2,162 research outputs found

    Uncovering the underlying mechanisms and whole-brain dynamics of deep brain stimulation for Parkinson's disease

    Get PDF
    Deep brain stimulation (DBS) for Parkinson's disease is a highly effective treatment in controlling otherwise debilitating symptoms. Yet the underlying brain mechanisms are currently not well understood. Whole-brain computational modeling was used to disclose the effects of DBS during resting-state functional Magnetic Resonance Imaging in ten patients with Parkinson's disease. Specifically, we explored the local and global impact that DBS has in creating asynchronous, stable or critical oscillatory conditions using a supercritical bifurcation model. We found that DBS shifts global brain dynamics of patients towards a Healthy regime. This effect was more pronounced in very specific brain areas such as the thalamus, globus pallidus and orbitofrontal regions of the right hemisphere (with the left hemisphere not analyzed given artifacts arising from the electrode lead). Global aspects of integration and synchronization were also rebalanced. Empirically, we found higher communicability and coherence brain measures during DBS-ON compared to DBS-OFF. Finally, using our model as a framework, artificial in silico DBS was applied to find potential alternative target areas for stimulation and whole-brain rebalancing. These results offer important insights into the underlying large-scale effects of DBS as well as in finding novel stimulation targets, which may offer a route to more efficacious treatmentsIn this work, Gustavo Deco is supported by the ERC Advanced Grant: DYSTRUCTURE (n. 295129), by the Spanish Research Project PSI2016-75688-P and by the the European Union's Horizon 2020 research and innovation programme under grant agreement n. 720270 (HBP SGA1). Morten Kringelbach is supported by the ERC Consolidator Grant CAREGIVING (n. 615539) and the Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117). Victor M Saenger is supported by the Research Personnel Training program PSI2013-42091-P funded by the Spanish Ministry of Economy and Competitiveness.info:eu-repo/semantics/publishedVersio

    Deep brain stimulation and its effects on Parkinson disease spatiotemporal gait parameters.

    Get PDF
    Subthalamic (STN) deep brain stimulation (DBS) alleviates common appendicular PD symptoms, such as: tremor, rigidity and bradykinesia. However, the effect STN-DBS has on modulating axial gait features has not been properly quantified objectively. The purpose of the present thesis was to investigate the role STN-DBS plays in modulating specific gait features such as pace, asymmetry, variability, rhythm and postural control. It is hypothesized that axial gait function is regulated predominantly by non-dopaminergic control systems. In the acute immediate post-operative phase a surgical effect, named the microlesion effect (MLE), is thought to produce a transient improvement of appendicular and axial symptoms. It was hypothesized the MLE is a surgical effect, having a non-specific influence on both appendicular and axial symptoms. Following surgical recovery and 6 months of clinically optimized STN-DBS, it was expected that the true STN-DBS effects would be presented. It was hypothesized that STN-DBS plays an important role in the dopaminergic basal ganglia circuit and a lesser role in the non-dopaminergic system. 10 individuals with PD who were approved for STN-DBS along with 11 healthy age-matched controls were used in the study. The participants were asked to walk across a 7 metre long gait analysis carpet at a self-selected paced walk (SELF) and a fast-as-possible walk (FAST). However, in the current study we found no improvement on Unified Parkinson’s Disease Rating scale (UPDRS) appendicular scores and axial gait features at baseline, 1 week post-operation and 2 weeks post-operation. At 6 months, it was found that UPDRS scores improved for appendicular items but remained unchanged in the axial items. Furthermore, axial gait features remained unchanged in the SELF and FAST walks. Overall, axial gait function failed to improve from the MLE and STN-DBS. While the sample size was small, this finding may suggest an influence of regions outside the STN on axial function. Further analysis with more subjects should be conducted to verify the current findings

    Methodological considerations for neuroimaging in deep brain stimulation of the subthalamic nucleus in Parkinson’s disease patients

    Get PDF
    Deep brain stimulation (DBS) of the subthalamic nucleus is a neurosurgical intervention for Parkinson’s disease patients who no longer appropriately respond to drug treatments. A small fraction of patients will fail to respond to DBS, develop psychiatric and cognitive side-effects, or incur surgery-related complications such as infections and hemorrhagic events. In these cases, DBS may require recalibration, reimplantation, or removal. These negative responses to treatment can partly be attributed to suboptimal pre-operative planning procedures via direct targeting through low-field and low-resolution magnetic resonance imaging (MRI). One solution for increasing the success and efficacy of DBS is to optimize preoperative planning procedures via sophisticated neuroimaging techniques such as high-resolution MRI and higher field strengths to improve visualization of DBS targets and vasculature. We discuss targeting approaches, MRI acquisition, parameters, and post-acquisition analyses. Additionally, we highlight a number of approaches including the use of ultra-high field (UHF) MRI to overcome limitations of standard settings. There is a trade-off between spatial resolution, motion artifacts, and acquisition time, which could potentially be dissolved through the use of UHF-MRI. Image registration, correction, and post-processing techniques may require combined expertise of traditional radiologists, clinicians, and fundamental researchers. The optimization of pre-operative planning with MRI can therefore be best achieved through direct collaboration between researchers and clinicians

    Imaging the subthalamic nucleus in Parkinson’s disease

    Get PDF
    This thesis is comprised of a set of work that aims to visualize and quantify the anatomy, structural variability, and connectivity of the subthalamic nucleus (STN) with optimized neuroimaging methods. The study populations include both healthy cohorts and individuals living with Parkinson's disease (PD). PD was chosen specifically due to the involvement of the STN in the pathophysiology of the disease. Optimized neuroimaging methods were primarily obtained using ultra-high field (UHF) magnetic resonance imaging (MRI). An additional component of this thesis was to determine to what extent UHF-MRI can be used in a clinical setting, specifically for pre-operative planning of deep brain stimulation (DBS) of the STN for patients with advanced PD. The thesis collectively demonstrates that i, MRI research, and clinical applications must account for the different anatomical and structural changes that occur in the STN with both age and PD. ii, Anatomical connections involved in preparatory motor control, response inhibition, and decision-making may be compromised in PD. iii. The accuracy of visualizing and quantifying the STN strongly depends on the type of MR contrast and voxel size. iv, MRI at a field strength of 3 Tesla (T) can under certain circumstances be optimized to produce results similar to that of 7 T at the expense of increased acquisition time

    NM-MRI for treatment evaluation of Parkinson’s Disease patients

    Get PDF
    T1-weighted fast spin echo magnetic resonance imaging (MRI) sequences are able to depict neuromelanin (NM)-containing structures, such as the Substantia nigra (SN), as hyper-intense signal areas. NM-MRI can accurately discriminate Parkinson’s Disease (PD) patients from controls and could potentially be used to evaluate the effects of PD treatment - either surgery or medication. PD patients that are treated with Deep Brain Stimulation (DBS) can only undergo 1.5T MRI sequences with specific conditions that prevent the tissues surrounding the neurostimulators from overheating. However, NM-MRI sequences are usually not applied at 1.5T due to worse image quality. Nevertheless, it would be interesting to study how DBS and medication influence the NM signal as a path for a better understanding of the disease and to potentially evaluate the progression of PD after the surgical intervention. Firstly in this work, a NM-MRI sequence was adapted for scanning patients with implanted DBS systems at 1.5T. To evaluate the performance of the sequence, images were taken on the same day with 1.5T and 3T MRI systems. The contrast ratio of both sequences was evaluated and SN areas were measured resorting to a semi-automatic segmentation algorithm. The assessment of these measurements revealed a good agreement between the developed sequence and the original 3T sequence. A second study was carried out, in which SN areas of PD de novo patients were evaluated before and after two months of initiating pharmacological treatment. The median SN area tended to be increased after treatment, suggesting a potential increase of NM related to dopamine therapy. In conclusion, this work presented the first 1.5T NM-MRI sequence that enables SN area measurement of patients with implanted neurostimulators, for further investigation of this method as a diagnostic tool for assessment of disease progression and to better understand clinical effects on NM-MRI and PD itself
    • …
    corecore