Individual-specific functional connectivity of the amygdala: A substrate for precision psychiatry

Chad M. Sylvester; Qiongru Yu; A. Benjamin Srivastava; Scott Marek; Annie Zheng; Dimitrios Alexopoulos; Christopher D. Smyser; Joshua S. Shimony; Mario Ortega; Donna L. Dierker; Gaurav H. Patel; Steven M. Nelson; Adrian W. Gilmore; Kathleen B. McDermott; Jeffrey J. Berg; Andrew T. Drysdale; Michael T. Perino; Abraham Z. Snyder; Ryan V. Raut; Timothy O. Laumann; Evan M. Gordon; Deanna M. Barch; Cynthia E. Rogers; Deanna J. Greene; Marcus E. Raichle; Nico U.F. Dosenbach

doi:10.1073/pnas.1910842117

Individual-specific functional connectivity of the amygdala: A substrate for precision psychiatry

Chad M. Sylvester, Qiongru Yu, A. Benjamin Srivastava, Scott Marek, Annie Zheng, Dimitrios Alexopoulos, Christopher D. Smyser, Joshua S. Shimony, Mario Ortega, Donna L. Dierker, Gaurav H. Patel, Steven M. Nelson, Adrian W. Gilmore, Kathleen B. McDermott, Jeffrey J. Berg, Andrew T. Drysdale, Michael T. Perino, Abraham Z. Snyder, Ryan V. Raut, Timothy O. LaumannEvan M. Gordon, Deanna M. Barch, Cynthia E. Rogers, Deanna J. Greene, Marcus E. Raichle, Nico U.F. Dosenbach

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

76 Scopus citations

Abstract

The amygdala is central to the pathophysiology of many psychiatric illnesses. An imprecise understanding of how the amygdala fits into the larger network organization of the human brain, however, limits our ability to create models of dysfunction in individual patients to guide personalized treatment. Therefore, we investigated the position of the amygdala and its functional subdivisions within the network organization of the brain in 10 highly sampled individuals (5 h of fMRI data per person). We characterized three functional subdivisions within the amygdala of each individual. We discovered that one subdivision is preferentially correlated with the default mode network; a second is preferentially correlated with the dorsal attention and fronto-parietal networks; and third subdivision does not have any networks to which it is preferentially correlated relative to the other two subdivisions. All three subdivisions are positively correlated with ventral attention and somatomotor networks and negatively correlated with salience and cingulo-opercular networks. These observations were replicated in an independent group dataset of 120 individuals. We also found substantial across-subject variation in the distribution and magnitude of amygdala functional connectivity with the cerebral cortex that related to individual differences in the stereotactic locations both of amygdala subdivisions and of cortical functional brain networks. Finally, using lag analyses, we found consistent temporal ordering of fMRI signals in the cortex relative to amygdala subdivisions. Altogether, this work provides a detailed framework of amygdala–cortical interactions that can be used as a foundation for models relating aberrations in amygdala connectivity to psychiatric symptoms in individual patients.

Original language	English (US)
Pages (from-to)	3808-3818
Number of pages	11
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	117
Issue number	7
DOIs	https://doi.org/10.1073/pnas.1910842117
State	Published - Feb 18 2020
Externally published	Yes

Bibliographical note

Funding Information:
We thank Joel Price for assistance in interpreting data and Michael Myers for assistance in data analysis. This research was supported by National Institute of Health Grants K23 MH109983 (to C.M.S.), T32 DA 007294-26 (to A.B.S.), K02 NS089852 (to C.D.S.), R01 MH113570 (to C.D.S. and C.E.R.), R01 MH113883 (to C.D.S.), U54 HD087011 (to C.D.S., J.S.S., C.E.R., and D.A.), K23 MH105179 (to C.E.R.), NS088590 (to N.U.F.D.), T32 MH100019 (M.T.P. and S.M.), K23 MH108711 (to G.H.P.), T32 MH018870 (to G.H.P.), K01 MH104592 (to D.J.G.), R01 MH090786 (to D.M.B.), R25 MH112473 (to T.O.L. and A.T.D.), P30 NS098577 (to A.Z.S.); the McDonnell Center for Systems Neuroscience (C.M.S. and N.U.F.D.); the Taylor Family Institute (C.M.S.); the Parker Fund (C.M.S.); Career Development Award #1IK2CX001680 (to E.M.G.) from the US Department of Veterans Affairs Clinical Sciences Research and Development Service; the American Psychological Association Dissertation Research Award (to A.W.G.); the Jacobs Foundation Grant 2016121703 (to N.U.F.D.); the Child Neurology Foundation (N.U.F.D.); the Mallinckrodt Institute of Radiology Grant 1140911 (to N.U.F.D.); the Hope Center for Neurological Disorders (N.U.F.D.); the Brain and Behavior Research Foundation (C.M.S. and G.H.P.); the American Psychiatric Association (G.H.P.); the Sidney R. Baer Foundation (G.H.P.); the Leon Levy Foundation (G.H.P.); and National Science Foundation Grants DGE-1745038 (to R.V.R.) and DGE-1143954 (to A.W.G.). The contents of this manuscript do not represent the views of the US Department of Veterans Affairs of the United States Government.

Funding Information:
ACKNOWLEDGMENTS. We thank Joel Price for assistance in interpreting data and Michael Myers for assistance in data analysis. This research was supported by National Institute of Health Grants K23 MH109983 (to C.M.S.), T32 DA 007294-26 (to A.B.S.), K02 NS089852 (to C.D.S.), R01 MH113570 (to C.D.S. and C.E.R.), R01 MH113883 (to C.D.S.), U54 HD087011 (to C.D.S., J.S.S., C.E.R., and D.A.), K23 MH105179 (to C.E.R.), NS088590 (to N.U.F.D.), T32 MH100019 (M.T.P. and S.M.), K23 MH108711 (to G.H.P.), T32 MH018870 (to G.H.P.), K01 MH104592 (to D.J.G.), R01 MH090786 (to D.M.B.), R25 MH112473 (to T.O.L. and A.T.D.), P30 NS098577 (to A.Z.S.); the McDonnell Center for Systems Neuroscience (C.M.S. and N.U.F.D.); the Taylor Family Institute (C.M.S.); the Parker Fund (C.M.S.); Career Development Award #1IK2CX001680 (to E.M.G.) from the US Department of Veterans Affairs Clinical Sciences Research and Development Service; the American Psychological Association Dissertation Research Award (to A.W.G.); the Jacobs Foundation Grant 2016121703 (to N.U.F.D.); the Child Neurology Foundation (N.U.F.D.); the Mallinckrodt Institute of Radiology Grant 1140911 (to N.U.F.D.); the Hope Center for Neurological Disorders (N.U.F.D.); the Brain and Behavior Research Foundation (C.M.S. and G.H.P.); the American Psychiatric Association (G.H.P.); the Sidney R. Baer Foundation (G.H.P.); the Leon Levy Foundation (G.H.P.); and National Science Foundation Grants DGE-1745038 (to R.V.R.) and DGE-1143954 (to A.W.G.). The contents of this manuscript do not represent the views of the US Department of Veterans Affairs of the United States Government.

Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.

Keywords

Amygdala
FMRI
Functional connectivity

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10.1073/pnas.1910842117

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Sylvester, C. M., Yu, Q., Benjamin Srivastava, A., Marek, S., Zheng, A., Alexopoulos, D., Smyser, C. D., Shimony, J. S., Ortega, M., Dierker, D. L., Patel, G. H., Nelson, S. M., Gilmore, A. W., McDermott, K. B., Berg, J. J., Drysdale, A. T., Perino, M. T., Snyder, A. Z., Raut, R. V., ... Dosenbach, N. U. F. (2020). Individual-specific functional connectivity of the amygdala: A substrate for precision psychiatry. Proceedings of the National Academy of Sciences of the United States of America, 117(7), 3808-3818. https://doi.org/10.1073/pnas.1910842117

