Divergence and Variability of Language Maps in Autism

Summary

Principal Investigator: Ralph Axel Müller
Abstract: Despite a general consensus that autism has biological causes, the specific links between brain loci of abnormality and cognitive-behavioral impairments remain unknown. Functional neuroimaging studies do not provide a clear picture, possibly due to etiological heterogeneity of autism samples. We will explore potential abnormalities of functional brain organization in autism with specific focus on individual variability, using functional MRI (fMRI) -- an imaging technique with sufficient power for individual analyses. Thirty verbal individuals with autism, 24 subjects with Asperger syndrome (AS), and age, gender, and handedness-matched controls will be studied. Our project will focus on language -- a domain which not only differentiates autism and AS in terms of delay and deficit, but is also characterized by a wide spectrum of abilities within the adult autistic population. FMRI will be performed during auditory and phonological discrimination, and lexical semantic association. Several complementary data analysis paths (groupwise and intraindividually; in normalized and native space) will enable us: (i) to identify consistent abnormalities of functional maps for autism and AS groups; (ii) to quantify activation foci in each subject in terms of spatial divergence from normal and individual variability within patient groups; (iii) to relate varying patterns of abnormal functional maps with measures of language skill; and (iv) to distinguish effects of pathological disturbance of functional maps from those of compensatory plasticity. We will test hypotheses, according to which in autism (and to a lesser extent in AS) pathological disturbance of neural differentiation and impoverished interactive language experience during critical developmental periods result in aberrant neurofunctional maps and abnormally pronounced individual variability. Language delay in autism is further hypothesized to be associated with atypical hemispheric dominance for language. Finally, we expect that individually variable patterns of abnormal functional maps will be correlated with level of language outcome. Identifying such links between brain maps and level of functioning achieved in adults will elucidate the significance of individual variation in autism in terms of different pathways of etiology and abnormal development.
Funding Period: 2002-09-01 - 2010-08-31
more information: NIH RePORT

Top Publications

  1. pmc Reduced functional connectivity between V1 and inferior frontal cortex associated with visuomotor performance in autism
    Michele E Villalobos
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, CA 92120, USA
    Neuroimage 25:916-25. 2005
  2. pmc Atypical lexicosemantic function of extrastriate cortex in autism spectrum disorder: evidence from functional and effective connectivity
    Mark D Shen
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, CA 92120, USA
    Neuroimage 62:1780-91. 2012
  3. pmc Functional differentiation of posterior superior temporal sulcus in autism: a functional connectivity magnetic resonance imaging study
    Patricia Shih
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, 6363 Alvarado Ct, SanDiego, CA 92120, USA
    Biol Psychiatry 70:270-7. 2011
  4. pmc Underconnected, but how? A survey of functional connectivity MRI studies in autism spectrum disorders
    Ralph Axel Müller
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, CA 92120, USA
    Cereb Cortex 21:2233-43. 2011
  5. pmc Microstructural abnormalities of short-distance white matter tracts in autism spectrum disorder
    Dinesh K Shukla
    Department of Psychology, San Diego State University, San Diego, CA, USA
    Neuropsychologia 49:1378-82. 2011
  6. pmc White matter compromise of callosal and subcortical fiber tracts in children with autism spectrum disorder: a diffusion tensor imaging study
    Dinesh K Shukla
    Brain Development Imaging Laboratory, San Diego State University, San Diego, USA
    J Am Acad Child Adolesc Psychiatry 49:1269-78, 1278.e1-2. 2010
  7. ncbi Tract-specific analyses of diffusion tensor imaging show widespread white matter compromise in autism spectrum disorder
    Dinesh K Shukla
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, USA
    J Child Psychol Psychiatry 52:286-95. 2011
  8. pmc Atypical network connectivity for imitation in autism spectrum disorder
    Patricia Shih
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, CA 92120, United States
    Neuropsychologia 48:2931-9. 2010
  9. pmc Attentional networks in children and adolescents with autism spectrum disorder
    Brandon Keehn
    Joint Doctoral Program in Language and Communicative Disorders, San Diego State University University of California San Diego, 6363 Alvarado Ct 225N, San Diego, CA 92120, USA
    J Child Psychol Psychiatry 51:1251-9. 2010
  10. pmc Regional homogeneity of fMRI time series in autism spectrum disorders
    Dinesh K Shukla
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, CA 92120, United States
    Neurosci Lett 476:46-51. 2010

