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Biomedical subjects

G H Moll

Publications and source records attributed to G H Moll.

At least 19 recordsLinked to original sources

Methylphenidate and intracortical excitability: opposite effects in healthy subjects and attention-deficit hyperactivity disorder.

OBJECTIVE: To test the effects of a standard dosage of the psychostimulant methylphenidate (MPH) - which significantly enhances intracortical inhibition but had no effects on intracortical facilitation in children with attention-deficit hyperactivity disorder (ADHD) - on intracortical excitability in healthy subjects. METHOD: In 12 healthy subjects, aged 20-40 years, intracortical inhibition and facilitation were investigated before and 70 min after the intake of 10 mg MPH using the technique of transcranial magnetic stimulation (TMS) with the paired-stimulus paradigm. RESULTS: In comparison of the two TMS measurements, a significant enhancement in intracortical facilitation but no effects on intracortical inhibition could be stated under MPH administration. CONCLUSION: This study provides first evidence for opposite effects of MPH on intracortical excitability in healthy adult subjects showing enhanced intracortical facilitation in contrast to ADHD children in whom enhanced intracortical inhibition has recently been shown.

Adult↗

Time-on-task analysis using wavelet networks in an event-related potential study on attention-deficit hyperactivity disorder.

OBJECTIVE: The aim of this event-related potential (ERP) study was to test time-on-task analysis at the level of single sweeps in a clinical trial. Since inattentiveness is one of the main symptoms of attention-deficit hyperactivity disorder (ADHD), this child psychiatric disorder was chosen as an exemplary application. METHODS: Twenty-four healthy and 24 ADHD boys, aged 9--15 years, performed an auditory selective attention task for about 5 min. ERP single trials were analyzed using wavelet networks. Time-on-task analysis was applied to omission errors, reaction time and slow ERP components (frontal negativity, parietal positivity), represented by a low-frequency wavelet component. RESULTS: Both performance and ERP measures showed distinct temporal dynamics. Time-on-task effects were not only linear, but also of higher order and started after less than 1 min. For ADHD children, earlier time-on-task effects, i.e. an earlier increase of omission errors and frontal negativity, resulted. Healthy children could allocate more attentional resources during the course of the experiment. CONCLUSION: Time-on-task analysis at the level of single trials revealed phenomena probably reflecting ADHD children's attentional deficits. Thus, a more differentiated ERP analysis may provide a better understanding of the pathophysiological background in neuropsychiatric disorders.

Acoustic Stimulation↗

[Transcranial magnetic stimulation in child and adolescent psychiatry: excitability of the motor system in tic disorders and/or attention deficit hyperactivity disorders].

Motor system excitability can be investigated in vivo by means of single and paired pulse transcranial magnetic stimulation (TMS). Whereas the cortical silent period reflects the general degree of inhibitory mechanisms mainly within the sensorimotor loop, intracortical excitability measures the focused degree of inhibitory and facilitatory mechanisms within the motor cortex. In child and adolescent psychiatric disorders with uncontrollable motor behavior such as tics in tic disorder or motoric hyperactivity in attention deficit hyperactivity disorder (ADHD), different dysfunctional patterns of motor system excitability could be demonstrated compared to age-matched healthy controls: (1) In tic disorder, a shortened cortical silent period was observed, providing evidence of deficient inhibitory mechanisms within the sensorimotor loop, probably primarily at the level of the basal ganglia. (2) In ADHD, a decreased intracortical inhibition was found, probably reflecting deficient inhibitory mechanisms within the motor cortex (but enhancement of intracortical inhibition after oral intake of 10 mg methylphenidate). In order to investigate neurophysiological aspects of comorbidity, (3) motor system excitability was also measured in children with combined ADHD and tic disorder. The findings of a reduced intracortical inhibition as well as a shortened cortical silent period in these comorbid children provide evidence of additive effects at the level of motor system excitability. These decreased inhibitory mechanisms within the entire sensorimotor loop and especially the motor cortex could be essential neurobiological substrates of the deficient inhibitory motor control and regulation, respectively, in tic disorder and ADHD.

Adolescent↗

Early methylphenidate administration to young rats causes a persistent reduction in the density of striatal dopamine transporters.

