Thalamic Segmentation and Neural Activation Modeling Based on Individual Tissue Microstructure in Deep Brain Stimulation for Essential Tremor.

OBJECTIVE: Thalamic deep brain stimulation (DBS) is the primary surgical therapy for essential tremor (ET). Thalamic DBS traditionally uses an atlas-based targeting approach, which, although nominally accurate, may obscure individual anatomic differences from population norms. The objective of this study was to compare this traditional atlas-based approach with a novel quantitative modeling methodology grounded in individual tissue microstructure (N-of-1 approach). MATERIALS AND METHODS: The N-of-1 approach uses individual patient diffusion tensor imaging (DTI) data to perform thalamic segmentation and volume of tissue activation (VTA) modeling. For each patient, the thalamus was individually segmented into 13 nuclei using DTI-based k-means clustering. DBS-induced VTAs associated with tremor suppression and side effects were then computed for each patient with finite-element electric-field models incorporating DTI microstructural data. Results from N-of-1 and traditional atlas-based modeling were compared for a large cohort of patients with ET treated with thalamic DBS. RESULTS: The size and shape of individual N-of-1 thalamic nuclei and VTAs varied considerably across patients (N = 22). For both methods, tremor-improving therapeutic VTAs showed similar overlap with motor thalamic nuclei and greater motor than sensory nucleus overlap. For VTAs producing undesirable sustained paresthesia, 94% of VTAs overlapped with N-of-1 sensory thalamus estimates, whereas 74% of atlas-based segmentations overlapped. For VTAs producing dysarthria/motor contraction, the N-of-1 approach predicted greater spread beyond the thalamus into the internal capsule and adjacent structures than the atlas-based method. CONCLUSIONS: Thalamic segmentation and VTA modeling based on individual tissue microstructure explain therapeutic stimulation equally well and side effects better than a traditional atlas-based method in DBS for ET. The N-of-1 approach may be useful in DBS targeting and programming, particularly when patient neuroanatomy deviates from population norms.

Perceived social support declines after deep brain stimulation surgery in patients with Parkinson's disease.

INTRODUCTION: The Social Provisions Scale (SPS) measures a person's perceived social support. We evaluated the perceived social support in Parkinson's disease (PD) patients before and after subthalamic nucleus (STN) deep brain stimulation (DBS) and its impact on clinical outcomes following DBS. METHODS: We analyzed 55 PD patients who underwent STN DBS surgery and completed the SPS, PDQ-39, and MDS-UPDRS Parts I-IV before and 6-12 months after surgery. Some patients also completed global cognitive, mood and apathy scales. Caregivers completed the CBI at each visit. Linear regression models and linear mixed models evaluated the association between the SPS baseline score, MDS-UPDRS and PDQ-39 scores, the association between MDS-UPDRS, CBI and the SPS follow-up score, and the association between SPS, global cognition and other psychological variables. RESULTS: DBS implantation improved MDS-UPDRS I-IV and PDQ-39 scores. Perceived social support declined after DBS (baseline SPS total 82.55 ± 7.52 vs. follow-up SPS total 78.83 ± 9.02, p = 0.0001). Baseline SPS total score was not significantly associated with the MDS-UPDRS or PDQ-39 scores at follow-up. MDS-UPDRS scores and the CBI at follow-up had no significant association with SPS total score at follow-up. Measures of global cognition, mood and apathy were associated with the SPS before and after DBS, and the association was independent of STN DBS. CONCLUSION: After STN DBS, PD patients experienced a decrease in perceived social support, but baseline perceived social support did not impact clinical outcomes. It is important to further identify factors that may contribute to this perception of worsened social support.

A Light-Tolerant Wireless Neural Recording IC for Motor Prediction With Near-Infrared-Based Power and Data Telemetry.

Miniaturized and wireless near-infrared (NIR) based neural recorders with optical powering and data telemetry have been introduced as a promising approach for safe long-term monitoring with the smallest physical dimension among state-of-the-art standalone recorders. However, a main challenge for the NIR based neural recording ICs is to maintain robust operation in the presence of light-induced parasitic short circuit current from junction diodes. This is especially true when the signal currents are kept small to reduce power consumption. In this work, we present a light-tolerant and low-power neural recording IC for motor prediction that can fully function in up to 300 µW/mm2 of light exposure. It achieves best-in-class power consumption of 0.57 µW at 38° C with a 4.1 NEF pseudo-resistorless amplifier, an on-chip neural feature extractor, and individual mote level gain control. Applying the 20-channel pre-recorded neural signals of a monkey, the IC predicts finger position and velocity with correlation coefficient up to 0.870 and 0.569, respectively, with individual mote level gain control enabled. In addition, wireless measurement is demonstrated through optical power and data telemetry using a custom PV/LED GaAs chip wire bonded to the proposed IC.

