Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition

David Kareken, Mario Dzemidzic, Leah Wetherill, William Eiler, Brandon G. Oberlin, Jaroslaw Harezlak, Yang Wang, Sean O'Connor

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Rationale: Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA). One operational definition of impulsive behavior is the stop-signal task (SST) which measures the time needed to stop a ballistic hand movement. Objective: Employ functional magnetic resonance imaging (fMRI) to study right frontal responses to stop signals in heavy drinking subjects with and without FHA, and as a function of alcohol exposure. Methods: Twenty-two family history-positive (FHP; age = 22.7 years, SD = 1.9) and 18 family history-negative (FHN; age = 23.7, SD = 1.8) subjects performed the SST in fMRI in two randomized visits: once during intravenous infusion of alcohol, clamped at a steady-state breath alcohol (BrAC) concentration of 60 mg/dL, and once during infusion of placebo saline. An independent reference group (n = 13, age = 23.7, SD = 1.8) was used to identify a priori right prefrontal regions activated by successful inhibition (Inh) trials, relative to "Go" trials that carried no need for inhibition [Inh > Go]. Results: FHA interacted with alcohol exposure in right prefrontal cortex, where alcohol reduced [Inh > Go] activation in FHN subjects but not in FHP subjects. Within this right frontal cortical region, stop-signal reaction time also correlated negatively with [Inh > Go] activation, suggesting that the [Inh > Go] activity was related to inhibitory behavior. Conclusions: The results are consistent with the low level of response theory (Schuckit, J Stud Alcohol 55:149-158, 1980; Quinn and Fromme, Alcohol Clin Exp Res 35:1759-1770, 2011), with FHP being less sensitive to alcohol's effects.

Original languageEnglish
Pages (from-to)335-345
Number of pages11
JournalPsychopharmacology
Volume228
Issue number2
DOIs
StatePublished - Jul 2013

Fingerprint

Alcoholism
Alcohols
Brain
Impulsive Behavior
Magnetic Resonance Imaging
Inhibition (Psychology)
Prefrontal Cortex
Intravenous Infusions
Drinking
Reaction Time
Hand
Placebos

Keywords

  • Alcoholism
  • Family history
  • FMRI
  • Frontal lobes
  • Impulsivity
  • Inhibition
  • Stop signal

ASJC Scopus subject areas

  • Pharmacology

Cite this

Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition. / Kareken, David; Dzemidzic, Mario; Wetherill, Leah; Eiler, William; Oberlin, Brandon G.; Harezlak, Jaroslaw; Wang, Yang; O'Connor, Sean.

In: Psychopharmacology, Vol. 228, No. 2, 07.2013, p. 335-345.

Research output: Contribution to journalArticle

@article{f0a4927959264635a1c763494ad55fcb,
title = "Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition",
abstract = "Rationale: Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA). One operational definition of impulsive behavior is the stop-signal task (SST) which measures the time needed to stop a ballistic hand movement. Objective: Employ functional magnetic resonance imaging (fMRI) to study right frontal responses to stop signals in heavy drinking subjects with and without FHA, and as a function of alcohol exposure. Methods: Twenty-two family history-positive (FHP; age = 22.7 years, SD = 1.9) and 18 family history-negative (FHN; age = 23.7, SD = 1.8) subjects performed the SST in fMRI in two randomized visits: once during intravenous infusion of alcohol, clamped at a steady-state breath alcohol (BrAC) concentration of 60 mg/dL, and once during infusion of placebo saline. An independent reference group (n = 13, age = 23.7, SD = 1.8) was used to identify a priori right prefrontal regions activated by successful inhibition (Inh) trials, relative to {"}Go{"} trials that carried no need for inhibition [Inh > Go]. Results: FHA interacted with alcohol exposure in right prefrontal cortex, where alcohol reduced [Inh > Go] activation in FHN subjects but not in FHP subjects. Within this right frontal cortical region, stop-signal reaction time also correlated negatively with [Inh > Go] activation, suggesting that the [Inh > Go] activity was related to inhibitory behavior. Conclusions: The results are consistent with the low level of response theory (Schuckit, J Stud Alcohol 55:149-158, 1980; Quinn and Fromme, Alcohol Clin Exp Res 35:1759-1770, 2011), with FHP being less sensitive to alcohol's effects.",
keywords = "Alcoholism, Family history, FMRI, Frontal lobes, Impulsivity, Inhibition, Stop signal",
author = "David Kareken and Mario Dzemidzic and Leah Wetherill and William Eiler and Oberlin, {Brandon G.} and Jaroslaw Harezlak and Yang Wang and Sean O'Connor",
year = "2013",
month = "7",
doi = "10.1007/s00213-013-3038-4",
language = "English",
volume = "228",
pages = "335--345",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition

AU - Kareken, David

AU - Dzemidzic, Mario

AU - Wetherill, Leah

AU - Eiler, William

AU - Oberlin, Brandon G.

AU - Harezlak, Jaroslaw

AU - Wang, Yang

AU - O'Connor, Sean

PY - 2013/7

Y1 - 2013/7

N2 - Rationale: Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA). One operational definition of impulsive behavior is the stop-signal task (SST) which measures the time needed to stop a ballistic hand movement. Objective: Employ functional magnetic resonance imaging (fMRI) to study right frontal responses to stop signals in heavy drinking subjects with and without FHA, and as a function of alcohol exposure. Methods: Twenty-two family history-positive (FHP; age = 22.7 years, SD = 1.9) and 18 family history-negative (FHN; age = 23.7, SD = 1.8) subjects performed the SST in fMRI in two randomized visits: once during intravenous infusion of alcohol, clamped at a steady-state breath alcohol (BrAC) concentration of 60 mg/dL, and once during infusion of placebo saline. An independent reference group (n = 13, age = 23.7, SD = 1.8) was used to identify a priori right prefrontal regions activated by successful inhibition (Inh) trials, relative to "Go" trials that carried no need for inhibition [Inh > Go]. Results: FHA interacted with alcohol exposure in right prefrontal cortex, where alcohol reduced [Inh > Go] activation in FHN subjects but not in FHP subjects. Within this right frontal cortical region, stop-signal reaction time also correlated negatively with [Inh > Go] activation, suggesting that the [Inh > Go] activity was related to inhibitory behavior. Conclusions: The results are consistent with the low level of response theory (Schuckit, J Stud Alcohol 55:149-158, 1980; Quinn and Fromme, Alcohol Clin Exp Res 35:1759-1770, 2011), with FHP being less sensitive to alcohol's effects.

AB - Rationale: Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA). One operational definition of impulsive behavior is the stop-signal task (SST) which measures the time needed to stop a ballistic hand movement. Objective: Employ functional magnetic resonance imaging (fMRI) to study right frontal responses to stop signals in heavy drinking subjects with and without FHA, and as a function of alcohol exposure. Methods: Twenty-two family history-positive (FHP; age = 22.7 years, SD = 1.9) and 18 family history-negative (FHN; age = 23.7, SD = 1.8) subjects performed the SST in fMRI in two randomized visits: once during intravenous infusion of alcohol, clamped at a steady-state breath alcohol (BrAC) concentration of 60 mg/dL, and once during infusion of placebo saline. An independent reference group (n = 13, age = 23.7, SD = 1.8) was used to identify a priori right prefrontal regions activated by successful inhibition (Inh) trials, relative to "Go" trials that carried no need for inhibition [Inh > Go]. Results: FHA interacted with alcohol exposure in right prefrontal cortex, where alcohol reduced [Inh > Go] activation in FHN subjects but not in FHP subjects. Within this right frontal cortical region, stop-signal reaction time also correlated negatively with [Inh > Go] activation, suggesting that the [Inh > Go] activity was related to inhibitory behavior. Conclusions: The results are consistent with the low level of response theory (Schuckit, J Stud Alcohol 55:149-158, 1980; Quinn and Fromme, Alcohol Clin Exp Res 35:1759-1770, 2011), with FHP being less sensitive to alcohol's effects.

KW - Alcoholism

KW - Family history

KW - FMRI

KW - Frontal lobes

KW - Impulsivity

KW - Inhibition

KW - Stop signal

UR - http://www.scopus.com/inward/record.url?scp=84879967945&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879967945&partnerID=8YFLogxK

U2 - 10.1007/s00213-013-3038-4

DO - 10.1007/s00213-013-3038-4

M3 - Article

VL - 228

SP - 335

EP - 345

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 2

ER -