Conference Schedule

Day1: June 13, 2019

Keynote Forum

Biography

Mitra Assadi is director of the Headache Medicine and Pe¬diatric Neurology at the Capital Institute for Neurosciences. Board certified in neurology and clinical neurophysiology; she was among one of the first neurologists in the United States to obtain a board certification in headache medicine in 2008. She is actively involved in teaching and research. She is a Professor of Neurology at Robert Wood Johnson Medical School and the Director of the Neurology Clerkship at Capital Health system. Her research has mostly focused on neuro-genetic disorders, in particular leukodystrophies. She has served as a clinical investigator at the Center for Cell and Gene Therapy at the Rowan University since 2004. She has special expertise in Canavan Disease and her published research on the use of lithium in Canavan patients has estab¬lished the standard of care for these patients in the scientific community.

Abstract

This presentation uses the biography and works of Dostoevsky, one of the most powerful classical writers, to explore several topics in neuropsychology. We will begin by reviewing the author’s biography, in particular his history of epilepsy. We will then proceed to discuss his neuropsychological deficits including inability to experience negative emotions, hypo-sexuality, hyper-graphia and hyper-religiosity. Moreover, we will discuss the semiology pertaining to his seizures including his euphoric auras. We will confirm a diagnosis of right temporal lobe epilepsy with involvement of the amygdala. To further explore the above topics, we will use his novel “The Idiot”, which is considered (semi)autobiographical. At the end, we will discuss status epilepticus which was the fate of the protagonist of the novel.

Further, we will review author’s addiction to gambling and explore the potential underlying fronto-temporal networks responsible for addiction behavior in epilepsy. To this end, we will discuss yet another (semi) autobiographical masterpiece of the author: “The Gambler”. We will discuss the underlying neurological substrate for addiction behavior and impulse control, including the role of dopaminergic signalling in frontal lobe networks.

We will then proceed to discuss author’s greatest masterpiece, “Crime and Punishment”. The discussion will mostly focus on forensic psychology. At the end, we will review of the “Brothers Karamazov” mostly focusing on pseudo-seizures and criminal behavior.

In conclusion, Dostoevsky suffered with right temporal lobe epilepsy resulting in the classical triad of hypo-sexuality, hyper-graphia and hyper-religiosity seen in this condition. Due to the involvement of amygdala, he was unable to experience negative emotions. Conceivably, involvement of the fronto-temporal networks was responsible for his gambling addiction.

Biography

Marco Carotenuto is Associate Professor and Chief of Clinic of Child and Adolescent Neuropsychiatry at the Università degli Studi della Campania Luigi Vanvitelli in Italy.Presently, he is currently involved in specific clinical research area such as pediatric sleep disorders, autism spectrum disorders neurochemistry, neurochemical alterations in neurodevelopmental disorders.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by lifelong deficits in both socializing and non-verbal behaviors. Parents often reported children’s sleep disorders (about from 44% to 83% of cases), as difficulty in sleep onset at bedtime, and alterations in sleep stability and continuity.

The first aim of the present study is to evaluate the putative relationship between leptin plasmatic levels and sleep habits in a cohort of ASD children naïve to any antipsychotic drug treatment compared to a group of controls. The second aim is to investigate the relationship between social impairments and the leptin plasmatic levels.

Methodology and Theoretical Orientation: The ASD group included 76 ASD medication-naïve children (49 males/37 females) and the control group consisted of 105 typical developing children (40 males/65 females).

To evaluate sleep habits and disturbances, all children’s mothers filled out the Sleep Disturbances Scale for Children (SDSC). Serum leptin levels were measured using the commercial ELISA kit.

Findings: The analyses of the mean scores on the sleep disorder scale (SDSC) and its subscales revealed a significant group effect. Specifically, the ASD group showed a significantly higher rate of sleep disorders in all subscales investigated by the SDSC scale (Table 1). Also measures of serum leptin levels showed significant effect group with a higher rate in the ASD group (ASD: 1.69 ng/ml ± 0.09; TDC: 0.95 ng/ml ± 0.20; p < .0001]. Correlations were all significant and positive in the overall sample. (Table 2)

Conclusion and Significance: The present study findings showed not only that ASD could be considered as a relevant risk factor for referred sleep troubles disorders, but that plasmatic leptin levels may be a putative biochemical marker for them.

