scholarly journals Modulation of beta bursts in subthalamic sensorimotor circuits predicts improvement in bradykinesia

Brain ◽  
2020 ◽  
Author(s):  
Yasmine M Kehnemouyi ◽  
Kevin B Wilkins ◽  
Chioma M Anidi ◽  
Ross W Anderson ◽  
Muhammad Furqan Afzal ◽  
...  

Abstract No biomarker of Parkinson’s disease exists that allows clinicians to adjust chronic therapy, either medication or deep brain stimulation, with real-time feedback. Consequently, clinicians rely on time-intensive, empirical, and subjective clinical assessments of motor behaviour and adverse events to adjust therapies. Accumulating evidence suggests that hypokinetic aspects of Parkinson’s disease and their improvement with therapy are related to pathological neural activity in the beta band (beta oscillopathy) in the subthalamic nucleus. Additionally, effectiveness of deep brain stimulation may depend on modulation of the dorsolateral sensorimotor region of the subthalamic nucleus, which is the primary site of this beta oscillopathy. Despite the feasibility of utilizing this information to provide integrated, biomarker-driven precise deep brain stimulation, these measures have not been brought together in awake freely moving individuals. We sought to directly test whether stimulation-related improvements in bradykinesia were contingent on reduction of beta power and burst durations, and/or the volume of the sensorimotor subthalamic nucleus that was modulated. We recorded synchronized local field potentials and kinematic data in 16 subthalamic nuclei of individuals with Parkinson’s disease chronically implanted with neurostimulators during a repetitive wrist-flexion extension task, while administering randomized different intensities of high frequency stimulation. Increased intensities of deep brain stimulation improved movement velocity and were associated with an intensity-dependent reduction in beta power and mean burst duration, measured during movement. The degree of reduction in this beta oscillopathy was associated with the improvement in movement velocity. Moreover, the reduction in beta power and beta burst durations was dependent on the theoretical degree of tissue modulated in the sensorimotor region of the subthalamic nucleus. Finally, the degree of attenuation of both beta power and beta burst durations, together with the degree of overlap of stimulation with the sensorimotor subthalamic nucleus significantly explained the stimulation-related improvement in movement velocity. The above results provide direct evidence that subthalamic nucleus deep brain stimulation-related improvements in bradykinesia are related to the reduction in beta oscillopathy within the sensorimotor region. With the advent of sensing neurostimulators, this beta oscillopathy combined with lead location could be used as a marker for real-time feedback to adjust clinical settings or to drive closed-loop deep brain stimulation in freely moving individuals with Parkinson’s disease.

Author(s):  
Ashesh A. Thaker ◽  
Kartik M. Reddy ◽  
John A. Thompson ◽  
Pamela David Gerecht ◽  
Mark S. Brown ◽  
...  

<b><i>Introduction:</i></b> Deep brain stimulation of the zona incerta is effective at treating tremor and other forms of parkinsonism. However, the structure is not well visualized with standard MRI protocols making direct surgical targeting unfeasible and contributing to inconsistent clinical outcomes. In this study, we applied coronal gradient echo MRI to directly visualize the rostral zona incerta in Parkinson’s disease patients to improve targeting for deep brain stimulation. <b><i>Methods:</i></b> We conducted a prospective study to optimize and evaluate an MRI sequence to visualize the rostral zona incerta in patients with Parkinson’s disease (<i>n</i> = 31) and other movement disorders (<i>n</i> = 13). We performed a contrast-to-noise ratio analysis of specific regions of interest to quantitatively assess visual discrimination of relevant deep brain structures in the optimized MRI sequence. Regions of interest were independently assessed by 2 neuroradiologists, and interrater reliability was assessed. <b><i>Results:</i></b> Rostral zona incerta and subthalamic nucleus were well delineated in our 5.5-min MRI sequence, indicated by excellent interrater agreement between neuroradiologists for region-of-interest measurements (&#x3e;0.90 intraclass coefficient). Mean contrast-to-noise ratio was high for both rostral zona incerta (6.39 ± 3.37) and subthalamic nucleus (17.27 ± 5.61) relative to adjacent white matter. There was no significant difference between mean signal intensities or contrast-to-noise ratio for Parkinson’s and non-Parkinson’s patients for either structure. <b><i>Discussion/Conclusion:</i></b> Our optimized coronal gradient echo MRI sequence delineates subcortical structures relevant to traditional and novel deep brain stimulation targets, including the zona incerta, with high contrast-to-noise. Future studies will prospectively apply this sequence to surgical planning and postimplantation outcomes.


2019 ◽  
Vol 9 (3) ◽  
pp. 51 ◽  
Author(s):  
Rens Verhagen ◽  
Lo Bour ◽  
Vincent Odekerken ◽  
Pepijn van den Munckhof ◽  
P. Schuurman ◽  
...  

Motor improvement after deep brain stimulation (DBS) in the subthalamic nucleus (STN) may vary substantially between Parkinson’s disease (PD) patients. Research into the relation between improvement and active contact location requires a correction for anatomical variation. We studied the relation between active contact location relative to the neurophysiological STN, estimated by the intraoperative microelectrode recordings (MER-based STN), and contralateral motor improvement after one year. A generic STN shape was transformed to fit onto the stereotactically defined MER sites. The location of 43 electrodes (26 patients), derived from MRI-fused CT images, was expressed relative to this patient-specific MER-based STN. Using regression analyses, the relation between contact location and motor improvement was studied. The regression model that predicts motor improvement based on levodopa effect alone was significantly improved by adding the one-year active contact coordinates (R2 change = 0.176, p = 0.014). In the combined prediction model (adjusted R2 = 0.389, p < 0.001), the largest contribution was made by the mediolateral location of the active contact (standardized beta = 0.490, p = 0.002). With the MER-based STN as a reference, we were able to find a significant relation between active contact location and motor improvement. MER-based STN modeling can be used to complement imaging-based STN models in the application of DBS.


PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e43261 ◽  
Author(s):  
Diana M. E. Torta ◽  
Vincenzo Vizzari ◽  
Lorys Castelli ◽  
Maurizio Zibetti ◽  
Michele Lanotte ◽  
...  

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