Advertisement

Defining Critical White Matter Pathways Mediating Successful Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression

      Background

      Subcallosal cingulate white matter (SCC) deep brain stimulation (DBS) is an evolving investigational treatment for depression. Mechanisms of action are hypothesized to involve modulation of activity within a structurally defined network of brain regions involved in mood regulation. Diffusion tensor imaging was used to model white matter connections within this network to identify those critical for successful antidepressant response.

      Methods

      Preoperative high-resolution magnetic resonance imaging data, including diffusion tensor imaging, were acquired in 16 patients with treatment-resistant depression, who then received SCC DBS. Computerized tomography was used postoperatively to locate DBS contacts. The activation volume around the contacts used for chronic stimulation was modeled for each patient retrospectively. Probabilistic tractography was used to delineate the white matter tracts traveling through each activation volume. Patient-specific tract maps were calculated using whole-brain analysis. Clinical evaluations of therapeutic outcome from SCC DBS were defined at 6 months and 2 years.

      Results

      Whole-brain activation volume tractography demonstrated that all DBS responders at 6 months (n = 6) and 2 years (n = 12) shared bilateral pathways from their activation volumes to 1) medial frontal cortex via forceps minor and uncinate fasciculus; 2) rostral and dorsal cingulate cortex via the cingulum bundle; and 3) subcortical nuclei. Nonresponders did not consistently show these connections. Specific anatomical coordinates of the active contacts did not discriminate responders from nonresponders.

