Skip to main content

Advertisement

Log in

Personalized Connectome Mapping to Guide Targeted Therapy and Promote Recovery of Consciousness in the Intensive Care Unit

  • Take a closer look at trials
  • Published:
Neurocritical Care Aims and scope Submit manuscript

An Invited Commentary to this article was published on 13 August 2020

Abstract

There are currently no therapies proven to promote early recovery of consciousness in patients with severe brain injuries in the intensive care unit (ICU). For patients whose families face time-sensitive, life-or-death decisions, treatments that promote recovery of consciousness are needed to reduce the likelihood of premature withdrawal of life-sustaining therapy, facilitate autonomous self-expression, and increase access to rehabilitative care. Here, we present the Connectome-based Clinical Trial Platform (CCTP), a new paradigm for developing and testing targeted therapies that promote early recovery of consciousness in the ICU. We report the protocol for STIMPACT (Stimulant Therapy Targeted to Individualized Connectivity Maps to Promote ReACTivation of Consciousness), a CCTP-based trial in which intravenous methylphenidate will be used for targeted stimulation of dopaminergic circuits within the subcortical ascending arousal network (ClinicalTrials.gov NCT03814356). The scientific premise of the CCTP and the STIMPACT trial is that personalized brain network mapping in the ICU can identify patients whose connectomes are amenable to neuromodulation. Phase 1 of the STIMPACT trial is an open-label, safety and dose-finding study in 22 patients with disorders of consciousness caused by acute severe traumatic brain injury. Patients in Phase 1 will receive escalating daily doses (0.5–2.0 mg/kg) of intravenous methylphenidate over a 4-day period and will undergo resting-state functional magnetic resonance imaging and electroencephalography to evaluate the drug’s pharmacodynamic properties. The primary outcome measure for Phase 1 relates to safety: the number of drug-related adverse events at each dose. Secondary outcome measures pertain to pharmacokinetics and pharmacodynamics: (1) time to maximal serum concentration; (2) serum half-life; (3) effect of the highest tolerated dose on resting-state functional MRI biomarkers of connectivity; and (4) effect of each dose on EEG biomarkers of cerebral cortical function. Predetermined safety and pharmacodynamic criteria must be fulfilled in Phase 1 to proceed to Phase 2A. Pharmacokinetic data from Phase 1 will also inform the study design of Phase 2A, where we will test the hypothesis that personalized connectome maps predict therapeutic responses to intravenous methylphenidate. Likewise, findings from Phase 2A will inform the design of Phase 2B, where we plan to enroll patients based on their personalized connectome maps. By selecting patients for clinical trials based on a principled, mechanistic assessment of their neuroanatomic potential for a therapeutic response, the CCTP paradigm and the STIMPACT trial have the potential to transform the therapeutic landscape in the ICU and improve outcomes for patients with severe brain injuries.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Giacino JT, Fins JJ, Laureys S, et al. Disorders of consciousness after acquired brain injury: the state of the science. Nat Rev Neurol. 2014;10:99–114.

    Article  PubMed  Google Scholar 

  2. Giacino JT, Kalmar K. The vegetative and minimally conscious states: a comparison of clinical features and functional outcome. J Head Trauma Rehabil. 1997;12:36–51.

    Article  Google Scholar 

  3. Claassen J, Doyle K, Matory A, et al. Detection of brain activation in unresponsive patients with acute brain injury. N Engl J Med. 2019;380:2497–505.

    Article  PubMed  Google Scholar 

  4. Faugeras F, Rohaut B, Valente M, et al. Survival and consciousness recovery are better in the minimally conscious state than in the vegetative state. Brain Inj. 2018;32:72–7.

    Article  PubMed  Google Scholar 

  5. Fins JJ. Rights come to mind: brain injury, ethics, and the struggle for consciousness. New York: Cambridge University Press; 2015.

    Book  Google Scholar 

  6. Turgeon AF, Lauzier F, Simard JF, et al. Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicentre cohort study. CMAJ. 2011;183:1581–8.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Izzy S, Compton R, Carandang R, et al. Self-fulfilling prophecies through withdrawal of care: do they exist in traumatic brain injury, too? Neurocrit Care. 2013;19:347–63.

    Article  PubMed  Google Scholar 

  8. Peberdy MA, Kaye W, Ornato JP, et al. Cardiopulmonary resuscitation of adults in the hospital: a report of 14720 cardiac arrests from the National Registry of Cardiopulmonary Resuscitation. Resuscitation. 2003;58:297–308.

    Article  PubMed  Google Scholar 

  9. Snider SB, Bodien YG, Bianciardi M, et al. Disruption of the ascending arousal network in acute traumatic disorders of consciousness. Neurology. 2019;93:e1281–7.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Edlow BL, Haynes RL, Takahashi E, et al. Disconnection of the ascending arousal system in traumatic coma. J Neuropathol Exp Neurol. 2013;72:505–23.

    Article  PubMed  Google Scholar 

  11. Rosenblum WI. Immediate, irreversible, posttraumatic coma: a review indicating that bilateral brainstem injury rather than widespread hemispheric damage is essential for its production. J Neuropathol Exp Neurol. 2015;74:198–202.

    Article  PubMed  Google Scholar 

  12. Threlkeld ZD, Bodien YG, Rosenthal ES, et al. Functional networks reemerge during recovery of consciousness after acute severe traumatic brain injury. Cortex. 2018;106:299–308.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Demertzi A, Antonopoulos G, Heine L, et al. Intrinsic functional connectivity differentiates minimally conscious from unresponsive patients. Brain. 2015;138:2619–31.

    Article  PubMed  Google Scholar 

  14. Newcombe VF, Williams GB, Scoffings D, et al. Aetiological differences in neuroanatomy of the vegetative state: insights from diffusion tensor imaging and functional implications. J Neurol Neurosurg Psychiatry. 2010;81:552–61.

    Article  PubMed  Google Scholar 

  15. Maas AIR, Menon DK, Adelson PD, et al. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017;16:987–1048.

    Article  PubMed  Google Scholar 

  16. Diaz-Arrastia R, Kochanek PM, Bergold P, et al. Pharmacotherapy of traumatic brain injury: state of the science and the road forward: report of the Department of Defense Neurotrauma Pharmacology Workgroup. J Neurotrauma. 2014;31:135–58.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kochanek PM, Dixon CE, Mondello S, et al. Multi-center pre-clinical consortia to enhance translation of therapies and biomarkers for traumatic brain injury: operation brain trauma therapy and beyond. Front Neurol. 2018;9:640.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Smith DH, Hicks R, Povlishock JT. Therapy development for diffuse axonal injury. J Neurotrauma. 2013;30:307–23.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tononi G, Boly M, Massimini M, et al. Integrated information theory: from consciousness to its physical substrate. Nat Rev Neurosci. 2016;17:450–61.

    Article  CAS  PubMed  Google Scholar 

  20. Dehaene S, Changeux JP, Naccache L, et al. Conscious, preconscious, and subliminal processing: a testable taxonomy. Trends Cogn Sci. 2006;10:204–11.

    Article  PubMed  Google Scholar 

  21. Sharp DJ, Scott G, Leech R. Network dysfunction after traumatic brain injury. Nat Rev Neurol. 2014;10:156–66.

    Article  PubMed  Google Scholar 

  22. Izzy S, Mazwi NL, Martinez S, et al. Revisiting grade 3 diffuse axonal injury: not all brainstem microbleeds are prognostically equal. Neurocrit Care. 2017;27:199–207.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Jang SH, Kim SH, Lim HW, et al. Injury of the lower ascending reticular activating system in patients with hypoxic-ischemic brain injury: diffusion tensor imaging study. Neuroradiology. 2014;56:965–70.

    Article  PubMed  Google Scholar 

  24. Demertzi A, Tagliazucchi E, Dehaene S, et al. Human consciousness is supported by dynamic complex patterns of brain signal coordination. Sci Adv. 2019;5:eaat7603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Parvizi J, Damasio A. Consciousness and the brainstem. Cognition. 2001;79:135–60.

    Article  CAS  PubMed  Google Scholar 

  26. Edlow BL, Takahashi E, Wu O, et al. Neuroanatomic connectivity of the human ascending arousal system critical to consciousness and its disorders. J Neuropathol Exp Neurol. 2012;71:531–46.

    Article  PubMed  Google Scholar 

  27. Koch C, Massimini M, Boly M, et al. Neural correlates of consciousness: progress and problems. Nat Rev Neurosci. 2016;17:307–21.

    Article  CAS  PubMed  Google Scholar 

  28. Estraneo A, Moretta P, Loreto V, et al. Late recovery after traumatic, anoxic, or hemorrhagic long-lasting vegetative state. Neurology. 2010;75:239–45.

    Article  CAS  PubMed  Google Scholar 

  29. Voss HU, Uluc AM, Dyke JP, et al. Possible axonal regrowth in late recovery from the minimally conscious state. J Clin Investig. 2006;116:2005–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hammond FM, Giacino JT, Nakase Richardson R, et al. Disorders of consciousness due to traumatic brain injury: functional status ten years post-injury. J Neurotrauma. 2019;36:1136–46.

    Article  PubMed  Google Scholar 

  31. Ommaya AK, Gennarelli TA. Cerebral concussion and traumatic unconsciousness. Correlation of experimental and clinical observations of blunt head injuries. Brain. 1974;97:633–54.

    Article  CAS  PubMed  Google Scholar 

  32. Adams JH, Doyle D, Ford I, et al. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology. 1989;15:49–59.

    Article  CAS  PubMed  Google Scholar 

  33. Gentry LR, Godersky JC, Thompson BH. Traumatic brain stem injury: MR imaging. Radiology. 1989;171:177–87.

    Article  CAS  PubMed  Google Scholar 

  34. Edlow BL, Threlkeld ZD, Fehnel KP, et al. Recovery of functional independence after traumatic transtentorial herniation with duret hemorrhages. Front Neurol. 2019;10:1077.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Donnemiller E, Brenneis C, Wissel J, et al. Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPECT study using 123I-beta-CIT and 123I-IBZM. Eur J Nucl Med. 2000;27:1410–4.

    Article  CAS  PubMed  Google Scholar 

  36. Jenkins PO, De Simoni S, Bourke NJ, et al. Stratifying drug treatment of cognitive impairments after traumatic brain injury using neuroimaging. Brain. 2019;142:2367–79.

    Article  PubMed  Google Scholar 

  37. Fridman EA, Osborne JR, Mozley PD, et al. Presynaptic dopamine deficit in minimally conscious state patients following traumatic brain injury. Brain. 2019;142:1887–93.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Solt K, Cotten JF, Cimenser A, et al. Methylphenidate actively induces emergence from general anesthesia. Anesthesiology. 2011;115:791–803.

    Article  CAS  PubMed  Google Scholar 

  39. Swanson JM, Volkow ND. Serum and brain concentrations of methylphenidate: implications for use and abuse. Neurosci Biobehav Rev. 2003;27:615–21.

    Article  CAS  PubMed  Google Scholar 

  40. Taylor NE, Chemali JJ, Brown EN, et al. Activation of D1 dopamine receptors induces emergence from isoflurane general anesthesia. Anesthesiology. 2013;118:30–9.

    Article  CAS  PubMed  Google Scholar 

  41. Taylor NE, Van Dort CJ, Kenny JD, et al. Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia. Proc Natl Acad Sci USA. 2016;113:12826–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Solt K, Van Dort CJ, Chemali JJ, et al. Electrical stimulation of the ventral tegmental area induces reanimation from general anesthesia. Anesthesiology. 2014;121:311–9.

    Article  CAS  PubMed  Google Scholar 

  43. Fridman EA, Schiff ND. Neuromodulation of the conscious state following severe brain injuries. Curr Opin Neurobiol. 2014;29:172–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Thibaut A, Schiff N, Giacino J, et al. Therapeutic interventions in patients with prolonged disorders of consciousness. Lancet Neurol. 2019;18:600–14.

