Franz-Xaver Neubert

On the relationship between the “default mode network” and the “social brain”

The default mode network (DMN) of the brain consists of areas that are typically more active during rest than during active task performance. Recently however, this network has been shown to be activated by certain types of tasks. Social cognition, particularly higher-order tasks such as attributing mental states to others, has been suggested to activate a network of areas at least partly overlapping with the DMN. Here, we explore this claim, drawing on evidence from meta-analyses of functional MRI data and recent studies investigating the structural and functional connectivity of the social brain. In addition, we discuss recent evidence for the existence of a DMN in non-human primates. We conclude by discussing some of the implications of these observations.

Cortical and subcortical interactions during action reprogramming and their related white matter pathways

The right inferior frontal gyrus (rIFG) and the presupplementary motor area (pre-SMA) have been identified with cognitive control—the top-down influence on other brain areas when nonroutine behavior is required. It has been argued that they “inhibit” habitual motor responses when environmental changes mean a different response should be made. However, whether such “inhibition” can be equated with inhibitory physiological interactions has been unclear, as has the areas’ relationship with each other and the anatomical routes by which they influence movement execution. Paired-pulse transcranial magnetic stimulation (ppTMS) was applied over rIFG and primary motor cortex (M1) or over pre-SMA and M1 to measure their interactions, at a subsecond scale, during either inhibition and reprogramming of actions or during routine action selection. Distinct patterns of functional interaction between pre-SMA and M1 and between rIFG and M1 were found that were specific to action reprogramming trials; at a physiological level, direct influences of pre-SMA and rIFG on M1 were predominantly facilitatory and inhibitory, respectively. In a subsequent experiment, it was shown that the rIFGs inhibitory influence was dependent on pre-SMA. A third experiment showed that pre-SMA and rIFG influenced M1 at two time scales. By regressing white matter fractional anisotropy from diffusion-weighted magnetic resonance images against TMS-measured functional connectivity, it was shown that short-latency (6 ms) and longer latency (12 ms) influences were mediated by cortico-cortical and subcortical pathways, respectively, with the latter passing close to the subthalamic nucleus.

The Organization of Dorsal Frontal Cortex in Humans and Macaques

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.

Short-Latency Influence of Medial Frontal Cortex on Primary Motor Cortex during Action Selection under Conflict

Medial frontal cortex (MFC) is crucial when actions have to be inhibited, reprogrammed, or selected under conflict, but the precise mechanism by which it operates is unclear. Importantly, how and when the MFC influences the primary motor cortex (M1) during action selection is unknown. Using paired-pulse transcranial magnetic stimulation, we investigated functional connectivity between the presupplementary motor area (pre-SMA) part of MFC and M1. We found that functional connectivity increased in a manner dependent on cognitive context: pre-SMA facilitated the motor evoked-potential elicited by M1 stimulation only during action reprogramming, but not when otherwise identical actions were made in the absence of conflict. The effect was anatomically specific to pre-SMA; it was not seen when adjacent brain regions were stimulated. We discuss implications for the anatomical pathways mediating the observed effects.

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

Significance Because of the interest in reward-guided learning and decision making, these neural mechanisms have been studied in both humans and monkeys. But whether and how key brain areas correspond between the two species has been uncertain. Areas in the two species can be compared as a function of the brain circuits in which they participate, which can be estimated from patterns of correlation in brain activity measured with functional MRI. Taking such measurements in 38 humans and 25 macaques, we identified fundamental similarities between the species and one human frontal area with no monkey counterpart. Altogether these findings suggest that everyday human decision-making capitalizes on a neural apparatus similar to the one that supports monkeys when foraging in the wild. 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.

Connectivity profiles reveal the relationship between brain areas for social cognition in human and monkey temporoparietal cortex.

The human ability to infer the thoughts and beliefs of others, often referred to as “theory of mind,” as well as the predisposition to even consider others, are associated with activity in the temporoparietal junction (TPJ) area. Unlike the case of most human brain areas, we have little sense of whether or how TPJ is related to brain areas in other nonhuman primates. It is not possible to address this question by looking for similar task-related activations in nonhuman primates because there is no evidence that nonhuman primates engage in theory-of-mind tasks in the same manner as humans. Here, instead, we explore the relationship by searching for areas in the macaque brain that interact with other macaque brain regions in the same manner as human TPJ interacts with other human brain regions. In other words, we look for brain regions with similar positions within a distributed neural circuit in the two species. We exploited the fact that human TPJ has a unique functional connectivity profile with cortical areas with known homologs in the macaque. For each voxel in the macaque temporal and parietal cortex we evaluated the similarity of its functional connectivity profile to that of human TPJ. We found that areas in the middle part of the superior temporal cortex, often associated with the processing of faces and other social stimuli, have the most similar connectivity profile. These results suggest that macaque face processing areas and human mentalizing areas might have a similar precursor.

Comparing brains by matching connectivity profiles

The great promise of comparative neuroscience is to understand why brains differ by investigating the relations between variations in the organization of different brains, their evolutionary history, and their current ecological niche. For this approach to be successful, the organization of different brains needs to be quantifiable. Here, we present an approach to formally comparing the connectivity of different cortical areas across different brains. We exploit the fact that cortical regions can be characterized by the unique pattern of connectivity, the so-called connectivity fingerprint. By comparing connectivity fingerprints between cortical areas in the human and non-human primate brain we can identify between-species homologs, but also illustrate that is driving differences between species. We illustrate the approach by comparing the organization of the frontal cortex between humans and macaques, showing general similarities combined with some differences in the lateral frontal pole.

The extreme capsule fiber complex in humans and macaque monkeys: a comparative diffusion MRI tractography study.

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.

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.

Causal manipulation of functional connectivity in a specific neural pathway during behaviour and at rest

Correlations in brain activity between two areas (functional connectivity) have been shown to relate to their underlying structural connections. We examine the possibility that functional connectivity also reflects short-term changes in synaptic efficacy. We demonstrate that paired transcranial magnetic stimulation (TMS) near ventral premotor cortex (PMv) and primary motor cortex (M1) with a short 8-ms inter-pulse interval evoking synchronous pre- and post-synaptic activity and which strengthens interregional connectivity between the two areas in a pattern consistent with Hebbian plasticity, leads to increased functional connectivity between PMv and M1 as measured with functional magnetic resonance imaging (fMRI). Moreover, we show that strengthening connectivity between these nodes has effects on a wider network of areas, such as decreasing coupling in a parallel motor programming stream. A control experiment revealed that identical TMS pulses at identical frequencies caused no change in fMRI-measured functional connectivity when the inter-pulse-interval was too long for Hebbian-like plasticity. DOI: http://dx.doi.org/10.7554/eLife.04585.001