Search

Objective: Our aim is to explore the value of intraoperative facial motor evoked potentials (FMEP) for facial outcomes in cerebellopontine angle (CPA) tumor surgery to provide an evidence-based consensus standard for future clinical practice and prospective studies., Methods: Electronic databases were searched from inception to June 2023. Study quality was assessed with the QUADAS-2 tool. Bivariate and random-effects models for meta-analysis and meta-regression generated summary receiver operating characteristic curves (ROC) and forest plots for estimates of sensitivity and specificity., Results: We included 17 studies (1,206 participants). Sensitivity was lower in the immediate (IM) post-operative (0.76, 95% CI 0.65-0.84) compared to follow-up (FU) period (0.82, 95% CI 0.74-0.88) while specificity was similar in both groups (IM, 0.94, 95% CI 0.89-0.97; FU, 0.93, 95% CI 0.87-0.96). Data driven estimates improved FMEP performance but require confirmation from future studies. Amplitude cutoff criteria and studies that scored new deficits as worse than House-Brackmann (HB) grade 2 yielded best sensitivities., Conclusions: FMEP demonstrated statistically significant accuracy for facial function monitoring. Implementation of FMEPs varied widely across studies., Significance: Our study is the first systematic review with meta-analysis to demonstrate that intraoperative FMEP is valuable in CPA tumor surgery for facial outcomes. Meta-regression identified the methods that were most useful in the application of FMEPs., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: The aim of this study was to compare stimulation thresholds and current densities in the brain for transcranial motor evoked potentials (tcMEPs) from the hands and feet with linked quadripolar (LQP), M3-M4 and C1-C2 electrode montages., Methods: Twenty-five patients underwent cerebral vascular surgery with tcMEP monitoring. tcMEP voltage thresholds were compared between LQP (C1, M3, C2, M4), C1-C2, and M3-M4 montages. In a finite element model (FEM), hand, arm, and leg regions of interest (ROIs) on the cortical motor homunculus were segmented. Current densities in these ROIs at tcMEP thresholds were compared across tcMEP electrode montages., Results: LQP tcMEP thresholds were 61.5 volts for hands and 95.2 volts for feet. Thresholds were higher for M3-M4 (hands, 89.4 V; feet, 141.3 V) and C1-C2 (hands: 137.3 V; feet: 194.7 V). Total current at threshold voltage was greater for LQP (hands, 210.9 mA; feet, 311.3 mA) compared to M3-M4 (hands, 166.8 mA; feet, 256.6 mA), but similar to C1-C2 (hands, 246.7 mA; feet, 341.1 mA). In FEM simulations, current density and local current density topography in the hand ROI at threshold were very similar for LQP, M3-M4 and C1-C2., Conclusions: TcMEP voltage thresholds were least for LQP, and lesser for M3-M4 compared to C1-C2. In FEM simulations, resistance to current to hand ROI was ordered the same (LQP < M3-M4 < C1-C2). The local distribution of current density in motor cortex with tcMEP was mainly determined by cortical geometry., Significance: Current densities and resistance to current simulated with FEM may explain threshold requirements for tcMEP electrode montages., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Intraoperative neurophysiological monitoring (IONM) was investigated as a complex intervention (CI) as defined by the United Kingdom Medical Research Council (MRC) in published studies to identify challenges and solutions in estimating IONM's effects on postoperative outcomes., Methods: A scoping review to April 2022 of the influence of setting on what was implemented as IONM and how it influenced postoperative outcomes was performed for studies that compared IONM to no IONM cohorts. IONM complexity was assessed with the iCAT&#95;SR tool. Causal graphs were used to represent this complexity., Results: IONM implementation depended on the surgical procedure, institution and/or surgeon. "How" IONM influenced neurologic outcomes was attributed to surgeon or institutional experience with the surgical procedure, surgeon or institutional experience with IONM, co-interventions in addition to IONM, models of IONM service delivery and individual characteristics of the IONM provider. Indirect effects of IONM mediated by extent of tumor resection, surgical approach, changes in operative procedure, shorter operative time, and duration of aneurysm clipping were also described. There were no quantitative estimates of the relative contribution of these indirect effects to total IONM effects on outcomes., Conclusions: IONM is a complex intervention whose evaluation is more challenging than that of a simple intervention. Its implementation and largely indirect effects depend on specific settings that are usefully represented in causal graphs., Significance: IONM evaluation as a complex intervention aided by causal graphs and multivariable analysis could provide a valuable framework for future study design and assessments of IONM effectiveness in different settings., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Surgical treatment for symptomatic Chiari I malformation involves surgical decompression of the craniovertebral junction. Given the proximity of critical brainstem structures, intraoperative neuromonitoring (IONM) is employed for safe decompression in some institutions. However, IONM adds time and cost to the operation, and the benefit to the patient has not been defined. Given the diversity in surgical practices, there is no evidence-based standard of care regarding when to use IONM and which modalities are most helpful. The purpose of this study was to review a single-surgeon experience with IONM in order to determine the sensitivity, specificity, and predictive values of various IONM modalities routinely used in pediatric Chiari I decompression; to examine the associations between patient, clinical, and radiographic characteristics and IONM alerts; and to obtain data regarding the usefulness of these modalities during the surgical process to improve patient outcomes., Methods: A retrospective review was performed for 300 consecutive pediatric patients who underwent suboccipital craniectomy and C1 laminectomy for Chiari decompression performed by a single surgeon over a 15-year period. Clinical, radiographic, and IONM data were collected. Radiographic measurements of the skull base morphological abnormalities, including clival angle, Chamberlain's line, and Grabb-Oakes line, were compared between patients with and without true IONM signal changes., Results: A total of 291 cases were included, with an age range of 6 months to 19 years. Among 291 cases, somatosensory evoked potentials (SSEPs) were monitored in 291, motor evoked potentials (MEPs) in 209, cranial nerve spontaneous electromyography (sEMG) in 290, and brainstem auditory evoked potentials (BAEPs) in 110. Sensitivity, specificity, positive predictive value, and negative predictive value, respectively, were as follows: 1.00, 1.00, 1.00, and 1.00 for SSEPs; 1.00, 0.99, 0.67, and 1.00 for MEPs; 0.00, 0.88, 0.00, and 1.00 for sEMG; and not appliable, 1.00, not applicable, and 1.00 for BAEPs. Six patients had true IONM signal changes. These patients had radiographic evidence of more severe concomitant craniocervical instability and basilar invagination, with steeper clival angles (124° vs 146°, p = 0.02) and larger Grabb-Oakes lines (10.1 mm vs 6.7 mm, p = 0.02), when compared with the patients without any true IONM changes., Conclusions: Intraoperative neuromonitoring may be best utilized for patients who show radiographic features of abnormal skull base morphology, defined as a clival angle < 135° or Grabb-Oakes line > 9 mm. When IONM is employed, SSEP and MEP monitoring are the most useful modalities.

