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1.  The extreme capsule fiber complex in humans and macaque monkeys: a comparative diffusion MRI tractography study 
Brain Structure & Function  2015;221(8):4059-4071.
We compared the course and cortical projections of white matter fibers passing through the extreme capsule in humans and macaques. Previous comparisons of this tract have suggested a uniquely human posterior projection, but these studies have always employed different techniques in the different species. Here we used the same technique, diffusion MRI, in both species to avoid attributing differences in techniques to differences in species. Diffusion MRI-based probabilistic tractography was performed from a seed area in the extreme capsule in both human and macaques. We compared in vivo data of humans and macaques as well as one high-resolution ex vivo macaque dataset. Tractography in the macaque was able to replicate most results known from macaque tracer studies, including selective innervation of frontal cortical areas and targets in the superior temporal cortex. In addition, however, we also observed some tracts that are not commonly reported in macaque tracer studies and that are more reminiscent of results previously only reported in the human. In humans, we show that the ventrolateral prefrontal cortex innervations are broadly similar to those in the macaque. These results suggest that evolutionary changes in the human extreme capsule fiber complex are likely more gradual than punctuated. Further, they demonstrate both the potential and limitations of diffusion MRI tractography.
PMCID: PMC5065901  PMID: 26627483
Tractography; Comparative neuroscience; Temporal cortex; Ventrolateral prefrontal cortex; Surface projection
2.  Contrasting Roles for Orbitofrontal Cortex and Amygdala in Credit Assignment and Learning in Macaques 
Neuron  2015;87(5):1106-1118.
Recent studies have challenged the view that orbitofrontal cortex (OFC) and amygdala mediate flexible reward-guided behavior. We trained macaques to perform an object discrimination reversal task during fMRI sessions and identified a lateral OFC (lOFC) region in which activity predicted adaptive win-stay/lose-shift behavior. Amygdala and lOFC activity was more strongly coupled on lose-shift trials. However, lOFC-amygdala coupling was also modulated by the relevance of reward information in a manner consistent with a role in establishing how credit for reward should be assigned. Day-to-day fluctuations in signals and signal coupling were correlated with day-to-day fluctuation in performance. A second experiment confirmed the existence of signals for adaptive stay/shift behavior in lOFC and reflecting irrelevant reward in the amygdala in a probabilistic learning task. Our data demonstrate that OFC and amygdala each make unique contributions to flexible behavior and credit assignment.
•Orbitofrontal cortex determines future behavior on the basis of reward feedback•Variation in orbitofrontal cortex activity is correlated with variation in learning•Amygdala carries information about irrelevant reward•Amygdala-orbitofrontal interactions emphasize relevant not irrelevant reward
Chau et al. identify a posterior lateral OFC (lOFC) region in which activity predicts adaptive win-stay/lose-shift behavior. Amygdala activity predicts only lose-shift behavior but carries information about irrelevant rewards. lOFC-amygdala connectivity is modulated dynamically by the relevance of reward information.
PMCID: PMC4562909  PMID: 26335649
3.  The Organization of Dorsal Frontal Cortex in Humans and Macaques 
The Journal of Neuroscience  2013;33(30):12255-12274.
The human dorsal frontal cortex has been associated with the most sophisticated aspects of cognition, including those that are thought to be especially refined in humans. Here we used diffusion-weighted magnetic resonance imaging (DW-MRI) and functional MRI (fMRI) in humans and macaques to infer and compare the organization of dorsal frontal cortex in the two species. Using DW-MRI tractography-based parcellation, we identified 10 dorsal frontal regions lying between the human inferior frontal sulcus and cingulate cortex. Patterns of functional coupling between each area and the rest of the brain were then estimated with fMRI and compared with functional coupling patterns in macaques. Areas in human medial frontal cortex, including areas associated with high-level social cognitive processes such as theory of mind, showed a surprising degree of similarity in their functional coupling patterns with the frontal pole, medial prefrontal, and dorsal prefrontal convexity in the macaque. We failed to find evidence for “new” regions in human medial frontal cortex. On the lateral surface, comparison of functional coupling patterns suggested correspondences in anatomical organization distinct from those that are widely assumed. A human region sometimes referred to as lateral frontal pole more closely resembled area 46, rather than the frontal pole, of the macaque. Overall the pattern of results suggest important similarities in frontal cortex organization in humans and other primates, even in the case of regions thought to carry out uniquely human functions. The patterns of interspecies correspondences are not, however, always those that are widely assumed.
PMCID: PMC3744647  PMID: 23884933
4.  Primate comparative neuroscience using magnetic resonance imaging: promises and challenges 
Primate comparative anatomy is an established field that has made rich and substantial contributions to neuroscience. However, the labor-intensive techniques employed mean that most comparisons are often based on a small number of species, which limits the conclusions that can be drawn. In this review we explore how new developments in magnetic resonance imaging have the potential to apply comparative neuroscience to a much wider range of species, allowing it to realize an even greater potential. We discuss (1) new advances in the types of data that can be acquired, (2) novel methods for extracting meaningful measures from such data that can be compared between species, and (3) methods to analyse these measures within a phylogenetic framework. Together these developments will allow researchers to characterize the relationship between different brains, the ecological niche they occupy, and the behavior they produce in more detail than ever before.
PMCID: PMC4186285  PMID: 25339857
neuroecology; MRI; diffusion MRI; connectivity; phylogenetics
5.  Modulation of feedback-related negativity during trial-and-error exploration and encoding of behavioral shifts 
The feedback-related negativity (FRN) is a mid-frontal event-related potential (ERP) recorded in various cognitive tasks and associated with the onset of sensory feedback signaling decision outcome. Some properties of the FRN are still debated, notably its sensitivity to positive and negative reward prediction error (RPE)—i.e., the discrepancy between the expectation and the actual occurrence of a particular feedback,—and its role in triggering the post-feedback adjustment. In the present study we tested whether the FRN is modulated by both positive and negative RPE. We also tested whether an instruction cue indicating the need for behavioral adjustment elicited the FRN. We asked 12 human subjects to perform a problem-solving task where they had to search by trial and error which of five visual targets, presented on a screen, was associated with a correct feedback. After exploration and discovery of the correct target, subjects could repeat their correct choice until the onset of a visual signal to change (SC) indicative of a new search. Analyses showed that the FRN was modulated by both negative and positive prediction error (RPE). Finally, we found that the SC elicited an FRN-like potential on the frontal midline electrodes that was not modulated by the probability of that event. Collectively, these results suggest the FRN may reflect a mechanism that evaluates any event (outcome, instruction cue) signaling the need to engage adaptive actions.
PMCID: PMC3827557  PMID: 24294190
cingulate cortex; reward prediction error; feedback-related negativity; trial and error exploration
Despite the prominence of parietal activity in human neuromaging investigations of sensorimotor and cognitive processes there remains uncertainty about basic aspects of parietal cortical anatomical organization. Descriptions of human parietal cortex draw heavily on anatomical schemes developed in other primate species but the validity of such comparisons has been questioned by claims that there are fundamental differences between the parietal cortex in humans and other primates. A scheme is presented for parcellation of human lateral parietal cortex into component regions on the basis of anatomical connectivity and the functional interactions of the resulting clusters with other brain regions. Anatomical connectivity was estimated using diffusion-weighted magnetic resonance image (MRI) based tractography and functional interactions were assessed by correlations in activity measured with functional MRI (fMRI) at rest. Resting state functional connectivity was also assessed directly in the rhesus macaque lateral parietal cortex in an additional experiment and the patterns found reflected known neuroanatomical connections. Cross-correlation in the tractography-based connectivity patterns of parietal voxels reliably parcellated human lateral parietal cortex into ten component clusters. The resting state functional connectivity of human superior parietal and intraparietal clusters with frontal and extrastriate cortex suggested correspondences with areas in macaque superior and intraparietal sulcus. Functional connectivity patterns with parahippocampal cortex and premotor cortex again suggested fundamental correspondences between inferior parietal cortex in humans and macaques. In contrast, the human parietal cortex differs in the strength of its interactions between the central inferior parietal lobule region and the anterior prefrontal cortex.
PMCID: PMC3091022  PMID: 21411650
7.  Expectations, gains, and losses in the anterior cingulate cortex 
The anterior cingulate cortex (ACC) participates in evaluating actions and outcomes. Little is known on how action/reward values are processed in ACC and if the context in which actions are performed influences this processing. Here we report ACC unit activity of monkeys performing two tasks. The first tested whether the encoding of reward values is context-dependant i.e. dependant on the size of the other rewards available in the current block of trials. The second task tested whether unexpected events signaling a change in reward are represented. We show that the context created by a block design (i.e. the context of possible alternative rewards) influences the encoding of reward values, even if no decision or choice is required. ACC activity encodes the relative and not absolute expected reward values. Moreover, cingulate activity signals and evaluates when reward expectations are violated by unexpected stimuli indicating reward gains or losses.
PMCID: PMC2271114  PMID: 18189006
Animals; Conditioning; Operant; physiology; Electrodes; Implanted; Electrophysiology; Macaca mulatta; Male; Prefrontal Cortex; physiology; Psychomotor Performance; physiology; Reaction Time; physiology; Reward

Results 1-7 (7)