Fearful Stimuli Research Articles

Does enhanced memory of disgust vs. fear images extend to involuntary memory?

ABSTRACT People remember disgusting stimuli better than fearful stimuli, but do disgust’s memory-enhancing effects extend to involuntary memory? This question is important because disgust reactions occur following trauma, and trauma-related involuntary memories are a hallmark of Posttraumatic Stress Disorder (PTSD) symptoms. In two experiments, we presented participants (n = 88 Experiment 1; n = 106 Experiment 2) with disgust, fear, and neutral images during an attention-monitoring task. Participants then completed an undemanding vigilance task, responding any time an image involuntarily came to mind. We measured the frequency and characteristics of these involuntary memories (e.g. emotional intensity) immediately after encoding and over a 24-hour delay (Experiment 2 only). Our main findings were mixed: participants experienced similarly frequent (Experiment 2) – or more (Experiment 1) – disgust as fear involuntary memories. Therefore, when controlling for memory-enhancing confounds (e.g. distinctiveness), in-laboratory disgust memory enhancement does not extend to involuntary memory. Disgust memories were more emotionally intense than fear memories over the 24-hour delay– but not immediately after encoding – suggesting disgust elicits additional consolidation processes to fear. Participants paid more attention towards the disgust images, but the attention did not account for the memory of disgust. In sum, disgust and fear have both similar and distinct cognitive effects.

Neural mechanisms of fear responses to emotional stimuli: a preliminary study combining early posterior negativity and electroencephalogram source network analysis

Fear emotion is a typical negative emotion that is commonly present in daily life and significantly influences human behavior. A deeper understanding of the mechanisms underlying negative emotions contributes to the improvement of diagnosing and treating disorders related to negative emotions. However, the neural mechanisms of the brain when faced with fearful emotional stimuli remain unclear. To this end, this study further combined electroencephalogram (EEG) source analysis and cortical brain network construction based on early posterior negativity (EPN) analysis to explore the differences in brain information processing mechanisms under fearful and neutral emotional picture stimuli from a spatiotemporal perspective. The results revealed that neutral emotional stimuli could elicit higher EPN amplitudes compared to fearful stimuli. Further source analysis of EEG data containing EPN components revealed significant differences in brain cortical activation areas between fearful and neutral emotional stimuli. Subsequently, more functional connections were observed in the brain network in the alpha frequency band for fearful emotions compared to neutral emotions. By quantifying brain network properties, we found that the average node degree and average clustering coefficient under fearful emotional stimuli were significantly larger compared to neutral emotions. These results indicate that combining EPN analysis with EEG source component and brain network analysis helps to explore brain functional modulation in the processing of fearful emotions with higher spatiotemporal resolution, providing a new perspective on the neural mechanisms of negative emotions.

Oxytocin moderates fMRI connectivity and response to implicit threat processing in cocaine use disorder

Stressful social experiences play an important role in increasing vulnerability to substance use, including cocaine. Oxytocin (OXT), known for its anxiolytic properties and involvement in social functioning, has been suggested as a potential therapeutic for cocaine use disorder (CUD). However, limited research has explored OXT’s influence on social stress in CUD, and no study has examined its effects on neural response to subconscious (implicit) social threat cues in this population. To address this gap, the present study administered intranasal OXT (24 IU) or placebo (PBO) to participants with CUD (CUD+, N = 76) or without CUD (CUD-, N = 61) in a randomized parallel design. Participants then completed a functional magnetic resonance imaging (fMRI) task involving briefly presented facial fear and anger (i.e., threat) cues, followed by neutral face stimuli. Whole-brain activation and amygdala functional connectivity (using psychophysiological interaction modeling) were examined in response to the facial threat cues. OXT reduced activation in the thalamus and pontine reticular formation in response to fear cues, and in the supplementary motor area for both fear and anger cues, regardless of CUD status. Additionally, under PBO, amygdala-medial prefrontal cortex connectivity to fear stimuli was negative for the CUD+ group, but under OXT, this coupling was positive, similar to the positive coupling observed for the CUD- group under both PBO and OXT administration. The finding of OXT-mediated reversal of amygdala-prefrontal coupling was specific to CUD+ and suggests that OXT alters circuitry related to threat surveillance and implicit emotion regulation in CUD. However, additional research is needed to determine whether these alterations due to OXT have clinical significance in CUD.

