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Behavioural Brain Research xxx (2013) xxx– xxx

Contents lists available at ScienceDirect

Behavioural Brain Research

j ourna l h om epage: www.elsev ier .com/ locate /bbr

eview

uning to the significant: Neural and genetic processes underlyingffective enhancement of visual perception and memory

elena Markovica, Adam K. Andersonb,d, Rebecca M. Toddc,∗

University of British Columbia, Department of Philosophy, CanadaUniversity of Toronto, Department of Psychology, CanadaUniversity of British Columbia, Department of Psychology, CanadaCornell University, Department of Human Development, United States

i g h l i g h t s

Emotionally arousing events reach awareness more easily than more mundane events.Emotionally salient events are also perceived and remembered more vividly.We present the Biased Attention via Norepinephrine (BANE) model of affect-biased attention (ABA).BANE draws on genetic, neuromodulatory, neural and behavioural evidence to account for ABA.

r t i c l e i n f o

rticle history:eceived 26 June 2013eceived in revised form0 November 2013ccepted 12 November 2013vailable online xxx

a b s t r a c t

Emotionally arousing events reach awareness more easily and evoke greater visual cortex activation thanmore mundane events. Recent studies have shown that they are also perceived more vividly and thatemotionally enhanced perceptual vividness predicts memory vividness. We propose that affect-biasedattention (ABA) – selective attention to emotionally salient events – is an endogenous attentional systemtuned by an individual’s history of reward and punishment. We present the Biased Attention via Nore-pinephrine (BANE) model, which unifies genetic, neuromodulatory, neural and behavioural evidence toaccount for ABA. We review evidence supporting BANE’s proposal that a key mechanism of ABA is locuscoeruleus–norepinephrine (LC–NE) activity, which interacts with activity in hubs of affective salience net-works to modulate visual cortex activation and heighten the subjective vividness of emotionally salient
stimuli. We further review literature on biased competition and look at initial evidence for its potentialas a neural mechanism behind ABA. We also review evidence supporting the role of the LC–NE systemas a driving force of ABA. Finally, we review individual differences in ABA and memory including differ-ences in sensitivity to stimulus category and valence. We focus on differences arising from a variant of the ADRA2b gene, which codes for the alpha2b adrenoreceptor as a way of investigating influences of NEavailability on ABA in humans.
© 2013 Published by Elsevier B.V.

ontents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 002. Terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 003. Caveat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 004. Affective salience enhances visual perception and memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

4.1. Affective salience enhances the subjective quality of perception and memory. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 005. Potential neural pathways and mechanisms underlying affect-biased attention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

Please cite this article in press as: Markovic J, et al. Tuning to the significanvisual perception and memory. Behav Brain Res (2013), http://dx.doi.org/1

5.1. Neuroanatomical pathways mediating ABA . . . . . . . . . . . . . . . . . . . . . . .

5.2. Biased competition as a mechanism of ABA . . . . . . . . . . . . . . . . . . . . . . .

5.3. Acquisition of affective biases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

∗ Corresponding author. Tel.: +1 647 284 0634; fax: +1 647 284 0634.E-mail addresses: [email protected], [email protected] (R.M. Todd).

166-4328/$ – see front matter © 2013 Published by Elsevier B.V.ttp://dx.doi.org/10.1016/j.bbr.2013.11.018

t: Neural and genetic processes underlying affective enhancement of0.1016/j.bbr.2013.11.018

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dx.doi.org/10.1016/j.bbr.2013.11.018

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6. The role of norepinephrine in affect-biased attention and memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 006.1. The role of norepinephrine in ABA and memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

7. Individual differences in NE influence on affect-biased attention and memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 007.1. Individual differences in ABA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 007.2. Genetic influences on ABA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

8. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 009. Future directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

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References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. Introduction

Emotionally arousing events are experienced with a heightenedividness, and emotionally compelling objects in the environmentapture the eye as we navigate the world. It is, of course, wellnown that we continuously filter incoming sensory information,electively allocating attention to what is important to us anduppressing distracting or irrelevant information. Yet the neuralrocesses involved in attentional biases towards affectively signif-

cant aspects of the world remain relatively underspecified.There is a well-established literature documenting the ten-

ion between ‘top-down’ and ‘bottom-up’ processes in modulatingttention (for review see [1]). In this literature, ‘top-down’efers to effortful attentional processes mediated by frontopari-tal attentional networks and tuned to short-term goals, whereas

bottom-up’ refers to attentional capture by ‘objectively’ salienttimuli such as bright colours, motion, and high contrast [2–4].

Alongside other challenges to the original top-down/bottom-upistinction [5–7], we have argued that attention is also modulatedy longer-term subjective goals of increasing pleasure and avoidingain [8]. Such long-term goals can tune visual attention habituallyo emotionally significant, or affectively salient, stimuli such as anttractive person, an angry face, or a gruesome scene. Based onbservations that the amygdala and other brain regions key in tag-ing salience modulate visual cortex activation in a manner similaro the way frontoparietal regions do [9] we propose that affect-iased attention (ABA), which tunes visual attention to affectivelyalient stimuli, is distinct from both ‘classic’ executive top-townnd bottom-up visual attention, and is at least in part circum-cribed by a different set of neural mechanisms (see also [18]). Inhis paper we will propose the Biased Attention via Norepinephrine

odel (BANE), a multilevel model incorporating neuromodulatory,enetic, imaging and behavioural levels of analysis implicated inffective biasing of attention and memory. BANE focuses on thenfluence of noradrenergic processes on activation patterns in hubsf the ‘anterior affective system’ [10], including the amygdala andrbitofrontal cortex, which in turn modulate activity in other brainegions implicated in affect-biased visual attention and memory.his system is responsible for directing attention to and heighten-ng the subjective vividness of perceived emotional events, whichn turn enhances memory vividness. In this paper we will reviewvidence for BANE, arguing that affect biased attention can mod-late visual cortex activity in a manner distinct from – althought times overlapping and/or interacting with – the frontoparietalxecutive network.

We will first review literature on ABA, and will then discussotential neural mechanisms underlying ABA, particularly biasedompetition, which facilitates the influence of frontoparietal net-orks on the visual cortices in selective attention. We will further

eview recent evidence that biased competition may underlie ABAs well. We will then look at the role of norepinephrine (NE) and


he locus coeruleus (LC) of the brainstem in ABA and memory.E is produced by LC neurons, which have widespread projec-

ions throughout the brain [11], and facilitates processing of salientvents [12–14]. We will then review evidence about individual

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

differences in ABA and memory, focusing on individual differencesarising from a common variant of the ADRA2b gene coding for thealpha2b adrenoreceptor, which influences extracellular NE avail-ability. Finally we will present the BANE model in detail based onthe evidence previously discussed.

2. Terminology

Before we examine the literature, let us first clarify the key termsused in this paper. Salience is defined as the quality by which anaspect of the environment stands out relative to its surroundingsdue, perhaps, to its visual features (visual salience) or the goalsof the perceiver. For example, something may be visually salientbecause it is high in contrast or brightly coloured or high in motionin comparison with its surroundings. Because salience is a some-what circular term – some items catch our attention because theyare salient, and are salient because their qualities catch our atten-tion – we use the term in a manner that is descriptive rather thanexplanatory. As such, it can be a useful concept in that it allowsus to examine the properties that determine salience in a givencontext. Affective salience is the tendency of an item to stand outrelative to its neighbours due to an association between its seman-tic meaning and a history of emotional arousal [8]. Affect-biasedattention (ABA) is attention biased towards stimuli that are affec-tively salient because they have a developmental history of painand pleasure, approach and avoidance.

We have claimed that in affect-biased attention, motivationalgoals tune affective control settings, habitual ‘mental sets’ that areshaped by one’s history of emotionally arousing experiences [8].We suggest that, over time, affective control settings come to beapplied reflexively. Thus, whereas we may be tuned to stimuli thatare visually salient because evolution has tuned us to attend tomoving or high contrast aspects of the environment, we may besimilarly tuned to affectively salient stimuli because of our historyof emotional experience with them.

Building on the modulation hypothesis of McGaugh, Cahill andcolleagues [15,16], BANE proposes that ABA influences emotionalenhancement of memory. According to the modulation hypothe-sis, the effects of arousal on initial memory formation, or encoding,interact with the influence of arousal on longer-term memory con-solidation processes to bias memory for emotionally salient events.To encode an event is to process the relevant sensory informationinto a unified, coherent construct so that it may be remembered.Consolidation is divided into short- and long-term processes. Theformer is a set of molecular processes required for the creationand change of synaptic connections and occurs during the hoursafter the experience [17]. Long-term consolidation is the set of pro-cesses responsible for large-scale reorganization of neural memorysystems [17].

3. Caveat


Previous research has uncovered two functionally independentattentional systems in the cortex: a dorsal-frontoparietal networkinvolved in top-down selection of stimuli and responses which

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Fig. 1. Diagram of a dual-target rapid serial visual presentation (RSVP) task used tomeasure the attentional blink. Participants were instructed to ignore words appear-ing in black and to report the identity of the targets appearing in green. The timelag between the first (T1) and second (T2) target was varied. When T2 is presented

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nvolves the intraparietal cortex and superior frontal cortex and right-lateralized ventral-frontoparietal network sensitive to theottom-up salience of stimuli and which is centred on the tem-oroparietal cortex and inferior frontal cortex [2]. BANE is a modelf the ABA system. Though Corbetta and Shulman [2] state that theentral system is responsible for detecting behaviourally relevanttimuli, we should note that the ABA system is distinct from theight ventral-frontoparietal attentional system because it is respon-ible for directing attention to stimuli with an individual history ofeward and punishment. In contrast, Corbetta and Shulman’s rightentral frontoparietal system orients attention to objectively visu-lly salient, task relevant and unexpected stimuli (although someegions, such as lateral intraparietal cortex (LIP), may be key nodesn both affective salience and bottom-up salience systems).

. Affective salience enhances visual perception andemory

There is an extensive body of literature on ABA and its neu-al correlates, including how ABA interacts with classically definedop-down and bottom-up attentional systems, and a full review iseyond the scope of this paper (for reviews see [18,19]). In thisaper, following a brief overview of background research estab-

ishing prioritized processing of affective salience, and a review ofur own work revealing emotional enhancement of perceptual andnemonic vividness, we will focus on noradrenergic contributions

o ABA as illustrated by select studies.A large body of research has shown that affectively salient stim-

li elicit enhanced behavioural and neural processing comparedo more neutral stimuli. Emotional stimuli capture attention moreasily when they are at the threshold of awareness [20] and wheneveral stimuli are in competition for attention [21,22]. We are alsoore easily distracted by affectively salient stimuli when focusing

n another task [23,24]. Finally, we generally have better memoryor emotional than mundane events [25–29] (but see [30,31]).

At the neural level, affective salience has been strongly linked toncreased activity in sensory cortices. Neuroimaging studies havehown that affectively salient images evoke greater visual cortexctivation than mundane ones [32–36], an effect that is paralleledor affectively salient sounds in auditory cortex [37–39]. This effects found for social stimuli as well as emotionally arousing scenes:ace-specific regions of the fusiform cortex have been found tohow greater fMRI activation for fearful than neutral faces evenhen processing facial expression is not part of the task [40–42].

uch enhanced activation of fusiform cortex is also associated withetter detection of emotional faces [43,44].

Affectively salient stimuli also evoke enhanced event-relatedotentials (ERPs) at both early and late latencies, suggesting bothapid and extended prioritization of salient aspects of the world45,46]. Importantly, enhanced activity for affectively salient stim-li has been observed in very early ERP components which arelso sensitive to classic ‘top-down’ attention. These include the C147,48] a very early ERP generated by the striate cortex reflectingow-level visual features, and the P1 [49], a component primar-ly indexing extrastriate cortex activity [50]. Although there istill some controversy about the latency at which affective salientffects can be observed, these finding suggest that very early visualortex activation is sensitive to predictions/expectations related torior learning about affective salience.

One line of our own research has focused on enhanced percep-ual encoding of affectively salient stimuli as a marker of affectively


uned attentional sets. An experimental paradigm that has beenseful in indexing affective biases in attention is an emotional vari-nt of the attentional blink (AB) paradigm. In classic AB studies,wo target words are presented among a series of distractor stimuli

within 500 ms of T1, the attentional blink typically occurs. (For interpretation of thereferences to color in this figure legend, the reader is referred to the web version ofthe article.)

(Fig. 1). The attentional ‘blink’ itself is a phenomenon where par-ticipants are typically unable to report a target stimulus when it ispresented within ∼500 ms of a previous target in a rapid stream ofstimuli. According to one interpretation of the AB, the blink reflectsa failure to switch attentional sets from those tuned to the categoryof the T1 stimulus to those tuned to the T2 stimulus if it appearstoo quickly after T1, resulting in impaired perceptual awareness[51]. Anderson [22] used a version of the AB paradigm to examinewhether emotionally salient T2 stimuli are less subject to the atten-tional blink than neutral stimuli. The first experiment comparedAB for negatively valenced high-arousal words (e.g. “rape”), nega-tively valenced low-arousal words (e.g. “hurt”), and neutral words(e.g. “rule”). Results showed that negatively valenced high-arousalwords had a significantly smaller blink effect than negativelyvalenced low-arousal words, which themselves had a smaller ABeffect than neutral words. Thus, emotionally salient and negativelyvalenced words were easier to detect than neutral words or, inother words, that there was an emotional “sparing” of the blinkfor such words. The second study showed that this effect appliedto positively valenced target words as well, implying that what isimportant for detection of the stimuli is emotional arousal ratherthan valence. A further series of experiments ruled out potentialconfounds for the sparing of emotional words. In conclusion, theseexperiments revealed that when attentional resources are limited,emotionally salient stimuli are perceived more easily than neutralstimuli – a finding that may reflect more resilient attentional filtersfor affectively salient stimuli.

4.1. Affective salience enhances the subjective quality ofperception and memory

Another line of our research has focused on enhanced subjectiveexperience of perceptual and mnemonic vividness for affectivelysalient stimuli. While it was established that emotional eventsare typically (though not always) better remembered than mun-dane ones [52–54], it was not known whether emotional eventsare remembered more vividly because they are experienced asmore vivid in the first place. To investigate whether emotionalsalience influences the subjective experience of perceptual vivid-


ness, we employed an emotional version of a classic magnitudeestimation paradigm from psychophysics experiments of the 1950s[55,56]. In a classic magnitude estimation task, participants are pre-sented with a stimulus (e.g. a light or a tone) and are asked to

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ig. 2. Task design for Noise Estimation experiment. A standard, created by phase

he target image overlaid with 10%, 15%, or 20% noise. Following image offset, partrom “a lot less noise” to “same as standard” to “a lot more noise.”

ompare the magnitude of the stimulus to a standard presentedt a constant magnitude. In our adaptation, emotionally salientnd neutral images, which were equated for contrast and lumi-ance, were overlaid with one of three levels of Gaussian visualoise and standards were created for each image by scramblinghe image so its contents were not recognizable and overlaying atandard level of noise (Fig. 2). Participants were asked to judge theroportion of noisiness of each image relative to a standard [57].his design allowed us to look at the subjective vividness of affec-ively salient relative to neutral images measured as the signal ofhe underlying image relative to the overlaid noise. Results showedhat participants were very accurate in estimating objective levelsf noise. Crucially, both positive and negative arousing images wereerceived as less noisy, or more perceptually vivid, than neutral

mages. Even after controlling for the objective characteristics ofach image, participants still rated positive and negative images asontaining lower levels of noise, suggesting that affectively salientmages are subjectively experienced as more vivid than mundanenes. Moreover, when we created a direct measure of perceptualividness by calculating the inverse of the noise estimation ratings


NE−1, a measure of how clearly or vividly the image signal under-eath the noise was perceived), we found that, image by image,erceptual vividness predicted ratings of emotional salience.his relationship remained after controlling for computational

bling the target image, was overlaid with 15% noise. The standard was followed byts moved a cursor on a scale to indicated NE for the image relative to the standard

measures of objective visual salience, such as colour, image com-plexity, and a composite measure of visual salience [58,59],indicating that affective and objective salience make dissociablecontributions to perceived vividness. We refer to this influenceof emotional salience on perceptual vividness as emotionallyenhanced vividness (EEV).

Several control studies were performed to rule out confound-ing explanations. To eliminate the possibility that noise ratingswere driven by differential deployment of overt attention, we usedeye tracking to control for differences in looking patterns. Wefound that emotional salience did predict patterns of overt atten-tion, with more fixations for affectively salient images; however,emotional salience predicted perceptual vividness after control-ling for number of fixations, and fixations did not statisticallymediate emotional salience. Thus, deployment of overt attentiondid not account for the influence of affective salience on noiseestimation ratings. The main effect of affective salience on noiseestimation ratings was sustained in experiments using grayscaleimages, images with lower levels of noise and a single presen-tation of each image, indicating that greater perceived vividness


for affectively salient images is not affected by image colour ordifferential effects arising from repetition of emotional images;rather, it is due to the emotional content of the images themselves Q6(Fig. 3).

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Fig. 3. Noise estimation results. Arousing images were psychophysically scaled to contain less noise, i.e. were perceived as more perceptually vivid, despite equal levels ofo from

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bjective noise. The right side of the image illustrates a 15% decrement in noise levelontrolling for objective salience related to low-level featural characteristics of the

n left insula (left), LOC (right), and amygdala (bottom).

To see if the behavioural phenomenon of EEV reflected relativelyapid perceptual processes rather than later conceptual evaluativerocesses, we further examined the time course of ERP activity fol-

owing presentation of the images. We focused on the postsensory2, an early- to mid-latency positive peak measured at occipitallectrodes and implicated in object discrimination and enhancedttention to affectively salient images [60,61]. We found that P2mplitude was greatest for the least noisy images and impor-antly, that there was an effect of affective salience, with larger2 amplitudes for negative and positive versus neutral images.hat P2 amplitudes reflected objective perceptual vividness andubjective affective salience suggests that EEV involves relativelyapid perceptual processing and that emotionally salient imagesre perceived in the manner of objectively clearer images. Thisorresponds with the behavioural data indicating that participantserceive emotional images more vividly.

Finally, we employed fMRI to examine potential modulatoryources of EEV, to determine whether emotionally enhanced per-eption reflected enhanced visual cortex activation, and to examinehe relation between amygdala and visual cortex activation in rela-ion to EEV. We found that activations in the left amygdala as wells left lateral occipital cortex (LOC), which plays a role in objectiscrimination [62–64], and a region of left dorsal posterior insulahought to function as primary interoceptive cortex [65,66], modu-ated NE−1 for emotional images. Further analyses of co-activationPPI) found correlated activity between amygdala and visual cor-ex for affectively salient but not for neutral images. Statistically,mygdala activation mediated the influence of LOC and posteriornsula on EEV. These findings can be interpreted as reflecting theole of the amygdala in tagging affective salience, which in turn maynhance both the experience of seeing (reflected in LOC activation)nd gut feeling (reflected by posterior insula activation). Finally,ctivation in parietal and frontal regions which function as hubsn executive attentional networks was negatively correlated withE−1 suggesting that in this task there was a trade-off betweenxecutive attentional activity and amygdala-mediated modulationf ABA.

In short, we found that emotional salience modulates the sub-ective visual experience of seeing an image. Moreover, our resultsuggest that emotional salience modulates object-based atten-


ion, making a subjectively salient object appear more objectivelyalient. In this case, the amygdala, a hub of the anterior affectiveystem, accounted for enhanced visual cortex activation linked toEV in a manner that is consistent with the hypothesis that anterior

the left. (b) Image by image, emotional salience predicted perceptual vividness after. (c) fMRI activation parametrically modulated by emotionally enhanced vividness

affective networks modulate visual cortex activation similarly to,but dissociable from, frontoparietal networks. This result convergeswith electrophysiological findings that both affective salience [47]and state [67,68] modulate visual processing independently butsimilarly to executive top-down attention. Moreover, there was atradeoff between activation in anterior affective networks and fron-toparietal networks associated with top-down executive attention.Thus, in terms of executive attention, our results indicate that par-ticipants were not just attending more to affectively salient images– they were attending differently.

A second line of interest concerned whether EEV at the timeof encoding was related to memory vividness. Previous studieshave demonstrated that affectively salient images are typicallybetter recollected than neutral ones (e.g. [53] but see [69]). Morespecifically, participants show greater memory for the goal-relatedand emotionally salient aspects of images [70,71]. These effectsmay be due to differences at the time of perceptual processingbetween emotionally salient and neutral images. Emotional eventsare encoded more easily [22,32,44,72] and enhanced memory ofemotional images is associated with increased amygdala activa-tion [73,74] and high-level visual cortex activation [75,76] at thetime of encoding.

To test whether perceptual vividness at the time of encodingpredicts memory vividness we employed two memory tasks: acued recall task and a recognition memory task [57]. The cuedrecall study was performed 45 min after the completion of the noiseestimation task. Participants were given one-word cues that corre-sponded to one of the pictures seen in the noise estimation task andasked to provide a written description of the picture in as muchdetail as possible. Descriptions were rated for number of detailsrecalled from correctly remembered images, including thoughtsand emotions associated with the image. Participants recalled moredetails about affectively salient than neutral images, and inversenoise estimation was correlated with number of details recalledas well as associated thoughts and emotions. Thus, although par-ticipants were not more likely to recall an emotional image thana neutral one, it appears that the vividness with which we viewemotionally salient images modulates memory vividness as well.

In the recognition memory task, participants returned one weekafter performing the noise estimation task. They were shown all


of the images from the original task as well as unfamiliar imagesmatched for emotional salience, scene content and objective imagecharacteristics. Participants were asked to rate each image as oldor new and to rate the vividness of the memory. Again, NE−1

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ignificantly predicted memory vividness after controlling forbjective salience. Thus EEV contributes to some of the vividnessf emotional memory, though it is likely that post encoding con-olidation processes play a further role in memory vividness asell [77,78]. fMRI findings further revealed that the same regions

f amygdala and LOC that modulated EEV modulated subsequentatings of recognition memory vividness [79]; however memoryividness was uniquely modulated by additional activity in hip-ocampal and parahippocampal regions. These findings suggesthared neural substrates for the influence of emotional saliencen perceptual and mnemonic vividness, with amygdala and visualortex activation at encoding contributing to the experience of botherception and subsequent memory. However, memory vividness

s also predicted by unique patterns of neural activity.In summary, the noise estimation studies showed that affective

alience contributes not only to ease of detecting an image but alsoo the quality of one’s visual experience. Thus, not only do emo-ional images grab attention more easily, but we also see them morelearly. Affective salience is a distinct source of perceptual vivid-ess – contributing to an image’s vividness in a manner additionalo the image’s objective visual characteristics. The enhanced per-eptual vividness of emotional images is due to rapid perceptualrocessing rather than later conceptual processing. Furthermore,he enhanced processing received by affectively salient images athe time of perception trickles down to impact memory processes.he vividness of an image during perception and the emotionalalience of an image both contribute to the vividness of an imagen memory.

Thus, a large body of research has established that affectivelyalient stimuli enjoy prioritized attention and perceptual encod-ng, and elicit rapid and prioritized sensory enhancement. Our ownndings have established that they also enhance the vividness ofubjective perceptual experience, which in turn predicts memoryividness. Current research questions involve specifying in greateretail which aspects of an emotional stimulus influence attention,eural mechanisms underlying prioritization of affective stimulind how these may differ between individuals, and how affectiveiases are acquired through experience.

. Potential neural pathways and mechanisms underlyingffect-biased attention

.1. Neuroanatomical pathways mediating ABA

Previous research has established that feedback connectionsetween the amygdala and visual areas play an important role

n mediating enhancement of visual cortex activity for affectivelyalient stimuli [32,80–82]. There are bidirectional connectionsetween the amygdala and early visual areas in the striate andxtrastriate cortices [83,84]. Moreover, patients with amygdalaesions and an intact visual cortex lack the typically found enhancedeural response to affectively salient stimuli [80]. fMRI researchsing sophisticated analysis approaches such as dynamic causalodelling have provided functional evidence for amygdala mod-

lation of visual cortex when participants view affectively salienttimuli [85]. Yet although much research has focused on amygdalaathways, critics of an amygdalo-centric approach suggest that themygdala is not the sole hub of affective salience detection but isne hub among several participating in parallel cascades of acti-ations in networks mediating the influence of affectively salienttimuli on sensory processing [86,87]. Other regions that serve as


ubs in an “anterior affective system”, such as the orbitofrontalortex (OFC) are also potential modulators [10,44].

Pessoa and Adolphs further argue that visual information is pro-essed by multiple parallel channels, and that the cortex plays a

PRESS Research xxx (2013) xxx– xxx

large part in filtering visual information [87]. They propose that akey region for ABA is the pulvinar – especially its medial nucleus.The pulvinar receives visual input from the superior colliculus,retina and striate and extrastriate visual cortices, and its medialnucleus may be responsible for determining the behavioural rel-evance of a stimulus due to its connection with amygdala aswell as multiple cortical regions such as the OFC, cingulate cor-tex, insula and parietal regions [87]. These authors suggest thatthe amygdala is a “convergence zone” for information relevant toobject processing. The importance of the amygdala for ABA comesfrom its broad connectivity to other subcortical regions and to thecortex. The amygdala not only receives visual information fromhigher-order visual association cortices in the anterior temporallobe [84], it also has many connections to the cortex includingmedial, orbital and lateral regions of the prefrontal cortex [88].Thus, the amygdala impacts visual processing through both ofthese (direct and indirect) connections to the visual cortex. Anotherrecent model emphasizes the role of NE in amygdala entrainmentof widespread network co-activation in response to salient events[89]. In this paper we further emphasize the role of the LC/NEsystem in modulating specific neuronal mechanisms of selectiveattention in visual cortex in interaction with the anterior affectivesystem.

5.2. Biased competition as a mechanism of ABA

Neural mechanisms underlying modulation of the visual cor-tex by regions tagging affective salience are as yet underspecified;however, a potential mechanism is biased-competition, since thisis a well-mapped mechanism underlying executive influences onvisual attention. In biased-competition models of visual attention,top-down ‘attentional control settings’ bias attention to featuresof the environment that are relevant to one’s goals. Biased com-petition has been characterized in terms of three principles:competition, i.e. the brain systems that represent visual informa-tion are competitive and a gain in processing for one stimuluscomes at the cost of inhibition of activation tuned to other stimuli;control, i.e. there are mechanisms to allocate increased weight to acertain stimulus, and integration, i.e. when competition is resolvedin favour of a certain stimulus in one system this stimulus will gaindominance in other systems as well [90].

Beck and Kastner have reviewed evidence that stimuli competefor representation throughout the visual cortex and that competi-tion can be biased for spatial location as well as object features [91].For executive attentional biasing, frontoparietal networks modu-late visual cortex activation so that activity is enhanced in regionsresponsible for task-relevant stimuli and activation is suppressedin regions responsible for competing stimuli. For instance singlecell recordings of monkey visual cortex have shown that when amonkey attends to one of two competing stimuli within a neu-ron’s receptive field (RF), responses to the pair of stimuli in areasV2, V4 and MT are weighted to the attended stimuli, i.e. they aresimilar to response given to the attended stimulus presented alone[92–94]. Such findings are supported by fMRI studies on humans,which show increased activation in V4 and TEO in situations ofcompetition [95]. Thus in directing their attention, subjects wereable to enhance processing of one stimulus and suppress process-ing of competing stimuli. Beck and Kastner [90] review evidence ofexecutive modulation via the frontoparietal cortex based on spa-tial location and stimulus features, though they note that top-downmodulation is also possible based on memory or emotional mech-anisms.


We posit that activity in hubs of the anterior affective system(amygdala, orbitofrontal/ventromedial cortices) as well as thelocus coeruleus similarly modulates visual cortex activity based onthe affective salience of the stimulus. This hypothesis is supported

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responses to neighbouring frequencies while sparing response tothe best frequency [111]. It is also important for sensory gating,

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y recent findings in non-human primates that visual cortexctivation is modulated by stimulus reward value in the same wayhat it is modulated by executive attention [96,97]. The BANE modeluggests that findings related to reward value may extend to over-ll stimulus salience, and further propose that connections withey salience hubs modulate visual cortex activation for emotion-lly relevant stimuli while suppressing activation for competingtimuli.

The notion of affect-biased competition is still somewhat spec-lative, but recent work provides preliminary evidence of biasedompetition in visual cortex based on the affective salience of stim-li. EEG evidence of rapid primary visual cortex modulation byacial expressions is consistent with findings of biased competition

odulated by executive attention [47]. A study taking advantagef high temporal and spatial resolution of magnetic encephalog-aphy (MEG) [10] further employed dynamic causal modelling toredict MEG differentiation of affectively salient from neutral stim-li and found evidence for a top-down model that included bothortical and subcortical pathways allowing for rapid top-downodulation of visual processing by the anterior affective system.

he orbitofrontal/ventromedial prefrontal cortices play a key rolen this model. Convergent research further suggest that the anteriorffective system plays a key role in maintaining affective con-rol settings by maintaining templates for salient items based onast experience that function as a ‘predictive set’ that enhancesontext-dependent visual processing of salient stimuli [98]. More-ver, OFC/VMPFc activations based on implicitly learned stimulusssociations between facial features and personality traits haveeen found to predict subsequent inferotemporal activations [99],gain suggesting a key role for ventral prefrontal cortex in main-aining pre-existing templates linked to stimulus salience – or whate have called affective control settings – that modulate visual

ortex activity.In an innovative study specifically examining patterns of affect-

iased competition in visual cortex, Wieser et al. [100] employedteady state visually evoked potentials (ssVEPs) to examine pat-erns of ABA related to trait anxiety. The ssVEP is an oscillatory EEGesponse to flickering stimuli whose oscillatory frequency matcheshat of the driving stimulus. ssVEPs are useful indices of attentionalllocation, as ssVEP amplitude is linked to allocation of attentionesources to the driving stimulus, and it can be modulated byoth ‘bottom-up’ sensory processing and ‘top-down’ modulationf sensory activity. In this study participants viewed Gabor patchesgratings) which were superimposed over pictures of angry, neu-ral and happy faces [100]. Gabor patches and faces each oscillatedt a different frequency so that ssVEPs for each could be distin-uished. Participants were asked to detect changes in the directionf the grating of the Gabor patches, a task which required direct-ng attention away from the underlying face stimuli. Participants

ere selected for either high or low social anxiety (HSA and LSA)ased on a preliminary questionnaire. The study found that ssVEPmplitudes for Gabor patches were attenuated by angry faces rel-tive to neutral and happy faces for HSA individuals and by happyaces relative to angry and neutral faces for LSA individuals. Fur-hermore, the highest cost for processing of Gabor patches occurredhen the underlying face was angry for HSA individuals and happy

or LSA individuals. This evidence suggests that affective saliencean operate according to mechanisms of biased competition simi-ar to those that have been well mapped for visual attention, sinceompetition from the face stimuli resulted in diminished resourcellocation to the Gabor patch. Moreover, this study is an elegantemonstration that individuals may differ in patterns of ABA toifferently valenced stimuli. Thus, preliminary research suggestshat, at the level of neuronal populations, processes of biased com-


etition, potentially tuned via Hebbian learning, may subserveBA.

PRESS Research xxx (2013) xxx– xxx 7

5.3. Acquisition of affective biases

The question of the learning processes by which such biasesare acquired and sensory systems are tuned is essentially a devel-opmental question, as many things become salient over repeatedexperience in infancy, childhood, and beyond [8]. On a shorter timescale, such questions can be tractably addressed in the laboratoryin sessions where salience is learned through conditioning. We canthink about the process of conditioning in terms of the creationand tuning of affective control settings which track the stimuli thathave proved a significant source of punishment and reward. Humanconditioning studies have revealed that associative learning mech-anisms play a key role in acquisition of ABA. Convergent researchsuggests that learning history continuously retunes neuronal sen-sitivity to the features of salient stimuli, and that this effect can beobserved in early stages of visual processing. This may occur boththrough re-entrant activation of visual cortex from other regionsin affective salience networks, including the amygdala, OFC and LC,as well as increased local neuronal sensitivity in early visual cortex– processes that may operate at different time scales (for thor-ough review see [86]). Again, ssVEPs have been used effectively toindex enhancement of neuronal population of responses in specificlearning contexts. Recent evidence suggests that sensory tuningto the salience of conditioned stimuli is mediated by implicitlyacquired Hebbian mechanisms of temporally coordinated neuronalactivity, rather than explicit expectations, again suggesting someindependence from executive modulation of attention [101]. Alongsimilar lines, future research can examine the role of other learn-ing processes, such as vicarious learning, in the acquisition of ABA.Developmental research can address the question of whether thereare sensitive time windows in early life during which affective asso-ciations may be more easily acquired or changed.

6. The role of norepinephrine in affect-biased attentionand memory

6.1. The role of norepinephrine in ABA and memory

A further question concerns neuromodulatory influences onneuronal activity linked to ABA. A comprehensive body of researchon LC–NE activity indicates a potentially key role for this neuro-chemical system in driving aspects of ABA. Non-human animalstudies have found that motivationally relevant stimuli elicit LCresponse [for review see [14,13], and LC–NE activity has beenshown to directly modulate visual cortex activation [102]. More-over, NE activity in the amygdala is important for recruiting andcoordinating the brain regions that direct attention to emotionallysalient events [103,104]. Let us elaborate further on this evidence.

The LC is structurally well positioned to facilitate ABA. It receivesinputs from the central nucleus of the amygdala [12] as well asventral prefrontal regions important for stimulus evaluation anddecision-making (for review see [105]) facilitating tuning of LCactivity to what is motivationally relevant. The LC also projects toregions of the thalamus and visual cortex [106], allowing for rapidtuning of sensory responses.

A wide body of evidence suggests that LC neurons facilitateresponses to the behavioural and biological relevance of a stim-ulus [13], regardless of stimulus valence [12], while suppressingthose to less relevant stimuli. Arousing stimuli elicit phasic LC acti-vation resulting in release of NE [107–110]. Released NE may tunetarget neurons by improving their signal-to-noise ratio, inhibiting


allowing silent neurons to become responsive to relevant stimuli[13]. In non-human animal studies, increased extracellular NE has

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een shown to decrease spontaneous firing while leaving intactvoked response to sensory stimulation in somatosensory, olfac-ory and auditory pathways [112–114]. For example, NE appliedo auditory neurons in awake monkeys, who were presented with

series of conspecific vocalizations, resulted in a decrease inpontaneous activity but a spared response to the auditory stim-lus [115]. NE also improves spike timing and rhythmicity inomatosensory and olfactory neurons, suggesting that it provides

basis for encoding and perceptual accuracy [116–120]. All ofhese studies reinforce the view that the LC–NE system is sensitiveo the behavioural relevance of stimuli and influences perceptualesponses.

LC activity is also important in associative learning of what isalient. LC neurons fire in response to direct reward and pun-shment, and subsequently to any stimuli associated with thealient event [13]. NE modulation of long-term changes in synap-ic strength and gene transcription allow this system to guideehaviour based on stimulus salience within a given context [12].

Thus, the LC–NE system has the functional and anatomical con-ections needed to facilitate ABA. LC activity is driven by affectivelyalient stimuli and is capable of modulating visual cortex activation.ased on this evidence, BANE posits LC–NE activity as an importantriving force behind ABA. One hypothesis that emerges from thisodel is that, in humans, LC–NE activity modulates biased compe-

ition in the visual cortex, biasing processing of affectively salienttimuli (Fig. 5).

According to the modulation hypothesis [121] the influence ofE linked to arousal at encoding interacts with the influence ofE on more sustained consolidation processes, resulting in moreivid memories for emotionally salient stimuli. In this regard, non-uman animal studies have implicated NE in memory consolidationnd the formation of long-term memories [122]. The amygdaloidomplex influences memory consolidation processes in the hip-ocampus, caudate nucleus and other regions. It is also a keyarget site for the LC–NE system, possessing many NE receptors106]. Cahill and McGaugh [16] provide evidence that NE, stressormones, and the amygdala are part of an endogenous memoryodulating system, which influences recall based on the emo-

ional meaning of a stimulus. Noradrenergic activity is implicated inemory modulation, since infusion of adrenergic antagonists into

he amygdala eliminates memory modulation effects [123]. Non-uman animal studies provide further evidence that modulation oftress hormones influencing consolidation are mediated by beta-drenergic activity in the amygdala [16]. For instance, lesions ofhe amygdala and stria terminalis (a major amygdala output path)lock the memory-enhancing effects of adrenaline, glucocorticoids,nd drugs that affect the opiate and gabaergic systems [124,125].

The basolateral amygdala (BLA) plays a key role modulating theffects of other neurotransmitters and stress-released hormonesn memory consolidation [104,16]. Selective post-training inac-ivation of the BLA induces retrograde amnesia [126] and lesionsf the BLA block stress-hormone induced memory enhancement125]. BLA activation can also modulate synaptic plasticity in otherrain regions key for memory consolidation [15]. Moreover, theole of BLA in modulation of emotional memory consolidation haseen found to be in part mediated by alpha(2)-adrenoreceptors127]. In humans, NE activity has been found to play a role ineconfiguring brain network activity both during and subsequent toxposure to a stressor, suggesting that noradrenergic modulation ofncoding and memory occurs via reorganization of large-scale co-ctivation between regions sensitive to affective salience [85,89].hus, not only is NE activity key for ABA for salient stimuli within


ny given context, but noradrenergic activity in the amygdala atncoding may interact with NE activity implicated in memory con-olidation processes, ensuring that events tagged as most salientre not only more vividly perceived but better remembered. The


BANE model further hypothesizes that noradrenergic activity mod-ulates behavioural and neural correlates of emotionally enhancedperceptual and mnemonic vividness found in our previous studies(Fig. 5).

7. Individual differences in NE influence on affect-biasedattention and memory

7.1. Individual differences in ABA

Individuals differ both in the capacity for ABA and memoryand in the relative salience of different categories of stimulus – inparticular stimulus valence. In the study of individual differences,attentional biases are typically not measured by indices of ABA aswe have defined it in terms of affectively biased attentional setsthat pre-tune visual attention prior to encountering stimuli. Rather,biases are measured primarily by indices of difficulty in disengag-ing spatial attention from the location of affectively salient stimuliafter they have been presented [128] – as a kind of attentional“stickiness,” or failure of executive control processes.

Behavioural and ERP studies of attentional biases indicate thatindividuals with temperamental anxiety show greater attentionalstickiness to threatening stimuli than non-anxious individuals[129–131]. Attentional bias for threatening stimuli is also asso-ciated with lower threshold for amygdala activation to threat[130,132]. Recent reviews have summarized current research onthe relation between threat-bias and anxiety [133], including anexamination of the time course of responses to threat-related stim-uli in attentional bias [134], as well as biases associated withpersonality measures [135]. In the other direction, biases towardspositive stimuli have been linked to extraversion [136]. In addi-tion to being linked with traits, attentional biases can be learnedthrough conditioning and are associated with trauma [137–139].For instance, individuals with PTSD showed increased perceptualand amygdala sensitivity to stimuli associated with the trauma[140,141].

