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2.
Animals (Basel) ; 13(2)2023 Jan 13.
Article in English | MEDLINE | ID: mdl-36670819

ABSTRACT

As conservation efforts regarding green sea turtles, Chelonia mydas, continue, it is imperative to document behaviors and foraging habits/habitats of understudied populations. We have conducted an 18-month study dedicated to photographing the local population feeding alongside floating docks within the Guana Tolomato Matanzas estuary to determine the capability of matching head scale patterns efficiently through a pattern matching program: HotSpotter. To date, 195 unique sea turtles have been identified between two different marinas located in St. Augustine, FL. Of these, 98 were spotted more than once, with 39 of them being "tracked" for longer than a year. Temperature trends were also monitored in conjunction, showing that more individuals appeared during the warmer months of the year. The evidence, overall, indicates that these locations host a resident population of green sea turtles, leading to the need for a discussion on potential threats originating from the usage of these marinas by humans.

3.
Neurophotonics ; 2(1): 015007, 2015 Jan.
Article in English | MEDLINE | ID: mdl-26157986

ABSTRACT

Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients ([Formula: see text]) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and [Formula: see text]. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at [Formula: see text] and a [Formula: see text] safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans.

4.
Parkinsonism Relat Disord ; 20(7): 731-7, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24768120

ABSTRACT

BACKGROUND: Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. METHODS: Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. RESULTS: As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. CONCLUSIONS: This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD.


Subject(s)
Deep Brain Stimulation/methods , Parkinson Disease/diagnosis , Parkinson Disease/therapy , Subthalamic Nucleus/physiology , Aged , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Parkinson Disease/physiopathology , Pilot Projects , Prospective Studies , Single-Blind Method
5.
Front Neurol ; 5: 25, 2014.
Article in English | MEDLINE | ID: mdl-24678307

ABSTRACT

Patients with Parkinson's disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn-Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN in 15 patients with early PD (Hoehn-Yahr Stage II), using a combination of image guided surgery, microelectrode recordings, and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates and root mean squared activity) have previously been found to be lower than in later-stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson's patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early-stage PD using traditional methods.

6.
Stereotact Funct Neurosurg ; 91(3): 148-52, 2013.
Article in English | MEDLINE | ID: mdl-23445926

ABSTRACT

In the past 15 years, rapid improvements in imaging technology and methodology have had a tremendous impact on how we study the human brain. During deep brain stimulation surgeries, detailed anatomical images can be combined with physiological data obtained by microelectrode recordings and microstimulations to address questions relating to the location of specific motor or sensorial functions. The main advantage of techniques such as microelectrode recordings and microstimulations over brain imaging is their ability to localize patient physiological activity with a high degree of spatial resolution. Aggregating data acquired from large populations permits to build what are commonly referred to as statistical atlases. Data points from statistical atlases can be combined to produce probabilistic maps. A crucial step in this process is the intersubject spatial normalization that is required to relate a position in one subject's brain to a position in another subject's brain. In this paper, we study the impact of spatial normalization techniques on building statistical atlases. We find that the Talairach or anterior-posterior commissure coordinate system commonly used in the medical literature produces atlases that are more dispersed than those obtained with normalization methods that rely on nonlinear volumetric image registration. We also find that the maps produced using nonlinear techniques correlate with their expected anatomic positions.


Subject(s)
Brain Mapping/methods , Brain/physiology , Deep Brain Stimulation/methods , Humans , Image Processing, Computer-Assisted
7.
J Neurosurg ; 117(2): 316-23, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22631688

ABSTRACT

OBJECT: Traumatic brain injury (TBI) often causes an encephalopathic state, corresponding amplitude suppression, and disorganization of electroencephalographic activity. Clinical recovery in patients who have suffered TBI varies, and identification of patients with a poor likelihood of functional recovery is not always straightforward. The authors sought to investigate temporal patterns of electrophysiological recovery of neuronal networks in an animal model of TBI. Because thalamocortical circuit function is a critical determinant of arousal state, as well as electroencephalography organization, these studies were performed using a thalamocortical brain slice preparation. METHODS: Adult rats received a moderate parietal fluid-percussion injury and were allowed to survive for 1 hour, 2 days, 7 days, or 15 days prior to in vitro electrophysiological recording. Thalamocortical brain slices, 450-µm thick, were prepared using a cutting angle that preserved reciprocal connections between the somatosensory cortex and the ventrobasal thalamic complex. RESULTS: Extracellular recordings in the cortex of uninjured control brain slices revealed spontaneous slow cortical oscillations (SCOs) that are blocked by (2R)-amino-5-phosphonovaleric acid (50 µM) and augmented in low [Mg2+]o. These oscillations have been shown to involve simultaneous bursts of activity in both the cortex and thalamus and are used here as a metric of thalamocortical circuit integrity. They were absent in 84% of slices recorded at 1 hour postinjury, and activity slowly recovered to approximate control levels by Day 15. The authors next used electrically evoked SCO-like potentials to determine neuronal excitability and found that the maximum depression occurred slightly later, on Day 2 following TBI, with only 28% of slices showing evoked activity. In addition, stimulus intensities needed to create evoked SCO activity were elevated at 1 hour, 2 days, and 7 days following TBI, and eventually returned to control levels by Day 15. The SCO frequency remained low throughout the 15 days following TBI (40% of control by Day 15). CONCLUSIONS: The suppression of cortical oscillatory activity following TBI observed in the rat model suggests an injury-induced functional disruption of thalamocortical networks that gradually recovers to baseline at approximately 15 days postinjury. The authors speculate that understanding the processes underlying disrupted thalamocortical circuit function may provide important insights into the biological basis of altered consciousness following severe head injury. Moreover, understanding the physiological basis for this process may allow us to develop new therapies to enhance the rate and extent of neurological recovery following TBI.


Subject(s)
Brain Injuries/physiopathology , Cerebral Cortex/physiopathology , Disease Models, Animal , Electroencephalography , Nerve Net/physiopathology , Signal Processing, Computer-Assisted , Thalamus/physiopathology , Animals , Brain Injuries/pathology , Cerebral Cortex/pathology , Consciousness/physiology , Cortical Synchronization , Electric Stimulation , Evoked Potentials/physiology , Male , Nerve Net/pathology , Rats , Rats, Sprague-Dawley , Reference Values , Somatosensory Cortex/pathology , Somatosensory Cortex/physiopathology , Thalamus/pathology , Tissue Culture Techniques
8.
Med Image Anal ; 16(3): 744-53, 2012 Apr.
Article in English | MEDLINE | ID: mdl-20732828

ABSTRACT

A number of methods have been developed to assist surgeons at various stages of deep brain stimulation (DBS) therapy. These include construction of anatomical atlases, functional databases, and electrophysiological atlases and maps. But, a complete system that can be integrated into the clinical workflow has not been developed. In this paper we present a system designed to assist physicians in pre-operative target planning, intra-operative target refinement and implantation, and post-operative DBS lead programming. The purpose of this system is to centralize the data acquired a the various stages of the procedure, reduce the amount of time needed at each stage of the therapy, and maximize the efficiency of the entire process. The system consists of a central repository (CranialVault), of a suite of software modules called CRAnialVault Explorer (CRAVE) that permit data entry and data visualization at each stage of the therapy, and of a series of algorithms that permit the automatic processing of the data. The central repository contains image data for more than 400 patients with the related pre-operative plans and position of the final implants and about 10,550 electrophysiological data points (micro-electrode recordings or responses to stimulations) recorded from 222 of these patients. The system has reached the stage of a clinical prototype that is being evaluated clinically at our institution. A preliminary quantitative validation of the planning component of the system performed on 80 patients who underwent the procedure between January 2009 and December 2009 shows that the system provides both timely and valuable information.


Subject(s)
Brain Mapping/methods , Data Mining/methods , Databases, Factual , Deep Brain Stimulation/methods , Models, Biological , Software , Therapy, Computer-Assisted/methods , Computer Simulation , Humans , User-Computer Interface
9.
J Parkinsons Dis ; 2(3): 215-23, 2012.
Article in English | MEDLINE | ID: mdl-23938229

ABSTRACT

BACKGROUND: Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. OBJECTIVE: We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. METHODS: We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. RESULTS: Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. CONCLUSIONS: This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.


