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This review presents an overview of functional magnetic resonance imaging findings in autism spectrum disorders (ASDs), Although there is considerable heterogeneity with respect to results across studies, common themes have emerged, including: (i) hypoactivation in nodes of the “social brain” during social processing tasks, including regions within the prefrontal cortex, the posterior superior temporal sulcus, the amygdala, and the fusiform gyrus; (ii) aberrant frontostriatal activation during cognitive control tasks relevant to restricted and repetitive behaviors and interests, including regions within the dorsal prefrontal cortex and the basal ganglia; (iii) differential lateralization and activation of language processing and production regions during communication tasks; (iv) anomalous mesolimbic responses to social and nonsocial rewards; (v) task-based long-range functional hypoconnectivity and short-range hyper-connectivity; and (vi) decreased anterior-posterior functional connectivity during resting states. These findings provide mechanistic accounts of ASD pathophysiology and suggest directions for future research aimed at elucidating etiologic models and developing rationally derived and targeted treatments.
Cet article présente une synthèse des résultats de l'imagerie par résonance magnétique fonctionnelle dans les troubles autistiques (TA), En dépit d'une grande hétérogénéité due aux résultais des études, des thèmes communs ressortent comme: 1) une hypoactivation des nœuds du « cerveau social » au cours des tâches sociales, qui concerne les régions du cortex préfrontal, du sillon temporal postérosupérieur, de l'amygdale, et du gyrus fusiforme ; 2) une activation froniostriaiale aberrante du cortex dorsal préfrontal et des noyaux gris centraux lors des tâches de contrôle cognitif se rapportant à des intérêts et à des comportements restreints et répétitifs ; 3) une activation et une latéralisation différentielles des régions de production et de traitement du langage au cours des tâches de communication ; 4) des réponses mésolimbiques anormales aux récompenses sociales et non sociales ; 5) une hypoconnectivité fonctionnelle à longue distance et une hyperconnectivité de courte distance basées sur les tâches ; 6) une connectivité fonctionnelle antéropostérieure diminuée pendant les états de repos. Ces résultais donnent un aperçu mécanisie de la physiopathologie des TA et suggèrent des directions pour la recherche future afin d'élaborer des modèles étiologiques et de développer de façon rationnelle des traitements ciblés et dérivés.
Autism was first described by Leo Kanner1 and Hans Asperger2 in a series of clinical case studies. Both clinicians suggested that the conditions now referred to as autism spectrum disorders (ASDs) may have a neurobiological basis. With the relatively recent advent of modern brain imaging techniques, translational psychiatric research has embraced the systematic study of ASDs using these measurement tools to gain insight into the pathophysiology and possible etiology of ASDs. The ultimate promise of these approaches is to improve mechanistic accounts of ASDs as well as provide targets for novel intervention approaches.
ASDs emerge early in life and are generally associated with lifelong disability.3 The defining symptoms of the disorder include social and communicative deficits and restricted and repetitive behaviors and interests.4 Individuals with milder constellations of symptoms are classified as having an ASD, a term that reflects the highly heterogenous array of symptom presentations and that will likely be adopted to characterize individuals with a range of intellectual functioning in the next version of the Diagnostic and Statistical Manual of Mental Disorders.5 Geschwind and Levitt6 illustrated the complexity inherent to understanding the neurobiology of ASDs by suggesting that there are likely many “autisms,” each with non-overlapping etiologies and presentations. Given the highly heterogenous nature of ASDs, it is perhaps not surprising that brain imaging studies have yielded a wide array of candidate brain circuits affected by the disorder. This range of brain endophenotypes is consistent with the challenges associated with identifying genes that cause ASDs: although ASDs have a very strong genetic component, with an estimated heritability as high as 90%,7 the identification of reliable genetic markers remains elusive.
Functional magnetic resonance imaging (fMRI) has proven to be a useful tool to investigate aberrant neurobiological function in ASDs because of its excellent contrast properties, spatial resolution, and temporal resolution. fMRI uses specialized pulse sequences to localize metabolic correlates of neural activity linked to relevant neurocognitive processes. Additionally, unlike positron emission tomography (PET) and single-photon emission computed tomography (SPECT), fMRI does not rely on radiotracers and is noninvasive. The past two decades have witnessed a surge in fMRI research in ASDs, and the goal of this review is to provide an overview of the questions addressed by these studies, to identify consistent patterns across investigations, and to suggest directions for future research.