Individual differences in attentional biases have been observedearly in development, and can influence behavioural outcomes.Attentional stickiness to the location of threatening stimuli inchildren with temperamental inhibition has been found to pre-dict whether they would show social withdrawal behaviour atage five [142]. Such biases can be reinforced by experience overthe course of development. For instance, children with a shortversion of the 5HTTLPR (serotonin-transporter-linked polymorphicregion) in SLC6A4, the serotonin transporter gene, which is asso-ciated with temperamental fearfulness and amygdala sensitivityto threat [143,144], are more likely to have a family environmentthat emphasizes threat stimuli, thus exacerbating the underlyingtrait [145,146]. On the other hand, sensitivity to negative stimulican be attenuated by the ability to shift attention. Children highin negative affect and effortful control – a trait which includes theability to volitionally focus and shift attention – do not show theattentional bias to threat displayed by children with negative affectand low effortful control [147]. Clinical research has explored thepossibility of improving anxiety symptoms by training attention.Attentional Bias Modification (ABM) uses a cueing task to train par-ticipants’ attentional biases by placing targets more frequently atthe location of neutral than negative stimuli. ABM has diminishedattentional bias towards negatively valenced stimuli and reducedanxiety scores in clinical and non-clinical populations [148] as well


as children [149]. That training attentional biasing has an effecton anxiety scores suggests that attentional biases may be partiallyresponsible for producing anxiety symptoms. However, it shouldbe noted that ABM research is in its preliminary stages, effect sizes

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Fig. 4. ADRA2b influence on the attentional blink as measured by accuracy at Lag1, when the second target word directly follows the first and the attentional blinkeffect is greatest. Whereas both ADRA2b deletion carriers and non-carriers showedthe typical ‘emotional sparing,’ or greater accuracy for affectively salient words,only deletion carriers showed an additional sparing over non-carriers, suggesting

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re small, and replication studies are needed to confirm the effectf ABM on subsequent outcomes and emotional responses [150].

.2. Genetic influences on ABA

Now that we have reviewed the role of NE in ABA and mem-ry, we turn to genetic variations linked to NE availability thatay partly underlie these individual differences. A deletion vari-

nt of the ADRA2b gene coding the inhibitory noradrenergic �2Beceptor is missing 9 base pairs, which impairs receptor regulationy G protein-coupled receptor kinase leading to a loss of receptoresensitization [151]. As inhibitory activity is itself inhibited, car-ying the deletion variant results in higher levels of extracellularE availability.

A recent seminal study linked the ADRA2b deletion variant,hich was previously associated with vasoconstriction, to emo-

ional memory [152]. In this study, participants viewed neutral andffectively salient images and performed a free recall task shortlyfterward. Whereas all participants showed greater recall for therousing images, ADRA2b deletion carriers showed a significantlyreater emotional memory enhancement in the laboratory. Theame study found that survivors of Rwandan genocide who carriedhe deletion variant were more vulnerable to intrusive memoriesharacteristic of post-traumatic stress disorder (PTSD).

A further question concerns whether the ADRA2b influencesmotional memory by enhancing encoding, consolidation, or both.he hypothesis that ADRA2b plays a role in perception is supportedy evidence that deletion carriers show increased amygdala acti-ation to negative arousing images relative to non-carriers [153].urthermore, in a study using the emotional attentional blink, par-icipants given reboxetine (a selective NE reuptake inhibitor whichncreases the amount of available NE) showed a smaller blink formotional stimuli – a greater emotional sparing – than participantsiven a placebo [154]. In a recent study, we used an emotional atten-ional blink paradigm to directly examine the influence of ADRA2bn affective biases in perception in a large sample of healthy youngdults [155]. The study employed the AB task to investigate dif-erences in ABA for positive, negative, and neutral words betweeneletion variant carriers and non-carriers while controlling for sexs well as individual differences in trait neuroticism, working mem-ry, and other genes potentially implicated in attentional biases.hereas all participants showed the classic emotional sparing for

ositive and negative over neutral words, deletion carriers showed further sparing for negative over positive words (Fig. 4). Thus, thistudy showed that ADRA2b affects visual encoding, suggesting thatE has an important role in ABA.

LC activity has two phases, ongoing oscillatory tonic activitynd stimulus-locked phasic activity [156]. The ADRA2b deletionariant influences activity at NE �-receptors, leading to their desen-itization and putative greater NE availability [151]. Whereas NE-receptor activity is linked with the influence of phasic release ofE on the attention blink task [157], the emotional sparing effect

n the attentional blink task is associated with a tonic increasen synaptic NE [154]. Our finding that deletion carriers showed areater emotional sparing in the AB task suggests that �-receptorctivity may be the mechanism behind emotional sparing, andhus ABA, via increased tonic levels of NE. This interpretation isonsistent with a study by Cousijn et al. [158]. In this study, partic-pants viewed either a violent movie (stress condition) or a neutral

ovie (non-stress condition) and then saw sets of dynamic fear-ul and happy faces. Amygdala activation was measured during the

ovie and face stimuli. Non-carriers showed an increased amyg-


ala response to emotional faces only in the non-stress condition,hereas deletion carriers had such a response in both the stress andon-stress conditions. As the authors suggest, while non-deletionarriers seemed to be hitting a ceiling in their amygdala response

860

biased perceptual encoding of negative stimuli is associated with higher levels ofextracellular NE.

to emotional stimuli, deletion carriers possess a further range ofactivation. We may speculate that, as deletion carriers have lessactivity at inhibitory alpha2b receptors, a sustained mood induc-tion may increase tonic NE levels in carriers only, whereas it mayinhibit them in non-carriers. The greater tonic NE in deletion carri-ers would then interact with phasic activity to increase amygdalaactivation in non-carriers.

In our study, ADRA2b deletion carriers showed greater ABAtowards negative stimuli, consistent with previous findings thatcarriers show enhanced amygdala activation during perception ofnegative stimuli [153]. An outstanding question concerns whetherdeletion carriers show enhanced ABA for negative stimuli becausethey find negative stimuli to be more salient than non-carriers, orwhether they show enhanced NE-driven activity for stimuli that aregenerally salient to carriers and non-carriers alike (after controllingfor key trait differences), since young adults in this age group showan overall bias for negative stimuli (e.g. [159]).

