Habenula alterations in resting state functional connectivity among individuals with autism
Poster No:
302
Submission Type:
Abstract Submission
Authors:
Chloe Hampson1,2, Julio Peraza1, Lauren Guerrero1, Katherine Bottenhorn3, Michael Riedel1, Fahad Almuquin4, Donisha Smith5, Katherine Schmarder2,5, Erica Musser6, Yael Dai2,5, Rumi Agarwal2,7, Fahad Saeed4, Matthew Sutherland5, Angela Laird1,2
Institutions:
1Department of Physics, Florida International University, Miami, FL, 2FIU Embrace Center for Advancing Inclusive Communities, Florida International University, Miami, FL, 3Keck School of Medicine of USC, Los Angeles, CA, 4Knight Foundation School of Computing and Information Sciences, Florida International University, Miami, FL, 5Department of Psychology, Florida International University, Miami, FL, 6Department of Psychology, Barnard College, Columbia University, New York, NY, 7Department of Health Promotion and Disease Prevention, Florida International University, Miami, FL
First Author:
Chloe Hampson
Department of Physics, Florida International University|FIU Embrace Center for Advancing Inclusive Communities, Florida International University
Miami, FL|Miami, FL
Department of Physics, Florida International University|FIU Embrace Center for Advancing Inclusive Communities, Florida International University
Miami, FL|Miami, FL
Co-Author(s):
Fahad Almuquin
Knight Foundation School of Computing and Information Sciences, Florida International University
Miami, FL
Knight Foundation School of Computing and Information Sciences, Florida International University
Miami, FL
Katherine Schmarder
FIU Embrace Center for Advancing Inclusive Communities, Florida International University|Department of Psychology, Florida International University
Miami, FL|Miami, FL
FIU Embrace Center for Advancing Inclusive Communities, Florida International University|Department of Psychology, Florida International University
Miami, FL|Miami, FL
Yael Dai
FIU Embrace Center for Advancing Inclusive Communities, Florida International University|Department of Psychology, Florida International University
Miami, FL|Miami, FL
FIU Embrace Center for Advancing Inclusive Communities, Florida International University|Department of Psychology, Florida International University
Miami, FL|Miami, FL
Rumi Agarwal
FIU Embrace Center for Advancing Inclusive Communities, Florida International University|Department of Health Promotion and Disease Prevention, Florida International University
Miami, FL|Miami, FL
FIU Embrace Center for Advancing Inclusive Communities, Florida International University|Department of Health Promotion and Disease Prevention, Florida International University
Miami, FL|Miami, FL
Fahad Saeed
Knight Foundation School of Computing and Information Sciences, Florida International University
Miami, FL
Knight Foundation School of Computing and Information Sciences, Florida International University
Miami, FL
Angela Laird
Department of Physics, Florida International University|FIU Embrace Center for Advancing Inclusive Communities, Florida International University
Miami, FL|Miami, FL
Department of Physics, Florida International University|FIU Embrace Center for Advancing Inclusive Communities, Florida International University
Miami, FL|Miami, FL
Introduction:
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social interaction and communication difficulties, as well as restrictive and/or repetitive behaviors or interests (RRBI) (American Psychiatric Association, 2022). Given a behavioral emphasis on social function, studies have aimed to elucidate the underlying neurobiological mechanisms of ASD in areas of the "social brain" (Sato & Uono, 2019). However, to better capture the wide range of ASD behavioral manifestations, a reward-based framework emerged that is centered more broadly around constructs related to motivation and affect that link social deficits and RRBI observed in ASD (Tschida & Yerys, 2021). This framework is supported by robust evidence of altered cortico-striatal circuitry involved in reward processing (Soghomonian, 2024) across development (Evans et al., 2024). Evidence has shown that striatal dopaminergic activity is modulated by the habenula (Hb), a small epithalamic structure that plays a crucial role in motivation and emotion (Ables et al., 2023). While the Hb has been found to be structurally enlarged in ASD (Germann et al., 2021), its potential functional disruptions remain unexplored. Addressing this gap in the ASD literature, we accessed resting state fMRI data from the large-scale, multi-site Autism Brain Imaging Data Exchange (ABIDE) repository to explore Hb functional connectivity (FC) alterations underlying ASD.
