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Brown-Séquard plus syndrome (BSPS) or incomplete spinal cord injuries from stab injury have been widely reported. However, only four detailed cases of pure Brown-Séquard syndrome (BSS) from stab injury have been previously reported. Here we present the case of an 18-year-old man who sustained a penetrating knife stab injury to the right side of his back resulting in a pure Brown-Séquard syndrome with left lower extremity hemiplegia. Imaging revealed right-sided soft tissue and ligamentous damage traveling in a right-to-left fashion as well as left-sided T2-weighted MRI cord signal change at the level of T9. Given concern for a cerebrospinal fluid leak (CSF) leak, the patient was taken for wound exploration, irrigation, laminectomy, dural closure and lumbar drain placement. At three years follow up, the patient was almost full strength. This is the first case in the literature demonstrating radiographic and correlative intraoperative imaging of a hemisection of the spinal cord resulting in a pure Brown-Séquard syndrome.

Evidence regarding the functional subdivisions of human auditory cortex has been slow to converge on a definite model. In part, this reflects inadequacies of current understanding of how the cortex represents temporal information in acoustic signals. To address this, we investigated spatiotemporal properties of auditory responses in human posterolateral superior temporal (PLST) gyrus to acoustic click-train stimuli using intracranial recordings from neurosurgical patients. Subjects were patients undergoing chronic invasive monitoring for refractory epilepsy. The subjects listened passively to acoustic click-train stimuli of varying durations (160 or 1,000 ms) and rates (4-200 Hz), delivered diotically via insert earphones. Multicontact subdural grids placed over the perisylvian cortex recorded intracranial electrocorticographic responses from PLST and surrounding areas. Analyses focused on averaged evoked potentials (AEPs) and high gamma (70-150 Hz) event-related band power (ERBP). Responses to click trains featured prominent AEP waveforms and increases in ERBP. The magnitude of AEPs and ERBP typically increased with click rate. Superimposed on the AEPs were frequency-following responses (FFRs), most prominent at 50-Hz click rates but still detectable at stimulus rates up to 200 Hz. Loci with the largest high gamma responses on PLST were often different from those sites that exhibited the strongest FFRs. The data indicate that responses of non-core auditory cortex of PLST represent temporal stimulus features in multiple ways. These include an isomorphic representation of periodicity (as measured by the FFR), a representation based on increases in non-phase-locked activity (as measured by high gamma ERBP), and spatially distributed patterns of activity.

Wireless signal transmission will play a critical role in developing reliable subdural spinal cord stimulation systems. We have developed an approach to inductively coupling signals across the epidural spacing between the pial and epidural surfaces. The major design constraints include tolerance of coil misalignments from spinal cord geometries in addition to reasonable power efficiencies within the expected range of movement. The design of the primary side as a driving circuit is simplified by several turns of commercial magnetic wire, whereas the implanted secondary side is implemented in a micro-planar spiral coil tuned to a resonant frequency of 1.6 MHz. We present the results of wireless inductive coupling experiments that demonstrate the ability to transmit and receive a frequency modulated 1.6 MHz carrier signal between primary and secondary coil antennae scaled to 10 mm. Power delivery is in the range of 400 mW at a link efficiency of 32 % for strong coupling (coil separations of 0.5 mm ) and in the range of 70 mW at 4 % efficiency for weak coupling (coil separations of 10 mm).

The efficacy of spinal cord stimulators is dependent on the ability of the device to functionally activate targeted structures within the spinal cord, while avoiding activation of near-by non-targeted structures. In theory, these objectives can best be achieved by delivering electrical stimuli directly to the surface of the spinal cord. The current experiments were performed to study the influence of different stimulating electrode positions on patterns of spinal cord electrophysiological activation. A custom-designed spinal cord neurostimulator was used to investigate the effects of lead position and stimulus amplitude on cortical electrophysiological responses to spinal cord stimulation. Brain recordings were obtained from subdural grids placed in four adult sheep. We systematically varied the position of the stimulating lead relative to the spinal cord and the voltage delivered by the device at each position, and then examined how these variables influenced cortical responses. A clear relationship was observed between voltage and electrode position, and the magnitude of high gamma-band oscillations. Direct stimulation of the dorsal column contralateral to the grid required the lowest voltage to evoke brain responses to spinal cord stimulation. Given the lower voltage thresholds associated with direct stimulation of the dorsal column, and its possible impact on the therapeutic window, this intradural modality may have particular clinical advantages over standard epidural techniques now in routine use.

Head-of-bed (HOB) elevation is usually restricted in patients with aneurysmal subarachnoid hemorrhage (SAH). The goal of this study is to correlate HOB changes (0° and 90°) with cerebral blood flow using transcranial Doppler (TCD) and thermal diffusion probe in SAH patients. Thirteen patients with SAH were prospectively enrolled in the study. Eight patients underwent placement of a thermal diffusion probe for regional CBF measurement. CBF values were measured with the patients in flat (0°) and upright sitting positions (90°) at days 3, 7, and 10. The average increase in blood flow velocity when changing HOB from 0° to 90° was 7.8% on day 3, 0.1% on day 7, and 13.1% on day 10. The middle cerebral artery had the least changes in velocity. The average regional CBF measurement was 22.7 ± 0.3 mL/100 g/min in the supine position and 23.6 ± 9.1 mg/100 g/min in the sitting position. The changes were not statistically significant. None of the patients developed clinical cerebral vasospasm. Changing HOB position in the setting of SAH did not significantly affect cerebral or regional blood flow. These data suggest that early mobilization should be considered given the detrimental effects of prolonged bed rest.

Arterial spin labelling (ASL) is increasingly being applied to study the cerebral response to pain in both experimental human models and patients with persistent pain. Despite its advantages, scanning time and reliability remain important issues in the clinical applicability of ASL. Here we present the test-retest analysis of concurrent pseudo-continuous ASL (pCASL) and visual analogue scale (VAS), in a clinical model of on-going pain following third molar extraction (TME). Using ICC performance measures, we were able to quantify the reliability of the post-surgical pain state and ΔCBF (change in CBF), both at the group and individual case level. Within-subject, the inter- and intra-session reliability of the post-surgical pain state was ranked good-to-excellent (ICC > 0.6) across both pCASL and VAS modalities. The parameter ΔCBF (change in CBF between pre- and post-surgical states) performed reliably (ICC > 0.4), provided that a single baseline condition (or the mean of more than one baseline) was used for subtraction. Between-subjects, the pCASL measurements in the post-surgical pain state and ΔCBF were both characterised as reliable (ICC > 0.4). However, the subjective VAS pain ratings demonstrated a significant contribution of pain state variability, which suggests diminished utility for interindividual comparisons. These analyses indicate that the pCASL imaging technique has considerable potential for the comparison of within- and between-subjects differences associated with pain-induced state changes and baseline differences in regional CBF. They also suggest that differences in baseline perfusion and functional lateralisation characteristics may play an important role in the overall reliability of the estimated changes in CBF. Repeated measures designs have the important advantage that they provide good reliability for comparing condition effects because all sources of variability between subjects are excluded from the experimental error. The ability to elicit reliable neural correlates of on-going pain using quantitative perfusion imaging may help support the conclusions derived from subjective self-report.

The neural mechanisms underlying processing of auditory feedback during self-vocalization are poorly understood. One technique used to study the role of auditory feedback involves shifting the pitch of the feedback that a speaker receives, known as pitch-shifted feedback. We utilized a pitch shift self-vocalization and playback paradigm to investigate the underlying neural mechanisms of audio-vocal interaction. High-resolution electrocorticography (ECoG) signals were recorded directly from auditory cortex of 10 human subjects while they vocalized and received brief downward (-100 cents) pitch perturbations in their voice auditory feedback (speaking task). ECoG was also recorded when subjects passively listened to playback of their own pitch-shifted vocalizations. Feedback pitch perturbations elicited average evoked potential (AEP) and event-related band power (ERBP) responses, primarily in the high gamma (70-150 Hz) range, in focal areas of non-primary auditory cortex on superior temporal gyrus (STG). The AEPs and high gamma responses were both modulated by speaking compared with playback in a subset of STG contacts. From these contacts, a majority showed significant enhancement of high gamma power and AEP responses during speaking while the remaining contacts showed attenuated response amplitudes. The speaking-induced enhancement effect suggests that engaging the vocal motor system can modulate auditory cortical processing of self-produced sounds in such a way as to increase neural sensitivity for feedback pitch error detection. It is likely that mechanisms such as efference copies may be involved in this process, and modulation of AEP and high gamma responses imply that such modulatory effects may affect different cortical generators within distinctive functional networks that drive voice production and control.

Objective: Increasing evidence suggests a central nervous system (CNS) component underpinning persistent pain disease states. This study was undertaken to determine regional cerebral blood flow (rCBF) changes representing ongoing pain experienced by patients with painful osteoarthritis (OA) of the carpometacarpal (CMC) joint and to examine rCBF variability across sessions. We used pulsed continuous arterial spin labeling (pCASL), a perfusion magnetic resonance imaging (MRI) technique., Methods: The study included 16 patients with CMC OA and 17 matched controls. Two pCASL scans and numerical rating scale (NRS) estimates of ongoing pain were acquired in each of two identical sessions. Voxelwise general linear model analyses were performed to determine rCBF differences between OA and control groups, rCBF differences between sessions within each group, and whether sessionwise rCBF differences were related to variability in perceived ongoing pain., Results: In the OA group, rCBF increases representing ongoing pain were identified in the primary and secondary somatosensory, insula, and cingulate cortices; thalamus; amygdala; hippocampus; and dorsal midbrain/pontine tegmentum, including the periaqueductal gray/nucleus cuneiformis. Sessionwise rCBF differences in the OA group in the postcentral, rostral/subgenual cingulate, mid/anterior insula, prefrontal, and premotor cortices were related to changes in perceived ongoing pain. No significant sessionwise rCBF differences were observed in controls., Conclusion: This is the first quantitative endogenous perfusion MRI study of the cerebral representation of ongoing, persistent pain due to OA. Observed rCBF changes potentially indicate dysregulated CNS appraisal and modulation of pain, most likely the maladaptive neuroplastic sequelae of living with painful OA. Understanding the neural basis of ongoing pain is likely to be important in developing novel treatment strategies., (Copyright © 2012 by the American College of Rheumatology.)

We describe a novel spinal cord (SC) stimulator that is designed to overcome a major shortcoming of existing stimulator devices: their restricted capacity to selectively activate targeted axons within the dorsal columns. This device overcomes that limitation by delivering electrical stimuli directly to the pial surface of the SC. Our goal in testing this device was to measure its ability to physiologically activate the SC and examine its capacity to modulate somatosensory evoked potentials (SSEPs) triggered by peripheral stimulation. In this acute study on adult sheep (n = 7), local field potentials were recorded from a grid placed in the subdural space of the right hemisphere during electrical stimulation of the left tibial nerve and the spinal cord. Large amplitude SSEPs (>200 µV) in response to SC stimulation were consistently obtained at stimulation strengths well below the thresholds inducing neural injury. Moreover, stimulation of the dorsal columns with signals employed routinely by devices in standard clinical use, e.g., 50 Hz, 0.2 ms pulse width, produced long-lasting changes (>4.5 h) in the SSEP patterns produced by subsequent tibial nerve stimulation. The results of these acute experiments demonstrate that this device can be safely secured to the SC surface and effectively activate somatosensory pathways.

Background: To improve methods for the treatment of intractable pain, we are developing a novel intradural spinal cord stimulator that could be either attached to the dentate ligaments of the human spinal cord or fitted around the dorsal arc of the cord itself., Purpose: Our goal was to carry out the first in vivo tests of these attachment methods in an ovine model using custom-built devices and instrumentation. For eventual translational studies, we also explored methods of mimicking a human dentate ligament attachment technique in this large animal model., Methods: As a starting point, we investigated details of the gross and histological anatomy of the ovine denticulate ligaments, and compared them with their human counterpart. The gap between the dura and the spinal cord in the sheep is small; hence, the denticulate ligaments are not long enough to accommodate human-scaled attachment clips. Therefore, lateral strips of the spinal-canal dura were fashioned to serve this same device attachment function., Results: This form of dural anchoring was implemented surgically for fixation of a silicone membrane implant that had 12 electrodes, and somatosensory evoked potentials were obtained successfully when stimuli were applied to it. The dorsal arc clamping technique was also implemented., Conclusions: We demonstrated that the dural attachment method is an effective surrogate model for testing the human dentate ligament device fixation technique, and that this mode of fixation was preferable to dorsal arc attachment. The relevant surgical innovations, anatomical findings, and the preliminary electrophysiological data from a pial surface stimulator attached in this way are presented.

Background: Studies examining patterns of cancer care before 2000 have shown underuse of postmastectomy breast reconstruction as well as racial and socioeconomic disparities in its delivery. These findings prompted legislation designed to broaden use at the turn of the millennium. However, little is known about trends in these findings over the past decade., Study Design: Patients who underwent mastectomy for stage 0 to III breast cancer between 1998 and 2007 (n = 452,903) were studied using the National Cancer Data Base to evaluate trends in the receipt of immediate and early delayed breast reconstruction. Those who underwent mastectomy between 1998 and 2000 (n = 150,177) and between 2005 and 2007 (n = 123,518) were compared using logistic regression to identify factors influencing the use of breast reconstruction and how they changed over time., Results: The use of postmastectomy breast reconstruction increased from 13% to 26% from 1998 to 2007. This increase was statistically significant in almost all patient subsets. Independent factors associated with breast reconstruction included age less than 50 years old; higher census-derived household income; private or managed care insurance; non-African American race; and treatment in an academic hospital setting. Treatment in an academic hospital and higher income became stronger predictors of breast reconstruction over the study period, while age became less of a predictor., Conclusions: Although the use of breast reconstruction has increased from 1998 to 2007, it is still underused among many patient populations. Furthermore, racial and socioeconomic disparities in its delivery have persisted or widened. Additional effort is necessary to broaden the use of breast reconstruction and to ensure equitable access to it., (Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

We have designed, built and tested an anthropomorphic-scale surrogate spinal canal, for use in preliminary evaluations of the performance characteristics of a novel intradural spinal cord stimulator. The surrogate employs a silicone mock spinal cord with semi-major and semi-minor diameters of 10 and 6 mm, respectively, commensurate with those of actual thoracic-level spinal cord. The axial restoring force provided by the 300 µm thick silicone denticulate ligament constructs on the mock cord is ~ 0.32 N mm(-1) over a 1.5 mm range of displacement, which is within a factor of 2 of that measured by others in human cadaver specimens. Examples of testing protocols of prototype intradural stimulators that employ this device are discussed.

In this paper we examine the effect of Ga doping on the structure and conductivity of the high Li ion content garnet-related system, La(3)Zr(2)Li(7)O(12). Without Ga doping, La(3)Zr(2)Li(7)O(12) is tetragonal and has low Li ion conductivity. The introduction of Ga leads to a change to a cubic unit cell, and a large enhancement in the conductivity. Prior structural studies of La(3)Zr(2)Li(7)O(12) have shown the presence of both tetrahedral and distorted octahedral sites for Li, and the low conductivity can be explained by the ordered nature of the Li distribution. The present structural study of La(3)Zr(2)Ga(0.5)Li(5.5)O(12) shows that Ga substitutes onto the tetrahedral site. Despite the presence of non-mobile Ga(3+) on the Li sites, the conductivity is enhanced as a result of the introduction of vacancies in the Li sites, and consequent disorder on the Li sublattice. Further work has suggested that over time in air, there is some H(+)/Li(+) exchange, and consequently some variation in the conductivity.

Spontaneous cerebellar hemorrhage often requires surgical suboccipital decompression and clot evacuation. Predictors of postoperative neurological deficits and outcome are not widely addressed in the literature. A retrospective review was conducted on 37 consecutive patients with the diagnosis of cerebellar hemorrhage requiring suboccipital decompression and clot evacuation. Clinical and radiographic variables were analyzed. Outcome measures were postoperative Glasgow Coma Scale (GCS) score, and long-term outcome measured by Rankin score and Glasgow Outcome Scale (GOS) score. A multivariate statistical analysis was conducted. The average age of patients was 71.1 years. There was significant improvement of neurological exam from a mean preoperative GCS score of 8.8 to a mean postoperative GCS score of 13.0. The mortality rate was 37.9%. According to the Rankin scale, 58.6% were functionally independent, 3.4% had a moderate disability, and none had a major disability or was in a vegetative state. Using GOS score, 62.1% had a favorable outcome. The presence of multiple comorbidities was associated with worse postoperative GCS and long-term outcome. A worse preoperative neurological exam, age older than 70 years, and the presence of intraventricular hemorrhage correlated only with a worse postoperative exam but not with the long-term outcome. Patients improve neurologically after posterior fossa decompression for cerebellar hemorrhage and a high percentage attain long-term functional outcome. Only the presence of multiple clinical comorbidities was associated with a worse outcome. Since there are no other preoperative predictors of long-term outcome, we recommend suboccipital decompression, when indicated, for patients with cerebellar hemorrhage regardless of age, hematoma size, or preoperative neurological exam., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Myoclonus is characterized by sudden, brief involuntary movements, and its presence is debilitating. We identified a family suffering from adult onset, cortical myoclonus without associated seizures. We performed clinical, electrophysiological, and genetic studies to define this phenotype., Methods: A large, 4-generation family with a history of myoclonus underwent careful questioning, examination, and electrophysiological testing. Thirty-five family members donated blood samples for genetic analysis, which included single nucleotide polymorphism mapping, microsatellite linkage, targeted massively parallel sequencing, and Sanger sequencing. In silico and in vitro experiments were performed to investigate functional significance of the mutation., Results: We identified 11 members of a Canadian Mennonite family suffering from adult onset, slowly progressive, disabling, multifocal myoclonus. Somatosensory evoked potentials indicated a cortical origin of the myoclonus. There were no associated seizures. Some severely affected individuals developed signs of progressive cerebellar ataxia of variable severity late in the course of their illness. The phenotype was inherited in an autosomal dominant fashion. We demonstrated linkage to chromosome 16q21-22.1. We then sequenced all coding sequence in the critical region, identifying only a single cosegregating, novel, nonsynonymous mutation, which resides in the gene NOL3. Furthermore, this mutation was found to alter post-translational modification of NOL3 protein in vitro., Interpretation: We propose that familial cortical myoclonus is a novel movement disorder that may be caused by mutation in NOL3. Further investigation of the role of NOL3 in neuronal physiology may shed light on neuronal membrane hyperexcitability and pathophysiology of myoclonus and related disorders., (Copyright © 2012 American Neurological Association.)

Electrophysiological and fMRI-based investigations of the ventral temporal cortex of primates provide strong support for regional specialization for the processing of faces. These responses are most frequently found in or near the fusiform gyrus, but there is substantial variability in their anatomical location and response properties. An outstanding question is the extent to which ventral temporal cortex participates in processing dynamic, expressive aspects of faces, a function usually attributed to regions near the superior temporal cortex. Here, we investigated these issues through intracranial recordings from eight human surgical patients. We compared several different aspects of face processing (static and dynamic faces; happy, neutral, and fearful expressions) with power in the high-gamma band (70-150 Hz) from a spectral analysis. Detailed mapping of the response characteristics as a function of anatomical location was conducted in relation to the gyral and sulcal pattern on each patient's brain. The results document responses with high responsiveness for static or dynamic faces, often showing abrupt changes in response properties between spatially close recording sites and idiosyncratic across different subjects. Notably, strong responses to dynamic facial expressions can be found in the fusiform gyrus, just as can responses to static faces. The findings suggest a more complex, fragmented architecture of ventral temporal cortex around the fusiform gyrus, one that includes focal regions of cortex that appear relatively specialized for either static or dynamic aspects of faces.

We have designed, built and tested a novel device for placing intradural neurmodulator implants directly on the pial surface of the spinal cord. This applier tool is designed for ergonomic handling of delicate electro-mechanical devices such as the Iowa-Patch™ spinal cord stimulator implant, which is aimed at overcoming certain shortcomings in the performance of standard epidural stimulator devices. The applier is approximately 14 cm long, 6 mm in diameter, made of stainless steel components, and has simple and reliable mechanisms for the attachment and release of the implant from it. We describe the design of the device, details of its construction, and its performance during in vivo testing of somatosensory evoked potentials in an ovine model of intradural spinal cord stimulation.

Object: Vagus nerve stimulation (VNS) has demonstrated benefit in patients with medically intractable partial epilepsy. As in other therapies with mechanical devices, hardware failure occurs, most notably within the VNS lead, requiring replacement. However, the spiral-designed lead electrodes wrapped around the vagus nerve are often encased in dense scar tissue hampering dissection and removal. The objective in this study was to characterize VNS lead failure and lead revision surgery and to examine VNS efficacy after placement of a new electrode on the previously used segment of vagus nerve., Methods: The authors reviewed all VNS lead revisions performed between October 2001 and August 2011 at the University of Iowa Hospitals and Clinics. Twenty-four patients underwent 25 lead revisions. In all cases, the helical electrodes were removed, and a new lead was placed on the previously used segment of vagus nerve. All inpatient and outpatient records of the 25 lead revisions were retrospectively reviewed., Results: Four cases were second lead revisions, and 21 cases were first lead revisions. The average time to any revision was 5 years (range 1.8-11.1 years), with essentially no difference between a first and second lead revision. The most common reason for a revision was intrinsic lead failure resulting in high impedance (64%), and the most common symptom was increased seizure frequency (72%). The average duration of surgery for the initial implantation in the 15 patients whose VNS system was initially implanted at the authors' institution was much shorter (94 minutes) than the average duration of lead revision surgery (173 minutes). However, there was a significant trend toward shorter surgical times as more revision surgeries were performed. Sixteen of the 25 cases of lead revision were followed up for more than 3 months. In 15 of these 16 cases, the revision was as effective as the previous VNS lead. In most of these cases, both the severity and frequency of seizures were decreased to levels similar to those following the previous implantation procedure. Only 1 complication occurred, and there were no postoperative infections., Conclusions: Lead revision surgery involving the placement of a new electrode at the previously used segment of vagus nerve is effective at decreasing the seizure burden to an extent similar to that obtained following the initial VNS implantation. Even with multiple lead revisions, patients can obtain VNS efficacy similar to that following the initial lead implantation. There is a learning curve with revision surgery, and overall the duration of surgery is longer than for the initial implantation. Note, however, that complications and infection are rare.

Functional Magnetic Resonance Imaging (fMRI) shows significant potential as a tool for predicting clinically important information such as future disease progression or drug effect from brain activity. Multivariate techniques have been developed that combine fMRI signals from across the brain to produce more robust predictive capabilities than can be obtained from single regions. However, the high dimensionality of fMRI data makes overfitting a significant problem. Reliable methods are needed for transforming fMRI data to a set of signals reflecting the underlying spatially extended patterns of neural dynamics. This paper demonstrates a task-specific Independent Component Analysis (ICA) procedure which identifies signals associated with coherent functional brain networks, and shows that these signals can be used for accurate and interpretable prediction. The task-specific ICA parcellations outperformed other feature generation methods in two separate datasets including parcellations based on resting-state data and anatomy. The pattern of response of the task-specific ICA parcellations to particular feature selection strategies indicates that they identify important functional networks associated with the discriminative task. We show ICA parcellations to be robust and informative with respect to non-neural artefacts affecting the fMRI series. Together, these results suggest that task-specific ICA parcellation is a powerful technique for producing predictive and informative signals from fMRI time series. The results presented in this paper also contribute evidence for the general functional validity of the parcellations produced by ICA approaches., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We have designed, built and tested a novel spinal cord surrogate that mimics the low-amplitude cardiac-driven pulsations of the human spinal cord, for use in developing intradural implants to be used in a novel form of neuromodulation for the treatment of intractable pain and motor system dysfunction. The silicone surrogate has an oval cross section, 10 mm major axis × 6 mm minor axis, and incorporates a 3 mm diameter × 3 cm long angioplasty balloon that serves as the pulsation actuator. When pneumatically driven at 1 Hz and 1.5 atmospheres (≈ 1140 mm Hg), the surrogate's diametric pulsation is ≈ 100 μm, which corresponds well to in vivo observations. The applications for this surrogate are presented and discussed., (Copyright © 2012 Informa UK, Ltd.)

To clarify speech-elicited response patterns within auditory-responsive cortex of the posterolateral superior temporal (PLST) gyrus, time-frequency analyses of event-related band power in the high gamma frequency range (75-175 Hz) were performed on the electrocorticograms recorded from high-density subdural grid electrodes in 8 patients undergoing evaluation for medically intractable epilepsy. Stimuli were 6 stop consonant-vowel (CV) syllables that varied in their consonant place of articulation (POA) and voice onset time (VOT). Initial augmentation was maximal over several centimeters of PLST, lasted about 400 ms, and was often followed by suppression and a local outward expansion of activation. Maximal gamma power overlapped either the Nα or Pβ deflections of the average evoked potential (AEP). Correlations were observed between the relative magnitudes of gamma band responses elicited by unvoiced stop CV syllables (/pa/, /ka/, /ta/) and their corresponding voiced stop CV syllables (/ba/, /ga/, /da/), as well as by the VOT of the stimuli. VOT was also represented in the temporal patterns of the AEP. These findings, obtained in the passive awake state, indicate that PLST discriminates acoustic features associated with POA and VOT and serve as a benchmark upon which task-related speech activity can be compared.

In this work, we show that electrophysiological responses during pitch perception are best explained by distributed activity in a hierarchy of cortical sources and, crucially, that the effective connectivity between these sources is modulated with pitch strength. Local field potentials were recorded in two subjects from primary auditory cortex and adjacent auditory cortical areas along the axis of Heschl's gyrus (HG) while they listened to stimuli of varying pitch strength. Dynamic causal modeling was used to compare system architectures that might explain the recorded activity. The data show that representation of pitch requires an interaction between nonprimary and primary auditory cortex along HG that is consistent with the principle of predictive coding.

Object: The object of this study was to evaluate the causes of plunging events associated with automatic-releasing cranial perforators at the authors' institution., Methods: The authors analyzed a consecutive series of 1652 cranial procedures involving one type of automatic-releasing cranial perforator over a 2-year period. Plunging occurrences were recorded for 2 drill speeds: 1000 rpm in the 1st year and 800 rpm during the 2nd year. Intraoperative observations, neuroimaging studies, and clinical data were evaluated for each plunging event., Results: The authors identified 9 plunging events for an overall incidence of 0.54%. In the 1st year, they identified 2 plunging events at a speed of 1000 rpm for an incidence of 0.19%. In an effort to reduce this occurrence, the speed of the drill was lowered to 800 rpm. There were 7 additional events, for a significantly increased incidence of 1.16% (p = 0.014, Fisher exact test) after the change was implemented. These cases spanned a number of procedures in adults and pediatric patients, including ventriculostomy placement, craniotomies for tumor resection, tumor biopsy, and endoscopic third ventriculostomy. Despite plunging, no immediate postoperative complications were noted on clinical examination., Conclusions: While technology continues to improve cranial perforator performance, the use of such a device is still associated with a risk of complications causing dural lacerations and injury to the underlying cortex. Decreasing the drill speed may not decrease the incidence of plunging.

