Brain Stimulation Devices Research Articles

Risk Factor Analysis and Algorithmic Approach for Managing Deep Brain Stimulation Device-Related Wound Complications

Background: Although implanting deep brain stimulation (DBS) devices carries up to a 15% risk of complications, optimal management strategies remain poorly understood. This study aimed to review the risk factors for wound complications of DBS device implantation and develop an algorithm for proper management.Methods: Patients with Parkinson disease who underwent bilateral subthalamic nucleus DBS device implantation between 2005 and 2022 were retrospectively reviewed. All DBS-related wound complications such as infection, dehiscence, erosion, and displacement were recorded, and factors associated with device explantation were also assessed.Results: A total of 398 patients underwent DBS device implantation using 796 electrodes and implantable pulse generators. During the mean follow-up of 9.8 ± 5.5 years, 28 patients (7.0%) experienced wound complications that required reoperation, including 14 infection (50.0%), 22 dehiscence (78.6%), five skin erosion (17.9%), and two device displacement (7.1%). Complications were resolved with a single reoperation in 13 patients (46.4%), while nine patients underwent 2–3 surgical procedures (32.2%), and six patients in 6–8 operations (21.4%). The device was salvaged in 16 patients (57.1%) and removed in 12 (42.9%). Infection (P = 0.010), shorter time interval from device implantation to complications (P = 0.022), higher C-reactive protein levels (P = 0.026), methicillin-resistant <i>Staphylococcus aureus</i> growth (P = 0.044), and history of multiple previous revisions (P < 0.001) were associated with device removal.Conclusion: To maximize the therapeutic benefit of DBS and minimize the time, effort, and cost required for revision, temporary explantation in early stages followed by reimplantation of the device after the wound subsides should be considered in high-risk cases.

Primary central nervous system diffuse large B-cell lymphoma with MYC and BCL2 rearrangements associated with deep brain stimulation device.

Primary central nervous system diffuse large B-cell lymphoma with MYC and BCL2 rearrangements associated with deep brain stimulation device.

Beta Oscillations in the Sensory Thalamus During Severe Facial Neuropathic Pain Using Novel Sensing Deep Brain Stimulation

ObjectiveAdvancements in deep brain stimulation (DBS) devices provide a unique opportunity to record local field potentials longitudinally to improve the efficacy of treatment for intractable facial pain. We aimed to identify potential electrophysiological biomarkers of pain in the ventral posteromedial nucleus (VPM) of the thalamus and periaqueductal gray (PAG) using a long-term sensing DBS system. Materials and MethodsWe analyzed power spectra of ambulatory pain-related events from one patient implanted with a long-term sensing generator, representing different pain intensities (pain >7, pain >9) and pain qualities (no pain, burning, stabbing, and shocking pain). Power spectra were parametrized to separate oscillatory and aperiodic features and compared across the different pain states. ResultsOverall, 96 events were marked during a 16-month follow-up. Parameterization of spectra revealed a total of 62 oscillatory peaks with most in the VPM (77.4%). The pain-free condition did not show any oscillations. In contrast, β peaks were observed in the VPM during all episodes (100%) associated with pain >9, 56% of episodes with pain >7, and 50% of burning pain events (center frequencies: 28.4 Hz, 17.8 Hz, and 20.7 Hz, respectively). Episodes of pain >9 indicated the highest relative β band power in the VPM and decreased aperiodic exponents (denoting the slope of the power spectra) in both the VPM and PAG. ConclusionsFor this patient, an increase in β band activity in the sensory thalamus was associated with severe facial pain, opening the possibility for closed-loop DBS in facial pain.

Various pharmacological agents in the pipeline against intractable epilepsy.

