Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys

O’Reilly, Jill X.; Croxson, Paula L.; Jbabdi, Saâd; Sallet, Jérôme; Noonan, MaryAnn P.; Mars, Rogier B.; Browning, Philip J.; Wilson, Charles R.E.; Mitchell, Anna S.; Miller, Karla L.; Rushworth, Matthew F. S.; Baxter, Mark G.

doi:10.1073/pnas.1305062110

Cited by 209 publications

(189 citation statements)

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“…(iii) It ensures that judgments about similarities in the coupling patterns of frontal areas in humans and macaques are not influenced by interspecies differences in the way that target areas are interconnected with one another. However, it is important to remember that although it is the case that such coupling patterns reflect monosynaptic connections, they do not do so exclusively (15). In addition, a complementary analysis based on partial correlation is shown in SI Appendix, Fig.…”

Section: Methodsmentioning

confidence: 99%

“…We used fMRI in 25 monkeys and 38 humans to delineate the functional interactions of "decisionmaking regions" with other areas in the brain while subjects were at rest. Such interactions are reliant on anatomical connections between areas (15) and determine the information an area has access to and the way it can influence other areas, and thereby behavior. Each region of the brain has a defining set of interactions, a connectional or interactional "finger-print" (16), that can be compared across species (17)(18)(19).…”

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confidence: 99%

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Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex

Neubert

Mars

Sallet

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Reward-guided decision-making depends on a network of brain regions. Among these are the orbitofrontal and the anterior cingulate cortex. However, it is difficult to ascertain if these areas constitute anatomical and functional unities, and how these areas correspond between monkeys and humans. To address these questions we looked at connectivity profiles of these areas using resting-state functional MRI in 38 humans and 25 macaque monkeys. We sought brain regions in the macaque that resembled 10 human areas identified with decision making and brain regions in the human that resembled six macaque areas identified with decision making. We also used diffusion-weighted MRI to delineate key human orbital and medial frontal brain regions. We identified 21 different regions, many of which could be linked to particular aspects of reward-guided learning, valuation, and decision making, and in many cases we identified areas in the macaque with similar coupling profiles.orbitofrontal cortex | anterior cingulate cortex | decision making | resting state functional connectivity | comparative anatomy A s humans we make decisions by taking into account different types of information, weighing our options carefully, and eventually coming to a conclusion. We then learn from witnessing the outcome of our decisions. Human functional MRI (fMRI) has had a major impact on elucidating the neural networks mediating decision making and learning, but key insights can only be obtained in neural recording, stimulation, and focal lesion studies conducted in animal models, such as the macaque. Combining insights from human fMRI and animal studies is, however, not straightforward because there is uncertainty about basic issues, such as anatomical and functional correspondences between species (1). For example, although there are many reports of decision value-related activity in the human ventromedial prefrontal cortex (vmPFC) (2, 3), it is unclear whether they can be related to reports of reward-related activity either on the ventromedial surface of the frontal lobe (4, 5), in the adjacent medial orbitofrontal sulcus (6), or indeed to any macaque brain area. It is claimed that some areas implicated in rewardguided decision making and learning, such as parts of anterior cingulate cortex (ACC), are not found in macaques (7), but such theories have never been formally tested.In addition, there is uncertainty about the basic constituent components of decision-making and learning circuits. To return to the example of the vmPFC, although this region is often contrasted with similarly large subdivisions of the frontal cortex, such as the lateral orbitofrontal cortex (lOFC) and ACC (8), it is unclear whether, and if so how, it should be decomposed into further subdivisions. Moreover, there are sometimes fundamental disagreements about how brain areas contribute to decision making and learning. For example, it has been claimed both that the ACC does (9-11) and does not (12) contribute to reward-based decision making and that it is concerned with dist...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex

Neubert

Mars

Sallet

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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357

388

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“…Several factors may support this compensatory strategy, including (i) postlesion training or retraining and (ii) postlesion network reorganization (19)(20)(21). Thus, although lesion studies are useful in documenting altered function after injury, they cannot directly address the role of the hippocampus in the uninjured brain.…”

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confidence: 99%

Memory loss in a nonnavigational spatial task after hippocampal inactivation in monkeys

Forcelli

Palchik

Leath³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The hippocampus has a well-documented role for spatial navigation across species, but its role for spatial memory in nonnavigational tasks is uncertain. In particular, when monkeys are tested in tasks that do not require navigation, spatial memory seems unaffected by lesions of the hippocampus. However, the interpretation of these results is compromised by long-term compensatory adaptation occurring in the days and weeks after lesions. To test the hypothesis that hippocampus is necessary for nonnavigational spatial memory, we selected a technique that avoids long-term compensatory adaptation. We transiently disrupted hippocampal function acutely at the time of testing by microinfusion of the glutamate receptor antagonist kynurenate. Animals were tested on a self-ordered spatial memory task, the Hamilton Search Task. In the task, animals are presented with an array of eight boxes, each containing a food reinforcer; one box may be opened per trial, with trials separated by a delay. Only the spatial location of the boxes serves as a cue to solve the task. The optimal strategy is to open each box once without returning to previously visited locations. Transient inactivation of hippocampus reduced performance to chance levels in a delay-dependent manner. In contrast, no deficits were seen when boxes were marked with nonspatial cues (color). These results clearly document a role for hippocampus in nonnavigational spatial memory in macaques and demonstrate the efficacy of pharmacological inactivation of this structure in this species. Our data bring the role of the hippocampus in monkeys into alignment with the broader framework of hippocampal function.A lthough a role for the hippocampus in navigational spatial memory has been well documented in many species, including humans (1-4), rodents (5, 6), and monkeys (7-9), a role for hippocampus in nonnavigational spatial memory is less certain. Because nonhuman primates have a close neuroanatomical and behavioral homology to humans, they offer a unique opportunity to assess the neural substrates of spatial memory using nonnavigational tasks. However, studies using nonnavigational spatial tasks with nonhuman primates have found little or no effect of hippocampal lesions (10-15).The ability of hippocampal-lesioned monkeys to perform these tasks without impairment has been explained by the reliance on a strategy that is not dependent on hippocampus. Whereas the use of allocentric (world-centered) cues depends on the hippocampus, it is thought that the use of egocentric (body-centered) cues does not. Indeed, it has been suggested that the use of egocentric cues is supported by extrahippocampal substrates including striatum and parietal cortex (15)(16)(17)(18).Following a hippocampal lesion, subjects may learn to resolve a given task by developing a strategy distinct from that used in the presence of an intact hippocampus. Several factors may support this compensatory strategy, including (i) postlesion training or retraining and (ii) postlesion network reorganization (19-21). T...

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“…Other studies have compared structure-function relations across species (Miranda-Dominguez et al 2014). The notion that structural connections shape and/or constrain functional connections is not only supported through comparisons of anatomical and functional connectivity but is also reinforced by interventional studies that have reported changes in functional connectivity resulting from manipulations of the anatomical substrate (Johnston et al 2008;O'Reilly et al 2013). Extending this notion to brain and mental disorders, a large number of studies have attempted to link dysregulation of functional connectivity patterns to underlying disturbances of structural connectivity, e.g., in disrupted hub or rich club connections [reviewed in van den Heuvel and ].…”

Section: Macroscalementioning

confidence: 99%

Connectome Networks: From Cells to Systems

Sporns

2016

Research and Perspectives in Neurosciences

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Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys

Cited by 209 publications

References 59 publications

Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex

Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex

Memory loss in a nonnavigational spatial task after hippocampal inactivation in monkeys

Connectome Networks: From Cells to Systems

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