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Poster A56, Thursday, August 16, 10:15 am – 12:00 pm, Room 2000AB

Individual Pseudo-Lesioning to Assess Secondary White Matter Connectivity Changes in Post-Stroke Aphasia

Natalie Busby1, Ajay D. Halai1, Geoffrey J.M. Parker1,2, Matthew A. Lambon Ralph1;1University of Manchester, 2Bioxydyn Ltd.

Post-stroke aphasia patients are traditionally grouped based on aphasia classification, however these sub-categories are often fluid and arbitrary, and therefore other data-driven methods of classifying patients may be more clinically relevant. Groups of patients may recover behaviourally in different ways, however often subtle widespread white matter connectivity changes away from the lesion itself may be difficult to assess in comparisons with controls. If more sensitive measures of connectivity were possible, associations with behavioural improvement may be found. Sixty-six chronic post-stroke aphasia patients and twenty-two aged matched controls were recruited. Using hierarchical clustering patients were grouped into four clusters based on lesion size and location. Whole-brain connectivity maps were acquired for each patient using FSL’s probtrackx function to initiate streamlines from every voxel within the brain. Connectivity scores were calculated by summing the number of streamlines passing through each voxel. In this way, every voxel has a connectivity score which represents how well connected it is to the rest of the brain. These maps were termed Anatomical Connectivity Maps (ACMs) and reflected whole-brain connectivity. Initially, patient’s average connectivity scores in white matter tracts were compared to controls to determine tracts with significantly reduced connectivity. As a secondary analysis, each patient’s own binary lesion was used as an exclusion mask in the set of controls meaning no streamlines were initiated in or could enter this ‘lesion’. This resulted in each patient having a set of controls with their own ‘lesion’ (termed pseudo-patients). In this way we could emulate each individual’s lesion and therefore could compare the instantaneous effect of the lesion back to the patient’s actual connectivity. This sensitive measure allowed us to identify subtle long-range secondary connectivity changes which may be associated with behavioural improvements in language ability. Four clinically-relevant clusters of patients emerged and were termed insula, fronto-parietal, temporo-parietal and whole middle cerebral artery (MCA). Compared to controls, the largest lesion group (whole MCA) had the lowest connectivity scores in all white matter tracts tested. The insula cluster had significantly reduced connectivity the uncinate fasciculus and frontal portions of the superior longitudinal fasciculus (SLF) and inferior fronto-occipital fasciculus (IFOF). Conversely, the temporo-parietal lesion group had lower connectivity scores in posterior portions of the IFOF, SLF and inferior longitudinal fasciculus (ILF). In the fronto-parital group, connectivity was conserved in the majority of tracts except the SLF. Across all patients, increased connectivity scores within the left SLF and ILF positively correlated with phonology scores. Compared to their own set of pseudo-patients, a subset of patients showed widespread upregulation and/or Wallerian degeneration. Across patients, increases in chronic connectivity vs instantaneous connectivity was positively correlated with the left IFOF and uncinate, whilst connectivity in the left SLF negatively correlated with speech quanta. Therefore, grouping patients based on their lesion may be useful clinically as it reveals group-level connectivity changes associated with the lesion. However it does not capture the variability seen between patients. Individual ‘pseudo-lesioning’ may offer a sensitive measure to assess secondary whole brain connectivity associated with behavioural recovery post-stroke.

Topic Area: Language Disorders