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Duarte, S. E.

Publications and source records attributed to Duarte, S. E..

2 recordsLinked to original sources

Self-guided search in immersive VR reveals active hierarchical planning

Despite the ubiquitous nature of visual search in our daily lives, our knowledge of the underlying mechanisms is almost entirely derived from studies using simple, synthetic stimuli briefly flashed on a computer monitor. In real life, however, visual search occurs in three-dimensional environments over much longer timescales and involves the dynamic coordination of attention, memory, and action planning, generating novel predictions that cannot be tested with traditional approaches. Here, we examined how self-guided visual search unfolds under naturalistic conditions that extend over space and time. We asked participants (N=80) to find specific objects (e.g., a green lamp, an orange shelf) in an immersive, visually rich virtual reality environment using range-limited teleportation (2 m steps). Consistent with our hypotheses, we found that self-guided search engaged a hierarchical information-seeking policy characterized at each stage by recurring plan-and-execute cycles paired with subgoal-specific attentional priorities. Subgoal priorities progressed from wayfinding to identification of clusters of target-similar objects, and then to specific target features. These search priorities progressively narrowed the search space through coordinated eye, head, and body movements that recurred throughout the task. We conclude that naturalistic search is hierarchical, built from sequential subgoals with shifting attentional priorities that single-level tasks cannot capture. Moreover, immersive VR with eye-head-body tracking dissociates motor planning from execution moments and reveals how looking content shifts with each task subgoal while the person moves through space, something desktop tasks cannot capture.

animal behavior and cognition↗

Gabra2 is a genetic modifier of Dravet syndrome in mice

Pathogenic variants in epilepsy genes result in a spectrum of clinical presentation, ranging from benign phenotypes to intractable epilepsies with significant co-morbidities and increased risk of sudden unexpected death in epilepsy (SUDEP). One source of this phenotypic heterogeneity is modifier genes that affect penetrance, dominance or expressivity of a primary pathogenic variant. Mouse models of epilepsy also display varying degrees of clinical severity on different genetic backgrounds. Mice with heterozygous deletion of Scn1a (Scn1a+/-) model Dravet syndrome, a severe epilepsy most often caused by SCN1A haploinsufficiency. Scn1a+/- heterozygous mice recapitulate key features of Dravet syndrome, including febrile and afebrile spontaneous seizures, SUDEP, and cognitive and behavioral deficits. The Scn1a+/- mouse model also exhibits strain-dependent phenotype severity. Scn1a+/- mice maintained on the 129S6/SvEvTac (129) strain have normal lifespan and no overt seizures. In contrast, admixture with C57BL/6J (B6) results in severe epilepsy and premature lethality in [B6x129]F1.Scn1a+/- mice. In previous work, we identified Dravet Survival Modifier loci (Dsm1-Dsm5) responsible for strain-dependent differences in survival. Gabra2, encoding the GABAA 2 subunit, was nominated as the top candidate modifier at the Dsm1 locus on chromosome 5. Direct measurement of GABAA receptors found lower abundance of 2-containing receptors in hippocampal synapses of B6 mice relative to 129. We also identified a B6-specific single nucleotide intronic deletion within Gabra2 that lowers mRNA and protein by nearly 50%. Repair of this de novo deletion reestablished normal levels of Gabra2 transcript and protein expression. In the current study, we used B6 mice with the repaired Gabra2 allele to validate it as a modifier of phenotype severity in Scn1a+/- mice. Repair of Gabra2 restored transcript and protein expression, increased abundance of 2-containing GABAA receptors in hippocampal synapses, and improved seizure and survival phenotypes of Scn1a+/- mice. These findings validate Gabra2 as a genetic modifier of Dravet syndrome.

genetics↗