Scientific Experts

  • Ralph Axel Müller
  • Brandon Keehn
  • Natalia M Kleinhans
  • Dinesh K Shukla
  • Patricia Shih
  • Michael S Gaffrey
  • Akiko Mizuno
  • Michele E Villalobos
  • Mark D Shen
  • Kelly M Leyden
  • Birgit Ottl
  • Sarah K Noonan
  • Frank Haist
  • Branelle C Dahl
  • Daren M Smylie
  • Christopher L Keown
  • Jessica K Oram
  • Mark Shen
  • Alan J Lincoln
  • Eric Courchesne
  • Natacha Akshoomoff
  • Ashley Campbell
  • Molly M Davies
  • Nobuko Kemmotsu

Detail Information

Publications18

  1. pmc Reduced functional connectivity between V1 and inferior frontal cortex associated with visuomotor performance in autism
    Michele E Villalobos
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, CA 92120, USA
    Neuroimage 25:916-25. 2005
    ..More generally, our findings suggest that dorsal stream connectivity in autism may not be fully functional...
  2. pmc Atypical lexicosemantic function of extrastriate cortex in autism spectrum disorder: evidence from functional and effective connectivity
    Mark D Shen
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, CA 92120, USA
    Neuroimage 62:1780-91. 2012
    ..Furthermore, our findings are inconsistent with previous reports of functional underconnectivity in ASD, probably related to removal of task effects required to isolate intrinsic low-frequency fluctuations...
  3. pmc Functional differentiation of posterior superior temporal sulcus in autism: a functional connectivity magnetic resonance imaging study
    Patricia Shih
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, 6363 Alvarado Ct, SanDiego, CA 92120, USA
    Biol Psychiatry 70:270-7. 2011
    ..Abnormal development of posterior superior temporal sulcus (pSTS)--a key processing area for language, biological motion, and social context--could play a role in these deficits...
  4. pmc Underconnected, but how? A survey of functional connectivity MRI studies in autism spectrum disorders
    Ralph Axel Müller
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, CA 92120, USA
    Cereb Cortex 21:2233-43. 2011
    ..g., synaptic pruning). Both GU and NGU findings reflect important aspects of network dysfunction associated with sociocommunicative, cognitive, and sensorimotor impairments in ASD...
  5. pmc Microstructural abnormalities of short-distance white matter tracts in autism spectrum disorder
    Dinesh K Shukla
    Department of Psychology, San Diego State University, San Diego, CA, USA
    Neuropsychologia 49:1378-82. 2011
    ..Absence of typical age-related correlations with DTI indices may reflect altered maturation of short-distance tracts in ASD. Our results are inconsistent with a notion of selective sparing of short-distance connectivity in ASD...
  6. pmc White matter compromise of callosal and subcortical fiber tracts in children with autism spectrum disorder: a diffusion tensor imaging study
    Dinesh K Shukla
    Brain Development Imaging Laboratory, San Diego State University, San Diego, USA
    J Am Acad Child Adolesc Psychiatry 49:1269-78, 1278.e1-2. 2010
    ..We used diffusion tensor imaging (DTI) to examine white matter integrity for the whole brain and for corpus callosum, internal capsule, and middle cerebellar peduncle in children with ASD and typically developing (TD) children...
  7. ncbi Tract-specific analyses of diffusion tensor imaging show widespread white matter compromise in autism spectrum disorder
    Dinesh K Shukla
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, USA
    J Child Psychol Psychiatry 52:286-95. 2011
    ....
  8. pmc Atypical network connectivity for imitation in autism spectrum disorder
    Patricia Shih
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, CA 92120, United States
    Neuropsychologia 48:2931-9. 2010
    ..Our results suggest atypical connectivity of the imitation network with an enhanced role of dPFC, which may relate to behavioral impairments...
