stroke

Circadian regulation of reperfusion efficacy in acute ischemic stroke

Reperfusion with thrombectomy has changed the clinical landscape for ischemic stroke. Recently, some studies suggest that patients with “large cores” may still benefit from reperfusion. Why? If these “cores” represent dead brain, why should reperfusion help? One logical explanation is that currently used neuroimaging “cores”, do not always identify uniformly dead tissue. Our pilot data suggest that these “cores” include tissue with a wide range of injury, indicated as changes in relative CT Hounsfield Units (rHU). Importantly, circadian mechanisms may be involved. Ischemic tissue with less severe changes in rHU tend to occur in the morning (active phase) when responses to reperfusion are better. In mouse models of stroke, ischemic injury is also less severe when strokes occur during the nighttime (active phase for nocturnal animals). In contrast, more severe ischemic injury during the daytime (inactive phase for mice) is accompanied by dampened vasodilation and CBF response along with increased immunothrombosis and neutrophil extracellular traps (NETosis). Is it possible that understanding these circadian mechanisms may help identify patients who respond best to reperfusion? And is it possible that targeting these circadian mechanisms can help convert non- responders into responders? In this multi-PI project, we use a translational approach (clinical neuroimaging and biomarkers in stroke patients, mouse models of stroke, CT-PET imaging of tissue viability, molecular pharmacology) with three integrated aims that can be pursued in parallel. Aim 1 will use neuroimaging in stroke patients to show that less severe rHU values in reperfusion-responsive “cores” tend to occur in the morning, whereas more severe rHU values in reperfusion-non-responsive “cores” occur later. Aim 2 will use clinical biomarkers to show that more severe rHU “cores” that are not reperfusion-responsive correlate with circadian effects on vasodilation and immunothrombosis. Aim 3 will use mouse stroke models to test whether targeting these circadian mechanisms of vasodilation and immunothrombosis can convert reperfusion-non-responders into reperfusion-responders. Patients cannot choose when they have a stroke. So why should we pay attention to circadian mechanisms? There may be 2 reasons that are addressed by the present project. First, thrombectomy is resource-intensive, and in spite of the very low number-needed-to-treat, only 20% of “large core” patients do well after reperfusion. Our studies may help identify who (when) these responders are. Second, the pathophysiologic mechanisms of cerebral ischemia differ depending on time-of-day. Therefore, understanding and then targeting these circadian mechanisms may allow us to convert reperfusion non-responders into responders.

Mechanisms and consequences of cerebrovascular dysfunction in preeclampsia

PROJECT SUMMARY/ABSTRACT Preeclampsia (PE) is a common hypertensive disorder of pregnancy that causes significant maternal and fetal morbidity and mortality worldwide. PE women are at a high risk of stroke, including intracerebral hemorrhage, during the peripartum period, suggesting the sequelae of PE adversely impacts the cerebral circulation to promote hemorrhage. In addition, women with severe early-onset PE are at an 85-fold increased risk of death from intracerebral hemorrhage, importantly suggesting severity of disease promotes greater vulnerability of the cerebral circulation to degradation and rupture. However, the consequences of PE extend far beyond pregnancy and are associated with excessive cardiovascular and cerebrovascular disease risk later in life. Women with previous pregnancy complicated by PE can develop cognitive impairment as early as in their 30’s and 40’s, suggesting PE predisposes the brain to early-onset cognitive impairment. Studies have shown that formerly PE women have changes in gray matter volume and increased white matter lesion burden that occurs as a function of time from pregnancy, suggesting that PE continues to progressively damage the brain long after the affected pregnancy. Thus, our overall goal is to elucidate mechanisms by which women with PE are at risk of intracerebral hemorrhage in pregnancy and cognitive decline later in life. Our preliminary studies found greater vascular degradation, hematoma and cerebral edema in a model of severe PE that was associated with vascular inflammation and microglia activation (neuroinflammation). In addition, we found endothelial dysfunction and diminished neurovascular coupling in PE rats that persisted 5 months postpartum. Impaired neurovascular coupling is well-recognized as an underlying contributor to cognitive decline. These effects in postpartum animals with previous exposure to PE were associated with memory impairment that was not present in the pregnant state, suggesting neurovascular dysfunction precedes cognitive decline. Our central hypothesis is that the sequela of PE accelerates hypertension-induced cerebrovascular dysfunction that predisposes to intracerebral hemorrhage during pregnancy and its persistence postpartum results in early-onset cognitive decline. We will therefore elucidate mechanisms by which PE accelerates vascular degradation and worsens outcome from hemorrhagic stroke, probing pathways involved in oxidative degradative processes using multi-omics and multivariate analysis (Aim 1). We will also determine underlying molecular mechanisms that cause persistent cerebral microvascular dysfunction and cognitive decline postpartum, including oxidative stress-induced BBB leakage and persistent neuroinflammation that drives potassium channel dysfunction, reduced neurovascular coupling and neurovascular uncoupling (Aim 2). We will also use machine learning approaches together with multi-omics and outcome measures to identify factors and cellular pathways that are most impactful for prediction of intracerebral hemorrhage and cognitive impairment. The ability to predict and prevent devasting neurovascular disorders associated with PE has the potential to have long-lasting impacts on the lives of women with PE.

