Challenges in measuring individual differences in functional connectivity using fMRI: The case of healthy aging

Abstract

Many studies report individual differences in functional connectivity, such as those related to age. However, estimates of connectivity from fMRI are confounded by other factors, such as vascular health, head motion and changes in the location of functional regions. Here, we investigate the impact of these confounds, and pre‐processing strategies that can mitigate them, using data from the Cambridge Centre for Ageing & Neuroscience ( www.cam-can.com ). This dataset contained two sessions of resting‐state fMRI from 214 adults aged 18–88. Functional connectivity between all regions was strongly related to vascular health, most likely reflecting respiratory and cardiac signals. These variations in mean connectivity limit the validity of between‐participant comparisons of connectivity estimates, and were best mitigated by regression of mean connectivity over participants. We also showed that high‐pass filtering, instead of band‐pass filtering, produced stronger and more reliable age‐effects. Head motion was correlated with gray‐matter volume in selected brain regions, and with various cognitive measures, suggesting that it has a biological (trait) component, and warning against regressing out motion over participants. Finally, we showed that the location of functional regions was more variable in older adults, which was alleviated by smoothing the data, or using a multivariate measure of connectivity. These results demonstrate that analysis choices have a dramatic impact on connectivity differences between individuals, ultimately affecting the associations found between connectivity and cognition. It is important that fMRI connectivity studies address these issues, and we suggest a number of ways to optimize analysis choices. Hum Brain Mapp 38:4125–4156, 2017 . © 2017 Wiley Periodicals, Inc.

References 89

1. 1.

   Andrews‐Hanna JR, Snyder AZ, Vincent JL, Lustig C, Head D, Raichle ME, Buckner RL (2007 ): Disruption of large‐scale brain systems in advanced aging. Neuron 56:924–935.

   Not in our library10.1016/j.neuron.2007.10.038

2. 2.

   Arbabshirani MR, Damaraju E, Phlypo R, Plis S, Allen E, Ma S, Mathalon D, Preda A, Vaidya JG, Adali T, Calhoun VD (2014 ): Impact of autocorrelation on functional connectivity. Neuroimage 102:294–308.

   Not in our library10.1016/j.neuroimage.2014.07.045

3. 3.

   Ashburner J, Friston KJ (2000 ): Voxel‐based morphometry ‐ The methods. Neuroimage 11:805–821.

   Not in our library10.1006/nimg.2000.0582

4. 4.

   Baddeley A, Emslie H, Nimmo‐Smith I (1993 ): The Spot‐the‐Word test: a robust estimate of verbal intelligence based on lexical decision. Br J Clin Psychol 32:55–65.

   Not in our library10.1111/j.2044-8260.1993.tb01027.x

5. 5.

   Behzadi Y, Restom K, Liau J, Liu TT (2007 ): A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage 37:90–101.

   Not in our library10.1016/j.neuroimage.2007.04.042

6. 6.

   Betzel RF, Byrge L, He Y, Goñi J, Zuo X‐N, Sporns O (2014 ): Changes in structural and functional connectivity among resting‐state networks across the human lifespan. Neuroimage 102:345–357.

   Not in our library10.1016/j.neuroimage.2014.07.067

7. 7.

   Biswal BB, Mennes M, Zuo X‐N‐N, Gohel S, Kelly C, Smith SM, Beckmann CF, Adelstein JS, Buckner RL, Colcombe S, Dogonowski A‐M‐M, Ernst M, Fair D, Hampson M, Hoptman MJ, Hyde JS, Kiviniemi VJ, Kötter R, Li S‐J‐J, Lin C‐P‐P, Lowe MJ, Mackay C, Madden DJ, Madsen KH, Margulies DS, Mayberg HS, McMahon K, Monk CS, Mostofsky SH, Nagel BJ, Pekar JJ, Peltier SJ, Petersen SE, Riedl V, Rombouts SA, Rypma B, Schlaggar BL, Schmidt S, Seidler RD, Siegle GJ, Sorg C, Teng G‐J‐J, Veijola J, Villringer A, Walter M, Wang L, Weng X‐C‐C, Whitfield‐Gabrieli S, Williamson P, Windischberger C, Zang Y‐F‐F, Zhang H‐Y‐Y, Castellanos FX, Milham MP (2010 ): Toward discovery science of human brain function. Proc Natl Acad Sci USA 107:4734–4739.

   Not in our library10.1073/pnas.0911855107

8. 8.
   Beyond Noise: Using Temporal ICA to Extract Meaningful Information from High-Frequency fMRI Signal Fluctuations during Rest · 2013

   No notice
9. 9.
   Is fMRI “noise” really noise? Resting state nuisance regressors remove variance with network structure · 2015

   No notice
10. 10.

    Buckner RL (2013 ): The cerebellum and cognitive function: 25 years of insight from anatomy and neuroimaging. Neuron 80:807–815.

    Not in our library10.1016/j.neuron.2013.10.044

11. 11.

    Buckner RL, Krienen FM, Castellanos a, Diaz JC, Yeo BTT (2011 ): The organization of the human cerebellum estimated by intrinsic functional connectivity. J Neurophysiol 106:2322–2345.

    Not in our library10.1152/jn.00339.2011

12. 12.

    Campbell KL, Shafto MA, Wright P, Tsvetanov KA, Geerligs L, Cusack R, Tyler LK (2015 ): Neurobiology of Aging Idiosyncratic responding during movie‐watching predicted by age differences in attentional control. Neurobiol Aging 36:3045–3055.

    Not in our library10.1016/j.neurobiolaging.2015.07.028

13. 13.

    Cao M, Wang J‐H, Dai Z‐J, Cao X‐Y, Jiang L‐L, Fan F‐M, Song X‐W, Xia M‐R, Shu N, Dong Q, Milham MP, Castellanos FX, Zuo X‐N, He Y (2014 ): Topological organization of the human brain functional connectome across the lifespan. Dev Cogn Neurosci 7:76–93.

    Not in our library10.1016/j.dcn.2013.11.004

14. 14.

    Cattell RB, Cattell AKS (1960 ): Handbook for the individual or group Culture Fair Intelligence Test. Savoy, IL: Institute for Personality and Ability Testing.

    Not in our library

15. 15.

    Chai XJ, Castañán AN, Öngür D, Whitfield‐Gabrieli S (2012 ): Anticorrelations in resting state networks without global signal regression. Neuroimage 59:1420–1428.

    Not in our library10.1016/j.neuroimage.2011.08.048

16. 16.

    Chan MY, Park DC, Savalia NK, Petersen SE, Wig GS (2014 ): Decreased segregation of brain systems across the healthy adult lifespan. Proc Natl Acad Sci USA 111:E4997–E5006.

    Not in our library10.1073/pnas.1415122111

17. 17.

    Chen JE, Glover GH (2015 ): BOLD fractional contribution to resting‐state functional connectivity above 0.1Hz. Neuroimage 107:207–218.

    Not in our library10.1016/j.neuroimage.2014.12.012

18. 18.

    Chen G, Chen G, Xie C, Ward BD, Li W, Antuono P, Li S‐J (2012 ): A method to determine the necessity for global signal regression in resting‐state fMRI studies. Magn Reson Med 68:1828–1835.

    Not in our library10.1002/mrm.24201

19. 19.

    Chou Y‐H, Chen N‐K, Madden DJ (2013 ): Functional brain connectivity and cognition: Effects of adult age and task demands. Neurobiol Aging 34:1925–1934.

    Not in our library10.1016/j.neurobiolaging.2013.02.012

20. 20.

    Craddock RC, James GA, Holtzheimer PE, Hu XP, Mayberg HS (2012 ): A whole brain fMRI atlas generated via spatially constrained spectral clustering. Hum Brain Mapp 33:1914–1928.

    Not in our library10.1002/hbm.21333

21. 21.

    D'Esposito M, Zarahn E, Aguirre GK, Rypma B (1999 ): The effect of normal aging on the coupling of neural activity to the bold hemodynamic response. Neuroimage 10:6–14.

    Not in our library10.1006/nimg.1999.0444

22. 22.

    Dai Z, Yan C, Li K, Wang Z, Wang J, Cao M, Lin Q, Shu N, Xia M, Bi Y, He Y (2015 ): Identifying and mapping connectivity patterns of brain network hubs in Alzheimer' s disease. Cereb Cortex 25:3723–3742.

    Not in our library10.1093/cercor/bhu246

23. 23.

    Damoiseaux JS, Beckmann CF, Arigita EJS, Barkhof F, Scheltens P, Stam CJ, Smith SM, Rombouta SARB, Rombouts S. a RB (2008 ): Reduced resting‐state brain activity in the “default network” in normal aging. Cereb Cortex 18:1856–1864.

    Not in our library10.1093/cercor/bhm207

24. 24.

    Eklund A, Andersson M, Josephson C, Johannesson M, Knutsson H (2012 ): Does parametric fMRI analysis with SPM yield valid results?‐An empirical study of 1484 rest datasets. Neuroimage 61:565–578.

    Not in our library10.1016/j.neuroimage.2012.03.093

25. 25.

    Ferreira LK, Carolina A, Regina B, Kovacevic N, Morais G, Santos PP, Carneiro CDG, Kerr DS, Amaro E Jr, Mcintosh AR, Busatto GF (2016 ): Aging effects on whole‐brain functional connectivity in adults free of cognitive and psychiatric disorders. Cereb Cortex 26:3851–3865.

    Not in our library10.1093/cercor/bhv190

26. 26.

    Folstein MF, Folstein SE, McHugh PR (1975 ): “Mini mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198.

    Not in our library10.1016/0022-3956(75)90026-6

27. 27.

    Friston KJ, Glaser DE, Henson RNA, Kiebel S, Phillips C, Ashburner J (2002 ): Classical and Bayesian inference in neuroimaging: Applications. Neuroimage 16:484–512.

    Not in our library10.1006/nimg.2002.1091

28. 28.

    Geerligs L, Maurits NM, Renken RJ, Lorist MM (2014 ): Reduced specificity of functional connectivity in the aging brain during task performance. Hum Brain Mapp 35:319–330.

    Not in our library10.1002/hbm.22175

29. 29.

    Geerligs L, Renken RJ, Saliasi E, Maurits NM, Lorist MM (2015a ): A brain wide study of age‐related changes in functional connectivity. Cereb Cortex 25:1987–1999.

    Not in our library10.1093/cercor/bhu012

30. 30.

    Geerligs L, Rubinov M, Cam CAN, Henson RN (2015b ): State and trait components of functional connectivity: Individual differences vary with mental state. J Neurosci 35:13949–13961.

    Not in our library10.1523/jneurosci.1324-15.2015

31. 31.

    Geerligs L, Cam CAN, Henson RN (2016 ): Functional connectivity and structural covariance between regions of interest can be measured more accurately using multivariate distance correlation. Neuroimage 135:16–31.

    Not in our library10.1016/j.neuroimage.2016.04.047

32. 32.

    Glover GH, Li T, Ress D (2000 ): Image‐based method for retrospective correction of physiological motion effects in fMRI: RETROICOR. Magn Reson Med 44:162–167.

    Not in our library10.1002/1522-2594(200007)44:1<162::aid-mrm23>3.0.co;2-e

33. 33.

    Golestani AM, Chang C, Kwinta JB, Khatamian YB, Jean Chen J (2015 ): Mapping the end‐tidal CO2 response function in the resting‐state BOLD fMRI signal: Spatial specificity, test–retest reliability and effect of fMRI sampling rate. Neuroimage 104:266–277.

    Not in our library10.1016/j.neuroimage.2014.10.031

34. 34.

    Golestani AM, Kwinta JB, Strother SC, Khatamian YB, Chen JJ (2016 ): The association between cerebrovascular reactivity and resting‐state fMRI functional connectivity in healthy adults: The influence of basal carbon dioxide. Neuroimage 132:301–313.

    Not in our library10.1016/j.neuroimage.2016.02.051

35. 35.

    Gordon EM, Laumann TO, Adeyemo B, Huckins JF, Kelley WM, Petersen SE (2016 ): Generation and evaluation of a cortical area parcellation from resting‐state correlations. Cereb Cortex 26:288–303.

    Not in our library10.1093/cercor/bhu239

36. 36.

    Hafkemeijer A, Grond JVD, Rombouts SARB (2012 ): Imaging the default mode network in aging and dementia ☆. Biochim Biophys Acta J 1822:431–441.

    Not in our library10.1016/j.bbadis.2011.07.008

37. 37.

    Jenkinson M, Bannister P, Brady M, Smith S (2002 ): Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 17:825–841.

    Not in our library10.1016/s1053-8119(02)91132-8

38. 38.

    Jo HJ, Saad ZS, Simmons WK, Milbury LA, Cox RW (2010 ): Mapping sources of correlation in resting state FMRI, with artifact detection and removal. Neuroimage 52:571–582.

    Not in our library10.1016/j.neuroimage.2010.04.246

39. 39.

    Joel SE, Caffo BS, Van Zijl PCM, Pekar JJ (2011 ): On the relationship between seed‐based and ICA‐based measures of functional connectivity. Magn Reson Med 66:644–657.

    Not in our library10.1002/mrm.22818

40. 40.

    Kalaria RN (2010 ): Vascular basis for brain degeneration: Faltering controls and risk factors for dementia. Nutr Rev 68: S74–S87.

    Not in our library10.1111/j.1753-4887.2010.00352.x

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