Quantitative Sensory Testing of Spinal Cord and Dorsal Root Ganglion Stimulation in Chronic Pain Patients.

BACKGROUND/OBJECTIVES: The physiological mechanisms underlying the pain-modulatory effects of clinical neurostimulation therapies, such as spinal cord stimulation (SCS) and dorsal root ganglion stimulation (DRGS), are only partially understood. In this pilot prospective study, we used patient-reported outcomes (PROs) and quantitative sensory testing (QST) to investigate the physiological effects and possible mechanisms of action of SCS and DRGS therapies. MATERIALS AND METHODS: We tested 16 chronic pain patients selected for SCS and DRGS therapy, before and after treatment. PROs included pain intensity, pain-related symptoms (e.g., pain interference, pain coping, sleep interference) and disability, and general health status. QST included assessments of vibration detection theshold (VDT), pressure pain threshold (PPT) and tolerance (PPToL), temporal summation (TS), and conditioned pain modulation (CPM), at the most painful site. RESULTS: Following treatment, all participants reported significant improvements in PROs (e.g., reduced pain intensity [p < 0.001], pain-related functional impairment [or pain interference] and disability [p = 0.001 for both]; better pain coping [p = 0.03], sleep [p = 0.002]), and overall health [p = 0.005]). QST showed a significant treatment-induced increase in PPT (p = 0.002) and PPToL (p = 0.011), and a significant reduction in TS (p = 0.033) at the most painful site, but showed no effects on VDT and CPM. We detected possible associations between a few QST measures and a few PROs. Notably, higher TS was associated with increased pain interference scores at pre-treatment (r = 0.772, p = 0.009), and a reduction in TS was associated with the reduction in pain interference (r = 0.669, p = 0.034) and pain disability (r = 0.690, p = 0.027) scores with treatment. CONCLUSIONS: Our preliminary findings suggest significant clinical and therapeutic benefits associated with SCS and DRGS therapies, and the possible ability of these therapies to modulate pain processing within the central nervous system. Replication of our pilot findings in future, larger studies is necessary to characterize the physiological mechanisms of SCS and DRGS therapies.

Estimating Risk for Future Intracranial, Fully Implanted, Modular Neuroprosthetic Systems: A Systematic Review of Hardware Complications in Clinical Deep Brain Stimulation and Experimental Human Intracortical Arrays.

OBJECTIVE: A new age of neuromodulation is emerging: one of restorative neuroengineering and neuroprosthetics. As novel device systems move toward regulatory evaluation and clinical trials, a critical need arises for evidence-based identification of potential sources of hardware-related complications to assist in clinical trial design and mitigation of potential risk. MATERIALS AND METHODS: The objective of this systematic review is to provide a detailed safety analysis for future intracranial, fully implanted, modular neuroprosthetic systems. To achieve this aim, we conducted an evidence-based analysis of hardware complications for the most established clinical intracranial modular system, deep brain stimulation (DBS), as well as the most widely used intracranial human experimental system, the silicon-based (Utah) array. RESULTS: Of 2328 publications identified, 240 articles met the inclusion criteria and were reviewed for DBS hardware complications. The most reported adverse events were infection (4.57%), internal pulse generator malfunction (3.25%), hemorrhage (2.86%), lead migration (2.58%), lead fracture (2.56%), skin erosion (2.22%), and extension cable malfunction (1.63%). Of 433 publications identified, 76 articles met the inclusion criteria and were reviewed for Utah array complications. Of 48 human subjects implanted with the Utah array, 18 have chronic implants. Few specific complications are described in the literature; hence, implant duration served as a lower bound for complication-free operation. The longest reported duration of a person with a Utah array implant is 1975 days (~5.4 years). CONCLUSIONS: Through systematic review of the clinical and human-trial literature, our study provides the most comprehensive safety review to date of DBS hardware and human neuroprosthetic research using the Utah array. The evidence-based analysis serves as an important reference for investigators seeking to identify hardware-related safety data, a necessity to meet regulatory requirements and to design clinical trials for future intracranial, fully implanted, modular neuroprosthetic systems.

