Repetitive Behaviors In Autism Spectrum Disorders Research Articles

Heterogeneity of dynamic synergetic configurations of salience network in children with autism spectrum disorder.

Atypical functional connectivity (FC) patterns have been identified in autism spectrum disorders (ASD), especially within salience network (SN) and between SN and default mode network (DMN) and central executive network (CEN). But whether the dynamic configuration of intra-SN and inter-SN (SN with DMN and CEN) FC in ASD is also heterogeneous remains unknown. Based on the resting-state functional magnetic resonance imaging data from 105 ASD and 102 typically-developing controls (TC), we calculated the time-varying FC of intra-SN and inter-SN (SN with DMN and CEN). Then, the joint recurrence features for the time-varying FC were calculated to assess how the SN dynamically recruits different configurations of network segregation and integration in ASD, that is, synergies, from the dynamical systems perspective. We analyzed the differences in synergetic patterns between ASD subtypes obtained by k-means clustering algorithm based on the synergy of SN and TC, and investigated the relationships between synergy of SN and severity of clinical symptoms of ASD for ASD subtypes. Two ASD subtypes were revealed, where the synergy of SN in ASD subtype 1 has lower stability and periodicity compared to the TC, and ASD subtype 2 exhibits the opposite alteration. Synergy of SN for ASD subtype 1 and 2 was found to predict the severity of communication impairments and restricted and repetitive behaviors in ASD, respectively. These results suggest the existence of subtypes with distinct patterns of the synergy of SN in ASD, and provide insight into the complex pathophysiological mechanism of clinical manifestations of ASD.

Decreased functional concordance in male children with autism spectrum disorder.

Autism spectrum disorder (ASD) is an early-onset neurodevelopmental condition with altered function of the brain. At present, a variety of functional metrics from neuroimaging techniques have been used to explore ASD neurological mechanisms. However, the concordance of these functional metrics in ASD is still unclear. This study used resting-state functional magnetic resonance imaging data, which were obtained from the open-access Autism Brain Imaging Data Exchange database, including 105 children with ASD and 102 demographically matched typically developing (TD) children. Both voxel-wise and volume-wise functional concordance were calculated by combining the dynamic amplitude of low-frequency fluctuations, dynamic regional homogeneity, and dynamic global signal correlation. Furthermore, a two-sample t-test was performed to compare the functional concordance between ASD and TD groups. Finally, the relationship between voxel-wise functional concordance and Autism Diagnostic Observation Schedule subscores was analyzed using the multivariate support vector regression in the ASD group. Compared with the TD group, we found that ASD showed decreased voxel-wise functional concordance in the left superior temporal pole (STGp), right amygdala, and left opercular part of the inferior frontal gyrus (IFGoper). Moreover, decreased functional concordance was associated with restricted and repetitive behaviors in ASD. Our results found altered brain function in the left STGp, right amygdala, and left IFGoper in ASD by functional concordance, indicating that functional concordance may provide new insights into the neurological mechanisms of ASD.

Disentangling the Individual-Shared and Individual-Specific Subspace of Altered Brain Functional Connectivity in Autism Spectrum Disorder

BackgroundDespite considerable effort toward understanding the neural basis of autism spectrum disorder (ASD) using case-control analyses of resting-state functional magnetic resonance imaging data, findings are often not reproducible, largely due to biological and clinical heterogeneity among individuals with ASD. Thus, exploring the individual-shared and individual-specific altered functional connectivity (AFC) in ASD is important to understand this complex, heterogeneous disorder. MethodsWe considered 254 individuals with ASD and 295 typically developing individuals from the Autism Brain Imaging Data Exchange to explore the individual-shared and individual-specific subspaces of AFC. First, we computed AFC matrices of individuals with ASD compared with typically developing individuals. Then, common orthogonal basis extraction was used to project AFC of ASD onto 2 subspaces: an individual-shared subspace, which represents altered connectivity patterns shared across ASD, and an individual-specific subspace, which represents the remaining individual characteristics after eliminating the individual-shared altered connectivity patterns. ResultsAnalysis yielded 3 common components spanning the individual-shared subspace. Common components were associated with differences of functional connectivity at the group level. AFC in the individual-specific subspace improved the prediction of clinical symptoms. The default mode network–related and cingulo-opercular network–related magnitudes of AFC in the individual-specific subspace were significantly correlated with symptom severity in social communication deficits and restricted, repetitive behaviors in ASD. ConclusionsOur study decomposed AFC of ASD into individual-shared and individual-specific subspaces, highlighting the importance of capturing and capitalizing on individual-specific brain connectivity features for dissecting heterogeneity. Our analysis framework provides a blueprint for parsing heterogeneity in other prevalent neurodevelopmental conditions.

