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Blink associations with activation of brainstem AAN nuclei during rest (n = 14). (A) Sagittal images of midline brainstem depicting blink-related activation in AAN nuclei at −2TR. The color scale corresponds to z-values and associated t-values (compared with null distribution). The lower zvalue was thresholded at t > 1.8 for visualisation purposes. (B) Average z-values found by cross-correlation analysis for AAN systems prior to (from −7TRs), during (0) and post-(to +7TRs) blink for rest. Plotted lines were fitted to the raw data with method "gam" with a formulae y ∼ s(x, bs = "cs") in the geom_smooth function of R ggplot2 package. Abbreviations correspond to dorsal raphe (DR), locus coeruleus (LC), median raphe (MR), midbrain reticular formation (MRF), periaqueductal grey (PAG), parabrachial complex (PBC), pontis oralis (PO), pedunculopontine nucleus (PPN), ventral tegmental area (VTA), and substantia nigra (SN). Vertical dashed line at −2TR mark (2TRs before blink) the peaking point of the correlations with the highest z-values. frontal, premotor and motor thalamic ROIs. (Choice-reward task results are presented in the Supplementary Material, Fig. S4).
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Eye-blinking has been implicated in arousal and attention. Here we test the hypothesis that blinking-moments represent arousal surges associated with activation of the ascending arousal network (AAN) and its thalamic projections. For this purpose, we explored the temporal relationship between eye-blinks and fMRI BOLD activity in AAN and thalamic nu...
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... test this hypothesis, we assessed the dynamic temporal associations between AAN and thalamic nuclei and the eyeblinks during rest (and also during a choice-reward taskpresented in the Supplementary Material, Fig. S1) fMRI sessions by monitoring their activity prior to, during and post-blink. Blink-BOLD correlations are reported here as lagged cross-correlations between eye-blink f luctuations (Hemodynamic Response Function, HRF, convolved blink moments) and BOLD signal f luctuations in regions of interest in temporal lags (TRs) of −7TRs to +7TRs. ...
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... ROI analyses revealed blink associations with the activation of AAN nuclei during resting condition ( Figs. 1 and 2). The temporal association showed peak activations of most ROIs prior to the blink moment at around −2TRs (2TRs prior to blink). ...
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... et al. 2016) (but note that 7 T might have lower SNR in the brain-stem regions). Indeed, our spatial resolution was limited to a voxel size of 3 mm, which may have increased partial volume effects. Some previous studies used similar spatial resolutions to measure BOLD signals in small nuclei like LC ( DiNuzzo et al. 2019). Further, as shown in Figs. 1 and 2, blink-related activations are confined around the AAN nuclei and are not spread out all over the brain stem. Furthermore, the analyses in control regions did not show association with eye blinks (results presented in the Supplementary ...
Citations
... In this . Additionally, we also extracted ROI in periaqueductal gray (PAG), mid-brain reticular formation (MRF), parabrachial complex (PBC), similar to our previous publication (Demiral et al., 2023) . ...
The vigilance state and the excitability of cortical networks impose wide-range effects on brain dynamics that arousal surges could promptly modify. We previously reported an association between spontaneous eye-blinks and BOLD activation in the brain arousal ascending network (AAN) and in thalamic nuclei based on 3T MR resting state brain images. Here we aimed to replicate our analyses using 7T MR images in a larger cohort of participants collected from the Human Connectome Project (HCP), which also contained simultaneous eye-tracking recordings, and to assess the interaction between the blink-associated arousal surges and the vigilance states. For this purpose, we compared blink associated BOLD activity under a vigilant versus a drowsy state, a classification made based on the pupillary data obtained during the fMRI scans. We conducted two main analyses: i) Cross-correlation analysis between the BOLD signal and blink events (eye blink time-series were convolved with the canonical and also with the temporal derivative of the Hemodynamic Response Function, HRF) within preselected regions of interests (ROIs) (i.e., brainstem AAN, thalamic and cerebellar nuclei) together with an exploratory voxel-wise analyses to assess the whole-brain, and ii) blink-event analysis of the BOLD signals to reveal the signal changes onset to the blinks in the preselected ROIs. Consistent with our prior findings on 3T MRI, we showed significant positive cross correlations between BOLD peaks in brainstem and thalamic nuclei that preceded or were overlapping with blink moments and that sharply decreased post-blink. Whole brain analysis revealed blink-related activation that was strongest in cerebellum, insula, lateral geniculate nucleus (LGN) and visual cortex. Drowsiness impacted HRF BOLD (enhancing it), time-to-peak (delaying it) and post-blink BOLD activity (accentuating decreases). Responses in the drowsy state could be related to the differences in the excitability of cortical, subcortical and cerebellar tissue, such that cerebellar and thalamic regions involved in visual attention processing were more responsive for the vigilant state, but AAN ROIs, as well as cerebellar and thalamic ROIs connected to pre-motor, frontal, temporal and DMN regions were less responsive. Such qualitative and quantitative differences in the blink related BOLD signal changes could reflect delayed cortical processing and the ineffectiveness of arousal surges during states of drowsiness. Future studies that manipulate arousal are needed to corroborate a mechanistic interaction of arousal surges with vigilance states and cortical excitability.
... p = 0.0496; Supplementary Fig. 11B), with no significant differences in blink rate found between the two sexes for all movie clips (all p > 0.05 after FDR correction; Supplementary Fig. 11C). Blink rate has been thought to be associated with vigilance and attention allocation (Demiral et al., 2023;Maffei & Angrilli, 2019), thus potentially influencing the utility of brain signals for phenotype prediction and providing complementary information for stimulus selection. ...
