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David K. Menon

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10 papers
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10

YNICL Journal 2026 Journal Article

Association of acute blood biomarkers with diffusion tensor imaging and outcome in patients with traumatic brain injury presenting with GCS of 13–15

  • Malla Mononen
  • Mehrbod Mohammadian
  • Iftakher Hossain
  • Timo Roine
  • Olli Tenovuo
  • Kaj Blennow
  • Jessica Gill
  • Mark van Gils

The aim of the study was to assess the association between blood-based biomarkers of different cellular origins and later white matter integrity, measured using post-acute diffusion tensor metrics, and their relation to outcome in patients presenting with Glasgow Coma Scale of 13-15 after traumatic brain injury (TBI). Admission plasma samples for glial fibrillary acidic protein (GFAP), interleukin 10 (IL-10), heart fatty-acid binding protein (H-FABP), S100 calcium-binding protein B (S100B), total tau (T-tau), and amyloid beta 40 and 42 (Aβ40 and Aβ42) were taken for 92 patients. Diffusion-weighted magnetic resonance imaging (DW-MRI) and outcome evaluation was done ≥ 90 days post-injury. Outcome was assessed using Glasgow Outcome Scale-Extended (GOSE) and dichotomized as complete (GOSE 8) and incomplete (GOSE < 8) recovery. Mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the skeletonized white matter tracts of the whole brain. IL-10 and T-tau showed significant weak-moderate negative correlations with FA, and significant positive correlations with MD and RD in incompletely recovered patients. GFAP showed significant weak positive correlations with MD and RD, while its correlation with FA was slightly below significance threshold after correction for multiple comparison in incompletely recovered patients. Similar trends were observed in the whole cohort and in the CT-positive cohort, although these did not reach statistical significance. Higher acute levels of GFAP, IL-10 and T-tau may be associated with the development of axonal injury. If validated in future studies, these biomarkers may help identify patients who require closer follow-up and DW-MRI.

YNIMG Journal 2023 Journal Article

Reduced emergent character of neural dynamics in patients with a disrupted connectome

  • Andrea I. Luppi
  • Pedro A.M. Mediano
  • Fernando E. Rosas
  • Judith Allanson
  • John D. Pickard
  • Guy B. Williams
  • Michael M. Craig
  • Paola Finoia

High-level brain functions are widely believed to emerge from the orchestrated activity of multiple neural systems. However, lacking a formal definition and practical quantification of emergence for experimental data, neuroscientists have been unable to empirically test this long-standing conjecture. Here we investigate this fundamental question by leveraging a recently proposed framework known as "Integrated Information Decomposition," which establishes a principled information-theoretic approach to operationalise and quantify emergence in dynamical systems - including the human brain. By analysing functional MRI data, our results show that the emergent and hierarchical character of neural dynamics is significantly diminished in chronically unresponsive patients suffering from severe brain injury. At a functional level, we demonstrate that emergence capacity is positively correlated with the extent of hierarchical organisation in brain activity. Furthermore, by combining computational approaches from network control theory and whole-brain biophysical modelling, we show that the reduced capacity for emergent and hierarchical dynamics in severely brain-injured patients can be mechanistically explained by disruptions in the patients' structural connectome. Overall, our results suggest that chronic unresponsiveness resulting from severe brain injury may be related to structural impairment of the fundamental neural infrastructures required for brain dynamics to support emergence.

YNICL Journal 2022 Journal Article

Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study

  • Kamen A. Tsvetanov
  • Lennart R.B. Spindler
  • Emmanuel A. Stamatakis
  • Virginia F.J. Newcombe
  • Victoria C. Lupson
  • Doris A. Chatfield
  • Anne E. Manktelow
  • Joanne G. Outtrim

Human coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has multiple neurological consequences, but its long-term effect on brain health is still uncertain. The cerebrovascular consequences of COVID-19 may also affect brain health. We studied the chronic effect of COVID-19 on cerebrovascular health, in relation to acute severity, adverse clinical outcomes and in contrast to control group data. Here we assess cerebrovascular health in 45 patients six months after hospitalisation for acute COVID-19 using the resting state fluctuation amplitudes (RSFA) from functional magnetic resonance imaging, in relation to disease severity and in contrast with 42 controls. Acute COVID-19 severity was indexed by COVID-19 WHO Progression Scale, inflammatory and coagulatory biomarkers. Chronic widespread changes in frontoparietal RSFA were related to the severity of the acute COVID-19 episode. This relationship was not explained by chronic cardiorespiratory dysfunction, age, or sex. The level of cerebrovascular dysfunction was associated with cognitive, mental, and physical health at follow-up. The principal findings were consistent across univariate and multivariate approaches. The results indicate chronic cerebrovascular impairment following severe acute COVID-19, with the potential for long-term consequences on cognitive function and mental wellbeing.

