Replicability of reduced inter-subject functional connectivity in autism during movie-watching fMRI

Presented During:

Thursday, June 26, 2025: 11:30 AM - 12:45 PM
Brisbane Convention & Exhibition Centre  
Room: M1 & M2 (Mezzanine Level)  

Poster No:

282 

Submission Type:

Abstract Submission 

Authors:

Feng Lin1, Laura Albantakis2,3, Tuomo Noppari4,5, Severi Santavirta5, Marie-Luise Brandi2, Lihua Sun5,6, Lasse Lukkarinen5, Pekka Tani4, Juha Salmi7, Lauri Nummenmaa5, Juergen Dukart1,8, Leonhard Schilbach2, Juha Lahnakoski1,2

Institutions:

1Institute of Neuroscience and Medicine, Brain & Behaviour (INM‐7), Research Center Jülich, Jülich, Germany, 2Independent Max Planck Research Group for Social Neuroscience, Max Planck Institute of Psychiatry, Munich, Germany, 3Department of Psychiatry and Psychotherapy, Ludwig Maximilians University, Munich, Germany, 4Department of Psychiatry, Helsinki University Hospital, Helsinki, Finland, 5Turku PET Centre, University of Turku, Turku, Finland, 6Huashan Institute of Medicine, Huashan Hospital, Fudan University, Shanghai, China, 7Department of Neuroscience and Biomedical Engineering, School of Science, Aalto University, Espoo, Finland, 8Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

First Author:

Feng Lin  
Institute of Neuroscience and Medicine, Brain & Behaviour (INM‐7), Research Center Jülich
Jülich, Germany

Co-Author(s):

Laura Albantakis  
Independent Max Planck Research Group for Social Neuroscience, Max Planck Institute of Psychiatry|Department of Psychiatry and Psychotherapy, Ludwig Maximilians University
Munich, Germany|Munich, Germany
Tuomo Noppari  
Department of Psychiatry, Helsinki University Hospital|Turku PET Centre, University of Turku
Helsinki, Finland|Turku, Finland
Severi Santavirta  
Turku PET Centre, University of Turku
Turku, Finland
Marie-Luise Brandi  
Independent Max Planck Research Group for Social Neuroscience, Max Planck Institute of Psychiatry
Munich, Germany
Lihua Sun  
Turku PET Centre, University of Turku|Huashan Institute of Medicine, Huashan Hospital, Fudan University
Turku, Finland|Shanghai, China
Lasse Lukkarinen  
Turku PET Centre, University of Turku
Turku, Finland
Pekka Tani  
Department of Psychiatry, Helsinki University Hospital
Helsinki, Finland
Juha Salmi  
Department of Neuroscience and Biomedical Engineering, School of Science, Aalto University
Espoo, Finland
Lauri Nummenmaa  
Turku PET Centre, University of Turku
Turku, Finland
Juergen Dukart  
Institute of Neuroscience and Medicine, Brain & Behaviour (INM‐7), Research Center Jülich|Institute of Systems Neuroscience, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf
Jülich, Germany|Düsseldorf, Germany
Leonhard Schilbach  
Independent Max Planck Research Group for Social Neuroscience, Max Planck Institute of Psychiatry
Munich, Germany
Juha Lahnakoski  
Institute of Neuroscience and Medicine, Brain & Behaviour (INM‐7), Research Center Jülich|Independent Max Planck Research Group for Social Neuroscience, Max Planck Institute of Psychiatry
Jülich, Germany|Munich, Germany

Introduction:

Autism is a neurodevelopmental condition characterized by impaired social communication and interaction, restricted interests, stereotyped behaviors, and altered sensory responses to external stimuli (American Psychiatric Association, 2013). Many autistic individuals without intellectual impairment perform well in controlled tasks, such as recognizing emotional facial expressions (Keating et al., 2023), but their performance often declines in naturalistic settings requiring implicit social processing (Van de Cruys et al., 2014). Functional magnetic resonance imaging (fMRI), during naturalistic stimuli, such as movies, has proven effective for examining social brain activity (Finn et al., 2020). Inter-subject functional connectivity (ISFC) measures the interregional connectivity across individuals, by separating the shared and stimulus-driven component of fMRI responses from intrinsic brain activity and noise (Simony et al., 2016). Previous findings suggest idiosyncratic inter-subject functional connectivity patterns in autistic individuals (Bolton et al., 2018), but the precise regional differences remain unclear and may vary across movie segments. Addressing the reproducibility crisis in neuroimaging (Kelly & Hoptman, 2022), cross-center experiment design can validate the generalizability of findings. This study aimed to investigate the difference of inter-subject functional connectivity between autistic individuals and neurotypical controls and to evaluate replication across datasets.

Methods:

We analyzed inter-subject functional connectivity differences between autistic individuals and neurotypical controls using 3T fMRI data from two independent datasets collected in Germany (autism group: n = 22, mean age = 35.72 ± 10.58 years, range = 20-53 years, 12 males; neurotypical group: n = 25, mean age = 32.76 ± 12.20 years, range = 18-60 years, 7 males, 18 females;) and Finland (autism group: n = 18, mean age = 26.83 ± 5.86 years, range = 20-40 years, all males; neurotypical group: n = 19, mean age = 28.52 ± 7.69 years, range = 20-47 years, all males). Participants in both datasets watched similar short clips of Hollywood movies (~11 minutes in duration, 52 movie clips for the German dataset, 54 clips for the Finnish dataset) depicting scenes from five categories: emotion, neutral, social interaction, non-interaction, and pain. To account for varying English proficiency among German participants, the audio was removed from the clips. In contrast, the Finnish dataset retained the soundtracks, as participants were sufficiently proficient in English to understand the movie dialogues. Pairwise inter-subject functional connectivity was computed across 273 brain regions. Group differences were assessed using subject-wise permutation tests for each dataset (see Chen et al., 2016). Detailed methods are illustrated in Figure 1.
Supporting Image: Figure1.png
 

Results:

In both datasets, the autistic group exhibited lower ISFCs compared to the neurotypical group, specifically between visual (e.g., occipital gyrus, cuneus) and parietal regions (e.g., superior and inferior parietal lobules), as well as between visual regions and frontal regions (e.g., inferior frontal lobe, precentral gyrus). However, the magnitude of group differences was smaller in the German dataset. The Finnish sample exhibited higher overall ISFCs, especially in temporal regions associated with sound and speech processing. Detailed results are in Figure 2.
Supporting Image: Figure2.png
 

Conclusions:

This study confirmed the replicability of reduced ISFCs in autistic individuals during naturalistic movie-watching, especially between visual and parietal/frontal brain regions. Additionally, hyperconnectivity in superior temporal regions was observed among the autistic group from Finland. These findings underscore atypical sensory and attentional processing of naturalistic stimuli in autistic individuals, reinforcing the utility of ISFC and naturalistic fMRI in revealing stimulus-driven neural connectivity alterations associated with autism.

Disorders of the Nervous System:

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

Emotion, Motivation and Social Neuroscience:

Social Cognition

Modeling and Analysis Methods:

Connectivity (eg. functional, effective, structural)
fMRI Connectivity and Network Modeling 2

Keywords:

Autism
Other - Inter-subject functional connectivity; Naturalistic movie-watching fMRI; Subject-wise permutation; Replicability of fMRI study

1|2Indicates the priority used for review

Abstract Information

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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

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Was this research conducted in the United States?

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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

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Please indicate which methods were used in your research:

Functional MRI

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

Other, Please list  -   fMRIPrep; Nilearn

Provide references using APA citation style.

1. American Psychiatric Association, D. S. M. T. F., & American Psychiatric Association, D. S. (2013). Diagnostic and statistical manual of mental disorders: DSM-5 (Vol. 5, No. 5). Washington, DC: American psychiatric association.
2. Bolton, T. A., Jochaut, D., Giraud, A. L., & Van De Ville, D. (2018). Brain dynamics in ASD during movie‐watching show idiosyncratic functional integration and segregation. Human brain mapping, 39(6), 2391-2404.
3. Chen, G., Shin, Y. W., Taylor, P. A., Glen, D. R., Reynolds, R. C., Israel, R. B., & Cox, R. W. (2016). Untangling the relatedness among correlations, part I: Nonparametric approaches to inter-subject correlation analysis at the group level. Neuroimage, 142, 248-259.
4. Finn, E. S., Glerean, E., Khojandi, A. Y., Nielson, D., Molfese, P. J., Handwerker, D. A., & Bandettini, P. A. (2020). Idiosynchrony: From shared responses to individual differences during naturalistic neuroimaging. Neuroimage, 215, 116828.
5. Kelly Jr, R. E., & Hoptman, M. J. (2022). Replicability in brain imaging. Brain Sciences, 12(3), 397.
6. Keating, C. T., Ichijo, E., & Cook, J. L. (2023). Autistic adults exhibit highly precise representations of others’ emotions but a reduced influence of emotion representations on emotion recognition accuracy. Scientific Reports, 13(1), 11875.
7. Van de Cruys, S., Evers, K., Van der Hallen, R., Van Eylen, L., Boets, B., De-Wit, L., & Wagemans, J. (2014). Precise minds in uncertain worlds: predictive coding in autism. Psychological review, 121(4), 649.
8. Simony, E., Honey, C. J., Chen, J., Lositsky, O., Yeshurun, Y., Wiesel, A., & Hasson, U. (2016). Dynamic reconfiguration of the default mode network during narrative comprehension. Nature communications, 7(1), 12141.

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