Understanding brain states across spacetime informed by whole-brain modelling

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 dynamical system theory to study and characterize brain states. We show how different healthy and altered brain states are associated to characteristic spacetime dynamics which in turn may offer insights that in time can inspire new treatments for rebalancing brain states in disease. This article is part of the theme issue 'Emergent phenomena in complex physical and socio-technical systems: from cells to societies'

Moving from phenomenological to predictive modelling: Progress and pitfalls of modelling brain stimulation in-silico

Brain stimulation is an increasingly popular neuromodulatory tool used in both clinical and research settings; however, the effects of brain stimulation, particularly those of non-invasive stimulation, are variable. This variability can be partially explained by an incomplete mechanistic understanding, coupled with a combinatorial explosion of possible stimulation parameters. Computational models constitute a useful tool to explore the vast sea of stimulation parameters and characterise their effects on brain activity. Yet the utility of modelling stimulation in-silico relies on its biophysical relevance, which needs to account for the dynamics of large and diverse neural populations and how underlying networks shape those collective dynamics. The large number of parameters to consider when constructing a model is no less than those needed to consider when planning empirical studies. This piece is centred on the application of phenomenological and biophysical models in non-invasive brain stimulation. We first introduce common forms of brain stimulation and computational models, and provide typical construction choices made when building phenomenological and biophysical models. Through the lens of four case studies, we provide an account of the questions these models can address, commonalities, and limitations across studies. We conclude by proposing future directions to fully realise the potential of computational models of brain stimulation for the design of personalized, efficient, and effective stimulation strategies

A brief exposure to rightward prismatic adaptation changes resting-state network characteristics of the ventral attentional system.

A brief session of rightward prismatic adaptation (R-PA) has been shown to alleviate neglect symptoms in patients with right hemispheric damage, very likely by switching hemispheric dominance of the ventral attentional network (VAN) from the right to the left and by changing task-related activity within the dorsal attentional network (DAN). We have investigated this very rapid change in functional organisation with a network approach by comparing resting-state connectivity before and after a brief exposure i) to R-PA (14 normal subjects; experimental condition) or ii) to plain glasses (12 normal subjects; control condition). A whole brain analysis (comprising 129 regions of interest) highlighted R-PA-induced changes within a bilateral, fronto-temporal network, which consisted of 13 nodes and 11 edges; all edges involved one of 4 frontal nodes, which were part of VAN. The analysis of network characteristics within VAN and DAN revealed a R-PA-induced decrease in connectivity strength between nodes and a decrease in local efficiency within VAN but not within DAN. These results indicate that the resting-state connectivity configuration of VAN is modulated by R-PA, possibly by decreasing its modularity

Effects of classic psychedelic drugs on turbulent signatures in brain dynamics

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 prior hypothesis that psychedelics modulate (i.e., “compress”) the functional hierarchy and provide a quantification of these changes for two different psychedelics. Implications for therapeutic applications of psychedelics are discussed

Centering inclusivity in the design of online conferences: An OHBM-Open Science perspective

As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities. Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements of an online conference are still significant barriers to truly diverse participation: the tools used can be inaccessible for some individuals; the scheduling choices can favour some geographical locations; the set-up of the conference can provide more visibility to well-established researchers and reduce opportunities for early-career researchers. While acknowledging the benefits of an online setting, especially for individuals who have traditionally been underrepresented or excluded, we recognize that fostering social justice requires inclusivity to actively be centered in every aspect of online conference design. Here, we draw from the literature and from our own experiences to identify practices that purposefully encourage a diverse community to attend, participate in, and lead online conferences. Reflecting on how to design more inclusive online events is especially important as multiple scientific organizations have announced that they will continue offering an online version of their event when in-person conferences can resume

Synchronization in the connectome: metastable oscillatory modes emerge from interactions in the brain spacetime network

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 in the presence of background noise – approximating the short-lived gamma-frequency oscillations generated within neuronal circuits – coupled according to the diffusion weighted tractography between brain areas. Varying 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 of MOMs – as well as the frequency-specific envelope functional connectivity – can be controlled by global parameters, while the connectome structure remains unchanged. Grounded in the physics of delay-coupled oscillators, these numerical analyses demonstrate how interactions between locally generated fast oscillations in the connectome spacetime structure can lead to the emergence of collective brain rhythms organized in space and time

Stable biomarker identification for predicting schizophrenia in the human connectome.

