Sensory precision in persistent depression

All three studies examining covert attentional orienting found evidence of large validity effects in depressed participants relative to healthy controls. Given that validity effects reflect the influence of the cue, which adjusts prior expectations regarding the probable location of the target, these findings provide some support for the suggestion that perception and action in persistent depression are characterised by an overreliance on prior beliefs relative to sensory prediction error1_{. This hypothesis} is reflected in the outcomes of the Study 6 computational model, which demonstrated a supra-modal attenuation of sensory precision in the depressed group relative to healthy controls; underpinned by a generic reduction in basal sensory precision regardless of the modality or salience characteristics of the stimuli in any given trial. This finding is consistent with predictive processing models which posit that depression is characterised by reduced sensory precision in the interoceptive realm (Barrett et al., 2016; Paulus et al., 2019), but generalises this reduction to other sensory modalities including the somatic, auditory and visual modalities. Of interest, although estimates of basal precision were reduced on average in depressed participants relative to healthy controls, among the depressed group they were positively associated with anxiety scores. This may suggest that high arousal or hypervigilance associated with anxiety has an opposing influence on basal sensory precision relative to the dampening effect of longstanding depression; however, a larger study better able to characterise different presentations of anxiety and depression symptomatology will be required to

1 _{The relevant prior in this scenario (when cues are non-predictive) is the expectation that, following a sensory}

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confirm such a hypothesis. Importantly, these findings indicate that reduced sensory precision in persistent depression may generalise across sensory modalities.

Reduced sensory precision resulting from resource conservation strategies during top-down attention also emerged as a plausible explanation for the Study 2 findings. It is unclear, on the basis of the current evidence, whether such strategies are implicit or explicit and how frequently they are employed during day-to-day perception and action by individuals with persistent depressive illnesses. A functional imaging study which may provide information relevant to this question employed dynamic causal modelling to investigate attentional filtering of irrelevant visual information in depression (Desseilles et al., 2009; Desseilles et al., 2011). Depressed participants and healthy controls performed a selective attention task under conditions of high and low attentional load. Control participants demonstrated parietal inhibition of activity in visual cortex both directly and via inhibition of forward connections within visual cortex, but only in the high-load condition. This outcome was consistent with the hypothesis that in healthy individuals cognitive control processes suppress irrelevant sensory input under conditions of attentional challenge. In depressed participants, however, a similar parietal modulation of visual cortex was observed in both the high- and low-load conditions, demonstrating that even a pop-out task requiring minimal focused attention can recruit top-down suppression of irrelevant sensory input during a depressive episode. Assuming that this observation generalises more broadly to attentionally undemanding day-to-day situations, it might imply not only that relatively high levels of cognitive effort are required for precise perception even of attended sensory information in depression, but also that extraneous sensory information that would be available to a healthy individual may not be available to a depressed individual in the same circumstances. This interpretation is consistent with the hypothesis that the precision of sensory signals may be suppressed or attenuated in persistent depression during focused attention as a result of implicit or explicit resource conservation strategies.

The above studies imply that optimizing the precision of sensory information may be relatively costly in energy terms, or otherwise requires resources that are less available in persistent depression due, perhaps, to the effects of chronic stress on relevant neurobiological systems. At a neural level, it has been proposed that the optimization of sensory precision is underpinned by the cholinergic system (Parr & Friston, 2019; Yu & Dayan, 2003). Acetylcholine (ACh) transmission regulates the gain control of sensory channels in selective attention, enhances cortical sensitivity to salient sensory information, and contributes to top-down cortical control under conditions of attentional challenge (Ballinger, Ananth, Talmage, & Role, 2016; Sarter, Hasselmo, Bruno, & Givens, 2005; Schmitz & Duncan, 2018). Prefrontal cholinergic signalling has been associated with both slow volume transmission and fast

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phasic activity, perhaps contributing to maintenance and switching of task set respectively (Sarter & Lustig, 2019; but see Sarter & Lustig, 2020), and while thalamic cholinergic signalling may enhance the processing of salient sensory signals (Kim, Müller, Bohnen, Sarter, & Lustig, 2017), cortical cholinergic circuits may have the opposing function of inhibiting irrelevant sensory information and reducing distractibility and behavioural flexibility in order to maintain existing context representations and task set (Kim, Müller, Bohnen, Sarter, & Lustig, 2019; Thiele & Bellgrove, 2018).

There is evidence that both stress and depression modulate cholinergic activity (Dulawa & Janowsky, 2019; Han et al., 2017; Higley & Picciotto, 2014): in particular, an extensive literature implicates chronically elevated central cholinergic signalling in depression. Although both the causes and consequences of a putative hypercholinergic state in depression remain unclear, it is possible to speculate that such a state could be consistent with excessive top-down control of afferent sensory inputs, or with the effort required to maintain the task-set associated with an outdated context by habitual suppression of inconsistent sensory evidence; consistent with an overemphasis on prior precision at the expense of sensory precision. In an interesting simulation of a related situation, Avery, Nitz, Chiba, and Krichmar (2012), following Yu and Dayan (2005), tracked interactions between NA and ACh in an agent undertaking a behavioural task involving both expected and unexpected uncertainty. A simulated lesion to the LC was found to lead to perseverative errors resulting from failures in context updating, which also contributed to an increase of PFC activity and to persistently elevated ACh levels which no longer accurately tracked uncertainty.