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Perception of our linear motion – heading – is critical for postural control, gait, and locomotion, and it is impaired in Parkinson’s Disease (PD). Deep brain stimulation (DBS) has variable effects on vestibular heading perception, depending on the location of the electrodes within the subthalamic nucleus (STN). Here, we aimed to find the anatomical correlates of heading perception in PD. Fourteen PD participants with bilateral STN DBS performed a two-alternative forced-choice discrimination task where a motion platform delivered translational forward movements with a heading angle varying between 0 and 30 degrees to the left or to the right with respect to the straight-ahead direction. Using psychometric curves, we derived the heading discrimination threshold angle of each patient from the response data. We created patient-specific DBS models and calculated the percentages of stimulated axonal pathways that are anatomically adjacent to the STN and known to play a major role in vestibular information processing. We performed correlation analyses to investigate the extent of these white matter tracts’ involvement in heading perception. Significant positive correlations were identified between improved heading discrimination for rightward heading and the percentage of activated streamlines of the contralateral hyperdirect, pallido-subthalamic, and subthalamo-pallidal pathways. The hyperdirect pathways are thought to provide top-down control over STN connections to the cerebellum. In addition, STN may also antidromically activate collaterals of hyperdirect pathway that projects to the precerebellar pontine nuclei. In select cases there was strong activation of the cerebello-thalamic projections, but it was not consistently present in all participants. Large volumetric overlap between the volume of tissue activation and the STN in the left hemisphere positively impacted rightward heading perception. Altogether, the results suggest heavy involvement of basal ganglia cerebellar network in STN-induced modulation of vestibular heading perception in PD.

Background Spontaneity is a unique feature of the nervous system. One of the fundamentally critical and recognized forms of spontaneous motor activity is witnessed in the visuomotor system. Microsaccades, the miniature spontaneous eye movements, are critical for the visual perception. We hypothesized that microsaccades follow specific temporal patterns that are modulated by the basal ganglia output. Methods We used high-resolution video-oculography to capture microsaccades in 48 subjects (31 healthy and 17 with Parkinson's disease) when subjects were asked to hold their gaze on a straight-ahead target projected on white background. We analyzed spontaneous discharge patterns of microsaccades. Results The first analysis considering coefficient of variation in intersaccadic interval distribution demonstrated that microsaccades in Parkinson's disease are more dispersed than the control group. The second analysis scrutinized microsaccades' temporal variability and revealed 3 distinct occurrence patterns: regular rhythmic, clustered, and randomly occurring following a Poisson-like process. The regular pattern was relatively more common in Parkinson's disease. Subthalamic DBS modulated this temporal pattern. The amount of change in the temporal variability depended on the DBS-induced volume of tissue activation and its overlap with the subthalamic nucleus. The third analysis determined the autocorrelations of microsaccades within 2-second time windows. We found that Parkinson's disease altered local temporal organization in microsaccade generation, and DBS had a modulatory effect. Conclusion The microsaccades occur in 3 temporal patterns. The basal ganglia are one of the modulators of the microsaccade spontaneity.

Postural instability and balance impairment are common in Parkinson’s disease (PD). Multiple factors, such as increased tone, bradykinesia, freezing of gait, posture, axial stiffness, and involuntary appendicular movements, can affect balance. The recent studies found that PD patients have abnormal perception of self-motion in vestibular domain. We asked whether measures of balance function, such as perception of one’s motion, correlate with specific movement disorders seen in PD. Moving retinal image or self-motion in space triggers the perception of self-motion. We measured one’s linear motion (heading) perception when subjects were moved en bloc using a moving platform (vestibular heading). Similar motion perception was generated in the visual domain (visual heading) by having the subjects view a 3D optical flow with immersive virtual reality goggles. During both tasks, the subjects reported the motion direction in the two-alternative-forced-choice paradigm. The accuracy of perceived motion direction was calculated from the responses fitted to the psychometric function curves to estimate how accurately and precisely the subjects can perceive rightward versus leftward motion (i.e., threshold and slope). Response accuracies and psychometric parameters were correlated with the disease duration, disease severity (total Unified Parkinson’s Disease Rating Scale-III, UPDRS-III), and tremor, rigidity, axial, gait/posture components of UPRDS-III. We also correlated heading perception with the number of falls and subjective assessment of balance confidence using the Activities-Specific Balance Component (ABC) Scale. Accuracy, threshold, and sensitivity of vestibular heading perception significantly correlated with the disease duration and severity, particularly the tremor. Correlations were stronger for leftward heading perception in the vestibular domain. The visual heading perception was correlated with ABC Scale, especially with its items concerning optic-flow processing. There was asymmetry in leftward versus rightward vestibular heading perception. The level of asymmetry correlated with the axial component of UPDRS-III. Differences in the clinical parameters that correlate with visual versus vestibular heading perception suggest that two heading perception processes have different mechanistic underpinnings. The correlation of discordance between vestibular and visual heading perception with disease severity and duration suggests that visual function can be utilized for balance rehab in PD patients.

The primary target for deep brain stimulation (DBS) for medication refractory dystonia has traditionally been the globus pallidus internus (GPi), however alternate targets have also been explored with the hope they might offer similar or superior outcomes with less side effects and reduced battery demands. Recent studies have shown comparable outcomes with both pallidal and subthalamic (STN) DBS, although the level of evidence is still superior for the GPi. There may not be an “optimal target” for all dystonia patients, with both targets offering the potential for excellent control of dystonia but more comparison studies are needed. In this review, we will discuss the history, efficacy, as well as target specific benefits and possible side effects of STN DBS for dystonia.

Perception of our linear motion – heading – is critical for postural control, gait, and locomotion, and it is impaired in Parkinson’s Disease (PD). Deep brain stimulation (DBS) has variable effects on vestibular heading perception, depending on the location of the electrodes within the subthalamic nucleus (STN). Here, we aimed to find the anatomical correlates of heading perception in PD. 14 PD participants with bilateral STN DBS participated in a two-alternative forced-choice discrimination experiment where a motion platform delivered translational forward movements with a heading angle varying between 0 and 30 degrees to the left or to the right (with respect to the straight-ahead direction). Using psychometric curves, we derived the heading discrimination threshold angle of each patient from the response data. We also created patient-specific DBS models and calculated the percentages of stimulated axonal pathways that are anatomically adjacent to the STN and known to play a major role in vestibular information processing. We performed correlation analyses to investigate the extent of these white matter tracts’ involvement in heading perception. Significant positive correlations were identified between improved heading discrimination for rightward heading and the percentage of activated streamlines of the contralateral hyperdirect, pallido-subthalamic, and subthalamo-pallidal pathways. The hyperdirect pathways is thought to provide top-down control over STN connections to the cerebellum. In addition, STN may also antidromically activate collaterals of hyperdirect pathway that projects to the precerebellar pontine nuclei. In select cases there was strong activation of the cerebello-thalamic projections, but it was not consistently present in all participants. Large volumetric overlap between the volume of tissue activation and the STN in the left hemisphere positively impacted rightward heading perception. Altogether, the results suggest heavy involvement of basal ganglia cerebellar network in STN induced modulation of vestibular heading perception in PD.

Parkinson’s disease (PD) presents with visuospatial impairment and falls. It is critical to understand how subthalamic deep brain stimulation (STN DBS) modulates visuospatial perception. We hypothesized that DBS has different effects on visual and vestibular perception of linear motion (heading), a critical aspect of visuospatial navigation; and such effects are specific to modulated STN location. Two-alternative forced-choice experiments were performed in 14 PD patients with bilateral STN DBS and 19 age-matched healthy controls (HC) during passive en bloc linear motion and 3D optic-flow in immersive virtual reality measured vestibular and visual heading. Objective measure of perception with Weibull psychometric function revealed that PD has significantly lower accuracy [L: 60.71 (17.86)%, R: 74.82 (17.44)%] and higher thresholds [L: 16.68 (12.83), R: 10.09 (7.35)] during vestibular task in both directions compared to HC (p < 0.05). DBS significantly improved vestibular discrimination accuracy [81.40 (14.36)%] and threshold [4.12 (5.87), p < 0.05] in the rightward direction. There were no DBS effects on the slopes of vestibular psychometric curves. Visual heading perception was better than vestibular and it was comparable to HC. There was no significant effect of DBS on visual heading response accuracy or discrimination threshold (p > 0.05). Patient-specific DBS models revealed an association between change in vestibular heading perception and the modulation of the dorsal STN. In summary, DBS may have different effects on vestibular and visual heading perception in PD. These effects may manifest via dorsal STN putatively by its effects on the cerebellum.

