J. Nicole Bentley

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.

Optogenetics in epilepsy.

Optogenetics, the use of light to stimulate or inhibit neural circuits via viral transduction of protein channels, has emerged as a possible method of treating epilepsy. By introducing viral vectors carrying algal-derived cation or anion channels, known as opsins, neurons that initiate or propagate seizures may be silenced. To date, studies using this technique have been performed in animal models, and current efforts are moving toward more sophisticated nonhuman primate models. In this paper, the authors present a brief overview of the development of optogenetics and review recent studies investigating optogenetic modification of circuits involved in seizures. Further developments in the field are explored, with an emphasis on how optogenetics may influence future neurosurgical interventions.

Data-driven model comparing the effects of glial scarring and interface interactions on chronic neural recordings in non-human primates.

OBJECTIVE We characterized electrode stability over twelve weeks of impedance and neural recording data from four chronically-implanted Utah arrays in two rhesus macaques, and investigated the effects of glial scarring and interface interactions at the electrode recording site on signal quality using a computational model. APPROACH A finite-element model of a Utah array microelectrode in neural tissue was coupled with a multi-compartmental model of a neuron to quantify the effects of encapsulation thickness, encapsulation resistivity, and interface resistivity on electrode impedance and waveform amplitude. The coupled model was then reconciled with the in vivo data. Histology was obtained seventeen weeks post-implantation to measure gliosis. MAIN RESULTS From week 1-3, mean impedance and amplitude increased at rates of 115.8 kΩ/week and 23.1 μV/week, respectively. This initial ramp up in impedance and amplitude was observed across all arrays, and is consistent with biofouling (increasing interface resistivity) and edema clearing (increasing tissue resistivity), respectively, in the model. Beyond week 3, the trends leveled out. Histology showed that thin scars formed around the electrodes. In the model, scarring could not match the in vivo data. However, a thin interface layer at the electrode tip could. Despite having a large effect on impedance, interface resistivity did not have a noticeable effect on amplitude. SIGNIFICANCE This study suggests that scarring does not cause an electrical problem with regard to signal quality since it does not appear to be the main contributor to increasing impedance or significantly affect amplitude unless it displaces neurons. This, in turn, suggests that neural signals can be obtained reliably despite scarring as long as the recording site has sufficiently low impedance after accumulating a thin layer of biofouling. Therefore, advancements in microelectrode technology may be expedited by focusing on improvements to the recording site-tissue interface rather than elimination of the glial scar.

Patient misconceptions concerning lumbar spondylosis diagnosis and treatment

OBJECT Patient outcome measures are becoming increasingly important in the evaluation of health care quality and physician performance. Of the many novel measures currently being explored, patient satisfaction and other subjective measures of patient experience are among the most heavily weighted. However, these subjective measures are strongly influenced by a number of factors, including patient demographics, level of understanding of the disorder and its treatment, and patient expectations. In the present study, patients referred to a neurosurgery clinic for degenerative spinal disorders were surveyed to determine their understanding of lumbar spondylosis diagnosis and treatment. METHODS A multiple-choice, 6-question survey was distributed to all patients referred to a general neurosurgical spine clinic at a tertiary care center over a period of 11 months as a quality improvement initiative to assist the provider with individualized patient counseling. The survey consisted of questions designed to assess patient understanding of the role of radiological imaging in the diagnosis and treatment of low-back and leg pain, and patient perception of the indications for surgical compared with conservative management. Demographic data were also collected. RESULTS A total of 121 surveys were included in the analysis. More than 50% of the patients indicated that they would undergo spine surgery based on abnormalities found on MRI, even without symptoms; more than 40% of patients indicated the same for plain radiographs. Similarly, a large proportion of patients (33%) believed that back surgery was more effective than physical therapy in the treatment of back pain without leg pain. Nearly one-fifth of the survey group (17%) also believed that back injections were riskier than back surgery. There were no significant differences in survey responses among patients with a previous history of spine surgery compared with those without previous spine surgery. CONCLUSIONS These results show that a surprisingly high percentage of patients have misconceptions regarding the diagnosis and treatment of lumbar spondylosis, and that these misconceptions persist in patients with a history of spine surgery. Specifically, patients overemphasize the value of radiological studies and have mixed perceptions of the relative risk and effectiveness of surgical intervention compared with more conservative management. These misconceptions have the potential to alter patient expectations and decrease satisfaction, which could negatively impact patient outcomes and subjective valuations of physician performance. While these results are preliminary, they highlight a need for improved communication and patient education during surgical consultation for lumbar spondylosis.

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.

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 Parkinsons 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 Parkinsons 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.

