluation of electric field distribution and neural activation during Deep Brain Stimulation (DBS). It will be shown how a Volume Conductor Model (VCM) is constructed and examined using Python-controlled algorithms for generation, discretization and adaptive mesh refinement of the computational domain, as well as for incorporation of heterogeneous and anisotropic properties of the tissue and allocation of neuron models. The utilization of the platform is facilitated by a collection of predefined input setups and quick visualization routines. The accuracy of a VCM, created and optimized by the platform, was estimated by comparison with a commercial software. The results demonstrate no significant deviation between the models in the electric potential distribution. A qualitative estimation of different physics for the VCM shows an agreement with previous computational studies. The proposed computational platform is suitable for an accurate estimation of electric fields during DBS in scientific modeling studies. In future, we intend to acquire SDA and EMA approval. Successful incorporation of open-source software, controlled by in-house developed algorithms, provides a highly automated solution. The platform allows for optimization and uncertainty quantification (UQ) studies, while employment of the open-source software facilitates accessibility and reproducibility of simulations.

Quantification of Parkinson's Disease Motor Symptoms: A Wireless Motion Sensing Approach.

Parkinson's Disease (PD) is a neurodegenerative disease characterized by its hallmark motor symptoms of bradykinesia and tremor. Numerous studies have suggested novel quantification methods of its symptoms. However, there lacks the means to accurately assess improvements in an intraoperative setting during deep brain stimulation (DBS) electrode implantation. This study introduces a methodology to quantify selected PD motor symptoms in such a restrictive environment using a wireless Leap Motion sensor. The result suggests that utilizing the Leap Motion sensor intraoperatively is feasible for quantifying motor parameters for bradykinesia and resting tremor of a PD patient.

Factors Influencing Electrode Position and Bending of the Proximal Lead in Deep Brain Stimulation for Movement Disorders

Background: The introduction of intracranial air (ICA) during deep brain stimulation (DBS) surgery is thought to have a negative influence on targeting and clinical outcomes. Objective: To investigate ICA volumes following surgery and other patient-specific factors as potential variables influencing translocation of the DBS electrode and proximal lead bowing. Methods: High-resolution postoperative computed tomography scans (≤1.0 mm resolution in all directions) within 24 h following DBS surgery and 4–6 weeks of follow-up were acquired. A total of 50 DBS leads in 33 patients were available for analysis. DBS leads included Abbott/St. Jude Medical Infinity^TM, Boston Scientific Vercise^TM, and Medtronic 3389^TM. Results: Both ICA volume and anatomical target were significantly associated with measures of DBS electrode translocation. ICA volume and DBS lead model were found to be significant predictors of proximal lead bowing. Measures of proximal lead bowing and translocation along the electrode trajectory for the Medtronic 3389^TM DBS lead were significantly larger than measures for the Abbott/St. Jude Medical Infinity^TM and Boston Scientific Vercise^TM DBS leads. Conclusion: The association between ICA volume and translocation of the DBS electrode is small in magnitude and not clinically relevant for DBS cases within a normal range of postoperative subdural air volumes. Differences in proximal lead bowing observed between DBS leads may reflect hardware engineering subtleties in the construction of DBS lead models.

Striatal and Thalamic Auditory Response During Deep Brain Stimulation for Essential Tremor: Implications for Psychosis

The P50, a positive auditory-evoked potential occurring 50 msec after an auditory click, has been characterized extensively with electroencephalography (EEG) to detect aberrant auditory electrophysiology in disorders like schizophrenia (SZ) where 61-74% have an auditory gating deficit. The P50 response occurs in primary auditory cortex and several thalamocortical regions. In rodents, the gated P50 response has been identified in the reticular thalamic nucleus (RT)-a deep brain structure traversed during deep brain stimulation (DBS) targeting of the ventral intermediate nucleus (VIM) of the thalamus to treat essential tremor (ET) allowing for interspecies comparison. The goal was to utilize the unique opportunity provided by DBS surgery for ET to map the P50 response in multiple deep brain structures in order to determine the utility of intraoperative P50 detection for facilitating DBS targeting of auditory responsive subterritories. We developed a method to assess P50 response intraoperatively with local field potentials (LFP) using microelectrode recording during routine clinical electrophysiologic mapping for awake DBS surgery in seven ET patients. Recording sites were mapped into a common stereotactic space. Forty significant P50 responses of 155 recordings mapped to the ventral thalamus, RT and CN head/body interface at similar rates of 22.7-26.7%. P50 response exhibited anatomic specificity based on distinct positions of centroids of positive and negative responses within brain regions and the fact that P50 response was not identified in the recordings from either the internal capsule or the dorsal thalamus. Detection of P50 response intraoperatively may guide DBS targeting RT and subterritories within CN head/body interface-DBS targets with the potential to treat psychosis and shown to modulate schizophrenia-like aberrancies in mouse models.

Pallidal 1/f asymmetry in patients with cervical dystonia.

