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Acute alcohol challenge studies: Implications for cognitive control and the adaptive regulation of behavior John J. C

Reasons to be Interested ?. Primary focus on cognitive mechanisms underlying alcohol effects on behavior and emotionIndividual differences in these cognitive processes contribute to risk for alcohol use disorders (and maybe externalizing disorders)?Cognitive/attentional mechanisms necessary for

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Acute alcohol challenge studies: Implications for cognitive control and the adaptive regulation of behavior John J. C

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    1. Acute alcohol challenge studies: Implications for cognitive control and the adaptive regulation of behavior John J. Curtin, Ph.D. Department of Psychology University of Wisconsin- Madison

    2. Reasons to be Interested ? Primary focus on cognitive mechanisms underlying alcohol effects on behavior and emotion Individual differences in these cognitive processes contribute to risk for alcohol use disorders (and maybe externalizing disorders)? Cognitive/attentional mechanisms necessary for the adaptive regulation of behavior Acute/temporary pharmacologic lesion analogy Clarify processes involved in classic cognitive paradigms, ERP measures, and behavior regulation Before I jump into the meat of this talk, I wanted to take a brief moment to try to expand the interest value of the research I will be presenting today. The primary focus of this talk will be on the cognitive mechanisms that account for the acute effects of alcohol intoxication on the regulation of behavior and emotion in social or non-problem drinkers. However, for those in the audience with clinical interests, I’d like to hook you in by asking that you consider whether individual differences in the cognitive processes that I am talking about today may contribute to risk for the development of alcohol use disorders or maybe even externalizing disorders more generally. In fact, I will actually return explicitly to this idea at the conclusion of my talk. For individuals here whose interests are more cognitive, I’d like you to consider whether these data can advance our understanding of the basic cognitive/attentional mechanisms necessary for adaptive regulation of behavior. I’d like suggest that we can use results from alcohol challenge research as a way of grossly manipulating the integrity of certain cognitive processes and this may help us clarify the contribution of these processes in classic cognitive paradigms and more generally in the regulation of behavior. I will highlight the utility of this approach explicitly when I talk about our results in the flanker task but it will be an underlying theme throughout this talk.Before I jump into the meat of this talk, I wanted to take a brief moment to try to expand the interest value of the research I will be presenting today. The primary focus of this talk will be on the cognitive mechanisms that account for the acute effects of alcohol intoxication on the regulation of behavior and emotion in social or non-problem drinkers. However, for those in the audience with clinical interests, I’d like to hook you in by asking that you consider whether individual differences in the cognitive processes that I am talking about today may contribute to risk for the development of alcohol use disorders or maybe even externalizing disorders more generally. In fact, I will actually return explicitly to this idea at the conclusion of my talk. For individuals here whose interests are more cognitive, I’d like you to consider whether these data can advance our understanding of the basic cognitive/attentional mechanisms necessary for adaptive regulation of behavior. I’d like suggest that we can use results from alcohol challenge research as a way of grossly manipulating the integrity of certain cognitive processes and this may help us clarify the contribution of these processes in classic cognitive paradigms and more generally in the regulation of behavior. I will highlight the utility of this approach explicitly when I talk about our results in the flanker task but it will be an underlying theme throughout this talk.

    3. Intoxicated Behavior Aggression Sexual and other risk-taking activities Driving while intoxicated Altered emotional/stress response “Loss of control” drinking Deficits in response inhibition paradigms Go/No-Go [Finn, Justus, Mazas, & Steinmetz, 1999] Go/Stop [Fillmore & Vogel-Sprott, 1999] N-back* [Casbon, Curtin, Lang, & Patrick, 2003] Stroop tasks* [Curtin & Fairchild, 2003; Curtin & Rothwell, in prep] Flanker* [Curtin & Green, under review] Affective conflict*[Curtin, Patrick, Lang, Cacioppo, Birbaumer, 2001] When we think about intoxicated behavior, what comes to mind? Frequently we think of aggression, sexual and other risk taking behaviors, and more clinically, perhaps loss of control over the drinking behavior itself. In the laboratory recent research has demonstrated robust acute alcohol challenge effects on response inhibition, Go/No go tasks, Go/Stop tasks and I am going to present data today from these latter paradigms including variants of the Stroop and Flanker task. What I find most interesting about considering these effects integratively and thinking about mechanisms for these effects is that many if not all of these behaviors that we associate with alcohol appear to be characterized by response conflict. And by response conflict, I mean that these situations and tasks simultaneously activate competing incompatible responses. For instance, unprotected sexual intercourse may occur when a strong and immediate appetitive response tendency elicited by an attractive potential mate 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 which suggest alternative non-aggressive response. Thus, understanding the mechanisms that are important for adaptively addressing response conflict appears to be a reasonable starting point for examining possible mechanisms of action for alcohol. And this leads us immediately to consider attentional processes.When we think about intoxicated behavior, what comes to mind? Frequently we think of aggression, sexual and other risk taking behaviors, and more clinically, perhaps loss of control over the drinking behavior itself. In the laboratory recent research has demonstrated robust acute alcohol challenge effects on response inhibition, Go/No go tasks, Go/Stop tasks and I am going to present data today from these latter paradigms including variants of the Stroop and Flanker task. What I find most interesting about considering these effects integratively and thinking about mechanisms for these effects is that many if not all of these behaviors that we associate with alcohol appear to be characterized by response conflict. And by response conflict, I mean that these situations and tasks simultaneously activate competing incompatible responses. For instance, unprotected sexual intercourse may occur when a strong and immediate appetitive response tendency elicited by an attractive potential mate 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 which suggest alternative non-aggressive response. Thus, understanding the mechanisms that are important for adaptively addressing response conflict appears to be a reasonable starting point for examining possible mechanisms of action for alcohol. And this leads us immediately to consider attentional processes.

    4. Cognitive Neuroscience of Attention Attention is a broad construct Multiple functions include (Posner, 1995): Maintenance of alert state Sensory attention/orienting and stimulus evaluation Executive attention (Cognitive control) Different neural sub-systems responsible for these functions NE pathways from locus coeruleus for arousal/alerting Posterior system* involving cholinergic pathways for attentional engagement/disengagement and moving (parietal lobe, pulvinar, superior colliculus) Anterior cognitive control system involving dopaminergic pathways (ACC, PFC, SMA) In the alcohol and addiction area, we often see theory talking about attentional effects of alcohol to explain behavioral and emotional consequences of acute use. However, the construct of attention is used rather broadly and loosely and I think that is hindering our ability to advance theory in this area. Current cognitive neuroscience theory and data suggest that there are multiple functions of attention and that these different functions are accomplished within separable neurobiological attention networks. For example, when Posner and colleagues talk about attention they highlight three separate networks, one involving NE pathways from LC that are important for the maintenance of an alert state, one involving sensory orienting responsible for stimulus evaluation and this appears to be accomplished in a posterior neural system and lastly, an executive attention network which is important for pre-potent response inhibition during response conflict among other functions and is accomplished in an anterior network involving anterior cingulate and prefrontal cortex. Given the different neural structures and predominate neurotransmitter systems underlying these various attention functions, it is certainly reasonable if not expected that acute alcohol challenge might affect some but not other attention functions. So a major theme in the research I will present today is to separately examine various components of attentional function.In the alcohol and addiction area, we often see theory talking about attentional effects of alcohol to explain behavioral and emotional consequences of acute use. However, the construct of attention is used rather broadly and loosely and I think that is hindering our ability to advance theory in this area. Current cognitive neuroscience theory and data suggest that there are multiple functions of attention and that these different functions are accomplished within separable neurobiological attention networks. For example, when Posner and colleagues talk about attention they highlight three separate networks, one involving NE pathways from LC that are important for the maintenance of an alert state, one involving sensory orienting responsible for stimulus evaluation and this appears to be accomplished in a posterior neural system and lastly, an executive attention network which is important for pre-potent response inhibition during response conflict among other functions and is accomplished in an anterior network involving anterior cingulate and prefrontal cortex. Given the different neural structures and predominate neurotransmitter systems underlying these various attention functions, it is certainly reasonable if not expected that acute alcohol challenge might affect some but not other attention functions. So a major theme in the research I will present today is to separately examine various components of attentional function.

    5. Attention Networks in the Brain

    6. Cognitive Control Given its arguablely important role in situations involving response conflict, I’ve been particularly interested in the possibility that acute deficits in cognitive control processes can account for alcohol effects on behavior. Cognitive control has been defined as effortful activation and allocation of cognitive resources in the selection and processing of task-relevant information for purposes of maximizing performance on tasks involving high difficulty, complexity, response conflict, or novelty Cognitive control is important to guide behavior in a flexible fashion Biases processing of information in favor of task-relevant stimuli and adaptive responses, in particular when response conflict exists Establishes the appropriate stimulus-response mapping Incongruent color naming trials in the classic Stroop task are the perfect example of a situation that requires cognitive control for flexible, adaptive behavior. When participants are presented with the word RED written in blue ink, both Red and Blue response options are activated, but the word reading option is activated more strongly, presumably because of the vastly greater experience word reading vs. color naming. However, we all can indeed overcome the activation provided by the word and instead name the ink color and cognitive control processes are thought to provide the boost that allows the color naming response to win out when necessary. Given its arguablely important role in situations involving response conflict, I’ve been particularly interested in the possibility that acute deficits in cognitive control processes can account for alcohol effects on behavior. Cognitive control has been defined as effortful activation and allocation of cognitive resources in the selection and processing of task-relevant information for purposes of maximizing performance on tasks involving high difficulty, complexity, response conflict, or novelty Cognitive control is important to guide behavior in a flexible fashion Biases processing of information in favor of task-relevant stimuli and adaptive responses, in particular when response conflict exists Establishes the appropriate stimulus-response mapping Incongruent color naming trials in the classic Stroop task are the perfect example of a situation that requires cognitive control for flexible, adaptive behavior. When participants are presented with the word RED written in blue ink, both Red and Blue response options are activated, but the word reading option is activated more strongly, presumably because of the vastly greater experience word reading vs. color naming. However, we all can indeed overcome the activation provided by the word and instead name the ink color and cognitive control processes are thought to provide the boost that allows the color naming response to win out when necessary.

    7. Components of Cognitive Control Theory on cognitive control also draws important distinctions between two subcomponents of control. Evaluative control is responsible for monitoring the need for control and signaling when adjustments in control are necessary. In essence this is an action monitoring system that is designed to detect indicants that our current behavior is not working for us and more regulative attention is needed to behave adaptively. Response conflict is one such indicator and recent research suggests that evaluative control is accomplished in anterior cingulate cortex. Regulative control includes the processes related to the actual implementation of control. In other words, establishing of the appropriate stimulus response mappings and the biasing of response toward task relevant or goal directed behaviors. PFC is thought to be particularly important for regulative control. Theory on cognitive control also draws important distinctions between two subcomponents of control. Evaluative control is responsible for monitoring the need for control and signaling when adjustments in control are necessary. In essence this is an action monitoring system that is designed to detect indicants that our current behavior is not working for us and more regulative attention is needed to behave adaptively. Response conflict is one such indicator and recent research suggests that evaluative control is accomplished in anterior cingulate cortex. Regulative control includes the processes related to the actual implementation of control. In other words, establishing of the appropriate stimulus response mappings and the biasing of response toward task relevant or goal directed behaviors. PFC is thought to be particularly important for regulative control.

    8. Important Themes to Track and Clarify OK, I am going to take you through a series of five experimental studies that examine the effects of alcohol challenge on behavior and emotion. These studies are all tied together by a handful of important themes that I would like to emphasis up front to allow you to track and evaluate. First, I want to suggest that alcohol selectively alters behavior in situations characterized by response conflict. I put response conflict in quotes b/c I believe we have a bit more work to due in specifying exactly what that term means and clarifying potentially what types of response conflict, if there are types, are sensitive to alcohol. We will see a bit of this when I present results from the flanker task Second, when response conflict exists, alcohol will alter behavior by disinhibiting pre-potent responding. I highlight disinhibit b/c we frequently refer to intoxicated people as being disinhibited but when I present data on error rates from the n-back paradigm, we will see that this term needs some clarification as well, at least with respect to its lay usage. Similarly, I borrow the term pre-potent directly from writings on cognitive control, but central to the clarifications involving response conflict is a need to clarify what we mean when we say pre-potent as well. Finally, throughout all of the studies I will present, I will be suggesting that the behavioral and emotional effects of alcohol result from impairments in cognitive control processes but that other attentional functions related to stimulus evaluation, for example, are spared when intoxicated. OK, I am going to take you through a series of five experimental studies that examine the effects of alcohol challenge on behavior and emotion. These studies are all tied together by a handful of important themes that I would like to emphasis up front to allow you to track and evaluate. First, I want to suggest that alcohol selectively alters behavior in situations characterized by response conflict. I put response conflict in quotes b/c I believe we have a bit more work to due in specifying exactly what that term means and clarifying potentially what types of response conflict, if there are types, are sensitive to alcohol. We will see a bit of this when I present results from the flanker task Second, when response conflict exists, alcohol will alter behavior by disinhibiting pre-potent responding. I highlight disinhibit b/c we frequently refer to intoxicated people as being disinhibited but when I present data on error rates from the n-back paradigm, we will see that this term needs some clarification as well, at least with respect to its lay usage. Similarly, I borrow the term pre-potent directly from writings on cognitive control, but central to the clarifications involving response conflict is a need to clarify what we mean when we say pre-potent as well. Finally, throughout all of the studies I will present, I will be suggesting that the behavioral and emotional effects of alcohol result from impairments in cognitive control processes but that other attentional functions related to stimulus evaluation, for example, are spared when intoxicated.

    9. General Procedures 32-64 social drinkers from university community Beverage Group (BG) manipulated between subjects Alcohol (Target BALs of .075 - .080%) No-alcohol control (placebo in trial frequency Stroop) Short duration tasks on ascending limb of BAC Behavior (RT, % error) as outcome measures Event related brain potentials (P3, NSW, N2, ERN) Before moving on to specific experiments, let me specify some general procedures that are used across all experiments. The participants in these studies are social drinkers for the community. This is not a clinical or at risk sample. However, if interested, I can talk later about research I have begun with individuals recruited because of their increased risk for alcoholism. All studies will involve a between subjects manipulation of beverage. Target blood alcohol levels for these studies ranged from .075 to .080- about 2-3 drinks in a 150 man in an hour. Mild to moderately intoxicated. All but one of the studies involve true no-alcohol control groups. However, we have run one placebo control with some interesting expectancy effects which I could also talk about during question period if anyone is interested. All the tasks are designed to be short (20-30m max) and placed on the ascending limb of the blood alcohol curve b/c there is some evidence to suggest that the cognitive effects are different while blood alcohol levels are rising vs. post peak and falling. I will present behavioral or in one case emotional measures as the outcome measure of alcohol’s effect. In most of the studies, I will present ERP effects to index the potential cognitive mediators of these behavioral and emotional outcomes. Will focus on these 4 components: P3 which depending on the paradigm and task manipulations is sensitive to either stimulus evaluation or regulative control attentional processes, an anterior negative slow wave that appears to be sensitive to regulative control and then N2 and ERN which some recent evidence suggests are both indices of conflict monitoring processes in ACC. Before moving on to specific experiments, let me specify some general procedures that are used across all experiments. The participants in these studies are social drinkers for the community. This is not a clinical or at risk sample. However, if interested, I can talk later about research I have begun with individuals recruited because of their increased risk for alcoholism. All studies will involve a between subjects manipulation of beverage. Target blood alcohol levels for these studies ranged from .075 to .080- about 2-3 drinks in a 150 man in an hour. Mild to moderately intoxicated. All but one of the studies involve true no-alcohol control groups. However, we have run one placebo control with some interesting expectancy effects which I could also talk about during question period if anyone is interested. All the tasks are designed to be short (20-30m max) and placed on the ascending limb of the blood alcohol curve b/c there is some evidence to suggest that the cognitive effects are different while blood alcohol levels are rising vs. post peak and falling. I will present behavioral or in one case emotional measures as the outcome measure of alcohol’s effect. In most of the studies, I will present ERP effects to index the potential cognitive mediators of these behavioral and emotional outcomes. Will focus on these 4 components: P3 which depending on the paradigm and task manipulations is sensitive to either stimulus evaluation or regulative control attentional processes, an anterior negative slow wave that appears to be sensitive to regulative control and then N2 and ERN which some recent evidence suggests are both indices of conflict monitoring processes in ACC.

