EEG correlates of methylphenidate response among children with ADHD: a preliminary report.

BACKGROUND: Recent electrophysiologic studies have found fairly consistent differences between children with attention-deficit/hyperactivity disorder (ADHD) and age-matched control subjects. The present study examined electroencephalogram (EEG) changes associated with a double blind, placebo-controlled administration of methylphenidate among children with ADHD. METHODS: Subjects were 10 children, ages 8 to 13, with a primary diagnosis of ADHD. Brain electrical activity was recorded with 7 electrodes in the frontal, central, and midline areas during baseline and cognitive activation conditions. RESULTS: Repeated-measures ANOVAs indicate that children exhibiting a positive medication response had reductions of theta and alpha as well as increased beta in the frontal regions, while nonresponders showed the opposite pattern (p < .05). Significant correlations between improvement on a vigilance task and changes in beta activity in the frontal electrodes emerged as well. CONCLUSIONS: These preliminary findings indicate that there are different electrophysiologic correlates to methylphenidate among ADHD children who are medication responders and nonresponders.     

Effects of stimulant medications on children with attention-deficit/hyperactivity disorder and excessive beta activity in their EEG.

OBJECTIVE: This study investigated the effects of stimulant medications on the Electroencephalography (EEG) of children with the combined type of attention-deficit/hyperactivity disorder (ADHD) together with excessive beta activity in their EEG. METHODS: Twenty ADHD and 20 control subjects participated in this study. EEG was recorded from 21 sites during an eyes-closed resting condition and Fourier transformed to provide estimates for total power and absolute and relative power in the delta, theta, alpha and beta bands, and for the theta/alpha and theta/beta ratios. Subjects were placed on a 6-month trial of a stimulant medication and a second EEG was recorded at the end of the trial. RESULTS: The unmedicated ADHD group had greater absolute and relative beta, less absolute and relative alpha, a higher theta/alpha and a lower theta/beta ratio than the control group. In the frontal regions the ADHD group had an increase in total power, absolute theta, absolute and relative beta and the theta/beta ratio, with greater relative delta, relative theta, and absolute and relative alpha in posterior regions. With medication use, absolute beta activity and frontal total power decreased, although these changes represented a reduction in power, not a normalisation. CONCLUSIONS: These results indicate that ADHD children with excessive beta activity in their EEG are probably not hypoaroused as previously suggested, and that beta activity in these children is probably only associated with the impulsivity and/or hyperactivity aspects of the disorder, but may not necessarily be associated with inattention. SIGNIFICANCE: This study is the first to investigate effects of stimulant medications on the EEG of ADHD children with excessive beta activity in their EEG.     

The Effects of Methylphenidate on Neural Substrates Associated with Interference Suppression in Children with ADHD: A Preliminary Study Using Event Related fMRI

Objective

The core deficit of attention deficit hyperactivity disorder (ADHD) is associated with frontal cortex and related circuitry. Children with ADHD and a medication history have shown atypical brain activation in prefrontal and striatal brain regions during cognitive challenge. We investigated two cognitive control operations such as interference suppression (IS) and response inhibition (RI) in children with ADHD. We also assessed the brain functions affected by the methylphenidate (MPH) effect by comparing the blood-oxygen level dependent (BOLD) signals in ADHD children on and off medication.

Methods

Eight children (9-11 years of age) with combined-type ADHD underwent rapid event-related functional magnetic resonance imaging (fMRI) during performance of a modified flanker task. Two fMRI (3.0 T) scans were conducted with a one week interval-one with MPH treatment and the other without. Functional maps were generated through group averaging and performance-based correlational analyses.

Results

Performances of the two cognitive control operations did not differ significantly between on-MPH and off-MPH status other than the reaction time to incongruent stimuli in ADHD children. In those affected by MPH treatment, an increased activation in the right prefrontal cortex during incongruent task was observed relative to a neutral trial in children with ADHD.

Conclusion

On the treatment of MPH, the ADHD children exhibited increased activation of the right frontal cortex during interference suppression. This finding suggested that MPH affected the right frontal cortex in ADHD compensating for a reduced level of interference suppression. Future studies will be required to ascertain the MPH effect of cognitive brain regions among large number of children with ADHD.     