Lateralized differences in pallidal outflow are putatively linked to asymmetric tonic contractions of the neck muscles in cervical dystonia (CD). At the population level, the interhemispheric asymmetry has been traditionally studied for the estimation of the spectral power in specified frequency bands. Broadband spectral features, however, were not taken into consideration. The contemporary analysis revealed that the aperiodic (1/f) broadband activity could be a neurophysiological marker of the excitation/inhibition ratio. During deep brain stimulation (DBS) surgery, we measured bilateral pallidal local field potentials (LFP) in nine CD patients, examining the effects of lateralized asymmetry on 1/f broadband activity. All patients showed a trend towards an asymmetric difference in the 1/f broadband activity. The ipsilateral 1/f slope was significantly higher in internal (GPi) segment of the globus pallidus that is on the contralateral side of the direction of the dystonia. We also found lateralized differences in the beta oscillations for GPi and in the alpha oscillations for GPe. Our findings emphasize the importance of mainstreaming broadband activity in the estimation of LFP spectral features together with periodic features and provide further evidence for the pallidal asymmetry in CD patients.

Intraoperative Localization of STN During DBS Surgery Using a Data-Driven Model.

A new approach is presented for localizing the Subthalamic Nucleus (STN) during Deep Brain Stimulation (DBS) surgery based on microelectrode recordings (MERs). DBS is an accepted treatment for individuals living with Parkinson’s Disease (PD). This surgery involves implantation of a permanent electrode inside the STN to deliver electrical current. Since the STN is a very small region inside the brain, accurate placement of an electrode is a challenging task for the surgical team. Prior to placement of the permanent electrode, microelectrode recordings of brain activity are used intraoperatively to localize the STN. The placement of the electrode and the success of the therapy depend on this location. In this paper, an objective approach is implemented to help the surgical team in localizing the STN. This is achieved by processing the MER signals and extracting features during the surgery to be used in a Machine Learning (ML) algorithm for defining the neurophysiological borders of the STN. For this purpose, a new classification approach is proposed with the goal of detecting both the dorsal and the ventral borders of the STN during the surgical procedure. Results collected from 100 PD patients in this study, show that by calculating and extracting wavelet transformation features from MER signals and using a data-driven computational deep neural network model, it is possible to detect the borders of the STN with an accuracy of 92%. The proposed method can be implemented in real-time during the surgery to model the neurophysiological nonlinearity along the path of the electrode trajectory during insertion.

A high-performance 4 nV (√Hz)−1 analog front-end architecture for artefact suppression in local field potential recordings during deep brain stimulation

Objective. Recording of local field potentials (LFPs) during deep brain stimulation (DBS) is necessary to investigate the instantaneous brain response to stimulation, minimize time delays for closed-loop neurostimulation and maximise the available neural data. To our knowledge, existing recording systems lack the ability to provide artefact-free high-frequency (>100 Hz) LFP recordings during DBS in real time primarily because of the contamination of the neural signals of interest by the stimulation artefacts. Approach. To solve this problem, we designed and developed a novel, low-noise and versatile analog front-end (AFE) that uses a high-order (8th) analog Chebyshev notch filter to suppress the artefacts originating from the stimulation frequency. After defining the system requirements for concurrent LFP recording and DBS artefact suppression, we assessed the performance of the realised AFE by conducting both in vitro and in vivo experiments using unipolar and bipolar DBS (monophasic pulses, amplitude ranging from 3 to 6 V peak-to-peak, frequency 140 Hz and pulse width 100 µs). A full performance comparison between the proposed AFE and an identical AFE, equipped with an 8th order analog Bessel notch filter, was also conducted. Main results. A high-performance, 4 nV ()−1 AFE that is capable of recording nV-scale signals was designed in accordance with the imposed specifications. Under both in vitro and in vivo experimental conditions, the proposed AFE provided real-time, low-noise and artefact-free LFP recordings (in the frequency range 0.5–250 Hz) during stimulation. Its sensing and stimulation artefact suppression capabilities outperformed the capabilities of the AFE equipped with the Bessel notch filter. Significance. The designed AFE can precisely record LFP signals, in and without the presence of either unipolar or bipolar DBS, which renders it as a functional and practical AFE architecture to be utilised in a wide range of applications and environments. This work paves the way for the development of externalized research tools for closed-loop neuromodulation that use low- and higher-frequency LFPs as control signals.

