Heritability of brain activity related to response inhibition: A longitudinal genetic study in adolescent twins

Abstract

The ability to inhibit prepotent but context- or goal-inappropriate responses is essential for adaptive self-regulation of behavior. Deficits in response inhibition, a key component of impulsivity, have been implicated as a core dysfunction in a range of neuropsychiatric disorders such as ADHD and addictions. Identification of genetically transmitted variation in the neural underpinnings of response inhibition can help to elucidate etiological pathways to these disorders and establish the links between genes, brain, and behavior. However, little is known about genetic influences on the neural mechanisms of response inhibition during adolescence, a developmental period characterized by weak self-regulation of behavior. Here we investigated heritability of ERPs elicited in a Go/No-Go task in a large sample of adolescent twins assessed longitudinally at ages 12, 14, and 16. Genetic analyses showed significant heritability of inhibition-related frontal N2 and P3 components at all three ages, with 50 to 60% of inter-individual variability being attributable to genetic factors. These genetic influences included both common genetic factors active at different ages and novel genetic influences emerging during development. Finally, individual differences in the rate of developmental changes from age 12 to age 16 were significantly influenced by genetic factors. In conclusion, the present study provides the first evidence for genetic influences on neural correlates of response inhibition during adolescence and suggests that ERPs elicited in the Go/No-Go task can serve as intermediate neurophysiological phenotypes (endophenotypes) for the study of disinhibition and impulse control disorders.

Keywords: Brain; Heritability; No-Go; Response inhibition; Twins.

Fig. 1

The Go/No-Go Continuous Performance Task (CPT). An X following O is a target stimulus requiring a speeded response, while any other letter following O is a No-Go stimulus. Since O is relatively rare (20%), it serves as a warning stimulus triggering motor preparation and thus creating a response prepotency.

Fig. 2

Event-related brain potentials (ERPs) elicited at midline frontal (Fz), central (Cz), and parietal (Pz) scalp locations at ages 12, 14, and 16. No-Go stimuli produced a prominent frontal N2 potential and “anteriorized” P3 potential (P3n), whereas Go stimuli elicited a P3 wave peaking in the mid-parietal area (P3g), similar to a classical oddball P3.

Fig. 3

Scalp potential maps of ERPs in No-Go and Go conditions at ages 12, 14, and 16.

Fig. 4

Age-related changes in the amplitudes of ERP components (all trends are significant, p<.001).

Fig. 5

Path diagrams for structural equation models, No-Go P3 amplitude. A. Cholesky (triangular decomposition) model. Rectangles are observed (measured) ERP phenotypes, circles are latent factors (A, additive genetic; E, non-shared environmental). Arrows show causal paths from latent factors to phenotypes. Note that the paths from genetic factors at age 12 lead to the phenotype at all three ages, allowing for the possibility of genetic overlap across ages (i.e. continuity of genetic influences). Additional paths at ages 14 and 16 allow for the possibility of age-specific genetic influences (i.e. new genetic influences emerging in the course of development). Paths from the environmental factors have similar interpretation. B. Standardized solution showing proportions of variance attributable to genetic and environmental factors at each age, and the genetic and environmental correlations. Same models for other ERP phenotypes (N2 and Go P3) are presented in Supplementary Material.

Fig. 6

Heritability of ERP components at different ages. The proportions of variance attributable to genetic factors (heritability) is shown in red, the residual environmental variance including measurement error is shown in blue.