Functional effects of the DAT1 polymorphism on EEG measures in ADHD

OBJECTIVE: This paper examines whether dopamine transporter gene (DAT1) allele status mediates medication-related change in cognitive and neurophysiological measures among children with attention-deficiency/hyperactivity disorder (ADHD). METHOD: A single 10-mg dose of methylphenidate was given in a double-blind, placebo-controlled fashion to children with ADHD who were seen for cognitive testing and EEG recording. Buccal samples were obtained and genotyped for the DAT1 polymorphism. RESULTS: DAT1 allele status was associated with performance on a sustained attention task and medication-related EEG changes. Compared with those with one or more copies of the DAT1 9-repeat allele (9R), children with two copies of the 10-repeat allele (10R) exhibited poorer performance on the vigilance task. In addition, children with 10R exhibited medication-related EEG changes of increased central and parietal beta power, decreased right frontal theta power, and lower theta/beta ratios; 9R carriers showed the opposite pattern. CONCLUSIONS: The data suggest that the DAT1 polymorphism mediates medication-related changes in cortical activity among children with ADHD.     

Task-specific hypoactivation in prefrontal and temporoparietal brain regions during motor inhibition and task switching in medication-naive children and adolescents with attention deficit hyperactivity disorder

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.     

EEG-defined subtypes of children with attention-deficit/hyperactivity disorder.

OBJECTIVES: This study investigated the presence of EEG clusters within a sample of children with the combined type of attention-deficit/hyperactivity disorder (ADHD). METHODS: Subjects consisted of 184 boys with ADHD and 40 age-matched controls. EEG was recorded from 21 sites during an eyes-closed resting condition and Fourier transformed to provide estimates for total power, and relative power in the delta, theta, alpha and beta bands, and for the theta/beta ratio. Factor analysis was used to group sites into 3 regions, covering frontal, central and posterior regions. These data were subjected to cluster analysis. RESULTS: Three distinct EEG clusters of children with ADHD were found. These were characterized by (a) increased slow wave activity and deficiencies of fast wave, (b) increased high amplitude theta with deficiencies of beta activity, and (c) an excess beta group. CONCLUSIONS: These results indicate that children with ADHD do not constitute a homogenous group in EEG profile terms. This has important implications for studies of the utility of EEG in the diagnosis of ADHD. Efforts aimed at using EEG as a tool to discriminate ADHD children from normals must recognize the variability within the ADHD population if such a tool is to be valid and reliable in clinical practice.     

Cortical activity patterns in ADHD during arousal, activation and sustained attention

Objective

The goal of the present study is to test whether there are Attention-Deficit Hyperactivity Disorder (ADHD)-related differences in brain electrical activity patterns across arousal, activation and vigilance states.

Method

The sample consists of 80 adults (38 with ADHD and 42 non-ADHD controls) who were recruited for a family study on the genetics of ADHD. Patterns of cortical activity were measured using electroencephalography (EEG) during baseline and sustained attention conditions and compared according to ADHD diagnostic status. Cortical activity was examined separately for the first, middle, and last 5-min of the sustained attention task to assess whether patterns differed over time and according to ADHD status.

Results

In frontal and parietal regions, patterns of activation in the alpha (8-10 Hz) range differed according to ADHD status, indicating increased cortical arousal among ADHD subjects. Beta power (13-14 and 17-18 Hz) also differed between ADHD and controls, indicating increased cortical activation is associated with ADHD. Behavioral performance on the sustained attention task did not differ significantly by diagnosis. EEG correlates of cognitive performance differed significantly ADHD diagnosis and were primarily in frontal regions. Brain activation patterns recorded during the sustained attention task suggest that the ADHD group exhibited significantly increased cortical activation at the end of the task when compared to controls.

Conclusions

Adults with ADHD may have different neural organization primarily in frontal regions which results in the need for continually high levels of cortical activation to maintain sustained attention.     

Coherence in children with Attention-Deficit/Hyperactivity Disorder and excess beta activity in their EEG.

OBJECTIVE: This study investigated differences in coherence measures between two groups of children with Attention-Deficit/Hyperactivity Disorder (ADHD) - with the typical EEG profile (increased theta and decreased beta activity), and with excess beta activity - and a normal control group. METHODS: Thirty-four children with ADHD were included in each of the typical and excess beta groups, and were age and sex matched with 34 control subjects. EEG was recorded from 21 sites during an eyes-closed resting condition. Wave-shape coherence was calculated for eight intrahemispheric and eight interhemispheric electrode pairs, for the delta, theta, alpha and beta bands. RESULTS: In comparison to the controls, the typical ADHD group primarily had increased intrahemispheric theta and beta coherence at short-medium inter-electrode distances, and increased interhemispheric coherence for theta in the frontal and central/parietal/occipital regions. Their laterality effect for interhemispheric short-medium inter-electrode distances was reduced in the theta band. Differences between the excess beta group and the control group were primarily found in laterality of the intrahemispheric theta coherence at short-medium electrode distances, and increased interhemispheric theta coherence in the frontal regions. Reduced delta coherence in the temporal regions was also found. CONCLUSIONS: These results suggest that ADHD children with excess beta power have an underlying brain dysfunction in the frontal lobes which is found in common with children with the typical EEG profile. However a number of qualitative differences exist which could be associated with other aspects of the ADHD diagnosis or another comorbid condition. SIGNIFICANCE: This is the first study to investigate EEG coherence in ADHD children who have increased beta power.     

