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Mantwill, M.

Publications and source records attributed to Mantwill, M..

3 recordsLinked to original sources
bioRxiv2026

Spatial navigation impairment beyond episodic memory in autoimmune encephalitis

NMDAR and LGI1 encephalitis are the two most common forms of autoimmune encephalitis and are associated with persistent cognitive sequelae, particularly episodic memory impairment. Patients also report lasting difficulties with spatial orientation and navigation, yet these symptoms remain poorly characterized. Both disorders affect neural systems supporting spatial navigation, including prominent hippocampal pathology alongside cingulate, temporo-parietal, thalamic and cerebellar alterations identified in advanced neuroimaging studies. Here, we therefore investigated the frequency and clinical relevance of spatial navigation impairment in post-acute NMDAR and LGI1 encephalitis, its relationship with episodic memory dysfunction, and its structural correlates. We included 80 post-acute patients from the autoimmune encephalitis outpatient clinic at Charite - Universitatsmedizin Berlin: 50 with NMDAR encephalitis (mean age 35.0 years, range 19-71; 90% female; median 6.9 years from onset) and 30 with LGI1 encephalitis (mean age 63.6 years, range 33-84; 67% male; median 2.7 years from onset). Spatial navigation was assessed using a passive map-assisted task (VIENNA Young) and an active wayfinding task (Sea Hero Quest), and its relationship with verbal episodic memory was examined using the Rey Auditory Verbal Learning Test. Structural MRI analyses assessed cortical thickness, subcortical volumes and diffusion measures in preselected navigation- and memory-related regions. Patients with NMDAR and LGI1 encephalitis performed worse than matched controls on map-assisted navigation, and navigation performance showed strong convergence across the two navigation paradigms. Norm-referenced navigation impairment affected 57% of patients with NMDAR encephalitis and 70% with LGI1 encephalitis. In NMDAR encephalitis, selective navigation impairment was more common than selective memory impairment (41% versus 14%; {chi}2 = 6.26, p = .012), supporting partial dissociation. In LGI1 encephalitis, navigation and memory impairments were similarly frequent and strongly overlapping, with 53% of patients impaired in both domains. Older age was a shared risk factor for navigation impairment. Structurally, NMDAR encephalitis showed partly distinct navigation- and memory-related alteration patterns, with navigation-specific parietal-paracentral and cerebellar abnormalities and memory-specific temporal-hippocampal-thalamic involvement. LGI1 encephalitis showed more widespread, predominantly memory-related alterations without a robust navigation-specific structural signature. Our findings identify spatial navigation as a frequently affected but under-assessed cognitive domain in post-acute NMDAR and LGI1 encephalitis. They provide clinical evidence that navigation and episodic memory are partially dissociable yet overlapping functions whose degree of separability varies with the extent and distribution of network pathology. Incorporating norm-referenced navigation assessment into longitudinal follow-up could improve the characterization of cognitive profiles and related support needs, while reducing the risk that impairments relevant to everyday functioning and long-term quality of life remain undetected.

neuroscience↗
bioRxiv2025

Nurr1 orchestrates claustrum development and functionality

Claustrum is the part of the forebrain known to be most widely interconnected tissue with almost all global regions. It is believed to be involved in coordinating multiple cognitive behaviors including consciousness formation. However, little is known about the molecular mechanisms underlying its development and involvement in behavioral control. Here we show that Nurr1 (Nr4a2) is the key transcription factor orchestrating claustral morphogenesis, functional connectivity and thus behaviors. Nurr1 deficient claustral cells aberrantly migrate into insular cortex, shaping claustrum into an abnormal wing-like structure, and ectopically turn on insular corticex genetic program. Accordingly, functional connectivity of the claustrum is not properly formed and relevant behaviors are dysregulated in Nurr1 deficient mice. We show that Nurr1 regulates claustral neuron positioning by suppressing G-protein signaling.

neuroscience↗
bioRxiv2021

Fingerprinting and behavioural prediction rest on distinct functional systems of the human connectome

The prediction of inter-individual behavioural differences from neuroimaging data is a rapidly evolving field of research, focusing on individualised methods to describe human brain organisation on the single-subject level. One method that harnesses such individual signatures is functional connectome fingerprinting, which can reliably identify individuals from large study populations. While connectome fingerprints have been previously associated with individual cognitive function, these associations rest on indirect evidence. Contrasting with these previous reports, here we systematically investigate the link between connectome fingerprints and the prediction of behaviour on different levels of brain network organisation (individual edges, network interactions, topographical organisation, and edge variability), using 339 resting-state fMRI datasets from the Human Connectome Project. Our analysis revealed a significant divergence between connectivity signatures that discriminate between individuals and those predictive of behaviour on all levels of network organisation. Across different parcellation schemes, thresholds and prediction algorithms, we consistently find fingerprints in higher-order multimodal association cortices, while neural correlates of behaviour display a more variable topological distribution. Furthermore, we find the standard deviation of connections between subjects to be significantly higher in fingerprinting than in prediction, making inter-individual connection variability a possible separating marker. These results demonstrate that participant identification and behavioural prediction involve highly distinct functional systems of the human connectome, suggesting that connectome fingerprints are not as functionally relevant as previously believed. The present study thus calls for a re-evaluation of the significance of functional connectivity fingerprints in personalized medicine.

neuroscience↗