Neural substrates of inhibitory control deficits in 22q11.2 deletion syndrome

• Published in: Cerebral cortex (New York, N.Y. 1991) Vol. 25; no. 4; pp. 1069 - 1079
• Main Authors: Montojo, C A, Jalbrzikowski, M, Congdon, E, Domicoli, S, Chow, C, Dawson, C, Karlsgodt, K H, Bilder, R M, Bearden, C E
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.04.2015
• Subjects: Adolescent; Adult; Brain - physiopathology; DiGeorge Syndrome - physiopathology; Female; Humans; Inhibition, Psychological; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Psychomotor Performance - physiology; Severity of Illness Index; Young Adult; impulsivity; velocardiofacial syndrome; fronto-basal ganglia; response inhibition
• ISSN: 1047-3211; 1460-2199
• DOI: 10.1093/cercor/bht304

22q11.2 deletion syndrome (22q11DS) is associated with elevated levels of impulsivity, inattention, and distractibility, which may be related to underlying neurobiological dysfunction due to haploinsufficiency for genes involved in dopaminergic neurotransmission (i.e. catechol-O-methyltransferase). The Stop-signal task has been employed to probe the neural circuitry involved in response inhibition (RI); findings in healthy individuals indicate that a fronto-basal ganglia network underlies successful inhibition of a prepotent motor response. However, little is known about the neurobiological substrates of RI difficulties in 22q11DS. Here, we investigated this using functional magnetic resonance imaging while 45 adult participants (15 22q11DS patients, 30 matched controls) performed the Stop-signal task. Healthy controls showed significantly greater activation than 22q11DS patients within frontal cortical and basal ganglia regions during successful RI, whereas 22q11DS patients did not show increased neural activity relative to controls in any regions. Using the Barratt Impulsivity Scale, we also investigated whether neural dysfunction during RI was associated with cognitive impulsivity in 22q11DS patients. RI-related activity within left middle frontal gyrus and basal ganglia was associated with severity of self-reported cognitive impulsivity. These results suggest reduced engagement of RI-related brain regions in 22q11DS patients, which may be relevant to characteristic behavioral manifestations of the disorder.