UC Berkeley

Sleep is highly conserved across phylogeny, yet marked inter-individual differences in sleep physiology are expressed. In humans, such variability is especially evident for non-rapid eye movement (NREM) sleep spindle and slow wave oscillations, representing trait-like physiological "fingerprints". Nevertheless, the mechanisms accounting for these differences, and the functional consequences of this variability, remain largely unknown. This thesis combines structural MRI, sleep EEG, and cognitive memory paradigms to test the hypothesis that brain morphology represents one candidate factor explaining inter-individual differences in NREM oscillations, which, in turn, consequently predict functional learning and memory. From this central hypothesis, three inter-related, yet distinct, studies are presented. Study 1 demonstrates that inter-individual variability in NREM physiology is accounted by grey matter morphology in functionally relevant brain regions. Specifically, grey matter in the sleep-regulating center of the basal forebrain/hypothalamus, together with the medial prefrontal cortex, accounted for individual differences in NREM slow waves. In contrast, grey matter in interoceptive and exteroceptive cortices predicted slower NREM sleep spindles, whereas grey matter volume in bilateral hippocampus was associated with faster sleep spindles. Study 2 establishes that the substructure of the hippocampus--specifically, the CA3/DG subfield--determines inter-individual levels of learning impairment following sleep deprivation, yet conversely interacts with post-deprivation recovery NREM sleep in predicting learning restoration. Finally, Study 3 describes a beneficial influence of fast NREM sleep spindles on differentially gating the selective offline consolidation of memories, based on prior waking instructions, leading to the selective remembering and forgetting of discreet item information. Together, these data indicate that macroscopic differences in structural brain morphology represent one mechanism accounting for individual differences in NREM sleep physiology, as well as associated consequences for learning and memory. More generally, these findings offer translational relevance to the structural brain abnormalities present in conditions such as dementia, sleep apnea, attention-deficit hyperactivity disorder, and post-traumatic stress disorder, where sleep disruption and memory impairment are highly co-morbid.