Stereotyped Motor Behaviors Research Articles

ChangPu YuJin Tang improves Tourette disorder symptoms by modulating amino acid neurotransmitters in IDPN model rats.

Changpu Yujin Tang(CPYJT), a Chinese herbal compound, is an effective therapeutic strategy for pediatric patients with Tourette disorder (TD). Therefore, this work aims to investigate the therapeutic mechanisms of CPYJT. Behavioral and cellular ultrastructural evaluation of the therapeutic effects of CPYJT in TD model rats. Colorimetric methods, reverse transcription‑quantitative PCR, and Western Blot were used to measure the altered levels of GLU, GABA, and the levels of VGLUT1, GLUD1, GABRA3, and GAD65 in the cortex, striatum, and thalamus of the TD model rats after 7, 14, 21, and 28 days of CPYJT administration. CPYJT significantly reduced stereotypic behavior and motor behavior scores in TD model rats. CPYJT ameliorates myelin structural damage in TD model rat neuronal cells. CPYJT decreased GLU content, elevated GABA content, decreased GLUD1 and VGLUT1 levels, and elevated GAD65 and GABRA3 levels in TD model rats' cortex, striatum, and thalamus. CPYJT has different regulatory time points in the cortex, striatum, and thalamus for critical factors of amino acid-based neurotransmission. CPYJT protects behavioral and structural damage of neuronal cells in multiple brain regions in TD model rats.

Mapping Gilles de la Tourette syndrome through the distress and relief associated with tic-related behaviors: an fMRI study

Personal distress associated with tic urges or inhibition and relief associated with tic production are defining features of the personal experience in Gilles de la Tourette syndrome (GTS). These affective phenomena have not been studied using fMRI, hindering our understanding of GTS pathophysiology and possible treatments. Here, we present a novel cross-sectional fMRI study designed to map tic-related phenomenology using distress and relief as predicting variables. We adopted a mental imagery approach and dissected the brain activity associated with different phases of tic behaviors, premonitory urges, and the ensuing tic execution or inhibition: these were compared with the mental simulation of “relaxed situations” and pre-determined stereotyped motor behaviors. We then explored whether the ensuing brain patterns correlated with the distress or relief perceived for the different phases of the tasks. Patients experienced a higher level of distress during the imagery of tic-triggering scenarios and no relief during tic inhibition. On the other hand, patients experienced significant relief during tic imagery. Distress during tic-triggering scenarios and relief during tic imagery were significantly correlated. The distress perceived during urges correlated with increased activation in cortical sensorimotor areas, suggesting a motor alarm. Conversely, relief during tic execution was positively associated with the activity of a subcortical network. The activity of the putamen was associated with both distress during urges and relief during tic execution. These findings highlight the importance of assessing the affective component of tic-related phenomenology. Subcortical structures may be causally involved in the affective component of tic pathophysiology, with the putamen playing a central role in both tic urge and generation. We believe that our results can be readily translated into clinical practice for the development of personalized treatment plans tailored to each patient’s unique needs.

The Partial M1 Muscarinic Cholinergic Receptor Agonist, CDD-0102A, Differentially Modulates Glutamate Efflux in Striatal Subregions during Stereotyped Motor Behavior in the BTBR Mouse Model of Autism.

The BTBR T+ Itpr3tf/J (BTBR) mouse displays elevated repetitive motor behaviors. Treatment with the partial M1 muscarinic receptor agonist, CDD-0102A, attenuates stereotyped motor behaviors in BTBR mice. The present experiment investigated whether CDD-0102A modifies changes in striatal glutamate concentrations during stereotyped motor behavior in BTBR and B6 mice. Using glutamate biosensors, change in striatal glutamate efflux was measured during bouts of digging and grooming behavior with a 1 s time resolution. Mice displayed both decreases and increases in glutamate efflux during such behaviors. Magnitude of changes in glutamate efflux (decreases and increases) from dorsomedial and dorsolateral striatum were significantly greater in BTBR mice compared to those of B6 mice. In BTBR mice, CDD-0102A (1.2 mg/kg) administered 30 min prior to testing significantly reduced the magnitude change in glutamate decreases and increases from the dorsolateral striatum and decreased grooming behavior. Conversely, CDD-0102A treatment in B6 mice potentiated glutamate decreases and increases in the dorsolateral striatum and elevated grooming behavior. The findings suggest that activation of M1 muscarinic receptors modifies glutamate transmission in the dorsolateral striatum and self-grooming behavior.

Moria or Mania? Manic symptoms as the clinical manifestation of glioblastoma recurrence: a case report

IntroductionUp to 50% of patients with brain tumors experience psychiatric symptoms, and rates up to 80% have been reported in malignant neoplasms such as glioblastoma multiforme (GBM). Still, clinical presentation as mania-like syndromes is a rare phenomenon, mainly occurring when frontal structures are compromised.We present the case of a 42-year-old woman who was admitted to our hospital due to manic symptoms coinciding with a recurrence of a bifrontal GBM, for which she underwent surgery 5 months prior.Objectives1) To describe the clinical particularities of this case, focusing on the differential diagnosis.2) To review the association between manic symptoms and frontal dysfunction caused by brain tumors, with special interest on GBM.MethodsA review of the patient’s clinical history and complementary tests performed was carried out. Likewise, we reviewed the available literature in relation to manic symptoms related to brain tumors.ResultsThe patient’s GBM recurrence presented with late onset symptoms of mania, including euphoric mood, increased spending, ideas of grandiosity and hyper-religiosity. She had no previous psychiatric history but, interestingly, she had an extensive affective burden in her family, with 4 consummated suicides. However, she also presented other clinical signs, such as disorientation, perseveration, mild memory impairment and stereotyped motor behaviors, that pointed to relevant frontal lobe dysfunction, suggesting Moria as a possible contribution for the symptoms described.Manic symptoms in the context of brain tumors appear in 7-15% of patients with psychiatric symptoms, usually associated with right frontal dysfunction (75% of cases). Bifrontal affectation, such as this patient, is only described in 6% of cases. Although fast growing, malignant tumors have been associated with higher rates of psychiatric symptoms, no correlation has been described between these and brain tumor histology.Conclusions- The presence of atypical manic symptoms, such as those presented in this case, should raise clinical concern for secondary mania.- Moria shares similarities with mania, including mood elevation, tendency to hilarity or hyper-sexuality, that may hinder diagnosis of patients with frontal dysfunction.- This case outlines the difficulties in making a differential diagnosis in patient with both manic and neurological signs, and highlights the implication of frontal structures in the development of manic symptoms.Disclosure of InterestNone Declared

Impact of specific serotonin receptor modulation on restricted repetitive behaviors.

Restricted, repetitive behaviors (RRBs) are commonly divided into two behavioral categories, lower-order and higher-order RRBs. Individuals displaying lower-order motoric RRBs may express repetitive hand flapping behaviors, body rocking back and forth movements, and continuous body spinning. Higher-order RRBs most commonly cover the behavior inflexibility and cognitive rigidity commonly found in disorders such as autism spectrum disorder and obsessive-compulsive disorder. Various neuropsychiatric disorders are plagued by RRBs yet no FDA-approved treatments have been identified. In rodents, lower-order RRBs are commonly measured through various tasks, such as repetitive self-grooming, marble burying, and stereotypic motor behaviors. This review focuses on the effects that modulation of specific serotonin receptors have on lower-order RRBs. Although there is research examining how changes in 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT6, and 5-HT7 receptor modulation, more research has focused on the 5-HT1A, 5-HT2A, and 5-HT2C receptors. The accumulating data suggest that increasing 5-HT1A activation decreases RRBs while blocking 5-HT1A activation has no effect on RRBs. While there are mixed findings regarding the impact of 5-HT2A modulation on RRBs, the general trend shows mixed effects of 5-HT2A receptor activation RRB expression, whereas blockade generally decreases RRBs. 5-HT2C receptor activation can modulate RRBs in either direction depending on the 5-HT2C drug used, blocking 5-HT2C activation only seems to show therapeutic properties when 5-HT2C activation is already elevated. The other 5-HT receptors have been explored far less but show promise as potential targets for regulating RRBs. Although it is less clear due to the involvement of 5-HT1D, 5-HT1A activation increases RRBs, and blocking 5-HT1A tends to decrease RRBs. 5-HT2B activation could reduce RRBs, while inhibiting 5-HT2B does not impact RRBs. Increasing 5-HT3 has not been shown to affect RRBs. Yet, increases in RRBs have been observed in Htr3a KO mice. 5-HT6 receptor activation can increase RRBs, while blocking 5-HT6 activity tends to decrease RRBs. Lastly, neither increasing or blocking 5-HT7 activity can reduce RRBs. In sum, there is no uniform pattern in whether all specific 5-HT receptors affect RRBs in either direction, instead, there is evidence suggesting that different 5-HT receptors can modulate RRBs in different directions. Further researching the less explored receptors and aiming to understand why these receptors can differently modulate RRBs, may play a key role in developing therapeutics that treat RRBs.

Effects of the Partial M1 Muscarinic Cholinergic Receptor Agonist CDD-0102A on Stereotyped Motor Behaviors and Reversal Learning in the BTBR Mouse Model of Autism.

BackgroundAutism spectrum disorders (ASD) are a set of neurodevelopmental disorders marked by a lack of social interaction, restrictive interests, and repetitive behaviors. There is a paucity of pharmacological treatments to reduce core ASD symptoms. Various lines of evidence indicate that reduced brain muscarinic cholinergic receptor activity may contribute to an ASD phenotype.MethodsThe present experiments examined whether the partial M1 muscarinic receptor agonist, 5-(3-ethyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine hydrochloride (CDD-0102A), alleviates behavioral flexibility deficits and/or stereotyped motor behaviors in the BTBR mouse model of autism. Behavioral flexibility was tested using a reversal learning test. Stereotyped motor behaviors were measured by eliciting digging behavior after removal of nesting material in a home cage and by measuring repetitive grooming.ResultsCDD-0102A (0.2 and 0.6 mg/kg but not 1.2 mg/kg) injected prior to reversal learning attenuated a deficit in BTBR mice but did not affect performance in B6 mice. Acute CDD-0102A treatment (1.2 and 3 mg/kg) reduced self-grooming in BTBR mice and reduced digging behavior in B6 and BTBR mice. The M1 muscarinic receptor antagonist VU0255035 (3 mg/kg) blocked the effect of CDD-0102A on grooming behavior. Chronic treatment with CDD-0102A (1.2 mg/kg) attenuated self-grooming and digging behavior in BTBR mice. Direct CDD-0102A infusions (1 µg) into the dorsal striatum reduced elevated digging behavior in BTBR mice. In contrast, CDD-0102A injections in the frontal cortex were not effective.ConclusionsThe results suggest that treatment with a partial M1 muscarinic receptor agonist may reduce repetitive behaviors and restricted interests in autism in part by stimulating striatal M1 muscarinic receptors.

Effects of Physical Exercise Interventions on Stereotyped Motor Behaviours in Children with ASD: A Meta-Analysis.

Studies have reported that physical exercise reduces maladaptive stereotyped motor behaviours (SMB) in children with ASD, but these intervention studies vary in design and outcome. The present systematic review and meta-analysis included 22 studies, involving 274 children with ASD, to quantify the effect of exercise on SMB and its potential moderators. Multi-level modelling revealed a large overall effect, Hedges' g = 1.16, with significant heterogeneity across participant, treatment, and study levels. Further, a more appropriate model using between-case estimation for within-subject effects to improve comparability between single-case and group-design studies, yielded a smaller but still significant effect, g = 0.51. Lastly, higher exercise intensity, but not age, exercise duration or settings, reliably predicted treatment effectiveness. Implications for clinical practice and research are discussed.

Transneuronal delivery of designer cytokines: perspectives for spinal cord injury.

