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The relationship between SV2A levels, neural activity, and cognitive function in healthy humans: A [11C]UCB-J PET and
Ekaterina Shatalina1,2, Ellis Chika Onwordi1,2,3,4, Thomas Whitehurst1,2,3,4
1Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Abstract:
Synaptic terminal density is thought to influence cognitive function and neural activity, yet its role in cognition has not been explored in healthy humans. We examined these relationships using [11C]UCB-J positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) in 25 healthy adults performing cognitive function tasks in the scanner. We found a significant positive association between synaptic terminal density, indicated by [11C]UCB-J PET distribution volume ratio (DVRcs), and neural activity during task switching (PLS-CA, second canonical component, r = 0.63, p = 0.043) with the thalamus-putamen data positively contributing to this relationship (PLS-CA loading 0.679, exploratory Pearson's correlation r = 0.42, p = 0.044, uncorrected). Furthermore, synaptic terminal density predicted switch cost (PLS-R, R2 = 0.45, RMSE = 0.06, p = 0.022), with DVRcs negatively correlating with switch cost in key brain regions including the dorsolateral prefrontal cortex and posterior frontal cortex. Conversely, no significant relationships were observed between [11C]UCB-J DVRcs and neural activity or performance measures in the N-back working memory task, suggesting interindividual differences in synaptic terminal density may be more closely related to some cognitive functions and not others.
