Neurological Music Therapy Rebuilds Structural Connectome after Traumatic Brain Injury: Secondary Analysis from a Randomized Controlled Trial

Aleksi J Sihvonen, Sini-Tuuli Siponkoski, Noelia Martínez-Molina, Sari Laitinen, Milla Holma, Mirja Ahlfors, Linda Kuusela, Johanna Pekkola, Sanna Koskinen, Teppo Särkämö, Aleksi J Sihvonen, Sini-Tuuli Siponkoski, Noelia Martínez-Molina, Sari Laitinen, Milla Holma, Mirja Ahlfors, Linda Kuusela, Johanna Pekkola, Sanna Koskinen, Teppo Särkämö

Abstract

Background: Traumatic brain injury (TBI) is a common and devastating neurological condition, associated often with poor functional outcome and deficits in executive function. Due to the neuropathology of TBI, neuroimaging plays a crucial role in its assessment, and while diffusion MRI has been proposed as a sensitive biomarker, longitudinal studies evaluating treatment-related diffusion MRI changes are scarce. Recent evidence suggests that neurological music therapy can improve executive functions in patients with TBI and that these effects are underpinned by neuroplasticity changes in the brain. However, studies evaluating music therapy induced structural connectome changes in patients with TBI are lacking.

Design: Single-blind crossover (AB/BA) randomized controlled trial (NCT01956136).

Objective: Here, we report secondary outcomes of the trial and set out to assess the effect of neurological music therapy on structural white matter connectome changes and their association with improved execute function in patients with TBI.

Methods: Using an AB/BA design, 25 patients with moderate or severe TBI were randomized to receive a 3-month neurological music therapy intervention either during the first (AB, n = 16) or second (BA, n = 9) half of a 6-month follow-up period. Neuropsychological testing and diffusion MRI scans were performed at baseline and at the 3-month and 6-month stage.

Findings: Compared to the control group, the music therapy group increased quantitative anisotropy (QA) in the right dorsal pathways (arcuate fasciculus, superior longitudinal fasciculus) and in the corpus callosum and the right frontal aslant tract, thalamic radiation and corticostriatal tracts. The mean increased QA in this network of results correlated with improved executive function.

Conclusions: This study shows that music therapy can induce structural white matter neuroplasticity in the post-TBI brain that underpins improved executive function.

Keywords: DTI; TBI; connectometry; executive function; music therapy; rehabilitation; structural connectivity; traumatic brain injury.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram outlining the trial.
Figure 2
Figure 2
Music therapy induced structural white matter connectometry changes. Significant connectometry changes showing increased structural white matter connectivity between (A) music therapy and control group (TP2 > TP1) and (B) music therapy and control group (TP3 > TP2). Mean longitudinal QA change correlations (Spearman, two-tailed) to FAB score change are shown with scatter plots. Bar plots for mean QA in the significant connectivity results for both groups are shown: bar = mean, error-bar = standard error of mean, d = Cohen’s d, L = left, QA = quantitative anisotropy, R = Right, TP = time point.