    10. Modified N-Back Task OK, lets start first by considering alcohol effects on task performance in the n-back paradigm. We chose the n-back paradigm because it includes a well-validated manipulation of working memory load and working memory function is crucial for cognitive control. In this paradigm, participants view a series of letters presented sequentially on the computer monitor and are instructed to press a button every time the current letter matches a letter presented n trials back- in this case one or two. So for example, if you are in a 1-back condition, you simply have to identify when the current letter has been repeated and press the button. [DO EXAMPLE] OK, lets start first by considering alcohol effects on task performance in the n-back paradigm. We chose the n-back paradigm because it includes a well-validated manipulation of working memory load and working memory function is crucial for cognitive control. In this paradigm, participants view a series of letters presented sequentially on the computer monitor and are instructed to press a button every time the current letter matches a letter presented n trials back- in this case one or two. So for example, if you are in a 1-back condition, you simply have to identify when the current letter has been repeated and press the button. [DO EXAMPLE]

    11. Modified N-Back Task Whereas in the two back condition a substantially heavier load is placed on working memory function. On each trial you have to manipulate the contents in working memory to keep track of which is the last and which is two back and update this ordering on each trial [DO EXAMPLE] The n-back task can be varied from 0-back where you just detect a target letter through 3-4 back, but imaging work has demonstrated significantly greater activation of the PFC and related neural structures implicated in cognitive control processes during the 2 vs. 1 back conditions. In other words, there seems to be a qualitative shift in the processes involved in 1 vs. 2 back. Thus, if alcohol compromised cognitive control function, we should see these effects clearly in the two back condition. We also included a more novel manipulation that was tailored to our aim of examining behavior regulation in the presence of pre-potent response activation. We manipulated the stimuli and task instructions such that some blocks required responding on 80% of trials and other blocks required responding on only 20% of trials. The 80% response blocks were designed to produce a pre-potent response tendency to respond whereas the 20% response blocks, where the majority of trials required no response, were designed to produce a pre-potent response tendency to withhold response. This allowed us to determine if alcohol biased responding toward the prepotent response tendency and to determine if this effect differed based on the type of prepotent tendency we established.Whereas in the two back condition a substantially heavier load is placed on working memory function. On each trial you have to manipulate the contents in working memory to keep track of which is the last and which is two back and update this ordering on each trial [DO EXAMPLE] The n-back task can be varied from 0-back where you just detect a target letter through 3-4 back, but imaging work has demonstrated significantly greater activation of the PFC and related neural structures implicated in cognitive control processes during the 2 vs. 1 back conditions. In other words, there seems to be a qualitative shift in the processes involved in 1 vs. 2 back. Thus, if alcohol compromised cognitive control function, we should see these effects clearly in the two back condition. We also included a more novel manipulation that was tailored to our aim of examining behavior regulation in the presence of pre-potent response activation. We manipulated the stimuli and task instructions such that some blocks required responding on 80% of trials and other blocks required responding on only 20% of trials. The 80% response blocks were designed to produce a pre-potent response tendency to respond whereas the 20% response blocks, where the majority of trials required no response, were designed to produce a pre-potent response tendency to withhold response. This allowed us to determine if alcohol biased responding toward the prepotent response tendency and to determine if this effect differed based on the type of prepotent tendency we established.

    12. Modified N-Back Task To accomplish this goal, we examined commission and omission errors. If alcohol interferes with cognitive control processes necessary to overcome pre-potent responding when it conflicts with the weaker but correct response, you would expect to see increased commission errors in 80% response blocks. Conversely, we should observe increased omission errors in 20% blocks where the pre-potent tendency is to withhold response. To accomplish this goal, we examined commission and omission errors. If alcohol interferes with cognitive control processes necessary to overcome pre-potent responding when it conflicts with the weaker but correct response, you would expect to see increased commission errors in 80% response blocks. Conversely, we should observe increased omission errors in 20% blocks where the pre-potent tendency is to withhold response.

    13. Commission and Omission Error Rates When we consider specific error rates, this is exactly what we see. Here we are looking at commission errors by Beverage group, memory load and block response frequency. No alcohol on the left, alcohol on the right. Heavy load in gray, light load in white and 80% response blocks are indicated by diagonal lines. Remember that commission errors occur when the participant responds on a trial that he or she should not. First we see that as expected, commission errors are more common during 80% response frequency blocks. Also, we see that this pre-potent response errors are greater in general when working memory is loaded as expected if this working memory load interferes with cognitive control. Most importantly though, alcohol exacerbated this effect. In fact, we observe a nice 3-way interaction and if you perform the simple beverage group contrasts across memory load and block response frequency, we only observe a significant beverage effect for commission errors during heavy load 80% response frequency blocks. This is a nice demonstration about how alcohol can produce typical disinhibited behavior when you further tax working memory processes important for cognitive control. However, we were more excited still about the omission error data. When we consider specific error rates, this is exactly what we see. Here we are looking at commission errors by Beverage group, memory load and block response frequency. No alcohol on the left, alcohol on the right. Heavy load in gray, light load in white and 80% response blocks are indicated by diagonal lines. Remember that commission errors occur when the participant responds on a trial that he or she should not. First we see that as expected, commission errors are more common during 80% response frequency blocks. Also, we see that this pre-potent response errors are greater in general when working memory is loaded as expected if this working memory load interferes with cognitive control. Most importantly though, alcohol exacerbated this effect. In fact, we observe a nice 3-way interaction and if you perform the simple beverage group contrasts across memory load and block response frequency, we only observe a significant beverage effect for commission errors during heavy load 80% response frequency blocks. This is a nice demonstration about how alcohol can produce typical disinhibited behavior when you further tax working memory processes important for cognitive control. However, we were more excited still about the omission error data.

    14. Commission and Omission Error Rates On the right, we are now looking at omission error data, or failing to respond on trials where you were supposed to respond. Here, in contrast to commission errors, we see that omission errors were increased in 20% blocks, the blocks that established a pre-potent tendency to withhold response. And here, the data is even a bit more clean in displaying a selective effect of alcohol during heavy load. The majority of omission errors were committed by intoxicated participants in 20% response blocks during heavy load. So alcohol doesn’t just degrade performance in general. It actually produces a very specific type of error. Intoxicated participants perseverated the prepotent respond tendency of the current block they were in and that led to commission errors when it was a prepotent tendency to respond and omission errors when it was a prepotent tendency to withhold response. Moreover, it suggests an important clarification by what we mean when we say that alcohol produces disinhibited behavior. The inhibition failure in this study appears to be a failure to inhibit the prepotent response and in the right circumstances, this can lead an intoxicated person to appear what we might typically call inhibited. On the right, we are now looking at omission error data, or failing to respond on trials where you were supposed to respond. Here, in contrast to commission errors, we see that omission errors were increased in 20% blocks, the blocks that established a pre-potent tendency to withhold response. And here, the data is even a bit more clean in displaying a selective effect of alcohol during heavy load. The majority of omission errors were committed by intoxicated participants in 20% response blocks during heavy load. So alcohol doesn’t just degrade performance in general. It actually produces a very specific type of error. Intoxicated participants perseverated the prepotent respond tendency of the current block they were in and that led to commission errors when it was a prepotent tendency to respond and omission errors when it was a prepotent tendency to withhold response. Moreover, it suggests an important clarification by what we mean when we say that alcohol produces disinhibited behavior. The inhibition failure in this study appears to be a failure to inhibit the prepotent response and in the right circumstances, this can lead an intoxicated person to appear what we might typically call inhibited.

