How nature nurtures: Amygdala activity decreases as the result of a one-hour walk in nature

Since living in cities is associated with an increased risk for mental disorders such as anxiety disorders, depression and schizophrenia, it is essential to understand how exposure to urban and natural environments affects mental health and the brain. It has been shown that the amygdala is more activated during a stress task in urban compared to rural dwellers. However, no study so far has examined the causal effects of natural and urban environments on stress-related brain mechanisms. To address this question, we conducted an intervention study to investigate changes in stress-related brain regions as an effect of a one-hour walk in an urban (busy street) vs. natural environment (forest). Brain activation was measured in 63 healthy participants, before and after the walk, using a fearful faces task. Our findings reveal that amygdala activation decreases after the walk in nature, whereas it remains stable after the walk in an urban environment. These results suggest that going for a nature walk can have salutogenic effects for stress-related brain regions, and consequently, it may act as a preventive measure against mental strain and potentially disease. Given the rapidly increasing urbanization, the present results aim to influence urban planning to create more accessible green areas and to adapt urban environments in a way that will be beneficial for citizens’ mental health.

Trial-by-trial fluctuations in amygdala activity track motivational enhancement of desirable sensory evidence during perceptual decision-making

People are biased towards seeing outcomes that they are motivated to see. For example, sports fans of opposing teams often perceive the same ambiguous foul in favor of the team they support. Here, we test the hypothesis that amygdala-dependent allocation of visual attention facilitates motivational biases in perceptual decision-making. Human participants were rewarded for correctly categorizing an ambiguous image into one of two categories while undergoing fMRI. On each trial, we used a financial bonus to motivate participants to see one category over another. The reward maximizing strategy was to perform the categorization task accurately, but participants were biased towards categorizing the images as the category we motivated them to see. Heightened amygdala activity preceded motivation consistent categorizations, and participants with higher amygdala activation exhibited stronger motivational biases in their perceptual reports. Trial-by-trial amygdala activity was associated with stronger enhancement of neural activity encoding desirable percepts in sensory cortices, suggesting that amygdala-dependent effects on perceptual decisions arose from biased sensory processing. Analyses using a drift diffusion model provide converging evidence that trial-by-trial amygdala activity was associated with stronger motivational biases in the accumulation of sensory evidence. Prior work examining biases in perceptual decision-making have focused on the role of frontoparietal regions. Our work highlights an important contribution of the amygdala. When people are motivated to see one outcome over another, the amygdala biases perceptual decisions towards those outcomes.Significance StatementForming accurate perceptions of the environment is essential for adaptive behavior. People however are biased towards seeing what they want to see, giving rise to inaccurate perceptions and erroneous decisions. Here, we combined behavior, modeling, and fMRI to show that the bias towards seeing desirable percepts is related to trial-by-trial fluctuations in amygdala activity. In particular, during moments with higher amygdala activity, sensory processing is biased in favor of desirable percepts, such that participants are more likely to see what they want to see. These findings highlight the role of the amygdala in biasing visual perception, and shed light on the neural mechanisms underlying the influence of motivation and reward on how people decide what they see.

A systematic review of the effects of psychiatric medications on social cognition

Introduction Social cognition is an important area of mental functioning relevant to psychiatric disorders and social functioning, that may be affected by psychiatric drug treatments. The aim of this review was to investigate the effects of medications with sedative properties, on social cognition. Method This systematic review included experimental and neuroimaging studies investigating drug effects on social cognition. Data quality was assessed using a modified Downs and Black checklist (Trac et al. CMAJ 188: E120-E129, 2016). The review used narrative synthesis to analyse the data. Results 40 papers were identified for inclusion, 11 papers investigating benzodiazepine effects, and 29 investigating antipsychotic effects, on social cognition. Narrative synthesis showed that diazepam impairs healthy volunteer’s emotion recognition, with supporting neuroimaging studies showing benzodiazepines attenuate amygdala activity. Studies of antipsychotic effects on social cognition gave variable results. However, many of these studies were in patients already taking medication, and potential practice effects were identified due to short-term follow-ups. Conclusion Healthy volunteer studies suggest that diazepam reduces emotional processing ability. The effects of benzodiazepines on other aspects of social cognition, as well as the effects of antipsychotics, remain unclear. Interpretations of the papers in this review were limited by variability in measures, small sample sizes, and lack of randomisation. More robust studies are necessary to evaluate the impact of these medications on social cognition.

Cortical-subcortical structural connections support transcranial magnetic stimulation engagement of the amygdala

The amygdala processes valenced stimuli, influences affective states, and exhibits aberrant activity across anxiety disorders, depression, and PTSD. Interventions that modulate amygdala activity hold promise for treating transdiagnostic affective symptoms. We investigated (N=45) whether transcranial magnetic stimulation (TMS) elicits indirect changes in amygdala activity when applied to ventrolateral prefrontal cortex (vlPFC), a region important for affect regulation. Harnessing in-scanner interleaved TMS/functional MRI (fMRI), we reveal that vlPFC neurostimulation evoked acute, dose-dependent modulations of amygdala fMRI BOLD signal. Larger TMS-evoked changes in amygdala fMRI signal were associated with higher fiber density in a vlPFC-amygdala white matter pathway, suggesting this pathway facilitated stimulation-induced communication between cortex and subcortex. This work provides evidence of amygdala engagement by TMS, highlighting stimulation of vlPFC-amygdala circuits as a candidate treatment for affective psychopathology. More broadly, it indicates that targeting cortical-subcortical connections may enhance the impact of TMS on subcortical neural activity and, by extension, subcortex-subserved behaviors.

