Functional connectome of arousal and motor brainstem nuclei in living humans by 7 Tesla resting-state fMRI

Singh, Kavita; García‐Gomar, María Guadalupe; Stauder, Matthew; Vanello, Nicola; Passino, Claudio; Bianciardi, Marta

doi:10.1016/j.neuroimage.2021.118865

Cited by 32 publications

(43 citation statements)

References 151 publications

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“…The average tSNR across the AAS ROIs (Figure 2b; range: 23.3 - 72.9) and cortical regions (range: 49.6 - 106.3) were in line with previous reports (Brooks et al, 2013, Figure 1: brainstem range: ∼1-50 and cortex range ∼50-112; Sing et al, 2022, supplementary Figure 6: brainstem range: 0-50, cortex range: 0-50). We also replicated a recently reported pattern of positive (partial) correlations among the signal fluctuations in each pair of subcortical ROIs, controlled for activity in the pons (Figure 2c; van den Brink et al, 2019; see also Singh et al, 2022). Only the correlation between the DR and VTA was negative.…”

Section: Resultssupporting

confidence: 89%

Pupil size reflects activation of subcortical ascending arousal system nuclei during rest

Lloyd

Voogd²,

Mäki-Marttunen

et al. 2022

Preprint

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Neuromodulatory nuclei that are part of the ascending arousal system (AAS) play a crucial role in regulating cortical state and optimizing task performance. Pupil diameter, under constant luminance conditions, is increasingly used as an index of activity of these AAS nuclei. Indeed, task-based functional imaging studies in humans have begun to provide evidence of stimulus-driven pupil-AAS coupling. However, whether there is such a tight pupil-AAS coupling during rest is not clear. To address this question, we examined simultaneously acquired resting-state fMRI and pupil-size data from 74 participants, focusing on six AAS nuclei: the locus coeruleus, ventral tegmental area, substantia nigra, dorsal and median raphe nuclei, and cholinergic basal forebrain. Activation in all six AAS nuclei was optimally correlated with pupil size at 0- to 2-second lags, suggesting that spontaneous pupil changes were almost immediately followed by corresponding BOLD-signal changes in the AAS. These results suggest that spontaneous changes in pupil size that occur during states of rest can be used as a noninvasive general index of activity in AAS nuclei. Importantly, the nature of pupil-AAS coupling during rest appears to be vastly different from the relatively slow canonical hemodynamic response function that has been used to characterize task-related pupil-AAS coupling.

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Section: Resultssupporting

confidence: 89%

Pupil size reflects activation of subcortical ascending arousal system nuclei during rest

Lloyd

Voogd²,

Mäki-Marttunen

et al. 2022

Preprint

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“…For several subcortical structures, we failed to observe any traces of large-scale cortical network activity, including the GPi, STN, RN, PAG, and LC. None of these regions revealed unique whole-brain connectivity profiles that mirrored the activity in intrinsic connectivity networks, but rather showed evidence for stronger, local connectivity to other subcortical nuclei, consistent with prior work (Singh et al 2022). Although univariate (seed-based) FC studies have indicated correlations with widespread cortical activity patterns for some of these structures (Zhang et al 2016;Anteraper et al 2018), our multivariate analysis showed that partialing out adjacent subsignals does not result in a clear grouplevel pattern of cortical connectivity.…”

Section: Discussionsupporting

confidence: 86%

Echoes from intrinsic connectivity networks in the subcortex

Groot¹,

Miletić²,

Isherwood³

et al. 2022

Preprint

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Decades of research have greatly improved our understanding of human brain organization in terms of intrinsic connectivity networks and the transmodal hubs within the cortex at which they converge. However, subcortical substrates of multi-network integration remain mostly uncharted. In this study, we exploited recent advances in subcortical imaging and atlasing by combining state-of-the-art subcortical parcellations with ultra-high field imaging optimized for the subcortex to investigate the functional architecture of a large set of subcortical nuclei using a data-driven, multivariate analysis approach. We revealed an intricate system of signal repetitions, or echoes, from multiple intrinsic connectivity networks that indicates a functionally heterogeneous organization supportive of large-scale network convergence within various subcortical structures. Diversified network affiliations were especially prominent within the thalamus, striatum, claustrum, and hippocampus. Whereas subsignals within the globus pallidus externa, subsantia nigra, and ventral tegmental area also correlated with widely distributed functional networks, other structures including the subthalamic nucleus, red nucleus, and locus coeruleus demonstrated a stronger local connectivity profile indicative of more segregated functional processing. With these results, we present new evidence for the subcortical contributions to systems-level information integration, emphasizing the importance of regions beyond associative cortex for global brain communication.

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“…In recent years, advances in in vivo neuroimaging have allowed us to investigate the function of the ascending arousal system in human brainstem nuclei (Beissner et al, 2014 ; Bianciardi et al, 2015 ; Singh et al, 2022 ). The present study found that the ascending arousal nuclei were positively connected to each other within the AAN.…”

Section: Discussionmentioning

confidence: 99%

The role of ascending arousal network in patients with chronic insomnia disorder

Gong

Fang

et al. 2022

Human Brain Mapping

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The ascending arousal system plays a crucial role in individuals' consciousness. Recently, advanced functional magnetic resonance imaging (fMRI) has made it possible to investigate the ascending arousal network (AAN) in vivo. However, the role of AAN in the neuropathology of human insomnia remains unclear. Our study aimed to explore alterations in AAN and its connections with cortical networks in chronic insomnia disorder (CID). Resting‐state fMRI data were acquired from 60 patients with CID and 60 good sleeper controls (GSCs). Changes in the brain's functional connectivity (FC) between the AAN and eight cortical networks were detected in patients with CID and GSCs. Multivariate pattern analysis (MVPA) was employed to differentiate CID patients from GSCs and predict clinical symptoms in patients with CID. Finally, these MVPA findings were further verified using an external data set (32 patients with CID and 33 GSCs). Compared to GSCs, patients with CID exhibited increased FC within the AAN, as well as increased FC between the AAN and default mode, cerebellar, sensorimotor, and dorsal attention networks. These AAN‐related FC patterns and the MVPA classification model could be used to differentiate CID patients from GSCs with 88% accuracy in the first cohort and 77% accuracy in the validation cohort. Moreover, the MVPA prediction models could separately predict insomnia (data set 1, R 2 = .34; data set 2, R 2 = .15) and anxiety symptoms (data set 1, R 2 = .35; data set 2, R 2 = .34) in the two independent cohorts of patients. Our findings indicated that AAN contributed to the neurobiological mechanism of insomnia and highlighted that fMRI‐based markers and machine learning techniques might facilitate the evaluation of insomnia and its comorbid mental symptoms.

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Functional connectome of arousal and motor brainstem nuclei in living humans by 7 Tesla resting-state fMRI

Cited by 32 publications

References 151 publications

Pupil size reflects activation of subcortical ascending arousal system nuclei during rest

Pupil size reflects activation of subcortical ascending arousal system nuclei during rest

Echoes from intrinsic connectivity networks in the subcortex

The role of ascending arousal network in patients with chronic insomnia disorder

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