Thalamic Nuclei Differentially Coordinate Propagation of Cortical Slow Oscillations

Abstract

Sleep slow oscillations (SOs) vary in the spatial extent of their cortical propagation, ranging from widespread Global events to spatially restricted Frontal events. These distinctions could have functional consequences for memory consolidation. It remains unknown whether individual thalamic nuclei are differentially engaged across SO propagation types, and whether thalamic activity before SO onset predicts subsequent propagation. We analyzed simultaneous scalp EEG and thalamic stereo-EEG from 24 full-night recordings in 6 epilepsy patients, sampling 11 thalamic nuclei and enabling direct characterization of nucleus-specific thalamocortical interactions during naturally occurring sleep slow oscillations. Cortical SOs were classified by propagation type and thalamocortical coupling was characterized via peri-event histograms, phase-locking analysis, waveform morphology comparisons, and pre-onset spectral and cross-frequency coupling features. All well-sampled thalamic nuclei showed broad temporal co-occurrence with prefrontal SOs, yet occupied distinct phase positions within the cortical SO cycle. Medial pulvinar (PuM) showed the strongest phase locking across subjects, with significant preference for the ascending post-trough phase. Among the examined nuclei, Frontal SOs were associated with significant phase locking in PuM, whereas Global SOs preferentially synchronized the centromedian nucleus near the cortical down-state trough. Thalamic waveform morphology differed systematically with propagation extent, with opposing effects between pulvinar and intralaminar nuclei. Pre-onset PuM activity showed suppressed alpha, sigma, and beta power and delta-phase cross-frequency coupling before Global SOs (all p < 0.05). The human thalamus engages NREM sleep SOs through nucleus-specific, propagation-sensitive dynamics rather than as a functionally uniform structure. Pre-onset PuM activity contains predictive signatures of cortical SO propagation extent. This finding has implications for closed-loop neuromodulation targeting specific SO states, although replication in larger cohorts is needed.