Fig 1.
Neuroanatomy of upgaze with trigeminal proprioceptive activation to regulate a brainstem arousal mechanism.
Black arrows indicate voluntary contractions of the superior rectus and levator palpebrae superioris (LPSM) fast-twitch fibers via the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the oculomotor neurons. A red arrow indicates involuntary reflex contractions of the LPSM slow-twitch fibers. Green arrows indicate trigeminal proprioceptive stimulations to induce reflex contractions of the LPSM slow-twitch muscle fibers and stimulate the locus coeruleus (LC) via the mesencephalic trigeminal nucleus (MesV) through gap junctions. Blue arrows indicate efferent stimulations from the locus coeruleus (LC) to activate the ventromedial prefrontal cortex (vmPFC), palmar sweat glands, amygdala, and hippocampus. A blue dotted arrow indicates stimulation from the LC to the oculomotor neurons. The gray arrow indicates an afferent stimulation from the rostral ventrolateral medulla (RVLM) to the LC.
Fig 2.
Palmar sweating response during a 60° upgaze for 5 s.
(A–C) Three representative results showing various palmar sweating patterns. (D) No palmar sweating response in the same subject (C) on another day when he had insufficient sleep time. (E) The integrated absolute amounts of water loss during 5-s of 60° upgazes were compared with those in the preceding 5-s of 45° downgaze (*P < 0.05).
Fig 3.
Measurement of hemodynamic changes in the prefrontal cortex with functional near-infrared spectroscopy.
(A) Headgear with 28 mounted probes for 45 recording channels is securely placed on the scalp overlying mainly the prefrontal area while participants performed the 60° upgaze. The light-detection probe between channels 16 and 17 was located on the Fz, and the lowest probes were positioned along the Fp1–Fp2 line. (B) Typical concentration changes in deoxyhemoglobin (Deoxy-Hb), oxyhemoglobin (Oxy-Hb), and total hemoglobin (Total-Hb) during the 10-s 60° upgaze task at channel 41.
Fig 4.
Depiction of the activated ventromedial prefrontal cortex during a 10-s 60° upgaze as measured by functional near-infrared spectroscopy.
(A–C) Three representative examples show various activated prefrontal cortex areas due to the integrated concentration changes in deoxyhemoglobin (Deoxy-Hb), oxyhemoglobin (Oxy-Hb), and total hemoglobin (Total-Hb). (D) The accumulation of the integrated concentration changes from all 12 subjects depicts the ventromedial prefrontal cortex activation in deoxyhemoglobin (Deoxy-Hb), oxyhemoglobin (Oxy-Hb), and total hemoglobin (Total-Hb) concentrations.
Fig 5.
Degree-dependent ventromedial prefrontal cortex activation following changes in the degree of eyelid retraction.
Relative changes in the deoxyhemoglobin, oxyhemoglobin, total hemoglobin concentrations (mmol/L × cm) were measured at Fp1 and Fp2 according to the changes in the degree of eyelid retraction such as 45° downgaze (-45°), primary gaze (0°), 30° upgaze (+30°), and 60° upgaze (+60°). Three representative examples show bilateral activation for 5-s 30° upgaze (+30°) (A), 5-s asymmetrical bilateral activation from primary gaze (0°) (B), and unilateral activation and contralateral deactivation (C). (D) The integrated concentration of deoxyhemoglobin for 5 s was significantly and degree-dependently increased from the 30° upgaze (*P < 0.05).
Fig 6.
Impaired activation of the ipsilateral ventromedial prefrontal cortex by unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle.
Relative changes in the deoxyhemoglobin, oxyhemoglobin, total hemoglobin concentrations (mmol/L × cm) were measured at Fp1 and Fp2 according to the changes in the degree of eyelid retraction such as 45° downgaze (-45°), primary gaze (0°), 30° upgaze (+30°), and 60° upgaze (+60°) before (A1, B1, and C1) and after (A2, B2, and C2) anesthetization. Before anesthetization, three representative examples show bilateral activation (A1), asymmetrical bilateral activation (B1), and unilateral activation and contralateral deactivation for 5 s of 60° upgaze (+60°) (C1). After anesthetization, all of the examples show impaired activation at Fp1 or Fp2 on the anesthetized side (A2, B2, and C2). (D) On the anesthetized side, the increased integrated concentration of deoxyhemoglobin by 60° upgaze for 5 s after anesthetization was significantly smaller than that before anesthetization (*P < 0.01). However, on the non-anesthetized side, the increased integrated concentration of deoxyhemoglobin by 60° upgaze for 5 s after anesthetization was not significantly smaller than that before anesthetization.