Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-23T14:04:25.632Z Has data issue: false hasContentIssue false
  • English
  • Français

Elevated Intraindividual Variability in Executive Functions and Associations with White Matter Microstructure in Veterans with Mild Traumatic Brain Injury

Published online by Cambridge University Press:  24 September 2020

Scott F. Sorg Open the ORCID record for Scott F. Sorg [Opens in a new window] ,
Victoria C. Merritt Open the ORCID record for Victoria C. Merritt [Opens in a new window] ,
Alexandra L. Clark ,
Madeleine L. Werhane ,
Kelsey A. Holiday ,
Dawn M. Schiehser ,
Mark Bondi  and
Lisa Delano-Wood
Scott F. Sorg
Affiliation:
Psychology and Research Services, VA San Diego Healthcare System (VASDHS), San Diego, CA, USA Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
Victoria C. Merritt
Affiliation:
Psychology and Research Services, VA San Diego Healthcare System (VASDHS), San Diego, CA, USA
Alexandra L. Clark
Affiliation:
Psychology and Research Services, VA San Diego Healthcare System (VASDHS), San Diego, CA, USA
Madeleine L. Werhane
Affiliation:
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA
Kelsey A. Holiday
Affiliation:
San Diego State University/University of California, San Diego (SDSU/UCSD) Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA
Dawn M. Schiehser
Affiliation:
Psychology and Research Services, VA San Diego Healthcare System (VASDHS), San Diego, CA, USA Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System (VASDHS), San Diego, CA, USA
Mark Bondi
Affiliation:
Psychology and Research Services, VA San Diego Healthcare System (VASDHS), San Diego, CA, USA Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA
Lisa Delano-Wood*
Affiliation:
Psychology and Research Services, VA San Diego Healthcare System (VASDHS), San Diego, CA, USA Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System (VASDHS), San Diego, CA, USA
*
*Correspondence and reprint requests to: Lisa Delano-Wood, Ph.D., VA San Diego Healthcare System (151B), 3350 La Jolla Village Drive, San Diego, CA92161, USA. Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

We examined whether intraindividual variability (IIV) across tests of executive functions (EF-IIV) is elevated in Veterans with a history of mild traumatic brain injury (mTBI) relative to military controls (MCs) without a history of mTBI. We also explored relationships among EF-IIV, white matter microstructure, and posttraumatic stress disorder (PTSD) symptoms.

Method:

A total of 77 Veterans (mTBI = 43, MCs = 34) completed neuropsychological testing, diffusion tensor imaging (DTI), and PTSD symptom ratings. EF-IIV was calculated as the standard deviation across six tests of EF, along with an EF-Mean composite. DSI Studio connectometry analysis identified white matter tracts significantly associated with EF-IIV according to generalized fractional anisotropy (GFA).

Results:

After adjusting for EF-Mean and PTSD symptoms, the mTBI group showed significantly higher EF-IIV than MCs. Groups did not differ on EF-Mean after adjusting for PTSD symptoms. Across groups, PTSD symptoms significantly negatively correlated with EF-Mean, but not with EF-IIV. EF-IIV significantly negatively correlated with GFA in multiple white matter pathways connecting frontal and more posterior regions.

Conclusions:

Veterans with mTBI demonstrated significantly greater IIV across EF tests compared to MCs, even after adjusting for mean group differences on those measures as well as PTSD severity. Findings suggest that, in contrast to analyses that explore effects of mean performance across tests, discrepancy analyses may capture unique variance in neuropsychological performance and more sensitively capture cognitive disruption in Veterans with mTBI histories. Importantly, findings show that EF-IIV is negatively associated with the microstructure of white matter pathways interconnecting cortical regions that mediate executive function and attentional processes.

Keywords

Brain concussionTBIMild TBImTBICognitionAssessmentPatient outcomediffusion tensor imagingNeuroimagingExecutive control
Type
Regular Research
Information
Journal of the International Neuropsychological Society , Volume 27 , Issue 4 , April 2021 , pp. 305 - 314
Copyright
Copyright © INS. Published by Cambridge University Press, 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Bangen, K.J., Weigand, A.J., Thomas, K.R., Delano-Wood, L., Clark, L.R., Eppig, J., … Bondi, M.W. (2019). Cognitive dispersion is a sensitive marker for early neurodegenerative changes and functional decline in nondemented older adults. Neuropsychology, 33(5), 599–608. https://doi.org/10.1037/neu0000532 CrossRefGoogle ScholarPubMed
Belanger, H.G., Kretzmer, T., Vanderploeg, R.D., & French, L.M. (2010). Symptom complaints following combat-related traumatic brain injury: Relationship to traumatic brain injury severity and posttraumatic stress disorder. Journal of the International Neuropsychological Society, 16(1), 194–199. https://doi.org/10.1017/S1355617709990841 CrossRefGoogle ScholarPubMed
Bigler, E.D., & Maxwell, W.L. (2012). Neuropathology of mild traumatic brain injury: Relationship to neuroimaging findings. Brain Imaging and Behavior, 6(2), 108–136. https://doi.org/10.1007/s11682-011-9145-0 CrossRefGoogle ScholarPubMed
Binder, L.M., Iverson, G.L., & Brooks, B.L. (2009). To err is human: “abnormal” neuropsychological scores and variability are common in healthy adults. Archives of Clinical Neuropsychology, 24(1), 31–46. https://doi.org/10.1093/arclin/acn001 CrossRefGoogle Scholar
Buki, A., & Povlishock, J.T. (2006). All roads lead to disconnection?—Traumatic axonal injury revisited. Acta Neurochirurgica (Wien), 148(2), 181–193; discussion 193-4. https://doi.org/10.1007/s00701-005-0674-4 CrossRefGoogle Scholar
Clouston, S., Pietrzak, R.H., Kotov, R., Richards, M., Spiro, A., Scott, S., … Luft, B.J. (2017). Traumatic exposures, posttraumatic stress disorder, and cognitive functioning in World Trade Center responders. Alzheimer’s & Dementia (N Y), 3(4), 593–602. https://doi.org/10.1016/j.trci.2017.09.001 CrossRefGoogle ScholarPubMed
Cole, W.R., Gregory, E., Arrieux, J.P., & Haran, F.J. (2018). Intraindividual cognitive variability: An examination of ANAM4 TBI-MIL simple reaction time data from service members with and without mild traumatic brain injury. Journal of the International Neuropsychological Society, 24(2), 156–162. https://doi.org/10.1017/S1355617717001187 CrossRefGoogle ScholarPubMed
De Santis, S., Drakesmith, M., Bells, S., Assaf, Y., & Jones, D.K. (2014). Why diffusion tensor MRI does well only some of the time: Variance and covariance of white matter tissue microstructure attributes in the living human brain. Neuroimage, 89, 35–44. https://doi.org/10.1016/j.neuroimage.2013.12.003 CrossRefGoogle ScholarPubMed
Delano-Wood, L., Bangen, K.J., Sorg, S.F., Clark, A.L., Schiehser, D.M., Luc, N., … Bigler, E.D. (2015). Brainstem white matter integrity is related to loss of consciousness and postconcussive symptomatology in veterans with chronic mild to moderate traumatic brain injury. Brain Imaging and Behavior, 9(3), 500–512. https://doi.org/10.1007/s11682-015-9432-2 CrossRefGoogle ScholarPubMed
Delis, D., Kaplan, E., & Kramer, J.H. (2001). The Delis-Kaplan Executive Function System. San Antonio, TX: Psychological Corporation.Google Scholar
Delis, D., Kramer, J.H., Kaplan, E., & Ober, B. (2000). The California Verbal Learning Test: Second Edition. San Antonio, TX: Psychological Corporation.Google Scholar
Dolan, S., Martindale, S., Robinson, J., Kimbrel, N.A., Meyer, E.C., Kruse, M.I., … Gulliver, S.B. (2012). Neuropsychological sequelae of PTSD and TBI following war deployment among OEF/OIF veterans. Neuropsychology Review, 22(1), 21–34. https://doi.org/10.1007/s11065-012-9190-5 CrossRefGoogle ScholarPubMed