Sylvester, CM, Yu, Q, Benjamin Srivastava, A, Marek, S, Zheng, A, Alexopoulos, D, Smyser, CD, Shimony, JS, Ortega, M, Dierker, DL, Patel, GH, Nelson, SM, Gilmore, AW, McDermott, KB, Berg, JJ, Drysdale, AT, Perino, MT, Snyder, AZ, Raut, RV, Laumann, TO, Gordon, EM, Barch, DM, Rogers, CE, Greene, DJ, Raichle, ME & Dosenbach, NUF 2020, 'Individual-specific functional connectivity of the amygdala: A substrate for precision psychiatry', Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 7, pp. 3808-3818. https://doi.org/10.1073/pnas.1910842117

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title = "Individual-specific functional connectivity of the amygdala: A substrate for precision psychiatry",

abstract = "The amygdala is central to the pathophysiology of many psychiatric illnesses. An imprecise understanding of how the amygdala fits into the larger network organization of the human brain, however, limits our ability to create models of dysfunction in individual patients to guide personalized treatment. Therefore, we investigated the position of the amygdala and its functional subdivisions within the network organization of the brain in 10 highly sampled individuals (5 h of fMRI data per person). We characterized three functional subdivisions within the amygdala of each individual. We discovered that one subdivision is preferentially correlated with the default mode network; a second is preferentially correlated with the dorsal attention and fronto-parietal networks; and third subdivision does not have any networks to which it is preferentially correlated relative to the other two subdivisions. All three subdivisions are positively correlated with ventral attention and somatomotor networks and negatively correlated with salience and cingulo-opercular networks. These observations were replicated in an independent group dataset of 120 individuals. We also found substantial across-subject variation in the distribution and magnitude of amygdala functional connectivity with the cerebral cortex that related to individual differences in the stereotactic locations both of amygdala subdivisions and of cortical functional brain networks. Finally, using lag analyses, we found consistent temporal ordering of fMRI signals in the cortex relative to amygdala subdivisions. Altogether, this work provides a detailed framework of amygdala–cortical interactions that can be used as a foundation for models relating aberrations in amygdala connectivity to psychiatric symptoms in individual patients.",

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author = "Sylvester, {Chad M.} and Qiongru Yu and {Benjamin Srivastava}, A. and Scott Marek and Annie Zheng and Dimitrios Alexopoulos and Smyser, {Christopher D.} and Shimony, {Joshua S.} and Mario Ortega and Dierker, {Donna L.} and Patel, {Gaurav H.} and Nelson, {Steven M.} and Gilmore, {Adrian W.} and McDermott, {Kathleen B.} and Berg, {Jeffrey J.} and Drysdale, {Andrew T.} and Perino, {Michael T.} and Snyder, {Abraham Z.} and Raut, {Ryan V.} and Laumann, {Timothy O.} and Gordon, {Evan M.} and Barch, {Deanna M.} and Rogers, {Cynthia E.} and Greene, {Deanna J.} and Raichle, {Marcus E.} and Dosenbach, {Nico U.F.}",

