Parabrachial Complex

Anatomy

• In the dorsolateral upper pons, around the superior cerebellar peduncle (brachium conjunctivum); named for lying on both sides of this peduncle.
• Medial and lateral subnuclei; the neighboring Kölliker-Fuse nucleus takes part in breathing rhythm.
• Input: nucleus tractus solitarius (visceral sensation, taste, baroreflex) and the dorsal horn of the spinal cord (spinoparabrachial pathway: pain, temperature).
• Output: central nucleus of the amygdala, BNST, hypothalamus and preoptic area, thalamus (and from there the insula), PAG.

Functions

• The main station relaying interoceptive information from the internal organs (stomach, heart, breathing) to the limbic forebrain.
• General alarm: reports bodily dangers such as pain, excessive heat, nausea and breathlessness to the amygdala (Palmiter, 2018).
• Appetite and satiety: lateral parabrachial CGRP neurons suppress eating with nausea and satiety signals (Carter et al., 2013).
• Breathing: with the Kölliker-Fuse nucleus it tunes breathing rhythm; it triggers the arousal response when blood CO₂ rises (Kaur et al., 2013).
• Thermoregulation: relays warm and cold information from the skin to the preoptic area.

Connections and chemistry

• NTS → PBN (visceral sensation, taste): the book’s vagal afferent pathway
• Dorsal horn of the spinal cord → PBN (pain, temperature)
• PBN → central nucleus of the amygdala and BNST (alarm, the emotional side of pain)
• PBN → hypothalamus and preoptic area (temperature, appetite)
• PBN → thalamus → insula (interoception)
• Glutamate, CGRP; μ-opioid receptors

Development

Developmental course through childhood and adolescence.

• In the newborn, respiratory control and the arousal response to rising CO₂ are still maturing; failure of this response features in models trying to explain sudden infant death syndrome.
• Learning to avoid a food paired with nausea (conditioned taste aversion) depends on parabrachial circuits (animal studies).

Clinical

• Panic disorder: the “false suffocation alarm” theory, hypersensitivity to CO₂ (Klein, 1993); the parabrachial–amygdala pathway is one of the candidate circuits.
• Chronic pain and somatic symptom disorders: the spinoparabrachial–amygdala pathway carries the emotional load of pain.
• Eating problems and drug-related nausea: parabrachial CGRP neurons play a role in appetite suppression (animal studies).
• Opioid-related respiratory depression: μ-opioid receptors in the parabrachial and Kölliker-Fuse region contribute.

Treatment

This region from the perspective of medication, psychotherapy and neuromodulation. Letter badges are evidence levels.

• In panic disorder, interoceptive exposure (e.g. deliberate overbreathing, spinning, breath holding) is part of CBT; it aims at habituation to bodily alarm signals (the parabrachial–amygdala pathway). B
• Opioid-induced respiratory depression is reversed with naloxone; μ-opioid receptors in the parabrachial and Kölliker-Fuse region are among the main sites of this side effect. B
• Antiemetics for chemotherapy- and drug-related nausea; conditioned taste aversion (disgust toward a food paired with nausea) can disrupt children’s eating during treatment, and keeping new foods away from treatment days is advised. C

Assessment

Neuropsychological tasks and measures that probe this region's function.

• CO₂ inhalation test: increased sensitivity has been reported in panic disorder and childhood anxiety disorders (Pine et al., 2000)
• Interoceptive awareness tasks (heartbeat detection): indirect assessment
• Pain thresholds (quantitative sensory testing), taste thresholds

Lesions and damage

Clinical findings expected with damage or dysfunction.

• In animals, lateral parabrachial damage reduces emotional responses to pain and conditioned taste aversion, and abolishes the arousal response to rising CO₂.
• Lesions of the dorsolateral upper pons (pneumotaxic center) can disturb breathing rhythm.

In the model

How this structure is defined in the 3D model, and the data source.

Harvard AAN v2.0 parabrachial complex labels (right/left). Because the voxels are scattered in the atlas, the surface is a smoothed envelope around them; the medial and lateral subnuclei and the Kölliker-Fuse nucleus are not shown separately.

References

Full citations for the card; links go to the paper (DOI) or a PubMed search.

1. Carter ME et al. Genetic identification of a neural circuit that suppresses appetite. Nature 2013;503:111–114. DOI: 10.1038/nature12596
2. Kaur S et al. Glutamatergic signaling from the parabrachial nucleus plays a critical role in hypercapnic arousal. J Neurosci 2013;33(18):7627–7640. DOI: 10.1523/JNEUROSCI.0173-13.2013
3. Klein DF. False suffocation alarms, spontaneous panics, and related conditions: an integrative hypothesis. Arch Gen Psychiatry 1993;50(4):306–317. DOI: 10.1001/archpsyc.1993.01820160076009
4. Palmiter RD. The parabrachial nucleus: CGRP neurons function as a general alarm. Trends Neurosci 2018;41(5):280–293. DOI: 10.1016/j.tins.2018.03.007
5. Pine DS et al. Differential carbon dioxide sensitivity in childhood anxiety disorders and nonill comparison group. Arch Gen Psychiatry 2000;57(10):960–967. DOI: 10.1001/archpsyc.57.10.960