Stefan Heim

Testing anatomically specified hypotheses in functional imaging using cytoarchitectonic maps.

The statistical inference on functional imaging data is severely complicated by the embedded multiple testing problem. Defining a region of interest (ROI) where the activation is hypothesized a priori helps to circumvent this problem, since in this case the inference is restricted to fewer simultaneous tests, rendering it more sensitive. Cytoarchitectonic maps obtained from postmortem brains provide objective, a priori ROIs that can be used to test anatomically specified hypotheses about the localization of functional activations. We here analyzed three methods for the definition of ROIs based on probabilistic cytoarchitectonic maps. (1) ROIs defined by the volume assigned to a cytoarchitectonic area in the summary map of all areas (maximum probability map, MPM), (2) ROIs based on thresholding the individual probabilistic maps and (3) spherical ROIs build around the cytoarchitectonic center of gravity. The quality with which the thus defined ROIs represented the respective cytoarchitectonic areas as well as their sensitivity for detecting functional activations was subsequently statistically evaluated. Our data showed that the MPM method yields ROIs, which reflect most adequately the underlying anatomical hypotheses. These maps also show a high degree of sensitivity in the statistical analysis. We thus propose the use of MPMs for the definition of ROIs. In combination with thresholding based on the Gaussian random field theory, these ROIs can then be applied to test anatomically specified hypotheses in functional neuroimaging studies.

A systems perspective on the effective connectivity of overt speech production

The aim of this study was to provide a computational system model of effective connectivity in the human brain underlying overt speech production. Meta-analysis of neuroimaging studies and functional magnetic resonance imaging data acquired during a verbal fluency task revealed a core network consisting of Brodmanns area (BA) 44 in Brocas region, anterior insula, basal ganglia, cerebellum, premotor cortex (PMC, BA 6) and primary motor cortex (M1, areas 4a/4p). Dynamic causal modelling (DCM) indicated the highest evidence for a system architecture featuring the insula in a serial position between BA 44 and two parallel nodes (cerebellum/basal ganglia), from which information converges onto the PMC and finally M1. Parameter inference revealed that effective connectivity from the insular relay into the cerebellum/basal ganglia is primarily task driven (preparation) while the output into the cortical motor system strongly depends on the actual word production rate (execution). DCM hence allowed not only a quantitative characterization of the human speech production network, but also the distinction of a preparatory and an executive subsystem within it. The proposed model of physiological integration during speech production may now serve as a reference for investigations into the neurobiology of pathological states such as dysarthria and apraxia of speech.

Effective connectivity of the left BA 44, BA 45, and inferior temporal gyrus during lexical and phonological decisions identified with DCM

Distinct regions in the left inferior frontal gyrus (IFG) preferentially support the processing of different word‐types (e.g., real words, pseudowords) and tasks (e.g., lexical decisions, phonological decisions) in visual word recognition. However, the functional connectivity underlying the task‐related specialisation of regions in the left IFG is not yet well understood. In this study we investigated the neural mechanisms driving the interaction of WORD‐TYPE (real word vs. pseudoword) and TASK (lexical vs. phonological decision) in Brodmanns area (BA) 45 in the left IFG using dynamic causal modelling (DCM). Four different models were compared, all of which included left BA44, left BA45, and left inferior temporal gyrus (ITG). In each model, the visual presentation of words and pseudowords is assumed to directly evoke activity in the ITG and is then thought to be subsequently propagated to BA45 and to BA44 via direct intrinsic connections. The models differed with regard to which connections were modulated by the different tasks. Both tasks were assumed to either modulate the ITG_BA45 connection (Model #1), or the BA44_BA45 connection (Model #2), or both connections in parallel (Model #3). In Model #4 lexical decisions modulated the ITG_BA45 connection, whereas phonological decisions modulated the BA44_BA45 connection. Bayesian model selection revealed a superiority of Model #1. In this model, the strength of the ITG_BA45 connection was enhanced during lexical decisions. This model is in line with the hypothesis that left BA 45 supports explicit lexical decisions during visual word recognition based on lexical access in the ITG. Hum Brain Mapp, 2009.