Dosing and Deployment Trial: A Home-based Optokinetic Treatment for Ipsilesional Gaze Deviation

Stroke can have devastating consequences including ipsilesional gaze deviation (IGD), which directly impacts mobility and falls. IGD, a hallmark sign of spatial neglect (SN), is a major predictor of poor recovery and can persist after inpatient rehabilitation with targeted treatments. Our preliminary data show that more than half of stroke survivors who have SN at the time of admission to inpatient rehabilitation still have SN at time of discharge, even after treatment. Therefore, because of the challenges of the traditional rehabilitation paradigm we need to bring treatments into the home setting. We plan to examine the feasibility and deployment of Eyemove, an optokinetic stimulation treatment, which induces brain neural plasticity and improves spatial exploration, in turn reducing SN symptoms, including IGD. We hypothesize that by treating IGD, improvements in mobility and fall risk scores will occur, as participants can now interact with the space that was previously “neglected”. Here, we propose to test the following aims with 50 community-dwelling individuals with SN, by identifying the practical dosage associated with mobility improvement: Aim 1 will determine feasibility and acceptability of home deployment of Eyemove. We will collect qualitative information from stroke survivors and their care partners, to determine their pre-treatment and post-treatment perspectives of this home treatment. Aim 2 will determine whether Eyemove in the home is associated with improved mobility-related outcomes (including risk of falls) and to evaluate sufficient dosing. We will randomize participants into either 3 or 5 sessions of a 40-minute treatment given over a week-long intervention period. The primary outcome will be the Mobility Assessment Course and secondary outcomes will be the Stroke Assessment of Fall Risk and the Life Space Assessment. For Aim 1, we expect to learn practical suggestions for home implementation and obtain reports of post-experience enthusiasm and acceptability for specific aspects of the intervention. Our hypotheses for Aim 2 are: 1a-- After controlling for pre-treatment score changes (T2-T1), the intervention (T3) will lead to improved mobility/ fall risk compared to baseline (T1), regardless of treatment group; 1b-- The amount of mobility/ fall risk improvement (T3-T1) in the 3- session and 5-session groups will be different. The expected findings will provide critical insight into the use of Eyemove for spatial neglect remediation. Results from this research will be used to develop a subsequent R01 proposal that uses pragmatic, randomized clinical trial methods to determine the efficacy of Eyemove, in order to provide an effective, accessible treatment to remediate SN at home and improve individuals’ ability to move without spatial bias or risk of falls.

Adventures in Spin Labeling: Clinical Perfusion Imaging and the Path to Technical Innovation

Arterial spin labeling (ASL) MRI has become a vital tool in clinical neuroimaging, enabling noninvasive assessment of cerebral perfusion across a range of conditions including stroke, vascular malformations, and brain tumors. With broader clinical adoption, its practical strengths — as well as important limitations — have become increasingly clear.

Functional Plasticity in the Language Network – evidence from Neuroimaging and Neurostimulation

Efficient cognition requires flexible interactions between distributed neural networks in the human brain. These networks adapt to challenges by flexibly recruiting different regions and connections. In this talk, I will discuss how we study functional network plasticity and reorganization with combined neurostimulation and neuroimaging across the adult life span. I will argue that short-term plasticity enables flexible adaptation to challenges, via functional reorganization. My key hypothesis is that disruption of higher-level cognitive functions such as language can be compensated for by the recruitment of domain-general networks in our brain. Examples from healthy young brains illustrate how neurostimulation can be used to temporarily interfere with efficient processing, probing short-term network plasticity at the systems level. Examples from people with dyslexia help to better understand network disorders in the language domain and outline the potential of facilitatory neurostimulation for treatment. I will also discuss examples from aging brains where plasticity helps to compensate for loss of function. Finally, examples from lesioned brains after stroke provide insight into the brain’s potential for long-term reorganization and recovery of function. Collectively, these results challenge the view of a modular organization of the human brain and argue for a flexible redistribution of function via systems plasticity.

Virtual Brain Twins for Brain Medicine and Epilepsy

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.

Stroke : Brain networks and behavior

Movement planning as a window into hierarchical motor control

The ability to organise one's body for action without having to think about it is taken for granted, whether it is handwriting, typing on a smartphone or computer keyboard, tying a shoelace or playing the piano. When compromised, e.g. in stroke, neurodegenerative and developmental disorders, the individuals’ study, work and day-to-day living are impacted with high societal costs. Until recently, indirect methods such as invasive recordings in animal models, computer simulations, and behavioural markers during sequence execution have been used to study covert motor sequence planning in humans. In this talk, I will demonstrate how multivariate pattern analyses of non-invasive neurophysiological recordings (MEG/EEG), fMRI, and muscular recordings, combined with a new behavioural paradigm, can help us investigate the structure and dynamics of motor sequence control before and after movement execution. Across paradigms, participants learned to retrieve and produce sequences of finger presses from long-term memory. Our findings suggest that sequence planning involves parallel pre-ordering of serial elements of the upcoming sequence, rather than a preparation of a serial trajectory of activation states. Additionally, we observed that the human neocortex automatically reorganizes the order and timing of well-trained movement sequences retrieved from memory into lower and higher-level representations on a trial-by-trial basis. This echoes behavioural transfer across task contexts and flexibility in the final hundreds of milliseconds before movement execution. These findings strongly support a hierarchical and dynamic model of skilled sequence control across the peri-movement phase, which may have implications for clinical interventions.

Sampling the environment with body-brain rhythms

Since Darwin, comparative research has shown that most animals share basic timing capacities, such as the ability to process temporal regularities and produce rhythmic behaviors. What seems to be more exclusive, however, are the capacities to generate temporal predictions and to display anticipatory behavior at salient time points. These abilities are associated with subcortical structures like basal ganglia (BG) and cerebellum (CE), which are more developed in humans as compared to nonhuman animals. In the first research line, we investigated the basic capacities to extract temporal regularities from the acoustic environment and produce temporal predictions. We did so by adopting a comparative and translational approach, thus making use of a unique EEG dataset including 2 macaque monkeys, 20 healthy young, 11 healthy old participants and 22 stroke patients, 11 with focal lesions in the BG and 11 in the CE. In the second research line, we holistically explore the functional relevance of body-brain physiological interactions in human behavior. Thus, a series of planned studies investigate the functional mechanisms by which body signals (e.g., respiratory and cardiac rhythms) interact with and modulate neurocognitive functions from rest and sleep states to action and perception. This project supports the effort towards individual profiling: are individuals’ timing capacities (e.g., rhythm perception and production), and general behavior (e.g., individual walking and speaking rates) influenced / shaped by body-brain interactions?