    15. Stroop Task Method OK, lets switch now to a different task that is perhaps the prototypic response conflict task, the Stroop. As I highlight earlier, incongruent color-naming trials contain all the characteristics of a situation which should require cognitive control for adaptive behavior. There is response conflict between color-naming and word reading responses, and the adaptive or correct response requires execution of the weaker color-naming response given that word reading stimulus-response mappings are so well learned. Participants completed 432 trials of the standard Stroop task with both color naming and word reading task blocks and congruent, neutral and incongruent trials. Task was blocked and trial type frequencies were equal. I emphasize this because both of these factors can be manipulated to alter the cognitive control requirements of this task, but I will get back to that in a later study. We measured behavioral indicants of task performance and then three ERP components which I will suggest are electrophysiological indicants of various components of attention function in this task. P3- to index stimulus evaluation, N2 to index evaluative cognitive control and a negative slow wave to index regulative cognitive control. OK, lets switch now to a different task that is perhaps the prototypic response conflict task, the Stroop. As I highlight earlier, incongruent color-naming trials contain all the characteristics of a situation which should require cognitive control for adaptive behavior. There is response conflict between color-naming and word reading responses, and the adaptive or correct response requires execution of the weaker color-naming response given that word reading stimulus-response mappings are so well learned. Participants completed 432 trials of the standard Stroop task with both color naming and word reading task blocks and congruent, neutral and incongruent trials. Task was blocked and trial type frequencies were equal. I emphasize this because both of these factors can be manipulated to alter the cognitive control requirements of this task, but I will get back to that in a later study. We measured behavioral indicants of task performance and then three ERP components which I will suggest are electrophysiological indicants of various components of attention function in this task. P3- to index stimulus evaluation, N2 to index evaluative cognitive control and a negative slow wave to index regulative cognitive control.

    16. Stroop Task Performance Lets first consider task performance on Stroop. I am only presenting data from the color naming blocks. Alcohol had no effects on task performance when participants were required to execute the more strongly established word reading response. So here we are looking at error rate on the left and response time on the right during color naming blocks. Incongruent trials are in red, congruent in green and neutral in black. Participants in both beverage groups displayed the typical Stroop interference effect, with increased response time and error rates on incongruent color-naming trials. However, the magnitude of the deficits displayed by intoxicated compared to sober participants is most interesting. Specifically, alcohol only produced a relative increase in error rate and response time when color naming of incongruent stimuli was required. Thus, intoxicated participants displayed selective impairment on the trials for which cognitive control was most critical. Lets first consider task performance on Stroop. I am only presenting data from the color naming blocks. Alcohol had no effects on task performance when participants were required to execute the more strongly established word reading response. So here we are looking at error rate on the left and response time on the right during color naming blocks. Incongruent trials are in red, congruent in green and neutral in black. Participants in both beverage groups displayed the typical Stroop interference effect, with increased response time and error rates on incongruent color-naming trials. However, the magnitude of the deficits displayed by intoxicated compared to sober participants is most interesting. Specifically, alcohol only produced a relative increase in error rate and response time when color naming of incongruent stimuli was required. Thus, intoxicated participants displayed selective impairment on the trials for which cognitive control was most critical.

    17. Posterior/Parietal P3 (Stimulus Evaluation) Lets consider the ERPs now to examine potential attention deficits that might have produced the intoxicated behavior deficits in Stroop performance. P3 is a parietal positive deflection in the stimulus-locked ERP that likely represents the summation of activity of multiple neural generators in the service of separable cognitive processes. This idea that P3 as measured on the surface of the scalp is actually a blend of multiple discrete cognitive processes is an important point that I will return to later in this talk. However, most relevant to this project, substantial evidence indicates that P3 is sensitive primarily to stimulus evaluation processes in Stroop. Most important for us here is that alcohol did not affect P3 in this paradigm. Focusing on the red and green lines, we see no evidence of a significant delay or relative reduction in P3 on the incongruent trials in the alcohol group. P3 had a latency of about 350 ms across conditions in both beverage groups Therefore, it doesn’t appear that alcohol is exacerbating the Stroop interference effect by interfering with the ability to encode or evaluate the ink color on incongruent trials. Lets consider the ERPs now to examine potential attention deficits that might have produced the intoxicated behavior deficits in Stroop performance. P3 is a parietal positive deflection in the stimulus-locked ERP that likely represents the summation of activity of multiple neural generators in the service of separable cognitive processes. This idea that P3 as measured on the surface of the scalp is actually a blend of multiple discrete cognitive processes is an important point that I will return to later in this talk. However, most relevant to this project, substantial evidence indicates that P3 is sensitive primarily to stimulus evaluation processes in Stroop. Most important for us here is that alcohol did not affect P3 in this paradigm. Focusing on the red and green lines, we see no evidence of a significant delay or relative reduction in P3 on the incongruent trials in the alcohol group. P3 had a latency of about 350 ms across conditions in both beverage groups Therefore, it doesn’t appear that alcohol is exacerbating the Stroop interference effect by interfering with the ability to encode or evaluate the ink color on incongruent trials.

    18. Anterior N2 (Evaluative Control) Recently, researchers have observed two ERP components that are sensitive to the processes that underlie the Stroop interference effect. The first is a phasic anterior deflection called N2 that occurs at about 450 ms in Stroop. Available evidence suggests that this N2 may be an electrophysiological index of evaluative cognitive control. First, its phasic nature is consistent with a neural signal produced by the detection of response conflict. Its latency at about 450 ms makes sense as well. It occurs after stimulus evaluation, which as you saw with posterior P3 on the previous slide, occurred around 350ms. N2 is also before behavioral response which if you were watching closely earlier occurs between 60-750 ms on average. N2 is sensitive to the trial type with a greater N2 on incongruent trials relative to neutral trials, indexing the greater response conflict on these trials. Also, one recent source localization project has suggested that ACC may be the generator of this component in stroop. Moreover, N2 is observed in many other classic response conflict paradigms. In fact, in a psych review paper coming out later this year, Nick Yeung and Jon Cohen offer nice empirical and computational modeling evidence to suggest that N2 and ERN are both indicants of ACC instantiated evaluative control during response conflict that simply differ in their timing relative to response based on processing differences between correct and incorrect trials.Recently, researchers have observed two ERP components that are sensitive to the processes that underlie the Stroop interference effect. The first is a phasic anterior deflection called N2 that occurs at about 450 ms in Stroop. Available evidence suggests that this N2 may be an electrophysiological index of evaluative cognitive control. First, its phasic nature is consistent with a neural signal produced by the detection of response conflict. Its latency at about 450 ms makes sense as well. It occurs after stimulus evaluation, which as you saw with posterior P3 on the previous slide, occurred around 350ms. N2 is also before behavioral response which if you were watching closely earlier occurs between 60-750 ms on average. N2 is sensitive to the trial type with a greater N2 on incongruent trials relative to neutral trials, indexing the greater response conflict on these trials. Also, one recent source localization project has suggested that ACC may be the generator of this component in stroop. Moreover, N2 is observed in many other classic response conflict paradigms. In fact, in a psych review paper coming out later this year, Nick Yeung and Jon Cohen offer nice empirical and computational modeling evidence to suggest that N2 and ERN are both indicants of ACC instantiated evaluative control during response conflict that simply differ in their timing relative to response based on processing differences between correct and incorrect trials.

    19. Anterior N2 (Evaluative Control) For our purposes what is most important is that alcohol dramatically reduces this phasic negative N2 deflection. Specifically, the increased N2 deflection on incongruent relative to neutral trials is significantly reduced among intoxicated participants. So in contrast to robust stimulus evaluation when intoxicated indicated by P3 results, this alcohol effect on N2 suggests a deficit in evaluative cognitive control that may be important for the detection of response conflict and the recruitment of regulative control to overcome this conflict.For our purposes what is most important is that alcohol dramatically reduces this phasic negative N2 deflection. Specifically, the increased N2 deflection on incongruent relative to neutral trials is significantly reduced among intoxicated participants. So in contrast to robust stimulus evaluation when intoxicated indicated by P3 results, this alcohol effect on N2 suggests a deficit in evaluative cognitive control that may be important for the detection of response conflict and the recruitment of regulative control to overcome this conflict.