Background: There has been a dramatic rise in the consumption of alcohol mixed with energy drinks (AmED) in young people. AmED have been implicated in risky drinking practices and greater accidents and injuries have been associated with their consumption. Despite the increased popularity of these beverages (e.g., Red Bull and vodka), there is little laboratory research examining how the effects of AmED differ from alcohol alone. This experiment was designed to investigate if the consumption of AmED alters neurocognitive and subjective measures of intoxication compared with the consumption of alcohol alone., Methods: Participants (n=56) attended 1 session where they were randomly assigned to receive one of 4 doses (0.65 g/kg alcohol, 3.57 ml/kg energy drink, AmED, or a placebo beverage). Performance on a cued go/no-go task was used to measure the response of inhibitory and activational mechanisms of behavioral control following dose administration. Subjective ratings of stimulation, sedation, impairment, and level of intoxication were recorded., Results: Alcohol alone impaired both inhibitory and activational mechanisms of behavioral control, as evidenced by increased inhibitory failures and increased response times compared to baseline performance. Coadministration of the energy drink with alcohol counteracted some of the alcohol-induced impairment of response activation, but not response inhibition. For subjective effects, alcohol increased ratings of stimulation, feeling the drink, liking the drink, impairment, and level of intoxication, and alcohol decreased the rating of ability to drive. Coadministration of the energy drink with alcohol increased self-reported stimulation, but resulted in similar ratings of the other subjective effects as when alcohol was administered alone., Conclusions: An energy drink appears to alter some of the objective and subjective impairing effects of alcohol, but not others. Thus, AmED may contribute to a high-risk scenario for the drinker. The mix of impaired behavioral inhibition and enhanced stimulation is a combination that may make AmED consumption riskier than alcohol consumption alone., (Copyright © 2011 by the Research Society on Alcoholism.)

Object: The risk of surgical site infection (SSI) after craniotomies or craniectomies in patients in whom contaminated bone flaps have been reimplanted has not been determined. The objectives of this study were to identify the prevalence of bone flaps with positive cultures--especially those contaminated with Propionibacterium acnes--to assess the risk of SSI after reimplanting (either during the initial operation or subsequently) bone flaps with positive cultures, and to identify risk factors for SSI following the initial craniotomies or craniectomies., Methods: The authors conducted a retrospective review of cases in which patients underwent craniotomy/craniectomy procedures between January and October 2007 in the neurosurgery department at the University of Iowa Hospitals and Clinics. They also reviewed processes and procedures and did pulsed field gel electrophoresis of P. acnes isolates to look for a common source of contamination. They then conducted a prospective cohort study that included all patients who underwent craniotomy/craniectomy procedures between November 2007 and November 2008 and met the study criteria. For the cohort study, the authors obtained cultures from each patient's bone flap during the craniotomy/craniectomy procedures. Data about potential risk factors were collected by circulating nurses during the procedures or by a research assistant who reviewed medical records after the procedures. An infection preventionist independently identified SSIs through routine surveillance using the Centers for Disease Control and Prevention's definitions. Univariate and bivariate analyses were performed to determine the association between SSI and potential risk factors., Results: The retrospective review did not identify specific breaks in aseptic technique or a common source of P. acnes. Three hundred seventy-three patients underwent 393 craniotomy/craniectomy procedures during the cohort study period, of which 377 procedures met the study criteria. Fifty percent of the bone flaps were contaminated by microorganisms, primarily skin flora such as P. acnes, coagulase-negative staphylococci, and Staphylococcus aureus. Reimplanting bone flaps that had positive culture results did not increase the risk of infection after the initial craniotomy/craniectomy procedures and the subsequent cranioplasty procedures (p = 0.80). Allowing the skin antiseptic to dry before the procedures (p = 0.04, OR 0.26) was associated with lower risk of SSIs. Female sex (p = 0.02, OR = 3.49) was associated with an increased risk of SSIs; Gliadel wafer implants (p = 0.001, OR = 8.38) were associated with an increased risk of SSIs after procedures to treat tumors., Conclusions: Operative factors such as the way the skin is prepared before the incision rather than the skin flora contaminants on the bone flaps may play an important role in the pathogenesis of SSIs after craniotomy/craniectomy. Gliadel wafers significantly increased the risk of SSI after procedures to treat tumors.

Dlx transcription factors are important in the differentiation of GABAergic interneurons. In mice lacking Dlx1, early steps in interneuron development appear normal. Beginning at ∼ 1 mo of age, primarily dendrite-innervating interneuron subtypes begin to undergo apoptosis in Dlx1(-/-) mice; this is accompanied by a reduction in GABAergic transmission and late-onset epilepsy. The reported reduction of synaptic inhibition is greater than might be expected given that interneuron loss is relatively modest in Dlx1(-/-) mice. Here we report that voltage-clamp recordings of CA1 interneurons in hippocampal slices prepared from Dlx1(-/-) animals older than postnatal day 30 (>P30) revealed a significant reduction in excitatory postsynaptic current (EPSC) amplitude. No changes in EPSCs onto interneurons were observed in cells recorded from younger animals (P9-12). Current-clamp recordings from interneurons at these early postnatal ages showed that interneurons in Dlx1(-/-) mutants were immature and more excitable, although membrane properties normalized by P30. Terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling, caspase-3, and NeuN staining did not reveal frank cell damage or loss in area CA3 of hippocampal sections from adult Dlx1(-/-) mice. Delayed interneuron maturation may lead to interneuron hyperexcitability, followed by a compensatory reduction in the strength of excitatory transmission onto interneurons. This reduced excitation onto surviving interneurons, coupled with the loss of a significant fraction of GABAergic inputs to excitatory neurons starting at P30, may underlie cortical dysrhythmia and seizures previously observed in adult Dlx1(-/-) mice.

Object: Intracranial stenting has improved the ability to treat wide-neck aneurysms via endovascular techniques. However, stent placement necessitates the use of antiplatelet agents, and the latter may complicate the treatment of patients with acutely ruptured aneurysms who demonstrate hydrocephalus and require ventriculostomy. Antiplatelet agents in this setting could increase the incidence of ventriculostomy-related hemorrhagic complications, but there are insufficient data in the medical literature to quantify this potential risk. The aim of this study was to directly quantify the risk of ventriculostomy-related hemorrhage in patients with acute aneurysmal subarachnoid hemorrhage treated with stent-assisted coiling., Methods: The authors retrospectively identified 131 patients who underwent endovascular treatment for an acutely ruptured aneurysm as well as ventriculostomy or ventriculoperitoneal (VP) shunt placement. The rate of hemorrhagic complications associated with ventriculostomy or VP shunt insertion was compared between patients who underwent coiling without a stent (Group 1) and those who underwent stent-assisted coiling and dual antiplatelet therapy (Group 2)., Results: One hundred nine ventriculostomies or VP shunt placement procedures were performed in 91 patients in Group 1, and 50 procedures were undertaken in 40 patients in Group 2. The rates of radiographic hemorrhage and symptomatic hemorrhage were significantly higher in Group 2 (32% vs 14.7%, p = 0.02; and 8% vs 0.9%, p = 0.03, respectively). On multivariate analyses, Group 2 had 3.42 times the odds of a radiographic hemorrhage (95% CI 1.46-8.04, p = 0.0048) after adjusting for antiplatelet use prior to admission., Conclusions: The application of dual antiplatelet therapy in stent-assisted coiling of acutely ruptured aneurysms is associated with an increase in the risk of hemorrhagic complications following ventriculostomy or VP shunt placement, as compared with its use in a coiling procedure without a stent.

During speaking, auditory feedback is used to adjust vocalizations. The brain systems mediating this integrative ability have been investigated using a wide range of experimental strategies. In this report we examined how vocalization alters speech-sound processing within auditory cortex by directly recording evoked responses to vocalizations and playback stimuli using intracranial electrodes implanted in neurosurgery patients. Several new findings resulted from these high-resolution invasive recordings in human subjects. Suppressive effects of vocalization were found to occur only within circumscribed areas of auditory cortex. In addition, at a smaller number of sites, the opposite pattern was seen; cortical responses were enhanced during vocalization. This increase in activity was reflected in high gamma power changes, but was not evident in the averaged evoked potential waveforms. These new findings support forward models for vocal control in which efference copies of premotor cortex activity modulate sub-regions of auditory cortex.

Development of treatments for acute and chronic pain conditions remains a challenge, with an unmet need for improved sensitivity and reproducibility in measuring pain in patients. Here we used pulsed-continuous arterial spin-labelling [pCASL], a relatively novel perfusion magnetic-resonance imaging technique, in conjunction with a commonly-used post-surgical model, to measure changes in regional cerebral blood flow [rCBF] associated with the experience of being in ongoing pain. We demonstrate repeatable, reproducible assessment of ongoing pain that is independent of patient self-report. In a cross-over trial design, 16 participants requiring bilateral removal of lower-jaw third molars underwent pain-free pre-surgical pCASL scans. Following extraction of either left or right tooth, repeat scans were acquired during post-operative ongoing pain. When pain-free following surgical recovery, the pre/post-surgical scanning procedure was repeated for the remaining tooth. Voxelwise statistical comparison of pre and post-surgical scans was performed to reveal rCBF changes representing ongoing pain. In addition, rCBF values in predefined pain and control brain regions were obtained. rCBF increases (5-10%) representing post-surgical ongoing pain were identified bilaterally in a network including primary and secondary somatosensory, insula and cingulate cortices, thalamus, amygdala, hippocampus, midbrain and brainstem (including trigeminal ganglion and principal-sensory nucleus), but not in a control region in visual cortex. rCBF changes were reproducible, with no rCBF differences identified across scans within-session or between post-surgical pain sessions. This is the first report of the cerebral representation of ongoing post-surgical pain without the need for exogenous tracers. Regions of rCBF increases are plausibly associated with pain and the technique is reproducible, providing an attractive proposition for testing interventions for on-going pain that do not rely solely on patient self-report. Our findings have the potential to improve our understanding of the cerebral representation of persistent painful conditions, leading to improved identification of specific patient sub-types and implementation of mechanism-based treatments.

A growing consensus suggests that the brain makes simple choices by assigning values to the stimuli under consideration and then comparing these values to make a decision. However, the network involved in computing the values has not yet been fully characterized. Here, we investigated whether the human amygdala plays a role in the computation of stimulus values at the time of decision making. We recorded single neuron activity from the amygdala of awake patients while they made simple purchase decisions over food items. We found 16 amygdala neurons, located primarily in the basolateral nucleus that responded linearly to the values assigned to individual items.

It is widely assumed that intracranial recordings from the brain are only minimally affected by contamination due to ocular-muscle electromyogram (oEMG). Here we show that this is not always the case. In intracranial recordings from five surgical epilepsy patients we observed that eye movements caused a transient biphasic potential at the onset of a saccade, resembling the saccadic spike potential commonly seen in scalp EEG, accompanied by an increase in broadband power between 20 and 200 Hz. Using concurrently recorded eye movements and high-density intracranial EEG (iEEG) we developed a detailed overview of the spatial distribution and temporal characteristics of the saccade-related oculomotor signal within recordings from ventral, medial and lateral temporal cortex. The occurrence of the saccadic spike was not explained solely by reference contact location, and was observed near the temporal pole for small (<2 deg) amplitude saccades and over a broad area for larger saccades. We further examined the influence of saccade-related oEMG contamination on measurements of spectral power and interchannel coherence. Contamination manifested in both spectral power and coherence measurements, in particular, over the anterior half of the ventral and medial temporal lobe. Next, we compared methods for removing the contaminating signal and found that nearest-neighbor bipolar re-referencing and ICA filtering were effective for suppressing oEMG at locations far from the orbits, but tended to leave some residual contamination at the temporal pole. Finally, we show that genuine cortical broadband gamma responses observed in averaged data from ventral temporal cortex can bear a striking similarity in time course and band-width to oEMG contamination recorded at more anterior locations. We conclude that eye movement-related contamination should be ruled out when reporting high gamma responses in human intracranial recordings, especially those obtained near anterior and medial temporal lobe., (Copyright © 2010 Elsevier Inc. All rights reserved.)

There has been a dramatic rise in the consumption of glucose energy drinks (e.g., Amp, Monster, and Red Bull) in the past decade, particularly among high school and college students. However, little laboratory research has examined the acute objective and subjective effects of energy drinks. The purpose of this study was to investigate the acute effects of a glucose energy drink (Red Bull) on cognitive functioning. Participants (N = 80) were randomly assigned to one of five conditions: 1.8 ml/kg energy drink, 3.6 ml/kg energy drink, 5.4 ml/kg energy drink, placebo beverage, or no drink. Participants completed a well-validated behavioral control task (the cued go/no-go task) and subjective measures of stimulation, sedation, and mental fatigue both before and 30 minutes following beverage administration. The results indicated that compared with the placebo and no drink conditions, the energy drink doses decreased reaction times on the behavioral control task, increased subjective ratings of stimulation and decreased ratings of mental fatigue. Greatest improvements in reaction times and subjective measures were observed with the lowest dose and improvements diminished as the dose increased. The findings suggest that energy drink consumption can improve cognitive performance on a behavioral control task, potentially explaining the dramatic rise in popularity of these controversial new beverages., (PsycINFO Database Record (c) 2010 APA, all rights reserved.)

Spontaneous intracranial hypotension (SIH) is a syndrome with serious neurological sequelae. As demonstrated by the following report, recurrent episodes of SIH can be difficult to diagnose when associated with other neurosurgical procedures, such as craniectomies. In this paper, the authors demonstrate SIH presenting as a subdural hematoma with recurrence of CSF leaks. Spontaneous intracranial hypotension was further complicated by paradoxical herniation following a craniectomy. Treatment of SIH necessitated multiple epidural blood patches for CSF leaks at different spinal levels and at different times. The efficacy of each epidural blood patch was confirmed with radionuclide imaging. Confirmation of effective blood patch placement may be useful for identifying patients at risk for a failed epidural blood patch or for patients whose neurological examination results have not fully improved.

