🧬 biology

State and trait anxiety modulate hemodynamic amygdala responses to innocuous auditory stimulation

This study demonstrates that higher state and trait anxiety levels are associated with heightened right amygdala responses to neutral auditory stimuli, indicating a modality-specific increase in vigilance toward innocuous sounds rather than visual cues.

Original authors: Despina Kartsaki, Martina-Trisia Cinca-Tomás, Emmanouela Kosteletou-Kassotaki, Mara Cean, Debora Lombardo, Judith Domínguez-Borràs

Published 2026-07-22

📖 5 min read🧠 Deep dive

CC BY 4.0

Original authors: Despina Kartsaki, Martina-Trisia Cinca-Tomás, Emmanouela Kosteletou-Kassotaki, Mara Cean, Debora Lombardo, Judith Domínguez-Borràs

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ⚕️ This is an AI-generated explanation of a preprint that has not been peer-reviewed. It is not medical advice. Do not make health decisions based on this content. Read full disclaimer

Imagine your brain is a high-tech security system for a busy city. Its job is to spot danger—like a shadowy figure or a sudden crash—and sound the alarm so you can run or hide. One of the most important security guards in this system is a tiny, almond-shaped cluster of cells deep inside your brain called the amygdala. Think of the amygdala as the "threat detector." When it sees something scary, like a growling dog or a terrifying face, it lights up like a neon sign, telling your body, "Danger! Get ready!"

But here's the tricky part: sometimes, the alarm system gets a little too sensitive. This happens when a person feels anxiety. Anxiety isn't just a feeling; it's a state of mind that can change how your brain processes the world. Scientists have long known that anxious people are great at spotting real threats. But they've been wondering: Does anxiety also make the brain see danger where there isn't any? Does it make the security guard scream "Fire!" when someone just drops a spoon? This question is especially interesting when we look at what we hear versus what we see. We know a lot about how anxious eyes work, but we know very little about how anxious ears work.

The Great Brain Scan: When the Alarm Rings for Nothing

In this study, a team of researchers at the University of Barcelona decided to put this question to the test. They invited 36 healthy young adults (about half men and half women) into a giant, noisy magnet machine called an fMRI scanner. This machine acts like a super-powered camera that can take pictures of the brain's blood flow, showing us which parts are working hard at any given moment.

Before the scan, the researchers asked everyone to fill out a questionnaire called the STAI (State-Trait Anxiety Inventory). This test measures two things:

State Anxiety: How nervous you feel right now (like before a big test).
Trait Anxiety: How nervous you usually are as a person (your general personality).

Once inside the scanner, the participants had to listen to and look at different things. They saw pictures of faces (some looking terrified, some looking calm) and they listened to voices (some sounding scared, some sounding neutral). The goal was to see how the amygdala reacted to these "scary" versus "boring" signals.

The Big Surprise: The Ears Hear Ghosts

The researchers expected to see the amygdala light up when people heard or saw scary things. And it did! But the real magic happened when they looked at the people with higher anxiety scores.

Here is the twist: For people with higher anxiety, the amygdala didn't just react to the scary voices; it reacted more to the boring, neutral voices.

Imagine you are walking down a quiet street. A normal person hears a bird chirping and thinks, "Nice bird." But a person with high anxiety might hear that same chirp and think, "Wait, is that a bird? Or is it a signal? Is someone hiding?" Their brain treats the innocent noise as if it might be a threat.

The study found that for participants with higher anxiety (both the "right now" kind and the "usually" kind), the right side of their amygdala went into overdrive when they heard neutral voices compared to fearful voices. It was as if their internal alarm was ringing louder for the "nothing" than for the "something."

The Visual vs. Auditory Mystery

Here is where it gets even more interesting. The researchers also showed the participants scary and neutral faces. You might think, "If my anxiety makes me hear ghosts, maybe it also makes me see them in faces, right?"

Nope. The study found that this "over-reacting to neutral stuff" only happened with hearing, not with seeing.

When the participants looked at neutral faces, their anxious brains didn't treat them as threats. The amygdala stayed calm. But when they listened to neutral voices, the anxious brain said, "Hold on, that sounds suspicious!"

This suggests that our anxious ears might be more sensitive to "maybe-danger" than our anxious eyes. It's like having a security system that is hyper-vigilant about sounds but a bit more relaxed about what it sees.

What This All Means

The study suggests that anxiety isn't just about being scared of obvious monsters. It's about a heightened state of vigilance. When you are anxious, your brain might start treating innocent, harmless sounds (like a neutral voice) as if they could be dangerous. It's your brain trying to be extra safe by checking every single noise for hidden threats.

The researchers are careful to say that this was a small study with healthy people who had "subclinical" anxiety (meaning they were worried but didn't have a diagnosed disorder). So, while the findings are exciting, they are a suggestion of how the brain works, not a final rule for everyone. But it does give us a cool new way to think about anxiety: it's not just a fear of the dark; it's a brain that sometimes can't tell the difference between a whisper and a shout, even when the whisper is just a friend saying "hello."

Technical Summary: State and Trait Anxiety Modulate Hemodynamic Amygdala Responses to Innocuous Auditory Stimulation

Problem Statement
While extensive literature establishes the amygdala's role in processing threat-related and fearful stimuli, and while anxiety is known to bias attention toward threat, the specific neural mechanisms by which subclinical anxiety levels modulate the processing of innocuous or neutral information remain unclear. Furthermore, most neuroimaging research has focused on visual emotional processing, leaving a gap in understanding how anxiety influences auditory emotional processing and whether these effects differ across sensory modalities. Specifically, it is unknown whether anxiety leads to a generalized hyper-responsivity to emotional cues or a specific alteration in salience attribution to neutral stimuli, and if such effects are modality-dependent.

Methodology
The study employed a functional magnetic resonance imaging (fMRI) design with a sample of 36 healthy young adults (50% female, mean age 24.6 ± 5.52 years) recruited from the University of Barcelona. Participants had no history of psychiatric or neurological disorders and were not taking neurotropic medications.

Stimuli and Task: Participants underwent a block-design task inside a 3T Philips Ingenia CX scanner. They were presented with fearful and neutral human faces (visual modality) and fearful and neutral nonverbal vocalizations (auditory modality). The stimuli were derived from the Karolinska Directed Emotional Faces (KDEF) and Montreal Affective Voices databases. Each stimulus was presented for 500 ms with a 50 ms inter-stimulus interval.
Anxiety Assessment: Prior to scanning, state and trait anxiety were assessed using the State-Trait Anxiety Inventory (STAI). Scores were converted to normative percentiles.
Behavioral Measures: Post-scan, participants rated the valence and arousal of all stimuli on a 1-to-5 Likert scale to confirm emotional perception.
Data Analysis:
- Preprocessing: Standard SPM25 preprocessing included slice timing correction, realignment, coregistration, segmentation, normalization to MNI space, and smoothing with a 6-mm FWHM kernel.
- Statistical Modeling: A General Linear Model (GLM) was used with regressors for Modality (Face, Voice), Emotion (Fear, Neutral), and stimulus variants. Group-level analyses utilized flexible factorial designs.
- Regions of Interest (ROI): Given the a priori hypothesis, anatomically defined bilateral amygdala masks (based on the Saygin et al. parcellation atlas) were used for Small Volume Correction (SVC) analyses.
- Correlations: Spearman's rank-order correlations were conducted between STAI scores and mean parameter estimates extracted from spherical ROIs centered on peak voxels identified in interaction contrasts.

Key Results

Behavioral Ratings: Participants reliably perceived fearful stimuli as more negative and arousing than neutral stimuli in both modalities. However, the valence difference between fearful and neutral stimuli was significantly larger for faces than for voices. No significant correlations were found between anxiety scores and behavioral ratings.
Main Effects: Emotional stimuli (fearful > neutral) elicited increased responses in bilateral superior temporal gyri (STG), precentral cortex, and the amygdala. Modality-specific effects showed auditory stimuli activating bilateral STG and visual stimuli activating the fusiform gyrus.
Anxiety Modulation (State): State anxiety significantly moderated the interaction between Emotion and Modality. Specifically, higher state anxiety scores were associated with stronger right amygdala responses to neutral voices relative to fearful voices (VoiceNeu > VoiceFear). This effect was not observed for visual stimuli. A positive linear correlation was confirmed between STAI-State scores and right amygdala activity for neutral vs. fearful voices ( $\rho = 0.57, p = 0.0005$ ).
Anxiety Modulation (Trait): Trait anxiety similarly modulated auditory processing. Higher trait anxiety was associated with increased right amygdala responses to neutral relative to fearful voices. Additionally, higher trait anxiety was linked to increased left amygdala responses to voices relative to faces, driven by greater responses to neutral voices compared to neutral faces.
Specificity: The anxiety-related enhancement of amygdala responses to neutral stimuli was specific to the auditory modality. No significant modulation by state or trait anxiety was observed for the visual (face) modality in the amygdala.

Key Contributions

Modality-Specificity: The study provides evidence that anxiety-related neural modulation is not uniform across sensory domains, demonstrating a specific vulnerability in the auditory processing of neutral cues.
Neutral Stimuli Processing: It challenges the view that anxiety solely amplifies responses to explicit threats. Instead, it demonstrates that subclinical anxiety is associated with an enhanced amygdala response to innocuous (neutral) auditory signals, suggesting a shift in salience attribution rather than just threat detection.
State vs. Trait Convergence: Both state and trait anxiety measures converged on the same neural mechanism (enhanced right amygdala response to neutral voices), suggesting that both transient and stable anxiety dimensions influence the processing of ambiguous auditory cues.

Significance and Claims
The authors claim that these findings support theories proposing heightened vigilance in anxiety, where individuals assign greater salience or potential threat value to otherwise benign or ambiguous environmental cues. The results suggest that the neural mechanisms underlying anxiety involve an altered interpretation of neutral information, particularly in the auditory domain, which may be more transient and ambiguous than visual cues.

The paper modestly notes that these findings are based on subclinical anxiety levels in a healthy sample and that the passive nature of the task limits conclusions regarding specific cognitive mechanisms (e.g., attentional bias vs. perceptual bias). The authors conclude that understanding how anxiety shapes emotional processing across modalities is crucial for elucidating the neural basis of heightened vigilance and altered salience attribution in anxiety states.

The Great Brain Scan: When the Alarm Rings for Nothing

The Big Surprise: The Ears Hear Ghosts

The Visual vs. Auditory Mystery

What This All Means

Technical Summary: State and Trait Anxiety Modulate Hemodynamic Amygdala Responses to Innocuous Auditory Stimulation

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