Claudia Rottschy

A quantitative meta-analysis and review of motor learning in the human brain

Neuroimaging studies have improved our understanding of which brain structures are involved in motor learning. Despite this, questions remain regarding the areas that contribute consistently across paradigms with different task demands. For instance, sensorimotor tasks focus on learning novel movement kinematics and dynamics, while serial response time task (SRTT) variants focus on sequence learning. These differing task demands are likely to elicit quantifiably different patterns of neural activity on top of a potentially consistent core network. The current study identified consistent activations across 70 motor learning experiments using activation likelihood estimation (ALE) meta-analysis. A global analysis of all tasks revealed a bilateral cortical–subcortical network consistently underlying motor learning across tasks. Converging activations were revealed in the dorsal premotor cortex, supplementary motor cortex, primary motor cortex, primary somatosensory cortex, superior parietal lobule, thalamus, putamen and cerebellum. These activations were broadly consistent across task specific analyses that separated sensorimotor tasks and SRTT variants. Contrast analysis indicated that activity in the basal ganglia and cerebellum was significantly stronger for sensorimotor tasks, while activity in cortical structures and the thalamus was significantly stronger for SRTT variants. Additional conjunction analyses then indicated that the left dorsal premotor cortex was activated across all analyses considered, even when controlling for potential motor confounds. The highly consistent activation of the left dorsal premotor cortex suggests it is a critical node in the motor learning network.

Activation likelihood estimation meta-analysis of motor-related neural activity after stroke

Over the past two decades, several functional neuroimaging experiments demonstrated changes in neural activity in stroke patients with motor deficits. Conclusions from single experiments are usually constrained by small sample sizes and high variability across studies. Here, we used coordinate-based activation likelihood estimation meta-analyses to provide a quantitative synthesis of the current literature on motor-related neural activity after stroke. Of over 1000 PubMed search results through January 2011, 36 studies reported standardized whole-brain group coordinates. Meta-analyses were performed on 54 experimental contrasts for movements of the paretic upper limb (472 patients, 452 activation foci) and on 20 experiments comparing activation between patients and healthy controls (177 patients, 113 activation foci). We computed voxelwise correlations between activation likelihood and motor impairment, time post-stroke, and task difficulty across samples. Patients showed higher activation likelihood in contralesional primary motor cortex (M1), bilateral ventral premotor cortex and supplementary motor area (SMA) relative to healthy subjects. Activity in contralesional areas was more likely found for active than for passive tasks. Better motor performance was associated with greater activation likelihood in ipsilesional M1, pre-SMA, contralesional premotor cortex and cerebellum. Over time post-stroke, activation likelihood in bilateral premotor areas and medial M1 hand knob decreased. This meta-analysis shows that increased activation in contralesional M1 and bilateral premotor areas is a highly consistent finding after stroke despite high inter-study variance resulting from different fMRI tasks and motor impairment levels. However, a good functional outcome relies on the recruitment of the original functional network rather than on contralesional activity.

Ventral Visual Cortex in Humans: Cytoarchitectonic Mapping of Two Extrastriate Areas

The extrastriate visual cortex forms a complex system enabling the analysis of visually presented objects. To gain deeper insight into the anatomical basis of this system, we cytoarchitectonically mapped the ventral occipital cortex lateral to BA 18/V2 in 10 human postmortem brains. The anatomical characterization of this part of the ventral stream was performed by examination of cell‐body‐stained histological sections using quantitative cytoarchitectonic analysis. First, the gray level index (GLI) was measured in the ventral occipital lobe. Cytoarchitectonic borders, i.e., significant changes in the cortical lamination pattern, were then identified using an observer‐independent algorithm based on multivariate analysis of GLI profiles. Two distinct cytoarchitectonic areas (hOC3v, hOC4v) were characterized in the ventral extrastriate cortex lateral to BA 18/V2. Area hOC3v was found in the collateral sulcus. hOC4v was located in this sulcus and also covered the fusiform gyrus in more occipital sections. Topographically, these areas thus seem to represent the anatomical substrates of functionally defined areas, VP/V3v and V4/V4v. Following histological analysis, the delineated cytoarchitectonic areas were transferred to 3D reconstructions of the respective postmortem brains, which in turn were spatially normalized to the Montreal Neurological Institute reference space. A probabilistic map was generated for each area which describes how many brains had a representation of this area in a particular voxel. These maps can now be used to identify the anatomical correlates of functional activations observed in neuroimaging experiments to enable a more informed investigation into the many open questions regarding the organization of the human visual cortex. Hum Brain Mapp 2007.

Networks of task co-activations

Recent progress in neuroimaging informatics and meta-analytic techniques has enabled a novel domain of human brain connectomics research that focuses on task-dependent co-activation patterns across behavioral tasks and cognitive domains. Here, we review studies utilizing the BrainMap database to investigate data trends in the activation literature using methods such as meta-analytic connectivity modeling (MACM), connectivity-based parcellation (CPB), and independent component analysis (ICA). We give examples of how these methods are being applied to learn more about the functional connectivity of areas such as the amygdala, the default mode network, and visual area V5. Methods for analyzing the behavioral metadata corresponding to regions of interest and to their intrinsically connected networks are described as a tool for local functional decoding. We finally discuss the relation of observed co-activation connectivity results to resting state connectivity patterns, and provide implications for future work in this domain.

The role of the right temporoparietal junction in attention and social interaction as revealed by ALE meta-analysis

The right temporoparietal junction (rTPJ) is frequently associated with different capacities that to shift attention to unexpected stimuli (reorienting of attention) and to understand others’ (false) mental state [theory of mind (ToM), typically represented by false belief tasks]. Competing hypotheses either suggest the rTPJ representing a unitary region involved in separate cognitive functions or consisting of subregions subserving distinct processes. We conducted activation likelihood estimation (ALE) meta-analyses to test these hypotheses. A conjunction analysis across ALE meta-analyses delineating regions consistently recruited by reorienting of attention and false belief studies revealed the anterior rTPJ, suggesting an overarching role of this specific region. Moreover, the anatomical difference analysis unravelled the posterior rTPJ as higher converging in false belief compared with reorienting of attention tasks. This supports the concept of an exclusive role of the posterior rTPJ in the social domain. These results were complemented by meta-analytic connectivity mapping (MACM) and resting-state functional connectivity (RSFC) analysis to investigate whole-brain connectivity patterns in task-constrained and task-free brain states. This allowed for detailing the functional separation of the anterior and posterior rTPJ. The combination of MACM and RSFC mapping showed that the posterior rTPJ has connectivity patterns with typical ToM regions, whereas the anterior part of rTPJ co-activates with the attentional network. Taken together, our data suggest that rTPJ contains two functionally fractionated subregions: while posterior rTPJ seems exclusively involved in the social domain, anterior rTPJ is involved in both, attention and ToM, conceivably indicating an attentional shifting role of this region.

Laminar distribution and co-distribution of neurotransmitter receptors in early human visual cortex

The laminar distributions of 16 neurotransmitter receptor binding sites were analysed in visual cortical areas V1–V3 by quantitative in vitro receptor autoradiography. For each receptor (glutamatergic: AMPA, kainate, NMDA; cholinergic: M1, M2, M3, nicotinic; GABAergic: GABAA, GABAB, benzodiazepine binding-sites; adrenergic: α1, α2; serotoninergic: 5-HT1A, 5-HT2; dopaminergic: D1; Adenosine: A1), density profiles extracted perpendicular to the cortical surface were compared to cyto- and myeloarchitectonic profiles sampled at corresponding cortical sites. When testing for differences in laminar distribution patterns, all receptor-density profiles differed significantly from the cyto- and myeloarchitectonic ones. These results indicate that receptor distribution is an independent feature of the cortical architecture not predictable by densities of cell bodies or myelinated fibres. Receptor co-distribution was studied by cluster analyses, revealing several groups of receptors, which showed similar laminar distribution patterns across all analysed areas (V1–V3). Other receptors were co-distributed in extrastriate but not primary visual cortex. Finally, some receptors were not co-distributed with any of the analysed other ones. A comparison of the laminar patterns of receptor binding sites in the human visual cortex with those reported for non-human primates and other mammals showed that the laminar distributions of cholinergic and glutamatergic receptors seem largely preserved, while serotoninergic and adrenergic receptors appear to be more variable between different species.