Remembering immunity: Neuronal representation of immune responses

Accumulating data indicate that the brain can affect immunity, as evidenced, for example, by the effects of stress, stroke, and reward system activity on the peripheral immune system. However, our understanding of this neuroimmune interaction is still limited. Importantly, we do not know how the brain evaluates and represents the state of the immune system. In this talk, I will present our latest study from our lab, designed to test the existence of immune-related information in the brain and determine its relevance to immune regulation. We hypothesized that the InsCtx, specifically the posterior InsCtx (as a primary cortical site of interoception in the brain), is especially suited to contain such a representation of the immune system. Using activity-dependent cell labeling in mice (FosTRAP), we captured neuronal ensembles in the InsCtx that were active under two different inflammatory conditions (dextran sulfate sodium [DSS]-induced colitis and zymosan-induced peritonitis). Chemogenetic reactivation of these neuronal ensembles was sufficient to broadly retrieve the inflammatory state under which these neurons were captured. Moreover, using retrograde neuronal tracing, we found an anatomical efferent pathway linking these InsCtx neurons to the inflamed peripheral sites. Taken together, we show that the brain can store and retrieve specific immune responses, extending the classical concept of immunological memory to neuronal representations of inflammatory information.

The Brain Conference (the Guarantors of Brain)

Join the Brain Conference on 24-25 February 2022 for the opportunity to hear from neurology’s leading scientists and clinicians. The two-day virtual programme features clinical teaching talks and research presentations from expert speakers including neuroscientist Professor Gina Poe, and the winner of the 2021 Brain Prize, neurologist Professor Peter Goadsby." "Tickets for The Brain Conference 2022 cost just £30, but register with promotional code BRAINCONEM20 for a discounted rate of £25.

The Brain Conference (the Guarantors of Brain)

Join the Brain Conference on 24-25 February 2022 for the opportunity to hear from neurology’s leading scientists and clinicians. The two-day virtual programme features clinical teaching talks and research presentations from expert speakers including neuroscientist Professor Gina Poe, and the winner of the 2021 Brain Prize, neurologist Professor Peter Goadsby." "Tickets for The Brain Conference 2022 cost just £30, but register with promotional code BRAINCONEM20 for a discounted rate of £25.

Epilepsy Genetics – From Family Studies to Polygenic Risk Scores

Whilst epilepsy may be a consequence of an acquired insult including trauma, stroke, and brain tumours, the genetic component to epilepsies has been greatly under-estimated. Considerable progress has recently occurred in the understanding of epilepsy genetics, both at a clinical genetic level and in the basic science of epilepsies. The clinical evidence for genetic components will be first briefly discussed including data from population studies, twin analyses and multiplex family studies. Initial molecular discoveries occurred via classical methods of linkage and gene identification. Recent large-scale hypothesis-free whole exome studies searching for rare variants and genome-wide association studies detecting common variants have been very rewarding. These discoveries have now impacted on clinical practice, especially in severe childhood epilepsies but increasingly so in adult patients. The “genetic background” of patients has long been posited as part of the reason that some patients have epilepsy, or perhaps why some have more severe epilepsy. This has been unmeasurable but now, with the development of polygenic risk scores, the “background” is now in the research foreground. The current and future impact of polygenic risk scores will be explored.

Identification and treatment of advanced, rupture-prone plaques to reduce cardiovascular mortality

Atherosclerosis is the underlying cause of major cardiovascular events, including heart attack and stroke. The build-up of plaque in coronary arteries can be a major risk for events, but risk is significantly higher in patients with vulnerable rather than stable plaque. Diagnostic imaging of vulnerable plaque is extremely useful for both stratifying patient risk and for determining effectiveness of experimental intervention in reducing cardiovascular risk. In the preclinical setting, being able to distinguish between stable and vulnerable plaque development and pair this with biochemical measures is critical for identification of new experimental candidates. In this webinar, Professor Stephen Nicholls and Dr Kristen Bubb from the Victorian Heart Institute will discuss the benefits of being able to visualise vulnerable plaque for both clinical and preclinical research. Professor Stephen Nicholls is a clinician-researcher and the Head of the Victorian Heart Institute. He is the lead investigator on multiple large, international, cardiovascular outcomes trials. He has attracted over $100 million in direct research funding and published more than 400 peer-reviewed manuscripts. He is focused on both therapeutic intervention to reduce vascular inflammation and lipid accumulation and precision medicine approaches to prevent cardiovascular mortality. Dr Kristen Bubb is a biomedical researcher and Group Leader within the Monash Biomedicine Discovery Institute Cardiovascular Program and Victorian Heart Institute. She focuses on preclinical/translational research into mechanisms underlying vascular pathologies including atherosclerosis and endothelium-driven hypertension within specific vascular systems, including pulmonary and pregnancy-induced. She has published >30 high impact papers in leading cardiovascular journals and attracted category 1&2 funding of >$750,000.

Neural Population Dynamics for Skilled Motor Control

The ability to reach, grasp, and manipulate objects is a remarkable expression of motor skill, and the loss of this ability in injury, stroke, or disease can be devastating. These behaviors are controlled by the coordinated activity of tens of millions of neurons distributed across many CNS regions, including the primary motor cortex. While many studies have characterized the activity of single cortical neurons during reaching, the principles governing the dynamics of large, distributed neural populations remain largely unknown. Recent work in primates has suggested that during the execution of reaching, motor cortex may autonomously generate the neural pattern controlling the movement, much like the spinal central pattern generator for locomotion. In this seminar, I will describe recent work that tests this hypothesis using large-scale neural recording, high-resolution behavioral measurements, dynamical systems approaches to data analysis, and optogenetic perturbations in mice. We find, by contrast, that motor cortex requires strong, continuous, and time-varying thalamic input to generate the neural pattern driving reaching. In a second line of work, we demonstrate that the cortico-cerebellar loop is not critical for driving the arm towards the target, but instead fine-tunes movement parameters to enable precise and accurate behavior. Finally, I will describe my future plans to apply these experimental and analytical approaches to the adaptive control of locomotion in complex environments.

From Vulnerable Plaque to Vulnerable Brain: Understanding the Role of Inflammation in Vascular Health, Stroke, and Cerebrovascular Disease

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.

Understanding the Assessment of Spatial Neglect and its Treatment Using Prism Adaptation Training

Spatial neglect is a syndrome that is most frequently associated with damage to the right hemisphere, although damage to the left hemisphere can also result in signs of spatial neglect. It is characterised by absent or deficient awareness of the contralesional side of space. The screening and diagnosis of spatial neglect lacks a universal gold standard, but is usually achieved by using various modes of assessment. Spatial neglect is also difficult to treat, although prism adaptation training (PAT) has in the past reportedly showed some promise. This seminar will include highlights from a series of studies designed to identify knowledge gaps, and will suggest ways in which these can be bridged. The first study was conducted to identify and quantify clinicians’ use of assessment tools for spatial neglect, finding that several different tools are in use, but that there is an emerging consensus and appetite for harmonisation. The second study included PAT, and sought to uncover whether PAT can improve engagement in recommended therapy in order to improve the outcomes of stroke survivors with spatial neglect. The final study, a systematic review and meta-analysis, sought to investigate the scientific efficacy (rather than clinical effectiveness) of PAT, identifying several knowledge gaps in the existing literature and a need for a new approach in the study of PAT in the clinical setting.

Brain-Machine Interfaces: Beyond Decoding

A brain-machine interface (BMI) is a system that enables users to interact with computers and robots through the voluntary modulation of their brain activity. Such a BMI is particularly relevant as an aid for patients with severe neuromuscular disabilities, although it also opens up new possibilities in human-machine interaction for able-bodied people. Real-time signal processing and decoding of brain signals are certainly at the heart of a BMI. Yet, this does not suffice for subjects to operate a brain-controlled device. In the first part of my talk I will review some of our recent studies, most involving participants with severe motor disabilities, that illustrate additional principles of a reliable BMI that enable users to operate different devices. In particular, I will show how an exclusive focus on machine learning is not necessarily the solution as it may not promote subject learning. This highlights the need for a comprehensive mutual learning methodology that foster learning at the three critical levels of the machine, subject and application. To further illustrate that BMI is more than just decoding, I will discuss how to enhance subject learning and BMI performance through appropriate feedback modalities. Finally, I will show how these principles translate to motor rehabilitation, where in a controlled trial chronic stroke patients achieved a significant functional recovery after the intervention, which was retained 6-12 months after the end of therapy.

