Jose O. Maximo

The Implications of Brain Connectivity in the Neuropsychology of Autism

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.

Aberrant functioning of the theory-of-mind network in children and adolescents with autism

BackgroundTheory-of-mind (ToM), the ability to infer people’s thoughts and feelings, is a pivotal skill in effective social interactions. Individuals with autism spectrum disorders (ASD) have been found to have altered ToM skills, which significantly impacts the quality of their social interactions. Neuroimaging studies have reported altered activation of the ToM cortical network, especially in adults with autism, yet little is known about the brain responses underlying ToM in younger individuals with ASD. This functional magnetic resonance imaging (fMRI) study investigated the neural mechanisms underlying ToM in high-functioning children and adolescents with ASD and matched typically developing (TD) peers.MethodsfMRI data were acquired from 13 participants with ASD and 13 TD control participants while they watched animations involving two “interacting” geometrical shapes.ResultsParticipants with ASD showed significantly reduced activation, relative to TD controls, in regions considered part of the ToM network, the mirror network, and the cerebellum. Functional connectivity analyses revealed underconnectivity between frontal and posterior regions during task performance in the ASD participants.ConclusionsOverall, the findings of this study reveal disruptions in the brain circuitry underlying ToM in ASD at multiple levels, including decreased activation and decreased functional connectivity.

The role of mirroring and mentalizing networks in mediating action intentions in autism

BackgroundThe ability to interpret agents’ intent from their actions is a vital skill in successful social interaction. However, individuals with autism spectrum disorders (ASD) have been found to have difficulty in attributing intentions to others. The present study investigated the neural mechanisms of inferring intentions from actions in individuals with ASD.MethodsFunctional magnetic resonance imaging (fMRI) data were acquired from 21 high-functioning young adults with ASD and 22 typically developing (TD) control participants, while making judgments about the means (how an action is performed) and intention (why an action is performed) of a model’s actions.ResultsAcross both groups of participants, the middle and superior temporal cortex, extending to temporoparietal junction, and posterior cingulate cortex, responded significantly to inferring the intent of an action, while inferior parietal lobule and occipital cortices were active for judgments about the means of an action. Participants with ASD had significantly reduced activation in calcarine sulcus and significantly increased activation in left inferior frontal gyrus, compared to TD peers, while attending to the intentions of actions. Also, ASD participants had weaker functional connectivity between frontal and posterior temporal regions while processing intentions.ConclusionsThese results suggest that processing actions and intentions may not be mutually exclusive, with reliance on mirroring and mentalizing mechanisms mediating action understanding. Overall, inferring information about others’ actions involves activation of the mirror neuron system and theory-of-mind regions, and this activation (and the synchrony between activated brain regions) appears altered in young adults with ASD.

Changes in intrinsic connectivity of the brain's reading network following intervention in children with autism.

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 Brocas and Wernickes 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 Brocas and Wernickes areas in the ASD‐EXP group postintervention. Additionally, improvement in reading comprehension in the ASD‐EXP group was correlated with greater connectivity in both Brocas and Wernickes area in the GICA identified reading network component. In addition, increased connectivity between the Brocas area and right postcentral and right STG, and the Wernickes area and LIFG, were also correlated with greater improvement in reading comprehension. Overall, this study revealed widespread changes in functional connectivity of the brains 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 36:2965–2979, 2015.

Task-Dependent Changes in Frontal-Parietal Activation and Connectivity During Visual Search.

Visual search is an important skill in navigating and locating objects (a target) among distractors in our environment. Efficient and faster target detection involves reciprocal interaction between a viewers attentional resources as well as salient target characteristics. The neural correlates of visual search have been extensively investigated over the last decades, suggesting the involvement of a frontal-parietal network comprising the frontal eye fields (FEFs) and intraparietal sulcus (IPS). In addition, activity and connectivity of these network changes as the visual search become complex and more demanding. The current functional magnetic resonance imaging study examined the modulation of the frontal-parietal network in response to cognitive demand in 22 healthy adult participants. In addition to brain activity, changes in functional connectivity and effective connectivity in this network were examined in response to easy and difficult visual search. Results revealed significantly increased activation in FEF, IPS, and supplementary motor area, more so in difficult search than in easy search. Functional and effective connectivity analyses showed enhanced connectivity in the frontal-parietal network during difficult search and enhanced information transfer from left to right hemisphere during the difficult search process. Our overall findings suggest that cognitive demand significantly increases brain resources across all three measures of brain processing. In sum, we found that goal-directed visual search engages a network of frontal-parietal areas that are modulated in relation to cognitive demand.

The Action Imitation network and motor imitation in children and adolescents with autism

While deficits in imitation had been reported in children with autism spectrum disorder (ASD), its exact nature remains unclear. A dysfunction in mirroring mechanisms (through action imitation) has been proposed by some studies to explain this, although some recent evidence points against this hypothesis. The current study used behavior and functional MRI to examine the integrated functioning of the regions that are considered part of the Action Imitation network (AIN) in children and adolescents with ASD during a motor imitation task. Fourteen ASD and 15 age-and-IQ-matched typically developing (TD) children were asked to imitate a series of hand gestures in the MRI scanner. Intact performance on imitation (accurate imitation of hand gestures outside the scanner) in both ASD and TD groups was accompanied by significantly lower activity in ASD participants, relative to TD, in right angular gyrus, precentral gyrus, and left middle cingulate. In addition, autism traits were found to be significantly correlated with activation in the right angular gyrus. Overall, the findings of this study support the role of AIN in imitation and a potential difference in the recruitment of this network in ASD children.

“Decoding versus comprehension”: Brain responses underlying reading comprehension in children with autism

HighlightsWe used fMRI to examine reading comprehension deficits in children with autism.Children completed a word similarities task in the MRI scanner.Hypoactivation and underconnectivity found in ASD in semantic processing regions.Altered reading network response may underlie comprehension deficits in ASD. Abstract Despite intact decoding ability, deficits in reading comprehension are relatively common in children with autism spectrum disorders (ASD). However, few neuroimaging studies have tested the neural bases of this specific profile of reading deficit in ASD. This fMRI study examined activation and synchronization of the brain’s reading network in children with ASD with specific reading comprehension deficits during a word similarities task. Thirteen typically developing children and 18 children with ASD performed the task in the MRI scanner. No statistically significant group differences in functional activation were observed; however, children with ASD showed decreased functional connectivity between the left inferior frontal gyrus (LIFG) and the left inferior occipital gyrus (LIOG). In addition, reading comprehension ability significantly positively predicted functional connectivity between the LIFG and left thalamus (LTHAL) among all subjects. The results of this study provide evidence for altered recruitment of reading‐related neural resources in ASD children and suggest specific weaknesses in top‐down modulation of semantic processing.

Action simulation and mirroring in children with autism spectrum disorders

HighlightsPoor imitation skills have been a characteristic feature of children with autism.Findings of fMRI studies of imitation in ASD are less consistent.This fMRI study examines action simulation and the neural circuitry underlying it.Our findings show increased brain activation in ASD compared to control children.Autism symptoms were positively correlated with brain activation social actions. Abstract Mental imitation, perhaps a precursor to motor imitation, involves visual perspective‐taking and motor imagery. Research on mental imitation in autism spectrum disorders (ASD) has been rather limited compared to that on motor imitation. The main objective of this fMRI study is to determine the differences in brain responses underlying mirroring and mentalizing networks during mental imitation in children and adolescents with ASD. Thirteen high‐functioning children and adolescents with ASD and 15 age‐and‐ IQ‐matched typically developing (TD) control participants took part in this fMRI study. In the MRI scanner, participants were shown cartoon pictures of people performing everyday actions (Transitive actions: e.g., ironing clothes but with the hand missing; and Intransitive actions: e.g., clapping hands with the palms missing) and were asked to identify which hand or palm orientation would best fit the gap. The main findings are: 1) both groups performed equally while processing transitive and intransitive actions; 2) both tasks yielded activation in the bilateral inferior frontal gyrus (IFG) and inferior parietal lobule (IPL) in ASD and TD groups; 3) Increased activation was seen in ASD children, relative to TD, in left ventral premotor and right middle temporal gyrus during intransitive actions; and 4) ASD symptom severity positively correlated with activation in left parietal, right middle temporal, and right premotor regions across all subjects. Overall, our findings suggest that regions mediating mirroring may be recruiting more brain resources in ASD and may have implications for understanding social movement through modeling.

From word reading to multisentence comprehension: Improvements in brain activity in children with autism after reading intervention

Background Children with ASD show a unique reading profile characterized by decoding abilities equivalent to verbal abilities, but with lower comprehension skills. Neuroimaging studies have found recruitment of regions primarily associated with visual processing (e.g., fusiform gyrus and medial parietal cortex), but reduced activation in frontal and temporal regions, when reading in adults with ASD. The purpose of this study was to assess neural changes associated with an intense reading intervention program in children with ASD using three fMRI tasks of reading. Methods 25 children with ASD were randomly assigned to a treatment (ASD-EXP) or waitlist group (ASD-WLC). Children participated in a reading intervention program (4-hour sessions per day, 5 days a week for 10 weeks). We utilized three tasks: word, sentence, and multisentence processing, each with differential demands of reading comprehension. fMRI data were acquired at each of two scanning sessions 10-weeks apart. Results Across tasks, post-intervention results revealed that the ASD-EXP group showed greater activation in bilateral precentral gyrus and the postcentral gyrus, visual processing regions (e.g., occipital cortex, fusiform gyrus), and frontal regions. In the word task, left thalamus and the right angular gyrus (AG) activation was unique to the ASD-EXP group post-intervention. Sentence tasks showed differential activation of core language areas (e.g., IFG, IPL) post-intervention. Conclusions Our results provide evidence for differential recruitment of brain regions based on task demands in children with ASD, and support the potential of targeted interventions to alter brain activation in response to positive gains in treatment. Children with ASD have a different reading profile from other reading disorders that needs to be specifically targeted in interventions.

Changes in intrinsic local connectivity after reading intervention in children with autism

HighlightsGoal was to test the impact of reading intervention on brain in autism.Local connectivity examined in children with autism using resting‐state fMRI.Increase in local visuospatial connectivity was found in the experimental group.This change was correlated with changes in their reading comprehension skills.Findings underscore the role of behavioral intervention in changing the brain. Abstract Most of the existing behavioral and cognitive intervention programs in autism spectrum disorders (ASD) have not been tested at the neurobiological level, thus falling short of finding quantifiable neurobiological changes underlying behavioral improvement. The current study takes a translational neuroimaging approach to test the impact of a structured visual imagery‐based reading intervention on improving reading comprehension and assessing its underlying local neural circuitry. Behavioral and resting state functional MRI (rs‐fMRI) data were collected from children with ASD who were randomly assigned to an Experimental group (ASD‐EXP; n = 14) and a Wait‐list control group (ASD‐WLC; n = 14). Participants went through an established reading intervention training program (Visualizing and Verbalizing for language comprehension and thinking or V/V; 4‐h per day, 10‐weeks, 200 h of face‐to‐face instruction). Local functional connectivity was examined using a connection density approach from graph theory focusing on brain areas considered part of the Reading Network. The main results are as follows: (I) the ASD‐EXP group showed significant improvement, compared to the ASD‐WLC group, in their reading comprehension ability evidenced from change in comprehension scores; (II) the ASD‐EXP group showed increased local brain connectivity in Reading Network regions compared to the ASD‐WLC group post‐intervention; (III) intervention‐related changes in local brain connectivity were observed in the ASD‐EXP from pre to post‐intervention; and (IV) improvement in language comprehension significantly predicted changes in local connectivity. The findings of this study provide novel insights into brain plasticity in children with developmental disorders using targeted intervention programs.