Phonological processing during language production: fMRI evidence for a shared production-comprehension network.

Studies of phonological processes during language comprehension consistently report activation of the superior portion of Brocas area. In the domain of language production, however, there is no unequivocal evidence for the contribution of Brocas area to phonological processing. The present event-related fMRI study investigated the existence of a common neural network for phonological decisions in comprehension and production by using production tasks most comparable to those previously used in comprehension. Subjects performed two decision tasks on the initial phoneme of German picture names (/b/ or not? Vowel or not?). A semantic decision task served as a baseline for both phonological tasks. The contrasts between each phonological task and the semantic task were calculated, and a conjunction analysis was performed. There was significant activation in the superior portion of Brocas area (Brodmanns area (BA) 44) in the conjunction analysis, also present in each single contrast. In addition, further left frontal (BA 45/46) and temporal (posterior superior temporal gyrus) areas known to support phonological processing in both production and comprehension were activated. The results suggest the existence of a shared fronto-temporal neural network engaged in the processing of phonological information in both perception and production.

Distributed cortical networks for syntax processing: Broca's area as the common denominator

Different types of syntactic information (word category, grammatical gender) are processed at different times during word recognition. However, it is an open issue which brain systems support these processes. In the present event-related fMRI study, subjects performed either a syntactic gender decision task on German nouns (GEN), a word category decision task (WC, nouns vs. prepositions), or a physical baseline task (BASE). Reaction times in WC were faster than in GEN, supporting earlier electrophysiological results. Relative to BASE, both syntactic tasks activated the inferior tip of BA 44. In addition, BA 45 showed activation in GEN, whereas BA 47 was activated in WC. The imaging data indicate that the inferior portion of BA 44 together with type-specific prefrontal areas supports both initial word category related and later syntactic processes.

Different roles of cytoarchitectonic BA 44 and BA 45 in phonological and semantic verbal fluency as revealed by dynamic causal modelling

The interactions of left cytoarchitectonic BA 44 and BA 45 during semantic and phonological verbal fluency tasks were investigated using dynamic causal modelling (DCM). Three different models were tested, all of which featured BA 44 and BA 45 as top-down driven interconnected nodes projecting to the motor cortex as the final output region. Model #1 represents the hypothesis that BA 45 is involved in lexical retrieval including both semantic and phonological processes, while BA 44 supports other phonological processes. Model #2 reflects the notion of a clear-cut segregation of computational processes sustained by BA 44 (phonological processing) and BA 45 (semantic processing). Model #3 was based on the hypothesis that both BA 44 and BA 45 support semantic and phonological processing. When these models were compared against each other by Bayesian model selection, evidence emerged in favour of the first model, implying that BA 45 supports word retrieval processes whereas BA 44 is involved in processing phonological information during word generation. In a subsequent analysis of the derived model parameters for model #1, all connection strengths were significantly positive except for the inhibitory coupling between BA 44 and BA 45. This inhibition may reflect how the phonological analysis in BA 44 during word generation constrains lexical word retrieval in BA 45. To conclude, DCM provided additional insights into the roles of BA 44 and BA 45 during verbal fluency revealing the involvement of BA 45 in lexical retrieval and the relevance of BA 44 for phonological processing during word generation.

Are Numbers Special? Comparing the Generation of Verbal Materials From Ordered Categories (Months) to Numbers and Other Categories (Animals) in an fMRI Study

Months, days of the week, and numbers differ from other verbal concepts because they are ordered in a sequence, whereas no order is imposed on members of other categories, such as animals or tools. Recent studies suggest that numbers activate a representation of their quantity within the intraparietal sulcus (IPS) automatically, that is, in tasks that do not require the processing of quantity. It is unclear, however, whether ordered verbal materials in general and not only numbers activate the IPS in such tasks. In the present functional magnetic resonance imaging study word generation of months, numbers, and animals were compared. Word generation of numbers and nonnumerical materials from an ordered category (months) activated the IPS more strongly than generating items from a not‐ordered category such as animals or the verbal control conditions. An ROI analysis of three subregions within the anterior IPS revealed that the most anterior and lateral of these regions, human intraparietal area hIP2, shows a greater sensitivity to ordered materials than the other two areas, hIP1 and hIP3. Interestingly, no difference in activation was observed within the IPS between numbers and months suggesting that the activation of the IPS might not be modulated by the additional quantity information carried by numbers. Hum Brain Mapp, 2008.

Are abstract action words embodied? An fMRI investigation at the interface between language and motor cognition

The cognitive and neural representation of abstract words is still an open question for theories of embodied cognition. Generally, it is proposed that abstract words are grounded in the activation of sensorimotor or at least experiential properties, exactly as concrete words. Further behavioral theories propose multiple representations evoked by abstract and concrete words. We conducted a functional magnetic resonance imaging (fMRI) study to investigate the neural correlates of concrete and abstract multi-word expressions in an action context. Participants were required to read simple sentences which combined each concrete noun with an adequate concrete verb and an adequate abstract verb, as well as an adequate abstract noun with either kind of verbs previously used. Thus, our experimental design included a continuum from pure concreteness to mere abstractness. As expected, comprehension of both concrete and abstract language content activated the core areas of the sensorimotor neural network namely the left lateral (precentral gyrus) and medial (supplementary motor area) premotor cortex. While the purely concrete multi-word expressions elicited activations within the left inferior frontal gyrus (pars triangularis) and two foci within the left inferior parietal cortex, the purely abstract multi-word expressions were represented in the anterior part of left middle temporal gyrus that is part of the language processing system. Although the sensorimotor neural network is engaged in both concrete and abstract language contents, the present findings show that concrete multi-word processing relies more on the sensorimotor system, and abstract multi-word processing relies more on the linguistic system.

Assessing DTI data quality using bootstrap analysis

Diffusion tensor imaging (DTI) is an established method for characterizing and quantifying ultrastructural brain tissue properties. However, DTI‐derived variables are affected by various sources of signal uncertainty. The goal of this study was to establish an objective quality measure for DTI based on the nonparametric bootstrap methodology. The confidence intervals (CIs) of white matter (WM) fractional anisotropy (FA) and Clinear were determined by bootstrap analysis and submitted to histogram analysis. The effects of artificial noising and edge‐preserving smoothing, as well as enhanced and reduced motion were studied in healthy volunteers. Gender and age effects on data quality as potential confounds in group comparison studies were analyzed. Additional noising showed a detrimental effect on the mean, peak position, and height of the respective CIs at 10% of the original background noise. Inverse changes reflected data improvement induced by edge‐preserving smoothing. Motion‐dependent impairment was also well depicted by bootstrap‐derived parameters. Moreover, there was a significant gender effect, with females displaying less dispersion (attributable to elevated SNR). In conclusion, the bootstrap procedure is a useful tool for assessing DTI data quality. It is sensitive to both noise and motion effects, and may help to exclude confounding effects in group comparisons. Magn Reson Med 52:582–589, 2004.

Left cytoarchitectonic area 44 supports selection in the mental lexicon during language production

This functional magnetic resonance imaging (fMRI) study investigated the role of Broca’s region for selecting semantic, syntactic, and phonological information during picture naming. According to psycholinguistic theory, selection is reflected in speech latency differences, e.g. during priming. Here, homogenous (priming) blocks in which German picture names had the same semantic category, syntactic gender, or initial phoneme alternated with heterogeneous (non-priming) blocks. Speech latencies revealed a negative priming effect. Speech latencies were used as regressors for the fMRI data in order to tap selection processes. In Broca’s region (BA 44), among others, fMRI data showed repetition priming, which was positive for semantic and syntactic but negative for phonological selection. The different effects in area 44 are discussed in terms of psycholinguistic theory. Overall, the activation pattern is in line with the hypothesis that area 44 generally supports selection processes during noun production at several levels of the mental lexicon.