Basal Ganglia Neurometabolites and Executive Functions in Pediatric Attention-Deficit/Hyperactivity
Poster No:
258
Submission Type:
Abstract Submission
Authors:
Tasmia Hai1, Rose Swansburg2, Cynthia Kahl3, Jean-Francois Lemay3, Frank MacMaster4
Institutions:
1McGill University, Montreal, ON, 2University of Alberta, Edmonton, AB, 3University of Calgary, Calgary, AB, 4IWK Health, Halifax, Nova Scotia
First Author:
Co-Author(s):
Introduction:
Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent neurodevelopmental disorder which presents with developmentally inappropriate levels of inattention and/or hyperactivity and impulsivity. Behaviourally, children with ADHD also struggle with starting tasks, remaining on task, planning and completing other goal-oriented behaviours (Kofler et al., 2019). Neurobiologically, the basal ganglia have previously been implicated in managing these goal-oriented tasks (Chakravarthy et al., 2010). Specifically, previous studies have found differences in neurometabolite concentration, such as glutamate (Glu), Glutamate-glutamine (glx) and N-acetyl aspartate (NAA), in the basal ganglia in individuals with ADHD compared to their age-matched peers (Carrey et al., 2007; MacMaster et al., 2003; Perlov et al., 2009). However, limited studies have investigated the clinical implications of these neurometabolites.
Methods:
We studied 49 children (24 ADHD/25 typically developing children (TDC)). All participants in the ADHD group underwent a 48-hour stimulant medication washout period. Parents completed informant rating scales reporting on child attention, behaviour and executive functioning skills using the Conners-3 scale and the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2). Participants underwent a high-resolution MRI T1-weighted sequence using a 3 Tesla General Electric Discovery 750W MRI scanner with a 32-channel head coil. Structural MRI parameters were as follows: TR = 8.2ms, TE = 3.2ms, flip angle = 10°, field of view (FOV) = 256 mm2, acquisition matrix size = 300x300, voxels = 0.8mm3 isotropic. For proton magnetic resonance spectroscopy, short-echo point-resolved spectroscopy (PRESS) acquisition (repetition time, 1.8 seconds; echo time, 30 milliseconds; 64 averages) for NAA, Glu and Glx were applied to left basal ganglia (Figure 1; 15mm x 15mm x 20 mm voxel). Univariate analyses of variance (ANOVA) were conducted to measure group differences in neurometabolites concentration in the LBG. The magnetic resonance spectroscopy data were analyzed objectively using a linear combination model (Provencher, 2001).
Results:
Results indicated significantly higher levels of executive functioning difficulties in children with ADHD compared to control (F (5,43) = 20.89, p <.001, partial eta squared =.71). As well, children with ADHD had lower concentrations of Glu and NAA compared to healthy controls (p < .05) in the LBG. No group difference was observed in Glx concentration (p >.05). Significant correlations were observed with NAA concentration and parent ratings on the BRIEF-2 Emotion Regulation Index subscale (r = -.32, p = .03) and BRIEF-2 Cognitive Regulation Index subscale (r = -.33, p = .03). Similarly, BRIEF-2 Emotion Regulation Index subscale was significantly correlated with Glx concentration (r = -.32, p = .03).
Conclusions:
The study revealed significant difficulties in EF based on parent ratings and differences in neurometabolites in children with ADHD. The findings study supports existing literature highlighting neurochemical differences in children with ADHD, specifically in the basal ganglia. Overall, it suggests a possible brain-behaviour relationship between the neurobiology of the basal ganglia and executive function challenges. While these results are exploratory, it is likely that the basal ganglia may serve as a link between the dopaminergic reward systems, and ADHD symptomatology (Damiani et al., 2021).
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Higher Cognitive Functions:
Executive Function, Cognitive Control and Decision Making
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Subcortical Structures
Novel Imaging Acquisition Methods:
MR Spectroscopy 2
Keywords:
Attention Deficit Disorder
Glutamate
MR SPECTROSCOPY
MRI
PEDIATRIC
Sub-Cortical
1|2Indicates the priority used for review
Abstract Information
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Chakravarthy, V. S., Joseph, D., & Bapi, R. S. (2010). What do the basal ganglia do? A modeling perspective. Biological Cybernetics, 103(3), 237–253. https://doi.org/10.1007/s00422-010-0401-y
Damiani, S., Tarchi, L., Scalabrini, A., Marini, S., Provenzani, U., Rocchetti, M., Oliva, F., & Politi, P. (2021). Beneath the surface: Hyper-connectivity between caudate and salience regions in ADHD fMRI at rest. European Child & Adolescent Psychiatry, 30(4), 619–631. https://doi.org/10.1007/s00787-020-01545-0
Kofler, M. J., Irwin, L. N., Soto, E. F., Groves, N. B., Harmon, S. L., & Sarver, D. E. (2019). Executive functioning heterogeneity in pediatric ADHD. Journal of Abnormal Child Psychology, 47(2), 273–286. https://doi.org/10.1007/s10802-018-0438-2
MacMaster, F. P., Carrey, N., Sparkes, S., & Kusumakar, V. (2003). Proton spectroscopy in medication-free pediatric attention-deficit/hyperactivity disorder. Biological Psychiatry, 53(2), 184–187. https://doi.org/10.1016/S0006-3223(02)01401-4
Perlov, E., Philipsen, A., Matthies, S., Drieling, T., Maier, S., Bubl, E., Hesslinger, B., Buechert, M., Henning, J., Ebert, D., & Tebartz Van Elst, L. (2009). Spectroscopic findings in attention-deficit/hyperactivity disorder: Review and meta-analysis. World Journal of Biological Psychiatry, 10(4 Pt 2), 355–365. https://doi.org/10.1080/15622970802176032
Provencher, S. W. (2001). Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR in Biomedicine, 14(4), 260–264. https://doi.org/10.1002/nbm.698