Epilepsy is a noncommunicable chronic neurological disorder affecting people of all ages, with the highest prevalence in low and middle-income countries. Despite the pharmacological armamentarium, the plethora of drugs in the market, and other treatment options, 30%-35% of individuals still show resistance to the current medication, termed intractable epilepsy/drug resistance epilepsy, which contributes to 50% of the mortalities due to epilepsy. Therefore, the development of new drugs and agents is needed to manage this devastating epilepsy. We reviewed the pipeline of drugs in "ClinicalTrials. gov," which is the federal registry of clinical trials to identify drugs and other treatment options in various phases against intractable epilepsy. A total of 31 clinical trials were found regarding intractable epilepsy. Among them, 48.4% (15) are about pharmacological agents, of which 26.6% are in Phase 1, 60% are in Phase 2, and 13.3% are in Phase 3. The mechanism of action or targets of the majority of these agents are different and are more diversified than those of the approved drugs. In this article, we summarized various pharmacological agents in clinical trials, their backgrounds, targets, and mechanisms of action for the treatment of intractable epilepsy. Treatment options other than pharmacological ones, such as devices for brain stimulation, ketogenic diets, gene therapy, and others, are also summarized.

Local field potentials: Therapeutic implications for DBS in dystonia including adaptive DBS for dystonia

Local field potentials (LFPs) are signals generated primarily by the result of the synchronous discharge of post-synaptic potentials. Detection of LFPs from intracranial electrodes sited within the basal ganglia has led to the recognition that there are specific features of the LFP that could serve as neurophysiological biomarkers of different disease states. For example, in Parkinson’s disease peaks in the beta frequency range of the power spectrum are known to correlate with the degree of bradykinesia and rigidity, whereas low frequency, alpha-theta peaks are increasingly considered a biomarker of dystonic activity. The introduction of newer deep brain stimulation (DBS) devices capable of simultaneous stimulation and LFP detection creates opportunities to investigate new strategies for treating patients with dystonia. This review aims to summarise the LFP findings seen in patients with dystonia undergoing DBS with a particular focus on the potential implications for future clinical practice and the development of adaptive DBS systems.

Brain Neuromodulation Effects on Sport and Nutrition: A Narrative Review

Study purpose. At the end of the twentieth century, the development of highly reliable and painless non-invasive transcranial brain stimulation techniques and devices has aroused great scientific and clinical interest in numerous fields. In neuroscience, since the introduction of innovative and non-invasive devices such as the brain stimulator, the investigation of cortical processes and their neural basis has played a fundamental role. Furthermore, neuroscientists are attracted to therapeutic applications for the treatment of food craving. This narrative review is aimed to explain the growing and constant interest of neuroscientific experimentation in the field of non-invasive transcranial stimulation. Material and methods. After an introduction explaining the historical evolution of NIBS, we will try to provide an overview of the two stimulation techniques (TMS and tDCS); we will describe the different types of stimulation that can be performed using these techniques, the excitatory/inhibitory effects, and the various mechanisms of action at the level of brain activity. Results. We will also provide some elucidations regarding the implications of the facilitative/inhibitory effects, and how these stimulation methods can be used to advance knowledge of the neurofunctional organization of the brain. Conclusion. The results of the study showed the effect of brain neuromodulation on sports and nutrition.

Present and Prospective Advancements in the Field of Deep Brain Stimulation Technology

Deep brain stimulation (DBS) in the neurosurgery domain allows for precise control of particular neural circuits. DBS has shown significant therapeutic effectiveness in the management of essential tremor, dystonia, and Parkinson's disease (PD). Moreover, ongoing research is investigating the potential of DBS as a therapy modality for several additional conditions characterized by aberrant circuitry, including depression and dementia. Over the last two decades, there has been a gradual improvement in DBS (Deep Brain Stimulation) devices, which today integrate an extension wire, pulse generator, and intracranial electrode. These components have been borrowed from the field of cardiology. The present paradigm of DBS is expected to undergo significant changes due to recent breakthroughs in technology and imaging, as well as a more comprehensive understanding of brain illnesses. Anticipated advancements in the tolerability and efficacy of DBS may be attributed to progress made in several areas, including battery and electrodes designing, stimulation systems, on-demand and closed-loop stimulation, including sensor technologies. This review provides a comprehensive examination of the historical and projected trajectory of DBS technology. By retrospectively examining the progress of DBS, we may enhance our understanding and recognition of our current position, as well as proactively forecast the next obstacles and prospects.

