A developmental reduction of the excitation:inhibition ratio in association cortex during adolescence

Bart Larsen; Zaixu Cui; Azeez Adebimpe; Adam Pines; Aaron Alexander-Bloch; Max Bertolero; Monica E. Calkins; Raquel E. Gur; Ruben C. Gur; Arun S. Mahadevan; Tyler M. Moore; David R. Roalf; Jakob Seidlitz; Valerie J. Sydnor; Daniel H. Wolf; Theodore D. Satterthwaite

doi:10.1126/sciadv.abj8750

A developmental reduction of the excitation:inhibition ratio in association cortex during adolescence

Bart Larsen
, Zaixu Cui
, Azeez Adebimpe
, Adam Pines
, Aaron Alexander-Bloch
, Max Bertolero
, Monica E. Calkins
, Raquel E. Gur
, Ruben C. Gur
, Arun S. Mahadevan
, Tyler M. Moore
, David R. Roalf
, Jakob Seidlitz
, Valerie J. Sydnor
, Daniel H. Wolf
, Theodore D. Satterthwaite

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

Adolescence is hypothesized to be a critical period for the development of association cortex. A reduction of the excitation:inhibition (E:I) ratio is a hallmark of critical period development; however, it has been unclear how to assess the development of the E:I ratio using noninvasive neuroimaging techniques. Here, we used pharmacological fMRI with a GABAergic benzodiazepine challenge to empirically generate a model of E:I ratio based on multivariate patterns of functional connectivity. In an independent sample of 879 youth (ages 8 to 22 years), this model predicted reductions in the E:I ratio during adolescence, which were specific to association cortex and related to psychopathology. These findings support hypothesized shifts in E:I balance of association cortices during a neurodevelopmental critical period in adolescence.

Original language	English (US)
Article number	eabj8750
Journal	Science Advances
Volume	8
Issue number	5
DOIs	https://doi.org/10.1126/sciadv.abj8750
State	Published - Feb 2022
Externally published	Yes

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Publisher Copyright:
© 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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10.1126/sciadv.abj8750

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Larsen, B., Cui, Z., Adebimpe, A., Pines, A., Alexander-Bloch, A., Bertolero, M., Calkins, M. E., Gur, R. E., Gur, R. C., Mahadevan, A. S., Moore, T. M., Roalf, D. R., Seidlitz, J., Sydnor, V. J., Wolf, D. H., & Satterthwaite, T. D. (2022). A developmental reduction of the excitation:inhibition ratio in association cortex during adolescence. Science Advances, 8(5), Article eabj8750. https://doi.org/10.1126/sciadv.abj8750

Larsen, B, Cui, Z, Adebimpe, A, Pines, A, Alexander-Bloch, A, Bertolero, M, Calkins, ME, Gur, RE, Gur, RC, Mahadevan, AS, Moore, TM, Roalf, DR, Seidlitz, J, Sydnor, VJ, Wolf, DH & Satterthwaite, TD 2022, 'A developmental reduction of the excitation:inhibition ratio in association cortex during adolescence', Science Advances, vol. 8, no. 5, eabj8750. https://doi.org/10.1126/sciadv.abj8750

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title = "A developmental reduction of the excitation:inhibition ratio in association cortex during adolescence",

abstract = "Adolescence is hypothesized to be a critical period for the development of association cortex. A reduction of the excitation:inhibition (E:I) ratio is a hallmark of critical period development; however, it has been unclear how to assess the development of the E:I ratio using noninvasive neuroimaging techniques. Here, we used pharmacological fMRI with a GABAergic benzodiazepine challenge to empirically generate a model of E:I ratio based on multivariate patterns of functional connectivity. In an independent sample of 879 youth (ages 8 to 22 years), this model predicted reductions in the E:I ratio during adolescence, which were specific to association cortex and related to psychopathology. These findings support hypothesized shifts in E:I balance of association cortices during a neurodevelopmental critical period in adolescence.",

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note = "Publisher Copyright: {\textcopyright} 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).",

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AU - Cui, Zaixu

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AU - Alexander-Bloch, Aaron

AU - Bertolero, Max

AU - Calkins, Monica E.

AU - Gur, Raquel E.

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AU - Roalf, David R.

AU - Seidlitz, Jakob

AU - Sydnor, Valerie J.

AU - Wolf, Daniel H.

AU - Satterthwaite, Theodore D.

N1 - Publisher Copyright: © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

PY - 2022/2

Y1 - 2022/2

N2 - Adolescence is hypothesized to be a critical period for the development of association cortex. A reduction of the excitation:inhibition (E:I) ratio is a hallmark of critical period development; however, it has been unclear how to assess the development of the E:I ratio using noninvasive neuroimaging techniques. Here, we used pharmacological fMRI with a GABAergic benzodiazepine challenge to empirically generate a model of E:I ratio based on multivariate patterns of functional connectivity. In an independent sample of 879 youth (ages 8 to 22 years), this model predicted reductions in the E:I ratio during adolescence, which were specific to association cortex and related to psychopathology. These findings support hypothesized shifts in E:I balance of association cortices during a neurodevelopmental critical period in adolescence.

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A developmental reduction of the excitation:inhibition ratio in association cortex during adolescence

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