Biology subjects

Romanello, A.

Publications and source records attributed to Romanello, A..

8 recordsLinked to original sources

bioRxiv2025

Memory dysfunction and psychiatric outcomes in anti-NMDA receptor encephalitis are linked to altered structural brain complexity

IntroductionMost patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) experience long-term neuropsychiatric sequelae despite immunotherapy. However, how these residual symptoms relate to structural brain changes in the post-acute phase remains unclear. Recently, fractal dimensionality (FD) has emerged as a sensitive imaging marker of structural brain complexity in related conditions but has not been explored in autoimmune encephalitis. MethodsThis cross-sectional study combined clinical, cognitive, and neuroimaging analyses in 70 patients with post-acute NMDARE (median time from onset: 22 months), and 70 healthy controls matched for age (t=-0.57, p=0.57) and sex ({chi}2=0, p=1). High-resolution T1-weighted magnetic resonance imaging (MRI) data were analyzed with FreeSurfer and computational fractal analysis. Clinical outcomes were assessed with the modified Rankin Scale (mRS) and Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Psychiatric manifestations underwent phenotypical analyses, and memory performance was assessed with standardized neuropsychological tests. ResultsPatients with NMDARE were severely affected at peak illness but showed substantial overall improvement in the post-acute stage (median mRS at peak=5, post-acute=1, z=-7.2, p<0.001; median CASE at peak=11, post-acute=1, z=-7.2, p<0.001). However, 67% of patients showed residual CASE symptoms, with memory dysfunction (61%) and psychiatric symptoms (36%) representing the most prevalent domains. Therein, psychiatric symptoms showed a phenotypical shift from a schizophrenia-like phenotype at peak illness to an affective phenotype in the post-acute stage. Neuroimaging uncovered a characteristic pattern of reduced structural brain complexity, including the hippocampus bilaterally and a fronto-cingulo-temporal cluster in cortical gray matter and cerebral white matter. Importantly, normative modeling revealed that patients with residual symptoms showed stronger alterations of brain complexity than those without (psychiatric: t=-2.65, p=0.010; memory: t=-3.98, p<0.001; both vs. no symptoms: t=-5.46, p<0.001). Similarly, patients with stronger alterations of brain complexity showed lower scores of visuospatial and verbal memory (all pFDR<0.015). DiscussionPost-acute NMDARE is characterized by systematic reductions in structural brain complexity, consistently involving previously implicated regions while identifying changes in the cingulate cortex as a new morphological correlate. These changes are linked to residual psychiatric symptoms and memory dysfunction, highlighting FD as a promising new imaging marker of long-term outcomes. Our findings suggest that current treatment strategies may be insufficient to fully address the residual symptom burden after the acute phase of NMDARE.

neuroscience↗

bioRxiv2025

Functional connectivity is linked to symbolic BOLD patterns: replication, extension, and clinical application of the human 'complexome'

Functional connectivity (FC) quantifies the temporal coherence of blood-oxygen-level-dependent (BOLD) signals across brain regions. Recently, the information-theoretic "complexome" framework has linked FC to coinciding complexity drops: transient moments in which regional BOLD signals simultaneously become regular. Here, we replicate this relationship in an independent dataset and extend the framework by (i) integrating it with signal cofluctuation analysis through edge-timeseries, (ii) extending the previous binary concept of simultaneous complexity drops to a continuous, threshold-free calculation, (iii) providing evidence of clinical relevance in the model disease of anti-N-methyl-D-aspartate-receptor encephalitis, and (iv) deriving a novel measure of pairwise dissimilarity in local BOLD patterns. This index of pattern incongruency (IPI) explains clinically relevant FC reductions and maps onto novel associations with cognition. These findings show that global FC is closely related to local patterns within underlying BOLD signals, strengthening the link between complexity dynamics and the brains functional organization as a large-scale network.

neuroscience↗

bioRxiv2025

Triosephosphate Isomerase as a Quantum Logic Gate: Could quantum decoherence be toxic?