Background Parkinson disease (PD) impairs daily functioning for an increasing number of patients and has a growing national economic burden. Deep brain stimulation (DBS) may be the most broadly accepted procedural intervention for PD, but cost-effectiveness has not been established. Moreover, magnetic resonance image-guided focused ultrasound (FUS) is an emerging incisionless, ablative treatment that could potentially be safer and even more cost-effective. Objective To (1) quantify the utility (functional disability metric) imparted by DBS and radiofrequency ablation (RF), (2) compare cost-effectiveness of DBS and RF, and (3) establish a preliminary success threshold at which FUS would be cost-effective compared to these procedures. Methods We performed a meta-analysis of articles (1998-2018) of DBS and RF targeting the globus pallidus or subthalamic nucleus in PD patients and calculated utility using pooled Unified Parkinson Disease Rating Scale motor (UPDRS-3) scores and adverse events incidences. We calculated Medicare reimbursements for each treatment as a proxy for societal cost. Results Over a 22-mo mean follow-up period, bilateral DBS imparted the most utility (0.423 quality-adjusted life-years added) compared to (in order of best to worst) bilateral RF, unilateral DBS, and unilateral RF, and was the most cost-effective (expected cost: $32 095 ± $594) over a 22-mo mean follow-up. Based on this benchmark, FUS would need to impart UPDRS-3 reductions of ∼16% and ∼33% to be the most cost-effective treatment over 2- and 5-yr periods, respectively. Conclusion Bilateral DBS imparts the most utility and cost-effectiveness for PD. If our established success threshold is met, FUS ablation could dominate bilateral DBS's cost-effectiveness from a societal cost perspective.

BACKGROUND: Gangliosides are expressed in neuronal membranes, and play roles in neuronal differentiation and cell regulation during brain development. The ST3GAL5 gene encodes the enzyme GM3 synthase, and its deficiency causes a rare condition described to cause refractory epilepsy, profound intellectual disability, quadriplegia, choreoathetosis, and pigmentary skin changes. GM3 synthase deficiency is rarely reported to cause dystonia. We report five cases of GM3 synthase deficiency involving a dystonic phenotype. CASES: The five reported individuals were born of unaffected consanguineous parents from Old Order Amish families. They all developed refractory epilepsy and developmental regression within the first few months of life. They exhibit variable degrees of extrapyramidal movements, including orofacial, cervical, and limb dystonia, as well as choreoathetosis. CONCLUSIONS: We report five individuals with GM3 synthase deficiency who developed dystonic features. Dystonia has previously been reported in only one case of GM3 synthase deficiency.

Visual spatial dysfunction is not uncommon in Parkinson's disease. We hypothesized that visual search behavior is impaired in Parkinson's disease and the deficits correlate with changes in the amplitudes and frequency of fixational and non-fixational rapid eye movements. We measured eye movements, the horizontal and vertical angular position vectors of the right and left eye using high-resolution video oculography, in the Parkinsonian cohort who viewed a blank scene and pictures with real-life scene. Latter was associated with a task of searching an object hidden in a clutter, either at an expected or an unexpected location. Parkinsonian cohort took longer initial time to reach the region of interest. The ultimate response time was comparable in both Parkinson's disease and their healthy peers. The fixation duration was comparable in two cohorts but there was a trend wise decline for the ones located at unexpected locations. Parkinson's disease participants made more fixational saccades with significantly larger amplitude and less non-fixational saccades with significantly smaller amplitude during blank scene viewing. However, overall scanned area of the blank scene was not affected in Parkinson's disease. The Parkinson's disease participants made less non-fixational saccades with amplitudes comparable to healthy control during the visual search of a target object. Fixational saccades during visual search were larger in Parkinson's disease particularly when target was placed at an unexpected location, but the frequency was unchanged.

