Brain Imaging seminars

The brain represents the external world through the bottleneck of sensory organs. The network of hierarchically organized neurons is thought to recover the causes of sensory inputs to reconstruct the reality in the brain in idiosyncratic ways depending on individuals and their internal states. How can we understand the world model represented in an individual’s brain, or the neuroverse? My lab has been working on brain decoding of visual perception and subjective experiences such as imagery and dreaming using machine learning and deep neural network representations. In this talk, I will outline the progress of brain decoding methods and present how subjective experiences are externalized as images and how they could be shared across individuals via neural code conversion. The prospects of these approaches in basic science and neurotechnology will be discussed.

The hippocampus is crucial for spatial navigation and episodic memory formation. Hippocampal place cells exhibit spatially selective activity within an environment and have been proposed to form the neural basis of a cognitive map of space that supports these mnemonic functions. However, the direct influence of place cell activity on spatial navigation behaviour has not yet been demonstrated. Using an ‘all-optical’ combination of simultaneous two-photon calcium imaging and two-photon holographically targeted optogenetics, we identified and selectively activated place cells that encoded behaviourally relevant locations in a virtual reality environment. Targeted stimulation of a small number of place cells was sufficient to bias the behaviour of animals during a spatial memory task, providing causal evidence that hippocampal place cells actively support spatial navigation and memory. Time permitting, I will also describe new experiments aimed at understanding the fundamental encoding mechanism that supports episodic memory, focussing on the role of hippocampal sequences across multiple timescales and behaviours.

Modeling neural responses to naturalistic stimuli has been instrumental in advancing our understanding of the visual system. Dominant computational modeling efforts in this direction have been deeply rooted in preconceived hypotheses. In contrast, hypothesis-neutral computational methodologies with minimal apriorism which bring neuroscience data directly to bear on the model development process are likely to be much more flexible and effective in modeling and understanding tuning properties throughout the visual system. In this study, we develop a hypothesis-neutral approach and characterize response selectivity in the human visual cortex exhaustively and systematically via response-optimized deep neural network models. First, we leverage the unprecedented scale and quality of the recently released Natural Scenes Dataset to constrain parametrized neural models of higher-order visual systems and achieve novel predictive precision, in some cases, significantly outperforming the predictive success of state-of-the-art task-optimized models. Next, we ask what kinds of functional properties emerge spontaneously in these response-optimized models? We examine trained networks through structural ( feature visualizations) as well as functional analysis (feature verbalizations) by running `virtual' fMRI experiments on large-scale probe datasets. Strikingly, despite no category-level supervision, since the models are solely optimized for brain response prediction from scratch, the units in the networks after optimization act as detectors for semantic concepts like `faces' or `words', thereby providing one of the strongest evidences for categorical selectivity in these visual areas. The observed selectivity in model neurons raises another question: are the category-selective units simply functioning as detectors for their preferred category or are they a by-product of a non-category-specific visual processing mechanism? To investigate this, we create selective deprivations in the visual diet of these response-optimized networks and study semantic selectivity in the resulting `deprived' networks, thereby also shedding light on the role of specific visual experiences in shaping neuronal tuning. Together with this new class of data-driven models and novel model interpretability techniques, our study illustrates that DNN models of visual cortex need not be conceived as obscure models with limited explanatory power, rather as powerful, unifying tools for probing the nature of representations and computations in the brain.

To better understand human scene understanding, we extracted features from images using CLIP, a neural network model of visual concept trained with supervision from natural language. We then constructed voxelwise encoding models to explain whole brain responses arising from viewing natural images from the Natural Scenes Dataset (NSD) - a large-scale fMRI dataset collected at 7T. Our results reveal that CLIP, as compared to convolution based image classification models such as ResNet or AlexNet, as well as language models such as BERT, gives rise to representations that enable better prediction performance - up to a 0.86 correlation with test data and an r-square of 0.75 - in higher-level visual cortex in humans. Moreover, CLIP representations explain distinctly unique variance in these higher-level visual areas as compared to models trained with only images or text. Control experiments show that the improvement in prediction observed with CLIP is not due to architectural differences (transformer vs. convolution) or to the encoding of image captions per se (vs. single object labels). Together our results indicate that CLIP and, more generally, multimodal models trained jointly on images and text, may serve as better candidate models of representation in human higher-level visual cortex. The bridge between language and vision provided by jointly trained models such as CLIP also opens up new and more semantically-rich ways of interpreting the visual brain.

A recent approach to understanding the mammalian visual system is to show correspondence between the sequential stages of processing in the ventral stream with layers in a deep convolutional neural network (DCNN), providing evidence that visual information is processed hierarchically, with successive stages containing ever higher-level information. However, correspondence is usually defined as shared variance between brain region and model layer. We propose that task-relevant variance is a stricter test: If a DCNN layer corresponds to a brain region, then substituting the model’s activity with brain activity should successfully drive the model’s object recognition decision. Using this approach on three datasets (human fMRI and macaque neuron firing rates) we found that in contrast to the hierarchical view, all ventral stream regions corresponded best to later model layers. That is, all regions contain high-level information about object category. We hypothesised that this is due to recurrent connections propagating high-level visual information from later regions back to early regions, in contrast to the exclusively feed-forward connectivity of DCNNs. Using task-relevant correspondence with a late DCNN layer akin to a tracer, we used Granger causal modelling to show late-DCNN correspondence in IT drives correspondence in V4. Our analysis suggests, effectively, that no ventral stream region can be appropriately characterised as ‘early’ beyond 70ms after stimulus presentation, challenging hierarchical models. More broadly, we ask what it means for a model component and brain region to correspond: beyond quantifying shared variance, we must consider the functional role in the computation. We also demonstrate that using a DCNN to decode high-level conceptual information from ventral stream produces a general mapping from brain to model activation space, which generalises to novel classes held-out from training data. This suggests future possibilities for brain-machine interface with high-level conceptual information, beyond current designs that interface with the sensorimotor periphery.

The brain exhibits a rich repertoire of oscillatory patterns organized in space, time and frequency. However, despite ever more-detailed characterizations of spectrally-resolved network patterns, the principles governing oscillatory activity at the system-level remain unclear. Here, we propose that the transient emergence of spatially organized brain rhythms are signatures of weakly stable synchronization between subsets of brain areas, naturally occurring at reduced collective frequencies due to the presence of time delays. To test this mechanism, we build a reduced network model representing interactions between local neuronal populations (with damped oscillatory response at 40Hz) coupled in the human neuroanatomical network. Following theoretical predictions, weakly stable cluster synchronization drives a rich repertoire of short-lived (or metastable) oscillatory modes, whose frequency inversely depends on the number of units, the strength of coupling and the propagation times. Despite the significant degree of reduction, we find a range of model parameters where the frequencies of collective oscillations fall in the range of typical brain rhythms, leading to an optimal fit of the power spectra of magnetoencephalographic signals from 89 heathy individuals. These findings provide a mechanistic scenario for the spontaneous emergence of frequency-specific long-range phase-coupling observed in magneto- and electroencephalographic signals as signatures of resonant modes emerging in the space-time structure of the Connectome, reinforcing the importance of incorporating realistic time delays in network models of oscillatory brain activity.

Cognitive effort has long been an important explanatory factor in the study of human behavior in health and disease. Yet, the biophysical nature of cognitive effort remains far from understood. In this talk, I will offer a network perspective on cognitive effort. I will begin by canvassing a recent perspective that casts cognitive effort in the framework of network control theory, developed and frequently used in systems engineering. The theory describes how much energy is required to move the brain from one activity state to another, when activity is constrained to pass along physical pathways in a connectome. I will then turn to empirical studies that link this theoretical notion of energy with cognitive effort in a behaviorally demanding task, and with a metabolic notion of energy as accessible to FDG-PET imaging. Finally, I will ask how this structurally-constrained activity flow can provide us with insights about the brain’s non-equilibrium nature. Using a general tool for quantifying entropy production in macroscopic systems, I will provide evidence to suggest that states of marked cognitive effort are also states of greater entropy production. Collectively, the work I discuss offers a complementary view of cognitive effort as a dynamical process occurring atop a complex network.

This talk will focus on the generative modelling of resting state time series or endogenous neuronal activity. I will survey developments in modelling distributed neuronal fluctuations – spectral dynamic causal modelling (DCM) for functional MRI – and how this modelling rests upon functional connectivity. The dynamics of brain connectivity has recently attracted a lot of attention among brain mappers. I will also show a novel method to identify dynamic effective connectivity using spectral DCM. Further, I will summarise the development of the next generation of DCMs towards large-scale, whole-brain schemes which are computationally inexpensive, to the other extreme of the development using more sophisticated and biophysically detailed generative models based on the canonical microcircuits.

