Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder, yet it remains unclear whether cortical architecture can reveal biologically distinct subtypes with distinct molecular and serum biomarker signatures. Two hundred PD patients and 121 healthy controls underwent structural MRI. Subject-specific cortical similarity networks were constructed using Morphometric INverse Divergence (MIND), and subtypes were identified with HYDRA. Spatial patterns were linked to regional gene expression from the Allen Human Brain Atlas through partial least squares regression, followed by functional and cell-type enrichment analyses. Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified using single-molecule array assays. No significant MIND differences emerged when PD patients were analysed as a single group. HYDRA identified two subtypes (ARI = 0.85) with divergent cortical organization that only partially overlapped with conventional motor phenotypes. Cluster 1 exhibited temporo-parietal MIND increases associated with synaptic and oligodendroglial signatures, without serum biomarker associations. Cluster 2 showed widespread fronto-cingulate MIND reductions enriched for mitochondrial, lysosomal, and proteostatic pathways, including the KEGG Parkinson’s disease pathway, and these reductions correlated with higher serum NfL and GFAP. These findings reveal two biologically distinct PD subtypes with divergent molecular architecture and systemic neurodegeneration beyond conventional motor phenotyping.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms and widespread alterations in brain networks. Circulating biomarkers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) reflect neuroaxonal damage and astroglial activation, respectively, but their relationship with large-scale brain connectivity remains poorly understood. Seventy-three PD patients and thirty-four healthy controls underwent diffusion magnetic resonance imaging. Whole-brain tractography was used to reconstruct structural connectivity networks, and graph-theoretical measures were derived. Serum NfL and GFAP levels were quantified, and their associations with network metrics and clinical variables were assessed. PD patients showed significant alterations in global and nodal network organization compared to controls. Higher NfL and GFAP levels were associated with reduced global clustering coefficient and efficiency, as well as increased path length and modularity. At the regional level, higher biomarker levels were associated with reduced network measures in the right thalamus and right cerebellar cortex. No significant associations were observed in healthy controls. These findings demonstrate that circulating biomarkers of neurodegeneration are linked to both global and regional disruptions of structural brain connectivity in PD, supporting the integration of blood-based biomarkers and connectomics to better characterize disease-related network alterations.

Background/Objectives: This study evaluated the reproducibility of brain morphometric measurements obtained with different head coils and acceleration factors on a PET/MR scanner, with the aim of supporting reliability in longitudinal neuroimaging studies following major scanner hardware upgrades and introduction of higher-channel-density coils for improved image quality and shorter acquisition times. Methods: Fifteen healthy subjects underwent MPRAGE imaging on a 3T PET/MR scanner using a 16 channel head/neck coil with acceleration factor 2 and a 32 channel PET-transparent head coil with acceleration factors 2 and 4. Cortical thickness and subcortical volumes were measured with FreeSurfer. We performed correlation analyses to test the association between the values of cortical thickness and subcortical volumes derived from MPRAGE images acquired with either the 16- or the 32 channel coil. Test–retest variability and intraclass correlation coefficient were calculated to assess the reproducibility of the measurements for each brain region generated by each sequence and coil. Results: Cortical thickness and subcortical volume measurements from images acquired with different coils and acceleration factors showed high correlation (R = 0.96–1.00, p < 0.001) between protocols, with median test–retest variability below 4% for cortical thickness and a structure-dependent pattern for subcortical volumes, with higher variability in smaller structures such as the accumbens, reaching approximately 7.9% in cross-coil comparisons. Conclusions: Overall, brain morphometry measurements were reproducible across acquisition conditions. Coils with a higher number of channels were associated with improved signal-to-noise ratio, shorter acquisition times, and maintained quantitative consistency.

Background: Essential tremor (ET) is a common movement disorder characterized by postural and kinetic tremor. Some patients also show resting tremor, being classified as the ET-plus distinct subtype. The corpus callosum (CC) involvement is proven in several neurological diseases, including ET, but differences between ET with and without resting tremor have not been studied. In this study, we investigated structural characteristics of the CC in a cohort of ET and ET with resting tremor (ETrt) patients, compared to healthy controls (HC). Methods: We enrolled 128 participants (63 ET, 38 ETrt, and 27 HC). We performed a multimodal MRI evaluation (thickness, mean diffusivity [MD], and fractional anisotropy [FA]) of the CC’s genu, body, and splenium, using different statistical approaches. We first performed a traditional group-based comparison, controlling for relevant covariates. Then, we used an unsupervised classification model based on MRI data to explore potential subgroup distinctions. Results: Our evaluation showed significant changes in structural parameters of CC in both ET and ETrt patients compared to HC, mainly represented by thickness reductions across all regions and MD increase in the body. Notably, we found no differences between the ET and ETrt groups. Clustering analysis reinforced this observation, placing ET and ETrt in a single cluster with similar abnormalities in all MRI parameters and clearly separating them from HC. Discussion: Despite their clinical differences, ET with and without resting tremor patients showed analogous macro- and microstructural changes in the CC, suggesting shared pathophysiological processes within this brain region. Highlights We explored structural integrity of the Corpus Callosum in ET patients with and without resting tremor. We found a thinning of the corpus callosum and microstructural abnormalities overlapping in ET and ETrt groups, suggesting that despite their different clinical presentations, they share some underlying mechanisms.

Diffusion Tensor Imaging (DTI) is a non-invasive method to study integrity of fibers in white matter and could help detect microstructural alterations in MRI data not necessarily associated with volumetric or structural variations. In this study, we used DTI to identify changes in fractional anisotropy (FA) and mean diffusivity (MD) in temporal and extratemporal white matter in patients with mild MTLE (mMTLE) and drug-resistant MTLE (rMTLE) compared to Healthy Controls (HC). In this study we enrolled 21 mMTLE, 17 rMTLE and 31 age and sex matched HC. For each subject, FA and MD were extracted from the following regions of interest (ROI): right and left hippocampi, right and left white matter and gray matter of temporal lobe. In all MTLE patients we classified right and left ROI such as ipsilateral and contralateral zone according to epileptogenic activity on EEG. We investigated group-wise differences using ANOVA followed by Tukey's test setting threshold to < 0.05. In all tests, we found decreased FA in both mMTLE and rMTLE compared to HC, paralleled increased MD in all temporal white matter regions. These results were also confirmed classifying all ROIs as ipsilateral or contralateral to EEG side. These alterations support the idea that DTI measurements could help to individuate drug-resistant in patients with MTLE.