TY - JOUR
T1 - Effects of Altered Excitation-Inhibition Balance on Decision Making in a Cortical Circuit Model
AU - Lam, Norman H.
AU - Borduqui, Thiago
AU - Hallak, Jaime
AU - Roque, Antonio
AU - Anticevic, Alan
AU - Krystal, John H.
AU - Wang, Xiao Jing
AU - Murray, John D.
N1 - Publisher Copyright:
© 2022 the authors
PY - 2022/2/9
Y1 - 2022/2/9
N2 - The synaptic balance between excitation and inhibition (E/I balance) is a fundamental principle of cortical circuits, and disruptions in E/I balance are commonly linked to cognitive deficits such as impaired decision-making. Explanatory gaps remain in a mechanistic understanding of how E/I balance contributes to cognitive computations, and how E/I disruptions at the synaptic level can propagate to induce behavioral deficits. Here, we studied how E/I perturbations may impair perceptual decision-making in a biophysically-based association cortical circuit model. We found that both elevating and lowering E/I ratio, via NMDA receptor (NMDAR) hypofunction at inhibitory interneurons and excitatory pyramidal neurons, respectively, can similarly impair psychometric performance, following an inverted-U dependence. Nonetheless, these E/I perturbations differentially alter the process of evidence accumulation across time. Under elevated E/I ratio, decision-making is impulsive, overweighting early evidence and underweighting late evidence. Under lowered E/I ratio, decision-making is indecisive, with both evidence integration and winner-take-all competition weakened. The distinct time courses of evidence accumulation at the circuit level can be measured at the behavioral level, using multiple psychophysical task paradigms which provide dissociable predictions. These results are well captured by a generalized drift-diffusion model (DDM) with self-coupling, implementing leaky or unstable integration, which thereby links biophysical circuit modeling to algorithmic process modeling and facilitates model fitting to behavioral choice data. In general, our findings characterize critical roles of cortical E/I balance in cognitive function, bridging from biophysical to behavioral levels of analysis.
AB - The synaptic balance between excitation and inhibition (E/I balance) is a fundamental principle of cortical circuits, and disruptions in E/I balance are commonly linked to cognitive deficits such as impaired decision-making. Explanatory gaps remain in a mechanistic understanding of how E/I balance contributes to cognitive computations, and how E/I disruptions at the synaptic level can propagate to induce behavioral deficits. Here, we studied how E/I perturbations may impair perceptual decision-making in a biophysically-based association cortical circuit model. We found that both elevating and lowering E/I ratio, via NMDA receptor (NMDAR) hypofunction at inhibitory interneurons and excitatory pyramidal neurons, respectively, can similarly impair psychometric performance, following an inverted-U dependence. Nonetheless, these E/I perturbations differentially alter the process of evidence accumulation across time. Under elevated E/I ratio, decision-making is impulsive, overweighting early evidence and underweighting late evidence. Under lowered E/I ratio, decision-making is indecisive, with both evidence integration and winner-take-all competition weakened. The distinct time courses of evidence accumulation at the circuit level can be measured at the behavioral level, using multiple psychophysical task paradigms which provide dissociable predictions. These results are well captured by a generalized drift-diffusion model (DDM) with self-coupling, implementing leaky or unstable integration, which thereby links biophysical circuit modeling to algorithmic process modeling and facilitates model fitting to behavioral choice data. In general, our findings characterize critical roles of cortical E/I balance in cognitive function, bridging from biophysical to behavioral levels of analysis.
KW - NMDAR hypofunction
KW - computational model
KW - decision making
KW - drift-diffusion model
KW - excitation-inhibition balance
KW - psychophysics
KW - Humans
KW - Animals
KW - Computer Simulation
KW - Decision Making/physiology
KW - Neural Pathways/physiology
KW - Cerebral Cortex/physiology
KW - Models, Neurological
UR - http://www.scopus.com/inward/record.url?scp=85124444730&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85124444730&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1371-20.2021
DO - 10.1523/JNEUROSCI.1371-20.2021
M3 - Article
C2 - 34887320
AN - SCOPUS:85124444730
SN - 0270-6474
VL - 42
SP - 1035
EP - 1053
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 6
ER -