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Risk assessment: at the interface of cognition and emotion
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ScienceDirect Risk assessment: at the interface of cognition and emotion D Caroline Blanchard Risk Assessment (RA) is a core component of the defense survival system. Recent studies indicate substantial parallels between eliciting stimuli, behaviors, and functional outcomes for RA in animal models and people, and a rapidly growing literature suggests that some exaggerated or aberrant RA behaviors may be transdiagnostic components of anxiety and depressive disorders. Although the subcortical components of defense systems have been well mapped, RA, standing at the ‘interface of cognition and emotion’, appears to involve a more extensive cortical representation than other specific defenses. Recent analyses of metanetworks potentially interacting with the subcortical defense systems suggest that the Default Mode Network and the Salience Network may be strongly involved in RA. Address Pacific Biosciences Research Center, University of Hawaii at Manoa, Honolulu, HI 96825, USA Corresponding author: Blanchard, D Caroline ([email protected])
Current Opinion in Behavioral Sciences 2018, 24:69–74 This review comes from a themed issue on Survival circuits Edited by Dean Mobbs and Joe LeDoux
https://doi.org/10.1016/j.cobeha.2018.03.006 2352-1546/ã 2018 Published by Elsevier Ltd.
Risk Assessment Risk Assessment (RA) is the cognitive/attentional component of a pattern of defensive behaviors to threat or potential threat (e.g. [1]). The core overt behavior in RA is an intense orientation to, and sensory scanning of, the potential threat. This scanning, while multimodal, may involve different focal sensory modalities in different species, that is olfaction in rodents; vision in primates. RA occurs most clearly in response to stimuli for which there is an important element of threat ambiguity (e.g. [2]), and has a clear nonmonotonic relationship to threat intensity [3]. RA under the rubric of ‘vigilance’ has often been used as a major index of prey responsivity to predator risk (e.g. [4]). While this response is usually elicited by cues or potential cues from the predator itself, some animals may also respond to the defensive responses of conspecifics (e. g. [5]) or even those of other species [6]. www.sciencedirect.com
RA in nonhuman animals Much of the systematic work on RA has been done in laboratory settings, with wild as well as laboratory rats and mice, in seminatural habitats and in test batteries in which relevant stimulus and situational factors were varied (e.g. [7,8]). In these studies, RA has been measured in terms of a variety of specific behaviors, including ‘stretch attend’ (oriented to the stimulus but motionless except for scan/ sniff/ear-related movements) or during an approach (‘stretch approach); or from a place of concealment [9]. It typically involves ‘flat-back’ or ‘stretched’ postures or movements, reducing the probability that the threat stimulus will notice and respond to the risk-assessing animal. These patterns may be supplemented by other investigatory activities, such as burying the threat or throwing debris at it [10], potentially permitting a determination, by the movement of the threat, of its status as animate. Table 1 presents the results of a number of studies analyzing a range of defensive behaviors — flight, freezing, defensive threat/attack, defensive vocalizations, RA — in terms of the particular features of threat stimuli and situations in which the individual defenses were most likely to occur. These range from reflex-like behaviors such as the startle response, little modulated by situational characteristics, to RA, which functions to assess both stimulus and situational characteristics in order to facilitate the optimum choice of specific defenses in that situation. These behavioral differences are coming to be acknowledged in analyses of the neural systems in defense [11]. Particular defenses can occur in various combinations, reflecting different species-typical sensory and motor abilities of both prey and predator in a confrontation (e.g. [12,13]), but the core RA function of gathering information about potential threat sources is manifest in initial orientation to virtually any novel or unexpected stimulus, making RA a component, albeit not necessarily the focal defense, in almost every such encounter.
RA in people: the scenario studies These relationships were subsequently evaluated in people, who provided first choice responses to brief scenarios incorporating relevant threat stimuli or situational features. In these, correlations between threat ambiguity (rated by independent panels) and RA (‘check it out’) were +.86 and +.89 for women and men, respectively [14]. In subsequent replications done in Brazil [15,16] and the United Kingdom [17] as well as in the US [18] the Current Opinion in Behavioral Sciences 2018, 24:69–74
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Table 1 Defensive behaviors (rats, mice). Source of threat (and proximity) Discrete Discrete Discrete Discrete Discrete — close, animate Discrete — sudden Discrete — close, animate Uncertain — potential Uncertain — potential
Modulating features
Behavior
Typical outcome
‘Way out’ available No means of escape Conspecifics nearby Hiding place available No escape
Flight Freezing Alarm cry Hides Def. threat Startle Def. attack Risk assessment Defensive burying
Escape Reduces attack Warns conspecifics No detection/access Threatens attacker Startles attacker Hurts attacker painful Gains information Elicits movement
Substrate available
Table 1 presents common defensive behaviors, as analyzed in a number of rodent antipredator tests (e.g. [1,3,7–10,12,24]), along with relevant features of the eliciting (threat) stimulus; modulating situational features; and typical outcomes.
correlations of RA and threat ambiguity continued to be positive and significant. These scenarios all involved either potential or obvious physical threat from a conspecific. The Harrison et al. (2015) [18] study added new groups of scenarios, with results suggesting that correlations between threat ambiguity and RA are less apparent when social or psychological threats, such as gossip from coworkers or not being invited to a party, are involved. These typically elicited social/verbal means of mitigation, such as appeals to authority or verbal confrontation: notably, however, either of these could involve a substantial RA component. In addition, scenarios involving weather, or animals, also failed to show a substantial correlation with threat ambiguity, possibly for a different reason; a restricted (low) level of ambiguity in the threat potential of a hurricane, tornado, bear or being approached in the water by an animal that could be a shark. Facial expression studies provide additional support for a link between RA and threat ambiguity. Perkins et al. (2012) [19] asked volunteers to model expressions to short scenarios that were designed to elicit a range of emotions. Additional volunteers also labeled photographs/videos of responses to ambiguous threats as ‘anxious’ although expressions in response to clear threats were identified as ‘fear’. Moreover, the ‘anxious’ expressions were characterized by visual scanning behaviors, providing further face validity to the identification of anxiety with RA.
RA and anxiety On behavioral and functional grounds, RA appears to have a specific relationship to anxiety [1,20], with the failure to determine that a stimulus or situation is actually not dangerous being a particularly important mechanism in anxiety [21]. As RA often involves not only attention but also approach to potential danger, while flight constitutes avoidance of it, an RA/anxiety — flight/fear relationship has often been conceptualized in terms of an ‘Approach — Avoidance’ dichotomy as a component of an Current Opinion in Behavioral Sciences 2018, 24:69–74
influential theoretical treatment of anxiety [22]. Although providing a clear criterion for classification, this dichotomy fails to address the specific functional significance of RA, as opposed to the other ‘approach’ defense, defensive attack. Specifically, RA facilitates acquisition of information about threats and the situations in which they occur, permitting (if successful) the determination of an optimal defense for that particular threat stimulus and situation, including a return to nondefensive behavior if threat is not present (e.g. [2,23]). The view that RA is involved in anxiety has also been supported by a number of studies showing that anxiolytic drugs are particularly effective with RA measures in the elevated plus maze [24–26] or rat and mouse defense test batteries [8,27,28], while serotonergic agents often impact eye-gaze measures and rumination linked to anxiety in humans [29]. These findings provide support for a ‘vigilance’ hypothesis of anxiety [30], that is embedded in a substantial number of recent studies of eye-gaze tracking to threat stimuli (see [31,32] for review) in which anxious subjects typically show a faster response to threatening stimuli, sometimes coupled with subsequent avoidance, than do nonanxious individuals. In particular, anxious individuals show a nonvoluntary gaze shift toward peripheral threat cues, even when instructed to maintain central fixation [33]. The status of RA as an interface between cognitive processes and threat-elicited emotion state is also emphasized by its potential links to rumination, which is strongly associated with both anxiety and depression [34,35]. Rumination involves intensive and often intrusive thinking about problems, characterized by particularly passive, negative thoughts focusing on past events and on the ruminator’s emotional reaction to these, rather than on problem solving; suggesting a flawed or deficient form of RA [2]. Michl et al. (2013) [36], suggest that rumination may be responsible for much of the higher rate of anxiety in women than in men. Similarly, an RA-relevant category of ‘excessive’ or ‘uncontrollable’ worry, sometimes differentiated from rumination by its focus on future rather www.sciencedirect.com
Assessment: at the interface of cognition and emotion Blanchard 71
than past events [37] is also associated with anxiety and depression [38,39].
