Monitoring cortical excitability during repetitive transcranial magnetic stimulation in children with ADHD: a single-blind, sham-controlled TMS-EEG study

Background: Repetitive transcranial magnetic stimulation (rTMS) allows non-invasive stimulation of the human brain. However, no suitable marker has yet been established to monitor the immediate rTMS effects on cortical areas in children. Objective: TMS-evoked EEG potentials (TEPs) could present a well-suited marker for real-time monitoring. Monitoring is particularly important in children where only few data about rTMS effects and safety are currently available. Methods: In a single-blind sham-controlled study, twenty-five school-aged children with ADHD received subthreshold 1 Hz-rTMS to the primary motor cortex. The TMS-evoked N100 was measured by 64-channel-EEG pre, during and post rTMS, and compared to sham stimulation as an intraindividual control condition. Results: TMS-evoked N100 amplitude decreased during 1 Hz-rTMS and, at the group level, reached a stable plateau after approximately 500 pulses. N100 amplitude to supra-threshold single pulses post rTMS confirmed the amplitude reduction in comparison to the pre-rTMS level while sham stimulation had no influence. EEG source analysis indicated that the TMS-evoked N100 change reflected rTMS effects in the stimulated motor cortex. Amplitude changes in TMS-evoked N100 and MEPs (pre versus post 1 Hz-rTMS) correlated significantly, but this correlation was also found for pre versus post sham stimulation. Conclusion: The TMS-evoked N100 represents a promising candidate marker to monitor rTMS effects on cortical excitability in children with ADHD. TMS-evoked N100 can be employed to monitor real-time effects of TMS for subthreshold intensities. Though TMS-evoked N100 was a more sensitive parameter for rTMS-specific changes than MEPs in our sample, further studies are necessary to demonstrate whether clinical rTMS effects can be predicted from rTMS-induced changes in TMS-evoked N100 amplitude and to clarify the relationship between rTMS-induced changes in TMS-evoked N100 and MEP amplitudes. The TMS-evoked N100 amplitude reduction after 1 Hz-rTMS could either reflect a globally decreased cortical response to the TMS pulse or a specific decrease in inhibition

Maturation in auditory event-related potentials explains variation in language ability in children.

Processing of auditory information in the cortex continues to develop into later childhood and adolescence. Recent research has indicated that intraclass correlation (ICC) is the best method for capturing maturation in auditory event-related potentials (AEPs) of school-age children. However, the sensitivity of the ICC approach in discerning AEP changes in children has not been consistently demonstrated and positive results have not been replicated. We attempted this replication and further explored whether AEP maturation estimated using the ICC approach predicts cognitive and linguistic abilities in addition to chronological age. We measured AEPs in response to simple tones in groups of 7-, 8-, 9- and 10-year olds with typical development (N = 67) and used ICC to estimate the age equivalent of each child\u27s AEP (AEP-age). Results indicated that ICC differentiated 7- to 8-year-old children from 9- to 10-year-old children and that AEP-age predicted both chronological age and significant, unique variance in language ability, but not in nonverbal IQ. Our findings support the view that auditory organization in children reflects both general developmental maturation and more specific development of language skills, and support the future use of AEP-age to identify and understand individual differences in brain maturation in typically developing and clinical populations

Aberrant Neuromagnetic Activation in the Motor Cortex in Children with Acute Migraine: A Magnetoencephalography Study

Migraine attacks have been shown to interfere with normal function in the brain such as motor or sensory function. However, to date, there has been no clinical neurophysiology study focusing on the motor function in children with migraine during headache attacks. To investigate the motor function in children with migraine, twenty-six children with acute migraine, meeting International Classification of Headache Disorders criteria and age- and gender-matched healthy children were studied using a 275-channel magnetoencephalography system. A finger-tapping paradigm was designed to elicit neuromagnetic activation in the motor cortex. Children with migraine showed significantly prolonged latency of movement-evoked magnetic fields (MEF) during finger movement compared with the controls. The correlation coefficient of MEF latency and age in children with migraine was significantly different from that in healthy controls. The spectral power of high gamma (65–150 Hz) oscillations during finger movement in the primary motor cortex is also significantly higher in children with migraine than in controls. The alteration of responding latency and aberrant high gamma oscillations suggest that the developmental trajectory of motor function in children with migraine is impaired during migraine attacks and/or developmentally delayed. This finding indicates that childhood migraine may affect the development of brain function and result in long-term problems

