Autistic brain dynamics and responsivity to multi-target pharmaco-challenge with Cannabidivarin (CBDV)

Autism is associated with differences in the functional connectivity of whole-brain networks but results vary across studies. One reason for this is that conventional analyses average functional connectivity across the scan, ignoring potential group differences in dynamic (time-varying) brain fluctuations which may be captured across an fMRI session. Another possibility is that what is different in autism is not functional connectivity at ‘baseline’ but how responsive brain networks are to neurochemical challenges. Here we selected the cannabis compound cannabidivarin (CBDV) as a neurochemical challenge because of its pleiotropic action across multiple receptors rather than have a more restricted challenge. We then compared both core network strength and dynamic features (dwell time and fractional occupancy), of whole-brain intrinsic connectivity networks (ICNs) from resting-state functional MRI in autistic (n = 14) and non-autistic (n = 17) male participants at baseline (placebo) and following administration of a 600 mg dose of CBDV. Autistic participants showed longer dwell time and fractional occupancy of a default-mode-network (DMN)-occipital-auditory transient state than non-autistic controls at baseline. The effect of CBDV on the dwell time of DMN-subcortical and DMN-occipital-auditory states differed between non-autistic and autistic participants: within the non-autistic group, the dwell time was significantly increased but shifts within the autistic group did not reach statistical significance. These differences in networks responsible for introspection and sensory and salience processing may reflect atypical (i.e., ‘stickier’) autistic brain dynamics and a pharmacologically atypical autistic brain.