Methylphenidate is widely and effectively used for the treatment of attention deficit hyperactivity disorder during early childhood and adolescence, but until now possible effects of this treatment on brain development and the maturation of monoaminergic systems have not been investigated systematically. This experimental animal study describes the effects of methylphenidate administration (2 mg/kg/day) for 2 weeks to very young (prepubertal) and somewhat older (postpubertal) rats on the densities of dopamine, serotonin, and norepinephrine transporters in the striatum and in the midbrain. As shown by ligand-binding-assays, the K(D) values of all three transporters were unaffected by this treatment. No alterations were found for the Bmax values of [3H]-paroxetine and [3H]-nisoxetine binding, but the density of dopamine transporters (Bmax values of [3H]-GBR binding) in the striatum (but not in the midbrain) was significantly reduced after early methylphenidate administration (by 25% at day 45), and this decline reached almost 50% at adulthood (day 70), that is, long after termination of the treatment. This is the first empirical demonstration of long-lasting changes in the development of the central dopaminergic system caused by the administration of methylphenidate during early juvenile life.

Animals↗

Children with comorbid attention-deficit-hyperactivity disorder and tic disorder: evidence for additive inhibitory deficits within the motor system.

For children with attention-deficit-hyperactivity disorder (ADHD) or tic disorder (TD), we recently reported deficient inhibitory mechanisms within the motor system by using transcranial magnetic stimulation. These deficits--stated as reduced intracortical inhibition in ADHD and shortened cortical silent period in TD--could be seen as neurophysiological correlates of motor hyperactivity and tics, respectively. To investigate neurophysiological aspects of comorbidity, we measured motor system excitability for the first time also in children with combined ADHD and TD. The findings of a reduced intracortical inhibition as well as a shortened cortical silent period in these comorbid children provide evidence for additive effects at the level of motor system excitability.

Adolescent↗

Deficient intracortical inhibition in drug-naive children with attention-deficit hyperactivity disorder is enhanced by methylphenidate.

In children with attention-deficit hyperactivity disorder (ADHD), motoric hyperactivity is one of the striking abnormalities. Because this symptom might be due to an insufficient motor control, motor system excitability in 18 drug-naive ADHD-children aged 8-12 years was compared to 18 age-matched healthy children using the technique of transcranial magnetic stimulation (TMS). Whereas motor thresholds, cortical silent period, and intracortical facilitation did not differ between the two groups, ADHD-children had significantly reduced intracortical inhibition compared to healthy controls. In all ADHD-children, a second TMS could be started after their first intake of 10 mg methylphenidate. Under this medication, a significant enhancement in intracortical inhibition could be stated. This study provides the first evidence for inhibitory deficits within the motor cortex in ADHD-children and for an enhancement of inhibitory mechanisms in this brain region by methylphenidate.

Attention Deficit Disorder with Hyperactivity↗

Age-associated changes in the densities of presynaptic monoamine transporters in different regions of the rat brain from early juvenile life to late adulthood.

The binding parameters of highly selective ligands of serotonin (5-HT) transporters ([3H]paroxetine), noradrenaline (NE) transporters ([3H]nisoxetine), and of dopamine (DA) transporters ([3H]GBR-12935) were determined on membrane preparations from frontal cortex, striatum, midbrain and brain stem of Wistar rats on postnatal days 25, 50, 90 and 240, i.e., from the time of weaning till late adulthood. No age-dependent alterations in the affinity-parameters (K(D)-values) of all three monoamine transporters were observed. Age-associated changes in B(max)-values of the binding of all three specific ligands were most pronounced in the phylogenetically younger, late maturing brain regions (frontal cortex, striatum). Most likely, these changes reflect age-related changes in 5-HT, NE and DA-innervation densities. In the frontal cortex, 5-HT-transporter density increased steadily from weaning (day 25) till late adulthood, whereas the density of NE-transporters was highest at weaning, declined till puberty (day 50) and remained at this level until old age. DA-transporter density in the frontal cortex was not reliably measurable by [3H]GBR-binding assays. In the striatum, DA-transporter density increased till puberty and declined thereafter considerably and steadily to about one-fourth of the pubertal values at old age. No such age-associated changes in DA-transporter density were seen in the midbrain. Densities of 5-HT and NE remained at the level reached already at weaning until old age in the striatum, midbrain and brain stem. These findings provide the first comprehensive description of the normally occurring changes in the densities of all three presynaptically located monoamine transporters in the rat brain throughout the life span from weaning to late adulthood.

Aging↗

Comorbidity in ADHD-children: effects of coexisting conduct disorder or tic disorder on event-related brain potentials in an auditory selective-attention task.

