The Rhesus Monkey Connectome Predicts Disrupted Functional Networks Resulting from Pharmacogenetic Inactivation of the Amygdala

David S Grayson; Eliza Bliss-Moreau; Christopher J Machado; Jeffrey Bennett; Kelly Shen; Kathleen A Grant; Damien A Fair; David G Amaral

doi:10.1016/j.neuron.2016.06.005

The Rhesus Monkey Connectome Predicts Disrupted Functional Networks Resulting from Pharmacogenetic Inactivation of the Amygdala

Neuron. 2016 Jul 20;91(2):453-66. doi: 10.1016/j.neuron.2016.06.005.

Authors

David S Grayson¹, Eliza Bliss-Moreau², Christopher J Machado², Jeffrey Bennett³, Kelly Shen⁴, Kathleen A Grant⁵, Damien A Fair⁶, David G Amaral⁷

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, CA 95817, USA; The MIND Institute, University of California, Davis, Sacramento, CA 95817, USA; Center for Neuroscience, University of California, Davis, Davis, CA 95616, USA.
² Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, CA 95817, USA; California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA.
³ Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, CA 95817, USA; The MIND Institute, University of California, Davis, Sacramento, CA 95817, USA; California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA.
⁴ Rotman Research Institute, Baycrest Centre, Toronto, ON M6A 2E1, Canada.
⁵ Oregon National Primate Research Center, Beaverton, OR 97006, USA.
⁶ Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA; Department of Psychiatry, Oregon Health and Science University, Portland, OR 97239, USA; Advanced Imaging Research Center, Oregon Health and Science University, Portland, OR 97239, USA.
⁷ Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, CA 95817, USA; The MIND Institute, University of California, Davis, Sacramento, CA 95817, USA; Center for Neuroscience, University of California, Davis, Davis, CA 95616, USA; California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA. Electronic address: dgamaral@ucdavis.edu.

Abstract

Contemporary research suggests that the mammalian brain is a complex system, implying that damage to even a single functional area could have widespread consequences across the system. To test this hypothesis, we pharmacogenetically inactivated the rhesus monkey amygdala, a subcortical region with distributed and well-defined cortical connectivity. We then examined the impact of that perturbation on global network organization using resting-state functional connectivity MRI. Amygdala inactivation disrupted amygdalocortical communication and distributed corticocortical coupling across multiple functional brain systems. Altered coupling was explained using a graph-based analysis of experimentally established structural connectivity to simulate disconnection of the amygdala. Communication capacity via monosynaptic and polysynaptic pathways, in aggregate, largely accounted for the correlational structure of endogenous brain activity and many of the non-local changes that resulted from amygdala inactivation. These results highlight the structural basis of distributed neural activity and suggest a strategy for linking focal neuropathology to remote neurophysiological changes.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Amygdala / physiopathology*
Animals
Connectome / methods
Macaca mulatta
Magnetic Resonance Imaging / methods
Male
Models, Neurological*
Nerve Net / physiology
Nerve Net / physiopathology*
Neural Pathways / physiopathology*
Pharmacogenetics / methods

Abstract

Publication types

MeSH terms

Grants and funding