Likely due at least in part to the heterogeneity of symptom expression in ASDs, there is no unifying account of brain dysfunction that explains all the core symptoms of ASDs. Instead, the triad of defining ASD symptoms (ie, impaired social functioning, impaired communication, and restricted and repetitive behaviors and interests) suggests distinct neural systems. Additionally, it is common for some cognitive systems to be spared in individuals with ASDs (eg, even severe cases of ASDs may be accompanied by high intelligence and other so-called “islets of ability”8), suggesting that brain dysfunction in ASDs may be domain-specific. Likewise, task-based fMRI studies of ASDs have taken the piecemeal approach of investigating neurocognitive processes linked to specific symptom domains in relative isolation. Therefore, in this review studies are grouped based on these distinct neurocognitive processes. The clear majority of studies have used tasks that map onto the triad of defining ASD symptoms, and thus studies are first presented based on this trichotomy. However, emerging fMRI data addressing reward processing and resting-state functional connectivity do not clearly fit within these three domains, as thus are given separate sections in this review.
Most functional neuroimaging investigations in ASDs have addressed social perception (the automatic and preconscious processing of social information) and social cognition (processing meaning from emotional and social cues). Task-related fMRI studies addressing social functioning in ASDs have focused on nodes of the socalled “social brain,” including the medial prefrontal cortex, implicated in making inferences about others' intentions, the temporoparietal junction, mediating mentalizing, the posterior superior temporal sulcus, activated by biological motion, the inferior frontal gyrus, involved in emotional judgments, the interparietal sulcus, which guides spatial attention in social contexts, the amygdala, involved in recognizing emotions from facial expressions, the fusiform gyrus, critical for face processing, and the anterior insula, involved in understanding internal states and mimicking social expressions (see ref 9 for a review).
Perhaps the richest area of inquiry into social cognition deficits in ASDs has been studies of face processing (Table I). Faces are perhaps the quintessential social stimulus, and infants attend to and recognize faces from very early infancy.10 Studies of face processing in ASDs are theoretically grounded by behavioral evidence of impaired joint attention, eye contact, and face recognition and discrimination in ASDs, as well as impaired social emotional judgments about faces, reduced face emotion recognition and perception, and abnormal eye scanpaths when viewing faces.11,12
In neurotypical participants, the medial-lateral fusiform gyrus (FG) as well as the superior temporal sulcus, amygdala, and orbitofrontal cortex, activate in response to faces.13 The majority of fMRI studies in ASDs indicate FG hypoactivity to faces14-22 and to facial expressions.15,20,23-25 However, other reports suggest no differences in FG activation to familiar faces,26-29 stranger faces in the presence of an attentional cue,30 or when matching upright with inverted faces.31
These apparently inconsistent findings may be reconciled in a number of ways.32,33 The degree of visual attention to faces appears to be a critical factor moderating FG activation to faces in ASDs, with tasks that guide visual attention to faces or analytic approaches that account for point-of-regard resulting in relatively less FG hypoactivation in ASDs.21,30 This conclusion is supported by research indicating that face familiarity moderates FG responses to faces in ASDs28 and that impaired social cognition in ASDs may be mediated, at least in part, by attention to social cues, rather than by deficits in social cue processing per se.31,35 Similarly, lifelong amotivation to interact with faces may result in reduced perceptual skill when processing faces, and, in turn, cause FG hypoactivation to faces in ASDs that is perhaps a downstream consequence of reduced social experience rather than pathognomonic to ASDs.36 Moreover, the FG encodes not only face percepts, but social knowledge as well,37 suggesting that the FG may mediate: (i) the attribution of social meaning to stimuli: (ii) the retrieval of social semantic information; and (iii) self-referential experiences.28 Thus, the disparate results of the face processing literature in ASDs likely reflect the diverse and subtle social processes mediated by the FG and recruited by diverse fMRI tasks.
Amygdala response to faces in ASDs has also been extensively studied, and results in this area are decidedly mixed. There is evidence of no differences in amygdala activation to faces,18 of amygdala hypoactivation during face viewing15,16,26,31,38 and face matching,16 as well as evidence of amygdala hyperactivation to faces39,40 in ASDs, particularly when accounting for gaze time to faces21 (but see ref 41 for an exception). One study reported decreased amygdala habituation to the repeated presentation of faces, suggesting that social deficits in ASDs may be influenced by hyperarousal to faces due to protracted amygdala activation.42
Theory of mind and mental inferences have been examine in ASDs via fMRI studies that address the ability to infer feeling states and/or intentions (Table II), skills that typically develop during the first 4 or 5 years of life and that are critical for the development of social skills and for successful navigation of the social world.43 Such tasks include images, stories, and animations designed to elicit the attribution of mental states. Results from typically developing individuals indicate with remarkable consistency that theory of mind is mediated by the posterior superior temporal sulcus at the temporoparietal junction, the temporal poles, the amygdala, and dorsal medial and ventrolateral prefrontal cortex.44
The amygdala plays a critical role in multiple aspects of mentalizing, including determining emotional states of others from facial expressions,45 and a number of studies have reported aberrant amygdala activation in ASDs during tasks requiring inferring mental states from pictures of eyes46,47 and judging facial expressions,23 suggesting that the amygdala may fail to assign emotional relevance to social stimuli in ASDs. Other studies, however, have reported that ASDs are characterized by amygdala hyperactivity during face viewing48 and anticipation,49 suggesting that the so-called “amygdala theory of autism” may reflect impaired amygdala modulation rather than simply hypoactivation in social contexts.
Another brain region that has received scrutiny in fMRI studies of theory of mind in ASDs is the posterior superior temporal sulcus, a region recruited during tasks that involve interpreting other's mental states from biological motion cues.50 There are reports of posterior superior temporal sulcus hypoactivation while processing incongruent eye gaze shifts,51 while viewing direct and averted gaze,52 during intentional attribution to animated sequences of geometric figures,53 and during speech perception.54 A recent study of children with ASDs and their unaffected siblings found that activation in posterior superior temporal sulcus (as well as the amygdala and ventromedial prefrontal cortex) during biological motion perception differentiated children with ASDs both from their unaffected siblings and from matched control participants, suggesting that activation of this region may be related to phenotypic expression of social deficits in ASDs rather than genetic liability.55
Another area of inquiry has been functioning of the mirror neuron system (including, in humans, the pars opercularis in the inferior frontal gyrus). This system is active during imitation, action observation, intention understanding, and understanding emotional states of others.56 The inferior frontal gyrus has been reported to be relatively less active in ASDs during imitation and observation of faces57-59 and during imitation and observation of emotional expressions in ASDs,48,60 suggesting that mirror neuron dysfunction may account for social deficits in ASDs, though this contention has been questioned.61 Additionally, a recent metaanalysis of fMRI studies of social processing in ASDs revealed hypoactivation of the right anterior insula across studies (but see ref 62 for an exception), a region that is believed to be a relay station for projections from the IFG to the amygdala.63
Restricted and repetitive behaviors and interests constitute a multifaceted symptom domain in ASDs that comprises both lower-order motoric repetitive behaviors (eg, body rocking, hand flapping) as well as higher-order cognitive manifestations (eg, a need for predictability).64 Because fMRI requires minimal motion from research subjects, cognitive manifestations of restricted and repetitive behaviors have been the focus of fMRI research. Such studies have mostly relied on tasks requiring cognitive control because of linkages between deficits on neuropsychological cognitive control tasks and symptoms of restricted and repetitive behaviors and interests in ASDs.65
Animal lesion and nonclinical human neuroimaging studies indicate that cognitive control is mediated by frontostriatal brain systems, including the lateral prefrontal cortex, the inferior frontal cortex (including the insular cortex), the anterior cingulate cortex, the intraparietal sulcus, and the striatum.66 Functional MRI studies of cognitive control in ASDs have revealed anomalous activation in frontostriatal brain regions (Table III), including inferior and middle frontal gyri, dorsal anterior cingulate cortex, and the basal ganglia during cognitive control tasks. Such findings have been reported using go/no-go, Stroop, and switching tasks,67 tasks that require interference inhibition,68-72 response monitoring,73 novelty detection,74-75 spatial attention,68 working memory,76,77 and saccadic eye movements.78 These findings have been interpreted to reflect deficits in behavioral inhibition and/or generation of adaptive behaviors linked to the expression of restricted and repetitive behavior and interests. Although the direction of effects has varied across studies (ie, frontostriatal hyperactivation vs hypoactivation), likely due to task demands and analysis methods, anomalous frontostriatal activation during tasks requiring cognitive control has been a consistent result in ASD samples, with the majority of findings indicating frontostriatal hyperactivation that has been interpreted to reflect a neurof unctional compensatory mechanisms to overcome cortical inefficiency.70
