Aberrant Striatal Functional Connectivity in Children with Autism

Phyllis Green and Randolph Cōwen Institute for Pediatric Neuroscience, Child Study Center, New York University Langone Medical Center, New York, New York 10016, USA.
Biological psychiatry (Impact Factor: 10.26). 12/2010; 69(9):847-56. DOI: 10.1016/j.biopsych.2010.10.029
Source: PubMed


Models of autism spectrum disorders (ASD) as neural disconnection syndromes have been predominantly supported by examinations of abnormalities in corticocortical networks in adults with autism. A broader body of research implicates subcortical structures, particularly the striatum, in the physiopathology of autism. Resting state functional magnetic resonance imaging has revealed detailed maps of striatal circuitry in healthy and psychiatric populations and vividly captured maturational changes in striatal circuitry during typical development.
Using resting state functional magnetic resonance imaging, we examined striatal functional connectivity (FC) in 20 children with ASD and 20 typically developing children between the ages of 7.6 and 13.5 years. Whole-brain voxelwise statistical maps quantified within-group striatal FC and between-group differences for three caudate and three putamen seeds for each hemisphere.
Children with ASD mostly exhibited prominent patterns of ectopic striatal FC (i.e., functional connectivity present in ASD but not in typically developing children), with increased functional connectivity between nearly all striatal subregions and heteromodal associative and limbic cortex previously implicated in the physiopathology of ASD (e.g., insular and right superior temporal gyrus). Additionally, we found striatal functional hyperconnectivity with the pons, thus expanding the scope of functional alterations implicated in ASD. Secondary analyses revealed ASD-related hyperconnectivity between the pons and insula cortex.
Examination of FC of striatal networks in children with ASD revealed abnormalities in circuits involving early developing areas, such as the brainstem and insula, with a pattern of increased FC in ectopic circuits that likely reflects developmental derangement rather than immaturity of functional circuits.

