Browsing by Author "Bulluss, Kristian"

Now showing 1 - 6 of 6
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    Anatomical targeting for electrode localization in subthalamic nucleus deep brain stimulation: A comparative study.
    (Journal of NeuroImaging, 2023-06-08) Tonroe, Thomas; McDermott, Hugh; Pearce, Patrick; Acevedo, Nicola; Thevathasan, Wesley; Xu, San San; Bulluss, Kristian; Perera, Thushara
    In deep brain stimulation (DBS), accurate electrode placement is essential for optimizing patient outcomes. Localizing electrodes enables insight into therapeutic outcomes and development of metrics for use in clinical trials. Methods of defining anatomical targets have been described with varying accuracy and objectivity. To assess variability in anatomical targeting, we compare four methods of defining an appropriate target for DBS of the subthalamic nucleus for Parkinson's disease.
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    Deep brain stimulation for Parkinson's disease modulates high-frequency evoked and spontaneous neural activity
    (Elsevier, Inc., 2019-07) Sinclair, Nicholas; McDermott, Hugh; Fallon, James; Perera, Thushara; Brown, Peter; Bulluss, Kristian; Thevathasan, Wesley
    Deep brain stimulation is an established therapy for Parkinson's disease; however, its effectiveness is hindered by limited understanding of therapeutic mechanisms and the lack of a robust feedback signal for tailoring stimulation. We recently reported that subthalamic nucleus deep brain stimulation evokes a neural response resembling a decaying high-frequency (200-500Hz) oscillation that typically has a duration of at least 10ms and is localizable to the dorsal sub-region. As the morphology of this response suggests a propensity for the underlying neural circuitry to oscillate at a particular frequency, we have named it evoked resonant neural activity. Here, we determine whether this evoked activity is modulated by therapeutic stimulation - a critical attribute of a feedback signal. Furthermore, we investigated whether any related changes occurred in spontaneous local field potentials. Evoked and spontaneous neural activity was intraoperatively recorded from 19 subthalamic nuclei in patients with Parkinson's disease. Recordings were obtained before therapeutic stimulation and during 130Hz stimulation at increasing amplitudes (0.67-3.38mA), 'washout' of therapeutic effects, and non-therapeutic 20Hz stimulation. Therapeutic efficacy was assessed using clinical bradykinesia and rigidity scores. The frequency and amplitude of evoked resonant neural activity varied with the level of 130Hz stimulation (p<.001). This modulation coincided with improvement in bradykinesia and rigidity (p<.001), and correlated with spontaneous beta band suppression (p<.001). Evoked neural activity occupied a similar frequency band to spontaneous high-frequency oscillations (200-400Hz), both of which decreased to around twice the 130Hz stimulation rate. Non-therapeutic stimulation at 20Hz evoked, but did not modulate, resonant activity. These results indicate that therapeutic deep brain stimulation alters the frequency of evoked and spontaneous oscillations recorded in the subthalamic nucleus that are likely generated by loops within the cortico-basal ganglia-thalamo-cortical network. Evoked resonant neural activity therefore has potential as a tool for providing insight into brain network function and has key attributes of a dynamic feedback signal for optimizing therapy.
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    On the neural basis of deep brain stimulation evoked resonant activity
    (IOP Publishing, 2019-08) Sinclair, Nicholas; Fallon, James; Bulluss, Kristian; Thevathasan, Wesley; McDermott, Hugh
    Objective: Deep brain stimulation can be a remarkably effective treatment for Parkinson’s disease and other conditions; however, an electrophysiological feedback signal is needed to improve surgical accuracy and for optimising therapy according to patient needs. Evoked responses may provide such a signal, although it is crucial to determine that recorded potentials are of neural origin and not a consequence of stimulation artefacts. Here, we use several in vitro and in vivo methods to establish the neural basis of resonant deep brain stimulation evoked activity. Approach: Recordings were obtained from deep brain stimulation electrodes in saline, in feline brain regions not expected to produce resonant neural responses, and in fourteen subthalamic nuclei in people with Parkinson’s disease following stimulation with 60 μs per phase biphasic current pulses with different polarities. Main results: Electrodes in saline did not exhibit stimulation artefacts beyond 1 ms. Changing the pulse polarity reversed the stimulation artefact. Electrodes in feline brain elicited early latency activity (<5ms); however, the activity did not resemble a decaying oscillation. Electrodes in human subthalamic nuclei evoked resonant neural activity that was not reversed by changing the pulse polarity. The latency of resonant peaks from stimuli with opposing polarities differed by about the expected amount and were strongly correlated (ρ = 0.998, p < 0.001). Resonant peak amplitudes were also strongly correlated (ρ = 0.945, p < 0.001). Significance: The absence of resonant activity in recordings from electrodes in saline and feline brain, in addition to findings that resonant activity occurs in the subthalamic nucleus but not neighbouring white matter regions, demonstrates that such activity is not an artefact of the stimulation and recording system. Furthermore, non-reversal of resonant activity with changing pulse polarity in human subthalamic nuclei indicates that it is independent from stimulation artefact. Thus, these methods provide strong evidence of the neural basis of deep brain stimulation evoked resonant activity.
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    Subthalamic Nucleus Deep Brain Stimulation Evokes Resonant Neural Activity
    (Wiley Periodicals, Inc., 2018-05) Sinclair, Nicholas; McDermott, Hugh; Bulluss, Kristian; Fallon, James; Perera, Thushara; Xu, San San; Brown, Peter; Thevathasan, Wesley
    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.
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    Tailoring Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease Using Evoked Resonant Neural Activity
    (Frontiers in Human Neuroscience, 2020-02) Thevathasan, Wesley; Sinclair, Nicholas; Bulluss, Kristian; McDermott, Hugh
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    Targeting the centromedian thalamic nucleus for deep brain stimulation
    (BMJ Publishing Group Ltd, 2020-01) Warren, Aaron; Dalic, Linda; Thevathasan, Wesley; Roten, Annie; Bulluss, Kristian; Archer, John
    OBJECTIVES: Deep brain stimulation (DBS) of the centromedian thalamic nucleus (CM) is an emerging treatment for multiple brain diseases, including the drug-resistant epilepsy Lennox-Gastaut syndrome (LGS). We aimed to improve neurosurgical targeting of the CM by: (1) developing a structural MRI approach for CM visualisation, (2) identifying the CM's neurophysiological characteristics using microelectrode recordings (MERs) and (3) mapping connectivity from CM-DBS sites using functional MRI (fMRI). METHODS: 19 patients with LGS (mean age=28 years) underwent presurgical 3T MRI using magnetisation-prepared 2 rapid acquisition gradient-echoes (MP2RAGE) and fMRI sequences; 16 patients proceeded to bilateral CM-DBS implantation and intraoperative thalamic MERs. CM visualisation was achieved by highlighting intrathalamic borders on MP2RAGE using Sobel edge detection. Mixed-effects analysis compared two MER features (spike firing rate and background noise) between ventrolateral, CM and parafasicular nuclei. Resting-state fMRI connectivity was assessed using implanted CM-DBS electrode positions as regions of interest. RESULTS: The CM appeared as a hyperintense region bordering the comparatively hypointense pulvinar, mediodorsal and parafasicular nuclei. At the group level, reduced spike firing and background noise distinguished CM from the ventrolateral nucleus; however, these trends were not found in 20%-25% of individual MER trajectories. Areas of fMRI connectivity included basal ganglia, brainstem, cerebellum, sensorimotor/premotor and limbic cortex. CONCLUSIONS: In the largest clinical trial of DBS undertaken in patients with LGS to date, we show that accurate targeting of the CM is achievable using 3T MP2RAGE MRI. Intraoperative MERs may provide additional localising features in some cases; however, their utility is limited by interpatient variability. Therapeutic effects of CM-DBS may be mediated via connectivity with brain networks that support diverse arousal, cognitive and sensorimotor processes.