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1.
Neurology ; 100(11): e1177-e1192, 2023 03 14.
Article in English | MEDLINE | ID: mdl-36639237

ABSTRACT

BACKGROUND AND OBJECTIVES: Brain-computer interfaces (BCIs) are being developed to restore mobility, communication, and functional independence to people with paralysis. Though supported by decades of preclinical data, the safety of chronically implanted microelectrode array BCIs in humans is unknown. We report safety results from the prospective, open-label, nonrandomized BrainGate feasibility study (NCT00912041), the largest and longest-running clinical trial of an implanted BCI. METHODS: Adults aged 18-75 years with quadriparesis from spinal cord injury, brainstem stroke, or motor neuron disease were enrolled through 7 clinical sites in the United States. Participants underwent surgical implantation of 1 or 2 microelectrode arrays in the motor cortex of the dominant cerebral hemisphere. The primary safety outcome was device-related serious adverse events (SAEs) requiring device explantation or resulting in death or permanently increased disability during the 1-year postimplant evaluation period. The secondary outcomes included the type and frequency of other adverse events and the feasibility of the BrainGate system for controlling a computer or other assistive technologies. RESULTS: From 2004 to 2021, 14 adults enrolled in the BrainGate trial had devices surgically implanted. The average duration of device implantation was 872 days, yielding 12,203 days of safety experience. There were 68 device-related adverse events, including 6 device-related SAEs. The most common device-related adverse event was skin irritation around the percutaneous pedestal. There were no safety events that required device explantation, no unanticipated adverse device events, no intracranial infections, and no participant deaths or adverse events resulting in permanently increased disability related to the investigational device. DISCUSSION: The BrainGate Neural Interface system has a safety record comparable with other chronically implanted medical devices. Given rapid recent advances in this technology and continued performance gains, these data suggest a favorable risk/benefit ratio in appropriately selected individuals to support ongoing research and development. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT00912041. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the neurosurgically placed BrainGate Neural Interface system is associated with a low rate of SAEs defined as those requiring device explantation, resulting in death, or resulting in permanently increased disability during the 1-year postimplant period.


Subject(s)
Brain-Computer Interfaces , Spinal Cord Injuries , Adult , Humans , Feasibility Studies , Prospective Studies , Quadriplegia , Spinal Cord Injuries/surgery
2.
Nat Commun ; 13(1): 1236, 2022 03 22.
Article in English | MEDLINE | ID: mdl-35318316

ABSTRACT

Patients with amyotrophic lateral sclerosis (ALS) can lose all muscle-based routes of communication as motor neuron degeneration progresses, and ultimately, they may be left without any means of communication. While others have evaluated communication in people with remaining muscle control, to the best of our knowledge, it is not known whether neural-based communication remains possible in a completely locked-in state. Here, we implanted two 64 microelectrode arrays in the supplementary and primary motor cortex of a patient in a completely locked-in state with ALS. The patient modulated neural firing rates based on auditory feedback and he used this strategy to select letters one at a time to form words and phrases to communicate his needs and experiences. This case study provides evidence that brain-based volitional communication is possible even in a completely locked-in state.


Subject(s)
Amyotrophic Lateral Sclerosis , Brain-Computer Interfaces , Neurofeedback , Amyotrophic Lateral Sclerosis/therapy , Brain/physiology , Electroencephalography , Humans , Language , Male
3.
Childs Nerv Syst ; 38(2): 461-464, 2022 02.
Article in English | MEDLINE | ID: mdl-34131769

ABSTRACT

Hypophosphatasia (HPT) and cleidocranial dysplasia (CCD) are rare genetic disorders characterized by both defective ossification and bone mineralization. Patients usually present with craniosynostosis and cranial defects which in many cases require surgical repair. There is only 1 reported case of combined HPT and CCD in the literature. Our reported case involves a 3.5-year-old girl with concomitant homozygous CCD and heterozygous HPT. The child had an extended cranial defect since birth which improved with the administration of Strensiq and was followed until preschool age. Bone defects were relatively minor on revaluation. Due to the limited final defect, we decided not to intervene. In HPT-CCD patients, bone defects are overestimated due to osteomalacia, and thus, management strategy should be less aggressive. They should undergo surgical repair with cranioplasty with the use of cement and/or titanium meshes in case of extended final defects.


