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The therapeutic effects of centrally acting pharmaceuticals can manifest gradually and unreliably in patients, making the drug discovery process slow and expensive. Biological markers providing early evidence for clinical efficacy could help prioritize development of the more promising drug candidates. A potential source of such markers is functional magnetic resonance imaging (fMRI), a noninvasive imaging technique that can complement molecular imaging. fMRI has been used to characterize how drugs cause changes in brain activity. However, variation in study protocols and analysis techniques has made it difficult to identify consistent associations between subtle modulations of brain activity and clinical efficacy. We present and validate a general protocol for functional imaging-based assessment of drug activity in the central nervous system. The protocol uses machine learning methods and data from multiple published studies to identify reliable associations between drug-related activity modulations and drug efficacy, which can then be used to assess new data. A proof-of-concept version of this approach was developed and is shown here for analgesics (pain medication), and validated with eight separate studies of analgesic compounds. Our results show that the systematic integration of multistudy data permits the generalized inferences required for drug discovery. Multistudy integrative strategies of this type could help optimize the drug discovery and validation pipeline., (Copyright © 2015, American Association for the Advancement of Science.)

Selective attention enhances cortical activity representing an attended sound stream in human posterolateral superior temporal gyrus (PLST). It is unclear, however, what mechanisms are associated with a target detection task that necessitates sustained attention (vigilance) to a sound stream. We compared responses elicited by target and non-target sounds, and to sounds presented in a passive-listening paradigm. Subjects were neurosurgical patients undergoing invasive monitoring for medically refractory epilepsy. Stimuli were complex tones, band-limited noise bursts and speech syllables. High gamma cortical activity (70-150 Hz) was examined in all subjects using subdural grid electrodes implanted over PLST. Additionally, responses were measured from depth electrodes implanted within Heschl's gyrus (HG) in one subject. Responses to target sounds recorded from PLST were increased when compared to responses elicited by the same sounds when they were not-targets, and when they were presented during passive listening. Increases in high gamma activity to target sounds occurred during later portions (after 250 ms) of the response. These increases were related to the task and not to detailed stimulus characteristics. In contrast, earlier activity that did not vary across conditions did represent stimulus acoustic characteristics. Effects observed on PLST were not noted in HG. No consistent effects were noted in the averaged evoked potentials in either cortical region. We conclude that task dependence modulates later activity in PLST during vigilance. Later activity may represent feedback from higher cortical areas. Study of concurrently recorded activity from frontoparietal areas is necessary to further clarify task-related modulation of activity on PLST., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Recent reports of multivariate machine learning (ML) techniques have highlighted their potential use to detect prognostic and diagnostic markers of pain. However, applications to date have focussed on acute experimental nociceptive stimuli rather than clinically relevant pain states. These reports have coincided with others describing the application of arterial spin labeling (ASL) to detect changes in regional cerebral blood flow (rCBF) in patients with on-going clinical pain. We combined these acquisition and analysis methodologies in a well-characterized postsurgical pain model. The principal aims were (1) to assess the classification accuracy of rCBF indices acquired prior to and following surgical intervention and (2) to optimise the amount of data required to maintain accurate classification. Twenty male volunteers, requiring bilateral, lower jaw third molar extraction (TME), underwent ASL examination prior to and following individual left and right TME, representing presurgical and postsurgical states, respectively. Six ASL time points were acquired at each exam. Each ASL image was preceded by visual analogue scale assessments of alertness and subjective pain experiences. Using all data from all sessions, an independent Gaussian Process binary classifier successfully discriminated postsurgical from presurgical states with 94.73% accuracy; over 80% accuracy could be achieved using half of the data (equivalent to 15 min scan time). This work demonstrates the concept and feasibility of time-efficient, probabilistic prediction of clinically relevant pain at the individual level. We discuss the potential of ML techniques to impact on the search for novel approaches to diagnosis, management, and treatment to complement conventional patient self-reporting., (© 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.)

Retrieving the names of friends, loved ones, and famous people is a fundamental human ability. This ability depends on the left anterior temporal lobe (ATL), where lesions can be associated with impaired naming of people regardless of modality (e.g., picture or voice). This finding has led to the idea that the left ATL is a modality-independent convergence region for proper naming. Hypotheses for how proper-name dispositions are organized within the left ATL include both a single modality-independent (heteromodal) convergence region and spatially discrete modality-dependent (unimodal) regions. Here we show direct electrophysiologic evidence that the left ATL is heteromodal for proper-name retrieval. Using intracranial recordings placed directly on the surface of the left ATL in human subjects, we demonstrate nearly identical responses to picture and voice stimuli of famous U.S. politicians during a naming task. Our results demonstrate convergent and robust large-scale neurophysiologic responses to picture and voice naming in the human left ATL. This finding supports the idea of heteromodal (i.e., transmodal) dispositions for proper naming in the left ATL., (Copyright © 2015 the authors 0270-6474/15/351513-08$15.00/0.)

