Wong, Joshua K

AbstractBackgroundStimulation‐induced dyskinesias (SID) from deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) are uncommon; however, they are increasingly recognized. Once considered transient and indicative of effective neuromodulation, SID are now seen as potential therapy‐limiting side effects, akin to internal capsule activation. The mechanism and anatomical basis for SID remain poorly understood.MethodsWe conducted a retrospective study of individuals with Parkinson's disease with STN or GPi DBS who experienced SID in the dopaminergic medication OFF state during the monopolar review 1‐month post‐implantation.ResultsWe analyzed 137 monopolar stimulation observations (105 GPi, 32 STN). In the GPi cohort, discriminative fiber tract analysis showed a strong association between SID and the modulation of subthalamo‐pallidal fibers. This correlation was confirmed using leave‐one‐out and five‐fold cross‐validation. We further validated this model by predicting SID in independent STN and GPi cohorts, with the GPi‐based model accounting for significant variance in SID occurrence in both cohorts.ConclusionsSID from STN or GPi DBS likely shares a common pathway via subthalamo‐pallidal connectivity. DBS modulation of these fibers correlates with SID, as confirmed by multiple cross‐validation methods. These findings suggest that the fibers are part of a more extensive and yet‐to‐be‐fully‐characterized dyskinesia network. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Deep brain stimulation (DBS) is an effective neuromodulatory therapy for Parkinson’s disease (PD). Early studies using globus pallidus internus (GPi) DBS for PD profiled the nucleus as having two functional zones. This concept disseminated throughout the neuromodulation community as the “GPi triangle”. Although our understanding of the pallidum has greatly evolved over the past 20 years, we continue to reference the triangle in our clinical decision-making process. We propose a new direction, termed the spatial boundary hypothesis, to build upon the 2-dimensional outlook on GPi DBS. We believe an updated 3-D GPi model can produce more consistent, positive patient outcomes.

AbstractThe pathophysiology of dystonic tremor and essential tremor remains partially understood. In patients with medication-refractory dystonic tremor or essential tremor, deep brain stimulation (DBS) targeting the thalamus or posterior subthalamic area has evolved into a promising treatment option. However, the optimal DBS targets for these disorders remains unknown. This retrospective study explored the optimal targets for DBS in essential tremor and dystonic tremor using a combination of volumes of tissue activated estimation and functional and structural connectivity analyses. We included 20 patients with dystonic tremor who underwent unilateral thalamic DBS, along with a matched cohort of 20 patients with essential tremor DBS. Tremor severity was assessed preoperatively and approximately 6 months after DBS implantation using the Fahn-Tolosa-Marin Tremor Rating Scale. The tremor-suppressing effects of DBS were estimated using the percentage improvement in the unilateral tremor-rating scale score contralateral to the side of implantation. The optimal stimulation region, based on the cluster centre of gravity for peak contralateral motor score improvement, for essential tremor was located in the ventral intermediate nucleus region and for dystonic tremor in the ventralis oralis posterior nucleus region along the ventral intermediate nucleus/ventralis oralis posterior nucleus border (4 mm anterior and 3 mm superior to that for essential tremor). Both disorders showed similar functional connectivity patterns: a positive correlation between tremor improvement and involvement of the primary sensorimotor, secondary motor and associative prefrontal regions. Tremor improvement, however, was tightly correlated with the primary sensorimotor regions in essential tremor, whereas in dystonic tremor, the correlation was tighter with the premotor and prefrontal regions. The dentato-rubro-thalamic tract, comprising the decussating and non-decussating fibres, significantly correlated with tremor improvement in both dystonic and essential tremor. In contrast, the pallidothalamic tracts, which primarily project to the ventralis oralis posterior nucleus region, significantly correlated with tremor improvement only in dystonic tremor. Our findings support the hypothesis that the pathophysiology underpinning dystonic tremor involves both the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network. Further our data suggest that the pathophysiology of essential tremor is primarily attributable to the abnormalities within the cerebello-thalamo-cortical network. We conclude that the ventral intermediate nucleus/ventralis oralis posterior nucleus border and ventral intermediate nucleus region may be a reasonable DBS target for patients with medication-refractory dystonic tremor and essential tremor, respectively. Uncovering the pathophysiology of these disorders may in the future aid in further improving DBS outcomes.

AbstractDBS is an effective neuromodulatory therapy that has been applied in various conditions, including PD, essential tremor, dystonia, Tourette syndrome, and other movement disorders. There have also been recent examples of applications in epilepsy, chronic pain, and neuropsychiatric conditions. Innovations in neuroimaging technology have been driving connectomics, an emerging whole‐brain network approach to neuroscience. Two rising techniques are functional connectivity profiling and structural connectivity profiling. Functional connectivity profiling explores the operational relationships between multiple regions of the brain with respect to time and stimuli. Structural connectivity profiling approximates physical connections between different brain regions through reconstruction of axonal fibers. Through these techniques, complex relationships can be described in various disease states, such as PD, as well as in response to therapy, such as DBS. These advances have expanded our understanding of human brain function and have provided a partial in vivo glimpse into the underlying brain circuits underpinning movement and other disorders. This comprehensive review will highlight the contemporary concepts in brain connectivity as applied to DBS, as well as introduce emerging considerations in movement disorders. © 2020 International Parkinson and Movement Disorder Society