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01-06-2022 | Autism Spectrum Disorder | Original Article

Structural connectivity in ventral language pathways characterizes non-verbal autism

Authors: Guillem Olivé, Dominika Slušná, Lucía Vaquero, Jordi Muchart-López, Antoni Rodríguez-Fornells, Wolfram Hinzen

Published in: Brain Structure and Function | Issue 5/2022

Abstract

Language capacities in autism spectrum disorders (ASD) range from normal scores on standardized language tests to absence of functional language in a substantial minority of 30% of individuals with ASD. Due to practical difficulties of scanning at this severe end of the spectrum, insights from MRI are scarce. Here we used manual deterministic tractography to investigate, for the first time, the integrity of the core white matter tracts defining the language connectivity network in non-verbal ASD (nvASD): the three segments of the arcuate (AF), the inferior fronto-occipital (IFOF), the inferior longitudinal (ILF) and the uncinate (UF) fasciculi, and the frontal aslant tract (FAT). A multiple case series of nine individuals with nvASD were compared to matched individuals with verbal ASD (vASD) and typical development (TD). Bonferroni-corrected repeated measure ANOVAs were performed separately for each tract—Hemisphere (2:Left/Right) × Group (3:TD/vASD/nvASD). Main results revealed (i) a main effect of group consisting in a reduction in fractional anisotropy (FA) in the IFOF in nvASD relative to TD; (ii) a main effect of group revealing lower values of radial diffusivity (RD) in the long segment of the AF in nvASD compared to vASD group; and (iii) a reduced volume in the left hemisphere of the UF when compared to the right, in the vASD group only. These results do not replicate volumetric differences of the dorsal language route previously observed in nvASD, and instead point to a disruption of the ventral language pathway, in line with semantic deficits observed behaviourally in this group.

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Almairac F, Herbet G, Moritz-Gasser S, de Champfleur N, Duffau H (2015) The left inferior fronto-occipital fasciculus subserves language semantics: a multilevel lesion study. Brain Struct Funct 220(4):1983–1995CrossRefPubMed

Aoki Y, Abe O, Nippashi Y, Yamasue H (2013) Comparison of white matter integrity between autism spectrum disorder subjects and typically developing individuals: a meta-analysis of diffusion tensor imaging tractography studies. Mol Autism. https://doi.org/10.1186/2040-2392-4-25CrossRefPubMedPubMedCentral

Arunachalam S, Luyster RJ (2016) The integrity of lexical acquisition mechanisms in autism spectrum disorders: a research review. Autism Res 9:810–828CrossRefPubMed

ASLHA: American Speech-Language-Hearing Association (2021) Childhood apraxia of speech. https://www.asha.org/public/speech/disorders/childhood-apraxia-of-speech/. Accessed 9 June 2021

Aung W, Mar S, Benzinger T (2013) Diffusion tensor MRI as a biomarker in axonal and myelin damage. Imaging Med 5(5):427–440. https://doi.org/10.2217/iim.13.49CrossRefPubMedPubMedCentral

Binder J, Desai R, Graves W, Conant L (2009) Where is the semantic system? A critical review and meta-analysis of 120 functional neuroimaging studies. Cereb Cortex 19(12):2767–2796CrossRefPubMedPubMedCentral

Cantiani C, Choudhury NA, Yu YH, Shafer VL, Schwartz RG, Benasich AA (2016) From sensory perception to lexical-semantic processing: an ERP study in non-verbal children with autism. PLoS ONE 11(8):e0161637. https://doi.org/10.1371/journal.pone.0161637CrossRefPubMedPubMedCentral

Catani M, Thiebaut de Schotten M (2008) A diffusion tensor imaging tractography atlas for virtual in vivo dissections. Cortex 44(8):1105–1132. https://doi.org/10.1016/j.cortex.2008.05.004CrossRefPubMed

Catani M, Jones DK, Ffytche DH (2005) Perisylvian language networks of the human brain. Ann Neurol 57(1):8–16. https://doi.org/10.1002/ana.20319CrossRefPubMed

Catani M, Mesulam MM, Jakobsen E et al (2013) A novel frontal pathway underlies verbal fluency in primary progressive aphasia. Brain 136(8):2619–2628. https://doi.org/10.1093/brain/awt163CrossRefPubMedPubMedCentral

Catani M, Dell’Acqua F, Budisavljevic S et al (2016) Frontal networks in adults with autism spectrum disorder. Brain 139(2):616–630. https://doi.org/10.1093/brain/awv351CrossRefPubMedPubMedCentral

Chenausky K, Kernbach J, Norton A, Schlaug G (2017) White matter integrity and treatment-based change in speech performance in minimally verbal children with autism spectrum disorder. Front Hum Neurosci. https://doi.org/10.3389/fnhum.2017.00175CrossRefPubMedPubMedCentral

Chenausky KV, Tager-Flusberg H, Schlaug G (2018) Childhood apraxia of speech in minimally verbal children with ASD. Poster presented at the meeting of International Society for Autism Research annual meeting, Rotterdam

Chenausky K, Brignell A, Morgan A, Tager-Flusberg H (2019) Motor speech impairment predicts expressive language in minimally verbal, but not low verbal, individuals with autism spectrum disorder. Autism Dev Lang Impair 4:239694151985633. https://doi.org/10.1177/2396941519856333CrossRef

Dick AS, Bernal B, Tremblay P (2014) The language connectome: new pathways, new concepts. Neuroscientist 20(5):453–467. https://doi.org/10.1177/1073858413513502CrossRefPubMed

DiStefano C, Shih W, Kaiser A, Landa R, Kasari C (2016) Communication growth in minimally verbal children with ASD: the importance of interaction. Autism Res 9(10):1093–1102. https://doi.org/10.1002/aur.1594CrossRefPubMed

Dorrichi F, Thiebaut de Schotten M, Tomaiuolo F, Bartolomeo P (2008) White matter (dis)connections and gray matter (dys)functions in visual neglect: gaining insights into the brain networks of spatial awareness. Cortex 44:983–985CrossRef

Duffau H, Gatignol P, Mandonnet E, Peruzzi P, Tzourio-Mazoyer N, Capelle L (2005) New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical electrostimulations. Brain 128(4):797–810. https://doi.org/10.1093/brain/awh423CrossRefPubMed

Duffau H, Gatignol P, Moritz-Gasser S, Mandonnet E (2009) Is the left uncinate fasciculus essential for language? : a cerebral stimulation study. J Neurol 256(3):382–389. https://doi.org/10.1007/s00415-009-0053-9CrossRefPubMed

Elmer S, Hänggi J, Vaquero L, Olivé G, François C, Rodríguez-Fornells A (2019) Tracking the microstructural properties of the main white matter pathways underlying speech processing in simultaneous interpreters. Neuroimage 191:518–528. https://doi.org/10.1016/j.neuroimage.2019.02.056CrossRefPubMed

Fekonja L, Wang Z, Bährend I et al (2019) Manual for clinical language tractography. Acta Neurochir 161(6):1125–1137. https://doi.org/10.1007/s00701-019-03899-0CrossRefPubMed

Fields RD (2008) White matter in learning, cognition and psychiatric disorders. Trends Neurosci 31:361–370CrossRefPubMedPubMedCentral

Fletcher PT, Whitaker RT, Tao R et al (2010) Microstructural connectivity of the arcuate fasciculus in adolescents with high-functioning autism. Neuroimage 51(3):1117–1125. https://doi.org/10.1016/j.neuroimage.2010.01.083CrossRefPubMed

Friederici AD (2011) The brain basis of language processing: from structure to function. Physiol Rev 91(4):1357–1392. https://doi.org/10.1152/physrev.00006.2011CrossRefPubMed

Friederici AD (2015) White-matter pathways for speech and language processing. Handbook of clinical neurology, vol 129. Elsevier, pp 177–186. https://doi.org/10.1016/B978-0-444-62630-1.00010-XCrossRef

Friederici AD, Bahlmann J, Heim S, Schubotz RI, Anwander A (2006) The brain differentiates human and non-human grammars: functional localization and structural connectivity. Proc Natl Acad Sci USA 103(7):2458–2463. https://doi.org/10.1073/pnas.0509389103CrossRefPubMedPubMedCentral

Friedrich P, Fraenz C, Schlüter C, Ocklenburg S, Mädler B, Güntürkün O, Genç E (2020) The relationship between axon density, myelination, and fractional anisotropy in the human corpus callosum. Cereb Cortex 30(4):2042–2056. https://doi.org/10.1093/cercor/bhz221CrossRefPubMed

Garrido D, Carballo G, Franco V, García-Retamero R (2015) Language comprehension disorders in non-verbal children with autism spectrum disorders and their implications in the family quality of life. Rev Neurol 60(5):207–214. https://doi.org/10.33588/rn.6005.2014226CrossRefPubMed

