Electroencephalography as a neurophysiological marker to aid diagnosis and treatment response in Attention-Deficit/Hyperactivity Disorder.

Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental condition characterised by persistent difficulties in attention, impulse control and executive functioning. Despite advances in behavioural and clinical research, objective neurophysiological markers that can support diagnosis, clarify neurocognitive mechanisms and inform treatment remain limited. Electroencephalography (EEG) is a non-invasive method for examining neural processes with high temporal resolution, which has shown promise in ADHD research. The main goal of this thesis was to investigate the potential of EEG for identifying neurophysiological markers associated with ADHD diagnosis, methylphenidate response and comorbid symptom dimensions across developmental stages and experimental paradigms. This included examining differences between young people with ADHD and typically developing controls as well as dimensional relationships between ADHD-related symptoms, anxiety and neural function in an ADHD-enriched adult community sample. Chapter 1 was an introduction outlining the thesis background. It covered the cognitive profiles and neurobiology associated with ADHD, current treatment approaches, and the limitations of subjective medication decisions. The chapter introduced EEG – including resting-state and task-based paradigms – as a tool for biomarker research, highlighting the promise of novel at-home dry EEG technologies. It also presented aperiodic EEG activity as a candidate marker of cortical excitation/inhibition balance in ADHD. Chapter 2 used 128-channel laboratory-based EEG to examine group differences and diagnostic metrics of resting-state aperiodic EEG activity in 29 medication-naïve 10–17-year-olds with ADHD compared to 27 typically developing controls. Chapter 2 also investigated the effect of initiating methylphenidate treatment on aperiodic EEG activity. Young people with ADHD had significantly smaller aperiodic parameters (exponent and offset) across eyes-open and eyes-closed conditions, reflecting increased cortical excitation. Methylphenidate initiation did not significantly modify the exponent or offset. The eyes-closed exponent predicted ADHD diagnostic status with moderate accuracy. The findings of Chapter 2 suggest that resting-state EEG markers may reflect stable neurophysiological characteristics of ADHD rather than short-term stimulant effects. Chapter 3 extended the research of the previous chapter to task-based paradigms involving attention control and working memory in 28 10–17-year-olds with ADHD and 24 typically developing controls. Young people with ADHD had smaller exponents in both a three-stimulus oddball task and N-back task, and smaller offsets in the oddball task. Consistent with the findings of Chapter 2, methylphenidate treatment did not significantly alter aperiodic components. Exponent and offset measures from oddball target trials predicted ADHD diagnostic status with moderate accuracy; however, N-back measures were not predictive. The findings of Chapter 3 suggest that reduced aperiodic activity, indicating decreased cortical inhibition, during attentional control and working memory tasks may be a marker of ADHD. Chapter 4 adopted a mixed-methods approach to evaluate the feasibility, acceptability and usability of self-administered at-home dry EEG in 21 10–17-year-olds with ADHD and 12 age-matched controls. Quantitative analyses using a 16-channel dry EEG system demonstrated high adherence but low signal quality, failing to replicate established resting-state aperiodic group differences. Qualitative interviews with 7 participants and 7 parents identified flexibility and convenience as key facilitators of at-home research with dry EEG, and headset discomfort and signal reliability as primary barriers to this research. While families expressed openness to integrating such technology into clinical care, current dry EEG systems did not produce data of sufficient quality to support scalable biomarker development in paediatric ADHD. Chapter 5 employed a dimensional approach in an ADHD-enriched community sample of forty-six adults, in which over half of the participants had either an ADHD diagnosis or a family history of ADHD, to investigate the interaction between attention deficit symptoms and trait anxiety during an emotional stop-signal task using 64-channel laboratory-based EEG. This chapter extended the preceding categorical ADHD investigations by examining whether EEG markers associated with ADHD symptoms also varied dimensionally across individuals and whether comorbid anxiety influenced neural mechanisms underlying cognitive control. Findings indicated that trait anxiety moderated neural indices of conflict monitoring and post-error processing, with enhanced N2 and Pe amplitudes in individuals with elevated attention deficits and higher trait anxiety. Aperiodic activity was not associated with these individual differences, suggesting alterations in aperiodic activity may be specific to group status rather than dimensional variation. Chapter 6 integrated the findings across studies, highlighting the consistent reduction in aperiodic activity in 10–17-year-olds with ADHD, the absence of methylphenidate-related normalisation and the potential of dry EEG for at-home research, and the relevance of examining both categorical and dimensional approaches to understanding ADHD-related neural differences. This chapter also discussed the limitations of the research in this thesis and offered future research directions. Overall, this thesis demonstrated that EEG measures provide insight into neurophysiological differences associated with ADHD across both diagnostic groups and symptom dimensions. Aperiodic EEG activity was consistently associated with ADHD status in young people, providing insight into cortical excitation and neural dynamics, although it was not sensitive to methylphenidate-related changes or dimensional variation in symptom severity. The findings also highlight the challenges of at-home EEG research and parental support for neurotechnology.