Large-scale activation likelihood estimation meta-analysis of parkinsonian disorders

Elizabeth G Ellis; Juho Joutsa; Jordan Morrison-Ham; Ellen F P Younger; Jacqueline B Saward; Karen Caeyenberghs; Daniel T Corp

doi:10.1093/braincomms/fcad172

Large-scale activation likelihood estimation meta-analysis of parkinsonian disorders

Brain Commun. 2023 May 30;5(3):fcad172. doi: 10.1093/braincomms/fcad172. eCollection 2023.

Authors

Elizabeth G Ellis¹, Juho Joutsa^{2

3

4}, Jordan Morrison-Ham¹, Ellen F P Younger¹, Jacqueline B Saward¹, Karen Caeyenberghs¹, Daniel T Corp^{1

2}

Affiliations

¹ Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, VIC 3220, Australia.
² Center for Brain Circuit Therapeutics, Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
³ Turku Brain and Mind Center, Clinical Neurosciences, University of Turku, Turku 20520, Finland.
⁴ Turku PET Centre, Neurocenter, Turku University Hospital, Turku 20520, Finland.

Abstract

Parkinsonism is a feature of several neurodegenerative disorders, including Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome and multiple system atrophy. Neuroimaging studies have yielded insights into parkinsonian disorders; however, due to variability in results, the brain regions consistently implicated in these disorders remain to be characterized. The aim of this meta-analysis was to identify consistent brain abnormalities in individual parkinsonian disorders (Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome and multiple system atrophy) and to investigate any shared abnormalities across disorders. A total of 44 591 studies were systematically screened following searches of two databases. A series of whole-brain activation likelihood estimation meta-analyses were performed on 132 neuroimaging studies (69 Parkinson's disease; 23 progressive supranuclear palsy; 17 corticobasal syndrome; and 23 multiple system atrophy) utilizing anatomical MRI, perfusion or metabolism PET and single-photon emission computed tomography. Meta-analyses were performed in each parkinsonian disorder within each imaging modality, as well as across all included disorders. Results in progressive supranuclear palsy and multiple system atrophy aligned with current imaging markers for diagnosis, encompassing the midbrain, and brainstem and putamen, respectively. PET imaging studies of patients with Parkinson's disease most consistently reported abnormality of the middle temporal gyrus. No significant clusters were identified in corticobasal syndrome. When examining abnormalities shared across all four disorders, the caudate was consistently reported in MRI studies, whilst the thalamus, inferior frontal gyrus and middle temporal gyri were commonly implicated by PET. To our knowledge, this is the largest meta-analysis of neuroimaging studies in parkinsonian disorders and the first to characterize brain regions implicated across parkinsonian disorders.

Keywords: Parkinson disease; activation likelihood estimation; atypical parkinsonian disorders; meta-analysis; neuroimaging.