Brain microstructure plays a key role in driving the transport of drug molecules directly administered to the brain tissue as in Convection-Enhanced Delivery procedures. This study reports the first systematic attempt to characterize the cytoarchitecture of commissural, long association and projection fiber, namely: the corpus callosum, the fornix and the corona radiata. Ovine samples from three different subjects have been imaged using scanning electron microscope combined with focused ion beam milling. Particular focus has been given to the axons. For each tract, a 3D reconstruction of relatively large volumes (including a significant number of axons) has been performed. Namely, outer axonal ellipticity, outer axonal cross-sectional area and its relative perimeter have been measured. This study [1] provides useful insight into the fibrous organization of the tissue that can be described as composite material presenting elliptical tortuous tubular fibers, leading to a workflow to enable accurate simulations of drug delivery which include well-resolved microstructural features. As a demonstration of the use of these imaging and reconstruction techniques, our research analyses the hydraulic permeability of two white matter (WM) areas (corpus callosum and fornix) whose three-dimensional microstructure was reconstructed starting from the acquisition of the electron microscopy images. Considering that the white matter structure is mainly composed of elongated and parallel axons we computed the permeability along the parallel and perpendicular directions using computational fluid dynamics [2]. The results show a statistically significant difference between parallel and perpendicular permeability, with a ratio about 2 in both the white matter structures analysed, thus demonstrating their anisotropic behaviour. This is in line with the experimental results obtained using perfusion of brain matter [3]. Moreover, we find a significant difference between permeability in corpus callosum and fornix, which suggests that also the white matter heterogeneity should be considered when modelling drug transport in the brain. Our findings, that demonstrate and quantify the anisotropic and heterogeneous character of the white matter, represent a fundamental contribution not only for drug delivery modelling but also for shedding light on the interstitial transport mechanisms in the extracellular space. These and many other discoveries will be discussed during the talk." "1. https://www.researchsquare.com/article/rs-686577/v1, 2. https://www.pnas.org/content/118/36/e2105328118, 3. https://ieeexplore.ieee.org/abstract/document/9198110

In this talk I will present data from imaging studies that we have been conducting for the past 20 years trying to shed light on migraine physiopathology, from anatomical and functional MRI to positron emission tomography.

Multisensory perception is often studied through the effects of inter-sensory conflict, such as in the McGurk effect, the Ventriloquist illusion, and the Rubber Hand Illusion. Moreover, Bayesian approaches to cue fusion and causal inference overwhelmingly draw on cross-modal conflict to measure and to model multisensory perception. Given the prevalence of conflict, it is remarkable that accounts of multisensory perception have so far neglected the theory of conflict monitoring and cognitive control, established about twenty years ago. I hope to make a case for the role of conflict monitoring and resolution during multisensory perception. To this end, I will present EEG and fMRI data showing that cross-modal conflict in speech, resulting in either integration or segregation, triggers neural mechanisms of conflict detection and resolution. I will also present data supporting a role of these mechanisms during perceptual conflict in general, using Binocular Rivalry, surrealistic imagery, and cinema. Based on this preliminary evidence, I will argue that it is worth considering the potential role of conflict in multisensory perception and its incorporation in a causal inference framework. Finally, I will raise some potential problems associated with this proposal.

Given the intrinsically large and complex data sets collected in neuroimaging research, coupled with the extensive array of shared data and tools amassed in the research community, ReproNim seeks to lower the barriers for efficient: use of data; description of data and process; use of standards and best practices; sharing; and subsequent reuse of the collective ‘big’ data. Aggregation of data and reuse of analytic methods have become critical in addressing concerns about the replicability and power of many of today’s neuroimaging studies.

Macroscopic brain organisation emerges early in life, even prenatally, and continues to develop through adolescence and into early adulthood. The emergence and continual refinement of large-scale brain networks, connecting neuronal populations across anatomical distance, allows for increasing functional integration and specialisation. This process is thought crucial for the emergence of complex cognitive processes. But how and why is this process so diverse? We used structural neuroimaging collected from a large diverse cohort, to explore how different features of macroscopic brain organisation are associated with diverse cognitive trajectories. We used diffusion-weighted imaging (DWI) to construct whole-brain white-matter connectomes. A simulated attack on each child's connectome revealed that some brain networks were strongly organized around highly connected 'hubs'. The more children's brains were critically dependent on hubs, the better their cognitive skills. Conversely, having poorly integrated hubs was a very strong risk factor for cognitive and learning difficulties across the sample. We subsequently developed a computational framework, using generative network modelling (GNM), to model the emergence of this kind of connectome organisation. Relatively subtle changes within the wiring rules of this computational framework give rise to differential developmental trajectories, because of small biases in the preferential wiring properties of different nodes within the network. Finally, we were able to use this GNM to implicate the molecular and cellular processes that govern these different growth patterns.

The Miniscope Project -- an open-source collaborative effort—was created to accelerate innovation of miniature microscope technology and to increase global access to this technology. Currently, we are working on advancements ranging from optogenetic stimulation and wire-free operation to simultaneous optical and electrophysiological recording. Using these systems, we have uncovered mechanisms underlying temporal memory linking and investigated causes of cognitive deficits in temporal lobe epilepsy. Through innovation and optimization, this work aims to extend the reach of neuroscience research and create new avenues of scientific inquiry.

