Clinical benefit of transcutaneous afferent patterned stimulation (TAPS) in essential tremor patients with high unmet need: a secondary analysis of TAPS studies.

BACKGROUND: Transcutaneous afferent patterned stimulation (TAPS) is a noninvasive neuromodulation therapy that improves hand tremor in essential tremor (ET) patients. The benefits of TAPS in ET patients with high unmet need (severe tremor, non-responsive to medication, age ≥65 years) and early responders (substantial TAPS tremor improvement in the first month) remains unknown. RESEARCH DESIGN AND METHODS: Literature was surveyed for TAPS studies to assess the response in the high unmet need subgroup and early responders. Analyses were performed using previously collected Tremor Research Group Essential Tremor Rating Scale (TETRAS) scores, Bain & Findley activities of daily living (BF-ADL) scores, and tremor power. RESULTS: Significant differences in BF-ADL and TETRAS improvement were observed with TAPS over sham for the high unmet need subgroup in a randomized controlled study (P<0.03). During a 3-month open-label study, the high unmet need subgroup and early responders showed significant improvements in BF-ADL, TETRAS, and tremor power (P<0.001). Analysis of previous real-world evidence demonstrated that early responders maintained effectiveness and usage at 3 and 12 months (P<0.001). CONCLUSIONS: TAPS showed comparable improvements in ET with high unmet need as reported in the original studies, and greater efficacy in early responders. These findings inform patient selection and the trial process for identifying TAPS responders.

Transcutaneous Afferent Patterned Stimulation for Essential Tremor: Real-World Evidence with Long Term Follow-Up.

Background: Transcutaneous afferent patterned stimulation (TAPS) is a non-invasive neuromodulation therapy for the treatment of hand tremor in patients with essential tremor (ET). This retrospective post-market analysis evaluated the usage, effectiveness, and safety of TAPS in patients using TAPS beyond a 90-day trial period in a real-world setting. Methods: Study personnel screened a manufacturer's database for TAPS devices that had been prescribed for the treatment of ET and used beyond a 90-day trial period between August 2019 and January 2023. The device logs were collected to extract the therapy usage, accelerometry measurements, and on-board ratings of tremor improvement. Study personnel also evaluated results of a voluntary survey requested by the manufacturer after the 90-day trial period. Adverse events were assessed from patients' complaints reported to the manufacturer. Results: A total of 1,223 patients in the manufacturer's database met the study criteria. The patients had used therapy between 90 and 1,233 days, with average usage of 5.6 sessions per week. Accelerometry data indicated 89% of patients experienced tremor improvement, with an average 64% improvement. 63% of patients rated at least half of their sessions as improved. No significant habituation was observed in patients who used therapy for more than one year. Approximately 62% of survey respondents either had reduced medication or planned to consult physicians about their medication usage. No serious safety events were reported, and 10% of patients reported minor safety complaints. Discussion: The analysis demonstrates the real-world effectiveness and safety of TAPS beyond a 90-day trial period over a longer timeframe and in a larger population size than previously published evidence.

A framework for the design, implementation, and evaluation of output-based surveillance systems against zoonotic threats.

Output-based standards set a prescribed target to be achieved by a surveillance system, but they leave the selection of surveillance parameters, such as test type and population to be sampled, to the responsible party in the surveillance area. This allows proportionate legislative surveillance specifications to be imposed over a range of unique geographies. This flexibility makes output-based standards useful in the context of zoonotic threat surveillance, particularly where animal pathogens act as risk indicators for human health or where multiple surveillance streams cover human, animal, and food safety sectors. Yet, these systems are also heavily reliant on the appropriate choice of surveillance options to fit the disease context and the constraints of the organization implementing the surveillance system. Here we describe a framework to assist with designing, implementing, and evaluating output-based surveillance systems showing the effectiveness of a diverse range of activities through a case study example. Despite not all activities being relevant to practitioners in every context, this framework aims to provide a useful toolbox to encourage holistic and stakeholder-focused approaches to the establishment and maintenance of productive output-based surveillance systems.

Human Dorsal Root Ganglion Stimulation Reduces Sympathetic Outflow and Long-Term Blood Pressure.

This study hypothesized that dorsal root ganglion (DRG) stimulation would reduce sympathetic nerve activity and would alter hemodynamic variables. This study directly recorded muscle sympathetic nerve activity during ON and OFF stimulation of the DRG while measuring hemodynamic parameters. DRG stimulation significantly reduced the firing frequency of sympathetic nerves, as well as significantly reducing blood pressure, with greater reductions evident when stimulation was left-sided. Left-sided DRG stimulation lowers sympathetic nerve activity, leading to long-term phenotypic changes. This raises the potential of DRG stimulation being used to treat de novo autonomic disorders such as hypertension or heart failure.

Changes in Neuronal Activity in the Anterior Cingulate Cortex and Primary Somatosensory Cortex With Nonlinear Burst and Tonic Spinal Cord Stimulation.

INTRODUCTION: Although nonlinear burst and tonic SCS are believed to treat neuropathic pain via distinct pain pathways, the effectiveness of these modalities on brain activity in vivo has not been investigated. This study compared neuronal firing patterns in the brain after nonlinear burst and tonic SCS in a rat model of painful radiculopathy. METHODS: Neuronal activity was recorded in the ACC or S1 before and after nonlinear burst or tonic SCS on day 7 following painful cervical nerve root compression (NRC) or sham surgery. The amplitude of nonlinear burst SCS was set at 60% and 90% motor threshold to investigate the effect of lower amplitude SCS on brain activity. Neuronal activity was recorded during and immediately following light brush and noxious pinch of the paw. Change in neuron firing was measured as the percent change in spikes post-SCS relative to pre-SCS baseline. RESULTS: ACC activity decreases during brush after 60% nonlinear burst compared to tonic (p < 0.05) after NRC and compared to 90% nonlinear burst (p < 0.04) and pre-SCS baseline (p < 0.03) after sham. ACC neuron activity decreases (p < 0.01) during pinch after 60% and 90% nonlinear burst compared to tonic for NRC. The 60% of nonlinear burst decreases (p < 0.02) ACC firing during pinch in both groups compared to baseline. In NRC S1 neurons, tonic SCS decreases (p < 0.01) firing from baseline during light brush; 60% nonlinear burst decreases (p < 0.01) firing from baseline during brush and pinch. CONCLUSIONS: Nonlinear burst SCS reduces firing in the ACC from a painful stimulus; a lower amplitude nonlinear burst appears to have the greatest effect. Tonic and nonlinear burst SCS may have comparable effects in S1.

Increasing intensities of Anisakis simplex third-stage larvae (L3) in Atlantic salmon of coastal waters of Scotland.

BACKGROUND: Red Vent Syndrome (RVS), a haemorrhagic inflammation of the vent region in Atlantic salmon, is associated with high abundance of Anisakis simplex (s.s.) third-stage larvae (L3) in the vent region. Despite evidence suggesting that increasing A. simplex (s.s.) intensity is a causative factor in RVS aetiology, the definitive cause remains unclear. METHODS: A total of 117 Atlantic salmon were sampled from commercial fisheries on the East, West, and North coasts of Scotland and examined for ascaridoid parasites. Genetic identification of a subsample of Anisakis larvae was performed using the internal transcribed spacer (ITS) region of ribosomal DNA. To assess the extent of differentiation of feeding grounds and dietary composition, stable isotope analysis of carbon and nitrogen was carried out on Atlantic salmon muscle tissue. RESULTS: In the present study, the obtained ITS rDNA sequences matched A. simplex (s.s.) sequences deposited in GenBank at 99-100%. Not all isolated larvae (n = 30,406) were genetically identified. Therefore, the morphotype found in this study is referred to as A. simplex (sensu lato). Anisakis simplex (s.l.) was the most prevalent (100%) nematode with the highest mean intensity (259.9 ± 197.3), in comparison to Hysterothylacium aduncum (66.7%, 6.4 ± 10.2) and Pseudoterranova decipiens (s.l.) (14.5%, 1.4 ± 0.6). The mean intensity of A. simplex (s.l.) represents a four-fold increase compared to published data (63.6 ± 31.9) from salmon captured in Scotland in 2009. Significant positive correlations between A. simplex (s.l.) larvae intensities from the body and the vent suggest that they play a role in the emergence of RVS. The lack of a significant variation in stable isotope ratios of Atlantic salmon indicates that diet or feeding ground are not driving regional differences in A. simplex (s.l.) intensities. CONCLUSIONS: This paper presents the most recent survey for ascaridoid parasites of wild Atlantic salmon from three coastal regions in Scotland. A significant rise in A. simplex (s.l.) intensity could potentially increase both natural mortality rates of Atlantic salmon and possible risks for salmon consumers due to the known zoonotic role of A. simplex (s.s.) and A. pegreffii within the A. simplex (s.l.) species complex.