Overgeneralization of autonomic defensive reactions in obesity

Generalizing defensive responses to new stimuli resembling learned threats is an adaptive process within an ever-changing environment. However, evaluation mechanisms excessively biased toward generalization (i.e., overgeneralization) may underlie anxiety-related symptoms. In the context of obesity, fear memory and fear generalization processes have never been investigated. In this study, participants with obesity and healthy participants as controls underwent a single-cue auditory fear conditioning paradigm and recognition memory tasks. We analyzed the autonomic reactions evoked by threat-predictive and new stimuli, as well as the recognition performance towards the same cues. We found that participants with obesity displayed similar autonomic defensive responses to a learned fearful stimulus, but enhanced reactions to new stimuli, when compared with the controls. We detected no significant differences between groups in recognition abilities. Our results provided the first evidence that obesity may widen fear generalization patterns. This alteration may encourage future research in investigating the link between emotional dysregulation and clinical anxiety-related symptoms in obesity.

Over-the-counter analgesic usage: associations with attentional biases in young women.

The use of over-the-counter analgesics (OTCA) has been found to alter various aspects of emotional processing and has been linked to increased anxiety and depression symptoms. Attentional bias is an aspect of emotional processing that is closely related to anxiety and depression. Although OTCA and attentional bias have both been linked to anxiety and depression, the potential links between OTCA usage and attentional bias are not yet investigated. The present study aimed to determine whether the frequency of OTCA usage is associated with differences in attentional bias by comparing response-based measures of attentional bias in 62 women aged 19-30 years. The findings showed that the small group reporting high OTCA usage demonstrated more orientation avoidance to fearful stimuli than those reporting no or low usage. Based on these preliminary findings, further research on attentional bias and its relationship to high OTCA usage is recommended.

Interpersonal trauma Dissociates borderline from other personality disorders in social orienting

Patients with Borderline Personality Disorder (BPD), particularly with comorbid trauma-disorders, show an attentional bias towards angry facial expressions. This is often interpreted to reflect increased anxiety and sensitivity to social threats. Given BPDs severe problems in reacting to and interpreting social communication, we investigated whether this threat bias extends to social orienting. Using a gaze-cueing task, we assessed whether centrally presented dynamic fearful and happy gaze stimuli promote the detection of peripherally presented targets. Groups with BPD (N = 50) and other personality disorders (OPD, N = 51) were compared to healthy controls (HC, N = 46), and evaluated on the independent influence of traumatic experience, trait anxiety and trait anger. Across groups we find reliable gaze-cueing. In line with earlier evidence, trait anxiety predicts faster detection of targets signaled by a fearful gaze in HCs. This threat bias is however not present in BPDs and OPDs, thus the threat bias in BPD does not extend to social orienting. Instead, self-experienced trauma predicts amplified gaze-cueing in BPDs, but reduced gaze-cueing in OPDs. This not only emphasizes the importance of evaluating trauma exposure in personality disorders, but also suggests that the childhood adversity typically associated with the development of BPD promotes increased social orienting.

Loneliness and the persistence of fear: Perceived social isolation reduces evaluative fear extinction.

Loneliness has been linked to a host of harmful physical and mental health outcomes, detrimental effects that may stem from increases in threat-responding caused by altered fear learning in lonely individuals. In particular, the heightened threat-vigilance that is a hallmark of loneliness may augment the processes by which fear learning occurs, ultimately resulting in a greater number of perceived threatening cues in the environment. However, almost no research has examined how loneliness alters fear learning processes in humans. Here, we investigated the effect of loneliness on fear learning during an evaluative learning procedure in which participants (n = 782) were taught to associate fearful, positive, or neutral control stimuli with neutral images. Results showed that reduced extinction of evaluative fear associations occurred in high (vs. low) lonely individuals, but there was no difference in extinction of evaluative appetitive (also known as positive or reward) associations, suggesting this effect is specific to fear learning. In addition to shedding light on the link between loneliness and poor health, these results represent an important step forward in the growing understanding of the powerful impact of social bonds on fear learning processes.

The Effect of Attentional Bias on Emotions in Patients with Breast Cancer.

