As indicated on my homepage, my current research in my laboratory is organized around 2 broad aims. More detailed information about each of these aims is provided below.

Broad Aim 1:  Classic and contemporary theories of addiction indicate that AOD addiction results, in part, from neuroadaptive change in affect and motivation systems in response to repeated AOD use.  Many of these theories highlight adaptation in stress systems as an etiological mechanism in the development of addiction across many classes of drugs (Solomon & Corbit, 1974; Koob & LeMoal, 2008; Baker et al., 2004).   In short, repeated homeostatic adjustments in stress systems provoked by periods of acute intoxication eventually lead to compensatory chronic adaptations in the structures involved in affective response and its regulation.  These compensatory adaptations persist beyond periods of acute use and result in dysregulated negative affect (e.g., increased anxiety) on cessation of drug use. Further drug use by the addict is strongly motivated by the expected short-term reduction in negative affect provided by intoxication.  Animal addiction models that document neuroadaptive changes in stress systems resulting from repeated drug administration provide an important foundation for these theories (e.g., for review, see Koob & LeMoal, 2008).  Reliable self-report of increased negative affect during withdrawal from most common “addictive” drugs (e.g., alcohol, nicotine, opiates; see Baker et al 2004 for review) in humans provide preliminary (albeit weak) support for these theories.  A primary goal of my translational research program is to confirm and extend findings from animal addiction models to humans using similar laboratory procedures.  The use of similar methods (e.g., fear conditioning) and measures (e.g. fear-potentiated startle) provide an important translational bridge between research with animal models and human addiction research.  

My research uses drug administration studies in social users to identify the affective processes and neurobiological substrates that are altered during periods of acute intoxication (e.g., Curtin et al., 1998, 2001; Donohue, Curtin et al. 2006, Moberg & Curtin, under review; Curtin, Moberg, & Weber, in preparation).  This research is designed to identify (and characterize) the processes and associated neural substrates that would be expected to experience pressure to adapt in response to chronic drug use.  My research also uses acute and chronic drug withdrawal studies in drug dependent users to confirm that drug-opposite adaptations in these processes have occurred among addicts.  For practical reasons, I initiated this line of withdrawal research using nicotine withdrawal as a model (e.g., Hogle & Curtin, 2006, in preparation, Piper & Curtin, 2006;  McCarthy, Gloria, & Curtin, in press).  However, I have recently extended this research to include acute withdrawal from alcohol (Hefner & Curtin, in progress) and withdrawal following chronic marijuana use (Gloria & Curtin, in progress), with near term future plans to study opiate withdrawal.  My use of systematic laboratory drug administration and drug withdrawal studies in humans using varied addictive drugs in similar experimental paradigms provides an important method to identify stress-related adaptations that support addictive drug use.  Specifically, paradigms that reveal antagonistic/compensatory effects during drug administration vs. drug withdrawal provide strong support for these models of neuroadaptive changes in stress underlying addiction in humans.   

To my knowledge, this systematic comparison of drug administration and drug withdrawal effects in humans, using methods and measures that facilitate the development of animal-human research translational bridges, is unique to my laboratory.  To date, we have documented several mechanisms through which alcohol administration acutely reduces negative affective response.  At low to moderate doses, alcohol appears to reduce negative affect indirectly through alterations in attention function (Curtin et al., 1998, 2001).  At higher doses, alcohol selectively reduces negative affect (while sparing positive affective response), which is consistent with increased GABAergic inhibition of amygdala function when intoxicated (Donohue, Curtin, et al 2006; Curtin, Moberg, and Weber, in preparation).  However, we also have observed a specific reduction of anxiety (but not fear or other negative affect) even at moderate doses (Moberg & Curtin, under review).  This selective effect of moderate doses of alcohol on anxiety fits with other recent research with animals and humans indicating that fear and anxiety are distinct types of negative affective response with dissociable neural substrates (Walker et al., 2003; Grillon, 2007). Critically, recent research in our laboratory has determined that withdrawal from nicotine is characterized by selective increases in anxiety but not other types of negative affective response (Hogle & Curtin, in prep; Hogle & Curtin, 2006; Piper & Curtin, 2006).  We have observed similar evidence of selective anxiety increases in preliminary data generated in an ongoing study of acute alcohol withdrawal (Hefner & Curtin, in progress).  These observations of selective decrease in anxiety during alcohol intoxication and increase in anxiety during nicotine (and possibly acute alcohol) withdrawal provide the platform for our current cross drug investigations and for near term future investigations of individual differences in these effects associated with pre-morbid risk for addiction.  This research has the potential to address central questions in the field of addiction such as what is the nature of drug craving, how does craving develop, and what are the individual differences that confer risk for addiction. 