Schizophrenia, as a psychiatric disorder, has recognized brain alterations both at the structural and at the functional magnetic resonance imaging level. The developing field of connectomics has attracted much attention as it allows researchers to take advantage of powerful tools of network analysis in order to study structural and functional connectivity abnormalities in schizophrenia. Many methods have been proposed to identify biomarkers in schizophrenia, focusing mainly on improving the classification performance or performing statistical comparisons between groups. However, the stability of biomarkers selection has been for long overlooked in the connectomics field. In this study, we follow a machine learning approach where the identification of biomarkers is addressed as a feature selection problem for a classification task. We perform a recursive feature elimination and support vector machines (RFE-SVM) approach to identify the most meaningful biomarkers from the structural, functional, and multi-modal connectomes of healthy controls and patients. Furthermore, the stability of the retrieved biomarkers is assessed across different subsamplings of the dataset, allowing us to identify the affected core of the pathology. Considering our technique altogether, it demonstrates a principled way to achieve both accurate and stable biomarkers while highlighting the importance of multi-modal approaches to brain pathology as they tend to reveal complementary information

Distributed harmonic patterns of structure-function dependence orchestrate human consciousness

A central question in neuroscience is how consciousness arises from the dynamic interplay of brain structure and function. Here we decompose functional MRI signals from pathological and pharmacologically-induced perturbations of consciousness into distributed patterns of structure-function dependence across scales: the harmonic modes of the human structural connectome. `We show that structure-function coupling is a generalisable indicator of consciousness that is under bi-directional neuromodulatory control. We find increased structure-function coupling across scales during loss of consciousness, whether due to anaesthesia or brain injury, capable of discriminating between behaviourally indistinguishable sub-categories of brain-injured patients, tracking the presence of covert consciousness. The opposite harmonic signature characterises the altered state induced by LSD or ketamine, reflecting psychedelic-induced decoupling of brain function from structure and correlating with physiological and subjective scores. Overall, connectome harmonic decomposition reveals how neuromodulation and the network architecture of the human connectome jointly shape consciousness and distributed functional activation across scales.AIL, JV and PAMM would like to thank Lena Dorfschmidt for co-organising OxBridge BrainHack 2019, where this work began. We also thank all volunteers and patients who provided data. This work was supported by grants from The Wellcome Trust Research Training Fellowship (grant no. 083660/Z/07/Z), Raymond and Beverly Sackler Studentship, and the Cambridge Commonwealth Trust [RA]; the UK Medical Research Council (U.1055.01.002.00001.01) [JDP]; The James S. McDonnell Foundation [JDP]; the Canadian Institute for Advanced Research (CIFAR; grant RCZB/072 RG93193) [to DKM and EAS]; The National Institute for Health Research (NIHR, UK), Cambridge Biomedical Research Centre and NIHR Senior Investigator Awards [JDP and DKM]; The British Oxygen Professorship of the Royal College of Anaesthetists [DKM]; The Stephen Erskine Fellowship, Queens’ College, University of Cambridge [EAS]; The Evelyn Trust, Cambridge and the EoE CLAHRC fellowship [JA]; The Gates Cambridge Trust [AIL]; The Cambridge International Trust and the Howard Sidney Sussex Studentship [MMC]; The Oon Khye Beng Ch'Hia Tsio Studentship for Research in Preventive Medicine, Downing College, University of Cambridge [IP]; The Wellcome Trust (grant no. 210920/Z/18/Z) [PAMM]; The European Research Council Consolidator Grant CAREGIVING (615539) [MLK and SA]; The Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117) [MLK, SA and JV]; The Centre for Eudaimonia and Human Flourishing, funded by the Pettit and Carlsberg Foundations [MLK]; The Imperial College President’s Scholarship [LR]; The Alex Mosley Charitable Trust [RLCH]; The ketamine study was funded by the Bernard Wolfe Health Neuroscience Fund and the Wellcome Trust. The original LSD study received support from a Crowd Funding Campaign and the Beckley Foundation, as part of the Beckley-Imperial Research Programme. The research was also supported by the NIHR Brain Injury Healthcare Technology Co-operative based at Cambridge University Hospitals NHS Foundation Trust and University of Cambridge. Data used to obtain the human connectome were provided by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Brainhack: Developing a culture of open, inclusive, community-driven neuroscience

Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress