Oliver Tucha

Echogenicity of the substantia nigra in relatives of patients with sporadic Parkinson’s disease

Increased echogenicity of the substantia nigra (SN) on ultrasound is a typical sonographic finding in Parkinsons disease (PD). Sonographic signal intensity of the SN is related to tissue iron content with higher iron level being associated with increased echogenicity. Recent findings indicate that hyperechogenicity of the SN represents an important susceptibility factor for nigrostriatal degeneration. In this study we determined the prevalence of a characteristic ultrasound sign of Parkinsons disease in first-degree relatives of PD patients. Fourteen patients with sporadic PD and 58 of their relatives underwent neurological, neuropsychological, and ultrasound examination. In addition, four pairs of relatives (one member of each pair exhibiting increased echogenicity of the SN and the other with regular SN echogenicity) underwent (18)F-Dopa PET examination. On transcranial sonography, 26 of the 58 relatives exhibited SN hyperechogenicity. Twenty-four relatives showed minor signs of motor slowing. Relatives with SN hyperechogenicity more often showed signs of hypokinesia (16 v 8 relatives; U test, P = 0.01) and impaired executive functions (Tower of London task, problems solved with the minimum number of moves; U test, P = 0.012) than relatives without this echo pattern. In addition, (18)F-Dopa uptake (influx constants) at the putamen was reduced in subjects with SN hyperechogenicity compared to their relatives without this ultrasound sign (Wilcoxon, P = 0.03). In conclusion, approximately 45% of relatives of PD patients exhibited an increased echogenicity of the SN. This sign is associated with clinical findings and objective measurements, indicating some degree of impaired nigrostriatal function.

Kinematic analysis of dopaminergic effects on skilled handwriting movements in Parkinson's disease.

Summary.Patients with Parkinson’s disease (PD) exhibit impairments in the execution of highly practiced and skilled motor actions such as handwriting. The analysis of kinematic aspects of handwriting movements has demonstrated that size, speed, acceleration and stroke duration are affected in PD. Although beneficial effects of dopaminergic therapy in regard to execution of movements have been reported, the effects of pharmacological therapy on these measures have not been examined in detail. The present study has compared kinematic aspects of handwriting movements of 27 healthy subjects and 27 patients with PD both on their usual dopaminergic treatment and following withdrawal of dopaminergic medication. Healthy subjects were matched with PD patients according to age, sex, handedness and education level. A digitising tablet was used for the assessment of handwriting movements. Subjects were asked to perform a simple writing task. Movement time, distance, velocity, acceleration and measures of fluency of handwriting movements were measured. Compared with healthy subjects, the kinematics of handwriting movements in PD patients were markedly disturbed following withdrawal of dopaminergic medication. Although dopaminergic treatment in PD patients resulted in marked improvements in the kinematics of handwriting movements, PD patients did not reach an undisturbed level of performance. The results suggest that dopamine medication results in partial restoration of automatic movement execution.

Effects of methylphenidate on multiple components of attention in children with attention deficit hyperactivity disorder

RationaleMethylphenidate (MPH) has been shown to be effective in the treatment of attention deficits in children with attention deficit hyperactivity disorder (ADHD). Although a variety of studies have been performed, there is little available information as to which components of attentional functioning are disturbed in ADHD.ObjectivesThe aim of the present study was to monitor the effect of MPH on various measures of attention in children with ADHD.MethodsIn a double-blind, placebo-controlled, crossover study, the attentional functioning of 58 children diagnosed with ADHD without psychiatric comorbidity was examined. Assessment of attention was performed on their usual MPH treatment and following withdrawal of the drug. Furthermore, the attentional performance of 58 healthy children was assessed. The test battery consisted of reaction time tasks, including measures of alertness, vigilance, divided attention, flexibility, and aspects of selective attention such as focused attention, inhibition, and integration of sensory information.ResultsIn comparison to the test performance of healthy children, children with ADHD displayed impairments of vigilance, divided attention, flexibility, and aspects of selective attention including focused attention, inhibition, and integration of sensory information. Statistical comparison of attentional functioning of children with ADHD on and off MPH treatment revealed that the medication resulted in an improved task accuracy regarding vigilance, divided attention, inhibition, focused attention, integration of sensory information, and flexibility. ConclusionThe present findings indicate that various aspects of attention are markedly impaired in children with ADHD. Treatment with MPH was accompanied by improvements in attention functions of small to moderate sizes. Although MPH-induced improvements were observed in a broad range of attention measures, children with ADHD who were on MPH treatment nevertheless displayed serious deficits in a number of components of attention.

