Regional response to light illuminance across the human hypothalamus

Abstract

Light exerts multiple non-image-forming biological effects on physiology including the stimulation of alertness and cognition. However, the subcortical circuitry underlying the stimulating impact of light is not established in humans. We used 7 Tesla functional magnetic resonance imaging to assess the impact of variations in light illuminance on the regional activity of the hypothalamus while healthy young adults (N=26; 16 women; 24.3±2.9 y) were completing two auditory cognitive tasks. We find that, during both the executive and emotional tasks, higher illuminance triggered an activity increase over the posterior part of the hypothalamus, which includes part of the tuberomamillary nucleus and the posterior part of the lateral hypothalamus. In contrast, increasing illuminance evoked a decrease in activity over the anterior and ventral parts of the hypothalamus, encompassing notably the suprachiasmatic nucleus and another part of the tuberomammillary nucleus. Critically, the performance of the executive task was improved under higher illuminance and was negatively correlated with the activity of the posterior hypothalamus area. These findings reveal the distinct local dynamics of different hypothalamus regions that underlie the impact of light on cognition.

Keywords: 7T fMRI; circadian rhythm; cognition; human; hypothalamus; light; melanopsin; neuroscience.

Figure 1.. Experimental protocol.

(A) Overall timeline. After prior light history standardisation, participants performed executive (always first), emotional and attentional tasks (pseudo-randomly 2nd or 3rd, blue arrow). As the attentional task included fewer light conditions, it is not considered in the present manuscript (see Materials and methods for more details). (B) Spectral power distribution of light exposures. Monochromatic orange: 0.16 mel EDI lux; Polychromatic, blue-enriched light (6500 K); LOW, MID, HIGH: 37, 92, 190 mel EDI lux. For the present analyses, we discarded colour differences between the light conditions and only considered illuminance as indexed by mel EDI lux, constituting a limitation of our study. See Supplementary file 1b for full details). (C, D) Tasks procedures. Time is reported in seconds relative to session onset; participants were pseudo-randomly exposed to the 4 light conditions. (C) Executive task: alternation of letter detection blocks (0-back) and working memory blocks (2-back). (D) Emotional task: lure gender discrimination of vocalisations (50% angry (red), 50% neutral (white).

Figure 2.. Illuminance impact on the hypothalamus subparts.

(A) Segmentation of the hypothalamus in five subparts in a representative participant. The nuclei encompassed by the different subparts are indicated in the right inset – according to Billot et al., 2020. ARC: arcuate nucleus; DMH; dorsomedial nucleus; LH lateral hypothalamus; LTN: lateral tubular nucleus; MB: mamillary body; POA: preoptic area; PVN: paraventricular nucleus; PNH: posterior nucleus of the hypothalamus; SCN: suprachiasmatic nucleus; SON: supraoptic nucleus; TMN: tuberomammillary nucleus; VMN: ventromedial nucleus. (B, C) Estimates (beta; arbitrary unit – a.u.) of the collective impact of illuminance variation on the activity of each hypothalamus subpart (Refer to Table 1 full statistics). (B) Executive task: significant main effect of hypothalamus subparts (p=0.002), no significant main of task type (p=0.4) or subpart-by-task-type interaction (p=0.61). (C) Emotional task: significant main effect of hypothalamus subparts (p<0.0001), and of stimulus type (p=0.048) or subpart-by-stimulus-type interaction (p=0.74). (D–G) Whole brain analyses of the collective impact of the variations in illuminance over the hypothalamus area - for illustration. A local positive peak (red; p_uncorrected <0.001) was detected over the posterior hypothalamus subpart (light blue) in executive (E) and emotional (G). A local negative peak (red; p_uncorrected <0.001) was detected over the inferior-tubular hypothalamus subparts (light orange) during the executive task (D), while local negative peak (red; p_uncorrected <0.001) was detected over the inferior-anterior (yellow) and superior-anterior (blue) hypothalamus subparts during the emotional task (F) – insets correspond to enlargements over the hypothalamus area. Arrows from panels B and C arise from and are colour coded according to the hypothalamus subpart that is displayed in panels D to G. These results indicate that our finding does not arise from a nearby ‘leaking’ activation/deactivation. (H–K) Estimates of the impact of each illuminance on the activity of the hypothalamus subparts. (Refer for Table 2 and Supplementary file 1c–f for full statistics) Activity dynamics across illuminance for each subpart (colour code as in A). Results are displayed per task or stimulus type although no interactions with task or stimulus type were detected. Significant illuminance-by-hypothalamus-subpart interactions were detected for (H, I) the executive task (p=0.041) and (J, K) the emotional task (p=0.041). Small letter indicate significant difference (p<0.05) between the following subparts at illuminance: a. 92 mel EDI lux: posterior vs. superior-anterior & inferior-tubular; b. 190 mel EDI lux: posterior vs. inferior-anterior, superior-anterior and inferior-tubular; c. 0 mel EDI lux: posterior vs. superior-tubular; d. 92 mel EDI lux: posterior vs. superior-anterior; superior-anterior vs. superior-tubular; e. 190 mel EDI lux: posterior vs. inferior-anterior, superior-anterior and inferior-tubular; superior-tubular vs. superior-anterior, inferior-tubular and inferior-anterior. Means +- standard deviations are plotted.

Figure 3.. Impact of illuminance on performance and relationships with the activity of the posterior hypothalamus subpart.

(A) Accuracy (percentage of correct responses) to the 2-back increased with increasing illuminance (p=0.034). (B) Accuracy to the 2-back task is negatively correlated to the activity of the posterior hypothalamus subpart (p=0.0027). (C, D) Accuracy to the 2-back task is not correlated to the activity of the inferior-anterior (C) and inferior-tubular (D) hypothalamus subparts (p>0.4). Association between superior-anterior and superior-tubular subparts are not displayed but were not significant (p>0.6). See Supplementary file 1g for full details. (E) Accuracy to the 0-back task is not correlated to the activity of the posterior hypothalamus subpart (p=0.45). (F) Reaction times to the emotional stimuli did not significantly change with increasing illuminance (p=0.41). (G) Reaction times to the emotional stimuli are correlated to the activity of the posterior hypothalamus subpart (p=0.04) with higher activity associated to slower reaction times. (H) Reaction times to the neutral stimuli are not correlated to the activity of the posterior hypothalamus subpart (p=0.6). Box plots: horizontal line = median; box = higher/lower quartiles: vertical line = maximum/minimum. Regression plots: solid and dashed lines correspond to the significant and not significant linear regression lines, respectively.

Author response image 1.. Activity estimate variability per hypothalamus subpart and subpart size.