Motor problems in autism: Co-occurrence or feature?

Motor features of autism have long been acknowledged by clinicians, researchers, and community stakeholders. Current DSM-5 and ICD-11 guidelines allow clinicians to assign a co-occurring diagnosis of developmental [motor] coordination disorder (DCD) for autistic individuals with significant motor problems. DCD is characterized by poor motor proficiency with an onset of symptoms in early development. Studies have shown considerable overlap in the behavioral motor features observed in autism and DCD. However, others indicate that motor problems in autism and DCD may stem from different underlying sensorimotor mechanisms. Regardless of whether autism has a unique motor phenotype or an overlap with DCD, changes need to be made in the clinical pipeline to address motor problems in autism at the stages of recognition, assessment, diagnosis, and intervention. Consensus is needed to address unmet needs in research on the etiology of motor problems in autism and their overlap with DCD, to optimize clinical practice guidelines. The development of screening and assessment tools for motor problems that are valid and reliable for use with autistic individuals is essential, and an evidence-based clinical pipeline for motor problems in autism is urgently needed. WHAT THIS PAPER ADDS: Motor problems in autism are highly prevalent, yet underdiagnosed and poorly managed. An evidence-based clinical pipeline for motor problems in autism is urgently needed.

Disgust Processing and Potential Relationships with Behaviors in Autism.

PURPOSE OF REVIEW: While there are reports of differences in emotion processing in autism, it is less understood whether the emotion of disgust, in particular, plays a significant role in these effects. Here, we review literature on potential disgust processing differences in autism and its possible associations with autistic traits. RECENT FINDINGS: In autism, there is evidence for differences in physical disgust processing, pica behaviors, attention away from other's disgust facial expressions, and differences in neural activity related to disgust processing. In typically developing individuals, disgust processing is related to moral processing, but modulated by individual differences in interoception and alexithymia. Autistic individuals may experience atypical disgust, which may lead to difficulty avoiding contaminants and affect socio-emotional processing. In autism, such outcomes may lead to increased occurrences of illness, contribute to gastrointestinal issues, diminish vicarious learning of disgust expression and behaviors, and potentially contribute to differences in processes related to moral reasoning, though further research is needed.

Unique deficit in embodied simulation in autism: An fMRI study comparing autism and developmental coordination disorder.

A deficit in pre-cognitively mirroring other people's actions and experiences may be related to the social impairments observed in autism spectrum disorder (ASD). However, it is unclear whether such embodied simulation deficits are unique to ASD or instead are related to motor impairment, which is commonly comorbid with ASD. Here we aim to disentangle how, neurologically, motor impairments contribute to simulation deficits and identify unique neural signatures of ASD. We compare children with ASD (N = 30) to children with Developmental Coordination Disorder (DCD; N = 23) as well as a typically developing group (N = 33) during fMRI tasks in which children observe, imitate, and mentalize about other people's actions. Results indicate a unique neural signature in ASD: during action observation, only the ASD group shows hypoactivity in a region important for simulation (inferior frontal gyrus, pars opercularis, IFGop). However, during a motor production task (imitation), the IFGop is hypoactive for both ASD and DCD groups. For all tasks, we find correlations across groups with motor ability, even after controlling for age, IQ, and social impairment. Conversely, across groups, mentalizing ability is correlated with activity in the dorsomedial prefrontal cortex when controlling for motor ability. These findings help identify the unique neurobiological basis of ASD for aspects of social processing. Furthermore, as no previous fMRI studies correlated brain activity with motor impairment in ASD, these findings help explain prior conflicting reports in these simulation networks.

Laterality of Poststroke Cortical Motor Activity during Action Observation Is Related to Hemispheric Dominance.

