Take my breath away: Neural activation at breath-hold differentiates individuals with panic disorder from healthy controls
Abstract
There is neuroanatomical evidence of an "extended fear network" of brain structures involved in the etiology of panic disorder (PD). Although ventilatory distrubance is a primary symptom of PD these sensations may also trigger onset of a panic attack (PA). Here, a voluntary breath-holding paradigm was used to mimic the hypercapnia state in order to compare blood oxygen level-dependent (BOLD) response, at the peak of a series of 18 s breath-holds, of 21 individuals with PD to 21 low anxiety matched controls. Compared to the rest condition, BOLD activity at the peak (12 - 18 s) of the breath-hold was greater for PD versus controls within a number of structures implicated in the extended fear network, including hippocampus, thalamus, and brainstem. Activation was also observed in cortical structures that are shown to be involved in interoceptive and self-referential processing, such as right insula, middle frontal gyrus, and precuneus/posterior cingulate. In lieu of amygdala activation, our findings show elevated activity throughout an extended network of cortical and subcortical structures involved in contextual, interoceptive and self-referential processing when individuals with PD engage in voluntary breath-holding.
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Qualitative synthesis suggested that anxiety disorders may exhibit increased activation in the anterior and mid-insula during interoceptive tasks.
“Qualitative synthesis suggested potential insula hyperactivation in anxiety, aligning with theories of interoceptive hypervigilance.”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [45]
Studies of panic disorder specifically reported increased brainstem activation during CO2 reactivity tasks.
“Additionally, studies of PD specifically reported increased brainstem activation during CO2 reactivity tasks [44, 45].”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [45]
One whole-brain CO2 reactivity study in panic disorder identified increased activation in the right mid-insula, right posterior cingulate, right thalamus, bilateral cerebellum, brainstem, and left middle cingulate cortex.
“This study identified increased activation in individuals with PD during interoception in many brain regions, including the right mid-insula, right posterior cingulate, right thalamus, bilateral cerebellum, brainstem, and left middle cingulate cortex.”
From Neural correlates of altered interoception in depressive and anxiety disorders: a systematic review and meta-analysis (2026) · cites this paper as [45]
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Flagged first, then by citations
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Sorted by citations
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BackgroundDisrupted fronto-temporal function in panic disorder: a resting-state connectome study
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- Authors
- McIntosh, R. C., Hoshi, R. A., & Timpano, K. R.
- Affiliations
- University of Miami (US)
- Universidade de São Paulo (BR)
- Corresponding author
- McIntosh, R.C.
- Venue
- Respiratory Physiology & Neurobiology
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 277
- Pages
- 103427
- ISSN
- 1569-9048 (ISSN-L)
- OpenAlex
- W3008822865
- Cited by
- 14
- References
- 120
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 4
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Respiratory Physiology & Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute
- National Institutes of Health (K01HL139722)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- panic disorder, breath-holding, hypercapnia, BOLD signal, interoception, self-referential processing, hippocampus, thalamus, brainstem, insula, amygdala, panic attacks
- MeSH terms
- Adolescent, Adult, Fear, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Oxygen Consumption, Surveys and Questionnaires, Panic Disorder, Young Adult, Breath Holding, Healthy Volunteers
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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