Systematic dynamical profiling to discover and manipulate the dynamical regime of the primate brain

Neural activity and functional interactions are naturally variable from moment to moment,
resulting in various dynamic configurations of brain activity. Contemporary theories of brain structure and function emphasize systematic variations in cortical neurobiological properties (cell type composition, receptor density) that are also reflected in spontaneous neuronal activity at multiple temporal and spatial scales. The brain’s dynamical regime can be characterised at macroscale using non-invasive neuroimaging recordings. However, existing studies focus on hand-picked properties such as synchrony, power spectrum, or amplitude of slow fluctuations. In contrast, the time-series literature is vast and interdisciplinary, spanning thousands of potential time-series literature from neuroscience but also physics, economics, and beyond. This talk will outline how this vast time-series literature can be combined with the complementary strengths of electromagnetic imaging (MEG) and functional magnetic resonance imaging (fMRI) to comprehensively characterise the dynamical regime of the brain (Shafiei et al., 2020 eLife).

We can then systematically examine the relationship between slow- and fast-oscillating neural activity and heterogeneous cortical microarchitecture using measures such as intracortical myelin, excitatory and inhibitory receptors and transporters derived from in vivo PET, and transcriptomically-derived cell type composition (Shafiei et al., 2023 Nature Communications). Having identified neurobiological determinants of neural dynamics in the human brain, we examine how pharmacological manipulations impact neural activity. Systematically and reversibly perturbing brain function with anaesthesia while recording neural activity provides a unique opportunity for causal manipulation of the brain’s dynamical regime. We apply massive temporal feature extraction to generate more than 6000 dynamical features that comprehensively characterise local neural activity from functional MRI signals in humans and non-human primates, comparing wakefulness against a wide range of anaesthetics. We identify an evolutionarily conserved dynamical profile of anaesthesia that is underpinned by a phylogenetically conserved axis of gene expression pertaining to regulation of arousal and sleep-wake cycles. The dynamical signature of anaesthesia is reversed upon re-awakening induced by deep-brain stimulation (DBS) of the central thalamus in macaques. This work demonstrates that the global dynamical regime supporting consciousness is amenable to bi-directional control by pharmacology and local stimulation of the central thalamus, reconciling local and global views of brain function. More broadly, the combination of invasive brain stimulation and extensive dynamical phenotyping of neuroimaging recordings provides an exceptional opportunity for translational discovery, leveraging the greater experimental accessibility of animal models to obtain causal insight. Given the increasing evidence that anaesthesia and coma manifest as similar dynamical patterns in the human brain, this work holds promise for thalamic DBS as a potential treatment avenue for chronic disorders of consciousness.