Subject(s)
Deep Brain Stimulation , Parkinson Disease/therapy , Research Design , Subthalamic Nucleus/physiology , Aged , Feasibility Studies , Female , Humans , Male , Middle Aged , Odds Ratio , Pilot Projects , Single-Blind Method , Time Factors
10.
J Neurol Neurosurg Psychiatry ; 83(2): 164-70, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21890575

ABSTRACT

BACKGROUND: Recent evidence suggests that deep brain stimulation of the subthalamic nucleus (STN-DBS) may have a disease modifying effect in early Parkinson's disease (PD). A randomised, prospective study is underway to determine whether STN-DBS in early PD is safe and tolerable. OBJECTIVES/METHODS: 15 of 30 early PD patients were randomised to receive STN-DBS implants in an institutional review board approved protocol. Operative technique, location of DBS leads and perioperative adverse events are reported. Active contact used for stimulation in these patients was compared with 47 advanced PD patients undergoing an identical procedure by the same surgeon. RESULTS: 14 of the 15 patients did not sustain any long term (>3 months) complications from the surgery. One subject suffered a stroke resulting in mild cognitive changes and slight right arm and face weakness. The average optimal contact used in symptomatic treatment of early PD patients was: anterior -1.1±1.7 mm, lateral 10.7±1.7 mm and superior -3.3±2.5 mm (anterior and posterior commissure coordinates). This location is statistically no different (0.77 mm, p>0.05) than the optimal contact used in the treatment of 47 advanced PD patients. CONCLUSIONS: The perioperative adverse events in this trial of subjects with early stage PD are comparable with those reported for STN-DBS in advanced PD. The active contact position used in early PD is not significantly different from that used in late stage disease. This is the first report of the operative experience from a randomised, surgical versus best medical therapy trial for the early treatment of PD.


Subject(s)
Deep Brain Stimulation/methods , Neurosurgical Procedures/methods , Parkinson Disease/therapy , Aged , Deep Brain Stimulation/adverse effects , Disease Progression , Electrodes, Implanted , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neurologic Examination , Neurosurgical Procedures/adverse effects , Perioperative Period , Postoperative Complications/epidemiology , Prospective Studies , Retrospective Studies , Speech Disorders/etiology , Stroke/etiology , Subthalamic Nucleus/physiology , Subthalamic Nucleus/surgery
11.
Neuromodulation ; 14(2): 104-10; discussion 110, 2011.
Article in English | MEDLINE | ID: mdl-21992195

ABSTRACT

OBJECTIVES: Cerebrovascular hypoxia results in severe impairment and electrical dysfunction of cortical and thalamic neuronal networks. Typically cellular electrical activity returns if reoxygenation is established within 5-8 min. Electrical stimulation has been shown to reduce cellular apoptosis following cerebral hypoxia in animal models and clinical case reports. In this study, we wanted to analyze the electrophysiological repercussions of electrical stimulation on recovery of spontaneous thalamocortical oscillations (TCOs) following hypoxia in a thalamocortical slice preparation. MATERIALS AND METHODS: A hypoxia model of rat thalamocortical brain slices was used in which spontaneous TCO and cortical oscillation (CO) activity could be tracked with extracellular and intracellular recording techniques. Spontaneous TCO and CO activity was recorded prior to, during, and after hypoxia was induced in 15 brain slices. Bipolar, high-frequency stimulation (100 µsec, 150 Hz, 3 V) of somatosensory cortex was applied immediately after reoxygenation of slices was started and its effect on return of TCO activity compared with non-stimulated slices. RESULTS: Depolarization and suppression of extracellular TCOs and COs were demonstrated following the induction of hypoxia. TCO activity was lost after an average of 2.7 ± 0.5 min of hypoxia, whereas COs activity remained for an additional 3.2 ± 0.3 min in the presence of hypoxia. After loss of both TCOs and COs, oxygenated perfusate was restarted and TCOs spontaneously recovered in 6.8 ± 0.42 min. When 10 sec of high-frequency cortical stimulation was applied at the beginning of oxygenated perfusion, TCOs were observed to recover within 2.8 ± 0.76 min. If oxygenated perfusate was not restarted within 2 min following loss of either TCOs or COs, no recovery was seen. CONCLUSIONS: High-frequency cortical stimulation accelerated the recovery of thalamocortical network activity following hypoxia and reperfusion. Insight into the underlying mechanisms of this effect may enhance therapeutic interventions related to hypoxia following ischemic stroke.


