Convergent effects of different anesthetics are due to changes in phase alignment of cortical oscillations.

Many different anesthetics cause loss of responsiveness despite having diverse underlying molecular and circuit actions. To explore the convergent effects of these drugs, we examined how ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, and dexmedetomidine, an α2 adrenergic receptor agonist, affected neural oscillations in the prefrontal cortex of nonhuman primates. Previous work has shown that anesthesia increases phase locking of low-frequency local field potential activity across cortex. We observed similar increases with anesthetic doses of ketamine and dexmedetomidine in the ventrolateral and dorsolateral prefrontal cortex, within and across hemispheres. However, the nature of the phase locking varied between regions. We found that oscillatory activity in different prefrontal subregions within each hemisphere became more anti-phase with both drugs. Local analyses within a region suggested that this finding could be explained by broad cortical distance-based effects, such as a large traveling wave. By contrast, homologous areas across hemispheres increased their phase alignment. Our results suggest that the drugs induce strong patterns of cortical phase alignment that are markedly different from those in the awake state, and that these patterns may be a common feature driving loss of responsiveness from different anesthetic drugs.

Face neurons encode nonsemantic features.

The primate inferior temporal cortex contains neurons that respond more strongly to faces than to other objects. Termed "face neurons," these neurons are thought to be selective for faces as a semantic category. However, face neurons also partly respond to clocks, fruits, and single eyes, raising the question of whether face neurons are better described as selective for visual features related to faces but dissociable from them. We used a recently described algorithm, XDream, to evolve stimuli that strongly activated face neurons. XDream leverages a generative neural network that is not limited to realistic objects. Human participants assessed images evolved for face neurons and for nonface neurons and natural images depicting faces, cars, fruits, etc. Evolved images were consistently judged to be distinct from real faces. Images evolved for face neurons were rated as slightly more similar to faces than images evolved for nonface neurons. There was a correlation among natural images between face neuron activity and subjective "faceness" ratings, but this relationship did not hold for face neuron­evolved images, which triggered high activity but were rated low in faceness. Our results suggest that so-called face neurons are better described as tuned to visual features rather than semantic categories.

Phenotypic interpretation of complex chromosomal rearrangements informed by nucleotide-level resolution and structural organization of chromatin.

Molecular characterization of balanced chromosomal abnormalities constitutes a powerful tool in understanding the pathogenic mechanisms of complex genetic disorders. Here we report a male with severe global developmental delay in the presence of a complex karyotype and normal microarray and exome studies. The subject, referred to as DGAP294, has two de novo apparently balanced translocations involving chromosomes 1 and 14, and chromosomes 4 and 10, disrupting several different transcripts of adhesion G protein-coupled receptor L2 (ADGRL2) and protocadherin 15 (PCDH15). In addition, a maternally inherited inversion disrupts peptidyl arginine deiminase types 3 and 4 (PADI3 and PADI4) on chromosome 1. None of these gene disruptions explain the patient's phenotype. Using genome regulatory annotations and chromosome conformation data, we predict a position effect ~370 kb upstream of a translocation breakpoint located at 14q12. The position effect involves forkhead box G1 (FOXG1), mutations in which are associated with the congenital form of Rett syndrome and FOXG1 syndrome. We believe the FOXG1 position effect largely accounts for the clinical phenotype in DGAP294, which can be classified as FOXG1 syndrome like. Our findings emphasize the significance of not only analyzing disrupted genes by chromosomal rearrangements, but also evaluating potential long-range position effects in clinical diagnoses.