Biography

George Razay is General Physician, Geriatrician and the Di­rector of the Dementia Research Centre at the Launceston General Hospital. He has extensive research experience in Australia and the UK in the field of Alzheimer’s disease, es­pecially in the role of vascular risk factors. His early research explored the role of lipids and insulin in relation to alcohol consumption, smoking, obesity, menopause, and Alzhei­mer’s disease. His recent research investigated the role of obesity, the metabolic syndrome and blood pressure in Alz­heimer’s disease, and the prevalence and treatment of idio­pathic Normal Pressure Hydrocephalus. His research had been presented at national and international meetings and had been published in international journals.

Abstract

Cognitive and gait disorders are common in the elderly. Poo gait performance has been shown to predict the occurrence of dementia. However, there has been no studies looking at the association between gait performance and memory impairment in outpatient clinic setting. We have therefor investigated balance and gait performance among patients attending the memory disorders clinic, the only clinic in Northern Tasmania. 408 consecutive patients enrolled in the study between 2010 and 2014 following referral by medical practitioners. All patients had detailed history of memory, balance and gait symptoms including features suggesting dementia. A full examination included the Mini-Mental state examination and balance/gait functions by standing with eyes closed, on toes, and walking on straight line. All patients had brain CT scan. 182 (44.6%) had mild cognitive impairment,91 (22.3%) had Alzheimer’s disease, 62 (15.2) had idiopathic normal pressure hydrocephalus, 24 (5.9%) had mixed dementia, 11 (2.7%) had vascular dementia, 9 (2.2%) had parkinsonism, 4 (1%) had frontal lobe dementia, 2 (0.5%) had Lewy bod dementia and 23 (5.6%) had other dementia syndromes. 212 (52%) of patients had balance and gait problems, of whom 72% had difficulty standing with eyes closed, 94% standing on toes, 97% walking on straight line. We conclude that balance and gait dysfunctions are associated strongly with cognitive impairment in memory clinic population.

Biography

Michele Roccella is Associate Professor of Child Psychiatry at the Department of Psychology, Educational Science and Human Movement, University of Palermo, Italy . He gradu­ated in Medicine and Surgery and Specialization in Child Psychiatry at the University of Palermo. He is currently Di­rector of the School of Specialization in Child Neuropsychi­atry at the University of Palermo. He was Medical Director of the level at the Territorial Service of Mental Health USL 3 of Catania, District of Palagonia. He is the author of over 450 publications on national and international journals and has been awarded several prizes. The study of impairment in neuropsychological functioning in patients with epilepsy syn­dromes-chromosome genetic and headache in childhood is one of its main areas of clinical interest and research.

Abstract

Objective: Primary monosymptomatic nocturnal enuresis (PMNE) is a common problem in childhood worldwide, consisting in an “involuntary voiding of urine during the night, in the absence of congenital or acquired defects of the central nervous system or the urinary tract, in a child aged five years or over”. Presently the pathophysiogenetic mechanism seems not fully understood, and there is disagreement about the sleep quality of affected children.

Aim of study is assessing the sleep macrostructure and the NREM sleep instability (CAP analysis) among a sample of enuretic children.

Methods: 40 PMNE children (22 Males) (mean age 9,082; SD ± 2,28) underwent an overnight polysomnographic study and were compared with 52 healthy children overlapping for age and gender.

Results: PMNES children present a reduction in sleep duration parameters (p<0.001), and in REM% (p<0.001) and S1% (p=0.01) and an increased in SWS% (p=0.005) than controls (Table 1).

Among the CAP sleep parameters, the bedwetting group show differences in A1 and A2 representation (Table 2).

