Development of the visual white matter pathways mediates development of electrophysiological responses in visual cortex

The latency of neural responses in the visual cortex changes systematically across the lifespan. Here, we test the hypothesis that development of visual white matter pathways mediates maturational changes in the latency of visual signals. Thirty-eight children participated in a cross-sectional study including diffusion magnetic resonance imaging (MRI) and magnetoencephalography (MEG) sessions. During the MEG acquisition, participants performed a lexical decision and a fixation task on words presented at varying levels of contrast and noise. For all stimuli and tasks, early evoked fields were observed around 100 ms after stimulus onset (M100), with slower and lower amplitude responses for low as compared to high contrast stimuli. The optic radiations and optic tracts were identified in each individual's brain based on diffusion MRI tractography. The diffusion properties of the optic radiations predicted M100 responses, especially for high contrast stimuli. Higher optic radiation fractional anisotropy (FA) values were associated with faster and larger M100 responses. Over this developmental window, the M100 responses to high contrast stimuli became faster with age and the optic radiation FA mediated this effect. These findings suggest that the maturation of the optic radiations over childhood accounts for individual variations observed in the developmental trajectory of visual cortex responses

Increased Functional Connectivity in the Default Mode Network in Mild Cognitive Impairment: A Maladaptive Compensatory Mechanism Associated with Poor Semantic Memory Performance

Semantic memory decline and changes of default mode network (DMN) connectivity have been reported in mild cognitive impairment (MCI). Only a few studies, however, have investigated the role of changes of activity in the DMN on semantic memory in this clinical condition. The present study aimed to investigate more extensively the relationship between semantic memory impairment and DMN intrinsic connectivity in MCI. Twenty-one MCI patients and 21 healthy elderly controls matched for demographic variables took part in this study. All participants underwent a comprehensive semantic battery including tasks of category fluency, visual naming and naming from definition for objects, actions and famous people, word-association for early and late acquired words and reading. A subgroup of the original sample (16 MCI patients and 20 healthy elderly controls) was also scanned with resting state functional magnetic resonance imaging and DMN connectivity was estimated using a seed-based approach. Compared with healthy elderly, patients showed an extensive semantic memory decline in category fluency, visual naming, naming from definition, words-association, and reading tasks. Patients presented increased DMN connectivity between the medial prefrontal regions and the posterior cingulate and between the posterior cingulate and the parahippocampus and anterior hippocampus. MCI patients also showed a significant negative correlation of medial prefrontal gyrus connectivity with parahippocampus and posterior hippocampus and visual naming performance. Our findings suggest that increasing DMN connectivity may contribute to semantic memory deficits in MCI, specifically in visual naming. Increased DMN connectivity with posterior cingulate and medio-temporal regions seems to represent a maladaptive reorganization of brain functions in MCI, which detrimentally contributes to cognitive impairment in this clinical population

In-vivo vascular application via ultra-fast bioprinting for future 5D personalised nanomedicine

The design of 3D complex structures enables new correlation studies between the engineering parameters and the biological activity. Moreover, additive manufacturing technology could revolutionise the personalised medical pre-operative management due to its possibility to interplay with computer tomography. Here we present a method based on rapid freeze prototyping (RFP) 3D printer, reconstruction cutting, nano dry formulation, fast freeze gelation, disinfection and partial processes for the 5D digital models functionalisation. We elaborated the high-resolution computer tomography scan derived from a complex human peripheral artery and we reconstructed the 3D model of the vessel in order to obtain and verify the additive manufacturing processes. Then, based on the drug-eluting balloon selected for the percutaneous intervention, we reconstructed the biocompatible eluting-freeform coating containing 40\u2009nm fluorescent nanoparticles (NPs) by means of RFP printer and we tested the in-vivo feasibility. We introduced the NPs-loaded 5D device in a rat's vena cava. The coating dissolved in a few minutes releasing NPs which were rapidly absorbed in vascular smooth muscle cell (VSMC) and human umbilical vein endothelial cell (HUVEC) in-vitro. We developed 5D high-resolution self-dissolving devices incorporating NPs with the perspective to apply this method to the personalised medicine

