Connectivity correlates to predict essential tremor deep brain stimulation outcome: Evidence for a common treatment pathway.
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ABSTRACT: Background and purpose
Deep brain stimulation (DBS) is the most common surgical treatment for essential tremor (ET), yet there is variation in outcome and stimulation targets. This study seeks to consolidate proposed stimulation "sweet spots," as well as assess the value of structural connectivity in predicting treatment outcomes.Materials and methods
Ninety-seven ET individuals with unilateral thalamic DBS were retrospectively included. Using normative brain connectomes, structural connectivity measures were correlated with the percentage improvement in contralateral tremor, based on the Fahn-Tolosa-Marin tremor rating scale (TRS), after parameter optimization (range 3.1-12.9 months) using a leave-one-out cross-validation in 83 individuals. The predictive feature map was used for cross-validation in a separate cohort of 14 ET individuals treated at another center. Lastly, estimated volumes of tissue activated (VTA) were used to assess a treatment "sweet spot," which was compared to seven previously reported stimulation sweet spots and their relationship to the tract identified by the predictive feature map.Results
In the training cohort, structural connectivity between the VTA and dentato-rubro-thalamic tract (DRTT) correlated with contralateral tremor improvement (R = 0.41; p < 0.0001). The same connectivity profile predicted outcomes in a separate validation cohort (R = 0.59; p = 0.028). The predictive feature map represented the anatomical course of the DRTT, and all seven analyzed sweet spots overlapped the predictive tract (DRTT).Conclusions
Our results strongly support the possibility that structural connectivity is a predictor of contralateral tremor improvement in ET DBS. The results suggest the future potential for a patient-specific functionally based surgical target. Finally, the results showed convergence in "sweet spots" suggesting the importance of the DRTT to the outcome.
SUBMITTER: Middlebrooks EH
PROVIDER: S-EPMC8503569 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionThalamic deep brain stimulation (DBS) provides excellent tremor control in most patients with essential tremor (ET). However, not all tremor patients show clinically significant improvement after DBS surgery. Currently, there is no reliable clinical or instrument-based measure to predict how patients respond to DBS. Therefore, we set out to provide a method for tremor outcome prediction prior to surgery.MethodsWe retrospectively analysed quantitative tremor data collected with inertial measurement units (IMU) in 13 patients who underwent DBS surgery in the ventral intermediate nucleus of the thalamus (VIM). All patients were diagnosed with either ET or ET-plus according to current diagnostic criteria of the movement disorder society. We used linear and logistic regression models to evaluate the influence of different tremor characteristics on tremor outcome.ResultsWe found that the ratio between the amplitude of the first overtone and the amplitude of the fundamental frequency, denoted as the Harmonic Index, has a significant influence on tremor reduction after DBS surgery. This measure shows a strong correlation with the post-operative improvement of tremor outcome based on the Whiget Tremor Rating Scale.ConclusionBased on these findings, we propose a novel approach to predict tremor outcome after DBS surgery. Quantitative tremor assessment adds to the preoperative prediction of DBS response and might therefore have a relevant clinical impact in the management of patients suffering from pharmacoresistant tremor.
| S-EPMC8298798 | biostudies-literature
Project description:The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.
| S-EPMC5790021 | biostudies-literature
Project description:Background:Essential tremor (ET) is a common movement disorder characterized by kinetic and postural tremor in the upper extremities and frequently in the midline. Persons with ET often also exhibit gait ataxia. Previous studies have observed associations between midline tremor severity and gait ataxia in persons with ET, suggesting a common pathophysiology distinct from that of upper extremity tremor. However, a causal link between midline tremor and gait impairment has not been established. Methods:We investigated tremor and gait in 24 persons with ET before and after implantation of unilateral deep brain stimulation into the ventralis intermedius nucleus of the thalamus. Results:Stimulation significantly improved tremor in the targeted upper extremity and midline. However, gait was unaffected at the cohort level. Furthermore, improvement in midline tremor was not significantly associated with gait improvement. Discussion:These findings revealed that midline tremor and gait impairment may be dissociable in persons with ET.
