Methods for localizing the posteroventral globus pallidus intermus are described. The authors' techniques include the use of microelectrodes to record single-unit activity and to microstimulate in human pallidum and its surrounding structures. This technique allows a precise determination of the locations of characteristic cell types in sequential trajectories through the external and internal segments of the pallidum. The location of the optic tract can be determined from microstimulation-evoked visual sensations and recordings of flash-evoked potentials. In addition, microstimulation-evoked motor and sensory responses allow the internal capsule to be identified. The data collected using this technique are an important adjunct to selecting optimum sites to place electrocoagulation lesions for stereotactic posteroventral pallidotomy for refractory Parkinson's disease.
Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) is an effective treatment for generalized dystonia. Its role in the management of other types of dystonia is uncertain. Therefore we performed a prospective, single-blind, multicentre study assessing the efficacy and safety of bilateral GPi-DBS in 10 patients with severe, chronic, medication-resistant cervical dystonia. Two blinded neurologists assessed patients before surgery and at 6 and 12 months post-operatively using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). The primary outcome measure was the severity subscore (range 0-30, higher scores indicating greater impairment). Secondary outcomes included disability (0 to 30), pain (0 to 40) subscores and total scores of the TWSTRS, Short Form-36 and Beck depression inventory. Swallowing and neuropsychological assessment were also performed at baseline and 12 months. One-way repeated measures analysis of variance was used to analyse the data. The TWSTRS severity score improved from a mean (SD) of 14.7 (4.2) before surgery to 8.4 (4.4) at 12 months post-operatively (P = 0.003). The disability and pain scores improved from 14.9 (3.8) and 26.6 (3.6) before surgery, to 5.4 (7.0) and 9.2 (13.1) at 12 months, respectively (both P < 0.001). General health and physical functioning as well as depression scores improved significantly. Complications were mild and reversible in four patients. Some changes in neuropsychological tests were observed, although these did not impact daily life or employment. Our results support the efficacy and safety of GPi-DBS for the treatment of patients with severe and prolonged cervical dystonia who have failed medical management.
Many amputees have a sense of their missing 'phantom' limb. Amputation can alter the representation of the body's surface in the cerebral cortex and thalamus, but it is unclear how these changes relate to such phantom sensations. One possibility is that, in amputees who experience phantom sensations, the region of the thalamus that originally represented the missing limb remains functional and can give rise to phantom sensations even when some thalamic 'limb' neurons begin to respond to stimulation of other body regions. Here we use microelectrode recording and microstimulation during functional stereotactic mapping of the ventrocaudal thalamus in amputees to determine both the responses of the neurons to stimulation of the skin and the perceptual effects of electrical activation of these neurons. Thalamic mapping revealed an unusually large thalamic stump representation, consistent with the findings from animal experiments. We also found that thalamic stimulation in amputees with a phantom limb could evoke phantom sensations, including pain, even in regions containing neurons responsive to tactile stimulation of the stump. These findings support the hypothesis that the thalamic representation of the amputated limb remains functional in amputees with phantoms.
Synopsis Spinal cord injuries (SCI) can disrupt communications between the brain and the body, leading to a loss of control over otherwise intact neuromuscular systems. The use of electrical stimulation (ES) of the central and peripheral nervous system can take advantage of these intact neuromuscular systems to provide therapeutic exercise options, to allow functional restoration, and even to manage or prevent many medical complications following SCI. The use of ES for the restoration of upper extremity, lower extremity and truncal functions can make many activities of daily living a potential reality for individuals with SCI. Restoring bladder and respiratory functions and preventing pressure ulcers may significantly decrease the morbidity and mortality following SCI. Many of the ES devices are already commercially available and should be considered by all SCI clinicians routinely as part of the lifelong rehabilitation care plan for all eligible individuals with SCI.
High-frequency deep brain stimulation (DBS) in the thalamus alleviates most kinds of tremor, yet its mechanism of action is unknown. Studies in subthalamic nucleus and other brain sites have emphasized non-synaptic factors. To explore the mechanism underlying thalamic DBS, we simulated DBS in vitro by applying high-frequency (125 Hz) electrical stimulation directly into the sensorimotor thalamus of adult rat brain slices. Intracellular recordings revealed two distinct types of membrane responses, both of which were initiated with a depolarization and rapid spike firing. However, type 1 responses repolarized quickly and returned to quiescent baseline during simulated DBS whereas type 2 responses maintained the level of membrane depolarization, with or without spike firing. Individual thalamic neurones exhibited either type 1 or type 2 response but not both. In all neurones tested, simulated DBS-evoked membrane depolarization was reversibly eliminated by tetrodotoxin, glutamate receptor antagonists, and the Ca 2+ channel antagonist Cd 2+ . Simulated DBS also increased the excitability of thalamic cells in the presence of glutamate receptor blockade, although this non-synaptic effect induced no spontaneous firing such as that found in subthalamic nucleus neurones. Our data suggest that high-frequency stimulation when applied in the ventral thalamus can rapidly disrupt local synaptic function and neuronal firing thereby leading to a 'functional deafferentation' and/or 'functional inactivation'. These mechanisms, driven primarily by synaptic activation, help to explain the paradox that lesions, muscimol and DBS in thalamus all effectively stop tremor.
The neural pathways subserving the sensation of temperature are virtually unknown. However, recent findings in the monkey suggest that the sensation of cold may be mediated by an ascending pathway relaying in the posterior part of the thalamic ventromedial nucleus (VMpo). To test this hypothesis we examined the responses of neurons to thermal stimulation of the skin and determined the perceptual effects of microstimulation in the VMpo region in awake patients undergoing functional stereotactic surgery. In 16 patients, microstimulation in the VMpo region evoked cold sensations in a circumscribed body part. Furthermore, at some of these sites thalamic neurons were found that responded to innocuous cooling of the skin area corresponding to the stimulation-evoked cold sensations. These data provide the first direct demonstration of a pathway mediating cold sensation and its location in the human thalamus.
Deep brain stimulation (DBS) of the ventrolateral thalamus stops several forms of tremor. Microelectrode recordings in the humanthalamus have revealed tremor cells that fire synchronous with electromyographic tremor. The efficacy of DBS likely depends on its ability to modify the activity of these tremor cells either synaptically by stopping afferent tremor signals or by directly altering the intrinsic membrane currents of the neurons. To test these possibilities, whole-cell patch-clamp recordings of ventral thalamic neurons were obtained from rat brain slices. DBS was simulated (sDBS) using extracellular constant current pulse trains (125 Hz, 60 -80 s, 0.25-5 mA, 1-30 s) applied through a bipolar electrode. Using a paired-pulse protocol, we first established that thalamocortical relay neurons receive converging input from multiple independent afferent fibers. Second, although sDBS induced homosynaptic depression of EPSPs along its own pathway, it did not alter the response from a second independent pathway. Third, in contrast to the subthalamic nucleus, sDBS in the thalamus failed to inhibit the rebound potential and the persistent Na ϩ current but did activate the I h current. Finally, in eight patients undergoing thalamic DBS surgery for essential tremor, microstimulation was most effective in alleviating tremor when applied in close proximity to recorded tremor cells. However, stimulation could still suppress tremor at distances incapable of directly spreading to recorded tremor cells. These complementary data indicate that DBS may induce a "functional deafferentation" of afferent axons to thalamic tremor cells, thereby preventing tremor signal propagation in humans.
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