Multi-institutional evaluation of deep brain stimulation targeting using probabilistic connectivity-based thalamic segmentation

Clinical article

Restricted access


Due to the lack of internal anatomical detail with traditional MR imaging, preoperative stereotactic planning for the treatment of tremor usually relies on indirect targeting based on atlas-derived coordinates. The object of this study was to preliminarily investigate the role of probabilistic tractography–based thalamic segmentation for deep brain stimulation (DBS) targeting for the treatment of tremor.


Six patients undergoing bilateral implantation of DBS electrodes in the thalamus for the treatment of upper-extremity tremor were studied. All patients underwent stereotactic surgical implantation using traditional methods (based on indirect targeting methodologies and intraoperative macrostimulation findings) that were programmed for optimal efficacy, independent of tractography-based segmentations described in this report. Connectivity-based thalamic segmentations were derived by identifying with which of 7 cortical target regions each thalamic voxel had the highest probability of connectivity. The authors retrospectively analyzed the location of the optimal contact for treatment of tremor with connectivity-based thalamic segmentations. Findings from one institution (David Geffen School of Medicine at UCLA) were validated with results from 4 patients at another institution (University of Virginia Health System).


Of 12 electrodes implanted using traditional methodologies, all but one resulted in efficacious tremor control. Connectivity-based thalamic segmentation consistently revealed discrete thalamic regions having unique connectivity patterns with distinct cortical regions. Although the authors initially hypothesized that the most efficacious DBS contact for controlling tremor would colocalize with the thalamic region most highly connected with the primary motor cortex, they instead found it to highly colocalize with those thalamic voxels demonstrating a high probability of connectivity with premotor cortex (center-to-center distance: 0.36 ± 0.55 mm). In contrast to the high degree of colocalization with optimal stimulation site, the precise localization of the premotor cortex–defined thalamic region relative to the anterior and posterior commissures was highly variable. Having defined a connectivity-based target for thalamic stimulation in a cohort of patients at David Geffen School of Medicine at UCLA, the authors validated findings in 4 patients (5 electrodes) who underwent surgery at a different institution (University of Virginia Health System) by a different surgeon.


This report identifies and provides preliminary external validation of a novel means of targeting a patient-specific therapeutic thalamic target for the treatment of tremor based on individualized analysis of thalamic connectivity patterns. This novel thalamic targeting approach is based on identifying the thalamic region with the highest probability of connectivity with premotor and supplementary motor cortices. This approach may prove to be advantageous over traditional preoperative methods of indirect targeting, providing patient-specific targets that could improve the precision, efficacy, and efficiency of deep brain stimulation surgery. Prospective evaluation and development of methodologies to make these analyses more widely available to neurosurgeons are likely warranted.

Abbreviations used in this paper: AC = anterior commissure; DBS = deep brain stimulation; DGSOM = David Geffen School of Medicine at UCLA; DT = diffusion tensor; FTM = Fahn-Tolosa-Marin; PC = posterior commissure; PMC = premotor and supplementary motor cortices; UVAHS = University of Virginia Health System.

Article Information

Address correspondence to: Nader Pouratian, M.D., Ph.D., Department of Neurosurgery, David Geffen School of Medicine at UCLA, 10945 Le Conte Avenue, Suite 2120, Los Angeles, California 90095. email:

Please include this information when citing this paper: published online August 19, 2011; DOI: 10.3171/2011.7.JNS11250.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Methods for connectivity-based thalamic segmentation. Using previously described methodology, we segmented the thalamus based on differential patterns of connectivity with 7 predefined cortical targets. A: The thalamus was manually masked in each patient. B: Cortical target masks were likewise delineated in each patient. In this figure the prefrontal (green), premotor (red), and primary motor cortex (blue) targets masks are depicted. C–E: Using probabilistic tractography, the probability of each thalamic voxel connecting with the cortical target masks is defined. Specifically, thalamic connectivity with primary motor (C, blue), premotor (D, red-yellow), and prefrontal (E, green) cortices is illustrated. F: Once probabilistic patterns of connectivity with each cortical target have been defined, thalamic voxels are assigned to a group based on the region with which they have the highest probability of connection, resulting in thalamic segmentations reminiscent of previously published reports and known thalamic nuclear organization.

  • View in gallery

    Image registration. Final electrode position after DBS implantation was determined by merging postoperative images (a CT scan in this case) with the preoperative high-resolution T1-weighted MR images using a linear transformation. Connectivity-based maps, illustrated in Fig. 1, were similarly merged into the high-resolution T1-weighted MR imaging space for intermodality comparisons.

