Thesis defense Diego Lozano-Soldevilla (Donders series 201)
15 December 2015
Promotor: dr. O. Jensen, copromotor: prof. dr. R. Cools
GABAergic modulations of gamma and alpha oscillations; consequences for working memory performance
During the last 4 years I have gained important new insights regarding how GABAergic neurotransmission influences neuronal synchronization as measured with magnetoencephalographic (MEG) recordings in healthy humans. Lorazepam (LZP), a GABAergic enhancer, produced strong modulations in occipital oscillatory activity under rest and working memory (WM) conditions. My novel insight is that gamma oscillations associated to the stimulus period seem to share common neurophysiological mechanisms as the ones described in rat hippocampus models. Specifically, the increase of GABA efficacy by LZP increase stimulus-induced gamma oscillations increased in power while decreased in frequency. Conversely, alpha oscillations were implicated in functional inhibition during top-down periods, being also modulated by lorazepam (LZP). Importantly, I found that pharmacologically induced alpha-power reductions predicted WM performance decrease. However, I could not find relationship between the drug-related oscillatory activity changes with the endogenous GABA concentrations in occipital nor motor cortices as assessed with magnetic resonance spectroscopy (MRS). It remains unclear whether this absence of correlation is physiological in nature or explained by limitations in the recording techniques. During resting state and during WM information maintenance periods, I found that the amplitude envelope of the beta-low gamma band (20 – 45Hz) is locked to the ongoing phase of the alpha oscillations (8 – 12Hz). Only the highest LZP dosage during resting state affected the alpha to beta-low gamma cross-frequency coupling (CFC). However, the CFC metrics employed here did not allow me to distinguish a true neuronal cross-frequency interaction from spurious CFC due to the non-sinusoidal properties in the alpha band.