What’s the causal link dissociating insula responses to salience and bodily arousal?

Just reading this new paper by Lucina Uddin and felt like a quick post. It is a nice review of one of my favorite brain networks, the ever present insular cortex and ‘salience network’ (thalamus, AIC, MCC). As we all know AIC activation is one of the most ubiquitous in our field and generally shows up in everything. Uddin advances the well-supported idea that in addition to being sensitive to visceral, autonomic, bodily states (and also having a causal influence on them), the network responds generally to salient stimuli (like oddballs) across all sensory modalities. We already knew this but a thought leaped to my mind; what is the order of causation here? If the AIC responds to and causes arousal spikes, are oddball responses driven by the novelty of the stimuli or by a first order evoked response in the body? Your brainstem, spinal cord, and PNS are fully capable of creating visceral responses to unexpected stimuli. How can we dissociate ‘dry’ oddball responses from evoked physiological responses? It seems likely that arousal spikes accompany anything unexpected and that salience itself doesn’t really dissociate AIC responses from a more general role of bodily awareness. Recent studies show that oddballs evoke pupil dilation, which is related to arousal.

Check out this figure:


Clearly AIC and ACC not only receive physiological input but also can directly cause phsyio outputs. I’m immediately reminded of an excellent review by Markus Ullsperger and colleagues, where they run into a similar issue trying to work out how arousal cues contribute to conscious error awareness. Ultimately Ullsperger et al conclude that we can’t really dissociate whether arousal cues cause error awareness or error-awareness causes arousal spikes. This seems to also be true for a general salience account.


How can we tease these apart? It seems like we’d need to somehow both knock out and cause physiological responses during the presence and absence of salient stimuli. I’m not sure how we could do this – maybe de-afferentiated patients could get us part of the way there. But a larger problem looms also: the majority of findings cited by Uddin (and to a lesser extent Ullsperger) come from fMRI. Indeed, the original Seeley et al “salience network” paper (one of the top 10 most cited papers in neuroscience) and the original Critchley insula-interoception papers (also a top ten paper) is based on fMRI. Given that these areas are also heavily contaminated by pulse and respiration artifacts, how can we work out the causal loop between salience/perception and arousal? If a salient cue causes a pulse spike then it might also cause a corresponding BOLD artifact. It might be that there is a particularly non-artefactual relationship between salient things and arousal but currently we can’t seem to work out the direction of causation. Worse, it is possible the process driving the artifacts themselves are crucial for ‘salience’ computation, which would mean physio-correction would obscure these important relationships! A tough cookie indeed. Lastly, we’ll need to go beyond the somewhat psychological label of ‘salience’ if we really want to work out these issues. For my money, I think an account based on expected precision fits nicely with the pattern of results we see in these areas, providing a computational mechanism for ‘salience’.

In the end I suspect this is going be one for the direct recording people to solve. If you’ve got access to insula implantees, let me know! 😀

Note: folks on twitter said they’d like to see more of the cuff posts – here you go! This post was written in a flurry of thought in about 30 minutes, so please excuse any snarfs! 

One thought on “What’s the causal link dissociating insula responses to salience and bodily arousal?

  1. Nice post Micah:) I haven’t read the recent Uddin paper yet, but here are a few thoughts about the salience network in general.

    First, I agree that salience is a loaded term and really should be discarded in favour of more specific computations.
    Second, the majority of the literature on the ‘salience network’ annoys me because it has largely ignored decades of work on visual attention, which has mapped out in great detail how perceptual stimuli are initially registered as meaningful. In particular, an important point is that regions such as the intraparietal sulcus and frontal eye-fields combine bottom-up information (e.g., stimulus intensity and abruptness) with top-down factors (what stimulus is currently behaviorally-relevant – based on task demands or emotional significance) to represent the overall salience of a stimulus within a topographically organized map. As far as I know, the insula has not been shown to have a topographic representation corresponding to stimulus location. Given that this is a fundamental property of early sensory areas, this would suggest that the insula is involved in later stage processing (probably closer to arousal generation) after perceptual salience detection has occurred in other regions. The amygdala is also much better suited for a role in perceptual salience detection than the insula (based on anatomical connectivity and functional properties). An interesting question is whether there are difference salience detection networks. I know the IPS and FEFs represent visual and auditory salience, but not sure if people have examined other modalities. It would also be useful to examine stimulus-evoked latencies (via single unit recordings) in these regions verses the insula. I think that contrasting the functional properties of different regions needs more attention given the correlative nature of fMRI, and the fact that something like salience will correlate with numerous computations.

    My opinion (see Dixon et al 2014, Brain Research) is that the insula and cingulate cortex coordinate interoceptive and skeletomotor changes that accompany action selection. The location of cingulate cortex implicated in salience detection is a region that is heavily connected to the motor system and weakly connected to sensory regions. And given that salient stimuli naturally induce motor preparation, these action-oriented processes are highly correlated with perceptual salience, but in many ways better explain the roles of these regions.

    There is tons to think about in regards to this issue, and it disappoints me that the ‘salience network’ has become so reified and not thoroughly examined in terms of specific computations that may be correlated with saliency. We need more theoretical neuroscientists that can help to elucidate issues like this by pointing out discrepancies between literatures from different sub-areas and suggest important experiments that could help resolve them. I say this because we are coming upon a decade since the salience network gained widespread appreciation and we still have little clue about basic functional properties! Seems crazy to me! Fewer experiments and more theory I say 🙂

    Thanks for stimulating discussion on this issue!

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