Medial & Frontopolar Prefrontal Cortex

Anatomy

• Medial surface of the superior frontal gyrus and the frontal pole; BA 10 and medial BA 9.
• The ventromedial part (vmPFC) covers subdivisions of BA 10–11–32; it borders the subgenual cingulate (BA 25) and the OFC.
• Dorsomedial PFC (dmPFC) stands out for mentalizing, vmPFC for value and emotion regulation.
• Blood supply: ACA (frontopolar and medial orbitofrontal branches).

Functions

• Self-referential thinking; the anterior hub of the default mode network (DMN).
• Theory of mind: inferring others’ intentions and beliefs (dmPFC).
• Inhibitory control over the amygdala; recall of fear extinction (vmPFC).
• Value-based decision-making, moral judgment.
• Frontopolar: multitasking, prospective memory, switching between subgoals.

Connections and chemistry

• Amygdala (top-down regulation)
• Hippocampus (contextual memory, extinction)
• Posterior cingulate / precuneus (DMN)
• Hypothalamus and PAG (autonomic response)
• Nucleus accumbens
• Serotonin (raphe), dopamine (VTA)

Development

Developmental course through childhood and adolescence.

• Amygdala–mPFC connectivity shifts from positive in early childhood to negative (regulatory) in adolescence (Gee et al., 2013).
• In adolescence, mPFC activity during social-cognitive tasks is higher than in adults and declines with age (development of the “social brain”).
• Sensitivity to peer evaluation peaks in adolescence.

Clinical

• Autism spectrum disorder (ASD): differences in mPFC activation during mentalizing tasks.
• Anxiety and PTSD: insufficient regulation of the amygdala by the vmPFC, weak extinction memory. In healthy adults, those with a thicker vmPFC (medial OFC) recalled extinguished fear better the next day (Milad et al., 2005; 14 people). Small sample, pioneering finding. C
• Depression: a resting-state connectivity meta-analysis (556 patients, 518 controls) found reduced connectivity within the frontoparietal control network and with the attention network, and increased connectivity with the default mode network (including mPFC). Consistent with a shift toward inward thought (rumination) and withdrawal from the outside world (Kaiser et al., 2015). A
• Conduct disorder (CU traits): vmPFC differences in empathy and moral decision processes.

Treatment

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

• Exposure therapy uses extinction learning, which depends on the vmPFC; new “safe” learning does not erase the old fear memory but competes with it. This is why fear can return after relapse or a change of context. B
• Augmenting exposure with D-cycloserine (partial NMDA agonist): in an individual-participant meta-analysis of 21 studies (1,047 people) the effect was small and only at end of treatment; not considered clinically meaningful (Mataix-Cols et al., 2017). A
• Deep TMS (H7 coil, mPFC and ACC): FDA-cleared as add-on treatment for adult OCD (August 2018); response at 6 weeks about 38% vs 11% with sham. Individualized symptom provocation precedes each session. A

Assessment

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

• False-belief tasks (Sally-Anne), Faux Pas test
• Reading the Mind in the Eyes Test (RMET — child version)
• Fear conditioning and extinction paradigms
• Six Elements Test (BADS-C) — multitasking

Lesions and damage

Clinical findings expected with damage or dysfunction.

• vmPFC: impaired emotional decision-making (risky choices on the IGT), reduced social judgment and empathy.
• dmPFC / bilateral medial: apathy, abulia, reduced spontaneous behavior.

In the model

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

HCP-MMP1.0 areas (Glasser et al., 2016; MNI volumetric version: Horn, 2016): 9m, 8BM, 10d, 10r, 10v, 10pp, a10p, p10p (dmPFC, vmPFC and frontal pole) and the DLPFC areas falling on the medial surface.

References

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

1. Milad MR et al. Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory. PNAS 2005;102(30):10706–10711. Search PubMed
2. Kaiser RH et al. Large-scale network dysfunction in major depressive disorder: a meta-analysis of resting-state functional connectivity. JAMA Psychiatry 2015;72(6):603–611. Search PubMed
3. Mataix-Cols D et al. D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders. JAMA Psychiatry 2017;74(5):501–510. Search PubMed
4. BrainsWay Deep TMS H7, FDA De Novo, OKB, Ağustos 2018 (Carmi et al., pivotal çalışma). Search PubMed