YNIMG Journal 2022 Journal Article

Network dynamics scale with levels of awareness

  • Peter Coppola
  • Lennart R.B. Spindler
  • Andrea I. Luppi
  • Ram Adapa
  • Lorina Naci
  • Judith Allanson
  • Paola Finoia
  • Guy B. Williams

Small world topologies are thought to provide a valuable insight into human brain organisation and consciousness. However, functional magnetic resonance imaging studies in consciousness have not yielded consistent results. Given the importance of dynamics for both consciousness and cognition, here we investigate how the diversity of small world dynamics (quantified by sample entropy; dSW-E 1 1 dSW-E= dynamic small world entropy ) scales with decreasing levels of awareness (i. e. , sedation and disorders of consciousness). Paying particular attention to result reproducibility, we show that dSW-E is a consistent predictor of levels of awareness even when controlling for the underlying functional connectivity dynamics. We find that dSW-E of subcortical, and cortical areas are predictive, with the former showing higher and more robust effect sizes across analyses. We find that the network dynamics of intermodular communication in the cerebellum also have unique predictive power for levels of awareness. Consequently, we propose that the dynamic reorganisation of the functional information architecture, in particular of the subcortex, is a characteristic that emerges with awareness and has explanatory power beyond that of the complexity of dynamic functional connectivity.

YNICL Journal 2022 Journal Article

Presurgical diffusion metrics of the thalamus and thalamic nuclei in postoperative delirium: A prospective two-centre cohort study in older patients

  • Marinus Fislage
  • Stefan Winzeck
  • Emmanuel Stamatakis
  • Marta M. Correia
  • Jacobus Preller
  • Insa Feinkohl
  • Claudia D. Spies
  • Jeroen Hendrikse

BACKGROUND: The thalamus seems to be important in the development of postoperative delirium (POD) as previously revealed by volumetric and diffusion magnetic resonance imaging. In this observational cohort study, we aimed to further investigate the impact of the microstructural integrity of the thalamus and thalamic nuclei on the incidence of POD by applying diffusion kurtosis imaging (DKI). METHODS: Older patients without dementia (≥65 years) who were scheduled for major elective surgery received preoperative DKI at two study centres. The DKI metrics fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK) and free water (FW) were calculated for the thalamus and - as secondary outcome - for eight predefined thalamic nuclei and regions. Low FA and MK and, conversely, high MD and FW, indicate aspects of microstructural abnormality. To assess patients' POD status, the Nursing Delirium Screening Scale (Nu-DESC), Richmond Agitation Sedation Scale (RASS), Confusion Assessment Method (CAM) and Confusion Assessment Method for the Intensive Care Unit score (CAM-ICU) and chart review were applied twice a day after surgery for the duration of seven days or until discharge. For each metric and each nucleus, logistic regression was performed to assess the risk of POD. RESULTS: This analysis included the diffusion scans of 325 patients, of whom 53 (16.3 %) developed POD. Independently of age, sex and study centre, thalamic MD was statistically significantly associated with POD [OR 1.65 per SD increment (95 %CI 1.17 - 2.34) p = 0.004]. FA (p = 0.84), MK (p = 0.41) and FW (p = 0.06) were not significantly associated with POD in the examined sample. Exploration of thalamic nuclei also indicated that only the MD in certain areas of the thalamus was associated with POD. MD was increased in bilateral hemispheres, pulvinar nuclei, mediodorsal nuclei and the left anterior nucleus. CONCLUSIONS: Microstructural abnormalities of the thalamus and thalamic nuclei, as reflected by increased MD, appear to predispose to POD. These findings affirm the thalamus as a region of interest in POD research.

YNIMG Journal 2021 Journal Article

LSD alters dynamic integration and segregation in the human brain

  • Andrea I. Luppi
  • Robin L. Carhart-Harris
  • Leor Roseman
  • Ioannis Pappas
  • David K. Menon
  • Emmanuel A. Stamatakis

Investigating changes in brain function induced by mind-altering substances such as LSD is a powerful method for interrogating and understanding how mind interfaces with brain, by connecting novel psychological phenomena with their neurobiological correlates. LSD is known to increase measures of brain complexity, potentially reflecting a neurobiological correlate of the especially rich phenomenological content of psychedelic-induced experiences. Yet although the subjective stream of consciousness is a constant ebb and flow, no studies to date have investigated how LSD influences the dynamics of functional connectivity in the human brain. Focusing on the two fundamental network properties of integration and segregation, here we combined graph theory and dynamic functional connectivity from resting-state functional MRI to examine time-resolved effects of LSD on brain networks properties and subjective experiences. Our main finding is that the effects of LSD on brain function and subjective experience are non-uniform in time: LSD makes globally segregated sub-states of dynamic functional connectivity more complex, and weakens the relationship between functional and anatomical connectivity. On a regional level, LSD reduces functional connectivity of the anterior medial prefrontal cortex, specifically during states of high segregation. Time-specific effects were correlated with different aspects of subjective experiences; in particular, ego dissolution was predicted by increased small-world organisation during a state of high global integration. These results reveal a more nuanced, temporally-specific picture of altered brain connectivity and complexity under psychedelics than has previously been reported.