Effects of Vagus Nerve Stimulation on Arousal State and Cortical Excitation

The vagus nerve is a major pathway by which the brain and the body communicate. Electrical stimulation of the vagus nerve (VNS) is widely used as a therapeutic intervention for epilepsy and there is compelling evidence that it can enhance recovery following stroke. Our work demonstrates that VNS exerts a robust excitatory effect on the brain. First, we establish that VNS triggers an increase in arousal state as measured by behavioral state change. This behavioral state change is linked to an increase in excitatory activity within the cortex. We also show that cholinergic and noradrenergic neuromodulatory pathways are activated by VNS, providing a potential mechanism by which VNS may trigger cortical activation. Importantly, the effect of VNS on neuromodulation and cortical excitation persists in anesthetized mice, demonstrating that VNS-induced cortical activation cannot be fully explained by associated behavioral changes.

Regenerative Neuroimmunology - a stem cell perspective

There are currently no approved therapies to slow down the accumulation of neurological disability that occurs independently of relapses in multiple sclerosis (MS). International agencies are engaging to expedite the development of novel strategies capable of modifying disease progression, abrogating persistent CNS inflammation, and support degenerating axons in people with progressive MS. Understanding why regeneration fails in the progressive MS brain and developing new regenerative approaches is a key priority for the Pluchino Lab. In particular, we aim to elucidate how the immune system, in particular its cells called myeloid cells, affects brain structure and function under normal healthy conditions and in disease. Our objective is to find how myeloid cells communicate with the central nervous system and affect tissue healing and functional recovery by stimulating mechanisms of brain plasticity mechanisms such as the generation of new nerve cells and the reduction of scar formation. Applying combination of state-of-the-art omic technologies, and molecular approaches to study murine and human disease models of inflammation and neurodegeneration, we aim to develop experimental molecular medicines, including those with stem cells and gene therapy vectors, which slow down the accumulation of irreversible disabilities and improve functional recovery after progressive multiple sclerosis, stroke and traumatic injuries. By understanding the mechanisms of intercellular (neuro-immune) signalling, diseases of the brain and spinal cord may be treated more effectively, and significant neuroprotection may be achieved with new tailored molecular therapeutics.

Portable neuroscience: using devices and apps for diagnosis and treatment of neurological disease

Scientists work in laboratories; comfortable spaces which we equip and configure to be ideal for our needs. The scientific paradigm has been adopted by clinicians, who run diagnostic tests and treatments in fully equipped hospital facilities. Yet advances in technology mean that that increasingly many functions of a laboratory can be compressed into miniature devices, or even into a smartphone app. This has the potential to be transformative for healthcare in developing nations, allowing complex tests and interventions to be made available in every village. In this talk, I will give two examples of this approach from my recent work. In the field of stroke rehabilitation, I will present basic research which we have conducted in animals over the last decade. This reveals new ways to intervene and strengthen surviving pathways, which can be deployed in cheap electronic devices to enhance functional recovery. In degenerative disease, we have used Bayesian statistical methods to improve an algorithm to measure how rapidly a subject can stop an action. We then implemented this on a portable device and on a smartphone app. The measurement obtained can act as a useful screen for Parkinson’s Disease. I conclude with an outlook for the future of this approach, and an invitation to those who would be interesting in collaborating in rolling it out to in African settings.

Brain Awareness Week @ IITGN

Using Systems Neuroscience Approaches to Understand Motor Learning & Recovery Post-Stroke

Conscious access on the left in right parietal stroke

Phospholipid regulation in cognitive impairment and vascular dementia

An imbalance in lipid metabolism in neurodegeneration is still poorly understood. Phospholipids (PLs) have multifactorial participation in vascular dementia as Alzheimer, post-stroke dementia, CADASIL between others. Which include the hyperactivation of phospholipases, mitochondrial stress, peroxisomal dysfunction and irregular fatty acid composition triggering proinflammation in a very early stage of cognitive impairment. The reestablishment of physiological conditions of cholesterol, sphingolipids, phospholipids and others are an interesting therapeutic target to reduce the progression of AD. We propose the positive effect of BACE1 silencing produces a balance of phospholipid profile in desaturase enzymes-depending mode to reduce the inflammation response, and recover the cognitive function in an Alzheimer´s animal and brain stroke models. Pointing out there is a great need for new well-designed research focused in preventing phospholipids imbalance, and their consequent energy metabolism impairment, pro-inflammation and enzymatic over-processing, which would help to prevent unhealthy aging and AD progression.