Therapy Habituation at 12 Months: Spinal Cord Stimulation Versus Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome Type I and II.

The ACCURATE randomized, controlled trial compared outcomes of dorsal root ganglion (DRG) stimulation versus tonic spinal cord stimulation (SCS) in 152 subjects with chronic lower extremity pain due to complex regional pain syndrome (CRPS) type I or II. This ACCURATE substudy was designed to evaluate whether therapy habituation occurs with DRG stimulation as compared to SCS through 12-months. A modified intention-to-treat analysis was performed to assess percentage pain relief (PPR) and responder rates at follow-up visits (end-of-trial, 1, 3, 6, 9, 12-months postpermanent implant) for all subjects that completed trial stimulation (DRG:N = 73, SCS:N = 72). For both groups, mean PPR was significantly greater at end-of-trial (DRG = 82.2%, SCS =0 77.0%) than all other follow-ups. Following permanent DRG system implantation, none of the time points were significantly different from one another in PPR (range = 69.3-73.9%). For the SCS group, PPR at 9-months (58.3%) and 12-months (57.9%) was significantly less than at 1-month (66.9%). The responder rate also decreased for the SCS group from 1-month (68.1%) to 12-months (61.1%). After stratifying by diagnosis, it was found that only the CRPS-I population had diminishing pain relief with SCS. DRG stimulation resulted in more stable pain relief through 12-months, while tonic SCS demonstrated therapy habituation at 9- and 12-months. Trial Registration: The ACCURATE study was registered at ClinicalTrials.gov with Identifier NCT01923285. PERSPECTIVE: This article reports on an ACCURATE substudy, which found that long-term therapy habituation occurred at 12-months with SCS, but not DRG stimulation, in patients with CRPS. The underlying mechanisms of action for these results remain unclear, although several lines of inquiry are proposed.

Paresthesia-Free Dorsal Root Ganglion Stimulation: An ACCURATE Study Sub-Analysis.

INTRODUCTION: ACCURATE, a randomized controlled trial comparing dorsal root ganglion (DRG) stimulation to spinal cord stimulation, showed that DRG stimulation is a safe and effective therapy in individuals with lower extremity chronic pain due to complex regional pain syndrome (CRPS) type I or II. Investigators noted that DRG stimulation programming could be adjusted to minimize, or eliminate, the feeling of paresthesia while maintaining adequate pain relief. The present study explores treatment outcomes for DRG subjects who were paresthesia-free vs. those who experienced the sensation of paresthesia, as well as the factors that predicted paresthesia-free analgesia. METHODS: A retrospective analysis of therapy outcomes was conducted for 61 subjects in the ACCURATE study who received a permanent DRG neurostimulator. Outcomes of subjects who were paresthesia-free were compared to those who experienced paresthesia-present therapy at 1, 3, 6, 9, and 12-month follow-ups. Predictor variables for the presence or absence of paresthesias with DRG stimulation were also explored. RESULTS: The percentage of subjects with paresthesia-free pain relief increased from 16.4% at 1-month to 38.3% at 12-months. Paresthesia-free subjects generally had similar or better outcomes for pain severity, pain interference, quality of life, and mood state as subjects with paresthesia-present stimulation. Factors that increased the odds of a subject feeling paresthesia were higher stimulation amplitudes and frequencies, number of implanted leads, and younger age. CONCLUSIONS: Some DRG subjects achieved effective paresthesia-free analgesia in the ACCURATE trial. This supports the observation that paresthesia is not synonymous with pain relief or required for optimal analgesia with DRG stimulation.