The standard method for staining structures in the brain is to slice the brain into 2D sections. Each slice is treated using a technique such as in-situ hybridization to examine the spatial expression of a particular molecule at a given developmental timepoint. Depending on the brain structures being studied, slices can be made coronally, sagitally, or at any angle that is thought to be optimal for analysis. However, assimilating the information presented in the 2D slice images to gain quantitiative and informative 3D expression patterns is challenging. Even if expression levels are presented as voxels, to give 3D expression clouds, it can be difficult to compare expression across individuals and analysing such data requires significant expertise and imagination. In this talk, I will describe a new approach to examining histology slices, in which the user defines the brain structure of interest by drawing curves around it on each slice in a set and the depth of tissue from which to sample expression. The sampled 'curves' are then assembled into a 3D surface, which can then be transformed onto a common reference frame for comparative analysis. I will show how other neuroscientists can obtain and use the tool, which is called Stalefish, to analyse their own image data with no (or minimal) changes to their slice preparation workflow.

During our everyday lives, much of what we experience is familiar and predictable. We typically follow the same morning routine, take the same route to work, and encounter the same colleagues. However, every once in a while, we encounter a surprising event that violates our expectations. When we encounter such violations of our expectations, it is adaptive to update our internal model of the world in order to make better predictions in the future. The hippocampus is thought to support both the learning of the predictable structure of our environment, as well as the detection and encoding of violations. However, the hippocampus is a complex and heterogeneous structure, composed of different subfields that are thought to subserve different functions. As such, it is not yet known how the hippocampus accomplishes the learning and updating of structured knowledge. Using behavioral methods and high-resolution fMRI, I'll show that during learning of repeated and predicted events, hippocampal subfields differentially integrate and separate event representations, thus learning the structure of ongoing experience. I then move on to discuss how when events violate our predictions, there is a shift in communication between hippocampal subfields, potentially allowing for efficient encoding of the novel and surprising information. If time permits, I'll present an additional behavioral study showing that violations of predictions promote detailed memories. Together, these studies advance our understanding of how we adaptively learn and update our knowledge.

Every year around 100,000 people in the UK will have a stroke. Stroke is a leading cause of adult disability, and cerebrovascular disease more broadly is a major cause of dementia. Understanding these diseases – both acute and chronic manifestations of cerebrovascular disease – requires consideration not only of the brain itself, but also the blood vessels supplying it. Atherosclerosis – the hardening of arteries as we age – may predispose to stroke by triggering the formation of blood clots that block the blood supply to the brain, but also involves inflammation that may cause chronic damage to the brain and prime both the brain and body for injury. Understanding this interaction between systemic disease and brain health may have important implications for our understanding of healthy ageing and provide novel therapeutic approaches for reducing the burden of cerebrovascular disease. This talk will consider how advances in imaging may facilitate our understanding of the processes underlying atherosclerosis and how it affects the brain in stroke, as well as work currently underway to translate this understanding into improving treatments for stroke.

Cortical functions result from the conjoint activity of different, reciprocally connected areas working together as large-scale functionally specialized networks. In the macaque brain, neural tracers and functional data have provided evidence for functionally specialized large-scale cortical networks involving temporal, parietal, and frontal areas. One of these networks, the lateral grasping network, appears to play a primary role in controlling hand action organization and recognition. Available functional and tractograpy data suggest the existence of a human counterpart of this network.

Holding information in working memory is essential for cognition, but removing unwanted thoughts is equally important. There is great flexibility in how we can manipulate information in working memory, but the processes and consequences of these operations are poorly understood. In this talk I will discuss our recent findings using multivariate pattern analyses of fMRI brain data to demonstrate the successful removal of information from working memory using three different strategies: suppressing a specific thought, replacing a thought with a different one, and clearing the mind of all thought. These strategies are supported by distinct brain regions and have differential consequences on the encoding of new information. I will discuss implications of these results on theories of memory and I will highlight some new directions involving the use of real-time neurofeedback to investigate causal links between brain and behavior.

Predictive learning hypotheses posit that the neocortex learns a hierarchical model of the structure of features in the environment. Under these hypotheses, expected or predictable features are differentiated from unexpected ones by comparing bottom-up and top-down streams of data, with unexpected features then driving changes in the representation of incoming stimuli. This is supported by numerous studies in early sensory cortices showing that pyramidal neurons respond particularly strongly to unexpected stimulus events. However, it remains unknown how their responses govern subsequent changes in stimulus representations, and thus, govern learning. Here, I present results from our study of layer 2/3 and layer 5 pyramidal neurons imaged in primary visual cortex of awake, behaving mice using two-photon calcium microscopy at both the somatic and distal apical planes. Our data reveals that individual neurons and distal apical dendrites show distinct, but predictable changes in unexpected event responses when tracked over several days. Considering existing evidence that bottom-up information is primarily targeted to somata, with distal apical dendrites receiving the bulk of top-down inputs, our findings corroborate hypothesized complementary roles for these two neuronal compartments in hierarchical computing. Altogether, our work provides novel evidence that the neocortex indeed instantiates a predictive hierarchical model in which unexpected events drive learning.