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Available from: Rebecca Grzadzinski, Mar 29, 2014
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    • "Functional MRI studies show that dysfunctional anterior insula is strongly correlated with autism and has an important role in autism [20]. Moreover, insula hypoactivation has been reported in relation with social activities [21]. In healthy individuals, right anterior insula is activated during the vocal repeating of nonlyrical melodies, as speaking clearly requires left anterior insula [22]. "
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    ABSTRACT: To investigate any relation of behavior problems with cranial Diffusion Tensor Imaging (DTI) and Magnetic Resonance Spectroscopy (MRS) findings in autism spectrum disorders. A total of 20 males children (12 autistic patients and 8 healthy controls) was examined by cranial DTI and MRS. The Aberrant Behavior Checklist (ABC) was used to calculate the irritability, lethargy-social withdrawal, stereotypic behavior, hyperactivity, and speech disorder scores for each patient. The results of MRS and DTI were evaluated together with the ABC scores. Fractional anisotropy (FA) values demonstrated significant decreases in the left frontoparietal white matter, anterior limb of the right internal capsule, and left middle cerebellar peduncle as the behavior problem scores elevated (P < 0.05). With the exception of social withdrawal, as the behavior problem scores increased, metabolite levels increased, as well. The positive correlation between the MRS findings, behavior problem scores, and metabolite levels suggests the presence of a dysfunction leading to hypo and hyper neuronal function in various locations. Reduced FA values in DTI and negative correlation of behavior problems with FA values in the contralateral hemisphere, may indicate reduced myelination and abnormal axonal organization.
    International Journal of Clinical and Experimental Medicine 07/2015; 8(4):5621-30. · 1.28 Impact Factor
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    • "One interesting result that deserves mention is a significantly greater connectivity in ASD children, relative to TD children, between Broca's and left frontal regions, and Wernicke's area and calcarine gyrus. While initial literature in intrinsic connecitivity had focused on adults with ASD [e.g., Assaf et al., 2010; Kennedy and Courchesne, 2008; Monk et al., 2009; von dem Hagen et al., 2012], studies investigating intrinsitc connecitivity in children with ASD have consistently shown hyperconnecitivy compared to TD children [Supekar et al., 2013; Di Martino et al., 2011; Uddin et al., 2013]. This may suggest a developmental shift from hyperconnectivity to hypoconnectivity as individuals with ASD mature into adulthood. "
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    ABSTRACT: While task-based neuroimaging studies have identified alterations in neural circuitry underlying language processing in children with autism spectrum disorders [ASD], resting state functional magnetic resonance imaging [rsfMRI] is a promising alternative to the constraints posed by task-based fMRI. This study used rsfMRI, in a longitudinal design, to study the impact of a reading intervention on connectivity of the brain regions involved in reading comprehension in children with ASD. Functional connectivity was examined using group independent component analysis (GICA) and seed-based correlation analysis of Broca's and Wernicke's areas, in three groups of participants: an experimental group of ASD children (ASD-EXP), a wait list control group of ASD children (ASD-WLC), and a group of typically developing (TD) control children. Both GICA and seed-based analyses revealed stronger functional connectivity of Broca's and Wernicke's areas in the ASD-EXP group postintervention. Additionally, improvement in reading comprehension in the ASD-EXP group was correlated with greater connectivity in both Broca's and Wernicke's area in the GICA identified reading network component. In addition, increased connectivity between the Broca's area and right postcentral and right STG, and the Wernicke's area and LIFG, were also correlated with greater improvement in reading comprehension. Overall, this study revealed widespread changes in functional connectivity of the brain's reading network as a result of intervention in children with ASD. These novel findings provide valuable insights into the neuroplasticity of brain areas underlying reading and the impact of intensive intervention in modifying them in children with ASD. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 04/2015; DOI:10.1002/hbm.22821 · 5.97 Impact Factor
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    • "Resting-state fMRI has emerged over the past decade as a powerful tool for examining the large-scale organization and functional connectivity of brain networks in healthy and clinical populations (Fornito and Bullmore, 2010). It has been successfully used to map brain corticostriatal circuits in vivo, providing clear and compelling evidence for the existence of functionally organized dorsal and ventral circuits as well as specific alterations across diverse neuropsychiatric disorders including obsessive–compulsive disorder (Harrison et al., 2009; Harrison et al., 2013), psychosis (Dandash et al., 2014), autism (Di Martino et al., 2011) and depression (Furman et al., 2011). Perhaps surprisingly, evidence has emerged in support of primary functional connectivity alterations involving dorsal as opposed to ventral corticostriatal circuits in adults (Furman et al., 2011) and young (Gabbay et al., 2013) depressed populations . "
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    ABSTRACT: Background Altered basal ganglia function has been implicated in the pathophysiology of youth Major Depressive Disorder (MDD). Studies have generally focused on characterizing abnormalities in ventral “affective” corticostriatal loops supporting emotional processes. Recent evidence however, has implicated alterations in functional connectivity of dorsal “cognitive” corticostriatal loops in youth MDD. The contribution of dorsal versus ventral corticostriatal alterations to the pathophysiology of youth MDD remains unclear. Methods Twenty-one medication-free patients with moderate-to-severe MDD between the ages of 15 and 24 years old were matched with 21 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging we systematically investigated connectivity of eight dorsal and ventral subdivisions of the striatum. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the depressed and control groups. Results Depressed youths showed alterations in functional connectivity that were confined to the dorsal corticostriatal circuit. Compared to controls, depressed patients showed increased connectivity between the dorsal caudate nucleus and ventrolateral prefrontal cortex bilaterally. Increased depression severity correlated with the magnitude of dorsal caudate connectivity with the right dorsolateral prefrontal cortex. There were no significant between-group differences in connectivity of ventral striatal regions. Conclusions The results provide evidence that alterations in corticostriatal connectivity are evident at the early stages of the illness and are not a result of antidepressant treatment. Increased connectivity between the dorsal caudate, which is usually associated with cognitive processes, and the more affectively related ventrolateral prefrontal cortex may reflect a compensatory mechanism for dysfunctional cognitive-emotional processing in youth depression.
    Clinical neuroimaging 12/2014; 9. DOI:10.1016/j.nicl.2014.12.017 · 2.53 Impact Factor
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