Impact of light on task-evoked pupil responses during cognitive tasks.

Light has many non-image-forming functions including modulation of pupil size and stimulation of alertness and cognition. Part of these non-image-forming effects may be mediated by the brainstem locus coeruleus. The processing of sensory inputs can be associated with a transient pupil dilation that is likely driven in part by the phasic activity of the locus coeruleus. In the present study, we aimed to characterise the task-evoked pupil response associated with auditory inputs under different light levels and across two cognitive tasks. We continuously monitored the pupil of 20 young healthy participants (mean [SD] 24.05 [4.0] years; 14 women) whilst they completed an attentional and an emotional auditory task whilst exposed to repeated 30-40-s blocks of light interleaved with darkness periods. Blocks could either consist of monochromatic orange light (0.16 melanopic equivalent daylight illuminance (EDI) lux) or blue-enriched white light of three different levels [37, 92, 190 melanopic EDI lux; 6500 K]. For the analysis, 15 and then 14 participants were included in the attentional and emotional tasks, respectively. Generalised linear mixed models showed a significant main effect of light level on the task-evoked pupil responses triggered by the attentional and emotional tasks (p ≤ 0.0001). The impact of light was different for the target versus non-target stimulus of the attentional task but was not different for the emotional and neutral stimulus of the emotional task. There is a smaller sustained pupil size during brighter light blocks but, a higher light level triggers a stronger task-evoked pupil response to auditory stimulation, presumably through the recruitment of the locus coeruleus.

Impact of repeated short light exposures on sustained pupil responses in an fMRI environment.

Light triggers numerous non-image-forming, or non-visual, biological effects. The brain correlates of these non-image-forming effects have been investigated, notably using magnetic resonance imaging and short light exposures varying in irradiance and spectral quality. However, it is not clear whether non-image-forming responses estimation may be biased by having light in sequential blocks, for example, through a potential carryover effect of one light onto the next. We reasoned that pupil light reflex was an easy readout of one of the non-image-forming effects of light that could be used to address this issue. We characterised the sustained pupil light reflex in 13-16 healthy young individuals under short light exposures during three distinct cognitive processes (executive, emotional and attentional). Light conditions pseudo-randomly alternated between monochromatic orange light (0.16 melanopic equivalent daylight illuminance lux) and polychromatic blue-enriched white light of three different levels (37, 92, 190 melanopic equivalent daylight illuminance lux). As expected, higher melanopic irradiance was associated with larger sustained pupil light reflex in each cognitive domain. This result was stable over the light sequence under higher melanopic irradiance levels compared with lower ones. Exploratory frequency-domain analyses further revealed that sustained pupil light reflex was more variable under lower melanopic irradiance levels. Importantly, sustained pupil light reflex varied across tasks independently of the light condition, pointing to a potential impact of light history and/or cognitive context on sustained pupil light reflex. Together, our results emphasise that the distinct contribution and adaptation of the different retinal photoreceptors influence the non-image-forming effects of light and therefore potentially their brain correlates.

Light modulates task-dependent thalamo-cortical connectivity during an auditory attentional task.

Exposure to blue wavelength light stimulates alertness and performance by modulating a widespread set of task-dependent cortical and subcortical areas. How light affects the crosstalk between brain areas to trigger this stimulating effect is not established. Here we record the brain activity of 19 healthy young participants (24.05±2.63; 12 women) while they complete an auditory attentional task in darkness or under an active (blue-enriched) or a control (orange) light, in an ultra-high-field 7 Tesla MRI scanner. We test if light modulates the effective connectivity between an area of the posterior associative thalamus, encompassing the pulvinar, and the intraparietal sulcus (IPS), key areas in the regulation of attention. We find that only the blue-enriched light strengthens the connection from the posterior thalamus to the IPS. To the best of our knowledge, our results provide the first empirical data supporting that blue wavelength light affects ongoing non-visual cognitive activity by modulating task-dependent information flow from subcortical to cortical areas.

Locus coeruleus activity while awake is associated with REM sleep quality in older individuals.

