An fMRI study on Long-Term Brain Function in Youth with a Previous Enterovirus-71 Infection.

1781 

Abstract Submission 

Jasmine I Ali-Gami¹, Susan Shur-Fen Gau², Jung-Chi Chang³, Wen-Yih Tseng⁴, Luan-Yin Chang³, Hsiang-Yuan Lin⁵

¹University of Toronto, Toronto, Ontario, ²National Taiwan University College of Medicine, Taipei, Taiwan, ³National Taiwan University Hospital, Taipei, Taiwan, ⁴Institute of Medical Device and Imaging, College of Medicine, National Taiwan University, Taipei, Taiwan, ⁵Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario

Jasmine Ali-Gami, BSc  
University of Toronto
Toronto, Ontario

Susan Shur-Fen Gau  
National Taiwan University College of Medicine
Taipei, Taiwan

Jung-Chi Chang  
National Taiwan University Hospital
Taipei, Taiwan

Wen-Yih Tseng  
Institute of Medical Device and Imaging, College of Medicine, National Taiwan University
Taipei, Taiwan

Luan-Yin Chang  
National Taiwan University Hospital
Taipei, Taiwan

Hsiang-Yuan Lin  
Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto
Toronto, Ontario

An Enterovirus (EV) infection, particularly the EV-71 strain, is a common pediatric infectious disease. EV-71 is known to cause illnesses ranging from a low-grade fever, and hand-foot-and-mouth disease, to a severe central nervous system (CNS) disease.⁵ With a global presence, this life-altering infection poses a serious public health threat across the Asia-Pacific region and beyond.⁶ Among the manifestations and sequelae, the long-term impact of an EV CNS infection remains a critical concern with neuropsychiatric sequelae.³^,2 Specifically, numerous studies have shown the correlation between an EV-71 CNS infection and the development of attention-deficit/hyperactivity disorder (ADHD) and associated emotional-behavioural problems later in life.^3,1 However, no published evidence has studied the longitudinal brain development in this unique population of youth who are at a three times greater risk of developing ADHD following an EV-71 CNS infection earlier in life (will be referred to as EVA, henceforth). Our research investigated the longitudinal brain features of youth with a pediatric EV-71 CNS infection earlier in life. Specifically, our research aimed to address the following questions: "Are there abnormalities in functional connectivity of the midbrain and striatum that would link to the increased risk of developing ADHD?", and "Are there functional network connectivity-based differences in youth who have had an enterovirus infection with later ADHD development in comparison to idiopathic ADHD and Control groups".

This cohort study included 31 youth with a previous EV-71 CNS infection 6-18 years ago. Sixteen of them developed ADHD later in life. Additionally, this study included 53 age- and sex-matched youth with idiopathic ADHD, and 37 matched neurotypical youth as the control groups. Our methods utilized multi-echo resting-state functional magnetic resonance imaging (rs-fMRI) to examine the functional connectivity in two approaches. For the first approach, we took on a seed-based analysis of dopamine-associated structures within the midbrain and striatal regions.⁴ Following, our second approach utilized a whole brain functional connectome-based statistical approach to examine any atypical findings in neural networks across the groups.

Compared to youth who had an EV-71 CNS infection and did not develop ADHD, the group that developed ADHD showed lower functional connectivity between the right substantia nigra pars compacta, right ventral tegmental area, the left dorsal caudate and the left calcarine. Additionally, our connectome analysis showed that in comparison to the idiopathic ADHD group, the EVA group showed reduced functional connectivity in the subcortical, salience and default mode networks. In comparison to the neurotypical developing group, EVA subjects showed greater functional connectivity in the default mode and salience networks.

This is the first study investigating longitudinal functional brain patterns following a severe EV-71 CNS infection. We found that generally, youth with Enterovirus-facilitated ADHD had a similar intrinsic functional connectivity pattern at cortical and striatal levels. Altered midbrain functional connectivity is unique in Enterovirus-facilitated ADHD. Our study suggests a possible avenue for future studies, being dopamine dysregulation within the midbrain and striatal regions contributing to ADHD symptomology, which may facilitate the development of targeted intervention and rehabilitation strategies to enhance the quality of life and reduce disabilities in infected youth.

fMRI Connectivity and Network Modeling ¹

Subcortical Structures

BOLD fMRI ²

Attention Deficit Disorder

Brainstem

FUNCTIONAL MRI

Infections

PEDIATRIC

Sub-Cortical