Conclusion: The present study could open a new window in the management of PMNE, suggesting to consider it properly a neurologic disease in the next future. The Table 1 shows the differences among children affected by primary monosymptomatic nocturnal enuresis (PMNE) and control group in the following parameters: TIB, Time in bed; SPT, Sleep period time; TST, Total sleep time; SOL, Sleep onset latency; SS/h, Stage shifts per hour; AWN/h, Awakenings per hour; SE, Sleep efficiency; WASO, Wakefulness after sleep onset; S1 and S2, Sleep stages 1 and 2; SWS, Slow-wave sleep; REM, Rapid eye movement sleep; AHI, Apnea/Hypopnea Index; ODI, Oxygen Desaturation Index; PLM, Periodic Limb Movements. p values <0.05 were considered as significant.The Table 2 shows the mean differences among children affected by primary monosymptomatic nocturnal enuresis (PMNE) and control group in the following parameters: CAP refers to cyclic alternating pattern; CAP rate (percentage of total NREM sleep time occupied by CAP sequences); percentage and duration of each A phase subtype; A1 index (number of phases A1 per hour of NREM sleep, and of S1, S2 and SWS sleep stage); A2 index (number of phases A2 per hour of NREM sleep, and of S1, S2 and SWS sleep stage); A3 index (number of phases A3 per hour of NREM sleep, and of S1, S2 and SWS sleep stage); duration of B phases; number and duration of CAP sequences. p values <0.05 were considered as significant.

Biography

Ludmilla Morozova-Roche is a Professor in Medical Biophysics at the Umeå University, Sweden. She and her research group has been conducting research on S100 proteins in neurodegenerative and inflammatory diseases during last ten years and showed that S100A9 in particular plays critical role in driving the amyloid-neuroinflammatory cascade in Alzheimer’s, Parkinson’s and traumatic brain injury and therefore can be used as a prospective therapeutic and diagnostic target.

Abstract

Chronic neuroinflammation is a hallmark of neurodegenerative diseases, associated with increased levels of pro-inflammatory factors in the brain tissues.

Methodology and Theoretical Orientation:

The research was conducted by using a range of biophysical and biochemical techniques such as AFM, fluorescence, NMR, surface plasmon resonance, circular dichroism, ELISA and western blots; cell biological methods and immunohistochemistry and immunocytochemistry.

Findings:

We have shown that the pro-inflammatory mediator and highly amyloidogenic protein S100A9 is involved in the amyloid-neuroinflammatory cascades in Alzheimer’s disease, where it co-aggregates with Ab peptide, contributing to amyloid plaque formation and intracellular aggregation [1], in Parkinson’s disease – it forms co-aggregates with a-synuclein and involves in Lewy body formation [2], and in traumatic brain injury – S100A9  is highly abundant in the brain tissues and forms numerous precursor-plaques. In wild-type mouse model the intranasal administration of S100A9 amyloids induces wide-spread cellular stress responses in the brain tissues and Alzheimer’s-like behavioural impairment in passive avoidance test [3]. In vitro S100A9 easily aggregates under native pH 7.4 and 37 °C conditions and this process is well quantitatively described by generic Finke-Watzky two-step nucleation-autocatalytic growth model [4]. The co-aggregation of S100A9 with Ab peptide or a-synuclein occurs significantly faster and leads to formation of larger amyloid aggregates than the self-assembly of individual proteins. S100A9 amyloid oligomers are more toxic than those of Ab or α-synuclein, while the co-aggregation with Ab/ α-synuclein mitigates the cytotoxicity of S100A9 oligomers. The levels of S100A9 follow those of Ab in cerebrospinal fluid during the development of Alzheimer’s disease and S100A9 together with Ab can serve as a biomarker for early stages of Alzheimer’s disease, starting from mild cognitive impairment [5].

Conclusion and Significance:

The finding of S100A9 involvement in neurodegenerative diseases may open a new avenue for therapeutic interventions targeting pro-inflammatory S100A9 and preventing the amyloid self-assembly in affected brain tissues.

Tracks

  • Neurology and Neuroscience |Neurochemistry and Biochemistry| Neurological and Neurodegenerative Disorders |CNS and Brain Disorders| Psychiatric Disorders and Behavioral Therapy | Neuropharmacology and Neurogenetics | Neuroimaging and Diagnostic Techniques
Location:
Speaker

MARCO CAROTENUTO

University of Campania Luigi Vanvitelli, Italy

Chair

LUDMILLA A MOROZOVA-ROCHE

Umea University, Sweden

Co Chair

Biography

Arkadi F. Prokopov is founder and Scientific Director of Athletic HighTech S.L. a private company providing education in use of the normobaric intermittent hypoxic-hyperoxic treatment (the IHHT), as well as conducting research and development of related technology. After graduating from the First Setchenov Medical Institute in Moscow, Russia in 1980 he practiced medicine and worked for 10 years in biomedical research on saturation divers and astronauts. Since 1994 he has practiced integrative medicine in Heidelberg, Germany. In 2000 - 2004 he worked in the USA as medical consultant for the IHHT. He has several patents in the field of the IHHT, publishes articles in scientific journals and conducts workshops and seminars for physicians in Germany, Spain and Russia.

