Objective: Assess neural activity in various brain areas in sleep versus wakefulness in pediatric patients with movement disorders

Background: Pedunculopontine nucleus (PPN) is believed to play a key role in regulation of the sleep-wake cycle as part of the reticular activating system(1) and is hypothesized to play a significant role in rapid eye movement (REM) sleep given recent effects of stimulation in this area on REM-sleep behavior disorder in Parkinson’s disease patients(2). Assessment of neural activity during sleep has predominantly been examined via electroencephalography, or intracranial recordings in nonhuman primates(3).

Method: analysis of intracranial data collected during assessment of optimal targets for deep brain stimulation utilizing a previously reported technique(4). Electrode recording location was confirmed by merge of postoperative CT and preoperative MRI. Neural spike rasters were generated for intracranial signals recorded overnight, using a custom spike sorting pipeline. Firing rates ((number of spike)/second) were calculated for each recording channel by convolving a gaussian window to detected spike train. Video and electroencephalography were utilized to label periods of sleep versus wakefulness.

Results: In the six subjects assessed there was a substantial decrease in neuronal activity across all brain areas during sleep. Pedunculopontine nucleus demonstrated this same pattern in all subjects, with a decrease in neural activity during sleep and immediate increase during wakefulness. Firing rates were variable between subjects, but unchanged between PPN versus ventralis intermedius nucleus of thalamus (VIM.)

Conclusion: Neural activity in pedunculopontine nucleus decreases during sleep, as seen in other brain areas. This is seen across multiple subjects with dystonia of different underlying etiologies. This does not appear to fluctuate with sleep stages. Despite the role of PPN in sleep-wake cycle and effects of stimulation on REM sleep behavior disorder in Parkinson’s disease patients its neural firing rates during sleep are similar to other areas of brain. Further investigation is indicated to assess for neural activity changes in to better understand sleep patterns, and with a larger cohort to assess generalizability.

References: 1. Urbano FJ, D’Onofrio S, Luster B, Beck P, Hyde J, Bisagno V, et al. Pedunculopontine nucleus gamma band activity-preconscious awareness, waking, and REM sleep. Front Neurol. 2014 Oct 20;5(OCT):210.
2. Romigi A, Placidi F, Peppe A, Pierantozzi M, Izzi F, Brusa L, et al. LETTER TO THE EDITOR Pedunculopontine nucleus stimulation influences REM sleep in Parkinson’s disease.
3. Karachi C, Francois C. Role of the pedunculopontine nucleus in controlling gait and sleep in normal and parkinsonian monkeys. Journal of Neural Transmission 2017 125:3 [Internet]. 2017 Jan 13 [cited 2023 Mar 12];125(3):471–83. Available from: https://link.springer.com/article/10.1007/s00702-017-1678-y
4. Sanger TD, Liker M, Arguelles E, Deshpande R, Maskooki A, Ferman D, et al. Pediatric Deep Brain Stimulation Using Awake Recording and Stimulation for Target Selection in an Inpatient Neuromodulation Monitoring Unit. Brain Sciences 2018, Vol 8, Page 135 [Internet]. 2018 Jul 17 [cited 2022 Feb 18];8(7):135. Available from: https://www.mdpi.com/2076-3425/8/7/135/htm

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neural-activity-in-pedunculopontine-nucleus-during-sleep/