Neuroscience seminars

With this webinar series, the ALBA Disability & Accessibility Working Group aims to bring down the ivory tower of ableism among the brain research community, one extraordinary neuroscientist at a time. These webinars give a platform to scientists with disabilities across the globe and neuroscience disciplines, while reflecting on how to promote inclusive working environments and accessibility to research. For this 4th episode, Dr. Maria José Diógenes (iMM - ULisboa, PT) will talk about how her personal story changed her professional life: from the pharmacy to the laboratory bench and from ageing to Rett Syndrome.

Sound waves can be used to modify brain activity safely and transiently with unprecedented precision even deep in the brain - unlike traditional brain stimulation methods. In a series of studies in humans and non-human primates, I will show that Transcranial Ultrasound Stimulation (TUS) can have medium- to long-lasting effects. Multiple read-outs allow us to conclude that TUS can perturb neuronal tissues up to 2h after intervention, including changes in local and distributed brain network configurations, behavioural changes, task-related neuronal changes and chemical changes in the sonicated focal volume. Combined with multiple neuroimaging techniques (resting state functional Magnetic Resonance Imaging [rsfMRI], Spectroscopy [MRS] and task-related fMRI changes), this talk will focus on recent human TUS studies.

Neural entrainment has become a phenomenon of exceptional interest to neuroscience, given its involvement in rhythm perception, production, and overt synchronized behavior. Yet, traditional methods fail to quantify neural entrainment due to a misalignment with its fundamental definition (e.g., see Novembre and Iannetti, 2018; Rajandran and Schupp, 2019). The definition of entrainment assumes that endogenous oscillatory brain activity undergoes dynamic frequency adjustments to synchronize with environmental rhythms (Lakatos et al., 2019). Following this definition, we recently developed a method sensitive to this process. Our aim was to isolate from the electroencephalographic (EEG) signal an oscillatory component that is attuned to the frequency of a rhythmic stimulation, hypothesizing that the oscillation would adaptively speed up and slow down to achieve stable synchronization over time. To induce and measure these adaptive changes in a controlled fashion, we developed the event-related frequency adjustment (ERFA) paradigm (Rosso et al., 2023). A total of twenty healthy participants took part in our study. They were instructed to tap their finger synchronously with an isochronous auditory metronome, which was unpredictably perturbed by phase-shifts and tempo-changes in both positive and negative directions across different experimental conditions. EEG was recorded during the task, and ERFA responses were quantified as changes in instantaneous frequency of the entrained component. Our results indicate that ERFAs track the stimulus dynamics in accordance with the perturbation type and direction, preferentially for a sensorimotor component. The clear and consistent patterns confirm that our method is sensitive to the process of frequency adjustment that defines neural entrainment. In this Virtual Journal Club, the discussion of our findings will be complemented by methodological insights beneficial to researchers in the fields of rhythm perception and production, as well as timing in general. We discuss the dos and don’ts of using instantaneous frequency to quantify oscillatory dynamics, the advantages of adopting a multivariate approach to source separation, the robustness against the confounder of responses evoked by periodic stimulation, and provide an overview of domains and concrete examples where the methodological framework can be applied.

Subsecond timing underlies nearly all sensory and motor activities across species and is critical to survival. While subsecond temporal information has been found across cortical and subcortical regions, it is unclear if it is generated locally and intrinsically or if it is a read out of a centralized clock-like mechanism. Indeed, mechanisms of subsecond timing at the circuit level are largely obscure. Primary sensory areas are well-suited to address these question as they have early access to sensory information and provide minimal processing to it: if temporal information is found in these regions, it is likely to be generated intrinsically and locally. We test this hypothesis by training mice to perform an audio-visual temporal pattern sensory discrimination task as we use 2-photon calcium imaging, a technique capable of recording population level activity at single cell resolution, to record activity in primary visual cortex (V1). We have found significant changes in network dynamics through mice’s learning of the task from naive to middle to expert levels. Changes in network dynamics and behavioral performance are well accounted for by an intrinsic model of timing in which the trajectory of q network through high dimensional state space represents temporal sensory information. Conversely, while we found evidence of other temporal encoding models, such as oscillatory activity, we did not find that they accounted for increased performance but were in fact correlated with the intrinsic model itself. These results provide insight into how subsecond temporal information is encoded mechanistically at the circuit level.