Subthalamic nucleus deep brain stimulation improves dyskinesias in Parkinson's disease beyond levodopa reduction.

Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves motor fluctuations and dyskinesias in patients with Parkinson's disease (PD). Dyskinesia improvement with STN DBS is believed to result entirely from levodopa reduction. However, some studies suggest that STN DBS may also directly suppress dyskinesias. To determine whether bilateral STN DBS improves dyskinesias beyond what would be expected from levodopa reduction alone, we analyzed pre-operative and post-operative dyskinesia scores (sum of MDS-UPDRS items 4.1 and 4.2) from 61 PD patients with bilateral STN DBS. A multiple regression model (adjusted for disease severity, disease duration, active contacts above the STN, use of amantadine, high pre-operative levodopa-equivalent dose (LED), sex, and interaction between active contacts above the STN and amantadine use) was created to describe the relationship between dyskinesia scores and LED prior to DBS. Using this model, a post-operative dyskinesia score was estimated from post-operative LED and compared to the actual post-operative dyskinesia score. The regression model was statistically significant overall (p = 0.003, R2 = 0.34, adjusted R2 = 0.24). The actual post-operative dyskinesia score (1.0 ± 1.4) was significantly lower than the score predicted by the model (3.0 ± 1.1, p < 0.0001). Dyskinesias after STN DBS improved more than predicted by levodopa reduction alone. Our data support the idea that STN stimulation may directly improve dyskinesias.

Objective Measures to Characterize the Physiological Effects of Spinal Cord Stimulation in Neuropathic Pain: A Literature Review.

OBJECTIVE: The physiological mechanisms behind the therapeutic effects of spinal cord stimulation (SCS) are only partially understood. Our aim was to perform a literature review of studies that used objective measures to characterize mechanisms of action of SCS in neuropathic pain patients. MATERIALS AND METHODS: We searched the PubMed data base to identify clinical studies that used objective measures to assess the effects of SCS in neuropathic pain. We extracted the study factors (e.g., type of measure, diagnoses, painful area[s], and SCS parameters) and outcomes from the included studies. RESULTS: We included 67 studies. Of these, 24 studies used neurophysiological measures, 14 studies used functional neuroimaging techniques, three studies used a combination of neurophysiological and functional neuroimaging techniques, 14 studies used quantitative sensory testing, and 12 studies used proteomic, vascular, and/or pedometric measures. Our findings suggest that SCS largely inhibits somatosensory processing and/or spinal nociceptive activity. Our findings also suggest that SCS modulates activity across specific regions of the central nervous system that play a prominent role in the sensory and emotional functions of pain. CONCLUSIONS: SCS appears to modulate pain via spinal and/or supraspinal mechanisms of action (e.g., pain gating, descending pain inhibition). However, to better understand the mechanisms of action of SCS, we believe that it is necessary to carry out systematic, controlled, and well-powered studies using objective patient measures. To optimize the clinical effectiveness of SCS for neuropathic pain, we also believe that it is necessary to develop and implement patient-specific approaches.

Charting the road forward in psychiatric neurosurgery: proceedings of the 2016 American Society for Stereotactic and Functional Neurosurgery workshop on neuromodulation for psychiatric disorders.

OBJECTIVE: Refractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive-compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials. To discuss next steps, neurosurgeons, neurologists, psychiatrists and representatives from industry convened a workshop sponsored by the American Society for Stereotactic and Functional Neurosurgery in Chicago, Illinois, in June of 2016. DESIGN: Here we summarise the proceedings of the workshop. Participants discussed a number of issues of importance to the community. First, we discussed how to interpret results from the recent pivotal trials of DBS for OCD and depression. We then reviewed what can be learnt from lesions and closed-loop neurostimulation. Subsequently, representatives from the National Institutes of Health, the Food and Drug Administration and industry discussed their views on neuromodulation for psychiatric disorders. In particular, these third parties discussed their criteria for moving forward with new trials. Finally, we discussed the best way of confirming safety and efficacy of these therapies, including registries and clinical trial design. We close by discussing next steps in the journey to new neuromodulatory therapies for these devastating illnesses. CONCLUSION: Interest and motivation remain strong for deep brain stimulation for psychiatric disease. Progress will require coordinated efforts by all stakeholders.

Atlas-Independent, Electrophysiological Mapping of the Optimal Locus of Subthalamic Deep Brain Stimulation for the Motor Symptoms of Parkinson Disease.

BACKGROUND/AIMS: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease (PD). However, motor outcomes can be variable, perhaps due to inconsistent positioning of the active contact relative to an unknown optimal locus of stimulation. Here, we determine the optimal locus of STN stimulation in a geometrically unconstrained, mathematically precise, and atlas-independent manner, using Unified Parkinson Disease Rating Scale (UPDRS) motor outcomes and an electrophysiological neuronal stimulation model. METHODS: In 20 patients with PD, we mapped motor improvement to active electrode location, relative to the individual, directly MRI-visualized STN. Our analysis included a novel, unconstrained and computational electrical-field model of neuronal activation to estimate the optimal locus of DBS. RESULTS: We mapped the optimal locus to a tightly defined ovoid region 0.49 mm lateral, 0.88 mm posterior, and 2.63 mm dorsal to the anatomical midpoint of the STN. On average, this locus is 11.75 lateral, 1.84 mm posterior, and 1.08 mm ventral to the mid-commissural point. CONCLUSION: Our novel, atlas-independent method reveals a single, ovoid optimal locus of stimulation in STN DBS for PD. The methodology, here applied to UPDRS and PD, is generalizable to atlas-independent mapping of other motor and non-motor effects of DBS.

Correction to: Noninvasive Intracranial Pressure Assessment in Acute Liver Failure.

The authors note that the number 14 was inadvertently omitted from the formula listed on page 5 of the article. It currently reads.

Noninvasive Intracranial Pressure Assessment in Acute Liver Failure.

BACKGROUND: Elevated intracranial pressure (ICP) is an important cause of death following acute liver failure (ALF). While invasive ICP monitoring (IICPM) is most accurate, the presence of coagulopathy increases bleeding risk in ALF. Our objective was to evaluate the accuracy of three noninvasive ultrasound-based measures for the detection of concurrent ICP elevation in ALF-optic nerve sheath diameter (ONSD) using optic nerve ultrasound (ONUS); middle cerebral artery pulsatility index (PI) on transcranial Doppler (TCD); and ICP calculated from TCD flow velocities (ICPtcd) using the estimated cerebral perfusion pressure (CPPe) technique. METHODS: In this retrospective study, consecutive ALF patients admitted over a 6-year period who underwent IICPM as well as measurement of ONSD, TCD-PI or ICPtcd were included. ONSD was measured offline by a blinded investigator from deidentified videos. The ability of highest ONSD, TCD-PI, and ICPtcd to detect concurrent invasive ICP > 20 mmHg was assessed using receiver operating characteristic (ROC) curves. The ROC area under the curve (AUC) was calculated with 95% confidence interval (95% CI) and evaluated against the null hypothesis of AUC = 0.5. Noninvasive measures were also evaluated as predictors of in-hospital death. RESULTS: Forty-one ALF patients were admitted during the study period. In total, 27 (66%) underwent IICPM, of these, 23 underwent ONUS and 21 underwent TCD. Eleven out of 23 (48%) patients died (two from intracranial hypertension). Results of ROC analysis for detection of concurrent ICP > 20 mmHg were as follows: ONSD AUC = 0.59 (95% CI 0.37-0.79, p = 0.54); TCD-PI AUC = 0.55 (95% CI 0.34-0.75, p = 0.70); and ICPtcd AUC = 0.90 (0.72-0.98, p < 0.0001). None of the noninvasive measures were significant predictors of death. CONCLUSIONS: In patients with ALF, neither ONSD nor TCD-PI reliably detected concurrent ICP elevation on invasive monitoring. Estimation of ICP (ICPtcd) using the TCD CPPe technique was associated with concurrent ICP elevation. Additional studies of TCD CPPe in larger numbers of ALF patients may prove worthwhile.

Protocol based invasive intracranial pressure monitoring in acute liver failure: feasibility, safety and impact on management.