Subject(s)
Action Potentials/physiology , Cerebral Cortex/physiology , Cerebral Cortex/physiopathology , Electric Stimulation/methods , Hypoxia, Brain/physiopathology , Thalamus/physiology , Thalamus/physiopathology , Animals , Female , Humans , Hypoxia, Brain/pathology , Male , Nerve Net/physiology , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley
12.
Stereotact Funct Neurosurg ; 89(1): 34-41, 2011.
Article in English | MEDLINE | ID: mdl-21160241

ABSTRACT

BACKGROUND: The microTargeting™ platform (MTP) stereotaxy system (FHC Inc., Bowdoin, Me., USA) was FDA approved in 2001 utilizing rapid-prototyping technology to create custom platforms for human stereotaxy procedures. It has also been called the STarFix (surgical targeting fixture) system since it is based on the concept of a patient- and procedure-specific surgical fixture. This is an alternative stereotactic method by which planned trajectories are incorporated into custom-built, miniature stereotactic platforms mounted onto bone fiducial markers. Our goal is to report the clinical experience with this system over a 6-year period. METHODS: We present the largest reported series of patients who underwent deep brain stimulation (DBS) implantations using customized rapidly prototyped stereotactic frames (MTP). Clinical experience and technical features for the use of this stereotactic system are described. Final lead location analysis using postoperative CT was performed to measure the clinical accuracy of the stereotactic system. RESULTS: Our series included 263 patients who underwent 284 DBS implantation surgeries at one institution over a 6-year period. The clinical targeting error without accounting for brain shift in this series was found to be 1.99 mm (SD 0.9). Operating room time was reduced through earlier incision time by 2 h per case. CONCLUSION: Customized, miniature stereotactic frames, namely STarFix platforms, are an acceptable and efficient alternative method for DBS implantation. Its clinical accuracy and outcome are comparable to those associated with traditional stereotactic frame systems.


Subject(s)
Deep Brain Stimulation/instrumentation , Radiosurgery/instrumentation , Surgical Equipment , Deep Brain Stimulation/methods , Fiducial Markers , Humans , Implantable Neurostimulators , Movement Disorders/surgery , Radiosurgery/methods , Treatment Outcome
13.
J Neurosci Methods ; 192(1): 110-4, 2010 Sep 30.
Article in English | MEDLINE | ID: mdl-20654645

ABSTRACT

Transient electrical impulses are conventionally used to elicit physiological responses in excitable tissues. While electrical stimulation has many advantages, it requires an electrode-tissue interface, exhibits relatively low spatial selectivity and always produces a "stimulus artifact". Recently, it has been shown that pulsed, low-energy infrared laser light can evoke nerve, muscle and sensory responses similar to those induced by traditional electrical stimulation in a contact-free, damage-free, artifact-free and spatially selective manner. However, the effect of transient infrared laser light on neurotransmission in the CNS is still largely unknown. Here, we tested the effect of infrared laser light on GABAergic neurotransmission. We recorded spontaneous inhibitory postsynaptic currents (sIPSCs) from cultured rat cortical neurons prior to and after infrared laser stimulation. Using transient infrared laser light, we either stimulated the neuronal soma that had axonal projections to the recorded neuron or directly stimulated the axons that projected to the recorded neuron. Optical stimulation led to enhanced amplitude, decreased decay time constant and increased frequency of sIPSCs. These alterations of sIPSC properties produced by optical stimulation were specifically mediated by GABA(A) receptors and caused by the transient laser light per se since no exogenous substances such as caged compounds were used. These data show that optical stimulation using transient infrared laser light can alter GABAergic neurotransmission and demonstrate that it may be an alternative approach to electrical stimulation in studying GABAergic function.