Transneuronal delivery of designer cytokines: perspectives for spinal cord injury.

Stereotypy and spontaneous alternation in deer mice and its response to anti-adenosinergic intervention.

Repetitive behavioral phenotypes are a trait of several neuropsychiatric disorders, including obsessive-compulsive disorder (OCD). Such behaviors are typified by complex interactions between cognitive and neurobiological processes which most likely contribute to the suboptimal treatment responses often observed. To this end, exploration of the adenosinergic system may be useful, since adenosine-receptor modulation has previously shown promise to restore control over voluntary behavior and improve cognition in patients presenting with motor repetition. Here, we employed the deer mouse (Peromyscus maniculatus bairdii) model of compulsive-like behavioral persistence, seeking to investigate possible associations between stereotypic motor behavior and cognitive flexibility as measured in the T-maze continuous alternation task (T-CAT). The effect of istradefylline, a selective adenosine A2A receptor antagonist at two doses (10 and 20mgkg-1 day-1 ) on the expression of stereotypy and T-CAT performance in high (H) and non-(N) stereotypical animals, was investigated in comparison to a control intervention (six groups; n=8 or 9 per group). No correlation between H behavior and T-CAT performance was found. However, H but not N animals presented with istradefylline-sensitive spontaneous alternation and stereotypy, in that istradefylline at both doses significantly improved the spontaneous alternation scores and attenuated the stereotypical expression of H animals. Thus, evidence is presented that anti-adenosinergic drug action improves repetitive behavior and spontaneous alternation in stereotypical deer mice, putatively pointing to a shared psychobiological construct underlying naturalistic stereotypy and alterations in cognitive flexibility in deer mice.

Subarachnoid hemorrhage in C57BL/6J mice increases motor stereotypies and compulsive-like behaviors

ABSTRACT Objective Long-term behavioral, mood, and cognitive deficits affect over 30% of patients with subarachnoid hemorrhage (SAH). The aim of the present study was to examine the neurobehavioral outcomes following endovascular perforation induced SAH in mice. Methods C57BL/6 J (B6) mice were exposed to endovascular perforation induced SAH or control surgery. Three weeks later, mice received a series of behavioral tests, e.g. motor function, stereotypy, learning, memory, behavioral flexibility, depression and anxiety. The immunohistologic experiment examined neuronalloss in the cortex following SAH. Results SAH mice exhibited increased marble burying and nestlet shredding compared to that of control mice. Although SAH did not affect memory, learning or reversal learning,mice displayed greater overall object exploration in the novel object recognition test, as well as elevated perseveration during probabilistic reversal learning.In the forced swim and open field tests, SAH mice performed comparably to that of control mice. However, SAH mice exhibited an increased frequency in ‘jumping’ behavior in the open field test. Histological analyses revealed reduced neuron density in the parietal-entorhinal cortices of SAH mice on the injured side compared to that of control mice. Discussion The findings suggest that parietal-entorhinal damage from SAH increases stereotyped motor behaviors and ‘compulsive-like’ behaviors without affecting cognition (learning and memory) or mood (anxiety and depression). This model can be used to better understand the neuropathophysiology following SAH that contributes to behavioral impairments in survivors with no gross sensory-motor deficits.

Recording Channelrhodopsin-Evoked Field Potentials and Startle Responses from Larval Zebrafish.

Zebrafish are an excellent model organism to study many aspects of vertebrate sensory encoding and behavior. Their escape responses begin with a C-shaped body bend followed by several swimming bouts away from the potentially threatening stimulus. This highly stereotyped motor behavior provides a model for studying startle reflexes and the neural circuitry underlying multisensory encoding and locomotion. Channelrhodopsin (ChR2) can be expressed in the lateral line and ear hair cells of zebrafish and can be excited in vivo to elicit these rapid forms of escape. Here we review our methods for studying transgenic ChR2-expressing zebrafish larvae, including screening for positive expression of ChR2 and recording field potentials and high-speed videos of optically evoked escape responses. We also highlight important features of the acquired data and provide a brief review of other zebrafish research that utilizes or has the potential to benefit from ChR2 and optogenetics.

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.

Behavior of mice aboard the International Space Station

Interest in space habitation has grown dramatically with planning underway for the first human transit to Mars. Despite a robust history of domestic and international spaceflight research, understanding behavioral adaptation to the space environment for extended durations is scant. Here we report the first detailed behavioral analysis of mice flown in the NASA Rodent Habitat on the International Space Station (ISS). Following 4-day transit from Earth to ISS, video images were acquired on orbit from 16- and 32-week-old female mice. Spaceflown mice engaged in a full range of species-typical behaviors. Physical activity was greater in younger flight mice as compared to identically-housed ground controls, and followed the circadian cycle. Within 9–11 days after launch, younger (but not older), mice began to exhibit distinctive circling or ‘race-tracking’ behavior that evolved into a coordinated group activity. Organized group circling behavior unique to spaceflight may represent stereotyped motor behavior, rewarding effects of physical exercise, or vestibular sensation produced via self-motion. Affording mice the opportunity to grab and run in the RH resembles physical activities that the crew participate in routinely. Our approach yields a useful analog for better understanding human responses to spaceflight, providing the opportunity to assess how physical movement influences responses to microgravity.

Neuroanatomical Basis of Individuality in Muscle Tuning Function: Neural Correlates of Muscle Tuning.

In a conventional view of motor control, the human brain might employ an optimization principle that leads a stereotypical motor behavior which we observe as an averaged behavioral data over subjects. In this scenario, the inter-individual motor variability is considered as an observation noise. Here, we challenged this view. We considered a motor control task where the human participants manipulated arm force by coordinating shoulder and elbow torques and investigated the muscle-tuning function that represents how the brain distributed the ideal joint torques to multiple muscles. In the experimental data, we observed large inter-individual variability in the profile of a muscle-tuning function. This contradicts with a well-established optimization theory that is based on minimization of muscle energy consumption and minimization of motor variability. We then hypothesized the inter-subject differences in the structure of the motor cortical areas might be the source of the across-subjects variability of the motor behavior. This was supported by a voxel-based morphometry analysis of magnetic resonance imaging; The inter-individual variability of the muscle tuning profile was correlated with that of the gray matter volume in the premotor cortex which is ipsilateral to the used arm (i.e., right hemisphere for the right arm). This study suggests that motor individuality may originate from inter-individual variation in the cortical structure.

A central pattern generator in the spinal cord for the central control of micturition: An opportunity for first-in-class drug treatments

For non-neuroscientists, the spinal cord is often considered simply as a relay between the brain and peripheral organs such as the skin, smooth muscles, and skeletal muscles. However, its gray matter has also been shown to play a pivotal role in the control of stereotyped motor behaviors. Neuroscientists have indeed clearly shown recently that the spinal cord contains command centers also known as central pattern generators. Those spinal centers have been found to elicit, inhibit or modulate locomotion, ejaculation, defecation and micturition. This short communication briefly outlines the main characteristics of the central pattern generator for micturition and how it could become a therapeutic target for innovative drugs against micturition-related problems.

Forecast or Fall: Prediction's Importance to Postural Control.

To interact successfully with an uncertain environment, organisms must be able to respond to both unanticipated and anticipated events. For unanticipated events, organisms have evolved stereotyped motor behaviors mapped to the statistical regularities of the environment, which can be trigged by specific sensory stimuli. These “reflexive” responses are more or less hardwired to prevent falls and represent, maybe, the best available solution to maintaining posture given limited available time and information. With the gift of foresight, however, motor behaviors can be tuned or prepared in advance, improving the ability of the organism to compensate for, and interact with, the changing environment. Indeed, foresight's improvement of our interactive capacity occurs through several means, such as better action selection, processing, and conduction delay compensation and by providing a prediction with which to compare our actual behaviors to, thereby facilitating error identification and learning. Here we review the various roles foresight (prediction) plays in maintaining our postural equilibrium. We start by describing some of the more recent findings related to the prediction of instability. Specifically, we cover recent advancements in the understanding of anticipatory postural behaviors that are used broadly to stabilize volitional movement and compensate for impending postural disturbances. We also describe anticipatory changes in the state, or set, of the nervous system that may facilitate anticipatory behaviors. From changes in central set, we briefly discuss prediction of postural instability online before moving into a discussion of how predictive mechanisms, such as internal models, permit us to tune, perhaps our highest level predictive behaviors, namely the priming associated with motor affordances. Lastly, we explore methods best suited to expose the contribution of prediction to postural equilibrium control across a variety of contexts.

The autism spectrum phenotype in ADNP syndrome.

Pathogenic disruptions to the activity-dependent neuroprotector homeobox (ADNP) gene are among the most common heterozygous genetic mutations associated with autism spectrum disorders (ASDs). Individuals with ADNP disruptions share a constellation of medical and psychiatric features, including ASD, intellectual disability (ID), dysmorphic features, and hypotonia. However, the profile of ASD symptoms associated with ADNP may differ from that of individuals with another ASD-associated single gene disruption or with ASD without a known genetic cause. The current study examined the ASD phenotype in a sample of representative youth with ADNP disruptions. Participants (N = 116, ages 4-22 years) included a cohort with ADNP mutations (n = 11) and three comparison groups with either a mutation to CHD8 (n = 11), a mutation to another ASD-associated gene (other mutation; n = 53), or ASD with no known genetic etiology (idiopathic ASD; n = 41). As expected, individuals with ADNP disruptions had higher rates of ID but less severe social affect symptoms compared to the CHD8 and Idiopathic ASD groups. In addition, verbal intelligence explained more variance in social impairment in the ADNP group compared to CHD8, other mutation, and idiopathic ASD comparison groups. Restricted and repetitive behaviors in the ADNP group were characterized by high levels of stereotyped motor behaviors, whereas the idiopathic ASD group showed high levels of restricted interests. Taken together, these results underscore the role of ADNP in cognitive functioning and suggest that social impairments in ADNP syndrome are consistent with severity of verbal deficits. Autism Res 2018, 11: 1300-1310. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Disruptions to the ADNP gene (i.e., ADNP syndrome) have been associated with autism spectrum disorder (ASD). This article describes intellectual disability, mild social difficulties, and severe repetitive motor movements in a group of 11 youth with ADNP Syndrome. We found lower rates of ASD than previously reported. Verbal skills explained individual variability in social impairment. This pattern suggests that the ADNP gene is primarily associated with learning and memory, and level of social difficulties is consistent with level of verbal impairment.

The measurements and mechanisms of restricted and repetitive behaviors in autism spectrum disorders