  • View in gallery

    Efficacious contact position relative to thalamic M1 connectivity. Using probabilistic tractography, the probability of connectivity of each thalamic voxel with the anatomically defined primary motor cortex was determined. These probabilistic thalamic maps (blue overlays) and post-DBS implantation imaging (yellow overlays) were merged into a common space to compare relative position. Efficacious contact position (yellow) is consistently anterior to those voxels with the highest probability of connectivity with the primary motor cortex. Light blue indicates the highest probability of M1 connectivity; dark blue, the lower probability of M1 connectivity. Panels A–F correspond to each patient.

  • View in gallery

    Efficacious contact for thalamic stimulation colocalizes with thalamic voxels with the highest probability of connectivity with premotor and supplementary motor cortices. Using probabilistic tractography, the probability of connectivity of each thalamic voxel with the premotor cortex target mask (which includes lateral premotor and medial supplementary motor areas) was determined. These probabilistic thalamic maps (orange-yellow overlays) are illustrated for each patient (A–F) in the left column. Post-DBS implantation imaging (green overlays) were merged into a common space to compare relative position and plotted atop the thalamic probabilistic connectivity maps. Efficacious contact position (green) is consistently colocalized with those voxels with the highest probability of connectivity with the premotor cortex target mask. Yellow denotes the highest probability of PMC connectivity; red, the lower probability of PMC connectivity.

  • View in gallery

    Variability of PMC connectivity across patients in standard space. Using affine transformation to account for interpatient anatomical variability, thalamic PMC-connectivity maps were transformed into a common space, normalized, and averaged to assess the degree of interpatient spatial variability in PMC connectivity. Percentages denote an average normalized score of connectivity across patients, where 100% would indicate consistent maximal spatial concordance with respect to thalamic connectivity with premotor/supplementary motor areas. The highest score is 60%, suggesting significant interpatient variability in connectivity patterns even after anatomical differences are accounted for.

  • View in gallery

    Fiber tract projections from the thalamic region with maximal connectivity with PMC. Tractography from the thalamic region of interest (optimal target for efficacious stimulation for tremor control) demonstrates rostral projections to premotor and supplementary motor cortices and caudal projection to the cerebellum.

  • View in gallery

    External validation of colocalization of efficacious contacts and PMC connectivity maps. Four patients (A–D; 5 electrodes) were evaluated from a similar data set at UVAHS, demonstrating similar localization of efficacious contacts within thalamic areas with the highest probability of connectivity with the PMC cortical target mask. Refer to Fig. 4 for explanation of colors.



Anderson VCBurchiel KJHart MJBerk CLou JS: A randomized comparison of thalamic stimulation and lesion on self-paced finger movement in essential tremor. Neurosci Lett 462:1661702009


Barkhoudarian GKlochkov TSedrak MFrew AGorgulho ABehnke E: A role of diffusion tensor imaging in movement disorder surgery. Acta Neurochir (Wien) 152:208920952010


Behrens TEBerg HJJbabdi SRushworth MFWoolrich MW: Probabilistic diffusion tractography with multiple fibre orientations: what can we gain?. Neuroimage 34:1441552007


Behrens TEJohansen-Berg HWoolrich MWSmith SMWheeler-Kingshott CABoulby PA: Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nat Neurosci 6:7507572003


Behrens TEWoolrich MWJenkinson MJohansen-Berg HNunes RGClare S: Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magn Reson Med 50:107710882003


Boecker HWills AJCeballos-Baumann ASamuel MThomas DGMarsden CD: Stereotactic thalamotomy in tremor-dominant Parkinson's disease: an H2(15)O PET motor activation study. Ann Neurol 41:1081111997


Ceballos-Baumann AOBoecker HFogel WAlesch FBartenstein PConrad B: Thalamic stimulation for essential tremor activates motor and deactivates vestibular cortex. Neurology 56:134713542001


Coenen VAAllert NMädler B: A role of diffusion tensor imaging fiber tracking in deep brain stimulation surgery: DBS of the dentato-rubro-thalamic tract (drt) for the treatment of therapy-refractory tremor. Acta Neurochir (Wien) [epub ahead of print]2011


Coenen VAMädler BSchiffbauer HUrbach HAllert N: Individual fiber anatomy of the subthalamic region revealed with DTI: a concept to identify the DBS target for tremor suppression. Neurosurgery 153:157915852011


Dinov ILozev KPetrosyan PLiu ZEggert PPierce J: Neuroimaging study designs, computational analyses and data provenance using the LONI Pipeline. PLoS One 5:e130702010


Gattellaro GMinati LGrisoli MMariani CCarella FOsio M: White matter involvement in idiopathic Parkinson disease: a diffusion tensor imaging study. AJNR Am J Neuroradiol 30:122212262009