Subject(s)
Cleidocranial Dysplasia , Craniosynostoses , Hypophosphatasia , Child , Child, Preschool , Cleidocranial Dysplasia/complications , Cleidocranial Dysplasia/diagnostic imaging , Cleidocranial Dysplasia/genetics , Craniosynostoses/complications , Craniosynostoses/diagnostic imaging , Craniosynostoses/surgery , Female , Humans , Hypophosphatasia/complications , Hypophosphatasia/genetics , Hypophosphatasia/surgery , Neurosurgeons , Skull
4.
Front Hum Neurosci ; 12: 450, 2018.
Article in English | MEDLINE | ID: mdl-30524258

ABSTRACT

Planning and performing volitional movement engages widespread networks in the human brain, with motor cortex considered critical to the performance of skilled limb actions. Motor cortex is also engaged when actions are observed or imagined, but the manner in which ensembles of neurons represent these volitional states (VoSs) is unknown. Here we provide direct demonstration that observing, imagining or attempting action activates shared neural ensembles in human motor cortex. Two individuals with tetraplegia (due to brainstem stroke or amyotrophic lateral sclerosis, ALS) were verbally instructed to watch, imagine, or attempt reaching actions displayed on a computer screen. Neural activity in the precentral gyrus incorporated information about both cognitive state and movement kinematics; the three conditions presented overlapping but unique, statistically distinct activity patterns. These findings demonstrate that individual neurons in human motor cortex reflect information related to sensory inputs and VoS in addition to movement features, and are a key part of a broader network linking perception and cognition to action.

5.
Cardiovasc Intervent Radiol ; 39(12): 1722-1727, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27460257

ABSTRACT

PURPOSE: Primary hyperhidrosis is an excessive sweating due to an overactive sympathetic system. Our objective was to test the feasibility and provide early data on the safety/efficacy of CT-guided sympatholysis, for primary hyperhidrosis. MATERIALS AND METHODS: Nine consecutive patients with axillary-palmar hyperhidrosis were treated between 2013 and 2015. CT-guided sympathetic block was performed in the outpatients at T-2, T-3, and T-4, bilaterally using alcohol under local anesthesia. Immediate postprocedure CT was obtained to assess the complications as per Common Terminology Criteria for Adverse Events, version 4. Technical success and clinical success were recorded. Primary and secondary efficacy were assessed by phone and clinical visits; mean follow-up was 12 months (6-26 months). Descriptive statistics was used to report the outcomes. RESULTS: One procedure was aborted due to eyelid ptosis after lidocaine injection. All other eight patients (5:3, F:M) (median age 32) had immediate cessation of sweating. Two major complications (pneumothorax, one requiring a chest tube) occurred. Two patients recurred with unilateral and one with bilateral symptoms. One of the unilateral recurrence and the bilateral recurrence patients was retreated successfully. Median follow-up was 1 year. No cases of Horner's or compensatory hyperhidrosis were observed. CONCLUSIONS: CT-guided EtOH sympatholysis for axillary/palmar primary hyperhidrosis is feasible. Technical failure rate was 11 %. Primary and secondary efficacy are 75 and 94 %, respectively, to a median follow-up of 1 year. Risk profile appears favorable. Despite a small sample size, results confirm feasibility and encourage a larger study.


Subject(s)
Ethanol/administration & dosage , Hyperhidrosis/surgery , Radiography, Interventional/methods , Sympathectomy/methods , Tomography, X-Ray Computed/methods , Adult , Anesthesia, Local , Axilla , Female , Follow-Up Studies , Hand , Humans , Male , Patient Satisfaction , Postoperative Complications , Prospective Studies , Solvents/administration & dosage , Treatment Outcome , Young Adult
6.
Sci Transl Med ; 7(313): 313ra179, 2015 Nov 11.
Article in English | MEDLINE | ID: mdl-26560357

ABSTRACT

Brain-computer interfaces (BCIs) promise to restore independence for people with severe motor disabilities by translating decoded neural activity directly into the control of a computer. However, recorded neural signals are not stationary (that is, can change over time), degrading the quality of decoding. Requiring users to pause what they are doing whenever signals change to perform decoder recalibration routines is time-consuming and impractical for everyday use of BCIs. We demonstrate that signal nonstationarity in an intracortical BCI can be mitigated automatically in software, enabling long periods (hours to days) of self-paced point-and-click typing by people with tetraplegia, without degradation in neural control. Three key innovations were included in our approach: tracking the statistics of the neural activity during self-timed pauses in neural control, velocity bias correction during neural control, and periodically recalibrating the decoder using data acquired during typing by mapping neural activity to movement intentions that are inferred retrospectively based on the user's self-selected targets. These methods, which can be extended to a variety of neurally controlled applications, advance the potential for intracortical BCIs to help restore independent communication and assistive device control for people with paralysis.


Subject(s)
Brain-Computer Interfaces , Quadriplegia/physiopathology , Quadriplegia/rehabilitation , Self-Help Devices , Amyotrophic Lateral Sclerosis/complications , Calibration , Female , Humans , Male , Motor Cortex/physiopathology , Stroke/complications
7.
J Neurosci Methods ; 244: 94-103, 2015 Apr 15.
Article in English | MEDLINE | ID: mdl-25681017

ABSTRACT

BACKGROUND: Multiple types of neural signals are available for controlling assistive devices through brain-computer interfaces (BCIs). Intracortically recorded spiking neural signals are attractive for BCIs because they can in principle provide greater fidelity of encoded information compared to electrocorticographic (ECoG) signals and electroencephalograms (EEGs). Recent reports show that the information content of these spiking neural signals can be reliably extracted simply by causally band-pass filtering the recorded extracellular voltage signals and then applying a spike detection threshold, without relying on "sorting" action potentials. NEW METHOD: We show that replacing the causal filter with an equivalent non-causal filter increases the information content extracted from the extracellular spiking signal and improves decoding of intended movement direction. This method can be used for real-time BCI applications by using a 4ms lag between recording and filtering neural signals. RESULTS: Across 18 sessions from two people with tetraplegia enrolled in the BrainGate2 pilot clinical trial, we found that threshold crossing events extracted using this non-causal filtering method were significantly more informative of each participant's intended cursor kinematics compared to threshold crossing events derived from causally filtered signals. This new method decreased the mean angular error between the intended and decoded cursor direction by 9.7° for participant S3, who was implanted 5.4 years prior to this study, and by 3.5° for participant T2, who was implanted 3 months prior to this study. CONCLUSIONS: Non-causally filtering neural signals prior to extracting threshold crossing events may be a simple yet effective way to condition intracortically recorded neural activity for direct control of external devices through BCIs.

8.
Neurorehabil Neural Repair ; 29(5): 462-71, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25385765

ABSTRACT

A goal of brain-computer interface research is to develop fast and reliable means of communication for individuals with paralysis and anarthria. We evaluated the ability of an individual with incomplete locked-in syndrome enrolled in the BrainGate Neural Interface System pilot clinical trial to communicate using neural point-and-click control. A general-purpose interface was developed to provide control of a computer cursor in tandem with one of two on-screen virtual keyboards. The novel BrainGate Radial Keyboard was compared to a standard QWERTY keyboard in a balanced copy-spelling task. The Radial Keyboard yielded a significant improvement in typing accuracy and speed-enabling typing rates over 10 correct characters per minute. The participant used this interface to communicate face-to-face with research staff by using text-to-speech conversion, and remotely using an internet chat application. This study demonstrates the first use of an intracortical brain-computer interface for neural point-and-click communication by an individual with incomplete locked-in syndrome.


Subject(s)
Brain-Computer Interfaces , Communication , Quadriplegia/rehabilitation , User-Computer Interface , Communication Aids for Disabled , Female , Humans , Middle Aged
9.
J Neurosci Methods ; 236: 58-67, 2014 Oct 30.
Article in English | MEDLINE | ID: mdl-25128256

ABSTRACT

BACKGROUND: Multiple types of neural signals are available for controlling assistive devices through brain-computer interfaces (BCIs). Intracortically recorded spiking neural signals are attractive for BCIs because they can in principle provide greater fidelity of encoded information compared to electrocorticographic (ECoG) signals and electroencephalograms (EEGs). Recent reports show that the information content of these spiking neural signals can be reliably extracted simply by causally band-pass filtering the recorded extracellular voltage signals and then applying a spike detection threshold, without relying on "sorting" action potentials. NEW METHOD: We show that replacing the causal filter with an equivalent non-causal filter increases the information content extracted from the extracellular spiking signal and improves decoding of intended movement direction. This method can be used for real-time BCI applications by using a 4ms lag between recording and filtering neural signals. RESULTS: Across 18 sessions from two people with tetraplegia enrolled in the BrainGate2 pilot clinical trial, we found that threshold crossing events extracted using this non-causal filtering method were significantly more informative of each participant's intended cursor kinematics compared to threshold crossing events derived from causally filtered signals. This new method decreased the mean angular error between the intended and decoded cursor direction by 9.7° for participant S3, who was implanted 5.4 years prior to this study, and by 3.5° for participant T2, who was implanted 3 months prior to this study. CONCLUSIONS: Non-causally filtering neural signals prior to extracting threshold crossing events may be a simple yet effective way to condition intracortically recorded neural activity for direct control of external devices through BCIs.


Subject(s)
Action Potentials , Brain-Computer Interfaces , Brain/physiopathology , Motor Activity/physiology , Signal Processing, Computer-Assisted , Aged , Biomechanical Phenomena , Electrodes, Implanted , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Pilot Projects , Quadriplegia/physiopathology , Quadriplegia/therapy
10.
J Neural Eng ; 11(4): 046007, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24921388

ABSTRACT

OBJECTIVE: Action potentials and local field potentials (LFPs) recorded in primary motor cortex contain information about the direction of movement. LFPs are assumed to be more robust to signal instabilities than action potentials, which makes LFPs, along with action potentials, a promising signal source for brain-computer interface applications. Still, relatively little research has directly compared the utility of LFPs to action potentials in decoding movement direction in human motor cortex. APPROACH: We conducted intracortical multi-electrode recordings in motor cortex of two persons (T2 and [S3]) as they performed a motor imagery task. We then compared the offline decoding performance of LFPs and spiking extracted from the same data recorded across a one-year period in each participant. MAIN RESULTS: We obtained offline prediction accuracy of movement direction and endpoint velocity in multiple LFP bands, with the best performance in the highest (200-400 Hz) LFP frequency band, presumably also containing low-pass filtered action potentials. Cross-frequency correlations of preferred directions and directional modulation index showed high similarity of directional information between action potential firing rates (spiking) and high frequency LFPs (70-400 Hz), and increasing disparity with lower frequency bands (0-7, 10-40 and 50-65 Hz). Spikes predicted the direction of intended movement more accurately than any individual LFP band, however combined decoding of all LFPs was statistically indistinguishable from spike-based performance. As the quality of spiking signals (i.e. signal amplitude) and the number of significantly modulated spiking units decreased, the offline decoding performance decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the number of significantly modulated LFP signals and their decoding accuracy followed a similar trend (2.4[2.85]%/month, ANCOVA, p = 0.27[0.03]). SIGNIFICANCE: Field potentials provided comparable offline decoding performance to unsorted spikes. Thus, LFPs may provide useful external device control using current human intracortical recording technology. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00912041.).


Subject(s)
Electroencephalography/statistics & numerical data , Motor Cortex/physiology , Movement/physiology , Action Potentials/physiology , Brain-Computer Interfaces , Calibration , Humans , Imagination/physiology , Psychomotor Performance/physiology , Reproducibility of Results , Signal Processing, Computer-Assisted
11.
Stereotact Funct Neurosurg ; 91(6): 374-8, 2013.
Article in English | MEDLINE | ID: mdl-24108099

ABSTRACT

BACKGROUND: Deep brain stimulation (DBS) has shown promise as a treatment for severe, highly treatment-refractory obsessive-compulsive disorder (OCD) or major depressive disorder (MDD). We describe the neuropsychological outcome in 21 patients (10 OCD and 11 MDD) who received DBS in the anterior limb of the internal capsule/ventral striatum (VC/VS). METHODS: All patients completed a preoperative and postoperative neuropsychological battery. Average duration of DBS stimulation was 8.91 months (SD = 4.63) at the time of follow-up testing. Data were analyzed using practice-effect-corrected change scores. RESULTS: No significant cognitive declines were seen. There were significant improvements in prose passage recall after chronic DBS. The cognitive improvements were not related to change in severity of OCD, depression or global impairment. CONCLUSIONS: This preliminary study suggests that VC/VS DBS does not result in cognitive declines. The observations that verbal memory improved are consistent with current theories on the role of the VS in the memory, but require replication in larger studies.


Subject(s)
Basal Ganglia/physiopathology , Deep Brain Stimulation , Depressive Disorder, Major/therapy , Internal Capsule/physiopathology , Obsessive-Compulsive Disorder/therapy , Adult , Depressive Disorder, Major/physiopathology , Female , Humans , Male , Middle Aged , Obsessive-Compulsive Disorder/physiopathology , Treatment Outcome
12.
J Neural Eng ; 10(4): 046012, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23838067

ABSTRACT

OBJECTIVE: Brain-computer interfaces (BCIs) aim to provide a means for people with severe motor disabilities to control their environment directly with neural activity. In intracortical BCIs for people with tetraplegia, the decoder that maps neural activity to desired movements has typically been calibrated using 'open-loop' (OL) imagination of control while a cursor automatically moves to targets on a computer screen. However, because neural activity can vary across contexts, a decoder calibrated using OL data may not be optimal for 'closed-loop' (CL) neural control. Here, we tested whether CL calibration creates a better decoder than OL calibration even when all other factors that might influence performance are held constant, including the amount of data used for calibration and the amount of elapsed time between calibration and testing. APPROACH: Two people with tetraplegia enrolled in the BrainGate2 pilot clinical trial performed a center-out-back task using an intracortical BCI, switching between decoders that had been calibrated on OL versus CL data. MAIN RESULTS: Even when all other variables were held constant, CL calibration improved neural control as well as the accuracy and strength of the tuning model. Updating the CL decoder using additional and more recent data resulted in further improvements. SIGNIFICANCE: Differences in neural activity between OL and CL contexts contribute to the superiority of CL decoders, even prior to their additional 'adaptive' advantage. In the near future, CL decoder calibration may enable robust neural control without needing to pause ongoing, practical use of BCIs, an important step toward clinical utility.


Subject(s)
Algorithms , Brain Mapping/standards , Brain-Computer Interfaces/standards , Motor Cortex/physiopathology , Quadriplegia/physiopathology , Quadriplegia/rehabilitation , Task Performance and Analysis , Calibration , Feedback, Physiological , Female , Humans , Imagination , Middle Aged , Movement , Reproducibility of Results , Sensitivity and Specificity , United States
13.
J Neural Eng ; 10(3): 036004, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23574741

ABSTRACT

OBJECTIVE: Motor neural interface systems (NIS) aim to convert neural signals into motor prosthetic or assistive device control, allowing people with paralysis to regain movement or control over their immediate environment. Effector or prosthetic control can degrade if the relationship between recorded neural signals and intended motor behavior changes. Therefore, characterizing both biological and technological sources of signal variability is important for a reliable NIS. APPROACH: To address the frequency and causes of neural signal variability in a spike-based NIS, we analyzed within-day fluctuations in spiking activity and action potential amplitude recorded with silicon microelectrode arrays implanted in the motor cortex of three people with tetraplegia (BrainGate pilot clinical trial, IDE). MAIN RESULTS: 84% of the recorded units showed a statistically significant change in apparent firing rate (3.8 ± 8.71 Hz or 49% of the mean rate) across several-minute epochs of tasks performed on a single session, and 74% of the units showed a significant change in spike amplitude (3.7 ± 6.5 µV or 5.5% of mean spike amplitude). 40% of the recording sessions showed a significant correlation in the occurrence of amplitude changes across electrodes, suggesting array micro-movement. Despite the relatively frequent amplitude changes, only 15% of the observed within-day rate changes originated from recording artifacts such as spike amplitude change or electrical noise, while 85% of the rate changes most likely emerged from physiological mechanisms. Computer simulations confirmed that systematic rate changes of individual neurons could produce a directional 'bias' in the decoded neural cursor movements. Instability in apparent neuronal spike rates indeed yielded a directional bias in 56% of all performance assessments in participant cursor control (n = 2 participants, 108 and 20 assessments over two years), resulting in suboptimal performance in these sessions. SIGNIFICANCE: We anticipate that signal acquisition and decoding methods that can adapt to the reported instabilities will further improve the performance of intracortically-based NISs.


Subject(s)
Brain-Computer Interfaces , Circadian Rhythm , Electroencephalography/methods , Evoked Potentials, Motor , Motor Cortex/physiopathology , Nerve Net/physiopathology , Quadriplegia/physiopathology , Adult , Algorithms , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity
14.
Neuroimage ; 60(1): 117-29, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22197743

ABSTRACT

Meta-analysis based techniques are emerging as powerful, robust tools for developing models of connectivity in functional neuroimaging. Here, we apply meta-analytic connectivity modeling to the human caudate to 1) develop a model of functional connectivity, 2) determine if meta-analytic methods are sufficiently sensitive to detect behavioral domain specificity within region-specific functional connectivity networks, and 3) compare meta-analytic driven segmentation to structural connectivity parcellation using diffusion tensor imaging. Results demonstrate strong coherence between meta-analytic and data-driven methods. Specifically, we found that behavioral filtering resulted in cognition and emotion related structures and networks primarily localized to the head of the caudate nucleus, while perceptual and action specific regions localized to the body of the caudate, consistent with early models of nonhuman primate histological studies and postmortem studies in humans. Diffusion tensor imaging (DTI) revealed support for meta-analytic connectivity modeling's (MACM) utility in identifying both direct and indirect connectivity. Our results provide further validation of meta-analytic connectivity modeling, while also highlighting an additional potential, namely the extraction of behavioral domain specific functional connectivity.


Subject(s)
Behavior/physiology , Caudate Nucleus/anatomy & histology , Caudate Nucleus/physiology , Models, Neurological , Adult , Brain Mapping , Diffusion Tensor Imaging , Female , Humans , Male
15.
IEEE Trans Neural Syst Rehabil Eng ; 19(2): 193-203, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21278024

ABSTRACT

We present a point-and-click intracortical neural interface system (NIS) that enables humans with tetraplegia to volitionally move a 2-D computer cursor in any desired direction on a computer screen, hold it still, and click on the area of interest. This direct brain-computer interface extracts both discrete (click) and continuous (cursor velocity) signals from a single small population of neurons in human motor cortex. A key component of this system is a multi-state probabilistic decoding algorithm that simultaneously decodes neural spiking activity of a small population of neurons and outputs either a click signal or the velocity of the cursor. The algorithm combines a linear classifier, which determines whether the user is intending to click or move the cursor, with a Kalman filter that translates the neural population activity into cursor velocity. We present a paradigm for training the multi-state decoding algorithm using neural activity observed during imagined actions. Two human participants with tetraplegia (paralysis of the four limbs) performed a closed-loop radial target acquisition task using the point-and-click NIS over multiple sessions. We quantified point-and-click performance using various human-computer interaction measurements for pointing devices. We found that participants could control the cursor motion and click on specified targets with a small error rate (< 3% in one participant). This study suggests that signals from a small ensemble of motor cortical neurons (∼40) can be used for natural point-and-click 2-D cursor control of a personal computer.


