Day 1 :
RehabMed South, USA
Keynote: Value of evoke functional electroencephalography in diagnosis and management of mild to moderate brain injury: case series of 150 professional football players with multiple concussions
Time : 10:00-10:40
Introduction: A history of multiple sports-related concussions has been associated with impairment ranging from a mild dementia to Alzheimer’s disease to chronic traumatic encephalopathy. Quantifying such impairment is important to identifying and management.
Method: One hundred fifty retired professional American Football players with cognitive and memory loss was comprehensively evaluated including: comprehensive neuro-musculoskeletal examinations, brain MRI (concussion protocol), formal cognitive testing, and functional electroencephalography (Evoke NeuroScience).
Results: Males, ages 32 to 65 years, with professional football careers ranging from 1 to 18 years. All were ambulatory. 75% were currently employed. Physical exams included ataxia of speech and gait, word finding impairments, nystagmus, pendular reflexes, and abnormal affect. Neurocognitive testing revealed impairments from mild to marked in up to five cognitive domains. MRI (concussion protocol) revealed positive findings in 34%. Functional EEG findings included delayed P300a and P300b, slowed response times to visual and cognitive stimuli, low frontal EEG power, reduced neuronal capacity in regions associated with cognition and working memory, abnormal theta/beta ratios, abnormalities in visual, auditory processing, information processing and working memory. Abnormal midline FZ-CZ-PZ gradients and alterations in heart rate variability.
Conclusions: The physical-neurological exam provides objective findings, but is subtile. Brain MRI is abnormal in only 35%. Neurocognitive testing identified abnormalities in all cases. The functional EEG is objective, without evaluator bias. It adds confirmatory objective electrophysiological findings that correlate tightly with formal neurocognitive impairments, and correlates tightly with subjective symptoms. Additionally, identified specific abnormal physiological alterations can provide scientific clinical rationale for targeted treatment regimen, including neurofeedback.
Location: Gate 2
Time : 11:05 -11:50
Kim Baden Kristensen is the CEO and Co-founder of Brain+, which specializes in digital therapeutics for brain rehabilitation and remediation, specifically for the recovery of impaired cognitive functions due to injury or disease. Its award winning Brain+ apps are being clinically tested in Parkinson’s disease, major depressive disorder and traumatic brain injury patients, and is being used by Danish national team athletes to enhance cognitive performance. Brain+ is also working on pre-symptomatic detection of Alzheimer’s disease in collaboration with leading European universities, providers, and patient organizations
As our knowledge of brain disorders evolves, with new studies shedding new light on the underlying mechanisms and as new technologies become available that offer new means of measuring and collecting data, we need to evolve the way we measure, quantify, test brain disorders and the way we design and use health outcome measures, both in clinical practice and in scientific studies. In this workshop we will cover, discuss and analyze topics such as; patient reported outcomes, use of real world data and evidence, psychometric measures and tests, cognitive measures and tests, behavioral measures and tests, and more. The aim of the workshop is to share knowledge and map the possible future evolution of health outcome measures related to brain disorders.
- Ananlysis, Assessment and Diagnosis of Disorders, Cognition and Behaviour | Neurochemistry and Neuropharmacology
Location: Gate 2
John L Merritt
RehabMed South, USA
Carol Davila University of Medicine and Pharmacy, Romania
Title: Blowing resistance to pharmacotherapy by modulating the permeability of the blood-brain barrier – patho-physiological perspectives
Time : 11:50-12:20
Cristina Manuela Dragoi and Alina Crenguta Nicolae are associate professors at the Department of Biochemistry, Faculty of Pharmacy, University of Medicine and Farmacy “Carol Davila”, Bucharest, Romania. Their research in the field of biochemical mechanisms involved in multidrug resistance, and the passion and interest in investigating blood-brain-barrier pharmaco-therapeutical frontiers have remained as central pillars of their scientific activity. So far, the scientific research in this area is supported by over 40 articles published in ISI journals, 2 books and 5 book chapters published internationally. In addition, the research undertaken over these years has been appreciated by winning several awards
The efficiency of the central nervous system disorders pharmacotherapy is a major challenge, mainly due to the impossibility of many drugs to cross the blood-brain barrier (BBB) and reach sufficiently high concentrations in certain target areas in the brain. The BBB possesses an outstanding ability to protect the brain against xenobiotics and potentially poisonous metabolites. Owing to this, ATP binding cassette (ABC) export proteins have gained tremendous interest in research. Of these efflux transporters of the blood-brain barrier, the most studied in terms of the mechanisms of action and regulatory effects, is the P-glycoprotein (Pgp, ABCB1), which modulates the transport of a large number of therapeutic substances and is predominantly expressed in the cerebral capillary endothelium. The action on the cerebral tissue and the beneficial effects of drugs or xenobiotics are dependent on their ability to cross the blood-brain barrier. ABC transporters represent an integral part of the human transportome and are of particular interest at the BBB as they significantly contribute to brain homeostasis. In addition, they appear to be involved in many CNS diseases. Therefore studying their mechanisms of action as well as their signaling cascades and responses to internal and external stimuli will help us understand the pathogenesis of these diseases. Signaling cascades underlying the expression and function of these proteins will be discussed as well as their role in diseases such as Alzheimer’s disease, epilepsy, amyotrophic lateral sclerosis and brain tumors.
Neuroscientist, USA and Canadian University of Dubai, UAE
Title: Personal experiences as a neuroscientist recovering from a coma and recent generalized tonic–clonic seizure
Time : 12:20-12:50
Justin James Kennedy, “The Brain Coach” is a globally recognized Professor of Neuroscience, Executive Coach and Leadership Specialist. With over 20 years of C-Suite executive coaching experience globally in the USA, UK and South Africa, he translates his neuroscience research into practical business skills. His specialties include: coaching on performance leadership to deliver measurable business results; coaching on the business vision, brain management and corporate strategy; advising professionals on how to optimize systemic change and; improving executive brain functions to enhance mental focus, self and team performance. His first book "Brain Triggers" is co-authored by the world’s #1 coach, Dr. Marshall Goldsmith. He has also published innumerable corporate studies that demonstrate how to improve and sustain executive performance. In 2014, he delivered a TED talk on practical ways to control their brain to perform at peak and even increase IQ and memory.
We do know that the more severe the injury the less likely the person will fully recover. The length of time a person remains in a coma and duration of loss of memory (amnesia) following the coma are useful in predicting how one will recover. The Rancho Los Amigos Levels of Cognitive Functioning (RLCF) is one of the best and most widely used ways of describing recovery from brain injury. It describes ten levels of cognitive (thinking) recovery. Research has shown that the speed at which a person progresses through the levels of the RLCF can predict how fully a person will recover. Recently Dr. Kennedy had generalized tonic–clonic seizure (also known as a grand mal seizure) is a type of generalized seizure that affects the entire brain seizure/epileptic fit. He explains his personal traumatic neurological experiences in detail during this presentation.
- Young Researchers Forum
Location: Gate 2
Donders Institute for Brain, Cognition and Behaviour - Radboud University Medical Centre, Netherlands
Title: Association of contextual cues with morphine reward changes neural and synaptic plasticity in the ventral hippocampus of rats
Time : 13:50-14:15
Mina Sadighi Alvandi is a PhD candidate at the Radboud University, Nijmegen. Her research interest is in drug addiction. Through the use of behavioral, molecular and electrophysiological methods she studies the effects of the drug morphine on neural plasticity and neural activity of the hippocampus. She also has experience in electroencephalography from rats with absence epilepsy. She published more than 10 papers in the field of Neuroscience.