Methods:
We conducted a whole-brain resting-state FC analysis with 1,586 participants (N=703 ASD; mean age: 13.88±8.15 years). Neuroimaging data were preprocessed in fMRIPrep with quality control using MRIQC. The Hb ROI was manually delineated on the MNI 152 T1 template, and participant-level FC analyses were performed in AFNI. Averaged ROI voxelwise time series were entered into a GLM to generate Z-transformed correlation maps. Group-level regression models included diagnosis (ASD, NT) as a categorical factor and age as a continuous factor, controlling for sex and scanning site. Thresholded group-averaged (ASD+NT) and group-difference (ASD>NT) z-maps were generated and underwent functional decoding. Additional regression analyses examined age-effects and brain-behavior interactions, with beta coefficients entered into a linear regression model and corrected for multiple comparisons.
Results:
Group-averaged maps identified Hb FC with an extensive network of regions, including the thalamus and bilateral middle frontal gyri, which decoding suggests are related to fear, reward, and emotion processing. Group-difference maps (Fig. 1, A-B) included significantly increased Hb connectivity in ASD with the right middle temporal gyrus and the bilateral superior temporal gyri, which decoding revealed are associated with speech and language (Fig. 1, C). Regression analyses demonstrated age effects with the left culmen and left parahippocampus, which were associated with reward and negative outcomes (Fig. 2). A brain-behavior effect was found with daily living skills, executive functioning, and social motivation (but not social communication), with only social motivation surviving correction for multiple comparisons.
Conclusions:
Group-averaged results showed Hb FC with the dopaminergic reward system, in agreement with prior work (Ely et al., 2019; Torrisi et al., 2017). Group-difference results identified atypical Hb hyperconnectivity in ASD within the primary and associative auditory cortices. Age-related effects showed alterations in the anterior cerebellum that have been hypothesized to be a key component of ASD (Wang et al., 2014). Brain-behavior effects were identified with phenotypes linked to adaptive behavior, a domain in which ASD individuals showed marked impairments. These results provide new insight into a potential underlying neurobiological mechanism of ASD that links alterations in reward-based circuitry to known deficits in sensory processing and adaptive behavior.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Emotion, Motivation and Social Neuroscience:
Emotion and Motivation Other
Modeling and Analysis Methods:
Task-Independent and Resting-State Analysis 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Subcortical Structures
Novel Imaging Acquisition Methods:
BOLD fMRI
Keywords:
Autism
Development
FUNCTIONAL MRI
Open Data
Social Interactions
Sub-Cortical
Other - Reward; Habenula; Resting-State fMRI
1|2Indicates the priority used for review
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Provide references using APA citation style.
American Psychiatric Association. (2022). Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR). American Psychiatric Association Publishing. https://doi.org/10.1176/appi.books.9780890425787
Ely, B. A., Stern, E. R., Kim, J.-W., Gabbay, V., & Xu, J. (2019). Detailed mapping of human habenula resting-state functional connectivity. NeuroImage, 200, 621–634. https://doi.org/10.1016/j.neuroimage.2019.06.015
Evans, M. M., Kim, J., Abel, T., Nickl-Jockschat, T., & Stevens, H. E. (2024). Developmental Disruptions of the Dorsal Striatum in Autism Spectrum Disorder. Biological Psychiatry, 95(2), 102–111. https://doi.org/10.1016/j.biopsych.2023.08.015
Germann, J., Gouveia, F. V., Brentani, H., Bedford, S. A., Tullo, S., Chakravarty, M. M., & Devenyi, G. A. (2021). Involvement of the habenula in the pathophysiology of autism spectrum disorder. Scientific Reports, 11(1), 21168. https://doi.org/10.1038/s41598-021-00603-0
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Torrisi, S., Nord, C. L., Balderston, N. L., Roiser, J. P., Grillon, C., & Ernst, M. (2017). Resting state connectivity of the human habenula at ultra-high field. NeuroImage, 147, 872–879. https://doi.org/10.1016/j.neuroimage.2016.10.034
Tschida, J. E., & Yerys, B. E. (2021). A Systematic Review of the Positive Valence System in Autism Spectrum Disorder. Neuropsychology Review, 31(1), 58–88. https://doi.org/10.1007/s11065-020-09459-z
Wang, S. S.-H., Kloth, A. D., & Badura, A. (2014). The Cerebellum, Sensitive Periods, and Autism. Neuron, 83(3), 518–532. https://doi.org/10.1016/j.neuron.2014.07.016