Brain-Derived Neurotrophic Factor (BDNF) in Mechanisms of Autistic-like Behavior in BTBR Mice: Crosstalk with the Dopaminergic Brain System.

Disturbances in neuroplasticity undoubtedly play an important role in the development of autism spectrum disorders (ASDs). Brain neurotransmitters and brain-derived neurotrophic factor (BDNF) are known as crucial players in cerebral and behavioral plasticity. Such an important neurotransmitter as dopamine (DA) is involved in the behavioral inflexibility of ASD. Additionally, much evidence from human and animal studies implicates BDNF in ASD pathogenesis. Nonetheless, crosstalk between BDNF and the DA system has not been studied in the context of an autistic-like phenotype. For this reason, the aim of our study was to compare the effects of either the acute intracerebroventricular administration of a recombinant BDNF protein or hippocampal adeno-associated-virus-mediated BDNF overexpression on autistic-like behavior and expression of key DA-related and BDNF-related genes in BTBR mice (a widely recognized model of autism). The BDNF administration failed to affect autistic-like behavior but downregulated Comt mRNA in the frontal cortex and hippocampus; however, COMT protein downregulation in the hippocampus and upregulation in the striatum were insignificant. BDNF administration also reduced the receptor TrkB level in the frontal cortex and midbrain and the BDNF/proBDNF ratio in the striatum. In contrast, hippocampal BDNF overexpression significantly diminished stereotypical behavior and anxiety; these alterations were accompanied only by higher hippocampal DA receptor D1 mRNA levels. The results indicate an important role of BDNF in mechanisms underlying anxiety and repetitive behavior in ASDs and implicates BDNF-DA crosstalk in the autistic-like phenotype of BTBR mice.

Structural filtering of functional data offered discriminative features for autism spectrum disorder.

This study attempted to answer the question, "Can filtering the functional data through the frequency bands of the structural graph provide data with valuable features which are not valuable in unfiltered data"?. The valuable features discriminate between autism spectrum disorder (ASD) and typically control (TC) groups. The resting-state fMRI data was passed through the structural graph's low, middle, and high-frequency band (LFB, MFB, and HFB) filters to answer the posed question. The structural graph was computed using the diffusion tensor imaging data. Then, the global metrics of functional graphs and metrics of functional triadic interactions were computed for filtered and unfiltered rfMRI data. Compared to TCs, ASDs had significantly higher clustering coefficients in the MFB, higher efficiencies and strengths in the MFB and HFB, and lower small-world propensity in the HFB. These results show over-connectivity, more global integration, and decreased local specialization in ASDs compared to TCs. Triadic analysis showed that the numbers of unbalanced triads were significantly lower for ASDs in the MFB. This finding may indicate the reason for restricted and repetitive behavior in ASDs. Also, in the MFB and HFB, the numbers of balanced triads and the energies of triadic interactions were significantly higher and lower for ASDs, respectively. These findings may reflect the disruption of the optimum balance between functional integration and specialization. There was no significant difference between ASDs and TCs when using the unfiltered data. All of these results demonstrated that significant differences between ASDs and TCs existed in the MFB and HFB of the structural graph when analyzing the global metrics of the functional graph and triadic interaction metrics. Also, these results demonstrated that frequency bands of the structural graph could offer significant findings which were not found in the unfiltered data. In conclusion, the results demonstrated the promising perspective of using structural graph frequency bands for attaining discriminative features and new knowledge, especially in the case of ASD.

Dysregulated dynamic time-varying triple-network segregation in children with autism spectrum disorder.

One of the remarkable characteristics of autism spectrum disorder (ASD) is the dysregulation of functional connectivity of the triple-network, which includes the salience network (SN), default mode network (DMN), and central executive network (CEN). However, there is little known about the segregation of the triple-network dynamics in ASD. This study used resting-state functional magnetic resonance imaging data including 105 ASD and 102 demographically-matched typical developing control (TC) children. We compared the dynamic time-varying triple-network segregation and triple-network functional connectivity states between ASD and TC groups, and examined the relationship between dynamic triple-network segregation alterations and clinical symptoms of ASD. The average dynamic network segregation value of the DMN with SN and the DMN with CEN in ASD was lower but the coefficient of variation (CV) of dynamic network segregation of the DMN with CEN was higher in ASD. Furthermore, partially reduced triple-network segregation associated with the DMN was found in connectivity states analysis of ASD. These abnormal average values and CV of dynamic network segregation predicted social communication deficits and restricted and repetitive behaviors in ASD. Our findings indicate abnormal dynamic time-varying triple-network segregation of ASD and highlight the crucial role of the triple-network in the neural mechanisms underlying ASD.

Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is comprised of several conditions characterized by alterations in social interaction, communication, and repetitive behaviors. Genetic and environmental factors contribute to the heterogeneous development of ASD behaviors. Several rodent models display ASD-like phenotypes, including repetitive behaviors. In this review article, we discuss the potential neural mechanisms involved in repetitive behaviors in rodent models of ASD and related neuropsychiatric disorders. We review signaling pathways, neural circuits, and anatomical alterations in rodent models that display robust stereotypic behaviors. Understanding the mechanisms and circuit alterations underlying repetitive behaviors in rodent models of ASD will inform translational research and provide useful insight into therapeutic strategies for the treatment of repetitive behaviors in ASD and other neuropsychiatric disorders.

Clinical phenotype of autism spectrum disorders in children of preschool and school age, burdened epileptic seizures

Background. Clinical polymorphism and polymorphism are inherent in the clinical phenotype of children with autism spectrum disorders (ASD). There is a consensus, relatively high, between 5% and 38% of the prevalence of epilepsy in ASD. There are reasons to believe that ASD with epilepsy and specific epileptic activity on EEG and ASD with hyperkinetic symptoms without signs of epileptic process can be determined by different variants of genetic polymorphism or by different variants of gene expression, determined by different influences.
 Objective – to study the features of the clinical phenotype of ASD in preschool and school-age children with epileptic seizures and specific epileptic activity on EEG.
 Materials and methods. In the Department of Mental Disorders of Children and Adolescents of the Institute of Psychiatry of the Ministry of Health of Ukraine 116 children aged 2-10 years with ASD were examined. The study group was divided into three subgroups: subgroup A – 23 children with a history of epileptic seizures, subgroup B – 35 children with specific forms of epileptic activity on EEG without epileptic seizures, subgroup C – 19 children with ASD having specific epileptic activity for EEG repetitive involuntary movements (motor stereotypes, motor tics) and vocalizations (vocal tics). The control group consisted of 39 children with ASD non a history of seizures and specific epileptic activity on the EEG. The follow-up of children with ASD in the comparison groups was performed for 1-1.5 years. We used such research methods: clinical-psychopathological, psychodiagnostic, psychometric, statistical.
 Results. In children with ASD and comorbid epileptic seizures, disorders of social reciprocity are of crucial diagnostic importance. Communication disorders and recurrent, stereotyped behaviors, movements, and interests in children in this group are significantly less common than in comparison groups. Incidents of repetitive stereotypes in these children are associated with sensory impairments and autostimulations. Children with ASD, complicated by severe and frequent epileptic seizures, are characterized by impaired social reciprocity and communication against the background of regression or stagnation of speech and motor skills development.
 Disorders of communication and repetitive behavior in ASD in children of different ages are represented by different monoqualitative syndrome (phenotypes). Younger children less than 6 years of age are dominant in stereotypical movements, while children aged 6-8 years have repetitive behaviors associated with the overriding interests.
 Two subtypes of clinical phenotypes of ASD were identified: the variant with symptoms, which more closely determined the stereotypical sensor and motor behavior and the variant with symptoms of insistence on equality, with the overriding interests of preservation, identity. Movement stereotypes predominated in children with ASD without epileptic seizures and without epileptic activity on EEG. In children with ASD and epileptic activity on EEG, motor stereotypes and repetitive identity-preserving behavior were equally common.
 Conclusions. Disorders of social reciprocity, communication, repetitive behavior, in particular stereotyped movements are diagnostically significant signs of ASD, in particular ASD complicated by epileptic seizures, ASD with specific epileptic activity on EEG.
 According to the results of a long 1-1.5 years’ prospective study, it was established that the clinical phenotype of ASD with epileptic seizures, ASD without epileptic seizures with specific epileptic activity on EEG and RAS without epileptic seizures and changes in EEG are characterized by differing clinical picture and course.
 Qualitative communication disorders and stereotypical movements in addition to ASD are observed in other psychiatric disorders, including Tourette disorder, obsessive-compulsive disorders, and intellectual disability. Expressed repeated identity-preserving behavior is the basis for dual diagnosis of ASD and obsessive-compulsive disorder. Motor and vocal tics may be the basis for dual diagnosis of ASD and Tourette’s disorder.
 The presence of age-related pathoplasty of clinical manifestations of ASD in the comparison groups was established.

