Machine Learning for Deep Brain Stimulation Efficacy using Dense Array EEG

Background:Deep brain stimulation (DBS) of the ventralis intermedius (VIM) nucleus of the thalamus has been successful in mitigating upper limb tremor, but the effect on gait and balance performance is unclear. Here, we aim to examine the effectiveness of VIM DBS on stride length variability, sway path length, and task-relevant tremor of various body segments in essential tremor (ET).Methods:Seventeen ET individuals treated with DBS (ET DBS) and 17 age-and sex-matched healthy controls (HC) performed a postural balance and overground walking task. In separate and consecutive visits, ET DBS performed gait and balance tasks with DBS ON or OFF. The main outcome measures were sway path length, stride length variability, and tremor quantified from upper limb, lower limb, upper and lower trunk (axial) during the gait and balance tasks.Results:With DBS OFF, ET DBS exhibited significantly greater stride length variability, sway path length, and tremor during gait and balance task relative to HC. Relative to DBS OFF, DBS ON reduced stride length variability and sway path length in ET DBS. The DBS-induced reduction in stride length variability was associated with the reduction in both upper trunk tremor and upper limb tremor. The DBS-induced reduction in sway path length was associated with the reduction in upper trunk tremor.Discussion:The findings of this study revealed that VIM DBS was effective in improving gait and balance in ET DBS and that improvements in gait and postural balance were associated with a reduction of axial tremor during the tasks.Highlights:ET patients exhibit tremor in various body locations during gait and balance.DBS reduced stride length variability and sway path length.DBS-induced improvements in gait and balance were associated with reduction in axial tremor.

<h3>Objective:</h3> To identify existing racial disparities in Deep Brain Stimulation (DBS) utilization in those hospitalized for Parkinson Disease (PD), Essential Tremor (ET), and dystonia. <h3>Background:</h3> DBS is an effective surgical treatment option for those with PD, ET, and dystonia. Racial disparities in DBS utilization in patients with PD have been documented demonstrating that Black patients receive DBS at disproportionately lower rates compared to White patients. To our knowledge, no studies have investigated if this pattern of disuse persists in other movement disorders with FDA-approval for DBS: ET and dystonia. <h3>Design/Methods:</h3> The Nationwide Inpatient Sample (NIS) database from the Healthcare Cost and Utilization Project was queried for all hospitalizations from 2012–2018 with a primary diagnosis of PD, ET, or dystonia. A total of 21,964, 3,307, and 1,439 discharges were recorded for PD, ET, and dystonia, respectively. Within that sample, treatment with DBS was identified. The sex, race, age, payment method, income quartile, year of treatment, and mortality score of patients were extracted. Hospital characteristics included hospital size, urban/rural setting, teaching status, and geographic region. A multivariate logistic regression was performed to identify predictors for use of DBS. <h3>Results:</h3> Between the years 2012–2018, Black patients with PD, ET, and dystonia were all significantly less likely to receive DBS than White patients. Compared to White patients, Black patients with PD were nearly 8 times less likely to receive DBS (OR=0.13, CI=0.1–0.17, p&lt;0.0001), and Black patients with ET and dystonia were 4–5 times less likely to receive DBS (OR=0.21, CI=0.14–0.32, p&lt;0.0001; OR=0.22, CI=0.1–0.49, p=0.0002; respectively). Importantly, when controlling for all patient and hospital level characteristics, these racial disparities remained. <h3>Conclusions:</h3> Our analysis using the NIS database shows that Black patients with a diagnosis of PD, ET, or dystonia were less likely to be treated with DBS than White patients were between 2012 and 2018. <b>Disclosure:</b> Mr. Dorritie has nothing to disclose. Mohammad Faysel has nothing to disclose. Prof. Gruessner has nothing to disclose. Dr. Robakis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amneal pharmaceuticals.

Parkinson’s disease (PD) can produce postural abnormalities of the standing body position such as kyphosis. We investigated the effects of PD, deep brain stimulation (DBS) in the subthalamic nucleus (STN), vision and adaptation on body position in a well-defined group of patients with PD in quiet standing and during balance perturbations. Ten patients with PD and 25 young and 17 old control participants were recruited. Body position was measured with 3D motion tracking of the ankle, knee, hip, shoulder and head. By taking the ankle as reference, we mapped the position of the joints during quiet standing and balance perturbations through repeated calf muscle vibration. We did this to explore the effect of PD, DBS in the STN, and vision on the motor learning process of adaptation in response to the repeated stimulus. We found that patients with PD adopt a different body position with DBS ON vs. DBS OFF, to young and old controls, and with eyes open vs. eyes closed. There was an altered body position in PD with greater flexion of the head, shoulder and knee (p≤0.042) and a posterior position of the hip with DBS OFF (p≤0.014). With DBS ON, body position was brought more in line with the position taken by control participants but there was still evidence of greater flexion at the head, shoulder and knee. The amplitude of movement during the vibration period decreased in controls at all measured sites with eyes open and closed (except at the head in old controls with eyes open) showing adaptation which contrasted the weaker adaptive responses in patients with PD. Our findings suggest that alterations of posture and greater forward leaning with repeated calf vibration, are independent from reduced movement amplitude changes. DBS in the STN can significantly improve body position in PD although the effects are not completely reversed. Patients with PD maintain adaptive capabilities by leaning further forward and reducing movement amplitude despite their kyphotic posture.

The effects of subthalamic nucleus deep brain stimulation on parkinsonian tremor

BackgroundSleep dysfunction is a common and disabling non-motor symptom in Parkinson’s disease. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms and subjective sleep in PD, but alternative stimulation parameters to optimize sleep have not been explored. We hypothesized that low frequency STN DBS would improve objective sleep more than conventional settings.MethodsTwenty PD subjects with STN DBS (18 unilateral, 2 bilateral) underwent 3 non-consecutive nights of polysomnography: DBS off; DBS high frequency (≥130 Hz); and DBS low frequency (60 Hz). Motor symptom tolerability was assessed 30 minutes after resumption of baseline settings the morning following polysomnography. The primary outcome was change in sleep efficiency between high and low frequency nights measured with repeated measures ANOVA.ResultsThere was no difference in sleep efficiency between nights at high frequency (82.1% (72.6–90.1)) (median (IQR)), low frequency (81.2% (56.2–88.8)), or DBS off (82.8% (75.7–87.4)), p=0.241. Additionally, there was no difference in sleep stage percent, arousals, limb movements, subjective sleep quality, or objective vigilance measures. These outcomes did not change after adjusting for age, sex, disease duration, or side of surgery. No residual adverse motor effects were noted.ConclusionsAlthough well tolerated, low frequency STN DBS did not improve objective sleep in PD. Remarkably, objective measures of sleep were not worse with DBS off. These observations point to the potential for adaptive stimulation approaches, through which DBS settings could be optimized during sleep to meet individual needs. Additionally, these changes could preserve battery life without compromising patient outcomes.

Do patient's get angrier following STN, GPi, and thalamic deep brain stimulation

Tremor of the upper extremity is a significant cause of disability in some patients with multiple sclerosis (MS). The MS tremor is complex because it contains an ataxic intentional tremor component due to the involvement of the cerebellum and cerebellar outflow pathways by MS plaques, which makes the MS tremor, in general, less responsive to medications or deep brain stimulation (DBS) than those associated with essential tremor or Parkinson's disease. The cerebellar component has been thought to be the main reason for making DBS less effective, although it is not clear whether it is due to the lack of suppression of the ataxic tremor by DBS or else. The goal of this study was to clarify the effect of DBS on cerebellar tremor compared to non-cerebellar tremor in a patient with MS. By wearing an accelerometer on the index finger of each hand, we were able to quantitatively characterize kinetic tremor by frequency and amplitude, with cerebellar ataxia component on one hand and that without cerebellar component on the other hand, at the beginning and end of the hand movement approaching a target at DBS Off and On status. We found that cerebellar tremor surprisingly had as good a response to DBS as the tremor without a cerebellar component, but the function control on cerebellar tremor was not as good due to its distal oscillation, which made the amplitude of tremor increasingly greater as it approached the target. This explains why cerebellar tremor or MS tremor with cerebellar component has a poor functional transformation even with a good percentage of tremor control. This case study provides a better understanding of the effect of DBS on cerebellar tremor and MS tremor by using a wearable device, which could help future studies improve patient selection and outcome prediction for DBS treatment of this disabling tremor.

Redefining Bradykinesia.

Essential Tremor (ET) is the most common tremor syndrome seen in adults. The characteristic tremor in ET is postural and action tremors, with a frequency of 4–7 Hz; while in patients with Parkinson’s disease (PD), the dominant tremor is resting tremor with a typical frequency of 5 Hz. Deep brain stimulation (DBS) in the ventral intermediate nuclei (Vim) has been shown effective in treating action or intention tremors in medically resistant ET, while DBS in the subthalamic nucleus (STN) has been shown effective in treating rigidity, rest tremor and Dopa-induced dyskinesias in PD. However, chronic bilateral DBS, whether in Vim or STN, may have negative impact on speech production. We report two cases where both patients received DBS greater than one year and developed speech impairment. When the stimulation in Vim was turned off for 30 min in ET, the patient's speech returned to the baseline while turning the STN stimulation off for 30 min in PD, minimal changes were observed and 12 h with stimulation-off were required for speech to return to the non-stimulated state.

For more than 30 years, deep brain stimulation (DBS) has been used to target the symptoms of a number of neurological disorders and in particular movement disorders such as Parkinson’s disease (PD) and essential tremor (ET). It is known that the loss of dopaminergic neurons in the substantia nigra leads to PD, while the exact impact of this on the brain dynamics is not fully understood, the presence of beta-band oscillatory activity is thought to be pathological. The cause of ET, however, remains uncertain, however pathological oscillations in the thalamocortical-cerebellar network have been linked to tremor. Both of these movement disorders are treated with DBS, which entails the surgical implantation of electrodes into a patient’s brain. While DBS leads to an improvement in symptoms for many patients, the mechanisms underlying this improvement is not clearly understood, and computational modeling has been used extensively to improve this. Many of the models used to study DBS and its effect on the human brain have mainly utilized single neuron and single axon biophysical models. We have previously shown in separate models however, that the use of population models can shed much light on the mechanisms of the underlying pathological neural activity in PD and ET in turn, and on the mechanisms underlying DBS. Together, this work suggested that the dynamics of the cerebellar-basal ganglia thalamocortical network support oscillations at frequency range relevant to movement disorders. Here, we propose a new combined model of this network and present new results that demonstrate that both Parkinsonian oscillations in the beta band and oscillations in the tremor frequency range arise from the dynamics of such a network. We find regions in the parameter space demonstrating the different dynamics and go on to examine the transition from one oscillatory regime to another as well as the impact of DBS on these different types of pathological activity. This work will allow us to better understand the changes in brain activity induced by DBS, and allow us to optimize this clinical therapy, particularly in terms of target selection and parameter setting.

ObjectiveGait disturbances are frequent side effects occurring during chronic thalamic deep brain stimulation (DBS) in patients with essential tremor (ET). Adapting stimulation settings to shorter pulse widths has been shown...

