Neuronal morphology and physiology, functional brain networks and memory in temporal lobe epilepsy

ABSTRACT

Temporal lobe epilepsy patients are heterogeneous regarding cognitive functioning, with predominant risk of memory deficits. Despite major advances within cellular neuroscience, neuroimaging, and neuropsychology, it remains challenging to integrate memory performance with cellular characteristics and brain network topology. In a unique dataset, we investigate these cross-scale individual differences. Preoperatively, drug-resistant temporal lobe epilepsy patients (n = 31, 15 females) underwent functional magnetic resonance imaging, magnetoencephalography and/or memory testing. Macro-scale network centrality was determined, since the number of integrative functional connections a region has is crucial for memory functioning. Subsequently, non-pathological cortical tissue resected from the lateral middle temporal gyrus (default mode network) was used for single cell morphological (total dendritic length) and electrophysiological patch-clamp analysis (action potential rise speed). We expected greater macro-scale centrality to relate to longer micro-scale dendritic length and faster action potentials, and greater centrality to relate to better memory performance. Greater macro-scale centrality correlated with longer dendritic length and faster action potentials (canonical correlation coefficient = 0.329, p < 0.001). Moreover, greater macro-scale centrality was related to better memory performance (canonical correlation coefficient = 0.234, p = 0.013). We conclude that more complex neuronal morphology and faster action potential kinetics are mirrored by more integrative functional network topology of the middle temporal gyrus, which in turn is associated with better memory functioning. Thus, our cross-scale analyses reveal a significant relationship between cellular and imaging measures of network topology in the brain, which support cognitive performance in these patients.