The ADHD research studies noted here all look at the functional neurology of ADHD, or how the brain of a person with ADHD functions differently than the brain of a person without ADHD.
Author/s: Nicholas J. Cepeda Issue: June, 2000
The main goal of the present set of studies was to examine the efficiency of executive control processes and, more specifically, the control processes involved in task set inhibition and preparation to perform a new task in attention deficit hyperactivity disorder (ADHD) and non-ADHD children.
This was accomplished by having ADHD children, both on and off medication, and non-ADHD children perform the task-switching paradigm, which involves the performance of two simple tasks.
In nonswitch trials, an individual task is performed repeatedly for a number of trials. In switch trials, subjects must rapidly and accurately switch from one task to the other, either in a predictable or unpredictable sequence.
Switch costs are calculated by subtracting performance on the nonswitch trials from performance on the switch trials. These costs are assumed to reflect the executive control processes required for the coordination of multiple tasks.
ADHD children showed substantially larger switch costs than non-ADHD children. However, when on medication, the ADHD children's switch performance was equivalent to control children. In addition, medication was observed to improve the ADHD children's ability to inhibit inappropriate responses.
These data are discussed in terms of models of ADHD and cognition.
Anna B. Smith, Ph.D., Eric Taylor, M.D., Ph.D., Mick Brammer, Ph.D., Brian Toone, M.D. and Katya Rubia, Ph.D.
OBJECTIVE: A relatively small number of functional imaging studies of attention deficit hyperactivity disorder (ADHD) have shown abnormal prefrontal and striatal brain activation during tasks of motor response inhibition.
However, the potential confound of previous medication exposure has not yet been addressed, and no functional imaging study exists to date on medication-naive children and adolescents with ADHD.
The aim of this study was to investigate the neural substrates of a range of motor and cognitive inhibitory functions in a relatively large group of children and adolescents with ADHD who had never previously been exposed to medication.
METHOD: Nineteen boys with ADHD and 27 healthy age- and IQ-matched boys underwent functional MRI to compare brain activation during performance of tasks that assessed motor response inhibition (go/no go task), cognitive interference inhibition (motor Stroop task), and cognitive flexibility (switch task).
RESULTS: Boys with ADHD showed decreased activation in the left rostral mesial frontal cortex during the go/no go task and decreased activation in the bilateral prefrontal and temporal lobes and right parietal lobe during the switch task. No significant group differences were observed during motor Stroop task performance.
CONCLUSION: Abnormal brain activation was observed in medication-naive children and adolescents with ADHD during tasks involving motor inhibition and task switching, suggesting that hypoactivation in this patient group is unrelated to long-term stimulant exposure.
Furthermore, functional abnormalities are task-specific and extend from frontostriatal to parietal and temporal cortices.
Review of a journal article by Troy Janzen, Ken Graap, Stephan Stephanson, Wilma Marshall, and George Fitzsimmons
"Differences in Baseline EEG Measures for ADD and Normally Achieving Preadolescent Males"
Biofeedback and Self-Regulation, Vol. 20, No. 1, 1995, pp. 65-82.
Three well known tests (WISC-R, WRMT-R, WRAT-R) were administered to all subjects prior to the main part of the study, a series of cognitive tests performed while connected to a 19 lead EEG cap.
Findings: The most consistent finding was that ADD subjects have significantly higher theta amplitudes (p < .05) for all sites at both baseline and while performing cognitive tasks. There were also differences in the ratios of theta to beta and theta to SMR for baseline and all tasks at all sites, but the differences were significant only for some tasks at the parietal sites. The raw beta and SMR amplitudes themselves were not significantly different between the two groups.
The authors conclude that although the number of subjects was small, there were significant differences that could be observed. These findings form a starter set of data for additional efforts.
A neuropsychological study using the Six Elements Test and Hayling Sentence Completion Test
J Abnorm Child Psychol 2000 Oct;28(5):403-14
Clark C, Prior M, Kinsella GJ
School of Psychological Science, La Trobe University, Victoria, Australia.
[Record supplied by publisher]
Two neuropsychological measures of executive functions--Six Elements Tests (SET) and Hayling Sentence Completion Test (HSCT)-were administered to 110 adolescents, aged 12-15 years.
Participants comprised four groups: Attention Deficit Hyperactivity Disorder (ADHD) only (n = 35). ADHD and Oppositional Defiant Disorder/Conduct Disorder (ODD/CD) (n = 38), ODD/CD only (n = 11), and a normal community control group (n = 26).
Results indicated that adolescents with ADHD performed significantly worse on both the SET and HSCT than those without ADHD, whether or not they also had ODD/CD.
The adolescents with ADHD and with comorbid ADHD and ODD/CD were significantly more impaired in their ability to generate strategies and to monitor their ongoing behavior compared with age-matched controls and adolescents with ODD/CD only.
It is argued that among adolescents with clinically significant levels of externalizing behavior problems, executive function deficits are specific to those with ADHD.
The findings support the sensitivity of these two relatively new tests of executive functions and their ecological validity in tapping into everyday situations, which are potentially problematic for individuals with ADHD.
Executive functions and developmental psychopathology.
J Child Psychol Psychiatry 1996 Jan;37(1):51-87
Pennington BF, Ozonoff S
Department of Psychology, University of Denver, CO 80208, USA.
In this paper, we consider the domain of executive functions (EFs) and their possible role in developmental psychopathologies.
We first consider general theoretical and measurement issues involved in studying EFs and then review studies of EFs in four developmental psychopathologies: attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), autism, and Tourette syndrome (TS).
Our review reveals that EF deficits are consistently found in both ADHD and autism but not in CD (without ADHD) or in TS.
Moreover, both the severity and profile of EF deficits appears to differ across ADHD and autism. Molar EF deficits are more severe in the latter than the former. In the few studies of more specific EF tasks, there are impairments in motor inhibition in ADHD but not in autism, whereas there are impairments in verbal working memory in autism but not ADHD. We close with a discussion of implications for future research.
Author/s: Russell Schachar
Issue: June, 2000
The objective of this study was to determine whether deficient inhibitory control distinguishes children with a diagnosis of attention-deficit/hyperactivity (ADHD) disorder, conduct disorder (CD), and comorbid ADHD + CD from normally developing children.
Participants were rigorously diagnosed children (age 7 to 12 years) with ADHD (N = 72), CD (N = 13) or ADHD + CD (N = 47) and 33 control children (NC). We studied inhibitory control using the stop-signal paradigm, a laboratory task that assessed the ability to inhibit an ongoing action.
The ADHD group had significantly impaired inhibitory control compared to NC, CD, and ADHD + CD children.
These results indicate that children with ADHD have deficient inhibition as measured in the stop-signal paradigm and that ADHD occurring in the presence of ADHD + CD may represent a phenocopy of CD rather than a variant of ADHD.
Author/s: Rosemary Tannock Issue: June, 2000
Rosemary Tannock [1,2] Rhonda Martinussen [1] Jan Frijters [1]
This study investigated rapid automatized naming and effects of stimulant medication in school-age children with attention-deficit/hyperactivity disorder (ADHD) with and without concurrent reading disorder (RD).
Two ADHD groups (67 ADHD only; 21 ADHD + RD) and a control group of 27 healthy age-matched peers were compared on four variables: color naming speed, letter naming speed, phonologic decoding, and arithmetic computation. Discriminant function analysis (DFA) was conducted to predict group membership. The four variables loaded onto two discriminant functions with good specificity: phonologic decoding, letter naming speed, and arithmetic defined the first function; color naming speed defined the second function.
Both ADHD groups were significantly slower in color naming than controls, but did not differ from one another.
DFA correctly classified 96% of the control group, 91% of ADHD + RD, and 82% of ADHD only.
A subset of children in the ADHD groups participated subsequently in an acute, randomized, place bo-controlled, crossover trial with three single doses (10, 25, 20 mg) of methylphenidate.
Methylphenidate selectively improved color-naming speed but had no effect on the speed of naming letters or digits.
These findings challenge the tenet that naming speed deficits are specific to RD and implicate naming speed deficits associated with effortful semantic processing in ADHD, which are improved but not normalized by stimulant medication.
J Neuropsychiatry Clin Neurosci 1994 Summer;6(3):245-9
Aronowitz B, Liebowitz M, Hollander E, Fazzini E, Durlach-Misteli C, Frenkel M, Mosovich S, Garfinkel R, Saoud J, DelBene D, et al
Department of Psychiatry,
New York State Psychiatric Institute, New York.
Neuropsychiatric and neuropsychological evaluations were performed in a pilot study of adolescents with DSM-III-R disruptive behavior disorders, including conduct disorder (CD) and attention-deficit hyperactivity disorder (ADHD).
The following comparisons were made: 1) CD comorbid with ADHD vs. CD only; 2) all subjects with ADHD vs. all non-ADHD; and 3) all subjects with CD vs. all non-CD.
The CD + ADHD group had increased left-sided soft signs compared with the CD group.
CD + ADHD subjects significantly underperformed CD subjects on several executive functioning measures, with no differences on Verbal IQ subtests.
Results are discrepant with previous findings of deficient verbal functioning in delinquent populations.
Am J Psychiatry 1999 Aug;156(8):1216-22
Oie M, Rund BR
National Centre for Child and Adolescent Psychiatry, University of Oslo, Norway.
OBJECTIVE: Impaired neuropsychological performance involving abstraction-flexibility, memory, motor function, and attention has frequently been reported in schizophrenia as well as in attention deficit hyperactivity disorder (ADHD).
This study represents an attempt to compare groups of adolescents with schizophrenia and ADHD on a comprehensive neuropsychological test battery. Such a comparison affords the opportunity to ascertain differences in the degree, profile, and specificity of impairments.
Neuropsychological functioning of adults with attention deficit hyperactivity disorder.
J Clin Exp Neuropsychol 2000 Feb;22(1):115-24
Walker AJ, Shores EA, Trollor JN, Lee T, Sachdev PS
Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia.
The neuropsychological functioning of adults with Attention Deficit Hyperactivity Disorder (ADHD) was compared to that of healthy controls and individuals with mild psychiatric disorders including attentional complaints.
Thirty adults in each group were examined on the Conners' Continuous Performance Test (CPT) and measures of attention, executive function, psychomotor speed, and arithmetic skills.
The ADHD group performed lower than healthy controls on most measures.
However when compared to the psychiatric group, the performances of the ADHD group were not significantly lower on any of the measures.
J Child Psychol Psychiatry 1994 Oct;35(7):1229-45
Leung PW, Connolly KJ
Department of Psychology,
Chinese University of Hong Kong, Shatin, New Territories.
A random population sample of 1479 Chinese boys from Hong Kong was screened and diagnosed in a two-stage epidemiological study. Four groups, age 7-8, were distinguished: (1) a pure hyperactive group (HA), (2) a mixed hyperactive/conduct-disordered group (HA+CD), (3) a pure conduct-disordered group (CD), and (4) a normal control group (N).
On a visual search task, only the pure hyperactive (HA) children showed a specific processing deficit in performance.
Each group showed a performance decrement over time in the visual search task but the decrement did not differ between the four groups. This observation is not congruent with the reports of a short attention span in hyperactive children; explanations of this apparent contradiction are considered.
J. F. Lubar, M. O. Swartwood, J. N. Swartwood, D. L. Timmermann
University of Tennessee
Neurophysiological correlates of Attention Deficit Disorder with and without Hyperactivity (AD/HD) and effects of methylphenidate are explored using electroencephalographic (EEG) and auditory eventrelated potentials (ERPs).
In the first of four studies, a database of AD/HD individuals of varying ages and matched adolescent/adult controls is presented.
Study 2 compares controls and age-matched children with ADD, and children with ADHD on and off methylphenidate.
Study 3 examines habituation of the auditory ERPs of controls and children with ADHD both on and off methylphenidate.
The relationship between successful neurofeedback training and EEG changes is presented in Study 4.
Overall, these studies support a neurologic basis for AD/HD and raise questions regarding the role of methylphenidate in modulating cortical processing.
Source: Stanford University
Date: November 24, 1998
Science Daily — Stanford neuro-scientists have found a clear difference in brain functioning between boys who have attention deficit disorder [ADHD] and those who do not, a step that could lead to better diagnosis of the most common developmental disorder of childhood.
Follow-up studies will be required before the results of this study on a small number of boys can lead to brain-based methods of diagnosis, caution the lead researchers, Research Associate Chandan Vaidya and Associate Professor John Gabrieli of Stanford's Department of Psychology.