The increase in theta/beta ratio on resting-state EEG in boys with attention-deficit/hyperactivity disorder is mediated by slow alpha peak frequency

Attention-deficit/hyperactivity disorder (ADHD) was found to be characterized by a deviant pattern of electrocortical activity during resting state, particularly increased theta and decreased beta activity. The first objective of the present study is to confirm whether individuals with slow alpha peak frequency contribute to the finding of increased theta activity in ADHD. The second objective is to explore the relation between resting-state brain oscillations and specific cognitive functions. From 49 boys with ADHD and 49 healthy control boys, resting-state EEG during eyes open and eyes closed was recorded, and a variety of cognitive tasks were administered. Theta and beta power and theta/beta ratio were calculated using both fixed frequency bands and individualized frequency bands. As expected, theta/beta ratio, calculated using fixed frequency bands, was significantly higher in ADHD children than control children. However, this group effect was not significant when theta/beta ratio was assessed using individualized frequency bands. No consistent relation was found between resting-state brain oscillations and cognition. The present results suggest that previous findings of increased theta/beta ratio in ADHD may reflect individuals with slow alpha peak frequencies in addition to individuals with true increased theta activity. Therefore, the often reported theta/beta ratio in ADHD can be considered a non-specific measure combining several distinct neurophysiological subgroups such as frontal theta and slowed alpha peak frequencies. Future research should elucidate the functional role of resting-state brain oscillations by investigating neurophysiological subgroups, which may have a clearer relation to cognitive functions than single frequency bands.     

Reduced prefrontal hemodynamic response in children with ADHD during the Go/NoGo task: a NIRS study

The current study examined the hemodynamic response during the Go/NoGo task in children with/without attention deficit/hyperactivity disorder (ADHD). Using near-infrared spectroscopy, oxy-Hb and deoxy-Hb concentration changes in the frontal areas were compared during the conditions with/without inhibitory demand. Compared with typically developing children, children with ADHD showed significantly reduced activation during the conditions with inhibitory demand (NoGo-condition) in the frontal areas. However, no significant differences in activation during the conditions without inhibitory demand (Go-condition) were found between the two groups. The current findings revealed that children with ADHD exhibit an altered hemodynamic response specifically during response inhibition, but not during response execution, and suggested the clinical usefulness of near-infrared spectroscopy for the evaluation of response inhibition deficits in children with ADHD.     

Altered neural circuits related to sustained attention and executive control in children with ADHD: An event-related fMRI study

Objective

The aim of this study was to investigate the neural basis of sustained attention, executive processing, and cognitive control in children with attention deficit hyperactivity disorder (ADHD).

Methods

Event-related functional magnetic resonance imaging (fMRI) was used to compare brain activation of 28 medication-naïve children with ADHD aged 7–12 years and 31 healthy controls during a cued continuous performance task (AX-CPT) in three stimulus context conditions (Go, NoGo, Lure).

Results

The children with ADHD showed increased activation in the left middle frontal gyrus, bilateral middle temporal gyrus, left precuneus and right cerebellum posterior lobe under the Lure condition compared to the controls. In the Lure condition, in contrast to the NoGo condition, an increased activation in the left inferior frontal gyrus, right medial frontal gyrus and right inferior parietal gyrus was observed in ADHD children.

Conclusions

The results demonstrate that medication-naïve ADHD children show spatial and temporal abnormalities in neural activities involved in sustained attention and executive control.

Significance

These findings show that there are distinct alternations in neural circuits related to sustained attention and executive control in children with ADHD, and further improve our understanding of the neural substrates of cognitive impairment in children with ADHD.     

Functional magnetic resonance imaging evidence for abnormalities in response selection in attention deficit hyperactivity disorder: differences in activation associated with response inhibition but not habitual motor response

Impaired response inhibition is thought to be a core deficit in attention deficit hyperactivity disorder (ADHD). Prior imaging studies investigating response inhibition in children with ADHD have used tasks involving different cognitive resources, thereby complicating the interpretation of their findings. In this study, a classical go/no-go task with a well-ingrained stimulus-response association (green = go; red = no-go) was used in order to minimize extraneous cognitive demands. Twenty-five children with ADHD and 25 typically developing (TD) children between the ages of 8 and 13 years and group-matched for IQ and performance on the go/no-go task were studied using event-related functional magnetic resonance imaging (fMRI). Analyses were used to examine differences in activation between the ADHD and TD groups for "go" (habitual motor response) and "no-go" (requiring inhibition of the motor response) events. Region-of-interest analyses revealed no between-group difference in activation in association with "go" events. For "no-go" events, the children with ADHD demonstrated significantly less activation than did TD controls within a network important for inhibiting a motor response to a visual stimulus, with frontal differences localized to the pre-supplementary motor area. Although blood oxygenation level-dependent fMRI data show no differences between children with ADHD and TD children in association with a habituated motor "go" response, during "no-go" events, which require selecting not to respond, children with ADHD show diminished recruitment of networks important for response inhibition. The findings suggest that abnormalities in circuits important for motor response selection contribute to deficits in response inhibition in children with ADHD and lend support to the growing awareness of ADHD-associated anomalies in medial frontal regions important for the control of voluntary actions.     

Abnormal brain activation during inhibition and error detection in medication-naive adolescents with ADHD

OBJECTIVE: Patients with attention deficit hyperactivity disorder (ADHD) and a medication history have shown abnormal brain activation in prefrontal and striatal brain regions during cognitive challenge. Previous findings have been confounded, however, by potential long-term effects of stimulant medication exposure and group discrepancies in task performance. The aim of this study was to investigate whether medication-naive adolescents with ADHD would still show abnormal brain activation in prefrontal brain regions during motor response inhibition in a task designed to control for intergroup performance discrepancies. METHOD: Rapid, event-related functional magnetic resonance imaging was used to compare brain activation in 16 medication-naive ADHD adolescents and 21 IQ-, age-, and sex-matched healthy comparison volunteers during a challenging, idiosyncratically adjusted task that required withholding of a triggered motor response. The design, which manipulated task parameters to force each subject to fail on 50% of trials, ensured that subjects worked at the edge of their own inhibitory performance, thereby controlling for intersubject and intergroup performance discrepancies and furthermore allowing for investigation of differences in brain activation related to inhibition and inhibition failure. RESULTS: Medication-naive adolescents with ADHD showed significantly reduced brain activation in the right inferior prefrontal cortex during successful motor response inhibition and in the precuneus and posterior cingulate gyrus during inhibition failure, both of which correlated with behavioral scores of ADHD. CONCLUSIONS: The study shows that abnormal brain activation during inhibitory challenge in ADHD is specific to the disorder, since it persists when medication history and performance discrepancies are excluded.     

Altered neural substrates of cognitive control in childhood ADHD: evidence from functional magnetic resonance imaging

OBJECTIVE: The study compared the neural bases of two cognitive control operations, interference suppression and response inhibition, between children with and children without attention deficit hyperactivity disorder (ADHD). METHOD: Ten children (7-11 years of age) with combined-type ADHD and 10 comparison subjects matched for age and gender underwent rapid event-related functional magnetic resonance imaging (fMRI) during performance of a modified flanker task. Functional maps were generated through group averaging and performance-based correlational analyses. RESULTS: Interference suppression in ADHD subjects was characterized by reduced engagement of a frontal-striatal-temporal-parietal network that subserved healthy performance. In contrast, response inhibition performance relied upon different regions in the two groups, frontal-striatal in comparison subjects but right superior temporal in ADHD children. CONCLUSIONS: Alteration in the neural basis of two cognitive control operations in childhood ADHD was characterized by distinct, rather than unitary, patterns of functional abnormality. Greater between-group overlap in the neural network activated for interference suppression than in response inhibition suggests that components of cognitive control are differentially sensitive to ADHD. The ADHD children's inability to activate the caudate nucleus constitutes a core abnormality in ADHD. Observed functional abnormalities did not result from prolonged stimulant exposure, since most children were medication naive.     

EEG characteristics and visual cognitive function of children with attention deficit hyperactivity disorder (ADHD)

Using visual and auditory continuous performance tests (CPT) and EEG, cognitive function and EEG power were investigated in patients with attention deficit hyperactivity disorder (ADHD). CPT and EEG were conducted for 44 ADHD children and 44 healthy controls of comparable age and sex. The EEG power tests include relative power of theta, alpha, and beta, and theta/beta and theta/alpha ratios. ADHD patients showed significantly higher theta relative power, lower beta relative power, and higher theta/beta ratio (p < 0.05). ADHD patients showed a significantly lower score of auditory CPT (p < 0.05). The EEG power characteristics were correlated significantly with the visual attention function in ADHD children (p < 0.01). Higher-order level cognitive dysfunction affects ADHD pathogenesis. Cortical hypoarousal effects on several mechanisms including the fronto-striatal circuitry may be implicated in the inhibition of prepotent and premature responses.     