Investigations of communication deficits in ASDs have focused predominantly on brain regions mediating language perception, comprehension, and generation. The left hemisphere is typically language-dominant, and speech production is mediated by Broca's area at the junction of the frontal, parietal, and temporal lobes, whereas speech comprehension is mediated by Wernicke's area in the posterior temporal lobe.79 Heschl's gyrus, in the dorsal temporal lobe, contains primary auditory cortex as well as the angular gyrus, involved in higher-order language comprehension and cross-modal integration, and the inferior parietal lobule, involved in processing semantic content.80
fMRI studies of communication functions in ASDs have used tasks requiring listening to speech sounds,54,81,82 sentence comprehension,83-85 verbal fluency,86 pragmatic language comprehension,87 semantic judgments,88 responsenaming,89 and viewing body gestures90-91 (Table IV). Overall, findings indicate differential lateralization patterns in ASDs (ie, reduced left > right lateralization),82,84,86,87,89 decreased synchrony of brain regions processing language,83,92 decreased automaticity of language processing,93 greater neurofunctional deficits for speech than songs,94 and recruitment of brain regions that do not typically process language.83,95-97 A recent methodological innovation in the domain of language-based fMRI studies in ASDs has been to present speech stimuli to veryyoung children with ASDs (as young as 12 months old) while asleep.82,98 Although the diagnostic stability of ASDs for children in this age range must be considered, this approach has the potential to leverage task-based fMRI in far younger children with ASDs to examine altered developmental trajectories associated with impaired receptive language skills. Additionally, sleep fMRI would appear to be well suited to studying early emerging functional brain activation properties linked to speech processing in infant high-risk paradigms.
The social-communication deficits that characterize ASDs may reflect decreased motivation to engage in social behaviors in early childhood. This decreased motivation may result in fewer experiences with the social environment,99 further compounding social-communicative deficits.100 Reward processing is mediated primarily by dopaminergic projections from the ventral tegmental area to the striatum, orbitofrontal cortex, ventromedial prefrontal cortex, and the anterior cingulate cortex, forming a mesolimbic dopamine reward pathway.101 Emerging evidence suggests that the neural circuits that mediate reward processing may have evolved, at least in part, to facilitate social attachment,102 and reward mechanisms serve to encode and consolidate positive memories of social experiences, facilitating social functioning abilities hypothesized to be impaired in ASDs.103
Reward processing deficits in ASDs have been assessed in six fMRI studies to date (Table V). Schmitz and colleagues104 reported decreased left anterior cingulate gyrus and left midfrontal gyrus activation to rewarded trials during a sustained attention task in ASDs and that anterior cingulate gyrus activation predicted social symptom severity. Scott-Van Zeeland and colleagues105 reported ventral striatal hypoactivation during social and nonsocial learning in ASDs. During a rewarded go/no-go paradigm, Kohls and colleagues106 found ventral striatal hypoactivation to monetary rewards and amygdala and anterior cingulate cortex hypoactivation to monetary and social rewards in children with ASDs. Cascio and colleagues107 reported increased bilateral insula and anterior cingulate cortex activation to images of food in children with ASDs who had fasted for at least 4 hours. Two studies by Dichter and colleagues,49,108 using incentive delay tasks, found decreased nucleus accumbens activation during monetary anticipation, bilateral amygdala hyperactivation during face anticipation that predicted social symptom severity (Figure 1), insular cortex hyperactivation during face outcomes, and ventromedial prefrontal cortex hyperactivation while viewing images related to circumscribed interests in ASDs. Taken together, these results suggest that reward network dysfunction in ASDs may not be constrained to responses to social rewards, but rather may be characterized by anomalous responsivity that is contingent on the type of reward processed. When considered in light of empirical findings of dysfunctional reward circuitry in a number of psychiatric conditions, including substance use disorders, schizophrenia, affective disorders, and attention deficit/hyperactivity disorder, abnormal mesolimbic responses to rewards appears to be a common endophenotype that may cut across diagnostic boundaries.109
Whereas task-based fMRI studies focus on activity within specific brain regions evoked by cognitive tasks, studies of functional connectivity speak to the temporal dynamics of brain network activity. Hie integrity of brain connections affects integration and synchronization of information processing, and the study of functional connectivity in ASDs addresses circuitry-level questions believed to be central to dysfunction in ASDs.6 There is a confluence of evidence that ASDs are characterized by decreased connectivity, in particular between frontal and posterior-temporal cortical systems that play key roles in processing social-affective information.110 Although initial studies highlighted cortical underconnectivity in ASDs, more recent data suggests that ASDs may be characterized by both local overconnectivity and longdistance underconnectivity. It has been suggested that a cortical underconnectivity account of ASDs may address heterogeneity as well as broad information processing deficits in general, rather than the expression of specific core symptoms.111