Subject(s)
Lasers , Neurons/metabolism , Neurons/radiation effects , Synaptic Transmission/radiation effects , 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology , Animals , Benzylamines/pharmacology , Bicuculline/analogs & derivatives , Cells, Cultured , Cerebral Cortex/cytology , Dose-Response Relationship, Radiation , Embryo, Mammalian , Excitatory Amino Acid Antagonists/pharmacology , Female , GABA-A Receptor Antagonists/pharmacology , Inhibitory Postsynaptic Potentials/drug effects , Inhibitory Postsynaptic Potentials/radiation effects , Patch-Clamp Techniques/methods , Phosphinic Acids/pharmacology , Pregnancy , Rats , Synaptic Transmission/physiology , Temperature , Valine/analogs & derivatives , Valine/pharmacology
14.
Int J Comput Assist Radiol Surg ; 5(3): 221-8, 2010 May.
Article in English | MEDLINE | ID: mdl-20033503

ABSTRACT

PURPOSE: In the recent past many groups have tried to build functional atlases of the deep brain using intra-operatively acquired information such as stimulation responses or micro-electrode recordings. An underlying assumption in building such atlases is that anatomical structures do not move between pre-operative imaging and intra-operative recording. In this study, we present evidences that this assumption is not valid. We quantify the effect of brain shift between pre-operative imaging and intra-operative recording on the creation of functional atlases using intra-operative somatotopy recordings and stimulation response data. METHODS: A total of 73 somatotopy points from 24 bilateral subthalamic nucleus (STN) implantations and 52 eye deviation stimulation response points from 17 bilateral STN implantations were used. These points were spatially normalized on a magnetic resonance imaging (MRI) atlas using a fully automatic non-rigid registration algorithm. Each implantation was categorized as having low, medium or large brain shift based on the amount of pneumocephalus visible on post-operative CT. The locations of somatotopy clusters and stimulation maps were analyzed for each category. RESULTS: The centroid of the large brain shift cluster of the somatotopy data (posterior, lateral, inferior: 3.06, 11.27, 5.36 mm) was found posterior, medial and inferior to that of the medium cluster (2.90, 13.57, 4.53 mm) which was posterior, medial and inferior to that of the low shift cluster (1.94, 13.92, 3.20 mm). The coordinates are referenced with respect to the mid-commissural point. Euclidean distances between the centroids were 1.68, 2.44 and 3.59 mm, respectively for low-medium, medium-large and low-large shift clusters. We found similar trends for the positions of the stimulation maps. The Euclidian distance between the highest probability locations on the low and medium-large shift maps was 4.06 mm. CONCLUSION: The effect of brain shift in deep brain stimulation (DBS) surgery has been demonstrated using intra-operative somatotopy recordings as well as stimulation response data. The results not only indicate that considerable brain shift happens before micro-electrode recordings in DBS but also that brain shift affects the creation of accurate functional atlases. Therefore, care must be taken when building and using such atlases of intra-operative data and also when using intra-operative data to validate anatomical atlases.


Subject(s)
Atlases as Topic , Brain Mapping/methods , Brain/surgery , Deep Brain Stimulation/methods , Neurosurgical Procedures/methods , Surgery, Computer-Assisted/methods , Brain/pathology , Female , Humans , Image Interpretation, Computer-Assisted , Magnetic Resonance Imaging/methods , Male , Neurosurgical Procedures/instrumentation , Radiography, Interventional , Sensitivity and Specificity , Subthalamic Nucleus/surgery , Tomography, X-Ray Computed/methods
15.
Med Image Comput Comput Assist Interv ; 12(Pt 1): 557-64, 2009.
Article in English | MEDLINE | ID: mdl-20426032

ABSTRACT

To help surgeons to pre-operatively select the target location for DBS electrodes, functional atlases based on intra-operatively acquired data have been created in the past. Recently, many groups have reported on the occurrence of brain shift in stereotactic surgery and its impact on the procedure but not on the creation of such atlases. Due to brain shift, the pre- and intra-operative coordinates of anatomic structures are different. When building large population atlases, which rely on pre-operative images for normalization purposes, it is thus necessary to correct for this difference. In this paper, we propose a method to achieve this. We show evidence that electrophysiological maps built using corrected and uncorrected data are different and that the maps created using shift-corrected data correlate better than those created using uncorrected data with the final position of the implant. These findings suggest that brain-shift correction of intra-operatively recorded data is feasible for the construction of accurate shift-corrected electrophysiological atlases.


Subject(s)
Artifacts , Brain/pathology , Brain/physiopathology , Deep Brain Stimulation/methods , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Therapy, Computer-Assisted/methods , Humans , Image Interpretation, Computer-Assisted/methods , Reproducibility of Results , Sensitivity and Specificity
16.
Article in English | MEDLINE | ID: mdl-18979804

ABSTRACT

Electrophysiological maps based on a Gaussian kernel have been proposed as a means to visualize response to stimulation in deep brain stimulation (DBS) surgeries. However, the Gaussian model does not represent the underlying physiological phenomenon produced by stimulation. We propose a new method to create physiological maps, which relies on spherical shell kernels. We compare our new maps to those created with Gaussian kernels and show that, on simulated data, this new approach produces more realistic maps. Experiments we have performed with real patient data show that our new maps correlate well with the underlying anatomy. Finally, we present preliminary results on an ongoing study assessing the value of these maps as pre-operative planning and intra-operative guidance tools.


Subject(s)
Brain Mapping/methods , Brain/physiology , Deep Brain Stimulation/methods , Electrodes, Implanted , Models, Neurological , Prosthesis Implantation/methods , Surgery, Computer-Assisted/methods , Computer Simulation , Deep Brain Stimulation/instrumentation , Humans , Models, Statistical
17.
J Neurosurg ; 109(2): 325-9, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18671648

ABSTRACT

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective neurosurgical treatment for Parkinson disease. Tissue reaction to chronic DBS therapy and the definitive location of active stimulation contacts are best studied on a postmortem basis in patients who have undergone DBS. The authors report the postmortem analysis of STN DBS following 5 years and 11 months of effective chronic stimulation including the histologically verified location of the active contacts associated with bilateral implants. They also describe tissue response to intraoperative test passes with recording microelectrodes and stimulating semimacroelectrodes. The results indicated that 1) the neural tissue surrounding active and nonactive contacts responds similarly, with a thin glial capsule and foreign-body giant cell reaction surrounding the leads as well as piloid gliosis, hemosiderin-laden macrophages, scattered lymphocytes, and Rosenthal fibers; 2) there was evidence of separate tracts in the adjacent tissue for intraoperative microelectrode and semimacroelectrode passes together with reactive gliosis, microcystic degeneration, and scattered hemosiderin deposition; and 3) the active contacts used for approximately 6 years of effective bilateral DBS therapy lie in the zona incerta, just dorsal to the rostral STN. To the authors' knowledge, the period of STN DBS therapy herein described for Parkinson disease and subjected to postmortem analysis is the longest to date.


Subject(s)
Deep Brain Stimulation , Electrodes, Implanted , Parkinson Disease/pathology , Parkinson Disease/therapy , Subthalamic Nucleus/pathology , Aged, 80 and over , Fatal Outcome , Humans , Male , Microelectrodes , Time Factors
18.
J Neurophysiol ; 99(3): 1285-93, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18216225

ABSTRACT

Partial limbic seizures in rodents induced by pilocarpine progress from stages I-II (mouth and facial movements; head nodding) to stage III (forelimb clonus) and then progress rapidly to stages IV-V (generalized limbic seizures; rearing, and rearing with falling) followed by status epilepticus (SE). Although limbic seizures in rodents are terminated by benzodiazepines, a group of gamma-aminobutyric acid type A (GABA(A))-receptor positive modulators, significant pharmacoresistance to benzodiazepines develops within minutes during SE. The alterations of GABA(A)-receptor function and allosteric modulation during development of SE are poorly understood. We induced seizures in juvenile rats by administration of lithium followed by pilocarpine, and whole cell recordings of miniature inhibitory postsynaptic currents (mIPSCs) were obtained from hippocampal dentate granule cells in brain slices. Compared with a sham-treated group, mIPSC amplitude was reduced and decay was accelerated at onset of the first occurrence of stage III (S3) seizures [S3(0)], resulting in a reduction in the total charge transfer at S3(0). Recovery of mIPSC amplitude and prolongation of mIPSC decay occurred 30 min after onset of S3 seizures [S3(30)]. The mIPSC frequency was not altered for S3(0) and S3(30) neurons compared with sham neurons. The net enhancement of total charge transfer by diazepam was smaller for S3(30) than that for sham and S3(0) neurons; however, the net reduction of total charge transfer by zinc was greater for S3(30) than that for sham and S3(0) neurons. These findings suggest that substantial plastic changes of GABA(A)-receptor function and allosteric modulation occur rapidly in neurons from juvenile animals during development of SE.


