Progressive apraxia of speech (PAOS) is a clinical syndrome characterized by an impairment in speech motor planning and is most commonly associated with a 4-repeat tauopathy (4RT) (Duffy, Utianski, & Josephs, 2021; Keith. Josephs et al., 2021a, 2021b; Keith Josephs et al., 2012a, 2012b). Some patients with PAOS also present with agrammatic aphasia. Previous studies using multimodal imaging approaches have shown that PAOS patients have bilateral frontal grey matter (GM) loss, particularly located in the premotor and supplementary motor areas (SMA), as well as bilateral frontal white matter (WM) degeneration underlying these regions and involving the corpus callosum and white matter connections from the SMA (H. Botha et al., 2015; Keith Josephs et al., 2013; Keith Josephs et al., 2012a, 2012b; Valls Carbo et al., 2022). In addition, previous functional MRI (fMRI) studies assessing brain connectivity have demonstrated reduced connectivity between the SMA and the rest of the speech and language network (Hugo Botha et al., 2018) and shown that connectivity from the premotor cortex is associated with rates of brain neurodegeneration (Sintini et al., 2022). These findings suggest that breakdowns in WM interconnectivity are important components of the disease in PAOS.

The specific speech characteristics observed in patients with PAOS vary, and two subtypes have been described based on the relative prominence of phonetic or prosodic speech patterns (Keith Josephs et al., 2013; Rene Utianski et al., 2018a, 2018b). Phonetic PAOS (paos_ph) is characterized predominantly by distorted sound substitutions and additions, while prosodic PAOS (paos_pr) is characterized predominantly by slow, prosodically segmented speech (Duffy et al., 2021; Rene Utianski et al., 2018a, 2018b). We have shown that these two subtypes differ in their clinical evolution (Whitwell et al., 2017) and differ in underlying pathology, with phonetic PAOS more commonly associated with corticobasal degeneration and prosodic PAOS associated with progressive supranuclear palsy; both 4RT (Keith Josephs et al., 2021a, 2021b). On neuroimaging, both subtypes were associated with atrophy of the SMA, although PAOS_ph showed additional involvement of the prefrontal cortex and cerebellum (Rene Utianski et al., 2018a, 2018b). A voxel-based diffusion tensor imaging (DTI) analysis showed degeneration of the white matter underlying the SMA in both subtypes, with additional involvement of the body of the corpus callosum and cingulum in paos_ph and involvement of the superior cerebellar peduncle (SCP), likely related to the underlying progressive supranuclear palsy pathology, in paos_pr (Rene Utianski et al., 2018a, 2018b). However, no differences were identified between the two subtypes on direct comparison, suggesting that more sensitive methods are needed to identify patterns of structural connectivity disruption in PAOS subtypes. As such, studies based on neuropathological data suggested that differences between PAOS subtypes may be observed in cortical-striatal-pallido-Nigro-luysial networks (Keith. Josephs et al., 2021a, 2021b).

Diffusion tensor imaging has the advantage of approximating the reconstruction of the WM tracts allowing specific interrogation of WM tracts in the brain, such as those connecting specific regions supporting speech and language (Jeurissen, Descoteaux, Mori, & Leemans, 2019; Smits, Jiskoot, & Papma, 2014). A recent DTI tractography study in PAOS demonstrated abnormal diffusion in tracts connecting the SMA with the putamen, prefrontal cortex, Broca's area (frontal aslant tract), and motor cortex, and showed that degeneration of SMA to motor cortex tracts is associated with apraxia of speech severity (Valls Carbo et al., 2022). However, this study only assessed WM tracts from the SMA and did not assess differences between PAOS subtypes. Other studies have assessed diffusion tractography in patients with agrammatic aphasia (Catani et al., 2013; Mandelli et al., 2014), although these studies have not considered the role of apraxia of speech or PAOS subtypes.

Therefore, our study expands on previous tractography results by applying a multi-tract approach and specifically assessing differences between clinically defined PAOS subtypes. We hypothesized that the unique clinical presentations of PAOS subtypes will have specific patterns of WM microstructural degeneration. In addition, we propose that microstructural characteristics from each PAOS subtype would relate to distinct clinical features.