RA, anxiety, and brain systems Recent research has provided systematic and highly replicable evidence for parallel systems for defense in subcortical areas of rodent brains. These systems (see Canteras, this volume) may differ in sub-regional detail for different types of animate threats (e.g. dorsomedial VMH vs ventrolateral VMH activation in response to predators vs conspecific threats [40,41]) but they appear to follow similar trajectories, from amygdala through hypothalamus, to midbrain periaqueductal gray (PAG). Motta et al. (2017) [42] reviewed the connections and functions of the PAG, noting that both flight and RA are strongly responsive to stimulus and environmental features, and may depend on systems involving prosencephalic, in addition to subcortical, sites. They propose (Motta et al., 2017, Fig. 1 [42], illustrated in McNaughton and Corr, this volume) a specific pathway from the dPAG through the dorsolateral zone of the rostral part of the lateral septum, LSr.dl; to the ventral hippocampus (vHipp), and the medial prefrontal cortex (mPFC), to engage cortical systems in these defense processes. Notably, the LSr.dl is linked to the theta rhythm that is associated with anxiety responses (e.g. [43]), and, more specifically, with anxious rumination [44]; while lesions in the vHipp reduce RA [45], and the mPFC directly modulates fear expression in the amygdala (e.g. [46]). Chang and Grace (2018) [47], suggesting that anxiety disorders may result from aberrant functional connectivity in networks rather than in individual structures, outline some complex interactions between the mPFC and the orbitofrontal cortex (OFC), on activity modulated by GABAergic receptors in the lateral/basolateral amygdala. Nuss (2015) [48] also notes a central role for amygdala GABAA receptors, suggesting that these receptors and modulators of their allosteric sites may be involved in pathological anxiety. The mPFC is also a prominent component of the default mode network (DMN [49]). The major areas in this group, the mPFC, medial temporal lobes, and posterior cingulate cortex/retrosplenial cortex, show strong interconnections as well as synchronous EEG oscillations [50] that are higher during behavioral resting stages than in responsivity to external stimuli or during specific cognitive processing. In both anxiety and depression functional connectivity was increased in anterior portions of the DMN but decreased in posterior portions of this network [51]; interpreted as reflecting different functions of the two regions: self-referential and emotional processes for the former, but episodic memory and perceptual processing for the latter: Both anterior and posterior DMN connectivity were associated with clinical response after emotional regulation therapy that incorporated rumination-linked ‘decentering’ [52]. An additional link to RA www.sciencedirect.com
was the finding [53] of DMN intranetwork connectivity changes with worry severity and longer duration of illness in GAD patients. Increased functional connectivity between the DMN and the subgenual prefrontal cortex has been reported to predict depressive rumination [54], while connectivity between specific areas within the DMN was correlated with depression severity and earlier age of onset, for major depressive disorder patients [55]. Additionally, the salience network (SN [56]), consisting of a number of cortical structures originally identified as particularly responsive to novel events, is seen as orienting attention toward salient, often emotion-eliciting, stimuli. During acute stress, the SN appears to promote fear and vigilance [57]. There is also a positive relationship between subjective measures of stress and connectivity between the SN and the DMN, just after stress induction [58,59], while a recent review of fMRI studies [58] indicated that both the SN and the DMN show strong and relatively consistent responsivity to acute stress. Van Oort et al. (2017) [60] suggest that this relationship may reflect a hypervigilant state, in conjunction with selfreferential processing. A metaanalysis [61] reported structural and functional abnormalities in specific core cortical nodes of the SN in a range of psychopathologies. While these were associated with disruptive cognitive control, both the cognitive symptoms and the specifics of the SN abnormalities showed variation across and within psychiatric classifications. They (Peters et al., 2016 [61]) describe the need for better characterization of transdiagnostic cognitive pathologies, in accord with the Research Domain Criteria [62] as well as information on the brain system dysfunctions with which they may be specifically associated, for improved understanding of these relationships.
RA and survival circuits: summary and conceptualizations RA, ranging from vigilance behaviors to complex decision-making concerning threatening events, is the most ubiquitious component of defense: Its potential importance is further increased by suggested relationships to anxiety and depression, perhaps mediated by rumination and excessive worry. While the association of RA and other defensive behaviors with subcortical survival systems is well documented (e.g. [40,41]), and there is evidence of relevant connections from these to prosencephalic structures [42], the cortical systems involved in RA are only beginning to be analyzed or identified, making it difficult at present to conceptualize the relationships between subcortical and cortical components; for example are there two RA systems, one subcortical and the other cortical? Does a substantial cortical involvement in RA [63] call into question the view (McNaughton, this issue) of survival circuits as based in subcortical areas? What is the relationship between defensive RA systems and other important decision-making processes? Current Opinion in Behavioral Sciences 2018, 24:69–74
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Two conceptualizations of suboptimal RA, as rumination and excessive worry, appear to be correlated and also related to mood disorders such as anxiety and depression [37]. These specific RA manifestations, and their relationships to brain system functioning, can only be measured in humans, whereas more specific and precise — and typically invasive — techniques of brain manipulation and imaging are often only possible with animal subjects. LeDoux’ recent, and extensively documented, view that fear and anxiety necessarily involve conscious experience [64] might suggest that nonhuman animals, for which consciousness should not be assumed, are inappropriate subjects for research on these emotions. Although in general agreement that an assumption of consciousness in nonhumans is ill-advised, I suggest that the cognitive and decision-making aspects of RA can indeed be evaluated in the behaviors of nonhuman animals, and that we should seek methods for determining what are or are not appropriate/optimal RA-based decisions for dealing with threat risk across a range of situations. In turn, these behaviors and their origins in activities within particular neural systems should provide a much more precise and dynamic view of the functioning of RA for potential translation to humans, and possible validation or modification there. Consciousness may indeed contribute to the emotion of anxiety, but it would be extremely surprising if the basic outline of RA-related behavior patterns, so crucial to the core functions of defense, were to change substantially in the transition from nonhuman to human animals.
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Conflict of interest statement
14. Blanchard DC, Hynd AL, Minke KL, Minemoto T, Blanchard RJ: Human defensive behaviors to threat scenarios show parallels to fear- and anxiety-related defense patterns of non-human mammals. Neurosci Biobehav Rev 2001, 25:761-770.
Nothing declared.
Acknowledgments This research was supported by grants from the National Institute of Mental Health (NIH RO1MH081845) and the National Science Foundation (NSF BNS9111524) to DCB.
References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as: of special interest of outstanding interest 1.
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ScienceDirect Risk assessment: at the interface of cognition and emotion D Caroline Blanchard Risk Assessment (RA) is a core component of the defense survival system. Recent studies indicate substantial parallels between eliciting stimuli, behaviors, and functional outcomes for RA in animal models and people, and a rapidly growing literature suggests that some exaggerated or aberrant RA behaviors may be transdiagnostic components of anxiety and depressive disorders. Although the subcortical components of defense systems have been well mapped, RA, standing at the ‘interface of cognition and emotion’, appears to involve a more extensive cortical representation than other specific defenses. Recent analyses of metanetworks potentially interacting with the subcortical defense systems suggest that the Default Mode Network and the Salience Network may be strongly involved in RA. Address Pacific Biosciences Research Center, University of Hawaii at Manoa, Honolulu, HI 96825, USA Corresponding author: Blanchard, D Caroline ([email protected])
Current Opinion in Behavioral Sciences 2018, 24:69–74 This review comes from a themed issue on Survival circuits Edited by Dean Mobbs and Joe LeDoux
https://doi.org/10.1016/j.cobeha.2018.03.006 2352-1546/ã 2018 Published by Elsevier Ltd.
Risk Assessment Risk Assessment (RA) is the cognitive/attentional component of a pattern of defensive behaviors to threat or potential threat (e.g. [1]). The core overt behavior in RA is an intense orientation to, and sensory scanning of, the potential threat. This scanning, while multimodal, may involve different focal sensory modalities in different species, that is olfaction in rodents; vision in primates. RA occurs most clearly in response to stimuli for which there is an important element of threat ambiguity (e.g. [2]), and has a clear nonmonotonic relationship to threat intensity [3]. RA under the rubric of ‘vigilance’ has often been used as a major index of prey responsivity to predator risk (e.g. [4]). While this response is usually elicited by cues or potential cues from the predator itself, some animals may also respond to the defensive responses of conspecifics (e. g. [5]) or even those of other species [6]. www.sciencedirect.com
RA in nonhuman animals Much of the systematic work on RA has been done in laboratory settings, with wild as well as laboratory rats and mice, in seminatural habitats and in test batteries in which relevant stimulus and situational factors were varied (e.g. [7,8]). In these studies, RA has been measured in terms of a variety of specific behaviors, including ‘stretch attend’ (oriented to the stimulus but motionless except for scan/ sniff/ear-related movements) or during an approach (‘stretch approach); or from a place of concealment [9]. It typically involves ‘flat-back’ or ‘stretched’ postures or movements, reducing the probability that the threat stimulus will notice and respond to the risk-assessing animal. These patterns may be supplemented by other investigatory activities, such as burying the threat or throwing debris at it [10], potentially permitting a determination, by the movement of the threat, of its status as animate. Table 1 presents the results of a number of studies analyzing a range of defensive behaviors — flight, freezing, defensive threat/attack, defensive vocalizations, RA — in terms of the particular features of threat stimuli and situations in which the individual defenses were most likely to occur. These range from reflex-like behaviors such as the startle response, little modulated by situational characteristics, to RA, which functions to assess both stimulus and situational characteristics in order to facilitate the optimum choice of specific defenses in that situation. These behavioral differences are coming to be acknowledged in analyses of the neural systems in defense [11]. Particular defenses can occur in various combinations, reflecting different species-typical sensory and motor abilities of both prey and predator in a confrontation (e.g. [12,13]), but the core RA function of gathering information about potential threat sources is manifest in initial orientation to virtually any novel or unexpected stimulus, making RA a component, albeit not necessarily the focal defense, in almost every such encounter.
RA in people: the scenario studies These relationships were subsequently evaluated in people, who provided first choice responses to brief scenarios incorporating relevant threat stimuli or situational features. In these, correlations between threat ambiguity (rated by independent panels) and RA (‘check it out’) were +.86 and +.89 for women and men, respectively [14]. In subsequent replications done in Brazil [15,16] and the United Kingdom [17] as well as in the US [18] the Current Opinion in Behavioral Sciences 2018, 24:69–74
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Table 1 Defensive behaviors (rats, mice). Source of threat (and proximity) Discrete Discrete Discrete Discrete Discrete — close, animate Discrete — sudden Discrete — close, animate Uncertain — potential Uncertain — potential
Modulating features
Behavior
Typical outcome
‘Way out’ available No means of escape Conspecifics nearby Hiding place available No escape
Flight Freezing Alarm cry Hides Def. threat Startle Def. attack Risk assessment Defensive burying
Escape Reduces attack Warns conspecifics No detection/access Threatens attacker Startles attacker Hurts attacker painful Gains information Elicits movement
Substrate available
Table 1 presents common defensive behaviors, as analyzed in a number of rodent antipredator tests (e.g. [1,3,7–10,12,24]), along with relevant features of the eliciting (threat) stimulus; modulating situational features; and typical outcomes.
correlations of RA and threat ambiguity continued to be positive and significant. These scenarios all involved either potential or obvious physical threat from a conspecific. The Harrison et al. (2015) [18] study added new groups of scenarios, with results suggesting that correlations between threat ambiguity and RA are less apparent when social or psychological threats, such as gossip from coworkers or not being invited to a party, are involved. These typically elicited social/verbal means of mitigation, such as appeals to authority or verbal confrontation: notably, however, either of these could involve a substantial RA component. In addition, scenarios involving weather, or animals, also failed to show a substantial correlation with threat ambiguity, possibly for a different reason; a restricted (low) level of ambiguity in the threat potential of a hurricane, tornado, bear or being approached in the water by an animal that could be a shark. Facial expression studies provide additional support for a link between RA and threat ambiguity. Perkins et al. (2012) [19] asked volunteers to model expressions to short scenarios that were designed to elicit a range of emotions. Additional volunteers also labeled photographs/videos of responses to ambiguous threats as ‘anxious’ although expressions in response to clear threats were identified as ‘fear’. Moreover, the ‘anxious’ expressions were characterized by visual scanning behaviors, providing further face validity to the identification of anxiety with RA.
RA and anxiety On behavioral and functional grounds, RA appears to have a specific relationship to anxiety [1,20], with the failure to determine that a stimulus or situation is actually not dangerous being a particularly important mechanism in anxiety [21]. As RA often involves not only attention but also approach to potential danger, while flight constitutes avoidance of it, an RA/anxiety — flight/fear relationship has often been conceptualized in terms of an ‘Approach — Avoidance’ dichotomy as a component of an Current Opinion in Behavioral Sciences 2018, 24:69–74
influential theoretical treatment of anxiety [22]. Although providing a clear criterion for classification, this dichotomy fails to address the specific functional significance of RA, as opposed to the other ‘approach’ defense, defensive attack. Specifically, RA facilitates acquisition of information about threats and the situations in which they occur, permitting (if successful) the determination of an optimal defense for that particular threat stimulus and situation, including a return to nondefensive behavior if threat is not present (e.g. [2,23]). The view that RA is involved in anxiety has also been supported by a number of studies showing that anxiolytic drugs are particularly effective with RA measures in the elevated plus maze [24–26] or rat and mouse defense test batteries [8,27,28], while serotonergic agents often impact eye-gaze measures and rumination linked to anxiety in humans [29]. These findings provide support for a ‘vigilance’ hypothesis of anxiety [30], that is embedded in a substantial number of recent studies of eye-gaze tracking to threat stimuli (see [31,32] for review) in which anxious subjects typically show a faster response to threatening stimuli, sometimes coupled with subsequent avoidance, than do nonanxious individuals. In particular, anxious individuals show a nonvoluntary gaze shift toward peripheral threat cues, even when instructed to maintain central fixation [33]. The status of RA as an interface between cognitive processes and threat-elicited emotion state is also emphasized by its potential links to rumination, which is strongly associated with both anxiety and depression [34,35]. Rumination involves intensive and often intrusive thinking about problems, characterized by particularly passive, negative thoughts focusing on past events and on the ruminator’s emotional reaction to these, rather than on problem solving; suggesting a flawed or deficient form of RA [2]. Michl et al. (2013) [36], suggest that rumination may be responsible for much of the higher rate of anxiety in women than in men. Similarly, an RA-relevant category of ‘excessive’ or ‘uncontrollable’ worry, sometimes differentiated from rumination by its focus on future rather www.sciencedirect.com
Assessment: at the interface of cognition and emotion Blanchard 71
than past events [37] is also associated with anxiety and depression [38,39].
RA, anxiety, and brain systems Recent research has provided systematic and highly replicable evidence for parallel systems for defense in subcortical areas of rodent brains. These systems (see Canteras, this volume) may differ in sub-regional detail for different types of animate threats (e.g. dorsomedial VMH vs ventrolateral VMH activation in response to predators vs conspecific threats [40,41]) but they appear to follow similar trajectories, from amygdala through hypothalamus, to midbrain periaqueductal gray (PAG). Motta et al. (2017) [42] reviewed the connections and functions of the PAG, noting that both flight and RA are strongly responsive to stimulus and environmental features, and may depend on systems involving prosencephalic, in addition to subcortical, sites. They propose (Motta et al., 2017, Fig. 1 [42], illustrated in McNaughton and Corr, this volume) a specific pathway from the dPAG through the dorsolateral zone of the rostral part of the lateral septum, LSr.dl; to the ventral hippocampus (vHipp), and the medial prefrontal cortex (mPFC), to engage cortical systems in these defense processes. Notably, the LSr.dl is linked to the theta rhythm that is associated with anxiety responses (e.g. [43]), and, more specifically, with anxious rumination [44]; while lesions in the vHipp reduce RA [45], and the mPFC directly modulates fear expression in the amygdala (e.g. [46]). Chang and Grace (2018) [47], suggesting that anxiety disorders may result from aberrant functional connectivity in networks rather than in individual structures, outline some complex interactions between the mPFC and the orbitofrontal cortex (OFC), on activity modulated by GABAergic receptors in the lateral/basolateral amygdala. Nuss (2015) [48] also notes a central role for amygdala GABAA receptors, suggesting that these receptors and modulators of their allosteric sites may be involved in pathological anxiety. The mPFC is also a prominent component of the default mode network (DMN [49]). The major areas in this group, the mPFC, medial temporal lobes, and posterior cingulate cortex/retrosplenial cortex, show strong interconnections as well as synchronous EEG oscillations [50] that are higher during behavioral resting stages than in responsivity to external stimuli or during specific cognitive processing. In both anxiety and depression functional connectivity was increased in anterior portions of the DMN but decreased in posterior portions of this network [51]; interpreted as reflecting different functions of the two regions: self-referential and emotional processes for the former, but episodic memory and perceptual processing for the latter: Both anterior and posterior DMN connectivity were associated with clinical response after emotional regulation therapy that incorporated rumination-linked ‘decentering’ [52]. An additional link to RA www.sciencedirect.com
was the finding [53] of DMN intranetwork connectivity changes with worry severity and longer duration of illness in GAD patients. Increased functional connectivity between the DMN and the subgenual prefrontal cortex has been reported to predict depressive rumination [54], while connectivity between specific areas within the DMN was correlated with depression severity and earlier age of onset, for major depressive disorder patients [55]. Additionally, the salience network (SN [56]), consisting of a number of cortical structures originally identified as particularly responsive to novel events, is seen as orienting attention toward salient, often emotion-eliciting, stimuli. During acute stress, the SN appears to promote fear and vigilance [57]. There is also a positive relationship between subjective measures of stress and connectivity between the SN and the DMN, just after stress induction [58,59], while a recent review of fMRI studies [58] indicated that both the SN and the DMN show strong and relatively consistent responsivity to acute stress. Van Oort et al. (2017) [60] suggest that this relationship may reflect a hypervigilant state, in conjunction with selfreferential processing. A metaanalysis [61] reported structural and functional abnormalities in specific core cortical nodes of the SN in a range of psychopathologies. While these were associated with disruptive cognitive control, both the cognitive symptoms and the specifics of the SN abnormalities showed variation across and within psychiatric classifications. They (Peters et al., 2016 [61]) describe the need for better characterization of transdiagnostic cognitive pathologies, in accord with the Research Domain Criteria [62] as well as information on the brain system dysfunctions with which they may be specifically associated, for improved understanding of these relationships.
RA and survival circuits: summary and conceptualizations RA, ranging from vigilance behaviors to complex decision-making concerning threatening events, is the most ubiquitious component of defense: Its potential importance is further increased by suggested relationships to anxiety and depression, perhaps mediated by rumination and excessive worry. While the association of RA and other defensive behaviors with subcortical survival systems is well documented (e.g. [40,41]), and there is evidence of relevant connections from these to prosencephalic structures [42], the cortical systems involved in RA are only beginning to be analyzed or identified, making it difficult at present to conceptualize the relationships between subcortical and cortical components; for example are there two RA systems, one subcortical and the other cortical? Does a substantial cortical involvement in RA [63] call into question the view (McNaughton, this issue) of survival circuits as based in subcortical areas? What is the relationship between defensive RA systems and other important decision-making processes? Current Opinion in Behavioral Sciences 2018, 24:69–74
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Two conceptualizations of suboptimal RA, as rumination and excessive worry, appear to be correlated and also related to mood disorders such as anxiety and depression [37]. These specific RA manifestations, and their relationships to brain system functioning, can only be measured in humans, whereas more specific and precise — and typically invasive — techniques of brain manipulation and imaging are often only possible with animal subjects. LeDoux’ recent, and extensively documented, view that fear and anxiety necessarily involve conscious experience [64] might suggest that nonhuman animals, for which consciousness should not be assumed, are inappropriate subjects for research on these emotions. Although in general agreement that an assumption of consciousness in nonhumans is ill-advised, I suggest that the cognitive and decision-making aspects of RA can indeed be evaluated in the behaviors of nonhuman animals, and that we should seek methods for determining what are or are not appropriate/optimal RA-based decisions for dealing with threat risk across a range of situations. In turn, these behaviors and their origins in activities within particular neural systems should provide a much more precise and dynamic view of the functioning of RA for potential translation to humans, and possible validation or modification there. Consciousness may indeed contribute to the emotion of anxiety, but it would be extremely surprising if the basic outline of RA-related behavior patterns, so crucial to the core functions of defense, were to change substantially in the transition from nonhuman to human animals.
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Conflict of interest statement
14. Blanchard DC, Hynd AL, Minke KL, Minemoto T, Blanchard RJ: Human defensive behaviors to threat scenarios show parallels to fear- and anxiety-related defense patterns of non-human mammals. Neurosci Biobehav Rev 2001, 25:761-770.
Nothing declared.
Acknowledgments This research was supported by grants from the National Institute of Mental Health (NIH RO1MH081845) and the National Science Foundation (NSF BNS9111524) to DCB.
References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as: of special interest of outstanding interest 1.
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