Nicole J. Rinehart

Intranasal Oxytocin Improves Emotion Recognition for Youth with Autism Spectrum Disorders

BACKGROUND A diagnostic hallmark of autism spectrum disorders is a qualitative impairment in social communication and interaction. Deficits in the ability to recognize the emotions of others are believed to contribute to this. There is currently no effective treatment for these problems. METHODS In a double-blind, randomized, placebo-controlled, crossover design, we administered oxytocin nasal spray (18 or 24 IU) or a placebo to 16 male youth aged 12 to 19 who were diagnosed with Autistic or Aspergers Disorder. Participants then completed the Reading the Mind in the Eyes Task, a widely used and reliable test of emotion recognition. RESULTS In comparison with placebo, oxytocin administration improved performance on the Reading the Mind in the Eyes Task. This effect was also shown when analysis was restricted to the younger participants aged 12 to 15 who received the lower dose. CONCLUSIONS This study provides the first evidence that oxytocin nasal spray improves emotion recognition in young people diagnosed with autism spectrum disorders. Findings suggest the potential of earlier intervention and further evaluation of oxytocin nasal spray as a treatment to improve social communication and interaction in young people with autism spectrum disorders.

Movement preparation in high-functioning autism and Asperger disorder: a serial choice reaction time task involving motor reprogramming.

Autism and Asperger disorder have long been associated with movement abnormalities, although the neurobehavioural details of these abnormalities remain poorly defined. Clumsiness has traditionally been associated with Asperger disorder but not autism, although this is controversial. Others have suggested that both groups demonstrate a similar global motor delay. In this study we aimed to determine whether movement preparation or movement execution was atypical in these disorders and to describe any differences between autism and Asperger disorder. A simple motor reprogramming task was employed. The results indicated that individuals with autism and Asperger disorder have atypical movement preparation with an intact ability to execute movement. An atypical deficit in motor preparation was found in Asperger disorder, whereas movement preparation was characterized by a “lack of anticipation” in autism. The differences in movement preparation profiles in these disorders were suggested to reflect differential involvement of the fronto-striatal region, in particular the supplementary motor area and anterior cingulate.

Interpersonal motor resonance in autism spectrum disorder: evidence against a global "mirror system" deficit.

The mirror neuron hypothesis of autism is highly controversial, in part because there are conflicting reports as to whether putative indices of mirror system activity are actually deficient in autism spectrum disorder (ASD). Recent evidence suggests that a typical putative mirror system response may be seen in people with an ASD when there is a degree of social relevance to the visual stimuli used to elicit that response. Individuals with ASD (n = 32) and matched neurotypical controls (n = 32) completed a transcranial magnetic stimulation (TMS) experiment in which the left primary motor cortex (M1) was stimulated during the observation of static hands, individual (i.e., one person) hand actions, and interactive (i.e., two person) hand actions. Motor-evoked potentials (MEP) were recorded from the contralateral first dorsal interosseous, and used to generate an index of interpersonal motor resonance (IMR; a putative measure of mirror system activity) during action observation. There was no difference between ASD and NT groups in the level of IMR during the observation of these actions. These findings provide evidence against a global mirror system deficit in ASD, and this evidence appears to extend beyond stimuli that have social relevance. Attentional and visual processing influences may be important for understanding the apparent role of IMR in the pathophysiology of ASD.

White‐matter abnormalities in attention deficit hyperactivity disorder: A diffusion tensor imaging study

Current evidence suggests that attention deficit hyperactivity disorder (ADHD) involves dysfunction in wide functional networks of brain areas associated with attention and cognition. This study examines the structural integrity of white‐matter neural pathways, which underpin these functional networks, connecting fronto‐striatal and fronto‐parietal circuits, in children with ADHD. Fifteen right‐handed 8 to 18‐year‐old males with ADHD‐combined type and 15 right‐handed, age, verbal, and performance IQ‐matched, healthy males underwent diffusion tensor imaging. A recent method of tract‐based spatial statistics was used to examine fractional anisotropy (FA) and mean diffusivity within major white‐matter pathways throughout the whole‐brain. White‐matter abnormalities were found in several distinct clusters within left fronto‐temporal regions and right parietal‐occipital regions. Specifically, participants with ADHD showed greater FA in white‐matter regions underlying inferior parietal, occipito‐parietal, inferior frontal, and inferior temporal cortex. Secondly, eigenvalue analysis suggests that the difference in FA in ADHD may relate to a lesser degree of neural branching within key white‐matter pathways. Tractography methods showed these regions to generally form part of white‐matter pathways connecting prefrontal and parieto‐occipital areas with the striatum and the cerebellum. Our findings demonstrate anomalous white‐matter development in ADHD in distinct cortical regions that have previously been shown to be dysfunctional or hypoactive in fMRI studies of ADHD. These data add to an emerging picture of abnormal development within fronto‐parietal cortical networks that may underpin the cognitive and attentional disturbances associated with ADHD. Hum Brain Mapp, 2009.

A Deficit in Shifting Attention Present in High-Functioning Autism but not Asperger’s Disorder:

The aim of this study was to examine executive functioning, in particular, attentional set-shifting deficits in high-functioning autism (n = 12) and Asperger’s disorder (n = 12). A large or global digit composed of smaller or local digits was presented during each trial. The participants indicated the presence of 1s or 2s by pressing the appropriate button. These targets could appear globally or locally. Relative to IQ, sex and age matched controls, reaction time to global targets in individuals with autism was retarded when the previous target appeared locally. This deficiency in shifting from local to global processing, however, was not observed in individuals with Asperger’s disorder. The theoretical and neurobiological significance of this dissociation in executive functioning in these clinically related disorders was explored.

Gait function in newly diagnosed children with autism: Cerebellar and basal ganglia related motor disorder.

We investigated gait in newly diagnosed children with autism. From our previous study with 6- to 14-year-olds, we hypothesized that motor symptoms indicative of basal ganglia and cerebellar dysfunction would appear across the developmental trajectory of autism. Two groups were recruited: children with autism (eight males, three females; mean age 5 y 10 mo [SD 9 mo]; range 4 y 4 mo-6 y 9 mo) and a comparison group of typically developing children (eight males, three females; mean age 5 y 9 mo [SD 1 y 1 mo]; range 4 y 3 mo-7 y 2 mo). The GAITRite Walkway was used to gather data from average gait and intra-walk measurements. Experienced physiotherapists analyzed gait qualitatively. Groups were matched according to age, height, weight, and IQ; although not statistically significant, IQ was lower in the group with autism. Spatiotemporal gait data for children with autism were compatible with findings from patients with cerebellar ataxia: specifically, greater difficulty walking along a straight line, and the coexistence of variable stride length and duration. Children with autism were also less coordinated and rated as more variable and inconsistent (i.e. reduced smoothness) relative to the comparison group. Postural abnormalities in the head and trunk suggest additional involvement of the fronto-striatal basal ganglia region. Abnormal gait features are stable across key developmental periods and are, therefore, promising for use in clinical screening for autism.

Autism and ADHD: How far have we come in the comorbidity debate?

The potential for the coexistence of the developmental disorders autism and attention-deficit/hyperactivity disorder (ADHD) in any one individual has for a long time been a contentious issue. While from a neurobiological perspective it is possible, and even highly likely, that ADHD and autism might clinically co-exist, our major diagnostic classification systems (DSM-IV-TR and ICD-10) currently preclude such a dual-diagnosis. The aim of the current review is to summarise current diagnostic criteria and treatment strategies for the two disorders, relevant theories of developmental dysfunction, and update the state of the debate regarding comorbidity. Evidence from clinical, neuroimaging and neuropsychological domains is considered, and similarities and differences between the two disorders are identified. Suggestions for future research into the comorbid profiles of these disorders are proposed, with a strong emphasis placed on the neuropsychological assessment of executive functioning as a potentially useful tool for both identifying similarities, and differentiating the disorders.

Right parietal dysfunction in children with attention deficit hyperactivity disorder, combined type : a functional MRI study

Attention deficit hyperactivity disorder, combined type (ADHD-CT) is associated with spatial working memory deficits. These deficits are known to be subserved by dysfunction of neural circuits involving right prefrontal, striatal and parietal brain regions. This study determines whether decreased right prefrontal, striatal and parietal activation with a mental rotation task shown in adolescents with ADHD-CT is also evident in children with ADHD-CT. A cross-sectional study of 12 pre-pubertal, right-handed, 8–12-year-old boys with ADHD-CT and 12 pre-pubertal, right-handed, performance IQ-matched, 8–12-year-old healthy boys, recruited from local primary schools, was completed. Participants underwent functional magnetic resonance imaging while performing a mental rotation task that requires spatial working memory. The two groups did not differ in their accuracy or response times for the mental rotation task. The ADHD-CT group showed significantly less activation in right parieto-occipital areas (cuneus and precuneus, BA 19), the right inferior parietal lobe (BA 40) and the right caudate nucleus. Our findings with a child cohort confirm previous reports of right striatal-parietal dysfunction in adolescents with ADHD-CT. This dysfunction suggests a widespread maturational deficit that may be developmental stage independent.

Autism and Asperger's disorder: Are they movement disorders involving the cerebellum and/or basal ganglia?

Autism and Aspergers disorder (AD) are childhood developmental disorders of unknown aetiology. Autism and AD share several behavioural features, and it is not clear whether they are distinct disorders or variants of the same disorder. Recent studies indicate that disordered movement may be another feature of autism and AD, and that this may reflect dysfunction within the frontostriatal and/or cerebellar motor circuits. While disordered movement in autism and AD has been examined in a variety of ways, it is relatively under-researched compared to the cognitive, affective, and behavioural disturbances seen in these disorders. This review examines the role of the frontostriatal and cerebellar motor systems in the behavioural features of autism and AD, with gait as a proxy, and discusses difficulties with their diagnosis and their possible pathogenesis.

The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial

BACKGROUND There is increasing interest in oxytocin as a therapeutic to treat social deficits in autism spectrum disorders (ASD). The aim of this study was to investigate the efficacy of a course of oxytocin nasal spray to improve social behavior in youth with ASD. METHODS In a double-blind, placebo-controlled trial across two Australian university sites between February 2009 and January 2012, 50 male participants aged between 12 and 18 years, with Autistic or Aspergers Disorder, were randomized to receive either oxytocin (n = 26) or placebo (n = 24) nasal sprays (either 18 or 24 International Units), administered twice-daily for 8 weeks. Participants were assessed at baseline, after 4- and 8-weeks of treatment, and at 3-month follow-up. Primary outcomes were change in total scores on the caregiver-completed Social Responsiveness Scale and clinician-ratings on the Clinical Global Impressions-Improvement scale. Secondary assessments included caregiver reports of repetitive and other developmental behaviors and social cognition. CLINICAL TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry www.anzctr.org.au ACTRN12609000513213. RESULTS Participants who received oxytocin showed no benefit following treatment on primary or secondary outcomes. However, caregivers who believed their children received oxytocin reported greater improvements compared to caregivers who believed their child received placebo. Nasal sprays were well tolerated and there was no evidence of increased side effects resulting from oxytocin administration. CONCLUSIONS This is the first evaluation of the efficacy for a course of oxytocin treatment for youth with ASD. Although results did not suggest clinical efficacy, further research is needed to explore alternative delivery methods, earlier age of intervention, and the influence of caregiver expectation on treatment response.