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Cingulate Impairments in ADHD: Comorbidities, Connections, and Treatment

Cingulate Impairments in ADHD: Comorbidities, Connections, and Treatment

Brent A Vogt

Handb Clin Neurol. 2019;166:297-314.

PMID: 31731917

Abstract:

The entire cingulate cortex is engaged in the structure/function abnormalities found in attention-deficit/hyperactivity disorder (ADHD). In ADHD, which is the most common developmental disease, impaired impulse control and cognition often trace to anterior midcingulate cortex (aMCC) in Go/No-go tests, decoding and reading, the Stroop Color and Word Test, and the Wisconsin Card Sorting Test (WCST), with volume deficits in anterior cingulate cortex (ACC) and posterior midcingulate cortex (pMCC). Volumes in pMCC correlate positively with the WCST and negatively with total and nonperseverative errors on the WCST. Activation and connectivity on N-back tests show connections for high and low spatial working memory, but patients have increased activation in PCC and decreased connectivity between MCC and PCC for high load. Students struggle in class due to malfunctioning aMCC, pregenual anterior cingulate cortex (pACC), and dorsal posterior cingulate cortex (dPCC), and to core deficits in response/task switching in aMCC. Gene mutations are found in the DA transporter and DA4 and DA5 receptors. Methylphenidate decreases hyperactivity in aMCC. The DA system is controlled by cholinergic receptors in the daMCC and genetics show nAChR mutations in alpha 3, 4, and 7 receptors. At 25 years, a modified Eriksen flanker/No-go task and voxel-based morphometry (VBM) show prenatal smoking, lifetime smoking at 13 years, and novelty seeking. Prenatal exposure to nicotine exhibits weaker responses in aMCC during cognitive tasks for hyperactivity/impulsiveness but not inattention. AZD1446 (ɑ4β2 nAChR agonist) improves the Groton Maze task due to high nAChR in dPCC/RSC engaged in spatial orientation. Environmental factors associated with childhood ADHD relate to pesticides, organochlorine, and air pollutants. Network connection segregation shows increased amygdala local nodal, but decreased ACC and PCC connections, reflecting emphasis on local periamygdala connections at the expense of cortical connections. Thus, ADHD children/adolescents respond impulsively to the significance of stimuli without having cortical inhibition. Finally, controls show negative relationships between aMCC and the default mode network, and ADHD compromises this relationship, showing decreased connectivity between ACC and precuneus/PCC.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP103974294	AMCC		103974-29-4	Price

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