Neuroethics of Non-primary Brain Computer Interface: Focus on Potential Military Applications.

The field of neuroethics has had to adapt rapidly in the face of accelerating technological advancement; a particularly striking example is the realm of Brain-Computer Interface (BCI). A significant source of funding for the development of new BCI technologies has been the United States Department of Defense, and while the predominant focus has been restoration of lost function for those wounded in battle, there is also significant interest in augmentation of function to increase survivability, coordination, and lethality of US combat forces. While restoration of primary motor and sensory function (primary BCI) has been the main focus of research, there has been marked progress in interface with areas of the brain subserving memory and association. Non-Primary BCI has a different subset of potential applications, each of which also carries its own ethical considerations. Given the amount of BCI research funding coming from the Department of Defense, it is particularly important that potential military applications be examined from a neuroethical standpoint.

Occipital dysembryoplastic neuroepithelial tumor presenting as adult-onset temporal epilepsy.

Dysembryoplastic neuroepithelial tumor (DNET) is a benign brain tumor which commonly presents as childhood-onset temporal lobe epilepsy (TLE). We present a case of histologically proven DNET with a clinical presentation and scalp EEG suggestive of adult-onset TLE. MRI showed an occipital lesion. PET showed abnormal metabolism of the occipital lesion and the ipsilateral temporal lobe; raising concern for an abnormal functional network reorganization. Intracranial EEG showed interictal spikes and seizures originating from the occipital lesion with no seizures emanating from the temporal lobe. Occipital DNET due to their chronic nature can reorganize the network and mimic TLE.

Multiple hippocampal transections for intractable hippocampal epilepsy: Seizure outcome.

PURPOSE: The purpose of this study was to evaluate the seizure outcomes after transverse multiple hippocampal transections (MHTs) in 13 patients with intractable TLE. METHODS: Thirteen patients with normal memory scores, including 8 with nonlesional hippocampi on MRI, had temporal lobe epilepsy (TLE) necessitating depth electrode implantation. After confirming hippocampal seizure onset, they underwent MHT. Intraoperative monitoring was done with 5-6 hippocampal electrodes spaced at approximately 1-cm intervals and spike counting for 5-8min before each cut. The number of transections ranged between 4 and 7. Neuropsychological assessment was completed preoperatively and postoperatively for all patients and will be reported separately. RESULTS: Duration of epilepsy ranged between 5 and 55years. There were no complications. Intraoperatively, MHT resulted in marked spike reduction (p=0.003, paired t-test). Ten patients (77%) are seizure-free (average follow-up was 33months, range 20-65months) without medication changes. One of the 3 patients with persistent seizures had an MRI revealing incomplete transections, another had an additional neocortical seizure focus (as suggested by pure aphasic seizures), and the third had only 2 seizures in 4years, one of which occurred during antiseizure medication withdrawal. Verbal and visual memory outcomes will be reported separately. Right and left hippocampal volumes were not different preoperatively (n=12, p=0.64, Wilcoxon signed-rank test), but the transected hippocampal volume decreased postoperatively (p=0.0173). CONCLUSIONS: Multiple hippocampal transections provide an effective intervention and a safe alternative to temporal lobectomy in patients with hippocampal epilepsy.

Degree of distal trigeminal nerve atrophy predicts outcome after microvascular decompression for Type 1a trigeminal neuralgia.

OBJECT: Trigeminal neuralgia is often associated with nerve atrophy, in addition to vascular compression. The authors evaluated whether cross-sectional areas of different portions of the trigeminal nerve on preoperative imaging could be used to predict outcome after microvascular decompression (MVD). METHODS: A total of 26 consecutive patients with unilateral Type 1a trigeminal neuralgia underwent high-resolution fast-field echo MRI of the cerebellopontine angle followed by MVD. Preoperative images were reconstructed and reviewed by 2 examiners blinded to the side of symptoms and clinical outcome. For each nerve, a computerized automatic segmentation algorithm was used to calculate the coronal cross-sectional area at the proximal nerve near the root entry zone and the distal nerve at the exit from the porus trigeminus. Findings were correlated with outcome at 12 months. RESULTS: After MVD, 17 patients were pain free and not taking medications compared with 9 with residual pain. Across all cases, the coronal cross-sectional area of the symptomatic trigeminal nerve was significantly smaller than the asymptomatic side in the proximal part of the nerve, which was correlated with degree of compression at surgery. Atrophy of the distal trigeminal nerve was more pronounced in patients who had residual pain than in those with excellent outcome. Among the 7 patients who had greater than 20% loss of nerve volume in the distal nerve, only 2 were pain free and not taking medications at long-term follow-up. CONCLUSIONS: Trigeminal neuralgia is associated with atrophy of the root entry zone of the affected nerve compared with the asymptomatic side, but volume loss in different segments of the nerve has very different prognostic implications. Proximal atrophy is associated with vascular compression and correlates with improved outcome following MVD. However, distal atrophy is associated with a significantly worse outcome after MVD.

