Modulation of thalamic network connectivity using transcranial direct current stimulation based on resting-state functional magnetic resonance imaging to improve hypoxia-induced cognitive impairments

Abstract

Hypoxic conditions at high altitudes severely affect cognitive functions such as vigilance, attention, and memory and reduce cognitive ability. Hence, there is a critical need to investigate methods and associated mechanisms for improving the cognitive ability of workers at high altitudes. This study aimed to use transcranial direct current stimulation (tDCS) to modulate thalamic network functional connectivity to enhance cognitive ability. We recruited 20 healthy participants that underwent hypoxia exposure in a hypoxic chamber at atmospheric pressure to simulate a hypoxic environment at 4,000 m. Participants received both sham and real stimulation. tDCS significantly improved the participants' emotional status, including depression, fatigue, and energy level. These effects were sustained for more than 6 h (P < 0.05 at the second to fifth measurements). In addition, tDCS enhanced vigilance, but this was only effective within 2 h (P < 0.05 at the second and third measurements). Central fatigue was significantly ameliorated, and cerebral blood oxygen saturation was increased within 4 h (P < 0.05 at the second, third, and fourth measurements). Furthermore, functional connectivity results using the thalamus as a seed revealed enhanced connectivity between the thalamus and hippocampus, cingulate gyrus, and amygdala after tDCS. These results indicated that tDCS increased local cerebral blood oxygen saturation and enhanced thalamic network connectivity in a hypoxic environment, thereby improving vigilance, depression, fatigue, and energy levels. These findings suggest that tDCS may partially rescue the cognitive decline caused by hypoxia within a short period. This approach affords a safe and effective cognitive enhancement method for all types of high-altitude workers with a large mental load.

Keywords: cognitive function; functional connectivity; plateau hypoxia; resting-state functional magnetic resonance imaging; transcranial direct current stimulation.

FIGURE 1

Transcranial direct current stimulation montage. Saline-soaked anodal sponge electrodes (5 cm × 5 cm) are applied over the left M1 region, and a larger cathodal electrode (5 cm × 7 cm) is placed on the right supraorbital area.

FIGURE 2

Experimental procedures. The entire experiment consists of two sessions, i.e., sham and real sessions. The real session is separated from the sham session by 30 days to eliminate after-effects. rsfMRI scans are performed before and after the sham session to obtain baseline and post-sham functional images. After the real session, another rsfMRI scan is performed to obtain post-tDCS functional images.

FIGURE 3

Profile of mood states results. (A) Tension-anxiety results. (B) Anger-hostility results. (C) Confusion-bewilderment results. (D) Depression-dejection results. (E) Fatigue-inertia results. (F) Vigor-activity results. Asterisks indicate significant differences between real and sham tDCS conditions.

FIGURE 4

Critical flicker frequency and regional oxygen saturation results. (A) PVT results. (B) CFF results. (C)rSO₂ results. Asterisks indicate significant differences between real and sham tDCS conditions.

FIGURE 5

Functional connectivity changes are caused by hypoxia and anodal tDCS. The left figure depicts hypoxia-induced FC changes of the thalamic network using the contrast of baseline > post-sham. The right figure depicts anodal tDCS-induced FC changes of the thalamic network in the hypoxia environment using the contrast of post-tDCS > post-sham. The red dashed and solid lines represent decreased and increased FC, respectively.

FIGURE 6

Correlation results. (A) Cingulate correlation results. FC changes between the thalamus and cingulate are correlated with depression-dejection in the fifth test across all participants under the real tDCS condition. (B) Hippocampus correlation results. FC changes between the thalamus and hippocampus are correlated with the reaction time of PVT in the fifth test across all participants under the real tDCS condition. The coefficient of determination denoted R² in the figure indicates the proportion of depression-dejection that could be predicted from FC variation. FC, functional connectivity.