Locus Coeruleus Engagement Drives Network Connectivity Dynamics In Humans And Rats

Locus coeruleus integrity predicts ease of attaining and maintaining neural states of high attentiveness

“…We interpreted these results to mean that LC structure (neuromelanin and cell density) plays a meaningful role in the effectiveness of the squeeze manipulation and its consequent effects on brain dynamics, even in the cohort of healthy young adults used here. This is consistent with previous results showing similar causal relationships among LC structure integrity and arousal states in older adults (Hussain et al, 2019;Langley et al, 2021Langley et al, , 2020. However, because of LC's small size (~2mm in diameter), it is difficult to establish whether LC activity itself (measured via the BOLD response) could also drive these behaviors, a problem that is exacerbated by the poor temporal resolution of fMRI.…”

“…We interpreted these results to mean that LC structure (neuromelanin and cell density) plays a meaningful role in the effectiveness of the squeeze manipulation and its consequent effects on brain dynamics, even in the cohort of healthy young adults used here. This is consistent with previous results showing similar relationships between LC structure integrity and cognition in older adults [Hussain et al, 2019; Langley et al, 2020a; Langley et al, 2021a; Mather and Harley, 2016].…”

“…Notably, these results demonstrate that network-based approaches to studying the effects of LC up-regulation can identify meaningful patterns even in the absence of precise measurement of LC activity itself. That the squeeze manipulation also eased the transition into this arousal state from a state of relative deactivation is not only consistent with previous findings showing that arousal may be more easily achieved if LC is successfully engaged (Hussain et al, 2019;Kozłowski et al, 1973;Lake et al, 1976;Mather et al, 2020;Wallin et al, 1992Wallin et al, , 1987, but also allow us to examine what that state of arousal consists of: relative deactivation of nearly every other network in the brain studied here with the exception of two nodes in FPCN (left and right posterior inferior parietal lobule) and two nodes in DAN (left anterior prefrontal cortex and left anterior insula). In contrast, DMN was almost entirely deactivated in this arousal state, in stark contrast to its high degree of activation that likely occurred directly after presence in the arousal state (in the DMN-dominant state, S1).…”

“…All subjects first underwent a five-minute pure resting state block (RS0) prior to any squeeze. Following this RS0 block, subjects underwent a 12.8-minute experiment where they alternated between resting state and bringing their dominant hand to their chest to squeeze a squeeze-ball at maximum grip strength (SQ1-RS5) [Hussain et al, 2019; Mather et al, 2020]. All five squeeze periods lasted 18 seconds, while the interspersed five resting state periods had durations of two-, two-, five-, one-, and one-minute, respectively.…”

“…Anatomic images were collected using an MP-RAGE sequence (TE/TE/inversion time = 3.02/2600/800 ms, flip angle =8°, voxel size = 0.8×0.8×0.8 mm 3 ) and used for registration from subject space to common space. One subject was excluded due to a history of attention deficit hyperactive disorder and consumption of related medication, such that the final dataset contained n = 30 subjects [Hussain et al, 2019; Yaghoubi et al, 2019].…”