In children with attention-deficit hyperactivity disorder (ADHD) some deficits in auditory information processing seem to exist. Further, comorbidity of ADHD with conduct disorder (CD) and tic disorder (Tic) is quite common but not yet fully understood. Thus, we investigated the effects of these two disturbances, when combined with ADHD, on electrophysiological correlates of auditory information processing. An auditory selective-attention task was used, and temporal as well as frontal lobe sensitive event-related electrical brain activity indicators like mismatch negativity (MMN) and negative difference wave (Nd), as well as P300 were registered in four groups of children (healthy controls, ADHD-only, and combined ADHD + CD as well as ADHD + Tic; total number 42). Performance measures showed that ADHD + CD had a higher impact on errors and reaction times than ADHD + Tic. The MMN effect indicated that all ADHD groups showed lower MMN amplitudes compared to normals, but only the group with ADHD + CD suffered from a significant deficiency in automatic auditory information processing. Nd and P300 amplitudes showed no significant group differences. It may be assumed that neurodynamic sufficiency in ADHD-only and ADHD + Tic children seems to be similarly impaired while there might be a greater deficit in ADHD + CD.

Attention↗

Quantitative and qualitative aspects of obsessive-compulsive behaviour in children with attention-deficit hyperactivity disorder compared with tic disorder.

OBJECTIVE: Within the framework of associated psychopathology in child psychiatric disorders, this study focused on quantitative and qualitative aspects of obsessive-compulsive behaviour (OCB) in both attention-deficit hyperactivity disorder (ADHD) and chronic tic disorder/Tourette's disorder (TD). METHOD: Forty-two healthy controls, 41 children with ADHD and 38 children with TD, aged 9-13 years, were investigated using the Leyton Obsessional Inventory--Child Version (LOI-CV), the Child Behaviour Checklist (CBCL) and an expert-rated structured parent interview to reflect a cross-informant view of OCB. RESULTS: Unexpectedly, self-reports of children with ADHD rather than children with TD showed the highest OCB scores in the LOI-CV. Qualitatively, ADHD-related OCB focused on the item subsets concerning 'dirt and contamination', 'repetition', 'overconscientiousness', and 'hoarding'. In the parent-rated CBCL, similar levels of OCB were reported for ADHD and TD patients. In contrast, only children with TD showed clinically relevant OCB according to expert ratings. CONCLUSION: Not only young TD patients but also children with ADHD should be investigated and monitored carefully for quantitative and qualitative aspects of OCB comorbidity.

Adolescent↗

Deficient motor control in children with tic disorder: evidence from transcranial magnetic stimulation.

Decreased motor inhibition was reported in adult patients with tic disorder (TD) using the technique of transcranial magnetic stimulation. Since tics usually begin during childhood, motor threshold, cortical silent period (CSP) and intracortical inhibition/facilitation were measured in 21 TD children and 25 healthy children aged 10-16 years. In TD children motor threshold was normal. The CSP was significantly shortened compared to healthy controls but did not depend on tic localization. Intracortical inhibition and facilitation did not differ between the two groups. This study confirms that the finding of decreased motor control in adult patients also holds true for children wherever the tics in the latter group were located.

Adolescent↗

[Relationship between tics and compulsion].

In children and adolescents motor/vocal tics and obsessive-compulsive behavior are known to be closely related. Thereby, a continuum of symptoms ranging from single tics to a mixed picture of tics/rituals/obsessive-compulsive traits to clinically relevant obsessions and compulsions could be described. As neurobiological substrates dysfunctions in corresponding cortico-striato-thalamocortical circuits (sensorimotor circuit in tic symptomatology, orbitofrontal circuit in obsessive-compulsive behavior) were postulated. For both disturbances behavioral therapy can be used to improve control mechanisms to counterregulate tics and obsessive-compulsive behavior, respectively, and psychopharmacological agents can be administered to compensate dysbalances in neurotransmitter systems. In case of a mixed symptomatologic picture it is necessary to include interventions for both pols of the symptom-continuum in the therapeutic programme to achieve extensive improvement as a basis for a further positive development of the patient.

Adolescent↗

Persistently increased density of serotonin transporters in the frontal cortex of rats treated with fluoxetine during early juvenile life.

This experimental animal study was performed in order to assess possible long-term effects of the administration of the selective serotonin reuptake inhibitor fluoxetine (Prozac) during early periods of juvenile life on the developing central serotonergic and noradrenergic systems. Fluoxetine was administered via the drinking water (5 mg/kg/day) for a period of two weeks to very young (day 25) and somewhat older (day 50) rats. The effect of this treatment on the density of serotonin and noradrenaline transporters was measured by ligand-binding assays in various brain regions. The Bmax-values of [3H]-nisoxetine binding were not affected by either treatment schedule, but a significant increase of the Bmax-values of [3H]-paroxetine binding was found in the brains of early fluoxetine-treated rats. This increase was restricted to the frontal cortex and persisted long after the termination of the treatment into adulthood (day 90). The most likely explanation of this observation is a stimulatory effect of the fluoxetine treatment on the outgrowth of serotonergic projections in the frontal cortex of very young rats. This is the first empirical demonstration of long-lasting effects of the administration of a selective serotonin reuptake inhibitor during juvenile life on the maturation of the central serotonergic system.