The enhanced perceptual processing of emotional events dis-played by deletion carriers may result in enhanced emotionalmemory via NE �-receptors in the amygdala. A further study exam-ined whether subjective ratings of affective experience at encodingpredicted the accuracy and confidence of subsequent memory[160]. The same group of healthy young adults rated positive,negative, and neutral scenes for level of emotional arousal and sub-sequently performed a surprise recognition memory task one weeklater. Results showed that, for negative images, subjective ratingsof arousal at encoding predicted better memory accuracy one weeklater in deletion carriers. In contrast, non-carriers showed poorermemory when they rated images as higher in arousal. ADRA2bdeletion carriers also demonstrated a stronger overall relationshipbetween the subjective arousal level of each image at encodingand memory confidence for the same image one week later [160].According to the modulation hypothesis, phasic arousal related toperceptual vividness interacts with more tonic arousal extendingbeyond initial encoding to further enhance memory consolidation[121]. Our finding that carriers of the deletion variant showed agreater association between arousal at encoding and memory foremotionally salient images suggests that, for these individuals, it


is precisely this NE-mediated relationship between encoding andpost-encoding processes that is enhanced – at least for moder-ately arousing events [see also [122]]. Of course, noradrenergic

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Fig. 5. Key pathways emphasized by BANE model: Green dashed lines indicate NE pathways. Red lines indicate projections to the LC. Thicker lines indicate direct modulationof visual cortex activity in affect-biased attention. NE activity is implicated in both stimulus encoding and selective attention [13]. A salient stimulus activates LC neurons,which project widely to cortical and subcortical regions. LC neurons are highly sensitive to previously acquired associations between a stimulus and punishment or reward.Descending influences from amygdala (central nucleus) and ventral prefrontal cortices Aston-Jones et al., 2007) provide information about contextually determine relevance,Q10which can then modulate the pattern of LC firing accordingly. Activity from LC can modulate activity in visual cortex directly, facilitating gating and tuning of neuronal activitya l cortQ11a ry encl

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nd enhancing perceptual acuity directly as well as via the amygdala and prefrontas prefrontal regions and in turn modulates hippocampus activity related to memoegend, the reader is referred to the web version of the article.)

nfluences on perception, encoding, and memory do not work insolation, but interact with the influence of other neuromodulators13,14]. Although we did not find any interactions with genes mod-lating serotonin or dopamine, the influence of NE at adrenoceptorsound in terminals of serotonergic and dopaminergic neurons [14]

ay also play a role in the influence of ADRA2b on encoding andemory. Moreover, other neurochemicals may play a role in dif-

erent aspects of attentional biases. For example, whereas NE mayodulate activity in brain regions associated with object-based

spects of affective salience, serotonin may influence activity inegion sensitive to spatial attention/contextual aspects of affectivealience linked to attentional stickiness.

Future fMRI research can use ADRA2b groupings to examinehe role of NE in neural and behavioural markers of emotionallynhanced perceptual vividness and its relation to memory vivid-ess, on post-encoding processes in humans as well as potentialene-gene interactions (epistasis) and interactions with life expe-ience.

. Summary

The BANE model’s core claim is that ABA is partly driven byC–NE processes, which interact with activity in hubs of anteriorffective system key for tagging affective salience and modulat-ng activity in visual cortices. BANE provides a unified explanationor multiple streams of data related to ABA. Building on a largeody of evidence indicating that emotional stimuli elicit enhancedisual processing compared to neutral stimuli, convergent evidence


oints to the amygdala and OFC as among the regions that aremportant for modulation of visual cortex in ABA. Pharmacolog-cal and non-human animal studies have revealed that affectivealience related activity of this network is partly driven by LC–NE

ices. The amygdala receives contextual information from the hippocampus as welloding and consolidation. (For interpretation of the references to color in this figure

activity. A body of evidence indicates LC activation is implicated intuning and gating of perceptual responses to salient stimuli, allow-ing for enhanced responses to what is already salient as well aslearning of new associations. Thus, NE activity in the amygdalamay play an important role for recruiting visual cortex activationassociated with ABA (Fig. 5).

The importance of NE in ABA and memory is supported bygenetics studies on ADRA2b, a polymorphism that affects levels ofextracellular NE. ADRA2b deletion carriers are more sensitive toemotionally salient stimuli. They show greater ABA for negativestimuli, show a stronger relation between subjective arousal andmemory, experience greater emotional enhancement of memory,and are more likely to suffer from intrusive traumatic memories.However, it should be noted that is possible that higher levels oftonic NE availability associated with the deletion variant increaseresponsiveness to salient stimuli in general, and not just thosethat are affectively significant. It will be important to investigatewhether deletion carriers are more sensitive to low-level visual fea-tures than non-carriers and control for any such differences wheninvestigating the influence of ADRA2b in ABA. It is also important tonote that genetics studies reveal only a correlational relationshipbetween NE activity and ABA. Further pharmacological studies ofNE demonstrating a causal role for NE systems in human ABA wouldsubstantially strengthen the model.

The BANE model is similar to – and substantially overlaps with –another recent model of ABA, the MAGiC model [18]. According tothe MAGiC model, emotional stimuli gain enhanced perceptual pro-cessing via multiple amplification mechanisms operating in parallel


(and not via a single top-down modulatory source). The MAGiCmodel emphasizes the key causal role the amygdala plays in adap-tive gain processes subserving ABA, and the relative independenceof the amygdala-centred affective attention system. Thus, it focuses

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n the degree to which amygdala-centred systems can processffectively salient stimuli even when they are task-irrelevant [161]r when emotional information is presented outside the focus ofrontoparietal attention [80,162,163]. Like MAGiC, the BANE modelroposes that affectively salient stimuli bias perception through aentral attentional system – although according to BANE these doot necessarily operate independently from frontoparietal atten-ion (for a similar perspective see [164]). The BANE model furthermphasizes the additional role of the LC–NE system.

. Future directions

The BANE model makes a number of predictions that can beested by future research. First, we predict that NE availability

odulates individual differences in EEV, and that ADRA2b dele-ion carriers will show enhanced EEV supported by enhancedmygdala/ventromedial activation, which will in turn predict sub-equent memory vividness. Second, we predict that NE availabilitynfluences electrophysiological correlates of biased competitionnderlying ABA, and that ADRA2b deletion carriers will showreater evidence of biased competition for arousing stimuli thanon-carriers. Third, future research can use the ADRA2b genotypeo investigate noradrenergic contributions to post-encoding pro-esses associated with affectively enhanced memory. Fourth, theANE model can be integrated with computational models of influ-nce of affective salience on perceptual expectations that guidettention according to context [98,165,166]. Finally, pharmacolog-cal interventions can further probe causal effects of NE availabilityn ABA.

A longer term research programme can involve investigation ofhe role of NE in learning processes by which ABA develops overhe lifespan, and the influence of both genotype and life experi-nce in both normal and pathological patterns of ABA, extendingalience-based models of predictive coding to address ABA in aevelopmental context. Understanding the interaction betweenenotype and epigenetic changes due to specific types of experi-nce will be an important part of such a research programme.

Finally, an important area for future research is to understandhe role of ABA in post-traumatic stress-disorder (PTSD) in conjunc-ion with research on the influences of genotype, life experience,nd traumatic event on neurophysiological processes associatedith generation and perpetuation of PTSD symptoms. For exam-le are pre-existing patterns of ABA a risk factor for PTSD? DoDRA2b deletion carriers show evidence of greater ABA for trauma-elated stimuli than non-carriers and do these patterns of ABAredict intrusive memory? Ultimately understanding mechanismsnderlying individual differences in ABA and memory can help usnderstand mechanisms underlying how they are shaped by lifexperience over development and in trauma.

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