| S-EPMC6744814 | biostudies-literature
Project description:ObjectiveTo create probabilistic stimulation maps (PSMs) of deep brain stimulation (DBS) effects on tremor suppression and stimulation-induced side-effects in patients with essential tremor (ET).MethodMonopolar reviews from 16 ET-patients which consisted of over 600 stimulation settings were used to create PSMs. A spherical model of the volume of neural activation was used to estimate the spatial extent of DBS for each setting. All data was pooled and voxel-wise statistical analysis as well as nonparametric permutation testing was used to confirm the validity of the PSMs.ResultsPSMs showed tremor suppression to be more pronounced by stimulation in the zona incerta (ZI) than in the ventral intermediate nucleus (VIM). Paresthesias and dizziness were most commonly associated with stimulation in the ZI and surrounding thalamic nuclei.DiscussionOur results support the assumption, that the ZI might be a very effective target for tremor suppression. However stimulation inside the ZI and in its close vicinity was also related to the occurrence of stimulation-induced side-effects, so it remains unclear whether the VIM or the ZI is the overall better target. The study demonstrates the use of PSMs for target selection and evaluation. While their accuracy has to be carefully discussed, they can improve the understanding of DBS effects and can be of use for other DBS targets in the therapy of neurological or psychiatric disorders as well. Furthermore they provide a priori information about expected DBS effects in a certain region and might be helpful to clinicians in programming DBS devices in the future.
| S-EPMC5144752 | biostudies-literature
Project description:Background:DBS in the ventral intermediate nucleus (VIM) of the thalamus has been a revolutionary treatment for patients with essential tremor (ET) by reducing tremor. Unfortunately, some patients develop habituation to DBS and thus experience reduced efficacy and loss of tremor control. There are no standardized methods of addressing habituation to DBS. We propose alternating stimulation patterns as a way to reduce habituation. Methods:This was a randomized, placebo-controlled trial for patients with VIM DBS for ET. Patients were randomized to either experimental treatment arm of alternating stimulation patterns on a weekly basis or standard care arm of continuous stimulation settings for 12 weeks. Primary outcome was change in the performance subscale of The Essential Tremor Rating Assessment Scale (TETRAS), which was performed at initial visit and 12-week follow-up. Secondary outcome included change in the activities of daily living subscale of TETRAS. Results:Twenty-two patients were enrolled in the trial, and 16 were analyzed at follow-up. Experimental treatment subjects displayed sustained tremor control compared to standard care, as measured by the change in TETRAS performance subscale (-0.6 vs. 6.7 point change, respectively) with a 7.3 difference between the arms (P?=?0.006). Conclusion:Alternating stimulation patterns on a weekly basis for ET patients with VIM DBS reduced habituation in this pilot study. This study suggests that exposure to different stimulation groups may maintain better tremor control compared to constant stimulation parameters.
| S-EPMC6277363 | biostudies-literature
Project description:ObjectiveDeep brain stimulation is a treatment for medically refractory essential tremor. To improve the therapy, closed-loop approaches are designed to deliver stimulation according to the system's state, which is constantly monitored by recording a pathological signal associated with symptoms (e.g. brain signal or limb tremor). Since the space of possible closed-loop stimulation strategies is vast and cannot be fully explored experimentally, how to stimulate according to the state should be informed by modeling. A typical modeling goal is to design a stimulation strategy that aims to maximally reduce the Hilbert amplitude of the pathological signal in order to minimize symptoms. Isostables provide a notion of amplitude related to convergence time to the attractor, which can be beneficial in model-based control problems. However, how isostable and Hilbert amplitudes compare when optimizing the amplitude response to stimulation in models constrained by data is unknown.ApproachWe formulate a simple closed-loop stimulation strategy based on models previously fitted to phase-locked deep brain stimulation data from essential tremor patients. We compare the performance of this strategy in suppressing oscillatory power when based on Hilbert amplitude and when based on isostable amplitude. We also compare performance to phase-locked stimulation and open-loop high-frequency stimulation.Main resultsFor our closed-loop phase space stimulation strategy, stimulation based on isostable amplitude is significantly more effective than stimulation based on Hilbert amplitude when amplitude field computation time is limited to minutes. Performance is similar when there are no constraints, however constraints on computation time are expected in clinical applications. Even when computation time is limited to minutes, closed-loop phase space stimulation based on isostable amplitude is advantageous compared to phase-locked stimulation, and is more efficient than high-frequency stimulation.SignificanceOur results suggest a potential benefit to using isostable amplitude more broadly for model-based optimization of stimulation in neurological disorders.
