Project ID NS-MH2026_32

ThemeNS-MH

Co Supervisor 1A Dr Grainne McLoughlin Institute of Psychiatry, Psychology & Neuroscience, School of Mental Health & Psychological Sciences, Social, Genetic & Developmental Psychiatry CentreEmail

Co Supervisor 1B Prof Richard Emsley Institute of Psychiatry, Psychology & Neuroscience, School of Mental Health & Psychological Sciences, Department of Biostatistics & Health InformaticsEmail

SYNC-ADHD: Study of Young adults using Neuromodulation to investigate Symptom Change in ADHD

Attention-deficit/hyperactivity disorder (ADHD) involves impaired cognitive control specifically, difficulty maintaining task goals and suppressing distractions. Individuals with ADHD exhibit variability in behavioural performance indexed by reaction time, and in the timing of frontal theta oscillations (4–8 Hz), which underlie cognitive control. Correlational evidence shows that a greater theta phase variability predicts greater behavioural variability. To move beyond correlation, we will use rhythmic transcranial magnetic stimulation (rTMS) at theta frequency over frontal cortex to experimentally reduce phase variability and assess resulting changes in cognitive control performance in young adults with ADHD. Translationally, if theta-frequency rTMS can reliably enhance frontal midline theta (FMT) consistency and reduce reaction-time variability in ADHD, this noninvasive approach could be developed as a potential therapeutic intervention. We will also outline key translational considerations, including primary outcome measures, sample-size estimates, and safety monitoring protocols, to inform the design of future clinical efficacy studies. This study therefore advances basic understanding of how neural oscillatory dynamics drive attention and response consistency, while also potentially establishing proof-of-concept for a novel, directly targeted neuromodulation strategy in ADHD.

The student will design and code tasks; collect and preprocess EEG with rTMS; apply theta-frequency rTMS; analyse oscillatory phase variability and behaviour; and contribute to Patient and Public Involvement and Engagement (PPIE).

The overarching aims of the project are to causally link frontal theta phase consistency to reaction-time variability in adults with and without ADHD, determine whether theta-frequency rTMS reduces behavioural variability by stabilising neural oscillations, and lay the groundwork for non-pharmacological interventions targeting oscillatory dynamics in ADHD.

Yearly outline of the project:
Year 1: Establish ethical approval and rTMS–EEG integration. Develop, pilot, and validate cognitive-control tasks. Begin PPIE meetings to refine tasks. Generate initial healthy-control dataset.
Year 1-2: Extend data collection to adults with ADHD. Fine-tune stimulation parameters (intensity, pulse timing). Implement rTMS during tasks in healthy and ADHD participants. Continue PPIE.
Year 3: Complete data collection. Conduct analyses: quantify theta power, phase variability, and behavioural variability relationships. Begin manuscript preparation on mechanistic findings.
Year 4: Finalise data analysis, write up.

The rotation will focus on developing a robust EEG preprocessing pipeline for concurrent rTMS-EEG. The student will compare different artifact-removal methods and validate by measuring residual theta-phase variability during sham vs. real rTMS. Deliverable: a documented, reproducible pipeline and a short report recommending optimal preprocessing parameters for later project phases.

Representative Publications

Capp, S., De Burca, A., Aydin, Ü., Agnew-Blais, J., Lautarescu, A., Ronald, A., Happé, F., & McLoughlin, G. (2025). Depression and anxiety are increased in autism and ADHD: Evidence from a young adult community-based sample. JCPP Advances, e70003. https://doi.org/10.1002/jcv2.70003 Aydin, Ü., Gyurkovics, M., Ginestet, C., Capp, S., Greven, C.U., Palmer, J., McLoughlin, G. (2023) Genetic Overlap Between Midfrontal Theta Signals and Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in a Longitudinal Twin Cohort. Biological Psychiatry, 94(10), 823-832. doi: 10.1016/j.biopsych.2023.05.006. McLoughlin, G., Gyurkovics, M., Palmer, J., Makeig, S. (2022) Midfrontal Theta Activity in Psychiatric Illness: An Index of Cognitive Vulnerabilities Across Disorders. Biological Psychiatry, 91(2),173-182. doi: 10.1016/j.biopsych.2021.08.020.

Payne M, Stringer D, Carter B, Hardy A, Emsley R. Reviewing methodological approaches to dose-response modelling in complex interventions: insights and perspectives. BMC Med Res Methodol. 2025 May 16;25(1):135. doi: 10.1186/s12874-025-02585-3. PMID: 40380134; PMCID: PMC12082932. Pickles A, Edwards D, Horvath L, Emsley R. Research Reviews: Advances in methods for evaluating child and adolescent mental health interventions. J Child Psychol Psychiatry. 2023 Dec;64(12):1765-1775. doi: 10.1111/jcpp.13892. Epub 2023 Oct 4. PMID: 37793673. Garety PA, Edwards CJ, Jafari H, Emsley R, Huckvale M, Rus-Calafell M, Fornells-Ambrojo M, Gumley A, Haddock G, Bucci S, McLeod HJ, McDonnell J, Clancy M, Fitzsimmons M, Ball H, Montague A, Xanidis N, Hardy A, Craig TKJ, Ward T. Digital AVATAR therapy for distressing voices in psychosis: the phase 2/3 AVATAR2 trial. Nat Med. 2024 Dec;30(12):3658-3668. doi: 10.1038/s41591-024-03252-8. Epub 2024 Oct 28. PMID: 39468363; PMCID: PMC11645260.