Enhancing Fetal Brain Imaging: ALPS-FMEG Technique Achieves Accurate Signal Extraction by Mitigating Movement Artifacts Amer Zaylaa, Jürgen Dax, Katrin Sippel, Lorenzo Semeia, Joel Frohlich, Alban Gallard, Fabrice Wallois, Hari Eswaran, Andreas L. Birkenfeld, Hubert Preissl Annals of Biomedical Engineering, 2026 Purpose Fetal magnetoencephalography (fMEG) enables non-invasive monitoring of fetal brain function with high temporal resolution. However, how can we isolate low signal-to-noise ratio signals of the developing brain when disruptive artifacts arise from maternal and fetal movements? Addressing this challenge is critical for understanding brain development. We present Advanced Localization and Processing of fMEG Signals based on Maternal and Gross fetal body Movement Exclusion (ALPS-FMEG), a MATLAB-based framework that improves fetal brain signals by removing fetal and maternal movement artifacts. Methods ALPS-FMEG integrates Independent Component Analysis for separation and reconstruction of fetal brain, fetal and maternal cardiac signal components in sensor space, Empirical Mode Decomposition for noise reduction, and a movement artifact detection-and-exclusion technique based on actogramCOG associated with heart rate patterns. This novel integration modifies the actogramCOG approach by pre-interpolating R waves for enhanced robustness and combines it with HRV-based logic gates, representing a first in fMEG processing to achieve artifact-free signals while preserving physiological latencies. Results ALPS-FMEG was applied to 50 fMEG datasets from 28 to 39 weeks of gestation, enhancing signal quality. For group analysis, 45 datasets were retained after excluding recordings with auditory event-related field (fAEF) latencies < 70 ms. In these, it significantly improved signal-to-noise ratio and fAEF amplitudes ( p < 0.0001), with preserved latencies. fAEF latency showed a significant negative correlation with gestational age ( p < 0.001). Conclusion ALPS-FMEG improves fetal brain signal extraction by addressing movement artifacts. This method supports robust fetal brain analysis and may be adaptable to future fMEG systems, including optically pumped magnetometers, enhancing prenatal neurophysiology and clinical research, though manual steps currently limit scalability and could be addressed via automation for broader practical use.
Natural language analysis of the structure of altered states of consciousness Daria Dikovskaya, Bhargav Srinivasa Desikan, Joel Frohlich, Naureen Hossain, Giani Panariello, Luke Johnson, Conor H. Murray Journal of Psychedelic Studies, 2025 Background and aimsAltered states of consciousness (ASC) represent acute and marked deviations from normal waking consciousness. Investigations into ASC are significant to problems in medicine, science, and philosophy, including the structure of conscious experience. Here, we conducted a preliminary investigation into the structure of ASC while addressing the role of psychedelics, which purportedly manifest features of mind.MethodsWe performed quantitative and qualitative analyses of 300 narrative reports across 12 ASC induction methods: meditation, float tank, psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-DMT (5-MeO-DMT), ketamine, salvia, 3,4-methylenedioxymethamphetamine (MDMA), cannabis, datura, and diphenhydramine (DPH). We hypothesized that reports from the psychedelics (serotonin 5-HT2A receptor agonists) would contain similar content with non-pharmacological induction methods, alongside greater positive sentiment and reported authenticity relative to reports from other substances.ResultsIn quantitative analysis, most psychedelics, except LSD, as well as salvia and ketamine, shared similar content with non-pharmacological methods. In qualitative analysis, most psychedelics, except LSD, were deemed both positive and authentic, with authenticity predicting positive sentiment across the 12 ASC induction methods (R = 0.68; p = 0.015). We uncovered latent themes charting a trajectory of ASC from baseline to metaphysical experience, incorporating text-to-image generative artificial intelligence to illustrate underlying phenomenological structure.ConclusionsOur findings suggest that reproducible structural observations may be externally validated across methods to support a “mind-manifesting” characterization for some ASC induction methods, such as salvia, ketamine, or 5-MeO-DMT, but not for others, such as LSD, datura, or DPH, together informing future studies of psychedelics, ASC, and structuralism.
Neural complexity in preterm infants is predicted by developmental variables Lorenzo Semeia, Amer Zaylaa, Dimitrios Metaxas, Mina Nourhashemi, Mahdi Mahmoudzadeh, Andreas L. Birkenfeld, Katrin Sippel, Pedro A. M. Mediano, Hubert Preissl, Fabrice Wallois, Joel Frohlich Plos Complex Systems, 2025 Neural complexity, measured as the entropy of noninvasively recorded electrophysiological signals, evolves with age in early infancy, differentiates between typical and atypical development, and likely serves as a surrogate marker of brain maturation. However, the reason for this evolution of neural entropy in early infant development remains unclear. To understand this evolution, we measured the proportion of time that the infant brain spent in a bursting pattern of activity and related this activity pattern to the neural complexity (i.e., entropy or entropy rate). Additionally, we sought to predict neural complexity using each infant’s gestational age and to replicate sex-related complexity differences previously reported in age-equivalent fetuses. Four distinct complexity estimator algorithms – Lempel-Ziv (LZ) complexity, multiscale entropy (MSE), complexity via state-space entropy rate (CSER), and context tree weighting (CTW) – were applied to 8-channel infant electroencephalogram (EEG) recordings in 28 preterm infants (27–34 weeks gestational age). To explore factors influencing signal complexity, we modeled relationships between complexity estimates, on the one hand, and spontaneous activity transients, gestational age, and sex, on the other hand. We calculated channel-averages for each complexity estimate separately, as derived either from entire EEG recordings or separately from burst and interburst periods. Our results suggest that increased EEG signal continuity with maturation may drive increases in neural complexity as quiescent periods subside. Additionally, our results largely recapitulate previous findings linking neural complexity to biological sex in third-trimester fetuses. We also observed unexpected differences between entropy rate results obtained using CSER (a newer algorithm) and older algorithms. These findings support further research into neural complexity as a potential predictor of clinical outcomes in infants at high risk for neurodevelopmental disorders.
Markers of consciousness in infants: Towards a ‘cluster-based’ approach Joel Frohlich, Tim Bayne Acta Paediatrica International Journal of Paediatrics, 2025 As recently as the 1980s, it was not uncommon for paediatric surgeons to operate on infants without anaesthesia. Today, the same omission would be considered criminal malpractice, and there is an increased concern with the possibility of consciousness in the earliest stage of human infancy. This concern reflects a more general trend that has characterised science since the early 1990s of taking consciousness seriously. While this attitude shift has opened minds towards the possibility that our earliest experiences predate our first memories, convincing demonstrations of infant consciousness remain challenging given that infants cannot report on their experiences. Furthermore, while many behavioural and neural markers of consciousness that do not rely on language have been validated in adults, no one specific marker can be confidently translated to infancy. For this reason, we have proposed the ‘cluster‐based’ approach, in which a consensus of evidence across many markers, all pointing towards the same developmental period, could be used to argue convincingly for the presence of consciousness.ConclusionWe review the most promising markers for early consciousness, arguing that consciousness is likely to be in place by 5 months of age if not earlier.
Paradoxical pharmacological dissociations result from drugs that enhance delta oscillations but preserve consciousness Joel Frohlich, Pedro A. M. Mediano, Francesco Bavato, Alireza Gharabaghi Communications Biology, 2023 Low-frequency (<4 Hz) neural activity, particularly in the delta band, is generally indicative of loss of consciousness and cortical down states, particularly when it is diffuse and high amplitude. Remarkably, however, drug challenge studies of several diverse classes of pharmacological agents—including drugs which treat epilepsy, activate GABAB receptors, block acetylcholine receptors, or produce psychedelic effects—demonstrate neural activity resembling cortical down states even as the participants remain conscious. Of those substances that are safe to use in healthy volunteers, some may be highly valuable research tools for investigating which neural activity patterns are sufficient for consciousness or its absence.
Consciousness in the cradle: on the emergence of infant experience Tim Bayne, Joel Frohlich, Rhodri Cusack, Julia Moser, Lorina Naci Trends in Cognitive Sciences, 2023 Although each of us was once a baby, infant consciousness remains mysterious and there is no received view about when, and in what form, consciousness first emerges. Some theorists defend a 'late-onset' view, suggesting that consciousness requires cognitive capacities which are unlikely to be in place before the child's first birthday at the very earliest. Other theorists defend an 'early-onset' account, suggesting that consciousness is likely to be in place at birth (or shortly after) and may even arise during the third trimester. Progress in this field has been difficult, not just because of the challenges associated with procuring the relevant behavioral and neural data, but also because of uncertainty about how best to study consciousness in the absence of the capacity for verbal report or intentional behavior. This review examines both the empirical and methodological progress in this field, arguing that recent research points in favor of early-onset accounts of the emergence of consciousness.