Background: Although there are few reports of radiofrequency lesions performed through deep brain stimulation (DBS) electrodes in patients with movement disorders, experience with this method is scarce. Methods: We present 2 patients who had been previously treated with DBS of subthalamic nuclei (STN) and the ventral intermediate (VIM) nucleus of the thalamus for Parkinson's disease and essential tremor, respectively, and underwent a radiofrequency lesion through their DBS electrodes after developing a hardware infection. The authors conduct a review of the literature regarding this method. Results: Both patients had a good clinical outcome after 20 and 8 months, respectively, as assessed by a reduction in Fahn-Tolosa-Marin Scale and Unified Parkinson's Disease Rating Scale scores. The second patient underwent a second DBS system implantation surgery after his radiofrequency treatment to optimize his management, achieving optimal clinical control with lower current and drug requirements than before the radiofrequency intervention. No adverse effects were observed. Conclusions: Radiofrequency lesions through DBS electrodes allow the creation of small and localized lesions. Its effectiveness and low-risk profile, in addition to its low cost, make this procedure suitable and a possible alternative in the therapeutic repertoire for the surgical treatment of movement disorders.

Deep Brain Stimulation and Movement Disorder Treatment

Deep brain stimulation has provided an efficacious alternative for the treatment of progressive neurodegenerative movement disorders, such as Parkinson’s disease and Essential tremor, for more than a quarter of a century. This intervention strategy offers an adjustable and even reversible therapy by contrast to the permanency of lesion inducing neurosurgery, especially if medication has been deemed intractable. Furthermore, deep brain stimulation has been affirmed as a long-term means of suppressing movement disorder symptoms, although the foundational mechanisms remain to be conclusively ascertained. Target selection is specific to the type of neurodegenerative movement disorder diagnosed, and primary risks pertain to surgery and adverse effects resultant from the activation of stimulation. The general aspects that comprise the deep brain stimulation system are discussed from a system-level perspective, such as the implantable pulse generator, battery, connecting wire, and electrode lead. Even after the expert implantation of a deep brain stimulation system, the acquisition of an optimal parameter configuration presents a rather daunting and time-consuming process even for the highly talented and skilled clinician. The sheer quantity of permutations for optimizing parameters, such as polarity, amplitude of stimulation, rate of stimulation, and pulse width, presents a labor-intensive endeavor. The parameter configuration and operation of the deep brain stimulation system are modulated by the clinician programmer and patient programmer. Future concepts for deep brain stimulation are discussed, such as closed-loop acquisition of configuration parameters. Foundational to the perspective of deep brain stimulation optimization is the application of wearable and wireless systems, such as the smartphone, for objectively quantified feedback of movement disorder status. These envisioned technology evolutions advocate the prominence of Network Centric Therapy for the treatment of neurodegenerative movement disorders, such as Parkinson’s disease and Essential tremor.

Conventional deep brain stimulation (DBS) for movement disorders is a well-established clinical treatment. Over the last few decades, over 200,000 people have been treated by DBS worldwide for several neurological conditions, including Parkinson's disease and Essential Tremor. DBS involves implanting electrodes into disorder-specific targets in the brain and applying an electric current. Although the hardware has developed in recent years, the clinically used stimulation pattern has remained as a regular frequency square pulse. Recent studies have suggested that phase-locking, coordinated reset or irregular patterns may be as or more effective at desynchronising the pathological neural activity. Such studies have shown efficacy using detailed neuron models or highly simplified networks and considered one frequency band. We previously described a population level model which generates oscillatory activity in both the beta band (20 Hz) and the tremor band (4 Hz). Here we use this model to look at the impact of applying regular, irregular and phase dependent bursts of stimulation, and show how this influences both tremor- and beta-band activity. We found that bursts are as or more effective at suppressing the pathological oscillations compared to continuous DBS. Importantly however, at higher amplitudes we found that the stimulus drove the network activity, as seen previously. Strikingly, this suppression was most apparent for the tremor band oscillations, with beta band pathological activity being more resistant to the burst stimulation compared to continuous, conventional DBS. Furthermore, our simulations showed that phase-locked bursts of stimulation did not convey much improvement on regular bursts of oscillation. Using a genetic algorithm optimisation approach to find the best stimulation parameters for regular, irregular and phase-locked bursts, we confirmed that tremor band oscillations could be more readily suppressed. Our results allow exploration of stimulation mechanisms at the network level to formulate testable predictions regarding parameter settings in DBS.