RT Journal Article
SR Electronic
T1 Behavioral flexibility is associated with changes in structure and function distributed across a frontal cortical network in macaques
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 603530
DO 10.1101/603530
A1 Jérôme Sallet
A1 MaryAnn P Noonan
A1 Adam Thomas
A1 Jill X O’Reilly
A1 Jesper Anderson
A1 Georgios K Papageorgiou
A1 Franz X Neubert
A1 Bashir Ahmed
A1 Jackson Smith
A1 Andrew H Bell
A1 Mark J Buckley
A1 Léa Roumazeilles
A1 Steven Cuell
A1 Mark E Walton
A1 Kristine Krug
A1 Rogier B Mars
A1 Matthew FS Rushworth
YR 2019
UL http://biorxiv.org/content/early/2019/04/10/603530.abstract
AB One of the most influential accounts of central orbitofrontal cortex– that it mediates behavioral flexibility – has been challenged by the finding that discrimination reversal in macaques –the classic test of behavioral flexibility –is unaffected when lesions are made by excitotoxin injection rather than aspiration. This suggests the critical brain circuit mediating behavioral flexibility in reversal tasks lies beyond the central orbitofrontal cortex. To determine its identity a group of nine macaques were taught discrimination reversal learning tasks and its impact on grey matter was measured. Magnetic resonance imaging scans were taken before and after learning and compared with scans from two control groups each comprising ten animals. One control group learned similar discrimination tasks but which lacked any reversal component and the other control group engaged in no learning. Grey matter changes were prominent in posterior orbitofrontal cortex/anterior insula but also were found in three other frontal cortical regions: lateral orbitofrontal cortex (12o), cingulate cortex, and lateral prefrontal cortex. In a second analysis, neural activity in posterior orbitofrontal cortex/anterior insula was measured at rest and its pattern of coupling with the other frontal cortical regions was assessed. Activity coupling increased significantly in the reversal learning group in comparison to controls. In a final set of experiments we used similar structural imaging procedures and analyses to demonstrate that aspiration lesion of central orbitofrontal cortex, of the type known to affect discrimination learning, affected structure and activity in the same frontal cortical circuit. The results identify a distributed frontal cortical circuit associated with behavioral flexibility.