Objective: Evaluation of a data-driven, model-based classification approach to discriminate idiopathic Parkinson’s disease (PD) patients from healthy controls (HC) based on between-network connectivity in whole-brain resting-state functional MRI (rs-fMRI). Methods: Whole-brain rs-fMRI (EPI, TR = 2.2 s, TE = 30 ms, flip angle = 90°. resolution = 3.1 × 3.1 × 3.1 mm, acquisition time ≈ 11 min) was assessed in 42 PD patients (medical OFF) and 47 HC matched for age and gender. Between-network connectivity based on full and L2-regularized partial correlation measures were computed for each subject based on canonical functional network architectures of two cohorts at different levels of granularity (Human Connectome Project: 15/25/50/100/200 networks; 1000BRAINS: 15/25/50/70 networks). A Boosted Logistic Regression model was trained on the correlation matrices using a nested cross-validation (CV) with 10 outer and 10 inner folds for an unbiased performance estimate, treating the canonical functional network architecture and the type of correlation as hyperparameters. The number of boosting iterations was fixed at 100. The model with the highest mean accuracy over the inner folds was trained using an non-nested 10-fold 20-repeats CV over the whole dataset to determine feature importance. Results: Over the outer folds the mean accuracy was found to be 76.2% (median 77.8%, SD 18.2, IQR 69.4 – 87.1%). Mean sensitivity was 81% (median 80%, SD 21.1, IQR 75 – 100%) and mean specificity was 72.7% (median 75%, SD 20.4, IQR 66.7 – 80%). The 1000BRAINS 50-network-parcellation, using full correlations, performed best over the inner folds. The top features predominantly included sensorimotor as well as sensory networks. Conclusion: A rs-fMRI whole-brain-connectivity, data-driven, model-based approach to discriminate PD patients from healthy controls shows a very good accuracy and a high sensitivity. Given the high sensitivity of the approach, it may be of use in a screening setting. Advances in knowledge: Resting-state functional MRI could prove to be a valuable, non-invasive neuroimaging biomarker for neurodegenerative diseases. The current model-based, data-driven approach on whole-brain between-network connectivity to discriminate Parkinson’s disease patients from healthy controls shows promising results with a very good accuracy and a very high sensitivity.

A wide homology between human and macaque striatum is often assumed as in both the striatum is involved in cognition, emotion and executive functions. However, differences in functional and structural organization between human and macaque striatum may reveal evolutionary divergence and shed light on human vulnerability to neuropsychiatric diseases. For instance, dopaminergic dysfunction of the human striatum is considered to be a pathophysiological underpinning of different disorders, such as Parkinson's disease (PD) and schizophrenia (SCZ). Previous investigations have found a wide similarity in structural connectivity of the striatum between human and macaque, leaving the cross-species comparison of its functional organization unknown. In this study, resting-state functional connectivity (RSFC) derived striatal parcels were compared based on their homologous cortico-striatal connectivity. The goal here was to identify striatal parcels whose connectivity is human-specific compared to macaque parcels. Functional parcellation revealed that the human striatum was split into dorsal, dorsomedial, and rostral caudate and ventral, central, and caudal putamen, while the macaque striatum was divided into dorsal, and rostral caudate and rostral, and caudal putamen. Cross-species comparison indicated dissimilar cortico-striatal RSFC of the topographically similar dorsal caudate. We probed clinical relevance of the striatal clusters by examining differences in their cortico-striatal RSFC and gray matter (GM) volume between patients (with PD and SCZ) and healthy controls. We found abnormal RSFC not only between dorsal caudate, but also between rostral caudate, ventral, central and caudal putamen and widespread cortical regions for both PD and SCZ patients. Also, we observed significant structural atrophy in rostral caudate, ventral and central putamen for both PD and SCZ while atrophy in the dorsal caudate was specific to PD. Taken together, our cross-species comparative results revealed shared and human-specific RSFC of different striatal clusters reinforcing the complex organization and function of the striatum. In addition, we provided a testable hypothesis that abnormalities in a region with human-specific connectivity, i.e., dorsal caudate, might be associated with neuropsychiatric disorders.

Many functional magnetic resonance imaging (fMRI) studies and presurgical mapping applications rely on mass-univariate inference with subsequent multiple comparison correction. Statistical results are frequently visualized as thresholded statistical maps. This approach has inherent limitations including the risk of drawing overly-selective conclusions based only on selective results passing such thresholds. This article gives an overview of both established and newly emerging scientific approaches to supplement such conventional analyses by incorporating information about subthreshold effects with the aim to improve interpretation of findings or leverage a wider array of information. Topics covered include neuroimaging data visualization, p-value histogram analysis and the related Higher Criticism approach for detecting rare and weak effects. Further examples from multivariate analyses and dedicated Bayesian approaches are provided.

BACKGROUND: Spreading depolarization describes a near-complete electrical discharge with altered local cerebral blood flow. It is described in association with acute and chronic diseases like hemorrhagic stroke or migraine. Moyamoya vasculopathy is a chronic, progressive cerebrovascular disorder leading to cerebral hypoperfusion, hemodynamically insufficient basal collateralization, and increased cortical microvascularization. METHODS: In a prospective case series, we monitored for spontaneous spreading depolarization activity by using intraoperative laser speckle imaging for real-time visualization and measurement of cortical perfusion and cerebrovascular reserve capacity during cerebral revascularization in 4 consecutive patients with moyamoya. RESULTS: Spontaneous spreading depolarization occurrence was documented in a patient with moyamoya before bypass grafting. Interestingly, this patient also exhibited a marked preoperative increase in angiographic collateral vessel formation. CONCLUSIONS: The spontaneous occurrence of SDs in moyamoya vasculopathy could potentially provide an explanation for localized cortical infarction and increased cortical microvascular density in these patients.

Speech production relies on the interplay of different brain regions. Healthy aging leads to complex changes in speech processing and production. Here, we investigated how the whole-brain functional connectivity of healthy elderly individuals differs from that of young individuals. In total, 23 young (aged 24.6 ± 2.2 years) and 23 elderly (aged 64.1 ± 6.5 years) individuals performed a picture naming task during functional magnetic resonance imaging. We determined whole-brain functional connectivity matrices and used them to compute group averaged speech production networks. By including an emotionally neutral and an emotionally charged condition in the task, we characterized the speech production network during normal and emotionally challenged processing. Our data suggest that the speech production network of elderly healthy individuals is as efficient as that of young participants, but that it is more functionally segregated and more modularized. By determining key network regions, we showed that although complex network changes take place during healthy aging, the most important network regions remain stable. Furthermore, emotional distraction had a larger influence on the young group’s network than on the elderly’s. We demonstrated that, from the neural network perspective, elderly individuals have a higher capacity for emotion regulation based on their age-related network re-organization.

Many functional magnetic resonance imaging (fMRI) studies rely on mass-univariate inference with subsequent multiple comparison correction. Statistical results are frequently visualized as thresholded statistical maps. This approach has inherent limitations including the risk of drawing overly-selective conclusions based only on selective results passing such thresholds. This article gives an overview of both established and newly emerging approaches to supplement such conventional analyses by incorporating information about subthreshold effects with the aim to improve interpretation of findings or leverage a wider array of information. Topics covered include neuroimaging data visualization, p-value histogram analysis and the related Higher Criticism approach for detecting rare and weak effects as well as multivariate analyses and dedicated Bayesian approaches.