bioRxiv (Cold Spring Harbor Laboratory), Apr 9, 2024
A fundamental topological principle is that the container always shapes the content. In neuroscie... more A fundamental topological principle is that the container always shapes the content. In neuroscience, this translates into how the brain anatomy shapes brain dynamics. From neuroanatomy, the topology of the mammalian brain can be approximated by local connectivity, accurately described by an exponential distance rule (EDR). The compact, folded geometry of the cortex is shaped by this local connectivity and the geometric harmonic modes can reconstruct much of the functional dynamics. However, this ignores the fundamental role of the rare long-range cortical connections, crucial for improving information processing in the mammalian brain, but not captured by local cortical folding and geometry. Here we show the superiority of harmonics mode combining rare long-range with EDR (EDR+LR) in capturing functional dynamics (specifically long-range functional connectivity and task-evoked brain activity) compared to geometry and EDR representations. Importantly, the orchestration of dynamics is carried out by a more efficient manifold made up of a low number of fundamental EDR+LR modes. Our results show the importance of long-range connectivity for capturing the complexity of functional brain activity through a low-dimensional manifold shaped by fundamental EDR+LR modes.
Disorders of consciousness (DoC) are a challenging and complex group of neurological conditions c... more Disorders of consciousness (DoC) are a challenging and complex group of neurological conditions characterised by absent or impaired awareness. The current range of therapeutic options for DoC patients is limited, offering few non-invasive pharmacological alternatives. This situation has sprung a growing interest in the development of novel treatments, such as the proposal to study the efficacy of 5HT2A receptor agonists (also known as psychedelics) to restore impaired consciousness. Given the ethical implications of exploring novel compounds in non-communicative individuals, we assessed in silico their effects in the whole-brain dynamics of DoC patients. We embedded the whole-brain activity of patients in a low-dimensional space, and then used this representation to visualise the effects of simulated neuromodulation across a range of receptors representing potential drug targets. Our findings show that activation of serotonergic and opioid receptors shifted brain dynamics of DoC patients towards patterns typically seen in conscious and awake individuals, and that this effect was mediated by the brain-wide density of activated receptors. These results showcase the role of whole-brain models in the discovery of novel pharmacological treatments for neuropsychiatric conditions, while also supporting the feasibility of accelerating the recovery of consciousness with serotonergic psychedelics. .
bioRxiv (Cold Spring Harbor Laboratory), Nov 24, 2022
Stroke-related disruptions in functional connectivity (FC) often spread beyond lesioned areas and... more Stroke-related disruptions in functional connectivity (FC) often spread beyond lesioned areas and, given the localized nature of lesions, it is unclear how the recovery of FC is orchestrated on a global scale. Since recovery is accompanied by long-term changes in excitability, we propose excitatory-inhibitory (E-I) homeostasis as a driving mechanism. We present a large-scale model of the neocortex, with synaptic scaling of local inhibition, showing how E-I homeostasis can drive the post-lesion restoration of FC and linking it to changes in excitability. We show that functional networks could reorganize to recover disrupted modularity and small-worldness, but not network dynamics, suggesting the need to consider forms of plasticity beyond synaptic scaling of inhibition. On average, we observed widespread increases in excitability, with the emergence of complex lesiondependent patterns related to biomarkers of relevant side effects of stroke, such as epilepsy, depression and chronic pain. In summary, our results show that the effects of E-I homeostasis extend beyond local E-I balance, driving the restoration of global properties of FC, and relating to post-stroke symptomatology. Therefore, we suggest the framework of E-I homeostasis as a relevant theoretical foundation for the study of stroke recovery and for understanding the emergence of meaningful features of FC from local dynamics. .
bioRxiv (Cold Spring Harbor Laboratory), Apr 20, 2023
One of the potential and promising adjuvant therapies for Alzheimer's disease is that of noninvas... more One of the potential and promising adjuvant therapies for Alzheimer's disease is that of noninvasive transcranial neurostimulation to potentiate cognitive training interventions. Conceptually, this is achieved by driving brain dynamics towards an optimal state for an effective facilitation of cognitive training interventions. However, current neurostimulation protocols rely on experimental trial-and-error approaches that result in variability of symptom improvements and suboptimal progress. Here, we leveraged whole-brain computational modelling by assessing the regional susceptibility towards optimal brain dynamics from Alzheimer's disease. In practice, we followed the three-part concept of Dynamic Sensitivity Analysis by first understanding empirical differences between healthy controls and patients with mild cognitive impairment and mild dementia due to Alzheimer's Disease; secondly, by building computational models for all individuals in the mild cognitive impairment and mild dementia cohorts; and thirdly, by perturbing brain regions and assessing the impact on the recovery of brain dynamics to the healthy state (here defined in functional terms, summarised by a measure of metastability for the healthy group). By doing so, we show the importance of key regions, along the anterior-posterior medial line, in driving in-silico improvement of mild dementia and mild cognitive impairment groups. Moreover, this subset consists mainly of regions with high structural nodal degree. Overall, this in-silico perturbational approach could inform the design of stimulation strategies for re-establishing healthy brain dynamics, putatively facilitating effective cognitive interventions targeting the cognitive decline in Alzheimer's disease.
Brain signal irreversibility has been shown to be a promising approach to study neural dynamics. ... more Brain signal irreversibility has been shown to be a promising approach to study neural dynamics. Nevertheless, the relation with cortical hierarchy and the influence of different electrophysiological features is not completely understood. In this study, we recorded local field potentials (LFPs) during spontaneous behavior, including awake and sleep periods, using custom micro-electrocorticographic (μECoG) arrays implanted in ferrets. In contrast to humans, ferrets remain less time in each state across the sleep-wake cycle. We deployed a diverse set of metrics in order to measure the levels of complexity of the different behavioral states. In particular, brain irreversibility, which allows us to quantify the level of non-equilibrium captured by the arrow of time of the signal, revealed the hierarchical organization of the ferret’s cortex. We found different signatures of irreversibility and functional hierarchy of large-scale dynamics in three different brain states (active awake, qu...
One of the potential and promising adjuvant therapies for Alzheimer’s disease is that of non-inva... more One of the potential and promising adjuvant therapies for Alzheimer’s disease is that of non-invasive transcranial neurostimulation to potentiate cognitive training interventions. Conceptually, this is achieved by driving brain dynamics towards an optimal state for an effective facilitation of cognitive training interventions. However, current neurostimulation protocols rely on experimental trial-and-error approaches that result in variability of symptom improvements and suboptimal progress. Here, we leveraged whole-brain computational modelling by assessing the regional susceptibility towards optimal brain dynamics from Alzheimer’s disease. In practice, we followed the three-part concept of Dynamic Sensitivity Analysis by first understanding empirical differences between healthy controls and patients with mild cognitive impairment and mild dementia due to Alzheimer’s Disease; secondly, by building computational models for all individuals in the mild cognitive impairment and mild de...
Current whole-brain models are generally tailored to the modelling of a particular modality of da... more Current whole-brain models are generally tailored to the modelling of a particular modality of data (e.g., fMRI or MEG/EEG). Although different imaging modalities reflect different aspects of neural activity, we hypothesise that this activity arises from common network dynamics. Building on the universal principles of self-organising delay-coupled nonlinear systems, we aim to link distinct electromagnetic and metabolic features of brain activity to the dynamics on the brain’s macroscopic structural connectome.To jointly predict dynamical and functional connectivity features of distinct signal modalities, we consider two large-scale models generating local short-lived 40 Hz oscillations with various degrees of realism - namely Stuart Landau (SL) and Wilson and Cowan (WC) models. To this end, we measure features of functional connectivity and metastable oscillatory modes (MOMs) in fMRI and MEG signals - and compare them against simulated data.We show that both models can represent MEG...
Stroke-related disruptions in functional connectivity (FC) often spread beyond lesioned areas and... more Stroke-related disruptions in functional connectivity (FC) often spread beyond lesioned areas and, given the localized nature of lesions, it is unclear how the recovery of FC is orchestrated on a global scale. Since recovery is accompanied by long-term changes in excitability, we propose excitatory-inhibitory (E-I) homeostasis as a driving mechanism. We present a large-scale model of the neocortex, with synaptic scaling of local inhibition, showing how E-I homeostasis can drive the post-lesion restoration of FC and linking it to changes in excitability. We show that functional networks could reorganize to recover disrupted modularity and small-worldness, but not network dynamics, suggesting the need to consider forms of plasticity beyond synaptic scaling of inhibition. On average, we observed widespread increases in excitability, with the emergence of complex lesion-dependent patterns related to biomarkers of relevant side effects of stroke, such as epilepsy, depression and chronic ...