A perspective on translating genomic discoveries into targets for brain-machine interface and deep brain stimulation devices.

Mental illnesses have a huge impact on individuals, families, and society, so there is a growing need for more efficient treatments. In this context, brain-computer interface (BCI) technology has the potential to revolutionize the options for neuropsychiatric therapies. However, the development of BCI-based therapies faces enormous challenges, such as power dissipation constraints, lack of credible feedback mechanisms, uncertainty of which brain areas and frequencies to target, and even which patients to treat. Some of these setbacks are due to the large gap in our understanding of brain function. In recent years, large-scale genomic analyses uncovered an unprecedented amount of information regarding the biology of the altered brain function observed across the psychopathology spectrum. We believe findings from genetic studies can be useful to refine BCI technology to develop novel treatment options for mental illnesses. Here, we assess the latest advancements in both fields, the possibilities that can be generated from their intersection, and the challenges that these research areas will need to address to ensure that translational efforts can lead to effective and reliable interventions. Specifically, starting from highlighting the overlap between mechanisms uncovered by large-scale genetic studies and the current targets of deep brain stimulation treatments, we describe the steps that could help to translate genomic discoveries into BCI targets. Because these two research areas have not been previously presented together, the present article can provide a novel perspective for scientists with different research backgrounds. This article is categorized under: Neurological Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Biomedical Engineering.

A - 88 Parkinson's Disease and Deep Brain Stimulation (DBS) Device Settings: Effects of Amplitude, Pulse Width, and Frequency on Cognitive Performance.

Frontal systems decline after DBS for Parkinson's disease has been consistently reported, with high frequency settings (>130Hz) correlating with decreased executive functioning and verbal fluency. The present study replicates and expands upon these findings. Six DBS recipients underwent standardized pre/post-surgical neuropsychological testing. Two-tailed T-tests assessed changes in cognitive scores. Correlational analyses explored relationships between cognitive scores and UPDRS, H&Y, and stimulator settings (amplitude, pulse width, and frequency). All participants underwent bilateral STN stimulation. Pre/post averages were: UPDRS (43.0 and 26.2) and H&Y (2.7 and 2.3) with average stimulator settings of amplitude (2.7V), pulse width (60.8μs), and frequency (151.7Hz). Pre/post neuropsychological testing revealed significant decline on the Behavioral Dyscontrol Scale (p = <0.01) with an average raw score decline of 3.17 points. All other cognitive scores showed non-significant improvement (p-value range = 0.22-0.89). H&Y change significantly correlated with semantic fluency (r = 0.96). UPDRS change significantly correlated with motoric processing speed (r = 0.91), semantic fluency (r = -0.93), and confrontation naming (r = -0.86). Stimulator amplitude significantly correlated with auditory attention (r = 0.82); simple planning (r = 0.96); and verbal memory (r = -0.86). Stimulator frequency significantly correlated with auditory attention (r = 0.87), simple planning (r = 0.97), and verbal memory (r = -0.96). Simulator pulse width was not significant. The study examines effects of bilateral STN stimulation on cognitive outcomes in patients with PD. A significant improvement in motor function was accompanied by a significant decline in performance on upper motor bilateral dexterity and inhibition. Correlation analysis shows the relationship between changes in cognition and motor function, as well as the correlation between stimulator settings and specific cognitive functions.

