Medical Bionics - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 20
-
ItemNo Preview AvailableCan brain signals and anatomy refine contact choice for deep brain stimulation in Parkinson's disease?(BMJ PUBLISHING GROUP, 2022-05-18)INTRODUCTION: Selecting the ideal contact to apply subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease is time-consuming and reliant on clinical expertise. The aim of this cohort study was to assess whether neuronal signals (beta oscillations and evoked resonant neural activity (ERNA)), and the anatomical location of electrodes, can predict the contacts selected by long-term, expert-clinician programming of STN-DBS. METHODS: We evaluated 92 hemispheres of 47 patients with Parkinson's disease receiving chronic monopolar and bipolar STN-DBS. At each contact, beta oscillations and ERNA were recorded intraoperatively, and anatomical locations were assessed. How these factors, alone and in combination, predicted the contacts clinically selected for chronic deep brain stimulation at 6 months postoperatively was evaluated using a simple-ranking method and machine learning algorithms. RESULTS: The probability that each factor individually predicted the clinician-chosen contact was as follows: ERNA 80%, anatomy 67%, beta oscillations 50%. ERNA performed significantly better than anatomy and beta oscillations. Combining neuronal signal and anatomical data did not improve predictive performance. CONCLUSION: This work supports the development of probability-based algorithms using neuronal signals and anatomical data to assist programming of deep brain stimulation.
-
ItemNo Preview AvailableParoxysmal fast activity is a biomarker of treatment response in deep brain stimulation for Lennox-Gastaut syndrome(WILEY, 2022-10-05)OBJECTIVE: Epilepsy treatment trials typically rely on seizure diaries to determine seizure frequency, but these are time-consuming and difficult to maintain accurately. Fast, reliable, and objective biomarkers of treatment response are needed, particularly in Lennox-Gastaut syndrome (LGS), where high seizure frequency and comorbid cognitive and behavioral issues are additional obstacles to accurate diary-keeping. Here, we measured generalized paroxysmal fast activity (GPFA), a key interictal electrographic feature of LGS, and correlated GPFA burden with seizure diaries during a thalamic deep brain stimulation (DBS) treatment trial (Electrical Stimulation of the Thalamus in Epilepsy of Lennox-Gastaut Phenotype [ESTEL]). METHODS: GPFA and electrographic seizure counts from intermittent, 24-h electroencephalograms (EEGs) were compared to 3-month diary-recorded seizure counts in 17 young adults with LGS (mean age ± SD = 24.9 ± 6.6) in the ESTEL study, a randomized clinical trial of DBS lasting 12 months (comprising a 3-month baseline and 9 months of postimplantation follow-up). RESULTS: Baseline median seizures measured by diaries numbered 2.6 (interquartile range [IQR] = 1.4-5) per day, compared to 284 (IQR = 120.5-360) electrographic seizures per day, confirming that diaries capture only a small fraction of seizure burden. Across all patient EEGs, the average number of GPFA discharges per hour of sleep was 138 (IQR =72-258). GPFA duration and frequency, quantified over 2-h windows of sleep EEG, were significantly associated with diary-recorded seizure counts over 3-month intervals (p < .001, η2 p = .30-.48). For every GPFA discharge, there were 20-25 diary seizures witnessed over 3 months. There was high between-patient variability in the ratio between diary seizure burden and GPFA burden; however, within individual patients, the ratio was similar over time, such that the percentage change from pre-DBS baseline in seizure diaries strongly correlated with the percentage change in GPFA. SIGNIFICANCE: When seeking to optimize treatment in patients with LGS, monitoring changes in GPFA may allow rapid titration of treatment parameters, rather than waiting for feedback from seizure diaries.
-
ItemNo Preview AvailableCognition, adaptive skills and epilepsy disability/severity in patients with Lennox-Gastaut syndrome undergoing deep brain stimulation for epilepsy in the ESTEL trial(W B SAUNDERS CO LTD, 2022-08-03)PURPOSE: We previously reported seizure and EEG outcomes of the ESTEL study (Electrical Stimulation of Thalamus for Epilepsy of Lennox-Gastaut phenotype). To assess potential cognitive and behavioral changes during chronic, duty-cycle stimulation of bilateral thalamic centromedian nucleus, we compared standardized cognitive and behavioral measurements, as well as caregiver assessments of disability/severity, before implantation and after 3-months stimulation. METHODS: Twenty patients with LGS (17-37 years;13 females) were studied; one participant was not randomized due to DBS device removal, with outcomes of 19 remaining participants reported here. Cognitive and behavioral measurements were performed at baseline (i.e., before DBS implantation), at the end of the blinded stimulation phase, and at study exit. Instruments measured cognition (NIH toolbox cognitive battery, NIHTB-CB), adaptive skills (ABAS-3), epilepsy severity (GASE) and disability (GAD), quality of life (QOLIE-31), and depression (PHQ-9). Changes in scores after 3-months of stimulation relative to baseline were explored using Wilcoxon matched-pairs signed rank tests. RESULTS: After 3-months of stimulation, caregiver-reported epilepsy severity (GASE) and disability (GAD) improved (p<0.05). No other instrument showed a significant change from baseline. Measurements that required direct participant involvement, rather than caregivers, was completed by only a subset of higher-functioning individuals (NIHTB-CB, n = 13; QOLIE-31, n = 3; and PHQ-9, n = 6). In addition to cognitive impairments, behavioral and physical limitations were common obstacles to instrument completion. Standardized scores were hindered by 'floor effects'; however, raw scores better reflected clinical impressions of participants' functioning and were more sensitive to caregiver-reported changes following treatment. CONCLUSION: DBS treatment is associated with reduced epilepsy severity and disability in young adults with LGS. Performing cognitive and behavioral outcome measurement in patients with cognitive impairment is challenging but possible and requires careful selection of instruments and modifications of score interpretation to avoid floor effects.
-
ItemThe Optimal Target and Connectivity for Deep Brain Stimulation in Lennox-Gastaut Syndrome(WILEY, 2022-04-28)OBJECTIVE: Deep brain stimulation (DBS) can reduce seizures in Lennox-Gastaut syndrome (LGS). However, little is known about the optimal target and whether efficacy depends on connectivity of the stimulation site. Using outcome data from the ESTEL trial, we aimed to determine the optimal target and connectivity for DBS in LGS. METHODS: A total of 20 patients underwent bilateral DBS of the thalamic centromedian nucleus (CM). Outcome was percentage seizure reduction from baseline after 3 months of DBS, defined using three measures (monthly seizure diaries, 24-hour scalp electroencephalography [EEG], and a novel diary-EEG composite). Probabilistic stimulation mapping identified thalamic locations associated with higher/lower efficacy. Two substitute diffusion MRI datasets (a normative dataset from healthy subjects and a "disease-matched" dataset from a separate group of LGS patients) were used to calculate structural connectivity between DBS sites and a map of areas known to express epileptic activity in LGS, derived from our previous EEG-fMRI research. RESULTS: Results were similar across the three outcome measures. Stimulation was most efficacious in the anterior and inferolateral "parvocellular" CM border, extending into the ventral lateral nucleus (posterior subdivision). There was a positive association between diary-EEG composite seizure reduction and connectivity to areas of a priori EEG-fMRI activation, including premotor and prefrontal cortex, putamen, and pontine brainstem. In contrast, outcomes were not associated with baseline clinical variables. INTERPRETATION: Efficacious CM-DBS for LGS is linked to stimulation of the parvocellular CM and the adjacent ventral lateral nucleus, and is associated with connectivity to, and thus likely modulation of, the "secondary epileptic network" underlying the shared electroclinical manifestations of LGS. ANN NEUROL 2022;92:61-74.
-
ItemTowards guided and automated programming of subthalamic area stimulation in Parkinson's disease(OXFORD UNIV PRESS, 2022-01-04)Selecting the ideal contact to apply subthalamic nucleus deep brain stimulation in Parkinson's disease can be an arduous process, with outcomes highly dependent on clinician expertise. This study aims to assess whether neuronal signals recorded intraoperatively in awake patients, and the anatomical location of contacts, can assist programming. In a cohort of 14 patients with Parkinson's disease, implanted with subthalamic nucleus deep brain stimulation, the four contacts on each lead in the 28 hemispheres were ranked according to proximity to a nominated ideal anatomical location and power of the following neuronal signals: evoked resonant neural activity, beta oscillations and high-frequency oscillations. We assessed how these rankings predicted, on each lead: (i) the motor benefit from deep brain stimulation applied through each contact and (ii) the 'ideal' contact to apply deep brain stimulation. The ranking of contacts according to each factor predicted motor benefit from subthalamic nucleus deep brain stimulation, as follows: evoked resonant neural activity; r 2 = 0.50, Akaike information criterion 1039.9, beta; r 2 = 0.50, Akaike information criterion 1041.6, high-frequency oscillations; r 2 = 0.44, Akaike information criterion 1057.2 and anatomy; r 2 = 0.49, Akaike information criterion 1048.0. Combining evoked resonant neural activity, beta and high-frequency oscillations ranking data yielded the strongest predictive model (r 2 = 0.61, Akaike information criterion 1021.5). The 'ideal' contact (yielding maximal benefit) was ranked first according to each factor in the following proportion of hemispheres; evoked resonant neural activity 18/28, beta 17/28, anatomy 16/28, high-frequency oscillations 7/28. Across hemispheres, the maximal available deep brain stimulation benefit did not differ from that yielded by contacts chosen by clinicians for chronic therapy or contacts ranked first according to evoked resonant neural activity. Evoked resonant neural activity, beta oscillations and anatomy similarly predicted how motor benefit from subthalamic nucleus deep brain stimulation varied across contacts on each lead. This could assist programming by providing a probability ranking of contacts akin to a 'monopolar survey'. However, these factors identified the 'ideal' contact in only a proportion of hemispheres. More advanced signal processing and anatomical techniques may be needed for the full automation of contact selection.
-
ItemHow accurately are subthalamic nucleus electrodes implanted relative to the ideal stimulation location for Parkinson's disease?(PUBLIC LIBRARY SCIENCE, 2021-07-15)INTRODUCTION: The efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) depends on how closely electrodes are implanted relative to an individual's ideal stimulation location. Yet, previous studies have assessed how closely electrodes are implanted relative to the planned location, after homogenizing data to a reference. Thus here, we measured how accurately electrodes are implanted relative to an ideal, dorsal STN stimulation location, assessed on each individual's native imaging. This measure captures not only the technical error of stereotactic implantation but also constraints imposed by planning a suitable trajectory. METHODS: This cross-sectional study assessed 226 electrodes in 113 consecutive PD patients implanted with bilateral STN-DBS by experienced clinicians utilizing awake, microelectrode guided, surgery. The error (Euclidean distance) between the actual electrode trajectory versus a nominated ideal, dorsal STN stimulation location was determined in each hemisphere on native imaging and predictive factors sought. RESULTS: The median electrode location error was 1.62 mm (IQR = 1.23 mm). This error exceeded 3 mm in 28/226 electrodes (12.4%). Location error did not differ between hemispheres implanted first or second, suggesting brain shift was minimised. Location error did not differ between electrodes positioned with (48/226), or without, a preceding microelectrode trajectory shift (suggesting such shifts were beneficial). There was no relationship between location error and case order, arguing against a learning effect. DISCUSSION/CONCLUSION: The proximity of STN-DBS electrodes to a nominated ideal, dorsal STN, stimulation location is highly variable, even when implanted by experienced clinicians with brain shift minimized, and without evidence of a learning effect. Using this measure, we found that assessments on awake patients (microelectrode recordings and clinical examination) likely yielded beneficial intraoperative decisions to improve positioning. In many patients the error is likely to have reduced therapeutic efficacy. More accurate methods to implant STN-DBS electrodes relative to the ideal stimulation location are needed.
-
ItemAssociation between hemorrhagic transformation after endovascular therapy and poststroke seizures(WILEY, 2018-02-01)OBJECTIVE: Endovascular therapy has recently become standard therapy for select patients with acute ischemic stroke. Infarcted brain tissue may undergo hemorrhagic transformation (HT) after endovascular therapy. We investigated the association between HT and occurrence of poststroke seizures in patients treated with endovascular therapy. METHODS: Consecutive patients treated with endovascular therapy for acute anterior circulation ischemic stroke were included. HT was assessed with computed tomography/magnetic resonance imaging (CT/MRI) at 24 h after stroke onset. Patients were followed for up to 2 years for seizure occurrence. RESULTS: A total of 205 (57.1% male) patients were analyzed. Median age was 69 years (interquartile range [IQR] 57-78). Among patients with HT, 17.9% (10/56) developed poststroke seizures compared with 4.0% (6/149) among those without HT (hazard ratio [HR] 5.52; 95% confidence interval [CI] 2.00-15.22; P = .001). The association remained significant after adjustment for cortical involvement, baseline National Institutes of Health Stroke Scale score, age and use of intravenous tissue plasminogen activator and clot retrieval (HR 4.85; 95% CI 1.60-14.76; P = .005). In patients who developed seizures within the follow-up period, median time to first seizure was 111 days (IQR 28-369) in patients with HT and 36 days (IQR 0.5-183) in patients without HT. SIGNIFICANCE: A patient who develops HT following endovascular therapy for acute ischemic stroke had a nearly 5 times higher rate of developing poststroke seizures within 2 years. HT may be used as an imaging biomarker for poststroke seizures.
-
Item
-
ItemCortex leads the thalamic centromedian nucleus in generalized epileptic discharges in Lennox-Gastaut syndrome(WILEY, 2020-10)Objective We aimed to assess the roles of the cortex and thalamus (centromedian nucleus [CM]) during epileptic activity in Lennox‐Gastaut syndrome (LGS) patients undergoing deep brain stimulation (DBS) surgery as part of the ESTEL (Electrical Stimulation of the Thalamus for Epilepsy of Lennox‐Gastaut Phenotype) trial. Methods Twelve LGS patients (mean age = 26.8 years) underwent bilateral CM‐DBS implantation. Intraoperatively, simultaneous electroencephalogram (EEG) was recorded (range = 10‐34 minutes) from scalp electrodes and bilateral thalamic DBS electrodes. Temporal onsets of epileptic discharges (generalized paroxysmal fast activity [GPFA] and slow spike‐and‐wave [SSW]) were manually marked on recordings from scalp (ie, "cortex") and thalamus (ie, CM‐DBS electrodes). Phase transfer entropy (PTE) analysis quantified the degree of information transfer from cortex to thalamus within different frequency bands around GPFA events. Results GPFA was captured in eight of 12 patients (total event number across patients = 168, cumulative duration = 358 seconds). Eighty‐six percent of GPFA events were seen in both scalp and thalamic recordings. In most events (83%), onset occurred first at scalp, with thalamic onset lagging by a median of 98 milliseconds (interquartile range = 78.5 milliseconds). Results for SSW were more variable and seen in 11 of 12 patients; 25.4% of discharges were noted in both scalp and thalamus. Of these, 74.5% occurred first at scalp, with a median lag of 75 milliseconds (interquartile range = 228 milliseconds). One to 0.5 seconds and 0.5‐0 seconds before GPFA onset, PTE analysis showed significant energy transfer from scalp to thalamus in the delta (1‐3 Hz) frequency band. For alpha (8‐12 Hz) and beta (13‐30 Hz) frequencies, PTE was greatest 1‐0.5 seconds before GPFA onset. Significance Epileptic activity is detectable in CM of thalamus, confirming that this nucleus participates in the epileptic network of LGS. Temporal onset of GPFA mostly occurs earlier at the scalp than in the thalamus. This supports our prior EEG–functional magnetic resonance imaging results and provides further evidence for a cortically driven process underlying GPFA in LGS.
-
ItemProceedings of the Seventh Annual Deep Brain Stimulation Think Tank: Advances in Neurophysiology, Adaptive DBS, Virtual Reality, Neuroethics and Technology(FRONTIERS MEDIA SA, 2020-03-27)The Seventh Annual Deep Brain Stimulation (DBS) Think Tank held on September 8th of 2019 addressed the most current: (1) use and utility of complex neurophysiological signals for development of adaptive neurostimulation to improve clinical outcomes; (2) Advancements in recent neuromodulation techniques to treat neuropsychiatric disorders; (3) New developments in optogenetics and DBS; (4) The use of augmented Virtual reality (VR) and neuromodulation; (5) commercially available technologies; and (6) ethical issues arising in and from research and use of DBS. These advances serve as both "markers of progress" and challenges and opportunities for ongoing address, engagement, and deliberation as we move to improve the functional capabilities and translational value of DBS. It is in this light that these proceedings are presented to inform the field and initiate ongoing discourse. As consistent with the intent, and spirit of this, and prior DBS Think Tanks, the overarching goal is to continue to develop multidisciplinary collaborations to rapidly advance the field and ultimately improve patient outcomes.