Here we discuss the impact of issues recently raised about theories of consciousness in light of ... more Here we discuss the impact of issues recently raised about theories of consciousness in light of the so-called "unfolding argument" [7, 11, 6] and the more general falsification requirements [14, 10] on causal structure theories of consciousness. These arguments potentially affect the algorithmic information theory of consciousness (KT) [19], where the structure of a computational system is seen to shape subjective experience. We discuss this from the point of view of computational hierarchies [3] and limited physical resources to point to some novel considerations in the unfolding argument and its extensions.
Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanis... more Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used whole-brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a heathy one. Binarizing the sample into treatment responders (>50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-HT2A and 5-HT1A, which ...
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
In order to survive in a complex environment, the human brain relies on the ability to flexibly a... more In order to survive in a complex environment, the human brain relies on the ability to flexibly adapt ongoing behaviour according to intrinsic and extrinsic signals. This capability has been linked to specific whole-brain activity patterns whose relative stability (order) allows for consistent functioning, supported by sufficient intrinsic instability needed for optimal adaptability. The emergent, spontaneous balance between order and disorder in brain activity over spacetime underpins distinct brain states. For example, depression is characterized by excessively rigid, highly ordered states, while psychedelics can bring about more disordered, sometimes overly flexible states. Recent developments in systems, computational and theoretical neuroscience have started to make inroads into the characterization of such complex dynamics over space and time. Here, we review recent insights drawn from neuroimaging and whole-brain modelling motivating using mechanistic principles from dynamica...
Psychedelic drugs show promise as safe and effective treatments for neuropsychiatric disorders, y... more Psychedelic drugs show promise as safe and effective treatments for neuropsychiatric disorders, yet their mechanisms of action are not fully understood. A fundamental hypothesis is that psychedelics work by dose-dependently changing the functional hierarchy of brain dynamics, but it is unclear whether different psychedelics act similarly. Here, we investigated the changes in the brain’s functional hierarchy associated with two different psychedelics (LSD and psilocybin). Using a novel turbulence framework, we were able to determine the vorticity, that is, the local level of synchronization, that allowed us to extend the standard global time-based measure of metastability to become a local-based measure of both space and time. This framework produced detailed signatures of turbulence-based hierarchical change for each psychedelic drug, revealing consistent and discriminate effects on a higher level network, that is, the default mode network. Overall, our findings directly support a p...
A rich repertoire of oscillatory signals is detected from human brains with electro- and magnetoe... more A rich repertoire of oscillatory signals is detected from human brains with electro- and magnetoencephalography (EEG/MEG). However, the principles underwriting coherent oscillations and their link with neural activity remain under debate. Here, we revisit the mechanistic hypothesis that transient brain rhythms are a signature of metastable synchronization, occurring at reduced collective frequencies due to delays between brain areas. We consider a system of damped oscillators – approximating the short-lived gamma-frequency oscillations generated within neuronal circuits – coupled according to the diffusion weighted tractography between brain areas. Varying only the global coupling strength and conduction speed, we identify a critical regime where spatially and spectrally resolved metastable oscillatory modes (MOMs) emerge at sub-gamma frequencies, approximating the MEG power spectra from 89 healthy individuals at rest. Further, we demonstrate that the frequency, duration, and scale ...
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
ABSTRACTRecent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) ... more ABSTRACTRecent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used ‘connectome-harmonic decomposition’, a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.
The human brain is a complex system, whose activity exhibits flexible and continuous reorganisati... more The human brain is a complex system, whose activity exhibits flexible and continuous reorganisation across space and time. The decomposition of whole-brain recordings into harmonic modes has revealed a repertoire of gradient-like activity patterns associated with distinct brain functions. However, the way these activity patterns are expressed over time with their changes in various brain states remains unclear. In this study, we develop the Harmonic Decomposition of Spacetime (HADES) framework that characterises how different harmonic modes defined inspaceare expressed overtime, and, as a proof-of-principle, demonstrate the sensitivity and robustness of this approach to specific changes induced by the serotonergic psychedelic N,N-Dimethyltryptamine (DMT) in healthy participants. HADES demonstrates significant decreases in contributions across most low-frequency harmonic modes in the DMT-induced brain state. When normalizing the contributions by condition (DMT and non-DMT), we detect...
