Resting state magnetoencephalography functional connectivity in traumatic brain injury

Clinical article

View More View Less
  • 1 Departments of Neurological Surgery and
  • | 2 Radiology and Biomedical Imaging, University of California, San Francisco, California
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
Print or Print + Online

Object

Traumatic brain injury (TBI) is one of the leading causes of morbidity worldwide. One mechanism by which blunt head trauma may disrupt normal cognition and behavior is through alteration of functional connectivity between brain regions. In this pilot study, the authors applied a rapid automated resting state magnetoencephalography (MEG) imaging technique suitable for routine clinical use to test the hypothesis that there is decreased functional connectivity in patients with TBI compared with matched controls, even in cases of mild TBI. Furthermore, they posit that these abnormal reductions in MEG functional connectivity can be detected even in TBI patients without specific evidence of traumatic lesions on 3-T MR images. Finally, they hypothesize that the reductions of functional connectivity can improve over time across serial MEG scans during recovery from TBI.

Methods

Magnetoencephalography maps of functional connectivity in the alpha (8- to 12-Hz) band from 21 patients who sustained a TBI were compared with those from 18 age- and sex-matched controls. Regions of altered functional connectivity in each patient were detected in automated fashion through atlas-based registration to the control database. The extent of reduced functional connectivity in the patient group was tested for correlations with clinical characteristics of the injury as well as with findings on 3-T MRI. Finally, the authors compared initial connectivity maps with 2-year follow-up functional connectivity in a subgroup of 5 patients with TBI.

Results

Fourteen male and 7 female patients (17–53 years old, median 29 years) were enrolled. By Glasgow Coma Scale (GCS) criteria, 11 patients had mild, 1 had moderate, and 3 had severe TBI, and 6 had no GCS score recorded. On 3-T MRI, 16 patients had abnormal findings attributable to the trauma and 5 had findings in the normal range. As a group, the patients with TBI had significantly lower functional connectivity than controls (p < 0.01). Three of the 5 patients with normal findings on 3-T MRI showed regions of abnormally reduced MEG functional connectivity. No significant correlations were seen between extent of functional disconnection and injury severity or posttraumatic symptoms (p > 0.05). In the subgroup undergoing 2-year follow-up, the second MEG scan demonstrated a significantly lower percentage of voxels with decreased connectivity (p < 0.05) than the initial MEG scan.

Conclusions

A rapid automated resting-state MEG imaging technique demonstrates abnormally decreased functional connectivity that may persist for years after TBI, including cases classified as “mild” by GCS criteria. Disrupted MEG connectivity can be detected even in some patients with normal findings on 3-T MRI. Analysis of follow-up MEG scans in a subgroup of patients shows that, over time, the abnormally reduced connectivity can improve, suggesting neuroplasticity during the recovery from TBI. Resting state MEG deserves further investigation as a prognostic and predictive biomarker for TBI.

Abbreviations used in this paper:

FDR = false discovery rate; GCS = Glasgow Coma Scale; HISC = Head Injury Symptom Checklist; IC = imaginary coherence; ICC = intraclass correlation coefficient; MEG = magnetoencephalography; TBI = traumatic brain injury.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
  • 1

    Aertsen AM, , Gerstein GL, , Habib MK, & Palm G: Dynamics of neuronal firing correlation: modulation of “effective connectivity. J Neurophysiol 61:900917, 1989

    • Search Google Scholar
    • Export Citation
  • 2

    Bartolomei F, , Bosma I, , Klein M, , Baayen JC, , Reijneveld JC, & Postma TJ, et al.: How do brain tumors alter functional connectivity? A magnetoencephalography study. Ann Neurol 59:128138, 2006

    • Search Google Scholar
    • Export Citation
  • 3

    Castellanos NP, , Paul N, , Ordonez VE, , Demuynck O, , Bajo R, & Campo P, et al.: Reorganization of functional connectivity as a correlate of cognitive recovery in acquired brain injury. Brain 133:23652381, 2010

    • Search Google Scholar
    • Export Citation
  • 4

    da Silva FH, , van Lierop TH, , Schrijer CF, & van Leeuwen WS: Organization of thalamic and cortical alpha rhythms: spectra and coherences. Electroencephalogr Clin Neurophysiol 35:627639, 1973

    • Search Google Scholar
    • Export Citation
  • 5

    Dalal SS, , Zumer JM, , Guggisberg AG, , Trumpis M, , Wong DD, & Sekihara K, et al.: MEG/EEG source reconstruction, statistical evaluation, and visualization with NUTMEG. Comput Intell Neurosci 2011:758973, 2011

    • Search Google Scholar
    • Export Citation
  • 6

    Douw L, , Baayen H, , Bosma I, , Klein M, , Vandertop P, & Heimans J, et al.: Treatment-related changes in functional connectivity in brain tumor patients: a magnetoencephalography study. Exp Neurol 212:285290, 2008