Restricted and repetitive behaviors (RRBs) are one of the core features of autism spectrum disorders (ASD). RRBs encompass a broad range of heterogeneous behaviors, such as repetitive and stereotyped motor behavior or speech, atypical sensory behavior, inflexible interest and rituals, and insistence on the sameness of environment. While a large amount of previous research has focused on social deficits in ASD, little attention has been paid to their RRBs. The definition, classification, and underlying mechanism of RRBs have remained to be clarified. Recently, Diagnostic and Statistical Manual of Mental Disorders (5th ed, DSM-V) has classified RRBs into several subcategories and renewed the diagnostic criteria of RRBs. New theories and evidence from neurobiological, cognitive psychological, and developmental psychological research are also emerging about the etiology of RRBs. The first aim of this review is to introduce the newest definition and subcategories of RRBs based on DSM-V. We also discuss and compare different structural models of RRBs derived from several factor analysis studies. The second aim is to summarize the current assessment tools of RRBs in autism. Besides the “golden standard” -- the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R), and several common used questionnaires such as Repetitive Behavior Scale-Revised (RBS-R) and Repetitive Behavior Questionnaire-2 (RBQ-2), new techniques including eye-tracking, accelerometry, and electrodermal activity (EDA) have been applied into the studies of RRBs. The third aim of this review is to discuss the potential causal origins underlying the RRBs. The neurobiological and cognitive mechanism of RRBs, as well as other factors that directly related to the onset of RRBs have been summarized. The neurobiological evidence indicates that the atypical activity of neurotransmitters, the imbalanced activity among the corticostriatal circuits, and the neuroanatomical alterations play important roles on the RRBs. From the perspective of cognitive psychology, classical theories such as executive functions, weak central coherence, extreme male brain theory, and operational conditioning all offer their own explanations for the onset of RRBs. Besides, the hyper- or hypo-arousal theory indicates that RRBs may function as coping strategies for the individuals with ASD to regulate levels of arousal or anxiety, with the intolerance of uncertainty as the mediator. The evidence from developmental psychology focus on the developmental trajectory of RRBs across age. Results from longitudinal studies identify the significant influence of age and intelligence on the developmental trajectory of RRBs. Severe impacts of environmental deprivation and social isolation on the RRBs have also been shown in animal and human studies and provide implication for early intervention. Finally, several future directions for the research on RRBs in ASD have also been proposed based on the current literature. We recommend future research that focuses on the united standard for classification and the direct connection between neurobiology and behavior. Also, a clear understanding of the developmental trajectories of RRBs in typical developing children and children with ASD is of importance for effective early interventions. Last but not least, the characteristics of parents and the prenatal maternal stress are worthy of future investigations.

Loss of Cntnap2 Causes Axonal Excitability Deficits, Developmental Delay in Cortical Myelination, and Abnormal Stereotyped Motor Behavior.

Contactin-associated protein-like 2 (Caspr2) is found at the nodes of Ranvier and has been associated with physiological properties of white matter conductivity. Genetic variation in CNTNAP2, the gene encoding Caspr2, has been linked to several neurodevelopmental conditions, yet pathophysiological effects of CNTNAP2 mutations on axonal physiology and brain myelination are unknown. Here, we have investigated mouse mutants for Cntnap2 and found profound deficiencies in the clustering of Kv1-family potassium channels in the juxtaparanodes of brain myelinated axons. These deficits are associated with a change in the waveform of axonal action potentials and increases in postsynaptic excitatory responses. We also observed that the normal process of myelination is delayed in Cntnap2 mutant mice. This later phenotype is a likely modulator of the developmental expressivity of the stereotyped motor behaviors that characterize Cntnap2 mutant mice. Altogether, our results reveal a mechanism linked to white matter conductivity through which mutation of CNTNAP2 may affect neurodevelopmental outcomes.

A rare case of sleep - related rhythmic movement disorder in adult with literature review

Sleep - related rhythmic movement disorder (RMD) is characterized by repetitive,stereotyped and rhythmic motor behaviors (not tremors) that occur predominantly during drowsiness or sleep and involve large muscle groups. The onset of RMD is typically in early childhood, rarely continue into adolescence and adulthood. This paper retrospectively analyzed the diagnosis and treatment in a case of adult-onset RMD. A 76 -year-old male mainly presented rhythmic forehead banging during sleep. The number of forehead banging ranged from dozens to tens of seconds, pause seconds after the second attack, lasting 1 to 2 h and can not be recalled after waking up. Polysomnography (PSG) showed sleep efficiency decreased, awakening time prolonged, times of wakefulness increased, sleep structure disordered, non-rapid eye movement (NREM) 1 and 2 sleep increased, rapid eye movement (REM) sleep decreased, sleep latency of REM prolonged. Apnea hypopnea index (AHI) was 8.40. Several abnormal behavior attacks were observed, each attack lasting 3 to 18 s, 0.60 to 1.20 Hz, total time lasting 6 min. The diagnosis was RMD, clonazepam 0.50 mg/night and pramipexole 0.0625 mg/night were given and the result of 33 months follow-up showed effective. By literature review, we know the clinical features, diagnosis and treatment of RMD. We also analyze the reasons of misdiagnosis for reducing diagnostic errors and mistreatments. DOI: 10.3969/j.issn.1672-6731.2017.09.008