Hartley C, Trainer A, Allen ML (2019) Investigating the relationship between language and picture understanding in children with autism spectrum disorder. Autism 23(1):187–198. https://doi.org/10.1177/1362361317729613CrossRefPubMed

Harvey DY, Wei T, Ellmore TM, Hamilton AC, Schnur TT (2013) Neuropsychological evidence for the functional role of the uncinate fasciculus in semantic control. Neuropsychologia 51(5):789–801. https://doi.org/10.1016/j.neuropsychologia.2013.01.028CrossRefPubMed

Herbet G, Moritz-Gasser S, Lemaitre AL, Almairac F, Duffau H (2019) Functional compensation of the left inferior longitudinal fasciculus for picture naming. Cogn Neuropsychol 36(3–4):140–157. https://doi.org/10.1080/02643294.2018.1477749CrossRefPubMed

Hickok G, Poeppel D (2004) Dorsal and ventral streams: a framework for understanding aspects of the functional anatomy of language. Cognition 92(1–2):67–99. https://doi.org/10.1016/j.cognition.2003.10.011CrossRefPubMed

Hickok G, Poeppel D (2007) The cortical organization of speech understanding. Nature 8(May):393–402

Jones D, Knösche T, Turner R (2013) White matter integrity, fiber count, and other fallacies: the do's and don'ts of diffusion MRI. Neuroimage 73:239–254. https://doi.org/10.1016/j.neuroimage.2012.06.081CrossRefPubMed

Joseph RM, Fricker Z, Fenoglio A, Lindgren KA, Knaus TA, Tager-Flusberg H (2014) Structural asymmetries of language-related gray and white matter and their relationship to language function in young children with ASD. Brain Imaging Behav 8(1):60–72. https://doi.org/10.1007/s11682-013-9245-0CrossRefPubMed

Jou RJ, Mateljevic N, Kaiser MD, Sugrue DR, Volkmar FR, Pelphrey KA (2011) Structural neural phenotype of autism: Preliminary evidence from a diffusion tensor imaging study using tract-based spatial statistics. Am J Neuroradiol 32(9):1607–1613. https://doi.org/10.3174/ajnr.A2558CrossRefPubMedPubMedCentral

Li Y, Zhou Z, Chang C et al (2019) Anomalies in uncinate fasciculus development and social defects in preschoolers with autism spectrum disorder. BMC Psychiatry. https://doi.org/10.1186/s12888-019-2391-1CrossRefPubMedPubMedCentral

Liu J, Tsang T, Jackson L et al (2019) Altered lateralization of dorsal language tracts in 6-week-old infants at risk for autism. Dev Sci. https://doi.org/10.1111/desc.12768CrossRefPubMed

López-Barroso D, Catani M, Ripollés P, Dell’Acqua F, Rodríguez-Fornells A, De Diego-Balaguer R (2013) Word learning is mediated by the left arcuate fasciculus. Proc Natl Acad Sci USA 110(32):13168–13173. https://doi.org/10.1073/pnas.1301696110CrossRefPubMedPubMedCentral

Lord C, Rutter M, DiLavore P, Risi S, Gotham K, Bishop S (2012) Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) Manual (Part I): Modules 1–4. 2nd Editio. Torrance, CA.: Western Psychological Services. https://psycnet.apa.org/doiLanding?doi=10.1037%2Ft17256-000. Accessed 10 June 2021

Marno H, Farroni T, Vidal Dos Santos Y, Ekramnia M, Nespor M, Mehler J (2015) Can you see what I am talking about? Human speech triggers referential expectation in four-month-old infants. Sci Rep 5(1):13594CrossRefPubMedPubMedCentral

Martino J, Brogna C, Robles SG, Vergani F, Duffau H (2010) Anatomic dissection of the inferior fronto-occipital fasciculus revisited in the lights of brain stimulation data. Cortex 46(5):691–699. https://doi.org/10.1016/j.cortex.2009.07.015CrossRefPubMed

Pickles A, Anderson DK, Lord C (2014) Heterogeneity and plasticity in the development of language: a 17-year follow-up of children referred early for possible autism. J Child Psychol Psychiatry Allied Discip 55(12):1354–1362. https://doi.org/10.1111/jcpp.12269CrossRef

Plaza M, Gatignol P, Cohen H, Berger B, Duffau H (2008) A discrete area within the left dorsolateral prefrontal cortex involved in visual-verbal incongruence judgment. Cereb Cortex 18:1253–1259CrossRefPubMed

Preissler MA (2008) Associative learning of pictures and words by low-functioning children with autism. Autism 12(3):231–248. https://doi.org/10.1177/1362361307088753CrossRefPubMed