<strong><em>Data Acquisition</em></strong> The cohort consists of a total... more <strong><em>Data Acquisition</em></strong> The cohort consists of a total of 27 healthy participants (age 35 ± 6.8 years) and 27 schizophrenic patients (age 41 ± 9.6), scanned in a 3-Tesla MRI scanner (Trio, Siemens Medical, Germany) using a 32-channel head-coil. The schizophrenic patients are from the Service of General Psychiatry at the Lausanne University Hospital (CHUV). All of them were diagnosed with schizophrenic and schizoaffective disorders after meeting the DSM-IV criteria (American Psychiatric Association (2000): Diagnostic and Statistical Manual of Mental Disorders, 4th ed. DSM-IV-TR. American Psychiatric Pub, Arlington, VA22209, USA). The Diagnostic Interview for Genetic Studies assessment was used to recruits the healthy controls (Preisig et al. 1999). 24 out of the 27 schizophrenics were under medication with mean chlorpromazine equivalent dose (CPZ) of 431 ± 288 mg. The written consent was obtained for all subjects - in accordance with institutional guidelines of the Ethics Committee of Clinical Research of the Faculty of Biology and Medicine, University of Lausanne, Switzerland, #82/14, #382/11, #26.4.2005). All subjects were fully anonymised. The session protocol consisted of (1) a magnetization-prepared rapid acquisition gradient echo (MPRAGE) sequence sensitive to white/gray matter contrast (1-mm in-plane resolution, 1.2-mm slice thickness), (2) a Diffusion Spectrum Imaging (DSI) sequence (128 diffusion-weighted volumes and a single b0 volume, maximum b-value 8,000 s/mm<sup>2</sup>, 2.2x2.2x3.0 mm voxel size), and (3) a gradient echo EPI sequence sensitive to BOLD contrast (3.3-mm in-plane resolution and slice thickness with a 0.3-mm gap, TE 30 ms, TR 1,920 ms, resulting in 280 images per participant). During the fMRI scan, participants were not engaged in any overt task, and the scan was treated as eyes-open resting-state fMRI (rs-fMRI). <strong><em>Data Pre-processing </em></strong> Initial signal processing of all MPRAGE, DSI, and rs-fMRI data was performed using the Connectome Mapper pipel [...]
bioRxiv (Cold Spring Harbor Laboratory), Apr 9, 2024
A fundamental topological principle is that the container always shapes the content. In neuroscie... more A fundamental topological principle is that the container always shapes the content. In neuroscience, this translates into how the brain anatomy shapes brain dynamics. From neuroanatomy, the topology of the mammalian brain can be approximated by local connectivity, accurately described by an exponential distance rule (EDR). The compact, folded geometry of the cortex is shaped by this local connectivity and the geometric harmonic modes can reconstruct much of the functional dynamics. However, this ignores the fundamental role of the rare long-range cortical connections, crucial for improving information processing in the mammalian brain, but not captured by local cortical folding and geometry. Here we show the superiority of harmonics mode combining rare long-range with EDR (EDR+LR) in capturing functional dynamics (specifically long-range functional connectivity and task-evoked brain activity) compared to geometry and EDR representations. Importantly, the orchestration of dynamics is carried out by a more efficient manifold made up of a low number of fundamental EDR+LR modes. Our results show the importance of long-range connectivity for capturing the complexity of functional brain activity through a low-dimensional manifold shaped by fundamental EDR+LR modes.
Disorders of consciousness (DoC) are a challenging and complex group of neurological conditions c... more Disorders of consciousness (DoC) are a challenging and complex group of neurological conditions characterised by absent or impaired awareness. The current range of therapeutic options for DoC patients is limited, offering few non-invasive pharmacological alternatives. This situation has sprung a growing interest in the development of novel treatments, such as the proposal to study the efficacy of 5HT2A receptor agonists (also known as psychedelics) to restore impaired consciousness. Given the ethical implications of exploring novel compounds in non-communicative individuals, we assessed in silico their effects in the whole-brain dynamics of DoC patients. We embedded the whole-brain activity of patients in a low-dimensional space, and then used this representation to visualise the effects of simulated neuromodulation across a range of receptors representing potential drug targets. Our findings show that activation of serotonergic and opioid receptors shifted brain dynamics of DoC patients towards patterns typically seen in conscious and awake individuals, and that this effect was mediated by the brain-wide density of activated receptors. These results showcase the role of whole-brain models in the discovery of novel pharmacological treatments for neuropsychiatric conditions, while also supporting the feasibility of accelerating the recovery of consciousness with serotonergic psychedelics. .