    20. Negative Slow Wave (Regulative Control) A second component, a negative slow wave, has also been observed to be sensitive to the Stroop interference effect and available evidence suggests that it may be an attractive index of regulative control. Its more tonic nature is consistent with the necessary time course of regulative control. It too is greater on incongruent trials and its topography is consistent with a generator in PFC, a neural structure which is strongly implicated in regulative control. Finally, its timing also makes sense as it follows the detection of response conflict signaled by N2. In fact, Angus Macdonald from your department and his colleagues have a nice Stroop imaging paper in science out last month where they demonstrate that ACC based evaluative control activity on the current trial leads to additional recruitment of PFC based regulative control on the subsequent trial.A second component, a negative slow wave, has also been observed to be sensitive to the Stroop interference effect and available evidence suggests that it may be an attractive index of regulative control. Its more tonic nature is consistent with the necessary time course of regulative control. It too is greater on incongruent trials and its topography is consistent with a generator in PFC, a neural structure which is strongly implicated in regulative control. Finally, its timing also makes sense as it follows the detection of response conflict signaled by N2. In fact, Angus Macdonald from your department and his colleagues have a nice Stroop imaging paper in science out last month where they demonstrate that ACC based evaluative control activity on the current trial leads to additional recruitment of PFC based regulative control on the subsequent trial.

    21. Negative Slow Wave (Regulative Control) As with N2, alcohol also significantly reduced the NSW. Specifically, the displacement (in the negative direction) of NSW on incongruent trials relative to neutral trials was significantly reduced. So to summarize, in the standard stroop, we observed a relatively specific behavioral deficit when intoxicated. Alcohol selectively exacerbated task performance deficits only on incongruent color naming trials where participants had to overcome conflict from relatively prepotent competing word information. ERP results suggested that this deficit did not result from increased difficulty evaluating or encoding color information but instead from a deficit at a later stage in the processing stream where conflict between word and color information is typically detected and results in a call for regulative control resources to aid task relevant responses. So we were pretty excited about this, but one thing I have been wondering about is whether we can parse apart the observed evaluative and regulative control deficits. In this study, N2 and NSW are significantly correlated, as you would expect if detection of response conflict via evaluative control served as the signal to recruit regulative control resources. However, ideally, I’d like to be able to work with some paradigms that allow for the selective manipulation of each of these two components. And as it turns out, variants of Stroop have been designed for just this purpose. We’ve just completed one of these studies a couple of weeks ago and I’ll show you some of the preliminary behavioral data that I am excited about. And if time permits at the end, I will tell you a bit about another study we are collecting data on now. As with N2, alcohol also significantly reduced the NSW. Specifically, the displacement (in the negative direction) of NSW on incongruent trials relative to neutral trials was significantly reduced. So to summarize, in the standard stroop, we observed a relatively specific behavioral deficit when intoxicated. Alcohol selectively exacerbated task performance deficits only on incongruent color naming trials where participants had to overcome conflict from relatively prepotent competing word information. ERP results suggested that this deficit did not result from increased difficulty evaluating or encoding color information but instead from a deficit at a later stage in the processing stream where conflict between word and color information is typically detected and results in a call for regulative control resources to aid task relevant responses. So we were pretty excited about this, but one thing I have been wondering about is whether we can parse apart the observed evaluative and regulative control deficits. In this study, N2 and NSW are significantly correlated, as you would expect if detection of response conflict via evaluative control served as the signal to recruit regulative control resources. However, ideally, I’d like to be able to work with some paradigms that allow for the selective manipulation of each of these two components. And as it turns out, variants of Stroop have been designed for just this purpose. We’ve just completed one of these studies a couple of weeks ago and I’ll show you some of the preliminary behavioral data that I am excited about. And if time permits at the end, I will tell you a bit about another study we are collecting data on now.

    22. Trial Frequency Stroop Task Method Let me now describe a variant of the standard Stroop task that is designed to selectively manipulate the contribution of evaluative control to task performance. This task again involves the typical trial type manipulation with congruent, neutral and incongruent trials. However, in the standard Stroop task, the frequencies of congruent, neutral and incongruent trials are equal. In this variant, we actually manipulate the frequencies to form a mostly congruent condition where 80% of trials are congruent with 10% each of incongruent and neutral and a Mostly incongruent condition where 80% of the trials are incongruent. It turns out that trial frequency condition is a powerful manipulation of ACC evaluative control activation. In the Mostly Incongruent condition, because of the high frequency of incongruent trials, participants adopt a strategy where regulative control is tonically active across trials. In other words, individuals quickly recognize how difficult these trials are and focus across all trials on suppressing word information. Thus, evaluative control becomes less important. There is no need to recruit regulative control because its already active and its tonic activation reduces the conflict from word information. In contrast, in the Mostly congruent condition, participants are seduced so to speak into using word information b/c it aids performance on the majority of trials. However, on the infrequent but critical incongruent trials in this condition, they now experience a high degree of response conflict and we would expect strong ACC involvement to aid performance on these trials. Let me now describe a variant of the standard Stroop task that is designed to selectively manipulate the contribution of evaluative control to task performance. This task again involves the typical trial type manipulation with congruent, neutral and incongruent trials. However, in the standard Stroop task, the frequencies of congruent, neutral and incongruent trials are equal. In this variant, we actually manipulate the frequencies to form a mostly congruent condition where 80% of trials are congruent with 10% each of incongruent and neutral and a Mostly incongruent condition where 80% of the trials are incongruent. It turns out that trial frequency condition is a powerful manipulation of ACC evaluative control activation. In the Mostly Incongruent condition, because of the high frequency of incongruent trials, participants adopt a strategy where regulative control is tonically active across trials. In other words, individuals quickly recognize how difficult these trials are and focus across all trials on suppressing word information. Thus, evaluative control becomes less important. There is no need to recruit regulative control because its already active and its tonic activation reduces the conflict from word information. In contrast, in the Mostly congruent condition, participants are seduced so to speak into using word information b/c it aids performance on the majority of trials. However, on the infrequent but critical incongruent trials in this condition, they now experience a high degree of response conflict and we would expect strong ACC involvement to aid performance on these trials.

    23. Carter et al., (2000) ACC Activity during MC And in fact, Cameron Carter and colleagues demonstrated this selective involvement of ACC on incongruent trials in the Mostly congruent condition with fMRI. Here we are looking at ACC activation on congruent in blue and incongruent in red trials. Solid markers are from the mostly congruent condition and open markers are from mostly incongruent condition. We see significant activation of ACC only on incongruent trials in the Mostly congruent condition. So this Stroop variant provides a nice test bed to potentially separate alcohol effects on evaluative control and regulative control. Regulative control is activated regardless of Trial frequency condition but evaluative control is necessary only during incongruent trials in the Mostly congruent condition. Therefore, alcohol induced deficits across both conditions would suggest problems with regulative control whereas, selective deficits only in the Mostly Congruent condition would suggest a more specific problem with evaluative control when intoxicated. And in fact, Cameron Carter and colleagues demonstrated this selective involvement of ACC on incongruent trials in the Mostly congruent condition with fMRI. Here we are looking at ACC activation on congruent in blue and incongruent in red trials. Solid markers are from the mostly congruent condition and open markers are from mostly incongruent condition. We see significant activation of ACC only on incongruent trials in the Mostly congruent condition. So this Stroop variant provides a nice test bed to potentially separate alcohol effects on evaluative control and regulative control. Regulative control is activated regardless of Trial frequency condition but evaluative control is necessary only during incongruent trials in the Mostly congruent condition. Therefore, alcohol induced deficits across both conditions would suggest problems with regulative control whereas, selective deficits only in the Mostly Congruent condition would suggest a more specific problem with evaluative control when intoxicated.

    24. Trial Frequency Stroop Task As I said, at this point we’ve just completed data collection and so I am only going to give you a teaser with some behavioral data. Here is the error rate data from this task. Placebo control group on the left, and the alcohol group on the right. Within each of these graphs, the left set of bars are in the mostly incongruent condition and the right set are the mostly congruent. We see what looks like a relatively specific effect of alcohol on the error rate on incongruent trials in the mostly congruent condition which is consistent with a selective effect of alcohol on evaluative control. I’d like to hedge on this strong statement though for a bit. Both because there is a some indication of an alcohol effect on incongruent trials in the mostly incongruent condition as well, though it isn't significant and also because I haven't worked through the ERP data yet. I expect to be able to use the ERP data to more directly examine the specificity of these effects. As I said, at this point we’ve just completed data collection and so I am only going to give you a teaser with some behavioral data. Here is the error rate data from this task. Placebo control group on the left, and the alcohol group on the right. Within each of these graphs, the left set of bars are in the mostly incongruent condition and the right set are the mostly congruent. We see what looks like a relatively specific effect of alcohol on the error rate on incongruent trials in the mostly congruent condition which is consistent with a selective effect of alcohol on evaluative control. I’d like to hedge on this strong statement though for a bit. Both because there is a some indication of an alcohol effect on incongruent trials in the mostly incongruent condition as well, though it isn't significant and also because I haven't worked through the ERP data yet. I expect to be able to use the ERP data to more directly examine the specificity of these effects.

    25. Flanker Task Methods Lets leave the Stroop task now and examine alcohol effects in another paradigm which is often thought of as a response conflict task: The flanker task. Participants completed 400 trials of a modified Flanker task. The stimuli were 5 character letter strings consisting of H’s and S’s. Participants task was to indicate the identity of the target center letter by pressing one of two buttons held in separate hands and to ignore the surrounding flanker letters. So for example if H was associated with the right hand button, the task might look like this: {DO DEMO}Lets leave the Stroop task now and examine alcohol effects in another paradigm which is often thought of as a response conflict task: The flanker task. Participants completed 400 trials of a modified Flanker task. The stimuli were 5 character letter strings consisting of H’s and S’s. Participants task was to indicate the identity of the target center letter by pressing one of two buttons held in separate hands and to ignore the surrounding flanker letters. So for example if H was associated with the right hand button, the task might look like this: {DO DEMO}

    26. Flanker Task Methods So as you can see, there were two primary manipulations. The standard task involves a Flanker compatibility manipulation, such that in the compatible condition, the Flanker letters matched the target letter and in the incompatible condition the target and flanker letters were different. This manipulation is frequently discussed as a response conflict manipulation, but its interesting because it differs from the previous two response conflict manipulations that I’ve presented. On incongruent trials in Stroop, there are strong asymmetries between word reading and color naming mappings that aren't present in this H-S version of the Flanker. Neither H-nor S are inherently strongly mapped to right or left button pressing response. In the response frequency manipulation in n-back, participants likely activated the prepotent response prior to the start of the trial because they understood what response was likely in that context. So this is quite a different manipulation of response conflict here in flanker. Also, although for some reason not emphasized in the literature, Mike Coles and colleagues have demonstrated that a large portion, and in fact the majority of the behavioral interference in the H-S version is actually due to stimulus evaluation deficits which you can see in the P3 ERP. So going into this study, we were somewhat agnositc about how alcohol would affect this manipulation. We also manipulated the target frequency. The frequency of the two target letters was varied such that one target and associated response occurred on 80% of trials and the other target and response on only 20% of trials. This manipulation was designed to establish a pre-potent response due to the repeated frequent execution over blocks of one response. Thus, it was expected that participants would have to inhibit the frequent target button response on the trials where the infrequent target was presented. We also explicitly analyzed block as a factor because we expected that the prepotent response would grow over time.So as you can see, there were two primary manipulations. The standard task involves a Flanker compatibility manipulation, such that in the compatible condition, the Flanker letters matched the target letter and in the incompatible condition the target and flanker letters were different. This manipulation is frequently discussed as a response conflict manipulation, but its interesting because it differs from the previous two response conflict manipulations that I’ve presented. On incongruent trials in Stroop, there are strong asymmetries between word reading and color naming mappings that aren't present in this H-S version of the Flanker. Neither H-nor S are inherently strongly mapped to right or left button pressing response. In the response frequency manipulation in n-back, participants likely activated the prepotent response prior to the start of the trial because they understood what response was likely in that context. So this is quite a different manipulation of response conflict here in flanker. Also, although for some reason not emphasized in the literature, Mike Coles and colleagues have demonstrated that a large portion, and in fact the majority of the behavioral interference in the H-S version is actually due to stimulus evaluation deficits which you can see in the P3 ERP. So going into this study, we were somewhat agnositc about how alcohol would affect this manipulation. We also manipulated the target frequency. The frequency of the two target letters was varied such that one target and associated response occurred on 80% of trials and the other target and response on only 20% of trials. This manipulation was designed to establish a pre-potent response due to the repeated frequent execution over blocks of one response. Thus, it was expected that participants would have to inhibit the frequent target button response on the trials where the infrequent target was presented. We also explicitly analyzed block as a factor because we expected that the prepotent response would grow over time.

    27. Flanker Task Methods In this task, we measured response time to determine the effects of alcohol and these two manipulations on task performance. With respect to ERPs, we focused on three components a priori. First, we were interested in what I will refer to as flanker compatibility P3. As I mentioned, we were aware that incompatible flankers would interfere with target stimulus evaluation and we believed that we should be able to see this stimulus evaluation deficit as a reduction in P3 on incompatible relative to compatible flankers. We were also interested in what I will call Target frequency P3. The infrequent targets require that the participant inhibit the prepotent frequent target response and produce an alternative response. Dealing with this conflict will require regulative cognitive control much like incongruent trials in Stroop. In fact, recent imaging evidence has documented activation of prefrontal cortex on a similar infrequent target detection task substantiating this claim. Moreover, there is a much evidence that P3 in target frequent manipulations taps into working memory processes which as I mentioned earlier are central to regulative control. Thus we believed that we could use this increase in P3 to infrequent relative to frequent targets as an index of regulative control. Finally, we also measured error related negativity or ERN. ERN is a frontal negative deflection that occurs 80 ms post response on trials in which individuals commit an error. There is currently some debate on the exact mechanism that produces ERN. Jon Cohen and others have argued that ERN is produced by the response conflict between correct and incorrect responses that is observed on incorrect trials. Others have suggested that ERN is more narrowly related to error detection. However, all agree that this component is the result of action monitoring in the ACC and therefore it makes an attractive index of evaluative control.In this task, we measured response time to determine the effects of alcohol and these two manipulations on task performance. With respect to ERPs, we focused on three components a priori. First, we were interested in what I will refer to as flanker compatibility P3. As I mentioned, we were aware that incompatible flankers would interfere with target stimulus evaluation and we believed that we should be able to see this stimulus evaluation deficit as a reduction in P3 on incompatible relative to compatible flankers. We were also interested in what I will call Target frequency P3. The infrequent targets require that the participant inhibit the prepotent frequent target response and produce an alternative response. Dealing with this conflict will require regulative cognitive control much like incongruent trials in Stroop. In fact, recent imaging evidence has documented activation of prefrontal cortex on a similar infrequent target detection task substantiating this claim. Moreover, there is a much evidence that P3 in target frequent manipulations taps into working memory processes which as I mentioned earlier are central to regulative control. Thus we believed that we could use this increase in P3 to infrequent relative to frequent targets as an index of regulative control. Finally, we also measured error related negativity or ERN. ERN is a frontal negative deflection that occurs 80 ms post response on trials in which individuals commit an error. There is currently some debate on the exact mechanism that produces ERN. Jon Cohen and others have argued that ERN is produced by the response conflict between correct and incorrect responses that is observed on incorrect trials. Others have suggested that ERN is more narrowly related to error detection. However, all agree that this component is the result of action monitoring in the ACC and therefore it makes an attractive index of evaluative control.

