Spelling interface using intracortical signals in a completely locked-in patient enabled via auditory neurofeedback training.

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.

Hypophosphatasia and cleidocranial dysplasia-a case report and review of the literature: the role of the neurosurgeon.

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.

Watch, Imagine, Attempt: Motor Cortex Single-Unit Activity Reveals Context-Dependent Movement Encoding in Humans With Tetraplegia.

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.

Point-and-click cursor control with an intracortical neural interface system by humans with tetraplegia.

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.

Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression.

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.

Primary motor cortex tuning to intended movement kinematics in humans with tetraplegia.

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.

Stereotactic radiosurgery for functional disorders.

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.

Neuroanatomical localization of the 'precentral knob' with computed tomography imaging.

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.

Decoding movement intent from human premotor cortex neurons for neural prosthetic applications.

Primary motor cortex (M1), a key region for voluntary motor control, has been considered a first choice as the source of neural signals to control prosthetic devices for humans with paralysis. Less is known about the potential for other areas of frontal cortex as prosthesis signal sources. The frontal cortex is widely engaged in voluntary behavior. Single-neuron recordings in monkey frontal cortex beyond M1 have readily identified activity related to planning and initiating movement direction, remembering movement instructions over delays, or mixtures of these features. Human functional imaging and lesion studies also support this role. Intraoperative mapping during deep brain stimulator placement in humans provides a unique opportunity to evaluate potential prosthesis control signals derived from nonprimary areas and to expand our understanding of frontal lobe function and its role in movement disorders. This study shows that recordings from small groups of human prefrontal/premotor cortex neurons can provide information about movement planning, production, and decision-making sufficient to decode the planned direction of movement. Thus, additional frontal areas, beyond M1, may be valuable signal sources for human neuromotor prostheses.

Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) of the anterior limb of the internal capsule has been shown to be beneficial in the short term for obsessive-compulsive disorder (OCD) patients who exhaust conventional therapies. Nuttin et al, who published the first DBS for OCD series, found promising results using a capsule target immediately rostral to the anterior commissure extending into adjacent ventral capsule/ventral striatum (VC/VS). Published long-term outcome data are limited to four patients. In this collaborative study, 10 adult OCD patients meeting stringent criteria for severity and treatment resistance had quadripolar stimulating leads implanted bilaterally in the VC/VS. DBS was activated openly 3 weeks later. Eight patients have been followed for at least 36 months. Group Yale-Brown Obsessive Compulsive Scale (YBOCS) scores decreased from 34.6+/-0.6 (mean+/-SEM) at baseline (severe) to 22.3+/-2.1 (moderate) at 36 months (p < 0.001). Four of eight patients had a > or =35% decrease in YBOCS severity at 36 months; in two patients, scores declined between 25 and 35%. Global Assessment of Functioning scores improved from 36.6+/-1.5 at baseline to 53.8+/-2.5 at 36 months (p < 0.001). Depression and anxiety also improved, as did self-care, independent living, and work, school, and social functioning. Surgical adverse effects included an asymptomatic hemorrhage, a single seizure, and a superficial infection. Psychiatric adverse effects included transient hypomanic symptoms, and worsened depression and OCD when DBS was interrupted by stimulator battery depletion. This open study found promising long-term effects of DBS in highly treatment-resistant OCD.

Neuronal ensemble control of prosthetic devices by a human with tetraplegia.

Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a 'neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.

Vagus nerve stimulation and deep brain stimulation for treatment resistant depression.

Neurostimulation techniques are potentially useful options for severely depressed patients who have failed trial after trial of medication and psychotherapy. Cervical VNS therapy for chronic or recurrent depression which does not resolve with pharmacotherapy was recently approved by the FDA. DBS for severe intractable depression has been studied in two pilot studies with very few patients to date. Further investigations are currently underway in order to more fully evaluate both of these neurostimulation therapies, with the hope of substantially improving the treatment of refractory depression.

Targeting the cranial nerve: microradiosurgery for trigeminal neuralgia with CISS and 3D-flash MR imaging sequences.

OBJECT: The authors undertook a study to identify magnetic resonance (MR) imaging techniques that can be used reliably during gamma knife surgery (GKS) to identify the trigeminal nerve, surrounding vasculature, and areas of compression. METHODS: Preoperative visualization of the trigeminal nerve and surrounding vasculature as well as targeting the area of vascular compression may increase the effectiveness of GKS for trigeminal neuralgia. During the past years our gamma knife centers have researched different MR imaging sequences with regard to their ability to visualize cranial nerves and vascular structures. Constructive interference in steady-state (CISS) fusion imaging with three-dimensional gradient echo sequences (3D-Flash) was found to be of greatest value in the authors' 25 most recent patients. In 24 (96%) out of the 25 patients, the fifth cranial nerve, surrounding vessels, and areas of compression could be reliably identified using CISS/3D-Flash. The MR images were acceptable despite patients' history of microvascular decompression, radiofrequency (RF) ablation, or concomitant disease. In one of 25 patients with a history of multiple RF lesions, the visualization was inadequate due to severe trigeminal nerve atrophy. CONCLUSIONS: The CISS/3D-Flash fusion imaging has become the preferred imaging method at the authors' institutions during GKS for trigeminal neuralgia. It affords the best visualization of the trigeminal nerve, surrounding vasculature, and the precise location of vascular compression.

Brain-machine and brain-computer interfaces.

The idea of connecting the human brain to a computer or machine directly is not novel and its potential has been explored in science fiction. With the rapid advances in the areas of information technology, miniaturization and neurosciences there has been a surge of interest in turning fiction into reality. In this paper the authors review the current state-of-the-art of brain-computer and brain-machine interfaces including neuroprostheses. The general principles and requirements to produce a successful connection between human and artificial intelligence are outlined and the authors' preliminary experience with a prototype brain-computer interface is reported.

Cervical vagus nerve stimulation for treatment-resistant depression.

Therapeutic brain stimulation through left cervical VNS now has established safety and efficacy as a long-term adjunct treatment for medication-resistant epilepsy. There is considerable evidence from both animal and human studies that the vagus nerve carries afferent signals to limbic and higher cortical brain regions, providing a rationale for its possible role in the treatment of psychiatric disorders. Open-label studies in patients with treatment-resistant depression have produced promising results, especially when response rates at longer term (1 year and 2 years) follow-up time points are considered. Short-term (10 weeks) treatment with VNS failed to demonstrate statistical superiority over sham treatment in a recently completed double-blind study, so antidepressant efficacy has not yet been established. Longer term data on VNS in depressed patients as well as further information regarding the possible dose-response relation will help to determine the place of VNS in the armament of therapeutic modalities available for major depression.