Theirs is the first study, however, to show that Ritalin, the drug most commonly used to treat ADD, has different effects on the brains of people with and without ADD, and where those differences occur in the brain. The findings are reported in the Nov. 24 issue of the Proceedings of the National Academy of Sciences.
The study is also the first to use functional magnetic resonance imaging [FMRI] in the study of ADD. This imaging method can show brain differences in individual people, instead of in averages of differences of two groups. This is critical for diagnosis, which has to be established on an individual basis. Unlike methods used in other studies of ADD, FMRI does not require injection or inhalation of radioactive substances. It relies instead on naturally occurring changes in brain function, which makes it appropriate for research and clinical purposes for children.
Co-authors of the study are medical doctors Glenn Austin and Hugh Ridlehuber and school psychologist Gary Kirkorian of the Community/Academia Coalition in Los Altos, Calif. and Gary Glover and John Desmond of the Stanford Medical Center's Radiology Department.
The findings have drawn considerable attention from neuroscientists because "ADD is so widespread, so controversial and confusing, and these are among the few clear findings in that field," said Gabrieli, who heads the brain imaging laboratory where the research was done.
Attention deficit disorder, which often includes hyperactivity, is currently diagnosed on the basis of subjective observations of youngsters' behavior. If the new findings can be replicated, he said, it might be possible to make a biological diagnosis of the disorder by using FMRI. Since the common treatment for ADD is a prescription drug whose long-term effects on brain function are not known, parents and pediatricians most likely would welcome a more definitive way to diagnose the disorder.
Comparing the brain images later, researchers found a clear difference in the activation of neuronal tissue in two structures in the striatal region, which is known to be involved in motor control. The brain activation differences between the boys with ADD and those without were even more dramatic when the subjects were asked to perform the same task after taking the drug Ritalin. Ritalin is a stimulant medication used to temporarily relieve symptoms of ADD, such as inattention, impulsivity and hyperactivity.
"Both the normal kids and the ADD kids got better in their impulse control when they had taken the drug," Vaidya said. "Ritalin improved everyone's performance, but how it actually did it differed in the brains."
The boys with ADD showed more activity in the affected striatal structures (specifically known as the caudate and putamen) when taking the drug than when not. The healthy boys, in contrast, showed the reverse - less activity in those areas when taking the drug than when not.
"From past work with adults and children, some of which required injecting radioactive material, a consensus developed that it is the frontal striatal circuitry of the brain that is what's not right with this disorder," Vaidya said. "That is why we imaged this part of the brain, and our study confirmed that these structures are, indeed, important for ADD."
Ritalin primarily, but not exclusively, influences dopamine neurotransmission. The opposite effects of Ritalin on boys with ADD and boys without the disorder suggest that ADD involves atypical dopamine modulation in the striatum, she said.
The researchers caution that the study was conducted with a small group and needs to be replicated with girls as well as with more boys before they can be certain they have found a universal neurobiological marker for the disorder. They also reported that they tried the experiment on three other boys who had not been diagnosed with ADD but who had siblings with the diagnosis. Two of the three siblings of ADD boys showed some Ritalin enhancement of the striatum, as did their affected brothers.
"This would lend some support to the idea that ADD may involve atypical genetic influences on dopamine modulation," Vaidya said, but more studies would be necessary to establish a genetic influence.
Because of the widespread interest in ADD, the researchers also were careful to point out other limitations of their study. A fraction of people diagnosed with ADD have not responded to Ritalin treatment, and this study did not include such children, they said. It also did not attempt to investigate possible changes in brain activation that might occur with the drug over time. The ADD boys did show a different brain activation level when not on the drug, but all of them had been taking Ritalin previously as part of their ongoing treatment.
Despite these limitations, the study points to new directions for research into brain function that could improve individuals' performance.
"This is one of the few studies to examine brain function in children, and to further our knowledge about normal and abnormal brain development," Gabrieli said. "It suggests that FMRI is a powerful tool to examine brain and behavior in the context of both normal and abnormal development."
Currently, ADD impairs the function of an estimated 3 to 7 percent of youngsters in home and school, and the long-term consequences include lower educational and vocational accomplishments for them as adults as well as an increased risk for drug abuse and other risky behaviors.
The study was funded by a grant from the El Camino Hospital District Board in Mountain View, Calif.
Note: This story has been adapted from a news release issued by Stanford University.