Two decades of genetic studies in autism spectrum disorder (ASD) have identified more than 100 genes harbouring rare risk mutations1-13. Despite this substantial heterogeneity, transcriptomic and epigenetic analyses have identified convergent patterns of dysregulation across the ASD postmortem brain14,15-17. To identify shared and distinct mechanisms of ASD-linked mutations, we assembled a large patient collection of human induced pluripotent stem (hiPS) cells, consisting of 70 hiPS cell lines after stringent quality control representing 8 ASD-associated mutations, idiopathic ASD, and 20 lines from non-affected control individuals. Here we used these hiPS cell lines to generate human cortical organoids, profiling by RNA sequencing at four distinct time points up to 100 days after in vitro differentiation. Early time points harboured the largest mutation-specific changes, but different mutations converged on shared transcriptional changes as development progressed. We identified a shared RNA and protein interaction network, which was enriched in ASD risk genes and predicted to drive the observed downstream changes in gene expression. CRISPR-Cas9 screening of these candidate transcriptional regulators in induced human neural progenitors validated their downstream convergent molecular effects. These data illustrate how risk associated with genetically defined forms of ASD can propagate by means of transcriptional regulation to affect convergently dysregulated pathways, providing new insight into the convergent impact of ASD genetic risk on human neurodevelopment.

Progressive decline in episodic memory is a hallmark of Alzheimer's disease (AD). Emotional arousal is known to enhance memory. Enhanced encoding of emotionally arousing stimuli or events may improve memory in patients with AD; however, whether this effect is present in patients with AD remains unclear. Here we conducted a systematic search of the literature to identify relevant literature on emotional enhancement of memory in AD. Inclusion criteria were studies that (1) included individuals with Alzheimer's disease and (2) assessed emotional memory, particularly episodic memory. Thirty-five studies were included. Twelve out of 35 studies (34.3%) showed clear emotional enhancement of memory for episodic memory among participants with mild AD, while 13 studies (37.1%) found no effect. Ten studies (28.6%) found that emotional enhancement of memory was influenced by stimuli type, valence of emotion, level of encoding or intensity of emotion. Studies including brain imaging showed that amygdala and hippocampus volume are strong predictors of emotional enhancement of memory in AD, regardless of level of cognitive impairment. Evaluating volumes or networks of brain regions known to be involved in emotional memory processing may be a key factor influencing the preservation of enhanced encoding of emotional information. Future studies are needed to confirm whether atrophy of memory-related brain regions diminishes emotional enhancement of memory in AD.