Assistant Professor of Psychology
In the course of a conversation, have you ever found yourself observing another person’s puzzled expression and stopped what you were saying in mid-sentence? In such situations, you may find it easy or difficult to resume what you were saying. Why is it that some people have an easy time altering their ongoing behavior, while others appear to have great difficulty shifting away from or stopping their ongoing behavior? Humans are constantly altering and adapting their behaviors to coincide with the current environmental context or the demands of the task to which they are currently attending. This alteration of ongoing behavior often occurs so that we engage in the most fitting behavioral responses given the current context, and inhibit those behaviors deemed inappropriate to the current situation. In social situations, the evaluation of emotional information conveyed by the facial expression and body language of other individuals becomes a central aspect of this decision-making process.
The generation of appropriate behaviors in response to changing situations requires several mental (or “cognitive”) and behavioral processes acting in concert with one another. We must first evaluate the global rules governing behavior in a given context, then select the most fitting response among competing possibilities, inhibit any ongoing behavioral response (if necessary), and generate an appropriate response. However, the mental activities that go along with decision making do not end there. Following a decision and its resulting behavioral response, we must also monitor our responses for appropriateness, determine whether we have made any errors, and update our responses as necessary. Further, we may have prepotent responses to a given situation, which are responses that are most likely to occur but may not be the most appropriate response for the task at hand. This seemingly incredibly complex set of mental activities often occurs within a matter of seconds (sometimes in a fraction of a second), and under normal circumstances can be carried out without a huge amount of conscious mental effort.
Assisting in this decision-making process is a collection of mental processes that psychologists refer to as executive functions. Although not completely agreed upon, the list of executive functions includes inhibiting ongoing or prepotent responses, initiating and monitoring responses, planning, and shifting attention where necessary (Denckla, 1996). These mental processes allow us to maintain cognitive flexibility and to have flexible behaviors in dynamic situations. As such, they have also been referred to as our cognitive control mechanism. Although executive functions tend to work seamlessly under most circumstances, many psychiatric disorders are marked by dysregulation of executive functioning, including attention-deficit/ hyperactivity disorder (ADHD), autism, schizophrenia, and obsessivecompulsive disorder. In these disorders, people often find themselves unable to flexibly adapt their behavior or to stop ongoing behavioral responses. Therefore, these disorders, among others, are marked by maladaptive behavioral responses.
In the last few decades, psychologists have created a number of standardized neuropsychological tests designed to measure various aspects of executive functioning. One of these tasks, the Wisconsin Card Sorting Test, measures an individual’s ability to generate a set of rules governing behavior and the ability to alter behavioral responses when those rules change. Another task, the Tower of Hanoi, requires participants to rearrange a set of disks on a pegboard while following a set of rules. This task evaluates the ability to plan a series of subgoals necessary to achieve a final goal. In the color-word Stroop task, participants are shown names of colors that are written using a particular color of ink. While most trials have the ink match the printed name of the color, some involve conflicting ink color and printed color name. The participant must verbally name the color of the ink and not the word. Because reading is a very salient activity, this is a difficult task even for those familiar with the task. The Stroop task involves several components of executive functioning, including response monitoring, selective attention, and inhibition of prepotent responses.
In addition to these standardized measures, psychologists have devised a number of experimental measures that are used to determine executive functioning in different populations. The go/no-go task is a measure of inhibition in which the participant is instructed to respond to all stimuli except for a pre-assigned target. The participant must withhold responding when this target is presented. Omitting responses when they are required (errors of omission) demonstrates inattention, while inappropriately responding to non-target stimuli (errors of commission) is indicative of impulsivity, or lack of inhibitory control.
One of the most significant advances in the field of psychology is the advent of functional magnetic resonance imaging (fMRI). fMRI is a noninvasive brain imaging technique that uses strong magnetic fields to detect subtle changes in blood flow in regions of the brain that are utilized during a particular mental activity. When researchers compare the blood flow to a particular brain region during one mental activity with blood flow to that region during an alternate activity, they can determine which regions of the brain are recruited, or “activated,” for a particular mental task. In this manner, we can create a map of the brain that pinpoints the function of each brain region. Because fMRI poses very little danger to most participants, the technique can be used in children as well as adults, and people can be repeatedly scanned without adverse effects. Thus, we can examine developmental changes in brain activity patterns, and some researchers are even using the technique to examine brain structural changes in developing fetuses.