Not with a “zap” but with a “beep”: Measuring the origins of perinatal experience Joel Frohlich, Tim Bayne, Julia S. Crone, Alessandra DallaVecchia, Asger Kirkeby-Hinrup, Pedro A.M. Mediano, Julia Moser, Karolina Talar, Alireza Gharabaghi, Hubert Preissl Neuroimage, 2023 When does the mind begin? Infant psychology is mysterious in part because we cannot remember our first months of life, nor can we directly communicate with infants. Even more speculative is the possibility of mental life prior to birth. The question of when consciousness, or subjective experience, begins in human development thus remains incompletely answered, though boundaries can be set using current knowledge from developmental neurobiology and recent investigations of the perinatal brain. Here, we offer our perspective on how the development of a sensory perturbational complexity index (sPCI) based on auditory ("beep-and-zip"), visual ("flash-and-zip"), or even olfactory ("sniff-and-zip") cortical perturbations in place of electromagnetic perturbations ("zap-and-zip") might be used to address this question. First, we discuss recent studies of perinatal cognition and consciousness using techniques such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and, in particular, magnetoencephalography (MEG). While newborn infants are the archetypal subjects for studying early human development, researchers may also benefit from fetal studies, as the womb is, in many respects, a more controlled environment than the cradle. The earliest possible timepoint when subjective experience might begin is likely the establishment of thalamocortical connectivity at 26 weeks gestation, as the thalamocortical system is necessary for consciousness according to most theoretical frameworks. To infer at what age and in which behavioral states consciousness might emerge following the initiation of thalamocortical pathways, we advocate for the development of the sPCI and similar techniques, based on EEG, MEG, and fMRI, to estimate the perinatal brain's state of consciousness.
Consciousness is supported by near-critical slow cortical electrodynamics Daniel Toker, Ioannis Pappas, Janna D. Lendner, Joel Frohlich, Diego M. Mateos, Suresh Muthukumaraswamy, Robin Carhart-Harris, Michelle Paff, Paul M. Vespa, Martin M. Monti, Friedrich T. Sommer, Robert T. Knight, Mark D’Esposito Proceedings of the National Academy of Sciences of the United States of America, 2022
Properties of beta oscillations in Dup15q syndrome Vidya Saravanapandian, Joel Frohlich, Joerg F. Hipp, Carly Hyde, Aaron W. Scheffler, Peyman Golshani, Edwin H. Cook, Lawrence T. Reiter, Damla Senturk, Shafali S. Jeste Journal of Neurodevelopmental Disorders, 2020
Mechanisms underlying the EEG biomarker in Dup15q syndrome Joel Frohlich, Lawrence T. Reiter, Vidya Saravanapandian, Charlotte DiStefano, Scott Huberty, Carly Hyde, Stormy Chamberlain, Carrie E. Bearden, Peyman Golshani, Andrei Irimia, Richard W. Olsen, Joerg F. Hipp, Shafali S. Jeste Molecular Autism, 2019
Electrophysiological Phenotype in Angelman Syndrome Differs Between Genotypes Joel Frohlich, Meghan T. Miller, Lynne M. Bird, Pilar Garces, Hannah Purtell, Marius C. Hoener, Benjamin D. Philpot, Michael S. Sidorov, Wen-Hann Tan, Maria-Clemencia Hernandez, Alexander Rotenberg, Shafali S. Jeste, Michelle Krishnan, Omar Khwaja, Joerg F. Hipp Biological Psychiatry, 2019
Ketamine and the Dissociatives: Comparisons with Schizophrenia Joel Frohlich, John Darrell Van Horn Neuropathology of Drug Addictions and Substance Misuse Volume 2 Stimulants Club and Dissociative Drugs Hallucinogens Steroids Inhalants and International Aspects, 2016
Enhancing Fetal Brain Imaging: ALPS-FMEG Technique Achieves Accurate Signal Extraction by Mitigating Movement Artifacts: A. Zaylaa et al. A Zaylaa, J Dax, K Sippel, L Semeia, J Frohlich, A Gallard, F Wallois, ... Annals of Biomedical Engineering, 1-19 , 2026 2026