Combining Structural Magnetic Resonance Imaging and Visuospatial Tests to Classify Mild Cognitive Impairment

Background: Recently, efforts have been made to combine complementary perspectives in the assessment of Alzheimer type dementia. Of particular interest is the definition of the fingerprints of an early stage of the disease known as Mild Cognitive Impairment or prodromal Alzheimer's Disease. Machine learning approaches have been shown to be extremely suitable for the implementation of such a combination. Methods: In the present pilot study we combined the machine learning approach with structural magnetic resonance imaging and cognitive test assessments to classify a small cohort of 11 healthy participants and 11 patients experiencing Mild Cognitive Impairment. Cognitive assessment included a battery of standardised tests and a battery of experimental visuospatial memory tests. Correct classification was achieved in 100% of the participants, suggesting that the combination of neuroimaging with more complex cognitive tests is suitable for early detection of Alzheimer Disease. Results: In particular, the results highlighted the importance of the experimental visuospatial memory test battery in the efficiency of classification, suggesting that the high-level brain computational framework underpinning the participant's performance in these ecological tests may represent a “natural filter” in the exploration of cognitive patterns of information able to identify early signs of the disease

Dementia-related genetic variants in an Italian population of early-onset Alzheimer’s disease

Early-onset Alzheimer’s disease (EOAD) is the most common form of early-onset dementia. Although three major genes have been identified as causative, the genetic contribution to the disease remains unsolved in many patients. Recent studies have identified pathogenic variants in genes representing a risk factor for developing Alzheimer’s disease (AD) and in causative genes for other degenerative dementias as responsible for EOAD. To study them further, we investigated a panel of candidate genes in 102 Italian EOAD patients, 45.10% of whom had a positive family history and 21.74% with a strong family history of dementia. We found that 10.78% of patients carried pathogenic or likely pathogenic variants, including a novel variant, in PSEN1, PSEN2, or APP, and 7.84% showed homozygosity for the ε4 APOE allele. Additionally, 7.84% of patients had a moderate risk allele in PSEN1, PSEN2, or TREM2 genes. Besides, we observed that 12.75% of our patients carried only a variant in genes associated with other neurodegenerative diseases. The combination of these variants contributes to explain 46% of cases with a definite familiarity and 32% of sporadic forms. Our results confirm the importance of extensive genetic screening in EOAD for clinical purposes, to select patients for future treatments and to contribute to the definition of overlapping pathogenic mechanisms between AD and other forms of dementia

The NeuroDante Project: Neurometric measurements of participant’s reaction to literary auditory stimuli from dante’s “divina commedia”

Neurodante. Progetto di analisi neurometrica di alcuni brani della Commedi

Hippocampal vascularization patterns: A high-resolution 7 Tesla time-of-flight magnetic resonance angiography study

Considerable evidence suggests a close relationship between vascular and degenerative pathology in the human hippocampus. Due to the intrinsic fragility of its vascular network, the hippocampus appears less able to cope with hypoperfusion and anoxia than other cortical areas. Although hippocampal blood supply is generally provided by the collateral branches of the posterior cerebral artery (PCA) and the anterior choroidal artery (AChA), different vascularization patterns have been detected postmortem. To date, a methodology that enables the classification of individual hippocampal vascularization patterns in vivo has not been established. In this study, using high-resolution 7 Tesla time-of-flight angiography data (0.3 mm isotropic resolution) in young adults, we classified individual variability in hippocampal vascularization patterns involved in medial temporal lobe blood supply in vivo. A strong concordance between our classification and previous autopsy findings was found, along with interesting anatomical observations, such as the variable contribution of the AChA to hippocampal supply, the relationships between hippocampal and PCA patterns, and the different distribution patterns of the right and left hemispheres. The approach presented here for determining hippocampal vascularization patterns in vivo may provide new insights into not only the vulnerability of the hippocampus to vascular and neurodegenerative diseases but also hippocampal vascular plasticity after exercise training