Journal: Nature Human Behaviour

Article Title: Self-regulating arousal via pupil-based biofeedback

doi: 10.1038/s41562-023-01729-z

Figure Lengend Snippet: a , b , Average changes in pupil size during 15 s upregulation ( a ) and downregulation ( b ) are shown for the pupil-BF ( n = 27) and initial control group ( n = 27) for training sessions on days 1, 2 and 3, and for the no-feedback post-training session of experiment 1A. c , The pupil modulation index reflects the difference between the average pupil size during the two conditions (Up–Down) and is shown for each session (days 1, 2 and 3, and for the no-feedback post-training session) and group (initial control group vs pupil-BF group of experiment 1A; dots and squares represent individual participants). Pupil modulation indices were generally higher in the pupil-BF group ( n = 27) compared with the initial control group ( n = 27; robust ANOVA, main effect of group: F (1,21.58) = 21.49; P = 0.001, η p 2 = 0.50; other main effects/interaction P ≥ 0.07) d , Time series of pupil modulation index measured during the no-feedback session before (pre, light grey) and after pupil-BF training (post, dark grey) in experiment 1B (independent cohort, n = 25). Solid black line at the top indicates clusters of significantly higher modulation indices after training compared with before (SPM1D repeated-measures ANOVA; main effect session; z* = 11.84; largest cluster P = 0.037; smallest cluster P = 0). Shaded areas indicate s.e.m. Boxplots indicate median (centre line), 25th and 75th percentiles (box), and maximum and minimum values (whiskers). For a replication of results in control group II, see Supplementary Fig. . All post-hoc tests were two-tailed and corrected for multiple comparisons. For more detailed information on statistical parameters, see Supplementary Table .

Article Snippet: We statistically compared these time series before and after pupil-BF training by subjecting the data to a two-way repeated-measures ANOVA with the within-subjects factors ‘condition’ (Up vs Down) and ‘session’ (before and after pupil-BF training) using the MATLAB-based SPM1D toolbox for one-dimensional data (SPM1D M.0.4.8; https://spm1d.org/ ).

Techniques: Two Tailed Test

Journal: Nature Human Behaviour

Article Title: Self-regulating arousal via pupil-based biofeedback

doi: 10.1038/s41562-023-01729-z

Figure Lengend Snippet: a , Pupil size changes averaged across participants for Up and Down trials showing successful pupil size self-regulation during brainstem fMRI recording. The solid black line at the bottom indicates a cluster of significantly higher baseline-corrected pupil sizes during Up than during Down trials (two-tailed SPM1D paired-samples t -test; P = 0; z * = 3.45). b , Activity during Up versus Down phases of pupil self-regulation in the different ROIs. Statistical comparisons ( n = 22) revealed significant effects (Up > Down) in the LC and the SN/VTA but not in the SC and DRN (two-tailed paired-samples t- test). Results for the NBM (two-tailed Wilcoxon signed-rank test) did not survive multiple comparison correction. c , Correlation between continuous pupil size changes and BOLD response changes shown as z -values for the different ROIs. Statistical comparison (against 0; two-tailed; n = 22) revealed significant effects for the LC, SN/VTA, NBM and DRN (one-sample t -test) but not for the SC (Wilcoxon signed-rank test). All ROI analyses in b and c were sequential Bonferroni-corrected for multiple comparison. Squares represent individual data d , Top: correlation analysis revealed that LC BOLD activity covaries significantly with continuous changes in pupil diameter (GLM; cluster-corrected for multiple comparisons at z = 2.3; P < 0.05). Bottom: brainstem areas other than the LC exhibited a significant correlation between changes in pupil diameter and BOLD activity (GLM; cluster-corrected for multiple comparisons at z = 2.3; P < 0.05). For a complete overview of regions, see Supplementary Table . White outlines in d indicate different brainstem – and basal forebrain regions . e , A-priori-defined ROIs in the brainstem – and basal forebrain in MNI space. Boxplots indicate median (centre), 25th and 75th percentiles (box), maximum and minimum values (whiskers). Shaded areas and error bars indicate s.e.m. Post-hoc comparisons were corrected for multiple comparisons. For detailed information on statistical parameters, see Supplementary Table .

Article Snippet: We statistically compared these time series before and after pupil-BF training by subjecting the data to a two-way repeated-measures ANOVA with the within-subjects factors ‘condition’ (Up vs Down) and ‘session’ (before and after pupil-BF training) using the MATLAB-based SPM1D toolbox for one-dimensional data (SPM1D M.0.4.8; https://spm1d.org/ ).