    28. Flanker, Target, & Block Effects So with this in mind, lets first look at the overall behavioral effects associated with the two manipulations. We see that both the flanker compatibility and the target frequency manipulations produced comparable interference effects on behavior. Specifically on the left we see that participants were about 60 ms slower to respond to trials with incompatible flankers vs. compatible flankers. Similarly, participants were about 60 ms slower to respond to infrequent target trials vs. the frequent target. Thus, infrequent target trials and incompatible flanker trials were both comparably difficult for participants. I also need to call your attention to an apparent fatigue effect. Participants only received a break between blocks 2-3 so what we see is participants getting somewhat slower across blocks 1 and 2, speeding up after the break between blocks 2-3 and then slowing down again across blocks 3 and 4. You will see this cubic block effect riding through all the graphs.So with this in mind, lets first look at the overall behavioral effects associated with the two manipulations. We see that both the flanker compatibility and the target frequency manipulations produced comparable interference effects on behavior. Specifically on the left we see that participants were about 60 ms slower to respond to trials with incompatible flankers vs. compatible flankers. Similarly, participants were about 60 ms slower to respond to infrequent target trials vs. the frequent target. Thus, infrequent target trials and incompatible flanker trials were both comparably difficult for participants. I also need to call your attention to an apparent fatigue effect. Participants only received a break between blocks 2-3 so what we see is participants getting somewhat slower across blocks 1 and 2, speeding up after the break between blocks 2-3 and then slowing down again across blocks 3 and 4. You will see this cubic block effect riding through all the graphs.

    29. Beverage X Flanker Effect Now lets examine what alcohol challenge does to each of these two interference effects. Here we are looking at the Flanker compatibility interference effect by block for the no-alcohol group. We see the significant flanker compatibility interference effect that is consistent across blocks. Now lets examine what alcohol challenge does to each of these two interference effects. Here we are looking at the Flanker compatibility interference effect by block for the no-alcohol group. We see the significant flanker compatibility interference effect that is consistent across blocks.

    30. Beverage X Flanker Effect What most important though is that the magnitude of this flanker compatibility effect is comparable across beverage groups. Both sober and intoxicated participants have difficulty responding on trials with incompatible flankers, but there is no indication that alcohol exacerbates this deficit. Neither the BGXFC or BGXFCXBLK interactions are anywhere near significant. This suggests that the stimulus evaluation processes that are being taxed by the flanker compatibility manipulation are robust to alcohol effects and whatever response conflict is elicited by this particular manipulation is also not sensitive to alcohol.What most important though is that the magnitude of this flanker compatibility effect is comparable across beverage groups. Both sober and intoxicated participants have difficulty responding on trials with incompatible flankers, but there is no indication that alcohol exacerbates this deficit. Neither the BGXFC or BGXFCXBLK interactions are anywhere near significant. This suggests that the stimulus evaluation processes that are being taxed by the flanker compatibility manipulation are robust to alcohol effects and whatever response conflict is elicited by this particular manipulation is also not sensitive to alcohol.

    31. Beverage X Target Frequency Effect Lets contrast this flanker compatibility effect with the Target frequency effect. Here we see the Target frequency effect by Block for the no-alcohol group. As with the Flanker effect, the Target frequency effect is significant and consistent across blocks among the sober participants. Participants are slower to respond to infrequent targets than frequent targets. Lets contrast this flanker compatibility effect with the Target frequency effect. Here we see the Target frequency effect by Block for the no-alcohol group. As with the Flanker effect, the Target frequency effect is significant and consistent across blocks among the sober participants. Participants are slower to respond to infrequent targets than frequent targets.

    32. Beverage X Target Frequency Effect However, unlike the flanker effect, this target frequency interference effect is sensitive to alcohol challenge. There is a significant Beverage X Target Frequency X Block interaction. Specifically, a significant linear block effect is observed only for intoxicated participants on the infrequent target trials. This is exactly what you would expect if alcohol interfered with prepotent response inhibition. As I suggested earlier, as participants repeatedly execute the frequent target response, it becomes more and more prepotent over blocks. Sober participants appear to have no difficulty inhibiting this growing prepotent response in favor of the correct infrequent response when necessary. However as the prepotency of the frequent response grows, intoxicated participants display increasing deficits inhibiting it on infrequent target trials.However, unlike the flanker effect, this target frequency interference effect is sensitive to alcohol challenge. There is a significant Beverage X Target Frequency X Block interaction. Specifically, a significant linear block effect is observed only for intoxicated participants on the infrequent target trials. This is exactly what you would expect if alcohol interfered with prepotent response inhibition. As I suggested earlier, as participants repeatedly execute the frequent target response, it becomes more and more prepotent over blocks. Sober participants appear to have no difficulty inhibiting this growing prepotent response in favor of the correct infrequent response when necessary. However as the prepotency of the frequent response grows, intoxicated participants display increasing deficits inhibiting it on infrequent target trials.

    33. Flanker Compatibility P3 (Stimulus Evaluation) Lets move on now to consider ERP indicants of the cognitive/attentional processes underlying the flanker and target frequency deficits. First lets examine the impact of the flanker compatibility manipulation on P3. To the left we see the waveforms for the alcohol group represented by the thick lines and the no-alcohol group by the thin lines. Incompatible flanker trials are presented as dotted. We can see that there is a main effect of flanker compatibility on P3 with the reduced P3 on incompatible flanker trials representing the information loss or difficulty evaluating and categorizing the target stimulus when the flankers do not match the target letter. More importantly for our purposes though and consistent with the behavioral results, there is no effect of alcohol on this modulation of P3 produced by the flanker manipulation. Both intoxicated and non-intoxicated participants display comparable reduction and small latency delay in P3 on incompatible flankers.Lets move on now to consider ERP indicants of the cognitive/attentional processes underlying the flanker and target frequency deficits. First lets examine the impact of the flanker compatibility manipulation on P3. To the left we see the waveforms for the alcohol group represented by the thick lines and the no-alcohol group by the thin lines. Incompatible flanker trials are presented as dotted. We can see that there is a main effect of flanker compatibility on P3 with the reduced P3 on incompatible flanker trials representing the information loss or difficulty evaluating and categorizing the target stimulus when the flankers do not match the target letter. More importantly for our purposes though and consistent with the behavioral results, there is no effect of alcohol on this modulation of P3 produced by the flanker manipulation. Both intoxicated and non-intoxicated participants display comparable reduction and small latency delay in P3 on incompatible flankers.

    34. Target Frequency P3 (Regulative Control) We can also see Target frequency effects on P3 as well. Here again are the alcohol and no alcohol waveforms with alcohol group presented as thick lines. Frequent trials are presented in green and infrequent in red. We observe a significant increase in P3 on infrequent relative to frequent trials that likely represents greater allocation of regulative resources to infrequent target which requires inhibition of the more typical frequent trial response. In contrast to the Flanker P3 effect, this target frequency P3 effect is sensitive to alcohol. Intoxicated participants display a smaller increase in P3 to infrequent targets than do sober participants. Thus, consistent with the increased behavioral deficit observed among intoxicated participants on infrequent trials, we see a reduction of the allocation of regulative attentional resources that are important for executing this weaker infrequent response. Moreover, we see a nice dissociation in alcohol’s effect both behaviorally and electrophysiologically, with robust stimulus evaluation and impaired regulative control necessary for response inhibition.We can also see Target frequency effects on P3 as well. Here again are the alcohol and no alcohol waveforms with alcohol group presented as thick lines. Frequent trials are presented in green and infrequent in red. We observe a significant increase in P3 on infrequent relative to frequent trials that likely represents greater allocation of regulative resources to infrequent target which requires inhibition of the more typical frequent trial response. In contrast to the Flanker P3 effect, this target frequency P3 effect is sensitive to alcohol. Intoxicated participants display a smaller increase in P3 to infrequent targets than do sober participants. Thus, consistent with the increased behavioral deficit observed among intoxicated participants on infrequent trials, we see a reduction of the allocation of regulative attentional resources that are important for executing this weaker infrequent response. Moreover, we see a nice dissociation in alcohol’s effect both behaviorally and electrophysiologically, with robust stimulus evaluation and impaired regulative control necessary for response inhibition.