Parkinson's disease (PD) presents with visuospatial impairment and falls. It is critical to understand how subthalamic deep brain stimulation (STN DBS) modulates visuospatial perception. We hypothesized that DBS has different effects on visual and vestibular perception of linear motion (heading), a critical aspect of visuospatial navigation; and such effects are specific to modulated STN location. Two-alternative forced-choice experiments were performed in 14 PD patients with bilateral STN DBS and 19 age-matched healthy controls (HC) during passive en bloc linear motion and 3D optic-flow in immersive virtual reality measured vestibular and visual heading. Objective measure of perception with Weibull psychometric function revealed that PD has significantly lower accuracy [L: 60.71 (17.86)%, R: 74.82 (17.44)%] and higher thresholds [L: 16.68 (12.83), R: 10.09 (7.35)] during vestibular task in both directions compared to HC (p 0.05). DBS significantly improved vestibular discrimination accuracy [81.40 (14.36)%] and threshold [4.12 (5.87), p 0.05] in the rightward direction. There were no DBS effects on the slopes of vestibular psychometric curves. Visual heading perception was better than vestibular and it was comparable to HC. There was no significant effect of DBS on visual heading response accuracy or discrimination threshold (p 0.05). Patient-specific DBS models revealed an association between change in vestibular heading perception and the modulation of the dorsal STN. In summary, DBS may have different effects on vestibular and visual heading perception in PD. These effects may manifest via dorsal STN putatively by its effects on the cerebellum.

Objectives Parkinson's disease (PD) commonly affects visuospatial navigation causing postural instability and falls. Our overarching aim was to examine the visual and vestibular systems governing visuospatial navigation in PD. We hypothesize that PD affects vestibular and visual motion perception but to a different extent. The effects of PD on motion perception are dependent on the severity of the disease. Methods The two-alternative-forced-choice task objectively measured the motion perception during two experiments. One experiment examined the vestibular motion perception with en bloc movement of the platform. The second experiment tested the visual motion perception using an immersive virtual reality goggle. Results We found that accuracy, threshold, and precision of vestibular perception were more impaired in advanced-PD patients compared to those with a mild form of the disease. The parameters also correlated with the disease duration, overall axial motor impairment causing postural instability and falls, and subjective rating of the balance function. Such changes were present but less severe in visual motion perception. Conclusion We conclude that PD affects motion perception in the visual and vestibular domains in a severity-dependent manner. The impact of the disease in the vestibular domain is more severe compared to the visual domain. © 2020 International Parkinson and Movement Disorder Society.

Background Facial expressions require the complex coordination of 43 different facial muscles. Parkinson disease (PD) affects facial musculature leading to “hypomimia” or “masked facies.” Objective We aimed to determine whether modern computer vision techniques can be applied to detect masked facies and quantify drug states in PD. Methods We trained a convolutional neural network on images extracted from videos of 107 self-identified people with PD, along with 1595 videos of controls, in order to detect PD hypomimia cues. This trained model was applied to clinical interviews of 35 PD patients in their on and off drug motor states, and seven journalist interviews of the actor Alan Alda obtained before and after he was diagnosed with PD. Results The algorithm achieved a test set area under the receiver operating characteristic curve of 0.71 on 54 subjects to detect PD hypomimia, compared to a value of 0.75 for trained neurologists using the United Parkinson Disease Rating Scale-III Facial Expression score. Additionally, the model accuracy to classify the on and off drug states in the clinical samples was 63% (22/35), in contrast to an accuracy of 46% (16/35) when using clinical rater scores. Finally, each of Alan Alda’s seven interviews were successfully classified as occurring before (versus after) his diagnosis, with 100% accuracy (7/7). Conclusions This proof-of-principle pilot study demonstrated that computer vision holds promise as a valuable tool for PD hypomimia and for monitoring a patient’s motor state in an objective and noninvasive way, particularly given the increasing importance of telemedicine.

BACKGROUND Facial expressions require the complex coordination of 43 different facial muscles. Parkinson disease (PD) affects facial musculature leading to “hypomimia” or “masked facies.” OBJECTIVE We aimed to determine whether modern computer vision techniques can be applied to detect masked facies and quantify drug states in PD. METHODS We trained a convolutional neural network on images extracted from videos of 107 self-identified people with PD, along with 1595 videos of controls, in order to detect PD hypomimia cues. This trained model was applied to clinical interviews of 35 PD patients in their on and off drug motor states, and seven journalist interviews of the actor Alan Alda obtained before and after he was diagnosed with PD. RESULTS The algorithm achieved a test set area under the receiver operating characteristic curve of 0.71 on 54 subjects to detect PD hypomimia, compared to a value of 0.75 for trained neurologists using the United Parkinson Disease Rating Scale-III Facial Expression score. Additionally, the model accuracy to classify the on and off drug states in the clinical samples was 63% (22/35), in contrast to an accuracy of 46% (16/35) when using clinical rater scores. Finally, each of Alan Alda’s seven interviews were successfully classified as occurring before (versus after) his diagnosis, with 100% accuracy (7/7). CONCLUSIONS This proof-of-principle pilot study demonstrated that computer vision holds promise as a valuable tool for PD hypomimia and for monitoring a patient’s motor state in an objective and noninvasive way, particularly given the increasing importance of telemedicine.

Seesaw nystagmus is characterized by the rhythmic combination of vertical and torsional dysconjugate oscillations where one eye moves up and inward while the other moves down and outward. Common association of seesaw nystagmus with accessory optic track lesions lead to traditional hypothesis that it is due to the mismatch in the vision and vestibular systems. Here we propose a novel mechanism for seesaw nystagmus. We hypothesize that reverberations due to abnormal increases in the excitability of the reciprocally innervating circuit of excitatory burst neuron in the midbrain interstitial nucleus of Cajal causes the seesaw nystagmus. Analogous oscillations of the brainstem burst generators may be responsible for generation of saccadic oscillations or opsoclonus. The key difference is that the interstitial nucleus of Cajal lacks inhibitory burst neurons, hence the lack of post-inhibitory rebound, and relatively lower frequency of the oscillatory cycles causing pendular seesaw nystagmus. In contrast the brainstem burst generator, with reciprocally innervating excitatory and inhibitory burst neurons, and further inhibitory influence of the omnipause neurons results in the post-inhibitory rebound at the burst neurons, hence high oscillation frequency. This novel concept is supported by a unique observation in a patient with antineuronal nuclear autoantibody type 2 due to breast cancer who had combined seesaw nystagmus and superimposed saccadic oscillations. The patient neither had cerebellar deficits typically thought to cause paraneoplastic opsoclonus nor visual deficits that are known cause of seesaw nystagmus. We propose that hyperexcitability of the burst neurons in the interstitial nucleus of Cajal due to paraneoplastic antibody caused pendular seesaw nystagmus. On the other hand, increased excitability of brainstem burst generators and reduced efficacy of the omnipause neurons caused saccadic oscillations.

Objective: Parkinson's disease (PD) frequently affects vergence eye movements interfering with the perception of depth and dimensionality critical for mitigating falls. We examined neural strategies that compensate for abnormal vergence and their mechanistic underpinning in PD.Approach:Thea priorihypothesis was that impaired vergence is compensated by incorporating rapid eye movements (saccades) to accomplish gaze shifts at different depths. Our experiments examined the hypothesis by simulating biologically plausible computational models of saccade-vergence interactions in PD and validating predictions in the actual patient data.Main results:We found four strategies to accomplish 3D gaze shift; pure vergence eye movements, pure saccadic eye movements, combinations of vergence followed by a saccade, and combination of saccade followed by vergence. The gaze shifting strategy of the two eyes was incongruent in PD. The latency of vergence was prolonged, and it was more so when the saccades preceded the vergence or when the saccades only made 3D gaze shift. Computational models predicted at least two possible mechanisms triggering saccades along with vergence. One is based on the lack of foveal accuracy when the vergence gain is suboptimal. The second mechanism reflects the noise in the gating mechanism, the omnipause neurons, for vergence and saccades. None of the two model predictions alone were completely supported by the patient data. However, a combined model incorporating both abnormal vergence velocity gain and impaired gating accurately simulated the results from PD patients.Significance:The combined strategy is biologically plausible for two reasons: (a) The basal ganglia that is prominently affected in PD projects to the vergence velocity neurons in the midbrain via the cerebellum. The projection directly affects the vergence velocity gain. (b) The basal ganglia, via superior colliculus, influences the pattern of omnipause neuronal activity. Abnormal basal ganglia activity may introduce noise in the omnipause neurons.

Opsoclonus-myoclonus syndrome (OMS) refers to the combination of irregular, multidirectional, and chaotic eye movements that occur in all planes of gaze and is exacerbated with smooth pursuit. In addition, myoclonus, ataxia, or behavioral changes occur. Although often associated with neuroblastoma, OMS was first described in cases of encephalitis, but can occur due to various etiologies such as infections, a paraneoplastic phenomenon, or an idiopathic syndrome. OMS is rare. The pathophysiology of OMS remains unknown; however, several hypotheses have been proposed and will be discussed in this chapter. Patients usually present subacutely and require prompt workup which includes blood and cerebrospinal fluid for infections and paraneoplastic antibodies as well as imaging for occult malignancies. Treatment options include various immunomodulatory medications; however, chronic sequelae are common.

Background Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner. Methods Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa® PC+S, Medtronic, Inc., Food and Drug Administration– Investigational Device Exemption (IDE)-, institutional review board–approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states. Results Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P

OBJECT Holmes tremor (HT) is characterized by irregular, low-frequency (< 4.5 Hz) tremor occurring at rest, with posture, and with certain actions, often affecting proximal muscles. Previous reports have tended to highlight the use of thalamic deep brain stimulation (DBS) in cases of medication-refractory HT. In this study, the authors report the clinical outcome and analysis of single-unit recordings in patients with medication-refractory HT treated with globus pallidus internus (GPi) DBS. METHODS The authors retrospectively reviewed the medical charts of 4 patients treated with pallidal DBS for medication-refractory HT at the University of California, San Francisco, and San Francisco Veterans Affairs Medical Center. Clinical outcomes were measured at baseline and after surgery using an abbreviated motor-severity Fahn-Tolosa-Marin (FTM) tremor rating scale. Intraoperative microelectrode recordings were performed with patients in the awake state. The neurophysiological characteristics identified in HT were then also compared with characteristics previously described in Parkinson's disease (PD) studied at the authors' institution. RESULTS The mean percentage improvement in tremor motor severity was 78.87% (range 59.9%–94.4%) as measured using the FTM tremor rating scale, with an average length of follow-up of 33.75 months (range 18–52 months). Twenty-eight GPi neurons were recorded intraoperatively in the resting state and 13 of these were also recorded during contralateral voluntary arm movement. The mean firing rate at rest in HT was 56.2 ± 28.5 Hz, and 63.5 ± 19.4 Hz with action, much lower than the GPi recordings in PD. GPi unit oscillations of 2–8 Hz were prominent in both patients with HT and those with PD, but in HT, unlike PD, these oscillations were not suppressed by voluntary movement. CONCLUSIONS The efficacy of GPi DBS exceeded that reported in prior studies of ventrolateral thalamus DBS and suggest GPi may be a better target for treating HT. These clinical and neurophysiological findings help illuminate evolving models of HT and highlight the importance of cerebellar–basal ganglia interactions.

Background: X-linked dystonia parkinsonism (XDP) causes adult-onset progressive dystonia and parkinsonism, which may not respond to pharmacotherapy. Objective: Previous case reports have reported beneficial effects from bilateral pallidal (GPi) deep brain stimulation (DBS). Here, we report the long-term clinical outcomes of 3 patients treated at our center. Methods: All patients presented with medication refractory dystonia and parkinsonism. They were followed prospectively. Clinical evaluations included the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and the Unified Parkinson’s Disease Rating Scale (UPDRS). Adverse events were recorded. Results: The average length of follow-up was 45.7 months. No serious adverse events occurred. All patients experienced an immediate and sustained improvement in dystonia. Mean percentage improvement in motor subscores of BFMDRS was 63.5% at the last follow-up visit. Parkinsonism was less responsive to neuromodulation, with a mean improvement in UPDRS-III of 39.5%. Standard pallidal stimulation parameters were used. Freezing of gait developed after DBS therapy in 2 patients, stimulation-induced in one and due to disease progression in the other. Conclusion: Bilateral pallidal DBS resulted in significant and sustained improvement in dystonia and moderate improvement in parkinsonism. Pallidal DBS represents an important treatment option for XPD for the management of motor symptoms.

Background: Deep brain stimulation (DBS) is an effective therapy for advanced movement disorders, but its optimal use is still controversial. One factor that could play a role in the proper delivery of therapeutic stimulation by current DBS devices is the variability of the impedance at the interface between the electrode surface and surrounding tissue. Objective: To analyze variability and trends in the impedance of chronically-implanted DBS electrodes in subjects with movement disorders. Methods: We reviewed impedance values from medical records of DBS patients at an academic tertiary-care movement disorders center. The standard deviation of data recorded within individual subjects and single contacts were used as measures of longitudinal impedance variability. A generalized linear mixed model (GLMM) determined if a number of effects had significant influences on impedance. Results: We analyzed 2863 impedance measurements from 94 subjects. Median variability, for subjects with follow-up from 6 months to 5 years (n = 77), was 194 Ω for individual subjects and 141 Ω for individual contacts, with a range spanning from 18 to over 600 Ω. The GLMM, incorporating all subjects (n = 94), identified time, electrical activity, implanted target, contact position on the electrode and side of implantation as significant predictors of impedance. Age and disease duration at surgery, gender or ethnicity were not significant predictors. Conclusions: Our analysis suggests that a significant amount of impedance variability can be expected in chronically implanted DBS electrodes and indicates a number of factors with possible predictive value. Further studies are needed to link impedance characteristics to clinical outcomes.

Objective Determine the incidence of resting state oscillations in alpha/beta, high frequency (HFO) bands, and their phase amplitude coupling (PAC) in a large cohort in Parkinson's disease (PD). Methods Intra-operative local field potentials (LFPs) from subthalamic nucleus (STN) were recorded from 100 PD subjects, data from 74 subjects were included in the analysis. Results Alpha/beta oscillations were evident in >99%, HFO in 87% and PAC in 98% of cases. Alpha/beta oscillations ( P P =0.03). Alpha/beta oscillations were primarily found in 13–20Hz (low beta). Beta and HFO frequencies with the greatest coupling, were positively correlated ( P =0.001). Tremor attenuated alpha ( P =0.002) and beta band oscillations ( P Conclusions STN alpha/beta band oscillations and PAC were evident in ⩾98% cases and were greater in MA hemisphere. Resting tremor attenuated underlying alpha/beta band oscillations. Significance Beta band LFP power may be used to drive adaptive deep brain stimulation (aDBS), augmented by a kinematic classifier in tremor dominant PD.

Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner.Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa(®) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states.Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P0.003, n = 14), and this was voltage dependent (P0.001).Beta power was conserved during resting and forward walking states and was attenuated in a voltage-dependent manner during 140-Hz DBS. Phenotype may be an important consideration if this is used for closed-loop DBS.

Background Deep brain stimulation (DBS) is a recent treatment modality. Few studies have examined referral practices for DBS. Objective To review referral patterns to a large movement disorders center to investigate the current level of knowledge surrounding DBS candidacy. Design Retrospective analysis. Setting Tertiary care medical center. Patients Reviewed were 197 medical records of patients referred for DBS between December 1, 2005, and November 30, 2009. Main Outcome Measures Standardized criteria for DBS patient selection were used to categorize referred DBS candidates as the following: good candidates, possible future candidates, poor candidates because of neurological contraindications, or poor candidates because of medical contraindications. Yearly percentages were computed. Referral sources were categorized as movement disorder specialists vs non–movement disorder physicians and self-referred. Results In total, 165 referrals (83.8%) had ailments for which DBS was indicated, and 100 referrals (50.8%) were good candidates (62 with idiopathic Parkinson disease, 35 with dystonia, and 3 with essential tremor). Referrals by movement disorder specialists vs other sources differed significantly in their percentages of good candidates (66.7% vs 40.4%, P = .002) and possible future candidates (14.7% vs 32.7%, P = .02) but not poor candidates (18.7% vs 25.0%, P = .60). Over the observed period of referrals, the yearly percentages significantly decreased for good candidates and increased for possible future candidates and poor candidates. Conclusions Compared with findings in prior studies, the quality of DBS referrals has improved. The increase in referral of possible future candidates and poor candidates may reflect greater confidence in the procedure.