Neurons of the cochlear nuclei are anatomically and physiologically specialized to optimally encode temporal and spectral information about sound stimuli, in part for binaural auditory processing. The avian cochlear nucleus magnocellularis (NM) integrates excitatory eighth nerve inputs and depolarizing GABAergic inhibition such that temporal fidelity is enhanced across the synapse. The biophysical mechanisms of this depolarizing inhibition, and its role in temporal processing, are not fully understood. We used whole-cell electrophysiology and computational modeling to examine how subthreshold excitatory inputs are integrated and how depolarizing IPSPs affect spike thresholds and synaptic integration by chick NM neurons. We found that both depolarizing inhibition and subthreshold excitatory inputs cause voltage threshold accommodation, nonlinear temporal summation, and shunting. Inhibition caused such large changes in threshold that subthreshold excitatory inputs were followed by a refractory period. We hypothesize that these large shifts in threshold eliminate spikes to asynchronous inputs, providing a mechanism for the enhanced temporal fidelity seen across the eighth nerve/cochlear nucleus synapse. Thus, depolarizing inhibition and threshold shifting hone the temporal response properties of this system so as to enhance the temporal fidelity that is essential for auditory perception.

Pitch is a fundamental percept with a complex relationship to the associated sound structure. Pitch perception requires brain representation of both the structure of the stimulus and the pitch that is perceived. We describe direct recordings of local field potentials from human auditory cortex made while subjects perceived the transition between noise and a noise with a regular repetitive structure in the time domain at the millisecond level called regular-interval noise (RIN). RIN is perceived to have a pitch when the rate is above the lower limit of pitch, at approximately 30 Hz. Sustained time-locked responses are observed to be related to the temporal regularity of the stimulus, commonly emphasized as a relevant stimulus feature in models of pitch perception (e.g., [1]). Sustained oscillatory responses are also demonstrated in the high gamma range (80-120 Hz). The regularity responses occur irrespective of whether the response is associated with pitch perception. In contrast, the oscillatory responses only occur for pitch. Both responses occur in primary auditory cortex and adjacent nonprimary areas. The research suggests that two types of pitch-related activity occur in humans in early auditory cortex: time-locked neural correlates of stimulus regularity and an oscillatory response related to the pitch percept., (Copyright 2010 Elsevier Ltd. All rights reserved.)

A wide range of devices is used to obtain intracranial electrocorticography recordings in patients with medically refractory epilepsy, including subdural strip and grid electrodes and depth electrodes. Penetrating depth electrodes are required to access some brain regions, and 1 target site that presents a particular technical challenge is the first transverse temporal gyrus, or Heschl gyrus (HG). The HG is located within the supratemporal plane and has an oblique orientation relative to the sagittal and coronal planes. Large and small branches of the middle cerebral artery abut the pial surface of the HG and must be avoided when planning the electrode trajectory. Auditory cortex is located within the HG, and there are functional connections between this dorsal temporal lobe region and medial sites commonly implicated in the pathophysiology of temporal lobe epilepsy. At some surgical centers, depth electrodes are routinely placed within the supratemporal plane, and the HG, in patients who require intracranial electrocorticography monitoring for presumed temporal lobe epilepsy. Information from these recordings is reported to facilitate the identification of seizure patterns in patients with or without auditory auras. To date, only one implantation method has been reported to be safe and effective for placing HG electrodes in a large series of patients undergoing epilepsy surgery. This well-established approach involves inserting the electrodes from a lateral trajectory while using stereoscopic stereotactic angiography to avoid vascular injury. In this report, the authors describe an alternative method for implantation. They use frameless stereotaxy and an oblique insertion trajectory that does not require angiography and allows for the simultaneous placement of subdural grid arrays. Results in 19 patients demonstrate the safety and efficacy of the method.

Proteins of the PSD-95-like membrane-associated guanylate kinase (PSD-MAGUK) family are vital for trafficking AMPA receptors (AMPARs) to synapses, a process necessary for both basal synaptic transmission and forms of synaptic plasticity. Synapse-associated protein 97 (SAP97) exhibits protein interactions, such as direct interaction with the GluA1 AMPAR subunit, and subcellular localization (synaptic, perisynaptic, and dendritic) unique within this protein family. Due in part to the lethality of the germline knockout of SAP97, this protein's role in synaptic transmission and plasticity is poorly understood. We found that overexpression of SAP97 during early development traffics AMPARs and NMDA receptors (NMDARs) to synapses, and that SAP97 rescues the deficits in AMPAR currents normally seen in PSD-93/-95 double-knockout neurons. Mature neurons that have experienced the overexpression of SAP97 throughout development exhibit enhanced AMPAR and NMDAR currents, as well as faster NMDAR current decay kinetics. In loss-of-function experiments using conditional SAP97 gene deletion, we recorded no deficits in glutamatergic transmission or long-term potentiation. These results support the hypothesis that SAP97 is part of the machinery that traffics glutamate receptors and compensates for other PSD-MAGUKs in knockout mouse models. However, due to functional redundancy, other PSD-MAGUKs can presumably compensate when SAP97 is conditionally deleted during development.

Object: In this study the authors sought to determine whether any correlations existed between postimplantation head CT findings and the need to perform decompression surgery in patients with grid electrodes., Methods: The authors identified 74 patients who underwent intracranial electrode monitoring for medically refractory epilepsy from January 2000 through June 2008. Only the 46 patients who had head CT scans available for review were included in the study. The authors were able to determine the number and types of electrodes placed as well as complications experienced. They reviewed the CT scans for abnormal findings including extraaxial fluid collections, intracranial hemorrhages, and signs of mass effect., Results: All patients developed some degree of extraaxial fluid collection following the placement of intracranial electrodes. The maximum width of the extraaxial fluid collection and the degree of midline shift were not predictive of the need for decompressive surgery. The presence, but not degree, of midline shift was associated with the need for decompressive surgery. Likewise, the presence of ventricular asymmetry was correlated with the need for removal of the electrodes and bone flap. Patients without midline shift or ventricular asymmetry on CT did not require decompressive surgery., Conclusions: After undergoing placement of intracranial electrodes all patients develop extraaxial fluid collections. In addition, many patients develop signs of mass effect including midline shift and ventricular asymmetry. When these findings are absent it is highly unlikely that surgical decompression is required.

Speech comprehension relies on temporal cues contained in the speech envelope, and the auditory cortex has been implicated as playing a critical role in encoding this temporal information. We investigated auditory cortical responses to speech stimuli in subjects undergoing invasive electrophysiological monitoring for pharmacologically refractory epilepsy. Recordings were made from multicontact electrodes implanted in Heschl's gyrus (HG). Speech sentences, time compressed from 0.75 to 0.20 of natural speaking rate, elicited average evoked potentials (AEPs) and increases in event-related band power (ERBP) of cortical high-frequency (70-250 Hz) activity. Cortex of posteromedial HG, the presumed core of human auditory cortex, represented the envelope of speech stimuli in the AEP and ERBP. Envelope following in ERBP, but not in AEP, was evident in both language-dominant and -nondominant hemispheres for relatively high degrees of compression where speech was not comprehensible. Compared to posteromedial HG, responses from anterolateral HG-an auditory belt field-exhibited longer latencies, lower amplitudes, and little or no time locking to the speech envelope. The ability of the core auditory cortex to follow the temporal speech envelope over a wide range of speaking rates leads us to conclude that such capacity in itself is not a limiting factor for speech comprehension.

The occurrence of spontaneous acute epidural hematomas is rare in patients with sickle cell disease. The authors report the case of a patient with sickle cell anemia who presented with a sickle cell crisis that was complicated by the development of multiple acute epidural and subgaleal hematomas requiring surgical evacuation. Possible underlying mechanisms are discussed. Although rare, clinicians should be aware of this phenomenon as part of a spectrum of neurological complications in these patients.

The amygdala processes and directs inputs and outputs that are key to fear behavior. However, whether it directly senses fear-evoking stimuli is unknown. Because the amygdala expresses acid-sensing ion channel-1a (ASIC1a), and ASIC1a is required for normal fear responses, we hypothesized that the amygdala might detect a reduced pH. We found that inhaled CO(2) reduced brain pH and evoked fear behavior in mice. Eliminating or inhibiting ASIC1a markedly impaired this activity, and localized ASIC1a expression in the amygdala rescued the CO(2)-induced fear deficit of ASIC1a null animals. Buffering pH attenuated fear behavior, whereas directly reducing pH with amygdala microinjections reproduced the effect of CO(2). These data identify the amygdala as an important chemosensor that detects hypercarbia and acidosis and initiates behavioral responses. They also give a molecular explanation for how rising CO(2) concentrations elicit intense fear and provide a foundation for dissecting the bases of anxiety and panic disorders.

The capacity of auditory cortex on Heschl's gyrus (HG) to encode repetitive transients was studied in human patients undergoing surgical evaluation for medically intractable epilepsy. Multicontact depth electrodes were chronically implanted in gray matter of HG. Bilaterally presented stimuli were click trains varying in rate from 4 to 200 Hz. Averaged evoked potentials (AEPs) and event-related band power (ERBP), computed from responses at each of 14 recording sites, identified two auditory fields. A core field, which occupies posteromedial HG, was characterized by a robust polyphasic AEP on which could be superimposed a frequency following response (FFR). The FFR was prominent at click rates below approximately 50 Hz, decreased rapidly as click rate was increased, but could reliably be detected at click rates as high as 200 Hz. These data are strikingly similar to those obtained by others in the monkey under essentially the same stimulus conditions, indicating that mechanisms underlying temporal processing in the auditory core may be highly conserved across primate species. ERBP, which reflects increases or decreases of both phase-locked and non-phase-locked power within given frequency bands, showed stimulus-related increases in gamma band frequencies as high as 250 Hz. The AEPs recorded in a belt field anterolateral to the core were typically of low amplitude, showing little or no evidence of short-latency waves or an FFR, even at the lowest click rates used. The non-phase-locked component of the response extracted from the ERBP showed a robust, long-latency response occurring here in response to the highest click rates in the series.

Object: Control signals for brain-machine interfaces may be obtained from a variety of sources, each with their own relative merits. Electrocorticography (ECoG) provides better spatial and spectral resolution than scalp electroencephalography and does not include the risks attendant upon penetration of the brain parenchyma associated with single and multiunit recordings. For these reasons, subdural electrode recordings have been proposed as useful primary or adjunctive control signals for brain-machine interfaces. The goal of the present study was to determine if 2D control signals could be decoded from ECoG., Methods: Six patients undergoing invasive monitoring for medically intractable epilepsy using subdural grid electrodes were asked to perform a motor task involving moving a joystick in 1 of 4 cardinal directions (up, down, left, or right) and a fifth condition ("trigger"). Evoked activity was synchronized to joystick movement and analyzed in the theta, alpha, beta, gamma, and high-gamma frequency bands., Results: Movement-related cortical potentials could be accurately differentiated from rest with very high accuracy (83-96%). Further distinguishing the movement direction (up, down, left, or right) could also be resolved with high accuracy (58-86%) using information only from the high-gamma range, whereas distinguishing the trigger condition from the remaining directions provided better accuracy., Conclusions: Two-dimensional control signals can be derived from ECoG. Local field potentials as measured by ECoG from subdural grids will be useful as control signals for a brain-machine interface.

Background: The efficacy of stereotactic neurosurgery procedures is critically dependent on the accuracy of the device placement procedure. The first step in this process involves correctly identifying the target location in three-dimensional brain space. In some clinical applications, this targeting process cannot be accomplished using MRI images of gross anatomical structures alone. The amygdala complex is a case in point, in that it consists of multiple histologically defined subnuclei with different functional characteristics., Methods: In this report, we describe an elastic atlas brain-morphing method that projects amygdala subnuclear anatomical information onto the MRI volumes of individual subjects., Results: The accuracy of this method was tested in 5 representative subjects using quantitative image-matching analytical techniques. The results demonstrate a high degree of intersubject variability in medial temporal lobe anatomy, and markedly superior anatomical matching performance by the elastic morphing method compared to Affine transformation., Conclusion: Nonlinear elastic morphing technique provides superior performance on fitting atlas templates to individual brain. The strengths and limitations of this and other atlas morphing methods are discussed in the context of emerging functional neurosurgery applications., (Copyright 2009 S. Karger AG, Basel.)

Most seizures stop spontaneously; however, the molecular mechanisms that terminate seizures remain unknown. Observations that seizures reduced brain pH and that acidosis inhibited seizures indicate that acidosis halts epileptic activity. Because acid-sensing ion channel 1a (ASIC1a) is exquisitely sensitive to extracellular pH and regulates neuron excitability, we hypothesized that acidosis might activate ASIC1a, which would terminate seizures. Disrupting mouse ASIC1a increased the severity of chemoconvulsant-induced seizures, whereas overexpressing ASIC1a had the opposite effect. ASIC1a did not affect seizure threshold or onset, but shortened seizure duration and prevented seizure progression. CO2 inhalation, long known to lower brain pH and inhibit seizures, required ASIC1a to interrupt tonic-clonic seizures. Acidosis activated inhibitory interneurons through ASIC1a, suggesting that ASIC1a might limit seizures by increasing inhibitory tone. Our results identify ASIC1a as an important element in seizure termination when brain pH falls and suggest both a molecular mechanism for how the brain stops seizures and new therapeutic strategies.

Averaged auditory evoked potentials (AEPs) to bilaterally presented 100 Hz click trains were recorded from multiple sites simultaneously within Heschl's gyrus (HG) and on the posterolateral surface of the superior temporal gyrus (STG) in epilepsy-surgery patients. Three auditory fields were identified based on AEP waveforms and their distribution. Primary (core) auditory cortex was localized to posteromedial HG. Here the AEP was characterized by a robust polyphasic low-frequency field potential having a short onset latency and on which was superimposed a smaller frequency-following response to the click train. Core AEPs exhibited the lowest response threshold and highest response amplitude at one HG site with threshold rising and amplitude declining systematically on either side of it. The AEPs recorded anterolateral to the core, if present, were typically of low amplitude, with little or no evidence of short-latency waves or the frequency-following response that characterized core AEPs. We suggest that this area is part of a lateral auditory belt system. Robust AEPs, with waveforms demonstrably different from those of the core or lateral belt, were localized to the posterolateral surface of the STG and conform to previously described field PLST.