ERP Markers of Auditory Go/NoGo Processing

The Sequential Processing Schema is a data-driven model that uses event-related potential (ERP) components to chart the important psychophysiological processes activated when completing auditory equiprobable Go/NoGo tasks. This model is useful for measuring experimental effects on basic cognitive processes and provides a valuable framework to synthesise and test ERP component theories. Determining the cognitive and behavioural correlates of ERP components is critical for understanding their functional significance and utility in psychology. Additional research is also needed to refine the conceptualisation of the ERP components and cognitive processing requirements in equiprobable Go/NoGo tasks, which are commonly used in psychophysiological research. To do that, robust data-driven methods such as temporal Principal Components Analysis (PCA) are needed for effective ERP component quantification and analyses of the Go/NoGo ERP component ‘processing’ series. This doctoral thesis aimed to clarify ERP component functionality and refine our understanding of equiprobable Go/NoGo tasks by developing the Sequential Processing Schema and exploring how ERP/PCA components relate to cognitive and behavioural processing under different Go/NoGo task conditions. Study 1 compared the ERP component processing series associated with auditory equiprobable and oddball variants of the Go/NoGo task. The manipulation of probability and the relevant modulation of the ERP component series reflected a shift in particular cognitive demands or task requirements, which promoted the conceptual development of component functionality and the generalisability of the Schema. The results of Study 1 questioned the identity of a core ERP component (i.e., Processing Negativity) previously linked to auditory Go/NoGo processing; this was pursued in detail in Study 2, which aimed to clarify the ERP components associated with early information processing in auditory equiprobable and ‘frequent Go’ variants of the Go/NoGo task. Stimulus probability differences (this time the inverse of Study 1) were again used to elucidate component functionality and provide insight into the cognitive task demands. Study 3 and 4 explored ERP component functionality by examining Go stimulus- and response-locked ERP averaging effects, and the link between the equiprobable NoGo P3a and motor response inhibition. Studies 1–4 provided insight into the sequential processing requirements in auditory equiprobable Go/NoGo tasks, and the associated ERP/PCA components, promoting the development of common ERP components as indices of cognitive processes. These outcomes clarified the utility of the equiprobable Go/NoGo task, and highlight important similarities and differences between Go/NoGo and oddball processing, encouraging ERP theory development and integration between those common research paradigms. An update to the Schema was proposed to accommodate the ERP findings and reflect the refined interpretation of equiprobable Go/NoGo processing developed in this thesis, including a shift in the conceptualisation of the sensory processing and inhibitory requirements in the equiprobable task. This was considered to improve the conceptual framework of the Schema and its utility for charting the cognitive and behavioural processing in different task conditions. The outcomes also provide novel insight into how healthy young adults process information and encourage further studies of sequential processing to help delineate abnormalities in cognitive processing related to different psychopathologie

Relation of spontaneous and evoked brain activity to language development in young children

Separate studies have shown connections between spontaneous alpha oscillations and language ability in 4-6 year-olds, and between auditory evoked potential (AEP) maturity and language in 7-10-year-olds. The thesis aimed to further our understanding of how these spontaneous and evoked neural measures relate to language development in younger children than previously studied. In this thesis, I first propose a method to investigate spontaneous alpha oscillations and language in 1-4-year-olds. Next, I examined alpha oscillations, AEP maturity, and language ability in 5-6-year-olds. Results revealed that AEP maturity did not predict language ability and correlated with alpha long-range-temporal-correlation but not with alpha power or flexibility. Next, I examined the possibility that this study did not have enough AEP trials. Using a new index called standardized measurement error, I found that AEP trial-by-trial noise decreases with age between 4-7 years, suggesting that future studies of AEP maturity may need more trials for younger ages

Depression, Lernen und langsame Hirnpotenziale : Eine Untersuchung zur Erfassung von Gedächtnisprozessen bei depressiven Patienten

Ziel der Arbeit war es, die neuronalen Prozesse des aversiven, differentiellen Spurenkonditionierens bei gesunden Kontrollpersonen sowie bei depressiven Patienten abzubilden. Untersucht wurde die Fragestellung, ob die stimulus preceding negativity (SPN) eher ein frontozentrales Maximum (affektive Antizipation) oder ein zentroparietales Maximum (sensorische Verarbeitung) aufweist. Des weiteren wurde untersucht, ob die Analyse der SPN eine Möglichkeit bietet, deklaratives Lernen abzubilden. Die Ergebnisse zeigen, dass die SPN eher einen auf den relevanten Reiz gerichteten Aufmerksamkeitsprozess abbildet. Die wichtigsten Befunde aus den durchgeführten Untersuchungen lauten 1.Beide SPN-Intervalle (SPN1 und SPN2) unterscheiden sich bis auf die okzipitale Aktivierung aufgrund des anhaltenden visuellen Stimulus im ersten Intervall nicht in ihrer Topographie: Die Überbrückung der Lücke zwischen CS offset und US onset erfordert keine zusätzliche Aktivierung. 2.Die SPN der vorliegenden Studie bildet nicht deklaratives Lernen ab sondern repräsentiert eher eine kognitive Antizipation bzw. eine Aufmerksamkeits-Fokussierung. Trotz des aversiven Charakters der Studie scheint die Antizipation des US nicht affektiv geprägt zu sein. 3.Zumindest während der akuten depressiven Episode weisen depressive Patienten Defizite im Aufmerksamkeitsnetzwerk auf. 4.Das Aufmerksamkeitsdefizit der Depressiven ist ein spezifisches, gerichtetes Defizit, das bei Konditionierungsprozessen eine Rolle spielt; andere Prozesse (z.B. visuelle Aktivierung, Präsenz des LPC) sind intakt. Die gefundenen Ergebnisse weisen eher auf ein state-abhängiges Defizit hin, dies sollte in einer weiteren Studie verifiziert werden