Browsing by Author "Moffat, Bradford"

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    Functional neuroplasticity in response to cerebello-thalamic injury underpins the clinical presentation of tremor in multiple sclerosis
    (SAGE Publishing, 2019-03) Boonstra, Frederique; Noffs, Gustavo; Perera, Thushara; Jokubaitis, Vilija; Vogel, Adam; Moffat, Bradford; Butzkueven, Helmut; Evans, Andrew; van der Walt, Anneke; Kolbe, Scott
    BACKGROUND:: Tremor is present in almost half of multiple sclerosis (MS) patients. The lack of understanding of its pathophysiology is hampering progress in development of treatments. OBJECTIVES:: To clarify the structural and functional brain changes associated with the clinical phenotype of upper limb tremor in people with MS. METHODS:: Fifteen healthy controls (46.1 +/- 15.4 years), 27 MS participants without tremor (46.7 +/- 11.6 years) and 42 with tremor (46.6 +/- 11.5 years) were included. Tremor was quantified using the Bain score (0-10) for overall severity, handwriting and Archimedes spiral drawing. Functional magnetic resonance imaging activations were compared between participants groups during performance of a joystick task designed to isolate tremulous movement. Inflammation and atrophy of cerebello-thalamo-cortical brain structures were quantified. RESULTS:: Tremor participants were found to have atrophy of the cerebellum and thalamus, and higher ipsilateral cerebellar lesion load compared to participants without tremor ( p < 0.020). We found higher ipsilateral activation in the inferior parietal lobule, the premotor cortex and supplementary motor area in MS tremor participants compared to MS participants without tremor during the joystick task. Finally, stronger activation in those areas was associated with lower tremor severity. CONCLUSION:: Subcortical neurodegeneration and inflammation along the cerebello-thalamo-cortical and cortical functional neuroplasticity contribute to the severity of tremor in MS.
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    Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity
    (Nature Publishing Group, 2016-02-08) Oxley, Thomas; Opie, Nicholas; John, Sam; Rindl, Gil; Ronayne, Stephen; Wheeler, Tracey; Judy, Jack; McDonald, Alan; Dornom, Anthony; Lovell, Timothy; Steward, Christopher; Garrett, David; Moffat, Bradford; Lui, Elaine; Yassi, Nawaf; Campbell, Bruce; Wong, Yan; Fox, Kate; Nurse, Ewan; Bennett, Iwan; Bauquier, Sebastien; Lyanage, Kishan; van de Nagel, Nicole; Perucca, Piero; Ahnood, Arman; Gill, Katherine; Yan, Bernard; Churilov, Leonid; French, Christopher; Desmond, Patricia; Horne, Malcolm; Kiers, Lynette; Prawer, Steven; Davis, Stephen; Burkitt, Anthony; Mitchell, Peter; Grayden, David; May, Clive; O'Brien, Terence
    High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode). We achieved implantation into a superficial cortical vein overlying the motor cortex via catheter angiography and demonstrate neural recordings in freely moving sheep for up to 190 d. Spectral content and bandwidth of vascular electrocorticography were comparable to those of recordings from epidural surface arrays. Venous internal lumen patency was maintained for the duration of implantation. Stentrodes may have wide ranging applications as a neural interface for treatment of a range of neurological conditions.
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    Novel Functional MRI Task for Studying the Neural Correlates of Upper Limb Tremor
    (Frontiers in Neurology, 2018-07) Boonstra, Frederique; Perera, Thushara; Noffs, Gustavo; Marotta, Cassandra; Vogel, Adam; Evans, Andrew; Butzkueven, Helmut; Moffat, Bradford; Van der Walt, Anneke; Kolbe, Scott
    INTRODUCTION: Tremor of the upper limbs is a disabling symptom that is present during several neurological disorders and is currently without treatment. Functional MRI (fMRI) is an essential tool to investigate the pathophysiology of tremor and aid the development of treatment options. However, no adequately or standardised protocols for fMRI exists at present. Here we present a novel, online available fMRI task that could be used to assess the in vivo pathology of tremor. OBJECTIVE: This study aims to validate the tremor-evoking potential of the fMRI task in a small group of tremor patients outside the scanner and assess the reproducibility of the fMRI task related activation in healthy controls. METHODS: Twelve HCs were scanned at two time points (baseline and after 6-weeks). There were two runs of multi-band fMRI and the tasks included a ‘brick-breaker’ joystick game. The game consisted of three conditions designed to control for most of the activation related to performing the task by contrasting the conditions: WATCH (look at the game without moving joystick), MOVE (rhythmic left/right movement of joystick without game), and PLAY (playing the game). Task fMRI was analysed using FSL FEAT to determine clusters of activation during the different conditions. Maximum activation within the clusters was used to assess the ability to control for task related activation and reproducibility. Four tremor patients have been included to test ecological and construct validity of the joystick task by assessing tremor frequencies captured by the joystick. RESULTS: In HCs the game activated areas corresponding to motor, attention and visual areas. Most areas of activation by our game showed moderate to good reproducibility (intraclass correlation coefficient (ICC) 0.531 to 0.906) with only inferior parietal lobe activation showing poor reproducibility (ICC 0.446). Furthermore, the joystick captured significantly more tremulous movement in tremor patients compared to HCs (p=0.01) during PLAY, but not during MOVE. CONCLUSION: Validation of our novel task confirmed tremor-evoking potential and reproducibility analyses yielded acceptable results to continue further investigations into the pathophysiology of tremor. The use of this technique in studies with tremor patient will no doubt provide significant insights into the treatment options.
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    OnabotulinumtoxinA treatment for MS-tremor modifies fMRI tremor response in central sensory-motor integration areas
    (Elsevier B.V., 2020-02) Boonstra, Frederique; Evans, Andrew; Noffs, Gustavo; Perera, Thushara; Jokubaitis, Vilija; Stankovich, Jim; Vogel, Adam; Moffat, Bradford; Butzkueven, Helmut; Kolbe, Scott; van der Walt, Anneke
    Background: Treatment of tremor in MS is an unmet need. OnabotulinumtoxinA (BoNT-A) has shown promising results; however, little is known regarding its effects on the brain. The clinical presentation of tremor MS is shown to depend on subcortical neural damage and cortical neural plasticity. This study aimed to identify effects of onabotulinumtoxinA (BoNT-A) on brain activation in MS and upper-limb tremor using functional MRI. Methods: Forty-three MS participants with tremor were randomized to receive intramuscular injections of placebo (n = 22) or BoNT-A (n = 21). Tremor was quantified using the Bain score (0–10) for severity, handwriting and Archimedes drawing at baseline, 6 weeks and 12 weeks. Functional MRI activation within two previously identified clusters, ipsilateral inferior parietal cortex (IPL) and remotor/supplementary motor cortex (SMC) of compensatory activity, was measured at baseline and 6 weeks. Results: Treatment with BoNT-A resulted in improved handwriting tremor at 6 weeks (p = 0.049) and 12 weeks (p= 0.014), and tremor severity -0.79 (p=0.007) at 12 weeks. Furthermore, the patients that received BoNT-A showed a reduction in activation within the IPL (p = 0.034), but not in the SMC. The change in IPL activation correlated with the reduction in tremor severity from baseline to 12 weeks (β = 0.608; p = 0.015) in the BoNTA group. No tremor and fMRI changes were seen in the placebo treated group. Conclusion: We have shown that reduction in MS-tremor severity after intramuscular injection with BoNT-A is associated with changes in brain activity in sensorimotor integration regions.