In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic, and motor systems by high spatial resolution 7-Tesla fMRI

Abstract

Object To map the in vivo human functional connectivity of several brainstem nuclei with the rest of the brain by using seed-based correlation of ultra-high magnetic field functional magnetic resonance imaging (fMRI) data. Materials and Methods We used the recently developed template of 11 brainstem nuclei derived from multi-contrast structural MRI at 7 Tesla as seed regions to determine their connectivity to the rest of the brain. To achieve this, we utilized the increased contrast-to-noise ratio of 7 Tesla fMRI compared to 3 Tesla and the time efficient simultaneous multi-slice imaging to cover the brain with high spatial resolution (1.1 mm-isotropic nominal resolution) while maintaining a short repetition time (2.5 s). Results The delineated Pearson’s correlation-based functional connectivity diagrams (connectomes) of 11 brainstem nuclei of the ascending arousal, motor and autonomic systems from 12 controls are presented and discussed in the context of existing histology and animal work. Conclusion Considering that the investigated brainstem nuclei play a crucial role in several vital functions, the delineated preliminary connectomes might prove useful for future in vivo research and clinical studies of human brainstem function and pathology, including disorders of consciousness, sleep disorders, autonomic disorders, Parkinson’s disease and other motor disorders.

Disrupted reinforcement learning during post-error slowing in ADHD

“…B). In TD, confirmatory whole brain correlation with post-error slowing activity in raphe nucleus replicated previous findings using PET and resting state fMRI (Beliveau et al, 2015;Bianciardi et al, 2016) of positive correlations in parahippocampus, anterior insula, ACC/OFC, superior temporal and precuneus, and negative correlations in bilateral pre/post/paracentral and left superior frontal gyrus (S7 Fig.). The only correlation from Beliveau et al (2015) that was not present in TD was with right superior parietal lobule.…”

“…Our results also show that the low field large voxel approach can successfully identify rapidly changing connectivities with specific brainstem nuclei on errors in the SST. In particular, confirmatory whole brain correlation analyses with post-error slowing activity in SN and raphe nuclei were consistent with their known connectivity patterns, providing definitive evidence that these activities reflect the same kind of neurotransmitter function that has been identified with PET and time series analyses using high-field fMRI (Beliveau et al, 2015;Bianciardi et al, 2016), and rules out previous assertions that SN activity identified with this approach instead reflects subthalamic nucleus (Danielmeier and Ullsperger, 2011). LC is large enough to be detectable using low field large voxel fMRI (Chen and Ogawa, 1999) and has similar levels of neighboring noise (Brooks et al, 2013) and less distortion (Jezzard and Balaban, 1995;Napadow et al, 2006) than raphe nucleus across multiple field strengths.…”

“…Due to the lack of a standardized atlas for raphe nucleus and its proximity to other brainstem nuclei, we performed a confirmatory whole-brain correlation analysis (see 2.7.3), as suggested in (Beissner, 2015). We compared post-error slowing correlations with raphe nucleus in TD with correlations from a previous whole brain connectivity study with raphe nucleus at rest using 3T MRI and validated with PET of 5HT transporter binding (Beliveau et al, 2015), which are also consistent with resting state connectivity measured at 7T (Bianciardi et al, 2016).…”

“…In order to confirm that seed activities in neurotransmitter nuclei identified here reflect associated neurotransmitter function and not noise, we performed confirmatory whole-brain correlation analyses on post-error slowing seed activity in SN and raphe nucleus, in which whole-brain connectivity patterns are well characterized (Beliveau et al, 2015;Bianciardi et al, 2016). Post-error slowing activity in the medial septal seed was inspected for correlation with cholinergic basal forebrain as a way of estimating whether medial septal activity reflected cholinergic function.…”

Investigating resting-state functional connectivity in the cervical spinal cord at 3T

“…These organized resting-state fluctuations are not an exclusively cortical phenomenon, but have also been observed in subcortical regions as low as the pons and medulla (Beissner et al, 2014;Bianciardi et al, 2016), raising the question whether they constitute a functional signature of the entire central nervous system and might thus be detectable in the spinal cord as well. However, answering this question is a difficult endeavour, because it is challenging to obtain reliable fMRI data from the spinal cord due to a number of issues (Giove et al, 2004;Summers et al, 2010), the most prominent of which are: 1) the spinal cord has a very small cross-sectional area (Fradet et al, 2014;Ko et al, 2004), 2) the detrimental influence of physiological noise from cardiac and respiratory sources is much more prominent in the spinal cord than in the brain (Piché et al, 2009;Verma and Cohen-Adad, 2014), and 3) signal loss and image distortion periodically occur along the spinal cord due to the different magnetic susceptibility of vertebrae and connective tissue (Cooke et al, 2004;Finsterbusch et al, 2012).…”