Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism

Autism spectrum disorder is a prevalent neurodevelopmental disorder with no established pharmacological treatment for its core symptoms. Although previous literature has shown that single-dose administration of oxytocin temporally mitigates autistic social behaviours in experimental settings, it remains in dispute whether such potentially beneficial responses in laboratories can result in clinically positive effects in daily life situations, which are measurable only in long-term observations of individuals with the developmental disorder undergoing continual oxytocin administration. Here, to address this issue, we performed an exploratory, randomized, double-blind, placebo-controlled, crossover trial including 20 high-functional adult males with autism spectrum disorder. Data obtained from 18 participants who completed the trial showed that 6-week intranasal administration of oxytocin significantly reduced autism core symptoms specific to social reciprocity, which was clinically evaluated by Autism Diagnostic Observation Scale (P = 0.034, PFDR < 0.05, Cohen's d = 0.78). Critically, the improvement of this clinical score was accompanied by oxytocin-induced enhancement of task-independent resting-state functional connectivity between anterior cingulate cortex and dorso-medial prefrontal cortex (rho = -0.60, P = 0.011), which was measured by functional magnetic resonance imaging. Moreover, using the same social-judgement task as used in our previous single-dose oxytocin trial, we confirmed that the current continual administration also significantly mitigated behavioural and neural responses during the task, both of which were originally impaired in autistic individuals (judgement tendency: P = 0.019, d = 0.62; eye-gaze effect: P = 0.03, d = 0.56; anterior cingulate activity: P = 0.00069, d = 0.97; dorso-medial prefrontal activity: P = 0.0014, d = 0.92; all, PFDR < 0.05). Furthermore, despite its longer administration, these effect sizes of the 6-week intervention were not larger than those seen in our previous single-dose intervention. These findings not only provide the evidence for clinically beneficial effects of continual oxytocin administration on the core social symptoms of autism spectrum disorder with suggesting its underlying biological mechanisms, but also highlight the necessity to seek optimal regimens of continual oxytocin treatment in future studies

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

Diminished Medial Prefrontal Activity behind Autistic Social Judgments of Incongruent Information

Individuals with autism spectrum disorders (ASD) tend to make inadequate social judgments, particularly when the nonverbal and verbal emotional expressions of other people are incongruent. Although previous behavioral studies have suggested that ASD individuals have difficulty in using nonverbal cues when presented with incongruent verbal-nonverbal information, the neural mechanisms underlying this symptom of ASD remain unclear. In the present functional magnetic resonance imaging study, we compared brain activity in 15 non-medicated adult males with high-functioning ASD to that of 17 age-, parental-background-, socioeconomic-, and intelligence-quotient-matched typically-developed (TD) male participants. Brain activity was measured while each participant made friend or foe judgments of realistic movies in which professional actors spoke with conflicting nonverbal facial expressions and voice prosody. We found that the ASD group made significantly less judgments primarily based on the nonverbal information than the TD group, and they exhibited significantly less brain activity in the right inferior frontal gyrus, bilateral anterior insula, anterior cingulate cortex/ventral medial prefrontal cortex (ACC/vmPFC), and dorsal medial prefrontal cortex (dmPFC) than the TD group. Among these five regions, the ACC/vmPFC and dmPFC were most involved in nonverbal-information-biased judgments in the TD group. Furthermore, the degree of decrease of the brain activity in these two brain regions predicted the severity of autistic communication deficits. The findings indicate that diminished activity in the ACC/vmPFC and dmPFC underlies the impaired abilities of individuals with ASD to use nonverbal content when making judgments regarding other people based on incongruent social information

Observation of radio emissions from electron beams using an ice target

To observe high energy cosmogenic neutrinos above 50 PeV, the large neutrino telescope ARA is being built at the South Pole. The ARA telescope detects neutrinos by observing radio signals by the Askaryan effect. We performed an experiment using 40 MeV electron beams of the Telescope Array Electron Light Source to verify the understanding of the Askaryan emission as well as the detector responses used in the ARA experiment. Clear coherent polarized radio signals were observed with and without an ice target. We found that the observed radio signals are consistent with simulation, showing that our understanding of the radio emissions and the detector responses are within the systematic uncertainties of the ARAcalTA experiment which is at the level of 30%

Study of Microwave Radiation from the Electron Beam at the Telescope Array Site

International audienceThe Telescope Array (TA) experiment installed the electron accelerator in order to calibrate the fluorescence detector by shooting 40 MeV electrons into the atmosphere. This accelerator also works to investigate the radio detection techniques used for the cosmic ray observations. Using this accelerator, four experimental groups have studied individual radio detection methods at different frequency bands ranging from 50 MHz to 12 GHz. All of these experiments have observed the microwave radiation from the electron beam itself. We have studied the radiation by combining all the measured results and constructed a model of this phenomena. Results of four experiments and model expectation are in good agreement within the systematic uncertainty

Coherent radio emission from the electron beam sudden appearance

International audienceWe report on radio frequency measurements of the electron beam sudden appearance signal from the Telescope Array Electron Light Source (TA-ELS). The TA-ELS is constructed to calibrate the Telescope Array fluorescence telescope, and as such it can be used to mimic a cosmic-ray or neutrino induced particle cascade. This makes the TA-ELS the perfect facility to study new detection techniques such as the radio detection method. We report on the data obtained by four independent radio detection set-ups. Originally searching for either the direct Askaryan radio emission, or a radar echo from the induced plasma, all these experiments measured a very strong transient signal when the beam exits the accelerator. Due to the different scope of the individual experiments, we have detected the beam sudden appearance signal at different frequencies, ranging between 50 MHz and 12.5 GHz. The direct application in nature for this signal is found in cosmic-ray or neutrino induced particle cascades traversing through different media, such as air, ice, and rock. These measurements are compared to the theoretical predictions for this signal, where it follows that theory and experiment match very well over the full spectrum