Daniel Yoshor

Activation of mammalian target of rapamycin in cytomegalic neurons of human cortical dysplasia

The cortex of patients with cortical dysplasia contains several abnormal cell types. Among the dysplastic cells, cytomegalic neurons are known to be electrically hyperactive and may contribute to epileptic activity. In this study, we sought to identify molecular markers of cytomegalic neurons in focal or hemispheric cortical dysplasia and to determine whether the activity of the mammalian target of rapamycin (mTOR) kinase is abnormally high in these cells.

Bariatric surgery for the treatment of idiopathic intracranial hypertension

OBJECT The purpose of this study was to review the literature on the effectiveness of bariatric surgery for obese patients with idiopathic intracranial hypertension (IIH) with regard to both symptom resolution and resolution of visual deficits. METHODS The published literature was reviewed using manual and electronic search techniques. Data from each relevant manuscript were gathered, analyzed, and compared. These included demographic data, pre- and postoperative symptoms, pre- and postoperative visual field deficits, bariatric procedure type, absolute weight loss, changes in body mass index, and changes in CSF opening pressure. RESULTS Eleven relevant publications (including 6 individual case reports) were found, reporting on a total of 62 patients. The Roux-en-Y gastric bypass was the most common bariatric procedure performed. Fifty-six (92%) of 61 patients with recorded postoperative clinical history had resolution of their presenting IIH symptoms following bariatric surgery. Thirty-four (97%) of 35 patients who had undergone pre- and postoperative funduscopy were found to have resolution of papilledema postoperatively. Eleven (92%) of 12 patients who had undergone pre- and postoperative formal visual field testing had complete or nearly complete resolution of visual field deficits, and the remaining patient had stabilization of previously progressive vision loss. In 13 patients both pre- and postoperative CSF pressures were recorded, with an average postoperative pressure decrease of 254 mm H(2)O. Changes in weight loss and body mass index varied depending on the reported postoperative follow-up interval. CONCLUSIONS The published Class IV evidence suggests that bariatric surgery may be an effective treatment for IIH in obese patients, both in terms of symptom resolution and visual outcome. Prospective, controlled studies are necessary for better elucidation of its role.

Brain stimulation for the treatment of epilepsy.

The treatment of patients with refractory epilepsy has always been challenging. Despite the availability of multiple antiepileptic medications and surgical procedures with which to resect seizure foci, there is a subset of epilepsy patients for whom little can be done. Currently available treatment options for these unfortunate patients include vagus nerve stimulation, the ketogenic diet, and electric stimulation, both direct and indirect, of brain nuclei thought to be involved in epileptogenesis. Studies of electrical stimulation of the brain in epilepsy treatment date back to the early 20th century, beginning with research on cerebellar stimulation. The number of potential targets has increased over the years to include the hippocampus, subthalamic nucleus, caudate nucleus, centromedian nucleus, and anterior nucleus of the thalamus (ANT). Recently the results of a large randomized controlled trial, the electrical Stimulation of the Anterior Nucleus of Thalamus for Epilepsy (SANTE) trial, were published, demonstrating a significant reduction in mean seizure frequency with ANT stimulation. Soon after, in 2011, the results of a second randomized, controlled trial-the NeuroPace RNS trial-were published. The RNS trial examined closed-loop, responsive cortical stimulation of seizure foci in patients with refractory partial epilepsy, again finding significant reduction in seizure frequency. In the present review, the authors examine the modern history of electrical stimulation of the brain for the treatment of epilepsy and discuss the results of 2 important, recently published trials, the SANTE and RNS trials.

Comparison of thalamotomy and pallidotomy for the treatment of dystonia.