Gradinaru VMogri MThompson KRHenderson JMDeisseroth K: Optical deconstruction of parkinsonian neural circuitry. Science 324:3543592009


Halsband UMatsuzaka YTanji J: Neuronal activity in the primate supplementary, pre-supplementary and premotor cortex during externally and internally instructed sequential movements. Neurosci Res 20:1491551994


Haslinger BBoecker HBüchel CVesper JTronnier VMPfister R: Differential modulation of subcortical target and cortex during deep brain stimulation. Neuroimage 18:5175242003


Heckemann RAHajnal JVAljabar PRueckert DHammers A: Automatic anatomical brain MRI segmentation combining label propagation and decision fusion. Neuroimage 33:1151262006


Jenkinson MSmith S: A global optimisation method for robust affine registration of brain images. Med Image Anal 5:1431562001


Johansen-Berg HBehrens TESillery ECiccarelli OThompson AJSmith SM: Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus. Cereb Cortex 15:31392005


Johansen-Berg HGutman DABehrens TEMatthews PMRushworth MFKatz E: Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression. Cereb Cortex 18:137413832008


Lemaire JJSakka LOuchchane LCaire FGabrillargues JBonny JM: Anatomy of the human thalamus based on spontaneous contrast and microscopic voxels in high-field magnetic resonance imaging. Neurosurgery 66:3 Suppl OperativeONS161ONS1722010


Li WLiu JSkidmore FLiu YTian JLi K: White matter microstructure changes in the thalamus in Parkinson disease with depression: a diffusion tensor MR imaging study. AJNR Am J Neuroradiol 31:186118662010


Littlechild PVarma TREldridge PRFox SForster AFletcher N: Variability in position of the subthalamic nucleus targeted by magnetic resonance imaging and microelectrode recordings as compared to atlas co-ordinates. Stereotact Funct Neurosurg 80:82872003


Menke RAJbabdi SMiller KLMatthews PMZarei M: Connectivity-based segmentation of the substantia nigra in human and its implications in Parkinson's disease. Neuroimage 52:117511802010


Nowinski WLBelov DPollak PBenabid AL: A probabilistic functional atlas of the human subthalamic nucleus. Neuroinformatics 2:3813982004


Nowinski WLBelov DThirunavuukarasuu ABenabid AL: A probabilistic functional atlas of the VIM nucleus constructed from pre-, intra- and postoperative electrophysiological and neuroimaging data acquired during the surgical treatment of Parkinson's disease patients. Stereotact Funct Neurosurg 83:1901962005


O'Gorman RLShmueli KAshkan KSamuel MLythgoe DJShahidiani A: Optimal MRI methods for direct stereotactic targeting of the subthalamic nucleus and globus pallidus. Eur Radiol 21:1301362011


Perlmutter JSMink JWBastian AJZackowski KHershey TMiyawaki E: Blood flow responses to deep brain stimulation of thalamus. Neurology 58:138813942002


Pouratian NBookheimer SY: The reliability of neuroanatomy as a predictor of eloquence: a review. Neurosurg Focus 28:2E32010


Remy PZilbovicius MLeroy-Willig ASyrota ASamson Y: Movement- and task-related activations of motor cortical areas: a positron emission tomographic study. Ann Neurol 36:19261994


Rex DEMa JQToga AW: The LONI Pipeline Processing Environment. Neuroimage 19:103310482003


Rushworth MFBehrens TEJohansen-Berg H: Connection patterns distinguish 3 regions of human parietal cortex. Cereb Cortex 16:141814302006


Traynor CHeckemann RAHammers AO'Muircheartaigh JCrum WRBarker GJ: Reproducibility of thalamic segmentation based on probabilistic tractography. Neuroimage 52:69852010


Tu ZNarr KLDollar PDinov IThompson PMToga AW: Brain anatomical structure segmentation by hybrid discriminative/generative models. IEEE Trans Med Imaging 27:4955082008


Wiegell MRTuch DSLarsson HBWedeen VJ: Automatic segmentation of thalamic nuclei from diffusion tensor magnetic resonance imaging. Neuroimage 19:3914012003


Zhang KYu CZhang YWu XZhu CChan P: Voxel-based analysis of diffusion tensor indices in the brain in patients with Parkinson's disease. Eur J Radiol 77:2692732011


Ziyan UTuch DWestin CF: Segmentation of thalamic nuclei from DTI using spectral clustering. Med Image Comput Comput Assist Interv 9:8078142006




All Time Past Year Past 30 Days
Abstract Views 61 61 22
Full Text Views 145 145 16
PDF Downloads 112 112 6
EPUB Downloads 0 0 0


Google Scholar