This chapter provides an overview of current invasive recording methodology and experimental paradigms used in the studies of human auditory cortex. Invasive recordings can be obtained from neurosurgical patients undergoing clinical electrophysiologic evaluation for medically refractory epilepsy or brain tumors. This provides a unique research opportunity to study the human auditory cortex with high resolution both in time (milliseconds) and space (millimeters) and to generate valuable information about its organization and function. A historic overview presents the development of the experimental approaches from the pioneering works of Wilder Penfield to modern day. Practical issues regarding research subject population, stimulus presentation, data collection, and analysis are discussed for acute (intraoperative) and chronic experiments. Illustrative examples are provided from experimental paradigms, including studies of spectrotemporal processing, functional connectivity, and functional lesioning in human auditory cortex., (© 2015 Elsevier B.V. All rights reserved.)

Extraskeletal Ewing's sarcoma (EES) is a rare presentation, representing only 15% of all primary Ewing's sarcoma cases. Even more uncommon is EES presenting as a primary focus in the spinal canal. These rapidly growing tumors often present with focal neurological symptoms of myelopathy or radiculopathy. There are no classic characteristic imaging findings and thus the physician must keep a high index of clinical suspicion. Diagnosis can only be definitively made by histopathological studies. In this report, we discuss a primary cervical spine EES in a 53-year-old man who presented with a two-month history of left upper extremity pain and acute onset of weakness. Imaging revealed a cervical spinal canal mass. After undergoing cervical decompression, histopathological examination confirmed a diagnosis of Ewing's sarcoma. A literature search revealed fewer than 25 reported cases of primary cervical spine EES published in the past 15 years and only one report demonstrating this pathology in a patient older than 30 years of age (age = 38). Given the low incidence of this pathology presenting in this age group and the lack of treatment guidelines, each patient's plan should be considered on a case-by-case basis until further studies are performed to determine optimal evidence based treatment.

When exposed to rhythmic stimulation, the human brain displays rhythmic activity across sensory modalities and regions. Given the ubiquity of this phenomenon, how sensory rhythms are transformed into neural rhythms remains surprisingly inconclusive. An influential model posits that endogenous oscillations entrain to external rhythms, thereby encoding environmental dynamics and shaping perception. However, research on neural entrainment faces multiple challenges, from ambiguous definitions to methodological difficulties when endogenous oscillations need to be identified and disentangled from other stimulus-related mechanisms that can lead to similar phase-locked responses. Yet, recent years have seen novel approaches to overcome these challenges, including computational modeling, insights from dynamical systems theory, sophisticated stimulus designs, and study of neuropsychological impairments. This review outlines key challenges in neural entrainment research, delineates state-of-the-art approaches, and integrates findings from human and animal neurophysiology to provide a broad perspective on the usefulness, validity, and constraints of oscillatory models in brain–environment interaction. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to examine the analgesic efficacy of varying doses of hydromorphone hydrochloride in conjunction with absorbable gelatin sponge for postoperative pain management in elderly individuals undergoing lumbar fusion surgery. Additionally, the study aims to assess the sustained release analgesic properties of this combination and to determine the optimal dosage of hydromorphone hydrochloride for effective pain relief. Methods: A total of 113 elderly patients (aged ≥ 65 years old) meeting the criteria for 1-2-level posterior lumbar fusion surgery at Ganzhou City People's Hospital between July 2022 and August 2023 were randomly assigned to four groups: group A (0.2 mg hydromorphone hydrochloride 1 ml), group B (0.3 mg hydromorphone hydrochloride 1.5 ml), group C (0.4 mg hydromorphone hydrochloride 2 ml), and group D (0.9% normal saline 2 ml) for standard anesthesia induction and maintenance. Prior to suturing the incision, gelfoam was utilized to administer epidural analgesia to each group. Following the surgical procedure, an intravenous analgesia pump was utilized for pain management. The baseline infusion rate was set at 0.5 ml/h. Patient-controlled analgesia (PCA) was administered at a dose of 2 ml, with a lockout interval of 20 min, allowing the patient to self-administer as needed. Pain relief was assessed using the visual analogue scale (VAS) prior to surgery, as well as at 1 day and 3 days post-operation. The frequency of PCA requests within the initial 48-h postoperative period, the remedial analgesia with dezocine, postoperative adverse reactions, and duration of hospitalization were documented for analysis. Results: The VAS scores of groups B and C were found to be significantly lower than those of group D 1 day after the operation. Additionally, VAS scores at 3 days post-operation, remedial rate of dezocine and PCA follow-up times at 48 h in groups A, B, and C were significantly lower compared to group D (P < 0.001). There was no statistically significant difference between group B and group C in VAS scores at 1 day and 3 days post-operation, as well as PCA follow-up times at 48 h post-operation (P < 0.001). Furthermore, the VAS scores of groups B and C were lower than those of group A at 1 day and 3 days post-operation (P < 0.05). The PCA frequency of group C was also lower than that of group A at 48 h post-operation (P < 0.05). Conclusion: The combination of hydromorphone hydrochloride and absorbable gelatin sponge epidural analgesia has been shown to enhance postoperative pain management. A dosage of 0.4 mg of hydromorphone hydrochloride may be considered an appropriate analgesic dose, as it can provide effective pain relief without eliciting adverse reactions. Trial Registration: ChiCTR.org.cn(ChiCTR2200064863). Registered on October 20, 2022. [ABSTRACT FROM AUTHOR]