References

    1. Maas A.I.R., Menon D.K., David Adelson P.D., Andelic N., Bell M.J., Belli A., Bragge P., Brazinova A., Büki A., Chesnut R.M., et al. Traumatic brain injury: Integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017;16:987–1048. doi: 10.1016/S1474-4422(17)30371-X.
    1. Colantonio A., Ratcliff G., Chase S., Kelsey S., Escobar M., Vernich L. Long term outcomes after moderate to severe traumatic brain injury. Disabil. Rehabil. 2004;26:253–261. doi: 10.1080/09638280310001639722.
    1. Strich S.J. Diffuse degeneration of the cerebral white matter in severe dementia following head injury. J. Neurol. Neurosurg. Psychiatry. 1956;19:163–185. doi: 10.1136/jnnp.19.3.163.
    1. Peerless S.J., Rewcastle N.B. Shear injuries of the brain. Can. Med. Assoc. J. 1967;96:577–582.
    1. Hoofien D., Gilboa A., Vakil E., Donovick P.J. Traumatic brain injury (TBI) 10–20 years later: A comprehensive outcome study of psychiatric symptomatology, cognitive abilities and psychosocial functioning. Brain Inj. 2001;15:189–209. doi: 10.1080/026990501300005659.
    1. Langlois J.A., Rutland-Brown W., Wald M.M. The epidemiology and impact of traumatic brain injury: A brief overview. J. Head Trauma Rehabil. 2006;21:375–378. doi: 10.1097/00001199-200609000-00001.
    1. Dikmen S.S., Corrigan J.D., Levin H.S., MacHamer J., Stiers W., Weisskopf M.G. Cognitive outcome following traumatic brain injury. J. Head Trauma Rehabil. 2009;24:430–438. doi: 10.1097/HTR.0b013e3181c133e9.
    1. McDonald B.C., Flashman L.A., Saykin A.J. Executive dysfunction following traumatic brain injury: Neural substrates and treatment strategies. NeuroRehabilitation. 2002;17:333–344. doi: 10.3233/NRE-2002-17407.
    1. Kinnunen K.M., Greenwood R., Powell J.H., Leech R., Hawkins P.C., Bonnelle V., Patel M.C., Counsell S.J., Sharp D.J. White matter damage and cognitive impairment after traumatic brain injury. Brain. 2011;134:449–463. doi: 10.1093/brain/awq347.
    1. Sharp D.J., Scott G., Leech R. Network dysfunction after traumatic brain injury. Nat. Rev. Neurol. 2014;10:156–166. doi: 10.1038/nrneurol.2014.15.
    1. Scheid R., Walther K., Guthke T., Preul C., Von Cramon D.Y. Cognitive sequelae of diffuse axonal injury. Arch. Neurol. 2006;63:418–424. doi: 10.1001/archneur.63.3.418.
    1. Brandstack N., Kurki T., Tenovuo O. Quantitative diffusion-tensor tractography of long association tracts in patients with traumatic brain injury without associated findings at routine MR imaging. Radiology. 2013;267:231–239. doi: 10.1148/radiol.12112570.
    1. Palacios E.M., Owen J.P., Yuh E.L., Wang M.B., Vassar M.J., Ferguson A.R., Diaz-Arrastia R., Giacino J.T., Okonkwo D.O., Robertson C.S., et al. The evolution of white matter microstructural changes after mild traumatic brain injury: A longitudinal DTI and NODDI study. Sci. Adv. 2020;6:eaaz6892. doi: 10.1126/sciadv.aaz6892.
    1. Douglas D.B., Iv M., Douglas P.K., Anderson A., Vos S.B., Bammer R., Zeineh M., Wintermark M. Diffusion tensor imaging of TBI: Potentials and challenges. Top. Magn. Reson. Imaging. 2015;24:241–251. doi: 10.1097/RMR.0000000000000062.
    1. Johnson V.E., Stewart J.E., Begbie F.D., Trojanowski J.Q., Smith D.H., Stewart W. Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain. 2013;136:28–42. doi: 10.1093/brain/aws322.
    1. Farbota K.D., Bendlin B.B., Alexander A.L., Rowley H.A., Dempsey R.J., Johnson S.C. Longitudinal diffusion tensor imaging and neuropsychological correlates in traumatic brain injury patients. Front. Hum. Neurosci. 2012;6:160. doi: 10.3389/fnhum.2012.00160.
    1. Hellstrøm T., Westlye L.T., Kaufmann T., Trung Doan N., Søberg H.L., Sigurdardottir S., Nordhøy W., Helseth E., Andreassen O.A., Andelic N. White matter microstructure is associated with functional, cognitive and emotional symptoms 12 months after mild traumatic brain injury. Sci. Rep. 2017;7:1–14. doi: 10.1038/s41598-017-13628-1.
