Resting-state connectivity predicts patient-specific effects of deep brain stimulation for Parkinson’s disease

AbstractNeural circuit-based guidance for optimizing patient screening, target selection and parameter tuning for deep brain stimulation (DBS) remains limited. To this end, we propose a functional brain connectome-based modeling approach that simulates network-spreading effects of stimulating different brain regions and quantifies rectification of abnormal network topology in silico. We validate these analyses by predicting nuclei in basal-ganglia circuits as top-ranked targets for 43 local patients with Parkinson’s disease and 90 patients from public database. However, individual connectome-based predictions demonstrate that globus pallidus and subthalamic nucleus (STN) constituted as the best choice for 21.1% and 19.5% of patients, respectively. Notably, the priority rank of STN significantly correlated with motor symptom severity in the local cohort. By introducing whole-brain network diffusion dynamics, these findings unfold a new dimension of brain connectomics and underscore the importance of neural network modeling for personalized DBS therapy, which warrants experimental investigation to validate its clinical utility.

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Electrode Location in a Microelectrode Recording-Based Model of the Subthalamic Nucleus Can Predict Motor Improvement After Deep Brain Stimulation for Parkinson’s Disease

Brain Sciences ◽

10.3390/brainsci9030051 ◽

2019 ◽

Vol 9 (3) ◽

pp. 51 ◽

Cited By ~ 2

Author(s):

Rens Verhagen ◽

Lo Bour ◽

Vincent Odekerken ◽

Pepijn van den Munckhof ◽

P. Schuurman ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Anatomical Variation ◽

Patient Specific ◽

One Year ◽

Motor Improvement ◽

Deep Brain

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.

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14 Pathological oscillatory activity in Parkinson’s disease; what does it mean and how should we treat it?

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-bnpa.14 ◽

2020 ◽

Vol 91 (8) ◽

pp. e6.1-e6

Author(s):

Peter Brown

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Basal Ganglia ◽

Side Effects ◽

Brain Stimulation ◽

Neural Circuit ◽

Symptom Control ◽

Oscillatory Activity ◽

Deep Brain

Professor Peter Brown is Professor of Experimental Neurology and Director of the Medical Research Council Brain Network Dynamics Unit at the University of Oxford. Prior to 2010 he was a Professor of Neurology at University College London.For decades we have had cardiac pacemakers that adjust their pacing according to demand and yet therapeutic adaptive stimulation approaches for the central nervous system are still not clinically available. Instead, to treat patients with advanced Parkinson’s disease we stimulate the basal ganglia with fixed regimes, unvarying in frequency or intensity. Although effective, this comes with side-effects and in terms of sophistication this treatment approach could be compared to having central heating system on all the time, regardless of temperature. This talk will describe recent steps being taken to define the underlying circuit dysfunction in Parkinson’s and to improve deep brain stimulation by controlling its delivery according to the state of pathological activity.Evidence is growing that motor symptoms in Parkinson’s disease are due, at least in part, to excessive synchronisation between oscillating neurons. Recordings confirm bursts of oscillatory synchronisation in the basal ganglia centred around 20 Hz. The bursts of 20 Hz activity are prolonged in patients withdrawn from their usual medication and the dominance of these long duration bursts negatively correlates with motor impairment. Longer bursts attain higher amplitudes, indicative of more pervasive oscillatory synchronisation within the neural circuit. In contrast, in heathy primates and in treated Parkinson’s disease bursts tend to be short. Accordingly, it might be best to use closed-loop controlled deep brain stimulation to selectively terminate longer, bigger, pathological beta bursts to both save power and to spare the ability of underlying neural circuits to engage in more physiological processing between long bursts. It is now possible to record and characterise bursts on-line during stimulation of the same site and trial adaptive stimulation. Thus far, this has demonstrated improvements in efficiency and side-effects over conventional continuous stimulation, with at least as good symptom control in Parkinsonian patients.

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7T MRI and Computational Modeling Supports a Critical Role of Lead Location in Determining Outcomes for Deep Brain Stimulation: A Case Report

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.631778 ◽

2021 ◽

Vol 15 ◽

Author(s):

Lauren E. Schrock ◽

Remi Patriat ◽

Mojgan Goftari ◽

Jiwon Kim ◽

Matthew D. Johnson ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Side Effects ◽

Computational Modeling ◽

Brain Stimulation ◽

Critical Role ◽

7 Tesla ◽

Patient Specific ◽

Deep Brain

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established therapy for Parkinson’s disease motor symptoms. The ideal site for implantation within STN, however, remains controversial. While many argue that placement of a DBS lead within the sensorimotor territory of the STN yields better motor outcomes, others report similar effects with leads placed in the associative or motor territory of the STN, while still others assert that placing a DBS lead “anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the STN (based on stereotactic atlas coordinates) produces similar clinical efficacy.” These discrepancies likely result from methodological differences including targeting preferences, imaging acquisition and the use of brain atlases that do not account for patient-specific anatomic variability. We present a first-in-kind within-patient demonstration of severe mood side effects and minimal motor improvement in a Parkinson’s disease patient following placement of a DBS lead in the limbic/associative territory of the STN who experienced marked improvement in motor benefit and resolution of mood side effects following repositioning the lead within the STN sensorimotor territory. 7 Tesla (7 T) magnetic resonance imaging (MRI) data were used to generate a patient-specific anatomical model of the STN with parcellation into distinct functional territories and computational modeling to assess the relative degree of activation of motor, associative and limbic territories.

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Theta Oscillations at Subthalamic Region Predicts Hypomania State After Deep Brain Stimulation in Parkinson's Disease

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.797314 ◽

2021 ◽

Vol 15 ◽

Author(s):

Yi-Chieh Chen ◽

Hau-Tieng Wu ◽

Po-Hsun Tu ◽

Chih-Hua Yeh ◽

Tzu-Chi Liu ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Emotional Processing ◽

Motor Impairment ◽

Field Potential ◽

Low Frequency ◽

Patient Specific ◽

Deep Brain

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for the motor impairments of patients with advanced Parkinson's disease. However, mood or behavioral changes, such as mania, hypomania, and impulsive disorders, can occur postoperatively. It has been suggested that these symptoms are associated with the stimulation of the limbic subregion of the STN. Electrophysiological studies demonstrate that the low-frequency activities in ventral STN are modulated during emotional processing. In this study, we report 22 patients with Parkinson's disease who underwent STN DBS for treatment of motor impairment and presented stimulation-induced mood elevation during initial postoperative programming. The contact at which a euphoric state was elicited by stimulation was termed as the hypomania-inducing contact (HIC) and was further correlated with intraoperative local field potential recorded during the descending of DBS electrodes. The power of four frequency bands, namely, θ (4–7 Hz), α (7–10 Hz), β (13–35 Hz), and γ (40–60 Hz), were determined by a non-linear variation of the spectrogram using the concentration of frequency of time (conceFT). The depth of maximum θ power is located approximately 2 mm below HIC on average and has significant correlation with the location of contacts (r = 0.676, p < 0.001), even after partializing the effect of α and β, respectively (r = 0.474, p = 0.022; r = 0.461, p = 0.027). The occurrence of HIC was not associated with patient-specific characteristics such as age, gender, disease duration, motor or non-motor symptoms before the operation, or improvement after stimulation. Taken together, these data suggest that the location of maximum θ power is associated with the stimulation-induced hypomania and the prediction of θ power is frequency specific. Our results provide further information to refine targeting intraoperatively and select stimulation contacts in programming.

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Selection of deep brain stimulation contacts using volume of tissue activated software following subthalamic nucleus stimulation

Journal of Neurosurgery ◽

10.3171/2020.6.jns192157 ◽

2020 ◽

pp. 1-8

Author(s):

Mathilde Devaluez ◽

Melissa Tir ◽

Pierre Krystkowiak ◽

Mickael Aubignat ◽

Michel Lefranc

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Subthalamic Nucleus ◽

Clinical Data ◽

Brain Stimulation ◽

Therapeutic Window ◽

Patient Specific ◽

Subthalamic Nucleus Stimulation ◽

Deep Brain

OBJECTIVEHigh-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in the treatment of motor symptoms of Parkinson’s disease. Using a patient-specific lead and volume of tissue activated (VTA) software, it is possible to visualize contact positions in the context of the patient’s own anatomy. In this study, the authors’ aim was to demonstrate that VTA software can be used in clinical practice to help determine the clinical effectiveness of stimulation in patients with Parkinson’s disease undergoing DBS of the STN.METHODSBrain images of 26 patients undergoing STN DBS were analyzed using VTA software. Preoperative clinical and neuropsychological data were collected. Contacts were chosen by two experts in DBS blinded to the clinical data. A therapeutic window of amplitude was determined. These results were compared with the parameter settings for each patient. Data were obtained at 3 months and 1 year postsurgery.RESULTSIn 90.4% (95% CI 82%–98%) of the patients, the contacts identified by the VTA software were concordant with the clinically effective contacts or with an effective contact in contact-by-contact testing. The therapeutic window of amplitude selected virtually included 81.3% of the clinical amplitudes.CONCLUSIONSVTA software appears to present significant concordance with clinical data for selecting contacts and stimulation parameters that could help in postoperative follow-up and programming.

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