BACKGROUND: Acute liver failure (ALF) may result in elevated intracranial pressure (ICP). While invasive ICP monitoring (IICPM) may have a role in ALF management, these patients are typically coagulopathic and at risk for intracranial hemorrhage (ICH). Contemporary ICP monitoring techniques and coagulopathy reversal strategies may be associated with a lower risk of hemorrhage. Our objective was to evaluate the safety, feasibility, impact on clinical management and outcomes associated with protocol-directed use of IICPM in ALF. METHODS: Adult patients admitted between June 2011 and October 2016, with ALF and grade-4 encephalopathy with a reasonable likelihood of survival, were eligible for IICPM. The coagulopathy reversal protocol included administration of recombinant Factor VIIa (rFVIIa) and desmopressin, a goal platelet count >50,000/mm3 and fibrinogen >100 mg/dL. Monitor insertion was performed within an hour of the rFVIIa dose. Only intraparenchymal monitors were used. Computed tomography of the brain was performed prior to and within 24 hours of monitor placement. Outcomes of interest included ICH, sustained intracranial hypertension, therapeutic intensity level (TIL) for ICP management, mortality and functional outcome on the Glasgow Outcome Scale (GOS) at discharge and 6 months. RESULTS: A total of 24/37 patients (65%) with ALF underwent IICPM. The most common reason for exclusion was encephalopathy grade <4. Four patients underwent liver transplantation. There was one asymptomatic ICH following IICPM, in a patient who had an excellent outcome. Sustained intracranial hypertension occurred in 13/24 monitored patients (54%), 5/24 (21%) required extreme measures (TIL-4) for ICP control, which were successful in 4 patients: 12/24 patients (50%) died but only 4 deaths (17%) were attributed to intracranial hypertension. Six of the 8 survivors with 6-month follow up had good functional outcome (GOS >3). CONCLUSIONS: Protocol-directed use of IICPM in ALF is feasible, associated with a low incidence of serious complications and has a significant impact on clinical management.

Influence of Intracranial Air on Electrode Position and Clinical Outcomes following Deep Brain Stimulation for Parkinson's Disease.

BACKGROUND: The introduction of intracranial air during deep brain stimulation (DBS) surgery is believed to negatively impact targeting accuracy and clinical outcomes. OBJECTIVE: To quantify the relationship between intracranial air (ICA) volumes, targeting accuracy, and clinical outcomes in patients undergoing subthalamic nucleus (STN) DBS for Parkinson's disease. METHODS: ICA in 73 consecutive STN DBS cases (146 leads) was measured by high-resolution CT and correlated with proximal lead bowing, electrode displacement, targeting accuracy, and clinical outcomes at 6 and 12 months. RESULTS: There was a statistically significant correlation of ICA volume (mean ± SEM: 21.3 ± 13.7 cm3) and proximal lead bowing (2.8 ± 1.4 mm, r = 0.34, p = 0.01). There was no significant correlation of ICA with targeting error (2.0 ± 1.2 mm), distal contact deviation (1.2 ± 0.7 mm), motor Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III improvement at 6 months (42.3 ± 4.5%) or 12 months (30.3 ± 7.7%), or dopaminergic medication reduction at 6 months (44.7± 4.2%) or 12 months (32.9 ± 5.9%). Comparison of top and bottom ICA quintile extremes also revealed no differences in these measures. CONCLUSIONS: Though the proximal DBS lead bends in association with ICA, movement of the distal contact, targeting error, and clinical outcomes are not affected by ICA. This unexpected finding is maintained at ICA quintile extremes.

Disruption of corticocortical information transfer during ketamine anesthesia in the primate brain.

The neural mechanisms of anesthetic-induced unconsciousness have yet to be fully elucidated, in part because of the diverse molecular targets of anesthetic agents. We demonstrate, using intracortical recordings in macaque monkeys, that information transfer between structurally connected cortical regions is disrupted during ketamine anesthesia, despite preserved primary sensory representation. Furthermore, transfer entropy, an information-theoretic measure of directed connectivity, decreases significantly between neuronal units in the anesthetized state. This is the first direct demonstration of a general anesthetic disrupting corticocortical information transfer in the primate brain. Given past studies showing that more commonly used GABAergic drugs inhibit surrogate measures of cortical communication, this finding suggests the potential for a common network-level mechanism of anesthetic-induced unconsciousness.

Treatment of medically refractory cancer pain with a combination of intrathecal neuromodulation and neurosurgical ablation: case series and literature review.

