Julian Caspers

The mid-fusiform sulcus: A landmark identifying both cytoarchitectonic and functional divisions of human ventral temporal cortex

Human ventral temporal cortex (VTC) plays a pivotal role in high-level vision. An under-studied macroanatomical feature of VTC is the mid-fusiform sulcus (MFS), a shallow longitudinal sulcus separating the lateral and medial fusiform gyrus (FG). Here, we quantified the morphological features of the MFS in 69 subjects (ages 7-40), and investigated its relationship to both cytoarchitectonic and functional divisions of VTC with four main findings. First, despite being a minor sulcus, we found that the MFS is a stable macroanatomical structure present in all 138 hemispheres with morphological characteristics developed by age 7. Second, the MFS is the locus of a lateral-medial cytoarchitectonic transition within the posterior FG serving as the boundary between cytoarchitectonic regions FG1 and FG2. Third, the MFS predicts a lateral-medial functional transition in eccentricity bias representations in children, adolescents, and adults. Fourth, the anterior tip of the MFS predicts the location of a face-selective region, mFus-faces/FFA-2. These findings are the first to illustrate that a macroanatomical landmark identifies both cytoarchitectonic and functional divisions of high-level sensory cortex in humans and have important implications for understanding functional and structural organization in the human brain.

Functional characterization and differential coactivation patterns of two cytoarchitectonic visual areas on the human posterior fusiform gyrus

The ventral stream of the human extrastriate visual cortex shows a considerable functional heterogeneity from early visual processing (posterior) to higher, domain‐specific processing (anterior). The fusiform gyrus hosts several of those “high‐level” functional areas. We recently found a subdivision of the posterior fusiform gyrus on the microstructural level, that is, two distinct cytoarchitectonic areas, FG1 and FG2 (Caspers et al., Brain Structure & Function, 2013). To gain a first insight in the function of these two areas, here we studied their behavioral involvement and coactivation patterns by means of meta‐analytic connectivity modeling based on the BrainMap database (www.brainmap.org), using probabilistic maps of these areas as seed regions. The coactivation patterns of the areas support the concept of a common involvement in a core network subserving different cognitive tasks, that is, object recognition, visual language perception, or visual attention. In addition, the analysis supports the previous cytoarchitectonic parcellation, indicating that FG1 appears as a transitional area between early and higher visual cortex and FG2 as a higher‐order one. The latter area is furthermore lateralized, as it shows strong relations to the visual language processing system in the left hemisphere, while its right side is stronger associated with face selective regions. These findings indicate that functional lateralization of area FG2 relies on a different pattern of connectivity rather than side‐specific cytoarchitectonic features. Hum Brain Mapp 35:2754–2767, 2014.

Two New Cytoarchitectonic Areas on the Human Mid-Fusiform Gyrus

Abstract Areas of the fusiform gyrus (FG) within human ventral temporal cortex (VTC) process high‐level visual information associated with faces, limbs, words, and places. Since classical cytoarchitectonic maps do not adequately reflect the functional and structural heterogeneity of the VTC, we studied the cytoarchitectonic segregation in a region, which is rostral to the recently identified cytoarchitectonic areas FG1 and FG2. Using an observer‐independent and statistically testable parcellation method, we identify 2 new areas, FG3 and FG4, in 10 human postmortem brains on the mid‐FG. The mid‐fusiform sulcus reliably identifies the cytoarchitectonic transition between FG3 and FG4. We registered these cytoarchitectonic areas to the common reference space of the single‐subject Montreal Neurological Institute (MNI) template and generated probability maps, which reflect the intersubject variability of both areas. Future studies can relate in vivo neuroimaging data with these microscopically defined cortical areas to functional parcellations. We discuss these results in the context of both large‐scale functional maps and fine‐scale functional clusters that have been identified within the human VTC. We propose that our observer‐independent cytoarchitectonic parcellation of the FG better explains the functional heterogeneity of the FG compared with the homogeneity of classic cytoarchitectonic maps.

Receptor architecture of visual areas in the face and word-form recognition region of the posterior fusiform gyrus

Abstract Recently, two extrastriate visual areas on the posterior fusiform gyrus, areas FG1 and FG2, were identified based on cytoarchitectonical criteria (Caspers et al. in Brain Struct Funct 218:511–526, 2013a). They are located within the object-related ventral visual stream at the transition between early and higher-order (category-specific) visual areas. FG2 has a topographical position which is best comparable to the face or visual word-form recognition area. However, the precise function of FG2 is presently unknown. Since transmitter receptors are key molecules of neurotransmission, we analysed the regional and laminar distribution of 15 different receptor binding sites by means of quantitative in vitro receptor autoradiography. Significant differences between receptor densities of both areas were found for NMDA, GABAB, M3, nicotinic α4/β2 and 5-HT1A receptors as well as for GABAA associated benzodiazepine binding sites. These results support the cytoarchitectonic segregation of FG1 and FG2 into two distinct cortical areas. In addition, principal component and hierarchical cluster analyses of the multireceptor data of both fusiform areas and 24 visual, auditory, somatosensory and multimodal association areas not only revealed the typical receptor architectonic characteristics of visual areas for FG1 and FG2, but also suggest their putative function as object recognition regions due to the similarity of their receptor fingerprints with those of areas of the ventral visual stream. Furthermore, FG1 and FG2 build a cluster with the multimodal association areas of the inferior parietal lobule. This underlines their hierarchically high position in the visual system of the human cerebral cortex.

Gadolinium Brain Deposition after Macrocyclic Gadolinium Administration: A Pediatric Case-Control Study

Purpose To determine whether signal intensity (SI) in T1 sequences as a potential indicator of gadolinium deposition increases after repeated administration of the macrocyclic gadolinium-based contrast agents (GBCAs) gadoteridol and gadoterate meglumine in a pediatric cohort. Materials and Methods This retrospective case-control study of children with brain tumors who underwent nine or more contrast material-enhanced brain magnetic resonance (MR) imaging studies from 2008 to 2015 was approved by the local ethics board. Informed consent was obtained for MR imaging. Twenty-four case patients aged 5-18 years and appropriate control patients with nonpathologic MR neuroimaging findings (and no GBCA administration), matched for age and sex, were inculded. SI was measured on unenhanced T1-weighted MR images for the following five regions of interest (ROIs): the dentate nucleus (DN), pons, substantia nigra (SN), pulvinar thalami, and globus pallidus (GP). Paired t tests were used to compare SI and SI ratios (DN to pons, GP to thalamus) between case patients and control patients. Pearson correlations between relative signal changes and the number of GBCA administrations and total GBCA dose were calculated. Results The mean number of GBCA administrations was 14.2. No significant differences in mean SI for any ROI and no group differences were found when DN-to-pons and GP-to-pulvinar ratios were compared (DN-to-pons ratio in case patients: mean, 1.0083 ± 0.0373 [standard deviation]; DN-to-pons ratio in control patients: mean, 1.0183 ± 0.01917; P = .37; GP-to-pulvinar ratio in case patients: mean, 1.1335 ± 0.04528; and GP-to-pulvinar ratio in control patients: mean, 1.1141 ± 0.07058; P = .29). No correlation was found between the number of GBCA administrations or the total amount of GBCA administered and signal change for any ROI. (Number of GBCA applications: DN: r = -0.254, P = .31; pons: r = -0.097, P = .65; SN: r = -0.194, P = .38; GP: r = -0.175, P = .41; pulvinar: r = -0.067, P = .75; total amount of administered GBCA: DN: r = 0.091, P = .72; pons: r = 0.106, P = .62; SN: r = -0.165, P = .45; GP: r = 0.111, P = .61; pulvinar: r = 0.173, P = .42.) Conclusion Multiple intravenous administrations of these macrocyclic GBCAs in children were not associated with a measurable increase in SI in T1 sequences as an indicator of brain gadolinium deposition detectable by using MR imaging. Additional imaging and pathologic studies are needed to confirm these findings.

The Cytoarchitecture of Domain-specific Regions in Human High-level Visual Cortex

Abstract A fundamental hypothesis in neuroscience proposes that underlying cellular architecture (cytoarchitecture) contributes to the functionality of a brain area. However, this hypothesis has not been tested in human ventral temporal cortex (VTC) that contains domain‐specific regions causally involved in perception. To fill this gap in knowledge, we used cortex‐based alignment to register functional regions from living participants to cytoarchitectonic areas in ex vivo brains. This novel approach reveals 3 findings. First, there is a consistent relationship between domain‐specific regions and cytoarchitectonic areas: each functional region is largely restricted to 1 cytoarchitectonic area. Second, extracting cytoarchitectonic profiles from face‐ and place‐selective regions after back‐projecting each region to 20‐&mgr;m thick histological sections indicates that cytoarchitectonic properties distinguish these regions from each other. Third, some cytoarchitectonic areas contain more than 1 domain‐specific region. For example, face‐, body‐, and character‐selective regions are located within the same cytoarchitectonic area. We summarize these findings with a parsimonious hypothesis incorporating how cellular properties may contribute to functional specialization in human VTC. Specifically, we link computational principles to correlated axes of functional and cytoarchitectonic segregation in human VTC, in which parallel processing across domains occurs along a lateral‐medial axis while transformations of information within domain occur along an anterior‐posterior axis.

An age-related shift of resting-state functional connectivity of the subthalamic nucleus: a potential mechanism for compensating motor performance decline in older adults.

Healthy aging is associated with decline in basic motor functioning and higher motor control. Here, we investigated age-related differences in the brain-wide functional connectivity (FC) pattern of the subthalamic nucleus (STN), which plays an important role in motor response control. As earlier studies revealed functional coupling between STN and basal ganglia, which both are known to influence the conservativeness of motor responses on a superordinate level, we tested the hypothesis that STN FC with the striatum becomes dysbalanced with age. To this end, we performed a seed-based resting-state analysis of fMRI data from 361 healthy adults (mean age: 41.8, age range: 18–85) using bilateral STN as the seed region of interest. Age was included as a covariate to identify regions showing age-related changes of FC with the STN seed. The analysis revealed positive FC of the STN with several previously described subcortical and cortical regions like the anterior cingulate and sensorimotor cortex, as well as not-yet reported regions including central and posterior insula. With increasing age, we observed reduced positive FC with caudate nucleus, thalamus, and insula as well as increased positive FC with sensorimotor cortex and putamen. Furthermore, an age-related reduction of negative FC was found with precuneus and posterior cingulate cortex. We suggest that this reduced de-coupling of brain areas involved in self-relevant but motor-unrelated cognitive processing (i.e. precuneus and posterior cingulate cortex) from the STN motor network may represent a potential mechanism behind the age-dependent decline in motor performance. At the same time, older adults appear to compensate for this decline by releasing superordinate motor control areas, in particular caudate nucleus and insula, from STN interference while increasing STN-mediated response control over lower level motor areas like sensorimotor cortex and putamen.

Functional Connectivity Differences of the Subthalamic Nucleus Related to Parkinson's Disease

A typical feature of Parkinsons disease (PD) is pathological activity in the subthalamic nucleus (STN). Here, we tested whether in patients with PD under dopaminergic treatment functional connectivity of the STN differs from healthy controls (HC) and whether some brain regions show (anti‐) correlations between functional connectivity with STN and motor symptoms. We used functional magnetic resonance imaging to investigate whole‐brain resting‐state functional connectivity with STN in 54 patients with PD and 55 HC matched for age, gender, and within‐scanner motion. Compared to HC, we found attenuated negative STN‐coupling with Crus I of the right cerebellum and with right ventromedial prefrontal regions in patients with PD. Furthermore, we observed enhanced negative STN‐coupling with bilateral intraparietal sulcus/superior parietal cortex, right sensorimotor, right premotor, and left visual cortex compared to HC. Finally, we found a decline in positive STN‐coupling with the left insula related to severity of motor symptoms and a decline of inter‐hemispheric functional connectivity between left and right STN with progression of PD‐related motor symptoms. Motor symptom related uncoupling of the insula, a key region in the saliency network and for executive function, from the STN might be associated with well‐known executive dysfunction in PD. Moreover, uncoupling between insula and STN might also induce an insufficient setting of thresholds for the discrimination between relevant and irrelevant salient environmental stimuli, explaining observations of disturbed response control in PD. In sum, motor symptoms in PD are associated with a reduced coupling between STN and a key region for executive function. Hum Brain Mapp 37:1235–1253, 2016.

Coordinate-Based Pattern-Mining on Functional Neuroimaging Databases

Aiming to exploit the rich fundus of available functional neuroimaging data, we present a coordinate-based pattern-mining approach. Gaussian mixture modeling is applied on three-dimensional brain coordinates obtained from neuroimaging databases collecting peak activations seen in functional neuroimaging experiments. We show how the Apriori algorithm used in association analysis can be applied to the obtained results, revealing frequent patterns of the identified coordinate clusters. These patterns can be interpreted as common networks of functionally connected brain regions and hence give deeper insights into the functional organization of the human brain.

PaMiNI: A comprehensive system for mining frequent neuronal patterns of the human brain

Large-scale neuroimaging databases provide a rich fundus of functional neuroimaging experiments exhibiting maximum activation coordinates for specific task conditions. Aiming to explore major neuronal networks of the human brain, we developed a meta-analytic pattern-mining approach which combines Gaussian mixture modeling with the Apriori algorithm to identify frequent activation patterns within these databases. The approach has been implemented in the PaMiNI (Pattern Mining in NeuroImaging) system, providing manifold facilities for the finding, inspection, and analysis of relevant patterns. After briefly sketching the background of PaMiNI, we give an overview of the system and describe its architecture. Using an example application, a system walkthrough illustrates how PaMiNI can be used for the discovery of networks comprising functionally connected brain regions.