Pulsed inhibition of corticospinal excitability by the thalamocortical sleep spindle
Thalamocortical sleep spindles, i.e., oscillatory bursts at ∼12–15 Hz of waxing and waning amplitude, are a hallmark feature of non-rapid eye movement (NREM) sleep and believed to play a key role in memory reactivation and consolidation. Generated in the thalamus and projecting to neocortex and hipp...
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| Format: | Article |
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Elsevier
2025-03-01
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| Series: | Brain Stimulation |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1935861X25000464 |
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| author | Umair Hassan Prince Okyere Milad Amini Masouleh Christoph Zrenner Ulf Ziemann Til Ole Bergmann |
| author_facet | Umair Hassan Prince Okyere Milad Amini Masouleh Christoph Zrenner Ulf Ziemann Til Ole Bergmann |
| author_sort | Umair Hassan |
| collection | DOAJ |
| description | Thalamocortical sleep spindles, i.e., oscillatory bursts at ∼12–15 Hz of waxing and waning amplitude, are a hallmark feature of non-rapid eye movement (NREM) sleep and believed to play a key role in memory reactivation and consolidation. Generated in the thalamus and projecting to neocortex and hippocampus, they are phasically modulated by neocortical slow oscillations (<1 Hz) and in turn phasically modulate hippocampal sharp-wave ripples (>80 Hz). This hierarchical cross-frequency nesting, where slower oscillations group faster ones into certain excitability phases, may enable phase-dependent plasticity in the neocortex, and spindles have thus been considered windows of plasticity in the sleeping brain. However, the assumed phasic excitability modulation had not yet been demonstrated for spindles. Utilizing a recently developed real-time spindle detection algorithm, we applied spindle phase-triggered transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) hand area to characterize the corticospinal excitability profile of spindles via motor evoked potentials (MEP). MEPs showed net suppression during spindles, driven by a “pulse of inhibition” during its falling flank with no inhibition or facilitation during its peak, rising flank, or trough. This unidirectional (“asymmetric”) modulation occurred on top of the general sleep-related inhibition during spindle-free NREM sleep and did not extend into the refractory post-spindle periods. We conclude that spindles exert “asymmetric pulsed inhibition'' on corticospinal excitability. These findings and the developed real-time spindle targeting methods enable future studies to investigate the causal role of spindles in phase-dependent synaptic plasticity and systems memory consolidation during sleep by repetitively targeting relevant spindle phases. |
| format | Article |
| id | doaj-art-619d40ec5a9d4924a4dccc3d690c0b81 |
| institution | DOAJ |
| issn | 1935-861X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Stimulation |
| spelling | doaj-art-619d40ec5a9d4924a4dccc3d690c0b812025-08-20T03:03:42ZengElsevierBrain Stimulation1935-861X2025-03-0118226527510.1016/j.brs.2025.02.015Pulsed inhibition of corticospinal excitability by the thalamocortical sleep spindleUmair Hassan0Prince Okyere1Milad Amini Masouleh2Christoph Zrenner3Ulf Ziemann4Til Ole Bergmann5Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University Medical Center, Mainz, Germany; Leibniz Institute for Resilience Research (LIR), Mainz, Germany; Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Stanford University, USA; Wu-Tsai Neurosciences Institute, Stanford University, USA; Corresponding author;Leibniz Institute for Resilience Research (LIR), Mainz, GermanyNeuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University Medical Center, Mainz, Germany; School of Psychology, University of Surrey, Guildford, UKNeuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University Medical Center, Mainz, Germany; Department of Psychology and Neurosciences, Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystraße 67, Dortmund, Germany; Psychology Department, Ruhr University Bochum, Bochum, GermanyTemerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, Faculty of Medicine, And Institute for Biomedical Engineering, And Institute of Medical Science, University of Toronto, Toronto, CanadaDepartment of Neurology & Stroke, Eberhard Karls University of Tübingen, Tübingen, Germany; Hertie Institute for Clinical Brain Research, Eberhard Karls University of Tübingen, Tübingen, GermanyNeuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University Medical Center, Mainz, Germany; Leibniz Institute for Resilience Research (LIR), Mainz, Germany; Corresponding author;Leibniz Institute for Resilience Research (LIR), Mainz, GermanyThalamocortical sleep spindles, i.e., oscillatory bursts at ∼12–15 Hz of waxing and waning amplitude, are a hallmark feature of non-rapid eye movement (NREM) sleep and believed to play a key role in memory reactivation and consolidation. Generated in the thalamus and projecting to neocortex and hippocampus, they are phasically modulated by neocortical slow oscillations (<1 Hz) and in turn phasically modulate hippocampal sharp-wave ripples (>80 Hz). This hierarchical cross-frequency nesting, where slower oscillations group faster ones into certain excitability phases, may enable phase-dependent plasticity in the neocortex, and spindles have thus been considered windows of plasticity in the sleeping brain. However, the assumed phasic excitability modulation had not yet been demonstrated for spindles. Utilizing a recently developed real-time spindle detection algorithm, we applied spindle phase-triggered transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) hand area to characterize the corticospinal excitability profile of spindles via motor evoked potentials (MEP). MEPs showed net suppression during spindles, driven by a “pulse of inhibition” during its falling flank with no inhibition or facilitation during its peak, rising flank, or trough. This unidirectional (“asymmetric”) modulation occurred on top of the general sleep-related inhibition during spindle-free NREM sleep and did not extend into the refractory post-spindle periods. We conclude that spindles exert “asymmetric pulsed inhibition'' on corticospinal excitability. These findings and the developed real-time spindle targeting methods enable future studies to investigate the causal role of spindles in phase-dependent synaptic plasticity and systems memory consolidation during sleep by repetitively targeting relevant spindle phases.http://www.sciencedirect.com/science/article/pii/S1935861X25000464 |
| spellingShingle | Umair Hassan Prince Okyere Milad Amini Masouleh Christoph Zrenner Ulf Ziemann Til Ole Bergmann Pulsed inhibition of corticospinal excitability by the thalamocortical sleep spindle Brain Stimulation |
| title | Pulsed inhibition of corticospinal excitability by the thalamocortical sleep spindle |
| title_full | Pulsed inhibition of corticospinal excitability by the thalamocortical sleep spindle |
| title_fullStr | Pulsed inhibition of corticospinal excitability by the thalamocortical sleep spindle |
| title_full_unstemmed | Pulsed inhibition of corticospinal excitability by the thalamocortical sleep spindle |
| title_short | Pulsed inhibition of corticospinal excitability by the thalamocortical sleep spindle |
| title_sort | pulsed inhibition of corticospinal excitability by the thalamocortical sleep spindle |
| url | http://www.sciencedirect.com/science/article/pii/S1935861X25000464 |
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