Meningiomas are the most common intradural extramedullary tumors, followed by nerve sheath tumors that can also grow extradurally. Metastases are the most frequent extradural tumors and most commonly affect the thoracic vertebrae. Spinal fractures with column dislocation and/or instability require surgical fixation. Spine surgery for an extramedullary tumor or fracture usually involves decompression of neural elements and instrumentation for stabilization. These procedures risk spinal cord and nerve root injury. The incidence of nerve root deficits after resection of nerve sheath tumors is particularly high since the tumor grows from the rootlets. Intraoperative neurophysiologic monitoring and mapping techniques have been introduced to prevent iatrogenic neurologic deficits. These include motor and sensory evoked potentials, electromyography, compound muscle action potentials, and the bulbocavernosus reflex. The combination of techniques chosen for a particular procedure depends on the surgical level and the character of the lesion., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To evaluate and compare efficacy of intraoperative neurophysiological monitoring (IONM) and intraoperative transcranial Doppler (TCD) techniques for identification of hypoperfusion during carotid artery clamp and hyperperfusion after release of occlusion during carotid endarterectomy., Methods: This was a retrospective, consecutive case series of 152 patients undergoing carotid endarterectomy between June 2018 and March 2020. Somatosensory evoked potentials, motor evoked potentials, electroencephalogram, and TCD were obtained., Results: Three patient cohorts were observed after clamping the carotid artery: A, in 132 of 152 patients (87%), TCD blood flow velocity decreased by <50% and there were no changes in IONM; B, in 5 of 152 (3%) patients, TCD blood flow rate was reduced 50%-100% with no changes in IONM; C, in 15 patients (10%), blood flow velocity was reduced by 50%-100% and all IONM modalities met warning criteria. With increased blood pressure, IONM and blood flow velocities improved to less than warning criteria in 8 of 15 patients. In 6 of the 7 remaining patients, IONM modalities recovered to baseline immediately after clamps were removed from the carotid artery. The 1 patient with persistent motor evoked potential deterioration experienced postoperative proximal muscle weakness, which recovered 48 hours later. In 22 patients, TCD detected hyperperfusion at the moment of clamp release., Conclusions: TCD blood flow velocity is correlated with motor evoked potential and somatosensory evoked potential amplitude changes after clamping. After declamping, TCD can detect hyperperfusion and help regulate blood pressure to prevent hyperperfusion., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: At our institution, in vivo facial nerve mapping (FNM) is used during vascular anomaly (VAN) surgeries involving the facial nerve (FN) to create an FN map and prevent injury. During mapping, FN anatomy seemed to vary with VAN type. This study aimed to characterize FN branching patterns compared to published FN anatomy and VAN type., Study Design: Retrospective study of surgically relevant facial nerve anatomy., Methods: VAN patients (n = 67) with FN mapping between 2005 and 2018 were identified. Results included VAN type, FN relationship to VAN, FNM image with branch pattern, and surgical approach. A Fisher exact test compared FN relationships and surgical approach between VAN pathology, and FN branching types to published anatomical studies. MATLAB quantified FN branching with Euclidean distances and angles. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) analyzed quantitative FN patterns amongst VAN types., Results: VANs included were hemangioma, venous malformation, lymphatic malformation, and arteriovenous malformation (n = 17, 13, 25, and 3, respectively). VAN FN patterns differed from described FN anatomy (P < .001). PCA and HCA in MATLAB-quantified FN branching demonstrated no patterns associated with VAN pathology (P = .80 and P = .91, one-way analysis of variance for principle component 1 (PC1) and priniciple component 2 (PC2), respectively). FN branches were usually adherent to hemangioma or venous malformation as compared to coursing through lymphatic malformation (both P = .01, Fisher exact)., Conclusions: FN branching patterns identified through electrical stimulation differ from cadaveric dissection determined FN anatomy. This reflects the high sensitivity of neurophysiologic testing in detecting small distal FN branches. Elongated FN branches traveling through lymphatic malformation may be related to abnormal nerve patterning in these malformations., Level of Evidence: NA Laryngoscope, 130:2708-2713, 2020., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To improve estimates of motor evoked potential (MEP) performance during spine deformity surgeries by accounting for potential confounders., Methods: A meta-analysis of MEPs for spine deformity surgeries determined the probability of a MEP deterioration which recovered by the end of surgery, P(RSC), and the conditional probability of no new post-operative deficit given an RSC, P(NND|RSC), stratified by category of intraoperative adverse event associated with the MEP deterioration. A structural causal model (SCM) and propensity score matching accounted for intraoperative adverse events and patient diagnosis as potential confounders., Results: MEPs changes (either reversible, RSC or irreversible, IRREV) were reported for 295 of 5055 cases (6%) in 21 studies. The probability of no new motor deficit, P(NND), plotted against the probability of a RSC, P(RSC), for studies in the meta-analysis was highly significant (r = 0.71, p < 0.001). P(RSC) was 0.76 for an alert associated with correction, less for osteotomies (0.48, p = 0.0008), and tended to be higher for hypotension (0.92, p = 0.06). P(NND|RSC) was 0.94 for correction, less for positioning (0.82), and osteotomies (0.86), and greater for hypotension (1.0). In the SCM, a RSC after an alert was a highly significant and independent predictor of no new motor deficits (odds 25.2, p < 0.001)., Conclusion: There are significant differences in P(RSC) for hypotension and osteotomies, and in P(NND) for osteotomies and instrumentation, compared to correction. P(RSC) is a significant and independent predictor of outcomes., Significance: When MEPs are used for spine deformity surgeries, accounting for adverse events associated with an alert and patient diagnosis as potential confounders is expected to improve RSC prediction of post-operative outcomes and estimates of RSC efficacy in improving outcomes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The article Is the new ASNM intraoperative neuromonitoring supervision "guideline" a trustworthy guideline? A commentary, written by Stanley A. Skinner, Elif Ilgaz Aydinlar, Lawrence F. Borges, Bob S. Carter, Bradford L. Currier, Vedran Deletis, Charles Dong, John Paul Dormans, Gea Drost, Isabel Fernandez‑Conejero, E. Matthew Hoffman, Robert N. Holdefer, Paulo Andre Teixeira Kimaid, Antoun Koht, Karl F. Kothbauer, David B. MacDonald, John J. McAuliffe III, David E. Morledge, Susan H. Morris, Jonathan Norton, Klaus Novak, Kyung Seok Park, Joseph H. Perra, Julian Prell, David M. Rippe, Francesco Sala, Daniel M. Schwartz, Martín J. Segura, Kathleen Seidel, Christoph Seubert, Mirela V. Simon, Francisco Soto, Jeffrey A. Strommen, Andrea Szelenyi, Armando Tello, Sedat Ulkatan, Javier Urriza and Marshall Wilkinson, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 05 January 2019 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on 30 January 2019 to © The Author(s) 2019 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. The original article has been corrected.

