Doctoral thesis (Dissertations and theses)
Multimodal Investigation of Non-Image Forming Effects of Light on the Brain: Impact of Time of Day and Developmental Stage
Sharifpour, Roya
2025
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Keywords :
Light; Non-Image Forming (NIF); Adolescents; Brain; fMRI; TMS-EEG; Hypothalamus; Effective Connectivity; Cortical Excitability; Time of Day
Abstract :
[en] Lighting can significantly influence various aspects of our life, including health, performance, and behavior. Inappropriate lighting is associated with numerous challenges in these areas, while appropriate lighting can enhance well-being and functionality. Key factors such as timing, intensity, and spectral composition play crucial roles in determining appropriate versus inappropriate lighting conditions. The human brain processes light via two pathways: the classical visual system, responsible for image formation, and the non-image forming (NIF) system, which reacts to environmental light levels. The NIF system is especially sensitive to shorter blue wavelengths (~480 nm), influencing circadian rhythms, neuroendocrine functions, and neurobehavioral responses. Over the years, lighting technology has transitioned from incandescent and fluorescent bulbs to energy-efficient light emitting diodes (LEDs). This shift has altered the spectral composition of indoor lighting, increasing the prevalence of blue light, as typical "white" LEDs peak between 440- 460 nm. Moreover, the widespread use of LEDs has extended our exposure to blue-enriched light into biological night, which can be detrimental to health by disrupting circadian rhythms and other physiological processes. Given these developments, it is essential to understand how light interacts with the brain and influences its functions beyond vision. Furthermore, the understanding of the NIF system, combined with advancements in LED technology, has given rise to the concept of integrative lighting, which aims to optimize both visual clarity and biological effects. To maximize the health benefits of integrative lighting and minimize adverse impacts, it is essential to investigate how light affects brain function and how factors like age and timing of exposure modulate these effects. To further explore the NIF effects of light on human brain, we employed ultra-high-field 7 Tesla (UHF 7T) functional magnetic resonance imaging (fMRI) for its high resolution, allowing us to image small subcortical structures affected by light, such as the hypothalamus and thalamus nuclei. Healthy adolescents and young adults participated in an fMRI protocol at various times of day while exposed to different light intensities and engaged in auditory cognitive tasks. Additionally, we used transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) to assess NIF effects at the cortical level, with participants completing a TMS-EEG protocol in the afternoon under varying light conditions. In this thesis, we initially focused on understanding how light affects one of its primary targets: the hypothalamus. This involved two studies. We first investigated whether there were regional variations in response to light exposure within the human hypothalamus during cognitive tasks in the morning among young adults. The results indicated distinct response patterns to increasing light levels across different regions of the hypothalamus. Notably, higher light levels led to increased activity in the posterior hypothalamus, while the anterior and ventral regions showed reduced activity. This suggests that the posterior hypothalamus may be a key area where light stimulates cognition and alertness, potentially through mechanisms involving orexin and histamine signaling. We expanded this investigation by doing fMRI in the evening and including adolescents to assess how time-of-day and developmental age influence hypothalamic response dynamics. The findings reinforced the anterior-posterior gradient observed in response to varying light levels. Specifically, increased illuminance continued to activate the posterior hypothalamus while decreasing activity in the anterior and ventral regions during the evening and in adolescents. Time-of-day did not alter the hypothalamic response, while age did; adolescents exhibited a stronger response to light compared to adults, showing more significant deactivation in the anterior and ventral regions. This suggests greater sensitivity in adolescents and highlights other functional differences related to age. Next, we investigated the thalamus' established role in NIF functions, as highlighted in the literature. Given its key position as a central hub in the brain' signaling network, the thalamus likely plays a crucial role in relaying NIF signals to the cortex, thereby influencing alertness and cognitive function. In this context, we hypothesized that the impact of light on cognition might extends beyond altering regional activity to also affect functional connectivity throughout the brain. Our third study focused therefore on how light affects functional connectivity between the thalamus and two cortical regions involved in executive functions, particularly working memory. We examined how light modulates connectivity among these areas while considering age and time-of-day differences. Our findings revealed that moderate illuminance blue-enriched light enhanced a cortico-cortical connectivity across all groups. Interestingly, low illuminance orange light also strengthened a connectivity from the thalamus to one of the cortical regions. Additionally, both time-of-day and age influenced how light affected connectivity. For instance, the highest illuminance blue-enriched light strengthened the thalamus-to-medial frontal gyrus connectivity in the morning among adults. Moreover, moderate illuminance blue-enriched light positively impacted the thalamus-to-supramarginal gyrus connectivity in adolescents. This investigation deepens our understanding of the complex neural mechanisms by which light affects cognitive processes and highlights the role of time-of-day and age. In the final study, we extended our investigation to cortical level by using TMS-EEG to examine, for the first time, the effect of light on cortical excitability. Our findings revealed a distinct response between adolescents and adults. While cortical excitability in adults followed an apparent inverted U-shaped function with increasing illuminance, light showed no effect on cortical excitability in adolescents. These results further emphasize the different sensitivity of adolescents to light. Overall, this thesis explores aspects of the brain circuitry involved in how light affects cognitive functions. It emphasizes the significance of factors like time-of-day and age, highlighting that a deeper understanding of how light influences cognitive processes and its modulatory factors can lead to integrative lighting solutions that promote health and well-being in the future.
Research Center/Unit :
GIGA-SLEEP - GIGA CRC In vivo Imaging-Sleep and chronobiology - ULiège
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Sharifpour, Roya  ;  Université de Liège - ULiège > GIGA
Language :
English
Title :
Multimodal Investigation of Non-Image Forming Effects of Light on the Brain: Impact of Time of Day and Developmental Stage
Defense date :
16 January 2025
Institution :
GIGA Institute , CRC Human Imaging Unit [Medicine], Liege, Belgium
Degree :
Doctor of Philosophy
Promotor :
Vandewalle, Gilles  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques
President :
Maquet, Pierre  ;  Université de Liège - ULiège > Département des sciences cliniques > Neurologie
Secretary :
Bahri, Mohamed Ali  ;  Université de Liège - ULiège > Département de physique
Jury member :
Philips, Jean-Christophe ;  Université de Liège - ULiège > Département des sciences de la santé publique
Goffaux, Valerie;  UC Louvain > Institute of Neuroscience (IONS)
Cajochen, Christian;  Psychiatric Hospital of the University of Basel > Centre for Chronobiology
European Projects :
H2020 - 860613 - LIGHTCAP - LIGHTCAP: Light, Cognition, Attention, Perception
Name of the research project :
TEENLIGHT
Funders :
Marie Skłodowska-Curie Actions
F.R.S.-FNRS - Fonds de la Recherche Scientifique
Leon Fredericq Foundation
European Union
Available on ORBi :
since 30 January 2025

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