Cerebellar volume in substance use disorders: a mega-analysis by the ENIGMA addiction working group

Poster No:

692 

Submission Type:

Abstract Submission 

Authors:

Jalil Rasgado Toledo1, Alfonso Fajardo-Valdez2, Ian Harding3, Scott Mackey4, Hugh Garavan5, Eduardo Garza-Villarreal1

Institutions:

1Universidad Nacional Autónoma de México, Queretaro, Mexico, 2McGill University, Montreal, Quebec, 3Monash University, Melbourne, Australia, 4The University of Vermont, Burlington, VT, 5University of Vermont, Burlington, VT

First Author:

Jalil Rasgado Toledo  
Universidad Nacional Autónoma de México
Queretaro, Mexico

Co-Author(s):

Alfonso Fajardo-Valdez  
McGill University
Montreal, Quebec
Ian Harding  
Monash University
Melbourne, Australia
Scott Mackey  
The University of Vermont
Burlington, VT
Hugh Garavan  
University of Vermont
Burlington, VT
Eduardo A. Garza-Villarreal, MD, PhD  
Universidad Nacional Autónoma de México
Queretaro, Mexico

Introduction:

The cerebellum contributes in among a wide variety of higher-order processes, including rewarding and emotional functions (Zhang et al. 2023) and evidence suggests the involvement of the cerebellum in substance use disorders (SUDs) and addiction. A recent meta-analysis showed addiction to any substance was related to low brain volume in cerebellar white matter, while long-term use was related to high brain volume in cerebellar gray matter (Pando-Naude et al. 2021). In this study, we wanted to determine the brain volume of the cerebellum and subdivisions in different SUDs using a mega-analysis.

Methods:

We used MRI T1w sequences from 3,172 individuals with SUDs (AUD n = 914, ATS n = 111, CANN n = 49, COC n = 405, COH = 30, NIC n = 577, OPI n = 58, Controls n = 1,028) across 60 sites from the ENIGMA-addiction working group. After QC, we tested 2 methods: 1) a deep-learning-based approach for automatic cerebellar parcellation (ACAPULCO) using an anatomical atlas (Han et al. 2020) and 2) the spatially unbiased infratentorial template (SUIT) toolbox (Diedrichsen 2006) for voxel-based morphometry (VBM). To study functionally defined ROIs we also obtained the mean volume for 10 cerebellar regions from the Multi-Domain Task Battery atlas (MDTB) (King et al. 2019) using the SUIT toolbox. We then independently compared the ACAPULCO and MDTB volumes and the SUIT-VBM between groups (patients vs controls) in general and with Subtance subgroups with a permutation Welch Two Sample t-tests analysis. Each test was controlled for age, sex, intracranial volume, and site. The Benjamini-Hochberg procedure was used to control for multiple comparisons (p-FDR < 0.05).

Results:

We found significant volume differences between SUDs and controls, which varied between types of substances. We found that SUD subjects displayed differences mainly in subregions 1, 4, 6, 9 and 10. In particular, the greatest effects appeared to be related to nicotine use disorder, with volume differences in almost all subregions, followed by amphetamine and alcohol. Subregions with the most group differences were 1 and 2. All group comparisons showed low to medium effect sizes. A set of affected regions were related depending on the substance, but some subregions of regions 1 and 4 according to the MDTB atlas, were found to have higher changes.
Supporting Image: cer.png
   ·Voxel-base morphometry results of the comparison between each substance with controls. Color bars indicate t-values.
Supporting Image: Volumes_differences.png
   ·Significant volumes differences of each region of Multi-Domain Task Battery atlas (MDTB) between substance use disorder groups compared with controls. Abbreviations = healthy controls (HC); Substance
 

Conclusions:

Our results suggest that specific cerebellum regions are affected in SUDs, and some regions are affected in all SUDS, while other regions are only affected by substance. Regional variations may be associated with interference resolution, motor planning, active maintenance, and verbal comprehension, according to the MDTB atlas results.

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1

Emotion, Motivation and Social Neuroscience:

Reward and Punishment 2

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Neuroanatomy Other

Keywords:

Cerebellum
Morphometrics
MRI
Psychiatric
STRUCTURAL MRI

1|2Indicates the priority used for review

Provide references using author date format

Diedrichsen, J. (2006). A spatially unbiased atlas template of the human cerebellum. NeuroImage, 33(1), 127–138.
Han, S., Carass, A., He, Y., & Prince, J. L. (2020). Automatic cerebellum anatomical parcellation using U-Net with locally constrained optimization. NeuroImage, 218, 116819.
King, M., Hernandez-Castillo, C. R., Poldrack, R. A., Ivry, R. B., & Diedrichsen, J. (2019). Functional boundaries in the human cerebellum revealed by a multi-domain task battery. Nature Neuroscience, 22(8), 1371–1378.
Pando-Naude, V., Toxto, S., Fernandez-Lozano, S., Parsons, C. E., Alcauter, S., & Garza-Villarreal, E. A. (2021). Gray and white matter morphology in substance use disorders: a neuroimaging systematic review and meta-analysis. Translational Psychiatry, 11(1), 29.
Zhang, P., Duan, L., Ou, Y., Ling, Q., Cao, L., Qian, H., Zhang, J., Wang, J., & Yuan, X. (2023). The cerebellum and cognitive neural networks. Frontiers in Human Neuroscience, 17, 1197459.