Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women
Stavros Trakoshis,
Pablo Martínez-Cañada,
Federico Rocchi,
Carola Canella,
Wonsang You,
Bhismadev Chakrabarti,
Amber NV Ruigrok,
Edward T Bullmore,
John Suckling,
Marija Markicevic,
Valerio Zerbi,
MRC AIMS Consortium,
Simon Baron-Cohen,
Alessandro Gozzi,
Meng-Chuan Lai,
Stefano Panzeri,
Michael V Lombardo
Affiliations
Stavros Trakoshis
Laboratory for Autism and Neurodevelopmental Disorders, Center for Neuroscience and Cognitive Systems @UniTn, Istituto Italiano di Tecnologia, Rovereto, Italy; Department of Psychology, University of Cyprus, Nicosia, Cyprus
Pablo Martínez-Cañada
Neural Computation Laboratory, Center for Neuroscience and Cognitive Systems @UniTn, Istituto Italiano di Tecnologia, Rovereto, Italy; Optical Approaches to Brain Function Laboratory, Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy
Federico Rocchi
Functional Neuroimaging Laboratory, Center for Neuroscience and Cognitive Systems @UniTn, Istituto Italiano di Tecnologia, Rovereto, Italy
Carola Canella
Functional Neuroimaging Laboratory, Center for Neuroscience and Cognitive Systems @UniTn, Istituto Italiano di Tecnologia, Rovereto, Italy
Wonsang You
Artificial Intelligence and Image Processing Laboratory, Department of Information and Communications Engineering, Sun Moon University, Asan, Republic of Korea
Bhismadev Chakrabarti
Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, Reading, United Kingdom
Amber NV Ruigrok
Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
Edward T Bullmore
Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge, United Kingdom; Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
John Suckling
Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
Marija Markicevic
Neural Control of Movement Lab, D-HEST, ETH Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland
Neural Control of Movement Lab, D-HEST, ETH Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland
MRC AIMS Consortium
Simon Baron-Cohen
Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge, United Kingdom
Functional Neuroimaging Laboratory, Center for Neuroscience and Cognitive Systems @UniTn, Istituto Italiano di Tecnologia, Rovereto, Italy
Meng-Chuan Lai
Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; The Margaret and Wallace McCain Centre for Child, Youth & Family Mental Health, Azrieli Adult Neurodevelopmental Centre, and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry and Autism Research Unit, The Hospital for Sick Children, Toronto, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Canada; Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Laboratory for Autism and Neurodevelopmental Disorders, Center for Neuroscience and Cognitive Systems @UniTn, Istituto Italiano di Tecnologia, Rovereto, Italy; Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in-silico modeling and in-vivo chemogenetic manipulations in mice, we first show that a time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social-communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently.