Improving our understanding of speech and language outcome in neurosurgery patients

Malignant gliomas remain incurable and result in more years of life lost than any other tumours. Surgical resection is strongly recommended but carries a risk of causing functional impairment. This thesis aims to demonstrate how state-of-the-art functional magnetic resonance imaging (fMRI) language paradigms can contribute to neurosurgical planning. The first three experiments use a multitask fMRI language paradigm to functionally segregate left posterior temporal and left posterior frontal regions involved in the perception and production of speech. Experiment 1 demonstrated three functionally distinct responses in the left posterior superior temporal sulcus (STS), left temporo-parietal junction and anterior ascending terminal branch of the left STS. Experiment 2 validates these findings in an independent group of participants, increasing confidence that they are robust. Experiment 3 dissociates the response of three different parts of the left premotor cortex during speech production. Experiment 4 shows that left posterior temporal regions are more consistently activated, in neurotypical controls, when a picture naming task presents pairs of objects rather than single objects. Further work could therefore test whether paired object naming is a more sensitive task for pre- and intra-operative language mapping. Finally, Experiment 5 found that successful reading before and after surgery, in two patients with gliomas affecting the left temporo-parietal junction, enhanced activation in bilateral perirhinal regions that were associated with semantic identification of visually presented objects in neurotypical controls. Future studies can now test whether patients who undergo resection of the left temporo-parietal junction have better reading, post-surgery, when bilateral perirhinal activation is enhanced prior to surgery. Taken together, this work expands our knowledge of the functional anatomy of language, proposes a new way of utilising fMRI data from neurotypical controls to tailor pre- and intra-operative language mapping strategies and provides an insight into how the reading system reorganises itself after brain damage

Degeneracy in the neurological model of auditory speech repetition

Both classic and contemporary models of auditory word repetition involve at least four left hemisphere regions: primary auditory cortex for processing sounds; pSTS (within Wernicke's area) for processing auditory images of speech; pOp (within Broca's area) for processing motor images of speech; and primary motor cortex for overt speech articulation. Previous functional-MRI (fMRI) studies confirm that auditory repetition activates these regions, in addition to many others. Crucially, however, contemporary models do not specify how regions interact and drive each other during auditory repetition. Here, we used dynamic causal modelling, to test the functional interplay among the four core brain regions during single auditory word and pseudoword repetition. Our analysis is grounded in the principle of degeneracy-i.e., many-to-one structure-function relationships-where multiple neural pathways can execute the same function. Contrary to expectation, we found that, for both word and pseudoword repetition, (i) the effective connectivity between pSTS and pOp was predominantly bidirectional and inhibitory; (ii) activity in the motor cortex could be driven by either pSTS or pOp; and (iii) the latter varied both within and between individuals. These results suggest that different neural pathways can support auditory speech repetition. This degeneracy may explain resilience to functional loss after brain damage