Chronic Pallidal Local Field Potentials Are Associated With Dystonic Symptoms in Children

BackgroundNovel deep brain stimulation devices can record local field potentials (LFPs), which represent the synchronous synaptic activity of neuronal populations. The clinical relevance of LFPs in patients with dystonia remains unclear. ObjectivesWe sought to determine whether chronic LFPs recorded from the globus pallidus internus (GPi) were associated with symptoms of dystonia in children. Materials and MethodsTen patients with heterogeneous forms of dystonia (genetic and acquired) were implanted with neurostimulators that recorded LFP spectral snapshots. Spectra were compared across parent-reported asymptomatic and symptomatic periods, with daily narrowband data superimposed in 24 one-hour bins. ResultsSpectral power increased during periods of registered dystonic symptoms: mean increase = 102%, CI: (76.7, 132). Circadian rhythms within the LFP narrowband time series correlated with dystonic symptoms: for delta/theta-waves, correlation = 0.33, CI: (0.18, 0.47) and for alpha waves, correlation = 0.27, CI: (0.14, 0.40). ConclusionsLFP spectra recorded in the GPi indicate a circadian pattern and are associated with the manifestation of dystonic symptoms.

Periosteal Turnover Flap for Coverage and Salvage of Exposed Deep Brain Stimulation Device.

Implanted deep brain stimulation (DBS) devices are crucial in the treatment of movement disorders. Hardware extrusion is among the most frequent complications of the implantation process and requires reconstruction with well-vascularized tissues. The authors present a case of periosteal turnover flap for coverage of an exposed DBS device. An 11-year-old female patient with spastic cerebral palsy presented with an exposed DBS device located in the right parietal area. The exposed device was covered by a proximally based periosteal flap. Postoperative evaluations at months 1, 2, 3, and 8 revealed no signs of infection or dehiscence. This brief clinical study shows that reconstruction with periosteal turnover flaps is both an easy and excellent choice for secondary closure of exposed DBS devices.

Technical note: System uncertainty on four- and eight-channel parallel RF transmission for safe MRI of deep brain stimulation devices.

Parallel radiofrequency transmission (pTx) remains a promising technology for addressing high-field magnetic resonance imaging (MRI) challenges, particularly regarding the safety of patients with implanted deep brain stimulation (DBS) devices. Radiofrequency (RF) shim optimization methods utilizing pTx technology have shown the potential to minimize induced RF heating effects at the electrode tips of DBS devices at 3 T. Research pTx system implementations often involve the combination of custom and commercial hardware that are integrated onto an existing MRI system. As a result, system characterization is important to ensure implant-friendly safe imaging conditions are satisfied for the operating range of the hardware. Utilizing electromagnetic and thermal simulations, the impact of system uncertainty is studied for the proposed 4- and 8-channel pTx system setupand its associated "safe mode" for DBS applications. Electromagnetic simulations indicated that instrumentation errors can affect the overall electric field strength experienced at the DBS lead tip, and a worst-case system uncertainty analysis predicted temperature elevations of +1.5°C in the 4-channel setup and +0.9°C in the 8-channel setup. In conclusion, system uncertainty can impact the precision of pTx RF inputs which in the worst-case, may lead to an unsafe imaging scenario and the proposed 8-channel setup may provide more robustness and thus, safer conditions for MRI of DBS patients.

Incorporating Next-Generation Views on Changes in Personality, Mood, and Behavior in Adaptive Deep Brain Stimulation Devices

Incorporating Next-Generation Views on Changes in Personality, Mood, and Behavior in Adaptive Deep Brain Stimulation Devices

Brain Recording Analysis and Visualization Online (BRAVO): An open-source visualization tool for deep brain stimulation data

BackgroundDeep brain stimulation (DBS) devices with neural recording capabilities are commercially available and may potentially improve clinical care and advance research. However, tools, to visualize neural recording data have been limited. These tools in general, require custom-made software for processing and analysis. The development of new tools will be critical for clinicians and researchers to fully leverage the latest device capabilities. ObjectiveThere is an urgent need for a user-friendly tool for in-depth visualization and analysis of brain signals and of DBS data. Methods and resultsThe Brain Recording Analysis and Visualization Online (BRAVO) platform was developed to easily import, visualize, and analyze brain signals. This Python-based web interface has been designed and implemented on a Linux server. The tool processes the session files from DBS programming generated by a clinical ‘programming’ tablet. The platform is capable of parsing and organizing neural recordings for longitudinal analysis. We present the platform and cases exemplifying its application and use. ConclusionThe BRAVO platform is an accessible easy-to-use, open-source web interface for clinicians and researchers to apply for analysis of longitudinal neural recording data. The tool can be used for both clinical and research applications.

Ventricular Fibrillation Simulated Electrocardiogram Artifact by a Deep Brain Stimulator

Deep brain stimulation devices can disrupt cardiac rhythm interpretation by causing electrocardiogram artifact. We report the case of a deep brain stimulating device initiating ventricular fibrillation simulated electrocardiogram artifact in the prehospital setting. Mimicked ventricular fibrillation due to a deep brain stimulator has not been documented, and if unrecognized could influence unwarranted or potentially harmful clinical decisions.

How to entrain a selected neuronal rhythm but not others: open-loop dithered brain stimulation for selective entrainment

Objective. While brain stimulation therapies such as deep brain stimulation for Parkinson’s disease (PD) can be effective, they have yet to reach their full potential across neurological disorders. Entraining neuronal rhythms using rhythmic brain stimulation has been suggested as a new therapeutic mechanism to restore neurotypical behaviour in conditions such as chronic pain, depression, and Alzheimer’s disease. However, theoretical and experimental evidence indicate that brain stimulation can also entrain neuronal rhythms at sub- and super-harmonics, far from the stimulation frequency. Crucially, these counterintuitive effects could be harmful to patients, for example by triggering debilitating involuntary movements in PD. We therefore seek a principled approach to selectively promote rhythms close to the stimulation frequency, while avoiding potential harmful effects by preventing entrainment at sub- and super-harmonics. Approach. Our open-loop approach to selective entrainment, dithered stimulation, consists in adding white noise to the stimulation period. Main results. We theoretically establish the ability of dithered stimulation to selectively entrain a given brain rhythm, and verify its efficacy in simulations of uncoupled neural oscillators, and networks of coupled neural oscillators. Furthermore, we show that dithered stimulation can be implemented in neurostimulators with limited capabilities by toggling within a finite set of stimulation frequencies. Significance. Likely implementable across a variety of existing brain stimulation devices, dithering-based selective entrainment has potential to enable new brain stimulation therapies, as well as new neuroscientific research exploiting its ability to modulate higher-order entrainment.

Brain abscess in a patient with generalized dystonia after deep brain stimulation: illustrative case.

Infections related to deep brain stimulation (DBS) devices are not rare, but abscess formation in brain parenchyma is extremely rare. A 50-year-old man with generalized dystonia had undergone DBS of bilateral globus pallidus internus. The authors attempted to remove the bilateral DBS system due to repeated device infections caused by metal allergies. However, the intracranial lead had to be left in place, because the lead was strongly adherent to brain parenchyma. Five years later, magnetic resonance imaging showed ring-like enhancement localized around the tip of the intracranial lead, suggesting brain abscess. In response to the symptoms, the remaining left intracranial electrode was removed. Brain abscesses require several months of treatment with appropriate antibiotics, but good outcomes can be achieved with appropriate treatment. Brain abscess is a rare complication of DBS. In the present case, the infection spread from the subcutaneous infected foci to the intracranial area through the lead, resulting in the formation of a brain abscess. Removing as much of the device as possible from the body is therefore important, even if adhesions with brain parenchyma or other tissues are present, because of the risk of serious complications, as seen in this case.

Effect of field strength on RF power deposition near conductive leads: A simulation study of SAR in DBS lead models during MRI at 1.5 T-10.5 T.

