Jill X. O'Reilly

Distinct and Overlapping Functional Zones in the Cerebellum Defined by Resting State Functional Connectivity

The cerebellum processes information from functionally diverse regions of the cerebral cortex. Cerebellar input and output nuclei have connections with prefrontal, parietal, and sensory cortex as well as motor and premotor cortex. However, the topography of the connections between the cerebellar and cerebral cortices remains largely unmapped, as it is relatively unamenable to anatomical methods. We used resting-state functional magnetic resonance imaging to define subregions within the cerebellar cortex based on their functional connectivity with the cerebral cortex. We mapped resting-state functional connectivity voxel-wise across the cerebellar cortex, for cerebral-cortical masks covering prefrontal, motor, somatosensory, posterior parietal, visual, and auditory cortices. We found that the cerebellum can be divided into at least 2 zones: 1) a primary sensorimotor zone (Lobules V, VI, and VIII), which contains overlapping functional connectivity maps for domain-specific motor, somatosensory, visual, and auditory cortices; and 2) a supramodal zone (Lobules VIIa, Crus I, and II), which contains overlapping functional connectivity maps for prefrontal and posterior-parietal cortex. The cortical connectivity of the supramodal zone was driven by regions of frontal and parietal cortex which are not directly involved in sensory or motor processing, including dorsolateral prefrontal cortex and the frontal pole, and the inferior parietal lobule.

Tools of the Trade: Psychophysiological Interactions and Functional Connectivity

Psychophysiological interactions (PPIs) analysis is a method for investigating task-specific changes in the relationship between activity in different brain areas, using functional magnetic resonance imaging (fMRI) data. Specifically, PPI analyses identify voxels in which activity is more related to activity in a seed region of interest (seed ROI) in a given psychological context, such as during attention or in the presence of emotive stimuli. In this tutorial, we aim to give a simple conceptual explanation of how PPI analysis works, in order to assist readers in planning and interpreting their own PPI experiments.

Diffusion-Weighted Imaging Tractography-Based Parcellation of the Human Parietal Cortex and Comparison with Human and Macaque Resting-State Functional Connectivity

Despite the prominence of parietal activity in human neuroimaging 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 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 10 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.

Social network size affects neural circuits in macaques.

Executing social cognition successfully requires more brain power. It has been suggested that variation in brain structure correlates with the sizes of individuals’ social networks. Whether variation in social network size causes variation in brain structure, however, is unknown. To address this question, we neuroimaged 23 monkeys that had been living in social groups set to different sizes. Subject comparison revealed that living in larger groups caused increases in gray matter in mid-superior temporal sulcus and rostral prefrontal cortex and increased coupling of activity in frontal and temporal cortex. Social network size, therefore, contributes to changes both in brain structure and function. The changes have potential implications for an animal’s success in a social context; gray matter differences in similar areas were also correlated with each animal’s dominance within its social network.

The Cerebellum Predicts the Timing of Perceptual Events

Prospective (forward) temporal–spatial models are essential for both action and perception, but the literature on perceptual prediction has primarily been limited to the spatial domain. In this study we asked how the neural systems of perceptual prediction change, when change-over-time must be modeled. We used a naturalistic paradigm in which observers had to extrapolate the trajectory of an occluded moving object to make perceptual judgments based on the spatial (direction) or temporal–spatial (velocity) characteristics of object motion. Using functional magnetic resonance imaging we found that a region in posterior cerebellum (lobule VII crus 1) was engaged specifically when a temporal–spatial model was required (velocity judgment task), suggesting that circuitry involved in motor forward-modeling may also be engaged in perceptual prediction when a model of change-over-time is required. This cerebellar region appears to supply a temporal signal to cortical networks involved in spatial orienting: a frontal-parietal network associated with attentional orienting was engaged in both (spatial and temporal–spatial) tasks, but functional connectivity between these regions and the posterior cerebellum was enhanced in the temporal–spatial prediction task. In addition to the oculomotor spatial orienting network, regions involved in hand movements (aIP and PMv) were recruited in the temporal–spatial task, suggesting that the nature of perceptual prediction may bias the recruitment of sensory-motor networks in orienting. Finally, in temporal–spatial prediction, functional connectivity was enhanced between the cerebellum and the putamen, a structure which has been proposed to supply the brains metric of time, in the temporal–spatial prediction task.