    • Search Google Scholar
    • Export Citation
  • 7

    Eliassen JC, , Boespflug EL, , Lamy M, , Allendorfer J, , Chu WJ, & Szaflarski JP: Brain-mapping techniques for evaluating post-stroke recovery and rehabilitation: a review. Top Stroke Rehabil 15:427450, 2008

    • Search Google Scholar
    • Export Citation
  • 8

    Faul M, , Xu L, , Wald MM, & Coronado VG: Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations, and Deaths Atlanta, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, 2010. (http://www.cdc.gov/traumaticbraininjury/pdf/blue_book.pdf) [Accessed March 14, 2013]

    • Search Google Scholar
    • Export Citation
  • 9

    Fein G, , Raz J, , Brown FF, & Merrin EL: Common reference coherence data are confounded by power and phase effects. Electroencephalogr Clin Neurophysiol 69:581584, 1988

    • Search Google Scholar
    • Export Citation
  • 10

    Finkelstein EA, , Corso PS, & Miller TR: The Incidence and Economic Burden of Injuries in the United States New York, Oxford University Press, 2006

    • Search Google Scholar
    • Export Citation
  • 11

    Friston KJ, , Frith CD, , Liddle PF, & Frackowiak RS: Functional connectivity: the principal-component analysis of large (PET) data sets. J Cereb Blood Flow Metab 13:514, 1993

    • Search Google Scholar
    • Export Citation
  • 12

    Guggisberg AG, , Honma SM, , Findlay AM, , Dalal SS, , Kirsch HE, & Berger MS, et al.: Mapping functional connectivity in patients with brain lesions. Ann Neurol 63:193203, 2008

    • Search Google Scholar
    • Export Citation
  • 13

    Guo CC, , Kurth F, , Zhou J, , Mayer EA, , Eickhoff SB, & Kramer JH, et al.: One-year test-retest reliability of intrinsic connectivity network fMRI in older adults. Neuroimage 61:14711483, 2012

    • Search Google Scholar
    • Export Citation
  • 14

    Hinkley LB, , Owen JP, , Fisher M, , Findlay AM, , Vinogradov S, & Nagarajan SS: Cognitive impairments in schizophrenia as assessed through activation and connectivity measures of magnetoencephalography (MEG) data. Front Hum Neurosci 3:73, 2010

    • Search Google Scholar
    • Export Citation
  • 15

    Hinkley LB, , Vinogradov S, , Guggisberg AG, , Fisher M, , Findlay AM, & Nagarajan SS: Clinical symptoms and alpha band resting-state functional connectivity imaging in patients with schizophrenia: implications for novel approaches to treatment. Biol Psychiatry 70:11341142, 2011

    • Search Google Scholar
    • Export Citation
  • 16

    Huang MX, , Theilmann RJ, , Robb A, , Angeles A, , Nichols S, & Drake A, et al.: Integrated imaging approach with MEG and DTI to detect mild traumatic brain injury in military and civilian patients. J Neurotrauma 26:12131226, 2009

    • Search Google Scholar
    • Export Citation
  • 17

    Jenkins WM, & Merzenich MM: Reorganization of neocortical representations after brain injury: a neurophysiological model of the bases of recovery from stroke. Prog Brain Res 71:249266, 1987

    • Search Google Scholar
    • Export Citation
  • 18

    Lachaux JP, , Rodriguez E, , Martinerie J, & Varela FJ: Measuring phase synchrony in brain signals. Hum Brain Mapp 8:194208, 1999

  • 19

    Le Van Quyen M, , Foucher J, , Lachaux J, , Rodriguez E, , Lutz A, & Martinerie J, et al.: Comparison of Hilbert transform and wavelet methods for the analysis of neuronal synchrony. J Neurosci Methods 111:8398, 2001

    • Search Google Scholar
    • Export Citation
  • 20

    Lee RG, & van Donkelaar P: Mechanisms underlying functional recovery following stroke. Can J Neurol Sci 22:257263, 1995

  • 21

    Lewine JD, , Davis JT, , Bigler ED, , Thoma R, , Hill D, & Funke M, et al.: Objective documentation of traumatic brain injury subsequent to mild head trauma: multimodal brain imaging with MEG, SPECT, and MRI. J Head Trauma Rehabil 22:141155, 2007

    • Search Google Scholar
    • Export Citation
  • 22

    Lewine JD, , Davis JT, , Sloan JH, , Kodituwakku PW, & Orrison WW Jr: Neuromagnetic assessment of pathophysiologic brain activity induced by minor head trauma. AJNR Am J Neuroradiol 20:857866, 1999

    • Search Google Scholar
    • Export Citation
  • 23

    Martino J, , Honma SM, , Findlay AM, , Guggisberg AG, , Owen JP, & Kirsch HE, et al.: Resting functional connectivity in patients with brain tumors in eloquent areas. Ann Neurol 69:521532, 2011