OBJECTIVEThalamotomy and, more recently, pallidotomy have been used to treat selected patients with intractable dystonia, although few studies have compared the effectiveness of these two surgical procedures. In this study, we compare our results using thalamotomy and pallidotomy to treat patients with different forms of dystonia, and we discuss our results in the context of other published series. METHODSThirty-two patients with intractable dystonia underwent thalamotomy (n = 18) or pallidotomy (n = 14). Dystonia was classified according to cause and distribution, and each patient was evaluated postoperatively at two or more time points, using a global outcome scale. RESULTSAlthough comparisons are limited by differences between the two surgical groups, including longer follow-up periods for the thalamotomy group, differences in symptom distribution, and more bilateral procedures for the pallidotomy group, patients with primary dystonia who underwent pallidotomies demonstrated significantly better long-term outcomes than did patients who underwent thalamotomies (P = 0.0467). Patients with secondary dystonia experienced more modest improvements after either procedure, with little or no difference in outcomes between the two procedures. CONCLUSIONFor patients with primary dystonia, pallidotomy seems to result in better outcomes than does thalamotomy.

Elevated Thalamic Low-Voltage-Activated Currents Precede the Onset of Absence Epilepsy in the SNAP25-Deficient Mouse Mutant Coloboma

Recessive mutations in genes encoding voltage-gated Ca2+ channel subunits alter high-voltage-activated (HVA) calcium currents, impair neurotransmitter release, and stimulate thalamic low-voltage-activated (LVA) currents that contribute to a cortical spike-wave epilepsy phenotype in mice. We now report thalamic LVA current elevations in a non-Ca2+ channel mutant. EEG analysis of Coloboma (Cm/+), an autosomal dominant mutant mouse lacking one copy of the gene for a synaptosomal-associated protein (SNAP25) that interacts with HVA channels, reveals abnormal spike-wave discharges (SWDs) in the behaving animal. We compared the biophysical properties of both LVA and HVA currents in Cm/+ and wild-type thalamic neurons and observed a 54% increase in peak current density of LVA currents evoked at –50 mV from –110 mV in Cm/+ before the developmental onset of seizures relative to control. The midpoint voltage for steady-state inactivation of LVA currents in Cm/+ was shifted in a depolarized direction by 8 mV before epilepsy onset, and the mean time constant for decay of LVA Ca2+ currents at –50 mV was also prolonged. No significant differences were found in recovery from inactivation of LVA currents or in HVA current densities and kinetics. Our data demonstrate that a non-Ca2+ channel subunit gene mutation leads to potentiated thalamic LVA currents that precede the appearance of SWDs and that altered somatodendritic HVA currents are not required for abnormal thalamocortical oscillations. We suggest that presynaptic release defects shared by these mutants lead to postsynaptic LVA excitability increases in thalamic pacemaker neurons that favor rebound bursting and absence epilepsy.

Perception Matches Selectivity in the Human Anterior Color Center

Human ventral cortex contains at least two visual areas selective for color [1]: a posterior center in the lingual gyrus labeled V4 [2-4], V8 [5], or VO-1 [6] and an anterior center in the medial fusiform that has been labeled V4alpha[3, 4]. We examined the properties of the anterior color center using electrical recording and electrical stimulation in a subject with an electrode implanted over the anterior color center, as determined with BOLD fMRI in the same subject. Presentation of visual stimuli evoked local field potentials from the electrode. Consistent with fMRI, the potentials were larger for chromatic than achromatic stimuli. The potentials differed depending on stimulus color, with blue-purple colors evoking the largest response. The spatial receptive field of the electrode was central/parafoveal with a contralateral bias. In the absence of a visual stimulus, electrical stimulation of the electrode produced an artificial visual percept of a blue-purple color near the center of gaze. These results provide direct evidence of a tight link between selectivity and perception in ventral temporal cortex. Electrical stimulation of the anterior color center is sufficient to produce the conscious percept of a color whose identity is determined by the selectivity of the stimulated neurons.