Affordable Robots/Computer Systems to Identify, Assess, and Treat Impairment After Brain Injury

Non-traumatic brain injury due to stroke, cerebral palsy and HIV often result in serious long-term disability worldwide, affecting more than 150 million persons globally; with the majority of persons living in low and middle income countries. These diseases often result in varying levels of motor and cognitive impairment due to brain injury which then affects the person’s ability to complete activities of daily living and fully participate in society. Increasingly advanced technologies are being used to support identification, diagnosis, assessment, and therapy for patients with brain injury. Specifically, robot and mechatronic systems can provide patients, physicians and rehabilitation clinical providers with additional support to care for and improve the quality of life of children and adults with motor and cognitive impairment. This talk will provide a brief introduction to the area of rehabilitation robotics and, via case studies, illustrate how computer/technology-assisted rehabilitation systems can be developed and used to assess motor and cognitive impairment, detect early evidence of functional impairment, and augment therapy in high and low-resource settings.

Electrophysiology application for optic nerve and the central nervous system diseases

Electrophysiology of eye and visual pathway is useful tool in ophthalmology and neurology. It covers a few examinations to find out if defect of vision is peripheral or central. Visual evoked potentials (VEP) are most frequently used in neurology and neuroophthalmology. VEP are evoked by flash or pattern stimulations. The combination of these both examinations gives more information about the visual pathway. It is very important to remember that VEP originate in the retina and reflect its function as well. In many cases not only VEP but also electroretinography (ERG) is essential for diagnosis. The seminar presents basic electrophysiological procedures used for diagnosis and follow-up of optic neuropathies and some of central nervous system diseases which affect vision (mostly multiple sclerosis, CNS tumors, stroke, traumas, intracranial hypertension).

Neuroscience Investigations in the Virgin Lands of African Biodiversity

Africa is blessed with a rich diversity and abundance in rodent and avian populations. This natural endowment on the continent portends research opportunities to study unique anatomical profiles and investigate animal models that may confer better neural architecture to study neurodegenerative diseases, adult neurogenesis, stroke and stem cell therapies. To this end, African researchers are beginning to pay closer attention to some of her indigenous rodents and birds in an attempt to develop spontaneous laboratory models for homegrown neuroscience-based research. For this presentation, I will be showing studies in our lab, involving cellular neuroanatomy of two rodents, the African giant rat (AGR) and Greater cane rat (GCR), Eidolon Bats (EB) and also the Striped Owl (SO). Using histological stains (Cresyl violet and Rapid Golgi) and immunohistochemical biomarkers (GFAP, NeuN, CNPase, Iba-1, Collagen 2, Doublecortin, Ki67, Calbindin, etc), and Electron Microscopy, morphology and functional organizations of neuronal and glial populations of the AGR , GCR, EB and SO brains have been described, with our work ongoing. In addition, the developmental profiles of the prenatal GCR brains have been chronicled across its entire gestational period. Brains of embryos/foetuses were harvested for gross morphological descriptions and then processed using immunofluorescence biomarkers to determine the pattern, onset, duration and peak of neurogenesis (Pax6, Tbr1, Tbr2, NF, HuCD, MAP2) and the onset and peak of glial cell expressions and myelination in the prenatal GCR. The outcome of these research efforts has shown unique neuroanatomical expressions and networks amongst Africa’s rich biodiversity. It is hopeful that continuous effort in this regard will provide sufficient basic research data on neural developments and cellular neuroanatomy with subsequent translational consequences.

