Reticular Formation (Mesencephalic and Pontine)

Anatomy

• An area in the center of the brainstem tegmentum without sharp borders, where neurons are scattered among fiber bundles (reticular: net-like).
• Two parts in the model: the mesencephalic reticular formation (mRt; midbrain) and the nucleus pontis oralis (PnO; upper pons).
• Ascending reticular activating system (ARAS): reaches the cortex via the intralaminar nuclei of the thalamus (dorsal route) and via the hypothalamus and basal forebrain (ventral route).
• The Harvard AAN atlas mapped the nodes of this arousal network in the postmortem human brainstem with histology and MRI (Edlow et al., 2012; atlas version 2.0, 2023).

Functions

• Maintaining wakefulness and the level of consciousness.
• Sleep–wake transitions; the PnO takes part in generating REM sleep.
• Muscle tone and posture (reticulospinal tracts); contribution to the muscle atonia of REM sleep.
• Orienting and arousal responses to new and unexpected stimuli.
• Integration with breathing and circulatory regulation together with the reticular areas of the lower brainstem.

Connections and chemistry

• mRt/PnO → intralaminar nuclei of the thalamus → cortex (dorsal ARAS route)
• Reticular formation → hypothalamus and basal forebrain (ventral ARAS route)
• Arousal network together with the PPN/LDT (acetylcholine), locus coeruleus (noradrenaline) and raphe (serotonin)
• Reticulospinal tracts → spinal cord (muscle tone, posture)
• Glutamate, acetylcholine, GABA

Development

Developmental course through childhood and adolescence.

• In the newborn, sleep and wakefulness are scattered across the day; daytime wakefulness and night sleep consolidate in the first months.
• Brainstem maturation can be followed with ABR in preterm infants.

Clinical

• Disorders of consciousness (coma, minimally conscious state): damage to the brainstem arousal network; the main causes in children are traumatic brain injury and hypoxic-ischemic injury.
• ADHD: theories of low arousal and arousal regulation highlight brainstem and thalamic arousal systems; the evidence is indirect.
• Childhood brainstem tumors (e.g. diffuse midline glioma) and Chiari malformation can affect consciousness, sleep and autonomic functions.

Treatment

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

• Amantadine: in 184 adults (aged 16–65; in a vegetative or minimally conscious state after traumatic brain injury weeks 4–16), 4 weeks of treatment accelerated functional recovery; 2 weeks after stopping the drug the difference between groups disappeared (Giacino et al., 2012). Whether the effect is lasting or only an acceleration is unclear. Evidence in children is limited to case series. B
• In disorders of consciousness, structured assessment (e.g. the Coma Recovery Scale-Revised) reduces misdiagnosis; versions adapted for children are being studied. C
• Drugs that act on the arousal system (sedating antihistamines, benzodiazepines, antipsychotics) can show up in children as daytime sleepiness and attention problems.

Assessment

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

• Level of consciousness: Glasgow Coma Scale (pediatric version)
• EEG: waking rhythms and sleep stages
• Brainstem auditory evoked potentials (ABR): brainstem integrity

Lesions and damage

Clinical findings expected with damage or dysfunction.

• Damage to the pontomesencephalic tegmentum, especially when bilateral, causes coma (Parvizi and Damasio, 2003).
• With damage limited to the ventral pons, consciousness is preserved (locked-in syndrome); whether the tegmentum is involved is decisive.

In the model

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

Harvard AAN v2.0 mesencephalic reticular formation (mRt) and pontis oralis (PnO) labels (right/left). The reticular areas of the medulla are not in the atlas.

References

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

1. Giacino JT et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med 2012;366:819–826. Search PubMed