Single neurons in the thalamus and subthalamic nucleus process cardiac and respiratory signals in humans.

Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at the cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: ventral intermedius nucleus (Vim) and ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. A substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals.

Case report - Asterixis Post High Frequency Focused-Ultrasound Thalamotomy.

Background: High frequency focused ultrasound is used for treatment of essential tremor. Side effects associated with the procedure may resolve over time. We report a case of negative myoclonus, which has not been reported with this procedure. Case report: A 73-year-old left-handed man underwent focused ultrasound thalamotomy for treatment of essential tremor. Immediately post procedure he was noted to have negative myoclonus in the treated limb. This side effect resolved over the course of 6 months. Discussion: Although asterixis has been associated with thalamic infarcts in the past, this has not yet been reported in the literature with MRgFUS procedure and is a novel observation. Occupational and physical therapy may be considered to address this side effect. It is important to counsel patients about the rare occurrence of this complication of therapy but also its potential for complete resolution over time.

Full-Body Photobiomodulation Therapy Is Associated with Reduced Sleep Durations and Augmented Cardiorespiratory Indicators of Recovery.

Research is emerging on the use of Photobiomodulation therapy (PBMT) and its potential for augmenting human performance, however, relatively little research exists utilizing full-body administration methods. As such, further research supporting the efficacy of whole-body applications of PBMT for behavioral and physiological modifications in applicable, real-world settings are warranted. The purpose of this analysis was to observe cardiorespiratory and sleep patterns surrounding the use of full-body PBMT in an elite cohort of female soccer players. Members of a women's soccer team in a "Power 5 conference" of the National Collegiate Athletic Association (NCAA) were observed across one competitive season while wearing an OURA Ring nightly and a global positioning system (GPS) sensor during training. Within-subject comparisons of cardiorespiratory physiology, sleep duration, and sleep composition were evaluated the night before and after PBMT sessions completed as a standard of care for team recovery. Compared to pre-intervention, mean heart rate (HR) was significantly lower the night after a PBMT session (p = 0.0055). Sleep durations were also reduced following PBMT, with total sleep time (TST) averaging 40 min less the night after a session (p = 0.0006), as well as significant reductions in light sleep (p = 0.0307) and rapid eye movement (REM) sleep durations (p = 0.0019). Sleep durations were still lower following PBMT, even when controlling for daily and accumulated training loads. Enhanced cardiorespiratory indicators of recovery following PBMT, despite significant reductions in sleep duration, suggest that it may be an effective modality for maintaining adequate recovery from the high stress loads experienced by elite athletes.

Transcranial magnetic stimulation, deep brain stimulation, and other forms of neuromodulation for substance use disorders: Review of modalities and implications for treatment.

Given the high prevalence of individuals diagnosed with substance use disorder, along with the elevated rate of relapse following treatment initiation, investigating novel approaches and new modalities for substance use disorder treatment is of vital importance. One such approach involves neuromodulation which has been used therapeutically for neurological and psychiatric disorders and has demonstrated positive preliminary findings for the treatment of substance use disorder. The following article provides a review of several forms of neuromodulation which warrant consideration as potential treatments for substance use disorder. PubMed, PsycINFO, Ovid MEDLINE, and Web of Science were used to identify published articles and clinicaltrials.gov was used to identify currently ongoing or planned studies. Search criteria for Brain Stimulation included the following terminology: transcranial direct current stimulation, transcranial magnetic stimulation, theta burst stimulation, deep brain stimulation, vagus nerve stimulation, trigeminal nerve stimulation, percutaneous nerve field stimulation, auricular nerve stimulation, and low intensity focused ultrasound. Search criteria for Addiction included the following terminology: addiction, substance use disorder, substance-related disorder, cocaine, methamphetamine, amphetamine, alcohol, nicotine, tobacco, smoking, marijuana, cannabis, heroin, opiates, opioids, and hallucinogens. Results revealed that there are currently several forms of neuromodulation, both invasive and non-invasive, which are being investigated for the treatment of substance use disorder. Preliminary findings have demonstrated the potential of these various neuromodulation techniques in improving substance treatment outcomes by reducing those risk factors (e.g. substance craving) associated with relapse. Specifically, transcranial magnetic stimulation has shown the most promise with several well-designed studies supporting the potential for reducing substance craving. Deep brain stimulation has also shown promise, though lacks well-controlled clinical trials to support its efficacy. Transcranial direct current stimulation has also demonstrated promising results though consistently designed, randomized trials are also needed. There are several other forms of neuromodulation which have not yet been investigated clinically but warrant further investigation given their mechanisms and potential efficacy based on findings from other studied indications. In summary, given promising findings in reducing substance use and craving, neuromodulation may provide a non-pharmacological option as a potential treatment and/or treatment augmentation for substance use disorder. Further research investigating neuromodulation, both alone and in combination with already established substance use disorder treatment (e.g. medication treatment), warrants consideration.

Predictors of Outcomes After Focused Ultrasound Thalamotomy.

BACKGROUND: Magnetic resonance-guided focused ultrasound thalamotomy (FUS-T) is an emerging treatment for essential tremor (ET). OBJECTIVE: To determine the predictors of outcomes after FUS-T. METHODS: Two treatment groups were analyzed: 75 ET patients enrolled in the pivotal trial, between 2013 and 2015; and 114 patients enrolled in the postpivotal trials, between 2015 and 2016. All patients had medication-refractory, disabling ET, and underwent unilateral FUS-T. The primary outcome (hand tremor score, 32-point scale with higher scores indicating worse tremor) and the secondary outcome variables (Clinical Rating Scale for Tremor Part C score: 32-point scale with higher scores indicating more disability) were assessed at baseline and 1, 3, 6, and 12 mo. The operative outcome variables (ie, peak temperature, number of sonications) were analyzed. The results between the 2 treatment groups, pivotal and postpivotal, were compared with repeated measures analysis of variance and adjusted for confounding variables. RESULTS: A total of 179 patients completed the 12-mo evaluation. The significant predictors of tremor outcomes were patient age, disease duration, peak temperature, and number of sonications. A greater improvement in hand tremor scores was observed in the postpivotal group at all time points, including 12 mo (61.9% ± 24.9% vs 52.1% ± 24.9%, P = .009). In the postpivotal group, higher energy was used, resulting in higher peak temperatures (56.7 ± 2.5 vs 55.6 ± 2.8°C, P = .004). After adjusting for age, years of disease, number of sonications, and maximum temperature, the treatment group was a significant predictor of outcomes (F = 7.9 [1,165], P = .005). CONCLUSION: We observed an improvement in outcomes in the postpivotal group compared to the pivotal group potentially reflecting a learning curve with FUS-T. The other associations of tremor outcomes included patient age, disease duration, peak temperature, and number of sonications.

Safety and efficacy of sphenopalatine ganglion stimulation for chronic cluster headache: a double-blind, randomised controlled trial.