Donnelly, K., Donnelly, J.P., Warner, G.C., Kittleson, C.J., & King, P.R. (2018). Longitudinal study of objective and subjective cognitive performance and psychological distress in OEF/OIF veterans with and without traumatic brain injury. The Clinical Neuropsychologist, 32(3), 436-455.CrossRefGoogle ScholarPubMed
French, L.M., Lange, R.T., & Brickell, T. (2014). Subjective cognitive complaints and neuropsychological test performance following military-related traumatic brain injury. Journal of Rehabilitation Research and Development, 51(6), 933–950. https://doi.org/10.1682/JRRD.2013.10.0226 CrossRefGoogle ScholarPubMed
Hill, B.D., Rohling, M.L., Boettcher, A.C., & Meyers, J.E. (2013). Cognitive intra-individual variability has a positive association with traumatic brain injury severity and suboptimal effort. Archives of Clinical Neuropsychology, 28(7), 640–648. https://doi.org/10.1093/arclin/act045 CrossRefGoogle Scholar
Hines, L.J., Miller, E.N., Hinkin, C.H., Alger, J.R., Barker, P., Goodkin, K., … Multicenter, A.C.S. (2016). Cortical brain atrophy and intra-individual variability in neuropsychological test performance in HIV disease. Brain Imaging and Behavior, 10(3), 640–651. https://doi.org/10.1007/s11682-015-9441-1 CrossRefGoogle ScholarPubMed
Jones, D.K., Horsfield, M.A., & Simmons, A. (1999). Optimal strategies for measuring diffusion in anisotropic systems by magnetic resonance imaging. Magnetic Resonance in Medicine, 42(3), 515–525.3.0.CO;2-Q>CrossRefGoogle ScholarPubMed
Jones, J.D., Kuhn, T., Mahmood, Z., Singer, E.J., Hinkin, C.H., & Thames, A.D. (2018). Longitudinal intra-individual variability in neuropsychological performance relates to white matter changes in HIV. Neuropsychology, 32(2), 206–212. https://doi.org/10.1037/neu0000390 CrossRefGoogle ScholarPubMed
Kelly, A.M., Uddin, L.Q., Biswal, B.B., Castellanos, F.X., & Milham, M.P. (2008). Competition between functional brain networks mediates behavioral variability. Neuroimage, 39(1), 527–537. https://doi.org/10.1016/j.neuroimage.2007.08.008 CrossRefGoogle ScholarPubMed
Kongs, K.S. (2000). Wisconsin Card Sorting Test-64 Card Version (WCST-64). Odessa, FL: Psychological Assessment Resources.Google Scholar
Mac Donald, C.L., Barber, J., Jordan, M., Johnson, A.M., Dikmen, S., Fann, J.R., & Temkin, N. (2017). Early clinical predictors of 5-year outcome after concussive blast traumatic brain injury. JAMA Neurology, 74(7), 821–829. https://doi.org/10.1001/jamaneurol.2017.0143 CrossRefGoogle ScholarPubMed
MacDonald, S.W., Li, S.C., & Backman, L. (2009). Neural underpinnings of within-person variability in cognitive functioning. Psychology and Aging, 24(4), 792–808. https://doi.org/10.1037/a0017798 CrossRefGoogle ScholarPubMed
McCrea, M., Iverson, G.L., McAllister, T.W., Hammeke, T.A., Powell, M.R., Barr, W.B., & Kelly, J.P. (2009). An integrated review of recovery after mild traumatic brain injury (MTBI): Implications for clinical management. Clinical Neuropsychologist, 23(8), 1368–1390. https://doi.org/10.1080/13854040903074652 CrossRefGoogle ScholarPubMed
Merritt, V.C., Clark, A.L., Crocker, L.D., Sorg, S.F., Werhane, M.L., Bondi, M.W., … Delano-Wood, L. (2018). Repetitive mild traumatic brain injury in military veterans is associated with increased neuropsychological intra-individual variability. Neuropsychologia, 119, 340–348. https://doi.org/10.1016/j.neuropsychologia.2018.08.026 CrossRefGoogle ScholarPubMed
Miller, D.R., Hayes, J.P., Lafleche, G., Salat, D.H., & Verfaellie, M. (2016). White matter abnormalities are associated with chronic postconcussion symptoms in blast-related mild traumatic brain injury: White Matter Abnormalities and PCS. Human Brain Mapping, 37(1), 220–229. https://doi.org/10.1002/hbm.23022 CrossRefGoogle Scholar
Moore, B.A., & Donders, J. (2004). Predictors of invalid neuropsychological test performance after traumatic brain injury. Brain Injury, 18(10), 975–984. https://doi.org/10.1080/02699050410001672350 CrossRefGoogle ScholarPubMed
Morey, R.A., Haswell, C.C., Selgrade, E.S., Massoglia, D., Liu, C., Weiner, J., … McCarthy, G. (2013). Effects of chronic mild traumatic brain injury on white matter integrity in Iraq and Afghanistan war veterans. Hum Brain Mapping, 34(11), 2986–2999. https://doi.org/10.1002/hbm.22117 CrossRefGoogle ScholarPubMed
Morgan, E.E., Woods, S.P., Delano-Wood, L., Bondi, M.W., Grant, I., & H. I. V. Neurobehavioral Research Program Group. (2011). Intraindividual variability in HIV infection: Evidence for greater neurocognitive dispersion in older HIV seropositive adults. Neuropsychology, 25(5), 645–654. https://doi.org/10.1037/a0023792 CrossRefGoogle ScholarPubMed
Nilsson, M., Latt, J., Stahlberg, F., van Westen, D., & Hagslatt, H. (2012). The importance of axonal undulation in diffusion MR measurements: A Monte Carlo simulation study. NMR in Biomedicine, 25(5), 795–805. https://doi.org/10.1002/nbm.1795 CrossRefGoogle ScholarPubMed
Oouchi, H., Yamada, K., Sakai, K., Kizu, O., Kubota, T., Ito, H., & Nishimura, T. (2007). Diffusion anisotropy measurement of brain white matter is affected by voxel size: Underestimation occurs in areas with crossing fibers. American Journal of Neuroradiology, 28(6), 1102–1106. https://doi.org/10.3174/ajnr.A0488 CrossRefGoogle ScholarPubMed
Rabinowitz, A.R., & Arnett, P.A. (2013). Intraindividual cognitive variability before and after sports-related concussion. Neuropsychology, 27(4), 481–490. https://doi.org/10.1037/a0033023 CrossRefGoogle ScholarPubMed
Reese, T.G., Heid, O., Weisskoff, R.M., & Wedeen, V.J. (2003). Reduction of eddy-current-induced distortion in diffusion MRI using a twice-refocused spin echo. Magnetic Resonance in Medicine, 49(1), 177–182. https://doi.org/10.1002/mrm.10308 CrossRefGoogle ScholarPubMed
Rohling, M.L., Binder, L.M., Demakis, G.J., Larrabee, G.J., Ploetz, D.M., & Langhinrichsen-Rohling, J. (2011). A meta-analysis of neuropsychological outcome after mild traumatic brain injury: Re-analyses and reconsiderations of Binder et al. (1997), Frencham et al. (2005), and Pertab et al. (2009). Clinical Neuropsychologist, 25(4), 608–623. https://doi.org/10.1080/13854046.2011.565076 CrossRefGoogle Scholar
Sorg, S.F., Delano-Wood, L., Luc, N., Schiehser, D.M., Hanson, K.L., Nation, D.A., … Bondi, M.W. (2014). White matter integrity in veterans with mild traumatic brain injury: Associations with executive function and loss of consciousness. Journal of Head Trauma Rehabilitation, 29(1), 21–32. https://doi.org/10.1097/HTR.0b013e31828a1aa4 CrossRefGoogle ScholarPubMed
Sorg, S.F., Schiehser, D.M., Bondi, M.W., Luc, N., Clark, A.L., Jacobson, M.W., … Delano-Wood, L. (2016). White matter microstructural compromise is associated with cognition but not posttraumatic stress disorder symptoms in military veterans with traumatic brain injury. Journal of Head Trauma Rehabilitation, 31(5), 297–308. https://doi.org/10.1097/HTR.0000000000000189 CrossRefGoogle Scholar
Strauss, E., Slick, D.J., Levy-Bencheton, J., Hunter, M., MacDonald, S.W., & Hultsch, D.F. (2002). Intraindividual variability as an indicator of malingering in head injury. Archives of Clinical Neuropsychology, 17(5), 423–444.CrossRefGoogle ScholarPubMed
Swick, D., Honzel, N., Larsen, J., & Ashley, V. (2013). Increased response variability as a marker of executive dysfunction in veterans with post-traumatic stress disorder. Neuropsychologia, 51(14), 3033–3040. https://doi.org/10.1016/j.neuropsychologia.2013.10.008 CrossRefGoogle ScholarPubMed
