Deficiency of FRMD5 results in neurodevelopmental dysfunction and autistic-like behavior in mice.

The pathophysiology of autism spectrum disorders (ASDs) is causally linked to postsynaptic scaffolding proteins, as evidenced by numerous large-scale genomic studies [1, 2] and in vitro and in vivo neurobiological studies of mutations in animal models [3, 4]. However, due to the distinct phenotypic and genetic heterogeneity observed in ASD patients, individual mutation genes account for only a small proportion (<2%) of cases [1, 5]. Recently, a human genetic study revealed a correlation between de novo variants in FERM domain-containing-5 (FRMD5) and neurodevelopmental abnormalities [6]. In this study, we demonstrate that deficiency of the scaffolding protein FRMD5 leads to neurodevelopmental dysfunction and ASD-like behavior in mice. FRMD5 deficiency results in morphological abnormalities in neurons and synaptic dysfunction in mice. Frmd5-deficient mice display learning and memory dysfunction, impaired social function, and increased repetitive stereotyped behavior. Mechanistically, tandem mass tag (TMT)-labeled quantitative proteomics revealed that FRMD5 deletion affects the distribution of synaptic proteins involved in the pathological process of ASD. Collectively, our findings delineate the critical role of FRMD5 in neurodevelopment and ASD pathophysiology, suggesting potential therapeutic implications for the treatment of ASD.

Characterization of the Neurochemical and Behavioral Effects of the Phenethylamine 2-Cl-4,5-MDMA in Adolescent and Adult Male Rats.

BACKGROUND: The proliferation of novel psychoactive substances (NPS) in the drug market raises concerns about uncertainty on their pharmacological profile and the health hazard linked to their use. Within the category of synthetic stimulant NPS, the phenethylamine 2-Cl-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) has been linked to severe intoxication requiring hospitalization. Thereby, the characterization of its pharmacological profile is urgently warranted. METHODS: By in vivo brain microdialysis in adolescent and adult male rats we investigated the effects of 2-Cl-4,5-MDMA on dopamine (DA) and serotonin (5-HT) neurotransmission in two brain areas critical for the motivational and rewarding properties of drugs, the nucleus accumbens (NAc) shell and the medial prefrontal cortex (mPFC). Moreover, we evaluated the locomotor and stereotyped activity induced by 2-Cl-4,5-MDMA and the emission of 50-kHz ultrasonic vocalizations (USVs) to characterize its affective properties. RESULTS: 2-Cl-4,5-MDMA increased dialysate DA and 5-HT in a dose-, brain area-, and age-dependent manner. Notably, 2-Cl-4,5-MDMA more markedly increased dialysate DA in the NAc shell and mPFC of adult than adolescent rats, while the opposite was observed on dialysate 5-HT in the NAc shell, with adolescent rats being more responsive. Furthermore, 2-Cl-4,5-MDMA stimulated locomotion and stereotyped activity in both adolescent and adult rats, although to a greater extent in adolescents. Finally, 2-Cl-4,5-MDMA did not stimulate the emission of 50-kHz USVs. CONCLUSIONS: This is the first pharmacological characterization of 2-Cl-4,5-MDMA demonstrating that its neurochemical and behavioral effects may differ between adolescence and adulthood. These preclinical data could help understanding the central effects of 2-Cl-4,5-MDMA by increasing awareness on possible health damage in users.

Effects of association between resveratrol and ketamine on behavioral and biochemical analysis in mice.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a phenol commonly found in grapes and wine, has been associated as protective in experimental models involving alterations in different neurotransmitter systems. However, studies are reporting that resveratrol could have adverse effects. This study evaluated if the association of a low dose of ketamine and resveratrol could induce behavioral manifestations associated with biochemical alterations. Moreover, the effects of treatment with resveratrol and/or ketamine on monoamine oxidase (MAO) activity, oxidative stress markers, and IL-6 levels in the brain were also investigated. Male Swiss mice received a low dose of ketamine (20 mg/kg) for 14 consecutive days, and resveratrol (10, 30, or 100 mg/kg) from day 8 up to day 14 of the experimental period, intraperitoneally. Locomotor, stereotyped behavior, Y-maze, novel recognition object test (NORT), and social interaction were quantified as well as ex vivo analysis of MAO activity, IL-6 levels, and oxidative stress markers (TBARS and total thiol levels) in brain tissues. Ketamine per se reduced the number of bouts of stereotyped behavior on day 8 of the experimental period. Resveratrol per se reduced the locomotor and exploratory activity in the open field, the time of exploration of new objects in the NORT, MAO-A activity in the striatum and increased the IL-6 levels in the cortex. These effects were attenuated when the mice were co-treated with ketamine and resveratrol. There was a decrease in MAO-A activity in the cortex of mice treated with ketamine + resveratrol 100 mg/kg. No significant alterations were found in oxidative stress markers. Resveratrol does not appear to cause summative effects with ketamine on behavioral alterations. However, the effect of resveratrol per se, mainly on locomotor and exploratory activity, should be better investigated.

Social communication and restricted, repetitive behavior as assessed with a diagnostic tool for autism (ADOS-2) in women with anorexia nervosa.

OBJECTIVE: In anorexia nervosa (AN), the traits of autism spectrum disorder (ASD) are associated with poor outcomes. However, the subtle nature of these characteristics remains poorly understood. We investigated the in-depth patterns of ASD traits using Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) in women with AN. METHODS: Of 28 women with ICD-10 AN, 16 (age 19-30 years) participated in the ADOS-2, a video-recorded, semistructured diagnostic assessment for social communication and interaction and restricted, repetitive behaviors and interests related to ASD. None of the participants had previously been diagnosed with ASD. Other measurements included the Eating Disorder Examination Questionnaire and the Wechsler Abbreviated Scale of Intelligence-IV. RESULTS: Five individuals (18% of all, 31% of those assessed) scored above the cutoff for autism in ADOS-2. They had challenges in social communication and interaction, manifesting as sustained difficulties in social relationships and deficits in conversation skills. Few described being frequently misunderstood by others, including in the eating disorder treatment settings. Three individuals showed prominent restricted and repetitive behaviors such as ritual seeking, eating-related routines, sensory sensitivity related to food texture and selective eating, and intense interest in specific topics. The mean duration of AN in women above the cutoff was twice as long compared with those below (12.3 vs. 6.2 years). DISCUSSION: The ASD-related characteristics and behavior appear to contribute to the manifestation and duration of AN in a subgroup of women. Among these women, the traits of ASD appear to be mixed with eating disorder symptoms, which should be taken into account in the treatment.

Making physical activity fun and accessible to adults with intellectual disabilities: A pilot study of a gamification intervention.

BACKGROUND: Only about 9% of individuals with intellectual disabilities reach the government's physical activity (PA) recommendations. Combining gamification and technology seems particularly promising in overcoming personal and environmental barriers to PA participation. METHOD: Eighteen adults with varying levels of intellectual disabilities completed a pilot study to assess the initial effects of a cycling gamification intervention on levels of PA, fitness, psychosocial outcomes, and challenging behaviours. The study comprised three designs: pre-post single group, AB single-case, and qualitative. Social validity, implementation barriers and facilitators were also explored. RESULTS: Nearly all 18 participants cycled daily. Time and distance cycled daily increase during the intervention while a decrease in stereotyped behaviours was observed. Participants and staff found the intervention enjoyable and socially valid. CONCLUSIONS: Results of the multiple-design study suggest that gamification interventions may be a suitable, enjoyable, and promising way to contribute to PA participation of adults with intellectual disabilities.

Behavior of polar bear (Ursus maritimus) cubs post-den emergence at the Detroit Zoo.

