Medical Bionics - Research Publications

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    How accurately are subthalamic nucleus electrodes implanted relative to the ideal stimulation location for Parkinson's disease?
    Pearce, P ; Bulluss, K ; Xu, SS ; Kim, B ; Milicevic, M ; Perera, T ; Thevathasan, W ; Toft, M (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.
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    Cortex leads the thalamic centromedian nucleus in generalized epileptic discharges in Lennox-Gastaut syndrome
    Dalic, LJ ; Warren, AEL ; Young, JC ; Thevathasan, W ; Roten, A ; Bulluss, KJ ; Archer, JS (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.
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    Subthalamic nucleus deep brain stimulation evokes resonant neural activity
    Sinclair, NC ; McDermott, HJ ; Bulluss, KJ ; Fallon, JB ; Perera, T ; Xu, SS ; Brown, P ; Thevathasan, W (WILEY, 2018-05-01)
    Deep brain stimulation (DBS) is a rapidly expanding treatment for neurological and psychiatric conditions; however, a target-specific biomarker is required to optimize therapy. Here, we show that DBS evokes a large-amplitude resonant neural response focally in the subthalamic nucleus. This response is greatest in the dorsal region (the clinically optimal stimulation target for Parkinson disease), coincides with improved clinical performance, is chronically recordable, and is present under general anesthesia. These features make it a readily utilizable electrophysiological signal that could potentially be used for guiding electrode implantation surgery and tailoring DBS therapy to improve patient outcomes. Ann Neurol 2018;83:1027-1031.
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    Tailoring Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease Using Evoked Resonant Neural Activity
    Thevathasan, W ; Sinclair, NC ; Bulluss, KJ ; McDermott, HJ (FRONTIERS MEDIA SA, 2020-02-28)