Search bioRxiv⌕ Search

bioRxiv · 10.1101/2025.01.07.631687

Human sleep spindles track experimentally excited brain circuits

Abstract

Spindles are hallmark oscillations during non-rapid-eye-movement (NREM) sleep. Together with slow oscillations (SOs), they are thought to play a mechanistic role in the consolidation of learned information. The quantity and spatial distribution of spindles has been linked to brain activity during learning before sleep and to memory performance after sleep. If spindles are drawn to cortical areas excited through pre-sleep learning tasks, this begs the question whether the spatial distribution of spindles is flexible, and whether their regional expression can also be manipulated with experimental brain stimulation. We used excitatory transcranial direct current stimulation (tDCS) to stimulate the left and right motor cortex in a repeated-measures experimental design. After stimulation, we recorded high-density electroencephalography (EEG) during sleep to test how local stimulation modulated the regional expression of sleep spindles. Indeed, we show that excitatory tDCS of local cortical sites before sleep biases the expression of spindles to the excited locations during subsequent sleep. No effects of localised tDCS excitation were seen for SOs. These results demonstrate that the spatial topography of sleep spindles is neither hard-wired nor random, with spindles being flexibly directed to exogenously excited cortical circuits. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/631687v2_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@fb33c1org.highwire.dtl.DTLVardef@2f291org.highwire.dtl.DTLVardef@1831f08org.highwire.dtl.DTLVardef@16a7f6a_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG Statement of SignificanceSpindles are signatures of NREM sleep linked to memory consolidation, intelligence, and neurological disorders. Recent work shows the spatial distribution of spindles mirrors cortical activation patterns during learning. If spindles are preferentially expressed at cortical sites engaged during prior waking, the question arises whether spindles can be directed by inducing excitation exogenously with non-invasive brain stimulation. Here, we applied anodal-tDCS to either left or right motor areas before a nap. Indeed, we found that spindle (and not SO) rates are greater at cortical sites excited by tDCS. This result suggests the spatial distribution of spindles is flexible and is sensitive to experimental excitatory stimulation. This has implications for targeted rehabilitation of specific cortical areas and for developing sleep-based brain-computer interfaces.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Thom, J. L., Staresina, B. P.. 2025-01-07. Human sleep spindles track experimentally excited brain circuits. https://doi.org/10.1101/2025.01.07.631687

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Functional validation of allele-specific LMNB1 silencing in patient-derived astrocytes as a therapeutic option for Autosomal Dominant Leukodystrophy

Adult-onset Autosomal Dominant Leukodystrophy (ADLD) is a rare fatal leukodystrophy caused by increased LMNB1 gene dosage, most commonly resulting from duplication of the LMNB1 locus. Because ADLD is a gene dosage disorder, selective reduction of pathological LMNB1 expression represents a rational therapeutic strategy. Although allele-specific RNA interference has previously been shown to lower LMNB1 levels in patient-derived fibroblasts and directly reprogrammed neurons, its therapeutic effects have not been evaluated in disease-relevant human glial cells or using functional efficacy endpoints. Here, we established human induced pluripotent stem cell-derived astrocytes from ADLD patients as a human glial model in which to validate allele-specific LMNB1 silencing across molecular, cellular, and functional readouts. ADLD astrocytes recapitulated increased LMNB1 expression and characteristic nuclear abnormalities and displayed transcriptional alterations affecting extracellular matrix organization, calcium homeostasis, metabolism and RNA processing. Functionally, these cells also exhibited functional phenotypes suitable for therapeutic evaluation: astrocyte-conditioned medium impaired the viability of both murine and human oligodendroglial cultures, while conditioned-medium and direct astrocyte-seeding paradigms revealed impaired post-lesion myelin recovery in lysolecithin-treated cerebellar organotypic slices. Allele-specific LMNB1 silencing restored physiological LMNB1 levels, corrected nuclear abnormalities, attenuated astrocyte-mediated oligodendroglial toxicity, improved post-lesion myelin recovery, and was associated with selective transcriptional programs associated with extracellular support and cholesterol metabolism. Together, these findings provide molecular, cellular, and functional validation of allele-specific LMNB1 dosage correction in patient-derived human astrocytes and offer key support for LMNB1-lowering strategies in disease-relevant human glial cells.

neuroscience↗

Perceptual integration of multisensory haptic, visual, and auditory feedback for roughness discrimination in augmented reality

Understanding how our different senses interact to shape our perception is essential to design realistic and immersive virtual and augmented reality (VR/AR) experiences. The present study investigated how roughness perception can be modulated through haptic, visual, and auditory cues in AR using a vibrotactile wristband. Participants compared virtual textures varying in vibration frequency/amplitude, visual grain size, and friction sound. Results revealed strong linear relationships between stimulus parameters and perceived roughness, with haptic frequency and visual cues driving the highest discrimination performance. Adding non-informative sensory feedback reduced perceptual sensitivity, acting as noise. Individual differences emerged: participants who rated haptic as the easiest modality showed greater sensitivity to haptic variations, while visual-reliant participants performed better with visual cues. We conclude that roughness in AR can be systematically manipulated, but is vulnerable to perceptual interference from irrelevant inputs, where our work provides actionable insights for implementing optimized and adaptive AR/VR interfaces.

neuroscience↗

Structural and functional MRI signatures of Gambling Disorder: a case-control study

Gambling disorder (GD) is a behavioural addiction that may help identify addiction-related neural features without the direct neurobiological effects of a primary substance of dependence. We examined regional grey matter volume (GMV) and resting-state functional connectivity (rsFC) in the same well-characterised sample. Eighteen men with GD and 21 matched healthy controls underwent high-resolution structural and resting-state functional MRI. GMV was quantified across 214 cortical and subcortical regions, and seed-based rsFC analyses focused on striatal subdivisions and mesocorticolimbic regions. Group differences were evaluated using permutation testing and cluster-corrected mixed-effects modelling. GD was associated with lower GMV in the ventromedial prefrontal cortex, orbitofrontal regions and other cortical and subcortical areas, alongside higher GMV in a subset of limbic and default-mode regions. Participants with GD also showed lower connectivity between the limbic striatum and the hippocampus, thalamus and putamen. In exploratory analyses, somatomotor connectivity was positively associated with gambling severity (Problem Gambling Severity Index: Spearman's rho = 0.71, p = 0.003, false-discovery-rate-adjusted q = 0.016). Structural and functional findings overlapped spatially in regions associated with valuation, memory, reward and habit formation, but regional GMV did not mediate group differences in rsFC. These findings are broadly consistent with corticostriatal models of GD and identify candidate circuit-level differences for independent replication. Larger, more diverse and longitudinal samples are required to establish their reproducibility, temporal direction and clinical relevance.

neuroscience↗