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Focal mediodorsal thalamus stroke impairs sleep-wake stability, thalamocortical oscillations, and working memory, and auditory stimulation restores these deficits in mice

Optically guided photothrombotic stroke of the mediodorsal thalamus in awake mice increased wake-NREMS-wake transitions, elevated slow-wave activity during wakefulness, and reduced frontal slow waves and spindles during NREMS compared to sham controls (P=0.03 to P<0.001). These changes were accompanied by impaired working memory and pain hypersensitivity (P<0.001). Daily 1-Hz auditory stimulation during NREMS-rich periods normalized sleep continuity, restored SW-spindle coupling, and improved working memory to sham levels.

Last updated: Jul 18, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score26/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Optical Ministroke Reveals Dual-Role Frontal Thalamocortical Networks in Sleep Quality and Memory.

observational

Borsa M, Lenzi I, Obrist C, Rusterholz T, Bassetti CL, Adamantidis A, Gutierrez C · Stroke (2026)

Participants: N/A
Duration: 20 days (with 10-day auditory stimulation subset)
Intervention: Optically guided photothrombotic stroke of the mediodorsal thalamus (MD) with intraperitoneal Rose Bengal (10 mg/mL) and 532-nm light (10 mW, 6 min) in awake mice; subset received daily 1-Hz auditory stimulation (~1 h/session for 10 days during NREMS-rich periods)
Outcome: Sleep-wake features and oscillations (EEG/EMG), working memory (Y-maze errors), pain sensitivity, SW-spindle coupling, MD-anterior cingulate cortex connectivity
Effect Size: r=-0.88 (working memory errors vs. spindle rate), r=-0.81 (working memory errors vs. SW-spindle coupling)
Population: Male C57BL/6JRj mice aged 10-16 weeks (8 cohorts, n=8-12/group)

Result:

PubMed: 42454410DOI: 10.1161/STROKEAHA.126.056284

Mechanism Graph

Focal MD lesion disrupts thalamocortical slow-wave and spindle generation
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Impaired SW-spindle coupling and increased sleep-wake transitions
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Reduced MD-anterior cingulate cortex connectivity to parvalbumin-positive interneurons
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Auditory stimulation restores SW-spindle coupling, sleep continuity, and cognitive function

Limitations

  • ⚠Study conducted in male mice only, limiting generalizability to females
  • ⚠Small sample sizes per cohort (n=8-12) and potential selection bias from exclusion of animals with poor signals or incomplete testing

Frequently Asked Questions

What is the optically guided photothrombotic stroke model?▼

It is a method to induce focal lesions in deep brain structures like the mediodorsal thalamus in awake, freely behaving mice using intraperitoneal Rose Bengal and targeted 532-nm light, avoiding anesthesia.

How did auditory stimulation affect sleep and memory after thalamic stroke?▼

Daily 1-Hz auditory stimulation during NREMS-rich periods normalized sleep continuity, restored slow-wave-spindle coupling, and improved working memory to sham levels in mice with MD strokes.

What were the main outcomes measured in this study?▼

Primary outcomes included longitudinal sleep-wake features (e.g., transitions, slow-wave activity, spindles), working memory (Y-maze errors), and pain sensitivity over 20 days.

Does this study have human relevance?▼

Yes, the authors note that the observed deficits recapitulate hallmark features of paramedian thalamic infarcts in humans, suggesting translational potential.

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References

  1. 1.Borsa M, Lenzi I, Obrist C, Rusterholz T, Bassetti CL, Adamantidis A, Gutierrez C. "Optical Ministroke Reveals Dual-Role Frontal Thalamocortical Networks in Sleep Quality and Memory.." Stroke, 2026. PMID: 42454410 DOI: 10.1161/STROKEAHA.126.056284
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.