Attentional bias may influence the emotional experiences of breast cancer patients, both positively and negatively. This study aimed to investigate attentional bias in breast cancer patients and its impact on their emotions. Thirty-eight breast cancer patients completed a modified dot-probe task and the Depression Anxiety and Stress Scale to assess attentional bias and emotional states. Attentional bias was measured by analyzing response times to different stimuli in the modified dot-probe task. Emotional stimuli included 80 pairs of facial images depicting sad-neutral, fearful-neutral, happy-neutral, and neutral-neutral expressions. Attentional bias components were observed at stimulus presentation durations of 300ms and 1500ms. Differences in emotional responses among breast cancer patients with varying attentional biases were compared. Breast cancer patients exhibited attentional avoidance of sad and happy stimuli at 300ms. Further analysis revealed that patients who exhibited attentional avoidance of sad stimuli at 300ms reported higher levels of anxiety and stress. Those with attentional avoidance of fearful stimuli at 1500ms reported increased anxiety, while individuals showing attentional avoidance of happy stimuli or difficulty disengaging from happy stimuli at 1500ms reported higher levels of depression and stress. Breast cancer patients demonstrated an attentional bias toward emotional stimuli, particularly avoidance of sad and happy stimuli in 300ms. Different components of attentional bias were associated with distinct negative emotional outcomes.

Contamination in Trypophobia: investigating the role of disgust

ABSTRACT Trypophobia is a relatively common aversion to clusters of holes. There is no consensus yet on which emotions are involved in Trypophobia nor in its functional utility. This report investigates the role of disgust using contamination tasks in two studies, which contrast people with an aversion to trypophobic stimuli to those without. In Study 1, participants reported their emotional reactions to imagined contamination of trypophobic images. In Study 2, participants evaluated physically present trypophobic, disgust, fear, and control stimuli. The capacity of these stimuli to contaminate other objects was established using a chain of contagion task. Across both studies, contamination was present, however, only those with an aversion to trypophobic stimuli evidenced contamination on the chain of contagion task, a hallmark of disgust responding. Elevated levels were not only reported for disgust, but also alongside fear/anxiety. Participant reports suggest an underlying disease avoidance mechanism in Trypophobia, with trypophobic participants demonstrating an exaggerated response to such stimuli involving disgust and fear/anxiety, which is also seen in small animal phobia, BII, and C-OCD. Implications, particularly for treatment are discussed.

Are you ready for a challenge? Personality traits influence dairy calves' responses to disease, pain, and nutritional challenges

Dairy calves routinely experience disease, pain, and nutritional stressors such as diarrhea, dehorning, and weaning early in life. These stressors lead to changes in behavioral expression that varies in magnitude between individuals, where a greater magnitude change would suggest lower resilience in individuals to a stressor. Thus, this study first aimed to quantify the individual variation in magnitude change in feeding behaviors and activity in response to a bout of diarrhea, dehorning, and weaning. The next objective was to then investigate if personality traits were related to this magnitude of behavioral response in dairy calves, and thus their resilience toward these stressors. Calves were followed with 2 precision livestock technologies (e.g.: an automatic feeding system (AFS), and leg accelerometer) to track behavioral changes in response during the time when the stressors were present. The AFS provided daily measures of milk intake, drinking speed, rewarded and unrewarded visits to the milk feeding station, and calf starter intake. The leg accelerometer provided daily measures of steps, activity index, lying time, and lying bouts. At 23 ± 3 d of age, Holstein dairy calves (n = 49) were subjected to a series of standardized personality tests that exposed calf to novelty and fear stimuli. Factors extracted from a principal component analysis on the behaviors from the personality test were utilized to represent personality traits: Factor 1 ('Fearful'), Factor 2 ('Active') and Factor 3 ('Explorative'). The magnitude change in behaviors from the precision livestock technologies were calculated relative to the behavior performed on the day the stressor occurred (i.e., day of diagnosis; day of dehorning; day weaned). Linear regression models were utilized to determine if calf scores on each factor were associated with magnitude change in behavior for each of the stressor periods with day relative to the stressor included as a repeated measure. Models were run independently for the period leading up to and following each stressor. We found that calves varied in their behavioral responses to diarrhea, dehorning, and weaning stressors, despite being reared in the same environment and experiencing consistent management procedures. Additionally, personality traits measured from standardized tests were associated to both the direction and magnitude of change in behaviors around each stressor. For instance, with diarrhea, calves that were highly 'Fearful' had a greater magnitude change in milk intake and drinking speed following diagnosis than the least 'Fearful' calves. With dehorning, calves that were highly 'Explorative' had a greater magnitude change in lying time when dehorned, but a smaller magnitude change in lying bouts and drinking speed following dehorning, than the least 'explorative' calves. With weaning, calves that were highly 'Active' had a smaller magnitude change in unrewarded visits leading up to and following weaning than calves that were the least 'Active'. Each of the personality traits had a significant association with change in behavior surrounding each of the stressors evaluated, although these associations depended on the type of stressor. These results have implications for how individual calves experience each stressor and therefore individual animal welfare.

Individual differences in intracortical inhibition predict action control when facing emotional stimuli.

Efficient inhibitory control in the context of prepotent actions is vital. However, such action inhibition may be profoundly influenced by affective states. Interestingly, research indicates that action control can be either impaired or improved by emotional stimuli. Thus, a great deal of confusion surrounds our knowledge of the complex dynamics subtending emotions and action control. Here, we aimed to investigate whether negative stimuli, even when non-consciously presented and task-irrelevant, can affect action control relative to neutral stimuli. Additionally, we tested whether individual differences in intracortical excitability may predict action control capabilities. To address these issues, we asked participants to complete a modified version of the Stop Signal Task (SST) in which fearful or neutral stimuli were subliminally presented before the go signals as primes. Moreover, we assessed participants' resting-state corticospinal excitability, short intracortical inhibition (SICI), and intracortical facilitation (ICF). Results demonstrated better action control capabilities when fearful stimuli were subliminally presented and interindividual SICI predicted stronger action inhibition capabilities. Taken together, these results shed new light on the intricate dynamics between action, consciousness, and motor control, suggesting that intracortical measures can be used as potential biomarkers of reduced motor inhibition in research and clinical settings.

Modulation of response times in early-stage Parkinson’s disease during emotional processing of embodied and non-embodied stimuli

Valence (positive and negative) and content (embodied vs non-embodied) characteristics of visual stimuli have been shown to influence motor readiness, as tested with response time paradigms. Both embodiment and emotional processing are affected in Parkinson’s disease (PD) due to basal ganglia dysfunction. Here we aimed to investigate, using a two-choice response time paradigm, motor readiness when processing embodied (emotional body language [EBL] and emotional facial expressions [FACS]) vs non-embodied (emotional scenes [IAPS]) stimuli with neutral, happy, and fearful content. We enrolled twenty-five patients with early-stage PD and twenty-five age matched healthy participants. Motor response during emotional processing was assessed by measuring response times (RTs) in a home-based, forced two-choice discrimination task where participants were asked to discriminate the emotional stimulus from the neutral one. Rating of valence and arousal was also performed. A clinical and neuropsychological evaluation was performed on PD patients. Results showed that RTs for PD patients were longer for all conditions compared to HC and that RTs were generally longer in both groups for EBL compared to FACS and IAPS, with the sole exception retrieved for PD, where in discriminating fearful stimuli, RTs for EBL were longer compared to FACS but not to IAPS. Furthermore, in PD only, when discriminating fearful respect to neutral stimuli, RTs were shorter when discriminating FACS compared to IAPS. This study shows that PD patients were faster in discriminating fearful embodied stimuli, allowing us to speculate on mechanisms involving an alternative, compensatory, emotional motor pathway for PD patients undergoing fear processing.

Threat-dependent scaling of prelimbic dynamics to enhance fear representation

Promptly identifying threatening stimuli is crucial for survival. Freezing is a natural behavior displayed by rodents toward potential or actual threats. Although it is known that the prelimbic cortex (PL) is involved in both risk evaluation and in fear and anxiety-like behavior expression, here we explored whether PL neuronal activity can dynamically represent different internal states of the same behavioral output (i.e., freezing). We found that freezing can always be decoded from PL activity at a population level. However, the sudden presentation of a fearful stimulus quickly reshaped the PL to a new neuronal activity state, an effect not observed in other cortical or subcortical regions examined. This shift changed PL freezing representation and is necessary for fear memory expression. Our data reveal the unique role of the PL in detecting threats and internally adjusting to distinguish between different freezing-related states in both unconditioned and conditioned fear representations.

Single point motion kinematics convey emotional signals in children and adults.

This study investigates whether humans recognize different emotions conveyed only by the kinematics of a single moving geometrical shape and how this competence unfolds during development, from childhood to adulthood. To this aim, animations in which a shape moved according to happy, fearful, or neutral cartoons were shown, in a forced-choice paradigm, to 7- and 10-year-old children and adults. Accuracy and response times were recorded, and the movement of the mouse while the participants selected a response was tracked. Results showed that 10-year-old children and adults recognize happiness and fear when conveyed solely by different kinematics, with an advantage for fearful stimuli. Fearful stimuli were also accurately identified at 7-year-olds, together with neutral stimuli, while, at this age, the accuracy for happiness was not significantly different than chance. Overall, results demonstrates that emotions can be identified by a single point motion alone during both childhood and adulthood. Moreover, motion contributes in various measures to the comprehension of emotions, with fear recognized earlier in development and more readily even later on, when all emotions are accurately labeled.

How does chronic pain impact the lives of dogs: an investigation of factors that are associated with pain using the Animal Welfare Assessment Grid.

Chronic pain can profoundly affect the wellbeing of dogs and our understanding is limited regarding the multidimensional impact it has on dog quality of life. This study aimed to assess the factors that are significant and predictive of behavior problems in dogs using the Animal Welfare Assessment Grid (AWAG) to further understand what factors influence their welfare. Seventy six AWAG assessments were undertaken across 46 dogs that clinicians diagnosed as having musculoskeletal conditions that caused chronic pain. Wilcoxon-rank sum tests were used to assess the difference in scores between dogs with behavior disorders and a cohort of healthy dogs (n = 143). All physical factors besides body condition, and all psychological, environmental, and procedural factors were significantly different between healthy dogs and dogs with chronic pain, evidencing how chronic pain impacts all domains of a dog's life. Spearman Rank Correlation Coefficient (RS) revealed several significant strong positive correlations such as the association between the severity of clinical symptoms with poorer mobility and the frequency at which the dog experienced fearful stimuli. Logistic regression showed that fears and anxieties frequency, the dog's reaction to stressors, engagement with enrichment, and social interactions were significant predictors of chronic pain in dogs. This highlights that typical signs of musculoskeletal disorders such as gait changes, stiffness, lameness might manifest after behavioral changes such as increased fearfulness, prolonged recovery from a stressful event, a reduced interested in social interactions, toys or play. Owners only seeking veterinary attention when the presence of physical signs of disease are evident may result in a delayed veterinary attention resulting in reduced welfare. Regular veterinary assessments combined with use of the AWAG can proactively identify these behavioral indicators and result in prompt treatment and improved quality of life.

Specialization of amygdala subregions in emotion processing.

The amygdala is important for human fear processing. However, recent research has failed to reveal specificity, with evidence that the amygdala also responds to other emotions. A more nuanced understanding of the amygdala's role in emotion processing, particularly relating to fear, is needed given the importance of effective emotional functioning for everyday function and mental health. We studied 86 healthy participants (44 females), aged 18-49 (mean 26.12 ± 6.6) years, who underwent multiband functional magnetic resonance imaging. We specifically examined the reactivity of four amygdala subregions (using regions of interest analysis) and related brain connectivity networks (using generalized psycho-physiological interaction) to fear, angry, and happy facial stimuli using an emotional face-matching task. All amygdala subregions responded to all stimuli (p-FDR < .05), with this reactivity strongly driven by the superficial and centromedial amygdala (p-FDR < .001). Yet amygdala subregions selectively showed strong functional connectivity with other occipitotemporal and inferior frontal brain regions with particular sensitivity to fear recognition and strongly driven by the basolateral amygdala (p-FDR < .05). These findings suggest that amygdala specialization to fear may not be reflected in its local activity but in its connectivity with other brain regions within a specific face-processing network.

The effects of parental presence on amygdala and mPFC activation during fear conditioning: An exploratory study.

Learning safe versus dangerous cues is crucial for survival. During development, parents can influence fear learning by buffering their children's stress response and increasing exploration of potentially aversive stimuli. Rodent findings suggest that these behavioral effects are mediated through parental presence modulation of the amygdala and medial prefrontal cortex (mPFC). Here, we investigated whether similar parental modulation of amygdala and mPFC during fear learning occurs in humans. Using a within-subjects design, behavioral (final N=48, 6-17 years, mean=11.61, SD=2.84, 60% females/40% males) and neuroimaging data (final N=39, 6-17 years, mean=12.03, SD=2.98, 59% females/41% males) were acquired during a classical fear conditioning task, which included a CS+ followed by an aversive noise (US; 75% reinforcement rate) and a CS-. Conditioning occurred once in physical contact with the participant's parent and once alone (order counterbalanced). Region of interest analyses examined the unconditioned stress response by BOLD activation to the US (vs. implicit baseline) and learning by activation to the CS+ (vs. CS-). Results showed that during US presentation, parental presence reduced the centromedial amygdala activity, suggesting buffering of the unconditioned stress response. In response to learned stimuli, parental presence reduced mPFC activity to the CS+ (relative to the CS-), although this result did not survive multiple comparisons' correction. These preliminary findings indicate that parents modulate amygdala and mPFC activity during exposure to unconditioned and conditioned fear stimuli, potentially providing insight into the neural mechanisms by which parents act as a social buffer during fear learning. RESEARCH HIGHLIGHTS: This study used a within-participant experimental design to investigate how parental presence (vs. absence) affects youth's neural responses in a classical fear conditioning task. Parental presence reduced the youth's centromedial amygdala activation to the unconditioned stimulus (US), suggesting parental buffering of the neural unconditioned response (UR). Parental presence reduced the youth's mPFC activation to a conditioned threat cue (CS+) compared to a safety cue (CS-), suggesting possible parental modulation of fear learning.

The circadian molecular clock in the suprachiasmatic nucleus is necessary but not sufficient for fear entrainment

We show that nocturnal aversive stimuli presented to mice while they are eating and drinking outside of their safe nest can entrain circadian behaviors, leading to a shift toward daytime activity. We also show that the canonical molecular circadian clock is necessary for fear entrainment and that an intact molecular clockwork in the suprachiasmatic nucleus, the site of the central circadian pacemaker, is necessary but not sufficient to sustain fear entrainment of circadian rhythms. Our results demonstrate that entrainment of a circadian clock by cyclic fearful stimuli can lead to severely mistimed circadian behavior that persists even after the aversive stimulus is removed. Together, our findings support the interpretation that circadian and sleep symptoms associated with fear and anxiety disorders are, in part, the output of a fear-entrained clock, and provide a mechanistic insight into this clock.

Gender effect in affective processing: Alpha EEG source analysis on emotional slides and film-clips.

Past research on gender-related brain asymmetries in emotions was limited and not univocal. The present study analyzed EEG alpha activity (indexing cortical de-activation) from 64 scalp sites in 20 women and 20 men during a counterbalanced block presentation of emotional slides and short video-clips. Stimuli consisted of 45 brief clips of 13 s, divided into 15 erotic (pleasant), 15 neutral and 15 fear (unpleasant) contents. Slides consisted in 45 photo shots (presented for 13 s each) extracted from the videos. As expected, women perceived fear stimuli as more arousing and more unpleasant compared to men. Alpha EEG source analysis revealed gender effects depending on stimulus. Emotional film-clips elicited in both groups a pattern of greater right than left occipital activation. Instead, emotional pictures activated opposite occipital regions, as women showed greater activation in the left, men in the right hemisphere. Men also showed greater activation to Erotic compared to Fear stimuli (i.e., pictures/clips) in the posterior parietal complex. Results point to the relevance of emotional stimulus type to reveal gender effects: clips are ecological, dynamic and engaging, and forced a unified pattern of emotional responses that reset individual differences. Emotional pictures, less engaging, allowed individual differences to emerge and interact with the stimulus category.

Control of defensive behavior by the nucleus of Darkschewitsch GABAergic neurons

Abstract The nucleus of Darkschewitsch (ND), mainly composed of GABAergic neurons, is widely recognized as a component of the eye-movement controlling system. However, the functional contribution of ND GABAergic neurons (NDGABA) in animal behavior is largely unknown. Here, we show that NDGABA neurons were selectively activated by different types of fear stimuli, such as predator odor and foot-shock. Optogenetic and chemogenetic manipulations revealed that NDGABA neurons mediate freezing behavior. Moreover, using circuit-based optogenetic and neuroanatomical tracing methods, we identified an excitatory pathway from the lateral periaqueductal grey (lPAG) to the ND that induces freezing by exciting ND inhibitory outputs to the motor-related gigantocellular reticular nucleus, ventral part (GiV). Together, these findings indicate the NDGABA population as a novel hub for controlling defensive response by relaying fearful information from lPAG to GiV, a mechanism critical for understanding how the freezing behavior is encoded in the mammalian brain.