Importance: Facial vascular anomalies are surgical challenges due to their vascularity and facial nerve distortion. To assist facial vascular anomaly surgical treatment, presurgical percutaneous facial nerve stimulation and recording of compound motor action potentials can be used to map the facial nerve branches. During surgery, the nerve map and continuous intraoperative motor end plate potential monitoring can be used to reduce nerve injury., Objective: To investigate if preoperative facial nerve mapping (FNM) is associated with intraoperative facial nerve injury risk and safe surgical approach options compared with standard nerve integrity monitoring (NIM)., Design, Setting, and Participants: This investigation was a historically controlled study at a tertiary vascular anomaly center in Seattle, Washington. Participants were 92 pediatric patients with facial vascular anomalies undergoing definitive anomaly surgery (from January 1, 1999, through January 1, 2015), with 2 years' follow-up. In retrospective review, a consecutive FNM patient cohort after 2005 (FNM group) was compared with a consecutive historical cohort (1999-2005) (NIM group)., Main Outcomes and Measures: Postoperative facial nerve function and selected surgical approach. For NIM and FNM comparisons, statistical analysis calculated odds ratios of nerve injury and operative approach, and time-to-event methods analyzed operative time., Results: The NIM group had 31 patients (median age, 3.3 years [interquartile range, 2.2-11.4 years]; 20 [65%] male), and the FNM group had 61 patients (median age, 4.4 years [interquartile range, 1.5-11.0 years]; 26 [43%] male). In both groups, lymphatic malformation resection was most common (19 of 31 [61%] in the NIM group and 32 of 61 [52%] in the FNM group), and the median anomaly volumes were similar (52.4 mL; interquartile range, 12.8-183.3 mL in the NIM group and 65.4 mL; interquartile range, 18.8-180.2 mL in the FNM group). Weakness in the facial nerve branches at 2 years after surgery was more common in the NIM group (6 of 31 [19%]) compared with the FNM group (1 of 61 [2%]) (percentage difference, 17%; 95% CI, 3%-32%). Anterograde facial nerve dissection was used more in the NIM group (27 of 31 [87%]) compared with the FNM group (28 of 61 [46%]) (percentage difference, 41%; 95% CI, 24%-58%). Treatment with retrograde dissection without identification of the main trunk of the facial nerve was performed in 21 of 61 (34%) in the FNM group compared with 0 of 31 (0%) in the NIM group. Operative time was significantly shorter in the FNM group, and patients in the FNM group were more likely to complete surgery sooner (adjusted hazard ratio, 5.36; 95% CI, 2.00-14.36)., Conclusions and Relevance: Facial nerve mapping before facial vascular anomaly surgery was associated with less intraoperative facial nerve injury and shorter operative time. Mapping enabled direct identification of individual intralesional and perilesional nerve branches, reducing the need for traditional anterograde facial nerve dissection, and allowed for safe removal of some lesions after partial nerve dissection through transoral or direct excision.

