The effects of sleep on the neural correlates of pattern separation.

Effective memory representations must be specific to prevent interference between episodes that may overlap in terms of place, time, or items present. Pattern separation, a computational process performed by the hippocampus, overcomes this interference by establishing nonoverlapping memory representations. Although it is widely accepted that declarative memories are consolidated during sleep, the effects of sleep on pattern separation have yet to be elucidated. We used whole-brain, high-resolution functional neuroimaging to investigate the effects of sleep on a task that places high demands on pattern separation. Sleep had a selective effect on memory specificity and not general recognition memory. Activity in brain regions related to memory retrieval and cognitive control demonstrated an interaction between sleep and delay. Surprisingly, there was no effect of sleep on hippocampal activity using a group-level analysis. To further understand the role of the hippocampus on our task, we performed a representational similarity analysis, which showed that hippocampal activation was biased toward pattern separation relative to cortical activation and that this bias increased following a delay (regardless of sleep). Cortical activation, conversely, was biased toward pattern completion and this bias was preferentially enhanced by sleep.

Structural and functional correlates of behavioral pattern separation in the hippocampus and medial temporal lobe.

Structures of the medial temporal lobe (MTL) are known to be involved in declarative memory processes. However, little is known about how age-related changes in MTL structures, white matter integrity, and functional connectivity affect pattern separation processes in the MTL. In this study, we used magnetic resonance imaging (MRI) to measure the volumes of MTL regions of interest, including hippocampal subfields (dentate gyrus, CA3, CA1, and subiculum) in healthy older and younger adults. Additionally, we used diffusion tensor imaging to measure white matter integrity for both groups. Finally, we used functional MRI to acquire resting functional connectivity measures for both groups. We show that, along with age, the volume of left CA3/dentate gyrus predicts memory performance. Differences in fractional anisotropy and the strength of resting functional connections between the hippocampus and other cortical structures implicated in memory processing were not significant predictors of performance. As previous studies have only hinted, it seems that the size of left CA3/dentate gyrus contributes more to successful discrimination between similar mnemonic representations than other hippocampal sub-fields, MTL structures, and other neuroimaging correlates. Accordingly, the implications of aging and atrophy on lure discrimination capacities are discussed.

Atypical Amygdala Response to Fear Conditioning in Autism Spectrum Disorder.

BACKGROUND: Anxiety is the most common comorbid psychiatric concern in individuals diagnosed with autism spectrum disorder (ASD) and can cause significant functional impairment. Fear conditioning tasks offer a useful neurodevelopmental model for anxiety, yet there are no published neuroimaging studies of fear conditioning using ASD samples. METHODS: Twenty adults diagnosed with ASD and 19 healthy adult control subjects completed a standard fear conditioning and extinction paradigm while undergoing functional magnetic resonance imaging scanning. A burst of air on the base of the neck was the unconditioned stimulus. Participants returned 1 day later for scanning during an extinction recall phase. A priori regions of interest were analyzed with a familywise error correction rate < 0.05. RESULTS: All regions of interest demonstrated significantly greater response to threat than safe conditions during initial fear acquisition. Compared with age-matched control subjects, the ASD group showed a significantly decreased differential response to threat versus safe cues in right amygdala during the initial fear acquisition phase and decreased response in left amygdala during the first run of extinction recall on the second day of scanning. CONCLUSIONS: Symptoms of severe anxiety in ASD may arise from atypical neural mechanisms especially related to the differentiation of threat versus safe cues. An inability to effectively identify safety contexts may underlie chronically increased levels of anxiety in many individuals diagnosed with ASD.