Using steerable needles to enable course correction and curved trajectories can improve surgical outcomes in numerous clinical interventions including electrode placement for deep brain stimulation. In this work, a physically motivated kinematic model for an actively steered magnetic-tipped needle is used in closed-loop control to perform insertion trajectories. The applied control law is derived using the Lyapunov redesign. Simulation results show this control method to be accurate for a wide range of conditions including randomized target trajectories. Control is performed experimentally in a brain tissue phantom for both initial position offset recovery and curved trajectories. Converged error results average 0.52 mm from target trajectory. Simulation results demonstrate the robustness of the control implementation, while experimental results exceed the accuracy required for the target application, encouraging future use in a clinical setting. Beyond needle insertion, this work has implications in general vehicle steering, as this model and control can apply to systems with similar kinematics such as boats and wheeled vehicles that could benefit from a relaxed slip constraint. [ABSTRACT FROM AUTHOR]

Aim: Patients frequently use YouTube for information. This study aimed to evaluate the quality of Turkish YouTube videos on age-related macular degeneration (AMD). Methods: Turkish translations of "AMD" and "yellow spot disease" were searched on August 16, 2023. The first 100 videos were grouped as useful, misleading, or irrelevant. Video properties and quality scores [Journal of American Medical Association (JAMA), Global Quality Score (GQS), DISCERN] were evaluated. Results: We classified 74 videos as useful, 16 as misleading, and 10 as irrelevant. The most common uploaders were television shows and social media. The mean JAMA score was 1.94±1.09, the mean GQS score was 2.49±1.29, and the mean DISCERN score was 36.82±16.53. The mean JAMA, GQS, and DISCERN scores were higher in the useful group than in the misleading group (p=0.0001, p=0.001, p=0.0001). The number of likes and view ratio were higher in the misleading group than in the useful group (p=0.019, p=0.037). The main content of the misleading group was treatment, and the uploaders were related to industry and commercial interests. Conclusion: The quality of the AMD videos was insufficient. Although misleading videos had lower quality, they were more popular. This may be due to patients' hope for new treatments, as misleading videos have discussed this topic. [ABSTRACT FROM AUTHOR]

Background Depression is a heterogeneous disorder with high morbidity and disability rates that poses serious problems regarding mental health care. It is now well established that N-methyl D-aspartate receptor (NMDAR) modulators are being increasingly explored as potential therapeutic options for treating depression, although relatively little is known about their mechanisms of action. NMDARs are glutamate-gated ion channels that are ubiquitously expressed in the central nervous system (CNS), and they have been shown to play key roles in excitatory synaptic transmission. GluN2A, the predominant Glu2N subunit of functional NMDARs in neurons, is involved in various physiological processes in the CNS and is associated with diseases such as anxiety, depression, and schizophrenia. However, the role of GluN2A in the pathophysiology of depression has not yet been elucidated. Methods We reviewed several past studies to better understand the function of GluN2A in depression. Additionally, we also summarized the pathogenesis of depression based on the regulation of GluN2A expression, particularly its interaction with neuroinflammation and neurogenesis, which has received considerable critical attention and is highly implicated in the onset of depression. Results These evidence suggests that GluN2A overexpression impairs structural and functional synaptic plasticity, which contributes to the development of depression. Consequently, this knowledge is vital for the development of selective antagonists targeting GluN2A subunits using pharmacological and molecular methods. Conclusions Specific inhibition of the GluN2A NMDAR subunit is resistant to chronic stress-induced depressive-like behaviors, making them promising targets for the development of novel antidepressants. [ABSTRACT FROM AUTHOR]

Purpose of the Review: Chronic tinnitus affects millions of people worldwide, but it remains an unmet clinical problem, particularly from a therapeutic perspective. Recent Findings: Neuroimaging and neurophysiological investigations have consistently unveiled that tinnitus can be considered as a form of maladaptive plasticity taking place not only in primary and associative auditory areas but also involving large-scale brain networks. Based on these premises, treatment strategies that aim to manipulate in a controllable way plastic capabilities of the brain are being under investigation as emerging treatments. Summary: here, we review the rationale for using so called Non-Invasive Brain stimulation (NiBS) techniques, such as navigated repetitive transcranial magnetic stimulation (rTMS) and other forms of transcranial electrical stimulation (tES) or peripheral stimulations, to alleviate tinnitus. We also provide an overview of available clinical results of these various non-invasive neuromodulatory approaches, trying to identify how to translate their unquestionable therapeutic potential into real-life contexts, beyond the lab boundaries. [ABSTRACT FROM AUTHOR]

Garnet-type oxide materials show high Li-ion conductivity and may be used as solid-state electrolytes in lithium-ion batteries to address safety concerns. In this study, Nb-doped Li7Nd2.8Ca0.2Zr1.8Nb0.2O12 (LNdCZNbO) and Ta-doped Li7Nd2.8Ca0.2Zr1.8Ta0.2O12 (LNdCZTaO) garnet-type compositions were prepared to examine the impact of Nb- and Ta-doping on ionic conductivity of Li7Nd3Zr2O12 (LNdZO). XRD patterns showed the crystallization of major phase of these garnet-structured oxides in tetragonal symmetry. Impedance measurements were recorded from room temperature to 450°C using a Novocontrol make impedance analyzer (Alpha-A high-performance frequency analyzer) in the frequency range of 1 Hz–40 MHz. The maximum total conductivity of parent composition LNdZO was 5.12 × 10−5 S cm−1 at 25°C. The compositions of LNdCZNbO and LNdCZTaO showed conductivity 7.05 × 10−4 and 8.23 × 10−4 S cm−1, respectively, at 25°C. On higher temperature of 350°C, these doped compositions, LNdCZNbO and LNdCZTaO, showed enhanced conductivity of 3.30 × 10−3 and 2.63 × 10−3 S cm−1, respectively, as compared to the parent LNdZO composition’s conductivity of 4.42 × 10−4 S cm−1. Analysis of the Cole–Cole plots fitting showed the nature of Li ionic conduction and the existence of bulk and grain boundary impedances in these compositions. The activation energy was found to be higher for the compositions of LNdCZNbO (0.18 ± 0.01 eV) and LNdCZTaO (0.17 ± 0.01 eV) in comparison with the activation energy of undoped composition Li7Nd3Zr2O12 (0.14 ± 0.00 eV) due to the change in garnet lattice by doping of Ca and Nb/Ta. [ABSTRACT FROM AUTHOR]

The model for functional organization of human auditory cortex is in part based on findings in non-human primates, where the auditory cortex is hierarchically delineated into core, belt and parabelt fields. This model envisions that core cortex directly projects to belt, but not to parabelt, whereas belt regions are a major source of direct input for auditory parabelt. In humans, the posteromedial portion of Heschl's gyrus (HG) represents core auditory cortex, whereas the anterolateral portion of HG and the posterolateral superior temporal gyrus (PLST) are generally interpreted as belt and parabelt, respectively. In this scheme, response latencies can be hypothesized to progress in serial fashion from posteromedial to anterolateral HG to PLST. We examined this hypothesis by comparing response latencies to multiple stimuli, measured across these regions using simultaneous intracranial recordings in neurosurgical patients. Stimuli were 100 Hz click trains and the speech syllable /da/. Response latencies were determined by examining event-related band power in the high gamma frequency range. The earliest responses in auditory cortex occurred in posteromedial HG. Responses elicited from sites in anterolateral HG were neither earlier in latency from sites on PLST, nor more robust. Anterolateral HG and PLST exhibited some preference for speech syllable stimuli compared to click trains. These findings are not supportive of a strict serial model envisioning principal flow of information along HG to PLST. In contrast, data suggest that a portion of PLST may represent a relatively early stage in the auditory cortical hierarchy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Use of human acellular dermal matrix (ADM) during prosthetic breast reconstruction has increased. Several ADM products are available produced by differing manufacturing techniques. It is not known if outcomes vary with different products. This study reports the complication prevalence following use of a tutoplast-derived ADM (T-ADM) in prosthetic breast reconstruction. We performed a retrospective chart review of 203 patients (mean follow-up times 12.2 months) who underwent mastectomy and immediate prosthetic breast reconstruction utilizing T-ADM, recording demographic data, surgical indications and complication (infection, seroma, hematoma, wound healing exceeding three weeks and reconstruction failure). During a four-year period, 348 breast reconstructions were performed Complications occurred in 16.4% of reconstructed breasts. Infection occurred in 6.6% of breast reconstructions (3.7% - major infection, requiring intravenous antibiotics and 2.9% minor infection, requiring oral antibiotics only). Seromas occurred in 3.4% and reconstruction failure occurred in 0.6% of breast reconstructions. Analysis suggested that complication prevalence was significantly higher in patients with a BMI >30 (p = 0.03). The complication profile following T-ADM use is this series is comparable to that reported for with other ADM products. T-ADM appears to be a safe and acceptable option for use in ADM-assisted breast reconstruction., (Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Diurnal rhythms have been observed in human behaviors as diverse as sleep, olfaction, and learning. Despite its potential impact, time of day is rarely considered when brain responses are studied by neuroimaging techniques. To address this issue, we explicitly examined the effects of circadian and homeostatic regulation on functional connectivity (FC) and regional cerebral blood flow (rCBF) in healthy human volunteers, using whole-brain resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). In common with many circadian studies, we collected salivary cortisol to represent the normal circadian activity and functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Intriguingly, the changes in FC and rCBF we observed indicated fundamental decreases in the functional integration of the default mode network (DMN) moving from morning to afternoon. Within the anterior cingulate cortex (ACC), our results indicate that morning cortisol levels are negatively correlated with rCBF. We hypothesize that the homeostatic mechanisms of the HPA axis has a role in modulating the functional integrity of the DMN (specifically, the ACC), and for the purposes of using fMRI as a tool to measure changes in disease processes or in response to treatment, we demonstrate that time of the day is important when interpreting resting-state data.

Background: Sensitive outcome measures are needed to quantify the effects of neuromodulation in mood disorders., Objective: This study examined the utility of a novel affective bias (AB) task in identifying transient mood changes induced by amygdala stimulation in a single rare participant., Methods: Localized, pulsed electrical stimulation was delivered for 8 min during measures of AB and self-reported mood. Responses were compared with those gathered without stimulation on the same day in the same setting, using paired t-tests., Results: Stimulation of the basolateral nucleus of the right amygdala at 50 Hz, 15 V, and 200 μs pulse-width produced a significant positive shift in AB (t = -2.864, df = 53, P = .006), despite equivocal findings on self-reported mood (t = -.184, df = 12, P = .857)., Conclusion: Affective bias may be more sensitive to stimulation-induced fluctuations in mood than subjective report, suggesting utility as an outcome measure in neuromodulation studies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Speech perception requires that sounds be transformed into speech-related objects with lexical and semantic meaning. It is unclear at what level in the auditory pathways this transformation emerges. Primary auditory cortex has been implicated in both representation of acoustic sound attributes and sound objects. While non-primary auditory cortex located on the posterolateral superior temporal gyrus (PLST) is clearly involved in acoustic-to-phonetic pre-lexical representations, it is unclear what role this region plays in auditory object formation. Additional data support the importance of prefrontal cortex in the formation of auditory objects, while other data would implicate this region in auditory object selection. To help clarify the respective roles of auditory and auditory-related cortex in the formation and selection of auditory objects, we examined high gamma activity simultaneously recorded directly from Heschl's gyrus (HG), PLST and prefrontal cortex, while subjects performed auditory semantic detection tasks. Subjects were patients undergoing evaluation for treatment of medically intractable epilepsy. We found that activity in posteromedial HG and early activity on PLST was robust to sound stimuli regardless of their context, and minimally modulated by tasks. Later activity on PLST could be strongly modulated by semantic context, but not by behavioral performance. Activity within prefrontal cortex also was related to semantic context, and did co-vary with behavior. We propose that activity in posteromedial HG and early activity on PLST primarily reflect the representation of spectrotemporal sound attributes. Later activity on PLST represents a pre-lexical processing stage and is an intermediate step in the formation of word objects. Activity in prefrontal cortex appears directly involved in word object selection. The roles of other auditory and auditory-related cortical areas in the formation of word objects remain to be explored.

The authors are developing a novel type of spinal cord stimulator, designed to be placed directly on the pial surface of the spinal cord, for more selective activation of target tissues within the dorsal columns. For pre-clinical testing of the device components, an ovine model has been implemented which utilizes the agility and flexibility of a sheep's cervical and upper thoracic regions, thus providing an optimal environment of accelerated stress-cycling on small gauge lead wires implanted along the dorsal spinal columns. The results are presented of representative biomechanical measurements of the angles of rotation and the angular velocities and accelerations associated with the relevant head, neck and upper back motions, and these findings are interpreted in terms of their impact on assessing the robustness of the stimulator implant systems.

Spinal cord stimulation currently relies on extradural electrode arrays that are separated from the spinal cord surface by a highly conducting layer of cerebrospinal fluid. It has recently been suggested that intradural placement of the electrodes in direct contact with the pial surface could greatly enhance the specificity and efficiency of stimulation. The present computational study aims at quantifying and comparing the electrical current distributions as well as the spatial recruitment profiles resulting from extra- and intra-dural electrode arrangements. The electrical potential distribution is calculated using a 3D finite element model of the human thoracic spinal canal. The likely recruitment areas are then obtained using the potential as input to an equivalent circuit model of the pre-threshold axonal response. The results show that the current threshold to recruitment of axons in the dorsal column is more than an order of magnitude smaller for intradural than extradural stimulation. Intradural placement of the electrodes also leads to much higher contrast between the stimulation thresholds for the dorsal root entry zone and the dorsal column, allowing better focusing of the stimulus.

Temporopolar cortex plays a crucial role in the pathogenesis of temporal lobe epilepsy and subserves important cognitive functions. Because of its shape and position in the middle cranial fossa, complete electrode coverage of the temporal pole (TP) is difficult to achieve using existing devices. We designed a novel TP electrode array that conforms to the surface of temporopolar cortex and achieves dense electrode coverage of this important brain region. A multi-pronged electrode array was designed that can be placed over the surface of the TP using a straightforward insertion technique. Twelve patients with medically intractable epilepsy were implanted with the TP electrode array for purposes of seizure localization. Select patients underwent cognitive mapping by electrocorticographic (ECoG) recording from the TP during a naming task. Use of the array resulted in excellent TP electrode coverage in all patients. High quality ECoG data were consistently obtained for purposes of delineating seizure activity and functional mapping. During a naming task, significant increases in ECoG power were observed within localized subregions of the TP. One patient developed a transient neurological deficit thought to be related to the mass effect of multiple intracranial recording arrays, including the TP array. This deficit resolved following removal of all electrodes. The TP electrode array overcomes limitations of existing devices and enables clinicians and researchers to obtain optimal multi-site recordings from this important brain region.

Abnormal GABAergic interneuron density, and imbalance of excitatory versus inhibitory tone, is thought to result in epilepsy, neurodevelopmental disorders, and psychiatric disease. Recent studies indicate that interneuron cortical density is determined primarily by the size of the precursor pool in the embryonic telencephalon. However, factors essential for regulating interneuron allocation from telencephalic multipotent precursors are poorly understood. Here we report that Olig1 represses production of GABAergic interneurons throughout the mouse brain. Olig1 deletion in mutant mice results in ectopic expression and upregulation of Dlx1/2 genes in the ventral medial ganglionic eminences and adjacent regions of the septum, resulting in an ∼30% increase in adult cortical interneuron numbers. We show that Olig1 directly represses the Dlx1/2 I12b intergenic enhancer and that Dlx1/2 functions genetically downstream of Olig1. These findings establish Olig1 as an essential repressor of Dlx1/2 and interneuron production in developing mammalian brain., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The place of the posterolateral superior temporal (PLST) gyrus within the hierarchical organization of the human auditory cortex is unknown. Understanding how PLST processes spectral information is imperative for its functional characterization. Pure-tone stimuli were presented to subjects undergoing invasive monitoring for refractory epilepsy. Recordings were made using high-density subdural grid electrodes. Pure tones elicited robust high gamma event-related band power responses along a portion of PLST adjacent to the transverse temporal sulcus (TTS). Responses were frequency selective, though typically broadly tuned. In several subjects, mirror-image response patterns around a low-frequency center were observed, but typically, more complex and distributed patterns were seen. Frequency selectivity was greatest early in the response. Classification analysis using a sparse logistic regression algorithm yielded above-chance accuracy in all subjects. Classifier performance typically peaked at 100-150 ms after stimulus onset, was comparable for the left and right hemisphere cases, and was stable across stimulus intensities. Results demonstrate that representations of spectral information within PLST are temporally dynamic and contain sufficient information for accurate discrimination of tone frequencies. PLST adjacent to the TTS appears to be an early stage in the hierarchy of cortical auditory processing. Pure-tone response patterns may aid auditory field identification.

Object: Many studies that have evaluated surgical site infections (SSIs) after craniotomy or craniectomy (CRANI) did not use robust methods to assess risk factors for SSIs or outcomes associated with SSIs. The authors conducted the current study to identify risk factors for SSIs after CRANI procedures and to evaluate outcomes attributed to SSIs., Methods: The authors performed a nested case-control study of patients undergoing CRANI procedures between 2006 and 2010 at the University of Iowa Hospitals and Clinics. They identified 104 patients with SSIs and selected 312 controls. They collected data from medical records and used multivariate analyses to identify risk factors and outcomes associated with SSIs., Results: Thirty-two percent of SSIs were caused by Staphylococcus aureus, 88% were deep incisional or organ space infections, and 70% were identified after discharge. Preoperative length of stay (LOS) ≥ 1 day was the only significant patient-related factor in the preoperative model (OR 2.1 [95% CI 1.2-3.4]) and in the overall model (OR 1.9 [95% CI 1.1-3.3]). Procedure-related risk factors that were significant in the overall model included Gliadel wafer use (OR 6.7 [95% CI 2.5-18.2]) and postoperative CSF leak (OR 3.5 [95% CI 1.4-8.5]). The preoperative SSI risk index, including body mass index, previous brain operation, chemotherapy on admission, preoperative LOS, procedure reason, and preoperative glucose level, had better predictive efficacy (c-statistic = 0.664) than the National Healthcare Safety Network risk index (c-statistic = 0.547; p = 0.004). Surgical site infections were associated with increased LOS during the initial hospitalizations (average increase of 50%) or readmissions (average increase of 100%) and with an increased risk of readmissions (OR 7.7 [95% CI 4.0-14.9]), reoperations (OR 36 [95% CI 14.9-87]), and death (OR 3.4 [95% CI 1.5-7.4])., Conclusions: Surgeons were able to prospectively assess a patient's risk of SSI based on preoperative risk factors and they could modify some processes of care to lower the risk of SSI. Surgical site infections substantially worsened patients' outcomes. Preventing SSIs after CRANI could improve patient outcomes and decrease health care utilization.