Understanding individual differences and brain-behaviour relationships is an essential goal of human neuroscience. Recent studies have shown the great potential of naturalistic stimuli, e.g., movie clips, in advancing this pursuit. While the use of naturalistic stimuli attracts increasing interest, the influence of stimulus selection remains largely unclear. In this study, we show that brain activity is generally sensitive to the choice of movie stimuli at both group and individual subject levels. Using sex classification as an example, we demonstrate that brain activity elicited by different stimuli can lead to distinct prediction performance and unique predictive features. The stimuli that yield better classification performance often elicit stronger synchrony of brain activity across all subjects and are mostly derived from Hollywood films with rich social content and cohesive narratives. Our results highlight the importance of stimulus selection and provide practical guidance for choosing appropriate stimuli, opening up new avenues for future studies on individual differences and brain-behaviour relationships.
... Although not directly associated with our discussion of dopamine, more recent work is beginning to systematically examine the brain responses coincident with eye blinks. Rather than ERPs, for example, Demiral et al. [74] used fMRI to track activity in brain networks, including the default mode network and associated blink responses. This approach offers a more comprehensive understanding of the brain's involvement in blink phenomena and may contribute to our knowledge of cognitive and neural processes related to eye blinks. ...
The present study examined music-induced dopamine release, as measured by a proxy measure of spontaneous eye blinks. Specifically, we explored the effects of uplifting and sombre tones in different sections of Vivaldi’s Four Seasons to investigate the affective content of musical pieces within one composition. Seventeen participants listened to four concertos (Major modes: “Spring” and “Autumn”, Minor modes: “Summer” and “Winter”) and a silence condition while completing a three-stimulus odd-ball attention task. Electrooculograms were recorded from electrodes placed above and under the left eye. Self-reported arousal and music preference measures were also gathered during the testing session. In addition, the P3a Event-Related Potential (ERP) component was analysed as another potential index of dopamine function. Results revealed significant differences in the blink rates during music listening and silence, with the largest effect observed for the sad, melancholic “Winter” concerto. However, no significant correlation was found between blink rate and music preference or arousal. Furthermore, no reliable association was found between blink rate and the P3a ERP component, suggesting that these measures tap into different aspects of dopamine function. These findings contribute to understanding the link between dopamine and blink rate, particularly in response to classical music. Crucially, the study’s discovery that the “Winter” concerto, with its sorrowful tone, significantly increased the blink rate highlights the significance of sad music and perhaps the programmatic qualities of this concerto to induce a strong emotional response.
... Luminancerelated changes directly modulate the feedforward response of V1 (striate cortex) that is independent of psychological factors like attentional load (Bombeke et al., 2016), suggesting that changes in pupil size due to autonomic regulation also affect visual perception to some degree. Note that while blinks are often considered informative of attentional or other arousal states (Demiral et al., 2023;Kawashima et al., 2022;Schwabe et al., 2011), their effect on pupil size is probably rather related to basic visual function. ...
Pupil size covaries with the diffusion rate of the cholinergic and noradrenergic neurons throughout the brain, which are essential to arousal. Recent findings suggest that slow pupil fluctuations during locomotion are an index of sustained activity in cholinergic axons, whereas phasic dilations are related to the activity of noradrenergic axons. Here, we investigated movement induced arousal (i.e., by singing and swaying to music), hypothesising that actively engaging in musical behaviour will provoke stronger emotional engagement in participants and lead to different qualitative patterns of tonic and phasic pupil activity. A challenge in the analysis of pupil data is the turbulent behaviour of pupil diameter due to exogenous ocular activity commonly encountered during motor tasks and the high variability typically found between individuals. To address this, we developed an algorithm that adaptively estimates and removes pupil responses to ocular events, as well as a functional data methodology, derived from Pfaffs' generalised arousal, that provides a new statistical dimension on how pupil data can be interpreted according to putative neuromodulatory signalling. We found that actively engaging in singing enhanced slow cholinergic-related pupil dilations and having the opportunity to move your body while performing amplified the effect of singing on pupil activity. Phasic pupil oscillations during motor execution attenuated in time, which is often interpreted as a measure of sense of agency over movement.
Shifting motor actions from reflexively reacting to an environmental stimulus to predicting it allows for smooth synchronization of behavior with the outside world. This shift relies on the identification of patterns within the stimulus – knowing when a stimulus is predictable and when it is not – and launching motor actions accordingly. Failure to identify predictable stimuli results in movement delays whereas failure to recognize unpredictable stimuli results in early movements with incomplete information that can result in errors. Here we used a metronome task, combined with video-based eye-tracking, to quantify temporal predictive learning and performance to regularly paced visual targets at 5 different interstimulus intervals (ISIs). We compared these results to the random task where the timing of the target was randomized at each target step. We completed these tasks in female pediatric psychiatry patients (age range: 11–18 years) with borderline personality disorder (BPD) symptoms, with (n = 22) and without (n = 23) a comorbid attention-deficit hyperactivity disorder (ADHD) diagnosis, against controls (n = 35). Compared to controls, BPD and ADHD/BPD cohorts showed no differences in their predictive saccade performance to metronome targets, however, when targets were random ADHD/BPD participants made significantly more anticipatory saccades (i.e., guesses of target arrival). The ADHD/BPD group also significantly increased their blink rate and pupil size when initiating movements to predictable versus unpredictable targets, likely a reflection of increased neural effort for motor synchronization. BPD and ADHD/BPD groups showed increased sympathetic tone evidenced by larger pupil sizes than controls. Together, these results support normal temporal motor prediction in BPD with and without ADHD, reduced response inhibition in BPD with comorbid ADHD, and increased pupil sizes in BPD patients. Further these results emphasize the importance of controlling for comorbid ADHD when querying BPD pathology.
