Altered Plasticity of Prefrontal Cortex in Adult Autism Spectrum Disorder

Background: Altered metaplasticity is hypothesized in psychiatric disorders including neurodevelopmental disorders. However, stimulation-induced neuroplastic changes in human prefrontal cortex have not been sufficiently elucidated due to lack of reliable biomarkers like motor evoked potentials (MEP).

Objectives: The study was aimed to establish reliable biomarkers of TMS-evoked potentials (TEP), which could evaluate the neuroplasticity in the heteromodal association cortices.

Methods: Neurophysiological changes followed by rTMS over dorsolateral prefrontal cortex (DLPFC) were longitudinally investigated using resting-state EEG (64ch recording) and TEP. TEP measurements followed by intermittent theta burst stimulation (iTBS) or sham stimulation were applied to twenty adult patients with autism spectrum disorder (ASD) and 21 matched healthy adults of typical development (TD).

Results: TEP components (mainly N45) revealed that facilitatory iTBS could enhance prefrontal TEP amplitudes for around an hour in healthy volunteers as compared with sham condition (t=2.37, p=0.026), accompanied by tentative cognitive enhancement in working memory task. However, adult ASD patients did not show the enhancement of TEP components and also cognitive enhancement. In terms of responder rate, 67% of TD adults and 25% of ASD adults were electrophysiological responders, which showed N45 amplitude enhancement more than 2 SD range of N45 amplitude variation observed in the sham group.

Conclusions: The TEP component of N45 could be a candidate for biomarker for functional neuroplasticity induced by rTMS. The present result suggested that prefrontal cortex of adult ASD may not have enough capacity to induce the long-term potentiation (LTP)-like effects, possibly due to saturated synaptic strength.