The internal and external world is thought to be represented by distributed patterns of cortical activity. The emergence of these cortical representations over the course of development remains an unresolved question. In this talk, I share results from a series of recent studies combining theory and experiments in the cortex of the ferret, a species with a well-defined columnar organization and modular network of orientation-selective responses in visual cortex. I show that prior to the onset of structured sensory experience, endogenous mechanisms set up a highly organized cortical network structure that is evident in modular patterns of spontaneous activity characterized by strong, clustered local and long-range correlations. This correlation structure is remarkably consistent across both sensory and association areas in the early neocortex, suggesting that diverse cortical representations initially develop according to similar principles. Next, I explore a classical candidate mechanism for producing modular activity – local excitation and lateral inhibition. I present the first empirical test of this mechanism through direct optogenetic cortical activation and discuss a plausible circuit implementation. Then, focusing on the visual cortex, I demonstrate that these endogenously structured networks enable orientation-selective responses immediately after eye opening. However, these initial responses are highly variable, lacking the reliability and low-dimensional structure observed in the mature cortex. Reliable responses are achieved after an experience-dependent co-reorganization of stimulus- evoked and spontaneous activity following eye opening. Based on these observations, I propose the hypothesis that the alignment between feedforward inputs and the recurrent network plays a crucial role in transforming the initially variable responses into mature and reliable representations. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2023-11-22. Recording duration: 00:56:31.

Over the past decade we have demonstrated that the fusion of subject-specific structural information of the human brain with mathematical dynamic models allows building biologically realistic brain network models, which have a predictive value, beyond the explanatory power of each approach independently. The network nodes hold neural population models, which are derived using mean field techniques from statistical physics expressing ensemble activity via collective variables. Our hybrid approach fuses data-driven with forward-modeling-based techniques and has been successfully applied to explain healthy brain function and clinical translation including aging, stroke and epilepsy. Here we illustrate the workflow along the example of epilepsy: we reconstruct personalized connectivity matrices of human epileptic patients using Diffusion Tensor weighted Imaging (DTI). Subsets of brain regions generating seizures in patients with refractory partial epilepsy are referred to as the epileptogenic zone (EZ). During a seizure, paroxysmal activity is not restricted to the EZ, but may recruit other healthy brain regions and propagate activity through large brain networks. The identification of the EZ is crucial for the success of neurosurgery and presents one of the historically difficult questions in clinical neuroscience. The application of latest techniques in Bayesian inference and model inversion, in particular Hamiltonian Monte Carlo, allows the estimation of the EZ, including estimates of confidence and diagnostics of performance of the inference. The example of epilepsy nicely underwrites the predictive value of personalized large-scale brain network models. The workflow of end-to-end modeling is an integral part of the European neuroinformatics platform EBRAINS and enables neuroscientists worldwide to build and estimate personalized virtual brains.

Note the later time in the USA!

In this talk, I will focus on recent work that has uncovered the diversity of intrinsically photosensitive retinal ganglion cells (ipRGCs). These are a unique type of retinal ganglion cell that contains the photopigment melanopsin. ipRGCs are the retinal neurons responsible for driving non-imaging forming behaviors and reflexes, such as circadian entrainment and pupil constriction, amongst many others. My lab has recently focused on uncovering the diversity of ipRGCs, their distribution throughout the mammalian retina, and their axon projections in the brain.

On Thursday, October 26th, we will host Anastasia Yendiki and Suzanne Haber. Anastasia Yendiki, PhD, is an Associate Professor in Radiology at the Harvard Medical School and an Associate Investigator at the Massachusetts General Hospital and Athinoula A. Martinos Center. Suzanne Haber, PhD, is a Professor at the University of Rochester and runs a lab at McLean hospital at Harvard Medical School in Boston. She has received numerous awards for her work on neuroanatomy. Beside her scientific presentation, she will give us a glimpse at the “Person behind the science”. The talks will be followed by a shared discussion. You can register via talks.stimulatingbrains.org to receive the (free) Zoom link!

Epileptogenesis is a gradual and dynamic process leading to difficult-to-treat seizures. Several cellular, molecular, and pathophysiologic mechanisms, including the activation of inflammatory processes. The use of human brain tissue represents a crucial strategy to advance our understanding of the underlying neuropathology and the molecular and cellular basis of epilepsy and related cognitive and behavioral comorbidities, The mounting evidence obtained during the past decade has emphasized the critical role of inflammation in the pathophysiological processes implicated in a large spectrum of genetic and acquired forms of focal epilepsies. Dissecting the cellular and molecular mediators of the pathological immune responses and their convergent and divergent mechanisms, is a major requisite for delineating their role in the establishment of epileptogenic networks. The role of small regulatory molecules involved in the regulation of specific pro- and anti-inflammatory pathways and the crosstalk between neuroinflammation and oxidative stress will be addressed. The observations supporting the activation of both innate and adaptive immune responses in human focal epilepsy will be discussed and elaborated, highlighting specific inflammatory pathways as potential targets for antiepileptic, disease-modifying therapeutic strategies.

We continuously detect sensory data, like sights and sounds, and use this information to guide our behaviour. However, rather than relying on single sensory channels, which are noisy and can be ambiguous alone, we merge information across our senses and leverage this combined signal. In biological networks, this process (multisensory integration) is implemented by multimodal neurons which are often thought to receive the information accumulated by unimodal areas, and to fuse this across channels; an algorithm we term accumulate-then-fuse. However, it remains an open question how well this theory generalises beyond the classical tasks used to test multimodal integration. Here, we explore this by developing novel multimodal tasks and deploying probabilistic, artificial and spiking neural network models. Using these models we demonstrate that multimodal units are not necessary for accuracy or balancing speed/accuracy in classical multimodal tasks, but are critical in a novel set of tasks in which we comodulate signals across channels. We show that these comodulation tasks require multimodal units to implement an alternative fuse-then-accumulate algorithm, which excels in naturalistic settings and is optimal for a wide class of multimodal problems. Finally, we link our findings to experimental results at multiple levels; from single neurons to behaviour. Ultimately, our work suggests that multimodal neurons may fuse-then-accumulate evidence across channels, and provides novel tasks and models for exploring this in biological systems. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2023-10-25. Recording duration: 00:30:13.

With this webinar series, the ALBA Disability & Accessibility Working Group aims to bring down the ivory tower of ableism among the brain research community, one extraordinary neuroscientist at a time. These webinars give a platform to scientists with disabilities across the globe and neuroscience disciplines, while reflecting on how to promote inclusive working environments and accessibility to research. For this 3rd episode, Dr. Donna Rose Addis (Rotman Research Institute, Baycrest & University of Toronto, Canada) will talk about her research and experience.

Sleep and epilepsy are tightly interconnected: On the one hand disturbed sleep is known to negatively affect epilepsy, whereas on the other hand epilepsy negatively impacts sleep. In this talk, we leverage on the unique opportunity provided by simultaneous stereo-EEG and sleep recordings to disentangle these relationships. We will discuss latest evidence on if anatomy (temporal vs. extratemporal), time (early vs. late sleep), and type of epileptic activity (ictal vs. interictal) influence how epileptic activity is modulated by sleep. After this talk, attendees will have a more nuanced understanding of the contributions of location, time and type of epileptic activity in the relationship between sleep and epilepsy.

Much as Santiago Ramón y Cajal is the godfather of neuronal computation, which occurs among neurons that communicate predominantly via threshold logic, Camillo Golgi is the inadvertent godfather of neurovascular signaling, in which the endothelial cells that form the lumen of blood vessels communicate via electrodiffusion as well as threshold logic. I will address questions that define spatiotemporal patterns of constriction and dilation that develop across the network of cortical vasculature: First - is there a common topology and geometry of brain vasculature (our work)? Second - what mechanisms govern neuron-to-vessel and vessel-to-vessel signaling (work of Mark Nelson at U Vermont)? Last - what is the nature of competition among arteriole smooth muscle oscillators and the underlying neuronal drive (our work)? This answers to these questions bear on fundamental aspects of brain science as well as practical issues, including the relation of fMRI signals to neuronal activity and the impact of vascular dysfunction on cognition. Challenges and opportunities for experimentalists and theorists alike will be discussed. The organizer explicitly announced an exceptional 11:15 am ET start. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2023-10-11. Recording duration: 00:56:46.

Detecting the direction of image motion is important for visual navigation, predator avoidance and prey capture, and thus essential for the survival of all animals that have eyes. However, the direction of motion is not explicitly represented at the level of the photoreceptors: it rather needs to be computed by subsequent neural circuits, involving a comparison of the signals from neighboring photoreceptors over time. The exact nature of this process represents a classic example of neural computation and has been a longstanding question in the field. Much progress has been made in recent years in the fruit fly Drosophila melanogaster by genetically targeting individual neuron types to block, activate or record from them. Our results obtained this way demonstrate that the local direction of motion is computed in two parallel ON and OFF pathways. Within each pathway, a retinotopic array of four direction-selective T4 (ON) and T5 (OFF) cells represents the four Cartesian components of local motion vectors (leftward, rightward, upward, downward). Since none of the presynaptic neurons is directionally selective, direction selectivity first emerges within T4 and T5 cells. Our present research focuses on the cellular and biophysical mechanisms by which the direction of image motion is computed in these neurons.

The neurobiological mechanisms of arousal and anesthesia remain poorly understood. Recent evidence highlights the key role of interactions between the cerebral cortex and the diffusely projecting matrix thalamic nuclei. Here, we interrogate these processes in a whole-brain corticothalamic neural mass model endowed with targeted and diffusely projecting thalamocortical nuclei inferred from empirical data. This model captures key features seen in propofol anesthesia, including diminished network integration, lowered state diversity, impaired susceptibility to perturbation, and decreased corticocortical coherence. Collectively, these signatures reflect a suppression of information transfer across the cerebral cortex. We recover these signatures of conscious arousal by selectively stimulating the matrix thalamus, recapitulating empirical results in macaque, as well as wake-like information processing states that reflect the thalamic modulation of largescale cortical attractor dynamics. Our results highlight the role of matrix thalamocortical projections in shaping many features of complex cortical dynamics to facilitate the unique communication states supporting conscious awareness.