The Mysterious Island: Insula and Its Dual Function in Sleep and Wakefulness

Abstract

In the recent sleep studies, it was shown that afferentation of many cortical areas switches during sleep to the interoceptive one. However, it was unclear whether the insular cortex, which is often considered as the main cortical visceral representation, maintains the same effective connectivity in both states of vigilance, or processes interoceptive information predominantly in one state. We investigated neuronal responses of the cat insular cortex to electrical stimulations of the intestinal wall delivered during wakefulness and natural sleep. Marked increase was observed in the number of insular neurons responding to this stimulation in sleep comparing to wakefulness, and enlarged amplitudes of evoked local field potentials were found as well. Moreover, most of the cells responding to intestinal stimulation in wakefulness never responded to identical stimuli during sleep and vice versa. It was also shown that applied low intensity intestinal stimulations had never compromised sleep quality. In addition, experiments with microstimulation of the insular cortex and recording of intestinal myoelectric activity demonstrated that effective insula-to-gut propagation also happened only during sleep. On the other hand, the same insular stimulations in wakefulness led to contractions of orofacial muscles. The evoked face movements gradually disappeared in the course of sleep development. These findings demonstrate that pattern of efficient afferent and efferent connections of the insular cortex changes with transition from wakefulness to sleep.

Somatovisceral Convergence in Sleep-Wake Cycle: Transmitting Different Types of Information via the Same Pathway

“…This connectivity is strongest in wakefulness and progressively decreases in REM, light sleep and deep sleep (Bashan et al, 2012;Balagué et al, 2020;Rizzo et al, 2020). Our earlier observations are consistent with this view as electrical stimulation of the insular cortex produced robust muscle response in wakefulness that disappeared as soon as sleep started developing (Levichkina et al, 2021).…”

“…For Experiment 2 electrodes needed to be repositioned to increase the number of recorded units, thus we inserted robust tungsten varnish-coated microelectrodes via plastic conical guiding tubes and moved them using miniaturized custommade micromanipulators (electrode manufacturing and many of the related implantation techniques were described in detail in Pigarev et al, 2009;Levichkina et al, 2021). However, protrusion of the electrodes was restricted to 1 mm superficial part of the pathway to avoid tissue damage related to animal's movements.…”

“…Adjustment of the sensory thresholds during transition from wakefulness to sleep is a well-known phenomenon in various sensory modalities including downregulation of somatosensory signaling in sleep (Mukhametov and Rizzolatti, 1970;Gücer, 1979;Livingstone and Hubel, 1981;Issa and Wang, 2008). Indirect evidence of the adjustment has been provided for the upregulation of the visceral signals propagation in SWS as well, since responses to visceral or vagal stimulation increased during sleep in both the insular and somatosensory cortices (Levichkina et al, 2021;Rembado et al, 2021). Presented data are well compatible with the previous results describing sleep-related and wakefulnessrelated networks existing in the insular cortex.…”

“…Thus, some component of spinal activity seems likely to be associated with sleep and to promote sleep in a similar way to the largely visceral vagal input. We have recently reported that neurons of cat insular cortex, the area involved in viscerosensory and visceromotor processing, are three times more likely to respond to innocuous visceral stimulation in SWS in comparison to wakefulness (Levichkina et al, 2021), indicating that processing of visceral signals is enhanced in sleep. Moreover, the majority of insular cells responding in sleep do not respond during wakefulness and vice versa, demonstrating a possibility of segregation between networks in different states of vigilance.…”

Is the insula linked to sleep? A systematic review and narrative synthesis

“… Levichkina et al. [ 27 ] Cat Electrodes for electrical stimulation and recording Insula has a dual role in sleep and wakefulness Chen et al. [ 28 ] Rat Record with sleep monitor The anterior insula is involved in regulating sleep and wakefulness.…”