Hartmut Heinrich

Association of ADHD and conduct disorder – brain electrical evidence for the existence of a distinct subtype

BACKGROUND To evaluate the impact of psychopathological comorbidity with oppositional defiant/conduct disorder (ODD/CD) on brain electrical correlates in children with attention deficit hyperactivity disorder (ADHD) and to study the pathophysiological background of comorbidity of ADHD+ODD/CD. METHOD Event-related potentials (ERPs) were recorded during a cued continuous performance test (CPT-A-X) in children (aged 8 to 14 years) with ICD-10 diagnoses of either hyperkinetic disorder (HD; n = 15), hyperkinetic conduct disorder (HCD; n = 16), or ODD/CD (n = 15) and normal children (n = 18). HD/HCD diagnoses in all children were fully concordant with the DSM-IV diagnosis of ADHD-combined type. ERP-microstates, i.e., time segments with stable brain electrical map topography were identified by adaptive segmentation. Their characteristic parameters and behavioral measures were further analyzed. RESULTS Children with HD but not comorbid children showed slower and more variable reaction times compared to control children. Children with HD and ODD/CD-only but not comorbid children displayed reduced P3a amplitudes to cues and certain distractors (distractor-X) linked to attentional orienting. Correspondingly, global field power of the cue-CNV microstate related to anticipation and preparation was reduced in HD but not in HCD. Topographical alterations of the HD occurred already in the cue-P2/N2 microstate. In sum, the comorbid group was less deviant than both the HD-group and the ODD/CD-group. CONCLUSIONS The findings suggest that HD children (ADHD-combined type without ODD/CD) suffer from a more general deficit (e.g., suboptimal energetical state regulation) including deficits of attentional orienting and response preparation than just a responseinhibitory deficit, backing the hypothesis of an involvement of a dysregulation of the central noradrenergic networks. The results contradict the hypothesis that ADHD+ODD/CD represents an additive co-occurrence of ADHD and ODD/CD and strongly suggest that it represents a separate pathological entity as considered in the ICD-10 classification system, which differs from both HD and ODD/CD-only.

Training of slow cortical potentials in attention-deficit/hyperactivity disorder: evidence for positive behavioral and neurophysiological effects

BACKGROUND Learned self-control of slow cortical potentials (SCPs) may lead to behavioral improvement in attention-deficit/hyperactivity disorder (ADHD). Hence, training effects should also be reflected at the neurophysiological level. METHODS Thirteen children with ADHD, aged 7-13 years, performed 25 SCP training sessions within 3 weeks. Before and after training, the German ADHD rating scale was completed by parents, and event-related potentials were recorded in a cued continuous performance test (CPT). For a waiting-list group of nine children with ADHD, the same testing was applied. RESULTS ADHD symptomatology was reduced by approximately 25% after SCP training. Moreover, a decrease of impulsivity errors and an increase of the contingent negative variation were observed in the CPT task. CONCLUSIONS This study provides first evidence for both positive behavioral and specific neurophysiological effects of SCP training in children with ADHD.

Distinct EEG effects related to neurofeedback training in children with ADHD: a randomized controlled trial.

In a randomized controlled trial, neurofeedback (NF) training was found to be superior to a computerised attention skills training concerning the reduction of ADHD symptomatology (Gevensleben et al., 2009). The aims of this investigation were to assess the impact of different NF protocols (theta/beta training and training of slow cortical potentials, SCPs) on the resting EEG and the association between distinct EEG measures and behavioral improvements. In 72 (of initially 102) children with ADHD, aged 8-12, EEG changes after either a NF training (n=46) or the control training (n=26) could be studied. The combined NF training consisted of one block of theta/beta training and one block of SCP training, each block comprising 18 units of 50 minutes (balanced order). Spontaneous EEG was recorded in a two-minute resting condition before the start of the training, between the two training blocks and after the end of the training. Activity in the different EEG frequency bands was analyzed. In contrast to the control condition, the combined NF training was accompanied by a reduction of theta activity. Protocol-specific EEG changes (theta/beta training: decrease of posterior-midline theta activity; SCP training: increase of central-midline alpha activity) were associated with improvements in the German ADHD rating scale. Related EEG-based predictors were obtained. Thus, differential EEG patterns for theta/beta and SCP training provide further evidence that distinct neuronal mechanisms may contribute to similar behavioral improvements in children with ADHD.

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.

Evaluation of neurofeedback in ADHD: the long and winding road

Among the clinical applications of neurofeedback, most research has been conducted in ADHD. As an introduction a short overview of the general history of neurofeedback will be given, while the main part of the paper deals with a review of the current state of neurofeedback in ADHD. A meta-analysis on neurofeedback from 2009 found large effect sizes for inattention and impulsivity and medium effects sizes for hyperactivity. Since 2009 several new studies, including 4 placebo-controlled studies, have been published. These latest studies are reviewed and discussed in more detail. The review focuses on studies employing (1) semi-active, (2) active, and (3) placebo-control groups. The assessment of specificity of neurofeedback treatment in ADHD is discussed and it is concluded that standard protocols such as theta/beta, SMR and slow cortical potentials neurofeedback are well investigated and have demonstrated specificity. The paper ends with an outlook on future questions and tasks. It is concluded that future controlled clinical trials should, in a next step, focus on such known protocols, and be designed along the lines of learning theory.

