Biology subjects

Finke, C.

Publications and source records attributed to Finke, C..

At least 19 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

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

Long-term memory reorganization of navigational episodes

During navigation, the brain builds representations of self-motion and of environmental information for future action. The classic view suggests that these representations consolidate and eventually stabilize. However, there is no data on their fate at extended memory delays. Here, we investigated memory of navigational episodes from a real-world setting across memory delays of up to three decades. We show that memory of navigational episodes does not achieve a stable state, but rather continues to transform for many years. Our data suggest that at any given point in time, memory of navigational episodes is a changing combination of episode-independent schematic information with several interacting spatial representations that directly relate to a navigational episode and that show distinct decay rates. Consistent with recent accounts of memory reorganization, we further show that neither current theories of systems consolidation nor classic models of forgetting fully explain spatial memory performance at extended memory delays.

neuroscience↗

bioRxiv2025

Propofol differentially modulates consolidation of schema-congruent and -incongruent memory

Congruency of newly learned information with previous knowledge (i.e. a mental schema) leads to facilitated encoding and rapid integration into neocortical memory networks. It is less known whether this is associated with a differential involvement of the hippocampus in consolidation of schema-congruent and -incongruent information. Here, we used the GABAA-ergic anesthetic propofol to transiently modulate hippocampal neural activity shortly after encoding of schema-congruent and -incongruent information in human patients. We found a significant difference in memory of schema-congruent and -incongruent words in patients that was absent in controls. This effect was driven by a benefit for schema-congruent words, thus suggesting that propofol administration facilitated consolidation of previously encoded schema-congruent items. Our results suggest that schema-congruency of newly learned information significantly modulates involvement of hippocampus-dependent networks during memory consolidation. They further support the hypothesis of a competitive interaction between hippocampus and extra-hippocampal networks during early memory consolidation.

neuroscience↗

bioRxiv2025

Convergent Evolutionary Traces of Genomic Innovations and Depletions in Socially Parasitic Ants

Parasitism, a common strategy across life, often involves genomic reduction. Socially parasitic "slavemaking" ants provide an excellent model to study the evolution of this lifestyle. Here, we compared the genomes of four closely related, independently evolved parasite-host pairs and their outgroups to identify convergent patterns. While genome size and gene numbers remain relatively stable, parasites show increased positive and relaxed selection, more putative de novo genes which have recently emerged from previously non-coding regions, and a significant loss of chemical receptors, particularly those associated with the evolution of sociality. Hosts, however, retain many duplicated genes. Gene co-expression networks associated with nest-defence in hosts are rather conserved, while the network structure of raiding parasites is much more variable and reflects the independent evolutionary origin of social parasitism. Our findings suggest that while hosts primarily rely on existing molecular mechanisms for defence, parasite genome evolution is characterised by extensive, convergent gene loss, innovation, and network rewiring.

evolutionary biology↗

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↗

bioRxiv2024

Adaptive Integration of Perceptual and Reward Information in an Uncertain World

Perceptual uncertainty and salience both impact decision-making, but how these factors precisely impact trial-and-error reinforcement learning is not well understood. Here, we test the hypotheses that (H1) perceptual uncertainty modulates reward-based learning and that (H2) economic decision-making is driven by the value and the salience of sensory information. For this, we combined computational modeling with a perceptual uncertainty-augmented reward-learning task in a human behavioral experiment (N = 98). In line with our hypotheses, we found that subjects regulated learning behavior in response to the uncertainty with which they could distinguish choice options based on sensory information (belief state), in addition to the errors they made in predicting outcomes. Moreover, subjects considered a combination of expected values and sensory salience for economic decision-making. Taken together, this shows that perceptual and economic decision-making are closely intertwined and share a common basis for behavior in the real world.

neuroscience↗

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

Maternofetal transfer of human NMDAR antibodies leads to cortical network defect in the adult

Anti-N-methyl-D-aspartate-receptor IgG-antibodies (NMDAR-Ab) can be detected in up to 1% of the healthy population. Because maternal IgG can cross the placental barrier during pregnancy, these antibodies may influence fetal neurodevelopment. Using a mouse model of maternofetally transferred human NMDAR-Ab, we asked whether in utero exposure impacts functional brain dynamics later in life. We conducted two-photon calcium imaging and fMRI in adolescent mice, to evaluate both local and global neuronal network integrity. At the microcircuit scale, NMDAR-Ab exposed offspring exhibited lower spontaneous activity, reduced firing variability, and reduced orientation selectivity upon visual stimulation. Globally, fMRI revealed a selective bilateral functional hypoconnectivity of the entorhinal-hippocampal pathway while overall functional connectivity is unaffected. Together, our data indicates that maternal-fetal transfer of NMDAR-Ab leads to a lasting impairment in sensory processing and memory-routing circuits, revealing a vulnerability of the developing fetal brain to maternal autoantibodies.

neuroscience↗

bioRxiv2023

Hippocampal hub failure is linked to long-term memory impairment in anti-NMDA-receptor encephalitis -Insights from structural connectome graph theoretical network analysis

IntroductionAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is characterized by distinct structural and functional brain alterations, predominantly affecting the medial temporal lobes and the hippocampus. Structural connectome analysis with graph-based investigations of network properties allows for an in-depth characterization of global and local network changes and their relationship with clinical deficits in NMDAR encephalitis. ObjectiveTo investigate changes in structural connectivity and network efficiency in NMDAR encephalitis by use of probabilistic whole-brain tractography and graph theoretical analysis of structural brain networks. MethodsStructural networks from sixty-one NMDAR encephalitis patients in the post-acute stage (median time from acute hospital discharge: 18 months) and sixty-one age- and sex-matched healthy controls (HC) were analyzed using diffusion-weighted imaging (DWI)-based probabilistic anatomically-constrained tractography and spherical deconvolution-informed filtering of tractograms. We calculated global, modular, and nodal graph measures indicative of structural connectivity and network reorganization with special focus on default-mode network, medial temporal lobe, and hippocampus. Pathologically altered metrics were included in multiple regression analyses to investigate their potential association with clinical course, disease severity, and cognitive outcome. ResultsPatients with NMDAR encephalitis showed regular global graph metrics, but bilateral reductions of hippocampal node strength (left: p=0.049; right: p=0.013) and increased node strength of right precuneus (p=0.013) compared to HC. Betweenness centrality was decreased for left-sided entorhinal cortex (p=0.042) and left caudal middle frontal gyrus (p = 0.037). Correlation analyses showed a significant association between reduced left hippocampal node strength and verbal long-term memory impairment (p=0.021) ConclusionFocal network property changes of the medial temporal lobes indicate hippocampal hub failure that is associated with memory impairment in NMDAR encephalitis at the post-acute stage, while global structural network properties remain unaltered. Graph theory analysis provides new pathophysiological insight into structural network changes and their association with persistent cognitive deficits in NMDAR encephalitis.

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↗

bioRxiv2022

Impaired functional connectivity of the hippocampus in murine models of NMDA-receptor antibody associated pathology

IntroductionWhile decreased hippocampal connectivity and disruption of functional networks are established MRI features in human anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, the underlying pathophysiology for brain network alterations remains poorly understood. Application of patient-derived monoclonal antibodies against the NR1 subunit of the NMDAR allows for the investigation of potential functional connectivity alterations in experimental murine NMDAR antibody disease models. ObjectiveTo explore functional connectivity changes in NR1 antibody mouse models using resting-state functional MRI (rs-fMRI). MethodsAdult C57BL/6J mice (n=10) were intrathecally injected with a recombinant human NR1 antibody over 14 days and then studied using rs-fMRI at 7 Tesla. In addition, a newly established mouse model with in utero exposure to a human recombinant NR1 antibody characterized by a neurodevelopmental disorder (NR1-offspring) was investigated with rs-fMRI at the age of 8 weeks (n=15) and 10 months (n=14). Mice exposed to isotype-matched control antibodies served as controls. Independent component analysis (ICA) and dual regression analysis were performed to compare functional connectivity between NMDAR antibody mouse models and control mice. ResultsAdult NR1-antibody injected mice showed significantly impaired functional connectivity within the dentate gyrus of the left hippocampus in comparison to controls, resembling impaired hippocampal functional connectivity patterns observed in human patients with NMDAR encephalitis. Similarly, analyses showed significantly reduced functional connectivity in the dentate gyrus in NR1-offspring compared after 8 weeks, and impaired connectivity in the dentate gyrus and CA3 hippocampal subregion in NR1-offspring at the age of 10 months. ConclusionFunctional connectivity changes within the hippocampus resulting from both direct application and in utero exposure to NMDAR antibodies can be modeled in experimental murine systems. With this translational approach, we successfully reproduced functional MRI alterations previously observed in human NMDAR encephalitis patients. Future experimental studies will identify the detailed mechanisms that cause functional network alterations and may eventually allow for non-invasive monitoring of disease activity and therapeutic effects in autoimmune encephalitis.

neuroscience↗

bioRxiv2021

Post-encoding modulation of spatial memory by a GABAA-agonist

We investigated the role of the post-encoding period for consolidation of self-centered (egocentric) and world-centered (allocentric) spatial memory in neurologically normal human subjects. We used the GABAA-ergic anesthetic propofol to transiently modulate neural activity during the early stage of spatial memory consolidation. A total of 52 patients undergoing minor surgery learned to navigate to a target in a five-armed maze derived from animal experiments immediately prior to injection of propofol (early group) or more than 60 minutes before injection (late group). Two hundred and forty minutes after anesthesia, subjects were tested for memory-guided navigation. Our results show a selective impairment of memory-guided navigation in the early group and near-normal performance in the late group. Both egocentric and allocentric navigation were affected, albeit with distinct error patterns. In the egocentric condition, early group patients navigated significantly more often to a wrong alley of the maze but showed normal navigation times, thus suggesting a deficit mainly for memory of sequences of path segments. By contrast, in the allocentric condition, early group patients mostly navigated to the correct alley of the maze but showed a significant increase in detours and prolonged navigation times, thus suggesting a weakened representation of the relationship between landmarks. We conclude that presumably hippocampus-dependent networks contribute to early consolidation of representations underlying both egocentric and allocentric memory-guided navigation. Distinct aspects of these representations are susceptible to GABAA-ergic modulation within a post-encoding time-window of less than 60 minutes, indicating a redistribution and reconfiguration of spatial memory networks early during consolidation. Significance statementO_LIPropofol modulates consolidation of spatial representations underlying human spatial navigation. C_LIO_LIFollowing administration of propofol, memory-guided navigation using self-centered (egocentric) and world-centered (allocentric) spatial information is impaired. C_LIO_LIError patterns after administration of propofol suggest modulation of a post-encoding integration process relevant for ego- and allocentric memory representations. C_LIO_LIThe transient susceptibility of this process to GABAA-ergic modulation is consistent with rapid reconfiguration of networks for spatial memory shortly after learning. C_LIO_LIPropofol provides a pharmacological tool to investigate spatial memory consolidation in humans. C_LI

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↗

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↗