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Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) can markedly reduce muscle rigidity in people with Parkinson's disease (PD); however, the mechanisms mediating this effect are poorly understood. Computational modeling of DBS provides a method to estimate the relative contributions of neural pathway activations to changes in outcomes. In this study, we generated patient-specific biophysical models of GPi DBS (derived from individual 7T MRI) - including pallidal efferent, putamenal efferent and internal capsule pathways - to investigate how activation of neural pathways contributed to changes in forearm rigidity in PD. Ten individuals (17 arms) were tested off medication under four conditions: off stimulation, on clinically optimized stimulation, and on stimulation specifically targeting the dorsal GPi or ventral GPi. Quantitative measures of forearm rigidity, with and without a contralateral activation maneuver, were obtained using a robotic manipulandum. Clinically optimized GPi DBS settings significantly reduced forearm rigidity (p < 0.001), which aligned with GPi efferent fiber activation. The model demonstrated that GPi efferent axons could be activated at any location along the GPi dorsal-ventral axis. These results provide evidence that rigidity reduction produced by GPi DBS is mediated by preferential activation of GPi efferents to the thalamus, likely leading to a reduction in excitability of the muscle stretch reflex via overdriving pallidofugal output.
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BACKGROUND: The anterior limb of the internal capsule (ALIC) is a white matter structure connecting the prefrontal cortex (PFC) to the brainstem, thalamus, and subthalamic nucleus. It is a target for deep brain stimulation (DBS) for obsessive-compulsive disorder. There is strong interest in improving DBS targeting by using diffusion tractography to reconstruct and target specific ALIC fiber pathways, but this methodology is susceptible to errors and lacks validation. To address these limitations, we developed a novel diffusion tractography pipeline that generates reliable and biologically validated ALIC white matter reconstructions. METHODS: Following algorithm development and refinement, we analyzed 43 control subjects each with 2 sets of 3T MRI data and a subset of 5 controls with 7T data from the Human Connectome Project. We generated 22 segmented ALIC fiber bundles (11 per hemisphere) based on prefrontal PFC regions of interest, and we analyzed the relationships among bundles. RESULTS: We successfully reproduced the topographies established by prior anatomical work using images acquired at both 3T and 7T. Quantitative assessment demonstrated significantly smaller intra-subject variability relative to inter-subject variability for both test and retest groups across all but one PFC region. We examined the overlap between fibers from different PFC regions and a response tract for obsessive-compulsive disorder deep brain stimulation, and we reconstructed the PFC hyperdirect pathway using a modified version of our pipeline. DISCUSSION: Our dMRI algorithm reliably generates biologically validated ALIC white matter reconstructions, allowing for more precise modelling of fibers for neuromodulation therapies.
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The thalamus is a centrally located and heterogeneous brain structure that plays a critical role in various sensory, motor, and cognitive processes. However, visualizing the individual subnuclei of the thalamus using conventional MRI techniques is challenging. This difficulty has posed obstacles in targeting specific subnuclei for clinical interventions such as deep brain stimulation (DBS). In this paper, we present DiMANI, a novel method for directly visualizing the thalamic subnuclei using diffusion MRI (dMRI). The DiMANI contrast is computed by averaging, voxelwise, diffusion-weighted volumes enabling the direct distinction of thalamic subnuclei in individuals. We evaluated the reproducibility of DiMANI through multiple approaches. First, we utilized a unique dataset comprising 8 scans of a single participant collected over a 3-year period. Secondly, we quantitatively assessed manual segmentations of thalamic subnuclei for both intra-rater and inter-rater reliability. Thirdly, we qualitatively correlated DiMANI imaging data from several patients with Essential Tremor with the localization of implanted DBS electrodes and clinical observations. Lastly, we demonstrated that DiMANI can provide similar features at 3T and 7T MRI, using varying numbers of diffusion directions. Our results establish that DiMANI is a reproducible and clinically relevant method to directly visualize thalamic subnuclei. This has significant implications for the development of new DBS targets and the optimization of DBS therapy.