Techniques: Two Tailed Test, Activity Assay, Comparison

Journal: Nature Human Behaviour

Article Title: Self-regulating arousal via pupil-based biofeedback

doi: 10.1038/s41562-023-01729-z

Figure Lengend Snippet: a , Changes in pupil size averaged across all participants for Up (red) and Down (blue) trials showing successful self-regulation of pupil size during whole-brain fMRI recordings. The solid black line at the bottom indicates a cluster of significantly higher baseline-corrected pupil sizes during Up than during Down trials (two-tailed SPM1D paired-samples t -test; P = 0; z * = 3.38). b , Whole-brain maps showing brain regions where BOLD activity correlates with pupil size changes throughout the fMRI runs (GLM). c , Whole-brain maps depicting brain regions that showed significant activation during Up (as compared to Down) trials (GLM). All activation maps in b and c are thresholded at z > 3.1 and FWE-corrected for multiple comparisons using a cluster significance level of P < 0.05. d , Estimated BOLD response represented by z -values for Up vs rest and Down vs rest extracted from the peak voxel of each significant cluster shown in c ( n = 24). Boxplots indicate median (centre line), 25th and 75th percentiles (box), and maximum and minimum values (whiskers). Squares indicate individual participants ( n = 24). Shaded areas indicate s.e.m.

Article Snippet: We statistically compared these time series before and after pupil-BF training by subjecting the data to a two-way repeated-measures ANOVA with the within-subjects factors ‘condition’ (Up vs Down) and ‘session’ (before and after pupil-BF training) using the MATLAB-based SPM1D toolbox for one-dimensional data (SPM1D M.0.4.8; https://spm1d.org/ ).

Techniques: Two Tailed Test, Activity Assay, Activation Assay

Journal: Nature Human Behaviour

Article Title: Self-regulating arousal via pupil-based biofeedback

doi: 10.1038/s41562-023-01729-z

Figure Lengend Snippet: a , Schematic depiction of an example trial (Up) of experiment 3. Participants reacted to targets (black sound-icon) by button press and ignored standards (grey sound-icon) while simultaneously upregulating, downregulating pupil size or counting backwards in steps of seven (control). b , Pupil size changes averaged across participants for Up, Down and control trials showing 1 s of the baseline and the 18 s modulation phase. c , Pupil size changes from baseline during modulation averaged across the respective condition showing significantly lower values in Down than in control and Up trials (robust repeated-measures ANOVA; n = 20 ; F (1.52,16.67) = 9.33, P = 0.003, η p 2 = 0.46; Down vs Up: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\hat{\psi }=-0.23{;\; P}=0.001$$\end{document} ψ ^ = − 0.23 ; P = 0.001 ; Down vs control: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\hat{\psi }=-0.14{;P}=0.005$$\end{document} ψ ^ = − 0.14 ; P = 0.005 ; for Up vs control: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\hat{\psi }$$\end{document} ψ ˆ = 0.10; P = 0.06; two-tailed post-hoc tests; corrected for multiple comparisons using Hochberg’s method). d , Baseline-corrected pupil dilation evoked by targets (left) and standards (right) for Up, Down and control trials. Solid lines indicate time windows of significantly smaller responses to targets in Up than in Down and control trials (left) and significantly larger responses to standards in Up and control than in Down trials (right; two-tailed post-hoc tests of SPM1D repeated-measures ANOVA ; largest P = 0.017; smallest P = 0; Bonferroni-corrected). e , Left: behavioural performance of 21 participants depicting faster responses to targets during Down than during Up trials (repeated-measures ANOVA: F (2,40) = 35.97, P < 0.001, η p 2 = 0.64, Down vs Up: t (20) = −2.87, P = 0.009, d = 0.63) and control trials (Down vs control: t (20) = −7.19, P < 0.001, d = 1.57; Up vs control: t (20) = −6.04, P < 0.001, d = 1.32). Right: responses were also less variable in Down than in control trials ( t (20) = −3.01, P = 0.02, d = 0.66; post-hoc tests of repeated-measures ANOVA on reaction time and s.d. of reaction times were two-tailed and sequential Bonferroni-corrected). Squares in c and e represent individual data. Boxplots indicate median (centre), 25th and 75th percentiles (box), maximum and minimum values (whiskers). Shaded areas indicate s.e.m.

Article Snippet: We statistically compared these time series before and after pupil-BF training by subjecting the data to a two-way repeated-measures ANOVA with the within-subjects factors ‘condition’ (Up vs Down) and ‘session’ (before and after pupil-BF training) using the MATLAB-based SPM1D toolbox for one-dimensional data (SPM1D M.0.4.8; https://spm1d.org/ ).

Techniques: Two Tailed Test