Prefrontal-hippocampal interactions supporting the extinction of emotional memories: the retrieval stopping model

Neuroimaging has revealed robust interactions between the prefrontal cortex and the hippocampus when people stop memory retrieval. Efforts to stop retrieval can arise when people encounter reminders to unpleasant thoughts they prefer not to think about. Retrieval stopping suppresses hippocampal and amygdala activity, especially when cues elicit aversive memory intrusions, via a broad inhibitory control capacity enabling prepotent response suppression. Repeated retrieval stopping reduces intrusions of unpleasant memories and diminishes their affective tone, outcomes resembling those achieved by the extinction of conditioned emotional responses. Despite this resemblance, the role of inhibitory fronto-hippocampal interactions and retrieval stopping broadly in extinction has received little attention. Here we integrate human and animal research on extinction and retrieval stopping. We argue that reconceptualising extinction to integrate mnemonic inhibitory control with learning would yield a greater understanding of extinction’s relevance to mental health. We hypothesize that fear extinction spontaneously engages retrieval stopping across species, and that controlled suppression of hippocampal and amygdala activity by the prefrontal cortex reduces fearful thoughts. Moreover, we argue that retrieval stopping recruits extinction circuitry to achieve affect regulation, linking extinction to how humans cope with intrusive thoughts. We discuss novel hypotheses derived from this theoretical synthesis.

A Systematic Review of the Effects of Psychiatric Medications on Social Cognition

IntroductionSocial cognition is an important area of mental functioning relevant to psychiatric disorders and social functioning, that may be affected by psychiatric drug treatments. The aim of this review was to investigate the effects of medications with sedative properties, on social cognition. MethodThis systematic review included experimental and neuroimaging studies investigating drug effects on social cognition. Data quality was assessed using a modified Downs and Black checklist [40]. The review used narrative synthesis to analyse the data.Results40 papers were identified for inclusion, 11 papers investigating benzodiazepine effects, and 29 investigating antipsychotic effects, on social cognition.Narrative synthesis showed that diazepam impairs healthy volunteer’s emotion recognition, with supporting neuroimaging studies showing benzodiazepines attenuate amygdala activity. Studies of antipsychotic effects on social cognition gave variable results. However, many of these studies were in patients already taking medication, and potential practice effects were identified due to short-term follow-ups.ConclusionHealthy volunteer studies suggest that diazepam reduces emotional processing ability. The effects of benzodiazepines on other aspects of social cognition, as well as the effects of antipsychotics, remain unclear. Interpretations of the papers in this review were limited by variability in measures, small sample sizes, and lack of randomisation. More robust studies are necessary to evaluate the impact of these medications on social cognition.

Theta oscillations synchronize human medial prefrontal cortex and amygdala during fear learning

Numerous animal studies have demonstrated that fear acquisition and expression rely on the coordinated activity of medial prefrontal cortex (mPFC) and amygdala and that theta oscillations support interregional communication within the fear network. However, it remains unclear whether these results can be generalized to fear learning in humans. We addressed this question using intracranial electroencephalography recordings in 13 patients with epilepsy during a fear conditioning paradigm. We observed increased power and inter-regional synchronization of amygdala and mPFC in theta (4 to 8 hertz) oscillations for conditioned stimulus (CS+) versus CS−. Analysis of information flow revealed that the dorsal mPFC (dmPFC) led amygdala activity in theta oscillations. Last, a computational model showed that trial-by-trial changes in amygdala theta oscillations predicted the model-based associability (i.e., learning rate). This study provides compelling evidence that theta oscillations within and between amygdala, ventral mPFC, and dmPFC constitute a general mechanism of fear learning across species.

Modulating amygdala activation to traumatic memories with a single ketamine infusion

NMDA receptor antagonists have a vital role in extinction, learning, and reconsolidation processes. During the reconsolidation window, memories are activated into a labile state and can be stored in an altered form. This concept might have significant clinical implications in treating PTSD. Using amygdala activity as a major biomarker of fear response, we tested the potential of a single subanesthetic intravenous infusion of ketamine (NMDA receptor antagonist) to enhance post-retrieval extinction of PTSD trauma memories. Post-extinction, ketamine recipients (vs midazolam) showed a lower amygdala and hippocampus reactivation to trauma memories. Post-retrieval ketamine administration was also associated with decreased connectivity between the amygdala and hippocampus, with no change in amygdala-vmPFC connectivity, which suggests that ketamine may enhance post-retrieval extinction of PTSD trauma memory in humans. These findings demonstrate the capacity to rewrite human traumatic memories and to modulate the fear response for at least 30 days post-extinction.