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.

Time is of the essence.

Timing is essential to human behaviour, but the neural mechanisms underlying time perception are still unclear. New findings from a brain-imaging study by Coull et al. show that activity in a network of motor-related areas varies parametrically with attention to time. Given that a system in which timing is important (but not the primary function) is recruited when temporal judgements are required, we should perhaps reassess the notion of a dedicated timing system in the brain.

Dissociable effects of surprise and model update in parietal and anterior cingulate cortex

Significance This study investigates the brain mechanisms by which people disregard their previous beliefs about their environment and start forming new beliefs. Surprising events are often a signal that one’s previous beliefs are no longer valid. Using brain imaging, we identified separate brain systems involved in dealing with the immediate consequences of surprise (i.e., reprogramming actions) and in updating one’s beliefs about the environment to predict future events accurately. We present a mathematical and neuroanatomical model of how brains adjust to change in their environment that may inform our understanding of neurological disorders in which this adjustment process fails. Brains use predictive models to facilitate the processing of expected stimuli or planned actions. Under a predictive model, surprising (low probability) stimuli or actions necessitate the immediate reallocation of processing resources, but they can also signal the need to update the underlying predictive model to reflect changes in the environment. Surprise and updating are often correlated in experimental paradigms but are, in fact, distinct constructs that can be formally defined as the Shannon information (IS) and Kullback–Leibler divergence (DKL) associated with an observation. In a saccadic planning task, we observed that distinct behaviors and brain regions are associated with surprise/IS and updating/DKL. Although surprise/IS was associated with behavioral reprogramming as indexed by slower reaction times, as well as with activity in the posterior parietal cortex [human lateral intraparietal area (LIP)], the anterior cingulate cortex (ACC) was specifically activated during updating of the predictive model (DKL). A second saccade-sensitive region in the inferior posterior parietal cortex (human 7a), which has connections to both LIP and ACC, was activated by surprise and modulated by updating. Pupillometry revealed a further dissociation between surprise and updating with an early positive effect of surprise and late negative effect of updating on pupil area. These results give a computational account of the roles of the ACC and two parietal saccade regions, LIP and 7a, by which their involvement in diverse tasks can be understood mechanistically. The dissociation of functional roles between regions within the reorienting/reprogramming network may also inform models of neurological phenomena, such as extinction and Balint syndrome, and neglect.

Organizing conceptual knowledge in humans with a gridlike code

Coding abstract concepts in the brain Grid cells are thought to provide the neuronal code that underlies spatial knowledge in the brain. Grid cells have mostly been studied in the context of path integration. However, recent theoretical studies have suggested that they may have a broader role in the organization of general knowledge. Constantinescu et al. investigated whether the neural representation of concepts follows a structure similar to the representation of space in the entorhinal cortex. Several brain regions, including the entorhinal cortex and the ventromedial prefrontal cortex, showed gridlike neural representation of conceptual space. Science, this issue p. 1464 Grid cells in the brain can also represent nonspatial knowledge. It has been hypothesized that the brain organizes concepts into a mental map, allowing conceptual relationships to be navigated in a manner similar to that of space. Grid cells use a hexagonally symmetric code to organize spatial representations and are the likely source of a precise hexagonal symmetry in the functional magnetic resonance imaging signal. Humans navigating conceptual two-dimensional knowledge showed the same hexagonal signal in a set of brain regions markedly similar to those activated during spatial navigation. This gridlike signal is consistent across sessions acquired within an hour and more than a week apart. Our findings suggest that global relational codes may be used to organize nonspatial conceptual representations and that these codes may have a hexagonal gridlike pattern when conceptual knowledge is laid out in two continuous dimensions.

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

In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states.