Summary: Researchers report that temporarily turning off an area of the brain changes patterns of activity across much of the remaining brain.
Source: UC Davis.
Minimally invasive method allows researchers to better understand brain networks in rhesus monkeys.
Capitalizing on experimental genetic techniques, researchers at the California National Primate Research Center, or CNPRC, at the University of California, Davis, have demonstrated that temporarily turning off an area of the brain changes patterns of activity across much of the remaining brain.
The research suggests that alterations in the functional connectivity of the brain in humans may be used to determine the sites of pathology in complex disorders such as schizophrenia and autism.
The research is published online July 20 in the journal Neuron.
The research, led by David Amaral, distinguished professor in the Department of Psychiatry and Behavioral Sciences, and spearheaded by graduate student David Grayson, targeted the amygdala — a small, almond-shaped region deep within brain. The amygdala is known to be important for emotions, especially fear.
Using a technology called “designer receptors exclusively activated by designer drugs,” or DREADDs, the team genetically modified the neurons of the amygdala to produce molecular on-off switches, or receptors, that are triggered by a drug administered to the animal. When the drug is injected, the receptors shut down activity in the amygdala — effectively turning off this brain region.
Amaral and his colleagues then evaluated the activity in the rest of the brain using functional magnetic resonance imaging, or fMRI, when the amygdala was either on or turned off. FMRI allows researchers to measure what is called functional connectivity — the extent to which different brain regions coordinate their activity and form networks.
The team demonstrated that when the amygdala was turned off, patterns of brain activity in other brain regions either decreased or increased. Areas known to be well-connected to the amygdala were particularly affected, but so were brain regions that have no known connections to the amygdala.
“This type of study, where a brain region is turned on and off while carrying out functional imaging, has never been done previously in a monkey,” said Amaral, who is also the director of research at the UC Davis MIND Institute. “This technology establishes a new era of behavioral neuroscience that reduces the number of animal subjects since each subject acts as its own control. We see very direct linkage between this research and our overarching interest in understanding the neural alterations associated with autism.”
John Morrison, director of the CNPRC, said the findings represent “groundbreaking research that has enormous clinical potential. Similar techniques in the future may control abnormal activity in disorders such as epilepsy and Parkinson’s disease. Understanding how brain areas form networks is critical for determining the origin of pathology and eventually developing effective interventions.”
Other study authors include Eliza Bliss-Moreau, Christopher J. Machado and Jeffrey Bennett, all of UC Davis; Kelly Shen of the Rotman Research Institute, Baycrest Centre, Toronto; and Kathleen A. Grant and Damien A. Fair, Oregon Health and Science University, Portland, Oregon.
Funding: Study funded by National Institutes of Health.
Source: Andy Fell – UC Davis
Image Source: This NeuroscienceNews.com image is credited to David Amaral/UC Davis.
Original Research: Abstract for “The Rhesus Monkey Connectome Predicts Disrupted Functional Networks Resulting from Pharmacogenetic Inactivation of the Amygdala” by David S. Grayson, Eliza Bliss-Moreau, Christopher J. Machado, Jeffrey Bennett, Kelly Shen, Kathleen A. Grant, Damien A. Fair, and David G. Amaral in Neuron. Published online July 20 2016 doi:10.1016/j.neuron.2016.06.005
The Rhesus Monkey Connectome Predicts Disrupted Functional Networks Resulting from Pharmacogenetic Inactivation of the Amygdala
•The amygdala was remotely inactivated using the DREADDs technique
•Coupled activity was disrupted throughout cortical networks involving the amygdala
•Altered global dynamics increased coupling between other topologically distant areas
•Simulated anatomical lesions are correlated with diverse network effects
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.
“The Rhesus Monkey Connectome Predicts Disrupted Functional Networks Resulting from Pharmacogenetic Inactivation of the Amygdala” by David S. Grayson, Eliza Bliss-Moreau, Christopher J. Machado, Jeffrey Bennett, Kelly Shen, Kathleen A. Grant, Damien A. Fair, and David G. Amaral in Neuron. Published online July 20 2016 doi:10.1016/j.neuron.2016.06.005