An Enhanced Default Approach Bias Following Amygdala Lesions in Humans

Approach and avoidance constitute a basic dimension of all animal behavior. Although a large number of studies have investigated approach and avoidance elicited by specific sensory stimuli, comparatively little is known about default approach biases when stimulus information is absent or reduced. The amygdala is well known to contribute to approach and avoidance behaviors in response to specific sensory stimuli; we tested whether the amygdala’s role might extend to situations in which stimulus information is reduced. In a novel task, 3 patients with rare bilateral amygdala lesions (and control subjects) made approach-related judgments about photos of intact faces and of the same faces with all internal facial features occluded. Direct comparisons of the judgments of these stimuli isolated a default bias. The patients showed a greater tendency than the control subjects to rate occluded faces as more approachable than whole faces. These findings suggest that the amygdala’s role in approach behavior extends beyond responses to specific stimuli

Social motives in a patient with bilateral selective amygdala lesions: Shift in prosocial motivation but not in social value orientation

Humans hold social motives that are expressed in social preferences and influence how they evaluate and share payoffs. Established models in psychology and economics quantify social preferences such as general social value orientation, which captures people's tendency to be prosocial or individualistic. Prosocials further differ by how much they maximize joint gains or minimize inequality. Functional neuroimaging studies have linked increased amygdala activity in prosocials to payoff inequality between self and other. However, it is unclear whether amygdala lesions alter social motives. We used two tasks to test a patient with selective bilateral amygdala lesions and three healthy samples (a priori matched control sample N = 20, online sample N = 603, student sample N = 40), which allowed us to assess and model social motives across a relatively large number of participants. In a social value orientation task, the patient was categorized as prosocial and her social value orientation score did not differ from healthy participants. Importantly, the patient differed in prosocial motivation by maximizing joint gains rather than minimizing payoff inequality. In a joint payoff evaluation task, Bayesian model comparisons revealed that participants' evaluations were best described by models, which link participants' evaluations to the payoff magnitude and to inequality. Overall, amygdala lesions did not seem to alter general social value orientation but shifted prosocial motivation toward maximizing joint gains

Disentangling Hippocampal and Amygdala Contribution to Human Anxiety-Like Behavior

Anxiety comprises a suite of behaviors to deal with potential threat and is often modeled in approach–avoidance conflict tasks. Collectively, these tests constitute a predominant preclinical model of anxiety disorder. A body of evidence suggests that both ventral hippocampus and amygdala lesions impair anxiety-like behavior, but the relative contribution of these two structures is unclear. A possible reason is that approach–avoidance conflict tasks involve a series of decisions and actions, which may be controlled by distinct neural mechanisms that are difficult to disentangle from behavioral readouts. Here, we capitalize on a human approach–avoidance conflict test, implemented as computer game, that separately measures several action components. We investigate three patients of both sexes with unspecific unilateral medial temporal lobe (MTL) damage, one male with selective bilateral hippocampal (HC), and one female with selective bilateral amygdala lesions, and compare them to matched controls. MTL and selective HC lesions, but not selective amygdala lesions, increased approach decision when possible loss was high. In contrast, MTL and selective amygdala lesions, but not selective HC lesions, increased return latency. Additionally, selective HC and selective amygdala lesions reduced approach latency. In a task targeted at revealing subjective assumptions about the structure of the computer game, MTL and selective HC lesions impacted on reaction time generation but not on the subjective task structure. We conclude that deciding to approach reward under threat relies on hippocampus but not amygdala, whereas vigor of returning to safety depends on amygdala but not on hippocampus

Preferential attention to animals and people is independent of the amygdala

The amygdala is thought to play a critical role in detecting salient stimuli. Several studies have taken ecological approaches to investigating such saliency, and argue for domain-specific effects for processing certain natural stimulus categories, in particular faces and animals. Linking this to the amygdala, neurons in the human amygdala have been found to respond strongly to faces, and also to animals. Yet the amygdala’s necessary role for such category-specific effects at the behavioral level remains untested. Here we tested four rare patients with bilateral amygdala lesions on an established change-detection protocol. Consistent with prior published studies, healthy controls showed reliably faster and more accurate detection of people and animals, as compared to artifacts and plants. But so did all four amygdala patients: there were no differences in phenomenal change blindness, in behavioral reaction time to detect changes, or in eye-tracking measures. The findings provide decisive evidence against a critical participation of the amygdala in rapid, initial processing of attention to animate stimuli, suggesting that the necessary neural substrates for this phenomenon arise either in other subcortical structures (such as the pulvinar) or within cortex itself

Amygdala Lesions Reduce Anxiety-like Behavior in a Human Benzodiazepine-Sensitive Approach-Avoidance Conflict Test

BACKGROUND: Rodent approach-avoidance conflict tests are common preclinical models of human anxiety disorder. Their translational validity mainly rests on the observation that anxiolytic drugs reduce rodent anxiety-like behavior. Here, we capitalized on a recently developed approach-avoidance conflict computer game to investigate the impact of benzodiazepines and of amygdala lesions on putative human anxiety-like behavior. In successive epochs of this game, participants collect monetary tokens on a spatial grid while under threat of virtual predation. METHODS: In a preregistered, randomized, double-blind, placebo-controlled trial, we tested the effect of a single dose (1 mg) of lorazepam (n = 59). We then compared 2 patients with bilateral amygdala lesions due to Urbach-Wiethe syndrome with age- and gender-matched control participants (n = 17). Based on a previous report, the primary outcome measure was the effect of intra-epoch time (i.e., an adaptation to increasing potential loss) on presence in the safe quadrant of the spatial grid. We hypothesized reduced loss adaptation in this measure under lorazepam and in patients with amygdala lesions. RESULTS: Lorazepam and amygdala lesions reduced loss adaptation in the primary outcome measure. We found similar results in several secondary outcome measures. The relative reduction of anxiety-like behavior in patients with amygdala lesions was qualitatively and quantitatively indistinguishable from an impact of anterior hippocampus lesions found in a previous report. CONCLUSIONS: Our results establish the translational validity of human approach-avoidance conflict tests in terms of anxiolytic drug action. We identified the amygdala, in addition to the hippocampus, as a critical structure in human anxiety-like behavior

Emotion-induced retrograde amnesia varies as a function of noradrenergic-glucocorticoid activity

RATIONALE: Privileged episodic encoding of an aversive event often comes at a cost of neutral events flanking the aversive event, resulting in decreased episodic memory for these neutral events. This peri-emotional amnesia is amygdala-dependent and varies as a function of norepinephrine activity. However, less is known about the amnesiogenic potential of cortisol. OBJECTIVE: We used a strategy of pharmacologically potentiating cortisol and norepinephrine activity to probe the putative neurochemical substrates of peri-emotional amnesia. MATERIALS AND METHODS: Fifty-four healthy individuals participated in a randomized double-blind placebo-controlled study. Within the experimental context of an established peri-emotional amnesia paradigm, we tested the amnesiogenic potential of hydrocortisone (30 mg p.o.) in the presence or absence of the norepinephrine-reuptake inhibitor reboxetine (4 mg p.o.). RESULTS: Under dual challenge conditions, we observed a linear dose-response relationship in the magnitude and duration of emotion-induced retrograde amnesia. CONCLUSIONS: Our results are consistent with a phenotypic expression of retrograde amnesia varying as a function of norepinephrine and cortisol coactivation during episodic encoding of aversive events. Our study demonstrates that the adverse cognitive and behavioral sequelae of aversive emotion can be experimentally modeled by a pharmacological manipulation of its putative neurochemical substrates

Amygdala lesions do not compromise the cortical network for false-belief reasoning

The amygdala plays an integral role in human social cognition and behavior, with clear links to emotion recognition, trust judgments, anthropomorphization, and psychiatric disorders ranging from social phobia to autism. A central feature of human social cognition is a theory-of-mind (ToM) that enables the representation other people's mental states as distinct from one's own. Numerous neuroimaging studies of the best studied use of ToM—false-belief reasoning—suggest that it relies on a specific cortical network; moreover, the amygdala is structurally and functionally connected with many components of this cortical network. It remains unknown whether the cortical implementation of any form of ToM depends on amygdala function. Here we investigated this question directly by conducting functional MRI on two patients with rare bilateral amygdala lesions while they performed a neuroimaging protocol standardized for measuring cortical activity associated with false-belief reasoning. We compared patient responses with those of two healthy comparison groups that included 480 adults. Based on both univariate and multivariate comparisons, neither patient showed any evidence of atypical cortical activity or any evidence of atypical behavioral performance; moreover, this pattern of typical cortical and behavioral response was replicated for both patients in a follow-up session. These findings argue that the amygdala is not necessary for the cortical implementation of ToM in adulthood and suggest a reevaluation of the role of the amygdala and its cortical interactions in human social cognition

Panic Anxiety in Humans with Bilateral Amygdala Lesions: Pharmacological Induction via Cardiorespiratory Interoceptive Pathways

We previously demonstrated that carbon dioxide inhalation could induce panic anxiety in a group of rare lesion patients with focal bilateral amygdala damage. To further elucidate the amygdala-independent mechanisms leading to aversive emotional experiences, we retested two of these patients (B.G. and A.M.) to examine whether triggering palpitations and dyspnea via stimulation of non-chemosensory interoceptive channels would be sufficient to elicit panic anxiety. Participants rated their affective and sensory experiences following bolus infusions of either isoproterenol, a rapidly acting peripheral β-adrenergic agonist akin to adrenaline, or saline. Infusions were administered during two separate conditions: a panic induction and an assessment of cardiorespiratory interoception. Isoproterenol infusions induced anxiety in both patients, and full-blown panic in one (patient B.G.). Although both patients demonstrated signs of diminished awareness for cardiac sensation, patient A.M., who did not panic, reported a complete lack of awareness for dyspnea, suggestive of impaired respiratory interoception. These findings indicate that the amygdala may play a role in dynamically detecting changes in cardiorespiratory sensation. The induction of panic anxiety provides further evidence that the amygdala is not required for the conscious experience of fear induced via interoceptive sensory channels

Anthropomorphizing without Social Cues Requires the Basolateral Amygdala

Anthropomorphism, the attribution of distinctively human mental characteristics to nonhuman animals and objects, illustrates the human propensity for extending social cognition beyond typical social targets. Yet, its processing components remain challenging to study because they are typically all engaged simultaneously. Across one pilot study and one focal study, we tested three rare people with basolateral amygdala lesions to dissociate two specific processing components: those triggered by attention to social cues (e.g., seeing a face) and those triggered by endogenous semantic knowledge (e.g., imbuing a machine with animacy). A pilot study demonstrated that, like neurologically intact control group participants, the three amygdala-damaged participants produced anthropomorphic descriptions for highly socially salient stimuli but not for stimuli lacking clear social cues. A focal study found that the three amygdala participants could anthropomorphize animate and living entities normally, but anthropomorphized inanimate stimuli less than control participants. Yet, amygdala participants could anthropomorphize across all stimuli when explicitly questioned, demonstrating that the ability to make social attributions as such is intact. Our findings suggest that the amygdala contributes to how we anthropomorphize stimuli that are not explicitly social