Renate Drechsler

The feedback-related negativity (FRN) revisited: New insights into the localization, meaning and network organization

Changes in response contingencies require adjusting ones assumptions about outcomes of behaviors. Such adaptation processes are driven by reward prediction error (RPE) signals which reflect the inadequacy of expectations. Signals resembling RPEs are known to be encoded by mesencephalic dopamine neurons projecting to the striatum and frontal regions. Although regions that process RPEs, such as the dorsal anterior cingulate cortex (dACC), have been identified, only indirect evidence links timing and network organization of RPE processing in humans. In electroencephalography (EEG), which is well known for its high temporal resolution, the feedback-related negativity (FRN) has been suggested to reflect RPE processing. Recent studies, however, suggested that the FRN might reflect surprise, which would correspond to the absolute, rather than the signed RPE signals. Furthermore, the localization of the FRN remains a matter of debate. In this simultaneous EEG-functional magnetic resonance imaging (fMRI) study, we localized the FRN directly using the superior spatial resolution of fMRI without relying on any spatial constraint or other assumption. Using two different single-trial approaches, we consistently found a cluster within the dACC. One analysis revealed additional activations of the salience network. Furthermore, we evaluated the effect of signed RPEs and surprise signals on the FRN amplitude. We considered that both signals are usually correlated and found that only surprise signals modulate the FRN amplitude. Last, we explored the pathway of RPE signals using dynamic causal modeling (DCM). We found that the surprise signals are directly projected to the source region of the FRN. This finding contradicts earlier theories about the network organization of the FRN, but is in line with a recent theory stating that dopamine neurons also encode surprise-like saliency signals. Our findings crucially advance the understanding of the FRN. We found compelling evidence that the FRN originates from the dACC. Furthermore, we clarified the functional role of the FRN, and determined the role of the dACC within the RPE network. These findings should enable us to study the processing of surprise and adjustment signals in the dACC in healthy and also in psychiatric patients.

Decision-making on an explicit risk-taking task in preadolescents with attention-deficit/hyperactivity disorder

Summary.Inappropriate risk-taking and disadvantageous decision-making have been described as major behavioural characteristics of patients with attention-deficit/hyperactivity disorder (ADHD). However these behaviours are difficult to measure in laboratory contexts and recent studies have yielded inconsistent results which might be related to task characteristics. The present study adopted the Game of Dice Task, a test procedure in which risks are made explicit and the load on working memory is minimal. As a result, preadolescents with ADHD (N = 23) made significantly more risky choices and suffered major losses of money compared to normal controls (N = 24) but only when they played the game a second time. Differences in risk-taking correlated significantly with hyperactivity as rated by parents and with inhibitory control, but not with working memory performance. The results are discussed in the context of current theories of ADHD.

Mapping Attention-Deficit/Hyperactivity Disorder from Childhood to Adolescence—No Neurophysiologic Evidence for a Developmental Lag of Attention but Some for Inhibition

BACKGROUND The role of a developmental lag for deficits of higher brain functions in attention-deficit/hyperactivity disorder (ADHD) has not yet been tested in longitudinal studies. We examined the development of neurophysiological markers of attention (Cue P300; contingent negative variation [CNV]) and inhibition (NoGo P300) in ADHD and control groups from childhood to adolescence for support of the developmental lag hypothesis of ADHD. METHODS ADHD (n = 28/3 girls) and control (n = 22/5 girls) subjects were assessed at baseline (Time 1; ADHD age 10.8 +/- 1.8 years, controls 10.4 +/- 1.1 years) and at two follow-up examinations (Time 2 after 1.2 years, Time 3 after 2.5 years). Event-related potential maps were recorded during a cued Continuous Performance Test (CPT) at all assessments and analyzed using scalp and source (sLORETA) measures. RESULTS CPT performance showed common effects of ADHD and younger age, consistent with (but not specific to) developmental lag. The NoGo P300 developed earlier and became stronger in control subjects than in the ADHD group, again consistent with an initial developmental lag. In contrast, the attenuation of the Cue P300 and the CNV with ADHD at all assessments was opposite to the enhancement with younger age and thus inconsistent with developmental lag. The sLORETA source localization also differed between ADHD and developmental effects. CONCLUSIONS These results provide strong evidence for multiple and persistent neural processing deficits in ADHD. They do not support the developmental lag hypothesis for attentional dysfunction in ADHD despite partial evidence that developmental lag contributes to inhibitory brain dysfunction during early adolescence.

Differences in Neurophysiological Markers of Inhibitory and Temporal Processing Deficits in Children and Adults with ADHD

We compared ADHD-related temporal processing and response inhibition deficits in children and adults using event-related potentials (ERPs) during cued continuous performance tasks (CPT, O-X-version, plus a more demanding flanker version). ERP markers of temporal processing (Cue CNV) and inhibition (NoGo P300) were obtained in matched groups of children (32 with ADHD, mean age 11.2 years, and 31 controls, mean age 11.1 years) and adults (22 ADHD, mean age 42.7 years, and 22 controls, mean age 44.0 years). ERP markers and performance reflected both age and ADHD status. Performance was poorer, and Cue CNV and NoGo P300 were weaker in ADHD children and adults compared to their matched controls. ADHD-related ERP differences in children were more prominent at posterior scalp sites but more pronounced at anterior scalp sites in adults, paralleling the prominent topographic changes of both ERP markers with development. The fact that differences in the same test and the same processing period appear in both childr...

Are treatment effects of neurofeedback training in children with ADHD related to the successful regulation of brain activity? A review on the learning of regulation of brain activity and a contribution to the discussion on specificity

While issues of efficacy and specificity are crucial for the future of neurofeedback training, there may be alternative designs and control analyses to circumvent the methodological and ethical problems associated with double-blind placebo studies. Surprisingly, most NF studies do not report the most immediate result of their NF training, i.e., whether or not children with ADHD gain control over their brain activity during the training sessions. For the investigation of specificity, however, it seems essential to analyze the learning and adaptation processes that take place in the course of the training and to relate improvements in self-regulated brain activity across training sessions to behavioral, neuropsychological and electrophysiological outcomes. To this aim, a review of studies on neurofeedback training with ADHD patients which include the analysis of learning across training sessions or relate training performance to outcome is presented. Methods on how to evaluate and quantify learning of EEG regulation over time are discussed. “Non-learning” has been reported in a small number of ADHD-studies, but has not been a focus of general methodological discussion so far. For this reason, selected results from the brain-computer interface (BCI) research on the so-called “brain-computer illiteracy”, the inability to gain control over one’s brain activity, are also included. It is concluded that in the discussion on specificity, more attention should be devoted to the analysis of EEG regulation performance in the course of the training and its impact on clinical outcome. It is necessary to improve the knowledge on characteristic cross-session and within-session learning trajectories in ADHD and to provide the best conditions for learning.

First clinical trial of tomographic neurofeedback in attention-deficit/hyperactivity disorder : evaluation of voluntary cortical control

OBJECTIVE Tomographic neurofeedback (tNF) training was evaluated as a treatment for attention-deficit/hyperactivity disorder (ADHD). To investigate the specificity of the treatment, outcomes were related to learning during tNF. METHODS Thirteen children with ADHD trained over 36 lessons to regulate their brain activity in the anterior cingulate cortex (ACC) using both theta-beta frequency and slow cortical potential (SCP) protocols. Thirty-channel electroencephalogram (EEG) was used to calculate low-resolution electromagnetic tNF and to assess the course of the training. Pre- and post-assessments included questionnaires, tests of attention, EEG recordings, and cognitive event-related potentials. RESULTS Despite behavioural improvement and EEG artefact reduction, only partial learning was found for ACC parameters. Successful regulation was observed only for a simple feedback variant of SCP training, but with ACC-specific effects. Over training, resting EEG analysis indicated individual frequency normalisation rather than unidirectional changes across subjects. CONCLUSIONS These results indicate that clinical improvement after ACC-tNF training can parallel artefact reduction without substantial learning of improved cortical control. However, individual normalisation of resting EEG activity and partial SCP control proved possible in this specific brain region affected in ADHD using tNF. Further studies are needed to clarify which critical aspects mediate region-specific learning in neurofeedback. SIGNIFICANCE This study is the first to systematically investigate tNF in children suffering from a psychiatric disorder.

Clinical course of attention-deficit/hyperactivity disorder from childhood toward early adolescence

OBJECTIVE To study the course of attention-deficit/hyperactivity disorder (ADHD) in late childhood to adolescence using a multi-informant and multi-assessment procedure. METHOD Subjects were 35 children with ADHD and 35 matched controls with a mean age of 10 years at first assessment. DSM-III-R-based structured diagnostic interviews and behavioral questionnaires based on parents, teachers, and youth informants were used. Cross-informant behavioral syndromes were obtained by use of the Child Behavior Checklist, the Teachers Report Form, and the Youth Self-Report. Subjects were reassessed after 1.5 and 2.6 years. RESULTS Behavioral differences between the two groups were significant for the majority of scales for all three informants at all three times. Diagnostic interviews revealed a persistence rate of 46% over 2.6 years. However, there were only few significant behavioral differences across informants between the nonpersistent and the persistent groups. The fit between interview-derived syndrome scores reflecting subtypes of ADHD and both parents and youth questionnaire data was good, whereas for the teacher ratings it was poor. A high rate of 89% correct classification of the outcome diagnoses was possible based on behavioral data at time 1. CONCLUSIONS The study of the course of ADHD should be based both on interview and questionnaire data and should include several informants. Operationally defined diagnoses alone may lead to an underestimation of persistent behavioral problems.

Decision making with uncertain reinforcement in children with attention deficit/hyperactivity disorder (ADHD).

Reward-related processes are impaired in children with ADHD. Whether these deficits can be ascribed to an aversion to delay or to an altered responsiveness to magnitude, frequency, valence, or the probability of rewards still needs to be explored. In the present study, children with ADHD and normal controls aged 7 to 10 years performed a simple probabilistic discounting task. They had to choose between alternatives where the magnitude of rewards was inversely related to the probability of outcomes. As a result, children with ADHD opted more frequently for less likely but larger rewards than normal controls. Shifts of the response category after positive or negative feedback, however, occurred as often in children with ADHD as in control children. In children with ADHD, the frequency of risky choices was correlated with neuropsychological measures of response time variability but unrelated to measures of inhibitory control. It is concluded that the tendency to select less likely but larger rewards possibly represents a separate facet of dysfunctional reward processing, independent of delay aversion or altered responsiveness to feedback.

Comparing tomographic EEG neurofeedback and EMG biofeedback in children with attention-deficit/hyperactivity disorder

Two types of biofeedback (BF), tomographic electroencephalogram (EEG) neurofeedback (NF) and electromyographic biofeedback (EMG-BF), both with phasic and tonic protocols, were compared for treatment effects and specificity in attention-deficit/hyperactivity disorder (ADHD). Thirteen children with ADHD trained their brain activity in the anterior cingulate cortex (ACC), and twelve trained activity of arm muscles involved in fine motor skills. In each training session, resting state 24-channel EEG and training performances were recorded. Both groups showed similar behavioral improvements and artifact reduction in selected conditions, with no significant advantages despite medium effect sizes on primary outcomes for NF. Only the EMG-BF group, however, showed clear improvement in training regulation performance, and specific motor coordination effects. The NF group tended to present individual normalization of trained frequency bands in the ACC during rest across training. The results provide evidence for some specific effects in our small sample, albeit only to a small extent.

Zur klinischen Validität einer computergestützten Aufmerksamkeitstestbatterie für Kinder (KITAP) bei 7- bis 10-jährigen Kindern mit ADHS

Obwohl neuropsychologische Tests zwischen Kindern mit und ohne ADHS unterscheiden, ist doch ihr Beitrag zur klinischen Diagnose oft unklar. Daher wurde untersucht, wie gut eine computergestutzte Testbatterie zur Aufmerksamkeitsprufung bei Kindern (KITAP) zwischen Kindern mit und ohne ADHS trennt und welchen Beitrag sie bei der diagnostischen Klassifikation leisten kann. In der Studie fuhrten 50 Kinder mit ADHS und 50 gesunde Kinder im Alter von sieben bis zehn Jahren Untertests zu Alertness, Flexibilitat, Inhibitionskontrolle, Daueraufmerksamkeit, geteilter Aufmerksamkeit und Ablenkbarkeit durch. Es zeigte sich, dass vier der sechs Aufgaben zwischen den Gruppen signifikant trennten. Die Kombination von zwei oder mehr beeintrachtigten Untertests erwies sich zwar als bester Pradiktor fur ADHS, war aber fur klinisch-diagnostische Zwecke unzureichend. Es wird die Schlussfolgerung gezogen, dass eine computergestutzte Testbatterie zwar wichtige Hinweise auf das individuelle Leistungsprofil gibt, sich eine diagn...