Dorothee Saur

Ventral and dorsal pathways for language

Built on an analogy between the visual and auditory systems, the following dual stream model for language processing was suggested recently: a dorsal stream is involved in mapping sound to articulation, and a ventral stream in mapping sound to meaning. The goal of the study presented here was to test the neuroanatomical basis of this model. Combining functional magnetic resonance imaging (fMRI) with a novel diffusion tensor imaging (DTI)-based tractography method we were able to identify the most probable anatomical pathways connecting brain regions activated during two prototypical language tasks. Sublexical repetition of speech is subserved by a dorsal pathway, connecting the superior temporal lobe and premotor cortices in the frontal lobe via the arcuate and superior longitudinal fascicle. In contrast, higher-level language comprehension is mediated by a ventral pathway connecting the middle temporal lobe and the ventrolateral prefrontal cortex via the extreme capsule. Thus, according to our findings, the function of the dorsal route, traditionally considered to be the major language pathway, is mainly restricted to sensory-motor mapping of sound to articulation, whereas linguistic processing of sound to meaning requires temporofrontal interaction transmitted via the ventral route.

Combining functional and anatomical connectivity reveals brain networks for auditory language comprehension

Cognitive functions are organized in distributed, overlapping, and interacting brain networks. Investigation of those large-scale brain networks is a major task in neuroimaging research. Here, we introduce a novel combination of functional and anatomical connectivity to study the network topology subserving a cognitive function of interest. (i) In a given network, direct interactions between network nodes are identified by analyzing functional MRI time series with the multivariate method of directed partial correlation (dPC). This method provides important improvements over shortcomings that are typical for ordinary (partial) correlation techniques. (ii) For directly interacting pairs of nodes, a region-to-region probabilistic fiber tracking on diffusion tensor imaging data is performed to identify the most probable anatomical white matter fiber tracts mediating the functional interactions. This combined approach is applied to the language domain to investigate the network topology of two levels of auditory comprehension: lower-level speech perception (i.e., phonological processing) and higher-level speech recognition (i.e., semantic processing). For both processing levels, dPC analyses revealed the functional network topology and identified central network nodes by the number of direct interactions with other nodes. Tractography showed that these interactions are mediated by distinct ventral (via the extreme capsule) and dorsal (via the arcuate/superior longitudinal fascicle fiber system) long- and short-distance association tracts as well as commissural fibers. Our findings demonstrate how both processing routines are segregated in the brain on a large-scale network level. Combining dPC with probabilistic tractography is a promising approach to unveil how cognitive functions emerge through interaction of functionally interacting and anatomically interconnected brain regions.

Damage to ventral and dorsal language pathways in acute aphasia

Converging evidence from neuroimaging studies and computational modelling suggests an organization of language in a dual dorsal–ventral brain network: a dorsal stream connects temporoparietal with frontal premotor regions through the superior longitudinal and arcuate fasciculus and integrates sensorimotor processing, e.g. in repetition of speech. A ventral stream connects temporal and prefrontal regions via the extreme capsule and mediates meaning, e.g. in auditory comprehension. The aim of our study was to test, in a large sample of 100 aphasic stroke patients, how well acute impairments of repetition and comprehension correlate with lesions of either the dorsal or ventral stream. We combined voxelwise lesion-behaviour mapping with the dorsal and ventral white matter fibre tracts determined by probabilistic fibre tracking in our previous study in healthy subjects. We found that repetition impairments were mainly associated with lesions located in the posterior temporoparietal region with a statistical lesion maximum in the periventricular white matter in projection of the dorsal superior longitudinal and arcuate fasciculus. In contrast, lesions associated with comprehension deficits were found more ventral-anterior in the temporoprefrontal region with a statistical lesion maximum between the insular cortex and the putamen in projection of the ventral extreme capsule. Individual lesion overlap with the dorsal fibre tract showed a significant negative correlation with repetition performance, whereas lesion overlap with the ventral fibre tract revealed a significant negative correlation with comprehension performance. To summarize, our results from patients with acute stroke lesions support the claim that language is organized along two segregated dorsal–ventral streams. Particularly, this is the first lesion study demonstrating that task performance on auditory comprehension measures requires an interaction between temporal and prefrontal brain regions via the ventral extreme capsule pathway.

Structural Connectivity for Visuospatial Attention: Significance of Ventral Pathways

In the present study, we identified the most probable trajectories of point-to-point segregated connections between functional attentional centers using a combination of functional magnetic resonance imaging and a novel diffusion tensor imaging-based algorithm for pathway extraction. Cortical regions activated by a visuospatial attention task were subsequently used as seeds for probabilistic fiber tracking in 26 healthy subjects. Combining probability maps of frontal and temporoparietal regions yielded a network that consisted of dorsal and ventral connections. The dorsal connections linked temporoparietal cortex with the frontal eye field and area 44 of the inferior frontal gyrus (IFG). Traveling along superior longitudinal and arcuate fascicles, these fibers are well described in relation to spatial attention. However, the ventral connections, which traveled in the white matter between insula (INS) cortex and putamen parallel to the sylvian fissure, were not previously described for visuospatial attention. Linking temporoparietal cortex with anterior INS and area 45 of IFG, these connections may provide an anatomical substrate for crossmodal cortical integration needed for stimulus perception and response in relation to current intention. The newly anatomically described integral network for visuospatial attention might improve the understanding of spatial attention deficits after white matter lesions.

Early functional magnetic resonance imaging activations predict language outcome after stroke

An accurate prediction of system-specific recovery after stroke is essential to provide rehabilitation therapy based on the individual needs. We explored the usefulness of functional magnetic resonance imaging scans from an auditory language comprehension experiment to predict individual language recovery in 21 aphasic stroke patients. Subjects with an at least moderate language impairment received extensive language testing 2 weeks and 6 months after left-hemispheric stroke. A multivariate machine learning technique was used to predict language outcome 6 months after stroke. In addition, we aimed to predict the degree of language improvement over 6 months. 76% of patients were correctly separated into those with good and bad language performance 6 months after stroke when based on functional magnetic resonance imaging data from language relevant areas. Accuracy further improved (86% correct assignments) when age and language score were entered alongside functional magnetic resonance imaging data into the fully automatic classifier. A similar accuracy was reached when predicting the degree of language improvement based on imaging, age and language performance. No prediction better than chance level was achieved when exploring the usefulness of diffusion weighted imaging as well as functional magnetic resonance imaging acquired two days after stroke. This study demonstrates the high potential of current machine learning techniques to predict system-specific clinical outcome even for a disease as heterogeneous as stroke. Best prediction of language recovery is achieved when the brain activation potential after system-specific stimulation is assessed in the second week post stroke. More intensive early rehabilitation could be provided for those with a predicted poor recovery and the extension to other systems, for example, motor and attention seems feasible.

Neurobiology of Language Recovery After Stroke: Lessons From Neuroimaging Studies

Language is organized in large-scale, predominantly left-lateralized, temporo-parieto-frontal networks in the human brain. After focal brain damage (eg, ischemic stroke), this network organization enables the brain to adaptively reorganize language functions in order to compensate lesion effects. Here, we summarize how structural and functional neuroimaging methods contribute to the current understanding of loss and recovery of language functions after stroke. This includes voxelwise lesion-behavior mapping, functional imaging for mapping reorganizational mechanisms from acute to chronic stroke, as well as imaging based outcome prediction. The review is complemented by an introductory section on language organization in the healthy brain.

Connecting and merging fibres: pathway extraction by combining probability maps.

Probability mapping of connectivity is a powerful tool to determine the fibre structure of white matter in the brain. Probability maps are related to the degree of connectivity to a chosen seed area. In many applications, however, it is necessary to isolate a fibre bundle that connects two areas. A frequently suggested solution is to select curves, which pass only through two or more areas. This is very inefficient, especially for long-distance pathways and small areas. In this paper, a novel probability-based method is presented that is capable of extracting neuronal pathways defined by two seed points. A Monte Carlo simulation based tracking method, similar to the Probabilistic Index of Connectivity (PICo) approach, was extended to preserve the directional information of the main fibre bundles passing a voxel. By combining two of these extended visiting maps arising from different seed points, two independent parameters are determined for each voxel: the first quantifies the uncertainty that a voxel is connected to both seed points; the second represents the directional information and estimates the proportion of fibres running in the direction of the other seed point (connecting fibre) or face a third area (merging fibre). Both parameters are used to calculate the probability that a voxel is part of the bundle connecting both seed points. The performance and limitations of this DTI-based method are demonstrated using simulations as well as in vivo measurements.

Please don’t underestimate the ventral pathway in language

In a recent article entitled ‘Pathways to language’ [1], Friederici describes the dorsal pathway, along the arcuate fascicle as ‘of particular importance for higher-order language processing’. She supports her notion by misquoting a recent publication of ours [2] that ‘the dorsal route to be responsible for sound-to-meaning mapping’, which is contrary to our findings. We found that the dorsal pathway connects regions activated during repetition of pseudowords, that we interpreted as used for ‘sensorimotor mapping of sound to articulation’ [3].

Perturbation of the left inferior frontal gyrus triggers adaptive plasticity in the right homologous area during speech production

Significance The role of the right hemisphere in aphasia recovery is unclear. We demonstrate that a virtual lesion of left inferior frontal gyrus (IFG) decreased activity in the targeted area and increased activity in the contralateral homologous area during pseudoword repetition. This was associated with a stronger facilitatory drive from the right IFG to the left IFG. Importantly, responses became faster with increased influence of the right IFG on the left IFG. Our results shed new light on the dynamic regulation of interhemispheric interactions in the human brain. Particularly, these findings are of potential importance for understanding language recovery after left-hemispheric stroke, indicating that homologous right hemisphere areas actively contribute to language function after a left hemisphere lesion. The role of the right hemisphere in aphasia recovery after left hemisphere damage remains unclear. Increased activation of the right hemisphere has been observed after left hemisphere damage. This may simply reflect a release from transcallosal inhibition that does not contribute to language functions. Alternatively, the right hemisphere may actively contribute to language functions by supporting disrupted processing in the left hemisphere via interhemispheric connections. To test this hypothesis, we applied off-line continuous theta burst stimulation (cTBS) over the left inferior frontal gyrus (IFG) in healthy volunteers, then used functional MRI to investigate acute changes in effective connectivity between the left and right hemispheres during repetition of auditory and visual words and pseudowords. In separate sessions, we applied cTBS over the left anterior IFG (aIFG) or posterior IFG (pIFG) to test the anatomic specificity of the effects of cTBS on speech processing. Compared with cTBS over the aIFG, cTBS over the pIFG suppressed activity in the left pIFG and increased activity in the right pIFG during pseudoword vs. word repetition in both modalities. This effect was associated with a stronger facilitatory drive from the right pIFG to the left pIFG during pseudoword repetition. Critically, response became faster as the influence of the right pIFG on left pIFG increased, indicating that homologous areas in the right hemisphere actively contribute to language function after a focal left hemisphere lesion. Our findings lend further support to the notion that increased activation of homologous right hemisphere areas supports aphasia recovery after left hemisphere damage.

Iomazenil-Single-Photon Emission Computed Tomography Reveals Selective Neuronal Loss in Magnetic Resonance-Defined Mismatch Areas

Background and Purpose— The mismatch of hypoperfused tissue on perfusion imaging and ischemic tissue on diffusion-weighted imaging is used as a surrogate marker for thrombolytic therapy in the extended time window. Mismatch tissue may recover completely, progress toward infarction, or proceed toward incomplete infarction with selective loss of cortical neurons. We used [123I]iomazenil–single-photon emission computed tomography (IMZ-SPECT) to characterize the neuronal integrity of reperfused “tissue at risk of infarction” that appeared morphologically intact on follow-up magnetic resonance imaging (MRI). Methods— Twelve patients with acute stroke with striatocapsular (SC) infarctions were examined with multimodal MRI at days 0, 1, and 7; IMZ-SPECT was performed at days 5 to 15. The PI at day 0, fluid-attenuated inversion recovery (FLAIR) image at day 7, and IMZ-SPECT were coregistered and stereotactically normalized. The mismatch volume of interest (VOI) was defined as the initial PI lesion subtracted by the FLAIR lesion at day 7. An asymmetry ratio (AR) was computed by dividing the mean IMZ uptake of the mismatch VOI by the unaffected mirror VOI. The same AR was computed for signal intensity on FLAIR images at day 7. Three patients with cortical infarctions were included for calibration of the AR. In this group, the VOI consisted of the FLAIR lesion at day 7. Results— All patients with SC infarctions had a large mismatch of initially hypoperfused (112±31 mL; mean±SD) and finally infarcted tissue (19±14 mL). Mean AR of cortical IMZ uptake was 0.85±0.01 in cortical infarctions and 0.95±0.03 in SC infarctions; thereby AR showed a continuous distribution from clearly reduced (0.89) to normal (1.01) in SC infarctions. Mean AR for FLAIR signal intensity was 1.84±0.14 for cortical infarctions and normal (1.01+0.03) for SC infarctions. Conclusions— IMZ-SPECT detected a selective loss of cortical neurons in patients with SC infarctions in transient hypoperfused tissue, which was morphologically intact on MRI.