Aquahenosis: A non-pharmacological altered state of consciousness induced by Floatation-REST T Tobel, A Cone, E Choquette, MK Garland, MA Johnson, K Mink, ... 2026
Natural language analysis of the structure of altered states of consciousness D Dikovskaya, BS Desikan, J Frohlich, N Hossain, G Panariello, ... Journal of Psychedelic Studies 9 (4), 395-411 , 2025 2025 Citations: 4
Neural complexity in preterm infants is predicted by developmental variables L Semeia, A Zaylaa, D Metaxas, M Nourhashemi, M Mahmoudzadeh, ... PLOS Complex Systems 2 (10), e0000056 , 2025 2025 Citations: 1
Frequency tagging evidence supports perceptual separation of rapid stimuli in human fetuses J Frohlich, J Moser, D Metaxas, K Sippel, L Batterink, H Preissl bioRxiv, 2025.06. 06.658307 , 2025 2025
EEG entropy reflects both intrinsic and stimulation-induced corticospinal excitability S Ruch, J Frohlich, M Keute, G Tang, N Keksel, A Gharabaghi bioRxiv, 2025.05. 16.654439 , 2025 2025
Predictive processing frameworks for perception can explain recent drone sightings in the United States J Frohlich, L Christov-Moore, N Reggente arXiv preprint arXiv:2505.03013 , 2025 2025
Markers of consciousness in infants: Towards a ‘cluster‐based’approach J Frohlich, T Bayne Acta Paediatrica 114 (2), 285-291 , 2025 2025 Citations: 4
Recent pseudoscience accusation echoes historic pushback against general relativity J Frohlich, A Safron, N Reggente PsyArXiv , 2024 2024 Citations: 4
Deep learning architectures encoding neural complexity patterns across different regimes of cortical dynamics L Fiorillo, F Mallus, G Monachino, M Bechny, J Frohlich, V Agostini, ... JOURNAL OF SLEEP RESEARCH 33 , 2024 2024
Infants and markers: reply to Taylor and Bremner T Bayne, J Frohlich, R Cusack, J Moser, L Naci Trends in Cognitive Sciences 28 (7), 588-589 , 2024 2024 Citations: 1
Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine CH Murray, J Frohlich, CJ Haggarty, I Tare, R Lee, H de Wit Neuropsychopharmacology 49 (7), 1120-1128 , 2024 2024 Citations: 37
Brain signal complexity and aperiodicity predict human corticospinal excitability J Frohlich, S Ruch, BH Trunk, M Keute, PAM Mediano, A Gharabaghi bioRxiv, 2024.02. 09.579457 , 2024 2024
Sex differences in prenatal development of neural complexity in the human brain J Frohlich, J Moser, PAM Mediano, H Preissl, A Gharabaghi Nature Mental Health, 1 - 16 , 2024 2024 Citations: 15
Consciousness in the cradle: on the emergence of infant experience T Bayne, J Frohlich, R Cusack, J Moser, L Naci Trends in cognitive sciences 27 (12), 1135-1149 , 2023 2023 Citations: 70
Neural entrainment induced by periodic audiovisual stimulation: A large-sample EEG study J Frohlich, N Simonian, G Hanada, C Kothe, N Reggente bioRxiv, 2023.10. 25.563865 , 2023 2023 Citations: 5
Dissociations between neural activity and conscious state: a key to understanding consciousness J Frohlich, JS Crone, PAM Mediano, D Toker, D Bor Frontiers in Human Neuroscience 17, 1256168 , 2023 2023 Citations: 2
Paradoxical pharmacological dissociations result from drugs that enhance delta oscillations but preserve consciousness J Frohlich, PAM Mediano, F Bavato, A Gharabaghi Communications Biology 6 (1), 654 , 2023 2023 Citations: 21
Not with a “zap” but with a “beep”: measuring the origins of perinatal experience J Frohlich, T Bayne, JS Crone, A DallaVecchia, A Kirkeby-Hinrup, ... NeuroImage, 120057 , 2023 2023 Citations: 34
Impact of neuromodulation on post-stroke aphasia: a multimodal randomized controlled study ZS Zheng, KXL Wang, H Millan, S Lee, M Howard, A Rothbart, J Frohlich, ... medRxiv, 2023.02. 12.23285828 , 2023 2023 Citations: 2
MOST CITED SCHOLAR PUBLICATIONS
Reviewing the ketamine model for schizophrenia J Frohlich, JD Van Horn Journal of psychopharmacology 28 (4), 287-302 , 2014 2014 Citations: 431
Consciousness among delta waves: a paradox? J Frohlich, D Toker, MM Monti Brain 144 (8), 2257-2277 , 2021 2021 Citations: 227
