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The Ventral Intermediate Nucleus Differently Modulates Subtype-Related Networks in Parkinson's Disease.

ABSTRACT: Background: Posture instability gait difficulty-dominant (PIGD) and tremor-dominant (TD) are two subtypes of Parkinson's disease (PD). The thalamus is involved in the neural circuits of both subtypes. However, which subregion of the thalamus has an influence on the PD subtypes remains unclear. Objective: To explore the core subregion of the thalamus showing a significant influence on the PD subtypes and its directional interaction between the PD subtypes. Methods: A total of 79 PD patients (43 TD and 36 PIGD) and 31 normal controls (NC) were enrolled, and the gray matter volume and perfusion characteristics in the thalamus were compared between the three groups. The subregion of the thalamus with significantly different perfusion and volume among three groups was used as the seed of a Granger causality analysis (GCA) to compare the causal connectivity between different subtypes. Results: Perfusion with an increased gradient among the three groups (TD > PIGD > NC) in the bilateral ventral intermediate nucleus (Vim) was observed, which was positively correlated with the clinical tremor scores. The GCA revealed that TD patients had enhanced causal connectivity from the bilateral Vim to the bilateral paracentral gyrus, M1 and the cerebellum compared with the NC group, while the PIGD subtype revealed an increased causal connectivity from the bilateral Vim to the bilateral premotor cortex (preM) and putamen. Additionally, there were positive correlations between the tremor scores and a causal connectivity from the Vim to the cerebellum. The connectivity from the right Vim to the right preM and the right putamen was positively correlated with the PIGD scores. Conclusion: This multilevel analysis showed that the Vim had a significant influence on the PD subtypes and that it differentially mediated the TD and PIGD-related causal connectivity pattern in PD.

SUBMITTER: Zeng Q

PROVIDER: S-EPMC6421280 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Ventral Intermediate Nucleus Differently Modulates Subtype-Related Networks in Parkinson's Disease.

Zeng Qiaoling Q Guan Xiaojun X Guo Tao T Law Yan Lun Jason C F JCF Zhou Cheng C Luo Xiao X Shen Zhujing Z Huang Peiyu P Zhang Minming M Cheng Guanxun G

Frontiers in neuroscience 20190311

Background: Posture instability gait difficulty-dominant (PIGD) and tremor-dominant (TD) are two subtypes of Parkinson's disease (PD). The thalamus is involved in the neural circuits of both subtypes. However, which subregion of the thalamus has an influence on the PD subtypes remains unclear. Objective: To explore the core subregion of the thalamus showing a significant influence on the PD subtypes and its directional interaction between the PD subtypes. Methods: A total of ...[more]

PMID: 30914916

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Project description:BackgroundThe ventral intermediate nucleus of the thalamus is not readily visible on structural magnetic resonance imaging. Therefore, a method for its visualization for stereotactic targeting is desirable.ObjectiveThe objective of this study was to define a tractography-based methodology for the stereotactic targeting of the ventral intermediate nucleus.MethodsThe lateral and posterior borders of the ventral intermediate nucleus were defined by tracking the pyramidal tract and medial lemniscus, respectively. A thalamic seed was then created 3?mm medial and anterior to these borders, and its structural connections were analyzed. The application of this method was assessed in an imaging cohort of 14 tremor patients and 15 healthy controls, in which we compared the tractography-based targeting to conventional targeting. In a separate surgical cohort (3 tremor and 3 tremor-dominant Parkinson's disease patients), we analyzed the accuracy of this method by correlating it with intraoperative neurophysiology.ResultsTractography of the thalamic seed revealed the tracts corresponding to cerebellar input and motor cortical output fibers. The tractography-based target was more lateral (12.5 [1.2] mm vs 11.5?mm for conventional targeting) and anterior (8.5 [1.1] mm vs 6.7 [0.3] mm, anterior to the posterior commissure). In the surgical cohort, the Euclidian distance between the ventral intermediate nucleus identified by tractography and the surgical target was 1.6 [1.1] mm. The locations of the sensory thalamus, lemniscus, and pyramidal tracts were concordant within <1?mm between tractography and neurophysiology.InterpretationThe tractography-based methodology for identification of the ventral intermediate nucleus is accurate and useful. This method may be used to improve stereotactic targeting in functional neurosurgery procedures. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Project description:Ventral intermediate thalamic deep brain stimulation is a standard therapy for the treatment of medically refractory essential tremor and tremor-dominant Parkinson's disease. Despite the therapeutic benefits, the mechanisms of action are varied and complex, and the pathophysiology and genesis of tremor remain unsubstantiated. This intraoperative study investigated the effects of high frequency microstimulation on both neuronal firing and tremor suppression simultaneously. In each of nine essential tremor and two Parkinson's disease patients who underwent stereotactic neurosurgery, two closely spaced (600 µm) microelectrodes were advanced into the ventral intermediate nucleus. One microelectrode recorded action potential firing while the adjacent electrode delivered stimulation trains at 100 Hz and 200 Hz (2-5 s, 100 µA, 150 µs). A triaxial accelerometer was used to measure postural tremor of the contralateral hand. At 200 Hz, stimulation led to 68 ± 8% (P < 0.001) inhibition of neuronal firing and a 53 ± 5% (P < 0.001) reduction in tremor, while 100 Hz reduced firing by 26 ± 12% (not significant) with a 17 ± 6% (P < 0.05) tremor reduction. The degree of cell inhibition and tremor suppression were significantly correlated (P < 0.001). We also found that the most ventroposterior stimulation sites, closest to the border of the ventral caudal nucleus, had the best effect on tremor. Finally, prior to the inhibition of neuronal firing, microstimulation caused a transient driving of neuronal activity at stimulus onset (61% of sites), which gave rise to a tremor phase reset (73% of these sites). This was likely due to activation of the excitatory glutamatergic cortical and cerebellar afferents to the ventral intermediate nucleus. Temporal characteristics of the driving responses (duration, number of spikes, and onset latency) significantly differed between 100 Hz and 200 Hz stimulation trains. The subsequent inhibition of neuronal activity was likely due to synaptic fatigue. Thalamic neuronal inhibition seems necessary for tremor reduction and may function in effect as a thalamic filter to uncouple thalamo-cortical from cortico-spinal reflex loops. Additionally, our findings shed light on the gating properties of the ventral intermediate nucleus within the cerebello-thalamo-cortical tremor network, provide insight for the optimization of deep brain stimulation technologies, and may inform controlled clinical studies for assessing optimal target locations for the treatment of tremor.