    1. Braeckman K., Descamps B., Caeyenberghs K., Vanhove C. Longitudinal DTI changes following cognitive training therapy in a mild traumatic brain injury rat model. Front. Neurosci. 2018;12 doi: 10.3389/conf.fnins.2018.95.00074.
    1. Cernich A.N., Kurtz S.M., Mordecai K.L., Ryan P.B. Cognitive rehabilitation in traumatic brain injury. Curr. Treat. Options Neurol. 2010;12:412–423. doi: 10.1007/s11940-010-0085-6.
    1. Cicerone K., Levin H., Malec J., Stuss D., Whyte J., Edwards E. Cognitive rehabilitation interventions for executive function: Moving from bench to bedside in patients with traumatic brain injury. J. Cogn. Neurosci. 2006;18:1212–1222. doi: 10.1162/jocn.2006.18.7.1212.
    1. Sihvonen A.J., Särkämö T., Leo V., Tervaniemi M., Altenmüller E., Soinila S. Music-based interventions in neurological rehabilitation. Lancet Neurol. 2017;16:648–660. doi: 10.1016/S1474-4422(17)30168-0.
    1. Särkämö T., Tervaniemi M., Laitinen S., Forsblom A., Soinila S., Mikkonen M., Autti T., Silvennoinen H.M., Erkkilä J., Laine M., et al. Music listening enhances cognitive recovery and mood after middle cerebral artery stroke. Brain. 2008;131:866–876. doi: 10.1093/brain/awn013.
    1. Sihvonen A.J., Leo V., Ripollés P., Lehtovaara T., Ylönen A., Rajanaro P., Laitinen S., Forsblom A., Saunavaara J., Autti T., et al. Vocal music enhances memory and language recovery after stroke: Pooled results from two RCTs. Ann. Clin. Transl. Neurol. 2020;7:2272–2287. doi: 10.1002/acn3.51217.
    1. Sihvonen A.J., Ripollés P., Leo V., Saunavaara J., Parkkola R., Rodriguez-Fornells A., Soinila S., Särkämö T., Rodríguez-Fornells A., Soinila S., et al. Vocal music listening enhances post-stroke language network reorganization. eNeuro. 2021;8:34140351. doi: 10.1523/ENEURO.0158-21.2021.
    1. Särkämö T., Ripollés P., Vepsäläinen H., Autti T., Silvennoinen H.M., Salli E., Laitinen S., Forsblom A., Soinila S., Rodríguez-Fornells A. Structural changes induced by daily music listening in the recovering brain after middle cerebral artery stroke: A voxel-based morphometry study. Front. Hum. Neurosci. 2014;8:245. doi: 10.3389/fnhum.2014.00245.
    1. Siponkoski S.T., Martínez-Molina N., Kuusela L., Laitinen S., Holma M., Ahlfors M., Jordan-Kilkki P., Ala-Kauhaluoma K., Melkas S., Pekkola J., et al. Music Therapy Enhances Executive Functions and Prefrontal Structural Neuroplasticity after Traumatic Brain Injury: Evidence from a Randomized Controlled Trial. J. Neurotrauma. 2020;37:618–634. doi: 10.1089/neu.2019.6413.
    1. Martínez-Molina N., Siponkoski S.T., Kuusela L., Laitinen S., Holma M., Ahlfors M., Jordan-Kilkki P., Ala-Kauhaluoma K., Melkas S., Pekkola J., et al. Resting-State Network Plasticity Induced by Music Therapy after Traumatic Brain Injury. Neural Plast. 2021;2021:6682471. doi: 10.1155/2021/6682471.
    1. Yeh F.C., Badre D., Verstynen T. Connectometry: A statistical approach harnessing the analytical potential of the local connectome. Neuroimage. 2016;125:162–171. doi: 10.1016/j.neuroimage.2015.10.053.
    1. Hula W.D., Panesar S., Gravier M.L., Yeh F.C., Dresang H.C., Dickey M.W., Fernandez-Miranda J.C. Structural white matter connectometry of word production in aphasia: An observational study. Brain. 2020;143:2532–2544. doi: 10.1093/brain/awaa193.
    1. Dresang H.C., Hula W.D., Yeh F.-C., Warren T., Dickey M.W. White-Matter Neuroanatomical Predictors of Aphasic Verb Retrieval. Brain Connect. 2021;11:319–330. doi: 10.1089/brain.2020.0921.
    1. Traumatic Brain Injury Current Care Guidelines. Working group Set up by the Finnish Medical Society Duodecim, Finnish Neurological Society, Societas Medicinae Physicalis et Rehabilitationis Fenniae, Finnish Neurosurgical Society, Finnish Neuropsychological Society and Assocication of Finnish Insurance Medicine Doctors, Helsinki. Helsinki: The Finnish Medical Society Duodecim, 2021 (Referred 6.4.2022) [(accessed on 6 April 2022)]. Available online: .
    1. Wilson J.T.L., Pettigrew L.E.L., Teasdale G.M. Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: Guidelines for their use. J. Neurotrauma. 1998;15:573–580. doi: 10.1089/neu.1998.15.573.
    1. Wilde E.A., McCauley S.R., Kelly T.M., Weyand A.M., Pedroza C., Levin H.S., Clifton G.L., Schnelle K.P., Shah M.V., Moretti P. The neurological outcome scale for traumatic brain injury (NOS-TBI): I. Construct validity. J. Neurotrauma. 2010;27:983–989. doi: 10.1089/neu.2009.1194.
    1. Dubois B., Slachevsky A., Litvan I., Pillon B. The FAB: A frontal assessment battery at bedside. Neurology. 2000;55:1621–1626. doi: 10.1212/WNL.55.11.1621.
    1. Yeh F.C., Tseng W.Y.I. NTU-90: A high angular resolution brain atlas constructed by q-space diffeomorphic reconstruction. Neuroimage. 2011;58:91–99. doi: 10.1016/j.neuroimage.2011.06.021.
    1. Yeh F.C., Wedeen V.J., Tseng W.Y.I. Generalized q-sampling imaging. IEEE Trans. Med. Imaging. 2010;29:1626–1635. doi: 10.1109/TMI.2010.2045126.
    1. Schilling K.G., Yeh F.C., Nath V., Hansen C., Williams O., Resnick S., Anderson A.W., Landman B.A. A fiber coherence index for quality control of B-table orientation in diffusion MRI scans. Magn. Reson. Imaging. 2019;58:82–89. doi: 10.1016/j.mri.2019.01.018.
    1. Yeh F.C., Liu L., Hitchens T.K., Wu Y.L. Mapping immune cell infiltration using restricted diffusion MRI. Magn. Reson. Med. 2017;77:603–612. doi: 10.1002/mrm.26143.
    1. Yeh F.C., Vettel J.M., Singh A., Poczos B., Grafton S.T., Erickson K.I., Tseng W.Y.I., Verstynen T.D. Quantifying Differences and Similarities in Whole-Brain White Matter Architecture Using Local Connectome Fingerprints. PLoS Comput. Biol. 2016;12:e1005203. doi: 10.1371/journal.pcbi.1005203.
    1. Yeh F.C., Verstynen T.D., Wang Y., Fernández-Miranda J.C., Tseng W.Y.I. Deterministic diffusion fiber tracking improved by quantitative anisotropy. PLoS ONE. 2013;8:e80713. doi: 10.1371/journal.pone.0080713.
    1. Rolls E.T., Huang C.C., Lin C.P., Feng J., Joliot M. Automated anatomical labelling atlas 3. Neuroimage. 2020;206:116189. doi: 10.1016/j.neuroimage.2019.116189.
    1. Yeh F.C., Panesar S., Barrios J., Fernandes D., Abhinav K., Meola A., Fernandez-Miranda J.C. Automatic Removal of False Connections in Diffusion MRI Tractography Using Topology-Informed Pruning (TIP) Neurotherapeutics. 2019;16:52–58. doi: 10.1007/s13311-018-0663-y.
    1. Friedman N.P., Miyake A. Unity and diversity of executive functions: Individual differences as a window on cognitive structure. Cortex. 2017;86:186–204. doi: 10.1016/j.cortex.2016.04.023.
    1. Miyake A., Friedman N.P., Emerson M.J., Witzki A.H., Howerter A., Wager T.D. The Unity and Diversity of Executive Functions and Their Contributions to Complex “Frontal Lobe” Tasks: A Latent Variable Analysis. Cogn. Psychol. 2000;41:49–100. doi: 10.1006/cogp.1999.0734.
    1. Niendam T.A., Laird A.R., Ray K.L., Dean Y.M., Glahn D.C., Carter C.S. Meta-analytic evidence for a superordinate cognitive control network subserving diverse executive functions. Cogn. Affect. Behav. Neurosci. 2012;12:241–268. doi: 10.3758/s13415-011-0083-5.
    1. Shen K., Welton T., Lyon M., McCorkindale A.N., Sutherland G.T., Burnham S., Fripp J., Martins R., Grieve S.M. Structural core of the executive control network: A high angular resolution diffusion MRI study. Hum. Brain Mapp. 2020;41:1226–1236. doi: 10.1002/hbm.24870.
    1. Sasson E., Doniger G.M., Pasternak O., Tarrasch R., Assaf Y. White matter correlates of cognitive domains in normal aging with diffusion tensor imaging. Front. Neurosci. 2013;7:32. doi: 10.3389/fnins.2013.00032.
    1. Gallen C.L., Turner G.R., Adnan A., D’Esposito M. Reconfiguration of brain network architecture to support executive control in aging. Neurobiol. Aging. 2016;44:42–52. doi: 10.1016/j.neurobiolaging.2016.04.003.
    1. Zhang J., Tian L., Zhang L., Cheng R., Wei R., He F., Li J., Luo B., Ye X. Relationship between white matter integrity and post-traumatic cognitive deficits: A systematic review and meta-analysis. J. Neurol. Neurosurg. Psychiatry. 2019;90:98–107. doi: 10.1136/jnnp-2017-317691.
