Dataset Information

Anterior Thalamic Deep Brain Stimulation: Functional Activation Patterns in a Large Animal Model.

ABSTRACT: Deep brain stimulation (DBS) of the anterior thalamic nucleus (ATN) exerts its effects by modulating neural circuits involved in seizures. However, these networks remain incompletely characterized.Investigate the effects of ATN DBS on network activity in a large animal model using 3-T fMRI.Anesthetized swine underwent ATN DBS using stimulation parameters applied in the Stimulation of the Anterior Thalamus for the Treatment of Epilepsy (SANTE) trial. Stimulation amplitude, frequency, and temporal paradigm were varied and the resulting blood oxygen level-dependent signal was measured.ATN DBS resulted in activation within temporal, prefrontal, and sensorimotor cortex. An amplitude-dependent increase in cluster volume was observed at 60?Hz and 145?Hz stimulation.ATN DBS in swine induced parameter-dependent activation in cortical regions including but not limited to the Papez circuit. These findings may hold clinical implications for treatment of epilepsy in patients with temporal or extratemporal seizure foci.

SUBMITTER: Gibson WS

PROVIDER: S-EPMC5007150 | biostudies-literature | 2016 Sep-Oct

REPOSITORIES: biostudies-literature

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Anterior Thalamic Deep Brain Stimulation: Functional Activation Patterns in a Large Animal Model.

Gibson William S WS Ross Erika K EK Han Seong Rok SR Van Gompel Jamie J JJ Min Hoon-Ki HK Lee Kendall H KH

Brain stimulation 20160415 5

<h4>Background</h4>Deep brain stimulation (DBS) of the anterior thalamic nucleus (ATN) exerts its effects by modulating neural circuits involved in seizures. However, these networks remain incompletely characterized.<h4>Objective</h4>Investigate the effects of ATN DBS on network activity in a large animal model using 3-T fMRI.<h4>Methods</h4>Anesthetized swine underwent ATN DBS using stimulation parameters applied in the Stimulation of the Anterior Thalamus for the Treatment of Epilepsy (SANTE) ...[more]

PMID: 27160467

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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.

Project description:Deep brain stimulation (DBS) is an excellent treatment for tremor and is generally thought to be reversible by turning off stimulation. For tremor, DBS is implanted in the ventrointermedius (Vim) nucleus of the thalamus, a region that relays proprioceptive information for movement sensation (kinaesthesia). Gait disturbances have been observed with bilateral Vim DBS, but the long-term effects on proprioceptive processing are unknown. We aimed to determine whether Vim DBS surgical implantation or stimulation leads to proprioceptive deficits in the upper limb. We assessed two groups of tremor subjects on measures of proprioception (kinaesthesia, position sense) and motor function using a robotic exoskeleton. In the first group (Surgery), we tested patients before and after implantation of Vim DBS, but before DBS was turned on to determine if proprioceptive deficits were inherent to tremor or caused by DBS implantation. In the second group (Stim), we tested subjects with chronically implanted Vim DBS ON and OFF stimulation. Compared to controls, there were no proprioceptive deficits before or after DBS implantation in the Surgery group. Surprisingly, those that received chronic long-term stimulation (LT-stim, 3-10 years) displayed significant proprioceptive deficits ON and OFF stimulation not present in subjects with chronic short-term stimulation (ST-stim, 0.5-2 years). LT-stim had significantly larger variability and reduced workspace area during the position sense assessment. During the kinesthetic assessment, LT-stim made significantly larger directional errors and consistently underestimated the speed of the robot, despite generating normal movement speeds during motor assessment. Chronic long-term Vim DBS may potentially disrupt proprioceptive processing, possibly inducing irreversible plasticity in the Vim nucleus and/or its network connections. Our findings in the upper limb may help explain some of the gait disturbances seen by others following Vim DBS.

Dataset Information

Anterior Thalamic Deep Brain Stimulation: Functional Activation Patterns in a Large Animal Model.

Publications

Anterior Thalamic Deep Brain Stimulation: Functional Activation Patterns in a Large Animal Model.

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