note = "Funding Information: We thank Joel Price for assistance in interpreting data and Michael Myers for assistance in data analysis. This research was supported by National Institute of Health Grants K23 MH109983 (to C.M.S.), T32 DA 007294-26 (to A.B.S.), K02 NS089852 (to C.D.S.), R01 MH113570 (to C.D.S. and C.E.R.), R01 MH113883 (to C.D.S.), U54 HD087011 (to C.D.S., J.S.S., C.E.R., and D.A.), K23 MH105179 (to C.E.R.), NS088590 (to N.U.F.D.), T32 MH100019 (M.T.P. and S.M.), K23 MH108711 (to G.H.P.), T32 MH018870 (to G.H.P.), K01 MH104592 (to D.J.G.), R01 MH090786 (to D.M.B.), R25 MH112473 (to T.O.L. and A.T.D.), P30 NS098577 (to A.Z.S.); the McDonnell Center for Systems Neuroscience (C.M.S. and N.U.F.D.); the Taylor Family Institute (C.M.S.); the Parker Fund (C.M.S.); Career Development Award #1IK2CX001680 (to E.M.G.) from the US Department of Veterans Affairs Clinical Sciences Research and Development Service; the American Psychological Association Dissertation Research Award (to A.W.G.); the Jacobs Foundation Grant 2016121703 (to N.U.F.D.); the Child Neurology Foundation (N.U.F.D.); the Mallinckrodt Institute of Radiology Grant 1140911 (to N.U.F.D.); the Hope Center for Neurological Disorders (N.U.F.D.); the Brain and Behavior Research Foundation (C.M.S. and G.H.P.); the American Psychiatric Association (G.H.P.); the Sidney R. Baer Foundation (G.H.P.); the Leon Levy Foundation (G.H.P.); and National Science Foundation Grants DGE-1745038 (to R.V.R.) and DGE-1143954 (to A.W.G.). The contents of this manuscript do not represent the views of the US Department of Veterans Affairs of the United States Government. Funding Information: ACKNOWLEDGMENTS. We thank Joel Price for assistance in interpreting data and Michael Myers for assistance in data analysis. This research was supported by National Institute of Health Grants K23 MH109983 (to C.M.S.), T32 DA 007294-26 (to A.B.S.), K02 NS089852 (to C.D.S.), R01 MH113570 (to C.D.S. and C.E.R.), R01 MH113883 (to C.D.S.), U54 HD087011 (to C.D.S., J.S.S., C.E.R., and D.A.), K23 MH105179 (to C.E.R.), NS088590 (to N.U.F.D.), T32 MH100019 (M.T.P. and S.M.), K23 MH108711 (to G.H.P.), T32 MH018870 (to G.H.P.), K01 MH104592 (to D.J.G.), R01 MH090786 (to D.M.B.), R25 MH112473 (to T.O.L. and A.T.D.), P30 NS098577 (to A.Z.S.); the McDonnell Center for Systems Neuroscience (C.M.S. and N.U.F.D.); the Taylor Family Institute (C.M.S.); the Parker Fund (C.M.S.); Career Development Award #1IK2CX001680 (to E.M.G.) from the US Department of Veterans Affairs Clinical Sciences Research and Development Service; the American Psychological Association Dissertation Research Award (to A.W.G.); the Jacobs Foundation Grant 2016121703 (to N.U.F.D.); the Child Neurology Foundation (N.U.F.D.); the Mallinckrodt Institute of Radiology Grant 1140911 (to N.U.F.D.); the Hope Center for Neurological Disorders (N.U.F.D.); the Brain and Behavior Research Foundation (C.M.S. and G.H.P.); the American Psychiatric Association (G.H.P.); the Sidney R. Baer Foundation (G.H.P.); the Leon Levy Foundation (G.H.P.); and National Science Foundation Grants DGE-1745038 (to R.V.R.) and DGE-1143954 (to A.W.G.). The contents of this manuscript do not represent the views of the US Department of Veterans Affairs of the United States Government. Publisher Copyright: {\textcopyright} 2020 National Academy of Sciences. All rights reserved.",

year = "2020",

month = feb,

day = "18",

doi = "10.1073/pnas.1910842117",

language = "English (US)",

volume = "117",

pages = "3808--3818",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "7",

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TY - JOUR

T1 - Individual-specific functional connectivity of the amygdala

T2 - A substrate for precision psychiatry

AU - Sylvester, Chad M.

AU - Yu, Qiongru

AU - Benjamin Srivastava, A.

AU - Marek, Scott

AU - Zheng, Annie

AU - Alexopoulos, Dimitrios

AU - Smyser, Christopher D.

AU - Shimony, Joshua S.

AU - Ortega, Mario

AU - Dierker, Donna L.