Chronic changes in excitability and activity can induce homeostatic plasticity. These perturbations may be associated with neurological disorders, particularly those involving loss or dysfunction of GABA interneurons. In distal-less homeobox 1 (Dlx1(-/-)) mice with late-onset interneuron loss and reduced inhibition, we observed both excitatory synaptic silencing and decreased intrinsic neuronal excitability. These homeostatic changes do not fully restore normal circuit function, because synaptic silencing results in enhanced potential for long-term potentiation and abnormal gamma oscillations. Transplanting medial ganglionic eminence interneuron progenitors to introduce new GABAergic interneurons, we demonstrate restoration of hippocampal function. Specifically, miniature excitatory postsynaptic currents, input resistance, hippocampal long-term potentiation, and gamma oscillations are all normalized. Thus, in vivo homeostatic plasticity is a highly dynamic and bidirectional process that responds to changes in inhibition.

This study develops a means of delivering electrical stimuli directly to the pial surface of the spinal cord for treatment of intractable pain. This intradural implant must remain in direct contact with the cord as it moves within the spinal canal. Therefore, magnetic resonance imaging was used to measure the movement of the spinal cord between neutral and flexed-back positions in a series of volunteers (n = 16). Following flexion of the back, the mean change in the pedicle-to-spinal cord dorsal root entry zone distance at the T10-11 level was (8.5 ± 6.0) mm, i.e. a 71% variation in the range of rostral-caudal movement of the spinal cord across all patients. There will be a large spectrum of spinal cord strains associated with this observed range of rostral-caudal motions, thus calling for suitable axial compliance within the electrode bearing portion of the intradural implant.

Spinal cord stimulation has been utilized for decades in the treatment of numerous conditions such as failed back surgery and phantom limb syndromes, arachnoiditis, cancer pain, and others. The placement of the stimulating electrode array was originally subdural but, to minimize surgical complexity and reduce the risk of certain postsurgical complications, it became exclusively epidural eventually. Here we review the relevant clinical and experimental pathologic findings, including spinal cord compression, infection, hematoma formation, cerebrospinal fluid leakage, chronic fibrosis, and stimulation-induced neurotoxicity, associated with the early approaches to subdural electrical stimulation of the central nervous system, and the spinal cord in particular. These findings may help optimize the safety and efficacy of a new approach to subdural spinal cord stimulation now under development.

Much less is known about the organization of the human auditory cortex compared to non-human primate auditory cortices. In an effort to further investigate the response properties of human auditory cortex, we present preliminary findings from human subjects implanted with depth electrodes in Heschl's gyrus (HG) as part of their neurosurgical treatment of epilepsy. Each subject had electrocorticography (ECoG) responses taken from medial and lateral HG in response to both speech and non-speech stimuli, including during speech production. Responses were somewhat variable across subjects, but posteromedial HG demonstrated frequency following responses to the stimuli in all subjects to some degree. Results and implications are discussed.

We have designed, built, and tested an apparatus used for investigating the biomechanical response of a novel intradural spinal cord stimulator to the simulated physiological movement of the spinal cord within the thecal sac. In this apparatus, the rostral-caudal displacements of an anthropomorphic spinal cord surrogate can be controlled with a resolution of approximately 0.1% of a target value for up to 10(7) lateral movement cycles occurring at a repetition rate of 2 Hz. Using this system, we have been able to determine that the restoring force of the stimulator's suspension system works in concert with the frictional coupling between the electrode array and the surrogate to overcome the 0.42 μN inertial force associated with the lateral motion of the array. The result is a positional stability of the array on the surrogate (in air) of better than 0.2 mm over ~500,000 movement cycles. Design modifications that might lead to improved physiological performance are discussed.

The connection between auditory fields of the temporal lobe and prefrontal cortex has been well characterized in nonhuman primates. Little is known of temporofrontal connectivity in humans, however, due largely to the fact that invasive experimental approaches used so successfully to trace anatomical pathways in laboratory animals cannot be used in humans. Instead, we used a functional tract-tracing method in 12 neurosurgical patients with multicontact electrode arrays chronically implanted over the left (n = 7) or right (n = 5) perisylvian temporal auditory cortex (area PLST) and the ventrolateral prefrontal cortex (VLPFC) of the inferior frontal gyrus (IFG) for diagnosis and treatment of medically intractable epilepsy. Area PLST was identified by the distribution of average auditory-evoked potentials obtained in response to simple and complex sounds. The same sounds evoked little if there is any activity in VLPFC. A single bipolar electrical pulse (0.2 ms, charge-balanced) applied between contacts within physiologically identified PLST resulted in polyphasic evoked potentials clustered in VLPFC, with greatest activation being in pars triangularis of the IFG. The average peak latency of the earliest negative deflection of the evoked potential on VLPFC was 13.48 ms (range: 9.0-18.5 ms), providing evidence for a rapidly conducting pathway between area PLST and VLPFC.