    35. ERN (Evaluative Control) In addition to the Target frequency P3 deficits observed among the alcohol group that may represent deficits in regulative control, we also observe dysfunction among intoxicated participants in an ERP component that can be used to index evaluative cognitive control, the ERN. Here we see that alcohol produces a sizable and significant reduction in ERN both overall and specifically on error trials which suggests a deficit in evaluative control processes. Finally, it turns out that the P3 target frequency effect and this ERN effect are both significantly correlated with the behavioral deficit displayed by the intoxicated participants on the infrequent trials.In addition to the Target frequency P3 deficits observed among the alcohol group that may represent deficits in regulative control, we also observe dysfunction among intoxicated participants in an ERP component that can be used to index evaluative cognitive control, the ERN. Here we see that alcohol produces a sizable and significant reduction in ERN both overall and specifically on error trials which suggests a deficit in evaluative control processes. Finally, it turns out that the P3 target frequency effect and this ERN effect are both significantly correlated with the behavioral deficit displayed by the intoxicated participants on the infrequent trials.

    36. Flanker Summary

    37. Intoxicated Emotion OK, now I would like to really switch gears for a moment and change from talking about alcohol effects on behavior to instead consider alcohol effects on emotional response, and in particular, negative affect, stress, fear, anxiety. If I were to ask you all why people drink, one very common answer is that people drink to reduce stress. Its an expectation that is very consistently reported by social drinkers, problem drinkers, even kids who have had little experience with alcohol themselves. People clearly believe that alcohol reduces stress and anxiety. Interestingly enough though, demonstrations of alcohol effects on stress in the laboratory have been somewhat inconsistent. For as many studies that find a reduction in stress when intoxicated, just as many have found no effect, and some have even found an increase in stress when intoxicated. However, there are some situations where alcohol does appear to consistently affect stress. In animals, consistent behavioral indicants of stress response dampening have been observed in Approach avoidance conflict paradigms. Similarly, in humans SRD affects are consistently observed in divided attention conditions where the participants are simultaneously processing both stressor cues and cues that elicit approach motivation or positive affect. These situations could be thought of as characterized by affective conflict and therefore it is interesting to consider if the same mechanisms can account for both the emotional and behavioral consequences of alcohol use. In line with this, both cognitive and emotional sectors have been identified in ACC and PFC. OK, now I would like to really switch gears for a moment and change from talking about alcohol effects on behavior to instead consider alcohol effects on emotional response, and in particular, negative affect, stress, fear, anxiety. If I were to ask you all why people drink, one very common answer is that people drink to reduce stress. Its an expectation that is very consistently reported by social drinkers, problem drinkers, even kids who have had little experience with alcohol themselves. People clearly believe that alcohol reduces stress and anxiety. Interestingly enough though, demonstrations of alcohol effects on stress in the laboratory have been somewhat inconsistent. For as many studies that find a reduction in stress when intoxicated, just as many have found no effect, and some have even found an increase in stress when intoxicated. However, there are some situations where alcohol does appear to consistently affect stress. In animals, consistent behavioral indicants of stress response dampening have been observed in Approach avoidance conflict paradigms. Similarly, in humans SRD affects are consistently observed in divided attention conditions where the participants are simultaneously processing both stressor cues and cues that elicit approach motivation or positive affect. These situations could be thought of as characterized by affective conflict and therefore it is interesting to consider if the same mechanisms can account for both the emotional and behavioral consequences of alcohol use. In line with this, both cognitive and emotional sectors have been identified in ACC and PFC.

    38. Divided Attention Threat Task So it becomes reasonable to ask if alcohol is affecting emotion in situations that are characterized by affective conflict and if perhaps the same neural structures are involved in both the emotional and behavioral consequences of alcohol challenge. Let me present data from one study from my lab that provides preliminary support for this thesis. I used an instructed fear conditioning paradigm where participants viewed words from one of two semantic categories, animals or body parts and were instructed that shocks would follow words from one but not the other category. Lets say animals. Participants are then exposed to these word cues in two conditions, a threat only condition and a conflict task and threat condition. In the threat only condition, participants simply watch the words come up on the screen and are shocked after animal words. However, in the conflict condition, we superimpose a rewarding task on top of the threat words. We color the words red and green and tell them that if the word is green, they should press a button quickly when a second stimulus appears and if they do it quick enough, they will earn money. Thus, the stimulus becomes a conflict stimulus, it is both punished and rewarded much like in the typical approach avoidance paradigms in animals.So it becomes reasonable to ask if alcohol is affecting emotion in situations that are characterized by affective conflict and if perhaps the same neural structures are involved in both the emotional and behavioral consequences of alcohol challenge. Let me present data from one study from my lab that provides preliminary support for this thesis. I used an instructed fear conditioning paradigm where participants viewed words from one of two semantic categories, animals or body parts and were instructed that shocks would follow words from one but not the other category. Lets say animals. Participants are then exposed to these word cues in two conditions, a threat only condition and a conflict task and threat condition. In the threat only condition, participants simply watch the words come up on the screen and are shocked after animal words. However, in the conflict condition, we superimpose a rewarding task on top of the threat words. We color the words red and green and tell them that if the word is green, they should press a button quickly when a second stimulus appears and if they do it quick enough, they will earn money. Thus, the stimulus becomes a conflict stimulus, it is both punished and rewarded much like in the typical approach avoidance paradigms in animals.

    39. Next Block: THREAT ONLY Read each word as it is presented Shocks to animal words

    41. HEAD

    45. NECK

    49. BEAR

    51. !!!SHOCK!!!

    54. END BLOCK

    55. Next Block: TASK & THREAT Press button quickly to square after GREEN word Do not press button after RED word Shocks to ANIMAL words

    57. HAND

    61. MOUTH

    65. TIGER

    67. !!!SHOCK!!!

    69. END BLOCK

    70. 10 of 10 points earned in this block

    71. Fear Potentiated Startle

    72. P3 to Threat Cues

    73. P3 Difference (Threat Cue Attention)

    74. Summary of Behavioral/Emotion Effects

    75. Future Directions First, in both of the ERP and behavior projects we observed significant deficits in both evaluative and regulative control. But in both of those projects, activation of regulative control required intact evaluative control processes. Current work in my lab is utilizing variants of these paradigms that have been designed specifically to manipulate the relative contribution of one of these components in order to examine the selectivity of the alcohol effects on these specific cognitive control components. I presented preliminary evidence from the trial frequency stroop task and let me give a brief plug for another study we are currently running based on a paradigm developed by AngusFirst, in both of the ERP and behavior projects we observed significant deficits in both evaluative and regulative control. But in both of those projects, activation of regulative control required intact evaluative control processes. Current work in my lab is utilizing variants of these paradigms that have been designed specifically to manipulate the relative contribution of one of these components in order to examine the selectivity of the alcohol effects on these specific cognitive control components. I presented preliminary evidence from the trial frequency stroop task and let me give a brief plug for another study we are currently running based on a paradigm developed by Angus

    76. Task-Switching Stroop (MacDonald et al., 2000)

    77. Future Directions

    78. Future Directions Finally, alcohol and drug addiction itself can be thought of as a behavior regulation problem that is characterized by response conflict. Drugs produce strong positively reinforcing effects that support use. However, as frequency and quantity of use increase, drug use can begin to also cause problems that should suggest inhibiting use in favor of alternative behaviors. Thus, it is possible that individual differences in cognitive control might account for why some individuals are unsuccessful at regulating their use. Finally, alcohol and drug addiction itself can be thought of as a behavior regulation problem that is characterized by response conflict. Drugs produce strong positively reinforcing effects that support use. However, as frequency and quantity of use increase, drug use can begin to also cause problems that should suggest inhibiting use in favor of alternative behaviors. Thus, it is possible that individual differences in cognitive control might account for why some individuals are unsuccessful at regulating their use.

    79. Mechanism for Externalizing Problems

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