Drug addiction is associated with aberrant memory and permanent functional and structural changes in neural circuits. It is known that exposure to drugs like morphine is associated with positive emotional states and reward-related memory. In animal models conditioned place preference (CPP) paradigm is a behavioral model used to study the rewarding and aversive effects of drugs. By associating the rewarding effects of drugs with contextual information, this paradigm allows the assessment of drug-related emotional memories. Adult neurogenesis, the generation of neuronal precursors, is restricted to a very limited set of brain regions including subventricular zone (SVZ) of the lateral ventricle wall and subgranular lining of the hippocampal dentate gyrus. Dendritic spines have been considered as essential components for neuronal connectivity and synaptic plasticity. Neurogenesis and spinogenesis participate in hippocampal functions like learning and memory. However, the underlying mechanisms in terms of neural plasticity in the ventral hippocampus, a region involved in associative memory and emotional behaviors, are not fully understood. Therefore, we measured adult neurogenesis, dendritic spine density and brain-derived neurotrophic factor (BDNF) and TrkB mRNA expression as parameters for synaptic plasticity in the ventral hippocampus. Male Sprague Dawley rats were subjected to the CPP paradigm and received 10 mg/kg morphine. The rats were used to evaluate neurogenesis by immunohistochemical markers Ki67 and doublecortin (DCX). Golgi staining was done to measure spine density and real-time quantitative reverse transcription-polymerase chain reaction to assess BDNF/TrkB expression levels. We found that morphine-treated rats exhibited more place conditioning as compared with saline-treated rats and animals that were exposed to the CPP without any injections. Morphine induced CPP significantly increased the number of Ki67 and DCX-labeled cells in the ventral dentate gyrus. Additionally, we found increased dendritic spine density in both CA1 and dentate gyrus and an enhancement of BDNF/TrkB mRNA levels in the whole ventral hippocampus. In conclusion, we show that morphine-induced reward-related memory is associated with neural and synaptic plasticity changes in the ventral hippocampus. Such neural changes could underlie context-induced drug relapse.
Vavilov Institute of General Genetics, Russian Academy of Sciences, Russia
Title: Analysis of amyloid properties of the STXBP1 protein forming detergent-resistant aggregates in the brain of rat Rattus norvegicus
Time : 14:15-14:40
Vera Siniukova has received her Bachelor's degree from the Tomsk State University; Master's degree from the Saint Petersburg State University and now is a PhD student at the Vavilov Institute of General Genetics. She is an active member of all kinds of scientific activities, always has been among the top 5% students of the class in terms of academic achievements and has published several papers. Currently, she is also a Manager of the scientific project supported by Russian Foundation for Basic Research (RFBR).
Amyloids are the fibrillar protein aggregates with cross-β structure. Traditionally amyloids were associated exclusively with pathology: incurable diseases in animals and humans such as Alzheimer’s disease and Parkinson’s disease. However, nowadays more data is emerging about functional amyloids which are not linked with diseases but play essential roles in cellular processes. Until recently there were no universal methods for large-scale proteomic screening for amyloids. A new universal proteomic approach which may enable identification of a broad range of amyloid-forming proteins (PSIA LC-MALDI) was created in our laboratory. Using this method, we identified proteins which were candidates for the role of functional amyloids in young male rat’s brain. One of the identified proteins was STXBP1 (syntaxin-binding protein 1). This protein is synthesized in brain and takes part in vesicular transport and neurotransmitter secretion. It’s been shown that some mutations in this protein cause early infantile epileptic encephalopathy (EIEE), or Ohtahara syndrome, which is one of the most severe forms of age-related epileptic encephalopathies. Bioinformatical algorithm ArchCandy predicted 3 potentially amyloidogenic regions in C-terminal part of the STXBP1 protein. We checked the presence of amyloid aggregates of STXBP1 in rat’s brain using semi-denaturating detergent agarose gel electrophoresis (SDD-AGE) and protein fractionation. We found out that STXBP1 forms small detergent-insoluble aggregates, which is one of the basic characteristics of amyloids, so we can make an assumption that this protein has amyloid properties. Th e reported study was funded by RFBR according to the research project № 18-34-00419.
Ben Gurion University, Israel
Title: Early blood-brain barrier dysfunction predicts neurological outcome following aneurysmal subarachnoid hemorrhage
Time : 14:40-15:05
Svetlana Lublinsky is completing her PhD studies under supervision of Professor Alon Friedman and Professor Ilan Shelef (Ben Gurion University, Israel). She has a Bachelor's degree in Electromechanical Engineering, and a Master's degree in Biomedical Engineering (Technion, Israel). Her research focuses on development of image processing methods, identification of imaging biomarkers, building prognostic and diagnostic tools. She has published and co-authored at 16 papers in reputed journals.