OBJECTIVE: Up to 90% of patients with advanced cancer experience intractable pain. For these patients, oral analgesics are the mainstay of therapy, often augmented with intrathecal drug delivery. Neurosurgical ablative procedures have become less commonly used, though their efficacy has been well-established. Unfortunately, little is known about the safety of ablation in the context of previous neuromodulation. Therefore, the aim of this study is to present the results from a case series in which patients were treated successfully with a combination of intrathecal neuromodulation and neurosurgical ablation. DESIGN: Retrospective case series and literature review. SETTING: Three institutions with active cancer pain management programs in the United States. METHODS: All patients who underwent both neuroablative and neuromodulatory procedures for cancer pain were surveyed using the visual analog scale prior to the first procedure, before and after a second procedure, and at long-term follow-up. Based on initial and subsequent presentation, patients underwent intrathecal morphine pump placement, cordotomy, or midline myelotomy. RESULTS: Five patients (2 male, 3 female) with medically intractable pain (initial VAS = 10) were included in the series. Four subjects were initially treated with intrathecal analgesic neuromodulation, and 1 with midline myelotomy. Each patient experienced recurrence of pain (VAS ≥ 9) following the initial procedure, and was therefore treated with another modality (intrathecal, N = 1; midline myelotomy, N = 1; percutaneous radiofrequency cordotomy, N = 3), with significant long-term benefit (VAS 1-7). CONCLUSION: In cancer patients with medically intractable pain, intrathecal neuromodulation and neurosurgical ablation together may allow for more effective control of cancer pain.

Evaluating indirect subthalamic nucleus targeting with validated 3-tesla magnetic resonance imaging.

BACKGROUND/OBJECTIVES: Indirect targeting of the subthalamic nucleus (STN) is commonly utilized at deep brain stimulation (DBS) centers around the world. The superiority of either midcommissural point (MCP)-based or red nucleus (RN)-based indirect targeting remains to be established. METHODS: The location of the STN was determined and statistically compared to MCP- and RN-based predictions in 58 STN DBS patients, using a validated 3-tesla MRI protocol. The influence of additional neuroanatomical parameters on STN midpoint location was evaluated. Linear regression analysis was utilized to produce an optimized MCP/RN targeting model. Targeting coordinates at 1.5 T were compared to results at 3 T. RESULTS: Accuracy and precision for RN-based targeting was superior to MCP-based targeting to predict STN midpoint location for each coordinate dimension (p < 0.01 and p < 0.05, respectively). RN-based targeting was statistically equivalent to an optimized regression-based targeting strategy incorporating multiple neuroanatomical parameters, including third-ventricle width and overall brain size. RN-based targeting at 1.5 T yielded equivalent coordinates to targeting at 3 T. CONCLUSIONS: RN-based targeting is statistically superior to MCP-based STN targeting and accommodates broad variations in neuroanatomical parameters. Neurosurgeons utilizing indirect targeting of the STN may consider favoring RN-based over MCP-based indirect targeting methods.

Effect of Anisotropic Brain Conductivity on Patient-Specific Volume of Tissue Activation in Deep Brain Stimulation for Parkinson Disease.

OBJECTIVE: Deep brain stimulation (DBS) modeling can improve surgical targeting by quantifying the spatial extent of stimulation relative to subcortical structures of interest. A certain degree of model complexity is required to obtain accurate predictions, particularly complexity regarding electrical properties of the tissue around DBS electrodes. In this study, the effect of anisotropy on the volume of tissue activation (VTA) was evaluated in an individualized manner. METHODS: Tissue activation models incorporating patient-specific tissue conductivity were built for 40 Parkinson disease patients who had received bilateral subthalamic nucleus (STN) DBS. To assess the impact of local changes in tissue anisotropy, one VTA was computed at each electrode contact using identical stimulation parameters. For comparison, VTAs were also computed assuming isotropic tissue conductivity. Stimulation location was considered by classifying the anisotropic VTAs relative to the STN. VTAs were characterized based on volume, spread in three directions, sphericity, and Dice coefficient. RESULTS: Incorporating anisotropy generated significantly larger and less spherical VTAs overall. However, its effect on VTA size and shape was variable and more nuanced at the individual patient and implantation levels. Dorsal VTAs had significantly higher sphericity than ventral VTAs, suggesting more isotropic behavior. Contrastingly, lateral and posterior VTAs had significantly larger and smaller lateral-medial spreads, respectively. Volume and spread correlated negatively with sphericity. CONCLUSION: The influence of anisotropy on VTA predictions is important to consider, and varies across patients and stimulation location. SIGNIFICANCE: This study highlights the importance of considering individualized factors in DBS modeling to accurately characterize the VTA.

