How minimal variations in neuronal cytoskeletal integrity modulate cognitive control

Until recently, investigating microscopic changes in the integrity of human brain matter has not been possible in vivo. It has hence remained unknown whether and how small non-pathological variations in cytoskeletal neuronal integrity affect human cognitive functioning. We investigated the role of neuronal cytoskeleton integrity for complex multicomponent behavior, which is relevant to real-life situations, as complex goals are often achieved by assembling a series of sub-tasks. For this, we quantified scaffolding proteins (i.e. neurofilament light; NF-L) using a single-molecule array (SIMOA), a new and uniquely ultra-sensitive method, and integrated this with behavioral and neurophysiological (EEG) data. For the first time, we showcase that slightest non-pathological variations in cytoskeletal integrity strongly modulate the efficiency of cognitive control processes. We show that the architecture and efficiency of theta-oscillations networks during cognitive control processes reflects a mechanism that establishes the relationship between neuronal cytoskeleton integrity and multicomponent behavior. Attentional selection processes do however not seem to play a role. The efficiency and network architecture of theta oscillations provides an important missing neural link that helps to explain how diffuse and seemingly miniscule variations in neuronal integrity may lead to reduced or even impaired cognitive functioning that is important for everyday activities.