Impact of ketonic metabolism on cortical visual processing

INTRODUCTION: Abnormal metabolism can impact brain function. For example, obesity is associated with reduced plasticity and ketogenic diets have been employed in some forms of epilepsy. However, the extent to which ketone metabolism affects cortical excitability and neurotransmission is still an open question. Here we tested visual cortex function before and after oral supplementation of the main ketone body, Beta-Hydroxy Butyrate (BHB). We used Visual Evoked Potentials to evaluate the excitatory and inhibitory (cross-orientation inhibition) components of visual responses, combined with Magnetic Resonance Spectroscopy (MRS) to quantify the concentration of major metabolites and neurotransmitters. METHODS: After overnight fasting, participants (N=9) took an oral supplement that raised the concentration of BHB, inducing a state of ketosis. Steady-state visual evoked potentials were measured in response to a counter-phase flickering sinusoidal grating presented alone or superimposed with an orthogonal grating mask (1 c/deg grating, 50% contrast, temporal frequency 8.33Hz; orthogonal mask: 1 c/deg, 60% contrast, temporal frequency 7.1Hz). 3T MRS scans acquired immediately before and after VEPs measured the levels of BHB, GABA and the standard metabolites (including N-Acetyl Aspartate and Creatine) in a 2.5x2.5 cm voxel in the occipital cortex. RESULTS: Ketosis was associated with enhanced visual responses, as steady-state visual evoked potentials were significantly increased after BHB supplementation (vs. before administration: t(8)= 2.91, p<0.05). This effect was reliably associated with the change in occipital Creatine levels (r(9)= -0.78, p<0.05). Furthermore, the index of excitation/inhibition ratio of VEPs (defined as the VEP amplitude difference with and without the orthogonal mask) correlated strongly with changes in occipital GABA concentrations (r(9)= 0.71, p<0.05). CONCLUSIONS: Increasing the levels of BHB in the brain enhances visual cortex responses. The modulation of the excitation/inhibition ratio correlates with GABA changes, suggesting an effect of BHB in modulating GABAergic inhibition.