Action Monitoring in Boys With Attention-Deficit/Hyperactivity Disorder, Their Nonaffected Siblings, and Normal Control Subjects: Evidence for an Endophenotype

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) is a very common and highly heritable child psychiatric disorder associated with dysfunctions in fronto-striatal networks that control attention and response organization. The aim of this study was to investigate whether features of action monitoring related to dopaminergic functions represent endophenotypes that are brain functions on the pathway from genes and environmental risk factors to behavior. METHODS Action monitoring and error processing as indicated by behavioral and electrophysiological parameters during a flanker task were examined in boys with ADHD combined type according to DSM-IV (n = 68), their nonaffected siblings (n = 18), and healthy control subjects with no known family history of ADHD (n = 22). RESULTS Boys with ADHD displayed slower and more variable reaction-times. Error negativity (Ne) was smaller in boys with ADHD compared with healthy control subjects, whereas nonaffected siblings displayed intermediate amplitudes following a linear model predicted by genetic concordance. The three groups did not differ on error positivity (Pe). The N2 amplitude enhancement due to conflict (incongruent flankers) was reduced in the ADHD group. Nonaffected siblings also displayed intermediate N2 enhancement. CONCLUSIONS Converging evidence from behavioral and event-related potential findings suggests that action monitoring and initial error processing, both related to dopaminergically modulated functions of anterior cingulate cortex, might be an endophenotype related to ADHD.

Questioning inhibitory control as the specific deficit of ADHD – evidence from brain electrical activity

Summary.Objective: To investigate motor response control during a cued continuous performance test (CPT-A-X) by performance and ERP parameters in children with hyperkinetic disorder (HD), hyperkinetic conduct disorder (HCD) or oppositional deviant/conduct disorder (ODD/CD), to examine the evidence for an inhibition-specific deficit as indicated by these parameters, and to analyze whether possible deviations are specific for HD/HCD. Method: Behavioral parameters and event-related potentials (ERPs) were recorded during a CPT-A-X-task in children (aged 8 to 14 years) with either HD (n=15), HCD (n=16), or ODD/CD (n=15) and normal children (n=18) and analysed. ICD-10 diagnoses of HD/HCD diagnoses in all children were fully concordant with the DSM-IV diagnosis of ADHD-combined type. Results: Children with HCD committed more dyscontrol errors and differed most from normal children on ERP measures of motor response control, while children with HD-only were more impaired during processing of the warning stimuli for motor preparation. ERP measures specific for response inhibition were not different between the groups. Conclusions: The results show that ADHD cannot be fully explained by an inhibition-specific deficit and implicate impaired response execution processes as well. This indicates that comorbid children suffer from a reduced ability to control their prepared motor responses. Further, they seem to have difficulties in timely switching attention from monitoring the sensory input stream to the monitoring of own responses and actions.

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. Ann Neurol 2001;49:393–396

Neurofeedback in children with ADHD: Specific event-related potential findings of a randomized controlled trial

OBJECTIVE In a randomized controlled trial, we could demonstrate clinical efficacy of neurofeedback (NF) training for children with ADHD (Gevensleben et al., 2009a). The present investigation aimed at learning more about the neuronal mechanisms of NF training. METHODS Children with ADHD either completed a NF training or a computerized attention skills training (ratio 3:2). NF training consisted of one block of theta/beta training and one block of slow cortical potential (SCP) training, each comprising 18 training units. At three times (pre-training, between the two training blocks and at post-training), event-related potentials (ERP) were recorded during the Attention Network Test. ERP analysis focused on the P3, reflecting inter alia attentional resources for stimulus evaluation, and the contingent negative variation (CNV), primarily related to cognitive preparation. RESULTS After NF training, an increase of the CNV in cue trials could be observed, which was specific for the SCP training. A larger pre-training CNV was associated with a larger reduction of ADHD symptomatology for SCP training. CONCLUSIONS CNV effects reflect neuronal circuits underlying resource allocation during cognitive preparation. These distinct ERP effects are closely related to a successful NF training in children with ADHD. In future studies, neurophysiological recordings could help to optimize and individualize NF training. SIGNIFICANCE The findings contribute to a better understanding of the mechanisms underlying NF training in children with ADHD.

Neurofeedback and Basic Learning Theory: Implications for Research and Practice

Brain activity assessed by electroencephalography (EEG) has been demonstrated to respond to conditioning techniques. The concept of modulating this activity has been called EEG biofeedback, more recently neurofeedback, and is based on operant learning principles. Technological advancements have significantly enhanced the ease and affordability of recording and analyzing brain activity. Thus, properly trained practitioners can implement these conditioning strategies in their practice. Recent research indicating evidenced-based efficacy has made this technique a more viable option for clinical intervention. The objective of this article is to highlight the learning principles that have provided the fundamentals of this neuromodulatory approach. In addition, it is recommended that future applications in clinical work, research, and development adhere to these principles.