the reticular formation of the midbrain may lead to coma or death. Direct electrical stimulation of the ARAS produces pain responses in cats and elicits verbal reports of pain in humans. Ascending reticular activation in cats can produce mydriasis, which can result from prolonged pain. These results suggest some relationship between ARAS circuits and physiological pain pathways. Pathologies Some pathologies of the ARAS may be attributed to age, as there appears to be a general decline in reactivity of the ARAS with advancing years. Changes in electrical coupling have been suggested to account for some changes in ARAS activity: if coupling were down-regulated, there would be a corresponding decrease in higher-frequency synchronization (gamma band). Conversely, up-regulated electrical coupling would increase synchronization of fast rhythms that could lead to increased arousal and REM sleep drive. Specifically, disruption of the ARAS has been implicated in the following disorders: Narcolepsy: Lesions along the pedunculopontine (PPT/PPN) / laterodorsal tegmental (LDT) nuclei are associated with narcolepsy. There is a significant down-regulation of PPN output and a loss of orexin peptides, promoting the excessive daytime sleepiness that is characteristic of this disorder. Progressive supranuclear palsy (PSP) : Dysfunction of nitrous oxide signaling has been implicated in the development of PSP. Parkinson's disease: REM sleep disturbances are common in Parkinson's. It is mainly a dopaminergic disease, but cholinergic nuclei are depleted as well. Degeneration in the ARAS begins early in the disease process. Developmental influences There are several potential factors that may adversely influence the development of the ascending reticular activating system: Preterm birth: Regardless of birth weight or weeks of gestation, premature birth induces persistent deleterious effects on pre-attentional (arousal and sleep-wake abnormalities), attentional (reaction time and sensory gating), and cortical mechanisms throughout development. Smoking during pregnancy: Prenatal exposure to cigarette smoke is known to produce lasting arousal, attentional and cognitive deficits in humans. This exposure can induce up-regulation of α4β2 nicotinic receptors on cells of the pedunculopontine nucleus (PPN), resulting in increased tonic activity, resting membrane potential, and hyperpolarization-activated cation current. These major disturbances of the intrinsic membrane properties of PPN neurons result in increased levels of arousal and sensory gating, deficits (demonstrated by a diminished amount of habituation to repeated auditory stimuli). It is hypothesized that these physiological changes may intensify attentional dysregulation later in life. Descending reticulospinal tracts The reticulospinal tracts, also known as the descending or anterior reticulospinal tracts, are extrapyramidal motor