ABSTRACTFearful avoidance is a hallmark of anxiety disorders and often comes at a cost. It reduce... more ABSTRACTFearful avoidance is a hallmark of anxiety disorders and often comes at a cost. It reduces the probability of threat and of obtaining rewards. Theoretical models predict that threat-induced psychophysiological states, such as freezing-related bradycardia, facilitate arbitration of approach-avoidance decisions. We indeed show that bradycardia states are linked to the neurocomputational underpinnings of approach-avoidance arbitration when facing varying reward and threat magnitudes. Bradycardia was not only linked toaversive value-related avoidance decisions but also tovalue comparison(a stronger tendency to approach vs. avoid when expected reward outweighs potential threat). An amygdala-striatal-prefrontal neural circuit supported approach-avoidance arbitration under threat, with specific involvement of the amygdala and dorsal anterior cingulate (dACC) in integrating subjective outcome values and bradycardia states. These findings highlight the role of human freezing states i...
Highlights • We ran a randomized placebo-controlled fMRI study with a multispecies probiotic • Pr... more Highlights • We ran a randomized placebo-controlled fMRI study with a multispecies probiotic • Probiotics did not affect neurocognitive measures of emotion and cognitive control • Probiotics did affect stress-related working memory and neural correlates • Probiotics in healthy individuals can support cognition under stress
Anxious individuals consistently fail in controlling emotional behavior, leading to excessive avo... more Anxious individuals consistently fail in controlling emotional behavior, leading to excessive avoidance, a trait that prevents learning through exposure. Although the origin of this failure is unclear, one candidate system involves control of emotional actions, coordinated through lateral frontopolar cortex (FPl) via amygdala and sensorimotor connections. Using structural, functional, and neurochemical evidence, we show how FPl-based emotional action control fails in highly-anxious individuals. Their FPl is overexcitable, as indexed by GABA/glutamate ratio at rest, and receives stronger amygdalofugal projections than non-anxious male participants. Yet, high-anxious individuals fail to recruit FPl during emotional action control, relying instead on dorsolateral and medial prefrontal areas. This functional anatomical shift is proportional to FPl excitability and amygdalofugal projections strength. The findings characterize circuit-level vulnerabilities in anxious individuals, showing ...
Individuals with a social anxiety disorder (SAD) show hypofunctioning of the hypothalamus–pituita... more Individuals with a social anxiety disorder (SAD) show hypofunctioning of the hypothalamus–pituitary-gonadal (HPG) axis, which is linked to social fear and avoidance behavior. As testosterone administration has been shown to facilitate social-approach behavior in this population, it may enhance the effectiveness of exposure treatment. In this proof-of-concept study, we performed a randomized clinical assay in which 55 women diagnosed with SAD received two exposure therapy sessions. Session 1 was supplemented with either testosterone (0.50 mg) or placebo. Next, transfer effects of testosterone augmentation on within-session subjective fear responses and SAD symptom severity were assessed during a second, unenhanced exposure session (session 2) and at a 1-month follow-up, respectively. The participants having received testosterone showed a more reactive fear pattern, with higher peaks and steeper reductions in fear levels in session 2. Post-hoc exploration of moderating effects of endo...
Animals have sophisticated mechanisms for coping with danger. Freezing is a unique state that, up... more Animals have sophisticated mechanisms for coping with danger. Freezing is a unique state that, upon threat detection, allows evidence to be gathered, response possibilities to be previsioned and preparations to be made for worst-case fight or flight. We propose that-rather than reflecting a passive fear state-the particular somatic and cognitive characteristics of freezing help to conceal overt responses, while optimizing sensory processing and action preparation. Critical for these functions are the neurotransmitters noradrenaline and acetylcholine, which modulate neural information processing and also control the sympathetic and parasympathetic branches of the autonomic nervous system. However, the interactions between autonomic systems and the brain during freezing, and the way in which they jointly coordinate responses, remain incompletely explored. We review the joint actions of these systems and offer a novel computational framework to describe their temporally harmonized integration. This reconceptualization of freezing has implications for its role in decision-making under threat and for psychopathology.
Acutely challenging or threatening situations frequently require approach-avoidance decisions. Ac... more Acutely challenging or threatening situations frequently require approach-avoidance decisions. Acute threat triggers fast autonomic changes that prepare the body to freeze, fight or flee. However, such autonomic changes may also influence subsequent instrumental approach-avoidance decisions. Since defensive bodily states are often not considered in value-based decision-making models, it remains unclear how they influence the decision-making process. Here, we aim to bridge this gap by discussing the existing literature on the potential role of threat-induced bodily states on decision making and provide a new neurocomputational framework explaining how these effects can facilitate or bias approach-avoid decisions under threat. Theoretical accounts have stated that threat-induced parasympathetic activity is involved in information gathering and decision making. Parasympathetic dominance over sympathetic activity is particularly seen during threat-anticipatory freezing, an evolutionaril...
A better understanding of context in decision-making-that is, the internal and external condition... more A better understanding of context in decision-making-that is, the internal and external conditions that modulate decisions-is required to help bridge the gap between natural behaviors that evolved by natural selection and more arbitrary laboratory models of anxiety and fear. Because anxiety and fear are mechanisms evolved to manage threats from predators and other exigencies, the large behavioral, ecological and evolutionary literature on predation risk is useful for re-framing experimental research on human anxiety-related disorders. We review the trade-offs that are commonly made during antipredator decision-making in wild animals along with the context under which the behavior is performed and measured, and highlight their relevance for focused laboratory models of fear and anxiety. We then develop an integrative mechanistic model of decision-making under risk which, when applied to laboratory and field settings, should improve studies of the biological basis of normal and pathological anxiety and may therefore improve translational outcomes.
Damage to the ventromedial prefrontal cortex (VMPFC) can cause maladaptive social behavior, but t... more Damage to the ventromedial prefrontal cortex (VMPFC) can cause maladaptive social behavior, but the cognitive processes underlying these behavioral changes are still uncertain. Here, we tested whether patients with acquired VMPFC lesions show altered approach-avoidance tendencies to emotional facial expressions. Thirteen patients with focal VMPFC lesions and 31 age- and gender-matched healthy controls performed an implicit approach-avoidance task in which they either pushed or pulled a joystick depending on stimulus color. While controls avoided angry faces, VMPFC patients displayed an incongruent response pattern characterized by both increased approach and reduced avoidance of angry facial expressions. The approach bias was stronger in patients with higher self-reported impulsivity and disinhibition, and in those with larger lesions. We further used linear ballistic accumulator modelling to investigate latent parameters underlying approach-avoidance decisions. Controls displayed n...
Control over emotional action tendencies is essential for every-day interactions. This cognitive ... more Control over emotional action tendencies is essential for every-day interactions. This cognitive function can fail during socially challenging situations, and is chronically attenuated in social psychopathologies such as social anxiety and aggression. Previous studies have shown that control over social-emotional action tendencies depends on phase-amplitude coupling between prefrontal theta-band (6 Hz) rhythmic activity and broadband gamma-band activity in sensorimotor areas. Here, we delivered dual-site phase-coupled brain stimulation to facilitate theta-gamma phase-amplitude coupling between frontal regions known to implement that form of control, while participants were challenged to control their automatic action tendencies in a social-emotional approach/avoidance-task. Participants had increased control over their emotional action tendencies, depending on the relative phase and dose of the intervention. Concurrently measured fMRI effects of task and stimulation, and estimated c...
Regulation of emotional behavior is essential for human social interactions. Recent work has expo... more Regulation of emotional behavior is essential for human social interactions. Recent work has exposed its cognitive complexity, as well as its unexpected reliance on portions of the anterior prefrontal cortex (aPFC) also involved in exploration, relational reasoning, and counterfactual choice, rather than on dorsolateral and medial prefrontal areas involved in several forms of cognitive control. This study anatomically qualifies the contribution of aPFC territories to the regulation of social-emotional actions, and explores a possible structural pathway through which emotional regulation might be implemented.We provide converging evidence from task-based fMRI, diffusion-weighted imaging, and functional connectivity fingerprints for a novel neural element in emotional regulation. Task-based fMRI in human male participants (N = 40) performing a social-emotional approach-avoidance task identified aPFC territories involved in the regulation of social-emotional actions. Connectivity finge...
Improving extinction learning is essential to optimize psychotherapy for persistent fear-related ... more Improving extinction learning is essential to optimize psychotherapy for persistent fear-related disorders. In two independent studies (bothn= 24), we found that goal-directed eye movements activate a dorsal frontoparietal network and transiently deactivate the amygdala (ηp2= 0.17). Connectivity analyses revealed that this downregulation potentially engages a ventromedial prefrontal pathway known to be involved in cognitive regulation of emotion. Critically, when eye movements followed memory reactivation during extinction learning, it reduced spontaneous fear recovery 24 h later (ηp2= 0.21). Stronger amygdala deactivation furthermore predicted a stronger reduction in subsequent fear recovery after reinstatement (r= 0.39). In conclusion, we show that extinction learning can be improved with a noninvasive eye-movement intervention that triggers a transient suppression of the amygdala. Our finding that another task which taxes working memory leads to a similar amygdala suppression fur...
Animal and human studies have shown that both early-life traumatic events and ongoing stress epis... more Animal and human studies have shown that both early-life traumatic events and ongoing stress episodes affect neurodevelopment, however, it remains unclear whether and how they modulate normative adolescent neuro-maturational trajectories. We characterized effects of early-life (age 0-5) and ongoing stressors (age 14-17) on longitudinal changes (age 14 to17) in grey matter volume (GMV) of healthy adolescents (n = 37). Timing and stressor type were related to differential GMV changes. More personal early-life stressful events were associated with larger developmental reductions in GMV over anterior prefrontal cortex, amygdala and other subcortical regions; whereas ongoing stress from the adolescents' social environment was related to smaller reductions over the orbitofrontal and anterior cingulate cortex. These findings suggest that early-life stress accelerates pubertal development, whereas an adverse adolescent social environment disturbs brain maturation with potential mental h...
Memory recall is facilitated when retrieval occurs in the original encoding context. This context... more Memory recall is facilitated when retrieval occurs in the original encoding context. This context dependency effect likely results from the automatic binding of central elements of an experience with contextual features (i.e., memory "contextualization") during encoding. However, despite a vast body of research investigating the neural correlates of explicit associative memory, the neural interactions during encoding that predict implicit context-dependent memory remain unknown. Twenty-six participants underwent fMRI during encoding of salient stimuli (faces), which were overlaid onto unique background images (contexts). To index subsequent context-dependent memory, face recognition was tested either in intact or rearranged contexts, after scanning. Enhanced face recognition in intact relative to rearranged contexts evidenced successful memory contextualization. Overall subsequent memory effects (brain activity predicting whether items were later remembered vs. forgotten) ...
Testosterone plays an important role in social threat processing. Recent evidence suggests that t... more Testosterone plays an important role in social threat processing. Recent evidence suggests that testosterone administration has socially anxiolytic effects, but it remains unknown whether this involves early vigilance or later, more sustained, processing-stages. We investigated the acute effects of testosterone administration on social threat processing in 19 female patients with Social Anxiety Disorder (SAD) and 19 healthy controls. Eventrelated potentials (ERPs) were recorded during an emotional Stroop task with subliminally presented faces. Testosterone induced qualitative changes in early ERPs (< 200 ms after stimulus onset) in both groups. An initial testosterone-induced spatial shift reflected a change in the basic processing (N170/VPP) of neutral faces, which was followed by a shift for angry faces suggesting a decrease in early threat bias. These findings suggest that testosterone specifically affects early automatic social information processing. The decreased attentional bias for angry faces explains how testosterone can decrease threat avoidance, which is particularly relevant for SAD.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, Jan 19, 2017
Upon increasing levels of threat, animals activate qualitatively different defensive modes, inclu... more Upon increasing levels of threat, animals activate qualitatively different defensive modes, including freezing and active fight-or-flight reactions. Whereas freezing is a form of behavioural inhibition accompanied by parasympathetically dominated heart rate deceleration, fight-or-flight reactions are associated with sympathetically driven heart rate acceleration. Despite the potential relevance of freezing for human stress-coping, its phenomenology and neurobiological underpinnings remain largely unexplored in humans. Studies in rodents have shown that freezing depends on amygdala projections to the brainstem (periaqueductal grey). Recent neuroimaging studies in humans have indicated that similar brain regions may be involved in human freezing. In addition, flexibly shifting between freezing and active defensive modes is critical for adequate stress-coping and relies on fronto-amygdala connections. This review paper presents a model detailing these neural mechanisms involved in free...
The Hypothalamic-Pituitary-Adrenal (HPA)-axis plays an important role in the expression of defens... more The Hypothalamic-Pituitary-Adrenal (HPA)-axis plays an important role in the expression of defensive freezing. Adaptive freezing reactivity, characterized by an immediate increase in acute stress and timely termination upon threat offset or need to act, is essential for adequate stress coping. Blunted HPA-axis activity in animals is associated with blunted freezing reactivity and internalizing symptoms. Despite their potential relevance, it remains unknown whether these mechanisms apply to humans and human psychopathology. Using a well-established method combining electrocardiography and posturography, we assessed freezing before, immediately after, and one hour after a stress induction in 92 human adolescents. In line with animal models, human adolescents showed stress-induced freezing, as quantified by relative reductions in heart rate and body sway after, as compared to before, stress. Moreover, relatively lower basal cortisol was associated with reduced stress-induced freezing r...
ABSTRACTFearful avoidance is a hallmark of anxiety disorders and often comes at a cost. It reduce... more ABSTRACTFearful avoidance is a hallmark of anxiety disorders and often comes at a cost. It reduces the probability of threat and of obtaining rewards. Theoretical models predict that threat-induced psychophysiological states, such as freezing-related bradycardia, facilitate arbitration of approach-avoidance decisions. We indeed show that bradycardia states are linked to the neurocomputational underpinnings of approach-avoidance arbitration when facing varying reward and threat magnitudes. Bradycardia was not only linked toaversive value-related avoidance decisions but also tovalue comparison(a stronger tendency to approach vs. avoid when expected reward outweighs potential threat). An amygdala-striatal-prefrontal neural circuit supported approach-avoidance arbitration under threat, with specific involvement of the amygdala and dorsal anterior cingulate (dACC) in integrating subjective outcome values and bradycardia states. These findings highlight the role of human freezing states i...
Highlights • We ran a randomized placebo-controlled fMRI study with a multispecies probiotic • Pr... more Highlights • We ran a randomized placebo-controlled fMRI study with a multispecies probiotic • Probiotics did not affect neurocognitive measures of emotion and cognitive control • Probiotics did affect stress-related working memory and neural correlates • Probiotics in healthy individuals can support cognition under stress
Anxious individuals consistently fail in controlling emotional behavior, leading to excessive avo... more Anxious individuals consistently fail in controlling emotional behavior, leading to excessive avoidance, a trait that prevents learning through exposure. Although the origin of this failure is unclear, one candidate system involves control of emotional actions, coordinated through lateral frontopolar cortex (FPl) via amygdala and sensorimotor connections. Using structural, functional, and neurochemical evidence, we show how FPl-based emotional action control fails in highly-anxious individuals. Their FPl is overexcitable, as indexed by GABA/glutamate ratio at rest, and receives stronger amygdalofugal projections than non-anxious male participants. Yet, high-anxious individuals fail to recruit FPl during emotional action control, relying instead on dorsolateral and medial prefrontal areas. This functional anatomical shift is proportional to FPl excitability and amygdalofugal projections strength. The findings characterize circuit-level vulnerabilities in anxious individuals, showing ...
Individuals with a social anxiety disorder (SAD) show hypofunctioning of the hypothalamus–pituita... more Individuals with a social anxiety disorder (SAD) show hypofunctioning of the hypothalamus–pituitary-gonadal (HPG) axis, which is linked to social fear and avoidance behavior. As testosterone administration has been shown to facilitate social-approach behavior in this population, it may enhance the effectiveness of exposure treatment. In this proof-of-concept study, we performed a randomized clinical assay in which 55 women diagnosed with SAD received two exposure therapy sessions. Session 1 was supplemented with either testosterone (0.50 mg) or placebo. Next, transfer effects of testosterone augmentation on within-session subjective fear responses and SAD symptom severity were assessed during a second, unenhanced exposure session (session 2) and at a 1-month follow-up, respectively. The participants having received testosterone showed a more reactive fear pattern, with higher peaks and steeper reductions in fear levels in session 2. Post-hoc exploration of moderating effects of endo...
Animals have sophisticated mechanisms for coping with danger. Freezing is a unique state that, up... more Animals have sophisticated mechanisms for coping with danger. Freezing is a unique state that, upon threat detection, allows evidence to be gathered, response possibilities to be previsioned and preparations to be made for worst-case fight or flight. We propose that-rather than reflecting a passive fear state-the particular somatic and cognitive characteristics of freezing help to conceal overt responses, while optimizing sensory processing and action preparation. Critical for these functions are the neurotransmitters noradrenaline and acetylcholine, which modulate neural information processing and also control the sympathetic and parasympathetic branches of the autonomic nervous system. However, the interactions between autonomic systems and the brain during freezing, and the way in which they jointly coordinate responses, remain incompletely explored. We review the joint actions of these systems and offer a novel computational framework to describe their temporally harmonized integration. This reconceptualization of freezing has implications for its role in decision-making under threat and for psychopathology.
Acutely challenging or threatening situations frequently require approach-avoidance decisions. Ac... more Acutely challenging or threatening situations frequently require approach-avoidance decisions. Acute threat triggers fast autonomic changes that prepare the body to freeze, fight or flee. However, such autonomic changes may also influence subsequent instrumental approach-avoidance decisions. Since defensive bodily states are often not considered in value-based decision-making models, it remains unclear how they influence the decision-making process. Here, we aim to bridge this gap by discussing the existing literature on the potential role of threat-induced bodily states on decision making and provide a new neurocomputational framework explaining how these effects can facilitate or bias approach-avoid decisions under threat. Theoretical accounts have stated that threat-induced parasympathetic activity is involved in information gathering and decision making. Parasympathetic dominance over sympathetic activity is particularly seen during threat-anticipatory freezing, an evolutionaril...
A better understanding of context in decision-making-that is, the internal and external condition... more A better understanding of context in decision-making-that is, the internal and external conditions that modulate decisions-is required to help bridge the gap between natural behaviors that evolved by natural selection and more arbitrary laboratory models of anxiety and fear. Because anxiety and fear are mechanisms evolved to manage threats from predators and other exigencies, the large behavioral, ecological and evolutionary literature on predation risk is useful for re-framing experimental research on human anxiety-related disorders. We review the trade-offs that are commonly made during antipredator decision-making in wild animals along with the context under which the behavior is performed and measured, and highlight their relevance for focused laboratory models of fear and anxiety. We then develop an integrative mechanistic model of decision-making under risk which, when applied to laboratory and field settings, should improve studies of the biological basis of normal and pathological anxiety and may therefore improve translational outcomes.
Damage to the ventromedial prefrontal cortex (VMPFC) can cause maladaptive social behavior, but t... more Damage to the ventromedial prefrontal cortex (VMPFC) can cause maladaptive social behavior, but the cognitive processes underlying these behavioral changes are still uncertain. Here, we tested whether patients with acquired VMPFC lesions show altered approach-avoidance tendencies to emotional facial expressions. Thirteen patients with focal VMPFC lesions and 31 age- and gender-matched healthy controls performed an implicit approach-avoidance task in which they either pushed or pulled a joystick depending on stimulus color. While controls avoided angry faces, VMPFC patients displayed an incongruent response pattern characterized by both increased approach and reduced avoidance of angry facial expressions. The approach bias was stronger in patients with higher self-reported impulsivity and disinhibition, and in those with larger lesions. We further used linear ballistic accumulator modelling to investigate latent parameters underlying approach-avoidance decisions. Controls displayed n...
Control over emotional action tendencies is essential for every-day interactions. This cognitive ... more Control over emotional action tendencies is essential for every-day interactions. This cognitive function can fail during socially challenging situations, and is chronically attenuated in social psychopathologies such as social anxiety and aggression. Previous studies have shown that control over social-emotional action tendencies depends on phase-amplitude coupling between prefrontal theta-band (6 Hz) rhythmic activity and broadband gamma-band activity in sensorimotor areas. Here, we delivered dual-site phase-coupled brain stimulation to facilitate theta-gamma phase-amplitude coupling between frontal regions known to implement that form of control, while participants were challenged to control their automatic action tendencies in a social-emotional approach/avoidance-task. Participants had increased control over their emotional action tendencies, depending on the relative phase and dose of the intervention. Concurrently measured fMRI effects of task and stimulation, and estimated c...
Regulation of emotional behavior is essential for human social interactions. Recent work has expo... more Regulation of emotional behavior is essential for human social interactions. Recent work has exposed its cognitive complexity, as well as its unexpected reliance on portions of the anterior prefrontal cortex (aPFC) also involved in exploration, relational reasoning, and counterfactual choice, rather than on dorsolateral and medial prefrontal areas involved in several forms of cognitive control. This study anatomically qualifies the contribution of aPFC territories to the regulation of social-emotional actions, and explores a possible structural pathway through which emotional regulation might be implemented.We provide converging evidence from task-based fMRI, diffusion-weighted imaging, and functional connectivity fingerprints for a novel neural element in emotional regulation. Task-based fMRI in human male participants (N = 40) performing a social-emotional approach-avoidance task identified aPFC territories involved in the regulation of social-emotional actions. Connectivity finge...
Improving extinction learning is essential to optimize psychotherapy for persistent fear-related ... more Improving extinction learning is essential to optimize psychotherapy for persistent fear-related disorders. In two independent studies (bothn= 24), we found that goal-directed eye movements activate a dorsal frontoparietal network and transiently deactivate the amygdala (ηp2= 0.17). Connectivity analyses revealed that this downregulation potentially engages a ventromedial prefrontal pathway known to be involved in cognitive regulation of emotion. Critically, when eye movements followed memory reactivation during extinction learning, it reduced spontaneous fear recovery 24 h later (ηp2= 0.21). Stronger amygdala deactivation furthermore predicted a stronger reduction in subsequent fear recovery after reinstatement (r= 0.39). In conclusion, we show that extinction learning can be improved with a noninvasive eye-movement intervention that triggers a transient suppression of the amygdala. Our finding that another task which taxes working memory leads to a similar amygdala suppression fur...
Animal and human studies have shown that both early-life traumatic events and ongoing stress epis... more Animal and human studies have shown that both early-life traumatic events and ongoing stress episodes affect neurodevelopment, however, it remains unclear whether and how they modulate normative adolescent neuro-maturational trajectories. We characterized effects of early-life (age 0-5) and ongoing stressors (age 14-17) on longitudinal changes (age 14 to17) in grey matter volume (GMV) of healthy adolescents (n = 37). Timing and stressor type were related to differential GMV changes. More personal early-life stressful events were associated with larger developmental reductions in GMV over anterior prefrontal cortex, amygdala and other subcortical regions; whereas ongoing stress from the adolescents' social environment was related to smaller reductions over the orbitofrontal and anterior cingulate cortex. These findings suggest that early-life stress accelerates pubertal development, whereas an adverse adolescent social environment disturbs brain maturation with potential mental h...