Organizational Principles of Human Visual Cortex Revealed by Receptor Mapping

This receptorarchitectonic study of the human visual cortex investigated interareal differences in mean receptor concentrations and laminar distribution patterns of 16 neurotransmitter receptors in the dorsal and ventral parts of areas V1, V2, V3 as well as in adjoining areas V4 (ventrally) and V3A (dorsally). Both the functional hierarchy of these areas and a distinction between dorsal and ventral visual cortices were reflected by significant receptorarchitectonic differences. The observation that dorso-ventral differences existed in all extrastriate areas (including V2) is particularly important for the discussion about the relationship between dorsal and ventral V3 as it indicates that a receptorarchitectonic distinction between the ventral and dorsal visual cortices is present in but not specific to V3. This molecular specificity is mirrored by previously reported differences in retinal microstructure and functional differences as revealed in behavioral experiments demonstrating differential advantages for stimulus processing in the upper and lower visual fields. We argue that these anatomical and functional differences may be regarded as the result of an evolutionary optimization adapting to the processing of the most relevant stimuli occurring in the upper and lower visual fields.

Alternate-Form Reliability of the Montreal Cognitive Assessment Screening Test in a Clinical Setting

Aims: The Montreal Cognitive Assessment (MoCA) has gained recognition for its validity in detecting cognitive impairment in several clinical populations. For serial assessments, alternate forms are needed to overcome possible practice effects. Our objective was to investigate the reliability of two German MoCA alternate forms for longitudinal assessment applications. Methods: The original and one of two alternate forms of the MoCA were administered within a 60-min interval of a clinical interview in a counterbalanced order to 100 healthy elderly controls, 30 patients with mild cognitive impairment (MCI) and 30 patients with Alzheimer’s disease (AD). The diagnosis of the majority of patients was supported by in vivo AD pathology biomarkers. Results: There was a strong correlation between the alternate forms and the original MoCA in all groups, but particularly in the clinical samples. Total mean scores did not differ significantly between the MoCA versions, even taking into account the presentation order. As in previous studies, age and education influenced performance in the MoCA. The same pattern of group differences (controls > MCI > AD) was observed for each of the versions. Conclusion: All three forms can be reliably and interchangeably used in serial cognitive assessment, confirming the MoCA’s applicability in research and clinical longitudinal approaches.

Cytoarchitectonic mapping of the human dorsal extrastriate cortex.

The dorsal visual stream consists of several functionally specialized areas, but most of their cytoarchitectonic correlates have not yet been identified in the human brain. The cortex adjacent to Brodmann area 18/V2 was therefore analyzed in serial sections of ten human post-mortem brains using morphometrical and multivariate statistical analyses for the definition of areal borders. Two previously unknown cytoarchitectonic areas (hOc3d, hOc4d) were detected. They occupy the medial and, to a smaller extent, lateral surface of the occipital lobe. The larger area, hOc3d, is located dorso-lateral to area V2 in the region of superior and transverse occipital, as well as parieto-occipital sulci. Area hOc4d was identified rostral to hOc3d; it differed from the latter by larger pyramidal cells in lower layer III, thinner layers V and VI, and a sharp cortex-white-matter borderline. The delineated areas were superimposed in the anatomical MNI space, and probabilistic maps were calculated. They show a relatively high intersubject variability in volume and position. Based on their location and neighborhood relationship, areas hOc3d and hOc4d are putative anatomical substrates of functionally defined areas V3d and V3a, a hypothesis that can now be tested by comparing probabilistic cytoarchitectonic maps and activation studies of the living human brain.

Comparison of functional and cytoarchitectonic maps of human visual areas V1, V2, V3d, V3v, and V4(v).

Cytoarchitectonic maps of human striate and extrastriate visual cortex based upon post-mortem brains can be correlated with functionally defined cortical areas using, for example, fMRI. We here assess the correspondence of anatomical maps of the visual cortex with functionally defined in vivo visual areas using retinotopic mapping. To this end, anatomical maximum probability maps (aMPM) derived from individual cytoarchitectonic maps of striate and extrastriate visual areas were compared with functional localisers for the early visual areas. Using fMRI, we delineated dorsal and ventral human retinotopic areas V1, V2, and V3, as well as a quarter-field visual field representation lateral to V3v, V4(v), in 24 healthy subjects. Based on these individual definitions, a functional maximum probability map (fMPM) was then computed in analogy to the aMPM. Functional and anatomical MPMs were highly correlated at group level: 78.5% of activated voxels in the fMPM were correctly assigned by the aMPM. The group aMPM was less effective in predicting functional retinotopic areas in the individual brain due to the large inter-individual variability in the location and extent of visual areas (mean overlap 32-69%). We conclude that cytoarchitectonic maps of striate and extrastriate visual areas may provide a valuable method for assigning functional group activations and thus add valuable a priori knowledge to the analysis of functional imaging data of the visual cortex.