Abstract

Statement of the problem: Physical activity significantly reduces the risk and impede progress of Alzheimer’s disease. Studies indicate that the brain remains modifiable into late adulthood. Hippocampus and prefrontal lobes, which are most affected by AD, might be especially sensitive to the regenerative interventions. Studies confirm efficacy of physical training in AD prevention and treatment, though multiple obstacles remain unresolved. Thus, overcoming low compliance to physical exercising, particularly among senior and disabled patients, is important. Fortunately, all benefits of physical exercising, and much more, would be achieved without applying common exercising routine "per se", but using instead a particular mode of controlled normobaric intermittent oxygenation: The Intermittent Hypoxic - Hyperoxic Training (IHHT), which is applied with the help of special breathing training equipment. 

Clinical practice: The IHHT is based on the hypoxic preconditioning phenomenon. The method allows overcoming low compliance to physical exercising among AD patients. It provides alleviation of oxidative stress, suppression of neuroinflammation, as well as stimulation of neuroplasticity and brain tissue regeneration. IHHT induces mitochondrial rejuvenation and attenuates oxidative/nitrosative stress, stimulates the endogenous coenzyme Q10 synthesis, activates hypothalamic-pituitary-adrenocortical axis, activates Hsp 70 pathway, stimulates dopaminergic, noradrenergic, serotonergic neurotransmission, balances immune function, and boosts neurotrophic factors. The initial improvements (behavior, emotional balance, sleep normalisation) frequently observed during the first three to five IHHT sessions. Improvement of cognitive and executive functions can take weeks to months of treatment. The morphological recovery of brain tissues can be evaluated approximately 12 months after the beginning of the program. To facilitate intracellular repair pathways, an individualized supplementation and nutritional program is essential. The author published a case study of an elderly female patient diagnosed with AD in 2007. The integrative IHHT-based treatment began in 2008, resulting in a stable remission of AD and remarkable brain recovery

(functional and morphological) achieved during six months of continuous treatment. Until present (Nov. 2018), the patient continues a maintenance treatment program at home and shows stable cognitive and executive functionality and enjoys a high quality of life.

Conclusion and significance: Our experience, supported by published research, provides justification for the initiation of a pilot study with patients suffering from AD.

Keywords: Alzheimer’s disease, Dementia, the Intermittent Hypoxic-Hyperoxic Training (IHHT)

Biography

 Kazuto Kobayashi has his expertise in genetic manipulation of neural circuits by using transgenic and viral vector technologies. He has studied the neural mechanisms of motor control and learning through basal ganglia circuitry in rodents. In particular, his group developed a novel technology for conditional cell targeting with a recombinant immunotoxin (Kobayashi et al., 1995), and further a technology for selective neural pathway targeting by combing this immunotoxin targeting with a viral vector system for highly efficient retrograde gene transfer (Kato et al., 2011). He is interested in understanding the neural mechanisms on how cortico-basal ganglia-thalamic network controls action selection and behavioural flexibility in rodent and non-human primate model (common marmosets) brains.

Abstract

Selection of appropriate motor actions and flexible switching of those actions in response to environments are essential for survival and maintenance of individuals and species. The striatum, a key structure in the basal ganglia circuit, plays important roles in the coordination of instrumental motor actions and behavioral flexibility. The intralaminar thalamic nuclei provide the major sources of thalamostriatal inputs and contain multiple nuclear groups, including the central lateral nucleus (CL) and parafascicular nucleus (PF). However, little is known about behavioral roles of these pathways originating from the CL and PF.
Methodology: The behavioral functions were addressed by using the selective neural pathway targeting. A lentiviral vector for highly efficient retrograde gene transfer encoding a receptor for a recombinant immunotoxin was injected into the striatum, and then immunotoxin solution was injected into the CL or PF, resulting in selective elimination of thalamostriatal pathway from each nucleus. The functions were also studied by chemogenetic suppression of specific neural pathways.
Findings: Elimination of the CL thalamostriatal pathway resulted in impaired response selection and lengthening of response time in the performance phase of sensory discrimination with no impact on the behaviors in the acquisition phase and disturbed the reversal and attentional set-shifting of learned responses. Chemogenetic suppression of CL-derived pathway supported the importance of these neurons in reversal learning and set-shifting. In contrast, eliminating PF thalamostriatal pathway impaired mainly the acquisition phase of sensory discrimination, affecting transiently the response selection in the performance phase. 
Conclusion and Significance: Two thalamostriatal pathways have essential but distinct roles in the acquisition and performance phases of stimulus-response learning, suggesting a functional shift of neural circuit during learning processes. In addition, the CL thalamostriatal system plays a key role in behavioral flexibility in response to changes in the choice or strategy, suggesting the main contribution of this pathway in the control of basal ganglia circuit linked to the prefrontal cortex.

Biography

Xiao Xiao is an Associate Professor/Principle Investigator at Fudan University, Institute of Science and Technology for Brain-Inspired Intelligence (ISTBI). After receiving a B.S. in Biological engineering at Xi’an Jiaotong University, Xiao performed her Ph.D. studies with Yuqiu Zhang and Zhiqi Zhao at Fudan University, Institute of Neurobiology. Xiao’s thesis work focused on the circuitry and molecular mechanisms that mediate aversive behavior to pain, which was supported by the Excellent Doctor Project Foundation of the Ministry of Education in China. Xiao went on to do a postdoc fellowship with Anthony Koleske and Michael Higley at Yale University School of Medicine, where she identified molecular pathology of synapse stabilization and neural circuit plasticity. Xiao is the recipient of numerous awards including the Glaxo Smith Kline (GSK) Tomorrow’s Star Award, American Heart Association Postdoc Fellowship, etc. Xiao is interested in exploring neural circuit and molecular mechanism of pain related emotions and memories.

Abstract

The perinatal brain is dominated by immature excitatory synapses containing high release probability (Pr) presynaptic terminals coupled to postsynaptic specializations with GluN2B subunit-containing NMDA receptors (high Pr, GluN2B+ synapses). These synapses mature in an activity-dependent manner to low Pr, GluN2B-deficient synapses. Virtually nothing is known about how or why this transition occurs, including whether and how immature vs. mature synapses differentially contribute to circuit plasticity and stability. Answering these fundamental questions should provide essential clues to why synapses do not develop normally in autism and intellectual disability or destabilize prematurely in psychiatric and neurodegenerative diseases. Disruption of the Abl2/Arg kinase in mice yields a population of high Pr, GluN2B+ synapses that persist into early adulthood. The persistence of these immature synapses drives a significant net loss of hippocampal synapses between postnatal day (P) 21 and P42, and impairs synaptic plasticity and behavior. Building on these findings, we have identified new regulators of synapse maturation, and determined how they act to regulate synaptic function, plasticity, and stability.

Methodology and Theoretical Orientation:
Electrophysiological recording, Two-photon glutamate uncaging, Immunoblotting and immunostaining, Machine learning analysis                 

Findings:

  1. Identify the cell surface receptors that act via Arg to coordinate maturation from high Pr, GluN2B+ synapses to low Pr, GluN2B- synapses
  2. Determine why the persistence of immature high Pr, GluN2B+ synapses disrupts synaptic plasticity and stability

Conclusion and Significance:

We report here that loss of the integrin-regulated Arg kinase yields a significant population of “immature” high Pr, GluN2B+ synapses that persist into adolescence and early adulthood. NMDAR-mediated currents are larger at these synapses at P21, a time that precedes any observable defects in synapse or dendritic spine number or structure in arg–/– mice. Using focal glutamate uncaging at individual synapses, we find that only a subpopulation of synapses exhibit increased GluN2B-mediated responses. As arg–/– mice age, these synapses increase in proportion and spines at these synapses enlarge. These changes coincide with an overall net loss of spines and synapses. We also use this model system to address how retention of high Pr, GluN2B+ synapse impacts NMDAR-mediated plasticity. We demonstrate that although NMDAR dependent-LTP and -LTD are normal in P21 arg–/– slices, both forms of plasticity are significantly altered by P42 and these alterations are mediated by GluN2B-containing NMDARs. These data demonstrate that the integrin-regulated Arg kinase coordinates the maturation of pre- and post-synaptic compartments at a subset of hippocampal synapses in vivo and this coordination is critical for normal long-term synaptic stability and plasticity.

Biography

Mitra Assadi is director of the Headache Medicine and Pediatric Neurology at the Capital Institute for Neurosciences. Board certified in neurology and clinical neurophysiology; she was among one of the first neurologists in the United States to obtain a board certification in headache medicine in 2008. She is actively involved in teaching and research. She is a Professor of Neurology at Robert Wood Johnson Medical School and the Director of the Neurology Clerkship at Capital Health system. Her research has mostly focused on neuro-genetic disorders, in particular leukodystrophies. She has served as a clinical investigator at the Center for Cell and Gene Therapy at the Rowan University since 2004. She has special expertise in Canavan Disease and her published research on the use of lithium in Canavan patients has established the standard of care for these patients in the scientific community.

Abstract

Canavan disease (CD) is a severe childhood leukodystrophy caused by homozygous mutations in the aspartoacylase (ASPA) gene. Several mutations have been detected in Jewish and non-Jewish families.  We share our experience on the natural history of CD as well as treatment responses in a total of 34 cases with genetically confirmed CD.

In the absence of ASPA activity, large amounts of N-acetyl-aspartate (NAA) accumulate in the brain. This creates an osmotic pressure resulting in spongiform degeneration, macrocephaly and biosynthesis defect in myelination. The afflicted children suffer severe developmental regression despite the best conservative management and die prior to reaching their 10th birthday. We observed the natural history of CD in a cohort of 28 patients, out of which 13 received gene therapy. Using quantitative T1 sequences on the brain MRI, we monitored the brain volume and the myelin content. As expected, the untreated children demonstrated progressive brain atrophy and loss of myelin.

Proton MRS (HMRS) was utilized to quantify the NAA levels in target regions in the cortex and basal ganglia.  While in normal children the whole brain NAA level peaks at about 6 months of age, our data indicated that in children affected with CD, and NAA levels continue to increase with an anterior–posterior gradient (p<0.0001). 

We enrolled 13 patients in the gene therapy trial using AAV vector which was delivered through direct parenchymal injection into the frontal, parietal and occipital regions of the brain.  The intervention resulted in a decrease in elevated NAA levels and slowed progression of the brain atrophy. A significant drop in the NAA level was noted in the frontal (p<0.0008), peri-ventricular (p<0.00012) and basal ganglia (p<0.00049). Clinically speaking, using the Gross Motor Function Measure (GMFM), we demonstrated a small but statistically significant improvement in the motor milestones (p<0.017). Moreover, an improvement in the seizure frequency and overall stabilization of the clinical status was noted.  5-year follow-up indicated that the gene therapy was safe and the administration of the AAV vector was not associated with any long-term adverse effects.

Six cases were enrolled in a separate trial using lithium citrate 45 mg/kg/day for a period of 2 month and the above primary endpoints were utilized to assess the efficacy of the treatment.  The HMRS demonstrated a modest drop in the NAA levels in the above regions of interest, reaching statistical significance in the basal ganglia (p<0.02). The GMFM scores did not demonstrate any significant improvement in the motor milestones.

In conclusion, both the gene therapy and use of lithium citrate are safe in CD and effective in reducing the NAA levels in the brain.

Biography

Arkadi F. Prokopov is founder and Scientific Director of Athletic HighTech S.L. a private company providing education in use of the normobaric intermittent hypoxic-hyperoxic treatment (the IHHT), as well as conducting research and development of related technology. After graduating from the First Setchenov Medical Institute in Moscow, Russia in 1980 he practiced medicine and worked for 10 years in biomedical research on saturation divers and astronauts. Since 1994 he has practiced integrative medicine in Heidelberg, Germany. In 2000 - 2004 he worked in the USA as medical consultant for the IHHT. He has several patents in the field of the IHHT, publishes articles in scientific journals and conducts workshops and seminars for physicians in Germany, Spain and Russia.

