Age-related effects on the association between alcohol use severity and resting-state fMRI

423 

Abstract Submission 

Karis Colyer-Patel¹, Maik Derksen², Gabry Mies³, Steven Scholte³, Ingo Willuhn², Heidi Lesscher⁴, Janna Cousijn¹

¹Department of Psychology, Education & Child Studies, Erasmus University Rotterdam, Rotterdam, Netherlands, ²Department of Psychiatry, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands, ³Department of Psychology, University of Amsterdam, Amsterdam, Netherlands, ⁴Department of Population Health Sciences, Unit Animals in Science and Society, Utrecht University, Utrecht, Netherlands

Karis Colyer-Patel  
Department of Psychology, Education & Child Studies, Erasmus University Rotterdam
Rotterdam, Netherlands

Maik Derksen  
Department of Psychiatry, Amsterdam University Medical Centers, University of Amsterdam
Amsterdam, Netherlands

Gabry Mies  
Department of Psychology, University of Amsterdam
Amsterdam, Netherlands

Steven Scholte  
Department of Psychology, University of Amsterdam
Amsterdam, Netherlands

Ingo Willuhn  
Department of Psychiatry, Amsterdam University Medical Centers, University of Amsterdam
Amsterdam, Netherlands

Heidi Lesscher  
Department of Population Health Sciences, Unit Animals in Science and Society, Utrecht University
Utrecht, Netherlands

Janna Cousijn  
Department of Psychology, Education & Child Studies, Erasmus University Rotterdam
Rotterdam, Netherlands

Adolescence marks a period of neurodevelopmental and cognitive change, encompassing normative increases in reward sensitivity and risk-taking behaviour, alongside challenges in behavioural control. This is suggested to increase the risk of the initiation of alcohol use as well as later dependence [1,2]. One explanation for this increased risk, is suggested to be due to the impact of alcohol on neurodevelopment, particularly on the maturation of brain networks during this timeframe. There is currently limited evidence directly testing the differential impact of alcohol use during adolescence versus adulthood, as well as exploring the effects of low versus heavy alcohol consumption. The purpose of the present study was to investigate age-related differences on the association between resting-state functional connectivity (RSFC) and alcohol use severity in a sample of rodents that initiated low or heavy alcohol use during adolescence or adulthood.

Lister hooded rats were allowed to consume alcohol according to an intermittent alcohol access schedule across a two-month period starting from postnatal day 42 (adolescent-onset) or postnatal day 77 (adult-onset). In total 42 rats were selected: adolescent-onset low (N = 12) and high drinking (N= 7) rats, and adult-onset low (N = 11) and high drinking (N = 12) rats. Rats were anaesthetized with 2.0-3.0% isoflurane induction and isoflurane was continuously delivered. Once positioned, a bolus injection of 0.020 mg/kg dexmedetomidine was administered, followed with a maintenance dose of 0.040 mg/kg/h. Importantly, this allowed the rats to remain conscious during the MRI scans. Resting-state fMRI was measured at a resolution of 6002 × 20 slices with a FOV of 32.4, slice thickness of 1.0mm, and voxel size of 3 x 10 x 3mm. The preprocessing of fMRI images was conducted using RABIES software [3] which included highpass filtering (0.01Hz), and spatial Gaussian smoothing filtering (0.3mm FWHM). As part of the RABIES pipeline, the timeseries of all scans were concatenated to compute a group-ICA decomposition. Dual regression was performed using FSL to model the individualised connectivity of brain networks first identified through group-ICA. Permutation tests (N =5000) using FSL randomise were conducted with threshold-free cluster enhancement and family-wise error correction (=.05), to test for main effects of age of onset of alcohol use, severity of use, and interactive effects.

There was significantly higher RSFC in regions of the sensorimotor network (SMN), namely the globus pallidus, in high alcohol drinking rats compared to low alcohol drinking rats. Additionally, there was higher RSFC in the caudoputamen and motor area of the SMN, as well as the salience network (SN), of low alcohol drinking rats compared to high alcohol drinking rats. No significant differences in RSFC were found between adolescent and adult-onset rats. There were significant interactions effects; adult-onset high drinking rats compared to adolescent-onset high drinking rats showed higher RSFC in the SMN. Whereas adolescent-onset high drinking rats compared to adult-onset high drinking rats showed higher RSFC in the SN. No differences were found when comparing adolescent-onset low drinking to adult-onset low drinking rats and vice versa.

As expected, heavy alcohol use was found to be associated with higher RSFC in the SMN, a network associated with habitual formation. However, contrary to expectations, higher RSFC was found in the SN of low alcohol drinking rats. The higher RSFC in the SN of adolescent-onset high drinking rats likely reflects heightened reward sensitivity in adolescents compared to adults. And the higher RSFC in the SMN of high drinking adult rats likely reflects the shift to habitual responding in adults compared to adolescents. These findings highlight the importance of considering age when investigating processes associated with the development and maintenance of Alcohol Use Disorder.

Neurodevelopmental/ Early Life (eg. ADHD, autism) ¹

Executive Function, Cognitive Control and Decision Making

Connectivity (eg. functional, effective, structural)

Task-Independent and Resting-State Analysis ²

Addictions

ANIMAL STUDIES

Cognition

Design and Analysis

Development

fMRI CONTRAST MECHANISMS

Limbic Systems

MRI