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  • Magnetoencephalographic and fMRI Examination of the Effects of VC/VS DBS on Post-stroke Pain

    Final Number:

    Raghavan Gopalakrishnan PhD MBA; Scott F Lempka; Richard Burgess; Kenneth B. Baker PhD; Stephen E Jones MD, PhD; Mark Lowe PhD; Andre Machado MD PhD

    Study Design:
    Clinical Trial

    Subject Category:

    Meeting: 2018 ASSFN Biennial Meeting

    Introduction: Post-stroke pain syndrome (PSPS) is an intractable disorder characterized by unrelenting chronic pain and hemiparesis. While traditional analgesic approaches largely fail to provide long-term relief, integrative approaches targeting affective-cognitive spheres are promising. Recently, we demonstrated1 that deep brain stimulation (DBS) of the VC/VS, significantly improved pain affect and quality of life in PSPS patients. Here, we explore if this clinical improvement was reflected in magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) correlates that could serve as objective signatures.

    Methods: We performed MEG and fMRI on 10 PSPS patients in the baseline, DBS-OFF and DBS-ON states. MEG: Visual cues evoked anticipation as patients awaited a painful (PS) or non-painful (NPS) stimulus to their non-affected or affected extremity. Whole brain event-related responses were examined. fMRI: We used a simple block paradigm. After initial preprocessing, the difference of fMRI z-map between ON-vs-OFF were generated on the MNI template in Talairach space for each patient and averaged as the final results.

    Results: There were no significant difference between PS-vs-NPS before surgery or in the DBS-OFF condition, suggesting a loss of salience in the untreated pain state. DBS significantly modulated the N1 (parietal/prefrontal) component of NPS anticipation, restoring discrimination capacity (Fig-1a). DBS enhanced the anterior N1 (anterior cingulate ACC) among treatment responders, reflecting emotional regulation (Fig-1b). fMRI: Comparing DBS ON-vs-OFF, we observed (Fig-2) stronger activation of 1. medial parietal and frontal lobes on the non-affected side. 2. ACC contralateral to pain for both extremities.

    Conclusions: DBS-induced changes in MEG correlates reflect treatment effects and could potentially serve as biomarkers for clinical outcomes. fMRI findings further corroborate MEG data showing modulation of behavioral and associative areas including ACC and fronto-parietal cortices. Overall, VC/VS DBS modulated the affective component of pain, as evidenced in clinical metrics, and greater involvement of associative-limbic structures during pain and pain anticipation.

    Patient Care: 1. MEG and fMRI signatures can characterize neural signatures that predict clinical outcomes after surgery. 2. Understanding spatio-temporal dynamics during pain processing will assist in developing novel neuromodulation strategies.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) characterize spatio-temporal activations of pain affect. 2) identify the functional correlates of VC/VS DBS modulation. 3) Understand fMRI and MEG objective signatures of pain affect.

    References: 1. Lempka SF, Malone DA, Hu B, Baker KB, Wyant A, Ozinga J, Plow EB, Pandya M, Kubu CS, Ford PJ, and Machado AG. Randomized clinical trial of deep brain stimulation for post-stroke pain. Annals of neurology 2017.

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