The majority of task-based studies in ASDs have documented reduced functional connectivity between frontal and parietal regions75,83,112 as well as between frontal and temporal and/or occipital regions.69,113 Tasks have included language comprehension,83,88,97 cognitive control,69,75,114 mentalizing,53,113,115 social processing,113 working memory,116 and visuospatial processing.112 A number of these studies have also indicated smaller and less synchronized cortical networks in ASDs.116-117 It should be noted, however, that some task-based studies have found long-range over-connectivity between subcortical and cortical regions118-119 as well as between frontal and temporal regions.120-122 Other studies have examined connectivity during task-related paradigms by filtering out taskrelated activity to examine connectivity patterns that are task-independent, and found evidence of decreased123-124 and increased118-121 functional connectivity.
Relatively fewer studies have examined brain connectivity in ASDs during resting state fMRI scans (Table VI). Cherkassky and colleagues125 reported decreased frontalposterior default network connectivity during task-based inter-trail intervals (see also refs 126-128) while others have found lower default-mode network connectivity at rest125,128-131 in ASDs. There are also reports of decreased connectivity between the anterior and posterior insula and a number of social processing brain regions in ASDs75,114,116 and less coherent endogenous low-frequency oscillations across multiple cortical and subcortical regions in ASDs.132 von dem Hagen and colleagues133 reported reduced functional connectivity within and between resting state networks incorporating “social brain regions” including the insula and amygdala within the default-mode and salience networks, respectively, and Di Martino and colleagues134 reported increased connectivity between multiple striatal regions and striatal hyperconnectivity with the pons. Monk and colleagues127 reported positive correlations between repetitive behavior symptoms and resting state connectivity between posterior cingulate cortex and the right parahippocampal gyrus in adults with ASDs, despite increased connectivity between the posterior cingulate cortex, the right temporal lobe, and the right parahippocampal gyrus, although Weng and collègues128 found correlations between social and repetitive behavior symptoms and a number of resting connectivity metrics in adolescents with ASDs.
Functional MRI results should ultimately be considered within a broader neuroimaging literature addressing brain structure and white matter connectivity in ASDs. Structural MRI yields information about brain anatomy, including gray- and white-matter volumes as well as gyrus and sulcus development, and this approach is wellsuited for studies seeking to predict future ASDs diagnoses in infants. Very briefly, the structural MRI literature indicates accelerated brain growth during earlydevelopment in ASDs.135,136 There are reports of significantly large head circumference137 and brain volume in children with autism.138 Longitudinal studies indicate that ASDs are characterized by an early transient period of postnatal brain overgrowth evident in 70% of children with ASDs before age 2 that is not present in adolescence and adulthood.139-140 Evidence of enlarged total brain size in ASDs is accompanied by studies showing smaller cerebellar vermis,141,142 amygdala, and hippocampus.138 Increased brain size in young children with ASDs has also been linked to increased frontal lobe white matter143 followed by reduced white matter in early and late adolescence and adulthood.144,145
Because the contrast properties of structural MRI are suboptimal for differentiating still-myelinating white matter from surrounding gray matter in children,146 diffusion tensor imaging (DTI), a measure of microstructural properties of white matter fibers, has emerged as a valuable tool to assess white-matter structure in very young samples.147 There is evidence of widespread abnormalities in white-matter fiber tract integrity in ASDs, but the extent and developmental course of these differences remains unclear.148-151 Two- to three-year-old children with ASDs are characterized by increased fractional anisotropy (an index of white matter fiber density) in the frontal lobes and in the corpus callosum,152 but in 5-year-old children with ASDs fractional anisotropy was reduced in frontal lobe tracts and no different from controls in tracts connecting frontal and posterior regions.153 In 10- to 18-year-old children with ASDs, there is evidence of reduced fractional anisotropy in frontal-posterior tracts154 and in hemispheric fractional anisotropy lateralization in the arcuate fasciculus,155,156 but fractional anisotropy was found to be reduced in adolescents with ASDs in prefrontal cortex and tempoparietal junction.157 It thus appears that young children with ASDs are characterized by increased fractional anisotropy- in brain areas mediating social communication, whereas adolescents and adults with ASDs are characterized by generally lower fractional anisotropy, a pattern that recapitulates patterns of brain overgrowth discussed earlier.
