6 Nov 2015

Age-related changes in rich-club structure in neurotypical and autistic brain networks

Watanabe T, Rees G. Age-associated changes in rich-club organisation in autistic and neurotypical human brains. Sci Rep. 2015;5:16152. doi:10.1038/srep16152.

 

Macroscopic structural networks in the human brain have a rich-club architecture comprising both highly inter-connected central regions and sparsely connected peripheral regions. Recent studies show that disruption of this functionally efficient organisation is associated with several psychiatric disorders.

However, despite increasing attention to this network property, whether age-associated changes in rich-club organisation occur during human adolescence remains unclear.

Here, analysing a publicly shared diffusion tensor imaging dataset, we found that, during adolescence, brains of typically developing (TD) individuals showed increases in rich-club organisation and inferred network functionality, whereas individuals with autism spectrum disorders (ASD) did not. These differences between TD and ASD groups were statistically significant for both structural and functional properties. Moreover, this typical age-related changes in rich-club organisation were characterised by progressive involvement of the right anterior insula. In contrast, in ASD individuals, did not show typical increases in grey matter volume, and this relative anatomical immaturity was correlated with the severity of ASD social symptoms.

These results provide evidence that rich-club architecture is one of the bases of functionally efficient brain networks underpinning complex cognitive functions in adult human brains. Furthermore, our findings suggest that immature rich-club organisation might be associated with some neurodevelopmental disorders.

22 Sept 2015

Six-week oxytocin seems to work for autistic social symptom

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Watanabe T, Kuroda M, Kuwabara H, Aoki Y, Iwashiro N, Tatsunobu N, Takao H, Nippashi Y, Kawakubo Y, Kunimatsu A, Kasai K, Yamasue H (2015) Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain:awv249.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder but is not given established medical treatment. Despite previous literatures showing temporal positive effects of single-dose administration of oxytocin in experimental settings, until now, it is still controversial whether such potentially beneficial reactions can yield clinically therapeutic effects after long-term intervention, which is currently impeding further development of medications for the developmental disorder.

Here, we performed a randomised, double-blind, placebo-controlled, crossover trial, and found that six-week continual administration of oxytocin significantly reduced the clinically evaluated core symptoms specifically in the social domain. Critically, this clinical improvement was associated with increases in brain activity and functional connectivity in medial prefrontal cortex. Furthermore, using the same psychological task as in our recent single-dose oxytocin trial, we showed that the long and continual administration did not magnify the effect sizes seen in the single-dose intervention, which might have made it difficult for previous trials to detect significant effects of long-term administration of this neuropeptide.

The current study, to our best of knowledge, provides the first direct clinical and biological evidence for therapeutic effects of long-term oxytocin administration; in addition, this research also indicates that we still need to seek the optimal dosing regimen to maximize such effects of continual oxytocin interventions. We believe that this study provides major observations that will stimulate and guide the future development of novel medical treatments for ASD.

27 Mar 2015

[New Paper] Cortico-basal-ganglia network for response inhibition

Watanabe, T., Hanajima, R., Shirota, Y., Tsutsumi, R., Shimizu, T., Hayashi, T., et al. (2015). Effects of rTMS of Pre-Supplementary Motor Area on Fronto Basal Ganglia Network Activity during Stop-Signal Task. The Journal of Neuroscience: 35(12), 4813–4823. 

Response inhibition is one of the key cognitive functions that enable humans to realise their own intentions, and is considered to be supported by fronto-basal-ganglia network. However, causal relationship inside the network has remained unclear.

Here, combining relatively long-lasting types of repetitive transcranial magnetic stimulation (rTMS) with functional magnetic resonance imaging (fMRI), we revealed causal effects of presupplementary motor area (PreSMA) on the network. Using well-established stop-signal task, we found that excitatory and inhibitory rTMS over PreSMA induced significant activity changes in a neural pathway consisting of PreSMA, striatum (STR) and globus pallidus pars interna (GPi). Furthermore, this effect on PreSMA–STR–GPi network activity was highly predictive of behavioral modulations. Interestingly, such causal effects were not seen in right inferior prefrontal cortex or subthalamic nucleus, both of which have been considered to mainly constitute neural mechanisms for response inhibition.

The work will not only demonstrate a causal relationship from PreSMA to basal ganglia during response inhibition, but also add direct evidence for the notion that the fronto-basal-ganglia network for response inhibition comprises multiple top-down regulation pathways in humans. 

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[New Paper] Energy landscape during bistable perception

Watanabe, T., Masuda, N., Megumi, F., Kanai, R., & Rees, G. (2014). Energy landscape and dynamics of brain activity during human bistable perception. Nature Communications, 5, 4765. doi:10.1038/ncomms5765

Bistable visual perception is a key paradigm for probing human and animal brainfunctions, and several studies have now shown an intriguing link between the dynamics of bistable perception and the grey matter volume in particular areas of cortex. However, the mechanisms that might link such anatomical features of the brain to subjective experience remained unclear. In this study, we established just such a link by characterising the energy landscapes of brain activity during bistable perception.

During bistable visual perception, we found that human brain activity patterns transited between three spatially distributed energy states. For each participant, this energy landscape predicted both the behavioural dynamics of their perceptual reports and the structural characteristics of focal cortical regions. These findings suggest that the dynamics of brain activity determined by the features of the energy landscape link individual differences in brain anatomy and subjective visual experience.

 

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