The Role of the Thalamus in the Neurological Mechanism of Subjective Sleepiness: An fMRI Study

Yuki Motomura; Shingo Kitamura; Kyoko Nakazaki; Kentaro Oba; Ruri Katsunuma; Yuri Terasawa; Akiko Hida; Yoshiya Moriguchi; Kazuo Mishima

doi:10.2147/NSS.S297309

The Role of the Thalamus in the Neurological Mechanism of Subjective Sleepiness: An fMRI Study

Nat Sci Sleep. 2021 Jun 28:13:899-921. doi: 10.2147/NSS.S297309. eCollection 2021.

Authors

Yuki Motomura^{1

2

3}, Shingo Kitamura¹, Kyoko Nakazaki¹, Kentaro Oba^{1

4}, Ruri Katsunuma^{1

3}, Yuri Terasawa^{1

5}, Akiko Hida¹, Yoshiya Moriguchi^{1

3}, Kazuo Mishima^{1

6

7}

Affiliations

¹ Department of Sleep-Wake Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, 187-8553, Japan.
² Faculty of Design, Kyushu University, Fukuoka, 815-8540, Japan.
³ Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Tokyo, 187-8553, Japan.
⁴ Department of Human Brain Science, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-8575, Japan.
⁵ Department of Psychology, Keio University, Kanagawa, 223-8521, Japan.
⁶ Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, 010-8543, Japan.
⁷ International Institute for Integrative Sleep Medicine, University of Tsukuba, Ibaraki, Japan.

Abstract

Purpose: The thalamus, the region that forms the attentional network and transmits external sensory signals to the entire brain, is important for sleepiness. Herein, we examined the relationship between activity in the thalamus-seed brain network and subjective sleepiness.

Materials and methods: Fifteen healthy male participants underwent an experiment comprising a baseline evaluation and two successive interventions, a 9-day sleep extension followed by 1-night total sleep deprivation. Pre- and post-intervention tests included the Karolinska sleepiness scale and neuroimaging for arterial spin labeling and functional connectivity. We examined the association between subjective sleepiness and the functional magnetic resonance imaging indices.

Results: The functional connectivity between the left or right thalamus and various brain regions displayed a significant negative association with subjective sleepiness, and the functional connectivity between the left and right thalamus displayed a significant positive association with subjective sleepiness. The graph theory analysis indicated that the number of positive functional connectivity related to the thalamus showed a strong negative association with subjective sleepiness, and conversely, the number of negative functional connectivity showed a positive association with subjective sleepiness. Arterial spin labeling analysis indicated that the blood flow in both the left and right thalami was significantly negatively associated with subjective sleepiness. Functional connectivity between the anterior cingulate cortex and salience network areas of the left insular cortex, and that between the anterior and posterior cingulate cortices showed a strong positive and negative association with subjective sleepiness, respectively.

Conclusion: Subjective sleepiness and the thalamic-cortical network dynamics are strongly related, indicating the application of graph theory to study sleepiness and consciousness. These results also demonstrate that resting functional connectivity largely reflects the "state" of the subject, suggesting that the control of sleep and conscious states is essential when using functional magnetic resonance imaging indices as biomarkers.

Keywords: ASL; consciousness; functional connectivity; graph theory; rCBF; sleep; subjective sleepiness.

Grants and funding

This study was supported by a Grant-in-Aid for the Strategic Research Program for Brain Sciences (Understanding of molecular and environmental bases for brain health) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, an Intramural Research Grant for Neurological and Psychiatric Disorders from the National Center of Neurology and Psychiatry (23-3), a JSPS KAKENHI (No. 25293255, 16K21657, 19H03578), and a Grant-in-Aid for JSPS Fellows (15J12161) and AMED (No JP19ak0101059).