Eli Muller

• The University of Sydney

Despite their widespread use, we have limited knowledge of the mechanisms by which sedatives mediate their effects on brain-wide networks. This is, in part, due to the technical challenge of observing activity across large populations of neurons in normal and sedated brains. In this study, we examined the effects of the sedative dexmedetomidine, an...

Working memory enables us to temporarily store and manipulate information, a crucial function for problem-solving. However, most working memory models emphasize cortical interactions ignoring contributions from subcortical and cerebellar regions. Given the dense connectivity between the cerebellum, subcortex, and cortex, we hypothesize that these r...

The ability to adapt to changes in the environment is essential for skilled performance, especially in competitive sports and events, where experts consistently perform at the highest level, rapidly adapting to unpredictable conditions. Current studies have identified cortical-cortical interactions between the premotor and primary motor cortex duri...

Brain recordings collected at different resolutions support statistically distinct signatures of information processing, leading to scale-dependent theories of brain function. Here, we demonstrate that these disparate neural-coding signatures emerge from the same multiscale functional organisation of neuronal activity across calcium-imaging recordi...

Despite their widespread use, we have limited knowledge of the mechanisms by which sedatives mediate their effects on brain-wide networks. This is, in part, due to the technical challenge of observing activity across large populations of neurons in normal and sedated brains. In this study, we examined the effects of the sedative dexmedetomidine, an...

While consciousness never fades during wakefulness, there is a paradoxical coexistence of consciousness during dreaming states. It’s also possible for sensory awareness to be either present or absent when awakened from seemingly-identical states of sedation and anaesthesia. Traditionally, these states have been characterised in terms of their elect...

A characteristic feature of human cognition is our ability to ‘multi-task’—performing two or more tasks in parallel—particularly when one task is well learned. How the brain supports this capacity remains poorly understood. Most past studies have focussed on identifying the areas of the brain—typically the dorsolateral prefrontal cortex—that are re...

Visual hallucinations in Parkinson’s disease can be viewed from a systems-level perspective, whereby abnormal communication between brain networks responsible for perception predisposes a person to hallucinate. To this end, abnormal functional interactions between higher-order and primary sensory networks have been implicated in the pathophysiology...

Perception is thought to rely upon evolving activity within a recurrent, distributed thalamocortical network whose interconnections are modulated by bursts of noradrenaline. To test this hypothesis, we leveraged a combination of pupillometry, fMRI and recurrent neural network modelling of an ambiguous figures task. Shifts in the perceptual interpre...

Perceptual updating has been proposed to rely upon evolving activity within a recurrent, distributed thalamocortical network whose interconnections are modulated by bursts of ascending neuromodulatory neurotransmitters, such as noradrenaline. To test this hypothesis mechanistically, we leveraged a combination of pupillometry, fMRI and recurrent neu...

Perceptual updating has been proposed to rely upon evolving activity within a recurrent, distributed thalamocortical network whose interconnections are modulated by bursts of ascending neuromodulatory neurotransmitters, such as noradrenaline. To test this hypothesis mechanistically, we leveraged a combination of pupillometry, fMRI and recurrent neu...

Perceptual updating has been proposed to rely upon evolving activity within a recurrent, distributed thalamocortical network whose interconnections are modulated by bursts of ascending neuromodulatory neurotransmitters, such as noradrenaline. To test this hypothesis mechanistically, we leveraged a combination of pupillometry, fMRI and recurrent neu...

Neuroscience has had access to high-resolution recordings of large-scale cortical activity and structure for decades, but still lacks a generally adopted basis to analyze and interrelate results from different individuals and experiments. Here it is argued that the natural oscillatory modes of the cortex—cortical eigenmodes—provide a physically pre...

Most human neuroscience research to date has focused on statistical approaches that describe stationary patterns of localized neural activity or blood flow. While these patterns are often interpreted in light of dynamic, information-processing concepts, the static, local, and inferential nature of the statistical approach makes it challenging to di...

Brain activity is constrained by local availability of chemical energy, which is generated through compartmentalized metabolic processes. By analyzing data of whole human brain gene expression, we characterize the spatial distribution of seven glucose and monocarboxylate membrane transporters that mediate astrocyte–neuron lactate shuttle transfer o...

A characteristic feature of human cognition is our ability to 'multi-task' - performing two or more tasks in parallel - particularly when one task is well-learned. How the brain supports this capacity remains poorly understood. Most past studies have focussed on identifying the areas of the brain - typically the dorsolateral prefrontal cortex - tha...

Neural dynamics are shaped and constrained by the projections of a small nucleus in the pons: the noradrenergic locus coeruleus (LC). Much like a bow to the brain’s violin, activity in the LC lacks content specificity, but instead dynamically shapes the excitability and receptivity of neurons across the brain. In this review, we explain how the sty...

New brain atlases with high spatial resolution and whole-brain coverage have rapidly advanced our knowledge of the brain's neural architecture, including the systematic variation of excitatory and inhibitory cell densities across the mammalian cortex. But understanding how the brain's microscale physiology shapes brain dynamics at the macroscale ha...

The emergence of distributed patterns of neural activity supporting brain functions and behavior can be understood by study of the brain’s low-dimensional topology. Functional neuroimaging demonstrates that brain activity linked to adaptive behavior is constrained to low-dimensional manifolds. In human participants, we tested whether these low-dime...

New brain atlases with high spatial resolution and whole-brain coverage have rapidly advanced our knowledge of the brain's neural architecture, including the systematic variation of excitatory and inhibitory cell densities across the mammalian cortex. But understanding how the brain's microscale physiology shapes brain dynamics at the macroscale ha...

Models of cognitive function typically focus on the cerebral cortex and hence overlook functional links to subcortical structures. This view does not consider the role of the highly-conserved ascending arousal system’s role and the computational capacities it provides the brain. We test the hypothesis that the ascending arousal system modulates cor...

Dimensionality reduction techniques offer a unique perspective on brain state dynamics, in which systems-level activity can be tracked through the engagement of a small number of component trajectories. Used in combination with neuroimaging data collected during the performance of cognitive tasks, these approaches can expose the otherwise latent di...

To remain adaptable to a dynamic environment, coordinated neural activity in the brain must be simultaneously flexible and reliable. There is evidence that the brain facilitates this adaptive response using highly-conserved metabotropic neuromodulatory neurotransmitters, such as noradrenaline and acetylcholine. While we understand how these neuromo...

Decades of neurobiological research have disclosed the diverse manners in which the response properties of neurons are dynamically modulated to support adaptive cognitive functions. This neuromodulation is achieved through alterations in the biophysical properties of the neuron. However, changes in cognitive function do not arise directly from the...

Models of cognitive function typically focus on the cerebral cortex, ignoring functional links to subcortical structures. This view neglects the highly-conserved ascending arousal system’s role and the computational capacities it provides the brain. In this study, we test the hypothesis that the ascending arousal system modulates cortical neural ga...

The biological mechanisms that allow the brain to balance flexibility and integration remain poorly understood. A potential solution may lie in a unique aspect of neurobiology, which is that numerous brain systems contain diffuse synaptic connectivity. Here, we demonstrate that increasing diffuse cortical coupling within a validated biophysical cor...

Recent neuroimaging experiments have defined low-dimensional gradients of functional connectivity in the cerebral cortex that subserve a spectrum of capacities that span from sensation to cognition. Despite well-known anatomical connections to the cortex, the subcortical areas that support cortical functional organization have been relatively overl...

The biological mechanisms that allow the brain to balance flexibility and integration remain poorly understood. A potential solution to this mystery may lie in a unique aspect of neurobiology, which is that numerous brain systems contain diffuse synaptic connectivity. In this manuscript, we demonstrate that increasing diffuse cortical coupling with...

This scientific commentary refers to ‘Cognitive load amplifies Parkinson’s tremor through excitatory network influences onto the thalamus’, by Dirkx etal. (doi: 10.1093/brain/awaa083).

Recent neuroimaging experiments have defined low-dimensional gradients of functional connectivity in the cerebral cortex that subserve a spectrum of capacities that span from sensation to cognition. Despite well-known anatomical connections to the cortex, the subcortical areas that support cortical functional organization have been relatively overl...

Cognitive activity emerges from large-scale neuronal dynamics that are constrained to a low-dimensional manifold. How this low-dimensional manifold scales with cognitive complexity, and which brain regions regulate this process, are not well understood. We addressed this issue by analyzing sub-second high-field fMRI data acquired during performance...

A neural field model of the corticothalamic-basal ganglia system is developed that describes enhanced beta activity within subthalamic and pallidal circuits in Parkinson's disease (PD) via system resonances. A model of deep brain stimulation (DBS) of typical clinical targets, the subthalamic nucleus (STN) and globus pallidus internus (GPi), is adde...

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is modeled to explore the mechanisms of this effective, but poorly understood, treatment for motor symptoms of drug-refractory Parkinson’s disease and dystonia. First, a neural field model of the corticothalamic-basal ganglia (CTBG) system is developed that reproduces key clinical featur...

The mechanisms underlying pathologically synchronized neural oscillations in Parkinson’s disease (PD) and generalized epilepsies are explored in parallel via a physiologically-based neural field model of the corticothalamic-basal ganglia (CTBG) system. The basal ganglia (BG) are approximated as a single effective population and their roles in the m...