Disease progression and delayed neurological complications are common after aneurysmal subarachnoid hemorrhage (aSAH). We aimed at targeting the potential of quantitative blood-brain barrier (BBB) imaging to predict disease progression and neurological outcome. We retrospectively, blindly and semi-automatically, analyzed magnetic resonance images from 124 aSAH patients scanned at four time points (24-48 h, 6-8 days, 12-15 days and 6-12 months) after the initial hemorrhage. Volume of brain with apparent pathology and BBB-dysfunction, subarachnoid space and lateral ventricles were measured. Neurological status on admission was scored using the Rosen-Macdonald scores (RMS). Clinical outcome at >six months was assessed using the extended Glasgow outcome scale. Based on repeated volumetric measures of pathological brain tissue and CSF, patients were grouped into progressive and non-progressive disease course. No differences were found between the groups in aneurysm locations, neurological status on admission or initial brain pathology. Females were older and more likely to have a non-progressive course compared to males. Progressive course was associated with worse outcome at >six months. A significant brain volume with BBB-dysfunction was found already 24-48 hours after admission, and persisted at all-time points. Brain volume with BBB-dysfunction was significantly larger in patients with progressive compared with non-progressive course. BBB-dysfunction increased the likelihood of a normal brain tissue to turn into a pathological one. A multi-linear regression model revealed a significant power for BBB-dysfunction in combination with RMS at 24-48 hours to predict patient outcome. We suggest that early identification of BBB-dysfunction may serve as a key predictive biomarker for neurological outcome in aSAH.
Charles University in Prague, Czech Republic
Time : 15:05-15:30
Redina Hasani is a sixth-year student in the Second Faculty of Medicine in Charles University in Prague. Her involvement in Pediatrics and in issues in her home country that can find improvement has found her as part of the medical community every summer. Amongst her projects are helping assess methods to aid children in need and families through the foundation “Femijet ne Nevoje”. She is also the Coordinator for Albania and Kosovo for the newest research project in cystic fibrosis by Vertex Pharmaceutical.
Expressed emotions and caregiver’s burden perceived by the family members has an impact on remission and relapses in children with autism. The expressed emotions and burden perceived by the parents of children with autism living in nuclear families in a country such as Albania where social security is far from perfect, gives an indication of the impact these emotions have in children with autism. Parents of 71 children with autism (>3 yrs. & without any comorbid disorder), in age range 4.9±0.2 yrs., attending the Community Center of Mental Health No.1 Tirana, Albania, were enrolled for a standardized interview after taking informed consent. Tools used were burden assessment schedule (BAS). 62 children (40 M, 22 F) had both the parents while nine had a single parent. Mean BAS score for mothers and fathers of male patients were 56±8.56 and 42±10.34 respectively, for female patients were 56±7.36 and 40±9.25 respectively. Mean criticism score for mothers and fathers of male patients were 1.97±0.46 & 2.48±0.31 respectively while for female patients were 1.85±0.48 and 2.17±0.49 respectively. Thus, mothers and fathers of children with autism behave differently of perceived burden and expressed emotions and the response for female and male child is also different. Burden perceived (BAS score) by mothers is higher than by fathers for both male and female child. Mothers showed more emotional involvement (more for male than female child) while fathers showed more criticism.
University of Tehran, Iran
Time : 15:50-16:15
Saeed Akhavan is a joint PhD student between University of Grenoble (France) and University of Tehran (Iran). His PhD thesis is in the field of Biomedical Engineering and Neuroscience.