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in people of all ages. Following the acute mechanical insult, TBI evolves over the ensuing minutes and days. Understanding the secondary factors that contribute to TBI might suggest therapeutic strategies to reduce the long-term consequences of brain trauma. To assess secondary factors that contribute to TBI, we studied a lateral fluid percussion injury (FPI) model in mice. Following FPI, the brain cortex became acidic, consistent with data from humans following brain trauma. Administering HCO3 (-) after FPI prevented the acidosis and reduced the extent of neurodegeneration. Because acidosis can activate acid sensing ion channels (ASICs), we also studied ASIC1a(-/-) mice and found reduced neurodegeneration after FPI. Both HCO3 (-) administration and loss of ASIC1a also reduced functional deficits caused by FPI. These results suggest that FPI induces cerebral acidosis that activates ASIC channels and contributes to secondary injury in TBI. They also suggest a therapeutic strategy to attenuate the adverse consequences of TBI.

Background and Importance: Dabigatran is a direct thrombin inhibitor gaining popularity as a stroke prevention agent in patients with atrial fibrillation. In comparison with warfarin, dabigatran showed superiority in stroke prevention, but lower rates of major hemorrhage and intracerebral hemorrhage. Although warfarin has a well-established reversal strategy, there is far less experience reversing dabigatran., Clinical Presentation: We present our experience with 3 patients who experienced an intracranial hemorrhage either spontaneously or after low-energy cranial trauma and review the available literature describing dabigatran use in patients with traumatic brain injury., Conclusion: Intracranial hemorrhage in patients taking anticoagulants and/or antiplatelets can have either a benign or malignant clinical course. At this time, there is little experience with dabigatran reversal; however, several strategies for rapid reversal have been proposed. All patients with intracranial hemorrhage taking dabigatran should be admitted for close neurological monitoring and serial imaging.

Classification schemes for thoracolumbar fractures attempt to categorize them as either stable or unstable. Stable fractures heal with conservative treatment strategies such as bracing, while unstable fractures require operative internal fixation. Until recently, most classification schemes recognized the importance of the pattern and location of bony disruption in segregating stable and unstable fractures. Recently, the integrity of the posterior ligamentous complex was found to influence the degree of the stability of thoracolumbar fractures. Disruption of the intervertebral disc and ligaments increases spinal instability. Unlike bone, it is thought that these ligaments do not have the capacity to heal. However, this notion is not founded by substantial evidence. It is, hence, important to determine the extent of ligamentous healing in the spine as this will influence directing therapy towards not only bony fusion, but also ligamentous union., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

While the importance of oxygen to the wound healing process is well accepted, research and technological advances continue in this field and efforts are ongoing to further utilize oxygen as a therapeutic modality. In this paper, the authors briefly review the role of oxygen in wound healing and discuss the distinct mechanism of action as well as the advantages and disadvantages of the three major oxygen-based therapies currently in clinical use (Hyperbaric Oxygen and Topical Oxygen and Continuous Diffusion of Oxygen), as well as review the existing literature regarding these distinct therapeutic modalities., (© 2013 by the Wound Healing Society.)

Electrical stimulation of the auditory nerve with a cochlear implant (CI) is the method of choice for treatment of severe-to-profound hearing loss. Understanding how the human auditory cortex responds to CI stimulation is important for advances in stimulation paradigms and rehabilitation strategies. In this study, auditory cortical responses to CI stimulation were recorded intracranially in a neurosurgical patient to examine directly the functional organization of the auditory cortex and compare the findings with those obtained in normal-hearing subjects. The subject was a bilateral CI user with a 20-year history of deafness and refractory epilepsy. As part of the epilepsy treatment, a subdural grid electrode was implanted over the left temporal lobe. Pure tones, click trains, sinusoidal amplitude-modulated noise, and speech were presented via the auxiliary input of the right CI speech processor. Additional experiments were conducted with bilateral CI stimulation. Auditory event-related changes in cortical activity, characterized by the averaged evoked potential and event-related band power, were localized to posterolateral superior temporal gyrus. Responses were stable across recording sessions and were abolished under general anesthesia. Response latency decreased and magnitude increased with increasing stimulus level. More apical intracochlear stimulation yielded the largest responses. Cortical evoked potentials were phase-locked to the temporal modulations of periodic stimuli and speech utterances. Bilateral electrical stimulation resulted in minimal artifact contamination. This study demonstrates the feasibility of intracranial electrophysiological recordings of responses to CI stimulation in a human subject, shows that cortical response properties may be similar to those obtained in normal-hearing individuals, and provides a basis for future comparisons with extracranial recordings.