Abstract
Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I elevation. To test predictions, we examined restingstate functional MRI in 161 schizophrenia patients and 164 healthy subjects. As predicted, patients exhibited elevated functional connectivity that correlated with symptom levels, and was most prominent in association cortices, such as the fronto-parietal control network. This pattern was absent in patients with bipolar disorder (n = 73). To account for the pattern observed in schizophrenia, we integrated neurobiologically plausible, hierarchical differences in association vs. sensory recurrent neuronal dynamics into our model. This in silico architecture revealed preferential vulnerability of association networks to E/I imbalance, which we verified empirically. Reported effects implicate widespread microcircuit E/I imbalance as a parsimonious mechanism for emergent inhomogeneous dysconnectivity in schizophrenia.
| Original language | English (US) |
|---|---|
| Pages (from-to) | E219-E228 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 113 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 12 2016 |
| Externally published | Yes |
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Keywords
- Computational modeling
- Functional connectivity
- Schizophrenia
ASJC Scopus subject areas
- General
Cite this
Functional hierarchy underlies preferential connectivity disturbances in schizophrenia. / Yang, Genevieve J.; Murray, John D.; Wang, Xiao Jing; Glahn, David C.; Pearlson, Godfrey D.; Repovs, Grega; Krystal, John H.; Anticevic, Alan.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 2, 12.01.2016, p. E219-E228.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Functional hierarchy underlies preferential connectivity disturbances in schizophrenia
AU - Yang, Genevieve J.
AU - Murray, John D.
AU - Wang, Xiao Jing
AU - Glahn, David C.
AU - Pearlson, Godfrey D.
AU - Repovs, Grega
AU - Krystal, John H.
AU - Anticevic, Alan
PY - 2016/1/12
Y1 - 2016/1/12
N2 - Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I elevation. To test predictions, we examined restingstate functional MRI in 161 schizophrenia patients and 164 healthy subjects. As predicted, patients exhibited elevated functional connectivity that correlated with symptom levels, and was most prominent in association cortices, such as the fronto-parietal control network. This pattern was absent in patients with bipolar disorder (n = 73). To account for the pattern observed in schizophrenia, we integrated neurobiologically plausible, hierarchical differences in association vs. sensory recurrent neuronal dynamics into our model. This in silico architecture revealed preferential vulnerability of association networks to E/I imbalance, which we verified empirically. Reported effects implicate widespread microcircuit E/I imbalance as a parsimonious mechanism for emergent inhomogeneous dysconnectivity in schizophrenia.
AB - Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I elevation. To test predictions, we examined restingstate functional MRI in 161 schizophrenia patients and 164 healthy subjects. As predicted, patients exhibited elevated functional connectivity that correlated with symptom levels, and was most prominent in association cortices, such as the fronto-parietal control network. This pattern was absent in patients with bipolar disorder (n = 73). To account for the pattern observed in schizophrenia, we integrated neurobiologically plausible, hierarchical differences in association vs. sensory recurrent neuronal dynamics into our model. This in silico architecture revealed preferential vulnerability of association networks to E/I imbalance, which we verified empirically. Reported effects implicate widespread microcircuit E/I imbalance as a parsimonious mechanism for emergent inhomogeneous dysconnectivity in schizophrenia.
KW - Computational modeling
KW - Functional connectivity
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=84954348490&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84954348490&partnerID=8YFLogxK
U2 - 10.1073/pnas.1508436113
DO - 10.1073/pnas.1508436113
M3 - Article
C2 - 26699491
AN - SCOPUS:84954348490
VL - 113
SP - E219-E228
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 2
ER -