Burst & High-Frequency Spinal Cord Stimulation Differentially Effect Spinal Neuronal Activity After Radiculopathy.

Although burst and high-frequency (HF) spinal cord stimulation (SCS) relieve neuropathic pain, their effects on neuronal hyperexcitability have not been compared. Specifically, it is unknown how the recharge components of burst SCS-either actively balanced or allowed to passively return-and/or different frequencies of HF SCS compare in altering neuronal activity. Neuronal firing rates were measured in the spinal dorsal horn on day 7 after painful cervical nerve root compression in the rat. Motor thresholds (MTs) and evoked neuronal recordings were collected during noxious stimuli before (baseline) and after delivery of SCS using different SCS modes: 10 kHz HF, 1.2 kHz HF, burst with active recharge, or burst with passive recharge. Spontaneous firing rates were also evaluated at baseline and after SCS. The average MT for 10 kHz SCS was significantly higher (p < 0.033) than any other mode. Burst with passive recharge was the only SCS mode to significantly reduce evoked (p = 0.019) and spontaneous (p = 0.0076) firing rates after noxious pinch. This study demonstrates that HF and burst SCS have different MTs and effects on both evoked and spontaneous firing rates, indicating they have different mechanisms of providing pain relief. Since burst with passive recharge was the only waveform to reduce firing, that waveform may be important in the neurophysiological response to stimulation.

Comparing Current Steering Technologies for Directional Deep Brain Stimulation Using a Computational Model That Incorporates Heterogeneous Tissue Properties.

OBJECTIVE: A computational model that accounts for heterogeneous tissue properties was used to compare multiple independent current control (MICC), multi-stim set (MSS), and concurrent activation (co-activation) current steering technologies utilized in deep brain stimulation (DBS) on volume of tissue activated (VTA) and power consumption. METHODS: A computational model was implemented in Sim4Life v4.0 with the multimodal image-based detailed anatomical (MIDA) model, which accounts for heterogeneous tissue properties. A segmented DBS lead placed in the subthalamic nucleus (STN). Three milliamperes of current (with a 90 µs pseudo-biphasic waveform) was distributed between two electrodes with various current splits. The laterality, directional accuracy, volume, and shape of the VTAs using MICC, MSS and co-activation, and their power consumption were computed and compared. RESULTS: MICC, MSS, and coactivation resulted in less laterality of steering than single-segment activation. Both MICC and MSS show directional inaccuracy (more pronounced with MSS) during radial current steering. Co-activation showed greater directional accuracy than MICC and MSS at centerline between the two activated electrodes. MSS VTA volume was smaller and more compact with less current spread outside the active electrode plane than MICC VTA. There was no consistent pattern of power drain between MSS and MICC, but electrode co-activation always used less power than either fractionating paradigm. CONCLUSION: While current fractionalization technologies can achieve current steering between two segmented electrodes, this study shows that there are important limitations in accuracy and focus of tissue activation when tissue heterogeneity is accounted for.

A Review of Spinal and Peripheral Neuromodulation and Neuroinflammation: Lessons Learned Thus Far and Future Prospects of Biotype Development.