Long-Term Reductions in Opioid Medication Use After Spinal Stimulation: A Claims Analysis Among Commercially-Insured Population.

Purpose: Chronic, non-cancer pain significantly and negatively impacts patient quality of life. Neuromodulation is a major component of multi-modal interdisciplinary approaches to chronic pain management, which includes opioid and nonopioid medications. In randomized controlled trials, spinal cord stimulation (SCS) has been shown to reduce pain and decrease short-term opioid use for patients. This study sought to evaluate the effect of SCS on longer term opioid and non-opioid pain medication usage among patients over ≥3 years of follow-up. Patients and Methods: Claims analysis was conducted using the Merative™ MarketScan® Commercial Database. Patients aged ≥18 who initiated SCS between 1/1/2010 and 3/31/2021 with ≥1 year of baseline data and ≥3 years of follow-up data were included. Opioid discontinuation, daily dose (DD) reduction, proportion of days covered (PDC), concomitant co-medication with benzodiazepines and/or gabapentinoids, and polypharmacy were evaluated during the baseline and follow-up periods. Adjusted logistic regression was used to evaluate the impact of baseline dosages on discontinuation and dose reduction. Results: During follow-up, 60% of 2,669 SCS patients either discontinued opioid use or reduced opioid DD by at least 20% from baseline; another 15% reduced DD by 1-19%. Logistic regression showed patients with higher baseline dosages were less likely to discontinue opioids completely (odds ratio[OR] 95% confidence intervals[CI]: 0.31[0.18,0.54]) but more likely to reduce their daily dose (OR[CI]: 7.14[4.00,12.73], p<0.001). Mean PDC with opioids decreased from 0.58 (210 of 365 days) at baseline to 0.51 at year 3 (p<0.001). With SCS, co-medication with benzodiazepines decreased from 47.3% at baseline to 30.3% at year 3, co-medication with gabapentinoids reduced from 58.6% to 42.2%, and polypharmacy dropped from 15.6% to 9.6% (all p<0.001). Conclusion: Approximately three-quarters of patients who received SCS therapy either discontinued or reduced systemic opioid use over the study period. SCS could assist in reducing long-term reliance on opioids and other pain medications to treat chronic non-cancer pain.

Modeling electrical impedance in brain tissue with diffusion tensor imaging for functional neurosurgery applications.

Objective.Decades ago, neurosurgeons used electrical impedance measurements in the brain for coarse intraoperative tissue differentiation. Over time, these techniques were largely replaced by more refined imaging and electrophysiological localization. Today, advanced methods of diffusion tensor imaging (DTI) and finite element method (FEM) modeling may permit non-invasive, high-resolution intracerebral impedance prediction. However, expectations for tissue-impedance relationships and experimentally verified parameters for impedance modeling in human brains are lacking. This study seeks to address this need.Approach.We used FEM to simulate high-resolution single- and dual-electrode impedance measurements along linear electrode trajectories through (1) canonical gray and white matter tissue models, and (2) selected anatomic structures within whole-brain patient DTI-based models. We then compared intraoperative impedance measurements taken at known locations along deep brain stimulation (DBS) surgical trajectories with model predictions to evaluate model accuracy and refine model parameters.Main results.In DTI-FEM models, single- and dual-electrode configurations performed similarly. While only dual-electrode configurations were sensitive to white matter fiber orientation, other influences on impedance, such as white matter density, enabled single-electrode impedance measurements to display significant spatial variation even within purely white matter structures. We compared 308 intraoperative single-electrode impedance measurements in five DBS patients to DTI-FEM predictions at one-to-one corresponding locations. After calibration of model coefficients to these data, predicted impedances reliably estimated intraoperative measurements in all patients (R=0.784±0.116, n=5). Through this study, we derived an updated value for the slope coefficient of the DTI conductance model published by Tuch et al., k=0.0649 S·s/mm3(original k=0.844), for use specifically in humans at physiological frequencies.Significance.This is the first study to compare impedance estimates from imaging-based models of human brain tissue to experimental measurements at the same locations in vivo. Accurate, non-invasive, imaging-based impedance prediction has numerous applications in functional neurosurgery, including tissue mapping, intraoperative electrode localization, and DBS.