PhD Project 21

Contributions of dorsal and ventral neural pathways to speaking in health and disease

 

PhD-candidate: Nikki Janssen
PIs: Roy Kessels (WP6) and Ardi Roelofs (WP4)
Start date: 01 February 2016

(last update 2019-07-01)

Research Content

A hotly debated issue concerns the functional role of the dorsal and ventral white-matter pathways that connect temporal and frontal language areas. Tractography studies in healthy individuals provided evidence that the ventral pathway underlies language comprehension and the dorsal pathway underlies repetition, but language production has not been examined. Moreover, whereas evidence from stroke patients suggests that the dorsal pathway underpins language production, this view is challenged by evidence on dorsal pathway atrophy in primary progressive aphasia. The aim is to assess the functional contribution of the ventral and dorsal pathways to production in healthy speakers and patients with neurodegenerative disease.

Highlight

Subtracts of the arcuate fasciculus mediate conceptually driven generation and repetition of speech
Team members: Janssen, Roelofs, Mars, Beckmann, and Kessels

The left AF consists of two subtracts directly connecting posterior STG versus MTG to posterior IFG. It has been hypothesized that the subtracts mediate different functions in speech production, but direct evidence for this hypothesis is lacking. To functionally segregate the two segments of the AF with different hypothesized functions fMRI was combined with DTI tractography. The functional roles of the STG and MTG subtracts were determined using two prototypical speech production tasks, namely spoken pseudoword repetition (PwR) and verb generation (VG). Task-based activation nodes then served as seed regions for probabilistic tractography, which enables determining the most probable anatomical pathways linking two activated nodes.

In the temporal lobe, PwR and VG were associated with areas of activation in the left STG and left MTG, respectively, and both tasks showed activation in BA44. Fiber tracking based on these temporal and frontal fMRI-based seeds revealed a clear segmentation of the left AF into two subtracts.

Tractography results. Composite fiber networks subserving repetition (in blue-light blue) and verb generation (in red-yellow) in the left hemisphere computed by averaging the connections of 50 subjects based on seeds defined in the repetition and verb generation experiment, respectively.

Furthermore, the voxels of peak sample count of each of these subtracts showed a clear difference in distribution of y-coordinates within the arc of the AF (Fig. 2). In addition, a mean classification accuracy of 82.93% (std=0.29) was found, clearly showing that the location of peak sample count within the AF contains discriminative power to distinguish which of both tasks was being performed.

In panel A the histograms of anterior-posterior distributions (y-coordinates) of the peak voxel count within the arc of the AF for each task for all subjects. The 3D coordinates of these peak count voxels are shown in panel B per subject per task. PR = pseudoword repetition, VG = verb generation. Black dots = pseudoword repetition, Red dots = verb generation. In purple a decision surface for the three-dimensional LDA classifier is shown.

These findings corroborate evidence for the existence of two distinct subtracts of the AF with different functional roles, namely sublexical mapping of sound to articulation by the STG-tract and conceptually driven generation of words by the MTG-tract.
These results contribute to the unravelling of a century-old controversy concerning the functional role in speech production of a major fibre tract involved in language. The AF has undergone a major evolutionary change in humans, so that elucidating its contribution to language by examining individual differences will reveal what makes our brain language-ready and uniquely human, and what makes every speaker different from others.

The results of this study are followed up in unique patient group of PPA patients and thereby this project is the first to examine the functional contribution of the dorsal and ventral pathways to speaking by assessing whether connectivity measures predict language performance for both healthy speakers and patients.

Progress 2018

Data acquisition of 50 healthy younger and older adult participants to investigate the subtracts of the arcuate fasciculus and their functional role in language production is finished and both fMRI and DWI data have been analysed. The paper is in preparation.
The meta-analysis on memory in primary progressive aphasia (PPA) has been published in Neuroscience and Biobehavioral Reviews and results were presented at multiple conferences with a great variety of scopes (neuropsychology, frontotemporal dementia, language production).
A follow up of the first article on the implementation and validation of the SYDBAT-NL is in preparation. In addition to the SYDBAT-NL, another neuropsychological measure has been developed in collaboration with Piai (Tenure track, page 52) and De Swart (CLS): the SynTest. The SynTest is a sentence-to-picture matching tasks that assesses sentence comprehension with increasing grammatical complexity. It is specifically developed to aid in the differentiation between logopenic and non-fluent PPA patients and data collection for validation has started in multiple Dutch hospitals. Since it concerns a rare patient group and a unique database is being created.

Groundbreaking characteristics

This project is the first to examine the functional contribution of the ventral and dorsal pathways to speaking by assessing whether connectivity measures predict language performance for both healthy speakers and patients. Secondly, the project stimulates collaboration and interdisciplinarity since it integrates multiple disciplines and LiI work packages (neuropsychology, geriatrics, psycholinguistics, cognitive control, tractography, human connectome project. Also, the project involves a collaboration with the Radboud Alzheimer Centre. Furthermore, illuminating the pathway contributions is not only of fundamental but also practical importance, as it may further validate a clinical test for PPA in terms of underlying brain atrophy. Making the test available for the Dutch language adds to the clinical-translational output of LiI. Moreover, the AF but not the UF/EmC has undergone a major evolutionary change in humans, so that elucidating its contribution to language and cognitive control by examining individual differences will reveal what makes our brain language-ready and uniquely human, and what makes every speaker different from others.