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The nucleus accumbens (NAc) has been implicated in sleep, reward, and pain modulation, but the relationship between these functional roles is unclear. This study aimed to determine whether NAc function at the onset and offset of a noxious thermal stimulus is enhanced by rewarding music, and whether that effect is reversed by experimental sleep disruption. Twenty-one healthy subjects underwent functional magnetic resonance imaging scans on 2 separate days after both uninterrupted sleep and experimental sleep disruption. During functional magnetic resonance imaging scans, participants experienced noxious stimulation while listening to individualized rewarding or neutral music. Behavioral results revealed that rewarding music significantly reduced pain intensity compared with neutral music, and disrupted sleep was associated with decreased pain intensity in the context of listening to music. In whole-brain family-wise error cluster-corrected analysis, the NAc was activated at pain onset, but not during tonic pain or at pain offset. Sleep disruption attenuated NAc activation at pain onset and during tonic pain. Rewarding music altered NAc connectivity with key nodes of the corticostriatal circuits during pain onset. Sleep disruption increased reward-related connectivity between the NAc and the anterior midcingulate cortex at pain onset. This study thus indicates that experimental sleep disruption modulates NAc function during the onset of pain in a manner that may be conditional on the presence of competing reward-related stimuli. These findings point to potential mechanisms for the interaction between sleep, reward, and pain, and suggest that sleep disruption affects both the detection and processing of aversive stimuli that may have important implications for chronic pain.

Motor adaptation in cortico-striato-thalamo-cortical loops has been studied mainly in animals using invasive electrophysiology. Here, we leverage functional neuroimaging in humans to study motor circuit plasticity in the human subcortex. We employed an experimental paradigm that combined two weeks of upper-extremity immobilization with daily resting-state and motor task fMRI before, during, and after the casting period. We previously showed that limb disuse leads to decreased functional connectivity (FC) of the contralateral somatomotor cortex (SM1) with the ipsilateral somatomotor cortex, increased FC with the cingulo-opercular network (CON) as well as the emergence of high amplitude, fMRI signal pulses localized in the contralateral SM1, supplementary motor area and the cerebellum. From our prior observations, it remains unclear whether the disuse plasticity affects the thalamus and striatum. We extended our analysis to include these subcortical regions and found that both exhibit strengthened cortical FC and spontaneous fMRI signal pulses induced by limb disuse. The dorsal posterior putamen and the central thalamus, mainly CM, VLP and VIM nuclei, showed disuse pulses and FC changes that lined up with fmri task activations from the Human connectome project motor system localizer, acquired before casting for each participant. Our findings provide a novel understanding of the role of the cortico-striato-thalamo-cortical loops in human motor plasticity and a potential link with the physiology of sleep regulation. Additionally, similarities with FC observation from Parkinson Disease (PD) questions a pathophysiological link with limb disuse., Competing Interests: Competing Interests A.N.V. and N.U.F.D. have a financial interest in Turing Medical Inc. and may benefit financially if the company is successful in marketing FIRMM motion monitoring software products. A.N.V. and N.U.F.D. may receive royalty income based on FIRMM technology developed at Washington University School of Medicine and Oregon Health and Sciences University and licensed to Turing Medical Inc. N.U.F.D. are co-founders of Turing Medical Inc. These potential conflicts of interest have been reviewed and are managed by Washington University School of Medicine, Oregon Health and Sciences University and the University of Minnesota. A.N.V. is now an employee of Turing Medical Inc. The other authors declare no competing interests.

The red nucleus is a large brainstem structure that coordinates limb movement for locomotion in quadrupedal animals (Basile et al., 2021). The humans red nucleus has a different pattern of anatomical connectivity compared to quadrupeds, suggesting a unique purpose (Hatschek, 1907). Previously the function of the human red nucleus remained unclear at least partly due to methodological limitations with brainstem functional neuroimaging (Sclocco et al., 2018). Here, we used our most advanced resting-state functional connectivity (RSFC) based precision functional mapping (PFM) in highly sampled individuals (n = 5) and large group-averaged datasets (combined N ~ 45,000), to precisely examine red nucleus functional connectivity. Notably, red nucleus functional connectivity to motor-effector networks (somatomotor hand, foot, and mouth) was minimal. Instead, red nucleus functional connectivity along the central sulcus was specific to regions of the recently discovered somato-cognitive action network (SCAN; (Gordon et al., 2023)). Outside of primary motor cortex, red nucleus connectivity was strongest to the cingulo-opercular (CON) and salience networks, involved in action/cognitive control (Dosenbach et al., 2007; Newbold et al., 2021) and reward/motivated behavior (Seeley, 2019), respectively. Functional connectivity to these two networks was organized into discrete dorsal-medial and ventral-lateral zones. Red nucleus functional connectivity to the thalamus recapitulated known structural connectivity of the dento-rubral thalamic tract (DRTT) and could prove clinically useful in functionally targeting the ventral intermediate (VIM) nucleus. In total, our results indicate that far from being a 'motor' structure, the red nucleus is better understood as a brainstem nucleus for implementing goal-directed behavior, integrating behavioral valence and action plans.

Functional MRI (fMRI) data are severely distorted by magnetic field (B0) inhomogeneities which currently must be corrected using separately acquired field map data. However, changes in the head position of a scanning participant across fMRI frames can cause changes in the B0 field, preventing accurate correction of geometric distortions. Additionally, field maps can be corrupted by movement during their acquisition, preventing distortion correction altogether. In this study, we use phase information from multi-echo (ME) fMRI data to dynamically sample distortion due to fluctuating B0 field inhomogeneity across frames by acquiring multiple echoes during a single EPI readout. Our distortion correction approach, MEDIC (Multi-Echo DIstortion Correction), accurately estimates B0 related distortions for each frame of multi-echo fMRI data. Here, we demonstrate that MEDIC's framewise distortion correction produces improved alignment to anatomy and decreases the impact of head motion on resting-state functional connectivity (RSFC) maps, in higher motion data, when compared to the prior gold standard approach (i.e., TOPUP). Enhanced framewise distortion correction with MEDIC, without the requirement for field map collection, furthers the advantage of multi-echo over single-echo fMRI., Competing Interests: Competing Interests A.N.V., D.A.F. and N.U.F.D. have a financial interest in Turing Medical Inc. and may benefit financially if the company is successful in marketing FIRMM motion monitoring software products. A.N.V., D.A.F. and N.U.F.D. may receive royalty income based on FIRMM technology developed at Washington University School of Medicine and Oregon Health and Sciences University and licensed to Turing Medical Inc. D.A.F. and N.U.F.D. are co-founders of Turing Medical Inc. These potential conflicts of interest have been reviewed and are managed by Washington University School of Medicine, Oregon Health and Sciences University and the University of Minnesota. A.N.V. is now an employee of Turing Medical Inc. The other authors declare no competing interests.