YNICL Journal 2021 Journal Article

Preserved fractal character of structural brain networks is associated with covert consciousness after severe brain injury

  • Andrea I. Luppi
  • Michael M. Craig
  • Peter Coppola
  • Alexander R.D. Peattie
  • Paola Finoia
  • Guy B. Williams
  • Judith Allanson
  • John D. Pickard

Self-similarity is ubiquitous throughout natural phenomena, including the human brain. Recent evidence indicates that fractal dimension of functional brain networks, a measure of self-similarity, is diminished in patients diagnosed with disorders of consciousness arising from severe brain injury. Here, we set out to investigate whether loss of self-similarity is observed in the structural connectome of patients with disorders of consciousness. Using diffusion MRI tractography from N = 11 patients in a minimally conscious state (MCS), N = 10 patients diagnosed with unresponsive wakefulness syndrome (UWS), and N = 20 healthy controls, we show that fractal dimension of structural brain networks is diminished in DOC patients. Remarkably, we also show that fractal dimension of structural brain networks is preserved in patients who exhibit evidence of covert consciousness by performing mental imagery tasks during functional MRI scanning. These results demonstrate that differences in fractal dimension of structural brain networks are quantitatively associated with chronic loss of consciousness induced by severe brain injury, highlighting the close connection between structural organisation of the human brain and its ability to support cognitive function.

YNICL Journal 2020 Journal Article

Bedside EEG predicts longitudinal behavioural changes in disorders of consciousness

  • Corinne A. Bareham
  • Neil Roberts
  • Judith Allanson
  • Peter J.A. Hutchinson
  • John D. Pickard
  • David K. Menon
  • Srivas Chennu

Providing an accurate prognosis for prolonged disorder of consciousness (pDOC) patients remains a clinical challenge. Large cross-sectional studies have demonstrated the diagnostic and prognostic value of functional brain networks measured using high-density electroencephalography (hdEEG). Nonetheless, the prognostic value of these neural measures has yet to be assessed by longitudinal follow-up. We address this gap by assessing the utility of hdEEG to prognosticate long-term behavioural outcome, employing longitudinal data collected from a cohort of patients assessed systematically with resting hdEEG and the Coma Recovery Scale-Revised (CRS-R) at the bedside over a period of two years. We used canonical correlation analysis to relate clinical (including CRS-R scores combined with demographic variables) and hdEEG variables to each other. This analysis revealed that the patient's age, and the hdEEG theta band power and alpha band connectivity, contributed most significantly to the relationship between hdEEG and clinical variables. Further, we found that hdEEG measures recorded at the time of assessment augmented clinical measures in predicting CRS-R scores at the next assessment. Moreover, the rate of hdEEG change not only predicted later changes in CRS-R scores, but also outperformed clinical measures in terms of prognostic power. Together, these findings suggest that improvements in functional brain networks precede changes in behavioural awareness in pDOC. We demonstrate here that bedside hdEEG assessments conducted at specialist nursing homes are feasible, have clinical utility, and can complement clinical knowledge and systematic behavioural assessments to inform prognosis and care.

YNIMG Journal 2020 Journal Article

Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains

  • Thomas F. Varley
  • Robin Carhart-Harris
  • Leor Roseman
  • David K. Menon
  • Emmanuel A. Stamatakis

Psychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers investigating the neural origins of consciousness. Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of neural activity. While the concept of criticality is of central importance to this theory, few of the published studies on psychedelics investigate it directly, testing instead related measures such as algorithmic complexity or Shannon entropy. We propose using the fractal dimension of functional activity in the brain as a measure of complexity since findings from physics suggest that as a system organizes towards criticality, it tends to take on a fractal structure. We tested two different measures of fractal dimension, one spatial and one temporal, using fMRI data from volunteers under the influence of both LSD and psilocybin. The first was the fractal dimension of cortical functional connectivity networks and the second was the fractal dimension of BOLD time-series. In addition to the fractal measures, we used a well-established, non-fractal measure of signal complexity and show that they behave similarly. We were able to show that both psychedelic drugs significantly increased the fractal dimension of functional connectivity networks, and that LSD significantly increased the fractal dimension of BOLD signals, with psilocybin showing a non-significant trend in the same direction. With both LSD and psilocybin, we were able to localize changes in the fractal dimension of BOLD signals to brain areas assigned to the dorsal-attenion network. These results show that psychedelic drugs increase the fractal dimension of activity in the brain and we see this as an indicator that the changes in consciousness triggered by psychedelics are associated with evolution towards a critical zone.

YNICL Journal 2015 Journal Article

Factoring the brain signatures of anesthesia concentration and level of arousal across individuals

  • Pablo Barttfeld
  • Tristan A. Bekinschtein
  • Alejo Salles
  • Emmanuel A. Stamatakis
  • Ram Adapa
  • David K. Menon
  • Mariano Sigman

Combining resting-state functional magnetic resonance imaging (fMRI) connectivity and behavioral analysis during sedation, we factored out general effects of the anesthetic drug propofol and a specific index of conscious report, participants' level of responsiveness. The factorial analysis shows that increasing concentration of propofol in blood specifically decreases the connectivity strength of fronto-parietal cortical loops. In contrast, loss of responsiveness is indexed by a functional disconnection between the thalamus and the frontal cortex, balanced by an increase in connectivity strength of the thalamus to the occipital and temporal regions of the cortex.

v2026.09.13