bioRxiv (Cold Spring Harbor Laboratory), Nov 24, 2022
Stroke-related disruptions in functional connectivity (FC) often spread beyond lesioned areas and... more Stroke-related disruptions in functional connectivity (FC) often spread beyond lesioned areas and, given the localized nature of lesions, it is unclear how the recovery of FC is orchestrated on a global scale. Since recovery is accompanied by long-term changes in excitability, we propose excitatory-inhibitory (E-I) homeostasis as a driving mechanism. We present a large-scale model of the neocortex, with synaptic scaling of local inhibition, showing how E-I homeostasis can drive the post-lesion restoration of FC and linking it to changes in excitability. We show that functional networks could reorganize to recover disrupted modularity and small-worldness, but not network dynamics, suggesting the need to consider forms of plasticity beyond synaptic scaling of inhibition. On average, we observed widespread increases in excitability, with the emergence of complex lesiondependent patterns related to biomarkers of relevant side effects of stroke, such as epilepsy, depression and chronic pain. In summary, our results show that the effects of E-I homeostasis extend beyond local E-I balance, driving the restoration of global properties of FC, and relating to post-stroke symptomatology. Therefore, we suggest the framework of E-I homeostasis as a relevant theoretical foundation for the study of stroke recovery and for understanding the emergence of meaningful features of FC from local dynamics. .
bioRxiv (Cold Spring Harbor Laboratory), Apr 20, 2023
One of the potential and promising adjuvant therapies for Alzheimer's disease is that of noninvas... more One of the potential and promising adjuvant therapies for Alzheimer's disease is that of noninvasive transcranial neurostimulation to potentiate cognitive training interventions. Conceptually, this is achieved by driving brain dynamics towards an optimal state for an effective facilitation of cognitive training interventions. However, current neurostimulation protocols rely on experimental trial-and-error approaches that result in variability of symptom improvements and suboptimal progress. Here, we leveraged whole-brain computational modelling by assessing the regional susceptibility towards optimal brain dynamics from Alzheimer's disease. In practice, we followed the three-part concept of Dynamic Sensitivity Analysis by first understanding empirical differences between healthy controls and patients with mild cognitive impairment and mild dementia due to Alzheimer's Disease; secondly, by building computational models for all individuals in the mild cognitive impairment and mild dementia cohorts; and thirdly, by perturbing brain regions and assessing the impact on the recovery of brain dynamics to the healthy state (here defined in functional terms, summarised by a measure of metastability for the healthy group). By doing so, we show the importance of key regions, along the anterior-posterior medial line, in driving in-silico improvement of mild dementia and mild cognitive impairment groups. Moreover, this subset consists mainly of regions with high structural nodal degree. Overall, this in-silico perturbational approach could inform the design of stimulation strategies for re-establishing healthy brain dynamics, putatively facilitating effective cognitive interventions targeting the cognitive decline in Alzheimer's disease.
Brain signal irreversibility has been shown to be a promising approach to study neural dynamics. ... more Brain signal irreversibility has been shown to be a promising approach to study neural dynamics. Nevertheless, the relation with cortical hierarchy and the influence of different electrophysiological features is not completely understood. In this study, we recorded local field potentials (LFPs) during spontaneous behavior, including awake and sleep periods, using custom micro-electrocorticographic (μECoG) arrays implanted in ferrets. In contrast to humans, ferrets remain less time in each state across the sleep-wake cycle. We deployed a diverse set of metrics in order to measure the levels of complexity of the different behavioral states. In particular, brain irreversibility, which allows us to quantify the level of non-equilibrium captured by the arrow of time of the signal, revealed the hierarchical organization of the ferret’s cortex. We found different signatures of irreversibility and functional hierarchy of large-scale dynamics in three different brain states (active awake, qu...
One of the potential and promising adjuvant therapies for Alzheimer’s disease is that of non-inva... more One of the potential and promising adjuvant therapies for Alzheimer’s disease is that of non-invasive transcranial neurostimulation to potentiate cognitive training interventions. Conceptually, this is achieved by driving brain dynamics towards an optimal state for an effective facilitation of cognitive training interventions. However, current neurostimulation protocols rely on experimental trial-and-error approaches that result in variability of symptom improvements and suboptimal progress. Here, we leveraged whole-brain computational modelling by assessing the regional susceptibility towards optimal brain dynamics from Alzheimer’s disease. In practice, we followed the three-part concept of Dynamic Sensitivity Analysis by first understanding empirical differences between healthy controls and patients with mild cognitive impairment and mild dementia due to Alzheimer’s Disease; secondly, by building computational models for all individuals in the mild cognitive impairment and mild de...