In the wild, female polar bears (Ursus maritimus) with cubs may spend extended periods of time within the den following initial emergence. As a result, studying behavioral development of cubs at the denning site has been difficult and unreliable. Although care staff at zoological institutions have easier access to animals, every effort is made to minimize intrusions to maternal groups, which presents research limitations. Detroit Zoological Society staff used audio-equipped cameras installed in behind-the-scenes spaces to conduct approximately 9 weeks of monitoring on two female polar bear cubs of the same litter, one of whom (Laerke) was hand-reared while the other (Astra) was mother-reared. Monitoring spanned ages 14-24 weeks and consisted of 12, 5-min focal observations per observation day timed to evenly cover the entire 24-h day. Using generalized linear mixed models, we examined relationships between behavior and time of day, hour, and age. We also conducted descriptive analyses and used these to draw comparisons between the two cubs where appropriate. Despite different rearing environments, both cubs had highly comparable patterns of inactive, locomotory, and independent play behaviors. Astra generally decreased time spent nursing and in proximity to Suka as she aged. Data presented here represent a continuation of previous neonatal observations conducted on Astra, adding to the minimal body of knowledge currently available on first year polar bear cub development. We also report successful mitigation of stereotypic behavior in Laerke. Further studies of captive maternal groups can provide insight into this critical developmental stage, supporting both captive-based breeding efforts and in situ conservation efforts.

Do housing-induced changes in brain activity cause stereotypic behaviours in laboratory mice?

Abnormal repetitive stereotypic behaviours (SBs) (e.g. pacing, body-rocking) are common in animals with poor welfare (e.g. socially isolated/in barren housing). But how (or even whether) poor housing alters animals' brains to induce SBs remains uncertain. To date, there is little evidence for environmental effects on the brain that also correlate with individual SB performance. Using female mice from two strains (SB-prone DBA/2s; SB-resistant C57/BL/6s), displaying two forms of SB (route-tracing; bar-mouthing), we investigated how housing (conventional laboratory conditions vs. well-resourced 'enriched' cages) affects long-term neuronal activity as assessed via cytochrome oxidase histochemistry in 13 regions of interest (across cortex, striatum, basal ganglia and thalamus). Conventional housing reduced activity in the cortex and striatum. However, DBA mice had no cortical or striatal differences from C57 mice (just greater basal ganglia output activity, independent of housing). Neural correlates for individual levels of bar-mouthing (positive correlations in the substantia nigra and thalamus) were also independent of housing; while route-tracing levels had no clear neural correlates at all. Thus conventional laboratory housing can suppress cortico-striatal activity, but such changes are unrelated to SB (since not mirrored by congruent individual and strain differences). Furthermore, the neural correlates of SB at individual and strain levels seem to reflect underlying predispositions, not housing-mediated changes. To aid further work, hypothesis-generating model fit analyses highlighted this unexplained housing effect, and also suggested several regions of interest across cortex, striatum, thalamus and substantia nigra for future investigation (ideally with improved power to reduce risks of Type II error).

Lesions in a songbird vocal circuit increase variability in song syntax.

Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered syllables, controlled in part by the songbird premotor nucleus HVC (proper name). Here, we test whether one of HVC's recurrent inputs, mMAN (medial magnocellular nucleus of the anterior nidopallium), contributes to sequencing in adult male Bengalese finches (Lonchura striata domestica). Bengalese finch song includes several patterns: (1) chunks, comprising stereotyped syllable sequences; (2) branch points, where a given syllable can be followed probabilistically by multiple syllables; and (3) repeat phrases, where individual syllables are repeated variable numbers of times. We found that following bilateral lesions of mMAN, acoustic structure of syllables remained largely intact, but sequencing became more variable, as evidenced by 'breaks' in previously stereotyped chunks, increased uncertainty at branch points, and increased variability in repeat numbers. Our results show that mMAN contributes to the variable sequencing of vocal elements in Bengalese finch song and demonstrate the influence of recurrent projections to HVC. Furthermore, they highlight the utility of species with complex syntax in investigating neuronal control of ordered sequences.

The role of task preference in the effectiveness of response interruption and redirection.

Response interruption and redirection (RIRD) is a common treatment for automatically reinforced vocal stereotypy; it involves the contingent presentation of task instructions. Tasks that are included in RIRD are typically selected based on caregiver report, which may affect the efficacy of RIRD. The purpose of the current study was to evaluate the role of task preference in the efficacy of RIRD for four participants who engaged in vocal stereotypy. We conducted task-preference assessments and selected tasks of varying preferences to include in RIRD. For three out of four participants, the results showed that RIRD with higher preference tasks was not effective at reducing vocal stereotypy, whereas RIRD with lower preference tasks was effective for all participants.

Small apes adjust rhythms to facilitate song coordination.

Song coordination is a universal characteristic of human music. Many animals also produce well-coordinated duets or choruses that resemble human music. However, the mechanism and evolution of song coordination have only recently been studied in animals. Here, we studied the mechanism of song coordination in three closely related species of wild Nomascus gibbons that live in polygynous groups. In each species, song bouts were dominated by male solo sequences (referred to hereafter as male sequence), and females contributed stereotyped great calls to coordinate with males. Considering the function of rhythm in facilitating song coordination in human music and animal vocalizations, we predicted that adult males adjust their song rhythm to facilitate song coordination with females. In support of this prediction, we found that adult males produced significantly more isochronous rhythms with a faster tempo in male sequences that were followed by successful female great calls (a complete sequence with "introductory" and "wa" notes). The difference in isochrony and tempos between successful great call sequences and male sequences was smaller in N. concolor compared with the other two species, which may make it difficult for females to predict a male's precise temporal pattern. Consequently, adult females of N. concolor produced more failed great call (an incomplete sequence with only introductory notes) sequences. We propose that the high degree of rhythm change functions as an unambiguous signal that can be easily perceived by receivers. In this regard, gibbon vocalizations offer an instructive model to understand the origins and evolution of human music.

Environmental interventions reduced repetitive behavior in a mouse model.

Repetitive motor behaviors are associated with several neurodevelopmental disorders including autism spectrum disorder. Non-invasive environmental interventions that can ameliorate repetitive behavior and be introduced in early development could benefit many. In Experiment 1, we characterized the development of repetitive circling in mice reared in standard and enriched environments. Environmental enrichment was associated with reduced repetitive behavior. In Experiment 2, two weekly injections of an A2A adenosine receptor agonist reduced repetitive behavior in mice fed a ketogenic diet. Together, these two approaches modified the environment and reduced repetitive behavior with potential implications for increased functioning of the indirect basal ganglia pathway.

Physiological and behavioural adjustment of a wild rodent to laboratory conditions.

Wild animals are brought to captivity for different reasons, for example to be kept in zoos and rehabilitation centres, but also for basic research. Such animals usually undergo a process of adjustment to captive conditions. While this adjustment occurs on the behavioural and the physiological level, those are usually studied separately. The aim of this study was to assess both the physiological and behavioural responses of wild wood mice, Apodemus sylvaticus, while adjusting to laboratory conditions. Over the course of four weeks, we measured in wild-caught mice brought to the laboratory faecal corticosterone metabolites and body mass as physiological parameters, stereotypic behaviour and nest-quality, as welfare-linked behavioural parameters, and four personality measures as additional behavioural parameters. The results of our study indicate that mice exhibited an adjustment in both behaviour and physiology over time in the laboratory. While the hormonal stress response decreased significantly, body mass and the proportion of stereotypic behaviours showed a tendency to increase over time. The slight increase of stereotypic behaviours, although not statistically significant, suggests the development of repetitive and non-functional behaviours as a response to laboratory conditions. However, we suggest that those behaviours might have been used by animals as a coping strategy to decrease the physiological stress response. Other behavioural parameters measured, such as boldness and nestbuilding behaviour were stable over time. The information obtained in the present study hints at a complex interplay between behavioural and physiological adjustments of wild animals to laboratory conditions, which should be considered when intending to use wild animals in experimental research.

Effects of temporary access to environmental enrichment on measures of laboratory mouse welfare.