BACKGROUND: Chronic cluster headache is the most disabling form of cluster headache. The mainstay of treatment is attack prevention, but the available management options have little efficacy and are associated with substantial side-effects. In this study, we aimed to assess the safety and efficacy of sphenopalatine ganglion stimulation for treatment of chronic cluster headache. METHODS: We did a randomised, sham-controlled, parallel group, double-blind, safety and efficacy study at 21 headache centres in the USA. We recruited patients aged 22 years or older with chronic cluster headache, who reported a minimum of four cluster headache attacks per week that were unsuccessfully controlled by preventive treatments. Participants were randomly assigned (1:1) via an online adaptive randomisation procedure to either stimulation of the sphenopalatine ganglion or a sham control that delivered a cutaneous electrical stimulation. Patients and the clinical evaluator and surgeon were masked to group assignment. The primary efficacy endpoint, which was analysed with weighted generalised estimated equation logistic regression models, was the difference between groups in the proportion of stimulation-treated ipsilateral cluster attacks for which relief from pain was achieved 15 min after the start of stimulation without the use of acute drugs before that timepoint. Efficacy analyses were done in all patients who were implanted with a device and provided data for at least one treated attack during the 4-week experimental phase. Safety was assessed in all patients undergoing an implantation procedure up to the end of the open-label phase of the study, which followed the experimental phase. This trial is registered with ClinicalTrials.gov, number NCT02168764. FINDINGS: Between July 9, 2014, and Feb 14, 2017, 93 patients were enrolled and randomly assigned, 45 to the sphenopalatine ganglion stimulation group and 48 to the control group. 36 patients in the sphenopalatine ganglion stimulation group and 40 in the control group had at least one attack during the experimental phase and were included in efficacy analyses. The proportion of attacks for which pain relief was experienced at 15 min was 62·46% (95% CI 49·15-74·12) in the sphenopalatine ganglion stimulation group versus 38·87% (28·60-50·25) in the control group (odds ratio 2·62 [95% CI 1·28-5·34]; p=0·008). Nine serious adverse events were reported by the end of the open-label phase. Three of these serious adverse events were related to the implantation procedure (aspiration during intubation, nausea and vomiting, and venous injury or compromise). A fourth serious adverse event was an infection that was attributed to both the stimulation device and the implantation procedure. The other five serious adverse events were unrelated. There were no unanticipated serious adverse events. INTERPRETATION: Sphenopalatine ganglion stimulation seems efficacious and is well tolerated, and potentially offers an alternative approach to the treatment of chronic cluster headache. Further research is need to clarify its place in clinical practice. FUNDING: Autonomic Technologies.

Clinically Significant Gains in Skillful Grasp Coordination by an Individual With Tetraplegia Using an Implanted Brain-Computer Interface With Forearm Transcutaneous Muscle Stimulation.

OBJECTIVE: To demonstrate naturalistic motor control speed, coordinated grasp, and carryover from trained to novel objects by an individual with tetraplegia using a brain-computer interface (BCI)-controlled neuroprosthetic. DESIGN: Phase I trial for an intracortical BCI integrated with forearm functional electrical stimulation (FES). Data reported span postimplant days 137 to 1478. SETTING: Tertiary care outpatient rehabilitation center. PARTICIPANT: A 27-year-old man with C5 class A (on the American Spinal Injury Association Impairment Scale) traumatic spinal cord injury INTERVENTIONS: After array implantation in his left (dominant) motor cortex, the participant trained with BCI-FES to control dynamic, coordinated forearm, wrist, and hand movements. MAIN OUTCOME MEASURES: Performance on standardized tests of arm motor ability (Graded Redefined Assessment of Strength, Sensibility, and Prehension [GRASSP], Action Research Arm Test [ARAT], Grasp and Release Test [GRT], Box and Block Test), grip myometry, and functional activity measures (Capabilities of Upper Extremity Test [CUE-T], Quadriplegia Index of Function-Short Form [QIF-SF], Spinal Cord Independence Measure-Self-Report [SCIM-SR]) with and without the BCI-FES. RESULTS: With BCI-FES, scores improved from baseline on the following: Grip force (2.9 kg); ARAT cup, cylinders, ball, bar, and blocks; GRT can, fork, peg, weight, and tape; GRASSP strength and prehension (unscrewing lids, pouring from a bottle, transferring pegs); and CUE-T wrist and hand skills. QIF-SF and SCIM-SR eating, grooming, and toileting activities were expected to improve with home use of BCI-FES. Pincer grips and mobility were unaffected. BCI-FES grip skills enabled the participant to play an adapted "Battleship" game and manipulate household objects. CONCLUSIONS: Using BCI-FES, the participant performed skillful and coordinated grasps and made clinically significant gains in tests of upper limb function. Practice generalized from training objects to household items and leisure activities. Motor ability improved for palmar, lateral, and tip-to-tip grips. The expects eventual home use to confer greater independence for activities of daily living, consistent with observed neurologic level gains from C5-6 to C7-T1. This marks a critical translational step toward clinical viability for BCI neuroprosthetics.

A High Definition Noninvasive Neuromuscular Electrical Stimulation System for Cortical Control of Combinatorial Rotary Hand Movements in a Human With Tetraplegia.

OBJECTIVE: Paralysis resulting from spinal cord injury (SCI) can have a devastating effect on multiple arm and hand motor functions. Rotary hand movements, such as supination and pronation, are commonly impaired by upper extremity paralysis, and are essential for many activities of daily living. In this proof-of-concept study, we utilize a neural bypass system (NBS) to decode motor intention from motor cortex to control combinatorial rotary hand movements elicited through stimulation of the arm muscles, effectively bypassing the SCI of the study participant. We describe the NBS system architecture and design that enabled this functionality. METHODS: The NBS consists of three main functional components: 1) implanted intracortical microelectrode array, 2) neural data processing using a computer, and, 3) a noninvasive neuromuscular electrical stimulation (NMES) system. RESULTS: We address previous limitations of the NBS, and confirm the enhanced capability of the NBS to enable, in real-time, combinatorial hand rotary motor functions during a functionally relevant object manipulation task. CONCLUSION: This enhanced capability was enabled by accurate decoding of multiple movement intentions from the participant's motor cortex, interleaving NMES patterns to combine hand movements, and dynamically switching between NMES patterns to adjust for hand position changes during movement. SIGNIFICANCE: These results have implications for enabling complex rotary hand functions in sequence with other functionally relevant movements for patients suffering from SCI, stroke, and other sensorimotor dysfunctions.

Prospective Tractography-Based Targeting for Improved Safety of Focused Ultrasound Thalamotomy.

BACKGROUND: Focused ultrasound thalamotomy (FUS-T) was recently approved for the treatment of refractory essential tremor (ET). Despite its noninvasive approach, FUS-T reinitiated concerns about the adverse effects and long-term efficacy after lesioning. OBJECTIVE: To prospectively assess the outcomes of FUS-T in 10 ET patients using tractography-based targeting of the ventral intermediate nucleus (VIM). METHODS: VIM was identified at the intercommissural plane based on its neighboring tracts: the pyramidal tract and medial lemniscus. FUS-T was performed at the center of tractography-defined VIM. Tremor outcomes, at baseline and 3 mo, were assessed independently by the Tremor Research Group. We analyzed targeting coordinates, clinical outcomes, and adverse events. The FUS-T lesion location was analyzed in relation to unbiased thalamic parcellation using probabilisitic tractography. Quantitative diffusion-weighted imaging changes were also studied in fiber tracts of interest. RESULTS: The tractography coordinates were more anterior than the standard. Intraoperatively, therapeutic sonications at the tractography target improved tremor (>50% improvement) without motor or sensory side effects. Sustained improvement in tremor was observed at 3 mo (tremor score: 18.3 ± 6.9 vs 8.1 ± 4.4, P = .001). No motor weakness and sensory deficits after FUS-T were observed during 6-mo follow-up. Ataxia was observed in 3 patients. FUS-T lesions overlapped with the VIM parcellated with probablisitic tractography. Significant microstructural changes were observed in the white matter connecting VIM with cerebellum and motor cortex. CONCLUSION: This is the first report of prospective VIM targeting with tractography for FUS-T. These results suggest that tractography-guided targeting is safe and has satisfactory short-term clinical outcomes.

Neurological adverse event profile of magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor.

BACKGROUND: Magnetic resonance imaging-guided focused ultrasound thalamotomy is approved by the U.S. Food and Drug Administration for treatment of essential tremor. Although this incisionless technology creates an ablative lesion, it potentially avoids serious complications of open stereotactic surgery. OBJECTIVE: To determine the safety profile of magnetic resonance imaging-guided focused ultrasound unilateral thalamotomy for essential tremor, including frequency, and severity of adverse events, including serious adverse events. METHODS: Analysis of safety data for magnetic resonance imaging-guided focused ultrasound thalamotomy (186 patients, five studies). RESULTS: Procedure-related serious adverse events were very infrequent (1.6%), without intracerebral hemorrhages or infections. Adverse events were usually transient and were commonly rated as mild (79%) and rarely severe (1%). As previously reported, abnormalities in sensation and balance were the commonest thalamotomy-related adverse events. CONCLUSION: The overall safety profile of magnetic resonance imaging-guided focused ultrasound thalamotomy supports its role as a new option for patients with medically refractory essential tremor. © 2018 International Parkinson and Movement Disorder Society.

Technological innovations in implants used for pain therapies.

The field of pain management has experienced tremendous growth in implantable therapies secondary to the innovations of bioengineers, implanters, and industry. Every aspect of neuromodulation is amenable to innovation from implanting devices to anchors, electrodes, programming, and even patient programmers. Patients with previously refractory neuropathic pain syndromes have new and effective pain management strategies that are a direct result of innovations in implantable devices.

Long-term outcomes of spinal cord stimulation with paddle leads in the treatment of complex regional pain syndrome and failed back surgery syndrome.

INTRODUCTION: Spinal cord stimulation (SCS) is frequently used to treat chronic, intractable back, and leg pain. Implantation can be accomplished with percutaneous leads or paddle leads. Although there is an extensive literature on SCS, the long-term efficacy, particularly with paddle leads, remains poorly defined. Outcome measure choice is important when defining therapeutic efficacy for chronic pain. Numerical rating scales such as the NRS-11 remain the most common outcome measure in the literature, although they may not accurately correlate with quality of life improvements and overall satisfaction. METHODS: We reviewed the medical records of patients with failed back surgery syndrome (FBSS) or complex regional pain syndrome (CRPS) implanted with SCS systems using paddle leads between 1997 and 2008 at the Cleveland Clinic with a minimum six-month follow-up. Patients were contacted to fill out a questionnaire evaluating outcomes with the NRS-11 as well as overall satisfaction. RESULTS: A total of 35 eligible patients chose to participate. More than 50% of the patients with CRPS reported greater than 50% pain relief at a mean follow-up of 4.4 years. Approximately 30% of the FBSS patients reported a 50% or greater improvement at a mean follow-up of 3.8 years. However, 77.8% of patients with CRPS and 70.6% of patients with FBSS indicated that they would undergo SCS surgery again for the same outcome. CONCLUSION: Patients with CRPS and FBSS have a high degree of satisfaction, indexed as willingness to undergo the same procedure again for the same outcome at a mean follow-up of approximately four years. The percentage of satisfaction with the SCS system is disproportionally greater than the percentage of patients reporting 50% pain relief, particularly among patients with FBSS. This suggests that the visual analog scale may not be the optimal measure to evaluate long-term outcomes in this patient population.

Sphenopalatine ganglion interventions: technical aspects and application.

Recent research has highlighted the important role of the sphenopalatine ganglion (SPG) in cerebrovascular autonomic physiology and in the pathophysiology of cluster and migraine headaches as well as conditions of stroke and cerebral vasospasm. The relatively accessible location of the SPG within the pterygopalatine fossa and the development of options for minimally invasive approaches to the SPG make it an attractive target for neuromodulation approaches. The obvious advantage of SPG stimulation compared to ablative procedures on the SPG such as radiofrequency destruction and stereotactic radiosurgery is its reversibility and adjustable features. The on-going design of strategies for transient and continuous SPG stimulation on as needed basis using implantable SPG stimulators is an exciting new development which is expected to expand the clinical versatility of this technique.

Addressing neurological disorders with neuromodulation.

Neurological disorders are becoming increasingly common in developed countries as a result of the aging population. In spite of medications, these disorders can result in progressive loss of function as well as chronic physical, cognitive, and emotional disability that ultimately places enormous emotional and economic on the patient, caretakers, and the society in general. Neuromodulation is emerging as a therapeutic option in these patients. Neuromodulation is a field, which involves implantable devices that allow for the reversible adjustable application of electrical, chemical, or biological agents to the central or peripheral nervous system with the objective of altering its functioning with the objective of achieving a therapeutic or clinically beneficial effect. It is a rapidly evolving field that brings together many different specialties in the fields of medicine, materials science, computer science and technology, biomedical, and neural engineering as well as the surgical or interventional specialties. It has multiple current and emerging indications, and an enormous potential for growth. The main challenges before it are in the need for effective collaboration between engineers, basic scientists, and clinicians to develop innovations that address specific problems resulting in new devices and clinical applications.

Electrical stimulation of sphenopalatine ganglion for acute treatment of cluster headaches.