Background: Increased activity in the lesioned hemisphere has been related to improved poststroke motor recovery. However, the role of the dominant hemisphere-and its relationship to activity in the lesioned hemisphere-has not been widely explored. Objective: Here, we examined whether the dominant hemisphere drives the lateralization of brain activity after stroke and whether this changes based on if the lesioned hemisphere is the dominant hemisphere or not. Methods: We used fMRI to compare cortical motor activity in the action observation network (AON), motor-related regions that are active both during the observation and execution of an action, in 36 left hemisphere dominant individuals. Twelve individuals had nondominant, right hemisphere stroke, twelve had dominant, left-hemisphere stroke, and twelve were healthy age-matched controls. We previously found that individuals with left dominant stroke show greater ipsilesional activity during action observation. Here, we examined if individuals with nondominant, right hemisphere stroke also showed greater lateralized activity in the ipsilesional, right hemisphere or in the dominant, left hemisphere and compared these results with those of individuals with dominant, left hemisphere stroke. Results: We found that individuals with right hemisphere stroke showed greater activity in the dominant, left hemisphere, rather than the ipsilesional, right hemisphere. This left-lateralized pattern matched that of individuals with left, dominant hemisphere stroke, and both stroke groups differed from the age-matched control group. Conclusions: These findings suggest that action observation is lateralized to the dominant, rather than ipsilesional, hemisphere, which may reflect an interaction between the lesioned hemisphere and the dominant hemisphere in driving lateralization of brain activity after stroke. Hemispheric dominance and laterality should be carefully considered when characterizing poststroke neural activity.

Interoception in Autism: A Narrative Review of Behavioral and Neurobiological Data.

While exteroceptive sensory processing is a hallmark of autism spectrum disorder, how interoceptive processing may impact and contribute to symptomatology remains unclear. In this comprehensive narrative review on interoception in autism, we discuss: 1) difficulties with assessing interoception; 2) potential interoceptive differences; 3) interactions between neural systems for interoception, attention, sensorimotor processing, and cognition; and 4) potential differences in neural circuits involved in interoception. In general, there are mixed findings on potential interoception differences in autism. Nevertheless, some data indicate differences in integration of interoceptive and exteroceptive information may contribute to autism symptomatology. Neurologically, interoceptive processing in autism may be impacted by potential differences in the development, morphometry, and connectivity of key interoceptive hubs (vagal processing, brainstem, thalamus, insula), though much work is needed on this topic.

Caregiver and youth inter-rater assessment agreement in autism spectrum disorder, developmental coordination disorder, and typical development.

Youth diagnosed with autism spectrum disorder (ASD) and those with developmental coordination disorder (DCD) are at heightened risk for co-occurring mental health diagnoses, especially anxiety and attention-deficit/hyperactivity disorder (ADHD). However, caregiver-child agreement on presence of related symptoms in populations with neurodevelopmental conditions is not well understood. Here, we examine the extent to which 37 ASD, 26 DCD, and 40 typically developing children and their caregivers agree on the degree of the child's symptoms of anxiety and ADHD. All caregiver-child dyads completed the Screen for Child Anxiety Related Emotional Disorders and Conners 3 ADHD Index. Across groups, intraclass correlations indicated generally poor agreement on anxiety and ADHD symptomatology. Although youth generally reported greater internalizing symptoms (i.e., anxiety), caregivers tended to report more observable externalizing behaviors (i.e., ADHD). Together, the results of this study support the need for a multi-informant approach in assessments of anxiety and ADHD in youth with neurodevelopmental disorders.

Relationships between tryptophan-related gut metabolites, brain activity, and autism symptomatology.

Gut microbial metabolites have been theorized to play a causative role in the pathophysiology of autism spectrum disorder (ASD). This hypothesis is based on results from mechanistic preclinical studies and several correlational studies showing differences in gut microbial composition between ASD subjects and neurotypical (NT) controls. However, alterations in how the human brain interacts with the gut microbiome in ASD have not been examined. In this cross-sectional, case-control observational study, fecal metabolomics, task-based functional magnetic resonance imaging (fMRI), and behavioral assessments were obtained from 43 ASD and 41 NT children aged 8-17. The fMRI tasks were based on socio-emotional and sensory paradigms that commonly show strong evoked brain differences in ASD participants. General linear models and mediational modeling were applied to examine the links between tryptophan metabolism and evoked brain activity and behavior. Results indicated that fecal levels of specific tryptophan-related metabolites were associated with: 1) brain activity atypicalities in regions previously implicated in ASD (i.e., insula and cingulate); and 2) ASD severity and symptomatology (i.e., ADOS scores, disgust propensity, and sensory sensitivities). Importantly, activity in the mid-insula and mid-cingulate significantly mediated relationships between the microbial tryptophan metabolites, indolelactate and tryptophan betaine, and ASD severity and disgust sensitivity. To our knowledge, this is the first study to elucidate how interactions between gut metabolites and brain activity may impact autism symptomatology, particularly in functional brain pathways associated with vagal and interoceptive/emotion processing.

Correction: Raman et al. Relationships between Affect Recognition, Empathy, Alexithymia, and Co-Occurring Conditions in Autism. Brain Sci. 2023, 13, 1161.

In the original publication [...].

Modulating the motor system by action observation after stroke.

BACKGROUND AND PURPOSE: Much recent interest surrounds the use of action observation, which is observing another individual performing a motor task, in stroke rehabilitation, to promote motor recovery by engaging similar brain regions to action execution. This may be especially useful in individuals with limited mobility. Here, we assess how cortical motor activity during action observation is affected by stroke and by stroke-related motor deficits. METHODS: We used functional MRI to compare brain activity during right and left hand action observation in right-handed nondisabled participants and participants who were right-handed before left hemisphere stroke. All participants performed the same actions after their functional MRI. RESULTS: Nondisabled participants show greater bilateral cortical motor activity when observing actions made using the left hand, whereas participants with stroke show greater ipsilesional cortical motor activity when observing actions made using the right (paretic) hand (P<0.05; corrected). For both groups, action processing is modulated by motor capability: cortical motor activity is greater when observing the hand with lower motor scores (P<0.05; corrected). Furthermore, for stroke, the extent of ipsilesional activity correlates with lesion volume (P=0.049), in a pattern that suggests adaptive plasticity. CONCLUSIONS: We found that action observation activates specific motor plans in damaged motor circuits after stroke, and this activity is related to motor capability to perform the same actions. Cortical motor activity during action observation may be relevant to motor learning, and to motor relearning in stroke rehabilitation.

Experience with an amputee modulates one's own sensorimotor response during action observation.

Observing actions performed by others engages one's own sensorimotor regions, typically with greater activity for actions within one's own motor abilities or for which one has prior experience. However, it is unclear how experience modulates the neural response during the observation of impossible actions, beyond one's own abilities. Using fMRI, we scanned typically-developed participants as they observed actions performed by a novel biological effector (the residual limb of a woman born without arms) and a familiar biological effector (a hand). Participants initially demonstrated greater activity in the bilateral inferior and superior parietal cortices when observing actions made by the residual limb compared to the hand, with more empathic participants activating the right inferior parietal lobule, corresponding to the posterior component of the action observation network, more strongly. Activity in the parietal regions may indicate matching the kinematics of a novel effector to one's own existing sensorimotor system, a process that may be more active in more empathic individuals. Participants then received extended visual exposure to each effector, after which they showed little difference between activation in response to residual limb compared to hand actions, only in the right superior parietal lobule. This suggests that visual experience may attenuate the difference between how residual limb and hand actions are represented using one's own body representations, allowing us to flexibly map physically different others onto our own body representations.

Understanding otherness: the neural bases of action comprehension and pain empathy in a congenital amputee.

How do we understand and empathize with individuals whose bodies are drastically different from our own? We investigated the neural processes by which an individual with a radically different body, a congenital amputee who is born without limbs, engages her own sensory-motor representations as a means to understand other people's body actions or emotional states. Our results support the prediction that when the goal of the action is possible for the observer, one's own motor regions are involved in processing action observation, just as when individuals viewed those similar to themselves. However, when the observed actions are not possible, mentalizing mechanisms, relying on a different set of neural structures, are additionally recruited to process the actions. Furthermore, our results indicate that when individuals view others experiencing pain in body parts that they have, the insula and somatosensory cortices are activated, consistent with previous reports. However, when an individual views others experiencing pain in body parts that she does not have, the insula and secondary somatosensory cortices are still active, but the primary somatosensory cortices are not. These results provide a novel understanding for how we understand and empathize with individuals who drastically differ from the self.