Recent studies have shown that somatosensory cortex (SoCx) is the main starting region of absence epileptic seizures. This theory has been confirmed in several well-known animal models such as genetic absence epileptic rat from Strasbourg (GAERS). In this research, we locally analyze seizures using the data recorded from different layers of SoCx of a GAERS. An electrode with 16 sensors (sensors inter-distance: 150 mm, sampling rate: 20 kHz) was vertically implanted in SoCx and the data were recorded. We localize the active layers of SoCx during seizures, and investigate the temporal changes of seizures. We achieve our goals by exploration of spikes which are the most important characteristics of seizures. The spikes appear synchronously in different layers of SoCx because the data were acquired locally. Hence, when one spike appears, we can consider a spike column including 16 spikes recorded from different layers of SoCx. We first detect the spike columns then, the spike columns are clustered, and a center is assigned to each cluster. Therefore, each spike column is corresponded to a cluster center, and each seizure is described by a sequence of clusters. Based on the topology of clusters centers and the sequence of clusters, we present the spatio-temporal analysis of seizures. The obtained results show that there are two kinds of spike columns which randomly appear during seizures. One of them is dominant and the other one is unstable. Moreover, it is shown that layers II/III and VI of SoCx are the origins of these spike columns.
Ibn Tofail University, Morocco
Title: Stress-alcohol use disorders interactions in adolescent rat: neuroprotective role of argan oil
Time : 16:15-16:40
El Mostafi Hicham is a PhD student studying the interactions between stress and alcohol use disorders in adolescent rat and neuroprotective role of argan oil, at the Center for Doctoral Studies (4th year), Ibn Tofail University, Kenitra, Morocco. In 2015 he obtained his Master's degree in Human Neurocognition and Population Health. During this training he studied the causal links between school performance and drug use among a population of high school adolescent. Since 2015 he is a member of the Laboratory of Genetic, Neuroendocrinology and Biotechnology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco. He has been working on the effect of early life ethanol exposure (in utero and/or adolescence) on the vulnerability to develop alcohol dependence, cognitive and emotional disorders in young people. His studies are based on the use of the preclinical model to discover this phenomenon in rodents and explored the neurobiological mechanisms underlying long-term vulnerability to alcohol use disorders.
Adolescent intermittent ethanol (AIE) exposure can lead to the development of psychiatric disorders, including alcoholism in adulthood. This work aim to address the following questions: does AIE exposure alter response to subsequent stress challenge? And, does stress experience concurrent with AIE exposure further exacerbate increased drinking? Rats received intermittent ethanol exposure (ip 3g/kg/2jx8) during post-natal days (PND) 30–44, and emotional responses (anxio-depressive like behaviors) were measured after 6 weeks of the last AIE. Our results show that AIE exposed rats exhibited altered response to forced swim (FS) stress (increased immobility time) and open field (OF) stress (decreased locomotor activity). Similar results were obtained in rats exposed for 6 weeks consecutive (PND 44-85), to unpredictable mild chronic stress (UCMS), modeling depression. Also, when AIE is associated with UCMS in a third group of rats, the emotional response is severely impaired. In adulthood, the voluntary consumption of ethanol was measured in the two-bottle choice paradigm (water vs. ethanol 10%). AIE-exposed rats that received UCMS showed a greater increase in ethanol intake (~4.2 g/kg) compared to AIE no-stress rats (~3.1 g/kg) and control stress rats (~2.6 g/kg), after 6 weeks of free ethanol consumption. Collectively, these data indicate a reciprocal interaction between stress and alcoholism, with AIE exposure altered stress responsiveness and UCMS exposure further increasing AIE-induced escalation of drinking. Another question, our study aims to exploded is: does argan oil (AO) dietary affect the behavioral response, biochemical and oxidative profiles of amygdala involved in emotional responses to stress. The variation of these parameters was evaluated in AIE-rats receiving dietary 10 ml/kg/day of AO, starting from weaning, for 9 weeks (PND 21-114). Our results show that supplementation has resulted in an increase in locomotor activity, reduced sensitivity to frightening environments (OF, FS) in UCMS rats. Moreover, oxidative stress markers, and corticosterone show a tendency to be regulated. These results suggest, for the first time, a neuroprotective effect of AO against disorders induced by stress and alcohol use interaction in adolescence.