Differences in the expression of restricted repetitive behaviors in female and male BTBR T + tf/J mice

Autism spectrum disorder (ASD) is characterized by the expression of restricted repetitive behaviors (RRBs) and impairments in social recognition and communication. Epidemiological studies demonstrate males are three times more likely than females to be affected. Although this is the case, more recent studies suggest females may be underrepresented in these numbers due to standard clinical measures of RRBs and social behaviors. In addition, many studies examining mouse models of ASD exclude females due to the sex disparity in diagnoses. The present study examined how female and male BTBR T + Itpr3tf /J (BTBR) compare to control C57BL/6J mice on tests of RRBs (probabilistic reversal learning, repetitive grooming, spontaneous alternation, and marble burying) and social behaviors (three chambered social approach task). Utilizing a spatial reversal learning test with 80/20 probabilistic feedback, in which ASD individuals have exhibited deficits, we find that female BTBR mice do not show the same impairment found in male BTBR mice. Interestingly, control female C57BL/6J mice required more trials to reach criterion. Female BTBR mice expressed comparable rates of repetitive grooming, marble burying and spontaneous alternation compared to female C57BL/6J mice. Male BTBR mice expressed higher rates of grooming behavior and locomotor activity compared to male C57BL/6J mice, as found in previous studies. Similarly, male BTBR mice showed a reduction in both measures of social approach compared to controls. Both male and female BTBR mice showed a reduction in sniff time for the stranger mouse compared to controls. Together these findings demonstrate how female BTBR mice do not display the RRB profile expressed by male BTBR mice. Testing of repetitive behaviors in ASD needs to better reflect the sex differences in how RRBs manifest in females compared to their extensively researched male counterparts.