Current whole-brain models are generally tailored to the modelling of a particular modality of da... more Current whole-brain models are generally tailored to the modelling of a particular modality of data (e.g., fMRI or MEG/EEG). Although different imaging modalities reflect different aspects of neural activity, we hypothesise that this activity arises from common network dynamics. Building on the universal principles of self-organising delay-coupled nonlinear systems, we aim to link distinct electromagnetic and metabolic features of brain activity to the dynamics on the brain’s macroscopic structural connectome.To jointly predict dynamical and functional connectivity features of distinct signal modalities, we consider two large-scale models generating local short-lived 40 Hz oscillations with various degrees of realism - namely Stuart Landau (SL) and Wilson and Cowan (WC) models. To this end, we measure features of functional connectivity and metastable oscillatory modes (MOMs) in fMRI and MEG signals - and compare them against simulated data.We show that both models can represent MEG...
Stroke-related disruptions in functional connectivity (FC) often spread beyond lesioned areas and... more Stroke-related disruptions in functional connectivity (FC) often spread beyond lesioned areas and, given the localized nature of lesions, it is unclear how the recovery of FC is orchestrated on a global scale. Since recovery is accompanied by long-term changes in excitability, we propose excitatory-inhibitory (E-I) homeostasis as a driving mechanism. We present a large-scale model of the neocortex, with synaptic scaling of local inhibition, showing how E-I homeostasis can drive the post-lesion restoration of FC and linking it to changes in excitability. We show that functional networks could reorganize to recover disrupted modularity and small-worldness, but not network dynamics, suggesting the need to consider forms of plasticity beyond synaptic scaling of inhibition. On average, we observed widespread increases in excitability, with the emergence of complex lesion-dependent patterns related to biomarkers of relevant side effects of stroke, such as epilepsy, depression and chronic ...
Here we discuss the impact of issues recently raised about theories of consciousness in light of ... more Here we discuss the impact of issues recently raised about theories of consciousness in light of the so-called "unfolding argument" [7, 11, 6] and the more general falsification requirements [14, 10] on causal structure theories of consciousness. These arguments potentially affect the algorithmic information theory of consciousness (KT) [19], where the structure of a computational system is seen to shape subjective experience. We discuss this from the point of view of computational hierarchies [3] and limited physical resources to point to some novel considerations in the unfolding argument and its extensions.
Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanis... more Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used whole-brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a heathy one. Binarizing the sample into treatment responders (>50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-HT2A and 5-HT1A, which ...
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
In order to survive in a complex environment, the human brain relies on the ability to flexibly a... more In order to survive in a complex environment, the human brain relies on the ability to flexibly adapt ongoing behaviour according to intrinsic and extrinsic signals. This capability has been linked to specific whole-brain activity patterns whose relative stability (order) allows for consistent functioning, supported by sufficient intrinsic instability needed for optimal adaptability. The emergent, spontaneous balance between order and disorder in brain activity over spacetime underpins distinct brain states. For example, depression is characterized by excessively rigid, highly ordered states, while psychedelics can bring about more disordered, sometimes overly flexible states. Recent developments in systems, computational and theoretical neuroscience have started to make inroads into the characterization of such complex dynamics over space and time. Here, we review recent insights drawn from neuroimaging and whole-brain modelling motivating using mechanistic principles from dynamica...
Psychedelic drugs show promise as safe and effective treatments for neuropsychiatric disorders, y... more Psychedelic drugs show promise as safe and effective treatments for neuropsychiatric disorders, yet their mechanisms of action are not fully understood. A fundamental hypothesis is that psychedelics work by dose-dependently changing the functional hierarchy of brain dynamics, but it is unclear whether different psychedelics act similarly. Here, we investigated the changes in the brain’s functional hierarchy associated with two different psychedelics (LSD and psilocybin). Using a novel turbulence framework, we were able to determine the vorticity, that is, the local level of synchronization, that allowed us to extend the standard global time-based measure of metastability to become a local-based measure of both space and time. This framework produced detailed signatures of turbulence-based hierarchical change for each psychedelic drug, revealing consistent and discriminate effects on a higher level network, that is, the default mode network. Overall, our findings directly support a p...
