Nina Bechtel

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.

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.

Fatigue in multiple sclerosis : relation to depression, physical impairment, personality and action control

Athough fatigue is one of the most common symptoms of multiple sclerosis, it is yet poorly understood and therefore difficult to manage. To clarify the nature of fatigue we investigated its relationship to depression, physical impairment, personality and action control and compared these variables between a sample of 41 MS patients and 41 healthy controls. Physical impairment was assessed by the EDSS and all other dimensions, using questionnaires. Stepwise linear regression analyses revealed that physical impairment was related to physical fatigue in MS patients. Depression was the main factor influencing fatigue among both, MS patients and controls. What clearly differentiated the two groups was the correlation between fatigue and action control. Decreased levels of action control imply attentional and motivational deficits and were only found in fatigued MS patients. Our study indicates that motivational disturbances might be specific for MS related fatigue. Multiple Sclerosis 2007; 13: 1161—1167. http://msj.sagepub.com

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.

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.

Attention deficit/ hyperactivity disorder in childhood epilepsy: A neuropsychological and fMRI 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.

Congenital muscular dystrophy with dropped head phenotype and cognitive impairment due to a novel mutation in the LMNA gene

Mutations in A-type nuclear lamins are known to cause a variety of diseases, which can affect almost all organs of the human body including striated muscle. For lamin-related congenital muscular dystrophy two different phenotypes are known to date. Here, we describe a 3-year-old, white Caucasian girl with a novel de novo mutation in the LMNA gene with marked hypotonia of neck and trunk muscles with dropped head posture, loss of cervical lordosis and marked joint laxity. In addition to this novel mutation, the patient also had cerebral white matter lesions on MRI and cognitive impairment on developmental testing. This is only the second A-type lamin-related congenital muscular dystrophy patient in which white matter lesions are described. Thus, white matter involvement might be a feature in A-type lamin-related congenital muscular dystrophy, warranting screening of these patients for both white matter lesions and cognitive impairment.

Effects of gestational age on brain volume and cognitive functions in generally healthy very preterm born children during school-age : a Voxel-based morphometry study

Objective To determine whether the relationship of gestational age (GA) with brain volumes and cognitive functions is linear or whether it follows a threshold model in preterm and term born children during school-age. Study design We studied 106 children (M = 10 years 1 month, SD = 16 months; 40 females) enrolled in primary school: 57 were healthy very preterm children (10 children born 24–27 completed weeks’ gestation (extremely preterm), 14 children born 28–29 completed weeks’ gestation, 19 children born 30–31 completed weeks’ gestation (very preterm), and 14 born 32 completed weeks’ gestation (moderately preterm)) all born appropriate for GA (AGA) and 49 term-born children. Neuroimaging involved voxel-based morphometry with the statistical parametric mapping software. Cognitive functions were assessed with the WISC-IV. General Linear Models and multiple regressions were conducted controlling age, sex, and maternal education. Results Compared to groups of children born 30 completed weeks’ gestation and later, children born <28 completed weeks’ gestation had less gray matter volume (GMV) and white matter volume (WMV) and poorer cognitive functions including decreased full scale IQ, and processing speed. Differences in GMV partially mediated the relationship between GA and full scale IQ in preterm born children. Conclusions In preterm children who are born AGA and without major complications GA is associated with brain volume and cognitive functions. In particular, decreased brain volume becomes evident in the extremely preterm group (born <28 completed weeks’ gestation). In preterm children born 30 completed weeks’ gestation and later the relationship of GA with brain volume and cognitive functions may be less strong as previously thought.

Attention problems in children with epilepsy. How is the long-term outcome?

INTRODUCTION Attention deficit/hyperactivity disorder (ADHD) is one of the most common childhood disorders and frequently seen in other conditions like epilepsy as well. The prevalence of ADHD in the general paediatric population is estimated at 3-6% persisting into adulthood in up to one third of persons affected. The prevalence of ADHD in epilepsy is understood to be significantly higher. Approximately one third of children with epilepsy do also have a diagnosis of ADHD. How these attention problems develop over the years is however not clear. We therefore evaluated the severity of attention problems in children with epilepsy at late childhood and assessed it again in adolescence. Data was being compared with attention problems of children with developmental ADHD. METHOD 16 boys with diagnosed combined idiopathic epilepsy/ADHD and 14 boys with developmental ADHD were investigated twice; at a mean age of 10.94 (SD = 1.63) and then again at a mean age of 15.82 (SD = 2.0). At the baseline examination all patients completed Ravens Progressive Matrices to assess intelligence. To measure symptom severity of ADHD, parents were asked to complete the short version of the Conners Rating Scale for Parents at both times. Parents of children with combined epilepsy/ADHD furthermore gave information about seizure frequency and intake of anticonvulsants. RESULTS Patient groups did not significantly differ in age and IQ. Results of the baseline examination revealed elevated scores in both patient groups for the Conners Rating Scales; ADHD group: M = 16.86 (SD = 5.35); Epilepsy/ADHD group: M = 14.77 (SD = 4.76) but no differences between the groups (p = .29; z = .39). Qualitatively, patients with developmental ADHD showed more abnormalities in the area of hyperactivity/impulsivity while patients with epilepsy/ADHD had more problems with inattention. Results of the follow-up examination showed a significant reduction of symptoms in the ADHD group of minus 4.23 points; M = 12.63 (SD = 3.89) (p = .02); The reduction in the epilepsy/ADHD group was even bigger with minus 6.77 points; M = 8.00 (SD = 6.46) (p = .03). However, difference between the two groups reached no significance (p = .079; z = 1.19). None of the patients with epilepsy has had seizures in the meantime. CONCLUSION We found a significant reduction of ADHD symptoms in our patients from the time of late childhood to adolescence. That symptoms of ADHD, especially hyperactivity, lessen with age is known from the literature (Biedermann et al., 2010). We found the same data for patients with idiopathic epilepsy and ADHD. Over the same period of time problems of attention improved substantially. We conclude that development and brain maturation may have a similar positive effect on attention problems in children with epilepsy than in developmental ADHD.