Laboratory mice are typically housed in "shoebox" cages with limited opportunities to engage in natural behaviour. Temporary access to environments with increased space and complexity (playpens) may improve mouse welfare. Previous work by our group has shown that mice are motivated to access and use these environments, but it is unknown how other aspects of welfare are impacted. Female C57BL/6J, BALB/cJ, and DBA/2J mice (n = 21; 7 mice per strain) were housed in mixed-strain trios and given temporary access to a large playpen with their cage mates three times per week. Control mice (n = 21; 7 mice per strain) remained in their home cages. Home cage behaviour (development of stereotypic behaviour over time, aggression following cage-changing) and anxiety tests were used to assess how playpen access impacted welfare. Contrary to our predictions, we found increased time spent performing stereotypies in playpen mice; this difference may be related to negative emotional states, increased motivation to escape the home cage, or active coping strategies. Playpen access resulted in strain-dependent improvements in aggression and some measures of anxiety. Aggression was lower for C57BL/6J mice in the playpen treatment following cage changing than it was for C57BL/6J control mice, while playpen mice, and particularly the C57BL/6J strain, spent more time in the center of the open field test and produced fewer fecal boli during anxiety testing, supporting other research showing that strain differences play an important role in behaviour and stress resiliency.

[Autism and camouflage]. / Autismo y camuflaje.

Autism is a neurobiologically based neurodevelopmental disorder with high prevalence and a clear predominance in males. It is characterized by deficits in social cognition and communication, restricted interests, and stereotyped behaviors, frequently associated with sensory dysfunction others neurodevelopmental conditions, neuropsychiatric disorders, epilepsy, and/or sleep disorders. This condition will accompany people throughout their lives, which will generate various support and treatment needs. People with autism often need to "fit in" and for this they use techniques such as camouflage, also called masking. This attitude has been observed in people with typical development and in people with autism in childhood, adolescence and adult life, although in autistic people this behavior is more intense and takes longer and with more frequency and intensity in autistic adult women. This could explain the underreporting of autism, the later diagnosis, the delay in the therapeutic approach, and the greater presence of anxiety and depression disorders related to the effort that "appearing normal" implies. Even though camouflage people appear to be "normal" and fit in perfectly, this is not an attitude that we should promote and, on the contrary, it is imperativeto work to improve the environment and the understanding of each person. In this paper we will analyze the clinical aspects, their relationship with age, sex, and ways of detecting it.

El autismo es un trastorno del neurodesarrollo de base neurobiológica con alta prevalencia y claro predomino en varones. Se caracteriza por déficits en la cognición social y la comunicación, intereses restringidos y conductas estereotipadas, frecuentemente asociado a disfunciones sensoriales, otras condiciones del neurodesarrollo, trastornos neuropsiquiátricos, epilepsia y/o trastornos de sueño. Esta condición acompañará a las personas a lo largo de toda la vida, lo cual generará diversas necesidades de apoyo y tratamientos. Las personas con autismo muchas veces necesitan "encajar", para ello utilizan técnicas como el camuflaje, también denominada enmascaramiento. Esta actitud se ha observado en personas con desarrollo típico y en personas con autismo en la infancia, adolescencia y vida adulta, aunque en los autistas esta conducta es más intensa y lleva más tiempo, y se la identifica con más frecuencia e intensidad en mujeres adultas autistas. Esto podría explicar el subregistro de autismo, el diagnóstico más tardío, el retraso en el abordaje terapéutico y la mayor presencia de trastornos de ansiedad y depresión relacionados al esfuerzo que implica "parecer normal". Si bien las personas al camuflar parecen ser "normales" y encajan perfectamente, ésta no es una actitud que debiera propiciarse, por el contrario es imperativo trabajar para mejorar el entorno y la comprensión de cada persona. En este trabajo analizamos los aspectos clínicos, su relación con la edad, sexo, y formas de detección del mismo.

Relationship between serum cortisol levels, stereotypies, and the presence of autism spectrum disorder in patients with severe intellectual disability.

Stereotypies are one of the diagnostic criteria for autism spectrum disorder (ASD) and are common to both ASD and intellectual disability (ID). Previous studies have been inconclusive, with some showing a positive correlation between stereotypies and cortisol, while others have shown a negative correlation. We hypothesised and investigated the presence of ASD as one of the variables involved in this discrepancy. We tested the following hypotheses on serum cortisol in a total of 84 hospitalised patients with severe ID and ASD with severe ID. Hypothesis (1) Higher levels of stereotypies are associated with higher levels of serum cortisol. Hypothesis (2) The presence of ASD will moderate the association between stereotypies and high serum cortisol levels. The results of the analysis supported hypotheses (1) and (2). We also found that in the population with ID, serum cortisol levels were significantly lower in the ASD group compared to the non-ASD group. The present findings that the association between stereotypies and serum cortisol levels in people with severe ID is moderated by the presence of ASD suggest that the stress response system may function differently in people with ID and ASD than in the general population.

The NMDA receptor modulator zelquistinel durably relieves behavioral deficits in three mouse models of autism spectrum disorder.

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders characterized by deficient social communication and interaction together with restricted, stereotyped behaviors. Currently approved treatments relieve comorbidities rather than core symptoms. Since excitation/inhibition balance and synaptic plasticity are disrupted in ASD, molecules targeting excitatory synaptic transmission appear as highly promising candidates to treat this pathology. Among glutamatergic receptors, the NMDA receptor has received particular attention through the last decade to develop novel allosteric modulators. Here, we show that positive NMDA receptor modulation by zelquistinel, a spirocyclic ß-lactam platform chemical, relieves core symptoms in two genetic and one environmental mouse models of ASD. A single oral dose of zelquistinel rescued, in a dose-response manner, social deficits and stereotypic behavior in Shank3Δex13-16-/- mice while chronic intraperitoneal administration promoted a long-lasting relief of such autistic-like features in these mice. Subchronic oral mid-dose zelquistinel treatment demonstrated durable effects in Shank3Δex13-16-/-, Fmr1-/- and in utero valproate-exposed mice. Carry-over effects were best maintained in the Fmr1 null mouse model, with social parameters being still fully recovered two weeks after treatment withdrawal. Among recently developed NMDA receptor subunit modulators, zelquistinel displays a promising therapeutic potential to relieve core symptoms in ASD patients, with oral bioavailability and long-lasting effects boding well for clinical applications. Efficacy in three mouse models with different etiologies supports high translational value. Further, this compound represents an innovative pharmacological tool to investigate plasticity mechanisms underlying behavioral deficits in animal models of ASD.

Altered dynamic functional and effective connectivity in drug-naive children with Tourette syndrome.

Tourette syndrome (TS) is a developmental neuropsychiatric disorder characterized by repetitive, stereotyped, involuntary tics, the neurological basis of which remains unclear. Although traditional resting-state MRI (rfMRI) studies have identified abnormal static functional connectivity (FC) in patients with TS, dynamic FC (dFC) remains relatively unexplored. The rfMRI data of 54 children with TS and 46 typically developing children (TDC) were analyzed using group independent component analysis to obtain independent components (ICs), and a sliding-window approach to generate dFC matrices. All dFC matrices were clustered into two reoccurring states, the state transition metrics were obtained. We conducted Granger causality and nodal topological analyses to further investigate the brain regions that may play the most important roles in driving whole-brain switching between different states. We found that children with TS spent more time in state 2 (PFDR < 0.001), a state characterized by strong connectivity between ICs, and switched more quickly between states (PFDR = 0.025) than TDC. The default mode network (DMN) may play an important role in abnormal state transitions because the FC that changed the most between the two states was between the DMN and other networks. Additionally, the DMN had increased degree centrality, efficiency and altered causal influence on other networks. Certain alterations related to executive function (r = -0.309, P < 0.05) and tic symptom ratings (r = 0.282; 0.413, P < 0.05) may represent important aspects of the pathophysiology of TS. These findings facilitate our understanding of the neural basis for the clinical presentation of TS.

