Medical Bionics - Research Publications

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    Towards guided and automated programming of subthalamic area stimulation in Parkinson's disease
    Xu, SS ; Sinclair, NC ; Bulluss, KJ ; Perera, T ; Lee, W-L ; McDermott, HJ ; Thevathasan, W (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.
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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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    Proceedings of the Seventh Annual Deep Brain Stimulation Think Tank: Advances in Neurophysiology, Adaptive DBS, Virtual Reality, Neuroethics and Technology
    Ramirez-Zamora, A ; Giordano, J ; Gunduz, A ; Alcantara, J ; Cagle, JN ; Cernera, S ; Difuntorum, P ; Eisinger, RS ; Gomez, J ; Long, S ; Parks, B ; Wong, JK ; Chiu, S ; Patel, B ; Grill, WM ; Walker, HC ; Little, SJ ; Gilron, R ; Tinkhauser, G ; Thevathasan, W ; Sinclair, NC ; Lozano, AM ; Foltynie, T ; Fasano, A ; Sheth, SA ; Scangos, K ; Sanger, TD ; Miller, J ; Brumback, AC ; Rajasethupathy, P ; McIntyre, C ; Schlachter, L ; Suthana, N ; Kubu, C ; Sankary, LR ; Herrera-Ferra, K ; Goetz, S ; Cheeran, B ; Steinke, GK ; Hess, C ; Almeida, L ; Deeb, W ; Foote, KD ; Okun, MS (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.
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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)