BACKGROUND: There is increasing literature evidence both clinically and experimentally on the existence of potent, adaptive interactions between the central and peripheral aspects of the neuroimmune system in the genesis and maintenance of chronic neuropathic extremity pain and nociceptive back pain. The neuroinflammatory pathways are modulated by the interaction of pro- and anti-inflammatory cytokines and chemokines, which are released by peripheral immune system-derived cell species (macrophages and leukocytes). This review examines the possible impact of spinal and peripheral neurostimulation on the inflammatory response in the context of acute and chronic pain pathologies of different origin. STUDY DESIGN: A narrative review of preclinical and clinical studies addressed to the spinal cord and peripheral nerve stimulation and neuroinflammation. METHODS: Available literature was reviewed on neurostimulation technologies and both acute and chronic low-grade inflammation to identify primary outcome measures and to provide an overview of postulated mechanisms of action of neurostimulation on host inflammatory responses. Data sources included relevant literature identified through searches of PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles. RESULTS: A comprehensive review of the literature indicates an alternate or synergistic mechanism of action of neurostimulation, beyond modulating somatosensory pain pathways, in modifying inflammatory response associated with chronic pain, by promoting a systemic anti-inflammatory state with upregulation of anti-inflammatory mediators. CONCLUSIONS: These preliminary findings may have important implications on the potential applications of neurostimulation as an anti-inflammatory therapy and the role of molecular profiling as a preimplant screening modality and post-implant outcome validation. Thus, future targeted clinical and experimental research is highly warranted in this particular novel field of neuromodulation.

Burst Spinal Cord Stimulation: Review of Preclinical Studies and Comments on Clinical Outcomes.

BACKGROUND: Burst spinal cord stimulation (SCS) technology uses a novel waveform that consists of closely packed high-frequency electrical impulses followed by a quiescent period. Within the growing field of neuromodulation, burst stimulation is unique in that it mimics the natural burst firing of the nervous system, in particular the thalamo-cingulate rhythmicity, resulting in modulation of the affective and attentional components of pain processing (e.g., medial thalamic pathways). STUDY DESIGN: A review of preclinical and clinical studies regarding burst SCS for various chronic pain states. METHODS: Available literature was reviewed on burst stimulation technology. Data sources included relevant literature identified through searches of PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles. OUTCOME MEASURES: The primary outcome measure was to understand the mechanisms of action with regards to burst stimulation and to review clinical data on the indications of burst SCS for various chronic pain states. RESULTS: We present both mechanisms of action and review uses of burst stimulation for various pain states. CONCLUSIONS: Burst stimulation offers a novel pain reduction tool with the absence of uncomfortable paresthesia for failed back surgery syndrome, diabetic neuropathic pain, and anesthesia dolorosa. Preclinical models have emphasized that the potential mechanisms for burst therapy could be related to neural coding algorithms that mimic the natural nervous system firing patterns, resulting in effects on both the medial and lateral pain pathways. Other mechanisms include frequency dependent opioid release, modulation of the pain gate, and activation of electrical and chemical synapses.

Mechanisms of Dorsal Root Ganglion Stimulation in Pain Suppression: A Computational Modeling Analysis.

OBJECTIVE: The mechanisms of dorsal root ganglion (DRG) stimulation for chronic pain remain unclear. The objective of this work was to explore the neurophysiological effects of DRG stimulation using computational modeling. METHODS: Electrical fields produced during DRG stimulation were calculated with finite element models, and were coupled to a validated biophysical model of a C-type primary sensory neuron. Intrinsic neuronal activity was introduced as a 4 Hz afferent signal or somatic ectopic firing. The transmembrane potential was measured along the neuron to determine the effect of stimulation on intrinsic activity across stimulation parameters, cell location/orientation, and membrane properties. RESULTS: The model was validated by showing close correspondence in action potential (AP) characteristics and firing patterns when compared to experimental measurements. Subsequently, the model output demonstrated that T-junction filtering was amplified with DRG stimulation, thereby blocking afferent signaling, with cathodic stimulation at amplitudes of 2.8-5.5 × stimulation threshold and frequencies above 2 Hz. This amplified filtering was dependent on the presence of calcium and calcium-dependent small-conductance potassium channels, which produced a hyperpolarization offset in the soma, stem, and T-junction with repeated somatic APs during stimulation. Additionally, DRG stimulation suppressed somatic ectopic activity by hyperpolarizing the soma with cathodic or anodic stimulation at amplitudes of 3-11 × threshold and frequencies above 2 Hz. These effects were dependent on the stem axon being relatively close to and oriented toward a stimulating contact. CONCLUSIONS: These results align with the working hypotheses on the mechanisms of DRG stimulation, and indicate the importance of stimulation amplitude, polarity, and cell location/orientation on neuronal responses.

Impact of ventricular tachycardia ablation on health care utilization.

BACKGROUND: Catheter ablation of ventricular tachycardia (VT) has been shown to reduce the number of recurrent shocks in patients with an implantable cardioverter-defibrillator (ICD). However, how VT ablation affects postprocedural medical and pharmaceutical usage remains unclear. OBJECTIVE: The purpose of this study was to investigate changes in health care resource utilization (HCRU) after VT ablation. METHODS: This large-scale, real-world, retrospective study used the MarketScan databases to identify patients in the United States with an ICD or cardiac resynchronization therapy-defibrillator (CRT-D) undergoing VT ablation. We calculated cumulative medical and pharmaceutical expenditures, office visits, hospitalizations, and emergency room (ER) visits in the 1-year periods before and after ablation. RESULTS: A total of 523 patients met the study inclusion criteria. After VT ablation, median annual cardiac rhythm-related medical expenditures decreased by $5,408. Moreover, the percentage of patients with at least 1 cardiac rhythm-related hospitalization and ER visit decreased from 53% and 41% before ablation to 28% and 26% after ablation, respectively. Similar changes were observed in the number of all-cause hospitalizations and ER visits, but there were no significant changes in all-cause medical expenditures. During the year before VT ablation, there was an increasing rate of health care resource utilization, followed by drastic slowing after ablation. CONCLUSION: This retrospective study demonstrated that catheter ablation seems to reduce hospitalization and overall health care utilization in VT patients with an ICD or CRT-D in place.

Longer Delay From Chronic Pain to Spinal Cord Stimulation Results in Higher Healthcare Resource Utilization.

INTRODUCTION: A shorter delay time from chronic pain diagnosis to spinal cord stimulation (SCS) implantation may make it more likely to achieve lasting therapeutic efficacy with SCS. The objective of this analysis was to determine the impact of pain-to-SCS time on patients' post-implant healthcare resource utilization (HCRU). METHODS: A retrospective observational study was performed using a real-world patient cohort derived from MarketScan(®) Commercial and Medicare Supplemental claims data bases from April 2008 through March 2013. The predictor variable was the time from the first diagnosis of chronic pain to permanent SCS implant. Using multivariable analysis, we studied the impact of pain-to-SCS time on HCRU in the first year post-implant. For some regression tests, patients were grouped into terciles by HCRU. RESULTS: A total of 762 patients met inclusion criteria, with a median pain-to-SCS time of 1.35 years (Q1: 0.8, Q3: 1.9). For every one-year increase in pain-to-SCS time, the odds increased by 33% for being in the high medical expenditures group (defined using the upper tercile: $4133 over above) over the low group (first lower: $603 or less). The odds increased by 39% for being in the high opioid prescriptions group (10-58 prescriptions) over the low group (0-1). The odds increased by 44% and 55%, respectively, for being in the high office visits (8-77) or hospitalizations (3-28) group over the low office visits (0-2) or hospitalizations (0) group. CONCLUSIONS: HCRU increased in the year following SCS implantation with longer pain-to-SCS time. These results suggest that considering SCS earlier in the care continuum for chronic pain may improve patient outcomes, with reductions in hospitalizations, clinic visits, and opioid usage.

Modeling the impact of spinal cord stimulation paddle lead position on impedance, stimulation threshold, and activation region.

The effectiveness of spinal cord stimulation (SCS) for chronic pain treatment depends on selection of appropriate stimulation settings, which can be especially challenging following posture change or SCS lead migration. The objective of this work was to investigate the feasibility of using SCS lead impedance for determining the location of a SCS lead and for detecting lead migration, as well as the impact of axial movement and rotation of the St. Jude Medical PENTA™ paddle in the dorsal-ventral or medial-lateral directions on dorsal column (DC) stimulation thresholds and neural activation regions. We used a two-stage computational model, including a finite element method model of field potentials in the spinal cord during stimulation, coupled to a biophysical cable model of mammalian, myelinated nerve fibers to calculate tissue impedance and nerve fiber activation within the DC. We found that SCS lead impedance was highly sensitive to the distance between the lead and cerebrospinal fluid (CSF) layer. In addition, among all the lead positions studied, medial-lateral movement resulted in the most substantial changes to SC activation regions. These results suggest that impedance can be used for detecting paddle position and lead migration, and therefore for guiding SCS programming.

Measurement of evoked potentials during thalamic deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) treats the symptoms of several movement disorders, but optimal selection of stimulation parameters remains a challenge. The evoked compound action potential (ECAP) reflects synchronized neural activation near the DBS lead, and may be useful for feedback control and automatic adjustment of stimulation parameters in closed-loop DBS systems. OBJECTIVES: Determine the feasibility of recording ECAPs in the clinical setting, understand the neural origin of the ECAP and sources of any stimulus artifact, and correlate ECAP characteristics with motor symptoms. METHODS: The ECAP and tremor response were measured simultaneously during intraoperative studies of thalamic DBS, conducted in patients who were either undergoing surgery for initial lead implantation or replacement of their internal pulse generator. RESULTS: There was large subject-to-subject variation in stimulus artifact amplitude, which model-based analysis suggested may have been caused by glial encapsulation of the lead, resulting in imbalances in the tissue impedance between the contacts. ECAP recordings obtained from both acute and chronically implanted electrodes revealed that specific phase characteristics of the signal varied systematically with stimulation parameters. Further, a trend was observed in some patients between the energy of the initial negative and positive ECAP phases, as well as secondary phases, and changes in tremor from baseline. A computational model of thalamic DBS indicated that direct cerebellothalamic fiber activation dominated the clinically measured ECAP, suggesting that excitation of these fibers is critical in DBS therapy. CONCLUSIONS: This work demonstrated that ECAPs can be recorded in the clinical setting and may provide a surrogate feedback control signal for automatic adjustment of stimulation parameters to reduce tremor amplitude.

Proceedings of the Second Annual Deep Brain Stimulation Think Tank: What's in the Pipeline.

The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.

Analysis of deep brain stimulation electrode characteristics for neural recording.

OBJECTIVE: Closed-loop deep brain stimulation (DBS) systems have the potential to optimize treatment of movement disorders by enabling automatic adjustment of stimulation parameters based on a feedback signal. Evoked compound action potentials (ECAPs) and local field potentials (LFPs) recorded from the DBS electrode may serve as suitable closed-loop control signals. The objective of this study was to understand better the factors that influence ECAP and LFP recording, including the physical presence of the electrode, the geometrical dimensions of the electrode, and changes in the composition of the peri-electrode space across recording conditions. APPROACH: Coupled volume conductor-neuron models were used to calculate single-unit activity as well as ECAP responses and LFP activity from a population of model thalamic neurons. MAIN RESULTS: Comparing ECAPs and LFPs measured with and without the presence of the highly conductive recording contacts, we found that the presence of these contacts had a negligible effect on the magnitude of single-unit recordings, ECAPs (7% RMS difference between waveforms), and LFPs (5% change in signal magnitude). Spatial averaging across the contact surface decreased the ECAP magnitude in a phase-dependent manner (74% RMS difference), resulting from a differential effect of the contact on the contribution from nearby or distant elements, and decreased the LFP magnitude (25% change). Reductions in the electrode diameter or recording contact length increased signal energy and increased spatial sensitivity of single neuron recordings. Moreover, smaller diameter electrodes (500 µm) were more selective for recording from local cells over passing axons, with the opposite true for larger diameters (1500 µm). Changes in electrode dimensions had phase-dependent effects on ECAP characteristics, and generally had small effects on the LFP magnitude. ECAP signal energy and LFP magnitude decreased with tighter contact spacing (100 µm), compared to the original dimensions (1500 µm), with the opposite effect on the ECAP at longer contact-to-contact distances (2000 µm). Finally, acute edema reduced the single neuron and population ECAP signal energy, as well as LFP magnitude, and glial encapsulation had the opposite effect, after accounting for loss of cells in the peri-electrode space. SIGNIFICANCE: This study determined recording conditions and electrode designs that influence ECAP and LFP recording fidelity.