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A Comprehensive Review of Brain Connectomics and Imaging to Improve Deep Brain Stimulation Outcomes.

ABSTRACT: DBS is an effective neuromodulatory therapy that has been applied in various conditions, including PD, essential tremor, dystonia, Tourette syndrome, and other movement disorders. There have also been recent examples of applications in epilepsy, chronic pain, and neuropsychiatric conditions. Innovations in neuroimaging technology have been driving connectomics, an emerging whole-brain network approach to neuroscience. Two rising techniques are functional connectivity profiling and structural connectivity profiling. Functional connectivity profiling explores the operational relationships between multiple regions of the brain with respect to time and stimuli. Structural connectivity profiling approximates physical connections between different brain regions through reconstruction of axonal fibers. Through these techniques, complex relationships can be described in various disease states, such as PD, as well as in response to therapy, such as DBS. These advances have expanded our understanding of human brain function and have provided a partial in vivo glimpse into the underlying brain circuits underpinning movement and other disorders. This comprehensive review will highlight the contemporary concepts in brain connectivity as applied to DBS, as well as introduce emerging considerations in movement disorders. © 2020 International Parkinson and Movement Disorder Society.

SUBMITTER: Wong JK

PROVIDER: S-EPMC7556988 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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A Comprehensive Review of Brain Connectomics and Imaging to Improve Deep Brain Stimulation Outcomes.

Wong Joshua K JK Middlebrooks Erik H EH Grewal Sanjeet S SS Almeida Leonardo L Hess Christopher W CW Okun Michael S MS

Movement disorders : official journal of the Movement Disorder Society 20200412 5

DBS is an effective neuromodulatory therapy that has been applied in various conditions, including PD, essential tremor, dystonia, Tourette syndrome, and other movement disorders. There have also been recent examples of applications in epilepsy, chronic pain, and neuropsychiatric conditions. Innovations in neuroimaging technology have been driving connectomics, an emerging whole-brain network approach to neuroscience. Two rising techniques are functional connectivity profiling and structural con ...[more]

PMID: 32281147

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Project description:IntroductionDeep brain stimulation (DBS) is increasingly used to treat the symptoms of various neurologic and psychiatric conditions. People can undergo the procedure during reproductive years but the safety of DBS in pregnancy remains relatively unknown given the paucity of published cases. We thus conducted a review of the literature to determine the state of current knowledge about DBS in pregnancy and to determine how eligibility criteria are approached in clinical trials with respect to pregnancy and the potential for pregnancy.MethodsA literature review was conducted in EMBASE to identify articles involving DBS and pregnancy. Two reviewers independently analyzed the articles to confirm inclusion. Data extracted for analysis included conditions treated, complications at all stages of pregnancy, neonatal/pediatric outcomes, and DBS target. A second search was then conducted using www.clinicaltrials.gov. The same two reviewers then assessed whether each trial excluded pregnant individuals, lactating individuals, or persons of childbearing age planning to conceive. Also assessed was whether contraception had to be deemed adequate prior to enrollment.ResultsThe literature search returned 681 articles. Following independent analysis and agreement of two reviewers, 8 pregnancy related DBS articles were included for analysis. These articles described 27 subjects, 29 pregnancies (2 with subsequent pregnancies), and 31 infants (2 twin pregnancies). There was 1 preterm birth at 35 weeks, and 3 patients who experienced discomfort from the DBS battery (i.e., impulse generator) placement site. All 27 patients had a DBS device implanted before they became pregnant, which remained in use throughout their pregnancy. There was exclusion of pregnant individuals from 68% of 135 interventional trials involving DBS. Approximately 44% of these trials excluded persons of childbearing age not on "adequate contraception" or wishing to conceive in the coming years. Finally, 22% excluded breastfeeding persons.ConclusionThe data from 29 pregnancies receiving DBS treatment during pregnancy was not associated with unexpected pregnancy or post-partum complication patterns. Many clinical trials have excluded pregnant individuals. Documentation of outcomes in larger numbers of pregnancies will help clarify the safety profile and will help guide study designs that will safely include pregnant patients.

Project description:Deep brain stimulation (DBS) is a highly efficacious treatment option for movement disorders and a growing number of other indications are investigated in clinical trials. To ensure optimal treatment outcome, exact electrode placement is required. Moreover, to analyze the relationship between electrode location and clinical results, a precise reconstruction of electrode placement is required, posing specific challenges to the field of neuroimaging. Since 2014 the open source toolbox Lead-DBS is available, which aims at facilitating this process. The tool has since become a popular platform for DBS imaging. With support of a broad community of researchers worldwide, methods have been continuously updated and complemented by new tools for tasks such as multispectral nonlinear registration, structural/functional connectivity analyses, brain shift correction, reconstruction of microelectrode recordings and orientation detection of segmented DBS leads. The rapid development and emergence of these methods in DBS data analysis require us to revisit and revise the pipelines introduced in the original methods publication. Here we demonstrate the updated DBS and connectome pipelines of Lead-DBS using a single patient example with state-of-the-art high-field imaging as well as a retrospective cohort of patients scanned in a typical clinical setting at 1.5T. Imaging data of the 3T example patient is co-registered using five algorithms and nonlinearly warped into template space using ten approaches for comparative purposes. After reconstruction of DBS electrodes (which is possible using three methods and a specific refinement tool), the volume of tissue activated is calculated for two DBS settings using four distinct models and various parameters. Finally, four whole-brain tractography algorithms are applied to the patient's preoperative diffusion MRI data and structural as well as functional connectivity between the stimulation volume and other brain areas are estimated using a total of eight approaches and datasets. In addition, we demonstrate impact of selected preprocessing strategies on the retrospective sample of 51 PD patients. We compare the amount of variance in clinical improvement that can be explained by the computer model depending on the preprocessing method of choice. This work represents a multi-institutional collaborative effort to develop a comprehensive, open source pipeline for DBS imaging and connectomics, which has already empowered several studies, and may facilitate a variety of future studies in the field.

Project description:Patients with movement disorders treated by deep brain stimulation do not always achieve successful therapeutic alleviation of motor symptoms, even in cases where surgery is without complications. Magnetic resonance imaging (MRI) offers methods to investigate structural brain-related factors that may be predictive of clinical motor outcomes. This review aimed to identify features which have been associated with variability in clinical post-operative motor outcomes in patients with Parkinson's disease, dystonia, and essential tremor from structural MRI modalities. We performed a literature search for articles published between 1 January 2000 and 1 April 2022 and identified 5197 articles. Following screening through our inclusion criteria, we identified 60 total studies (39 = Parkinson's disease, 11 = dystonia syndromes and 10 = essential tremor). The review captured a range of structural MRI methods and analysis techniques used to identify factors related to clinical post-operative motor outcomes from deep brain stimulation. Morphometric markers, including volume and cortical thickness were commonly identified in studies focused on patients with Parkinson's disease and dystonia syndromes. Reduced metrics in basal ganglia, sensorimotor and frontal regions showed frequent associations with reduced motor outcomes. Increased structural connectivity to subcortical nuclei, sensorimotor and frontal regions was also associated with greater motor outcomes. In patients with tremor, increased structural connectivity to the cerebellum and cortical motor regions showed high prevalence across studies for greater clinical motor outcomes. In addition, we highlight conceptual issues for studies assessing clinical response with structural MRI and discuss future approaches towards optimizing individualized therapeutic benefits. Although quantitative MRI markers are in their infancy for clinical purposes in movement disorder treatments, structural features obtained from MRI offer the powerful potential to identify candidates who are more likely to benefit from deep brain stimulation and provide insight into the complexity of disorder pathophysiology.

Project description:Introduction: Although the benefit in motor symptoms for well-selected patients with deep brain stimulation (DBS) has been established, cognitive declines associated with DBS can produce suboptimal clinical responses. Small decrements in cognition can lead to profound effects on quality of life. The growth of indications, the expansion of surgical targets, the increasing complexity of devices, and recent changes in stimulation paradigms have all collectively drawn attention to the need for re-evaluation of DBS related cognitive outcomes. Methods: To address the impact of cognitive changes following DBS, we performed a literature review using PubMed. We searched for articles focused on DBS and cognition. We extracted information about the disease, target, number of patients, assessment of time points, cognitive battery, and clinical outcomes. Diseases included were dystonia, Tourette syndrome (TS), essential tremor (ET), and Parkinson's disease (PD). Results: DBS was associated with mild cognitive issues even when rigorous patient selection was employed. Dystonia studies reported stable or improved cognitive scores, however one study using reliable change indices indicated decrements in sustained attention. Additionally, DBS outcomes were convoluted with changes in medication dose, alleviation of motor symptoms, and learning effects. In the largest, prospective TS study, an improvement in attentional skills was noted, whereas smaller studies reported variable declines across several cognitive domains. Although, most studies reported stable cognitive outcomes. ET studies largely demonstrated deficits in verbal fluency, which had variable responses depending on stimulation setting. Recently, studies have focused beyond the ventral intermediate nucleus, including the post-subthalamic area and zona incerta. For PD, the cognitive results were heterogeneous, although deficits in verbal fluency were consistent and related to the micro-lesion effect. Conclusion: Post-DBS cognitive issues can impact both motor and quality of life outcomes. The underlying pathophysiology of cognitive changes post-DBS and the identification of pathways underpinning declines will require further investigation. Future studies should employ careful methodological designs. Patient specific analyses will be helpful to differentiate the effects of medications, DBS and the underlying disease state, including disease progression. Disease progression is often an underappreciated factor that is important to post-DBS cognitive issues.

Dataset Information

A Comprehensive Review of Brain Connectomics and Imaging to Improve Deep Brain Stimulation Outcomes.

Publications

A Comprehensive Review of Brain Connectomics and Imaging to Improve Deep Brain Stimulation Outcomes.

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