Neuropsychological assessment of attention in adults with different subtypes of attention-deficit/hyperactivity disorder

SummaryThere is only little information about varying attention functions of adults with different DSM-IV subtypes of attention-deficit/hyperactivity disorder (ADHD). In the present study groups of adult patients with ADHD – predominantly inattentive type, ADHD – predominantly hyperactive-impulsive type or ADHD – combined type and three healthy control groups were compared regarding multiple components of attention. Assessment of attention was performed using a computerized neuropsychological test battery for attentional functions. In comparison with healthy subjects, the three patient groups displayed impairments of vigilance, selective attention, divided attention, and flexibility. These impairments of attention of ADHD subgroups were primarily observed with regard to reaction time. With regard to tonic and phasic alertness no differences between patient and control groups could be found. Comparison between ADHD subgroups revealed that DSM-IV subtypes of ADHD differ in measures of divided attention, selective attention and flexibility. Differences between ADHD subgroups were primarily observed with regard to task accuracy. The results suggest that while distinct profiles of attentional functioning were observed between adult patients with ADHD and healthy adults indicating gross disturbances of various attention functions in patients with ADHD, differences between ADHD subgroups were only weak.

Methylphenidate-induced improvements of various measures of attention in adults with Attention Deficit Hyperactivity Disorder

Summary.The present study examined the effect of the stimulant medication methylphenidate (MPH) on attentional functioning of adults with ADHD. Sixteen adults with a diagnosed ADHD without comorbidity were assessed twice, at baseline off MPH and following MPH treatment. The assessment battery consisted of reaction time tasks of low complexity, including measures of alertness – subdivided into tonic and phasic alertness, vigilance, divided attention, flexibility and such aspects of selective attention as including focused attention, inhibition and integration of sensory information. In addition, 16 healthy participants who were matched to adults with ADHD according to sex, age, education level and intellectual functions were also assessed twice using the same test battery. The results of the present study suggest that adults with ADHD off stimulant medication are seriously impaired in various components of attention including vigilance, divided attention, selective attention and flexibility. These impairments of attention were observed primarily in regard to reaction time and its variability. Treatment of adults with ADHD using individually tailored doses of MPH has a positive effect on measures of alertness, vigilance, selective attention, divided attention and flexibility. However, even on MPH adults with ADHD displayed considerable deficits in vigilance and integration of sensory information. The present findings indicate that adults with ADHD are not differentially impaired in attentional processes but may suffer from a more global deficit of attention. Although MPH treatment has been found to be effective in the treatment of the attention deficit of adults with ADHD, additional treatment appears to be necessary.

Effects of methylphenidate on kinematic aspects of handwriting in hyperactive boys.

Poor handwriting in hyperactive children often contributes to academic failure. Beneficial effects of methylphenidate on the quality of handwriting have been shown. Using a digitizing tablet, the handwriting of 21 hyperactive boys was examined both during methylphenidate treatment and following withdrawal of the drug. Half of the hyperactive boys were tested first on methylphenidate and then following withdrawal of the drug and the remaining hyperactive boys were examined in the reverse order. Twenty-one control boys underwent the same examination. Velocity and acceleration of handwriting movements were measured. Furthermore, every writing specimen was independently rated by four examiners regarding the quality of handwriting. Following withdrawal of the drug, the quality of handwriting specimens of hyperactive boys was poorer than during treatment with methylphenidate. Statistical comparison of writing movements of hyperactive boys on and off methylphenidate revealed that the medication resulted in a deterioration in handwriting fluency. The results showed that following withdrawal of medication, hyperactive children did not differ from control boys in handwriting movements. The improvement in hyperactive behavior through methylphenidate was associated with increased legibility and greater accuracy of handwriting. The intention to write neatly may interfere with the fluent writing process.

Reduced memory and attention performance in a population-based sample of young adults with a moderate lifetime use of cannabis, ecstasy and alcohol

Abstract Regular use of illegal drugs is suspected to cause cognitive impairments. Two substances have received heightened attention: 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy’) and δ-9-tetrahydrocannabinol (THC or ‘cannabis’). Preclinical evidence, as well as human studies examining regular ecstasy consumers, indicated that ecstasy use may have negative effects on learning, verbal memory and complex attentional functions. Cannabis has also been linked to symptoms of inattention and deficits in learning and memory. Most of the published studies in this field of research recruited participants by means of newspaper advertisements or by using word-of-mouth strategies. Because participants were usually aware that their drug use was critical to the research design, this awareness may have caused selection bias or created expectation effects. Focussing on attention and memory, this study aimed to assess cognitive functioning in a community-based representative sample that was derived from a large-scale epidemiological study. Available data concerning drug use history allowed sampling of subjects with varying degrees of lifetime drug experiences. Cognitive functioning was examined in 284 young participants, between 22 and 34 years. In general, their lifetime drug experience was moderate. Participants completed a neuropsychological test battery, including measures for verbal learning, memory and various attentional functions. Linear regression analysis was performed to investigate the relationship between cognitive functioning and lifetime experience of drug use. Ecstasy and cannabis use were significantly related to poorer episodic memory function in a dose-related manner. For attentional measures, decrements of small effect sizes were found. Error measures in tonic and phasic alertness tasks, selective attention task and vigilance showed small but significant effects, suggesting a stronger tendency to experience lapses of attention. No indication for differences in reaction time was found. The results are consistent with decrements of memory and attentional performance described in previous studies. These effects are relatively small; however, it must be kept in mind that this study focussed on assessing young adults with moderate drug use from a population-based study.

Clustering and switching on verbal and figural fluency functions in adults with attention deficit hyperactivity disorder

Introduction. Neuropsychological studies of adult patients with ADHD have revealed marked disturbances of executive functions including impairments of attention, working memory, impulsivity, shifting, and divergent thinking. Phonemic fluency tasks, in particular, have been shown to be sensitive measures for the assessment of executive functions of adults with ADHD.Methods. The present study has examined figural fluency and both phonemic and semantic verbal fluency in 34 adult patients with ADHD and 34 healthy participants. For evaluation of fluency performance the number of words or designs, the number of repetitions and the number of deviations from test rules were calculated. Furthermore, clustering strategies and switching responses were analysed. In comparison with healthy participants, patients with ADHD produced significantly fewer words or designs, but they did not differ from healthy participants in the number of repetitions or rule violations.Results. Analysis of switching and clustering showed that patients produced significantly fewer switching responses on both verbal fluency tasks, although patients tended to generate smaller clusters. Switching on the figural fluency task was unimpaired.Conclusions. The results of the present study suggest that adult patients with ADHD may suffer from a dysfunction that may affect retrieval processes and the categorisation of knowledge.

Quality of life in patients with blepharospasm

Objectives– Administration of botulinum neurotoxin A (BONT/A) is a common and effective treatment of blepharospasm. There is, however, no information regarding the emotional and social well‐being of patients with blepharospasm and patient acceptance of BONT/A therapy. The purpose of this study was to investigate aspects of quality of life of patients with blepharospasm and level of patient satisfaction with treatment. Material and methods– Fifty‐one patients with blepharospasm who had been treated with BONT/A for years completed a questionnaire providing information about quality of life. Results– Results revealed reductions in social and emotional well‐being of patients but, nonetheless, good acceptance of BONT/A therapy. The positive effects of BONT/A therapy were, however, accompanied by fear of a decreasing effect of BONT/A injections. Conclusion– Although the objective findings following BONT/A injections in the treatment of blepharospasm are appreciated by the patients, their well‐being is affected by fears and depression.

Neural networks of response shifting: Influence of task speed and stimulus material

Functional magnetic resonance imaging (fMRI) was used in 14 healthy subjects to measure brain activation, while response shifting was performed. In the activation phase, subjects were asked to shift their attention between two different types of visually presented stimuli. In the baseline phase, subjects were required to attend to one stimulus type only. Subjects responded by pressing a left or right key according to the side of presentation of the target stimuli. In a verbal task, subjects were required to switch between letters and numbers. In a figural task, subjects reacted to round and square shapes. Stimuli were presented for 750 or 1500 ms. Response shifting revealed significantly increased activation compared to non-switching in the bilateral superior parietal cortex, right occipital cortex, left inferior frontal cortex, left and right striatum, and bilateral dorsolateral prefrontal cortex (DLPFC). Superior parietal and occipital cortex activation may be due to spatial analysis during response shifting. Subvocal rehearsal of the task instructions may have led to activation in the left inferior frontal cortex. Activation in the striatum was related to prefrontal activation and may represent the association between basal ganglia and prefrontal activation during executive control. However, the most important brain region involved in the execution of response shifting was the bilateral DLPFC. Higher task speed increased executive top-down attentional control and, therefore, significantly increased activity in the bilateral DLPFC. Brain activation did not differ significantly between verbal and figural stimulus material. This result suggests that brain activation in the present study illustrates the brain regions involved in the basic cognitive mechanisms of response shifting.