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Ryota Satoh

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3 papers

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YNICL Journal 2025 Journal Article

Functional connectivity abnormalities in clinical variants of progressive supranuclear palsy

Irene Sintini
Farwa Ali
Yehkyoung Stephens
Heather M. Clark
Julie A. Stierwalt
Mary M. Machulda
Ryota Satoh
Keith A. Josephs

Progressive supranuclear palsy (PSP) can present with different clinical variants which show distinct, but partially overlapping, patterns of neurodegeneration and tau deposition in a network of regions including cerebellar dentate, superior cerebellar peduncle, midbrain, thalamus, basal ganglia, and frontal lobe. We sought to determine whether disruptions in functional connectivity within this PSP network measured using resting-state functional MRI (rs-fMRI) differed between PSP-Richardson's syndrome (PSP-RS) and the cortical and subcortical clinical variants of PSP. Structural MRI and rs-fMRI scans were collected for 36 PSP-RS, 25 PSP-cortical and 34 PSP-subcortical participants who met the Movement Disorder Society PSP clinical criteria. Ninety participants underwent flortaucipir-PET scans. MRIs were processed using CONN Toolbox. Functional connectivity between regions of the PSP network was compared between each PSP group and 83 healthy controls, and between the PSP groups, covarying for age. The effect of flortaucipir uptake and clinical scores on connectivity was assessed. Connectivity was reduced in PSP-RS compared to controls throughout the network, involving cerebellar dentate, midbrain, basal ganglia, thalamus, and frontal regions. Frontal regions showed reduced connectivity to other regions in the network in PSP-cortical, particularly the thalamus, caudate and substantia nigra. Disruptions in connectivity in PSP-subcortical were less pronounced, with the strongest disruption between the pallidum and striatum. There was moderate evidence that elevated subcortical flortaucipir uptake correlated with both increased and reduced connectivity between regions of the PSP network. Lower connectivity within the PSP network correlated with worse performance on clinical tests, including PSP rating scale. Patterns of disrupted functional connectivity revealed both variant-specific and shared disease pathways within the PSP network among PSP clinical variants, providing insight into disease heterogeneity.

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YNIMG Journal 2024 Journal Article

Direct comparison between 18F-Flortaucipir tau PET and quantitative susceptibility mapping in progressive supranuclear palsy

Ryota Satoh
Farwa Ali
Hugo Botha
Val J. Lowe
Keith A. Josephs
Jennifer L. Whitwell

PURPOSE: The pattern of flortaucipir tau PET uptake is topographically similar to the pattern of magnetic susceptibility in progressive supranuclear palsy (PSP); both with increased signal in subcortical structures such as the basal ganglia and midbrain, suggesting that they may be closely related. However, their relationship remains unknown since no studies have directly compared these two modalities in the same PSP cohort. We hypothesized that some flortaucipir uptake in PSP is associated with magnetic susceptibility, and hence iron deposition. The aim of this study was to evaluate the regional relationship between flortaucipir uptake and magnetic susceptibility and to examine the effects of susceptibility on flortaucipir uptake in PSP. METHODS: Fifty PSP patients and 67 cognitively normal controls were prospectively recruited and underwent three Tesla MRI and flortaucipir tau PET scans. Quantitative susceptibility maps were reconstructed from multi-echo gradient-echo MRI images. Region of interest (ROI) analysis was performed to obtain flortaucipir and susceptibility values in the subcortical regions. Relationships between flortaucipir and susceptibility signals were evaluated using partial correlation analysis in the subcortical ROIs and voxel-based analysis in the whole brain. The effects of susceptibility on flortaucipir uptake were examined by using the framework of mediation analysis. RESULTS: Both flortaucipir and susceptibility were greater in PSP compared to controls in the putamen, pallidum, subthalamic nucleus, red nucleus, and cerebellar dentate (p<0.05). The ROI-based and voxel-based analyses showed that these two signals were positively correlated in these five regions (r = 0.36-0.59, p<0.05). Mediation analysis showed that greater flortaucipir uptake was partially explained by susceptibility in the putamen, pallidum, subthalamic nucleus, and red nucleus, and fully explained in the cerebellar dentate. CONCLUSIONS: These results suggest that some of the flortaucipir uptake in subcortical regions in PSP is related to iron deposition. These findings will contribute to our understanding of the mechanisms underlying flortaucipir tau PET findings in PSP and other neurodegenerative diseases.

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YNICL Journal 2023 Journal Article

Spatial patterns of elevated magnetic susceptibility in progressive apraxia of speech

Ryota Satoh
Arvin Arani
Matthew L. Senjem
Joseph R. Duffy
Heather M. Clark
Rene L. Utianski
Hugo Botha
Mary M. Machulda

PURPOSE: Progressive apraxia of speech (PAOS) is a neurodegenerative disorder affecting the planning or programming of speech. Little is known about its magnetic susceptibility profiles indicative of biological processes such as iron deposition and demyelination. This study aims to clarify (1) the pattern of susceptibility in PAOS patients, (2) the susceptibility differences between the phonetic (characterized by predominance of distorted sound substitutions and additions) and prosodic (characterized by predominance of slow speech rate and segmentation) subtypes of PAOS, and (3) the relationships between susceptibility and symptom severity. METHODS: Twenty patients with PAOS (nine phonetic and eleven prosodic subtypes) were prospectively recruited and underwent a 3 Tesla MRI scan. They also underwent detailed speech, language, and neurological evaluations. Quantitative susceptibility maps (QSM) were reconstructed from multi-echo gradient echo MRI images. Region of interest analysis was conducted to estimate susceptibility coefficients in several subcortical and frontal regions. We compared susceptibility values between PAOS and an age-matched control group and performed a correlation analysis between susceptibilities and an apraxia of speech rating scale (ASRS) phonetic and prosodic feature ratings. RESULTS: The magnetic susceptibility of PAOS was statistically greater than that of controls in subcortical regions (left putamen, left red nucleus, and right dentate nucleus) (p < 0.01, also survived FDR correction) and in the left white-matter precentral gyrus (p < 0.05, but not survived FDR correction). The prosodic patients showed greater susceptibilities than controls in these subcortical and precentral regions. The susceptibility in the left red nucleus and in the left precentral gyrus correlated with the prosodic sub-score of the ASRS. CONCLUSION: Magnetic susceptibility in PAOS patients was greater than controls mainly in the subcortical regions. While larger samples are needed before QSM is considered ready for clinical differential diagnosis, the present study contributes to our understanding of magnetic susceptibility changes and the pathophysiology of PAOS.

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