  9. pmc Attentional networks in children and adolescents with autism spectrum disorder
    Brandon Keehn
    Joint Doctoral Program in Language and Communicative Disorders, San Diego State University University of California San Diego, 6363 Alvarado Ct 225N, San Diego, CA 92120, USA
    J Child Psychol Psychiatry 51:1251-9. 2010
    ..The ubiquitous nature of attentional impairments in ASD has led some authors to hypothesize that atypical attentional modulation may be a factor in the development of higher-level sociocommunicative deficits...
  10. pmc Regional homogeneity of fMRI time series in autism spectrum disorders
    Dinesh K Shukla
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, CA 92120, United States
    Neurosci Lett 476:46-51. 2010
    ..Our findings suggest that ReHo is a sensitive measure for detecting cortical abnormalities in autism. However, impact of methodological factors (such as spatial resolution) on ReHo require further investigation...
  11. pmc Aberrant functional connectivity in autism: evidence from low-frequency BOLD signal fluctuations
    Sarah K Noonan
    Joint Doctoral Program in Clinical Psychology, San Diego State University and University of California, San Diego, CA 92120 1863, USA
    Brain Res 1262:48-63. 2009
    ..Taking into consideration methodological factors that might influence measured fcMRI effects, we suggest that ASD is associated with an inefficiency in optimizing network connections to achieve task performance...
  12. pmc From loci to networks and back again: anomalies in the study of autism
    Ralph Axel Müller
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, CA 92120 1863, USA
    Ann N Y Acad Sci 1145:300-15. 2008
    ..Here this approach is illustrated via data obtained from autism research that suggest impaired local cortical architecture and reduced long-range connectivity between cerebral regions...
  13. ncbi Functional brain organization for visual search in ASD
    Brandon Keehn
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, California, USA
    J Int Neuropsychol Soc 14:990-1003. 2008
    ..These results suggest that search efficiency in ASD may be related to enhanced discrimination (reflected in occipital activation) and increased top-down modulation of visual attention (associated with frontoparietal activation)...
  14. pmc Brief report: eye-movement patterns during an embedded figures test in children with ASD
    Brandon Keehn
    San Diego State University, San Diego, San Diego, CA, USA
    J Autism Dev Disord 39:383-7. 2009
    ..Eye-movement results indicate that RT advantage in ASD is related to both WCC and enhanced perceptual functioning...
  15. pmc Atypical functional lateralization of language in autism spectrum disorders
    Natalia M Kleinhans
    Department of Radiology, University of Washington, Seattle, WA 98195, USA
    Brain Res 1221:115-25. 2008
    ..Abnormal functional organization may contribute to the language impairment seen in ASD...
  16. pmc Atypical [corrected] participation of visual cortex during word processing in autism: an fMRI study of semantic decision
    Michael S Gaffrey
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, CA 92120, USA
    Neuropsychologia 45:1672-84. 2007
    ....
  17. pmc The study of autism as a distributed disorder
    Ralph Axel Müller
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, San Diego, California 92120 1863, USA
    Ment Retard Dev Disabil Res Rev 13:85-95. 2007
    ..The concepts and methodology of functional connectivity need to be refined and results need to be corroborated by anatomical studies (such as DTI tractography) before definitive conclusions can be drawn...
  18. ncbi Partially enhanced thalamocortical functional connectivity in autism
    Akiko Mizuno
    Brain Development Imaging Laboratory, Department of Psychology, San Diego State University, CA 92120, USA
    Brain Res 1104:160-74. 2006
    ....