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Cortical and subcortical alterations associated with precision visuomotor behavior in individuals with autism spectrum disorder.

ABSTRACT: In addition to core deficits in social-communication abilities and repetitive behaviors and interests, many patients with autism spectrum disorder (ASD) experience developmental comorbidities, including sensorimotor issues. Sensorimotor issues are common in ASD and associated with more severe clinical symptoms. Importantly, sensorimotor behaviors are precisely quantifiable and highly translational, offering promising targets for neurophysiological studies of ASD. We used functional MRI to identify brain regions associated with sensorimotor behavior using a visually guided precision gripping task in individuals with ASD (n = 20) and age-, IQ-, and handedness-matched controls (n = 18). During visuomotor behavior, individuals with ASD showed greater force variability than controls. The blood oxygen level-dependent signal for multiple cortical and subcortical regions was associated with force variability, including motor and premotor cortex, posterior parietal cortex, extrastriate cortex, putamen, and cerebellum. Activation in the right premotor cortex scaled with sensorimotor variability in controls but not in ASD. Individuals with ASD showed greater activation than controls in left putamen and left cerebellar lobule VIIb, and activation in these regions was associated with more severe clinically rated symptoms of ASD. Together, these results suggest that greater sensorimotor variability in ASD is associated with altered cortical-striatal processes supporting action selection and cortical-cerebellar circuits involved in feedback-guided reactive adjustments of motor output. Our findings also indicate that atypical organization of visuomotor cortical circuits may result in heightened reliance on subcortical circuits typically dedicated to motor skill acquisition. Overall, these results provide new evidence that sensorimotor alterations in ASD involve aberrant cortical and subcortical organization that may contribute to key clinical issues in patients.NEW & NOTEWORTHY This is the first known study to examine functional brain activation during precision visuomotor behavior in autism spectrum disorder (ASD). We replicate previous findings of elevated force variability in ASD and find these deficits are associated with atypical function of ventral premotor cortex, putamen, and posterolateral cerebellum, indicating cortical-striatal processes supporting action selection and cortical-cerebellar circuits involved in feedback-guided reactive adjustments of motor output may be key targets for understanding the neurobiology of ASD.

SUBMITTER: Unruh KE

PROVIDER: S-EPMC6843107 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Cortical and subcortical alterations associated with precision visuomotor behavior in individuals with autism spectrum disorder.

Unruh Kathryn E KE Martin Laura E LE Magnon Grant G Vaillancourt David E DE Sweeney John A JA Mosconi Matthew W MW

Journal of neurophysiology 20190717 4

In addition to core deficits in social-communication abilities and repetitive behaviors and interests, many patients with autism spectrum disorder (ASD) experience developmental comorbidities, including sensorimotor issues. Sensorimotor issues are common in ASD and associated with more severe clinical symptoms. Importantly, sensorimotor behaviors are precisely quantifiable and highly translational, offering promising targets for neurophysiological studies of ASD. We used functional MRI to identi ...[more]

PMID: 31314644

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Project description:IMPORTANCE:Individuals with autism spectrum disorder (ASD) exhibit severe difficulties in social interaction, motor coordination, behavioral flexibility, and atypical sensory processing, with considerable interindividual variability. This heterogeneous set of symptoms recently led to investigating the presence of abnormalities in the interaction across large-scale brain networks. To date, studies have focused either on constrained sets of brain regions or whole-brain analysis, rather than focusing on the interaction between brain networks. OBJECTIVES:To compare the intrinsic functional connectivity between brain networks in a large sample of individuals with ASD and typically developing control subjects and to estimate to what extent group differences would predict autistic traits and reflect different developmental trajectories. DESIGN, SETTING, AND PARTICIPANTS:We studied 166 male individuals (mean age, 17.6 years; age range, 7-50 years) diagnosed as having DSM-IV-TR autism or Asperger syndrome and 193 typical developing male individuals (mean age, 16.9 years; age range, 6.5-39.4 years) using resting-state functional magnetic resonance imaging (MRI). Participants were matched for age, IQ, head motion, and eye status (open or closed) in the MRI scanner. We analyzed data from the Autism Brain Imaging Data Exchange (ABIDE), an aggregated MRI data set from 17 centers, made public in August 2012. MAIN OUTCOMES AND MEASURES:We estimated correlations between time courses of brain networks extracted using a data-driven method (independent component analysis). Subsequently, we associated estimates of interaction strength between networks with age and autistic traits indexed by the Social Responsiveness Scale. RESULTS:Relative to typically developing control participants, individuals with ASD showed increased functional connectivity between primary sensory networks and subcortical networks (thalamus and basal ganglia) (all t???3.13, P?<?.001 corrected). The strength of such connections was associated with the severity of autistic traits in the ASD group (all r???0.21, P?<?.0067 corrected). In addition, subcortico-cortical interaction decreased with age in the entire sample (all r???-0.09, P?<?.012 corrected), although this association was significant only in typically developing participants (all r???-0.13, P?<?.009 corrected). CONCLUSIONS AND RELEVANCE:Our results showing ASD-related impairment in the interaction between primary sensory cortices and subcortical regions suggest that the sensory processes they subserve abnormally influence brain information processing in individuals with ASD. This might contribute to the occurrence of hyposensitivity or hypersensitivity and of difficulties in top-down regulation of behavior.

Project description:ObjectiveNeuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group.MethodThe sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach.ResultsThe case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions.ConclusionsThe ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.

Project description:Background: Individuals with autism spectrum disorder (ASD) show elevated levels of motor variability that are associated with clinical outcomes. Cortical-cerebellar networks involved in visuomotor control have been implicated in postmortem and anatomical imaging studies of ASD. However, the extent to which these networks show intrinsic functional alterations in patients, and the relationship between intrinsic functional properties of cortical-cerebellar networks and visuomotor impairments in ASD have not yet been clarified. Methods: We examined the amplitude of low-frequency fluctuation (ALFF) of cortical and cerebellar brain regions during resting-state functional MRI (rs-fMRI) in 23 individuals with ASD and 16 typically developing (TD) controls. Regions of interest (ROIs) with ALFF values significantly associated with motor variability were identified for for patients and controls respectively, and their functional connectivity (FC) to each other and to the rest of the brain was examined. Results: For TD controls, greater ALFF in bilateral cerebellar crus I, left superior temporal gyrus, left inferior frontal gyrus, right supramarginal gyrus, and left angular gyrus each were associated with greater visuomotor variability. Greater ALFF in cerebellar lobule VIII was associated with less visuomotor variability. For individuals with ASD, greater ALFF in right calcarine cortex, right middle temporal gyrus (including MT/V5), left Heschl's gyrus, left post-central gyrus, right pre-central gyrus, and left precuneus was related to greater visuomotor variability. Greater ALFF in cerebellar vermis VI was associated with less visuomotor variability. Individuals with ASD and TD controls did not show differences in ALFF for any of these ROIs. Individuals with ASD showed greater posterior cerebellar connectivity with occipital and parietal cortices relative to TD controls, and reduced FC within cerebellum and between lateral cerebellum and pre-frontal and other regions of association cortex. Conclusion: Together, these findings suggest that increased resting oscillations within visuomotor networks in ASD are associated with more severe deficits in controlling variability during precision visuomotor behavior. Differences between individuals with ASD and TD controls in the topography of networks showing relationships to visuomotor behavior suggest atypical patterns of cerebellar-cortical specialization and connectivity in ASD that underlies previously documented visuomotor deficits.

Project description:Background: Individual differences in gray-matter morphometry in the limbic system and frontal cortex have been linked to clinical features of cocaine use disorder (CUD). Self-administration paradigms can provide more direct measurements of the relationship between the regulation of cocaine use and gray-matter morphometry when compared to self-report assessments.Objectives: Our goal was to investigate associations with self-administration behavior in subcortical and cortical brain regions. We hypothesized the number of cocaine infusions self-administered would be correlated with gray-matter volumes (GMVs) in the striatum, amygdala, and hippocampus. Due to scarcity in human studies, we did not hypothesize subcortical directionality. In the frontal cortex, we hypothesized thickness would be negatively correlated with self-administered cocaine.Methods: We conducted an analysis of cocaine self-administration and structural MRI data from 33 (nFemales = 10) individuals with moderate-to-severe CUD. Self-administration lasted 60-minutes and cocaine (8, 16, or 32 mg/70 kg) was delivered on an FR1 schedule (5-minute lockout). Subcortical and cortical regression analyses were performed that included combined bilateral regions and age, experimental variables and use history as confounders.Results: Self-administered cocaine infusions were positively associated with caudal GMV (b = 0.18, p = 0.030) and negatively with putamenal GMV (b = -0.10, p = 0.041). In the cortical model, infusions were positively associated with insular thickness (b = 0.39, p = 0.008) and women appeared to self-administer cocaine more frequently (b = 0.23, p = 0.019).Conclusions: Brain morphometry features in the striatum and insula may contribute to cocaine consumption in CUD. These differences in morphometry may reflect consequences of prolonged use, predisposed vulnerability, or other possibilities.Clinical Trial Numbers: NCT01978431; NCT03471182.

Dataset Information

Cortical and subcortical alterations associated with precision visuomotor behavior in individuals with autism spectrum disorder.

Publications

Cortical and subcortical alterations associated with precision visuomotor behavior in individuals with autism spectrum disorder.

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