Connectivity differences between inferior frontal gyrus and mentalizing network in autism as compared to developmental coordination disorder and non-autistic youth.

Prior studies have compared neural connectivity during mentalizing tasks in autism (ASD) to non-autistic individuals and found reduced connectivity between the inferior frontal gyrus (IFG) and mentalizing regions. However, given that the IFG is involved in motor processing, and about 80% of autistic individuals have motor-related difficulties, it is necessary to explore if these differences are specific to ASD or instead similar across other developmental motor disorders, such as developmental coordination disorder (DCD). Participants (29 ASD, 20 DCD, 31 typically developing [TD]; ages 8-17) completed a mentalizing task in the fMRI scanner, where they were asked to think about why someone was performing an action. Results indicated that the ASD group, as compared to both TD and DCD groups, showed significant functional connectivity differences when mentalizing about other's actions. The left IFG seed revealed ASD connectivity differences with the: bilateral temporoparietal junction (TPJ), left insular cortex, and bilateral dorsolateral prefrontal cortex (DLPFC). Connectivity differences using the right IFG seed revealed ASD differences in the: left insula, and right DLPFC. These results indicate that connectivity differences between the IFG, mentalizing regions, emotion and motor processing regions are specific to ASD and not a result of potentially co-occurring motor differences.

The relationship between alexithymia, interoception, and neural functional connectivity during facial expression processing in autism spectrum disorder.

Neural processing differences of emotional facial expressions, while common in autism spectrum disorder (ASD), may be related to co-occurring alexithymia and interoceptive processing differences rather than autism per se. Here, we investigate relationships between alexithymia, interoceptive awareness of emotions, and functional connectivity during observation of facial expressions in youth (aged 8-17) with ASD (n = 28) compared to typically developing peers (TD; n = 37). Behaviorally, we found no significant differences between ASD and TD groups in interoceptive awareness of emotions, though alexithymia severity was significantly higher in the ASD group. In the ASD group, increased alexithymia was significantly correlated with lower interoceptive sensation felt during emotion. Using psycho-physiological interaction (PPI) analysis, the ASD group showed higher functional connectivity between the left ventral anterior insula and the left lateral prefrontal cortex than the TD group when viewing facial expressions. Further, alexithymia was associated with reduced left anterior insula-right precuneus connectivity and reduced right dorsal anterior insula-left ventral anterior insula connectivity when viewing facial expressions. In the ASD group, the degree of interoceptive sensation felt during emotion was positively correlated with left ventral anterior insula-right IFG connectivity when viewing facial expressions. However, across all participants, neither alexithymia nor interoceptive awareness of emotions predicted connectivity between emotion-related brain regions when viewing emotional facial expressions. To summarize, we found that in ASD compared to TD: 1) there is stronger connectivity between the insula and lateral prefrontal cortex; and 2) differences in interhemispheric and within left hemisphere connectivity between the insula and other emotion-related brain regions are related to individual differences in interoceptive processing and alexithymia. These results highlight complex relationships between alexithymia, interoception, and brain processing in ASD.

Relationships between alexithymia, interoception, and emotional empathy in autism spectrum disorder.

