Dataset Information

Deep brain stimulation induces BOLD activation in motor and non-motor networks: an fMRI comparison study of STN and EN/GPi DBS in large animals.

ABSTRACT: The combination of deep brain stimulation (DBS) and functional MRI (fMRI) is a powerful means of tracing brain circuitry and testing the modulatory effects of electrical stimulation on a neuronal network in vivo. The goal of this study was to trace DBS-induced global neuronal network activation in a large animal model by monitoring the blood oxygenation level-dependent (BOLD) response on fMRI. We conducted DBS in normal anesthetized pigs, targeting the subthalamic nucleus (STN) (n=7) and the entopeduncular nucleus (EN), the non-primate analog of the primate globus pallidus interna (n=4). Using a normalized functional activation map for group analysis and the application of general linear modeling across subjects, we found that both STN and EN/GPi DBS significantly increased BOLD activation in the ipsilateral sensorimotor network (FDR<0.001). In addition, we found differential, target-specific, non-motor network effects. In each group the activated brain areas showed a distinctive correlation pattern forming a group of network connections. Results suggest that the scope of DBS extends beyond an ablation-like effect and that it may have modulatory effects not only on circuits that facilitate motor function but also on those involved in higher cognitive and emotional processing. Taken together, our results show that the swine model for DBS fMRI, which conforms to human implanted DBS electrode configurations and human neuroanatomy, may be a useful platform for translational studies investigating the global neuromodulatory effects of DBS.

SUBMITTER: Min HK

PROVIDER: S-EPMC3487590 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Deep brain stimulation induces BOLD activation in motor and non-motor networks: an fMRI comparison study of STN and EN/GPi DBS in large animals.

Min Hoon-Ki HK Hwang Sun-Chul SC Marsh Michael P MP Kim Inyong I Knight Emily E Striemer Bryan B Felmlee Joel P JP Welker Kirk M KM Blaha Charles D CD Chang Su-Youne SY Bennet Kevin E KE Lee Kendall H KH

NeuroImage 20120810 3

The combination of deep brain stimulation (DBS) and functional MRI (fMRI) is a powerful means of tracing brain circuitry and testing the modulatory effects of electrical stimulation on a neuronal network in vivo. The goal of this study was to trace DBS-induced global neuronal network activation in a large animal model by monitoring the blood oxygenation level-dependent (BOLD) response on fMRI. We conducted DBS in normal anesthetized pigs, targeting the subthalamic nucleus (STN) (n=7) and the ent ...[more]

PMID: 22967832

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Project description:When formulating a deep brain stimulation (DBS) treatment plan for a patient with Parkinson's disease (PD), two critical questions should be addressed: 1- Which brain target should be chosen to optimize this patient's outcome? and 2- Should this patient's DBS operation be unilateral or bilateral? Over the past two decades, two targets have emerged as leading contenders for PD DBS; the subthalamic nucleus (STN) and the globus pallidus internus (GPi). While the GPi target does have a following, most centers have uniformly employed bilateral STN DBS for all Parkinson's disease cases (Figure 1). This bilateral STN "one-size-fits-all" approach was challenged by an editorial entitled "STN vs. GPi: The Rematch," which appeared in the Archives of Neurology in 2005. Since 2005, a series of well designed clinical trials and follow-up studies have addressed the question as to whether a more tailored approach to DBS therapy might improve overall outcomes. Such a tailored approach would include the options of targeting the GPi, or choosing a unilateral operation. The results of the STN vs. GPi 'rematch' studies support the conclusion that bilateral STN DBS may not be the best option for every Parkinson's disease surgical patient. Off period motor symptoms and tremor improve in both targets, and with either unilateral or bilateral stimulation. Advantages of the STN target include more medication reduction, less frequent battery changes, and a more favorable economic profile. Advantages of GPi include more robust dyskinesia suppression, easier programming, and greater flexibility in adjusting medications. In cases where unilateral stimulation is anticipated, the data favor GPi DBS. This review summarizes the accumulated evidence regarding the use of bilateral vs. unilateral DBS and the selection of STN vs. GPi DBS, including definite and possible advantages of different targets and approaches. Based on this evidence, a more patient-tailored, symptom specific approach will be proposed to optimize outcomes of PD DBS therapy. Finally, the importance of an interdisciplinary care team for screening and effective management of DBS patients will be reaffirmed. Interdisciplinary teams can facilitate the proposed patient-specific DBS treatment planning and provide a more thorough analysis of the risk-benefit ratio for each patient.

Project description:ObjectiveTo investigate the effects of subthalamic nucleus (STN) and globus pallidus internus (GPi), deep brain stimulation (DBS) on individual action tremor/postural tremor (AT) and rest tremor (RT) in Parkinson's disease (PD). Randomized DBS studies have reported marked benefit in tremor with both GPi and STN and DBS, however, there is a paucity of information available on AT vs RT when separated by the surgical target.MethodsWe retrospectively reviewed the 1-year clinical outcome of PD patients treated with STN and GPi DBS at the University of Florida. We specifically selected patients with moderate to severe AT. Eighty-eight patients (57 STN and 31 GPi) were evaluated at 6 and 12 months for changes in AT and RT in the OFF-medication/ON stimulation state. A comparison of "response" was performed and defined as greater than or equal to a 2-point decrease in tremor score.ResultsSTN and GPi DBS both improved AT at 6- and 12-months post-implantation (p < 0.001 and p < 0.001). The STN DBS group experienced a greater improvement in AT at 6 months compared to the GPi group (p = 0.005) but not at the 12 months follow-up (p = 0.301). Both STN and GPi DBS also improved RT at 6- and 12-months post-implantation (p < 0.001 and p < 0.001). There was no difference in RT scores between the two groups at 6 months (p = 0.23) or 12 months (p = 0.74). The STN group had a larger proportion of patients who achieved a "response" in AT at 6 months (p < 0.01), however, this finding was not present at 12 months (p = 0.23). A sub-analysis revealed that in RT, the STN group had a larger percentage of "responders" when followed through 12 months (p < 0.01).ConclusionBoth STN and GPi DBS reduced PD associated AT and RT at 12 months follow-up. There was no advantage of either brain target in the management of RT or AT. One nuance of the study was that STN DBS was more effective in suppressing AT in the early postoperative period, however, this effect diminished over time. Clinicians should be aware that it may take longer to achieve a similar tremor outcome when utilizing the GPi target.

Project description:ObjectiveTo study mood and behavioral effects of unilateral and staged bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for Parkinson's disease (PD).BackgroundThere are numerous reports of mood changes following DBS, however, most have focused on bilateral simultaneous STN implants with rapid and aggressive post-operative medication reduction.MethodsA standardized evaluation was applied to a subset of patients undergoing STN and GPi DBS and who were also enrolled in the NIH COMPARE study. The Unified Parkinson Disease Rating Scale (UPDRS III), the Hamilton depression (HAM-D) and anxiety rating scales (HAM-A), the Yale-Brown obsessive-compulsive rating scale (YBOCS), the Apathy Scale (AS), and the Young mania rating scale (YMRS) were used. The scales were repeated at acute and chronic intervals. A post-operative strategy of non-aggressive medication reduction was employed.ResultsThirty patients were randomized and underwent unilateral DBS (16 STN, 14 GPi). There were no baseline differences. The GPi group had a higher mean dopaminergic dosage at 1-year, however the between group difference in changes from baseline to 1-year was not significant. There were no differences between groups in mood and motor outcomes. When combining STN and GPi groups, the HAM-A scores worsened at 2-months, 4-months, 6-months and 1-year when compared with baseline; the HAM-D and YMRS scores worsened at 4-months, 6-months and 1-year; and the UPDRS Motor scores improved at 4-months and 1-year. Psychiatric diagnoses (DSM-IV) did not change. No between group differences were observed in the cohort of bilateral cases.ConclusionsThere were few changes in mood and behavior with STN or GPi DBS. The approach of staging STN or GPi DBS without aggressive medication reduction could be a viable option for managing PD surgical candidates. A study of bilateral DBS and of medication reduction will be required to better understand risks and benefits of a bilateral approach.

Project description:ObjectivesTo study whether 60-Hz stimulation, compared with routine 130 Hz, improves swallowing function and freezing of gait (FOG) in patients with Parkinson disease (PD) who undergo bilateral subthalamic nucleus (STN) deep brain stimulation (DBS).MethodsWe studied 7 patients with PD who experienced FOG that persisted despite routine 130-Hz stimulation and dopaminergic medication. Each patient received 3 modified barium swallow (MBS) studies in a single day under 3 DBS conditions in the medication-on state: 130 Hz, 60 Hz, or DBS off, in a randomized double-blind manner. The laryngeal penetration and aspiration events were cautiously assessed, and a swallowing questionnaire was completed. The Unified Parkinson's Disease Rating Scale, Part III motor score, axial subscore, tremor subscore, and FOG by a questionnaire and stand-walk-sit test were also assessed. The best DBS condition (60 Hz here) producing the least FOG was maintained for 3 to 8 weeks, and patients were assessed again. Changes in measurements between the 60 Hz and 130 Hz were analyzed using paired t test, with swallowing function as primary and the remainder as secondary outcomes. Changes between other DBS conditions were further explored with Bonferroni correction.ResultsCompared with the routine 130 Hz, 60-Hz stimulation significantly reduced aspiration frequency by 57% on MBS study and perceived swallowing difficulty by 80% on questionnaire. It also significantly reduced FOG, and axial and parkinsonian symptoms. The benefits at 60-Hz stimulation persisted over the average 6-week assessment.ConclusionsCompared with the routine 130 Hz, the 60-Hz stimulation significantly improved swallowing function, FOG, and axial and parkinsonian symptoms in patients with PD treated with bilateral STN-DBS, which persisted over the 6-week study period.Classification of evidenceThis study provides Class IV evidence that for patients with PD who experience FOG, STN-DBS at 60 Hz decreases aspiration events observed during MBS compared with DBS at 130 Hz.

Dataset Information

Deep brain stimulation induces BOLD activation in motor and non-motor networks: an fMRI comparison study of STN and EN/GPi DBS in large animals.

Publications

Deep brain stimulation induces BOLD activation in motor and non-motor networks: an fMRI comparison study of STN and EN/GPi DBS in large animals.

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