ORCID Profile
0000-0003-2054-1915
Current Organisations
McGill University
,
University of Toronto
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Publisher: Wiley
Date: 22-11-2022
DOI: 10.1002/MDS.28870
Abstract: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) is an emerging target to potentially treat cognitive dysfunction. The aim of this study is to achieve feasibility and safety of globus pallidus pars interna (GPi) and NBM DBS in advanced PD with cognitive impairment. We performed a phase-II double-blind crossover pilot trial in six participants to assess safety and cognitive measures, the acute effect of NBM stimulation on attention, motor and neuropsychological data at one year, and neuroimaging biomarkers of NBM stimulation. NBM DBS was well tolerated but did not improve cognition. GPi DBS improved dyskinesia and motor fluctuations (P = 0.04) at one year. NBM stimulation was associated with reduced right frontal and parietal glucose metabolism (P < 0.01) and increased low- and high-frequency power and functional connectivity. Volume of tissue activated in the left NBM was associated with stable cognition (P < 0.05). Simultaneous GPi and NBM stimulation is safe and improves motor complications. NBM stimulation altered neuroimaging biomarkers but without lasting cognitive improvement. © 2021 International Parkinson and Movement Disorder Society.
Publisher: Wiley
Date: 13-02-2022
DOI: 10.1002/MDS.28953
Abstract: Patients with Parkinson's disease might develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation. To study whether lateralized stimulation (unilateral 50% litude reduction) for ≥21 days results in ≥0.13 m/s faster gait velocity in the dopaminergic ON state in these patients, and its effects on motor and axial function, quantitative gait and speech measures, quality of life, and selected cognitive tasks. Randomized, double-blinded, double-crossover trial. In 22 participants (51-79 years old, 15 women), there were no significant changes in gait velocity, quality of life, cognitive, and speech measures. Reducing left-sided litude resulted in a 2.5-point improvement in axial motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (P = 0.005, uncorrected) and a 1.9-point improvement in the Freezing of Gait Questionnaire (P = 0.024, uncorrected). Lateralized subthalamic stimulation does not result in meaningful improvement in gait velocity in patients with Parkinson's disease who develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation. Left subthalamic overstimulation may contribute to axial deterioration in these patients. © 2022 International Parkinson and Movement Disorder Society.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Cambridge University Press (CUP)
Date: 05-11-2020
DOI: 10.1017/CJN.2020.243
Abstract: Microelectrode recordings (MERs) are used during deep brain stimulation surgery (DBS) to optimize patient outcomes and provide a unique method of collecting data regarding neurological conditions. However, MERs can be affected by anesthetics such as dexmedetomidine. Little is known about the effects of dexmedetomidine (DEX) on the globus pallidus interna (GPi), a common target for DBS. The primary aim of this study is to investigate the hypothesis that DEX is associated with alterations in GPi MERs. We conducted a retrospective analysis comparing MERs from patients with Parkinson’s disease (PD) and dystonia who underwent insertion of DBS of the GPi under DEX sedation with those who went through the same procedure without DEX (No DEX). Firing rates for GPi neurons in the DEX group were lower (57.44 ± 2.04 mean ± SEM, n = 163 cells) than the No DEX group (69.53 ± 2.06, n = 112 cells, P 0.0001). Overall, DEX was associated with a greater proportion of GPi cells classified as firing in bursty pattern compared to our No DEX group. (29.41%, n = 153 vs 14.81%, n = 108, P = 0.008). This effect was present for both PD and dystonia patients who underwent the procedure. High doses of DEX were associated with lower firing rates than low doses. Our results suggest that DEX is associated with a decrease in GPi firing rates and are associated with an increase in burstiness. Furthermore, these effects are similar between dystonia and PD patients. Lastly, the effects of DEX may differ between high doses and low doses.
Publisher: Cold Spring Harbor Laboratory
Date: 02-12-2020
DOI: 10.1101/2020.11.30.404269
Abstract: With the growing interest in the expansion of deep brain stimulation indications, we aimed to provide experimental and computational insights into the brain-region-specific and frequency-dependent effects of extracellular stimulation on human neuronal activity. Experimentally, we demonstrated microstimulation-evoked excitatory neuronal responses in the ventral intermediate nucleus and reticular thalamus, and inhibitory responses in the subthalamic nucleus and substantia nigra pars reticulata hypothesized to be the result of simultaneous activations of convergent afferent inputs. Higher stimulation frequencies led to a loss of site-specificity and convergence towards neuronal suppression hypothesized to be mediated by synaptic depression. These experimental findings were reproduced by a computational framework in which relative distributions of convergent excitatory/inhibitory afferents were embedded within a model of short-term synaptic plasticity for the prediction of site-specific and frequency-dependent responses to extracellular stimulation. This theoretical framework may aid in the design of physiologically-informed stimulation paradigms in existing or prospective deep brain stimulation indications.
Location: Denmark
No related grants have been discovered for Suneil Kalia.