Convergent Findings of Altered Functional and Structural Brain Connectivity in Individuals with High Functioning Autism: A Multimodal MRI Study

Institute of Clinical Radiology, Ludwig-Maximilians University Munich, Munich, Germany.
PLoS ONE (Impact Factor: 3.23). 06/2013; 8(6):e67329. DOI: 10.1371/journal.pone.0067329
Source: PubMed


Brain tissue changes in autism spectrum disorders seem to be rather subtle and widespread than anatomically distinct. Therefore a multimodal, whole brain imaging technique appears to be an appropriate approach to investigate whether alterations in white and gray matter integrity relate to consistent changes in functional resting state connectivity in individuals with high functioning autism (HFA). We applied diffusion tensor imaging (DTI), voxel-based morphometry (VBM) and resting state functional connectivity magnetic resonance imaging (fcMRI) to assess differences in brain structure and function between 12 individuals with HFA (mean age 35.5, SD 11.4, 9 male) and 12 healthy controls (mean age 33.3, SD 9.0, 8 male). Psychological measures of empathy and emotionality were obtained and correlated with the most significant DTI, VBM and fcMRI findings. We found three regions of convergent structural and functional differences between HFA participants and controls. The right temporo-parietal junction area and the left frontal lobe showed decreased fractional anisotropy (FA) values along with decreased functional connectivity and a trend towards decreased gray matter volume. The bilateral superior temporal gyrus displayed significantly decreased functional connectivity that was accompanied by the strongest trend of gray matter volume decrease in the temporal lobe of HFA individuals. FA decrease in the right temporo-parietal region was correlated with psychological measurements of decreased emotionality. In conclusion, our results indicate common sites of structural and functional alterations in higher order association cortex areas and may therefore provide multimodal imaging support to the long-standing hypothesis of autism as a disorder of impaired higher-order multisensory integration.

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Available from: Daniel Keeser, Oct 01, 2015
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    • "Establishing anatomical connectivity bases to alterations in functional connectivity in autism has been less explored (Just et al. 2007; Kana et al. 2006), although such relationships have been reported in typical population (Greicius et al. 2009). A few recent studies have examined connectivity in ASD using simultaneous DTI and fcMRI (Delmonte et al. 2013; Deshpande et al. 2013; Kana et al. 2012; Mueller et al. 2013; Nair et al. 2013). These studies provide two levels of investigation , although sometimes finding no significant direct relationship between the two. "
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    ABSTRACT: Autism is a neurodevelopmental disorder that has been associated with atypical brain functioning. Functional connectivity MRI (fcMRI) studies examining neural networks in autism have seen an exponential rise over the last decade. Such investigations have led to the characterization of autism as a distributed neural systems disorder. Studies have found widespread cortical underconnectivity, local overconnectivity, and mixed results suggesting disrupted brain connectivity as a potential neural signature of autism. In this review, we summarize the findings of previous fcMRI studies in autism with a detailed examination of their methodology, in order to better understand its potential and to delineate the pitfalls. We also address how a multimodal neuroimaging approach (incorporating different measures of brain connectivity) may help characterize the complex neurobiology of autism at a global level. Finally, we also address the potential of neuroimaging-based markers in assisting neuropsychological assessment of autism. The quest for a neural marker for autism is still ongoing, yet new findings suggest that aberrant brain connectivity may be a promising candidate.
    Neuropsychology Review 02/2014; 24(1). DOI:10.1007/s11065-014-9250-0 · 4.59 Impact Factor
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    • "This area of the frontal cortex was also observed to be a source of abnormal magnetoencephalographic (MEG) patterns of epileptiform activity (Lewine et al., 1999). In addition, other observers find the superior temporal gyrus demonstrates significantly decreased functional connectivity, which was also accompanied by gray matter volume reductions (Mueller et al., 2013), thus reinforcing the indications for investigation of gray matter architecture. "
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    ABSTRACT: Background: Autism spectrum disorders (ASDs) are developmental conditions of uncertain etiology which have now affected more than 1% of the school-age population of children in many developed nations. Transcranial ultrasonography (TUS) via the temporal bone appeared to be a potential window of investigation to determine the presence of both cortical abnormalities and increased extra-axial fluid (EAF). Methods: TUS was accomplished using a linear probe (10–5 MHz). Parents volunteered ASD subjects (N = 23; males 18, females 5) for evaluations (mean = 7.46 years ± 3.97 years), and 15 neurotypical siblings were also examined (mean = 7.15 years ± 4.49 years). Childhood Autism Rating Scale (CARS2®) scores were obtained and the ASD score mean was 48.08 + 6.79 (Severe). Results: Comparisons of the extra-axial spaces indicated increases in the ASD subjects. For EAF we scored based on the gyral summit distances between the arachnoid membrane and the cortical pia layer (subarachnoid space): (1) <0.05 cm, (2) 0.05–0.07 cm, (3) 0.08–0.10 cm, (4) >0.10 cm. All of the neurotypical siblings scored 1, whereas the ASD mean score was 3.41 ± 0.67. We also defined cortical dysplasia as the following: hypoechoic lesions within the substance of the cortex, or disturbed layering within the gray matter. For cortical dysplasia we scored: (1) none observed, (2) rare hypoechogenic lesions and/or mildly atypical cortical layering patterns, (3) more common, but separated areas of cortical hypoechogenic lesions, (4) very common or confluent areas of cortical hypoechogenicity. Again all of the neurotypical siblings scored 1, while the ASD subjects’ mean score was 2.79 ± 0.93. Conclusion: TUS may be a useful screening technique for children at potential risk of ASDs which, if confirmed with repeated studies and high resolution MRI, provides rapid, non-invasive qualification of EAF, and cortical lesions.
    Frontiers in Human Neuroscience 01/2014; 7:934. DOI:10.3389/fnhum.2013.00934 · 2.99 Impact Factor
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    • ") and has been used in autism studies to substantiate diagnosis (Yamasaki et al., 2010; Mueller et al., 2013). The AQ scale also significantly discriminated between the two study groups. "
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    ABSTRACT: Neurodevelopmental disconnections have been assumed to cause behavioral alterations in autism spectrum disorders (ASD). Here, we combined measurements of intrinsic functional connectivity (iFC) from resting-state fMRI with task-based fMRI to explore whether altered activity and/or iFC of the right posterior superior temporal sulcus (pSTS) mediates deficits in emotion recognition in ASD. Fifteen adults with ASD and fifteen matched-controls underwent resting-state and task-based fMRI, during which participants discriminated emotional states from point light displays (PLDs). Intrinsic FC of the right pSTS was further examined using 584 (278 ASD/306 controls) resting-state data of the Autism Brain Imaging Data Exchange (ABIDE).Participants with ASD were less accurate than controls in recognizing emotional states from PLDs. Analyses revealed pronounced ASD-related reductions both in task-based activity and resting-state iFC of the right pSTS with fronto-parietal areas typically encompassing the action observation network. Notably, pSTS-hypo-activity was related to pSTS-hypo-connectivity and both measures were predictive of emotion recognition performance with each measure explaining a unique part of the variance. Analyses with the large independent ABIDE-dataset replicated reductions in pSTS-iFC to fronto-parietal regions.These findings provide novel evidence that pSTS hypo-activity and hypo-connectivity with the fronto-parietal action observation network are linked to the social deficits characteristic of ASD.
    Social Cognitive and Affective Neuroscience 09/2013; 9(10). DOI:10.1093/scan/nst156 · 7.37 Impact Factor
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