Perceiving electrical stimulation of identified human visual areas

We studied whether detectable percepts could be produced by electrical stimulation of intracranial electrodes placed over human visual areas identified with fMRI. Identification of areas was confirmed by recording local-field potentials from the electrode, such as face-selective electrical responses from electrodes over the fusiform face area (FFA). The probability of detecting electrical stimulation of a visual area varied with the position of the area in the visual cortical hierarchy. Stimulation of early visual areas including V1, V2, and V3 was almost always detected, whereas stimulation of late visual areas such as FFA was rarely detected. When percepts were elicited from late areas, subjects reported that they were simple shapes and colors, similar to the descriptions of percepts from early areas. There were no reports of elaborate percepts, such as faces, even in areas like FFA, where neurons have complex response properties. For sites eliciting percepts, the detection threshold was determined by varying the stimulation current as subjects performed a forced-choice detection task. Current thresholds were similar for late and early areas. The similarity between both percept quality and threshold across early and late areas suggests the presence of functional microcircuits that link electrical stimulation with perception.

Spatial Attention Does Not Strongly Modulate Neuronal Responses in Early Human Visual Cortex

Attention can dramatically enhance behavioral performance based on a visual stimulus, but the degree to which attention modulates activity in early visual cortex is unclear. Whereas single-unit studies of spatial attention in monkeys have repeatedly revealed relatively modest attentional modulations in V1, human functional magnetic resonance imaging studies demonstrate a large attentional enhancement of the blood oxygen level-dependent (BOLD) signal in V1. To explore this discrepancy, we used intracranial electrodes to directly measure the effect of spatial attention on the responses of neurons near the human occipital pole. We found that spatial attention does not robustly modulate stimulus-driven local field potentials in early human visual cortex, but instead produces modest modulations that are consistent with those seen in monkey neurophysiology experiments. This finding suggests that the neuronal activity that underlies visual attention in humans is similar to that found in other primates and that behavioral state may alter the linear relationship between neuronal activity and BOLD.

Microvascular decompression for hemifacial spasm: Long-term results from 114 operations performed without neurophysiological monitoring

OBJECT Microvascular decompression (MVD) of the facial nerve is an effective treatment for hemifacial spasm (HFS), but the procedure is associated with a significant risk of complications such as hearing loss and facial weakness. Many surgeons advocate the use of intraoperative brainstem auditory evoked response (BAER) monitoring in an attempt to improve surgical outcomes. The authors critically assessed a large series of patients with HFS who underwent MVD without neurophysiological monitoring. METHODS The authors retrospectively identified 114 consecutive patients, with a history of HFS and without a history of HFS surgery, in whom MVD was performed by a single surgeon without the use of neurophysiological monitoring. Postoperative outcomes were determined by reviewing records and through telephone interviews. At least 1 year of postoperative follow-up data were available for 91 of the 114 patients, and the median follow-up duration in all cases was 8 years (range 3 months-23 years). A Kaplan-Meier analysis showed that 86% of the patients were spasm free at 10 years postoperatively. RESULTS There were no surgical deaths or major deficits, and complications included 1 case of postoperative deafness, 1 of permanent subtotal hearing loss, and 10 of delayed facial palsy, 2 of which did not completely resolve at last follow-up. The outcomes, rates of hearing loss, and other complications compared well with those reported in studies in which investigators used intraoperative monitoring. CONCLUSIONS The results suggest that MVD without neurophysiological monitoring is a safe and effective treatment option in patients with HFS. Although BAER monitoring may be a valuable adjunct to surgery at centers experienced with the modality, the absence of intraoperative monitoring should not prevent neurosurgeons from performing MVD in patients with HFS.

Electrocorticography links human temporoparietal junction to visual perception

Electrical stimulation of visual cortex can produce a visual percept (phosphene). We electrically stimulated visual cortex in humans implanted with subdural electrodes while recording from other brain sites. Phosphene perception occurred only if stimulation evoked high-frequency gamma oscillations in the temporoparietal junction (TPJ), a brain region associated with visual extinction and neglect. Electrical stimulation of TPJ modified the detectability of low-contrast visual stimuli.