 

Broad Aim 2:  Acute alcohol intoxication frequently results in various forms of dysregulated responding including aggression, sexual and other risk taking, alterations in emotional response, and even apparent temporary loss of control over alcohol use itself (e.g., Steele & Josephs, 1990; Curtin et al., 2001, 2003).  Many examples in which alcohol intoxication results in these dysregulated responses are characterized by conflict between strong, but inappropriate, response tendencies and incompatible alternative responses that are more adaptive yet weaker.  For instance, unprotected sexual intercourse may occur when a strong and immediate appetitive response tendency conflicts with the inclination to delay or abstain from intercourse until appropriate protection is available.  Similarly, aggressive response may result when salient physical or verbal provocation cues overcome competing environmental or internal cues (e.g., knowledge about potential adverse consequences of aggression) that suggest alternative non-aggressive response.   Thus, alcohol intoxication may impair the attention processes associated with the adaptive resolution of conflict.  One facet of this second broad aim of my research program is to confirm and clarify the nature of the effects of alcohol administration on attention function and to examine its consequences for intoxicated regulation of behavior.  

In a related vein, alcohol and other drug dependent users frequently experience conflict or ambivalence surrounding their AOD use itself (Curtin et al., 2005).  Available evidence suggests that AOD dependent users may be impaired in the attention functions that are necessary to adaptively resolve this conflict surrounding their use (e.g., Peoples, 2002).  In fact, theorists have recently speculated that the same attention mechanisms that account for the acute effects of alcohol administration described above may also be chronically impaired in individuals with AOD use and other externalizing disorders (Fillmore & Vogel-Sprott, 1999; Patrick, Curtin, & Kruger, in press).  In fact, this trait-like impaired attention function may be a pre-morbid risk factor for the development of AOD use disorders (Curtin et al., 2005) and more generally externalizing behaviors (e.g., aggression) and associated disorders (antisocial personality disorder, psychopathy).  Another facet of this second broad aim is to examine the interactions between cognitive and emotional processes as they relate to the cognitive control of AOD use and other externalizing behaviors. 

Unfortunately, “attention”, as it is typically used in AOD research, is a broad and somewhat ill-defined construct.  Research examining attention often inadvertently lumps together separate cognitive processes under this label and this shortcoming may have slowed progress.  Recent theory and basic cognitive neuroscience research has significantly advanced and refined understanding about the attention processes and underlying neurobiological structures that are necessary for the adaptive regulation of behavior and emotional response during conflict.  This research has identified discrete functions of the attention system including maintenance of an alert state, sensory orienting, and executive control function responsible for the control of cognitive operations (Posner & DiGirolamo, 2000).  In particular, executive control attention (and sub-components; evaluative, and regulative control) is crucial to overcome contextually maladaptive, strong and/or habitual responding in situations characterized by response conflict (Botvinick, 2001).  Thus, impairment in executive control processes may underlie dysregulared behavior when intoxicated and similar externalize problems in individuals at risk of AOD disorders and/or antisocial personality disorder.  