AU - Patel, Gaurav H.

AU - Nelson, Steven M.

AU - Gilmore, Adrian W.

AU - McDermott, Kathleen B.

AU - Berg, Jeffrey J.

AU - Drysdale, Andrew T.

AU - Perino, Michael T.

AU - Snyder, Abraham Z.

AU - Raut, Ryan V.

AU - Laumann, Timothy O.

AU - Gordon, Evan M.

AU - Barch, Deanna M.

AU - Rogers, Cynthia E.

AU - Greene, Deanna J.

AU - Raichle, Marcus E.

AU - Dosenbach, Nico U.F.

N1 - Funding Information: We thank Joel Price for assistance in interpreting data and Michael Myers for assistance in data analysis. This research was supported by National Institute of Health Grants K23 MH109983 (to C.M.S.), T32 DA 007294-26 (to A.B.S.), K02 NS089852 (to C.D.S.), R01 MH113570 (to C.D.S. and C.E.R.), R01 MH113883 (to C.D.S.), U54 HD087011 (to C.D.S., J.S.S., C.E.R., and D.A.), K23 MH105179 (to C.E.R.), NS088590 (to N.U.F.D.), T32 MH100019 (M.T.P. and S.M.), K23 MH108711 (to G.H.P.), T32 MH018870 (to G.H.P.), K01 MH104592 (to D.J.G.), R01 MH090786 (to D.M.B.), R25 MH112473 (to T.O.L. and A.T.D.), P30 NS098577 (to A.Z.S.); the McDonnell Center for Systems Neuroscience (C.M.S. and N.U.F.D.); the Taylor Family Institute (C.M.S.); the Parker Fund (C.M.S.); Career Development Award #1IK2CX001680 (to E.M.G.) from the US Department of Veterans Affairs Clinical Sciences Research and Development Service; the American Psychological Association Dissertation Research Award (to A.W.G.); the Jacobs Foundation Grant 2016121703 (to N.U.F.D.); the Child Neurology Foundation (N.U.F.D.); the Mallinckrodt Institute of Radiology Grant 1140911 (to N.U.F.D.); the Hope Center for Neurological Disorders (N.U.F.D.); the Brain and Behavior Research Foundation (C.M.S. and G.H.P.); the American Psychiatric Association (G.H.P.); the Sidney R. Baer Foundation (G.H.P.); the Leon Levy Foundation (G.H.P.); and National Science Foundation Grants DGE-1745038 (to R.V.R.) and DGE-1143954 (to A.W.G.). The contents of this manuscript do not represent the views of the US Department of Veterans Affairs of the United States Government. Funding Information: ACKNOWLEDGMENTS. We thank Joel Price for assistance in interpreting data and Michael Myers for assistance in data analysis. This research was supported by National Institute of Health Grants K23 MH109983 (to C.M.S.), T32 DA 007294-26 (to A.B.S.), K02 NS089852 (to C.D.S.), R01 MH113570 (to C.D.S. and C.E.R.), R01 MH113883 (to C.D.S.), U54 HD087011 (to C.D.S., J.S.S., C.E.R., and D.A.), K23 MH105179 (to C.E.R.), NS088590 (to N.U.F.D.), T32 MH100019 (M.T.P. and S.M.), K23 MH108711 (to G.H.P.), T32 MH018870 (to G.H.P.), K01 MH104592 (to D.J.G.), R01 MH090786 (to D.M.B.), R25 MH112473 (to T.O.L. and A.T.D.), P30 NS098577 (to A.Z.S.); the McDonnell Center for Systems Neuroscience (C.M.S. and N.U.F.D.); the Taylor Family Institute (C.M.S.); the Parker Fund (C.M.S.); Career Development Award #1IK2CX001680 (to E.M.G.) from the US Department of Veterans Affairs Clinical Sciences Research and Development Service; the American Psychological Association Dissertation Research Award (to A.W.G.); the Jacobs Foundation Grant 2016121703 (to N.U.F.D.); the Child Neurology Foundation (N.U.F.D.); the Mallinckrodt Institute of Radiology Grant 1140911 (to N.U.F.D.); the Hope Center for Neurological Disorders (N.U.F.D.); the Brain and Behavior Research Foundation (C.M.S. and G.H.P.); the American Psychiatric Association (G.H.P.); the Sidney R. Baer Foundation (G.H.P.); the Leon Levy Foundation (G.H.P.); and National Science Foundation Grants DGE-1745038 (to R.V.R.) and DGE-1143954 (to A.W.G.). The contents of this manuscript do not represent the views of the US Department of Veterans Affairs of the United States Government. Publisher Copyright: © 2020 National Academy of Sciences. All rights reserved.

PY - 2020/2/18

Y1 - 2020/2/18

N2 - The amygdala is central to the pathophysiology of many psychiatric illnesses. An imprecise understanding of how the amygdala fits into the larger network organization of the human brain, however, limits our ability to create models of dysfunction in individual patients to guide personalized treatment. Therefore, we investigated the position of the amygdala and its functional subdivisions within the network organization of the brain in 10 highly sampled individuals (5 h of fMRI data per person). We characterized three functional subdivisions within the amygdala of each individual. We discovered that one subdivision is preferentially correlated with the default mode network; a second is preferentially correlated with the dorsal attention and fronto-parietal networks; and third subdivision does not have any networks to which it is preferentially correlated relative to the other two subdivisions. All three subdivisions are positively correlated with ventral attention and somatomotor networks and negatively correlated with salience and cingulo-opercular networks. These observations were replicated in an independent group dataset of 120 individuals. We also found substantial across-subject variation in the distribution and magnitude of amygdala functional connectivity with the cerebral cortex that related to individual differences in the stereotactic locations both of amygdala subdivisions and of cortical functional brain networks. Finally, using lag analyses, we found consistent temporal ordering of fMRI signals in the cortex relative to amygdala subdivisions. Altogether, this work provides a detailed framework of amygdala–cortical interactions that can be used as a foundation for models relating aberrations in amygdala connectivity to psychiatric symptoms in individual patients.

AB - The amygdala is central to the pathophysiology of many psychiatric illnesses. An imprecise understanding of how the amygdala fits into the larger network organization of the human brain, however, limits our ability to create models of dysfunction in individual patients to guide personalized treatment. Therefore, we investigated the position of the amygdala and its functional subdivisions within the network organization of the brain in 10 highly sampled individuals (5 h of fMRI data per person). We characterized three functional subdivisions within the amygdala of each individual. We discovered that one subdivision is preferentially correlated with the default mode network; a second is preferentially correlated with the dorsal attention and fronto-parietal networks; and third subdivision does not have any networks to which it is preferentially correlated relative to the other two subdivisions. All three subdivisions are positively correlated with ventral attention and somatomotor networks and negatively correlated with salience and cingulo-opercular networks. These observations were replicated in an independent group dataset of 120 individuals. We also found substantial across-subject variation in the distribution and magnitude of amygdala functional connectivity with the cerebral cortex that related to individual differences in the stereotactic locations both of amygdala subdivisions and of cortical functional brain networks. Finally, using lag analyses, we found consistent temporal ordering of fMRI signals in the cortex relative to amygdala subdivisions. Altogether, this work provides a detailed framework of amygdala–cortical interactions that can be used as a foundation for models relating aberrations in amygdala connectivity to psychiatric symptoms in individual patients.

KW - Amygdala

KW - FMRI

KW - Functional connectivity

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U2 - 10.1073/pnas.1910842117

DO - 10.1073/pnas.1910842117

M3 - Article

C2 - 32015137

AN - SCOPUS:85079559070

SN - 0027-8424

VL - 117

SP - 3808

EP - 3818

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

IS - 7

ER -

Individual-specific functional connectivity of the amygdala: A substrate for precision psychiatry

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