Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women
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Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women. / MRC AIMS Consortium.
In: ELIFE, Vol. 9, e55684, 04.08.2020.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -