Attention-deficit/hyperactivity disorder in childhood epilepsy: a neuropsychological and functional imaging study.

PURPOSE: Children with epilepsy have a significant risk for attention-deficit/hyperactivity disorder (ADHD), which is often accompanied by deficits in working memory performance. However, it is not yet clear whether there are specific differences in the underlying mechanisms of working memory capability between children with epilepsy-related ADHD and those with developmental ADHD. There is evidence that methylphenidate can improve the behavioral difficulties in children with developmental ADHD. Whether this medication has the same effect on ADHD symptoms in patients with epilepsy is not yet well understood. The aim of the present study is, therefore, to evaluate whether boys with epilepsy-related ADHD and developmental ADHD share a common behavioral, pharmacoresponsive, and neurofunctional pathophysiology. METHODS: Seventeen boys with diagnosed combined epilepsy/ADHD, 15 boys with developmental ADHD, and 15 healthy controls (aged 8-14 years) performed on working memory tasks (N-back) while brain activation was recorded using functional magnetic resonance imaging. Each patient was tested twice: once after the intake of methylphenidate and once without in a counterbalanced order. KEY FINDINGS: On a behavioral level, we show that boys with epilepsy-related ADHD as well as those with developmental ADHD performed similarly poorly on tasks with high cognitive load when compared to healthy controls, and that intake of methylphenidate improved performance almost to normal levels in both ADHD groups. On the functional level, both patient groups showed similar reductions of activation in all relevant parts of the functional network of working memory when compared to controls. Of interest, intake of methylphenidate did not significantly alter this activity pattern. SIGNIFICANCE: Our data show strong similarities between epilepsy-related and developmental ADHD on the behavioral, pharmacoresponsive, and neural level, favoring the view that ADHD with and without epilepsy shares a common underlying neurobehavioral pathophysiology.

Structural and functional imaging approaches in attention deficit/hyperactivity disorder: does the temporal lobe play a key role?

Attention deficit/hyperactivity disorder (ADHD) is characterized by widespread structural and functional abnormalities in the brain. We applied different structural imaging techniques such as voxel-based morphometry (VBM), diffusion tensor imaging (DTI), and magnetization transfer imaging (MTI) to study anatomical differences between boys with ADHD and healthy controls, as well as functional magnetic resonance imaging (fMRI) together with independent component analysis (ICA) to detect functional alterations. 14 boys with ADHD and 12 controls were included in our study. Results of DTI showed the expected differences in frontal and cerebellar white matter. VBM and MTI indicated group differences in the temporal lobe. Applying ICA to fMRI data, we extracted four components; two positively correlated to our working memory paradigm and two negatively correlated. Positive components included activation in frontal and parietal regions. Negative components showed activation in anterior and posterior cingulate cortex/precuneus and temporal regions, and were interpreted as forming part of the default mode network. Group differences in the inferior temporal lobe were detected. Applying different techniques, we found differences between boys with ADHD and controls mainly located in the temporal lobe. Therefore, we postulate that research on ADHD should broaden its scope by including the temporal lobe as a potentially important locus of abnormalities in ADHD.

Reduced response to reward in smokers and cannabis users.

BACKGROUND: Cannabis is one of the most commonly used illicit drugs. Reduced neural and behavioral reactions to reward have been demonstrated in other forms of addiction, as expressed by reduced mood reactivity and lack of striatal activation to rewards, but this effect has not yet been investigated in cannabis users. METHODS: We hypothesized that cannabis users and tobacco smokers would evidence lower positive mood ratings in rewarded conditions than control participants and that this reduction would be greater in cannabis users than in smokers. We examined the influence of reward on mood and performance in a group of regular cannabis users, a group of tobacco smokers and a group of nonsmokers while they performed a spatial recognition task with delayed response that incorporated 3 levels of difficulty. Correct responses were either not reinforced or reinforced with money. We measured the accuracy of reactions, reaction times and mood ratings throughout the trials. RESULTS: Cannabis users rated their mood as significantly worse than the smokers and nonsmokers during the easiest level of the rewarded condition. A significant positive correlation between mood ratings and monetary reward was found in the nonsmokers but not in the cannabis users and smokers. The groups did not differ with regard to task performance. CONCLUSIONS: Our results suggest that regular cannabis use affects certain aspects of motivation and that both tobacco smoking and cannabis use lead to similar motivational changes. However, the use of cannabis seems to affect motivation in a stronger way than does tobacco smoking alone.

Decreased fractional anisotropy in the middle cerebellar peduncle in children with epilepsy and/or attention deficit/hyperactivity disorder: a preliminary study.

Children with epilepsy are at increased risk for attention deficit/hyperactivity disorder (ADHD). It has been shown that the cerebellum plays a major role in the pathophysiology of ADHD. We aimed to clarify whether children with combined epilepsy/ADHD have the same neurocerebellar pathophysiology as children with developmental ADHD. Eight boys with combined epilepsy/ADHD, 14 boys with developmental ADHD, and 12 healthy boys were investigated using diffusion tensor imaging generating fractional anisotropy (FA) maps. Healthy controls exhibited more FA in the left and in the right middle cerebellar peduncle compared with children with combined epilepsy/ADHD, and more FA in the right middle cerebellar peduncle compared with children with developmental ADHD. Our data show deficient cerebellar connections in both patient groups and endorse the crucial role of the cerebellum in the pathophysiology of ADHD. Our results suggest that ADHD seen in epilepsy might have the same cerebellar pathology as in developmental ADHD.

The Stroop task: comparison between the original paradigm and computerized versions in children and adults.

The Stroop task has a long-standing history in psychological research and diagnostics, and many variants have emerged. Computerized versions have recently gained popularity because of their applicability in brain-imaging studies. It remains unclear, however, whether computerized versions are content valid with reference to the original task. We compare the performance in the original task with two computerized versions. All three versions show high test-retest reliability and are able to elicit interference effects, but to varying degrees. However, performances in the computerized versions and in the original task do not correlate. The transition from oral to manual response and from listed to single stimulus presentation seems not only to diminish the interference effect, but also to alter its nature in such a way that it no longer looks genuinely "Stroop-like". These findings have important clinical implications on the use and interpretation of computerized Stroop tasks in children and adults.

Effects of methylphenidate on working memory functioning in children with attention deficit/hyperactivity disorder.

BACKGROUND AND AIMS: Children with attention deficit/hyperactivity disorder (ADHD) often show deficits in working memory performance. Methylphenidate (MPH) is an effective medication to improve these cognitive difficulties. This study aimed to clarify which effect MPH induces on the underlying functional networks of working memory. METHODS: Fourteen boys diagnosed with ADHD and 12 healthy controls were investigated using functional magnetic resonance imaging (fMRI). Each patient was tested twice, once with medication and once without. The fMRI experiments consisted of three verbal N-back tasks with increasing difficulty. Functional images were acquired on a 3 Tesla head scanner. RESULTS: On the behavioral level, medicated patients performed similar to healthy controls and significantly better than without medication. On the functional level, patients showed the expected frontal and parietal activations, which were more pronounced in the 2- and 3-back tasks. Healthy controls showed significantly more activation in these regions and additional activation in the cerebellum. Interestingly, patients showed an additional effect of laterality. Left-sided frontal and parietal activation in patients was significantly less pronounced than in controls. CONCLUSION: Functional data indicate different activation patterns in verbal working memory tasks between healthy controls and patients with ADHD irrespective of medication condition. Intake of MPH led to a clear improvement on a behavioral level. However, this effect was not reflected by changes in functional brain organization. MPH-induced changes leading to better performance in verbal working memory tasks might be very subtle and therefore not detectable by fMRI.