Clinical characteristics of adults with neurodevelopmental disorder: A medical records survey

Repetitive behaviors (RBs) are a core feature of autism spectrum disorders (ASD). They constitute a major barrier to learning and social adaptation. Research on potential causes of RBs is still at an early stage. However, promising new ideas and evidence are emerging from neurobiology. Instead of testing single neurotransmitter or hormone, the present study examined the associations of cortisol, serotonin, and oxytocin on subscales of repetitive behavior scales-revised (RBS-R). The results demonstrated that the individuals with ASD showed higher levels of cortisol areas under curve (cortisol AUC), higher levels of serotonin, and lower level of oxytocin compared with the typically developing (TD) individuals. For individuals with ASD, the levels of cortisol AUC, serotonin and oxytocin were all significantly associated with total scores measured by RBS-R. In addition, the cortisol AUC was positively associated with the stereotyped and restricted behavior subscales scores. The level of serotonin was positively associated with the stereotyped and self-injurious behavior subscales scores. The level of oxytocin was negatively associated with compulsive, sameness and restricted behavior subscales scores. Therefore, cortisol, serotonin and oxytocin may all be involved in the occurrence of RBs in ASD. The occurrence of RBs in ASD may due to a variety of pathological factors, not just one factor.

Links between looking and speaking in autism and first-degree relatives: insights into the expression of genetic liability to autism

BackgroundRapid automatized naming (RAN; naming of familiar items presented in an array) is a task that taps fundamental neurocognitive processes that are affected in a number of complex psychiatric conditions. Deficits in RAN have been repeatedly observed in autism spectrum disorder (ASD), and also among first-degree relatives, suggesting that RAN may tap features that index genetic liability to ASD. This study used eye tracking to examine neurocognitive mechanisms related to RAN performance in ASD and first-degree relatives, and investigated links to broader language and clinical-behavioral features.MethodsFifty-one individuals with ASD, biological parents of individuals with ASD (n = 133), and respective control groups (n = 45 ASD controls; 58 parent controls) completed RAN on an eye tracker. Variables included naming time, frequency of errors, and measures of eye movement during RAN (eye-voice span, number of fixations and refixations).ResultsBoth the ASD and parent-ASD groups showed slower naming times, more errors, and atypical eye-movement patterns (e.g., increased fixations and refixations), relative to controls, with differences persisting after accounting for spousal resemblance. RAN ability and associated eye movement patterns were correlated with increased social-communicative impairment and increased repetitive behaviors in ASD. Longer RAN times and greater refixations in the parent-ASD group were driven by the subgroup who showed clinical-behavioral features of the broad autism phenotype (BAP). Finally, parent-child dyad correlations revealed associations between naming time and refixations in parents with the BAP and increased repetitive behaviors in their child with ASD.ConclusionsDifferences in RAN performance and associated eye movement patterns detected in ASD and in parents, and links to broader social-communicative abilities, clinical features, and parent-child associations, suggest that RAN-related abilities might constitute genetically meaningful neurocognitive markers that can help bridge connections between underlying biology and ASD symptomatology.

Proactive control as a double-edged sword in autism spectrum disorder.

Proactive control refers to the active representation of contextual information to bias cognitive processing and facilitate goal-directed behavior. Despite research suggesting that proactive control may be impaired in autism spectrum disorder (ASD), the associations between proactive control and clinical symptoms of ASD remain underspecified. Here, we combined a children's version of the AX Continuous Performance Task (AX-CPT) with gold standard clinical assessments in children with ASD (N = 34) or typical development (TYP; N = 45). After controlling for full-scale IQ (FSIQ), measures of proactive control were similar between ASD and TYP. However, specifically within ASD we observed paradoxical relationships between proactive control and clinical symptoms. Increased reliance on proactive control was associated with reduced attention problems and increased restricted and repetitive behaviors in ASD. Therefore, proactive control appears to represent a double-edged sword in ASD: improved attentional control at the cost of heightened behavioral inflexibility. This represents a compelling and new characterization of the specific association between cognitive control processes isolated in computerized laboratory tasks and the multidimensional cognitive symptoms characteristic of ASD. (PsycINFO Database Record

Aberrant development of the asymmetry between hemispheric brain white matter networks in autism spectrum disorder

