Nonhuman primate and human studies have suggested that populations of neurons in the posterior parietal cortex (PPC) may represent high-level aspects of action planning that can be used to control external devices as part of a brain-machine interface. However, there is no direct neuron-recording evidence that human PPC is involved in action planning, and the suitability of these signals for neuroprosthetic control has not been tested. We recorded neural population activity with arrays of microelectrodes implanted in the PPC of a tetraplegic subject. Motor imagery could be decoded from these neural populations, including imagined goals, trajectories, and types of movement. These findings indicate that the PPC of humans represents high-level, cognitive aspects of action and that the PPC can be a rich source for cognitive control signals for neural prosthetics that assist paralyzed patients.

Summary:Purpose: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date.Methods: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal E05 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute E05 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study.Results: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures.Conclusions: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures. Key Words: Vagus nerve stimulation-Intractable epilepsy.Vagus nerve stimulation (VNS) has emerged as an effective treatment for medically intractable epilepsy ( 1-3). VNS uses an implantable, programmable pulse generator powered by a lithium battery, which is connected to a helical bipolar lead. The lead is attached to the midcervical portion of the left vagus nerve and delivers

Our understanding of a precise dose-response relationship for vagus nerve stimulation (VNS) therapy in the treatment of seizures is still evolving. Because several parameters are involved in VNS therapy, the individual contribution of each is not well understood. This review discusses the efficacy of stimulation parameters used in the VNS clinical trials. The background, influence on safety and efficacy, and role in helping to achieve seizure control are discussed for each VNS device parameter: output current, pulse duration, frequency, and duty cycle. Finally, we provide an algorithm for the adjustment of VNS device settings (see Appendices).

Objective: To explore the safety and efficacy of external trigeminal nerve stimulation (eTNS) in patients with drug-resistant epilepsy (DRE) using a double-blind randomized controlled trial design, and to test the suitability of treatment and control parameters in preparation for a phase III multicenter clinical trial.Methods: This is a double-blind randomized active-control trial in DRE. Fifty subjects with 2 or more partial onset seizures per month (complex partial or tonic-clonic) entered a 6-week baseline period, and then were evaluated at 6, 12, and 18 weeks during the acute treatment period. Subjects were randomized to treatment (eTNS 120 Hz) or control (eTNS 2 Hz) parameters.Results: At entry, subjects were highly drug-resistant, averaging 8.7 seizures per month (treatment group) and 4.8 seizures per month (active controls). On average, subjects failed 3.35 antiepileptic drugs prior to enrollment, with an average duration of epilepsy of 21.5 years (treatment group) and 23.7 years (active control group), respectively. eTNS was well-tolerated. Side effects included anxiety (4%), headache (4%), and skin irritation (14%). The responder rate, defined as .50% reduction in seizure frequency, was 30.2% for the treatment group vs 21.1% for the active control group for the 18-week treatment period (not significant, p 5 0.31, generalized estimating equation [GEE] model). The treatment group experienced a significant within-group improvement in responder rate over the 18-week treatment period (from 17.8% at 6 weeks to 40.5% at 18 weeks, p 5 0.01, GEE). Subjects in the treatment group were more likely to respond than patients randomized to control (odds ratio 1.73, confidence interval 0.59-0.51). eTNS was associated with reductions in seizure frequency as measured by the response ratio (p 5 0.04, analysis of variance [ANOVA]), and improvements in mood on the Beck Depression Inventory (p 5 0.02, ANOVA). Conclusions:This study provides preliminary evidence that eTNS is safe and may be effective in subjects with DRE. Side effects were primarily limited to anxiety, headache, and skin irritation. These results will serve as a basis to inform and power a larger multicenter phase III clinical trial. Drug-resistant epilepsy (DRE) affects 30% of all people with epilepsy, and may lead to disability and death. [1][2][3][4] Trigeminal nerve stimulation (TNS) is a novel investigational neuromodulation therapy for patients with DRE. Classification of evidence:5 TNS can be delivered noninvasively, bilaterally, and at high frequencies, with positive effects on mood.5-7 The anatomy and biology of the trigeminal nerve support potential mechanisms by which TNS may impact epilepsy and mood disorders, and animal data demonstrate that stimulation of the trigeminal nerve and its related structures

Humans shape their hands to grasp, manipulate objects, and to communicate. From nonhuman primate studies, we know that visual and motor properties for grasps can be derived from cells in the posterior parietal cortex (PPC). Are non-grasp-related hand shapes in humans represented similarly? Here we show for the first time how single neurons in the PPC of humans are selective for particular imagined hand shapes independent of graspable objects. We find that motor imagery to shape the hand can be successfully decoded from the PPC by implementing a version of the popular Rock-Paper-Scissors game and its extension Rock-Paper-Scissors-Lizard-Spock. By simultaneous presentation of visual and auditory cues, we can discriminate motor imagery from visual information and show differences in auditory and visual information processing in the PPC. These results also demonstrate that neural signals from human PPC can be used to drive a dexterous cortical neuroprosthesis.

Sensory feedback is a critical aspect of motor control rehabilitation following paralysis or amputation. Current human studies have demonstrated the ability to deliver some of this sensory information via brain-machine interfaces, although further testing is needed to understand the stimulation parameters effect on sensation. Here, we report a systematic evaluation of somatosensory restoration in humans, using cortical stimulation with subdural mini-electrocorticography (mini-ECoG) grids. Nine epilepsy patients undergoing implantation of cortical electrodes for seizure localization were also implanted with a subdural 64-channel mini-ECoG grid over the hand area of the primary somatosensory cortex (S1). We mapped the somatotopic location and size of receptive fields evoked by stimulation of individual channels of the mini-ECoG grid. We determined the effects on perception by varying stimulus parameters of pulse width, current amplitude, and frequency. Finally, a target localization task was used to demonstrate the use of artificial sensation in a behavioral task. We found a replicable somatotopic representation of the hand on the mini-ECoG grid across most subjects during electrical stimulation. The stimulus-evoked sensations were usually of artificial quality, but in some cases were more natural and of a cutaneous or proprioceptive nature. Increases in pulse width, current strength and frequency generally produced similar quality sensations at the same somatotopic location, but with a perception of increased intensity. The subjects produced near perfect performance when using the evoked sensory information in target acquisition tasks. These findings indicate that electrical stimulation of somatosensory cortex through mini-ECoG grids has considerable potential for restoring useful sensation to patients with paralysis and amputation.

Serum NSE levels were highest in complex partial and subclinical generalized convulsive SE. The extremely high levels of NSE in subclinical SE reflect the severity of the acute neurologic insults and poor outcome common to subclinical SE. High NSE levels in complex partial SE reflects the long duration of SE in this subgroup, and potential for brain injury.

VNS causes activation of several central areas including contralateral thalamus. Localization to the thalamus suggests a possible mechanism to explain the therapeutic benefit, consistent with the role of the thalamus as a generator and modulator of cerebral activity.