Treatment of AVM-Associated Epilepsy and the Factors Influencing Outcomes.

erebrovascular etiologies, including arteriovenous malformations (AVMs), account for up to 15% cases of C epilepsy (7). The risks of hemorrhage associated with these lesions have been well documented; however, the treatment of seizures in patients harboring cerebral AVMs is less well studied (16). Epilepsy is the most common clinical manifestation of unruptured AVMs and second only to hemorrhage in those with ruptures (12). Crawford et al. (4) studied the factors associated with AVMs that increase the likelihood of seizures and found that, overall, the incidence was low, with just 6% carrying a diagnosis of epilepsy before hemorrhage. This is in contrast to prior studies that cited an incidence of 17%e40% in unruptured AVMs (11, 13). Turjman et al. (16) reported their findings on seizure risk related to the angioarchitecture of the AVMs and found that superficial location with feeding by the external carotid artery, or a temporoparietal superficial location and feeding by the middle cerebral artery, were more predictive of epilepsy, an expected result when considering that proximity to cortex results in a more epileptogenic state. Most of these patients present with a first-time seizure; however, up to 43% of patients with newly diagnosed AVMs present with recurrent seizures (9).

A simple, inexpensive method for subcortical stereotactic targeting in nonhuman primates

BACKGROUND Many current neuroscience studies in large animal models have focused on recordings from cortical structures. While sufficient for analyzing sensorimotor systems, many processes are modulated by subcortical nuclei. Large animal models, such as nonhuman primates (NHP), provide an optimal model for studying these circuits, but the ability to target subcortical structures has been hampered by lack of a straightforward approach to targeting. NEW METHOD Here we present a method of subcortical targeting in NHP that uses MRI-compatible titanium screws as fiducials. The in vivo study used a cellular marker for histologic confirmation of accuracy. RESULTS Histologic results are presented showing a cellular stem cell marker within targeted structures, with mean errors ± standard deviations (SD) of 1.40 ± 1.19 mm in the X-axis and 0.9 ± 0.97 mm in the Z-axis. The Y-axis errors ± SD ranged from 1.5 ± 0.43 to 4.2 ± 1.72 mm. COMPARISON WITH EXISTING METHODS This method is easy and inexpensive, and requires no fabrication of equipment, keeping in mind the goal of optimizing a technique for implantation or injection into multiple interconnected areas. CONCLUSION This procedure will enable primate researchers to target deep, subcortical structures more precisely in animals of varying ages and weights.

Robust tactile sensory responses in finger area of primate motor cortex relevant to prosthetic control

OBJECTIVE Challenges in improving the performance of dexterous upper-limb brain-machine interfaces (BMIs) have prompted renewed interest in quantifying the amount and type of sensory information naturally encoded in the primary motor cortex (M1). Previous single unit studies in monkeys showed M1 is responsive to tactile stimulation, as well as passive and active movement of the limbs. However, recent work in this area has focused primarily on proprioception. Here we examined instead how tactile somatosensation of the hand and fingers is represented in M1. APPROACH We recorded multi- and single units and thresholded neural activity from macaque M1 while gently brushing individual finger pads at 2 Hz. We also recorded broadband neural activity from electrocorticogram (ECoG) grids placed on human motor cortex, while applying the same tactile stimulus. MAIN RESULTS Units displaying significant differences in firing rates between individual fingers (p  <  0.05) represented up to 76.7% of sorted multiunits across four monkeys. After normalizing by the number of channels with significant motor finger responses, the percentage of electrodes with significant tactile responses was 74.9%  ±  24.7%. No somatotopic organization of finger preference was obvious across cortex, but many units exhibited cosine-like tuning across multiple digits. Sufficient sensory information was present in M1 to correctly decode stimulus position from multiunit activity above chance levels in all monkeys, and also from ECoG gamma power in two human subjects. SIGNIFICANCE These results provide some explanation for difficulties experienced by motor decoders in clinical trials of cortically controlled prosthetic hands, as well as the general problem of disentangling motor and sensory signals in primate motor cortex during dextrous tasks. Additionally, examination of unit tuning during tactile and proprioceptive inputs indicates cells are often tuned differently in different contexts, reinforcing the need for continued refinement of BMI training and decoding approaches to closed-loop BMI systems for dexterous grasping.

Anatomy of the Posterior Cord and Its Branches

Abstract The posterior divisions from each of the three trunks of the brachial plexus join behind the clavicle to form the posterior cord. Three terminal branches arise directly from the cord at this level: the upper subscapular nerve, thoracodorsal nerve, and lower subscapular nerve. The main trunk continues distally, terminating as the axillary and radial nerves. The axillary nerve innervates the deltoid and provides a sensory branch to the skin overlying this muscle. The radial nerve continues into the arm and divides into superficial and deep branches at the elbow, the former supplying sensation to the dorsal hand, and the latter providing innervation to muscles in the extensor compartment of the distal arm. Variations at every level are described, extending from the nerve roots contributing to the plexus, to the pattern of innervation over the dorsal hand.