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Disentangling the neural correlates of corticobasal syndrome and corticobasal degeneration with systematic and quantitative ALE meta-analyses.

ABSTRACT: Corticobasal degeneration is a scarce neurodegenerative disease, which can only be confirmed by histopathological examination. Reported to be associated with various clinical syndromes, its classical clinical phenotype is corticobasal syndrome. Due to the rareness of corticobasal syndrome/corticobasal degeneration and low numbers of patients included in single studies, meta-analyses are particularly suited to disentangle features of the clinical syndrome and histopathology. Using PubMed, we identified 11 magnetic resonance imaging studies measuring atrophy in 22 independent cohorts with 200 patients contrasted to 318 healthy controls. The anatomic likelihood estimation method was applied to reveal affected brain regions across studies. Corticobasal syndrome was related to gray matter loss in the basal ganglia/thalamus, frontal, parietal, and temporal lobes. In corticobasal degeneration patients, atrophy in the thalamus, frontal, temporal, and occipital lobes were found. Finally, in a conjunction analysis, the bilateral thalamus, the bilateral posterior frontomedian cortex, posterior midcingulate cortex and premotor area/supplementary motor area, and the left posterior superior and middle frontal gyrus/precentral gyrus were identified as areas associated with both, corticobasal syndrome and corticobasal degeneration. Remarkably, atrophy in the premotor area/supplementary motor area and posterior midcingulate/frontomedian cortex seems to be specific for corticobasal syndrome/corticobasal degeneration, whereas atrophy in the thalamus and the left posterior superior and middle frontal gyrus/precentral gyrus are also associated with other neurodegenerative diseases according to anatomic likelihood estimation method meta-analyses. Our study creates a new conceptual framework to understand, and distinguish between clinical features (corticobasal syndrome) and histopathological findings (corticobasal degeneration) by powerful data-driven meta-analytic approaches. Furthermore, it proposes regional-specific atrophy as an imaging biomarker for diagnosis of corticobasal syndrome/corticobasal degeneration ante-mortem.

SUBMITTER: Albrecht F

PROVIDER: S-EPMC5459811 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Disentangling the neural correlates of corticobasal syndrome and corticobasal degeneration with systematic and quantitative ALE meta-analyses.

Albrecht Franziska F Bisenius Sandrine S Morales Schaack Rodrigo R Neumann Jane J Schroeter Matthias L ML

NPJ Parkinson's disease 20170331

Corticobasal degeneration is a scarce neurodegenerative disease, which can only be confirmed by histopathological examination. Reported to be associated with various clinical syndromes, its classical clinical phenotype is corticobasal syndrome. Due to the rareness of corticobasal syndrome/corticobasal degeneration and low numbers of patients included in single studies, meta-analyses are particularly suited to disentangle features of the clinical syndrome and histopathology. Using PubMed, we iden ...[more]

PMID: 28649612

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Project description:Patients with corticobasal degeneration can present with several different clinical syndromes, making ante-mortem diagnosis a challenge. Corticobasal syndrome is the clinical phenotype originally described for corticobasal degeneration, characterized by asymmetric rigidity and apraxia, cortical sensory deficits, dystonia and myoclonus. Some patients do not develop these features, but instead have clinical features consistent with the Richardson syndrome presentation of progressive supranuclear palsy, characterized by postural instability, early unexplained falls, vertical supranuclear gaze palsy, symmetric motor disability and dysphagia. The aim of this study was to identify differences in corticobasal degeneration presenting with corticobasal syndrome (n = 11) or Richardson syndrome (n = 15) with respect to demographic, clinical and neuropathological features. Corticobasal degeneration cases were also compared with patients with pathologically proven progressive supranuclear palsy with Richardson syndrome (n = 15). Cases with corticobasal degeneration, regardless of presentation, shared histopathological and tau biochemical characteristics, but they had differing densities of tau pathology in neuroanatomical regions that correlated with their clinical presentation. In particular, those with corticobasal syndrome had greater tau pathology in the primary motor and somatosensory cortices and putamen, while those with Richardson syndrome had greater tau pathology in limbic and hindbrain structures. Compared with progressive supranuclear palsy, patients with corticobasal degeneration and Richardson syndrome had less neuronal loss in the subthalamic nucleus, but more severe neuronal loss in the medial substantia nigra and greater atrophy of the anterior corpus callosum. Clinically, they had more cognitive impairment and frontal behavioural dysfunction. The results suggest that Richardson syndrome can be a clinicopathological presentation of corticobasal degeneration. Atrophy of anterior corpus callosum may be a potential neuroimaging marker to differentiate corticobasal degeneration from progressive supranuclear palsy in patients with Richardson syndrome.

Project description:ObjectiveThe clinical diagnosis of corticobasal syndrome (CBS) represents a challenge for physicians and reliable diagnostic imaging biomarkers would support the diagnostic work-up. We aimed to investigate the neural signatures of CBS using multimodal T1-weighted and resting-state functional magnetic resonance imaging (MRI).MethodsNineteen patients with CBS (age 67.0 ± 6.0 years; mean±SD) and 19 matched controls (66.5 ± 6.0) were enrolled from the German Frontotemporal Lobar Degeneration Consortium. Changes in functional connectivity and structure were respectively assessed with eigenvector centrality mapping complemented by seed-based analysis and with voxel-based morphometry. In addition to mass-univariate statistics, multivariate support vector machine (SVM) classification tested the potential of multimodal MRI to differentiate patients and controls. External validity of SVM was assessed on independent CBS data from the 4RTNI database.ResultsA decrease in brain interconnectedness was observed in the right central operculum, middle temporal gyrus and posterior insula, while widespread connectivity increases were found in the anterior cingulum, medial superior-frontal gyrus and in the bilateral caudate nuclei. Severe and diffuse gray matter volume reduction, especially in the bilateral insula, putamen and thalamus, characterized CBS. SVM classification revealed that both connectivity (area under the curve 0.81) and structural abnormalities (0.80) distinguished CBS from controls, while their combination led to statistically non-significant improvement in discrimination power, questioning the additional value of functional connectivity over atrophy. SVM analyses based on structural MRI generalized moderately well to new data, which was decisively improved when guided by meta-analytically derived disease-specific regions-of-interest.ConclusionsOur data-driven results show impairment of functional connectivity and brain structure in CBS and explore their potential as imaging biomarkers.

Project description:Background: Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) affect speech and language as well as motor functions. Clinical and neuropathological data indicate a close relationship between these two disorders and the non-fluent variant of primary progressive aphasia (nfvPPA). We use the recently developed Mini Linguistic State Examination tool (MLSE) to study speech and language disorders in patients with PSP, CBS, and nfvPPA, in combination with structural magnetic resonance imaging (MRI). Methods: Fifty-one patients (PSP N = 13, CBS N = 19, nfvPPA N = 19) and 30 age-matched controls completed the MLSE, the short form of the Boston Diagnostic Aphasia Examination (BDAE), and the Addenbrooke's Cognitive Examination III. Thirty-eight patients and all controls underwent structural MRI at 3 Tesla, with T1 and T2-weighted images processed by surface-based and subcortical segmentation within FreeSurfer 6.0.0 to extract cortical thickness and subcortical volumes. Morphometric differences were compared between groups and correlated with the severity of speech and language impairment. Results: CBS and PSP patients showed impaired MLSE performance, compared to controls, with a similar language profile to nfvPPA, albeit less severe. All patient groups showed reduced cortical thickness in bilateral frontal regions and striatal volume. PSP and nfvPPA patients also showed reduced superior temporal cortical thickness, with additional thalamic and amygdalo-hippocampal volume reductions in nfvPPA. Multivariate analysis of brain-wide cortical thickness and subcortical volumes with MLSE domain scores revealed associations between performance on multiple speech and language domains with atrophy of left-lateralised fronto-temporal cortex, amygdala, hippocampus, putamen, and caudate. Conclusions: The effect of PSP and CBS on speech and language overlaps with nfvPPA. These three disorders cause a common anatomical pattern of atrophy in the left frontotemporal language network and striatum. The MLSE is a short clinical screening tool that can identify the language disorder of PSP and CBS, facilitating clinical management and patient access to future clinical trials.