    Article  PubMed  Google Scholar 

  45. Giacino JT, Whyte J, Bagiella E, et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med. 2012;366:819–26.

    Article  CAS  PubMed  Google Scholar 

  46. Barra ME, Izzy S, Sarro-Schwartz A, et al. Stimulant therapy in acute traumatic brain injury: prescribing patterns and adverse event rates at 2 level 1 trauma centers. J Intensive Care Med. 2019. https://doi.org/10.1177/0885066619841603.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Whyte J, Hart T, Vaccaro M, et al. Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional, randomized, controlled trial. Am J Phys Med Rehabil. 2004;83:401–20.

    Article  PubMed  Google Scholar 

  48. McNab JA, Edlow BL, Witzel T, et al. The human connectome project and beyond: initial applications of 300 mT/m gradients. Neuroimage. 2013;80:234–45.

    Article  PubMed  Google Scholar 

  49. Morales M, Margolis EB. Ventral tegmental area: cellular heterogeneity, connectivity and behaviour. Nat Rev Neurosci. 2017;18:73–85.

    Article  CAS  PubMed  Google Scholar 

  50. Norton L, Hutchison RM, Young GB, et al. Disruptions of functional connectivity in the default mode network of comatose patients. Neurology. 2012;78:175–81.

    Article  CAS  PubMed  Google Scholar 

  51. Bodien YG, Threlkeld ZD, Edlow BL. Default mode network dynamics in covert consciousness. Cortex. 2019;119:571.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Kondziella D, Fisher PM, Larsen VA, et al. Functional MRI for assessment of the default mode network in acute brain injury. Neurocrit Care. 2017;27:401–6.

    Article  PubMed  Google Scholar 

  53. Vanhaudenhuyse A, Noirhomme Q, Tshibanda LJ, et al. Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. Brain. 2010;133:161–71.

    Article  PubMed  Google Scholar 

  54. Tritsch NX, Sabatini BL. Dopaminergic modulation of synaptic transmission in cortex and striatum. Neuron. 2012;76:33–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gale AS. The effect of methylphenidate (ritalin) on thiopental recovery. Anesthesiology. 1958;19:521–31.

    Article  CAS  PubMed  Google Scholar 

  56. Janowsky DS, Leichner P, Clopton P, et al. Comparison of oral and intravenous methylphenidate. Psychopharmacology. 1978;59:75–8.

    Article  CAS  PubMed  Google Scholar 

  57. Joyce PR, Nicholls MG, Donald RA. Methylphenidate increases heart rate, blood pressure and plasma epinephrine in normal subjects. Life Sci. 1984;34:1707–11.

    Article  CAS  PubMed  Google Scholar 

  58. Wang GJ, Volkow ND, Hitzemann RJ, et al. Behavioral and cardiovascular effects of intravenous methylphenidate in normal subjects and cocaine abusers. Eur Addict Res. 1997;3:49–54.

    Article  Google Scholar 

  59. Dodson ME, Fryer JM. Postoperative effects of methylphenidate. Br J Anaesth. 1980;52:1265–70.

    Article  CAS  PubMed  Google Scholar 

  60. Volkow ND, Wang GJ, Fowler JS, et al. Cardiovascular effects of methylphenidate in humans are associated with increases of dopamine in brain and of epinephrine in plasma. Psychopharmacology. 2003;166:264–70.

    Article  CAS  PubMed  Google Scholar 

  61. Carter CH, Maley MC. Parenteral use of methylphenidate (ritalin). Dis Nerv Syst. 1957;18:146–8.

    CAS  PubMed  Google Scholar 

  62. Clark CR, Geffen GM, Geffen LB. Role of monoamine pathways in attention and effort: effects of clonidine and methylphenidate in normal adult humans. Psychopharmacology. 1986;90:35–9.

    CAS  PubMed  Google Scholar 

  63. Chan YP, Swanson JM, Soldin SS, et al. Methylphenidate hydrochloride given with or before breakfast: II. Effects on plasma concentration of methylphenidate and ritalinic acid. Pediatrics. 1983;72:56–9.

    CAS  PubMed  Google Scholar 

  64. Joyce PR, Donald RA, Nicholls MG, et al. Endocrine and behavioral responses to methylphenidate in normal subjects. Biol Psychiatry. 1986;21:1015–23.

    Article  CAS  PubMed  Google Scholar 

  65. Volkow ND, Wang GJ, Fowler JS, et al. Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain. Life Sci. 1999;65:PL7–12.

    Article  CAS  PubMed  Google Scholar 

  66. Li CS, Morgan PT, Matuskey D, et al. Biological markers of the effects of intravenous methylphenidate on improving inhibitory control in cocaine-dependent patients. Proc Natl Acad Sci U S A. 2010;107:14455–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Christensen RO. A new agent for shortening recovery time in oral surgery. Oral Surg Oral Med Oral Pathol. 1958;11:999–1002.

    Article  CAS  PubMed  Google Scholar 

  68. Percheson PB, Carroll JJ, Screech G. Ritalin (methylphenidate): clinical experiences. Can Anaesth Soc J. 1959;6:277–82.

    Article  CAS  PubMed  Google Scholar 

  69. Gale AS. The comparative and additive effects of methylphenidate and bemegride. Anesthesiology. 1961;22:210–4.

    Article  CAS  PubMed  Google Scholar 

  70. Volkow ND, Wang GJ, Gatley SJ, et al. Temporal relationships between the pharmacokinetics of methylphenidate in the human brain and its behavioral and cardiovascular effects. Psychopharmacology. 1996;123:26–33.

    Article  CAS  PubMed  Google Scholar 

  71. Smith B, Adriani J. Studies on newer analeptics and the comparison of their action with pentylenetetrazole, nikethamide and picrotoxin. Anesthesiology. 1958;19:115.

    Article  Google Scholar 

  72. Ticktin H, Epstein J, Shea JG, et al. Effect of methylphenidate hydrochloride in antagonizing barbiturate-induced depression. Neurology. 1958;8:267–71.

    Article  CAS  PubMed  Google Scholar 

  73. Volkow ND, Wang GJ, Fowler JS, et al. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry. 1998;155:1325–31.

    Article  CAS  PubMed  Google Scholar 

  74. Setsompop K, Gagoski BA, Polimeni JR, et al. Blipped-controlled aliasing in parallel imaging for simultaneous multislice echo planar imaging with reduced g-factor penalty. Magn Reson Med. 2012;67:1210–24.

    Article  PubMed  Google Scholar 

  75. Glover GH, Li TQ, Ress D. Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR. Magn Reson Med. 2000;44:162–7.

    Article  CAS  PubMed  Google Scholar 

  76. Lindquist MA, Waugh C, Wager TD. Modeling state-related fMRI activity using change-point theory. Neuroimage. 2007;35:1125–41.

    Article  PubMed  Google Scholar 

  77. Cribben I, Wager TD, Lindquist MA. Detecting functional connectivity change points for single-subject fMRI data. Front Comput Neurosci. 2013;7:143.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Hutchison RM, Womelsdorf T, Allen EA, et al. Dynamic functional connectivity: promise, issues, and interpretations. Neuroimage. 2013;80:360–78.

    Article  PubMed  Google Scholar 

  79. Killick R, Eckley I. Changepoint: an R package for changepoint analysis. J Stat Softw. 2014;58:1–19.

    Article  Google Scholar 

  80. Piarulli A, Bergamasco M, Thibaut A, et al. EEG ultradian rhythmicity differences in disorders of consciousness during wakefulness. J Neurol. 2016;263:1746–60.

    Article  PubMed  Google Scholar 

  81. Engemann DA, Raimondo F, King JR, et al. Robust EEG-based cross-site and cross-protocol classification of states of consciousness. Brain. 2018;141:3179–92.

    Article  PubMed  Google Scholar 

  82. Cimenser A, Purdon PL, Pierce ET, et al. Tracking brain states under general anesthesia by using global coherence analysis. Proc Natl Acad Sci USA. 2011;108:8832–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil. 2004;85:2020–9.

    Article  PubMed  Google Scholar 

  84. Edlow BL, McNab JA, Witzel T, et al. The structural connectome of the human central homeostatic network. Brain Connect. 2016;6:187–200.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank the members of the Patient and Family Advisory Board of the Massachusetts General Hospital Laboratory for NeuroImaging of Coma and Consciousness for their feedback and insights regarding the ethical conduct of this clinical trial. We acknowledge Maryam Masood and Zora DiPucchio for their contributions to the regulatory oversight of the trial. We also thank Dr. David A. Schoenfeld for helpful statistical consultation.

Funding

The study was funded by the NIH Director’s Office (DP2HD101400), National Institute of Neurological Disorders and Stroke (K23NS094538, R21NS109627, RF1NS115268), American Academy of Neurology/American Brain Foundation, James S. McDonnell Foundation, Rappaport Foundation, and Tiny Blue Dot Foundation. We also acknowledge support from the National Institute of Neurological Disorders and Stroke Clinical Trial Methodology Course (R25NS088248). This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award UL 1TR002541) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health.

Author information

Authors and Affiliations

Authors

Contributions

BLE: study conception and design; data acquisition, processing, and analysis; data interpretation; drafting the article; final approval of the version to be published. MEB: design of treatment compounding and operating procedures and pharmacokinetic monitoring, critical review of manuscript, final approval of the version to be published. DWZ: design of EEG pharmacodynamic biomarker; data acquisition, processing, and analysis; critical review of manuscript, final approval of the version to be published. ASF: design of statistical plan; critical review of manuscript, final approval of the version to be published. SBS: design of structural MRI predictive biomarker; data acquisition, processing, and analysis; critical review of manuscript, final approval of the version to be published. ZDT: design of functional MRI pharmacodynamic biomarker; data acquisition, processing, and analysis; critical review of manuscript, final approval of the version to be published. SC: design of dynamic functional connectivity-based pharmacodynamic analysis; critical review of manuscript, final approval of the version to be published. JEK: design of functional MRI sequence; data acquisition, processing, and analysis; critical review of manuscript, final approval of the version to be published. SC: design of functional MRI physiologic monitoring; data acquisition, processing, and analysis; critical review of manuscript, final approval of the version to be published. SLM: design of functional MRI physiologic monitoring; data acquisition, processing, and analysis; critical review of manuscript, final approval of the version to be published. TPB: study design; critical review of manuscript, final approval of the version to be published. JJF: study design, ethical guidance, final approval of the version to be published. JTG: study design; critical review of manuscript, final approval of the version to be published. LRH: study design; critical review of manuscript, final approval of the version to be published. KS: development of investigational therapy; study design; critical review of manuscript, final approval of the version to be published. ENB: development of investigational therapy; study design; critical review of manuscript, final approval of the version to be published. YGB: study conception and design; data acquisition, processing, and analysis; data interpretation; drafting the article; final approval of the version to be published.

Corresponding author

Correspondence to Brian L. Edlow.

Ethics declarations

Conflict of interest

The authors have no relevant conflicts of interest to disclose.

Ethical approval/Informed consent

All biomarker data reported here were obtained with written informed consent provided by healthy control subjects or by surrogate decision-makers for patients with altered consciousness, as part of a separate Institutional Review Board-approved protocol.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article refers to the commentary by https://doi.org/10.1007/s12028-020-01065-4.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 2793 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Edlow, B.L., Barra, M.E., Zhou, D.W. et al. Personalized Connectome Mapping to Guide Targeted Therapy and Promote Recovery of Consciousness in the Intensive Care Unit. Neurocrit Care 33, 364–375 (2020). https://doi.org/10.1007/s12028-020-01062-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-020-01062-7

Keywords

Navigation