Svenja Caspers

ALE meta-analysis of action observation and imitation in the human brain.

Over the last decade, many neuroimaging studies have assessed the human brain networks underlying action observation and imitation using a variety of tasks and paradigms. Nevertheless, questions concerning which areas consistently contribute to these networks irrespective of the particular experimental design and how such processing may be lateralized remain unresolved. The current study aimed at identifying cortical areas consistently involved in action observation and imitation by combining activation likelihood estimation (ALE) meta-analysis with probabilistic cytoarchitectonic maps. Meta-analysis of 139 functional magnetic resonance and positron emission tomography experiments revealed a bilateral network for both action observation and imitation. Additional subanalyses for different effectors within each network revealed highly comparable activation patterns to the overall analyses on observation and imitation, respectively, indicating an independence of these findings from potential confounds. Conjunction analysis of action observation and imitation meta-analyses revealed a bilateral network within frontal premotor, parietal, and temporo-occipital cortex. The most consistently rostral inferior parietal area was PFt, providing evidence for a possible homology of this region to macaque area PF. The observation and imitation networks differed particularly with respect to the involvement of Brocas area: whereas both networks involved a caudo-dorsal part of BA 44, activation during observation was most consistent in a more rostro-dorsal location, i.e., dorsal BA 45, while activation during imitation was most consistent in a more ventro-caudal aspect, i.e., caudal BA 44. The present meta-analysis thus summarizes and amends previous descriptions of the human brain networks related to action observation and imitation.

The human inferior parietal cortex: Cytoarchitectonic parcellation and interindividual variability

The inferior parietal cortex (IPC) integrates information from different sensory modalities and plays an important role in a variety of higher cognitive functions. Brodmann (Brodmann, K., 1909. Vergleichende Lokalisationslehre der Grosshirnrinde. Barth, Leipzig) proposed a cytoarchitectonic subdivision of the IPC into only two cortical areas, a rostral (BA 40) and a caudal (BA 39) area. Although his scheme was repeatedly challenged by other observers, it is still used for the anatomical localization of functional imaging data. The apparent differences between all these cyto- and myeloarchitectonic maps may be caused partly by the observer-dependent procedure of defining cytoarchitectonic borders by pure visual inspection of histological sections and partly by the interindividual variability of cytoarchitecture. The present observations and the resulting cortical map of the IPC are based on quantitative, observer-independent definitions of cytoarchitectonic borders and take into account each areas topographical variability across brains. Ten human postmortem brains were scanned using an MRI 3-D FLASH sequence prior to histological processing. After embedding in paraffin, serial sections through whole brains were prepared, and the sections were stained for cell bodies. Following high-resolution digitization of sections containing the IPC, we defined the cytoarchitecture and borders of each cortical area of this brain region using a multivariate statistical analysis of laminar cell density profiles. In contrast to previous observations, we found seven cytoarchitectonic areas in the IPC: five in the rostral (covering the region of BA 40) and two in the caudal part (covering the region of BA 39). We observed considerable interindividual variability in the topography of each area. A consistent correspondence between macroanatomical landmarks and cytoarchitectonic borders was not found. This new cytoarchitectonic map of the human IPC demonstrates regional differences in the cortical microstructure that is suggestive of functional differentiation. Furthermore, the map is registered in three dimensions and thereby provides a robust anatomical base for interpreting functional imaging studies.

The human inferior parietal lobule in stereotaxic space

Recently, a new cytoarchitectonic map of the human inferior parietal lobule (IPL) has been proposed, with the IPL consisting of seven cytoarchitectonically distinct areas (Caspers et al. in Neuroimage 33(2):430–448, 2006). The aim of the present study was to investigate the different aspects of variability of these IPL areas. As one aspect of variability, we analysed the topographical relationship between the localisation of the borders of the areas and macroanatomical landmarks. Although five areas occupy the surface supramarginal gyrus and two the angular gyrus, their borders cannot be reliably detected by means of macroanatomy. To account for variability in size and extent of the areas in stereotaxic space, cytoarchitectonic probabilistic maps have been calculated for each IPL area. Hemisphere- and gender-related differences have been investigated on basis of volumes of cytoarchitectonic areas. For one of them, area PFcm, a significant gender difference in volume was found with males having larger volumes than females; this difference exceeds that of gender differences in total brain volume. The different aspects of variability and volumetric asymmetry may underlie some of the well-known functional asymmetries in the IPL, observed, for example during fMRI experiments analysing spatial attention or motor attention, and planning. The cytoarchitectonic probabilistic maps of the seven IPL areas provide a robust anatomical reference and open new perspectives for further structure–function investigations of the human IPL.

Co-activation patterns distinguish cortical modules, their connectivity and functional differentiation

The organization of the cerebral cortex into distinct modules may be described along several dimensions, most importantly, structure, connectivity and function. Identification of cortical modules by differences in whole-brain connectivity profiles derived from diffusion tensor imaging or resting state correlations has already been shown. These approaches, however, carry no task-related information. Hence, inference on the functional relevance of the ensuing parcellation remains tentative. Here, we demonstrate, that Meta-Analytic Connectivity Modeling (MACM) allows the delineation of cortical modules based on their whole-brain co-activation pattern across databased neuroimaging results. Using a model free approach, two regions of the medial pre-motor cortex, SMA and pre-SMA were differentiated solely based on their functional connectivity. Assessing the behavioral domain and paradigm class meta-data of the experiments associated with the clusters derived from the co-activation based parcellation moreover allows the identification of their functional characteristics. The ensuing hypotheses about functional differentiation and distinct functional connectivity between pre-SMA and SMA were then explicitly tested and confirmed in independent datasets using functional and resting state fMRI. Co-activation based parcellation thus provides a new perspective for identifying modules of functional connectivity and linking them to functional properties, hereby generating new and subsequently testable hypotheses about the organization of cortical modules.

Anatomical and Functional Connectivity of Cytoarchitectonic Areas within the Human Parietal Operculum

In monkeys, the somatosensory cortex on the parietal operculum can be differentiated into several distinct cortical fields. Potential human homologues for these areas have already been defined by cytoarchitectonic mapping and functional imaging experiments. Differences between the two most widely studied areas [operculum parietale (OP) 1 and OP 4] within this region particularly pertain to their connection with either the perceptive parietal network or the frontal motor areas. In the present study, we investigated differences in anatomical connection patterns probed by probabilistic tractography on diffusion tensor imaging data. Functional connectivity was then mapped by coordinate-based meta-analysis of imaging studies. Comparison between these two aspects of connectivity showed a good congruency and hence converging evidence for an involvement of these areas in matching brain networks. There were, however, also several instances in which anatomical and functional connectivity diverged, underlining the independence of these measures and the need for multimodal characterization of brain connectivity. The connectivity analyses performed showed that the two largest areas within the human parietal operculum region display considerable differences in their connectivity to frontoparietal brain regions. In particular, relative to OP 1, area OP 4 is more closely integrated with areas responsible for basic sensorimotor processing and action control, while OP 1 is more closely connected to the parietal networks for higher order somatosensory processing. These results are largely congruent with data on nonhuman primates. Differences between anatomical and functional connectivity as well as between species, however, highlight the need for an integrative view on connectivity, including comparison and cross-validation of results from different approaches.

Meta-analytical definition and functional connectivity of the human vestibular cortex

Contrary to most other sensory systems, no consensus has been reached within the scientific community about the exact locations and functions of human cortical areas processing vestibular information. Metaanalytical modelling using activation likelihood estimation (ALE) for the integration of neuroimaging results has already been successfully applied to several distinct tasks, thereby revealing the cortical localization of cognitive functions. We used the same algorithm and technique with all available and suitable PET and fMRI studies employing a vestibular stimulus. Most consistently across 28 experiments vestibular stimuli evoked activity in the right hemispheric parietal opercular area OP 2 implicating it as the core region for vestibular processing. Furthermore, we took our primary results as a seeding point and fed them into a functional connectivity analysis based on resting-state oscillations in 100 healthy subjects. This subsequent calculation confirmed direct connections of the area OP 2 with every other region found in the meta-analysis, in particular temporo-parietal regions, premotor cortex, and the midcingulate gyrus. Thus revealing a joint vestibular network in accordance with a concept from animal literature termed the inner vestibular circle. Moreover, there was also a significant vestibular connectivity overlap with frontal but not parietal cortical centres responsible for the generation of saccadic eye movements, likely to be involved in nystagmus fast phase generation. This was shown in an additional ocular motor meta-analysis. We conclude that the cytoarchitectonic area OP 2 in the parietal operculum, embedded in a joint vestibular network, should be the primary candidate for the human vestibular cortex. This area may represent the human homologue to the vestibular area PIVC as proposed by Guldin and Grüsser in non-human primates.