Finally, a prospective DTI study of 6- to 24-month-old infants at high-risk of developing ASDs found that fractional anisotropy trajectories for 12 of 15 fiber tracts examined differed between infants who later were identified as having an ASDs and those who did not. Infants who went on to have a diagnosis of an ASD had fiber tracts characterized by higher fractional anisotropy at 6 months of age, slower change between 6 and 24 months of age, and lower fractional anisotropy at 24 months of age.158
The goal of this review is to highlight consistencies in the ASD fMRI literature. Given the array of imaging tasks reviewed, it is perhaps not surprising that findings are heterogenous. Despite variations in findings, there is a sufficient degree of consistency to draw a number of substantive conclusions. Studies of social processes have generally found evidence of hypoactivation in nodes of the “social brain,” including the medial prefrontal cortex, the inferior frontal gyrus and the anterior insula, the posterior superior temporal sulcus, the interparietal sulcus, the amygdala, and the fusiform gyrus. Studies addressing cognitive control, designed to address neural mechanisms underlying restricted and repetitive behaviors and interests, have converged on aberrant frontostriatal functioning in ASDs, specifically in inferior and middle frontal gyri, anterior cingulate cortex, and the basal ganglia. Communication impairments in ASDs have been linked to differential patterns of language function lateralization, decreased synchrony- of brain regions processing language, and recruitment of brain regions that do not typically processing language. Reward processing studies have highlighted mesolimbic and mesocortical impairments when processing both social and nonsocial incentives in ASDs. Finally, task-based functional connectivity studies in ASDs have reported local overconnectivity and long-distance (ie, between frontal and posterior regions) underconnectivity-, whereas resting state connectivity studies indicate decreased anterior-posterior connectivity and less coherent endogenous low-frequency oscillations across multiple regions.
Most studies reviewed here focus on adulthood or adolescence, yet ASDs are present from very early childhood. It will be critical to address developmental profiles in children with ASDs to disambiguate proximal effects of altered brain function from downstream effects on learning and motivation. There also may be critical periods during early development when brain dysfunction creates a predisposition to develop a number of disorders, and understanding factors that influence these processes will be essential for the prevention of symptom onset. Indeed, emerging techniques allow for functional brain imaging in children as young as 12 months old, and future studies that focus on young samples are needed. Additionally, most studies reviewed here contain small samples, and larger samples will be needed to identify meaningful subgroups and track developmental profiles. Given the high costs associated with brain imaging and challenges recruiting large pediatric patient samples, it will be critical to leverage available bioinformatics tools to facilitate data sharing across research groups. Such tools are under development159 and the National Institutes of Health recently established a database for sharing ASDs neuroimaging data.160
There is also a need to move to designs that incorporate psychiatric comparisons to delineate brain activation patterns in ASDs that diverge and converge with other disorders characterized by social communication impairments and repetitive behaviors. Similarly, ASDs are commonly comorbid with other psychiatric and neurodevelopmental conditions,161 possibly due to shared genetic etiology and common socioenvironmental determinants, and thus it will be important to examine ASD samples with and without comorbid conditions to refine our understanding of neural endophenotypes in ASDs. Finally, the literature reviewed here is cross-sectional. Though these studies have elucidated aberrant patterns of brain activation in ASDs, these paradigms have rarelybeen applied to longitudinal treatment outcome studies aimed at understanding mechanisms of action of treatment response in ASDs. As neuroimaging and data-sharing techniques evolve, functional brain imaging will continue to improve our understanding of the pathophysiology of ASDs, with the ultimate goal of improved ASD identification and treatment.162
Preparation of this manuscript was supported by K23 MH081285 and R01 MH073402. I am grateful to Eleanor Hanna for administrative assistance with this manuscript.