Functional connectivity in mild traumatic brain injury.
OBJECTIVE
Research suggests that the majority of mild traumatic brain injury (mTBI) patients exhibit both cognitive and emotional dysfunction within the first weeks of injury, followed by symptom resolution 3-6 months postinjury. The neuronal correlates of said dysfunction are difficult to detect with standard clinical neuroimaging, complicating differential diagnosis and early identification of patients who may not recover. This study examined whether resting state functional magnetic resonance imaging (fMRI) provides objective markers of injury and predicts cognitive, emotional, and somatic complaints in mTBI patients semiacutely (<3 weeks postinjury) and in late recovery (3-5 month) phases.


METHODS
Twenty-seven semiacute mTBI patients and 26 gender, age, and education-matched controls were studied. Fifteen of 27 patients returned for a follow-up visit 3-5 months postinjury. The main dependent variables were spontaneous fluctuations (temporal correlation) in the default-mode (DMN) and fronto-parietal task-related networks as measured by fMRI.


RESULTS
Significant differences in self-reported cognitive, emotional, and somatic complaints were observed (all P < 0.05), despite normal clinical (T1 and T2) imaging and neuropsychological testing results. Mild TBI patients demonstrated decreased functional connectivity within the DMN and hyper-connectivity between the DMN and lateral prefrontal cortex. Measures of functional connectivity exhibited high levels of sensitivity and specificity for patient classification and predicted cognitive complaints in the semi-acute injury stage. However, no changes in functional connectivity were observed across a 4-month recovery period.


CONCLUSIONS
Abnormal connectivity between the DMN and frontal cortex may provide objective biomarkers of mTBI and underlie cognitive impairment.
The Mind Research Network, Albuquerque, New Mexico 87106, USA. amayer@mrn.org.
Andrew R
AR
Mayer
Maggie V
MV
Mannell
Josef
J
Ling
Charles
C
Gasparovic
Ronald A
RA
Yeo
D000328:Adult; D001930:Brain Injuries / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000473:pathology; D019416:Head Movements; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D020127:Recovery of Function
D010100:Oxygen
Neuroimage. 2009 Feb 1;44(3):893-905
18976716
J Neuropathol Exp Neurol. 2007 Sep;66(9):771-8
17805007
J Cogn Neurosci. 1999 Jan;11(1):80-95
9950716
J Cogn Neurosci. 2002 Jul 1;14(5):785-94
12167262
J Comput Assist Tomogr. 2006 Sep-Oct;30(5):695-715
16954916
Radiology. 2009 Sep;252(3):816-24
19567646
Hum Brain Mapp. 2009 Aug;30(8):2393-400
19350563
Hum Brain Mapp. 2009 Oct;30(10):3127-41
19235882
Neurology. 2008 Mar 18;70(12):948-55
18347317
Neuroimage. 2001 Nov;14(5):1004-12
11697932
J Neurotrauma. 2009 Aug;26(8):1183-96
19317591
Nature. 2008 Jun 12;453(7197):869-78
18548064
PLoS One. 2009 Dec 14;4(12):e8220
20011533
Cereb Cortex. 2009 Aug;19(8):1889-95
19068488
Science. 2007 Jan 19;315(5810):393-5
17234951
Magn Reson Med. 1995 May;33(5):636-47
7596267
NMR Biomed. 2002 Nov-Dec;15(7-8):561-9
12489102
Nat Neurosci. 2006 Jul;9(7):971-8
16767087
Ann N Y Acad Sci. 2008 Oct;1142:266-309
18990132
J Neurosurg. 2005 Aug;103(2):298-303
16175860
AJNR Am J Neuroradiol. 2002 May;23(5):794-802
12006280
Neurol Res. 2007 Oct;29(7):654-60
18173902
Ann N Y Acad Sci. 2008;1129:119-29
18591474
IEEE Trans Med Imaging. 2007 Nov;26(11):1448-55
18041260
Neurosci Biobehav Rev. 2009 Mar;33(3):279-96
18824195
Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13040-5
19620724
Acta Neuropathol. 2006 Jul;112(1):85-94
16718445
Proc Natl Acad Sci U S A. 2008 Apr 22;105(16):6173-8
18427123
Annu Rev Neurosci. 2009;32:75-94
19400718
Neuroimage. 2010 Feb 1;49(3):2467-78
19796693
Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):676-82
11209064
Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9673-8
15976020
Crit Care Med. 2007 Apr;35(4):1153-60
17334254
IEEE J Sel Top Signal Process. 2008 Dec 1;2(6):986-997
19777078
Comput Biomed Res. 1996 Jun;29(3):162-73
8812068
J Neurotrauma. 2009 Oct;26(10):1635-43
19355814
Brain. 2007 Oct;130(Pt 10):2508-19
17872928
Biol Psychiatry. 2008 Feb 1;63(3):332-7
17888409
Hum Brain Mapp. 2009 Sep;30(9):2789-803
19117278
J Cereb Blood Flow Metab. 2009 Mar;29(3):575-84
19088740
J Head Trauma Rehabil. 2007 May-Jun;22(3):141-55
17510590
Neurology. 2000 Apr 25;54(8):1625-33
10762504
Brain. 2008 Dec;131(Pt 12):3209-21
18952679
J Head Trauma Rehabil. 2005 Jan-Feb;20(1):76-94
15668572
J Int Neuropsychol Soc. 2008 Jan;14(1):1-22
18078527
Brain. 2010 Jan;133(Pt 1):161-71
20034928
Neurology. 2010 Feb 23;74(8):643-50
20089939
Hum Brain Mapp. 2009 Aug;30(8):2641-55
19086023
Hum Brain Mapp. 2009 Feb;30(2):625-37
18219617
J Neurotrauma. 2010 Mar;27(3):527-39
19938945
J Neuropsychiatry Clin Neurosci. 2007 Winter;19(1):5-20
17308222
Neuroimage. 2004 May;22(1):68-82
15109998
Ann Neurol. 2004 Apr;55(4):522-9
15048891
Nat Rev Neurosci. 2007 Sep;8(9):700-11
17704812
Annu Rev Neurosci. 2006;29:449-76
16776593
Brain Inj. 2008 Feb;22(2):115-22
18240040
Psychol Rev. 2001 Jul;108(3):624-52
11488380
Ann N Y Acad Sci. 2008 Mar;1124:1-38
18400922
Hum Brain Mapp. 2009 Dec;30(12):4152-66
19554558
IEEE Trans Neural Syst Rehabil Eng. 2010 Feb;18(1):11-9
20064767
J Neurophysiol. 2009 Jun;101(6):3270-83
19339462
J Neurotrauma. 2006 Oct;23(10):1450-67
17020482
Neurology. 1999 Oct 12;53(6):1300-8
10522888
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4637-42
15070770
J Cogn Neurosci. 2000 Jan;12(1):1-47
10769304
J Neurotrauma. 2009 Aug;26(8):1213-26
19385722
J Neurotrauma. 2007 Sep;24(9):1447-59
17892407
J Neurol Neurosurg Psychiatry. 2006 Apr;77(4):518-20
16543534
J Int Neuropsychol Soc. 2005 May;11(3):215-27
15892898