Astrocytic secretion of autotaxin dictates stroke outcome

Brain natriuretic peptide expression in acute ischaemic stroke clots is not associated with stroke aetiology, but heightened S100b expression is associated with post-thrombectomy intracranial haemorrhage

Brain Tissue Pulsations (BTPs) in Acute Stroke using Transcranial Tissue Doppler Technique (TCTD)

Challenging the role of the thalamus in cognition: the neuropsychological impact of chronic thalamic stroke

Cognitive phenotypes after left and right hemispheric stroke: a latent class analysis

The common descending neural drive to agonist and antagonist muscles is higher in stroke patients compared to controls

Contextual memory decline in a combined mouse model for ischemic stroke and Alzheimer's disease

Deep Learning Based Personalized Outcome Prediction after Acute Ischemic Stroke

Discovering new therapeutic strategies in stroke through APC/C-Cdh1-ROCK2 signalling pathway

Disrupted functional connectivity is associated with reduced reward sensitivity and learning deficits after stroke

The effect of minocycline on the ischemic area and improved motor function in cortical model of photo thrombotic ischemic stroke in rats

Effects of uroguanylin's signalling pathway on ischemic stroke

Evaluation of p53 expression and interaction with HDAC2 in the acute period after photothrombotic stroke in rats

Functional recovery caused by human adipose tissue mesenchymal stem cell-derived extracellular vesicles administered 24h after stroke in normotensive rats and some differences to hypertensive rats

Functional reorganization of the peri-infarct cortex promoting recovery of skilled motor functions after stroke

The heterogeneity of astrocytes in stroke: spatially resolved gene expression reveals the dynamics of astrocytes over time and their interactions with neighboring cells

Imaging increased metabolism in the spinal cord in a mouse model of ischemic stroke

Impact of visuospatial attention on motor control and hand function after stroke

Impaired reward processing in chronic stroke survivors

Impulsive behavior assessment in a preclinical model of stroke

Integrity of motor pathway and acute deficit contribute to post-stroke spontaneous recovery in mice

Intermittent hypoxia promotes post-stroke recovery in rodent striatum through neurogenesis

Intra-arterial mesenchymal stem cell therapy regulates Aquaporin 4 to alleviate perifocal vasogenic edema post-stroke in animal model of ischemic stroke

Introducing structural disconnection masks in whole-brain models: A mechanistic explanation of stroke patients’ effective connectivity

Investigating the electrical stimulation of subthalamic nucleus for the treatment of cortical stroke

Lesion-network mapping for post-stroke prediction of motor and action speed deficits

Microglial phagocytosis dysfunction during stroke is partially prevented by rapamycin

Mouse Reach: Automated Behavioral Readouts in Motor Recovery after Stroke

Multiparametric Evaluation of Functional Outcomes in Stroke Patients Using Connectomics

Neuroinflammatory Modulation of Pomalidomide and Its Analogs 3,6 & 1,6 Dithiopomalidomide through Pyroptosis and Ferroptosis after Stroke

Ongoing clinical, electrophysiological and biophysical evidence of high-density fronto-cerebellar transcranial direct current stimulation in motor stroke

Optimise dosage and effect size in virtual reality-based intervention for post-stroke survivors with coexistence of language and motor dysfunctions

Study on the efficacy and mechanism of ginsenoside in the prevention of cerebral ischemic stroke

FENS Forum 2024

Studying acute ischemic stroke (AIS) clots for novel stroke biomarker discovery

FENS Forum 2024

Plasma levels of BDNF and EGF are reduced in acute stroke patients compared to healthy age and gender matched controls

Please don't stop the music: Auditory spatial cueing reduces neglect after right-hemispheric stroke - a proof of concept study

Potential targeting of stroke by means of layered nano- and micro- particles

Proprioceptive deficits and visual compensation in stroke patients: a theoretical approach to reinterpret upper-limb sensory assessments

Protective effect of synthetic macamide against morphological and neurological deficit induced by focal brain ischemic stroke injury

Towards predicting Stroke Etiology from MRI and CT Imaging Data of Ischemic Stroke Patients

Bernstein Conference 2024