Biology subjects

Danieli, A.

Publications and source records attributed to Danieli, A..

4 recordsLinked to original sources

bioRxiv2026

Where is ADHD in the brain? Evidence for a neurodevelopmental continuum of brain dynamics

BackgroundAttention-deficit/hyperactivity disorder (ADHD) has traditionally been conceptualized categorically, with efforts to identify disorder-specific neurobiological endophenotypes. However, dimensional models suggest that brain-behavior organization may follow developmental axes that cut across diagnostic boundaries. We tested whether neural dynamics and cortical excitability differentiate those with ADHD diagnoses from typically developing (TD) peers, and whether brain-behavior covariance aligns with diagnostic or developmental dimensions. MethodsWe studied 84 participants aged 8-17 years (51 ADHD, 33 TD). High-density electrophysiological (hdEEG) measures included task-free source-resolved data used to derive mean global brain fluidity (variance of dynamic functional connectivity) and region-specific cortical excitability. Behavioural measures included self- and parent-report questionnaires, cognitive control (CC) tasks, and neuropsychological tests. Partial least squares (PLS) assessed multivariate brain-behavior associations including age, followed by clustering based on latent component scores. ResultsGroup differences emerged in parent-report questionnaires and CC tasks, but not in neuropsychological measures. ADHD individuals showed higher mean global brain fluidity and increased cortical excitability. The excitability-fluidity relationship was network-dependent: higher excitability predicted higher fluidity in task-positive networks and lower fluidity in default-mode and salience networks, with no group effects. PLS identified a latent dimension linking neural metrics with age, verbal fluency, inhibitory control, and positive affect, but it did not distinguish ADHD from TD. Clustering revealed two neurodevelopmental profiles spanning both groups. ConclusionsWhile ADHD is associated with mean-level differences in neural dynamics, brain-behaviour organization follows a developmental neurocognitive-affective axis that transcends the diagnostic boundary. These findings support a dimensional framework for understanding neurobiological variation in neurodevelopmental conditions.

neuroscience↗

bioRxiv2024

Excitation/Inhibition balance relates to cognitive function and gene expression in Temporal Lobe Epilepsy: an hdEEG assessment with aperiodic exponent

Patients with epilepsy are characterized by a dysregulation of excitation-inhibition balance (E/I). The assessment of E/I may inform clinicians during the diagnosis and therapy management, even though it is rarely performed. An accessible measure of the E/I of the brain represents a clinically relevant feature. Here we exploited the exponent of the aperiodic component of the power spectrum of EEG signal as a noninvasive and cost-effective proxy of the E/I balance. We recorded resting-state activity with high-density EEG from 65 patients with temporal lobe epilepsy (TLE) and 35 controls. We extracted the exponent of the aperiodic fit of the power spectrum from source-reconstructed EEG and tested differences between TLE and controls. Spearmans correlation was performed between the exponent and clinical variables (age of onset, epilepsy duration and neuropsychology) and cortical expression of epilepsy-related genes derived from Human Allen Brain Atlas. Patients with TLE showed a significantly larger exponent, corresponding to an inhibition directed E/I balance, in bilateral frontal and temporal regions. Lower E/I in the left entorhinal, and bilateral dorsolateral prefrontal cortices corresponded to a lower performance of short term verbal memory. Limited to TLE, we detected a significant correlation between the exponent and the cortical expression of GABRA1, GRIN2A, GABRD, GABRG2, KCNA2and PDYN. EEG aperiodic exponent maps the E/I balance non-invasively in patients with epilepsy and reveals a tight relationship between altered E/I patterns, cognition and genetics.

neuroscience↗

bioRxiv2023

Altered spread of large scale brain dynamics is influenced by cortical thickness organization in temporal lobe epilepsy: a MRI and hdEEG study

Temporal lobe epilepsy (TLE) is a brain network disorder characterized by alterations at both the structural and the functional level. It remains unclear how structure and function are related and whether this has any clinical relevance. In the present work, we adopted a novel methodological approach investigating how network structural features influence the large-scale dynamics. The functional network was defined by the spatio-temporal spreading of aperiodic bursts of activations (neuronal avalanches), as observed utilizing high-density electroencephalography (hdEEG) in TLE patients. The structural network was modeled as the region-based thickness covariance. Loosely speaking, we quantified the similarity of the cortical thickness of any two brain regions, both across groups, and at the individual level, the latter utilizing a novel approach to define the personalized covariance network (pCN). In order to compare the structural and functional networks (at the nodal level), we studied the correlation between the probability that a wave of activity would propagate from a source to a target region, and the similarity of the source region thickness as compared to other target brain regions. Building on the recent evidence that large-waves of activities pathologically spread through the epileptogenic network in TLE, also during resting state, we hypothesize that the structural cortical organization might influence such altered spatio-temporal dynamics. We observed a stable cluster of structure-function correlation in the bilateral limbic areas across subjects, highlighting group specific features for left, right and bilateral TLE. The involvement of contralateral areas was observed in unilateral TLE. We showed that in temporal lobe epilepsy alterations of structural and functional networks pair in the regions where seizures propagate and are linked to disease severity. In this study we leveraged on a well-defined model of neurological disease and pushed forward personalization approaches potentially useful in clinical practice. Finally, the methods developed here could be exploited to investigate the relationship between structure-function networks at subject level in other neurological conditions.

neuroscience↗

bioRxiv2018

Ykt6 membrane-to-cytosol cycling regulates exosomal Wnt secretion

Protein trafficking in the secretory pathway, for example the secretion of Wnt proteins, requires tight regulation. These ligands activate Wnt signaling pathways and are crucially involved in development and disease. Wnt is transported to the plasma membrane by its cargo receptor Evi, where Wnt/Evi complexes are endocytosed and sorted onto exosomes for long-range secretion. However, the trafficking steps within the endosomal compartment are not fully understood. The promiscuous SNARE Ykt6 folds into an auto-inhibiting conformation in the cytosol, but a portion associates with membranes by its farnesylated and palmitoylated C-terminus. Here, we demonstrate that membrane detachment of Ykt6 is essential for exosomal Wnt secretion. We identified conserved phosphorylation sites within the SNARE domain of Ykt6, which block Ykt6 cycling from the membrane to the cytosol. In Drosophila, Ykt6 RNAi-mediated block of Wg secretion is rescued by wildtype but not phosphomimicking Ykt6. We show that phosphomimicking Ykt6 accumulates at membranes, while wildtype Ykt6 regulates Wnt trafficking between the plasma membrane and multivesicular bodies in a dose-dependent manner. Taken together, we show that exosomal sorting of Wnts is fine-tuned by a regulatory switch in Ykt6 shifting it from a membrane-bound to cytosolic state at the level of endosomal maturation.

cell biology↗