Since the advent of magnetic resonance imaging (MRI) nearly four decades ago, there has been a quest for ever-higher magnetic field strengths. Strong incentives exist to do so, as increasing the magnetic field strength increases the signal-to-noise ratio of images. However, ensuring patient safety becomes more challenging at high and ultrahigh field MRI (i.e., ≥3 T) compared to lower fields. The problem is exacerbated for patients with conductive implants, such as those with deep brain stimulation (DBS) devices, as excessive local heating can occur around implanted lead tips. Despite extensive effort to assess radio frequency (RF) heating of implants during MRI at 1.5 T, a comparative study that systematically examines the effects of field strength and various exposure limits on RF heating is missing. This study aims to perform numerical simulations that systematically compare RF power deposition near DBS lead models during MRI at common clinical and ultra-high field strengths, namely 1.5, 3, 7, and 10.5 T. Furthermore, we assess the effects of different exposure constraints on RF power deposition by imposing limits on either the B1+ or global head specific absorption rate (SAR) as these two exposure limits commonly appear in MRI guidelines. We created 33 unique DBS lead models based on postoperative computed tomography (CT) images of patients with implanted DBS devices and performed electromagnetic simulations to evaluate the SAR of RF energy in the tissue surrounding lead tips during RF exposure at frequencies ranging from 64 MHz (1.5 T) to 447 MHz (10.5 T). The RF exposure was implemented via realistic MRI RF coil models created based on physical prototypes built in our institutions. We systematically examined the distribution of local SAR at different frequencies with the input coil power adjusted to either limit the B1+ or the global head SAR. The MRI RF coils at higher resonant frequencies generated lower SARs around the lead tips when the global head SAR was constrained. The trend was reversed when the constraint was imposed on B1+. At higher static fields, MRI is not necessarily more dangerous than at lower fields for patients with conductive leads. Specifically, when a conservative safety criterion, such as constraints on the global SAR, is imposed, coils at a higher resonant frequency tend to generate a lower local SAR around implanted leads due to the decreased B1+ and, by proxy, E field levels.

Mitigating Mismatch Compression in Differential Local Field Potentials.

Deep brain stimulation (DBS) devices capable of measuring differential local field potentials ( ∂ LFP) enable neural recordings alongside clinical therapy. Efforts to identify oscillatory correlates of various brain disorders, or disease readouts, are growing but must proceed carefully to ensure readouts are not distorted by brain environment. In this report we identified, characterized, and mitigated a major source of distortion in ∂ LFP that we introduce as mismatch compression (MC). Using in vivo, in silico, and in vitro models of MC, we showed that impedance mismatches in the two recording electrodes can yield incomplete rejection of stimulation artifact and subsequent gain compression that distorts oscillatory power. We then developed and validated an opensource mitigation pipeline that mitigates the distortions arising from MC. This work enables more reliable oscillatory readouts for adaptive DBS applications.

Electrophysiology-based Closed Loop Optogenetic Brain Stimulation Devices: Recent Developments and Future Prospects.

Closed loop optogenetic brain stimulation enhances the efficacy of the stimulation by adjusting the stimulation parameters based on direct feedback from the target area of the brain. It combines the principles of genetics, physiology, electrical engineering, optics, signal processing and control theory to create an efficient brain stimulation system. To read the underlying neuronal condition from the electrical activity of neurons, a sensor, sensor interface circuit, and signal conditioning are needed. Also, efficient feature extraction, classification, and control algorithms should be in place to interpret and use the sensed data for closing the feedback loop. Finally, a stimulation circuitry is required to effectively control a light source to deliver light based stimulation according to the feedback signal. Thus, the backbone to a functioning closed loop optogenetic stimulation device is a well-built electronic circuitry for sensing and processing of brain signals, running efficient signal processing and control algorithm, and delivering timed light stimulations. This paper presents a review of electronic and software concepts and components used in recent closed-loop optogenetic devices based on neuro-electrophysiological reading and an outlook on the future design possibilities with the aim of providing a compact and easy reference for developing closed loop optogenetic brain stimulation devices.