Abstract

Statement of the problem: A reduced cortical Direct Current (DC) potential correlates with brain metabolic depression and is a common sign in various Alzheimer's Disease (AD) forms. Reduced DC is associated with decreased blood brain flow, low glucose oxidation, mitochondrial impairment and increased oxidative stress that is common in AD patients. Neuroimaging methods, such as PET, SPECT and MRI that are used for brain metabolism evaluation have a common disadvantage of being costly and time-consuming, which limits their usefulness in monitoring of brain metabolism in AD patients.

Clinical practice: A complementary method called The Neuro-Metabolic Activity Mapping (NMAM) employs the principle of DC electroencephalography. The method is based on measurement of the DC potentials in the brain followed by computer analysis of acquired data and visual presentation of cortical metabolic map. The method employs correlation of a certain spectrum of DC potentials and metabolic activity of the brain. The method is similar to PET, though based on metabolic electro-physiology of the brain. The method provides mapping and visualization of changes of brain metabolism under various stimuli and helps evaluate response in the course of therapy. A comparison of a standard EEG and NMAM during challenges, such as hypercapnia and hypoxia shows that the NMAM analysis and visualization of cortical field potentials provides a more accurate picture of the actual metabolic functional state of brain cortex.

Conclusion and significance: The NMAM utilize qualitative visual neuroimaging towards prevention of cognitive decline in populations at high risk for dementia and neurodegeneration and is easy applicable in ambulation settings. The NMAM can help identify and differentiate early signs of metabolic perturbations in AD ambulation patients, as well as in TBI, brain tumors and stroke. The findings obtained by the NMAM method can facilitate beneficial lifestyle changes in patients to reduce risks for AD, neurodegenerative diseases and stroke.

Biography

Viola Angela Izzo is a PhD student working with Caterina Primi on the adaptation and development of scales measuring impulsivity. Her research interests mainly regard impulsivity, examined both in Attention Deficit/Hyperactivity Disorder and in the class of Impulse Control Disorders that often affects Parkinsonian
patients.

Abstract

Statement: Impulse Control Disorders (ICDs), including compulsive gambling, buying, sexual behavior, and eating, are not only a severe disorder that can affect the general, non-clinical population, but also a serious, increasingly recognized psychiatric complication in Parkinson’s disease (PD). Previous research detected some risk factors for their occurrence in PD patients and in the general population, such as impulsivity. However, impulsivity is a multidimensional construct, including reflection impulsivity and delay discounting.
Methodology and Theoretical Orientation: The present work assessed different facets of impulsivity in both PD patients and in the healthy controls (HCs) to examine whether they scored differently. Moreover, both PD and HC groups were divided in two subgroups based on the presence vs absence of ICDs (i.e., PD+ICD, PD-ICD, HC+ICD, and HC-ICD) to test whether the occurrence of ICDs in PD patients and in the HCs was predicted by different aspects of impulsivity. Differences between PD patients and healthy controls were tested using independent samples t-test. Moreover, a Decision Tree process was performed to examine whether ICDs in PD patients and in HCs were associated to different variables. Findings: Results showed that ICDs in PD patients were predicted by a strong preference for immediate rewards, whereas ICDs in the HCs were predicted by a deficient reflective ability.
 
Conclusion and Significance: The present findings may help neurologists in early identifying PD patients who may develop ICDs by simply assessing their impulsivity in terms of delay discounting. Furthermore, this work contributed to identify another risk factor for ICDs in the non-clinical population.

Biography

Ana Catalina Muñoz Arbelaez has her expertise in neurodevelopment, classification models and deep learning. She has been working on a proposed model to classify babblings according to acoustic patterns. She has built this model base on her experience in evaluation and intervention of neurodevelopmental diseases, and research in cognitive functions. Currently, she is a neurodevelopmental psychologist and a fellow of the research group on Sistemas aplicados a la Industria in the Master of Engineering at the Universidad Pontificia Bolivariana, with emphasis on artificial neural networks and speech development in young infants. The approach of the proposed methodology consists on an acoustic pattern recognition problem.