This study presents the hypothesis that triosephosphate isomerase (TIM), a pivotal enzyme in glycolysis, functions as a quantum logic gate. Utilizing quantum mechanics, we model TIMs catalytic conversion of dihydroxyacetone phosphate (DHAP) to glyceraldehyde-3-phosphate (G3P) as a quantum operation involving precise proton transfer. To explore the broader implications of this quantum behavior, we developed a quantum model to assess the impact of Sodium-glucose co-transporter 2 inhibitors (SGLT2i) on methylglyoxal formation, a toxic byproduct linked to advanced glycation end products (AGEs). Our model predicts that SGLT2i could reduce methylglyoxal by decreasing the likelihood of intermediate formation, providing a potential mechanism for their protective effects observed in clinical contexts, including vascular and renal protection in diabetes, nephropathy, and heart failure. By reframing TIM as a quantum logic gate, this study not only challenges traditional views of enzymatic function but also opens new avenues for quantum biology, offering profound implications for the future of metabolic disease research and drug development. Moreover considering methylglyoxal as a result of a quantum tunnel inefficiency, its possible to hypothesize a new "noxa patogena" explicating its action as quantum interference.

systems biology↗

bioRxiv2024

Persistent cognitive deficits in anti-LGI1 encephalitis are linked to a reorganization of structural brain networks

Structured AbstractO_ST_ABSImportanceC_ST_ABSDespite immunotherapy, most patients with anti-leucine-rich, glioma-inactivated 1 encephalitis (LGI1-E) develop long-term cognitive deficits that persist for years after peak illness. However, the structural brain changes that underlie these deficits remain poorly understood. ObjectiveTo study the relationship between cognitive outcomes and white matter (WM) networks in LGI1-E. DesignCross-sectional study. SettingGerman university center (Charite - Universitatsmedizin Berlin). Participants25 patients with LGI1-E (19/25 male [76%], mean age: 63 {+/-} 12 years) and 25 age- and sex-matched healthy controls (HC), recruited between January 2013 and April 2019. Main Outcomes and MeasuresClinical assessments including the modified Rankin Scale (mRS) and Clinical Assessment Scale in Autoimmune Encephalitis (CASE); comprehensive cognitive testing; WM tractography using diffusion-weighted MRI. ResultsAll patients had received first-line immunotherapy, and two-thirds underwent second-line immunotherapy. Patients showed a significant reduction in mRS scores from peak illness to post-acute follow-up (z = -3.8, p < 0.001, n = 20), with 85% presenting "good" functional outcomes (post-acute mRS [≤] 2), paralleled by a significant reduction in CASE scores (z = -3.5, p < 0.001, n = 20). Despite this overall improvement, however, cognitive symptoms were highly prevalent at peak illness (95% of patients affected) and strongly persisted into the post-acute disease stage (85% affected). Neuroimaging at post-acute follow-up (median: 12 months from onset) revealed that LGI1-E is characterized by (i) significantly reduced whole-brain structural connectivity (t = -2.16, p = 0.036, d = -0.61), (ii) a cortico-subcortical hypoconnectivity cluster that strongly affects the hippocampus but also severely impacts extra-limbic brain systems, (iii) systematic limbic and extra-limbic decreases in node degree -- a graph-theoretical measure of overall connectedness, and (iv) a "topological reorganization" of structural brain networks, marked by a bidirectional shift in the relative importance of individual brain regions in the network. Importantly, the extent of this network reorganization was significantly related to persistent cognitive deficits in the domains of verbal memory (r = -0.57, p = 0.007, n = 21), attention (r = -0.47, p = 0.030, n = 21), and executive functions (r = -0.60, p = 0.010, n = 17). Conclusion and RelevanceThis study characterizes LGI1-E as a network disease that affects both limbic and extra-limbic brain systems and shows that a reorganization of WM networks is linked to multi-domain cognitive deficits in the post-acute disease stage - despite immunotherapy and good overall recovery. These findings highlight the need for extended treatment strategies to improve long-term cognitive outcomes and propose a sensitive new neuroimaging marker to include in prospective clinical trials. Key PointsO_ST_ABSQuestionC_ST_ABSWhat structural brain changes underlie the persistent cognitive deficits observed in patients with anti-leucine-rich, glioma-inactivated 1 encephalitis (LGI1-E)? FindingsThis cross-sectional study shows that LGI1-E is characterized by a structural reorganization of white matter networks that affects both limbic and extra-limbic brain systems and correlates with persistent deficits in verbal memory, attention, and executive functions at post-acute follow-up - despite immunotherapy and good overall clinical recovery. MeaningThis study characterizes LGI1-E as a network disease -beyond focal damage to the limbic system- and shows that persistent cognitive deficits relate to immunotherapy-resistant changes in structural brain networks, highlighting the need for extended treatment strategies to improve long-term cognitive outcomes.