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Objective: To characterize how the proximity of deep brain stimulation (DBS) active contact locations relative to the cerebellothalamic tract (CTT) affect clinical outcomes in patients with essential tremor (ET). Background: DBS is an effective treatment for refractory ET. However, the role of the CTT in mediating the effect of DBS for ET is not well characterized. 7-Tesla (T) MRI-derived tractography provides a means to measure the distance between the active contact and the CTT more precisely. Methods: A retrospective review was conducted of 12 brain hemispheres in 7 patients at a single center who underwent 7T MRI prior to ventral intermediate nucleus (VIM) DBS lead placement for ET following failed medical management. 7T-derived diffusion tractography imaging was used to identify the CTT and was merged with the post-operative CT to calculate the Euclidean distance from the active contact to the CTT. We collected optimized stimulation parameters at initial programing, 1- and 2-year follow up, as well as a baseline and postoperative Fahn-Tolosa-Marin (FTM) scores. Results: The therapeutic DBS current mean (SD) across implants was 1.8 mA (1.8) at initial programming, 2.5 mA (0.6) at 1 year, and 2.9 mA (1.1) at 2-year follow up. Proximity of the clinically-optimized active contact to the CTT was 3.1 mm (1.2), which correlated with lower current requirements at the time of initial programming (R2 = 0.458, p = 0.009), but not at the 1- and 2-year follow up visits. Subjects achieved mean (SD) improvement in tremor control of 77.9% (14.5) at mean follow-up time of 22.2 (18.9) months. Active contact distance to the CTT did not predict post-operative tremor control at the time of the longer term clinical follow up (R2 = -0.073, p = 0.58). Conclusion: Active DBS contact proximity to the CTT was associated with lower therapeutic current requirement following DBS surgery for ET, but therapeutic current was increased over time. Distance to CTT did not predict the need for increased current over time, or longer term post-operative tremor control in this cohort. Further study is needed to characterize the role of the CTT in long-term DBS outcomes.
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BACKGROUND: While deep brain stimulation (DBS) therapy can be effective at suppressing tremor in individuals with medication-refractory Essential Tremor, patient outcome variability remains a significant challenge across centers. Proximity of active electrodes to the cerebellothalamic tract (CTT) is likely important in suppressing tremor, but how tremor control and side effects relate to targeting parcellations within the CTT and other pathways in and around the ventral intermediate (VIM) nucleus of thalamus remain unclear. METHODS: Using ultra-high field (7T) MRI, we developed high-dimensional, subject-specific pathway activation models for 23 directional DBS leads. Modeled pathway activations were compared with post-hoc analysis of clinician-optimized DBS settings, paresthesia thresholds, and dysarthria thresholds. Mixed-effect models were utilized to determine how the six parcellated regions of the CTT and how six other pathways in and around the VIM contributed to tremor suppression and induction of side effects. RESULTS: The lateral portion of the CTT had the highest activation at clinical settings (p < 0.05) and a significant effect on tremor suppression (p < 0.001). Activation of the medial lemniscus and posterior-medial CTT was significantly associated with severity of paresthesias (p < 0.001). Activation of the anterior-medial CTT had a significant association with dysarthria (p < 0.05). CONCLUSIONS: This study provides a detailed understanding of the fiber pathways responsible for therapy and side effects of DBS for Essential Tremor, and suggests a model-based programming approach will enable more selective activation of lateral fibers within the CTT.
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Estimulação Encefálica Profunda , Tremor Essencial , Humanos , Tremor Essencial/terapia , Tremor Essencial/etiologia , Tremor/terapia , Disartria/etiologia , Disartria/terapia , Estimulação Encefálica Profunda/métodos , Tálamo , Parestesia/etiologia , Resultado do TratamentoRESUMO
We present a method for suppressing motion artifacts in anatomical magnetic resonance acquisitions. Our proposed technique, termed MOTOR-MRI, can recover and salvage images which are otherwise heavily corrupted by motion induced artifacts and blur which renders them unusable. Contrary to other techniques, MOTOR-MRI operates on the reconstructed images and not on k-space data. It relies on breaking the standard acquisition protocol into several shorter ones (while maintaining the same total acquisition time) and subsequent efficient aggregation in Fourier space of locally sharp and consistent information among them, producing a sharp and motion mitigated image. We demonstrate the efficacy of the technique on T2-weighted turbo spin echo magnetic resonance brain scans with severe motion corruption from both 3 T and 7 T scanners and show significant qualitative and quantitative improvement in image quality. MOTOR-MRI can operate independently, or in conjunction with additional motion correction methods.