The use of intraoperative neurophysiological monitoring (IONM) has grown despite an absence of randomized controlled trials that might unequivocally demonstrate improved outcomes. At issue is how to demonstrate value when other evidence indicates patient harms (opportunity cost) if IONM is withheld for the sake of randomization. In this article we review other non-randomized methods to assess the effects of IONM on post-operative outcomes. We also examine how clinical equipoise may resolve whether (or not) an anticipated controlled study is ethical. We conclude that the value of IONM in a particular surgical setting should be determined by a benefits/harms analysis based on all the available evidence.

Objective: MEPs are used as surrogate endpoints to predict the effectiveness of interventions, made in response to MEP deterioration, in avoiding new postoperative deficits. MEP performance in capturing intervention effects on these outcomes was investigated., Methods: A meta-analysis of studies using MEPs during intracranial vascular surgeries between 2003 and 2014 was performed. MEP diagnostic performance and relative risk of new postoperative deficits for reversible compared with irreversible MEP changes were determined. Intervention efficacy in reversing MEP deterioration and postoperative outcomes was compared across studies., Results: MEP diagnostic performance compared favorably with that of other tests used in medicine, with all likelihood ratios >10. The summary relative risk comparing reversible and irreversible changes was 0.40, indicating a 60% decrease in new deficits for reversible MEP changes. The proportion of MEP deteriorations which recovered was negatively correlated with the proportion of new postoperative deficits (r=-0.81, p<.005)., Conclusions: The effectiveness of interventions in recovering an MEP decline was predictive of preserved neurologic status. MEPs are provisionally qualified as surrogate endpoints given potentially major harms to the patient if they are not used, compared to the minimal harms and costs associated with their use., Significance: The performance of MEPs as substitute, or surrogate, endpoints during intracranial vascular surgeries for new deficits in motor strength in the immediate postoperative period was directly assessed for ten recent studies., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

SEPs and MEPs (EPs) are often used as surrogates for postoperative clinical endpoints of muscle strength and sensory status, as these true endpoints are not available during surgery. EPs as surrogate endpoints were evaluated using a three step framework (Analytical Validation, Qualification, Utilization) recently proposed by the Institute of Medicine (USA). EP performance on Analytical Validation may surpass that of some other biomarkers used in medicine (tumor size, cardiac troponin). Qualification of EP surrogates was evaluated with guidelines for causation proposed by A.B. Hill, which supported causal links between surgical events and EP changes and revised estimates of EP diagnostic test performance for three illustrative studies. Qualification was also addressed with a 3×2 contingency analysis which demonstrated decreased deficit proportions for EP declines which recovered after surgeon intervention. Utilization of EP surrogates will depend on surgical procedure and alert criteria. EPs are often used as surrogate endpoints to avoid new postoperative deficits. Although not fully validated, their continued use as surrogates during surgical procedures with the potential for significant morbidity is justified by their potential to help avoid injury and the absence of "second best options.", (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Purpose: The aim was to compare the effects of propofol and desflurane anesthesia on transcranial motor evoked potentials (MEPs) from pediatric patients undergoing surgery for spinal deformities., Methods: Desflurane and propofol cohorts (25 patients each) were obtained retrospectively and matched for patient characteristics and surgical approach. MEPs from the thenar eminence and abductor hallucis were compared during maintenance anesthesia on desflurane (0.6-0.8 MAC) or propofol infusion (150-300 μg/kg/min). MEP amplitudes and durations were obtained for successive 30-min intervals for 150 min, beginning 60 min after maintenance anesthesia., Results: Mean peak to peak amplitudes of MEPs under desflurane anesthesia from the thenar eminence (419 μV) and abductor hallucis (386 μv) were not significantly different from those under propofol (608 μV, 343 μV, thenar, and abductor hallucis, respectively). Stimulation was greater by 42 V and 136 mA, and trains were slightly longer in the desflurane compared to the propofol group (p < 0.05). Most MEP amplitudes for the desflurane and propofol cohorts remained the same or increased (71 % of cases) when those after 150 min were compared to those in the first 30-min interval., Conclusions: MEPs with good amplitudes were obtained under desflurane only anesthesia that were comparable to propofol only anesthesia in pediatric patients during surgery for spinal deformities. There was no evidence for anesthetic fade over the time period examined. When used by itself, desflurane can be considered a viable alternative to propofol anesthesia.

Intervention-mediated recovery from adversely changed evoked potential recordings may provide evidence for improved outcomes during neurophysiological intraoperative monitoring. However, these reversible signal changes (RSCs) are ambiguous because the patient's neurologic status cannot be known either at signal decline or after intervention. This article describes methods to reduce this ambiguity. Randomized control trials are not always possible or ethical. Recent thought on grading evidence has acknowledged that guidelines first described by Sir Austin Bradford Hill may support evidence for causation. Causality guidelines identified RSCs most likely to be truly positive in three reported studies. Diagnostic statistics were revised accordingly. A range of revised positive predictive values and likelihood ratios was calculated in the three studies, using causality guidelines. The revised data were similar to those reported for other diagnostic tests used in medicine. The RSCs may be assessed using causality guidelines for more accurate reporting of diagnostic statistics while preserving information related to surgical intervention and recovery that is lost with end of surgery diagnostics or when RSCs are ignored. A method is described for including RSCs in diagnostic statistics. This approach will more readily permit assessment of the value of neurophysiological intraoperative monitoring in prediction and prevention of neurologic deficits.

Study Design: EMG threshold testing as a guide to accurate screw placement was examined during posterior cervical spine instrumentation. The accuracy of screw placements was compared with the surgeon blinded and unblinded to EMG thresholds., Objective: To determine the utility of EMG threshold testing in improving screw placements in the lateral mass and pedicles of the cervical/upper thoracic spine., Summary of Background Data: EMG threshold testing in the lumbar spine is generally thought to improve the accuracy of pedicle screw placements. These results may not generalize to the cervical spine, where smaller pedicles, bicortical pilot holes, and the orientation of lateral mass screws away from midline may result in different alert thresholds., Methods: Triggered EMG thresholds were obtained from pilot holes in 244 lateral mass and 113 pedicles from 32 patients. Thresholds were compared with the accuracy of screw placements as determined from postoperative computed tomography scans. The percentage of inaccurate and potentially dangerous (IAPD) screws with the surgeon blinded and unblinded to EMG thresholds was determined., Results: EMG threshold testing was more accurate in predicting IAPD screw trajectories in the pedicles (likelihood ratio 5.1) as compared with the lateral mass (likelihood ratio 2.9). In the pedicles, the number of IAPD screws decreased from 4.5% in the blinded controls to 0% in the unblinded group. In the lateral mass, there were no IAPD screw placements in the blinded control group, whereas 2% of the screws in the unblinded group were IAPD., Conclusions: EMG threshold testing in the cervical spine (C3, T1) is a moderately accurate diagnostic test and more predictive of potentially dangerous screw trajectories in the pedicles (C7, T1) as compared with the lateral mass (C3-C6). EMG threshold testing may decrease potentially dangerous screw placements in the pedicles, but may have less utility in the case of the lateral mass because of less reproducible placement of the stimulating probe.

During intracranial surgeries, cranial nerve (CN) X is most commonly monitored with electromyographic endotracheal tubes. Electrodes on these endotracheal tubes may be displaced from the vocal folds during positioning, and there is a learning curve for their correct placement. Cranial nerve XII is most commonly monitored with electrodes in the dorsum of the tongue, which are also prone to displacement because of their proximity to the endotracheal tube. A retrospective review was conducted of a consecutive series of 83 skull base surgeries using alternative sites for monitoring CN X and XII. On-going (spontaneous) and evoked electromyography (EMG) were obtained from the cricothyroid muscle for CN X and submental genioglossus for CN XII. Stimulation of CN X or XII evoked specific compound motor action potentials from these muscles, and well-defined on-going EMG was observed during tumor resection in the vicinity of CN X and XII. Volume-conducted responses from the adjacent platysma muscle during CN VII stimulation were identified by concomitant responses from the orbicularis oris and oculi. In conclusion, during skull base surgeries, CN X may be monitored with electrodes in the cricothyroid muscle and CN XII with electrodes in the submental genioglossus. These alternative sites are less prone to displacement of electrodes compared with the more commonly used EMG endotracheal tube and electrodes in the dorsum of the tongue. The cricothyroid muscle should not be used when the recurrent laryngeal nerve is at risk.

Oscillations in the beta frequency range (β-LFP) are widely distributed throughout the motor system, modulated by dopaminergic medications, and locally generated in the subthalamic nucleus (STN) and ventral intermediate nucleus of the thalamus (VIM). We investigated the feasibility of recording intraoperative β-LFP signals and their descriptive summary statistics during surgeries for deep brain stimulation (DBS). β-LFP from the microelectrode and stimulating lead were obtained from the STN in Parkinson's patients, and from the stimulating lead in the VIM of patients with Parkinson's disease or essential tremor. β-LFP power was obtained over 8 second epochs and displayed online as compressed spectral and density arrays and trend plots. In agreement with other studies, β-LFP power along microelectrode penetrations was greater in the STN as compared to sites dorsal and ventral to the nucleus. Differences in β-LFP power were also observed across the contacts of stimulating leads in the STN and VIM. The contact with greatest β-LFP power was either the most effective contact for clinical stimulation or adjacent to it. These results were obtained from conventional power measurements, spectral displays, and trend plots with equipment commonly used for intraoperative neuromonitoring. We conclude that β-LFP is an accessible and easily recorded signal intraoperatively with potential usefulness for DBS lead localization and clinical programming of the stimulating lead.

There remain conflicting models of the cerebellar control of limb movement, ranging from the suggestion that the inhibitory output from Purkinje cells (PCs) is meant to suppress unwanted muscle activity, to the hypothesis that the cerebellar cortex embodies complex internal models of limb dynamics. To test these ideas, we undertook a quantitative comparison of PC simple spike dynamics to those of muscle activity. We recorded simultaneously from Purkinje cells in the paravermal anterior lobe and from muscles of the hand and arm in the behaving monkey during a simple, sequential button pressing task. The task-related discharge of each neuron was determined from peri-event histograms aligned to the onset of the behavior. Bursts of discharge were more than twice as common as pauses, but there was no difference in their timing relative to movement. From the same recordings, the similarity between discharge and muscle activity was evaluated by calculating the cross correlation between firing rate and rectified EMG. Surprisingly, given the inhibitory projection of PCs, most of the bursts of PC discharge were positively correlated with muscle activity. Although our results do not support a simple correspondence of pauses and bursts with limb acceleration and deceleration respectively, they are consistent with a more complex PC regulation of cerebellar nuclear activity from task-related, corticopontine drive.

