Behavioural and neuroanatomical correlates of auditory speech analysis in primary progressive aphasias

Background Non-verbal auditory impairment is increasingly recognised in the primary progressive aphasias (PPAs) but its relationship to speech processing and brain substrates has not been defined. Here we addressed these issues in patients representing the non-fluent variant (nfvPPA) and semantic variant (svPPA) syndromes of PPA. Methods We studied 19 patients with PPA in relation to 19 healthy older individuals. We manipulated three key auditory parameters—temporal regularity, phonemic spectral structure and prosodic predictability (an index of fundamental information content, or entropy)—in sequences of spoken syllables. The ability of participants to process these parameters was assessed using two-alternative, forced-choice tasks and neuroanatomical associations of task performance were assessed using voxel-based morphometry of patients’ brain magnetic resonance images. Results Relative to healthy controls, both the nfvPPA and svPPA groups had impaired processing of phonemic spectral structure and signal predictability while the nfvPPA group additionally had impaired processing of temporal regularity in speech signals. Task performance correlated with standard disease severity and neurolinguistic measures. Across the patient cohort, performance on the temporal regularity task was associated with grey matter in the left supplementary motor area and right caudate, performance on the phoneme processing task was associated with grey matter in the left supramarginal gyrus, and performance on the prosodic predictability task was associated with grey matter in the right putamen. Conclusions Our findings suggest that PPA syndromes may be underpinned by more generic deficits of auditory signal analysis, with a distributed cortico-subcortical neuraoanatomical substrate extending beyond the canonical language network. This has implications for syndrome classification and biomarker development

Increased functional connectivity of thalamic subdivisions in patients with Parkinson's disease

Parkinson's disease (PD) affects 2-3% of the population over the age of 65 with loss of dopaminergic neurons in the substantia nigra impacting the functioning of basal ganglia-thalamocortical circuits. The precise role played by the thalamus is unknown, despite its critical role in the functioning of the cerebral cortex, and the abnormal neuronal activity of the structure in PD. Our objective was to more clearly elucidate how functional connectivity and morphology of the thalamus are impacted in PD (n = 32) compared to Controls (n = 20). To investigate functional connectivity of the thalamus we subdivided the structure into two important regions-of-interest, the first with putative connections to the motor cortices and the second with putative connections to prefrontal cortices. We then investigated potential differences in the size and shape of the thalamus in PD, and how morphology and functional connectivity relate to clinical variables. Our data demonstrate that PD is associated with increases in functional connectivity between motor subdivisions of the thalamus and the supplementary motor area, and between prefrontal thalamic subdivisions and nuclei of the basal ganglia, anterior and dorsolateral prefrontal cortices, as well as the anterior and paracingulate gyri. These results suggest that PD is associated with increased functional connectivity of subdivisions of the thalamus which may be indicative alterations to basal ganglia-thalamocortical circuitry

Grey and white matter brain network changes in frontotemporal dementia subtypes

Background: Frontotemporal dementia (FTD) comprises of three clinical syndromes, behavioural-variant frontotemporal dementia (bvFTD), semantic dementia (SV-PPA), and progressive nonfluent aphasia (NFV-PPA) with unique underlying neuroanatomical deficits. To date, however, grey matter structural differences and their connecting white matter tracts in this network have been mostly characterised in comparison to controls, whereas within FTD subtype comparisons in the same patients have not been explored.   Methodology: In 94 participants, including bvFTD (n = 16), SV-PPA (n = 16) and NFV-PPA (n = 16), as well as an age-matched control group (n = 46), we employed voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) to examine grey and white matter key signatures in each of the three FTD subtypes.   Results: Our results showed that bvFTD had specific ventromedial prefrontal cortex and striatum grey matter atrophy along with their connecting white matter tracts compared to other FTD subtypes. By contrast, SV-PPA showed additional temporal pole grey matter damage to bvFTD and grey and white matter temporal, amygdala and insula changes compared to NFV-PPA. Finally, NFV-PPA showed mild insula grey and white matter changes compared to bvFTD but differed from SV-PPA only on anterior corpus callosum white matter changes.   Conclusions: Our findings clearly indicate that not only grey matter regions of the FTD network but also their white matter connecting tracts have specific signatures for each FTD subtype. These promising findings highlight how neural network approaches can shed new light on neurodegenerative conditions and FTD in particular, which will inform future diagnostic and disease management