The Brainstem and Cerebral Activation

The upper brainstem is known to participate in brain activation, since the pioneering description of the Ascending Reticular System in the middle of twentieth century. Since the early works, waking state and paradoxical sleep were considered to be implicated in the same circuitry of activation. The consciousness cognitive process, which develops within a global cerebral workspace, and is directly linked with the waking state, is modulated by neurotransmitters, the most emblematic and historic being: amino acids, such as glutamate (excitatory), gamma-aminobutyric acid (inhibitory); monoamines, such as serotonin and noradrenaline; and acetylcholine. From animal research, the main thalamic and extra-thalamic pathways, originating from the tegmentum, were early precisely described. These two pathways are nowadays admitted in human, supporting the cortical activation from the deep brain. The superior cholinergic thalamic pathway originates within dorsolateral tegmental nuclei, and notably the pedunculopontine tegmental nucleus and the small laterodorsal tegmental nucleus, innervating the whole thalamus. The inferior, serotoninergic-noradrenergic basal-forebrain pathway, or extrathalamic, originates within the dorsal mesencephalon-pontine area, specifically the locus coeruleus and the dorsal raphe and central superior nuclei. Schematically, the thalamic and extra-thalamic pathways reach the hemispheric cortices, respectively through the thalamus and the hypothalamus. During several pathologic conditions, alterations of this deep brain circuitry lead to disorders of consciousness, but the detailed mechanisms of dysfunctions are still not deciphered.