    1. Filley C.M. White matter: Organization and functional relevance. Neuropsychol. Rev. 2010;20:158–173. doi: 10.1007/s11065-010-9127-9.
    1. Filley C.M., Kelly J.P. White Matter and Cognition in Traumatic Brain Injury. J. Alzheimers. Dis. 2018;65:345–362. doi: 10.3233/JAD-180287.
    1. Medana I.M., Esiri M.M. Axonal damage: A key predictor of outcome in human CNS diseases. Brain. 2003;126:515–530. doi: 10.1093/brain/awg061.
    1. Zatorre R.J., Fields R.D., Johansen-Berg H. Plasticity in gray and white: Neuroimaging changes in brain structure during learning. Nat. Neurosci. 2012;15:528–536. doi: 10.1038/nn.3045.
    1. Tomassini V., Matthews P.M., Thompson A.J., Fuglo D., Geurts J.J., Johansen-Berg H., Jones D.K., Rocca M.A., Wise R.G., Barkhof F., et al. Neuroplasticity and functional recovery in multiple sclerosis. Nat. Rev. Neurol. 2012;8:635–646. doi: 10.1038/nrneurol.2012.179.
    1. Cramer S.C., Sur M., Dobkin B.H., O’Brien C., Sanger T.D., Trojanowski J.Q., Rumsey J.M., Hicks R., Cameron J., Chen D., et al. Harnessing neuroplasticity for clinical applications. Brain. 2011;134:1591–1609. doi: 10.1093/brain/awr039.
    1. Murphy T.H., Corbett D. Plasticity during stroke recovery: From synapse to behaviour. Nat. Rev. Neurosci. 2009;10:861–872. doi: 10.1038/nrn2735.
    1. Fields R.D. A new mechanism of nervous system plasticity: Activity-dependent myelination. Nat. Rev. Neurosci. 2015;16:756–767. doi: 10.1038/nrn4023.
    1. Gibson E.M., Purger D., Mount C.W., Goldstein A.K., Lin G.L., Wood L.S., Inema I., Miller S.E., Bieri G., Zuchero J.B., et al. Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science. 2014;344:1252304. doi: 10.1126/science.1252304.
    1. Bettcher B.M., Mungas D., Patel N., Elofson J., Dutt S., Wynn M., Watson C.L., Stephens M., Walsh C.M., Kramer J.H. Neuroanatomical substrates of executive functions: Beyond prefrontal structures. Neuropsychologia. 2016;85:100–109. doi: 10.1016/j.neuropsychologia.2016.03.001.
    1. Vaquero L., Rousseau P.N., Vozian D., Klein D., Penhune V. What you learn & when you learn it: Impact of early bilingual & music experience on the structural characteristics of auditory-motor pathways. Neuroimage. 2020;213:116689. doi: 10.1016/j.neuroimage.2020.116689.
    1. Halwani G.F., Loui P., Rüber T., Schlaug G. Effects of practice and experience on the arcuate fasciculus: Comparing singers, instrumentalists, and non-musicians. Front. Psychol. 2011;2:156. doi: 10.3389/fpsyg.2011.00156.
    1. Engel A., Hijmans B.S., Cerliani L., Bangert M., Nanetti L., Keller P.E., Keysers C. Inter-individual differences in audio-motor learning of piano melodies and white matter fiber tract architecture. Hum. Brain Mapp. 2014;35:2483–2497. doi: 10.1002/hbm.22343.
    1. Loui P., Raine L.B., Chaddock-Heyman L., Kramer A.F., Hillman C.H. Musical instrument practice predicts white matter microstructure and cognitive abilities in childhood. Front. Psychol. 2019;10:1198. doi: 10.3389/fpsyg.2019.01198.
    1. Habibi A., Damasio A., Ilari B., Veiga R., Joshi A.A., Leahy R.M., Haldar J.P., Varadarajan D., Bhushan C., Damasio H. Childhood music training induces change in micro and macroscopic brain structure: Results from a longitudinal study. Cereb. Cortex. 2018;28:4336–4347. doi: 10.1093/cercor/bhx286.
    1. Bengtsson S.L., Nagy Z., Skare S., Forsman L., Forssberg H., Ullén F. Extensive piano practicing has regionally specific effects on white matter development. Nat. Neurosci. 2005;8:1148–1150. doi: 10.1038/nn1516.
    1. Siponkoski S.-T., Koskinen S., Laitinen S., Holma M., Ahlfors M., Jordan-Kilkki P., Ala-Kauhaluoma K., Martínez-Molina N., Melkas S., Laine M., et al. Effects of neurological music therapy on behavioural and emotional recovery after traumatic brain injury: A randomized controlled cross-over trial. Neuropsychol. Rehabil. 2021:1–33. doi: 10.1080/09602011.2021.1890138.

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