Abstracts

Rationale: Slow oscillations and sleep spindles are prominent brain oscillations during non-rapid eye movement (NREM) sleep that support sleep-dependent cognitive processes. Quiet sounds timed to the up-state of slow-oscillations (closed-loop auditory stimulation, CLAS) during NREM is a novel, non-invasive tool to increase slow oscillations and sleep-spindles with potential applications across many neurological and psychiatric disorders. Although slow oscillations originate in the cortex and sleep spindles are generated in the thalamus, the thalamocortical circuitry driving CLAS responses is not known.  We performed CLAS on participants with simultaneous scalp EEG and intracranial thalamic recordings to study the spatial and temporal impact of CLAS on thalamocortical oscillations.

Methods: We performed CLAS on 10 subjects (3F, ages 8.1-53.8 years old) with epilepsy from a variety of etiologies undergoing direct thalamic recordings during their epilepsy surgery evaluations. In each case, subjects wore headphones that delivered a quiet auditory click timed to the up state of slow oscillations (0.5-4 Hz) detected at FZ during NREM sleep. Following a night of CLAS, subjects slept with the headphones and slow oscillations were detected, but no stimulation delivered for a sham control. Electrode locations were confirmed on post-operative MRI or co-registration of pre-operative MRI and post-operative CT. Thalamic nuclei were reconstructed using FreeSurfer. The deepest thalamic electrodes and FZ and CZ referenced to a non-cephalic electrode placed on the second spinous process were analyzed. Data were divided into single trials centered on auditory stimulation. Trials were rejected if peak to peak amplitude exceeded a manually determined threshold for each channel. The evoked responses were compared between CLAS and sham nights in scalp EEG and the thalamus. 

Results: We report preliminary results on one subject with both anterior nucleus (AN) and centromedian nucleus (CM) thalamic recordings. CLAS-evoked cortical and thalamic slow oscillations were detected in each the FZ and CZ channels and the AN and CM thalamic nuclei (Figure 1). A stronger and earlier initial evoked response was observed in the CM. 

Conclusions: These results identify that CLAS evokes both cortical and thalamic slow oscillations. These data further suggest that the timing and amplitude of cortical and thalamic responses may be regionally specific. Future work will evaluate the remaining subjects and quantify thalamocortical slow oscillations and spindles following CLAS.

Funding: NIH NINDS R01NS115868