The Impact of Microelectrode Recording on Lead Location in Deep Brain Stimulation for the Treatment of Movement Disorders

During deep brain stimulation (DBS) surgery, microelectrode recording (MER) leads to target refinement from the initial plan in 30% to 47% of hemispheres; however, it is unclear whether the DBS lead ultimately resides within the MER-optimized target in relation to initial radiographic target coordinates in these hemispheres. This study aimed to determine the frequency of discordance between radiographic and neurophysiologic nucleus and whether target optimization with MER leads to a significant change in DBS lead location away from initial target. Consecutive cases of DBS surgery with MER using intraoperative computed tomography were included. Coordinates of initial anatomic target (AT), MER-optimized target (MER-O) and DBS lead were obtained. Hemispheres were categorized as "discordant" (D) if there was a suboptimal neurophysiologic signal despite accurate targeting of AT. Hemispheres where the first MER pass was satisfactory were deemed "concordant" (C). Coordinates and radial distances between 1) AT/MER-O; 2) MER-O/DBS; and 3) AT/DBS were calculated and compared. Of the 273 hemispheres analyzed, 143 (52%) were D, and 130 (48%) were C. In C hemispheres, DBS lead placement error (mean ± standard error of the mean) was 0.88 ± 0.07 mm. In D hemispheres, MER resulted in significant migration of DBS lead (mean AT-DBS error 2.11 ± 0.07 mm), and this distance was significantly greater than the distance between MER-O and DBS (2.11 vs. 1.09 mm, P < 0.05). Directional assessment revealed that the DBS lead migrated in the intended direction as determined by MER-O in D hemispheres, except when the intended direction was anterolateral. Discordance between radiographic and neurophysiologic target was seen in 52% of hemispheres, and MER resulted in appropriate deviation of the DBS lead toward the appropriate target. The actual value of the deviation, when compared with DBS lead placement error in C hemispheres, was, on average, small.

Anodic stimulation misunderstood: preferential activation of fiber orientations with anodic waveforms in deep brain stimulation

Objective. During deep brain stimulation (DBS), it is well understood that extracellular cathodic stimulation can cause activation of passing axons. Activation can be predicted from the second derivative of the electric potential along an axon, which depends on axonal orientation with respect to the stimulation source. We hypothesize that fiber orientation influences activation thresholds and that fiber orientations can be selectively targeted with DBS waveforms. Approach. We used bioelectric field and multicompartment NEURON models to explore preferential activation based on fiber orientation during monopolar or bipolar stimulation. Preferential fiber orientation was extracted from the principal eigenvectors and eigenvalues of the Hessian matrix of the electric potential. We tested cathodic, anodic, and charge-balanced pulses to target neurons based on fiber orientation in general and clinical scenarios. Main results. Axons passing the DBS lead have positive second derivatives around a cathode, whereas orthogonal axons have positive second derivatives around an anode, as indicated by the Hessian. Multicompartment NEURON models confirm that passing fibers are activated by cathodic stimulation, and orthogonal fibers are activated by anodic stimulation. Additionally, orthogonal axons have lower thresholds compared to passing axons. In a clinical scenario, fiber pathways associated with therapeutic benefit can be targeted with anodic stimulation at 50% lower stimulation amplitudes. Significance. Fiber orientations can be selectively targeted with simple changes to the stimulus waveform. Anodic stimulation preferentially activates orthogonal fibers, approaching or leaving the electrode, at lower thresholds for similar therapeutic benefit in DBS with decreased power consumption.

Deep Brain Stimulation Surgery without Sedation

Background: Sedatives and opioids used during deep brain stimulation (DBS) surgery interfere with optimal target localization and add to side effects and risks, and thus should be minimized. Objective: To retrospectively test the actual need for sedatives and opioids when cranial nerve blocks and specific therapeutic communication are applied. Methods: In a case series, 64 consecutive patients treated with a strong rapport, constant contact, non-verbal communication and hypnotic suggestions, such as dissociation to a “safe place,” reframing of disturbing noises and self-confirmation, were compared to 22 preceding patients under standard general anaesthesia or conscious sedation. Results: With introduction of the protocol the need for sedation dropped from 100% in the control group to 5%, and from a mean dose of 444 mg to 40 mg in 3 patients. Remifentanil originally used in 100% of the patients in an average dose of 813 µg was reduced in the study group to 104 µg in 31% of patients. There were no haemodynamic reactions indicative of stress during incision, trepanation, electrode insertion and closure. Conclusion: With adequate therapeutic communication, patients do not require sedation and no or only low-dose opioid treatment during DBS surgery, leaving patients fully awake and competent during surgery and testing.

Realtime phase-amplitude coupling analysis of micro electrode recorded brain signals.

ObjectiveTo demonstrate a method to calculate phase amplitude coupling (PAC) quickly and robustly for realtime applications.MethodsWe designed and implemented a multirate PAC algorithm with efficient filter bank processing and efficient computation of PAC for many frequency-pair combinations. We tested the developed algorithm for computing PAC on simulated data and on intraoperative neural recording data obtained during deep brain stimulation (DBS) electrode implantation surgery.ResultsA combination of parallelized frequency-domain filtering and modulation index for PAC estimation provided robust results that could be calculated in real time on modest computing hardware.ConclusionThe standard methods for calculating PAC can be optimized for quick and robust performance.SignificanceThese results demonstrated that PAC can be extracted in real time and is suitable for neurofeedback applications.