Role of corpus callosum in sleep spindle synchronization and coupling with slow waves

Abstract

Sleep spindles of non-REM sleep are transient, waxing-and-waning 10–16 Hz EEG oscillations, whose cortical synchronization depends on the engagement of thalamo-cortical loops. However, previous studies in animal models lacking the corpus callosum due to agenesis or total callosotomy and in humans with agenesis of the corpus callosum suggested that cortico-cortical connections may also have a relevant role in cortical (inter-hemispheric) spindle synchronization. Yet, most of these works did not provide direct quantitative analyses to support their observations. By studying a rare sample of callosotomized, split-brain patients, we recently demonstrated that the total resection of the corpus callosum is associated with a significant reduction in the inter-hemispheric propagation of non-REM slow waves. Interestingly, sleep spindles are often temporally and spatially grouped around slow waves (0.5–4 Hz), and this coordination is thought to have an important role in sleep-dependent learning and memory consolidation. Given these premises, here we set out to investigate whether total callosotomy may affect the generation and spreading of sleep spindles, as well as their coupling with sleep slow waves. To this aim, we analyzed overnight high-density EEG recordings (257 electrodes) collected in five patients who underwent total callosotomy due to drug-resistant epilepsy (age 40–53, two females), three non-callosotomized neurological patients (age 44–66, two females), and in a sample of 24 healthy adult control subjects (age 20–47, 13 females). Individual sleep spindles were automatically detected using a validated algorithm and their properties and topographic distributions were computed. All analyses were performed with and without a regression-based adjustment accounting for inter-subject age differences. The comparison between callosotomized patients and healthy subjects did not reveal systematic variations in spindle density, amplitude or frequency. However, callosotomized patients were characterized by a reduced spindle duration, which could represent the result of a faster desynchronization of spindle activity across cortical areas of the two hemispheres. In contrast with our previous findings regarding sleep slow waves, we failed to detect in callosotomized patients any clear, systematic change in the inter-hemispheric synchronization of sleep spindles. In line with this, callosotomized patients were characterized by a reduced extension of the spatial association between temporally coupled spindles and slow waves. Our findings are consistent with a dependence of spindles on thalamo-cortical rather than cortico-cortical connections in humans, but also revealed that, despite their temporal association, slow waves and spindles are independently regulated in terms of topographic expression.

In the event of memory

“…7 & 8), whereas in the latter case, the overlap was more widespread across the cortex bilaterally. Interestingly, crosshemispheric co-occurrence of cortical spindles is preserved in callosotomized patients, suggesting that cortical spindle spread may depend on thalamocortical instead of cortico-cortico connections (Bernardi et al, 2021). The results of the present study add to the currently limited literature on interhemispheric spindle co-occurrence by showing that cortical spread of spindle activity is related to the level of involvement of the thalamus.…”

Spatiotemporal patterns of sleep spindle activity in human anterior thalamus and cortex

“…7 & 8), whereas in the latter case, the overlap was more widespread across the cortex bilaterally. Interestingly, cross-hemispheric co-occurrence of cortical spindles is preserved in callosotomized patients, suggesting that cortical spindle spread may depend on thalamocortical instead of cortico-cortico connections (Bernardi et al, 2021). The results of the present study add to the currently limited literature on interhemispheric spindle co-occurrence by showing that cortical spread of spindle activity is related to the level of involvement of the thalamus.…”

White matter microstructure and sleep-wake disturbances in individuals at ultra-high risk of psychosis

“…CC has together with neuronal populations located to the brainstem been hypothesized to be involved in a complex synchronization of interhemispheric activity, regulating the timing and duration of rapid eye movement (REM) ( Nielsen et al, 1992 ). Indeed, different aspects of sleep quality have been linked to CC, such as sleep oscillations ( Piantoni et al, 2013 ), sleep efficiency, total sleep time ( Altendahl et al, 2020 ), REM as well as non-REM sleep ( Avvenuti et al, 2019 ; Bernardi et al, 2021 ). One study found that WM metrics of CC mediated associations between poor sleep quality and symptomatology in patients with depression ( Li et al, 2020 ).…”