Is There “One” DLPFC in Cognitive Action Control? Evidence for Heterogeneity From Co-Activation-Based Parcellation

The dorsolateral prefrontal cortex (DLPFC) has consistently been implicated in cognitive control of motor behavior. There is, however, considerable variability in the exact location and extension of these activations across functional magnetic resonance imaging (fMRI) experiments. This poses the question of whether this variability reflects sampling error and spatial uncertainty in fMRI experiments or structural and functional heterogeneity of this region. This study shows that the right DLPFC as observed in 4 different experiments tapping executive action control may be subdivided into 2 distinct subregions-an anterior-ventral and a posterior-dorsal one -based on their whole-brain co-activation patterns across neuroimaging studies. Investigation of task-dependent and task-independent connectivity revealed both clusters to be involved in distinct neural networks. The posterior subregion showed increased connectivity with bilateral intraparietal sulci, whereas the anterior subregion showed increased connectivity with the anterior cingulate cortex. Functional characterization with quantitative forward and reverse inferences revealed the anterior network to be more strongly associated with attention and action inhibition processes, whereas the posterior network was more strongly related to action execution and working memory. The present data provide evidence that cognitive action control in the right DLPFC may rely on differentiable neural networks and cognitive functions.

Probabilistic fibre tract analysis of cytoarchitectonically defined human inferior parietal lobule areas reveals similarities to macaques

The human inferior parietal lobule (IPL) is a multimodal brain region, subdivided in several cytoarchitectonic areas which are involved in neural networks related to spatial attention, language, and higher motor processing. Tracer studies in macaques revealed differential connectivity patterns of IPL areas as the respective structural basis. Evidence for comparable differential fibre tracts of human IPL is lacking. Here, anatomical connectivity of five cytoarchitectonic human IPL areas to 64 cortical targets was investigated using probabilistic tractography. Connection likelihood was assessed by evaluating the number of traces between seed and target against the distribution of traces from that seed to voxels in the same distance as the target. The main fibre tract pattern shifted gradually from rostral to caudal IPL: Rostral areas were predominantly connected to somatosensory and superior parietal areas while caudal areas more strongly connected with auditory, anterior temporal and higher visual cortices. All IPL areas were strongly connected with inferior frontal, insular and posterior temporal areas. These results showed striking similarities with connectivity patterns in macaques, providing further evidence for possible homologies between these two species. This shift in fibre tract pattern supports a differential functional involvement of rostral (higher motor functions) and caudal IPL (spatial attention), with probable overlapping language involvement. The differential functional involvement of IPL areas was further supported by hemispheric asymmetries of connection patterns which showed left-right differences especially with regard to connections to sensorimotor, inferior frontal and temporal areas.

Characterization of the temporo-parietal junction by combining data-driven parcellation, complementary connectivity analyses, and functional decoding

The right temporo-parietal junction (RTPJ) is consistently implicated in two cognitive domains, attention and social cognitions. We conducted multi-modal connectivity-based parcellation to investigate potentially separate functional modules within RTPJ implementing this cognitive dualism. Both task-constrained meta-analytic coactivation mapping and task-free resting-state connectivity analysis independently identified two distinct clusters within RTPJ, subsequently characterized by network mapping and functional forward/reverse inference. Coactivation mapping and resting-state correlations revealed that the anterior cluster increased neural activity concomitantly with a midcingulate-motor-insular network, functionally associated with attention, and decreased neural activity concomitantly with a parietal network, functionally associated with social cognition and memory retrieval. The posterior cluster showed the exact opposite association pattern. Our data thus suggest that RTPJ links two antagonistic brain networks processing external versus internal information.

Organization of the Human Inferior Parietal Lobule Based on Receptor Architectonics

Human inferior parietal lobule (IPL) plays a key role in various cognitive functions. Its functional diversity, including attention, language, and action processing, is reflected by its structural segregation into 7 cytoarchitectonically distinct areas, each with characteristic connectivity patterns. We hypothesized that commonalities of the cytoarchitectonic, connectional, and functional diversity of the IPL should be reflected by a correlated transmitter receptor–based organization. Since the function of a cortical area requires a well-tuned receptor balance, the densities of 15 different receptors were measured in each IPL area. A hierarchical cluster analysis of the receptor balance revealed a tripartite segregation of the IPL into a rostral, middle, and caudal group. Comparison with other cortical areas showed strong similarities with Brocas region for all 3 groups, with the superior parietal cortex for the middle, and with extrastriate visual areas for the caudal group. Notably, caudal-most area PGp has a receptor fingerprint very similar to that of ventral extrastriate visual cortex. We therefore propose a new organizational model of the human IPL, consisting of 3 clusters, which corresponds to its known cytoarchitectonic, connectional, and functional diversity at the molecular level. This might reflect a general organizational principle of human IPL, beyond specific functional domains.