Object. In this prospective study the authors' objective was to evaluate the accuracy of deep brain stimulation (DBS) electrode placement using image guidance for direct anatomical targeting with intraoperative CT.Methods. Preoperative 3-T MR images were merged with intraoperative CT images for planning. Electrode targets were anatomical, based on the MR images. A skull-mounted NexFrame system was used for electrode placement, and all procedures were performed under general anesthesia. After electrode placement, intraoperative CT images were merged with trajectory planning images to calculate accuracy. Accuracy was assessed by both vector error and deviation off the planned trajectory.Results. Sixty patients (33 with Parkinson disease, 26 with essential tremor, and 1 with dystonia) underwent the procedure. Patient's mean age was 64 ± 9.5 years. Over an 18-month period, 119 electrodes were placed (all bilateral, except one). Electrode implant locations were the ventral intermediate nucleus (VIM), globus pallidus internus (GPI), and subthalamic nucleus (STN) in 25, 23, and 12 patients, respectively. Target accuracy measurements were as follows: mean vector error 1.59 ± 1.11 mm and mean deviation off trajectory 1.24 ± 0.87 mm. There was no statistically significant difference between the accuracy of left and right brain electrodes. There was a statistically significant (negative) correlation between the distance of the closest approach of the electrode trajectory to the ventricular wall of the lateral ventricle and vector error (r 2 = -0.339, p < 0.05, n = 76), and the deviation from the planned trajectory (r 2 = -0.325, p < 0.05, n = 77). Furthermore, when the distance from the electrode trajectory and the ventricular wall was < 4 mm, the correlation of the ventricular distance to the deviation from the planned trajectory was stronger (r 2 = -0.419, p = 0.05, n = 19). Electrodes placed in the GPI were significantly more accurate than those placed in the VIM (p < 0.05). Only 1 of 119 electrodes required intraoperative replacement due to a vector error > 3 mm. In this series there was one infection and no intraparenchymal hemorrhages.Conclusions. Placement of DBS electrodes using an intraoperative CT scanner and the NexFrame achieves an accuracy that is at least comparable to other methods. eral anesthesia in whom an intraoperative CT scanner is used. Methods PatientsThe first 60 consecutive patients who underwent intraoperative CT-guided DBS electrode placement were prospectively included. The study was approved by the Oregon Health & Science University Institutional Review Board. All patients were evaluated in the movement disorder program of Oregon Health & Science University to establish surgical candidacy. ImagingPrior to surgery, 3-T MR images were obtained for DBS targets in all patients, using the following sequences: for the VIM, a standard 3D T1-weighted image with TE 4.61 msec, TR shortest, flip angle 30, voxel size 1.02, matrix 256 × 256; for the STN, a FLAIR sequence with TE 140 msec, TR 14,000 msec, sl...

Declarative memory encoding, consolidation, and retrieval require the integration of elements encoded in widespread cortical locations. The mechanism whereby such “binding” of different components of mental events into unified representations occurs is unknown. The “binding-by-synchrony” theory proposes that distributed encoding areas are bound by synchronous oscillations enabling enhanced communication. However, evidence for such oscillations is sparse. Brief high-frequency oscillations (“ripples”) occur in the hippocampus and cortex and help organize memory recall and consolidation. Here, using intracranial recordings in humans, we report that these ∼70-ms-duration, 90-Hz ripples often couple (within ±500 ms), co-occur (≥ 25-ms overlap), and, crucially, phase-lock (have consistent phase lags) between widely distributed focal cortical locations during both sleep and waking, even between hemispheres. Cortical ripple co-occurrence is facilitated through activation across multiple sites, and phase locking increases with more cortical sites corippling. Ripples in all cortical areas co-occur with hippocampal ripples but do not phase-lock with them, further suggesting that cortico-cortical synchrony is mediated by cortico-cortical connections. Ripple phase lags vary across sleep nights, consistent with participation in different networks. During waking, we show that hippocampo-cortical and cortico-cortical coripples increase preceding successful delayed memory recall, when binding between the cue and response is essential. Ripples increase and phase-modulate unit firing, and coripples increase high-frequency correlations between areas, suggesting synchronized unit spiking facilitating information exchange. co-occurrence, phase synchrony, and high-frequency correlation are maintained with little decrement over very long distances (25 cm). Hippocampo-cortico-cortical coripples appear to possess the essential properties necessary to support binding by synchrony during memory retrieval and perhaps generally in cognition.

Electrophysiological devices are critical for mapping eloquent and diseased brain regions and for therapeutic neuromodulation in clinical settings and are extensively used for research in brain-machine interfaces. However, the existing clinical and experimental devices are often limited in either spatial resolution or cortical coverage. Here, we developed scalable manufacturing processes with a dense electrical connection scheme to achieve reconfigurable thin-film, multithousand-channel neurophysiological recording grids using platinum nanorods (PtNRGrids). With PtNRGrids, we have achieved a multithousand-channel array of small (30 μm) contacts with low impedance, providing high spatial and temporal resolution over a large cortical area. We demonstrated that PtNRGrids can resolve submillimeter functional organization of the barrel cortex in anesthetized rats that captured the tissue structure. In the clinical setting, PtNRGrids resolved fine, complex temporal dynamics from the cortical surface in an awake human patient performing grasping tasks. In addition, the PtNRGrids identified the spatial spread and dynamics of epileptic discharges in a patient undergoing epilepsy surgery at 1-mm spatial resolution, including activity induced by direct electrical stimulation. Collectively, these findings demonstrated the power of the PtNRGrids to transform clinical mapping and research with brain-machine interfaces.

Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.

Deep brain stimulation (DBS) in the internal segment of the globus pallidus (GPi) relieves the motor symptoms of Parkinson's disease, yet the mechanism of action remains uncertain. To address the question of how therapeutic stimulation changes neuronal firing in the human brain, we studied the effects of GPi stimulation on local neurons in unanesthetized patients. Eleven patients with idiopathic Parkinson's disease consented to participate in neuronal recordings during stimulator implantation surgery. A recording microelectrode and a DBS macroelectrode were advanced through the GPi in parallel until a single neuron was isolated. After a baseline period, stimulation was initiated with varying voltages and different stimulation sites. The intra-operative stimulation parameters (1-8 V, 88-180 Hz, 0.1-ms pulses) were comparable with the postoperative DBS settings. Stimulation in the GPi did not silence local neuronal activity uniformly, but instead loosely entrained firing and decreased net activity in a voltage-dependent fashion. Most neurons had decreased activity during stimulation, although some increased or did not change firing rate. Thirty-three of 45 neurons displayed complex patterns of entrainment during stimulation, and burst-firing was decreased consistently after stimulation. Recorded spike trains from patients were used as input into a model of a thalamocortical relay neuron. Only spike trains that occurred during therapeutically relevant voltages significantly reduced transmission error, an effect attributable to changes in firing patterns. These data indicate that DBS in the human GPi does not silence neuronal activity, but instead disrupts the pathological firing patterns through loose entrainment of neuronal activity.

OBJECTIVECommon interbody graft options for anterior cervical discectomy and fusion (ACDF) include structural allograft and polyetheretherketone (PEEK). PEEK has gained popularity due to its radiolucency and its elastic modulus, which is similar to that of bone. The authors sought to compare the rates of pseudarthrosis, a lack of solid bone growth across the disc space, and the need for revision surgery with the use of grafts made of allogenic bone versus PEEK.METHODSThe authors retrospectively reviewed 127 cases in which patients had undergone a 1-level ACDF followed by at least 1 year of radiographic follow-up. Data on age, sex, body mass index, tobacco use, pseudarthrosis, and the reoperation rate for pseudarthrosis were collected. These data were analyzed by performing a Pearson’s chi-square test.RESULTSOf 127 patients, 56 had received PEEK implants and 71 had received allografts. Forty-six of the PEEK implants (82%) were stand-alone devices. There were no significant differences between the 2 treatment groups with respect to patient age, sex, or body mass index. Twenty-nine (52%) of 56 patients with PEEK implants demonstrated radiographic evidence of pseudarthrosis, compared to 7 (10%) of 71 patients with structural allografts (p < 0.001, OR 9.82; 95% CI 3.836–25.139). Seven patients with PEEK implants required reoperation for pseudarthrosis, compared to 1 patient with an allograft (p = 0.01, OR 10.00; 95% CI 1.192–83.884). There was no significant difference in tobacco use between the PEEK and allograft groups (p = 0.586).CONCLUSIONSThe results of this study demonstrate that the use of PEEK devices in 1-level ACDF is associated with a significantly higher rate of radiographically demonstrated pseudarthrosis and need for revision surgery compared with the use of allografts. Surgeons should be aware of this when deciding on interbody graft options, and reimbursement policies should reflect these discrepancies.

Background Deep learning enables accurate high-resolution mapping of cells and tissue structures that can serve as the foundation of interpretable machine-learning models for computational pathology. However, generating adequate labels for these structures is a critical barrier, given the time and effort required from pathologists. Results This article describes a novel collaborative framework for engaging crowds of medical students and pathologists to produce quality labels for cell nuclei. We used this approach to produce the NuCLS dataset, containing &gt;220,000 annotations of cell nuclei in breast cancers. This builds on prior work labeling tissue regions to produce an integrated tissue region- and cell-level annotation dataset for training that is the largest such resource for multi-scale analysis of breast cancer histology. This article presents data and analysis results for single and multi-rater annotations from both non-experts and pathologists. We present a novel workflow that uses algorithmic suggestions to collect accurate segmentation data without the need for laborious manual tracing of nuclei. Our results indicate that even noisy algorithmic suggestions do not adversely affect pathologist accuracy and can help non-experts improve annotation quality. We also present a new approach for inferring truth from multiple raters and show that non-experts can produce accurate annotations for visually distinctive classes. Conclusions This study is the most extensive systematic exploration of the large-scale use of wisdom-of-the-crowd approaches to generate data for computational pathology applications.

Venous thrombo-embolism (VTE) is frequently encountered in critically ill neurological and neurosurgical patients admitted to intensive care units. This patient population includes those with brain neoplasm, intracranial hemorrhage, ischemic stroke, subarachnoid hemorrhage, pre- and post-operative patients undergoing neurosurgical procedures and those with traumatic brain injury, and acute spinal cord injury (SCI). There is a wide variability in clinical practice for thromboprophylaxis in these patients, in part due to paucity of data based on randomized clinical trials. Here, we review the current literature on the incidence of VTE in the critically ill neurological and neurosurgical patients as well as appraise available data to support particular practice paradigms for specific subsets of these patients. Data synthesis was conducted via search of Medline, Cochrane databases, and manual review of article bibliographies. Critically ill neurological and neurosurgical patients have higher susceptibility to VTE. Intermittent compression devices with or without anti-thrombotics is generally the method of choice for thromboprophylaxis. Low molecular weight heparin is the method of choice in certain patient subgroups such as those with SCI and ischemic stroke. Inferior vena cava filters may play a role in thromboprophylaxis in selected cases. Without clear guidelines that can be universally applied to this diverse group of patients, prophylaxis for VTE should be tailored to the individual patient with cautious assessment of benefits versus risks. There is a need for higher level evidence to guide VTE prophylaxis in certain subgroups of this patient population.