Memory recall is facilitated when retrieval occurs in the original encoding context. This context... more Memory recall is facilitated when retrieval occurs in the original encoding context. This context dependency effect likely results from the automatic binding of central elements of an experience with contextual features (i.e., memory "contextualization") during encoding. However, despite a vast body of research investigating the neural correlates of explicit associative memory, the neural interactions during encoding that predict implicit context-dependent memory remain unknown. Twenty-six participants underwent fMRI during encoding of salient stimuli (faces), which were overlaid onto unique background images (contexts). To index subsequent context-dependent memory, face recognition was tested either in intact or rearranged contexts, after scanning. Enhanced face recognition in intact relative to rearranged contexts evidenced successful memory contextualization. Overall subsequent memory effects (brain activity predicting whether items were later remembered vs. forgotten) ...
Testosterone plays an important role in social threat processing. Recent evidence suggests that t... more Testosterone plays an important role in social threat processing. Recent evidence suggests that testosterone administration has socially anxiolytic effects, but it remains unknown whether this involves early vigilance or later, more sustained, processing-stages. We investigated the acute effects of testosterone administration on social threat processing in 19 female patients with Social Anxiety Disorder (SAD) and 19 healthy controls. Eventrelated potentials (ERPs) were recorded during an emotional Stroop task with subliminally presented faces. Testosterone induced qualitative changes in early ERPs (< 200 ms after stimulus onset) in both groups. An initial testosterone-induced spatial shift reflected a change in the basic processing (N170/VPP) of neutral faces, which was followed by a shift for angry faces suggesting a decrease in early threat bias. These findings suggest that testosterone specifically affects early automatic social information processing. The decreased attentional bias for angry faces explains how testosterone can decrease threat avoidance, which is particularly relevant for SAD.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, Jan 19, 2017
Upon increasing levels of threat, animals activate qualitatively different defensive modes, inclu... more Upon increasing levels of threat, animals activate qualitatively different defensive modes, including freezing and active fight-or-flight reactions. Whereas freezing is a form of behavioural inhibition accompanied by parasympathetically dominated heart rate deceleration, fight-or-flight reactions are associated with sympathetically driven heart rate acceleration. Despite the potential relevance of freezing for human stress-coping, its phenomenology and neurobiological underpinnings remain largely unexplored in humans. Studies in rodents have shown that freezing depends on amygdala projections to the brainstem (periaqueductal grey). Recent neuroimaging studies in humans have indicated that similar brain regions may be involved in human freezing. In addition, flexibly shifting between freezing and active defensive modes is critical for adequate stress-coping and relies on fronto-amygdala connections. This review paper presents a model detailing these neural mechanisms involved in free...
The Hypothalamic-Pituitary-Adrenal (HPA)-axis plays an important role in the expression of defens... more The Hypothalamic-Pituitary-Adrenal (HPA)-axis plays an important role in the expression of defensive freezing. Adaptive freezing reactivity, characterized by an immediate increase in acute stress and timely termination upon threat offset or need to act, is essential for adequate stress coping. Blunted HPA-axis activity in animals is associated with blunted freezing reactivity and internalizing symptoms. Despite their potential relevance, it remains unknown whether these mechanisms apply to humans and human psychopathology. Using a well-established method combining electrocardiography and posturography, we assessed freezing before, immediately after, and one hour after a stress induction in 92 human adolescents. In line with animal models, human adolescents showed stress-induced freezing, as quantified by relative reductions in heart rate and body sway after, as compared to before, stress. Moreover, relatively lower basal cortisol was associated with reduced stress-induced freezing r...
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