Brain connectivity in autism spectrum disorder I Mohammad-Rezazadeh, J Frohlich, SK Loo, SS Jeste Current opinion in neurology 29 (2), 137-147 , 2016 2016 Citations: 225
Electrophysiological biomarkers of diagnosis and outcome in neurodevelopmental disorders SS Jeste, J Frohlich, SK Loo Current opinion in neurology 28 (2), 110-116 , 2015 2015 Citations: 222
Consciousness is supported by near-critical slow cortical electrodynamics D Toker, I Pappas, JD Lendner, J Frohlich, DM Mateos, ... Proceedings of the National Academy of Sciences 119 (7), e2024455119 , 2022 2022 Citations: 179
Electrophysiological phenotype in Angelman syndrome differs between genotypes J Frohlich, MT Miller, LM Bird, P Garces, H Purtell, MC Hoener, BD Philpot, ... Biological psychiatry 85 (9), 752-759 , 2019 2019 Citations: 108
A quantitative electrophysiological biomarker of duplication 15q11. 2-q13. 1 syndrome J Frohlich, D Senturk, V Saravanapandian, P Golshani, LT Reiter, ... PloS one 11 (12), e0167179 , 2016 2016 Citations: 93
Consciousness in the cradle: on the emergence of infant experience T Bayne, J Frohlich, R Cusack, J Moser, L Naci Trends in cognitive sciences 27 (12), 1135-1149 , 2023 2023 Citations: 70
Mechanisms underlying the EEG biomarker in Dup15q syndrome J Frohlich, LT Reiter, V Saravanapandian, C DiStefano, S Huberty, ... Molecular autism 10 (1), 29 , 2019 2019 Citations: 67
Neural Complexity is a Common Denominator of Human Consciousness Across Diverse Regimes of Cortical Dynamics J Frohlich, JN Chiang, PAM Mediano, M Nespeca, V Saravanapandian, ... Communications Biology, 5(1), 1-17 , 2022 2022 Citations: 41
Neural complexity is increased after low doses of LSD, but not moderate to high doses of oral THC or methamphetamine CH Murray, J Frohlich, CJ Haggarty, I Tare, R Lee, H de Wit Neuropsychopharmacology 49 (7), 1120-1128 , 2024 2024 Citations: 37
Neural oscillations track recovery of consciousness in acute traumatic brain injury patients J Frohlich, JS Crone, MA Johnson, ES Lutkenhoff, NM Spivak, J Dell'Italia, ... Human Brain Mapping 43 (6), 1804-1820 , 2022 2022 Citations: 36
Not with a “zap” but with a “beep”: measuring the origins of perinatal experience J Frohlich, T Bayne, JS Crone, A DallaVecchia, A Kirkeby-Hinrup, ... NeuroImage, 120057 , 2023 2023 Citations: 34
Electrophysiological abnormalities in Angelman syndrome correlate with symptom severity JF Hipp, J Frohlich, M Keute, WH Tan, LM Bird Biological psychiatry global open science 1 (3), 201-209 , 2021 2021 Citations: 31
Functional connectivity during language processing in 3‐month‐old infants at familial risk for autism spectrum disorder XA Tran, N McDonald, A Dickinson, A Scheffler, J Frohlich, A Marin, ... European Journal of Neuroscience 53 (5), 1621-1637 , 2021 2021 Citations: 29
High-voltage, diffuse delta rhythms coincide with wakeful consciousness and complexity in Angelman syndrome J Frohlich, LM Bird, J Dell’Italia, MA Johnson, JF Hipp, MM Monti Neuroscience of consciousness 2020 (1), niaa005 , 2020 2020 Citations: 29
Properties of beta oscillations in Dup15q syndrome V Saravanapandian, J Frohlich, JF Hipp, C Hyde, AW Scheffler, ... Journal of neurodevelopmental disorders 12 (1), 22 , 2020 2020 Citations: 25
Paradoxical pharmacological dissociations result from drugs that enhance delta oscillations but preserve consciousness J Frohlich, PAM Mediano, F Bavato, A Gharabaghi Communications Biology 6 (1), 654 , 2023 2023 Citations: 21
Sex differences in prenatal development of neural complexity in the human brain J Frohlich, J Moser, PAM Mediano, H Preissl, A Gharabaghi Nature Mental Health, 1 - 16 , 2024 2024 Citations: 15
Sedation-induced burst suppression predicts positive outcome following traumatic brain injury J Frohlich, MA Johnson, DL Mcarthur, ES Lutkenhoff, J Dell'italia, C Real, ... Frontiers in Neurology, 2305 , 2021 2021 Citations: 14