A rich repertoire of oscillatory signals is detected from human brains with electro- and magnetoe... more A rich repertoire of oscillatory signals is detected from human brains with electro- and magnetoencephalography (EEG/MEG). However, the principles underwriting coherent oscillations and their link with neural activity remain under debate. Here, we revisit the mechanistic hypothesis that transient brain rhythms are a signature of metastable synchronization, occurring at reduced collective frequencies due to delays between brain areas. We consider a system of damped oscillators – approximating the short-lived gamma-frequency oscillations generated within neuronal circuits – coupled according to the diffusion weighted tractography between brain areas. Varying only the global coupling strength and conduction speed, we identify a critical regime where spatially and spectrally resolved metastable oscillatory modes (MOMs) emerge at sub-gamma frequencies, approximating the MEG power spectra from 89 healthy individuals at rest. Further, we demonstrate that the frequency, duration, and scale ...
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
ABSTRACTRecent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) ... more ABSTRACTRecent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used ‘connectome-harmonic decomposition’, a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.
The human brain is a complex system, whose activity exhibits flexible and continuous reorganisati... more The human brain is a complex system, whose activity exhibits flexible and continuous reorganisation across space and time. The decomposition of whole-brain recordings into harmonic modes has revealed a repertoire of gradient-like activity patterns associated with distinct brain functions. However, the way these activity patterns are expressed over time with their changes in various brain states remains unclear. In this study, we develop the Harmonic Decomposition of Spacetime (HADES) framework that characterises how different harmonic modes defined inspaceare expressed overtime, and, as a proof-of-principle, demonstrate the sensitivity and robustness of this approach to specific changes induced by the serotonergic psychedelic N,N-Dimethyltryptamine (DMT) in healthy participants. HADES demonstrates significant decreases in contributions across most low-frequency harmonic modes in the DMT-induced brain state. When normalizing the contributions by condition (DMT and non-DMT), we detect...
<strong><em>Data Acquisition</em></strong> The cohort consists of a total... more <strong><em>Data Acquisition</em></strong> The cohort consists of a total of 27 healthy participants (age 35 ± 6.8 years) and 27 schizophrenic patients (age 41 ± 9.6), scanned in a 3-Tesla MRI scanner (Trio, Siemens Medical, Germany) using a 32-channel head-coil. The schizophrenic patients are from the Service of General Psychiatry at the Lausanne University Hospital (CHUV). All of them were diagnosed with schizophrenic and schizoaffective disorders after meeting the DSM-IV criteria (American Psychiatric Association (2000): Diagnostic and Statistical Manual of Mental Disorders, 4th ed. DSM-IV-TR. American Psychiatric Pub, Arlington, VA22209, USA). The Diagnostic Interview for Genetic Studies assessment was used to recruits the healthy controls (Preisig et al. 1999). 24 out of the 27 schizophrenics were under medication with mean chlorpromazine equivalent dose (CPZ) of 431 ± 288 mg. The written consent was obtained for all subjects - in accordance with institutional guidelines of the Ethics Committee of Clinical Research of the Faculty of Biology and Medicine, University of Lausanne, Switzerland, #82/14, #382/11, #26.4.2005). All subjects were fully anonymised. The session protocol consisted of (1) a magnetization-prepared rapid acquisition gradient echo (MPRAGE) sequence sensitive to white/gray matter contrast (1-mm in-plane resolution, 1.2-mm slice thickness), (2) a Diffusion Spectrum Imaging (DSI) sequence (128 diffusion-weighted volumes and a single b0 volume, maximum b-value 8,000 s/mm<sup>2</sup>, 2.2x2.2x3.0 mm voxel size), and (3) a gradient echo EPI sequence sensitive to BOLD contrast (3.3-mm in-plane resolution and slice thickness with a 0.3-mm gap, TE 30 ms, TR 1,920 ms, resulting in 280 images per participant). During the fMRI scan, participants were not engaged in any overt task, and the scan was treated as eyes-open resting-state fMRI (rs-fMRI). <strong><em>Data Pre-processing </em></strong> Initial signal processing of all MPRAGE, DSI, and rs-fMRI data was performed using the Connectome Mapper pipel [...]
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