Price CJ (2000) The anatomy of language: contributions from functional neuroimaging. J Anat 197:335–359CrossRefPubMedPubMedCentral

Price CJ (2012) A review and synthesis of the first 20 years of PET and fMRI studies of heard speech, spoken language and reading. Neuroimage 62(2):816–847. https://doi.org/10.1016/j.neuroimage.2012.04.062CrossRefPubMed

Rauschecker JP, Scott SK (2009) Maps and streams in the auditory cortex: nonhuman primates illuminate human speech processing. Nat Neurosci 12(6):718–724. https://doi.org/10.1038/nn.2331CrossRefPubMedPubMedCentral

Ripollés P, Biel D, Peñaloza C, Kaufmann J, Marco-Pallarés J, Noesselt T, Rodríguez-Fornells A (2017) Strength of temporal white matter pathways predicts semantic learning. J Neurosci 37(46):11101–11113. https://doi.org/10.1523/jneurosci.1720-17.2017CrossRefPubMedPubMedCentral

Rutter M, Le Couteur A, Lord C (2003) Autism diagnostic interview-revised. Western Psychological Services, Los Angeles, CA, 29(2003), 30

Samson AC, Dougherty RF, Lee IA, Phillips JM, Gross JJ, Hardan AY (2016) White matter structure in the uncinate fasciculus: implications for socio-affective deficits in autism spectrum disorder. Psychiatry Res Neuroimaging 255:66–74. https://doi.org/10.1016/j.pscychresns.2016.08.004CrossRefPubMed

Sarubbo S, De Benedictis A, Maldonado IL, Basso G, Duffau H (2013) Frontal terminations for the inferior fronto-occipital fascicle: anatomical dissection, DTI study and functional considerations on a multi-component bundle. Brain Struct Funct 218(1):21–37. https://doi.org/10.1007/s00429-011-0372-3CrossRefPubMed

Saura D, Kreher BW, Schnell S et al (2008) Ventral and dorsal pathways for language. Proc Natl Acad Sci USA 105(46):18035–18040. https://doi.org/10.1073/pnas.0805234105CrossRef

Shin J, Rowley J, Chowdhury R et al (2019) Inferior longitudinal fasciculus’ role in visual processing and language comprehension: a combined MEG-DTI study. Front Neurosci. https://doi.org/10.3389/fnins.2019.00875CrossRefPubMedPubMedCentral

Sierpowska J, Gabarrós A, Fernández-Coello A, Camins À, Castañer S, Juncadella M, François C, Rodríguez-Fornells A (2019) White-matter pathways and semantic processing: intrasurgical and lesion-symptom mapping evidence. NeuroImage: Clin 22:101704CrossRef

Skeide MA, Friederici AD (2016) The ontogeny of the cortical language network. Nat Rev Neurosci 17(5):323–332. https://doi.org/10.1038/nrn.2016.23CrossRefPubMed

Skwerer DP, Jordan SE, Brukilacchio BH, Tager-Flusberg H (2016) Comparing methods for assessing receptive language skills in minimally verbal children and adolescents with autism spectrum disorders. Autism 20(5):591–604. https://doi.org/10.1177/1362361315600146CrossRef

Slusna D, Rodriguez A, Salvado B, Vicente A, Hinzen W (2021) Relations between language, non-verbal cognition and conceptualization in non- or minimally verbal individuals with ASD across the lifespan. J Autism Dev Disord. https://doi.org/10.1177/23969415211053264 (In press)CrossRef

Smith SM (2002) Fast robust automated brain extraction. Hum Brain Mapp 17(3):143–155. https://doi.org/10.1002/hbm.10062CrossRefPubMedPubMedCentral

Smith SM, Jenkinson M, Woolrich MW et al (2004) Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. https://doi.org/10.1016/j.neuroimage.2004.07.051CrossRefPubMed

Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TE (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31(4):1487–1505CrossRefPubMed

Song SK, Yoshino J, Le TQ, Lin SJ, Sun SW, Cross AH, Armstrong RC (2005) Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage 26:132–140CrossRefPubMed

Tager-Flusberg H, Kasari C (2013) Minimally verbal school-aged children with autism spectrum disorder: the neglected end of the spectrum. Autism Res 6(6):468–478. https://doi.org/10.1002/aur.1329CrossRefPubMed

Tek S, Jaffery G, Fein D, Naigles LR (2008) Do children with autism spectrum disorders show a shape bias in word learning? Autism Res 1(4):208–222. https://doi.org/10.1002/aur.38CrossRefPubMedPubMedCentral

Travers BG, Adluru N, Ennis C et al (2012) Diffusion tensor imaging in autism spectrum disorder: a review. Autism Res 5(5):289–313. https://doi.org/10.1002/aur.1243CrossRefPubMedPubMedCentral

Vaquero L, Rodríguez-Fornells A, Reiterer S (2016) The left, the better: white-matter brain integrity predicts foreign language imitation ability. Cereb Cortex. https://doi.org/10.1093/cercor/bhw199CrossRef

Vaquero L, Ramos-Escobar N, Cucurell D, François C, Putkinen V, Segura E et al (2021) Arcuate fasciculus architecture is associated with individual differences in pre-attentive detection of unpredicted music changes. Neuroimage 229:117759. https://doi.org/10.1016/j.neuroimage.2021.117759CrossRefPubMed

Vihla M, Laine M, Salmelin R (2006) Cortical dynamics of visual/ semantic vs. phonological analysis in picture confrontation. Neuroimage 33:732–738CrossRefPubMed

Von Der Heide RJ, Skipper LM, Klobusicky E, Olson IR (2013) Dissecting the uncinate fasciculus: disorders, controversies and a hypothesis. Brain 136(6):1692–1707. https://doi.org/10.1093/brain/awt094CrossRef

Wan CY, Marchina S, Norton A, Schlaug G (2012) Atypical hemispheric asymmetry in the arcuate fasciculus of completely nonverbal children with autism. Ann N Y Acad Sci 1252(1):332–337. https://doi.org/10.1111/j.1749-6632.2012.06446.xCrossRefPubMedPubMedCentral

Wang R, Benner T, Sorensen AG, Wedeen VJ (2007) Diffusion toolkit: a software package for diffusion imaging data processing and tractography. Proc Intl Soc Mag Reson Med 15:3720

Winklewski P, Sabisz A, Naumczyk P, Jodzio K, Szurowska E, Szarmach A (2018) Understanding the physiopathology behind axial and radial diffusivity changes—what do we know? Front Neurol. https://doi.org/10.3389/fneur.2018.00092CrossRefPubMedPubMedCentral

Winston GP (2012) The physical and biological basis of quantitative parameters derived from diffusion MRI. Quant Imaging Med Surg 2(4):254–265. https://doi.org/10.3978/j.issn.2223-4292.2012.12.05CrossRefPubMedPubMedCentral

Woolrich MW, Jbabdi S, Patenaude B et al (2009) Bayesian analysis of neuroimaging data in FSL. Neuroimage. https://doi.org/10.1016/j.neuroimage.2008.10.055CrossRefPubMed

Wu Y, Sun D, Wang Y, Wang Y (2016) Subcomponents and connectivity of the inferior fronto-occipital fasciculus revealed by diffusion spectrum imaging fiber tracking. Front Neuroanat 10(SEP):1–13. https://doi.org/10.3389/fnana.2016.00088CrossRef

Yeatman JD, Dougherty RF, Myall NJ, Wandell BA, Feldman HM (2012) Tract profiles of white matter properties: automating fiber-tract quantification. PLoS ONE 7:e49790. https://doi.org/10.1371/journal.pone.0049790CrossRefPubMedPubMedCentral

Yendiki A, Panneck P, Srinivasan P, Stevens A, Zöllei L, Augustinack J, Wang R, Salat D, Ehrlich S, Behrens T, Jbabdi S, Gollub R, Fischl B (2011) Automated probabilistic reconstruction of white-matter pathways in health and disease using an atlas of the underlying anatomy. Front Neuroinform 5:23. https://doi.org/10.3389/fninf.2011.00023CrossRefPubMedPubMedCentral

Zatorre RJ, Fields RD, Johansen-Berg H (2012) Plasticity in gray and white: neuroimaging changes in brain structure during learning. Nat Neurosci 15:528–536CrossRefPubMedPubMedCentral

Title: Structural connectivity in ventral language pathways characterizes non-verbal autism
Authors: Guillem Olivé
Dominika Slušná
Lucía Vaquero
Jordi Muchart-López
Antoni Rodríguez-Fornells
Wolfram Hinzen
Publication date: 01-06-2022
Publisher: Springer Berlin Heidelberg
Keyword: Autism Spectrum Disorder
Published in: Brain Structure and Function / Issue 5/2022
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-022-02474-1

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Structural connectivity in ventral language pathways characterizes non-verbal autism

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