Visual-spatial memory may be enhanced with theta burst deep brain stimulation of the fornix: a preliminary investigation with four cases.

Memory loss after brain injury can be a source of considerable morbidity, but there are presently few therapeutic options for restoring memory function. We have previously demonstrated that burst stimulation of the fornix is able to significantly improve memory in a rodent model of traumatic brain injury. The present study is a preliminary investigation with a small group of cases to explore whether theta burst stimulation of the fornix might improve memory in humans. Four individuals undergoing stereo-electroencephalography evaluation for drug-resistant epilepsy were enrolled. All participants were implanted with an electrode into the proximal fornix and dorsal hippocampal commissure on the language dominant (n = 3) or language non-dominant (n = 1) side, and stimulation of this electrode reliably produced a diffuse evoked potential in the head and body of the ipsilateral hippocampus. Each participant underwent testing of verbal memory (Rey Auditory-Verbal Learning Test), visual-spatial memory (Medical College of Georgia Complex Figure Test), and visual confrontational naming (Boston Naming Test Short Form) once per day over at least two consecutive days using novel test forms each day. For 50% of the trials, the fornix electrode was continuously stimulated using a burst pattern (200 Hz in 100 ms trains, five trains per second, 100 µs, 7 mA) and was compared with sham stimulation. Participants and examiners were blinded to whether stimulation was active or not, and the order of stimulation was randomized. The small sample size precluded use of inferential statistics; therefore, data were analysed using descriptive statistics and graphic analysis. Burst stimulation of the fornix was not perceived by any of the participants but was associated with a robust reversible improvement in immediate and delayed performance on the Medical College of Georgia Complex Figure Test. There were no apparent differences on either Rey Auditory-Verbal Learning Test or Boston Naming Test. There was no apparent relationship between performance and side of stimulation (language dominant or non-dominant). There were no complications. Preliminary evidence in this small sample of patients with drug-resistant epilepsy suggests that theta burst stimulation of the fornix may be associated with improvement in visual-spatial memory.

Vascular disease of the spine.

Vascular insults to the spinal cord are substantially less common than their corresponding events in the brain; it has been estimated, for example, that spinal cord infarcts make up ≤ 1% of ischemic events in the central nervous system. Although the public health burden of spinal cord injury remains severe, the majority of this burden stems from traumatic rather than vascular events. Still, vascular injuries in the spine are common enough and their consequences devastating enough that a familiarity with the pathophysiology, diagnosis, and treatment of the more common etiologies is essential to any practitioner of the clinical neurosciences. In this educational review, we will briefly outline the normal development and anatomy of the spinal vasculature, then focus on specific mechanisms of vascular injury to the spine. In particular, we will examine spontaneous and iatrogenic ischemic insults and their associated clinical syndromes, and then review vascular neoplasms and malformations of the spine with attention to the various management strategies that currently exist for these complex lesions. Finally, we will briefly address the future areas for exploration, including investigative avenues for neuroprotection, as well as the possible influence of atherosclerotic disease on spinal degenerative disease and low back pain.

The 3-dimensional grid: a novel approach to stereoelectroencephalography.

BACKGROUND: Successful surgical treatment of epilepsy requires accurate definition of areas of ictal onset and eloquent brain. Although invasive monitoring can help, subdural grids cannot sample sulci or subcortical tissue; traditional stereoelectroencephalography depth electrodes are usually placed too far apart to provide sufficient resolution for mapping. OBJECTIVE: To report a strategy of depth electrode placement in a dense array to allow precise anatomic localization of epileptic and eloquent cortex. METHODS: Twenty patients with medically intractable epilepsy either poorly localized or found to arise adjacent to eloquent areas underwent placement of arrays of depth electrodes into and around the putative area of seizure onset with the use of framed stereotaxy. Each array consisted of a "grid" of parallel electrodes in a rectangular pattern with 1 cm between entry sites. In a subset of patients, a few electrodes were placed initially, with additional electrodes placed in a second stage. Trajectories were modified to avoid cortical vessels defined on magnetic resonance imaging. Patients were monitored for 4 to 21 days to establish the precise location of seizure onset. Stimulation was performed to map cortical and subcortical eloquent regions. Electrode locations were coregistered for frameless stereotaxy during subsequent resection of seizure focus. RESULTS: Two hundred fifty-four electrodes were implanted. Discrete regions of seizure onset and functional cortex were identified, which were used during resection to remove epileptogenic tissue while preserving eloquent areas. There were no hemorrhagic or infectious complications; no patient suffered permanent neurological deficit. CONCLUSION: The 3-dimensional intraparenchymal grid is useful for identifying the location and extent of epileptic and eloquent brain.

Motor cortex stimulation for chronic pain.

Motor cortex stimulation produces significant relief of symptoms in many forms of refractory chronic pain disorders.

Decreased bursting and novel object-specific cell firing in the hippocampus after mild traumatic brain injury.

OBJECTIVE: mild traumatic brain injury (mTBI) can produce lasting memory deficits even in the absence of cell loss. We investigated changes in hippocampal firing patterns during exploration and during a novel object recognition (NOR) task. METHODS: six male Sprague-Dawley rats were subjected to mTBI via fluid percussion injury and were compared with sham-operated rats. Microelectrodes were implanted into CA1 and CA3 and multiple units were recorded from the pyramidal cell layer. Spontaneous "burst" characteristics were analyzed and temporal firing patterns were correlated with object encounters to establish object-specific firing patterns. RESULTS: mTBI was associated with significantly less hippocampal bursting (p<0.05) with a trend toward longer bursts and lower interburst spike frequency. mTBI was also associated with no preference for a novel object at 12h (p<0.05). During the NOR task, a subset of pyramidal cells were identified which consistently demonstrated a transiently increased firing rate upon encounter of a specific object ("object-specific" cell). Across both groups, there was a significant (p<0.05) correlation between preference for object novelty and the difference between the total number of novel object-specific cells and familiar object-specific cells. The proportion of object-specific cells that responded to the unexpected (novel) object compared to those responding to the familiar object was significantly smaller in rats that had been exposed to mTBI (p<0.05). CONCLUSION: memory deficits after mTBI are associated with decreased intrinsic burst activity and impaired context-specific firing patterns in the hippocampus during object exploration.

Improved learning and memory with theta-burst stimulation of the fornix in rat model of traumatic brain injury.

OBJECTIVE: Learning and memory deficits are a source of considerable morbidity after traumatic brain injury (TBI). We investigated the effect of different patterns of hippocampal stimulation via a fornix electrode on cognitively demanding tasks after TBI. METHODS: Male Sprague-Dawley rats underwent fluid-percussion injury and were compared with sham-operated rats. Electrodes were implanted into the fornix and hippocampus, and stimulation of the fornix produced robust evoked potentials in the hippocampus. A 60-s delayed non-match-to-sample (DNMS) swim T-maze was serially performed using four stimulation patterns: no stimulation (No Stim), low-frequency stimulation (LFS, 5 Hz), high-frequency stimulation (HFS, 130 Hz), and theta-burst stimulation (TBS, 200 Hz in 50 ms trains, five trains per second; 60 µA biphasic pulses). In a separate cohort of sham and injured animals, Morris water maze (MWM) was performed with or without TBS. RESULTS: In the DNMS swim T-maze, LFS and HFS did not significantly improve performance after TBI. However, there was a significant difference in performance between TBI + No Stim and TBI + TBS groups (P < 0.05) with no significant difference between Sham + No Stim and TBI + TBS. In the MWM, latency in the TBI + TBS group was significantly different from TBI + No Stim starting on day 2 (P < 0.05) and was not different from Sham + No Stim. The TBI + TBS group performed significantly more platform crossings in the probe trial (P < 0.01) and exhibited improved search strategy starting on day 3 (P < 0.05) compared with TBI + No Stim. CONCLUSIONS: Deficits in learning and memory after TBI are improved with TBS of the hippocampus. HFS and LFS do not appear to produce as great an effect as TBS.

Multitract orthogonal microelectrode localization of the subthalamic nucleus: description of a novel technique.

BACKGROUND: Microelectrode recording helps surgeons accurately localize boundaries of the subthalamic nucleus (STN) and surrounding structures in deep brain stimulation. OBJECTIVE: To describe a novel adaptation of the Ben gun device to optimize efficient mapping. METHODS: Patients who underwent STN deep brain stimulation over a 3-year period were reviewed. For the final year, the Ben gun was rotated 45° and the target was offset 1.4 mm lateral and anterior in the plane orthogonal to the intended trajectory to allow for simultaneous parallel tracks at target, 2.8 mm anterior (localizing the front of STN), and 2.8 mm lateral (identifying the internal capsule). Before this step, the initial pass consisted of 1 to 2 tracks with the frame center targeted to STN. The primary outcome measure was the number of passes required for accurate localization of the nucleus and boundaries. RESULTS: Eighty-three electrodes were implanted in 45 patients (mean age, 62; range, 37-78 years), of which 29 electrodes were placed by the use of the new technique. One electrode (4%) required more than 1 pass using the new technique compared with 36 (67%) using the older technique (P < .01). The distance from original target to final electrode position increased from 0.67 ± 0.13 mm to 1.06 ± 0.15 mm (P < .05) with a greater tendency to move the final electrode position posteriorly. There was no statistically significant difference in benefit from neurostimulation. CONCLUSION: This technique facilitates reliable localization of the STN with fewer passes, possibly decreasing the risks associated with more passes and longer duration of surgery.

Accuracy of frame-based stereotactic depth electrode implantation during craniotomy for subdural grid placement.

BACKGROUND: Frame-based stereotaxy and open craniotomy may seem mutually exclusive, but invasive electrophysiological monitoring can require broad sampling of the cortex and precise targeting of deeper structures. OBJECTIVES: The purpose of this study is to describe simultaneous frame-based insertion of depth electrodes and craniotomy for placement of subdural grids through a single surgical field and to determine the accuracy of depth electrodes placed using this technique. METHODS: A total of 6 patients with intractable epilepsy underwent placement of a stereotactic frame with the center of the planned cranial flap equidistant from the fixation posts. After volumetric imaging, craniotomy for placement of subdural grids was performed. Depth electrodes were placed using frame-based stereotaxy. Postoperative CT determined the accuracy of electrode placement. RESULTS: A total of 31 depth electrodes were placed. Mean distance of distal electrode contact from the target was 1.0 ± 0.15 mm. Error was correlated to distance to target, with an additional 0.35 mm error for each centimeter (r = 0.635, p < 0.001); when corrected, there was no difference in accuracy based on target structure or method of placement (prior to craniotomy vs. through grid, p = 0.23). CONCLUSION: The described technique for craniotomy through a stereotactic frame allows placement of subdural grids and depth electrodes without sacrificing the accuracy of a frame or requiring staged procedures.

N-butyl 2-cyanoacrylate (n-BCA) embolization of a cerebellar hemangioblastoma.

Hemangioblastomas (HBs) are highly vascular tumors whose resection can be associated with significant bleeding. Angioembolization has been used as an adjunct to surgical therapy, but particle embolization of cerebellar HBs has been associated with hemorrhage and resultant morbidity and mortality. We present a case of successful n-BCA embolization of an HB of the cerebellum.

A novel method of translabyrinthine cranioplasty using hydroxyapatite cement and titanium mesh: a technical report.

We report a novel technique for closure using titanium mesh cranioplasty in addition to hydroxyapatite cement and abdominal fat graft for acoustic neuroma. We reviewed 15 patients who underwent translabyrinthine craniectomy for resection of acoustic neuroma. Hearing loss was documented prior to surgical procedure. Over 2 years, patients underwent titanium mesh and hydroxyapatite cranioplasty with abdominal fat graft. Participants included seven men and eight women, age range 38 to 65. Main outcome measures included cosmetic outcome and incidence of cerebrospinal fluid (CSF) leak. The lesion was right-sided in seven patients and left-sided in eight. Cosmetic outcome was excellent in all. There were no cases of CSF leak. Closure used one-third the hydroxyapatite required for traditional closure. Our technique yields cosmetic results equivalent to hydroxyapatite cement alone and a comparable incidence of CSF leakage without leaving a drain in place postoperatively. The technique is easy to adopt, is more cost-effective than hydroxyapatite cement cranioplasty alone, offers greater ease of access for reoperation, and does not preclude later implantation of bone-anchored hearing aid.