This program of research respects these potentially important distinctions between components of the attention system.  This research involves the simultaneous measurement of behavior, cognitive function using event related brain potentials and in some instances affective response (using startle potentiation) in well-validated cognitive/cognitive neuroscience paradigms.  For example, in a pair of experiments published in Journal of Abnormal Psychology (Curtin & Fairchild, 2003; Casbon, Curtin, et al., 2003) using Stroop and n-back tasks, we demonstrated with behavioral and ERP measures that alcohol disinhibits maladaptive prepotent responding (established either contextually or through prior learning) through selective impairment of cognitive control processes.  More recent research funded by an active grant from NIAAA has indicated that these problems may more narrowly stem from deficits in evaluative cognitive control processes that are important for detecting conflict adjusting the level of top-down cognitive control as situational demands change (Curtin & Moberg, under review, Curtin Rothwell, & Gloria, in preparation).  In collaboration with my colleague Joe Newman at Wisconsin, we have demonstrated the abnormal affective response associated with individual differences in trait anxiety and psychopathy result, in part, from attention and working memory deficits (e.g., trait anxiety: Dvorak-Bertsch, Curtin et al., 2007; psychopathy relevant individual differences: Dvorak-Bertsch, Curtin et al., 2007; psychopathy in incarcerated criminal offenders: Newman, Curtin, et al. in prep).  Dr. Newman and I have an active R01 from NIMH to further clarify these initial findings among criminal offenders.  In collaboration with my colleague Edelyn Verona at the University of Illinois, we have examined affect-instigated aggressive responding in a series of experiments  using startle response and lateralized EEG indices (Verona & Curtin, 2006; Verona, Pole, Reed, & Curtin, 2007; Verona, Sadeh & Curtin, in press).  In general, research directed toward this broad aim has the potential to address critical questions in the field of addiction such as who is at risk to develop problems with AOD use, how do people successfully control strong urges when attempting to cease drug use, what contextual factors and individual differences affect risk for relapse after treatment, and more generally, what deficits underlie externalizing behavior and related disorders.

 

References from Research Statement

Note: Research from my laboratory is highlighted in bold in this reference list to distinguish it from basic science generated by other laboratories.  See my CV for full list of my publications.

 
Baker, T. B., Piper, M. E., McCarthy, D. E., Majeskie, M. R., & Fiore, M. C. (2004). Addiction motivation reformulated: an affective processing model of negative reinforcement. Psychological Review, 111, 33-51.

Botvinick, M. M., Braver, T. S., Barch, D. M., Carter, C. S., & Cohen, J. D. (2001). Conflict monitoring and cognitive control. Psychological Review, 108, 624-652.

Casbon, T. S., Curtin, J. J., Lang, A. R., & Patrick, C. J. (2003). Deleterious effects of alcohol intoxication: Diminished cognitive control and its behavioral consequences. Journal of Abnormal Psychology, 112, 476-487.

Curtin, J. J.,  Rothwell, P., & Gloria, R. (in preparation).  Alcohol expectancy and pharmacology: Cognitive mechanisms underlying behavior regulation effects.  In preparation.

Curtin, J. J., & Fairchild, B. A. (2003). Alcohol and cognitive control: Implications for regulation of behavior during response conflict. Journal of Abnormal Psychology, 112, 424-436.

Curtin, J. J., Lang, A. R., Patrick, C. J., & Stritzke, W. G. K. (1998). Alcohol and fear-potentiated startle:  The role of competing cognitive demands in the stress-reducing effects of intoxication. Journal of Abnormal Psychology, 107(4), 547-565.

Curtin, J. J., McCarthy, D. E., Piper, M. E., & Baker, T. B. (2005).  Implicit and explicit drug motivational processes: A model of boundary conditions.  In R. Reinout and A. Stacy (Eds.), Handbook on Implicit Cognition and Addiction (pp 233-250).  Sage Publications.

Curtin, J. J. & Moberg, C. A. (under review).  Alcohol and cognitive control: A mechanism for selective impairment of prepotent response inhibition during response conflict.  Under review.

Curtin, J. J., Moberg, C. A., & Weber, S. (in prep).  Alcohol dose response on fear potentiated startle across varying threat intensity.  In preparation.

Curtin, J. J., Patrick, C. J., Lang, A. R., Cacioppo, J. T., & Birbaumer, N. (2001). Alcohol affects emotion through cognition. Psychological Science, 12, 527-531.

Davidson, R. J. (1998). Affective style and affective disorders: Perspectives from affective neuroscience. Cognition and Emotion, 12(3), 307-330.

Davis, M., Falls, W. A., Campeau, S., & Kim, M. (1993). Fear-potentiated startle: A neural and pharmacological analysis. Behavioural Brain Research, 58, 175-198.

Donohue, K., Curtin, J. J., Patrick, C. J., & Lang, A. R. (2007). Intoxication Level and Emotional Response. Emotion, 7, 103–112.

Dvorak-Bertsch, J. D., Curtin, J. J., Rubinstein, T. J., & Newman, J. P. (2007). Anxiety moderates the interplay between cognitive and affective processing. Psychological Science, 18, 699-705.

Dvorak-Bertsch*, J. D., Curtin, J. J., Rubinstein*, T. J., & Newman, J. P. (in press).  Psychopathic traits moderate the interaction between cognitive and affective processing.  Psychophysiology.

Fillmore, M. T., & Vogel-Sprott, M. (1999). An alcohol model of impaired inhibitory control and its treatment in humans. Experimental and Clinical Psychopharmacology, 7, 49-55.

Gloria, R. & Curtin, J. J. (in progress).  Affective response during marijuana withdrawal: fear vs. anxiety effects.  In progress.

Grillon, C. (2007). Models and mechanisms of anxiety: Evidence from startle studies. Psychopharmacology.

Hefner, K. R. & Curtin, J. J. (in progress).  Affective response during acute alcohol withdrawal: fear vs. anxiety effects.  In progress.

Hogle, J. M., & Curtin, J. J. (2006). Sex differences in negative affective response during nicotine withdrawal. Psychophysiology, 43, 344-356.

Hogle, J. M. & Curtin, J. J. (in prep).  Nicotine deprivation selectively exacerbates anxiety: Implications for neuroadaptive changes in stress response in addiction.  Manuscript in preparation.

Koob, G. F., &LeMoal, M. L. (2008). Addiction and the Brain Antireward System. Annual Review of Psychology, 59, 29-53.

Lang, P. J. (1995). The emotion probe. Studies of motivation and attention. American Psychologist, 50, 372-385.

LeDoux, J. E. (1995). Emotion Clues from the brain. Annual Review of Psychology, 46, 209-235.

Miller, E., K., & Cohen, J. D. (2001). An integrative theory of prefrontal cortex function. Annual Review of Neuroscience, 24(167-202).

Moberg, C. A. & Curtin, J. J. (under review).  Alcohol selectively reduces anxiety but not fear: A single dissociation verified via startle response measurement.  Revise and re-submit at Journal of Abnormal Psychology.

McCarthy, D. E., Gloria, R., & Curtin, J. J. (in press).  Attention Bias in Nicotine Withdrawal and Under Stress.  Psychology of Addictive Behaviors.

Newman, J. P., Curtin, J. J., Baskin-Sommer, A, B., & Dvork-Bertsch, J. D. (in preparation).  Deficient fear response among psychopathic criminal offenders mediated by attentional focus and working memory impairment. Manuscript in preparation.

Patrick, C. J., Curtin, J. J., & Krueger, R. F. (in press) The externalizing spectrum: Structure and etiology.  In D. Barch (Ed.), Cognitive and Affective Neuroscience of Psychopathology.

Peoples, L. L. (2002). Neuroscience. Will, anterior cingulate cortex, and addiction. Science, 296(5573), 1623-1624.

Piper, M. E., & Curtin, J. J. (2006). Tobacco Withdrawal and Negative Affect: An Analysis of Initial Emotional Response Intensity and Voluntary Emotion Regulation. Journal of Abnormal Psychology, 115(1), 96-102.

Posner, M. I., & DiGirolamo, G. J. (2000). Attention in cognitive neuroscience: An overview. In M. S. Gazzaniga (Ed.), The new cognitive neurosciences (pp. 623-631).

Solomon, R. L., & Corbit, J. D. (1974). An opponent-process theory of motivation: I. Temporal dynamics of affect. Psychological Review, 81, 119-145.

Steele, C., & RA, J. (1990). Alcohol myopia. Its prized and dangerous effects. American psychologist, 45(8), 921-933.

Verona, E. & Curtin, J. J. (2006).  Gender differences in the negative affective priming of aggressive behavior.  Emotion, 6, 115-124.

Verona, E., Pole, M., Reed, A., & Curtin, J. J. (2007).  Gender differences in emotional and overt/covert aggressive responses to stress.  Aggressive Behavior, 33, 261-271.

Verona, E., Sadeh, N., & Curtin, J. (in press).  Fight or Flight: Stress Exposure, Frontal EEG-Alpha Asymmetry, and Aggressive Reactions.  Journal of Abnormal Psychology.

Walker, D. L., Toufexis, D. J., & Davis, M. (2003). Role of the bed nucleus of the stria terminalis versus the amygdala in fear, stress, and anxiety. European Journal of Pharmacology, 463, 199- 216.

[back to top]

 

© 2000 by the Board of Regents of the University of Wisconsin System.
Last Revised:
comments?