The occipital face area is causally involved in identity‑related visual‑semantic associations

Faces are processed in a network of areas within regions of the ventral visual stream. However, familiar faces typically are characterized by additional associated information, such as episodic memories or semantic biographical information as well. The acquisition of such non-sensory, identity-specific knowledge plays a crucial role in our ability to recognize and identify someone we know. The occipital face area (OFA), an early part of the core face-processing network, is recently found to be involved in the formation of identity-specific memory traces but it is currently unclear if this role is limited to unimodal visual information. The current experiments used transcranial magnetic stimulation (TMS) to test whether the OFA is involved in the association of a face with identity-specific semantic information, such as the name or job title of a person. We applied an identity-learning task where unfamiliar faces were presented together with a name and a job title in the first encoding phase. Simultaneously, TMS pulses were applied either to the left or right OFA or to Cz, as a control. In the subsequent retrieval phase, the previously seen faces were presented either with two names or with two job titles and the task of the participants was to select the semantic information previously learned. We found that the stimulation of the right or left OFA reduced subsequent retrieval performance for the face-associated job titles. This suggests a causal role of the OFA in the association of faces and related semantic information. Furthermore, in contrast to prior findings, we did not observe hemispherical differences of the TMS intervention, suggesting a similar role of the left and right OFAs in the formation of the visual-semantic associations. Our results suggest the necessity to reconsider the hierarchical face-perception models and support the distributed and recurrent models

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

PURPOSE: We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. METHODS: We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. RESULTS: These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. CONCLUSION: These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis