Visual sensitivity to parallel configurations of contours compared with sensitivity to other configurations.

peer reviewedPeople can perceive 3D information from contour drawings and some types of configurations of contours in such drawings are important for 3D perception. We know that our visual system is sensitive to these configurations. Koshmanova & Sawada (2019, Vision Research, 154, 97-104) showed that the sensitivity is higher to a parallel configuration of contours than to a perpendicular configuration of contours. In this study, two psychophysical experiments were conducted that compared the sensitivity to a parallel configuration to two different configurations. In Experiment 1, orientation thresholds were measured with parallel and converging configurations composed of three contours. In Experiment 2, orientation thresholds of configurations composed of two contours were measured with parallel, collinear, and perpendicular configurations. The results of Experiment 1 showed that the visual system is more sensitive to parallel configurations than to converging configurations. The results of Experiment 2 showed that the sensitivity to the parallel configuration is analogous to the sensitivity to the collinear configuration, and it is higher than the sensitivity to the perpendicular configuration. The role that the parallel configuration plays in the 3D perception of contour-drawings is discussed

Brain correlates of perceptual switch during perception rivalry: an ultra-high field 7T functional magnetic resonance imaging study

Introduction Perceptual rivalry while viewing ambiguous stimulus leads to repetitive switches between two perceptions of the same image1. Switches are considered to recruit bottom-up and top-down attentional processes. We aimed to investigate the neural mechanisms of perceptual switch using high resolution ultra-high-field 7-Tesla MRI. Methods 35 healthy subjects (18-70y; 28 women) were recruited. FMRI (voxel size 1.4 mm³) was recorded for 10 minutes while participants viewed a Necker cube 2 (10s breaks every minute). Subjects were instructed to report switch of their perception by pressing a button. Results Perceptual switches were associated with increased activation in the bilateral intraparietal sulcus (which is involved in attention), the insula (part of the salience network), the occipital cortex (including in an area compatible with V4, involved in shape detection), the left motor cortex, and the right cerebellum (whole-brain FWE corrected p<.05) (Fig1). Conclusions We report neural substrates compatible with the top-down and bottom-up attentional processes involved in resolving perceptual rivalry. Our results further suggest that perceptual changes of ambiguous figures are associated with a widespread set of brain activation. Funding: FNRS, ULiège, FEDER, SAO-FRA, Wallonia-Brussels federation References 1. Blake R, Logothetis NK. Visual competition. Nature Reviews Neuroscience. 2002;3(1):13-21. 2. Einhäuser W, Stout J, Koch C, Carter O. Pupil dilation reflects perceptual selection and predicts subsequent stability in perceptual rivalry. Proceedings of the National Academy of Sciences. 2008;105(5):1704-1709

Pitfalls in recording BOLD signal responses to light in small hypothalamic nuclei using Ultra-High-Field 7 Tesla MRI.

peer reviewe

Association between locus coeruleus activity during wakefulness and sleep features

editorial reviewedIntroduction The locus coeruleus (LC) is the main source of norepinephrine (NE) in the brain and sends monosynaptic projections to most of the brain (Szabadi, 2013). It contributes to multiple processes such as cognition and arousal (Mather & Harley, 2016). The LC further contributes heavily to the transition between sleep and wakefulness, and between slow wave sleep (SWS) and rapid eye movement sleep (REMS) (Cirelli, Tononi 2005). Through the local release of NE, it governs the synchrony of brain activity and is tightly linked to the oscillatory modes found during sleep, such as sleep spindles and slow waves in animals (Eschenko et al., 2012). While the LC appears to be an important structure for sleep, only limited imaging studies evaluated whether the LC is related to sleep variability due to the difficulty of imaging such a small size nucleus in vivo (Keren et al., 2009). We aimed to investigate the link between LC activity during wakefulness and electroencephalogram (EEG) features of sleep using ultra-high-field 7-Tesla MRI. To trigger a response of the LC, we used a perceptual rivalry task. Subjects saw an ambiguous stimulus which could trigger spontaneous switches between two perceptions of the same image (Blake & Logothetis, 2002). Switches are considered to recruit bottom-up and top-down attentional processes associated with activity of the LC (Einhauser et al., 2008; Murphy et al., 2014). Methods 50 healthy volunteers, including 33 young (age: 22.27y ± 3.21y; 29 women) and 17 late middle-aged (age: 61.35y ± 5.19y; 12 women) individuals completed the protocol. They first underwent a structural 7T MRI session, which allowed collecting high-resolution whole-brain T1-weighted images as well as a sequence dedicated to acquire 6cm LC slab. The latter was used to create in the brain space of each participant an individual LC-mask. All individual LC-masks were gathered into a probabilistic LC-mask in a standardized group brain space. Following 1 week of regular sleep times, participants completed an fMRI session in the morning, 2h to 3h after wake-up time, during which they were administered the perceptual rivalry task (TR= 2.34s; voxel size 1.4x1.4x1.4 mm³). Participant’s habitual and baseline sleep was recorded in-lab under EEG to extract 4 sleep features of interest depicting some of the most canonical characteristics of sleep (i.e., cumulated power of the theta frequency band during REMS, slow wave energy (SWE), sleep onset latency, and REMS percentage). We first conducted a general linear model with the Statistical Parametric Mapping 12 package (SPM12) over the entire brain. We then extracted the activity estimates over individual LC masks and then conducted generalized linear mixed models (GLMMs) to test for associations between the activity of the LC and EEG features of sleep, including age, sex, BMI, and total sleep time as covariates. Results Perceptual switches were associated with increased activation in the left LC after controlling for age, sex, BMI, and total sleep time (whole brain FDR-corrected p 3.055) (Fig1). This supported the extraction of individual LC activity in the individual space to associate with sleep EEG metrics. GLMMs on the LC activity and sleep EEG metrics revealed a positive association between the bilateral LC activity and SWE (cumulated EEG power over the .5-4Hz frequency band) (p = 0.02, F= 5.1), which reflects SWS intensity. A similar positive association was found between the LC activity and EEG cumulated power of the theta frequency band (4-8Hz) during REMS (p = 0.03, F=4.8), which is the dominant oscillatory mode of REMS. No other significant associations were detected. Conclusions These results show that a greater LC activity during wakefulness is associated with a more intense SWS and REMS. Future analyses will consider the relationship between LC activity and sleep microstructure. Funding: FNRS Belgium, ULiège, FEDER, Alzheimer Foundation (SAO-FRA), Wallonia-Brussels federation   References Blake, R., & Logothetis, N. K. (2002). Visual competition. Nature Reviews Neuroscience, 3(1), 13–21. Einhauser, W., Stout, J., Koch, C., & Carter, O. (2008). Pupil dilation reflects perceptual selection and predicts subsequent stability in perceptual rivalry. Proceedings of the National Academy of Sciences, 105(5), 1704–1709. https://doi.org/10.1073/pnas.0707727105 Eschenko, O., Magri, C., Panzeri, S., & Sara, S. J. (2012). Noradrenergic neurons of the locus coeruleus are phase locked to cortical up-down states during sleep. Cerebral Cortex, 22(2), 426–435. https://doi.org/10.1093/cercor/bhr121 Keren, N. I., Lozar, C. T., Harris, K. C., Morgan, P. S., & Eckert, M. A. (2009). In vivo mapping of the human locus coeruleus. NeuroImage, 47(4), 1261–1267. https://doi.org/https://doi.org/10.1016/j.neuroimage.2009.06.012 Mather, M., & Harley, C. W. (2016). The Locus Coeruleus: Essential for Maintaining Cognitive Function and the Aging Brain. Trends in Cognitive Sciences, 20(3), 214–226. https://doi.org/10.1016/j.tics.2016.01.001 Murphy, P. R., O’Connell, R. G., O’Sullivan, M., Robertson, I. H., & Balsters, J. H. (2014). Pupil diameter covaries with BOLD activity in human locus coeruleus. Human Brain Mapping, 35(8), 4140–4154. https://doi.org/10.1002/hbm.22466 Scammell, T. E., Arrigoni, E., & Lipton, J. O. (2017). Neural Circuitry of Wakefulness and Sleep. Neuron, 93(4), 747–765. https://doi.org/10.1016/j.neuron.2017.01.014 Szabadi, E. (2013). Functional neuroanatomy of the central noradrenergic system. Journal of Psychopharmacology, 27(8), 659–693. https://doi.org/10.1177/026988111349032

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

peer reviewedLight 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

Non-visual Impacts of Light on Effective Connectivity associated to executive brain responses

peer reviewedIntroduction: Beyond vision, light have many non-visual biological effect including the stimulation of alertness and cognition. These effect are considered to be mediated mainly through the recently discovered blue-light-sensitive intrinsically photosensitive retinal ganglion cells i.e. ipRGCs (Warthen, D. M., & Provencio, 2012)⁠⁠⁠ Direct projections of ipRGCs mainly reach subcortical structures, including the hypothalamus and thalamus. However, non-visual impact of light have also been reported on the activity of cortical regions, presumably through an initial subcortical impact. Here, we assessed the impact of blue-enriched light on the connectivity of a brain network sustained the brain activity associated with an ongoing auditory executive task in healthy young adults. We anticipated that blue-enriched light would mainly affect subcortical to cortical connectivity. Method: 20 healthy participants (60% Female, 23.2±4.1 years) who met our inclusion criteria assessing both physical and mental health in addition to having regular sleep habits, were included in the study. Participants started the study protocol by a structural 7T MRI scan in which high resolution T1-weighted structural images of their brain were collected. Following a loose sleep-wake schedule (±1.5h; verified with actigraphy) for 7 days, participants came to the lab, ~2 hours before/after their habitual sleep/wake time to do a functional 7T MRI scan (GRE-EPI sequence, TR = 2340 ms, TE = 24 ms, voxel size = 1.4 × 1.4 × 1.4 mm3). Participant completed an auditory working memory task (N-back: 0-back and 2-back) under different light conditions including an active blue-enriched polychromatic light, to stimulate ipRGCs (6500K; 190, 92 and 37 melanopic Equivalent Daylight Illumination (EDI) lux) and a control monochromatic orange light (590nm; 0.2 mel EDI luc), to which ipRGCs are almost nonresponsive. Based on a standard whole-brain GLM analyses using SPM12, 3 regions significantly involved in the N-back task (p FWE whole-brain < 0.05) were isolated: a dorsoposterior part of the thalamus corresponding to the pulvinar, the Intraparietal sulcus (IPS) and Anterior insula (AI) (Figure.1) Effective connectivity among the 3 region network and the modulatory effect of different light conditions on the inter-region connections were estimated using the Dynamic Causal Modeling as part of SPM12 (Figure.2A). Effects were considered robust for posterior probably (Pp) > .95. Results: The DCM analysis indicated that only the driving inputs of the 2-back task was effective for the IPS and AI) (Pp ≥ .95). The baseline effective connectivity showed that among the connections defined in the initial model, 3 connections were robust (Pp ≥ .95). The pulvinar to IPS and pulvinar to AI connectivity were excitatory while the AI to IPS connectivity was inhibitory (Figure.2B). Evaluation of the modulatory effect of light conditions (blue-enriched and orange) revealed a significant modulation of the connections going from the pulvinar to both the IPS and AI with only blue-enriched light was significantly strengthening the two aforementioned connectivity (Pp ≥ .95) (Figure.2C). Conclusion: These results are in line with an initial impact of non-visual light on the information flow going from subcortical to cortical areas(Vandewalle et al., 2005)⁠. In the context of an executive task, blue-enriched, but not orange light, seems to affect thalamo-cortical loops. Future analyses will considered the different level of blue-enriched light

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

Light triggers numerous non-image forming (NIF), or non-visual, biological effects. The brain correlates of these NIF effects have been investigated, notably using Magnetic Resonance Imaging (MRI) and short light exposures varying in irradiance and spectral quality. However, it is not clear whether having light in subsequent blocks may induce carry over effects of one light block onto the next, thus biasing the study. We reasoned that pupil light reflex (PLR) was an easy readout of one of the NIF effects of light that could be used to address this issue. We characterized the sustained PLR in 13 to 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 (mel EDI) lux] and polychromatic blue-enriched white light of three different levels [37, 92, 190 mel EDI lux]. As expected, higher melanopic irradiance was associated with larger sustained PLR in each cognitive domain. This result was stable over the light block sequence under higher melanopic irradiance levels as compared to lower ones. Exploratory frequency-domain analyses further revealed that PLR was more variable within a light block under lower melanopic irradiance levels. Importantly, PLR varied across tasks independently of the light condition pointing to a potential impact of the light history and/or cognitive context on PLR. Together, our results emphasize that the distinct contribution and adaptation of the different retinal photoreceptors influence the NIF effects of light and therefore potentially their brain correlates

Heterogeneity in the links between sleep arousals, amyloid-beta and cognition

peer reviewedBACKGROUND. Tight relationships between sleep quality, cognition and amyloid-beta (Aβ) accumulation, a hallmark of Alzheimer’s disease (AD) neuropathology, emerge in the literature. Sleep arousals become more prevalent with ageing and are considered to reflect poorer sleep quality. Yet, heterogeneity in arousals has been suggested while their associations with Aβ and cognition are not established. METHODS. We recorded undisturbed night-time sleep with EEG in 101 healthy individuals in late midlife (50-70y), devoid of cognitive and sleep disorders. We classified spontaneous arousals according to their association with muscular tone increase (M+/M-) and sleep stage transition (T+/T-). We assessed cortical Aβ burden over earliest affected regions via PET imaging, and cognition via extensive neuropsychological testing. RESULTS. Arousal types differed in their oscillatory composition in theta and beta EEG bands. Furthermore, T+M- arousals, which interrupt sleep continuity, were positively linked to Aβ burden (p=.0053, R²β*=0.08). By contrast, more prevalent T-M+ arousals, upholding sleep continuity, were associated with lower Aβ burden (p=.0003, R²β*=0.13), and better cognition, particularly over the attentional domain (p<.05, R²β*≥0.04). CONCLUSION. Contrasting with what is commonly accepted, we provide empirical evidence that arousals are diverse and differently associated with early AD-related neuropathology and cognition. This suggests that sleep arousals, and their coalescence with other brain oscillations during sleep, may actively contribute to the beneficial functions of sleep. This warrants re-evaluation of age-related sleep changes and suggests that spontaneous arousals could constitute a marker of favourable brain and cognitive health trajectories

Positive Effect of Cognitive Reserve on Episodic Memory, Executive and Attentional Functions Taking Into Account Amyloid-Beta, Tau, and Apolipoprotein E Status

peer reviewedStudies exploring the simultaneous influence of several physiological and environmental factors on domain-specific cognition in late middle-age remain scarce. Therefore, our objective was to determine the respective contribution of modifiable risk/protective factors (cognitive reserve and allostatic load) on specific cognitive domains (episodic memory, executive functions, and attention), taking into account non-modifiable factors [sex, age, and genetic risk for Alzheimer’s disease (AD)] and AD-related biomarker amount (amyloid-beta and tau/neuroinflammation) in a healthy late-middle-aged population. One hundred and one healthy participants (59.4 ± 5 years; 68 women) were evaluated for episodic memory, executive and attentional functioning via neuropsychological test battery. Cognitive reserve was determined by the National Adult Reading Test. The allostatic load consisted of measures of lipid metabolism and sympathetic nervous system functioning. The amyloid-beta level was assessed using positron emission tomography in all participants, whereas tau/neuroinflammation positron emission tomography scans and apolipoprotein E genotype were available for 58 participants. Higher cognitive reserve was the main correlate of better cognitive performance across all domains. Moreover, age was negatively associated with attentional functioning, whereas sex was a significant predictor for episodic memory, with women having better performance than men. Finally, our results did not show clear significant associations between performance over any cognitive domain and apolipoprotein E genotype and AD biomarkers. This suggests that domain-specific cognition in late healthy midlife is mainly determined by a combination of modifiable (cognitive reserve) and non-modifiable factors (sex and age) rather than by AD biomarkers and genetic risk for AD.Cognitive Fitness in Aging stud

ENIGMA-Sleep:Challenges, opportunities, and the road map

Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine