Recent advances in transducer technology have now enabled for the delivery of focused ultrasound (FUS) so that precise transcranial lesioning is now possible. MRI allows for contemporary stereotactic targeting and real-time monitoring of the treatment location and intensity with MR thermometry. Methods: An FDA-approved, phase 1 clinical trial was conducted in 15 patients with medication-refractory essential tremor where a unilateral Vim thalamotomy was performed with MRgFUS. Safety was

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... with adverse event recording and serial MRI. Initial efficacy was determined with the clinical rating scale for tremor (CRST), the quality of life questionaire for ET, and the physical performance test of daily activities. Results: FUS lesioning was accurate and tolerated without anesthesia. Side effects were generally mild, transient, and consisted of residual sensory sequelae in four patients. Upper limb tremor improved by 75% on the CRST at one year without significant change in the ipsilateral, untreated hand. Total CRST scores improved by 56%. Quality of life and functional abilities were also significantly improved. Neuromodulation was observed in four patients such that targeting could be adjusted during the procedure. Conclusions: Transcranial MRgFUS is feasible with initial safety and efficacy similar to other surgical procedures for tremor. A multicenter, pivotal study is being designed to further investigate this nonsurgical procedure. Stereotact Funct Neurosurg 2013;91(suppl 1): 1-334 -Introduction: Degeneration of cholinergic neurons in the basal forebrain correlates with cognitive decline in patients with Alzheimer´s disease (AD). These neurons depend on nerve growth factor (NGF) for survival. We have developed a technique where implanted encapsulated cells release NGF to cholinergic neuron populations. The aims of this study were to demonstrate that this technique is safe and well-tolerated -now with a higher dosage. Methods: The catheter-like cell implant consists of an NGF producing, genetically engineered human cell line encapsulated within a semipermeable hollow fiber membrane that allows for the influx of nutrients and the efflux of NGF. (Fig.1) . A total of 10 patients with mild to moderate AD have been implanted bilaterally. Patients were monitored regarding safety, tolerability, cognitive functions and with a variety of biomarkers. Results: All patients were implanted safely and accurately. The first 3 patients received bilateral implants in the nucleus basalis of Meynert (Ch4), and the following 7 were implanted both in Ch4 and in the vertical limb of the diagonal band (Ch2) (Fig. 2) .. The first six patients were studied for 12 months. Two of these patients showed improved cognitive scores, and increased cortical 11C-nicotine binding., Due to low levels of NGF released from retrieved devices at 12 months, a second generation implants were developed. Four AD patients were implanted with these devices and studied for 6 months. The higher dose was well tolerated. Device performance was markedly improved regarding cell survival and NGF production post explantation. Some clinical data correlate well with device performance. Conclusions: A new cell-based treatment of AD and other neurodegenerative diseases by local delivery of NGF to targets in the brain was tested in an open-label Phase 1b clinical study. Safety, tolerability and device functionality will be presented including data on a New generation device. Stereotact Funct Neurosurg 2013;91(suppl 1): 1-334 -Introduction: Cortical electrical stimulation (ES) has been shown to influence behavior and modulate perception; still, the manner in which ES acts on the underlying neuronal network to account for these effects is not well understood. The present study seeks to better understand the neuronal circuitry activated by ES in primary somatosensory and motor cortices. Methods: Data were obtained from anesthetized Squirrel Monkeys (N=2). Following functional mapping with optical imaging of digit representation in response of vibratory tactile stimuli of finger pads, a microelectrode was placed in the superficial and deep cortical layers of an imaged digit domain (350 µm and 1200-1400 µm below the surface respectively). Trains of electrical stimulation (bipolar, 0.4 ms pulse width, 250 Hz, 250 ms, 15-300 µA) were applied and optical images were acquired. Receptive field mapping of the imaged domains were also collected in response to tactile stimulation. Results: We find increasing electrical stimulus intensity leads to a greater area of local activation, as measured with optical imaging (p<0.001), and that at certain thresholds additional areas of activation are observed. ES of area 3b showed both local activation and additional activation sites in areas 1, 2, 3a, and M1. In superficial layers current amplitudes greater than 15 µA and in deep layers amplitudes greater than 50 µA elicited these secondary areas of activation. ES of area 3a showed activation locally and in adjacent modules in area 3a and M1. These secondary areas of activation appeared with ES at 100 µA in superficial layers, but not deep layers. Conclusions: To summarize, cortical ES evoked inter-areal activation patterns that appear to be consistent with known connectivity observed in anatomical tracing studies. Optical imaging of ES is an exciting approach to mapping cortical circuitry. Future studies will examine plasticity in these stimulated neuronal networks. Supported by NIH R01NS-44375. Stereotact Funct Neurosurg 2013;91(suppl 1): 1-334 - Implanted Brain Computer Interface as a Neurofeedback System for Neurorehabilitation Vincent ROUALDES, MD, University Hospital Nantes, Nantes, France Introduction: There is increasing evidence of Mental Motor Imaging practice efficiency for functionnal rehabilitation after brain lesions. This