Atypical frontal lobe activity during verbal working memory in youth with a family history of alcoholism

Abstract

Background Abnormal brain functioning during verbal working memory tasks has been shown in individuals with alcohol use disorders (AUDs). Since adolescents with a familial history of alcoholism (FHP) are at high risk for developing an AUD, it is important to consider whether atypical brain activity during verbal working memory may help to explain FHP vulnerability toward developing alcoholism. Methods To that end, using functional magnetic resonance imaging, we examined brain response during a verbal working memory 2-back task in 19 FHP adolescents and 16 age and gender-matched family history negative (FHN) controls. Results Despite no group differences in task accuracy, FHP youth had significantly slower average reaction time when making correct responses during the 2-back condition than FHN youth. In contrast to a vigilance control condition, while covarying for reaction time, FHP adolescents showed less activation during verbal working memory than FHN youth in multiple areas of the prefrontal cortex (PFC) – a brain region crucial to intact working memory skills. Conclusions These results suggest that even prior to heavy alcohol use, FHP adolescents show atypical executive brain functioning during verbal working memory, and that these differences are independent of slower working memory reaction time in FHP youth. Given the importance of working memory in numerous areas of day-to-day functioning, such as adaptive decision-making, these abnormalities may contribute to FHP youth vulnerability toward developing AUDs.

Increased Forebrain Activations in Youths with Family Histories of Alcohol and Other Substance Use Disorders Performing a Go/NoGo Task

“…Consistent with this, FH+ individuals have been show to have elevated forebrain activations during Stroop and simulated gambling tasks when task performance had contrasted with either rest or low level perceptual motor control conditions (Silveri et al, 2011, Acheson et al, 2009). Similarly, studies reporting relative decreases in forebrain activity in FH+ individuals have typically employed potentially more subtle task contrasts in an effort to isolate neural activity associated with specific cognitive processes (Cservenka and Nagel, 2012, Andrews et al, 2011, Spadoni et al, 2008, Cservenka et al, 2012). However, more studies employing resting or low level perceptual motor control contrast conditions are needed to confirm this hypothesis.…”

“…This risk is thought to be driven by behavioral and cognitive characteristics of “behavioral undercontrol” or “neurobehavioral disinhibition” consisting of increased sensation seeking and antisocial behaviors as well as deficits in executive functioning, impulse control, decision making, and attention (e.g., Stevens et al, 2003, Deckel, 1999, Corral et al, 2003, Acheson et al, 2011a, Acheson et al, 2011b, Lovallo et al, 2006, Tarter et al, 2003, Sher et al, 2004, Sher and Trull, 1994). Further, this increased risk may be at least partially driven by impaired or altered development of forebrain circuitry as FH+ youths and young adults appear to have impaired frontal white matter development (Herting et al, 2010, Acheson et al, 2014b, Acheson et al, 2014a) and show evidence of altered forebrain activity at both rest and while performing cognitive tasks (e.g., Schweinsburg et al, 2004, Acheson et al, 2009, Silveri et al, 2011, Heitzeg et al, 2010, Cservenka et al, 2012, Spadoni et al, 2008). 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.…”

The effect of alcohol use on human adolescent brain structures and systems

“…Teens with a positive family history have lower BOLD activation during a verbal working-memory task relative to teens with a negative family history (Cservenka et al, 2012). Family history-positive teens also showed aberrations on a spatial working-memory task in prefrontal, parietal, and cerebellar regions, suggesting these alterations may be a general risk factor for family history-positive youth (Mackiewicz et al, 2013).…”

Assessment of whole brain white matter integrity in youths and young adults with a family history of substance‐use disorders

“…This increased risk has a genetic basis as demonstrated by twin, adoption, cross-fostering, and pedigree analysis studies (Cloninger, et al, 1981; Merikangas, 1990; Reich, et al, 1998; Slutske, et al, 2002), and is associated with a phenotypic pattern of “behavioral undercontrol” characterized by increased sensation seeking, risk-taking, aggressiveness, and antisocial behaviors (Sher, et al, 2004; Sher and Trull, 1994; Tarter, et al, 2003). Likewise, FH+ individuals show deficits in executive functioning, impulse control, decision-making, and attention (Acheson, et al, 2011a; Acheson, et al, 2011b; Corral, et al, 2003; Deckel, 1999; Lovallo, et al, 2006; Stevens, et al, 2003) and altered activity in frontocortical and frontostriatal regions (Acheson, et al, 2009; Cservenka, et al, 2012; Glahn, et al, 2007; Heitzeg, et al, 2010; Schweinsburg, et al, 2004; Silveri, et al, 2011). These findings suggest FH+ individuals have impairments in frontocortical and frontostriatal functioning, although specific mechanisms underlying this impairment and as well as potential relationships to risk for substance use disorders remain elusive.…”