A systematic review of cannabidiol trials in neurodevelopmental disorders.

Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications. These phyto-cannabinoids have multiple biological targets, including the body's endocannabinoid system. There is growing scientific interest in the use of CBD, a non-intoxicating compound, to ameliorate symptoms associated with neurodevelopmental disorders. However, its suitability as a pharmaceutical intervention has not been reliably established in these clinical populations. This systematic review examines the nine published randomised controlled trials (RCTs) that have probed the safety and efficacy of CBD in individuals diagnosed with attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, Tourette Syndrome, and complex motor disorders. Studies were identified systematically through searching four databases: Medline, CINAHL complete, PsycINFO, and EMBASE. Inclusion criteria were randomised controlled trials involving CBD and participants with neurodevelopmental disorders. No publication year or language restrictions were applied. Relevant data were extracted from the identified list of eligible articles. After extraction, data were cross-checked between the authors to ensure consistency. Several trials indicate potential efficacy, although this possibility is currently too inconsistent across RCTs to confidently guide clinical usage. Study characteristics, treatment properties, and outcomes varied greatly across the included trials. The material lack of comparable RCTs leaves CBD's suitability as a pharmacological treatment for neurodevelopmental disorders largely undetermined. A stronger evidence base is urgently required to establish safety and efficacy profiles and guide the ever-expanding clinical uptake of cannabis-derived compounds in neurodevelopmental disorders. Prospero registration number: CRD42021267839.

Does fMRI repetition suppression reveal mirror neuron activity in the human brain? Insights from univariate and multivariate analysis.

Mirror neurons (MN) have been proposed as the neural substrate for a wide range of clinical, social and cognitive phenomena. Over the last decade, a commonly used tool for investigating MN activity in the human brain has been functional magnetic resonance (fMRI) repetition suppression (RS) paradigms. However, the available evidence is mixed, largely owing to inconsistent application of the methodological criteria necessary to infer MN properties. This raises concerns about the degree to which one can infer the presence (or absence) of MN activity from earlier accounts that adopted RS paradigms. We aimed to clarify this issue using a well-validated fMRI RS paradigm and tested for mirror properties by rigorously applying the widely accepted criteria necessary to demonstrate MN activity using traditional univariate techniques and Multivariate Pattern Analysis (MVPA). While univariate whole brain analysis in healthy adults showed uni-modal RS effects within the supplementary motor area, no evidence for cross-modal RS effects consistent with mirror neuron activity was found. MVPA on the other hand revealed a region along the anterior intraparietal sulcus that met the criteria for MN activity. Taken together, these results clarify disparate evidence from earlier RS studies, highlighting that traditional univariate analysis of RS data may not be sensitive for detecting MN activity when rigorously applying the requisite criteria. In light of these findings, we recommend that short of increasing sample sizes substantially, future studies using RS paradigms to investigate MNs across the human brain consider the use of MVPA.

Short communication: Sex-linked differences in gamma-aminobutyric acid (GABA) are related to social functioning in autism spectrum disorder.

Magnetic resonance spectroscopy (MRS) was utilized to investigate sex differences in gamma-aminobutyric acid (GABA) between adults with autism spectrum disorder (ASD) and neurotypical (NT) controls. GABA at the right superior temporal sulcus (STS) is reported for 12 ASD and 14 NT participants. The results show no group differences in GABA. There was, however, a significant positive association between GABA at the STS and autism-related social impairments in females with ASD. These findings provide preliminary support for sex differences in GABAergic distribution and processes that contribute to social functioning in ASD.

Do Handwriting Difficulties Correlate with Core Symptomology, Motor Proficiency and Attentional Behaviours?

Handwriting is commonly identified as an area of weakness in children with autism spectrum disorder (ASD), but precise deficits have not been fully characterised. Boys with ASD (n = 23) and matched controls (n = 20) aged 8-12 years completed a simple, digitised task to objectively assess handwriting performance using advanced descriptive measures. Moderate to large associations were identified between handwriting performance and attention, ASD symptoms and motor proficiency. The ASD group demonstrated significantly less smooth movements and significantly greater sizing variability and peak velocity relative to controls. These findings provide a clearer indication of the specific nature of handwriting impairments in children with ASD, and suggest a relationship with core clinical symptom severity, attention and motor behaviours.

Low-frequency brain stimulation to the left dorsolateral prefrontal cortex increases the negative impact of social exclusion among those high in personal distress.

The dorsolateral prefrontal cortex (DLPFC) is thought to play a key role in the cognitive control of emotion and has therefore, unsurprisingly, been implicated in the regulation of physical pain perception. This brain region may also influence the experience of social pain, which has been shown to activate similar neural networks as seen in response to physical pain. Here, we applied sham or active low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC, previously shown to exert bilateral effects in pain perception, in healthy participants. Following stimulation, participants played the "Cyberball Task"; an online ball-tossing game in which the subject participant is included or excluded. Compared to sham, rTMS did not modulate behavioural response to social exclusion. However, within the active rTMS group only, greater trait personal distress was related to enhanced negative outcomes to social exclusion. These results add further support to the notion that the effect of brain stimulation is not homogenous across individuals, and indicates the need to consider baseline individual differences when assessing response to brain stimulation. This seems particularly relevant in social neuroscience investigations, where trait factors may have a meaningful effect.