Stimulant drug action in attention deficit hyperactivity disorder (ADHD): inference of neurophysiological mechanisms via quantitative modelling.

OBJECTIVE: To infer the neural mechanisms underlying tonic transitions in the electroencephalogram (EEG) in 11 adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) before and after treatment with stimulant medication. METHODS: A biophysical model was used to analyse electroencephalographic (EEG) measures of tonic brain activity at multiple scalp sites before and after treatment with medication. RESULTS: It was observed that stimulants had the affect of significantly reducing the parameter controlling activation in the intrathalamic pathway involving the thalamic reticular nucleus (TRN) and the parameter controlling excitatory cortical activity. The effect of stimulant medication was also found to be preferentially localized within subcortical nuclei projecting towards frontal and central scalp sites. CONCLUSIONS: It is suggested that the action of stimulant medication occurs via suppression of the locus coeruleus, which in turn reduces stimulation of the TRN, and improves cortical arousal. The effects localized to frontal and central sites are consistent with the occurrence of frontal delta-theta EEG abnormalities in ADHD, and existing theories of hypoarousal. SIGNIFICANCE: To our knowledge, this is the first study where a detailed biophysical model of the brain has been used to estimate changes in neurophysiological parameters underlying the effects of stimulant medication in ADHD.     

Neural correlates (ERP/fMRI) of voluntary selection in adult ADHD patients

Deficits in executive functions, e.g. voluntary selection, are considered central to the attention-deficit/hyperactivity disorder (ADHD). The aim of this simultaneous EEG/fMRI study was to examine associated neural correlates in ADHD patients. Patients with ADHD and healthy subjects performed an adapted go/nogo task including a voluntary selection condition allowing participants to freely decide, whether to press the response button. Electrophysiologically, response inhibition and voluntary selection led to fronto-central responses. The fMRI data revealed increased medial/lateral frontal and parietal activity during the voluntary selection task. Frontal brain responses were reduced in ADHD patients compared to controls during free responses, whereas parietal brain functions seemed to be unaffected. These results may indicate that selection processes are related to dysfunctions, predominantly in frontal brain regions in ADHD patients.     

Sources of auditory selective attention and the effects of methylphenidate in children with attention-deficit/hyperactivity disorder.

BACKGROUND: The aim of this study was to determine 1) whether abnormal auditory selective attention in children with attention-deficit/hyperactivity disorder (ADHD), as reflected in the processing negativity (PN) of the event-related potential, is related to impaired frontal functioning; and 2) how methylphenidate (MPh) affects attentional functioning in ADHD. METHODS: Sources of electrical brain activity were estimated in healthy control children, in ADHD children without medication, and in children with ADHD during a placebo-controlled medication trial involving MPh. RESULTS: The source models showed that the PN is generated in the auditory cortex. Children with ADHD showed less activity related to selective attention in this brain region. Administration of MPh resulted in more frontally located sources. CONCLUSIONS: The results showed no evidence for an important role of the frontal cortex in abnormalities in selective attention in children with ADHD. Also, the data did not indicate that MPh normalizes brain activity in these children.     

Dissociation in response to methylphenidate on response variability in a group of medication naïve children with ADHD

Increased variability in reaction time (RT) has been proposed as a cardinal feature of attention deficit hyperactivity disorder (ADHD). Increased variability during sustained attention tasks may reflect inefficient fronto-striatal and fronto-parietal circuitry; activity within these circuits is modulated by the catecholamines. A disruption to dopamine signaling is suggested in ADHD that may be ameliorated by methylphenidate (MPH). This study investigated the effects of MPH administration on the variability in RT and error performance on a sustained attention task of a group of 31 medication naïve children with ADHD, compared with 22 non-ADHD, non-medicated, control children. All children performed the fixed-sequence sustained attention to response task (SART) at two time-points: at baseline and after six weeks. The children with ADHD were tested when medication naive at baseline and after six weeks of treatment with MPH and whilst on medication. The medication naïve children with ADHD performed the SART with greater errors of commission and omission when compared with the control group. They demonstrated greater standard deviation of RT and fast moment-to-moment variability. They did not differ significantly from the control group in terms of slow variability in RT. MPH administration resulted in reduced and normalised levels of commission errors and fast, moment-to-moment variability in RT. MPH did not affect the rate of omission errors, standard deviation of RT or slow frequency variability in RT. MPH administration may have a specific effect on those performance components that reflect sustained attention and top–down control rather than arousal.