Subject(s)
Receptors, GABA/physiology , Status Epilepticus/pathology , Status Epilepticus/physiopathology , Allosteric Regulation/physiology , Animals , Anticonvulsants/pharmacology , Benzodiazepines/pharmacology , Diazepam/pharmacology , Disease Models, Animal , Hippocampus/pathology , In Vitro Techniques , Inhibitory Postsynaptic Potentials/drug effects , Inhibitory Postsynaptic Potentials/physiology , Inhibitory Postsynaptic Potentials/radiation effects , Lithium , Male , Neurons/drug effects , Neurons/physiology , Patch-Clamp Techniques/methods , Pilocarpine , Rats , Rats, Sprague-Dawley , Receptors, GABA/chemistry , Receptors, GABA/drug effects , Status Epilepticus/chemically induced , Zinc/pharmacology
19.
Lasers Surg Med ; 39(6): 513-26, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17659590

ABSTRACT

BACKGROUND AND OBJECTIVE: Transient optical nerve stimulation is a promising new non-contact, spatially precise, artifact-free neural excitation technique useful in research and clinical settings. This study evaluates safety of this pulsed infrared laser technique by histopathologic examination of stimulated peripheral nerves. STUDY DESIGN/MATERIALS AND METHODS: Exposed rat sciatic nerves were functionally stimulated with the pulsed Holmium:YAG laser, previously validated as an effective tool for optical stimulation. Nerves were removed immediately and up to 2 weeks after stimulation and assessed histologically for thermal damage. Laser parameters studied include upper limits for radiant exposure, repetition rate, and duration of stimulation. RESULTS: Radiant exposures with <1% probability of thermal tissue damage (0.66-0.70 J/cm(2)) are significantly greater than radiant exposures required for reliable stimulation (0.34-0.48 J/cm(2)). The upper limit for safe laser stimulation repetition rate occurs near 5 Hz. Maximum duration for constant low repetition rate stimulation (2 Hz) is approximately 4 minutes with adequate tissue hydration. CONCLUSION: Results confirm that optical stimulation has the potential to become a powerful non-contact clinical and research tool for brief nerve stimulation with low risk of nerve thermal damage.


Subject(s)
Low-Level Light Therapy/methods , Sciatic Nerve/pathology , Sciatic Nerve/radiation effects , Action Potentials , Animals , Female , Low-Level Light Therapy/adverse effects , Male , Models, Animal , Rats , Rats, Sprague-Dawley , Sciatic Nerve/injuries , Sciatic Nerve/physiology
20.
J Neurosurg ; 107(1): 169-72, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17639889

ABSTRACT

The authors present a case in which high-frequency electrical stimulation of the cingulum using standard deep brain stimulation (DBS) technology resulted in pain relief similar to that achieved with cingulotomy and superior to that achieved with periventricular gray matter (PVG) stimulation. This patient had a complete spinal cord injury at the C-4 level and suffered from medically refractory neuropathic pain. He underwent placement of bilateral cingulum and unilateral PVG DBS electrodes and a 1-week blinded stimulation trial prior to permanent implantation of a pulse generator. During the stimulation trial, the patient's pain level was assessed using a visual analog scale, and pain medication usage was recorded. During this period the patient was blinded to stimulation parameters. Stimulation of the cingulum provided better pain control than PVG stimulation or medication alone. The authors believe that cingulum stimulation can benefit patients with severe neuropathic pain that is refractory to other treatments. Advantages over cingulotomy include reversibility and the ability to adjust stimulation parameters for optimum efficacy.


Subject(s)
Deep Brain Stimulation/methods , Gyrus Cinguli/physiology , Pain Management , Pain/etiology , Spinal Cord Injuries/complications , Adult , Electrodes, Implanted , Gyrus Cinguli/diagnostic imaging , Humans , Male , Tomography, X-Ray Computed , Ventral Thalamic Nuclei/diagnostic imaging , Ventral Thalamic Nuclei/physiology
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