      Conclusions

      Patient-specific activation volume tractography modeling may identify critical tracts that mediate SCC DBS antidepressant response. This suggests a novel method for patient-specific target and stimulation parameter selection.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Mayberg H.S.
        • Lozano A.M.
        • Voon V.
        • McNeely H.E.
        • Seminowicz D.
        • Hamani C.
        • et al.
        Deep brain stimulation for treatment-resistant depression.
        Neuron. 2005; 45: 651-660
        • Malone Jr, D.A.
        • Dougherty D.D.
        • Rezai A.R.
        • Carpenter L.L.
        • Friehs G.M.
        • Eskandar E.N.
        • et al.
        Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression.
        Biol Psychiatry. 2009; 65: 267-275
        • Bewernick B.H.
        • Hurlemann R.
        • Matusch A.
        • Kayser S.
        • Grubert C.
        • Hadrysiewicz B.
        • et al.
        Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression.
        Biol Psychiatry. 2010; 67: 110-116
        • Sartorius A.
        • Henn F.A.
        Deep brain stimulation of the lateral habenula in treatment resistant major depression.
        Med Hypotheses. 2007; 69: 1305-1308
        • Jimenez F.
        • Velasco F.
        • Salin-Pascual R.
        • Hernandez J.A.
        • Velasco M.
        • Criales J.L.
        • Nicolini H.
        A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle.
        Neurosurgery. 2005; 57: 585-593
        • Schlaepfer T.E.
        • Bewernick B.H.
        • Kayser S.
        • Madler B.
        • Coenen V.A.
        Rapid effects of deep brain stimulation for treatment-resistant major depression.
        Biol Psychiatry. 2013; 73: 1204-1212
        • Lozano A.M.
        • Mayberg H.S.
        • Giacobbe P.
        • Hamani C.
        • Craddock R.C.
        • Kennedy S.H.
        Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression.
        Biol Psychiatry. 2008; 64: 461-467
        • Lozano A.M.
        • Giacobbe P.
        • Hamani C.
        • Rizvi S.J.
        • Kennedy S.H.
        • Kolivakis T.T.
        • et al.
        A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression.
        J Neurosurg. 2012; 116: 315-322
        • Holtzheimer P.E.
        • Kelley M.E.
        • Gross R.E.
        • Filkowski M.M.
        • Garlow S.J.
        • Barrocas A.
        • et al.
        Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression.
        Arch Gen Psychiatry. 2012; 69: 150-158
        • Puigdemont D.
        • Perez-Egea R.
        • Portella M.J.
        • Molet J.
        • de Diego-Adelino J.
        • Gironell A.
        • et al.
        Deep brain stimulation of the subcallosal cingulate gyrus: Further evidence in treatment-resistant major depression.
        Int J Neuropsychopharmacol. 2012; 15: 121-133
        • Ramasubbu R.
        • Anderson S.
        • Haffenden A.
        • Chavda S.
        • Kiss Z.H.
        Double-blind optimization of subcallosal cingulate deep brain stimulation for treatment-resistant depression: A pilot study.
        J Psychiatry Neurosci. 2013; 38: 120-160
        • Guinjoan S.M.
        • Mayberg H.S.
        • Costanzo E.Y.
        • Fahrer R.D.
        • Tenca E.
        • Antico J.
        • et al.
        Asymmetrical contribution of brain structures to treatment-resistant depression as illustrated by effects of right subgenual cingulum stimulation.
        J Neuropsychiatry Clin Neurosci. 2010; 22: 265-277
        • Kennedy S.H.
        • Giacobbe P.
        • Rizvi S.J.
        • Placenza F.M.
        • Nishikawa Y.
        • Mayberg H.S.
        • Lozano A.M.
        Deep brain stimulation for treatment-resistant depression: Follow-up after 3 to 6 years.
        Am J Psychiatry. 2011; 168: 502-510
        • Merkl A.
        • Schneider G.H.
        • Schonecker T.
        • Aust S.
        • Kuhl K.P.
        • Kupsch A.
        • et al.
        Antidepressant effects after short-term and chronic stimulation of the subgenual cingulate gyrus in treatment-resistant depression.
        Exp Neurol. 2013; 249: 160-168
        • Seminowicz D.A.
        • Mayberg H.S.
        • McIntosh A.R.
        • Goldapple K.
        • Kennedy S.
        • Segal Z.
        • Rafi-Tari S.
        Limbic-frontal circuitry in major depression: A path modeling metanalysis.
        Neuroimage. 2004; 22: 409-418
        • Mayberg H.S.
        Targeted electrode-based modulation of neural circuits for depression.
        J Clin Invest. 2009; 119: 717-725
        • Mayberg H.S.
        • Brannan S.K.
        • Tekell J.L.
        • Silva J.A.
        • Mahurin R.K.
        • McGinnis S.
        • Jerabek P.A.
        Regional metabolic effects of fluoxetine in major depression: Serial changes and relationship to clinical response.
        Biol Psychiatry. 2000; 48: 830-843
        • Goldapple K.
        • Segal Z.
        • Garson C.
        • Lau M.
        • Bieling P.
        • Kennedy S.
        • Mayberg H.
        Modulation of cortical-limbic pathways in major depression: Treatment-specific effects of cognitive behavior therapy.
        Arch Gen Psychiatry. 2004; 61: 34-41
        • Nobler M.S.
        • Oquendo M.A.
        • Kegeles L.S.
        • Malone K.M.
        • Campbell C.C.
        • Sackeim H.A.
        • Mann J.J.
        Decreased regional brain metabolism after ect.
        Am J Psychiatry. 2001; 158: 305-308
        • Mayberg H.S.
        Limbic-cortical dysregulation: A proposed model of depression.
        J Neuropsychiatry Clin Neurosci. 1997; 9: 471-481
        • Mayberg H.S.
        • Liotti M.
        • Brannan S.K.
        • McGinnis S.
        • Mahurin R.K.
        • Jerabek P.A.
        • et al.
        Reciprocal limbic-cortical function and negative mood: Converging PET findings in depression and normal sadness.
        Am J Psychiatry. 1999; 156: 675-682
        • Freedman L.J.
        • Insel T.R.
        • Smith Y.
        Subcortical projections of area 25 (subgenual cortex) of the macaque monkey.
        J Comp Neurol. 2000; 421: 172-188
        • Ongur D.
        • Price J.L.
        The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans.
        Cereb Cortex. 2000; 10: 206-219
        • Carmichael S.T.
        • Price J.L.
        Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys.
        J Comp Neurol. 1996; 371: 179-207
        • Haber S.N.
        • Fudge J.L.
        • McFarland N.R.
        Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum.
        J Neurosci. 2000; 20: 2369-2382