Project description:ImportanceBipolar disorder (BD) is a debilitating mental illness associated with high costs to diagnosed individuals and society. Within the past 2 decades, increasing numbers of children and adolescents have been diagnosed as having BD. While functional magnetic resonance imaging (fMRI) studies have begun to investigate the neural mechanisms underlying BD, few have directly compared differences in youths with BD and adults with BD (hereafter BD-youths and BD-adults, respectively).ObjectiveTo test the hypothesis that BD-youths (<18 years old) would show greater convergence of amygdala hyperactivation and prefrontal cortical hypoactivation vs BD-adults.Data sourcesPubMed and PsycINFO databases were searched on July 17, 2013, for original, task-related coordinate-based fMRI articles.Study selectionIn total, 21 pediatric studies, 73 adult studies, and 2 studies containing distinct pediatric and adult groups within the same study met inclusion criteria for our ALE analyses.Data extraction and synthesisCoordinates of significant between-group differences were extracted from each published study. Recent improvements in GingerALE software were used to perform direct comparisons of pediatric and adult fMRI findings. We conducted activation likelihood estimation (ALE) meta-analyses directly comparing the voxelwise convergence of fMRI findings in BD-youths vs BD-adults, both relative to healthy control (HC) participants.ResultsAnalyses of emotional face recognition fMRI studies showed significantly greater convergence of amygdala hyperactivation among BD-youths than BD-adults. More broadly, analyses of fMRI studies using emotional stimuli showed significantly greater convergence of hyperactivation among BD-youths than BD-adults in the inferior frontal gyrus and precuneus. In contrast, analyses of fMRI studies using nonemotional cognitive tasks and analyses aggregating emotional and nonemotional tasks showed significantly greater convergence of hypoactivation among BD-youths than BD-adults in the anterior cingulate cortex.Conclusions and relevanceOur data suggest that amygdala, prefrontal, and visual system hyperactivation is important in the emotional dysfunction present in BD-youths, as well as that anterior cingulate cortex hypoactivation is relevant to the cognitive deficits in BD-youths. Future studies are required to determine if the developmental fMRI differences between BD-youths and BD-adults identified by our ALE meta-analyses are useful as brain-based diagnostic or treatment markers of BD, including either longitudinal neuroimaging studies of BD-youths as they become adults or cross-sectional imaging studies directly comparing BD-youths with BD-adults.

Project description:Alzheimer's disease is the most common form of dementia. Its prodromal stage amnestic mild cognitive impairment is characterized by deficits of anterograde episodic memory. The development of standardized imaging inclusion criteria has to be regarded as a prerequisite for future diagnostic systems. Moreover, successful treatment requires isolating imaging markers predicting the disease. Accordingly, we conducted a systematic and quantitative meta-analysis to reveal the prototypical neural correlates of Alzheimer's disease and its prodromal stage. To prevent any a priori assumptions and enable a data-driven approach only studies applying quantitative automated whole brain analysis were included. Finally, 40 studies were identified involving 1351 patients and 1097 healthy control subjects reporting either atrophy or decreases in glucose utilization and perfusion. The currently most sophisticated and best-validated of coordinate-based voxel-wise meta-analyses was applied (anatomical likelihood estimates). The meta-analysis reveals that early Alzheimer's disease affects structurally the (trans-)entorhinal and hippocampal regions, functionally the inferior parietal lobules and precuneus. Results further may suggest that atrophy in the (trans-)entorhinal area/hippocampus and hypometabolism/hypoperfusion in the inferior parietal lobules predicts most reliably the progression from amnestic mild cognitive impairment to Alzheimer's disease, whereas changes in the posterior cingulate cortex and precuneus are unspecific. Fully developed Alzheimer's disease involved additionally a frontomedian-thalamic network. In conclusion, the meta-analysis characterizes the prototypical neural substrates of Alzheimer's disease and its prodromal stage amnestic mild cognitive impairment. By isolating predictive markers it enables successful treatment strategies in the future and contributes to standardized imaging inclusion criteria for Alzheimer's disease as suggested for future diagnostic systems.

Dataset Information

Disentangling the neural correlates of corticobasal syndrome and corticobasal degeneration with systematic and quantitative ALE meta-analyses.

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Disentangling the neural correlates of corticobasal syndrome and corticobasal degeneration with systematic and quantitative ALE meta-analyses.

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