Dataset Information

Tractography-Based Ventral Intermediate Nucleus Targeting: Novel Methodology and Intraoperative Validation.

ABSTRACT:

Background

The 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.

Objective

The objective of this study was to define a tractography-based methodology for the stereotactic targeting of the ventral intermediate nucleus.

Methods

The 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.

Results

Tractography 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.

Interpretation

The 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.

SUBMITTER: Sammartino F

PROVIDER: S-EPMC5089633 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Publications

Tractography-Based Ventral Intermediate Nucleus Targeting: Novel Methodology and Intraoperative Validation.

Sammartino Francesco F Krishna Vibhor V King Nicolas Kon Kam NK Lozano Andres M AM Schwartz Michael L ML Huang Yuexi Y Hodaie Mojgan M

Movement disorders : official journal of the Movement Disorder Society 20160523 8

<h4>Background</h4>The 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.<h4>Objective</h4>The objective of this study was to define a tractography-based methodology for the stereotactic targeting of the ventral intermediate nucleus.<h4>Methods</h4>The lateral and posterior borders of the ventral intermediate nucleus were defined by tracking the pyramidal ...[more]

PMID: 27214406

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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.

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Project description:Deep brain stimulation therapy is an effective symptomatic treatment for Parkinson's disease, yet the precise mechanisms responsible for its therapeutic effects remain unclear. Although the targets of deep brain stimulation are grey matter structures, axonal modulation is known to play an important role in deep brain stimulation's therapeutic mechanism. Several white matter structures in proximity to the subthalamic nucleus have been implicated in the clinical benefits of deep brain stimulation for Parkinson's disease. We assessed the connectivity patterns that characterize clinically beneficial electrodes in Parkinson's disease patients, after deep brain stimulation of the subthalamic nucleus. We evaluated 22 patients with Parkinson's disease (11 females, age 57 ± 9.1 years, disease duration 13.3 ± 6.3 years) who received bilateral deep brain stimulation of the subthalamic nucleus at the National Institutes of Health. During an initial electrode screening session, one month after deep brain stimulation implantation, the clinical benefits of each contact were determined. The electrode was localized by coregistering preoperative magnetic resonance imaging and postoperative computer tomography images and the volume of tissue activated was estimated from stimulation voltage and impedance. Brain connectivity for the volume of tissue activated of deep brain stimulation contacts was assessed using probabilistic tractography with diffusion-tensor data. Areas most frequently connected to clinically effective contacts included the thalamus, substantia nigra, brainstem and superior frontal gyrus. A series of discriminant analyses demonstrated that the strength of connectivity to the superior frontal gyrus and the thalamus were positively associated with clinical effectiveness. The connectivity patterns observed in our study suggest that the modulation of white matter tracts directed to the superior frontal gyrus and the thalamus is associated with favourable clinical outcomes and may contribute to the therapeutic effects of deep brain stimulation. Our method can be further developed to reliably identify effective deep brain stimulation contacts and aid in the programming process.

Dataset Information

Tractography-Based Ventral Intermediate Nucleus Targeting: Novel Methodology and Intraoperative Validation.

Background

Objective

Methods

Results

Interpretation

Publications

Tractography-Based Ventral Intermediate Nucleus Targeting: Novel Methodology and Intraoperative Validation.

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