is of particular interest in upper limb and hand deficits that standard physical practice fails to improve. This subjective ability is difficult to evaluate, and maybe even to achieve for patients. Brain Computer Interface (BCI) technology can guide mental practice online by analysing brain activity and translating it into a direct comprehensible feedback. Mental imaging frees brain activity from pathological afferent/efferent loops and should increase brain plasticity. Methods: Two chronic hemiparetic patients (post-traumatic and post-stroke) where implanted whith epidural electrodes for Motor Cortex Stimulation as a neuropathic pain treatment. During the test period, a BCI system was used to evaluate from electrocorticographic signal the possibility to control and improve Mental Imaging and the subsequent effect on motor performance. Results: Both were able to control the BCI system after a few trials thanks to the great quality of the electrocorticographic signal offering significantly highter levels of information than EEG. Furthermore both achieved to use this feedback to increase their own brain activity. This immediatly resulted in an increase of motor performance including strengh, amplitude and velocity of movement. Conclusions: Minimal Invasive BCI using implanted epidural electrodes could constitute a powerfull way to teach paretic brain lesionned patients, how to produce a normal hight intensity cortical activity as a way to increase brain plasticity. Increasing evidence support this hypothesis and should soon lead to a new kind of neurorehabilitation protocols. Stereotact Funct Neurosurg 2013;91(suppl 1): 1-334 -Introduction: There is a long history of electrical stimulation of the CNS for induction of visual percepts (phosphenes). Bionic vision devices are developing rapidly in the preclinical phase and a retinal device (Second Sight) is commercially available for blind individuals. The main indication so far is retinitis pigmentosa. Retinal, optic nerve, lateral geniculate body and visual cortex are all possible stimulation sites. Methods: The various stimulation sites will be reviewed. The indications for retinal versus cortical devices will be presented as well as the theoretical advantages and disadvantages of each. The engineering challenges and the number and type of electrodes for functional implants will be discussed. Results: A brief history of bionic vision will be presented. The pioneering results of the cortical stimulation devices of Doctors Brindley and Dobelle will be presented. The results of the retinal device implants (Second Sight and the Melbourne Vision Group) in blind human subjects will be presented. The components and progress of the multi-tiled multi-electrode cortical visual prosthetic device of Monash University will be presented. This is a collaborative project between the Departments of Electrical and Computer Systems Engineering, Physiology, Surgery and Ophthalmology at Monash University and the Alfred Hospital. Commercial partners are MiniFAB™ and Grey Innovation. The miniaturization of the electronics, advanced wireless technology and the advanced computer vision processing algorithms based on robotic vision take this technology to an exciting stage of practical human application. The first human implant is planned for early 2014. Conclusions: Retinal prosthetics are improving rapidly but many blind individuals will be unsuitable candidates. The development of a cortical implant for bionic vision is achievable. Our University/private industry commercial partnership is a strong model for translational research in neurosurgery. The standardised biophysical assessment of the recipients will be vital. Stereotact Funct Neurosurg 2013;91(suppl 1): 1-334 -Introduction: Stereotactic laser ablation of epileptic foci --by computer-controlled laser induced interstitial thermal therapy (LITT) with real-time magnetic resonance thermal image guidance --is a novel minimally invasive technique to treat intractable seizures with potential advantages over traditional open resective surgery. Here we report our experience in 11 epilepsy patients: 9 with mesial temporal lobe epilepsy (MTLE), 1 with cavernous malformation (CM) and 1 with hypothalamic hamartoma (HH). Methods: A saline-cooled fiber optic laser applicator (Visualase, Inc.) was inserted under general anesthesia utilizing a CRW stereotactic frame (n=7) or Clearpoint system (n=4). Laser energy was delivered during continuous MR imaging. Temperaturesensitive phase images and estimates of thermal damage during heating were superimposed on anatomical images in real-time. Standard MRI scans were obtained immediately post-procedure, with reimaging at 6 months. Prospective baseline and post-operative seizure diaries, quality of life measures, and neuropsychometric testing were performed. Results: Nine patients (10 procedures; ages 18-64) had MTLE, 8 with ≥6 month follow-up. All five patients with mesial temporal sclerosis (MTS) have had excellent or good epilepsy outcomes (Engel 1 (n=4); Engel 2 (n=1)), whereas patients without MTS (n=3) had poor outcomes (Engel 3-4). One patient with temporal lobe CM is seizure free at 6 months, and one patient with HH no longer experiences gelastic seizures. One serious complication, a visual field defect, occurred in one patient due to initial stereotactic rod misalignment. Conclusions: Stereotactic laser ablation of epileptic foci is a promising, minimally invasive therapy for intractable epilepsy. Preliminary limited results indicate that seizure outcomes in MTLE might differ in patients with and without MTS. Laser treatment of cavernous malformations and hypothalamic hamartomas is also promising. The safety and efficacy of this novel technique needs to be carefully evaluated with larger cohorts over longer periods of follow-up. Stereotact Funct Neurosurg 2013;91(suppl 1): 1-334 -