Anterior Cingulate Cortex

Anatomy

• Anterior part of the cingulate gyrus wrapping around the front of the corpus callosum; BA 24, 32, 33 and subgenual BA 25.
• Subdivisions: dorsal ACC (cognitive control), pregenual/rostral ACC (affective), subgenual ACC (sgACC — mood and autonomic regulation).
• Contains von Economo neurons, together with the anterior insula.
• Blood supply: ACA (pericallosal and callosomarginal arteries).

Functions

• Error detection and conflict monitoring; source of the error-related negativity (ERN) on EEG.
• Adjusting cognitive control, effort and cost–benefit computation.
• The affective (unpleasant) dimension of pain; response to social exclusion.
• Motivation and initiation of behavior.
• Emotion regulation (rostral ACC); regulation of mood and the HPA axis (sgACC).
• Core of the salience network together with the insula.

Connections and chemistry

• DLPFC (cognitive control)
• Anterior insula (salience network)
• Amygdala and hypothalamus
• Caudate and ventral striatum
• Thalamus — anterior/mediodorsal
• Dopamine, serotonin and noradrenaline inputs

Development

Developmental course through childhood and adolescence.

• ERN amplitude increases from childhood to adolescence; error monitoring matures.
• ACC–prefrontal connections strengthen in adolescence; cognitive control becomes more efficient.

Clinical

• OCD: dACC hyperactivity and an enhanced ERN (an “excessive error signal”). In pediatric OCD the ERN is large and stays large even when symptoms improve with CBT; it behaves like a trait (endophenotype) marker rather than a state marker (Hajcak et al., 2008). B
• Anxiety disorders: children with a larger ERN at age 6 were more likely to develop a new anxiety disorder by age 9, even after accounting for baseline symptoms and maternal anxiety (236 children; Meyer et al., 2015). A candidate marker for early screening and prevention. B
• ADHD: dACC hypoactivation (Bush et al., 1999), differences in error monitoring.
• Depression: sgACC hyperactivity. In adult treatment-resistant depression, deep brain stimulation of the sgACC (subcallosal) looked promising in open studies (Mayberg et al., 2005), but in a multicenter sham-controlled trial it was not superior to placebo at 6 months (Holtzheimer et al., 2017). B
• A shared transdiagnostic finding: a meta-analysis of 193 VBM studies (about 15,900 people) found gray matter loss in schizophrenia, bipolar disorder, depression, addiction, OCD and anxiety converging on the same three regions: dorsal ACC and the bilateral insula. Reduction in this network relates to weaker executive function (Goodkind et al., 2015). A

Treatment

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

• TMS: the left DLPFC site most strongly anticorrelated with the sgACC is targeted; the ACC is modulated indirectly (Fox et al., 2012; SAINT). B
• Deep brain stimulation (subcallosal cingulate): experimental in treatment-resistant depression; efficacy was not shown in a sham-controlled trial (Holtzheimer et al., 2017). Adults only. B
• Cingulotomy: last-resort surgery for refractory OCD and cancer pain; not performed in children and adolescents. C
• Because the ERN does not change with treatment in OCD, it is used for risk identification rather than for tracking treatment response (Hajcak et al., 2008).

Assessment

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

• Stroop, Flanker (Eriksen), Simon task
• Go/No-Go; ERN and post-error slowing (EEG)
• Emotional Stroop

Lesions and damage

Clinical findings expected with damage or dysfunction.

• Akinetic mutism with bilateral lesions; apathy and abulia with unilateral lesions.
• Impaired error correction and attentional control, indifference to pain (cingulotomy).

In the model

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

Rostral and caudal anterior cingulate cortex (CerebrA); cingulate HCP-MMP1.0 areas falling on the frontal gyri (areas 25, s32, 24 and 32, 33pr) were also given to the ACC.

References

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

1. Hajcak G et al. Increased error-related brain activity in pediatric obsessive-compulsive disorder before and after treatment. Am J Psychiatry 2008;165(1). Search PubMed
2. Meyer A, Hajcak G et al. Enhanced error-related brain activity in children predicts the onset of anxiety disorders between the ages of 6 and 9. J Abnorm Psychol 2015;124(2):266–274. Search PubMed
3. Goodkind M et al. Identification of a common neurobiological substrate for mental illness. JAMA Psychiatry 2015;72(4):305–315. Search PubMed
4. Holtzheimer PE et al. Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. Lancet Psychiatry 2017;4(11):839–849. Search PubMed
5. Fox MD et al. 2012. Search PubMed