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Imageamento por Ressonância Magnética , HumanosRESUMO
Freezing of gait (FOG) is a particularly debilitating symptom of Parkinson's disease (PD) and is often refractory to treatment. A striking feature of FOG is that external sensory cues can be used to overcome freezing and improve gait. Local field potentials (LFPs) recorded from the subthalamic nucleus (STN) and globus pallidus (GP) show that beta-band power modulates with gait phase. In the STN, beta-band oscillations are modulated by external cues, but it is unknown if this relationship holds in the globus pallidus (GP). Here we report LFP data recorded from the left GP, using a Medtronic PC + S device, in a 68-year-old man with PD and FOG during treadmill walking. A "stepping stone" task was used during which stepping was cued using visual targets of constant color or targets that unpredictably changed color, requiring a step length adjustment. Gait performance was quantified using measures of treadmill ground reaction forces and center of pressure and body kinematics from video monitoring. Beta-band power (12-30 Hz) and number of freezing episodes were measured. Cues which unpredictably changed color improved FOG more than conventional cues and were associated with greater modulation of beta-band power in phase with gait. This preliminary finding suggests that cueing-induced improvement of FOG may relate to beta-band modulation.
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Deep brain stimulation (DBS) surgery has been shown to dramatically improve the quality of life for patients with various motor dysfunctions, such as those afflicted with Parkinson's disease (PD), dystonia, and essential tremor (ET), by relieving motor symptoms associated with such pathologies. The success of DBS procedures is directly related to the proper placement of the electrodes, which requires the ability to accurately detect and identify relevant target structures within the subcortical basal ganglia region. In particular, accurate and reliable segmentation of the globus pallidus (GP) interna is of great interest for DBS surgery for PD and dystonia. In this study, we present a deep-learning based neural network, which we term GP-net, for the automatic segmentation of both the external and internal segments of the globus pallidus. High resolution 7 Tesla images from 101 subjects were used in this study; GP-net is trained on a cohort of 58 subjects, containing patients with movement disorders as well as healthy control subjects. GP-net performs 3D inference in a patient-specific manner, alleviating the need for atlas-based segmentation. GP-net was extensively validated, both quantitatively and qualitatively over 43 test subjects including patients with movement disorders and healthy control and is shown to consistently produce improved segmentation results compared with state-of-the-art atlas-based segmentations. We also demonstrate a postoperative lead location assessment with respect to a segmented globus pallidus obtained by GP-net.
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Aprendizado Profundo , Globo Pálido/anatomia & histologia , Globo Pálido/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Transtornos dos Movimentos/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Interpretação de Imagem Assistida por Computador/normas , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/patologia , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND: The introduction of intracranial air (ICA) during deep brain stimulation (DBS) surgery is thought to have a negative influence on targeting and clinical outcomes. OBJECTIVE: To investigate ICA volumes following surgery and other patient-specific factors as potential variables influencing translocation of the DBS electrode and proximal lead bowing. METHODS: High-resolution postoperative computed tomography scans (≤1.0 mm resolution in all directions) within 24 h following DBS surgery and 4-6 weeks of follow-up were acquired. A total of 50 DBS leads in 33 patients were available for analysis. DBS leads included Abbott/St. Jude Medical InfinityTM, Boston Scientific VerciseTM, and Medtronic 3389TM. RESULTS: Both ICA volume and anatomical target were significantly associated with measures of DBS electrode translocation. ICA volume and DBS lead model were found to be significant predictors of proximal lead bowing. Measures of proximal lead bowing and translocation along the electrode trajectory for the Medtronic 3389TM DBS lead were significantly larger than measures for the Abbott/St. Jude Medical InfinityTM and Boston Scientific VerciseTM DBS leads. CONCLUSION: The association between ICA volume and translocation of the DBS electrode is small in magnitude and not clinically relevant for DBS cases within a normal range of postoperative subdural air volumes. Differences in proximal lead bowing observed between DBS leads may reflect hardware engineering subtleties in the construction of DBS lead models.