Designing and implementing a well-controlled fMRI study is not easy, however, and valid conclusions are sometimes difficult to draw because of the artificial experimental setting in which the studies take place. Participants must lie very still on a bed inside a confining MRI machine and can make responses only by pressing buttons on a response box. Moreover, brain activation can be determined only by comparing blood flow during one mental task with blood flow during another mental task. Therefore, all mental tasks in the MRI either involve alternating periods of different behaviors or thoughts, or require the participant to rapidly alter an ongoing behavior or thought pattern. Despite these limitations, the technique has become the most widely used and accepted tool to examine human brain function.
Over the past several years, my colleagues and I have used fMRI combined with neuropsychological testing to examine the brain basis for executive functions. We have focused on two areas of research: how emotional information interacts with brain regions responsible for cognitive control to produce flexible and adaptive behavior in social situations, and whether these brain regions are functioning properly in individuals with psychiatric disorders that are marked by executive dysfunction. We have focused particularly on ADHD and autism.
ADHD is an increasingly common childhood diagnosis characterized by symptoms of inattention, impulsivity, and hyperactivity (American Psychiatric Association, 2000). Official estimates suggest that 3-7 percent of school-aged children are affected by this disorder, although some estimates put the prevalence much higher. Symptoms often persist into young adulthood, and long-term consequences include lower educational and occupational achievement and increased risk for developing other psychiatric disorders. Part of the difficulty in properly diagnosing ADHD is that the symptoms overlap with (and may mask) other psychiatric disorders, including anxiety and mood disorders. The goal of my research program is to ultimately find patterns of brain activity that are specific to ADHD, with the hope of improving diagnosis and treatment of the disorder.
In one study, we examined whether Ritalin – one of the most commonly used drugs to treat the disorder – altered brain activation during a mental activity designed to engage two forms of attention: selective attention and divided attention (Shafritz, Marchione, Gore, Shaywitz, & Shaywitz, 2004). Participants in the study included adolescents with either ADHD, or reading disorder, or no psychiatric diagnosis. The participants in the ADHD and reading disorder groups participated in a drug trial in which they were tested on two different days. On one day, the participant would receive a single dose of Ritalin, and on an alternate day, he or she would receive a placebo pill. The participants were randomly assigned to receive either Ritalin first or placebo first, and neither the researchers nor the participants knew whether they were receiving Ritalin or placebo on a given day (a double-blind study). Due to ethical considerations of giving a stimulant medication to adolescents without ADHD, the comparison group did not go through the drug trial, and were instead tested in a single testing session.
During the study, participants were scanned in an MRI machine while they completed auditory and visual performance tests. Words were projected onto a screen and presented through a set of headphones. The words were either real English words or pronounceable nonsense words. During tests of selective attention, participants were prompted to pay attention to only one of the two presented words and to determine whether that word was a real word or a nonsense word. During tests of divided attention, participants saw and heard a word simultaneously and then needed to determine whether both the words were real words or nonsense words.
We found that the brain activation patterns were remarkably similar between the ADHD, reading disorder, and comparison groups, with one major exception. Part of the basal ganglia, a collection of structures deep within the brain that are known to help direct voluntary motor movements and coordinate behavioral actions, was less active in the ADHD and reading disorder participants when participants took the placebo. When given Ritalin, the activation in this structure increased and was equivalent to the activation in the comparison group. Interestingly, Ritalin did not affect performance on the task, nor did it differentially affect the brain activation patterns of the ADHD and reading disorder groups.
These results suggest that both ADHD and reading disorder are associated with dysfunction in the brain’s attentional and executive functioning circuitry and that Ritalin may act to normalize activity in this circuitry, especially within the basal ganglia. One of the most unexpected findings in the study was that the effects of Ritalin on brain activation appeared to be independent of psychiatric diagnosis. This may indicate that Ritalin has similar effects on brain function whether or not ADHD is present.
In another study, we examined the brain basis of executive functioning in a group of children and their parents, in which both the children and parents had a diagnosis of ADHD (Epstein et al., 2007). The children and parents participated in a double-blind medication trial with Ritalin. As before, participants were randomly assigned to receive Ritalin first or placebo first, and then received the alternate medication on a second testing day. Participants were then scanned using fMRI while they completed a go/ no-go response inhibition test. During the task, English letters appeared one at a time on a computer screen, and participants were instructed to press a button for all letters except “X.” Results from the group of children and parents with ADHD were compared to results from a group of child-parent dyads with no history of psychiatric disorder or learning disability. This comparison group did not participate in the medication trial.
