Objective: To localise brain networks of progressive supranuclear palsy (PSP), using a novel method termed ‘Coordinate Network Mapping’.

Background: PSP has multiple phenotypes including, but not limited to, the classic presentation of PSP-Richardson’s syndrome (PSP-RS), characterised by vertical gaze palsy and early onset postural instability, PSP with predominant parkinsonism (PSP-P). Whilst abnormality of the midbrain is a hallmark PSP pathology and a useful tool in the diagnostic workup, not all patients show midbrain atrophy and neuroimaging studies commonly report abnormalities in numerous brain areas outside of this region.

Method: A systematic search was conducted to identify whole-brain structural MRI, metabolic and perfusion PET and SPECT studies reporting significant abnormalities between PSP patients (diagnosed according to clinical research criteria^1–3) and healthy controls. Coordinates of significant brain abnormalities were extracted from included studies and combined at the study level, creating combined ‘study seeds’. Regions functionally connected to sites of abnormality in PSP were identified using a large dataset of rs-fMRI (N=1000). Connectivity maps from each study were binarised (connected=t ≥7, not connected=t<7) and overlaid, identifying regions significantly connected to all or most of the study seeds. Specificity of the resultant PSP functional network was tested by statistical comparison to the network previously identified in another neurodegenerative disorder: Alzheimer’s disease.

Results: 23 studies, reporting 355 coordinates of significant differences between 363 PSP patients and 425 healthy controls, were included. As many of the studies were relatively old, the exact clinical PSP phenotype according to current classification¹ was only reported in 7/23 studies (5 PSP-RS, one PSP-P and one with PSP-RS and PSP-P). Coordinates were widely dispersed throughout the brain, yet ≥20 of the 23 studies were functionally connected to a network encompassing the claustrum, basal ganglia, midbrain (positively connected), cuneus and precuneus (negatively connected).

Conclusion: Disparately located structural and molecular abnormalities in PSP localise to a functional brain network defined by connectivity to basal ganglia, midbrain and cuneus. These findings help to reconcile previous heterogeneous neuroimaging findings by demonstrating that they are part of a common brain network.

References: 1. Hoglinger, G. U., Respondek, G., Stamelou, M., et al. Clinical Diagnosis of Progressive Supranuclear Palsy: The Movement Disorder Society Criteria. Movement Disorders 2017; 32: 853–864.
2. Litvan, I., Agid, Y., Calne, D. & et al. Clinical Research Criteria for the Diagnosis of Progressive Supranuclear Gaze Palsy. Neurology 1996; 47: 1–9.
3. Litvan, I., Bhatia, K. P., Burn, D. J., et al. SIC task force appraisal of clinical diagnostic criteria for parkinsonian disorders. Movement Disorders 2003; 18: 467–486.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/localizing-a-brain-network-of-progressive-supranuclear-palsy/