BACKGROUNDThe locus coeruleus (LC) is the primary source of norepinephrine in the brain and regulates arousal and sleep. Animal research shows that it plays important roles in the transition between sleep and wakefulness, and between slow wave sleep and rapid eye movement sleep (REMS). It is unclear, however, whether the activity of the LC predicts sleep variability in humans.METHODSWe used 7-Tesla functional MRI, sleep electroencephalography (EEG), and a sleep questionnaire to test whether the LC activity during wakefulness was associated with sleep quality in 33 healthy younger (~22 years old; 28 women, 5 men) and 19 older (~61 years old; 14 women, 5 men) individuals.RESULTSWe found that, in older but not in younger participants, higher LC activity, as probed during an auditory attentional task, was associated with worse subjective sleep quality and with lower power over the EEG theta band during REMS. The results remained robust even when accounting for the age-related changes in the integrity of the LC.CONCLUSIONThese findings suggest that LC activity correlates with the perception of the sleep quality and an essential oscillatory mode of REMS, and we found that the LC may be an important target in the treatment of sleep- and age-related diseases.FUNDINGThis work was supported by Fonds National de la Recherche Scientifique (FRS-FNRS, T.0242.19 & J. 0222.20), Action de Recherche Concertée - Fédération Wallonie-Bruxelles (ARC SLEEPDEM 17/27-09), Fondation Recherche Alzheimer (SAO-FRA 2019/0025), ULiège, and European Regional Development Fund (Radiomed & Biomed-Hub).

Structural and functional characterization of the locus coeruleus in young and late middle-aged individuals.

Introduction: The brainstem locus coeruleus (LC) influences a broad range of brain processes, including cognition. The so-called LC contrast is an accepted marker of the integrity of the LC that consists of a local hyperintensity on specific Magnetic Resonance Imaging (MRI) structural images. The small size of the LC has, however, rendered its functional characterization difficult in humans, including in aging. A full characterization of the structural and functional characteristics of the LC in healthy young and late middle-aged individuals is needed to determine the potential roles of the LC in different medical conditions. Here, we wanted to determine whether the activation of the LC in a mismatch negativity task changes in aging and whether the LC functional response was associated to the LC contrast. Methods: We used Ultra-High Field (UHF) 7-Tesla functional MRI (fMRI) to record brain response during an auditory oddball task in 53 healthy volunteers, including 34 younger (age: 22.15y ± 3.27; 29 women) and 19 late middle-aged (age: 61.05y ± 5.3; 14 women) individuals. Results: Whole-brain analyses confirmed brain responses in the typical cortical and subcortical regions previously associated with mismatch negativity. When focusing on the brainstem, we found a significant response in the rostral part of the LC probability mask generated based on individual LC images. Although bilateral, the activation was more extensive in the left LC. Individual LC activity was not significantly different between young and late middle-aged individuals. Importantly, while the LC contrast was higher in older individuals, the functional response of the LC was not significantly associated with its contrast. Discussion: These findings may suggest that the age-related alterations of the LC structural integrity may not be related to changes in its functional response. The results further suggest that LC responses may remain stable in healthy individuals aged 20 to 70.

In vivo Locus Coeruleus activity while awake is associated with REM sleep quality in healthy older individuals.

The locus coeruleus (LC) is the primary source of norepinephrine (NE) in the brain, and the LC-NE system is involved in regulating arousal and sleep. It plays key roles in the transition between sleep and wakefulness, and between slow wave sleep (SWS) and rapid eye movement sleep (REMS). However, it is not clear whether the LC activity during the day predicts sleep quality and sleep properties during the night, and how this varies as a function of age. Here, we used 7 Tesla functional Magnetic Resonance Imaging (7T fMRI), sleep electroencephalography (EEG) and a sleep questionnaire to test whether the LC activity during wakefulness was associated with sleep quality in 52 healthy younger (N=33; ~22y; 28 women) and older (N=19; ~61y; 14 women) individuals. We find that, in older, but not in younger participants, higher LC activity, as probed during an auditory mismatch negativity task, is associated with worse subjective sleep quality and with lower power over the EEG theta band during REMS (4-8Hz), which are two sleep parameters significantly correlated in our sample of older individuals. The results remain robust even when accounting for the age-related changes in the integrity of the LC. These findings suggest that the activity of the LC may contribute to the perception of the sleep quality and to an essential oscillatory mode of REMS, and that the LC may be an important target in the treatment of sleep disorders and age-related diseases.