We found that compared with the group without ADHD, children and their parents with ADHD showed reduced activation in the basal ganglia and in regions of the frontal lobe of the cerebral cortex (a part of the brain often described as the brain’s CEO). Interestingly, Ritalin increased activation in the basal ganglia for both the children and parents with ADHD. These results indicate that the brain structures implicated in ADHD may not change over the course of development. Further, the results lend additional support to the idea that Ritalin exerts its behavioral and cognitive effects by altering the function of the basal ganglia.
In another line of research, my colleagues and I have been investigating the brain basis of executive functioning in autism. Although the most prominent symptoms of autism are impairments in social interaction and social communication, many individuals with autism also have repetitive, stereotyped patterns of behavior (American Psychiatric Association, 2000). It is believed that these repetitive behaviors are associated with a dysregulation of executive function. Although individuals with autism are not impaired on all laboratory measures of executive functioning, they have fairly consistent difficulties with altering ongoing behaviors (Hill, 2004).
To investigate the brain basis for these difficulties, my colleagues and I conducted an fMRI study in which the brain activation for a group of participants with autism was compared with the activation in a group of typically developing controls (Shafritz, Dichter, Baranek, & Belger, 2008). Study participants watched a computer screen as geometric shapes appeared one at a time. Most of the time, the shapes were squares, but occasionally, a triangle or circle appeared. At the start of each round of the task, either the triangle or circle was designated as the “target“ shape for that group of trials. Participants were required to press one response button for nontarget shapes and an alternate button when a target shape appeared. The shape that was designated as the target changed periodically throughout the task, in order to test whether the autism participants had difficulty maintaining mental flexibility (in addition to behavioral flexibility).
In terms of their behavioral responses, the participants with autism had difficulty altering their behavioral responses when target shapes appeared. Interestingly, participants were able to maintain certain aspects of mental flexibility, because they successfully altered response patterns when the target shape was changed during the task. The brain imaging findings showed that during the response shifting portion of the task, participants with autism had less activation compared with controls in three parts of the brain: the basal ganglia, the prefrontal cortex, and the parietal cortex. These regions are all part of the brain’s attention and executive function circuitry. We also found that activation in parts of these regions was correlated with participants’ scores on a scale measuring the severity of their repetitive behaviors. Taken together, these findings indicate that executive dysfunction is present in autism and is associated with reduced activation in certain brain regions.
As a follow-up to these findings, I am currently working on a project in conjunction with two researchers at North Shore-LIJ, Dr. Joel Bregman and Dr. Phil Szeszko. We are examining the brain basis of emotion recognition and executive functioning in autism to determine the brain regions that may be responsible for faulty social decision making in the disorder. We hope to find dysregulation in certain brain regions that may be specific to autism, because findings to date have shown a great degree of overlap in brain dysfunction for several related psychiatric disorders, including autism, ADHD, schizophrenia, and obsessivecompulsive disorder. Once brain regions are identified that may tie uniquely into each disorder, we will be able to find specific behavioral or drug treatments that target those specific brain regions. Moreover, by targeting treatments to specific brain regions, we hope not only to improve the outcomes of those treatments, but also to limit the side effects of medications that are used to treat the disorders.
The research described here was supported in part by grants from the National Institutes of Health (NIMH, NICHD, NIBIB). Thanks to Dr. Donna Lutz for helpful comments.
American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision. Washington, DC: APA.
Denckla, M. B. (1996). A theory and model of executive function: A neuropsychological approach. In G. R. Lyon & N. A. Krasnegor (Eds.), Attention, Memory, and Executive Function. Baltimore: Brookes Publishing Co.
Epstein, J. N., Casey, B. J., Tonev, S. T., Davidson, M. C., Reiss, A. L., Garrett, A., et al. (2007). ADHDand medication-related brain activation effects in concordantly affected parent-child dyads with ADHD. J Child Psychol Psychiatry, 48(9), 899-913.
Hill, E. L. (2004). Executive dysfunction in autism. Trends Cogn Sci, 8(1), 26-32.
Shafritz, K. M., Dichter, G. S., Baranek, G. T., & Belger, A. (2008). The neural circuitry mediating shifts in behavioral response and cognitive set in autism. Biol Psychiatry, 63(10), 974-980.
Shafritz, K. M., Marchione, K. E., Gore, J. C., Shaywitz, S. E., & Shaywitz, B. A. (2004). The effects of methylphenidate on neural systems of attention in attention deficit hyperactivity disorder. Am J Psychiatry, 161(11), 1990-1997.