Cerebellar network alterations in adult attention-deficit/hyperactivity disorder
Salla Parkkinen1, Joaquim Radua1, Derek S Andrews1
1From the Institute of Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK (Parkkinen, Andrews, Murphy, Dell'Acqua, Parlatini); the Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK (Parkkinen, Murphy, Dell'Acqua, Parlatini); the Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBERSAM, Instituto de Salud Carlos III, University of Barcelona, Barcelona, Spain (Radua); the Department of Psychiatry and Behavioral Sciences, The MIND Institute, University of California, Davis, Sacramento, CA, USA (Andrews); the Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK (Dell'Acqua); the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK (Dell'Acqua); the School of Psychology, University of Southampton, Southampton, UK (Parlatini); the Solent NHS Trust, Southampton, UK (Parlatini).
Background:
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition that often persists into adulthood. Underlying alterations in brain connectivity have been identified but some relevant connections, such as the middle, superior, and inferior cerebellar peduncles (MCP, SCP, and ICP, respectively), have remained largely unexplored; thus, we sought to investigate whether the cerebellar peduncles contribute to ADHD pathophysiology among adults.
Methods:
We applied diffusion-weighted spherical deconvolution tractography to dissect the cerebellar peduncles of male adults with ADHD (including those who did or did not respond to methylphenidate, based on at least 30% symptom improvement at 2 months) and controls. We investigated differences in tract metrics between controls and the whole ADHD sample and between controls and treatment-response groups using sensitivity analyses. Finally, we analyzed the association between the tract metrics and cliniconeuropsychological profiles.
Results:
We included 60 participants with ADHD (including 42 treatment responders and 18 nonresponders) and 20 control participants. In the whole ADHD sample, MCP fractional anisotropy (FA; t 78 = 3.24, p = 0.002) and hindrance modulated orientational anisotropy (HMOA; t 78 = 3.01, p = 0.004) were reduced, and radial diffusivity (RD) in the right ICP was increased (t 78 = -2.84, p = 0.006), compared with controls. Although case-control differences in MCP FA and HMOA, which reflect white-matter microstructural organization, were driven by both treatment response groups, only responders significantly differed from controls in right ICP RD, which relates to myelination (t 60 = 3.14, p = 0.003). Hindrance modulated orientational anisotropy of the MCP was significantly positively associated with hyperactivity measures.
Limitations:
This study included only male adults with ADHD. Further research needs to investigate potential sex- and development-related differences.
Conclusion:
These results support the role of the cerebellar networks, especially of the MCP, in adult ADHD pathophysiology and should encourage further investigation.
Clinical Trial Registration:
NCT03709940.
Related Concept Videos
01:30Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings....
01:14Role of Cerebellum and Prefrontal Cortex in Memory