Subject(s)
Motor Cortex/physiology , Quadriplegia , User-Computer Interface , Adult , Algorithms , Amyotrophic Lateral Sclerosis/complications , Feedback, Psychological , Female , Humans , Intention , Learning , Male , Middle Aged , Models, Neurological , Models, Statistical , Motor Cortex/cytology , Neurons/physiology , Psychomotor Performance/physiology , Quadriplegia/etiology , Stroke/complications
16.
Biol Psychiatry ; 65(4): 267-75, 2009 Feb 15.
Article in English | MEDLINE | ID: mdl-18842257

ABSTRACT

BACKGROUND: We investigated the use of deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) for treatment refractory depression. METHODS: Fifteen patients with chronic, severe, highly refractory depression received open-label DBS at three collaborating clinical sites. Electrodes were implanted bilaterally in the VC/VS region. Stimulation was titrated to therapeutic benefit and the absence of adverse effects. All patients received continuous stimulation and were followed for a minimum of 6 months to longer than 4 years. Outcome measures included the Hamilton Depression Rating Scale-24 item (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Global Assessment of Function Scale (GAF). RESULTS: Significant improvements in depressive symptoms were observed during DBS treatment. Mean HDRS scores declined from 33.1 at baseline to 17.5 at 6 months and 14.3 at last follow-up. Similar improvements were seen with the MADRS (34.8, 17.9, and 15.7, respectively) and the GAF (43.4, 55.5, and 61.8, respectively). Responder rates with the HDRS were 40% at 6 months and 53.3% at last follow-up (MADRS: 46.7% and 53.3%, respectively). Remission rates were 20% at 6 months and 40% at last follow-up with the HDRS (MADRS: 26.6% and 33.3%, respectively). The DBS was well-tolerated in this group. CONCLUSIONS: Deep brain stimulation of the VC/VS offers promise for the treatment of refractory major depression.


Subject(s)
Deep Brain Stimulation , Depressive Disorder/therapy , Neostriatum/physiology , Adolescent , Adult , Chronic Disease , Cognition/physiology , Deep Brain Stimulation/adverse effects , Depressive Disorder/psychology , Drug Resistance , Electrodes, Implanted , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating Scales , Recurrence , Treatment Outcome , Young Adult
17.
J Neurosci ; 28(5): 1163-78, 2008 Jan 30.
Article in English | MEDLINE | ID: mdl-18234894

ABSTRACT

The relationship between spiking activities in motor cortex and movement kinematics has been well studied in neurologically intact nonhuman primates. We examined the relationship between spiking activities in primary motor cortex (M1) and intended movement kinematics (position and velocity) using 96-microelectrode arrays chronically implanted in two humans with tetraplegia. Study participants were asked to perform two different tasks: imagined pursuit tracking of a cursor moving on a computer screen and a "neural cursor center-out" task in which cursor position was controlled by the participant's neural activity. In the pursuit tracking task, the majority of neurons were significantly tuned: 90% were tuned to velocity and 86% were tuned to position in one participant; 95% and 84%, respectively, in the other. Additionally, velocity and position of the tracked cursor could be decoded from the ensemble of neurons. In the neural cursor center-out task, tuning to direction of the intended target was well captured by a log-linear cosine function. Neural spiking soon after target appearance could be used to classify the intended target with an accuracy of 95% in one participant, and 80% in the other. It was also possible to extract information about the direction of the difference vector between the target position and the instantaneous neural cursor position. Our results indicate that correlations between spiking activity and intended movement velocity and position are present in human M1 after the loss of descending motor pathways, and that M1 spiking activities share many kinematic tuning features whether movement is imagined by humans with tetraplegia, or is performed as shown previously in able-bodied nonhuman primates.


Subject(s)
Motor Cortex/physiology , Movement/physiology , Quadriplegia/physiopathology , Action Potentials/physiology , Adult , Biomechanical Phenomena/instrumentation , Biomechanical Phenomena/methods , Clinical Trials as Topic/methods , Female , Humans , Male , Middle Aged , Pilot Projects , Psychomotor Performance/physiology
18.
Neurosurg Focus ; 23(6): E3, 2007.
Article in English | MEDLINE | ID: mdl-18081480

ABSTRACT

Stereotactic radiosurgery (SRS) with the Gamma Knife and linear accelerator has revolutionized neurosurgery over the past 20 years. The most common indications for radiosurgery today are tumors and arteriovenous malformations of the brain. Functional indications such as treatment of movement disorders or intractable pain only contribute a small percentage of treated patients. Although SRS is the only noninvasive form of treatment for functional disorders, it also has some limitations: neurophysiological confirmation of the target structure is not possible, and one therefore must rely exclusively on anatomical targeting. Furthermore, lesion sizes may vary, and shielding adjacent radiosensitive neural structures may be difficult or impossible. The most common indication for functional SRS is the treatment of trigeminal neuralgia. Radiosurgical treatment for epilepsy and certain psychiatric illnesses is performed in several centers as part of strict research protocols, and radiosurgical pallidotomy or medial thalamotomy is no longer recommended due to the high risk of complications. Radiosurgical ventrolateral thalamotomy for the treatment of tremor in patients with Parkinson disease or multiple sclerosis, as well as in the treatment of essential tremor, may be indicated for a select group of patients with advanced age, significant medical conditions that preclude treatment with open surgery, or patients who must receive anticoagulation therapy. A promising new application of SRS is high-dose radiosurgery delivered to the pituitary stalk. This treatment has already been successfully performed in several centers around the world to treat severe pain in patients with end-stage cancer.


Subject(s)
Epilepsy/surgery , Movement Disorders/surgery , Obsessive-Compulsive Disorder/surgery , Pain/surgery , Radiosurgery/methods , Humans , Magnetic Resonance Imaging/methods , Movement Disorders/pathology , Stereotaxic Techniques
20.
Stereotact Funct Neurosurg ; 85(4): 158-61, 2007.
Article in English | MEDLINE | ID: mdl-17259752

ABSTRACT

BACKGROUND/AIMS: The 'precentral knob', a cortical representation of the motor hand function, can be identified and localized consistently using magnetic resonance imaging (MRI) and functional MRI. We present a method of indirectly identifying and localizing the Omega-shaped precentral knob using the anatomical landmarks on computed tomography (CT). METHODS: CT and MRI obtained within 24 h from 10 patients undergoing a headache workup and found to be negative for any anatomical abnormalities were studied. First, the precentral knob was identified in the CT images. Then, the 'coronal suture line' and 'midline' were identified and used to measure the distance to the precentral knob on both hemispheres. MRI was used to confirm the location of the precentral knob in the CT images based on anatomical landmarks (i.e. sulcal configurations). RESULTS: The precentral knob is located 45.1 +/- 5.2 mm posterior with respect to the coronal suture line and 33.9 +/- 3.4 mm lateral to the midline on the right hemisphere, and 44.6 +/- 5.7 mm posterior and 33.2 +/- 2.5 mm lateral on the left hemisphere. CONCLUSION: We present a method of consistently identifying and localizing the Omega-shaped precentral knob, a cortical representation of the motor hand function, using CT.


Subject(s)
Brain Mapping/methods , Motor Cortex/diagnostic imaging , Psychomotor Performance/physiology , Adult , Aged , Algorithms , Female , Hand/innervation , Hand/physiology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Motor Cortex/anatomy & histology , Motor Cortex/physiology , Neuroanatomy/methods , Tomography, X-Ray Computed
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