LAY ABSTRACT: Empathy, the ability to understand and share the emotions of others, is a necessary skill for social functioning and can be categorized into cognitive and emotional empathy. There is evidence to suggest that individuals with autism spectrum disorder have difficulties with cognitive empathy, the ability to imagine how another person is thinking or feeling. However, it is unclear if individuals with autism spectrum disorder struggle with emotional empathy, the ability to share and feel emotions others are experiencing. Self-report and interview data were collected to explore the relationships between interoception (individuals' self-reported awareness of sensation from their body such as thirst, heartbeat, etc.), alexithymia (an individual's ability to describe and distinguish between their own emotions), and emotional empathy in 35 youth with autism spectrum disorder and 40 typically developing youth. Greater personal distress to others' emotions and greater difficulty describing and recognizing self-emotions were associated with reporting fewer physical sensations in the body when experiencing emotion in the autism spectrum disorder group. The results of this study suggest that while autism spectrum disorder youth with concomitant alexithymia may experience emotional empathy differently, it should not be characterized as an absence of a capacity for emotional empathy.

Relationships between Affect Recognition, Empathy, Alexithymia, and Co-Occurring Conditions in Autism.

Prior studies show differences in empathy and affect-recognition ability between those with autism spectrum disorder (ASD) and typically developing (TD) individuals. Autistic individuals also exhibit increased behavioral, gastrointestinal, and sleep issues. In the current study, we explored the differences in empathy and affect recognition between the ASD and TD groups; and we investigated their associations with conditions co-occurring in ASD. A total of 54 TD and 56 ASD children (8-17 years) were included. As compared to the TD group, the ASD group showed lower scores for affect recognition and perspective taking (PT) and higher scores for personal distress (PD). Interestingly, results from hierarchical linear regressions suggested that disparities in the PD and PT between the groups were primarily attributable to attenuated levels of alexithymia, rather than being mediated by the presence of an autism diagnosis. Differences in affect-recognition ability, however, were mediated by both an autism diagnosis and alexithymia. We also found significant correlations between empathy and affect recognition and measures of related conditions common in ASD. Alexithymia, hence, contributes to difficulties in empathy while both alexithymia and autism are associated with affect-recognition ability in ASD. Additionally, the association between affect recognition and empathic ability with co-occurring conditions in ASD needs to be considered during assessments and interventions.

Motor Signature Differences Between Autism Spectrum Disorder and Developmental Coordination Disorder, and Their Neural Mechanisms.

Autism spectrum disorder (ASD) and Developmental Coordination Disorder (DCD) are distinct clinical groups with overlapping motor features. We attempted to (1) differentiate children with ASD from those with DCD, and from those typically developing (TD) (ages 8-17; 18 ASD, 16 DCD, 20 TD) using a 5-min coloring game on a smart tablet and (2) identify neural correlates of these differences. We utilized standardized behavioral motor assessments (e.g. fine motor, gross motor, and balance skills) and video recordings of a smart tablet task to capture any visible motor, behavioral, posture, or engagement differences. We employed machine learning analytics of motor kinematics during a 5-min coloring game on a smart tablet. Imaging data was captured using functional magnetic resonance imaging (fMRI) during action production tasks. While subject-rated motor assessments could not differentiate the two clinical groups, machine learning computational analysis provided good predictive discrimination: between TD and ASD (76% accuracy), TD and DCD (78% accuracy), and ASD and DCD (71% accuracy). Two kinematic markers which strongly drove categorization were significantly correlated with cerebellar activity. Findings demonstrate unique neuromotor patterns between ASD and DCD relate to cerebellar function and present a promising route for computational techniques in early identification. These are promising preliminary results that warrant replication with larger samples.

Impact of motor stroke on novel and conventional action metaphor comprehension.

Previous studies indicate that damage to motor brain regions impacts comprehension of literal action-related language. However, whether such damage also impacts comprehension of action-metaphors remains unknown. Such a finding would support the notion that metaphors are grounded in sensorimotor representations. Here we tested this hypothesis by comparing comprehension of novel, conventional, and frozen action and non-action metaphors in 14 right-handed adults with right-sided mild to moderate paresis following left hemisphere motor stroke and 23 neurotypical participants. Consistent with our hypothesis, results indicated that only in the stroke group, accuracy for action metaphors was significantly lower than for non-action metaphors. Further, in the stroke group, accuracy was significantly worse in the following pattern: novel < conventional < frozen action metaphors. These results strongly support the notion that motor-related brain regions are important not only for literal action-related language comprehension, but also for action-related metaphor comprehension, especially for less familiar metaphors.

Motor performance, praxis, and social skills in autism spectrum disorder and developmental coordination disorder.

Previous research has shown that individuals with autism spectrum disorder (ASD) and developmental coordination disorder (DCD) may have overlapping social and motor skill impairments. This study compares ASD, DCD, and typically developing (TD) youth on a range of social, praxis and motor skills, and investigates the relationship between these skills in each group. Data were collected on participants aged 8-17 (n = 33 ASD, n = 28 DCD, n = 35 TD). Overall, the clinical groups showed some similar patterns of social and motor impairments but diverged in praxis impairments, cognitive empathy, and Theory of Mind ability. When controlling for both social and motor performance impairments, the ASD group showed significantly lower accuracy on imitation of meaningful gestures and gesture to command, indicating a prominent deficit in these praxis skills in ASD. LAY SUMMARY: Individuals with autism spectrum disorder (ASD) and developmental coordination disorder (DCD) have social and motor skill impairments to varying degrees. This study compares ASD, DCD, and typically developing (TD) youth on a range of social, praxis, and motor skills. ASD and DCD shared similar patterns of gross and fine motor skills, but differed in skills related to making gestures. Specifically, our results also suggest that ASD has a prominent deficit in gesture performance and meaningful imitation compared to TD and DCD groups.

Specific tractography differences in autism compared to developmental coordination disorder.

About 85% of children with autism spectrum disorder (ASD) experience comorbid motor impairments, making it unclear whether white matter abnormalities previously found in ASD are related to social communication deficits, the hallmark of ASD, or instead related to comorbid motor impairment. Here we aim to understand specific white matter signatures of ASD beyond those related to comorbid motor impairment by comparing youth (aged 8-18) with ASD (n = 22), developmental coordination disorder (DCD; n = 16), and typically developing youth (TD; n = 22). Diffusion weighted imaging was collected and quantitative anisotropy, radial diffusivity, mean diffusivity, and axial diffusivity were compared between the three groups and correlated with social and motor measures. Compared to DCD and TD groups, diffusivity differences were found in the ASD group in the mid-cingulum longitudinal and u-fibers, the corpus callosum forceps minor/anterior commissure, and the left middle cerebellar peduncle. Compared to the TD group, the ASD group had diffusivity differences in the right inferior frontal occipital/extreme capsule and genu of the corpus callosum. These diffusion differences correlated with emotional deficits and/or autism severity. By contrast, children with DCD showed unique abnormality in the left cortico-spinal and cortico-pontine tracts.Trial Registration All data are available on the National Institute of Mental Health Data Archive: https://nda.nih.gov/edit_collection.html?id=2254 .

Sensory Modulation in Children with Developmental Coordination Disorder Compared to Autism Spectrum Disorder and Typically Developing Children.

Developmental Coordination Disorder (DCD) is one of the least studied and understood developmental disorders. One area that has been minimally investigated in DCD is potential issues with sensory modulation. Further, in other neurodevelopmental disorders (e.g., autism spectrum disorder (ASD)) sensory modulation is related to many other challenges (e.g., social issues, repetitive behaviors, anxiety); however, such potential relationships in children with DCD have been largely unexplored. The purpose of this study is to explore sensory modulation differences in DCD and to understand the relationships between sensory modulation and social emotional measures, behavior, and motor skills in DCD in comparison to ASD and typically developing (TD) peers. Participants (aged 8-17) and their caregivers (DCD, N = 26; ASD, N = 57; and TD, N = 53) completed behavioral and clinical measures. The results indicated that 31% of the DCD group showed sensory modulation difficulties, with the DCD group falling between the ASD and TD groups. In the DCD group, sensory modulation was significantly associated with anxiety, empathic concern, repetitive behaviors, and motor skills. Data are compared to patterns seen in ASD and TD groups and implications for interventions are discussed.