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Review
. 2021 Aug;11(4):315-328.
doi: 10.2217/nmt-2021-0002. Epub 2021 Jul 15.

Neurophysiological biomarkers to optimize deep brain stimulation in movement disorders

Daniel Sirica  1 , Angela L Hewitt  1   2 , Christopher G Tarolli  1   3 , Miriam T Weber  1 , Carol Zimmerman  1 , Aida Santiago  1 , Andrew Wensel  1   4 , Jonathan W Mink  1   2 , Karlo J Lizárraga  1   3
Affiliations
Review

Neurophysiological biomarkers to optimize deep brain stimulation in movement disorders

Daniel Sirica et al. Neurodegener Dis Manag. 2021 Aug.

Abstract

Intraoperative neurophysiological information could increase accuracy of surgical deep brain stimulation (DBS) lead placement. Subsequently, DBS therapy could be optimized by specifically targeting pathological activity. In Parkinson's disease, local field potentials (LFPs) excessively synchronized in the beta band (13-35 Hz) correlate with akinetic-rigid symptoms and their response to DBS therapy, particularly low beta band suppression (13-20 Hz) and high frequency gamma facilitation (35-250 Hz). In dystonia, LFPs abnormally synchronize in the theta/alpha (4-13 Hz), beta and gamma (60-90 Hz) bands. Phasic dystonic symptoms and their response to DBS correlate with changes in theta/alpha synchronization. In essential tremor, LFPs excessively synchronize in the theta/alpha and beta bands. Adaptive DBS systems will individualize pathological characteristics of neurophysiological signals to automatically deliver therapeutic DBS pulses of specific spatial and temporal parameters.

Keywords: Parkinson’s disease; deep brain stimulation; dystonia; essential tremor; local field potentials; microelectrode recordings; neuromodulation; neurophysiological biomarkers.

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Conflict of interest statement

Financial & competing interests disclosure

KJ Lizarraga and C Zimmerman have been reimbursed for travel to educational activities sponsored by Abbott, Boston Scientific and Medtronic. KJ Lizarraga has received an educational grant by Medtronic. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.
Figure 1.. Measurement of local field potentials of the left subthalamic nucleus during initial deep brain stimulation programming in a patient with Parkinson’s disease.
Conventional monopolar review based on acute clinical responses during initial DBS programming yielded equivalent therapeutic windows for contacts E0 and E1. Consistent with the monopolar review, the LFP survey demonstrated low beta (13–20 Hz) frequency peaks of higher amplitude in the regions between contacts (A) E0 and E1, (C) E0 and E2 and (D) E0 and E3. There were no significant beta peaks in the regions between contacts (B) E1 and E2, (E) E1 and E3 and (F) E2 and E3. Thus, initial DBS settings were programmed using contact E0 since the three regions with low beta LFPs shared contact E0 and the highest amplitude (1.89 μVp) was found in the region between contacts (D) E0 and E1. LFP measurements were obtained in the dopaminergic medication OFF state by the Percept DBS system (Medtronic). DBS: Deep brain stimulation; LFP: Local field potential.
Figure 2.
Figure 2.. Optimization of left subthalamic deep brain stimulation therapy for the same patient with Parkinson’s disease described in Figure 1.
(A) During surgical implantation of the left STN DBS lead, microelectrode recordings and stimulation defined a physiologically optimized trajectory and target in the dorsolateral region of the anatomically defined left STN. (B) During the initial programming session described in Figure 1, contact E0 was chosen to deliver DBS to the region with the highest peak of low beta LFPs. Upon subsequent DBS amplitude increase, the patient developed subtle side effects due to lateral spread of stimulation toward the IC, which limited the benefits of DBS. (C) With directional stimulation using segmented leads, this lateral spread of stimulation could be theoretically avoided and DBS therapy could be further optimized. Reconstruction of neuroanatomical structures and DBS lead localization were performed by merging pre-operative brain MRI and post-operative CT using BrainLab. CT: Computed tomography; DBS: Deep brain stimulation; IC: Internal capsule; LFP: Local field potential; STN: Subthalamic nucleus.
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