        • Ghashghaei H.T.
        • Hilgetag C.C.
        • Barbas H.
        Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala.
        Neuroimage. 2007; 34: 905-923
        • Schaltenbrand G.W.
        Atlas for Stereotaxy of the Human Brain, 2nd ed.
        Thieme, Stuttgart, Germany1998
        • Hamani C.
        • Mayberg H.
        • Snyder B.
        • Giacobbe P.
        • Kennedy S.
        • Lozano A.M.
        Deep brain stimulation of the subcallosal cingulate gyrus for depression: Anatomical location of active contacts in clinical responders and a suggested guideline for targeting.
        J Neurosurg. 2009; 111: 1209-1215
        • Gradinaru V.
        • Mogri M.
        • Thompson K.R.
        • Henderson J.M.
        • Deisseroth K.
        Optical deconstruction of parkinsonian neural circuitry.
        Science. 2009; 324: 354-359
        • Whitmer D.
        • de Solages C.
        • Hill B.
        • Yu H.
        • Henderson J.M.
        • Bronte-Stewart H.
        High frequency deep brain stimulation attenuates subthalamic and cortical rhythms in Parkinsonʼs disease.
        Front Hum Neurosci. 2012; 6: 155
        • Lujan J.L.
        • Chaturvedi A.
        • Malone D.A.
        • Rezai A.R.
        • Machado A.G.
        • McIntyre C.C.
        Axonal pathways linked to therapeutic and nontherapeutic outcomes during psychiatric deep brain stimulation.
        Hum Brain Mapp. 2012; 33: 958-968
        • Miocinovic S.
        • Parent M.
        • Butson C.R.
        • Hahn P.J.
        • Russo G.S.
        • Vitek J.L.
        • McIntyre C.C.
        Computational analysis of subthalamic nucleus and lenticular fasciculus activation during therapeutic deep brain stimulation.
        J Neurophysiol. 2006; 96: 1569-1580
        • Behrens T.E.
        • Woolrich M.W.
        • Jenkinson M.
        • Johansen-Berg H.
        • Nunes R.G.
        • Clare S.
        • et al.
        Characterization and propagation of uncertainty in diffusion-weighted MR imaging.
        Magn Reson Med. 2003; 50: 1077-1088
        • Johansen-Berg H.
        • Gutman D.A.
        • Behrens T.E.
        • Matthews P.M.
        • Rushworth M.F.
        • Katz E.
        • et al.
        Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression.
        Cereb Cortex. 2008; 18: 1374-1383
        • Gutman D.A.
        • Holtzheimer P.E.
        • Behrens T.E.
        • Johansen-Berg H.
        • Mayberg H.S.
        A tractography analysis of two deep brain stimulation white matter targets for depression.
        Biol Psychiatry. 2009; 65: 276-282
        • Lehman J.F.
        • Greenberg B.D.
        • McIntyre C.C.
        • Rasmussen S.A.
        • Haber S.N.
        Rules ventral prefrontal cortical axons use to reach their targets: Implications for diffusion tensor imaging tractography and deep brain stimulation for psychiatric illness.
        J Neurosci. 2011; 31: 10392-10402
        • Butson C.R.
        • Cooper S.E.
        • Henderson J.M.
        • McIntyre C.C.
        Patient-specific analysis of the volume of tissue activated during deep brain stimulation.
        Neuroimage. 2007; 34: 661-670
        • Chaturvedi A.
        • Lujan J.
        • McIntyre C.
        Artificial neural network based characterization of the volume of tissue activated during deep brain stimulation.
        J Neural Eng. 2013; 10: 056023
        • Lujan J.L.
        • Chaturvedi A.
        • Choi K.S.
        • Holtzheimer P.E.
        • Gross R.E.
        • Mayberg H.S.
        • McIntyre C.C.
        Tractography-activation models applied to subcallosal cingulate deep brain stimulation.
        Brain Stimul. 2013; 6: 737-739
        • Frankemolle A.M.
        • Wu J.
        • Noecker A.M.
        • Voelcker-Rehage C.
        • Ho J.C.
        • Vitek J.L.
        • et al.
        Reversing cognitive-motor impairments in Parkinsonʼs disease patients using a computational modelling approach to deep brain stimulation programming.
        Brain. 2010; 133: 746-761
        • Hamilton M.
        A rating scale for depression.
        J Neurol Neurosurg Psychiatry. 1960; 23: 56-62
        • Griswold M.A.
        • Jakob P.M.
        • Heidemann R.M.
        • Nittka M.
        • Jellus V.
        • Wang J.
        • et al.
        Generalized autocalibrating partially parallel acquisitions (GRAPPA).
        Magn Reson Med. 2002; 47: 1202-1210
        • McIntyre C.C.
        • Miocinovic S.
        • Butson C.R.
        Computational analysis of deep brain stimulation.
        Expert Rev Med Devices. 2007; 4: 615-622
        • Smith S.M.
        • Jenkinson M.
        • Woolrich M.W.
        • Beckmann C.F.
        • Behrens T.E.
        • Johansen-Berg H.
        • et al.
        Advances in functional and structural MR image analysis and implementation as FSL.
        Neuroimage. 2004; 23: S208-S219
        • Jenkinson M.
        • Beckmann C.F.
        • Behrens T.E.
        • Woolrich M.W.
        • Smith S.M.
        FSL.
        Neuroimage. 2012; 62: 782-790
        • Jenkinson M.
        • Bannister P.
        • Brady M.
        • Smith S.
        Improved optimization for the robust and accurate linear registration and motion correction of brain images.
        Neuroimage. 2002; 17: 825-841
        • Li L.
        • Rilling J.K.
        • Preuss T.M.
        • Glasser M.F.
        • Hu X.
        The effects of connection reconstruction method on the interregional connectivity of brain networks via diffusion tractography.
        Hum Brain Mapp. 2012; 33: 1894-1913
        • Setsompop K.
        • Kimmlingen R.
        • Eberlein E.
        • Witzel T.
        • Cohen-Adad J.
        • McNab J.A.
        • et al.
        Pushing the limits of in vivo diffusion MRI for the Human Connectome Project.
        Neuroimage. 2013; 80: 220-233
        • Martens H.C.
        • Toader E.
        • Decre M.M.
        • Anderson D.J.
        • Vetter R.
        • Kipke D.R.
        • et al.
        Spatial steering of deep brain stimulation volumes using a novel lead design.
        Clin Neurophysiol. 2011; 122: 558-566
        • Tawfik V.L.
        • Chang S.Y.
        • Hitti F.L.
        • Roberts D.W.
        • Leiter J.C.
        • Jovanovic S.
        • Lee K.H.
        Deep brain stimulation results in local glutamate and adenosine release: Investigation into the role of astrocytes.
        Neurosurgery. 2010; 67: 367-375
        • Hamani C.
        • Nobrega J.N.
        Preclinical studies modeling deep brain stimulation for depression.
        Biol Psychiatry. 2012; 72: 916-923