Project description:There are many documented sex differences in the clinical course, symptom expression profile, and treatment response of Parkinson's disease, creating additional challenges for patient management. Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson's disease, the effects of sex on treatment outcome are still unclear. The aim of this retrospective observational study, was to examine sex differences in motor symptoms, non-motor symptoms, and quality of life after subthalamic nucleus deep brain stimulation. Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson's disease undergoing subthalamic nucleus deep brain stimulation aged 63.00 ± 8.01 years (55 men and 35 women). Outcomes of clinical evaluations were compared between sexes via a Student's t-test and within sex via a paired-sample t-test, and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex. We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation. Restless legs syndrome was alleviated to a greater extent in men than in women. Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation. Furthermore, Hoehn-Yahr stage was positively correlated with the treatment response in men, while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women. In conclusion, women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms, non-motor symptoms, and quality of life. We found sex-specific factors, i.e., Hoehn-Yahr stage and levodopa equivalent dose, that were related to motor improvements. These findings may help to guide subthalamic nucleus deep brain stimulation patient selection, prognosis, and stimulation programming for optimal therapeutic efficacy in Parkinson's disease.

Project description:BackgroundGait impairments are characteristic motor manifestations and significant predictors of poor quality of life in Parkinson's disease (PD). Neuroimaging biomarkers for gait impairments in PD could facilitate effective interventions to improve these symptoms and are highly warranted.ObjectiveThe aim of this study was to identify neural networks of discrete gait impairments in PD.MethodsFifty-five participants with early-stage PD and 20 age-matched healthy volunteers underwent quantitative gait assessment deriving 12 discrete spatiotemporal gait characteristics and [18 F]-2-fluoro-2-deoxyglucose-positron emission tomography measuring resting cerebral glucose metabolism. A multivariate spatial covariance approach was used to identify metabolic brain networks that were related to discrete gait characteristics in PD.ResultsIn PD, we identified two metabolic gait-related covariance networks. The first correlated with mean step velocity and mean step length (pace gait network), which involved relatively increased and decreased metabolism in frontal cortices, including the dorsolateral prefrontal and orbital frontal, insula, supplementary motor area, ventrolateral thalamus, cerebellum, and cuneus. The second correlated with swing time variability and step time variability (temporal variability gait network), which included relatively increased and decreased metabolism in sensorimotor, superior parietal cortex, basal ganglia, insula, hippocampus, red nucleus, and mediodorsal thalamus. Expression of both networks was significantly elevated in participants with PD relative to healthy volunteers and were not related to levodopa dosage or motor severity.ConclusionsWe have identified two novel gait-related brain networks of altered glucose metabolism at rest. These gait networks could serve as a potential neuroimaging biomarker of gait impairments in PD and facilitate development of therapeutic strategies for these disabling symptoms. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dataset Information

The Ventral Intermediate Nucleus Differently Modulates Subtype-Related Networks in Parkinson's Disease.

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The Ventral Intermediate Nucleus Differently Modulates Subtype-Related Networks in Parkinson's Disease.

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