Light as a Modulator of Non-Image-Forming Brain Functions-Positive and Negative Impacts of Increasing Light Availability.

Light use is rising steeply, mainly because of the advent of light-emitting diode (LED) devices. LEDs are frequently blue-enriched light sources and may have different impacts on the non-image forming (NIF) system, which is maximally sensitive to blue-wavelength light. Most importantly, the timing of LED device use is widespread, leading to novel light exposure patterns on the NIF system. The goal of this narrative review is to discuss the multiple aspects that we think should be accounted for when attempting to predict how this situation will affect the NIF impact of light on brain functions. We first cover both the image-forming and NIF pathways of the brain. We then detail our current understanding of the impact of light on human cognition, sleep, alertness, and mood. Finally, we discuss questions concerning the adoption of LED lighting and screens, which offer new opportunities to improve well-being, but also raise concerns about increasing light exposure, which may be detrimental to health, particularly in the evening.

Temporal and extratemporal atrophic manifestation of temporal lobe epilepsy using voxel-based morphometry and corticometry: clinical application in lateralization of epileptogenic zone.

BACKGROUND: Advances in MRI acquisition and data processing have become important for revealing brain structural changes. Previous studies have reported widespread structural brain abnormalities and cortical thinning in patients with temporal lobe epilepsy (TLE), as the most common form of focal epilepsy. METHODS: In this research, healthy control cases (n = 20) and patients with left TLE (n = 19) and right TLE (n = 14) were recruited, all underwent 3.0 T MRI with magnetization-prepared rapid gradient echo sequence to acquire T1-weighted images. Morphometric alterations in gray matter were identified using voxel-based morphometry (VBM). Volumetric alterations in subcortical structures and cortical thinning were also determined. RESULTS: Patients with left TLE demonstrated more prevailing and widespread changes in subcortical volumes and cortical thickness than right TLE, mainly in the left hemisphere, compared to the healthy group. Both VBM analysis and subcortical volumetry detected significant hippocampal atrophy in ipsilateral compared to contralateral side in TLE group. In addition to hippocampus, subcortical volumetry found the thalamus and pallidum bilaterally vulnerable to the TLE. Furthermore, the TLE patients underwent cortical thinning beyond the temporal lobe, affecting gray matter cortices in frontal, parietal, and occipital lobes in the majority of patients, more prevalently for left TLE cases. Exploiting volume changes in individual patients in the hippocampus alone led to 63.6% sensitivity and 100% specificity for lateralization of TLE. CONCLUSION: Alteration of gray matter volumes in subcortical regions and neocortical temporal structures and also cortical gray matter thickness were evidenced as common effects of epileptogenicity, as manifested by the majority of cases in this study.

Distinct patterns of hippocampal subfield volume loss in left and right mesial temporal lobe epilepsy.

OBJECTIVE: To investigate the pattern and severity of hippocampal subfield volume loss in patients with left and right mesial temporal lobe epilepsy (mTLE) using quantitative MRI volumetric analysis. METHODS: A total of 21 left and 14 right mTLE subjects, as well as 15 healthy controls, were enrolled in this cross-sectional study. A publically available magnetic resonance imaging (MRI) brain volumetry system (volBrain) was used for volumetric analysis of hippocampal subfields. The T1-weighted images were processed with a HIPS pipeline. RESULTS: A distinct pattern of hippocampal subfield atrophy was found between left and right mTLE patients when compared with controls. Patients with left mTLE exhibited ipsilateral hippocampal atrophy and segmental volume depletion of the Cornu Ammonis (CA) 2/CA3, CA4/dentate gyrus (DG), and strata radiatum-lacunosum-moleculare (SR-SL-SM). Those with right mTLE exhibited similar ipsilateral hippocampal atrophy but with additional segmental CA1 volume depletion. More extensive bilateral subfield volume loss was apparent with right mTLE patients. CONCLUSION: We demonstrate that left and right mTLE patients show a dissimilar pattern of hippocampal subfield atrophy, suggesting the pathophysiology of epileptogenesis in left and right mTLE to be different.

Quantification and reduction of respiratory induced artifacts in positron emission tomography/computed tomography using the time-of-flight technique.

OBJECTIVE: The aim of this study was to investigate the impact of time-of-flight (TOF) on quantification and reduction of respiratory artifacts. PATIENTS AND METHODS: The National Electrical Manufacturers Association phantom was used for optimization of reconstruction parameters. Twenty seven patients with lesions located in the diaphragmatic region were evaluated. The PET images were retrospectively reconstructed using non-TOF (routine protocol in our department) and TOF algorithms with different reconstruction parameters. Maximum standardized uptake value, estimated maximum tumor diameter, coefficient of variation, signal-to-noise ratio, and lesion-to-background-ratio were also evaluated. RESULTS: On the basis of phantom experiments, TOF algorithms with two iterations, 18 subsets, and 5.4 mm and 6.4 mm postsmoothing filter reduced the noise by 3.1 and 12.6% in phantom with 2 : 1 activity ratio, and 3.0 and 13.1% in phantom with 4 : 1 activity ratio. The TOF algorithm with two iterations, 18 subsets, and 6.4 mm postsmoothing filter had the highest signal-to-noise value, and was selected as the optimal TOF reconstruction. Mean relative difference for signal-to-noise between non-TOF and optimal TOF in phantom with 2 : 1 and 4 : 1 activity ratio were 11.6 and 18.7%, respectively. In clinical data, the mean relative difference for estimated maximum tumor diameter and maximum standardized uptake value between routine protocol and optimal TOF algorithm were -6.3% (range: -20.4 to -0.6%) and 13.2% (range: 0.3-57.6%), respectively. CONCLUSION: Integration of TOF in reconstruction algorithm remarkably improved the white band artifact in the diaphragmatic region. This technique affected the quantification accuracy and resulted in smaller tumor size and higher standardized uptake value in tumors located in/near the diaphragmatic region.

Impact of Time-of-Flight and Point-Spread-Function for Respiratory Artifact Reduction in PET/CT Imaging: Focus on Standardized Uptake Value.

BACKGROUND: The most important advantage of positron emission tomography/computed tomography (PET/CT) imaging is its capability of quantitative analysis. The aim of the current study was to choose the proper standardized uptake value (SUV) threshold, when the time-of-flight (TOF) and point spread function (PSF) were used for respiratory artifact reduction in the liver dome in a new-generation PET/CT scanner. MATERIALS AND METHODS: The current study was conducted using a National Electrical Manufacturers Association International Electrotechnical Commission body phantom, with activity ratios of 2:1 and 4:1. A total of 27 patients, with respiratory artifacts in the thorax region, were analyzed. PET images were retrospectively reconstructed using either a high definition (HD) + PSF (i.e., a routine protocol) algorithm or HD+PSF+TOF (PSF+TOF; i.e., to reduce the respiratory artifact) algorithms, with various reconstruction parameters. The SUVmax and SUVmean, at different thresholds (i.e., at 45%, 50%, and 75%), were also assessed. RESULTS: Although in comparison to the routine protocol a higher SUV was observed when using the PSF+TOF method, this approach was used to reduce the respiratory artifact. The appropriate threshold for SUV was strongly related to the lesion size, reconstruction parameters, and activity ratio. The mean of the relative difference between PSF+TOF algorithm and routine protocol for SUVmax varied from 10.58±14.99% up to 35.49±32.60% (which was dependent on reconstruction parameters). CONCLUSION: In comparison with other types of SUVs, the SUVmax value illustrated its significant overestimation, especially at the 4:1 activity ratio. The poor agreement between SUVmax and SUV50% was also observed. When the TOF and PSF are utilized to reduce respiratory artifacts, the SUV50% can be an accurate semi-quantitative parameter for PET/CT images, for all lesion sizes. For smaller lesions, however, a smaller filter size was required to observe an accurate SUV.