Psychogenic Hyperphagia: Excessive Eating as Stereotypy in a Patient with Catatonia.

Catatonia is a complex syndrome with unique cognitive, psychomotor, and mood features. Mannerisms and stereotypies are catatonic signs that have been extensively observed and described in the literature, mostly in the context of movements or motor acts. Stereotypies are commonly described as repetitive psychomotor or verbal acts with the abnormality not inherent in the act but in its frequency. Mannerisms, like stereotypies, are repetitive psychomotor or verbal acts, but they are fundamentally odd in nature. Recently, several reports have described these phenomena in the context of complex behaviors, such as eating and drinking. Identification and appreciation of personal and cultural norms, in addition to a careful analysis of behavioral processes and actions, are important tools for clinicians to identify these potentially elusive and often missed patterns of behavior in patients with catatonia. We present the case of a 30-year-old male with a psychiatric history of treatment-resistant, recurrent major depressive disorder with psychotic features who presented to the inpatient psychiatric unit with signs of catatonia, including repeated, purposeless eating. The patient's chart was reviewed, and a literature review was conducted using PubMed with the keywords catatonia, stereotypies, mannerisms, and hyperphagia. The patient, who was diagnosed with catatonia and expressed hyperphagia as a stereotypy, responded to lorazepam. This case shows that hyperphagia may present as a stereotypy in patients with catatonia.

Examining Procedural Variations of Delivering Competing Stimuli in the Treatment of Stereotypy.

Competing stimulus assessments (CSA) are effective tools for identifying stimuli that compete with automatically reinforced behavior. However, Jennett et al. suggests there are cases for which non-contingent access to competing stimuli are insufficient at decreasing target responding and additional treatment components may be necessary. The purpose of the current study was to examine procedural variations (i.e., rotating competing items and prompted engagement) when presenting competing stimuli on increasing functional engagement and decreasing stereotypy. Following a functional analysis, a CSA was conducted to identify competing stimuli for four individuals with autism. Items identified were then used with two procedural variations. Levels of stereotypy, functional engagement, and item contact were measured. Results showed that for two participants both treatments were effective, while for the other two participants prompting functional engagement was more effective. Prompting functional engagement is likely a productive strategy for enhancing engagement with competing stimuli for automatically reinforced problem behavior as it may result in functional engagement becoming reinforcing in and of itself.

Environmental enrichment reduces restricted repetitive behavior by altering gray matter microstructure.

Restricted, repetitive behaviors are common symptoms in neurodevelopmental disorders including autism spectrum disorder. Despite being associated with poor developmental outcomes, repetitive behaviors remain poorly understood and have limited treatment options. Environmental enrichment attenuates the development of repetitive behaviors, but the exact mechanisms remain obscure. Using the C58 mouse model of repetitive behavior, we performed diffusion tensor imaging to examine microstructural alterations associated with the development of repetitive behavior and its attenuation by environmental enrichment. The C57BL/6 mouse strain, which displays little or no repetitive behavior, was used as a control group. We observed widespread differences in diffusion metrics between C58 mice and C57BL/6 mice. In juvenile C58 mice, repetitive motor behavior displayed strong negative correlations with fractional anisotropy in multiple gray matter regions, whereas in young adult C58 mice, high repetitive motor behavior was most strongly associated with lower fractional anisotropy and higher radial diffusivity in the striatum. Environmental enrichment increased fractional anisotropy and axial diffusivity throughout gray matter regions in the brains of juvenile C58 mice and overlapped predominantly with cerebellar and sensory regions associated with repetitive behavior. Our results suggest environmental enrichment reduces repetitive behavior development by altering gray matter microstructure in the cerebellum, medial entorhinal cortex, and sensory processing regions in juvenile C58 mice. Under standard laboratory conditions, early pathology in these regions appears to contribute to later striatal and white matter dysfunction in adult C58 mice. Future studies should examine the role these regions play in the development of repetitive behavior and the relationship between sensory processing and cerebellar deficits and repetitive behavior.