As previously described, noninvasive functional imaging of the activated brain relies on the elevation of glucose and oxygen metabolism, blood flow, and oxygenation due to increased neuronal activity, leading to, for example, an increase of the blood oxygenation level-dependent (BOLD) MRI signal. Traditionally, functional activation is equated with increased excitatory synaptic activity, accompanied by an increase in energy metabolism and CBF and blood hyper-oxygenation. On the other hand, reduced activity can be caused either by a decrease in excitatory input to the region of interest (deactivation) or by active synaptic inhibition within the region of interest. Active inhibition is based on the excitation of g-aminobutyric acid (GABA)-releasing interneurons followed by the interaction of GABA, the main inhibitory neurotransmitter in the brain, with its target receptors. Whereas deactivation is accompanied by a decrease in energy metabolism and glucose consumption within the deactivated area, inhibition by activation of inhibitory interneurons is suppose to be associated with an increase in energy consumption. In line with these considerations, hypermetabolic areas can be defined as areas where excitatory as well as inhibitory neurons are activated. On the other hand, hypometabolic regions are regions with inacti-vation of both excitatory and inhibitory neurons.
Consequently, different patterns of cerebral microvascu-lar blood oxygenation changes can be expected during active inhibition compared to deactivation. Until now no convincing data have been shown regarding the characteristics of cerebral microvascular blood flow and oxygenation changes during purely or predominantly inhibitory GABAergic neuronal activity. However, during deactivation of the visual cortex it was demonstrated that, compared to classical activation, inverse changes for the microvascular oxygenation parameters occur. A decrease in cortical neuronal activity is accompanied by a decrease in regional blood flow, a decrease in the concentration of oxyhemoglo-bin, and an increase in the concentration of deoxyhemoglo-bin. In addition, a decrease in BOLD MRI signal can be detected . This finding implies that the transition from "deactivation" to "rest" to "activation" is a continuous equilibrium of cerebral microvascular blood flow and oxygenation.
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