| S-EPMC7610712 | biostudies-literature
Project description:BackgroundThe ventral intermediate nucleus (VIM) is the target of choice for Essential Tremor (ET) deep brain stimulation (DBS). Renewed interest in caudal zona incerta (cZI) stimulation for tremor control has recently emerged and some groups believe this approach may address long-term reduction of benefit seen with VIM-DBS.ObjectivesTo compare clinical outcomes and DBS programming in the long-term between VIM and cZI neurostimulation in ET-DBS patients.Materials and methodsA retrospective review of 53 DBS leads from 47 patients was performed. Patients were classified into VIM or cZI groups according to the location of the activated DBS contact. Demographics, DBS settings, and Tremor Rating Scale scores were compared between groups at baseline and yearly follow-up to 4 years after DBS. Student t-tests and analysis of variance (ANOVA) were used to compare variables between groups.ResultsRelative to baseline, an improvement in ON-DBS tremor scores was observed in both groups from 6 months to 4 years post-DBS (p < 0.05). Although improvement was still significant at 4 years, scores from month 6 to 2 years were comparable between groups but at 3 and 4 years post-DBS the outcome was better in the VIM group (p < 0.01). Stimulation settings were similar across groups, although we found a lower voltage in the VIM group at 3 years post-DBS.ConclusionsMore ventral DBS contacts in the cZI region do improve tremor, however, VIM-DBS provided better long-term outcomes. Randomized controlled trials comparing cZI vs VIM targets should confirm these results.
| S-EPMC6174382 | biostudies-literature
Project description:BackgroundHigh-frequency thalamic stimulation is an effective therapy for essential tremor, which mainly affects voluntary movements and/or sustained postures. However, continuous stimulation may deliver unnecessary current to the brain due to the intermittent nature of the tremor.ObjectiveWe proposed to close the loop of thalamic stimulation by detecting tremor-provoking movement states using local field potentials recorded from the same electrodes implanted for stimulation, so that the stimulation is only delivered when necessary.MethodsEight patients with essential tremor participated in this study. Patient-specific support vector machine classifiers were first trained using data recorded while the patient performed tremor-provoking movements. Then, the trained models were applied in real-time to detect these movements and triggered the delivery of stimulation.ResultsUsing the proposed method, stimulation was switched on for 80.37 ± 7.06% of the time when tremor-evoking movements were present. In comparison, the stimulation was switched on for 12.71 ± 7.06% of the time when the patients were at rest and tremor-free. Compared with continuous stimulation, a similar amount of tremor suppression was achieved while only delivering 36.62 ± 13.49% of the energy used in continuous stimulation.ConclusionsThe results suggest that responsive thalamic stimulation for essential tremor based on tremor-provoking movement detection can be achieved without any requirement for external sensors or additional electrocorticography strips. Further research is required to investigate whether the decoding model is stable across time and generalizable to the variety of activities patients may engage with in everyday life. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
| S-EPMC7610625 | biostudies-literature
Project description:ObjectiveTo assess longitudinal tremor outcomes with ventral intermediate nucleus deep brain stimulation (VIM DBS) in patients with dystonic tremor (DT) and to compare with DBS outcomes in essential tremor (ET).MethodsWe retrospectively investigated VIM DBS outcomes for 163 patients followed at our center diagnosed with either DT or ET. The Fahn-Tolosa-Marin tremor rating scale (TRS) was used to assess change in tremor and activities of daily living (ADL) at 6 months, 1 year, 2-3 years, 4-5 years, and ≥6 years after surgery.ResultsTwenty-six patients with DT and 97 patients with ET were analyzed. Compared to preoperative baseline, there were significant improvements in TRS motor up to 4-5 years (52.2%; p = 0.032) but this did not reach statistical significance at ≥6 years (46.0%, p = 0.063) in DT, which was comparable to the outcomes in ET. While the improvements in the upper extremity tremor, head tremor, and axial tremor were also comparable between DT and ET throughout the follow-up, the ADL improvements in DT were lost at 2-3 years follow-up.ConclusionOverall, tremor control with VIM DBS in DT and ET was comparable and remained sustained at long term likely related to intervention at the final common node in the pathologic tremor network. However, the long-term ADL improvements in DT were not sustained, possibly due to inadequate control of concomitant dystonia symptoms. These findings from a large cohort of DT indicate that VIM targeting is reasonable if the tremor is considerably more disabling than the dystonic features.Classification of evidenceThis study provides Class IV evidence that VIM DBS improves tremor in patients with DT or ET.
| S-EPMC7238918 | biostudies-literature
Project description:Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson's disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal modelling revealed a correlation between therapeutic effectiveness and attenuated within-region inhibitory connectivity in cerebellum. Finally, specific subregions of sensorimotor cortex were identified in which deep brain stimulation-evoked activation correlated with the presence of unwanted paraesthesias. These results suggest that thalamic deep brain stimulation in tremor likely exerts its effects through modulation of both olivocerebellar and thalamocortical circuits. In addition, our findings indicate that deep brain stimulation-evoked functional activation maps obtained intraoperatively may contain predictive information pertaining to the therapeutic and adverse effects induced by deep brain stimulation.media-1vid110.1093/brain/aww145_video_abstractaww145_video_abstract.
| S-EPMC4958905 | biostudies-literature