    • Search Google Scholar
    • Export Citation
  • 24

    Nakamura T, , Hillary FG, & Biswal BB: Resting network plasticity following brain injury. PLoS ONE 4:e8220, 2009

  • 25

    National Center for Injury Prevention and Control: Report to Congress on Mild Traumatic Brain Injury in the United States: Steps to Prevent a Serious Public Health Problem Atlanta, Centers for Disease Control and Prevention, 2003. (http://www.cdc.gov/ncipc/pub-res/mtbi/mtbireport.pdf) [Accessed March 14, 2013]

    • Search Google Scholar
    • Export Citation
  • 26

    Nolte G, , Bai O, , Wheaton L, , Mari Z, , Vorbach S, & Hallett M: Identifying true brain interaction from EEG data using the imaginary part of coherency. Clin Neurophysiol 115:22922307, 2004

    • Search Google Scholar
    • Export Citation
  • 27

    Nudo RJ, , Wise BM, , SiFuentes F, & Milliken GW: Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science 272:17911794, 1996

    • Search Google Scholar
    • Export Citation
  • 28

    Nunez PL, , Srinivasan R, , Westdorp AF, , Wijesinghe RS, , Tucker DM, & Silberstein RB, et al.: EEG coherency. I: Statistics, reference electrode, volume conduction, Laplacians, cortical imaging, and interpretation at multiple scales. Electroencephalogr Clin Neurophysiol 103:499515, 1997

    • Search Google Scholar
    • Export Citation
  • 29

    Quigley M, , Cordes D, , Wendt G, , Turski P, , Moritz C, & Haughton V, et al.: Effect of focal and nonfocal cerebral lesions on functional connectivity studied with MR imaging. AJNR Am J Neuroradiol 22:294300, 2001

    • Search Google Scholar
    • Export Citation
  • 30

    Salvador R, , Suckling J, , Coleman MR, , Pickard JD, , Menon D, & Bullmore E: Neurophysiological architecture of functional magnetic resonance images of human brain. Cereb Cortex 15:13321342, 2005

    • Search Google Scholar
    • Export Citation
  • 31

    Sekihara K, , Nagarajan SS, , Poeppel D, & Marantz A: Asymptotic SNR of scalar and vector minimum-variance beamformers for neuromagnetic source reconstruction. IEEE Trans Biomed Eng 51:17261734, 2004

    • Search Google Scholar
    • Export Citation
  • 32

    Sekihara K, , Nagarajan SS, , Poeppel D, , Marantz A, & Miyashita Y: Reconstructing spatio-temporal activities of neural sources using an MEG vector beamformer technique. IEEE Trans Biomed Eng 48:760771, 2001

    • Search Google Scholar
    • Export Citation
  • 33

    Sigurdardottir S, , Andelic N, , Roe C, , Jerstad T, & Schanke AK: Post-concussion symptoms after traumatic brain injury at 3 and 12 months post-injury: a prospective study. Brain Inj 23:489497, 2009

    • Search Google Scholar
    • Export Citation
  • 34

    Stam CJ, , Breakspear M, , van Cappellen van Walsum AM, & van Dijk BW: Nonlinear synchronization in EEG and whole-head MEG recordings of healthy subjects. Hum Brain Mapp 19:6378, 2003

    • Search Google Scholar
    • Export Citation
  • 35

    Stam CJ, , van Cappellen van Walsum AM, , Pijnenburg YA, , Berendse HW, , de Munck JC, & Scheltens P, et al.: Generalized synchronization of MEG recordings in Alzheimer's Disease: evidence for involvement of the gamma band. J Clin Neurophysiol 19:562574, 2002

    • Search Google Scholar
    • Export Citation
  • 36

    Vrba J, & Robinson SE: Signal processing in magnetoencephalography. Methods 25:249271, 2001

  • 37

    Wang JH, , Zuo XN, , Gohel S, , Milham MP, , Biswal BB, & He Y: Graph theoretical analysis of functional brain networks: test-retest evaluation on short- and long-term resting-state functional MRI data. PLoS ONE 6:e21976, 2011

    • Search Google Scholar
    • Export Citation
  • 38

    Westlake KP, & Nagarajan SS: Functional connectivity in relation to motor performance and recovery after stroke. Front Syst Neurosci 5:8, 2011

    • Search Google Scholar
    • Export Citation
  • 39

    Witte OW, & Stoll G: Delayed and remote effects of focal cortical infarctions: secondary damage and reactive plasticity. Adv Neurol 73:207227, 1997

    • Search Google Scholar
    • Export Citation
  • 40

    Zuo XN, , Kelly C, , Adelstein JS, , Klein DF, , Castellanos FX, & Milham MP: Reliable intrinsic connectivity networks: test-retest evaluation using ICA and dual regression approach. Neuroimage 49:21632177, 2010

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 1992 464 32
Full Text Views 406 28 1
PDF Downloads 221 29 1
EPUB Downloads 0 0 0