Atypical brain asymmetry/lateralization has long been hypothesized for autism spectrum disorder (ASD), and this model has been repeatedly supported by various neuroimaging studies. Recently, hemispheric network topologies have been found to be asymmetric, thereby providing a new avenue for investigating brain asymmetries under various conditions. To date, however, how network topological asymmetries are altered in ASD remains largely unexplored. To clarify this, the present study included ASD individuals from the newly released Autism Brain Imaging Data Exchange II database (58 right-handed male ASD individuals aged 5 to 26 years and 70 age- and IQ-matched typically developing (TD) individuals). Diffusion and structural magnetic resonance imaging were used to construct hemispheric white matter networks, and graph-theory approaches were applied to quantify topological efficiencies for hemispheric networks. Statistical analyses revealed a decreased rightward asymmetry of network efficiencies with increasing age in the TD group, but not in the ASD group. More specifically, the TD group did not exhibit an age-related increase in network efficiency in the right hemisphere, but the ASD group did. For the left hemisphere, no difference between the groups was observed for the developmental trajectory of network efficiencies. Intriguingly, within the ASD group, more severe restricted and repetitive behavior in ASD was found to be correlated with less rightward asymmetry of network local efficiency. These findings provide suggestive evidence of atypical network topological asymmetries and offer important insights into the abnormal development of ASD brains.

16p11.2 deletion syndrome mice perseverate with active coping response to acute stress - rescue by blocking 5-HT2A receptors.

In humans a chromosomal hemideletion of the 16p11.2 region results in variable neurodevelopmental deficits including developmental delay, intellectual disability, and features of autism spectrum disorder (ASD). Serotonin is implicated in ASD but its role remains enigmatic. In this study we sought to determine if and how abnormalities in serotonin neurotransmission could contribute to the behavioral phenotype of the 16p11.2 deletion syndrome in a mouse model (Del mouse). As ASD is frequently associated with altered response to acute stress and stress may exacerbate repetitive behavior in ASD, we studied the Del mouse behavior in the context of an acute stress using the forced swim test, a paradigm well characterized with respect to serotonin. Del mice perseverated with active coping (swimming) in the forced swim test and failed to adopt passive coping strategies with time as did their wild-type littermates. Analysis of monoamine content by HPLC provided evidence for altered endogenous serotonin neurotransmission in Del mice while there was no effect of genotype on any other monoamine. Moreover, we found that Del mice were highly sensitive to the 5-HT2A antagonists M100907, which at a dose of 0.1mg/kg normalized their level of active coping and restored the gradual shift to passive coping in the forced swim test. Supporting evidence for altered endogenous serotonin signaling was provided by observations of additional ligand effects including altered forebrain Fos expression. Taken together, these observations indicate notable changes in endogenous serotonin signaling in 16p11.2 deletion mice and support the therapeutic utility of 5-HT2A receptor antagonists.

Cognitive mechanisms of inhibitory control deficits in autism spectrum disorder.

Inhibitory control deficits are common in autism spectrum disorder (ASD) and associated with more severe repetitive behaviors. Inhibitory control deficits may reflect slower execution of stopping processes, or a reduced ability to delay the onset of behavioral responses in contexts of uncertainty. Previous studies have documented relatively spared stopping processes in ASD, but whether inhibitory control deficits in ASD reflect failures to delay response onset has not been systematically assessed. Further, while improvements in stopping abilities and response slowing are seen through adolescence/early adulthood in health, their development in ASD is less clear. A stop-signal test (SST) was administered to 121 individuals with ASD and 76 age and IQ-matched healthy controls (ages 5-28). This test included 'GO trials' in which participants pressed a button when a peripheral target appeared and interleaved 'STOP trials' in which they were cued to inhibit button-presses when a stop-signal appeared at variable times following the GO cue. STOP trial accuracy, RT of the stopping process (SSRT), and reaction time (RT) slowing during GO trials were examined. Relative to controls, individuals with ASD had reduced accuracy on STOP trials. SSRTs were similar across control and ASD participants, but RT slowing was reduced in patients compared to controls. Age-related increases in stopping ability and RT slowing were attenuated in ASD. Reduced stopping accuracy and RT slowing were associated with more severe repetitive behaviors in ASD. Our findings show that inhibitory control deficits in ASD involve failures to strategically delay behavioral response onset. These results suggest that reduced preparatory behavioral control may underpin inhibitory control deficits as well as repetitive behaviors in ASD. Typical age-related improvements in inhibitory control during late childhood/early adolescence are reduced in ASD, highlighting an important developmental window during which treatments may mitigate cognitive alterations contributing to repetitive behaviors.

Network over-connectivity differentiates autism spectrum disorder from other developmental disorders in toddlers: A diffusion MRI study.

Advanced connectivity studies in toddlers with Autism Spectrum Disorder (ASD) are increasing and consistently reporting a disruption of brain connectivity. However, most of these studies compare ASD and typically developing subjects, thus providing little information on the specificity of the abnormalities detected in comparison with other developmental disorders (other-DD). We recruited subjects aged below 36 months who received a clinical diagnosis of Neurodevelopmental Disorder (32 ASD and 16 other-DD including intellectual disability and language disorder) according to DSM-IV TR. Structural and diffusion MRI were acquired to perform whole brain probabilistic and anatomically constrained tractography. Network connectivity matrices were built encoding the number of streamlines (DNUM ) and the tract-averaged fractional anisotropy (DFA ) values connecting each pair of cortical and subcortical regions. Network Based Statistics (NBS) was finally applied on the connectivity matrices to evaluate the network differences between the ASD and other-DD groups. The network differences resulted in an over-connectivity pattern (i.e., higher DNUM and DFA values) in the ASD group with a significance of P < 0.05. No contra-comparison results were found. The over-connectivity pattern in ASD occurred in networks primarily involving the fronto-temporal nodes, known to be crucial for social-skill development and basal ganglia, related to restricted and repetitive behaviours in ASD. To our knowledge, this is the first network-based diffusion study comparing toddlers with ASD and those with other-DD. Results indicate the detection of different connectivity patterns in ASD and other-DD at an age when clinical differential diagnosis is often challenging. Hum Brain Mapp 38:2333-2344, 2017. © 2017 Wiley Periodicals, Inc.

Investigating the relationship between multiple grip forces and BOLD signal in the Cerebellum and dentate nuclei of MS subjects

Investigating the relationship between multiple grip forces and BOLD signal in the Cerebellum and dentate nuclei of MS subjects

Alterations in the functional neural circuitry supporting flexible choice behavior in autism spectrum disorders.

Restricted and repetitive behaviors, and a pronounced preference for behavioral and environmental consistency, are distinctive characteristics of autism spectrum disorder (ASD). Alterations in frontostriatal circuitry that supports flexible behavior might underlie this behavioral impairment. In an functional magnetic resonance imaging study of 17 individuals with ASD, and 23 age-, gender- and IQ-matched typically developing control participants, reversal learning tasks were used to assess behavioral flexibility as participants switched from one learned response choice to a different response choice when task contingencies changed. When choice outcome after reversal was uncertain, the ASD group demonstrated reduced activation in both frontal cortex and ventral striatum, in the absence of task performance differences. When the outcomes of novel responses were certain, there was no difference in brain activation between groups. Reduced activation in frontal cortex and ventral striatum suggest problems in decision-making and response planning, and in processing reinforcement cues, respectively. These processes, and their integration, are essential for flexible behavior. Alterations in these systems may therefore contribute to a rigid adherence to preferred behavioral patterns in individuals with an ASD. These findings provide an additional impetus for the use of reversal learning paradigms as a translational model for treatment development targeting the domain of restricted and repetitive behaviors in ASD.

Anatomical imbalance between cortical networks in autism.