neuroscience↗

bioRxiv2023

The formation of brain shape in human newborns

The neonatal period represents a critical phase of human brain development. During this time, the brain shows a dramatic increase in size, but it remains largely unclear how the morphology of the human brain develops in early post-partum life. Here we show that human newborns undergo a rapid formation of brain shape, beyond the expected growth in brain size. Using fractal analysis of structural neuroimaging data, we show that brain shape (i) strongly reflects infant maturity beyond differences in brain size, (ii) significantly outperforms brain size in predicting infant age at scan (mean error ~4 days), (iii) detects persistent alterations in prematurely born infants that are not captured by brain size, (iv) is consistently more sensitive to genetic similarity among neonates, and (v) is superior in predicting which newborns are twin siblings, with up to 97% accuracy. These findings identify the formation of brain shape as a fundamental maturational process in human brain development.

neuroscience↗

bioRxiv2022

Functional connectivity dynamics reflect disability and multi-domain clinical impairment in patients with relapsing-remitting multiple sclerosis

BackgroundFunctional neuroimaging studies have revealed complex and heterogeneous patterns of aberrant functional connectivity (FC) in multiple sclerosis (MS), yet it remains unclear how time-resolved FC relates to variance in clinical disease severity. ObjectivesTo characterize brain activity in MS patients with time-resolved FC analysis and explore the relationship between disease severity, multi-domain impairments, and altered network dynamics. MethodsResting-state functional MRI data were acquired from 101 MS patients and 101 age- and sex-matched healthy controls (HC). Dynamic FC analysis identified five connectivity states that were compared between HC and patients with high vs. low disability. ResultsPatients with higher disease severity exhibited a more widespread spatiotemporal pattern of altered FC and spent more time in a high-connectivity, low-occurrence state compared to patients with lower disease severity and HC. Depressive symptom severity was positively related to functional dynamics on global and network scales in patients, while fatigue and motor impairment were inversely related to frontoparietal network connectivity with the basal ganglia. ConclusionsTime-resolved FC analysis uncovered alterations in network dynamics and clinical correlations that remained undetected with a static account of brain activity. Such time-varying approaches are thus crucial for disentangling the relationship between brain dynamics, disease severity, and symptoms in MS.

neuroscience↗

bioRxiv2022

Reduced resilience of functional state transitions in patients with anti-NMDA receptor encephalitis

ObjectivePatients with anti-NMDA receptor encephalitis suffer from a severe neuropsychiatric syndrome, yet most patients show no abnormalities in routine magnetic resonance imaging. In contrast, advanced neuroimaging studies have consistently identified disrupted functional connectivity in these patients, with recent work suggesting increased volatility of functional state dynamics. Here, we investigate these network dynamics through the spatiotemporal trajectory of meta-state transitions, yielding a time-resolved account of brain state exploration in anti-NMDA receptor encephalitis. MethodsResting-state functional magnetic resonance imaging data were acquired in 73 patients with NMDAR encephalitis and 73 age- and sex-matched healthy controls. Time-resolved functional connectivity was clustered into brain meta-states, giving rise to a time-resolved transition network graph with states as nodes and transitions between brain meta-states as weighted, directed edges. Network topology, robustness, and transition cost of these transition networks were compared between groups. ResultsTransition networks of patients showed significantly lower local efficiency (t = -2.54, pFDR = 0.026), lower robustness (t = -2.01, pFDR = 0.048) and higher leap size (t = 2.33, pFDR = 0.026) compared to controls. Furthermore, the ratio of within-to-between module transitions and state similarity was significantly lower in patients. Importantly, alterations of brain state transitions correlated with disease severity. InterpretationThese findings reveal systematic alterations of transition networks in patients, suggesting that anti-NMDA receptor encephalitis is characterized by reduced stability of brain state transitions and that this reduced resilience of transition networks plays a clinically relevant role in the manifestation of the disease.

neuroscience↗

bioRxiv2021

A spatiotemporal complexity architecture of human brain activity

The human brain operates in large-scale functional networks. These networks are thought to arise from neural variability, yet the principles behind this link remain unknown. Here we report a mechanism by which the brains network architecture is tightly linked to critical episodes of neural regularity, visible as spontaneous complexity drops in functional MRI signals. These episodes support the formation of functional connections between brain regions, subserve the propagation of neural activity, and reflect inter-individual differences in age and behavior. Furthermore, complexity drops define neural states that dynamically shape the coupling strength, topological structure, and hierarchy of brain networks and comprehensively explain known structure-function relationships within the brain. These findings delineate a unifying complexity architecture of neural activity - a human complexome that underpins the brains functional network organization.

neuroscience↗