Abstract

Statement: Since young infants are born, they begin with the production of vocal sounds as a result of the interaction between breath, phonation, articulation, and central nervous system (Pachtner, 2017; I. Medicine, N. A. Sciences Engineering y Medicine, 2016; Kent & Hustad, 2009). During an infant’s first year, these vocal sounds have a continue and progressive development from crying, babbling and finally words (Najnin & Banerjee, 2017; Kent & Hustad, 2009).  Therefore, vocal sounds have acoustic patterns which may indicate a developmental stage or a pathological status (Woynaroski et al., 2016; Oller, 2014). Those patterns are being studied through feature extraction methods and classification algorithms. Previous studies have focused on crying using different approaches. Despite they have achieved successful outcomes, none of them have been established as a reliable method for clinical diagnosis (Hariharan et al., 2018; Chittora & Patil, 2017), for the reason databases have biases related with the number of patients signals vs controls signals, and with the number of recordings made per infant. Moreover, in some cases it is difficult to identify the original and real cause of each crying (Saraswathy, Hariharan, Yaacob & Khairunizam, 2012). As delays on the onset of expected babbling patterns is considered as a predictor of developmental impairment, this study set as hypothesis that infant’s patients and controls can be differentiated according to acoustic patterns in babblings.

Methodology and Theoretical Orientation:

Babblings were recorded with smartphones, and data related to early warnings or normal development were given by parents, with previous sign of the inform consent.  The acoustic data was normalized according to rms values, noise filter, and transform using the short time fourier transform. Then, a two steps methodology was proposed based on previous studies of crying classification: I Signal processing, and II Classification algorithms. Three types of signal processing were applied to extract acoustic features from signals: Linear Predictive Coding (LPC), Mel frequency Scale, and Mel-frequency Ceptrum Coefficients (MFCC). And two classification algorithms, to classify between infants’ patients and controls: K-nearest neighbours (K-nn) and Backpropagation Neural Network (BPNN). Each acoustic signal was tagged with the retrieved data referring to the neurodevelopmental status and the biological age. The data was divided into training (90%) and validation (10%) phases for the II. step, and the accuracy and the precision of each classification algorithm were evaluated.

Findings:

According to the results, the training phase achieved better values ​​of accuracy and precision compared to the validation phase. Having a better performance with the BPNN algorithm in both phases, and with the fourier data in both classification algorithms.
In addition, it seems that the validation phase is biased by the sample size of each set (Patients and Control).

Conclusion and Significance:

Despite more data is needed in order to validate different classification algorithms, the previous results indicate that it is possible to identify if a babbling corresponds to an infant control or patient during the training of classification algorithms phase. Furthermore, the classification of the fourier data seem to have patterns which are lost during the signal processing. Therefore, future projects should explore bigger data bases and extract features which can explain better the babbling’s patterns that represent the infant development.

 

Biography

Siva Nalabothu has his expertise in computational neuroscience, neurology, coding, and molecular neuroscience. With his group, they developed a new Myoelectric Computer Interface on the basis of the previous, flagship study on the MCI. After more than a year of experience in this field and working on this project, the final product is nearing completion. The foundation for this project is based on the paradigm initially designed by Tomic et al. that effectively utilized a game controlled by the MCI to reduce abnormal coactivation of muscles in stroke survivors. This foundation has allowed creating a device that can play a pivotal role in bringing severe stroke patients around the world an easier, more efficient method of rehabilitation.

Abstract

Abnormal coactivation patterns of arm muscles is a significant cause of impaired arm function after stroke. In our previous study, the Myoelectric Computer Interface (MCI) training paradigm was designed to help stroke survivors reduce this abnormal coactivation. The impacts that MCI training had on function and arm kinematics in 32 chronic stroke survivors were evaluated, and the results suggested that MCI training could potentially improve post-stroke arm function. The MCI training system in the previous study produced biofeedback for a single muscle pair. Now, we have designed a new paradigm with a biofeedback system returning feedback for three muscles at once and a sham paradigm to act as a control group. We are comparing patients using the original MCI paradigm and both of our new MCI systems, all over a six week period. We hypothesize that the original paradigm will still be effective in reducing coactivation, the sham paradigm will not be effective in reducing coactivation, and the three-muscle paradigm will be more effective in reducing coactivation than the original paradigm.

Day2: June 14, 2019

Keynote Forum

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