Giulia Sprugnoli

Background and objectives: Choroid plexus (ChP) is emerging as a key brain structure in the pathophysiology of neurodegenerative disorders. In this observational study we investigated ChP volume in a large cohort of frontotemporal lobar degeneration (FTLD) spectrum patients to explore a possible link between ChP volume and other disease-specific biomarkers. Methods: Participants included patients meeting clinical criteria for a probable syndrome in the FTLD spectrum. Structural brain MRI imaging, serum neurofilament light (NfL) and serum phosphorylated-Tau₁₈₁ (p-Tau₁₈₁), cognitive and behavioral data were collected. MRI ChP volumes were obtained from an ad-hoc segmentation model based on a Gaussian Mixture Models (GMM) algorithm. Results: Three-hundred and sixteen patients within FTLD spectrum were included in this study, specifically 135 patients diagnosed with behavioral variant frontotemporal dementia (bvFTD), 75 primary progressive aphasia (PPA), 46 progressive supranuclear palsy (PSP), 60 corticobasal syndrome (CBS). In addition, 82 age-matched healthy subjects were recruited as controls (HC). ChP volume was significantly larger in FTLD patients compared with HC, across the clinical subtype. Moreover, we found a significant difference in ChP volume between HC and patients stratified for disease-severity based on CDRplus NACC FTLD, including patients at very early stage of the disease. Interestingly, ChP volume correlated with serum NfL, cognitive/behavioural deficits, as well as with patterns of cortical atrophy. Finally, ChP volume seemed to discriminate HC from FTLD patients better than other previously identified brain structure volumes. Discussion: Considering the clinical, pathological, and genetic heterogeneity of the disease, ChP could represent a potential biomarker across the FTLD spectrum, especially at the early stage of disease. Further longitudinal studies are needed to establish its role in disease onset and progression. Classification of Evidence: This study provides Class III evidence that choroid plexus volume, as measured on MRI scan, can assist in differentiating patients with FTLD from healthy controls, and in characterizing disease severity.

Presence of residual neurovascular activity within glioma lesions have been recently demonstrated via functional MRI (fMRI) along with active electrical synapses between glioma cells and healthy neurons that influence survival. In this study, we aimed to investigate whether gliomas demonstrate synchronized neurovascular activity with the rest of the brain, by measuring Blood Oxygen Level Dependent (BOLD) signal synchronization, that is, functional connectivity (FC), while also testing whether the strength of such connectivity might predict patients’ overall survival (OS). Resting-state fMRI scans of patients who underwent pre-surgical brain mapping were analyzed (total sample, n = 54; newly diagnosed patients, n = 18; recurrent glioma group, n = 36). A seed-to-voxel analysis was conducted to estimate the FC signal profile of the tumor mass. A regression model was then built to investigate the potential correlation between tumor FC and individual OS. Finally, an unsupervised, cross-validated clustering analysis was performed including tumor FC and clinical OS predictors (e.g., Karnofsky Performance Status - KPS - score, tumor volume, and genetic profile) to verify the performance of tumor FC in predicting OS with respect to validated radiological, demographic, genetic and clinical prognostic factors. In both newly diagnosed and recurrent glioma patients a significant pattern of BOLD synchronization between the solid tumor and distant brain regions was found. Crucially, glioma-brain FC positively correlated with variance in individual survival in both newly diagnosed glioma group (r = 0.90–0.96; P < .001; R² = 81–92%) and in the recurrent glioma group (r = 0.72; P < .001; R² = 52%), outperforming standard clinical, radiological and genetic predictors. Results suggest glioma’s synchronization with distant brain regions should be further explored as a possible diagnostic and prognostic biomarker.

Over the past few years, the possibility of modulating fast brain oscillatory activity in the gamma (γ) band through transcranial alternating current stimulation (tACS) has been discussed in the context of both cognitive enhancement and therapeutic scenarios. However, the effects of tACS targeting regions outside the motor cortex, as well as its spatial specificity, are still unclear. Here, we present a concurrent tACS-fMRI block design study to characterize the impact of 40Hz tACS applied over the left and right dorsolateral prefrontal cortex (DLPFC) in healthy subjects. Results suggest an increase in blood oxygenation level-dependent (BOLD) activity in the targeted bilateral DLPFCs, as well as in surrounding brain areas affected by stimulation according to biophysical modeling, i.e., the premotor cortex and anterior cingulate cortex (ACC). However, off-target effects were also observed, primarily involving the visual cortices, with further effects on the supplementary motor areas (SMA), left subgenual cingulate, and right superior temporal gyrus. The specificity of 40Hz tACS over bilateral DLPFC and the possibility for network-level effects should be considered in future studies, especially in the context of recently promoted gamma-induction therapeutic protocols for neurodegenerative disorders.

Background and Purpose: Obstructive sleep apnea (OSA) syndrome is a sleep disorder characterized by excessive snoring, repetitive apneas, and nocturnal arousals, that leads to fragmented sleep and intermittent nocturnal hypoxemia. Morphometric and functional brain alterations in cortical and subcortical structures have been documented in these patients via magnetic resonance imaging (MRI), even if correlational data between the alterations in the brain and cognitive and clinical indexes are still not reported.Methods: We examined the impact of OSA on brain spontaneous activity by measuring the fractional amplitude of low‐frequency fluctuations (fALFF) in resting‐state functional MRI data of 20 drug‐naïve patients with OSA syndrome and 20 healthy controls matched for age, gender, and body mass index.Results: Patients showed a pattern of significantly abnormal subcortical functional activity as compared to controls, with increased activity selectively involving the thalami, specifically their intrinsic nuclei connected to somatosensory and motor‐premotor cortical regions. Using these nuclei as seed regions, the subsequent functional connectivity analysis highlighted an increase in patients’ thalamocortical connectivity at rest. Additionally, the correlation between fALFF and polysomnographic data revealed a possible link between OSA severity and fALFF of regions belonging to the central autonomic network.Conclusions: Our results suggest a hyperactivation in thalamic diurnal activity in patients with OSA syndrome, which we interpret as a possible consequence of increased thalamocortical circuitry activation during nighttime due to repeated arousals.

Background: Alzheimer’s disease (AD) is associated with alterations in cortical perfusion that correlate with cognitive impairment. Recently, neural activity in the gamma band has been identified as a driver of arteriolar vasomotion while, on the other hand, gamma activity induction on preclinical models of AD has been shown to promote protein clearance and cognitive protection. Methods: In two open-label studies, we assessed the possibility to modulate cerebral perfusion in 15 mild to moderate AD participants via 40Hz (gamma) transcranial alternating current stimulation (tACS) administered 1 h daily for 2 or 4 weeks, primarily targeting the temporal lobe. Perfusion-sensitive MRI scans were acquired at baseline and right after the intervention, along with electrophysiological recording and cognitive assessments. Results: No serious adverse effects were reported by any of the participants. Arterial spin labeling MRI revealed a significant increase in blood perfusion in the bilateral temporal lobes after the tACS treatment. Moreover, perfusion changes displayed a positive correlation with changes in episodic memory and spectral power changes in the gamma band. Conclusions: Results suggest 40Hz tACS should be further investigated in larger placebo-controlled trials as a safe, non-invasive countermeasure to increase fast brain oscillatory activity and increase perfusion in critical brain areas in AD patients. Trial registration: Studies were registered separately on ClinicalTrials.gov (NCT03290326, registered on September 21, 2017; NCT03412604, registered on January 26, 2018).

The newly discovered functional integration of glioma cells into brain networks in mouse models provides groundbreaking insight into glioma aggressiveness and resistance to treatments, also suggesting novel potential therapeutic avenues and targets. In the context of such neuron-to-glioma communication, noninvasive brain modulation techniques traditionally applied to modulate neuronal function in neurological and psychiatric diseases (eg, increase/decrease cortical excitability and plasticity) could now be tested in patients with brain tumors to suppress glioma’s activity and its pathological crosstalk with healthy brain tissue.

Transcranial electrical stimulation can safely and noninvasively modulate perfusion of brain tumors in humans.

Cross‐sectional data suggest videogaming as promoting modifications in perceptual and cognitive skills of players, as well as inducing structural brain changes. However, whether such changes are both possible after a systematic gaming exposure, and last beyond the training period, is not known. Here, we originally quantified immediate and long‐lasting cognitive and morphometric impact of a systematic gaming experience on a first‐person shooter (FPS) game. Thirty‐five healthy participants, assigned to a videogaming and a control group, underwent a cognitive assessment and structural magnetic resonance imaging at baseline (T0), immediately post‐gaming (T1) and after 3 months (T2). Enhancements of cognitive performance were found on perceptual and attentional measures at both T1 and T2. Morphometric analysis revealed immediate structural changes involving bilateral medial and posterior thalamic nuclei, as well as bilateral superior temporal gyrus, right precentral gyrus, and left middle occipital gyrus. Notably, significant changes in pulvinar volume were still present at T2, while a voxel‐wise regression analysis also linked baseline pulvinar volume and individual changes in gaming performance. Present findings extend over the notion that videogame playing might impact cognitive and brain functioning in a beneficial way, originally showing long‐term brain structural changes even months after gaming practice. The involvement of posterior thalamic structures highlights a potential link between FPS games and thalamo‐cortical networks related to attention mechanisms and multisensory integration processing.