Objective: We sought an electrical modeling approach to evaluate the potential application of finite element method (FEM) modeling to predict current pathways and intensities in the brain after transcranial electrical stimulation., Methods: A single coronal MRI section through the head, including motor cortex, was modeled using FEM. White matter compartments with both anatomically realistic anisotropies in resistivity and with a homogeneous resistivity were modeled. Current densities in the brain were predicted for electrode sites on the scalp and after theoretical application of a conductive head restraint device., Results: Localized current densities were predicted for the model with white matter anisotropies. Differences in predicted peak current densities were related to location of stimulation sites relative to deep sulci in the brain and scalp shunting that was predicted to increase with inter-electrode proximity. A conductive head restraint device was predicted to shunt current away from the brain when a constant current source was used., Conclusions: The complex geometry of different tissue compartments in the head and their contrasting resistivities may jointly determine the strength and location of current densities in the brain after transcranial stimulation. This might be predictable with FEM incorporating white matter anisotropies. Conductive head restraint devices during surgery may be contraindicated with constant current stimulation., Significance: Individually optimized tcMEP monitoring and localized transcranial activation in the brain might be possible through FEM modeling.

Limb movement-related neurons in the cerebellar nuclei (CN) typically produce bursts of discharge in association with movement. Consequently, given the inhibitory nature of the Purkinje cell (PC) projection to CN, it is puzzling that only a minority of movement-related PCs pause; the majority burst. Some of the movement-related CN activity may be the result of excitation from collaterals of mossy and climbing fiber projections to the cerebellar cortex. The only other input to CN is diffuse and neuromodulatory, from locus ceruleus and raphe nuclei. To investigate the role of the excitatory mossy fiber input, single units in CN were recorded in macaque monkeys during the performance of reaching and manipulation tasks, before and after blocking the PC input with local microinjections of GABA(A) antagonists (bicuculline or SR95531). After these injections, the movement-related modulation of CN discharge was greater and began earlier, compared with the modulation in the preinjection group of neurons. These observations indicate that an important excitatory drive is provided by extracerebellar inputs to CN, most likely from collaterals of mossy fibers. PCs may serve primarily to regulate this activity, by either pausing or bursting as necessary.

Many different kinematic and kinetic signals have been proposed as possible variables under the control of the primary motor cortex. Despite the presence of direct projections to motor neurons, muscle activation has received less attention as a controlled variable. Furthermore, although it is well known that descending fibers project to multiple motor pools, an objective, quantitative study of the relation between neuronal modulation and the activity of groups of muscles has not previously been reported. We have recorded the discharge of 310 neurons located in the primary motor cortex of two monkeys, along with the activity of a variety of arm and hand muscles. Data were recorded while the monkey reached to and pressed a series of illuminated buttons. The similarity of a given neuron's discharge with respect to each muscle was determined by calculating the linear cross-correlation between its discharge rate and each rectified, filtered electromyogram. A "functional linkage vector" was then constructed, which expressed the similarity of that neuron's discharge to the entire set of muscles. We discovered discrete groups of functional linkage vectors within the high order muscle space for both monkeys which corresponded to functional properties of the neurons measured by other methods. Several of these groups appeared to represent a functional synergy of muscles, such as those required to extend the limb, press a button, or open the hand in preparation for the press. When the dimensionality of this space was reduced by a principal components analysis, the originally identified clusters of neurons remained well separated. These results are consistent with the hypothesis that the discharge of individual neurons in the primary motor cortex encodes the activity of a relatively small number of functionally relevant groups of muscles. It will be important to determine whether these results will also apply to more complex behavior, and to what extent these functional muscle synergy representations remain fixed across behaviors.

We recorded the activity of cerebellar Purkinje cells (PCs), primary motor cortical (M1) neurons, and limb EMG signals while monkeys executed a sequential reaching and button pressing task. PC simple spike discharge generally correlated well with the activity of one or more forelimb muscles. Surprisingly, given the inhibitory projection of PCs, only about one quarter of the correlations were negative. The largest group of neurons burst during movement and were positively correlated with EMG signals, while another significant group burst and were negatively correlated. Among the PCs that paused during movement most were negatively correlated with EMG. The strength of these various correlations was somewhat weaker, on average, than equivalent correlations between M1 neurons and EMG signals. On the other hand, there were no significant differences in the timing of the onset of movement related discharge among these groups of PCs, or between the PCs and M1 neurons. PC discharge was modulated largely in phase, or directly out of phase, with muscle activity. The nearly synchronous activation of PCs and muscles yielded positive correlations, despite the fact that the synaptic effect of the PC discharge is inhibitory. The apparent function of this inhibition is to restrain activity in the limb premotor network, shaping it into a spatiotemporal pattern that is appropriate for controlling the many muscles that participate in this task. The observed timing suggests that the cerebellar cortex learns to modulate PC discharge predictively. Through the cerebellar nucleus, this PC signal is combined with an underlying cerebral cortical signal. In this manner the cerebellum refines the descending command as compared with the relatively crude version generated when the cerebellum is damaged.

Simultaneous single neuron and local field potential (LFP) recordings were made in arm-related areas of the cerebellar nuclei (CN) and primary motor cortex (M1) of two monkeys during a reaching and button pressing task. Microstimulation of focal sites in CN caused short latency (median = 3.0 ms) increases in discharge in 25% of 210 M1 neurons. Suppressive effects were less common (13%) and observed at longer latencies (median = 9.9 ms). Stimulation in CN also caused reciprocal facilitation and suppression in averages of antagonist muscle electromyograms (EMGs). The latency of these effects was approximately 8-11 ms. In contrast to the selectivity of unit and EMG effects, stimulation-evoked changes in LFP occurred over a broad range of sites. There were no significant short-latency effects detected in cross-correlation histograms between single neurons in CN and M1. However, CN spike-triggered averages of M1 LFPs were observed in a few cases (10% of 126 cases). In one-half of these, there were effects both before and after the CN spikes, which may reflect causal effects from M1 to CN, as well as from CN to M1. Overall, these results demonstrate a spatially specific, short latency, primarily excitatory pathway from CN to M1. The relatively rare effects at the single neuron level may have resulted from the difficulty in achieving optimal alignment between cerebellar and cerebral sites because of the specificity of these connections.

A laminar analysis of the receptive field properties of relay cells in the binocular region of the tree shrew dorsal lateral geniculate nucleus (LGN) found three main subdivisions. Lamina 1 (receiving ipsilateral eye input) and lamina 2 (contralateral) comprise a pair of layers that contain only ON-center neurons. Laminae 4 (contralateral) and 5 (ipsilateral) comprise a pair of layers with mostly OFF-center cells (86%). Laminae 3 and 6 (both contralaterally innervated) also form a distinct pair, although lamina 3 contains a mixture of cells with ON-centers (43%) or OFF-centers (57%), and lamina 6 contains mostly cells with ON-OFF centers and suppressive surrounds (81%). Cells located in the interlaminar zones resembled neurons in laminae 3 and 6. In comparison with the cells in the OFF-center laminae 4 and 5, the ON-center cells in laminae 1 and 2 had smaller, more elliptical receptive field centers with stronger responses to flashed visual stimuli. In addition, cells in the ipsilateral eye laminae 1 and 5 showed a greater change in center diameter, with eccentricity from the area centralis, than cells in the contralateral eye laminae 2 and 4. Principal components analysis using six receptive field properties (latency to optic chiasm stimulation, receptive field center diameter, maintained discharge rate, response onset latency, peak spike density, and phasic-tonic index) suggested that the cells in laminae 3 and 6 and the interlaminar zones are W-like. Principal components analysis of the same receptive field properties in laminae 1, 2, 4, and 5 did not reveal differences clearly related to X-like (parvocellular) and Y-like (magnocellular) categories. Ninety-seven percent of the cells tested for linearity of spatial summation in laminae 1, 2, 4, and 5 were linear. We conclude that the dominant organizational features of the tree shrew LGN are the ON-center, OFF-center, and W pairs of layers that project to different regions within the striate cortex.

Neurons in the locus coeruleus (LC) encode information related to behavioral state in a tonic pattern of firing and information related to the occurrence of a sensory stimulus in a phasic pattern of firing. The effects of phasic stimulation of the LC (6 pulses at 30 Hz), designed to approximate its physiological activation by sensory stimuli, were studied in the lateral geniculate nucleus (LGN) of anesthetized rats. Phasic stimulation of the LC significantly increased neuronal firing in the LGN with a mean latency 320 ms from onset of stimulation. Receiver operating characteristic analyses on a trial-by-trial basis showed that phasic LC stimulation can result in a highly discriminable signal in the LGN. This increased neuronal firing rate in the LGN was specific for the site of stimulation and was reduced by the norepinephrine synthesis inhibitor alpha-methyl-p-tyrosine and by intravenous WB-4101 (alpha 1-receptor antagonist). Neurons in the LGN have a single-spike firing mode when sensory information is faithfully relayed from retina to cortex and a burst-firing mode when the transfer of this information is degraded. Phasic LC stimulation reduced burst firing (2-5 ms interspike intervals, ISIs) at low frequencies (< or = 4 Hz) in the LGN, and for some neurons there was an absolute decrease in burst-like ISIs after LC stimulation, despite an increase in mean firing rate.

The present study had two primary aims. The first was to determine the extent of the visual field of the deprived eye of a monocularly deprived cat using visual perimetry techniques, since recent reports have been contrary to previous research. The second aim was to determine whether enucleation of the experienced eye of a monocularly deprived cat was associated with any increase in the extent of the visual field of the deprived eye compared to forced usage (reverse-suture). The results indicate that the extent of the visual field using the deprived eye is limited to the ipsilateral monocular visual field. Further, enucleation of the experienced eye leads to a rapid expansion of the visual field of the deprived eye to include the entire ipsilateral hemifield which does not occur following reverse-suture. Possible reasons for the conflicting reports in the literature are discussed.

D-Amphetamine, 4-OH amphetamine, and epinephrine have been shown in many behavioral studies to facilitate memory when given post-training. The effect of these drugs on the maintained discharge of cells in the locus coeruleus (LC) was investigated using a route of administration (intraperitoneal) and a log-dose range of these drugs comparable to those used in the behavioral experiments. D-Amphetamine profoundly suppressed maintained discharge: an inhibitory effect was observed at every dose (0.1, 1.0, 10.0 mg/kg). In contrast, only the highest dose of 4-OH amphetamine (8.2 mg/kg) inhibited activity in the LC, and this effect was a modest one. Unlike the amphetamines, epinephrine (500 micrograms/kg) elevated maintained discharge. These results are discussed in the context of the hypothesized involvement of the LC in the enhancement of memory by these drugs.

The lateral geniculate nucleus (LGN) receives input from the retina that is spatially organized into a receptive-field center and surround. It maintains this organization in the signal that it sends to the visual cortex. Previous studies have focused on changes in the receptive-field 'surround' that are generated at the LGN, possibly as a local contrast enhancement mechanism. The present study suggests a role for the LGN in regulating the receptive-field center sensitivity under the control of GABAergic circuitry. Local microiontophoresis of the GABAA receptor antagonist bicuculline increased the contrast sensitivity of LGN relay cells to many spatial frequencies. Difference of Gaussians analysis showed that the increased was due to an increased sensitivity of the receptive-field center. Similar increases in receptive-field center sensitivity may be produced during behavioral arousal by the action of pontine and mesencephalic pathways upon the activity of the LGN GABAergic circuitry.

Changes in visual acuity brought about by altering competitive interactions between the eyes of cats monocularly deprived (MD) from natural eye opening to 7-12 months of age were studied. In MD cats given binocular experience, median visual acuity using the deprived eye was 0.75 c/deg. If the deprived eye was given a slight competitive advantage via reverse-suture, median visual acuity reached 1.52 c/deg. Further, giving the deprived eye the greatest competitive advantage was accomplished by complete removal of the experienced eye which yielded a median deprived eye acuity of 2.3 c/deg. Obstacle avoidance and stimulus size data were also obtained. The previously published electrophysiological effects of these manipulations on striate cortical cells were noted to mirror these increases in visual acuity and this correlation was discussed, as were the effects of analogous manipulations in the monkey and man.

In this review we describe how video-based image analysis systems are used to measure immunocytochemically labeled tissue. The general principles underlying hardware and software procedures are emphasized. First, the characteristics of image analyzers are described, including the densitometric measure, spatial resolution, gray scale resolution, dynamic range, and acquisition and processing speed. The errors produced by these instruments are described and methods for correcting or reducing the errors are discussed. Methods for evaluating image analyzers are also presented, including spatial resolution, photometric transfer function, short- and long-term temporal variability, and measurement error. The procedures used to measure immunocytochemically labeled cells and fibers are then described. Immunoreactive profiles are imaged and enhanced using an edge sharpening operator and then extracted using segmentation, a procedure which captures all labeled profiles above a threshold gray level. Binary operators, including erosion and dilation, are applied to separate objects and to remove artifacts. The software then automatically measures the geometry and optical density of the extracted profiles. The procedures are rapid and efficient methods for measuring simultaneously the position, geometry, and labeling intensity of immunocytochemically labeled tissue, including cells, fibers, and whole fields. A companion paper describes non-biological standards we have developed to estimate antigen concentration from the optical density produced by antibody labeling (Nabors et al., 1988).

The distribution and ultrastructure of neurons and neuropil labeled by an antiserum to gamma-aminobutyric acid (GABA) were examined in the lateral geniculate nucleus (LGN) of the tree shrew (Tupaia belangeri). The LGN of this species segregates center type and cell class into three distinct pairs of laminae: a medial pair (laminae 1 and 2) containing ON-center cells, a more lateral pair (4, 5) containing OFF-center cells, and 2 laminae (3, 6) containing W-like cells. The relationship between this laminar segregation and the distribution of GABA immunoreactivity was investigated in the present study. GABA-immunoreactive neurons and neuropil were present in all six of the laminae. However, both the density of labeled cells (adjusted for neuronal density across laminae) and the density of labeled neuropil showed a medial-to-lateral gradient. The adjusted density of labeled cells was higher laterally than medially, and the density of labeled neuropil was significantly greater in the more lateral OFF-center laminae and W-like laminae than in the medial two ON-center laminae. Thus, inhibitory, GABAergic influences may modulate to different degrees the visual signals in the ON, OFF, and W pathways. Labeled cells had a mean cross-sectional area (107 microns 2) approximately one-half that of unlabeled cells (216 microns 2). They constitute 16-34% of the neurons in the LGN. At the electron microscope level, three different kinds of labeled profile were observed. Vesicle containing profiles like the F2 profiles of cat were postsynaptic to retinal terminals and presynaptic to conventional dendrites. F1 axon terminals with dense clusters of vesicles were also labeled as were some myelinated axons. Another labeled profile, which we suggest should be called an F3 process, was a large dendrite of irregular caliber with punctate groups of vesicles near the synapse. Our results suggest that GABAergic circuitry is an important part of the functional organization in the LGN of the tree shrew.

The lateral geniculate nucleus conveys the center-surround organized retinal receptive fields to the cortex in a way that does not significantly alter their spatial structure. However, non-retinal influences may change the 'strength' (detectability) of the signal under conditions of anesthesia, arousal and attention. A previous analysis of receiver operating characteristic curves in cat suggests that a reduction in signal detectability occurs in lateral geniculate nucleus (LGN) relay cells in anesthetized animals in comparison to the retinal afferents. In the present study, it was found that antagonism of GABAA receptors with bicuculline (BIC) increased signal detectability in LGN relay cells in the tree shrew (Tupaia belangeri). This change is consistent with the hypothesis that feedforward and/or feedback GABAergic circuits in the LGN differentially affect the retinogeniculate transfer ratio for visually driven activity versus maintained (spontaneous) activity. Under conditions of arousal or attention, signal detectability may be increased by brainstem activation, thus increasing the flow of information in the visual system.