Brainstem fMRI signaling of surprise across different types of deviant stimuli

Abstract

The ability to detect deviant stimuli is crucial to adapt our behavior. Previous work showed that infrequent (hence deviant) stimuli elicit phasic activation of the brainstem locus coeruleus (LC), which releases noradrenaline and controls central arousal. However, it is unclear whether deviance detection selectively recruits the LC or also other neuromodulatory systems related to dopamine, acetylcholine, and serotonin. It is also unclear whether deviant-related responses in those systems only track infrequent stimuli in a sequence (which can be computed with bottom-up processes), or also violations of the sequence structure (which requires higher-order processings). Here, we combined human fMRI recordings optimized for brainstem imaging with pupillometry (a peripheral marker of central arousal) to perform a mapping of deviant-related responses in subcortical structures. Participants were exposed to a local-global paradigm that distinguishes between deviance based on the stimulus probability and the sequence structure. fMRI responses to deviant stimuli were quite distributed, detected in the LC but also other subcortical nuclei and many cortical areas. Both types of deviance elicited responses in the pupil, LC and other neuromodulatory systems. Our results reveal that deviance detection in humans recruits several subcortical systems and generalizes across computationally different types of deviance.

Atrophy links lower novelty‐related locus coeruleus connectivity to cognitive decline in preclinical AD

“…In the absence of heart rate and respiration monitoring, physiological noise was countered with nuisance regression using white matter, lateral ventricle, and fourth ventricle CSF signals, as well as ICA‐based removal of global motion and physiology components. Second, our focus on the LC, driven by its early accumulation of AD pathology, might overlook contributions of other neuromodulatory systems, for example, the dopaminergic system, which are implicated in novelty processing as well 73,74 . Third, we found no evidence that atrophy in Braak regions above stage 2 would mediate the relationship between LC‐MTL FC and cognitive decline.…”

Violated predictions enhance the representational fidelity of visual features in perception

“…3e), which may be because there was a longer delay between the unpredicted stimulus and the reproduction response than the speeded response. In addition to previous work showing increased cortical activity in response to unexpected events 5,7-9 , recent fMRI work has found increased pupil diameter and increased activity in subcortical regions (including the locus coeruleus), which are associated with neuromodulatory systems (dopamine, serotonin, and acetylcholine) 11 . Our findings complete the characterization of this coordinated response to unexpected events, by revealing the perceptual consequences of potentially related cortical and subcortical activity, and their relationship with physiological markers of surprise.…”

“…Predictive coding theories argue that prediction errors are generated when bottom-up sensory inputs deviate from top-down expectations 2 . There is broad consensus that prediction errors are associated with increased neural activation [5][6][7][8][9] , which is typically observed during the initial processing cascade in sensory cortices associated with the unexpected stimulus 4,10 , but has also been reported in subcortical regions 11 . By contrast, it remains unclear how these modulations reshape the pattern activity that represents the unexpected stimulus.…”

Auditory accessory stimulus boosts pupil-linked arousal and reduces choice bias

“…Thus, the exact neuroanatomical and neurochemical source(s) of our observed effects of experimentally controlled phasic arousal on decision-making remain to be determined. Future work should track the activity of multiple neuromodulatory nuclei at once, with brainstem fMRI in humans (Colizoli et al, 2022;de Gee et al, 2017;Mazancieux et al, 2022) or multi-fiber photometry / multi-color 2-photon imaging (of axons) in mice (Mridha et al, 2021;Sych et al, 2019).…”