Tanner-Eggen, C., Balzer, C., Perrig, W.J., & Gutbrod, K. (2015). The neuropsychological assessment of cognitive deficits considering measures of performance variability. Archives of Clinical Neuropsychology, 30(3), 217–227. https://doi.org/10.1093/arclin/acv008 CrossRefGoogle ScholarPubMed
Tombaugh, T.N. (1996). Test of memory malingering (TOMM). Toronto, Ontario, Canada: Multi-Health Systems, Inc. Google Scholar
Traumatic Brain Injury Task Force. (2009). Report to the surgeon general: TBI task force. http://www.healthquality.va.gov/guidelines/Rehab/mtbi/concussion_mtbi_full_1_0.pdf.Google Scholar
Tuch, D.S. (2004). Q-ball imaging. Magnetic Resonance in Medicine, 52(6), 1358–1372. https://doi.org/10.1002/mrm.20279 CrossRefGoogle ScholarPubMed
Vanderploeg, R.D., Curtiss, G., & Belanger, H.G. (2005). Long-term neuropsychological outcomes following mild traumatic brain injury. Journal of the International Neuropsychological Society, 11(3), 228–236. https://doi.org/10.1017/S1355617705050289 CrossRefGoogle ScholarPubMed
Vasterling, J.J., & Dikmen, S. (2012). Mild traumatic brain injury and posttraumatic stress disorder: Clinical and conceptual complexities. Journal of the International Neuropsychological Society, 18(3), 390–393. https://doi.org/10.1017/S1355617712000367 CrossRefGoogle ScholarPubMed
Vanderploeg, R.D., Groer, S., & Belanger, H.G. (2012). Initial developmental process of a VA semistructured clinical interview for TBI identification. Journal of Rehabilitation Research and Development, 49(4), 545–556. https://doi.org/10.1682/jrrd.2011.04.0069 CrossRefGoogle Scholar
Verfaellie, M., Lafleche, G., Spiro, A., & Bousquet, K. (2014). Neuropsychological outcomes in OEF/OIF veterans with self-report of blast exposure: Associations with mental health, but not MTBI. Neuropsychology, 28(3), 337–346. https://doi.org/10.1037/neu0000027 CrossRefGoogle Scholar
Weathers, F., Huska, J., & Keane, T. (1991). The PTSD checklist military version (PCL-M). Boston, MA: National Center for PTSD, p. 42.Google Scholar
Yeh, F.C., Badre, D., & Verstynen, T. (2016). Connectometry: A statistical approach harnessing the analytical potential of the local connectome. Neuroimage, 125, 162–171. https://doi.org/10.1016/j.neuroimage.2015.10.053 CrossRefGoogle ScholarPubMed
Yeh, F.-C., Panesar, S., Barrios, J., Fernandes, D., Abhinav, K., Meola, A., & Fernandez-Miranda, J.C. (2019). Automatic removal of false connections in diffusion MRI tractography using topology-informed pruning (TIP). Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics, 16(1), 52–58. https://doi.org/10.1007/s13311-018-0663-y CrossRefGoogle Scholar
Yeh, F.C., Tang, P F., & Tseng, W.Y. (2013). Diffusion MRI connectometry automatically reveals affected fiber pathways in individuals with chronic stroke. NeuroImage: Clinical, 2, 912–921. https://doi.org/10.1016/j.nicl.2013.06.014 CrossRefGoogle ScholarPubMed
Yeh, F.C., & Tseng, W.Y. (2011). NTU-90: A high angular resolution brain atlas constructed by q-space diffeomorphic reconstruction. Neuroimage, 58(1), 91–99. https://doi.org/10.1016/j.neuroimage.2011.06.021 CrossRefGoogle ScholarPubMed
Yeh, F.C., Verstynen, T.D., Wang, Y., Fernandez-Miranda, J.C., & Tseng, W.Y. (2013). Deterministic diffusion fiber tracking improved by quantitative anisotropy. PLoS One, 8(11), e80713. https://doi.org/10.1371/journal.pone.0080713 CrossRefGoogle ScholarPubMed
Yurgil, K.A., Barkauskas, D.A., Vasterling, J.J., Nievergelt, C.M, Larson, G.E., Schork, N.J., … Marine Resiliency Study, T. (2014). Association between traumatic brain injury and risk of posttraumatic stress disorder in active-duty Marines. JAMA Psychiatry, 71(2), 149–157. https://doi.org/10.1001/jamapsychiatry.2013.3080 CrossRefGoogle ScholarPubMed