BackgroundYouths with a family history of alcohol and other drug use disorders (FH+) are at a greater risk of developing substance use disorders than their peers with no such family histories (FH-), and this increased risk may be related to impaired maturation of forebrain circuitry. FH+ individuals have shown altered forebrain activity at rest and while performing cognitive tasks. However, it is not fully understood how forebrain activity is altered in FH+ individuals, and ultimately how these alterations may contribute to substance use disorder risk. MethodsIn this study, we tested 72 FH+ and 32 FH- youths performing a go/no-go task and examined activations in blocks with only go trials (Go Only), blocks with 50% go and 50% no-go trials (Go/NoGo), and a contrast of those 2 blocks. ResultsFH+ youths had significantly greater cerebral activations in both the Go and Go/NoGo blocks than FH- youths in regions including the posterior cingulate/precuneus, bilateral middle/superior temporal gyrus, and medial superior frontal gyrus with no significant group differences in the subtraction between Go Only and Go/NoGo blocks. Additionally, FH+ youths had moderately slower reaction times on go trials in the Go Only blocks. ConclusionsOur findings suggest that global activation increase in FH+ youths are modulated by FH density and are not specific to the inhibitory components of the task. This pattern of increased activations in FH+ youths may be at least partially due to impaired forebrain white matter development leading to greater activations/less efficient neural communication during task performance.