Aging↗

Single-sweep analysis of event-related potentials by wavelet networks--methodological basis and clinical application.

OBJECTIVE: Trial-to-trial variabilities in event-related potentials (ERP's), which are neglected by investigating averaged ERP's, can be important to establish group-specific effects in clinical studies. Single ERP responses have to be analyzed to quantify these variations. In order to overcome the disadvantages of existing single-sweep estimators, we have developed a new procedure based on wavelet networks (WN's) and applied this novel approach in a study concerning attention deficit hyperactivity disorder (ADHD) in children. METHOD: WN's represent signals as a linear combination of wavelet nodes, i.e., components characterized by time-frequency features related to the wavelet transformation. In single-sweep analysis, each wavelet node is restricted to a specific region of the time-frequency plane during the recursive WN training process. This is achieved by means of tapering and bandpass filtering with Gaussian functions which are automatically adapted and closely related to the Morlet basis wavelet. The time course of a single event-related response can be reliably estimated. Furthermore, the WN method automatically provides well-defined parameters for single event-related responses, respectively ERP trial-to-trial variabilities. RESULTS: In a psychophysiological study on ADHD using auditory evoked potentials (AEP's), latency and amplitude parameters extracted from averaged ERP's did not reveal any significant differences between 25 control and 25 ADHD boys. In contrast, interesting group-specific differences could be established by WN single-sweep analysis. CONCLUSION: WN single-sweep analysis can be recommended as a sensitive tool for clinical ERP studies which should be applied in addition to the investigation of averaged responses. INDEX TERMS: Attention deficit hyperactivity disorder (ADHD), event-related potentials, single-sweep estimation, single-sweep parameterization, time-frequency method, wavelet networks.

Adolescent↗

[Lithium salts in child and adolescent psychiatry].

Lithium is--besides neuroleptics--the drug of choice for the treatment of manic episodes. If the use of antidepressive drugs, during unipolar depressive illness, does not lead to a positive response, the additional administration of lithium is appropriate, even during a depressive episode. Lithium is also considered as the drug of choice for prophylactic treatment of bipolar affective disorders. This holds true also for adolescents. In contrast to the indications in adults, in adolescents an early administration is desirable to reduce risk factors of psychosocial development. Additional indications may be the presence of severe aggressivity in conduct disordered children. In these cases, a treatment with lithium salts can result in a behavioral improvement. This may be also the case in impulsive self-injurious behavior. The dosage and serum levels of lithium, as well as its adverse effects are comparable with those known from adults. At present, lithium treatment cannot be recommended for children under 12 years of age--except under in-patient conditions.

Adolescent↗

Standard EEG and dyslexia in children--new evidence for specific correlates?

Contrary to the current assumption that there are no specific correlates of dyslexia in the standard clinical EEG, we have often noted a spontaneous "intermittent left parietal alpha desynchronization" (ILPAD) when visually evaluating the standard EEGs of children with delayed speech and language development and/or dyslexia. Visual evaluations of EEGs, as well as computer-assisted frequency analysis of three pairs of matched groups (healthy and hyperkinetic children with vs. without relatively "low levels" of verbal performance, as well as children with other child psychiatric disorders with vs. without dyslexia), revealed that healthy children did not display the ILPAD phenomenon. It was seen neither in healthy children with a homogeneous performance profile ("high level" of verbal performance) nor in those with a relatively "low level" of verbal performance. However, the ILPAD phenomenon was evident mainly in children with psychiatric disorders who suffered from dyslexia. Its intermittent occurrence prevented its detection by means of the usual computer-supported analyses of EEG power spectra. Nevertheless, auditory cognitive loading was accompanied by a decrease in alpha power in both healthy and hyperkinetic children with "high" or "low" levels of verbal performance. In a further group of 8-year-old children with dyslexia, but otherwise healthy, the ILPAD phenomenon was also observed if their CNS maturation as reflected in the EEG was normal for their age. These results seemed to indicate at least a deficit-specificity of the ILPAD phenomenon, which is interpreted as an electrophysiological correlate of a "brain-electrical developmental deviation" with regard to the "functions of communication": speech, language, reading and spelling.

Alpha Rhythm↗