Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

TY - JOUR

T1 - Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

AU - Trakoshis, Stavros

AU - Martínez-Cañada, Pablo

AU - Rocchi, Federico

AU - Canella, Carola

AU - You, Wonsang

AU - Chakrabarti, Bhismadev

AU - Ruigrok, Amber Nv

AU - Bullmore, Edward T

AU - Suckling, John

AU - Markicevic, Marija

AU - Zerbi, Valerio

AU - Baron-Cohen, Simon

AU - Gozzi, Alessandro

AU - Lai, Meng-Chuan

AU - Panzeri, Stefano

AU - Lombardo, Michael V

AU - MRC AIMS Consortium

N1 - © 2020, Trakoshis et al.

PY - 2020/8/4

Y1 - 2020/8/4

N2 - 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.

AB - 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.

KW - Adult

KW - Animals

KW - Autistic Disorder/physiopathology

KW - Communication

KW - England

KW - Female

KW - Humans

KW - Inhibition, Psychological

KW - Language

KW - Magnetic Resonance Imaging

KW - Male

KW - Mice

KW - Mice, Inbred C57BL/physiology

KW - Middle Aged

KW - Prefrontal Cortex/physiopathology

KW - Sex Factors

KW - Young Adult

U2 - 10.7554/eLife.55684

DO - 10.7554/eLife.55684

M3 - SCORING: Journal article

C2 - 32746967

VL - 9

JO - ELIFE

JF - ELIFE

SN - 2050-084X

M1 - e55684

ER -