Influential psychological models of autism spectrum disorder (ASD) have proposed that this prevalent developmental disorder results from impairment of global (integrative) information processing and overload of local (sensory) information. However, little neuroanatomical evidence consistent with this account has been reported. Here, we examined relative grey matter volumes (rGMVs) between three cortical networks, how they changed with age, and their relationship with core symptomatology. Using public neuroimaging data of high-functioning ASD males and age-/sex-/IQ-matched controls, we first identified age-associated atypical increases in rGMVs of the regions of two sensory systems (auditory and visual networks), and an age-related aberrant decrease in rGMV of a task-control system (fronto-parietal network, FPN) in ASD children. While the enlarged rGMV of the auditory network in ASD adults was associated with the severity of autistic socio-communicational core symptom, that of the visual network was instead correlated with the severity of restricted and repetitive behaviours in ASD. Notably, the atypically decreased rGMV of FPN predicted both of the two core symptoms. These findings suggest that disproportionate undergrowth of a task-control system (FPN) may be a common anatomical basis for the two ASD core symptoms, and relative overgrowth of the two different sensory systems selectively compounds the distinct symptoms.

IMPULSIVITY AND COMPULSIVITY: TRANSLATIONAL APPROACHES TO COMPULSIVITY IN AUTISM SPECTRUM DISORDERS

abstract Background Restricted and repetitive behaviors in Autism Spectrum Disorder (ASD) are heterogeneous, which has prompted attempts to classify repetitive behaviors into subtypes. We performed a factor analysis of repetitive behaviors in ASD that yielded four factors: obsessions, higher order behaviors, lower order repetitive behaviors, and hoarding. The “insistence on sameness” domain of symptoms is an understudied, yet significant, domain because its severity appears to be positively correlated with quality of life. Behaviors in this domain are manifested in behavioral and cognitive rigidity, likely due to difficulty adapting to change. Although several outcome measures assess compulsivity and repetitive behaviors in ASD, none specifically capture the inflexibility commonly exhibited. We developed the Montefiore-Einstein Rigidity Scales (MERS), a semi-structured interview, which focuses solely on changes in cognitive and behavioral rigidity over the course of time. Methods Factor analysis of repetitive behaviors using both clinician rated scales, the MERS and Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and caregiver rated scales, Repetitive Behavior Scale –Revised (RBS-R) and Social Responsiveness Scale (SRS). Data from these scales was collected during two separate ASD treatment studies of children aged 5 to 17, and adults aged 17 to 35. Results In Study 1 (TSO in Adults with ASD) subjects had significant improvements in cognitive/behavioral flexibility on the MERS; and significant improvements on Y-BOCS Compulsive Behavior subscale; SRS Repetitive Behavior subscale and RBS-R Sameness subscale. The Y-BOCs, SRS and RBS-R did not do an adequate job of capturing behavioral and cognitive rigidity. The Y-BOCS does not capture improvements in rigidity; it focuses on compulsive behaviors commonly exhibited in OCD. The SRS-Repetitive Behavior Subscale assesses stereotypic behaviors and restricted interests. The RBS-R Sameness subscale consists of specific examples of inflexible behaviors and therefore does not tap into many possible rigid behaviors. In Study 2 (Hyperthermia in Children with ASD) subjects had significant improvements on the SRS Repetitive Behavior subscale and RBS-R Compulsive Behavior subscale. Neither the SRS nor the RBS-R did an adequate job of capturing behavioral and cognitive rigidity. The SRS-Repetitive Behavior Subscale assesses stereotypic behaviors and restricted interests, while the RBS-R Compulsive Scale assesses more compulsive behaviors. Conclusion Both studies utilized novel treatment approaches in different age populations and significant improvements in repetitive behaviors were found on treatment versus placebo. Symptoms in the Rigidity-Insistence on Sameness domain emerged as responsive to treatment. This domain appears to be associated with quality of life measures, is linked to gene and chromosomal regions, and there is evidence of familiarity (2-4). We have developed and have refined the MERS to better understand and assess cognitive and behavioral rigidity and inflexibility in ASD, and to help track changes with treatment. The MERS measures 1. Degree of Behavioral Rigidity, 2. Degree of Cognitive Rigidity, 3. Interference associated with rigidity, and 4. Distress associated with Rigidity. Since this domain of symptoms may have a unique neurobiological origin and differential treatment response, we recommended future ASD studies utilize this measure to stratify patients into more homogeneous groups and/or as an outcome measure to track changes in rigid behaviors.