INTRODUCTION: Cluster headaches (CH) are primary headaches marked by repeated short-lasting attacks of severe, unilateral head pain and associated autonomic symptoms. Despite aggressive management with medications, oxygen therapy, nerve blocks, as well as various lesioning and neurostimulation therapies, a number of patients are incapacitated and suffering. The sphenopalatine ganglion (SPG) has been implicated in the pathophysiology of CH and has been a target for blocks, lesioning, and other surgical approaches. For this reason, it was selected as a target for an acute neurostimulation study. METHODS: Six patients with refractory chronic CH were treated with short-term (up to 1 hour) electrical stimulation of the SPG during an acute CH. Headaches were spontaneously present at the time of stimulation or were triggered with agents known to trigger clusters headache in each patient. A standard percutaneous infrazygomatic approach was used to place a needle at the ipsilateral SPG in the pterygopalatine fossa under fluoroscopic guidance. Electrical stimulation was performed using a temporary stimulating electrode. Stimulation was performed at various settings during maximal headache intensity. RESULTS: Five patients had CH during the initial evaluation. Three returned 3 months later for a second evaluation. There were 18 acute and distinct CH attacks with clinically maximal visual analog scale (VAS) intensity of 8 (out of 10) and above. SPG stimulation resulted in complete resolution of the headache in 11 attacks, partial resolution (>50% VAS reduction) in 3, and minimal to no relief in 4 attacks. Associated autonomic features of CH were resolved in each responder. Pain relief was noted within several minutes of stimulation. CONCLUSION: Sphenopalatine ganglion stimulation can be effective in relieving acute severe CH pain and associated autonomic features. Chronic long-term outcome studies are needed to determine the utility of SPG stimulation for management and prevention of CH.

Treatment of chronic pain with neurostimulation.

Chronic pain conditions are a complex and multifactorial problem generally requiring a multidisciplinary-type approach. The central nervous system at some point clearly becomes involved in the processing of these painful conditions with an integration of complex changes in neurophysiology and behavior. Many ablative techniques have been employed in the past to interrupt these signals. However, the results were often temporary and symptoms tended to recur. The more modern approach has suggested that modulation of the nervous elements may be a more resilient approach for treating such chronic pain disorders. We are realizing that many of these pain conditions are also dynamic and evolving, and as such need a similar treatment modality. Neurostimulation, thus, provides the ability of therapeutically dosing electrical current in a variety of pulse forms, amplitudes, pulse widths, and frequencies, to affect that system. Furthermore, it is not destructive, it is reversible, and it can be remotely adjusted and programmed over time; clear advantages to previous surgical therapies. This chapter reports on the current evidence for the use of neurostimulation (i.e. spinal cord stimulation, motor cortex stimulation and deep brain stimulation) in the treatment of chronic pain conditions.

Failure modes of spinal cord stimulation hardware.

OBJECT: Epidural spinal cord stimulation (SCS) is effective at treating refractory pain. The failure modes of the implanted hardware, however, have not been well studied. A better understanding of this could aid in improving the current procedure or designing future devices. METHODS: The authors reviewed electronic charts and operative reports of 289 patients who had undergone SCS implantation between 1998 and 2002 at the Cleveland Clinic Foundation. Data were collected on demographics, type of hardware, date of implantation procedure, indication for treatment, time to failure, and failure mode. Data were then analyzed to identify significant differences. A total of 577 procedures were performed, 43.5% of which involved revision or removal of SCS hardware. The most common indication was complex regional pain syndrome 1, and this was followed by failed-back surgery syndrome. The median number of procedures per patient was two. Approximately 80% of all leads were the percutaneous type. The majority (62%) of leads were placed in the thoracic region, and 33.5% of all leads required revision. Poor pain relief coverage was the most common indication for revision. Surgically implanted leads broke twice as often as percutaneous leads. In 46% of the patients, hardware revision was required, and multiple revisions were necessary in 22.5%. Three-way ANOVA revealed significant differences in failure mode rates according to location (cervical compared with thoracic, p = 0.037) and failure modes (p = 0.019). Laminotomy leads tended to break and migrate sooner than percutaneous leads. Thoracic leads became infected sooner than cervical leads. CONCLUSIONS: The results of this analysis of SCS hardware failures may be used as a basis for refining surgical technique and designing the next generation of SCS hardware.

Anatomy and physiology of the basal ganglia: implications for deep brain stimulation for Parkinson's disease.

Central to surgical management of movement disorders is an understanding of the anatomy and physiology of the basal ganglia. The basal ganglia have been a target for neuromodulation surgery since Russell Meyers' pioneering works in the late 1930s. With the development of deep brain stimulation as the gold standard of surgical intervention for movement disorders, there has been a concomitant evolution in the understanding of the role the basal ganglia plays in the genesis of normal and abnormal motor behaviors. The fundamental concept of the cortico-striato-pallido-thalamocortical loop will be explored in the context of deep brain stimulation. The current targets for deep brain stimulation for Parkinson's disease, the subthalamic nucleus, the globus pallidus internus, and the ventral intermediate nucleus, will be discussed in the framework of the current physiological and anatomical models of Parkinson's disease (PD). Finally, the current understandings of the mechanisms underpinning the beneficial effects of deep brain stimulation for PD will be discussed.

Temporal excitation properties of paresthesias evoked by thalamic microstimulation.

OBJECTIVE: The neuronal elements mediating the effects of deep brain stimulation (DBS) are unknown. The objective was to determine the strength-duration properties of the neuronal elements that mediate paresthesias evoked by thalamic microstimulation. METHODS: The strength-duration properties of the neuronal elements causing paresthesias were measured using intraoperative microstimulation of the human thalamus. The sample included both concordant (reported in the same region as the mapped sensory receptive fields) and discordant paresthesias (reported in a region different than the mapped sensory receptive fields). RESULTS: There were no significant differences between the chronaxies of concordant and discordant paresthesias. There was no significant correlation between chronaxie and rheobase for concordant paresthesias, but a strong negative correlation existed for discordant paresthesias. CONCLUSIONS: Chronaxies did not distinguish the neuronal elements mediating concordant and discordant paresthesias, but correlations between chronaxie and rheobase suggest that concordant paresthesias were produced by activation of local cells while discordant paresthesias were caused by activation of axons of passage. SIGNIFICANCE: The similarity between the strength-duration properties of paresthesias evoked by thalamic stimulation, tremor reduction evoked by thalamic DBS, and EMG responses to thalamic DBS does not mean that these effects are caused by the same neural elements.

Location of the active contact within the subthalamic nucleus (STN) in the treatment of idiopathic Parkinson's disease.

BACKGROUND: Chronic electrical stimulation of the subthalamic nucleus (STN) has been shown to be safe and effective in the treatment of medically refractory idiopathic Parkinson's disease. The clinically most relevant location of stimulation within the physiologically defined STN has not been confirmed. We reviewed the locations of active electrical contacts in 33 patients who underwent simultaneous bilateral STN deep brain stimulator (DBS) implantation. METHODS: The location of the microelectrode-defined dorsal STN border was compared to the location of the center of the active contact(s) employed in achieving optimal clinical results 6 to 18 months postoperatively. Furthermore, the location of this optimal contact was determined with respect to each individual patient's midcommissural point. Bilateral monopolar stimulation was employed in 30 patients using quadripolar DBS electrodes. RESULTS: After a minimum follow-up period of 6 months, the motor subscores (UPDRS Part III) in the postoperative on-stimulation/off-medication state were 64 +/- 18% (mean +/- SD) improved as compared to the preoperative off-medication state (p < 0.01). Additionally, an improvement of 53 +/- 38% was noted when comparing the postoperative on-stimulation/on-medication state to the preoperative on-medication state (p < 0.01). On average, the center of the optimal contact was 13.3 mm lateral, 0.5 mm posterior, 0.1 mm inferior to the mid-commissural point and was 0.1 +/- 2.1 mm dorsal to the physiologically defined dorsal STN border. CONCLUSIONS: While the achieved clinical results are comparable to those published in the literature, it appears that monopolar electrical stimulation at the anterior dorsolateral border of the STN yields optimal clinical results. Further studies are crucial in determining the precise mechanism of various modes of DBS in an effort to maximize clinical outcome.