Frank Haessler

Modulation of transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD) by medication with methylphenidate (MPH)

Motor hyperactivity is one of the most outstanding symptoms of attention deficit hyperactivity disorder (ADHD) which might be caused by a disturbed inhibitory motor control. Using focal transcranial magnetic stimulation (TMS) we tested the cortico-callosal inhibition (duration and latency of the ipsilateral Silent Period, iSP) in 23 children with ADHD (mean age 11+/-2.6 years) before and on treatment with methylphenidate (MPH). iSP latency was age correlated, whereas iSP duration as well as Conners scores were age independent. Analyses of mean differences revealed a significant prolongation of iSP duration (p=0.001), shortening of iSP latency (p=0.027) and reduction of Conners score (p=0.001) under medication. Increase of iSP duration and reduction of Conners score under medication were significantly correlated (t=-9.87, p=0.016). Reduced iSP duration and prolonged iSP latency in ADHD children could be the result of a disturbed transcallosally mediated inhibition, most probable due to a combination of maturation deficits of callosal fiber tracts as well as neuronal synaptical transmission within the neuronal network between ipsilaterally stimulated cortex layer III--the origin of transcallosal motor-cortical fibers--and contralateral layer V, the origin of the pyramidal tract. MPH may indirectly improve the dysbalance between excitatory and inhibitory interneuronal activities of this neuronal network via dopaminergic modulatory effects of the striato-thalamo-cortical loop.

Impaired transcallosally mediated motor inhibition in adults with attention-deficit/hyperactivity disorder is modulated by methylphenidate

Using transcranial magnetic stimulation (TMS) in children with ADHD, an impaired transcallosally mediated motor inhibition (ipsilateral silent period, iSP) was found, and its restoration was correlated with improvement of hyperactivity under medication with methylphenidate (MPH). Hyperactivity has been reported to decrease during transition into adulthood, although some motor dysfunction might persist. As one underlying neurophysiological process, a development-dependent normalization of motor cortical excitability might be postulated. In order to test this hypothesis, we measured the iSP in 21 adult ADHD patients and twenty-one sex- and age-matched healthy controls. In 16 of these patients, a second TMS was performed under treatment with MPH. Our results indicate a persistence of impaired transcallosally mediated motor cortical inhibition (shortened duration) in ADHD adults, which was correlated with clinical characteristics of hyperactivity and restlessness, and was restored by MPH. In contrast to ADHD in childhood, the iSP latency was not impaired, suggesting a partial development-dependent normalization of motor cortical excitability in ADHD adults. ISP duration appears to be a sensitive parameter for the assessment of disturbed intercortical inhibition in adults with ADHD.

The role of sleep problems and circadian clock genes in childhood psychiatric disorders.

CLOCK gene research and the analysis of circadian rhythmicity on the behavioural, cellular and molecular level are increasingly contributing to accumulate clinically relevant knowledge in the fields of neuroscience, psychopharmacology and adult psychiatry. However, the role of circadian phenomena, including sleep alterations in mental disorders during childhood and adolescence remains largely enigmatic. Fortunately, recent publications have addressed this problem and there is now some evidence available highlighting the relevance of CLOCK genes in conditions, such as ADHD, mood disorders, schizophrenia and anxiety disorders.

Intelligence moderates impulsivity and attention in ADHD children: an ERP study using a go/nogo paradigm.

Abstract Objectives. If the cardinal symptoms of ADHD – hyperactivity, impulsivity and inattention – are combined with a learning disability (70 ≥ IQ < 85), the question arises whether a child shows hyperkinetic behaviour because of intellectual overload in a challenging situation, for example at school. Perhaps, this behaviour is not a primary attention deficit disorder but an impulse control disorder, determined by the primarily intelligence level. It raised the question whether attention deficit and impulse control regarded as behavioural inhibition deficit may depend on intelligence and therefore should be separated into distinct clinical entities. Methods. A total of 45 children (15 with ADHD, 15 with learning disabilities (LD), 15 with ADHD and learning disabilities) were compared in a matched-pair design with 42 control children using a go/no go paradigm (visual continuous performance test, CPT). The dependent variable was the target P3 amplitude, averaged from a 10–20 EEG measurements under distinct trigger conditions. For statistical analysis, a three-factor analysis of variance (MANOVA) with repeated measurements was used. In a subsequent regression analysis with residuals, the influence of intelligence (IQ) was calculated and a “parallel analysis of variance” was conducted. Results. No differences in the P3 amplitudes in the comparison ADHD-control group were found. Reduced P3 amplitudes as main effects in the LD group compared with controls were found and a significant group-dependent interaction on reduced P3 amplitudes comparing ADHD + LD versus control group. Using residuals (IQ), this interaction was not longer verifiable. Conclusion. Impulsivity and attention deficit as the cardinal symptoms of ADHD, regarded as behavioural inhibition deficit, are essentially moderated by the primary intelligence, rather than by an attention deficit. The lower the IQ, the more ADHD surfaces as a disturbed impulsivity and lesser as an attention deficit.

Objective measurement of tissue tension in myofascial trigger point areas before and during the administration of anesthesia with complete blocking of neuromuscular transmission.

Objectives:Myofascial trigger points (MTPs) are extremely frequent in the human musculoskeletal system. Despite this, little is known about their etiology. Increased muscular tension in the trigger point area could be a major factor for the development of MTPs. To investigate the impact of muscular tension in the taut band with an MTP and thereby, the spinal excitability of associated segmental neurons, we objectively measured the tissue tension in MTPs before and during the administration of anesthesia using a transducer. Methods:Three target muscles (m. temporalis, upper part of m. trapezius, and m. extensor carpi radialis longus) with an MTP and 1 control muscle without an MTP were examined in 62 patients scheduled for an operation. Results:We found significant 2-way interactions (ANOVA, P<0.05) between the analyzed regions of the target muscles dependent on the time of measurement, that is, before and during a complete blocking of neuromuscular transmission. These effects could be demonstrated for each target muscle separately. Discussion:An increased muscle tension in MTPs, and not a primary local inflammation with enhanced viscoelasticity, was the main result of our investigation. We interpret this increased muscular tension in the taut band with an MTP as increased spinal segmental excitability. In line with this, we assume a predominant, but not unique, impact of increased spinal excitability resulting in an augmented tension of segmental-associated muscle fibers for the etiology of MTP. Consequently, postisometric relaxation might be a promising therapeutic option for MTPs.

The role of sleep problems and circadian clock genes in attention-deficit hyperactivity disorder and mood disorders during childhood and adolescence: an update.

A more recent branch of research describes the importance of sleep problems in the development and treatment of mental disorders in children and adolescents, such as attention-deficit hyperactivity disorder (ADHD) and mood disorders (MD). Research about clock genes has continued since 2012 with a focus on metabolic processes within all parts of the mammalian body, but particularly within different cerebral regions. Research has focused on complex regulatory circuits involving clock genes themselves and their influence on circadian rhythms of diverse body functions. Current publications on basic research in human and animal models indicate directions for the treatment of mental disorders targeting circadian rhythms and mechanisms. The most significant lines of research are described in this paper.