Possible mechanisms to improve sleep spindles via closed loop stimulation during slow wave sleep: A computational study

Abstract

Sleep spindles are one of the prominent EEG oscillatory rhythms of non-rapid eye movement sleep. In the memory consolidation, these oscillations have an important role in the processes of long-term potentiation and synaptic plasticity. Moreover, the activity (spindle density and/or sigma power) of spindles has a linear association with learning performance in different paradigms. According to the experimental observations, the sleep spindle activity can be improved by closed loop acoustic stimulations (CLAS) which eventually improve memory performance. To examine the effects of CLAS on spindles, we propose a biophysical thalamocortical model for slow oscillations (SOs) and sleep spindles. In addition, closed loop stimulation protocols are applied on a thalamic network. Our model results show that the power of spindles is increased when stimulation cues are applied at the commencing of an SO Down-to-Up-state transition, but that activity gradually decreases when cues are applied with an increased time delay from this SO phase. Conversely, stimulation is not effective when cues are applied during the transition of an Up-to-Down-state. Furthermore, our model suggests that a strong inhibitory input from the reticular (RE) layer to the thalamocortical (TC) layer in the thalamic network shifts leads to an emergence of spindle activity at the Up-to-Down-state transition (rather than at Down-to-Up-state transition), and the spindle frequency is also reduced (8–11 Hz) by thalamic inhibition.

Polarity-dependent modulation of sleep oscillations and cortical excitability in aging

“…This failure to modulate spindle activity could be attributed to several factors. First, while evidence indicates that synchronized cortical down-states can influence thalamic rebound spindles ( Mak-McCully et al, 2017 ), it is likely that an optimal timing and dynamic between down- and up-states is required for effective spindle initiation ( Niethard et al, 2018 ; Bazhenov et al, 2002 ; Mushtaq et al, 2024 ). Second, prolonging the down-state might not enhance this temporal pattern, possibly even disrupt it ( Bazhenov et al, 2002 ).…”

Polarity-dependent modulation of sleep oscillations and cortical excitability in aging

“…This failure to modulate spindle activity could be attributed to several factors. First, while evidence indicates that synchronized cortical down-states can influence thalamic rebound spindles ( Mak-McCully et al, 2017 ), it is likely that an optimal timing and dynamic between down- and up-states is required for effective spindle initiation ( Niethard et al, 2018 ; Bazhenov et al, 2002 ; Mushtaq et al, 2024 ). Second, prolonging the down-state might not enhance this temporal pattern, possibly even disrupt it ( Bazhenov et al, 2002 ).…”

Polarity-dependent modulation of sleep oscillations and cortical excitability in aging

“…This failure to modulate spindle activity could be attributed to several factors. First, while evidence indicates that synchronized cortical down-states can influence thalamic rebound spindles 15 , it is likely that an optimal timing and dynamic between down-and up-states is required for effective spindle initiation [30][31][32] . Second, prolonging the down-state might not enhance this temporal pattern, possibly even disrupt it 31 .…”

Polarity-dependent modulation of sleep oscillations and cortical excitability in aging

“…This failure to modulate spindle activity could be attributed to several factors. First, while evidence indicates that synchronized cortical down-states can influence thalamic rebound spindles ( Mak-McCully et al, 2017 ), it is likely that an optimal timing and dynamic between down- and up-states is required for effective spindle initiation ( Niethard et al, 2018 ; Bazhenov et al, 2002 ; Mushtaq et al, 2024 ). Second, prolonging the down-state might not enhance this temporal pattern, possibly even disrupt it ( Bazhenov et al, 2002 ).…”

Polarity-dependent modulation of sleep oscillations and cortical excitability in aging

“…This failure to modulate spindle activity could be attributed to several factors. First, while evidence indicates that synchronized cortical down-states can influence thalamic rebound spindles 15 , it is likely that an optimal timing and dynamic between down-and up-states is required for effective spindle initiation [30][31][32] . Second, prolonging the down-state might not enhance this temporal pattern, possibly even disrupt it 31 .…”

Polarity-dependent modulation of sleep oscillations and cortical excitability in aging

“…This failure to modulate spindle activity could be attributed to several factors. First, while evidence indicates that synchronized cortical down-states can influence thalamic rebound spindles ( Mak-McCully et al, 2017 ), it is likely that an optimal timing and dynamic between down- and up-states is required for effective spindle initiation ( Niethard et al, 2018 ; Bazhenov et al, 2002 ; Mushtaq et al, 2024 ). Second, prolonging the down-state might not enhance this temporal pattern, possibly even disrupt it ( Bazhenov et al, 2002 ).…”

Polarity-dependent modulation of sleep oscillations and cortical excitability in aging

“…This failure to modulate spindle activity could be attributed to several factors. First, while evidence indicates that synchronized cortical down-states can influence thalamic rebound spindles 15 , it is likely that an optimal timing and dynamic between down-and up-states is required for effective spindle initiation [30][31][32] . Second, prolonging the down-state might not enhance this temporal pattern, possibly even disrupt it 31 .…”