scholarly journals Brain Volume Alterations Using 3tesla Magnetic Resonance and Neuropsychological Findings in Gaucher Disease Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2060-2060
Author(s):  
Maria Giulia Tullo ◽  
Francesca Caramia ◽  
Gianmarco Tessari ◽  
Carlo Di Bonaventura ◽  
Rosaria Turchetta ◽  
...  
Keyword(s):  
Neuropsychological Assessment ◽  
Healthy Subjects ◽  
Multidisciplinary Approach ◽  
Short Term Memory ◽  
Cognitive Impairments ◽  
Type I ◽  
Short Term ◽  
The Brain ◽  
3T Mr ◽  
N370s Mutation

Abstract Gaucher Disease (GD) is a metabolic inherited disorder, that classically includes three clinical phenotypes. Type I GD (GD1) is considered as a non-neuronopathic variant and can mimic a hematologic disease; type II (GD2) is classified as an acute neuropathic form and type III (GD3) is characterized by a slower and progressive neurological involvement. A protective role of N370S mutation against neurological impairment had been previously hypothesized in GD1, however, increasing data and our experience show that patients with GD1 may present clinical signs of parkinsonism, frequently combined with cognitive impairment and behavioral alterations. Structural brain changes associated with cognitive impairments in GD patients, especially type I, has not yet been reported. The prospective study, called SENOPRO_GAUCHER, has investigated in depth, the neurological status in GD patients using a multidisciplinary approach, including 3Tesla magnetic resonance (3T MR). This study was approved by our Ethics Committee. Baseline data on neurological, psychological, psychiatric, somatosensory, and motor evaluations, and electroencephalography (EEG) surprisingly revealed two, or more, clinical and/or instrumental, neurological signs in all GD1 patients, and a wide spectrum of neurological abnormalities in all GD3 patients. We, hereby, report the results of investigations on brain structure of GD patients, compared to that of healthy subjects, using 3T MR, in order to evaluate whether brain alterations can predict neurocognitive impairment in GD patients, especially GD1. Out of 22 GD patients, assessed for neuropsychological and psychiatric functions, 19 (17 GD1, 2 GD3, median age = 44, range 17 - 68 years) underwent 3T MR examination. Regarding genotyping, all but one of the 17 GD1 patients was N370S mutation heterozygous. A Voxel-based Morphometry (VBM) analysis was performed to investigate brain structure in the 19 GD patients and in 19 healthy subjects with no neurological or neuropsychiatric disease. The healthy subjects, matched to patients by age, sex, and education, in addition to 3T MR, underwent neuropsychological assessment using Mini-Mental State Exam and Mental Deterioration Battery, to evaluate cognitive functions and mental deterioration, respectively. Qualitative MR examinations revealed unspecific abnormalities in 7/17 GD1 patients. In particular, cortical and/or subcortical areas of gliosis (4 patients), vascular ectasia extended from the left frontal surface of the brain to the lateral ventricle (1 patient), dilation of perivascular spaces in the sub-cortical and nucleus-basal area (1 patient), diffuse suffering of the brain white matter due to a chronic ischemic vascular damage (1 patient) were found. Concurrently, results of the VBM analysis revealed that a set of regions, mostly located in the prefrontal and parieto-occipital cortex, were significantly reduced in GD patients, compared to healthy subjects. The most affected regions included the frontal eye fields, the dorso-lateral prefrontal cortex, the posterior cingulate cortex, and the V3B area. Psychological and psychiatric evaluations underlined anxiety, depression, and somatic concerns in 10/17 GD1 patients, combined with cognitive impairments in two of them. Moreover, 1/2 GD3 and 5/17 GD1 patients showed cognitive impairments in attention, language, short-term memory, and executive cognitive functions. The local brain volume reductions, detected in GD1 patients, were in line with the cognitive impairments resulted in the neuropsychological assessment. Cortical reductions of fronto-parietal regions, responsible for the planning and execution of movements, are compatible with impairments in executive functions (digit-span) and visuo-spatial memory, found in GD1 patients. Moreover, impairments in short-term memory observed in GD1 patients are compatible with cortical reductions in the frontal cortex found by the VBM analysis. In conclusion, focal brain differences found between GD1 patients and healthy subjects may predict and clarify the cognitive impairments and behavioural alterations observed in GD patients. The brain structural analyses, associated with neuropsychological assessment, suggest that a multidisciplinary approach is necessary in evaluating GD1 patients. Disclosures Giona: Sanofi Genzyme: Consultancy, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Novartis: Consultancy.

Multi-Parameter Neurological Study Based on Combined Conventional and Functional Assessments in Gaucher Disease Patients (SENOPRO_GAUCHER Study)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-12
Author(s):  
Emanuele Cerulli Irelli ◽  
Carlo Di Bonaventura ◽  
Gianmarco Tessari ◽  
Tiziana Di Pippo ◽  
Rosaria Turchetta ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Research Funding ◽  
Cognitive Impairments ◽  
Cognitive Test ◽  
Type I ◽  
Brain White Matter ◽  
Neurological Abnormalities ◽  
The Brain ◽  
N370s Mutation ◽  
Sd Oct

Gaucher Disease (GD), a metabolic inherited disorder, includes three clinical phenotypes. Type I GD (GD1), that can mimic a hematologic disease, has been classically considered as a non-neuropathic variant; type II (GD2) and type III (GD3) are classified as acute and chronic neuropathic forms, respectively. A protective role of N370S mutation against neurological impairment had been previously hypothesized in GD1, however, clinical signs of parkinsonism have recently been reported in this category of patients. The aim of our observational, monocentric, and prospective study, called SENOPRO_GAUCHER, was to evaluate in depth the neurological and neuropsychiatric aspects in GD1 patients, using clinical and instrumental investigations, in order to identify clinical and subclinical neurological manifestations, including cognitive impairment and behavioural alterations. Neurological assessments were scheduled for 22 GD patients (19 GD1 and 3 GD3) aged >12 years. Clinical evaluation, including Severity Scoring Tool Unified Parkinson's Disease Rating scale and Epworth Sleepiness scale; psychological tests and psychiatric evaluation, using a cognitive test battery and two psychiatric (BPRS) and psychological (CBA 2.0) questionnaires; somatosensory, motor and visual evoked potential, spectral domain optical coherence tomography (SD-OCT), standard electroretinogram; electroencephalography (EEG), and magnetic resonance (MR) 3Tesla, were planned at baseline, after 12 and 24 months. Results at the baseline evaluation of all 22 enrolled patients (9 males and 13 females; median age at the study: 44.5 years, range 17 - 68) are here reported. Regarding genotyping, all but one of the 19 GD1 pts was heterozygous for the N370S mutation. Parkinsonian motor signs were found in 10/22 patients (9 GD1): 7 pts (6 GD1) had isolated bradykinesia and 3 GD1 patients presented bradykinesia combined with rigidity. Abnormal saccadic movements were found in all GD3 pts and in one GD1. Excessive daytime sleepiness (EDS) was detected in 9/22 patients (8 GD1). EEG revealed focal, or diffuse slow waves in 6 patients (5 GD1). Significant cognitive impairments in attention, language, memory and executive functions were found in 4/19 GD1 and in 2/3 GD3 patients. Moreover, psychological and psychiatric evaluations underlined anxiety, depression and somatic concerns in 10/22 patients (9 GD1), combined with cognitive impairments in 3/12. Sixteen patients (13 GD1) showed slight or moderate sensorineural hearing loss (SNHL), and 4 of them had a cookie and reverse cookie bite morphology, typically associated with genetic SNHL. Ophthalmological evaluation revealed a degree of retinal blood vessel tortuosity in all but one patient, and superficial corneal dystrophies in 3 patients (2 GD1). An increased latency and moderate reduction in the amplitudes of optic nerve function were found in 13/22 patients (10 GD1). The SD-OCT examination showed impairment in retinal nerve fibre layers in 7 patients (6 GD1), combined with macular damage in 2 of them. Qualitative MR 3Tesla examinations revealed unspecific abnormalities in 7/19 (37%) GD1 patients; in particular, cortical and/or subcortical areas of gliosis (4 patients), vascular ectasia extended from the left frontal surface of the brain to the lateral ventricle (1 patient), dilation of perivascular spaces in the sub-cortical and nucleus-basal area (1 patient), diffuse suffering of the brain white matter due to a chronic ischemic vascular damage (1 patient). In summary, all GD3 patients showed a wide spectrum of neurological abnormalities, as expected. Surprisingly, however, all GD1 pts also presented at least two, or more, clinical and/or instrumental, neurological signs. The high prevalence of EDS in our population suggests a possible underlying sleep disorder which should be further investigated. The N370S mutation did not impact the likelihood of developing neurological abnormalities in our cohort of GD1 patients. In conclusion, our results have demonstrated that a multidisciplinary, and in-depth approach is necessary in evaluating GD1 patients. Disclosures Giona: Sanofi Genzyme: Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Novartis: Research Funding.

Variables That Influence the Generation of Random Sequences: An Update

1997 ◽  
Vol 84 (2) ◽  
pp. 627-661 ◽  
Author(s):  
Peter Brugger
Keyword(s):  
Short Term Memory ◽  
Human Subjects ◽  
Complete Suppression ◽  
Random Generation ◽  
Short Term ◽  
Random Sequences ◽  
Potential Applications ◽  
Basic Experiments ◽  
The Brain ◽  
Relevant Work

This article updates Tune's 1964 review of variables influencing human subjects' attempts at generating random sequences of alternatives. It also covers aspects not included in the original review such as randomization behavior by patients with neurological and psychiatric disorders. Relevant work from animal research (spontaneous alternation paradigm) is considered as well. It is conjectured that Tune's explanation of sequential nonrandomness in terms of a limited capacity of short-term memory can no longer be maintained. Rather, interdependence among consecutive choices is considered a consequence of an organism's natural susceptibility to interference. Random generation is thus a complex action which demands complete suppression of any rule-governed behavior. It possibly relies on functions of the frontal lobes but cannot otherwise be “localized” to restricted regions of the brain. Possible developments in the field are briefly discussed, both with respect to basic experiments regarding the nature of behavioral nonrandomness and to potential applications of random-generation tasks.

scholarly journals Short-Term Memory Deficits in the SLEEP Inbred Panel

2019 ◽  
Vol 1 (4) ◽  
pp. 471-488 ◽  
Author(s):  
Shailesh Kumar ◽  
Kirklin R. Smith ◽  
Yazmin L. Serrano Negron ◽  
Susan T. Harbison
Keyword(s):  
Learning And Memory ◽  
Sleep Duration ◽  
Genetic Architecture ◽  
Short Term Memory ◽  
Morphological Changes ◽  
Brain Structures ◽  
Social Conditions ◽  
Short Term ◽  
The Relationship ◽  
The Brain

Although sleep is heritable and conserved across species, sleep duration varies from individual to individual. A shared genetic architecture between sleep duration and other evolutionarily important traits could explain this variability. Learning and memory are critical traits sharing a genetic architecture with sleep. We wanted to know whether learning and memory would be altered in extreme long or short sleepers. We therefore assessed the short-term learning and memory ability of flies from the Sleep Inbred Panel (SIP), a collection of 39 extreme long- and short-sleeping inbred lines of Drosophila. Neither long nor short sleepers had appreciable learning, in contrast to a moderate-sleeping control. We also examined the response of long and short sleepers to enriched social conditions, a paradigm previously shown to induce morphological changes in the brain. While moderate-sleeping control flies had increased daytime sleep and quantifiable increases in brain structures under enriched social conditions, flies of the Sleep Inbred Panel did not display these changes. The SIP thus emerges as an important model for the relationship between sleep and learning and memory.

scholarly journals Nearly Extensive Sequential Memory Lifetime Achieved by Coupled Nonlinear Neurons

2012 ◽  
Vol 24 (10) ◽  
pp. 2678-2699 ◽  
Author(s):  
Taro Toyoizumi
Keyword(s):  
Cognitive Processes ◽  
Neural Activity ◽  
Short Term Memory ◽  
Memory Performance ◽  
Linear Part ◽  
Network Size ◽  
Short Term ◽  
Time Step ◽  
Sequential Memory ◽  
The Brain

Many cognitive processes rely on the ability of the brain to hold sequences of events in short-term memory. Recent studies have revealed that such memory can be read out from the transient dynamics of a network of neurons. However, the memory performance of such a network in buffering past information has been rigorously estimated only in networks of linear neurons. When signal gain is kept low, so that neurons operate primarily in the linear part of their response nonlinearity, the memory lifetime is bounded by the square root of the network size. In this work, I demonstrate that it is possible to achieve a memory lifetime almost proportional to the network size, “an extensive memory lifetime,” when the nonlinearity of neurons is appropriately used. The analysis of neural activity revealed that nonlinear dynamics prevented the accumulation of noise by partially removing noise in each time step. With this error-correcting mechanism, I demonstrate that a memory lifetime of order [Formula: see text] can be achieved.

Pharmacological Foundations of Cannabis Chemovars

Planta Medica ◽  
2017 ◽  
Vol 84 (04) ◽  
pp. 225-233 ◽  
Author(s):  
Mark Lewis ◽  
Ethan Russo ◽  
Kevin Smith
Keyword(s):  
Short Term Memory ◽  
Symptomatic Relief ◽  
Breeding Program ◽  
Type I ◽  
Type Ii ◽  
Short Term ◽  
Content Type ◽  
Therapeutic Benefits ◽  
Predominant Type ◽  
Chemical Profiles

AbstractAn advanced Mendelian Cannabis breeding program has been developed utilizing chemical markers to maximize the yield of phytocannabinoids and terpenoids with the aim to improve therapeutic efficacy and safety. Cannabis is often divided into several categories based on cannabinoid content. Type I, Δ 9-tetrahydrocannabinol-predominant, is the prevalent offering in both medical and recreational marketplaces. In recent years, the therapeutic benefits of cannabidiol have been better recognized, leading to the promotion of additional chemovars: Type II, Cannabis that contains both Δ 9-tetrahydrocannabinol and cannabidiol, and cannabidiol-predominant Type III Cannabis. While high-Δ 9-tetrahydrocannabinol and high-myrcene chemovars dominate markets, these may not be optimal for patients who require distinct chemical profiles to achieve symptomatic relief. Type II Cannabis chemovars that display cannabidiol- and terpenoid-rich profiles have the potential to improve both efficacy and minimize adverse events associated with Δ 9-tetrahydrocannabinol exposure. Cannabis samples were analyzed for cannabinoid and terpenoid content, and analytical results are presented via PhytoFacts, a patent-pending method of graphically displaying phytocannabinoid and terpenoid content, as well as scent, taste, and subjective therapeutic effect data. Examples from the breeding program are highlighted and include Type I, II, and III Cannabis chemovars, those highly potent in terpenoids in general, or single components, for example, limonene, pinene, terpinolene, and linalool. Additionally, it is demonstrated how Type I – III chemovars have been developed with conserved terpenoid proportions. Specific chemovars may produce enhanced analgesia, anti-inflammatory, anticonvulsant, antidepressant, and anti-anxiety effects, while simultaneously reducing sequelae of Δ 9-tetrahydrocannabinol such as panic, toxic psychosis, and short-term memory impairment.

An Integrated Molar/Molecular Model of the Brain

1972 ◽  
Vol 30 (2) ◽  
pp. 343-368 ◽  
Author(s):  
Alan Einar Hendrickson
Keyword(s):  
Action Potentials ◽  
Short Term Memory ◽  
Molecular Model ◽  
Spike Trains ◽  
Mass Action ◽  
Small Species ◽  
Short Term ◽  
Term Memory ◽  
Anaesthetic Agents ◽  
The Brain

A model of the brain is presented at both molecular and molar levels. Communication between neurons is thought to be a kind of telegraph code, with the information being coded as the permutation of four possible interval values between successive action potentials in spike trains. A small species of RNA molecule is thought to be the memory molecule, and the four possible nucleotide bases of RNA correspond to the four possible interval values. The model is shown to account for generalization, speed of retrieval, mass action, long- and short-term memory, forgetting, operant and classical conditioning, intelligence, reaction time, the action of anaesthetic agents, and some aspects of personality. Some evidence from multidisciplinary sources is presented in support of the major features of the model.

A Mathematical Model of Short-Term Memory

SIMULATION ◽  
1964 ◽  
Vol 3 (6) ◽  
pp. 46-51
Author(s):  
W. Ross Adey ◽  
N.V. Findler
Keyword(s):  
Electromagnetic Waves ◽  
Short Term Memory ◽  
Threshold Value ◽  
Long Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Neuron Density ◽  
Receptor Neurons ◽  
The Brain

It is attempted in this paper to give a mathematical description of the short-term memory. Instead of using the microscopic properties of individual neu rons, such as the number of interconnections, neuron density, threshold value, etc., the cerebral cortex is regarded as a "neuron gas" that is a vast conglomer ate of neurons with statistically distributed charac teristics. Stimuli from the environment cause the receptor neurons to emit virtual electromagnetic waves into the brain. A self-optimizing process of the brain tis sue is here described by which the useful, informa tion-carrying energy reaching the long-term memory tends to maximum. It is emphasized that in the following a brain model is described and the physical processes in volved may have no direct equivalent in reality.

scholarly journals A Diverse Range of Factors Affect the Nature of Neural Representations Underlying Short-Term Memory

2018 ◽  
Author(s):  
A. Emin Orhan ◽  
Wei Ji Ma
Keyword(s):  
Neural Circuits ◽  
Short Term Memory ◽  
Persistent Activity ◽  
Short Term ◽  
Diverse Range ◽  
Term Memory ◽  
Temporal Complexity ◽  
Wide Range ◽  
Activity Models ◽  
The Brain

AbstractSequential and persistent activity models are two prominent models of short-term memory in neural circuits. In persistent activity models, memories are represented in persistent or nearly persistent activity patterns across a population of neurons, whereas in sequential models, memories are represented dynamically by a sequential pattern of activity across the population. Experimental evidence for both types of model in the brain has been reported previously. However, it has been unclear under what conditions these two qualitatively different types of solutions emerge in neural circuits. Here, we address this question by training recurrent neural networks on several short-term memory tasks under a wide range of circuit and task manipulations. We show that sequential and nearly persistent solutions are both part of a spectrum that emerges naturally in trained networks under different conditions. Fixed delay durations, tasks with higher temporal complexity, strong network coupling, motion-related dynamic inputs and prior training in a different task favor more sequential solutions, whereas variable delay durations, tasks with low temporal complexity, weak network coupling and symmetric Hebbian short-term synaptic plasticity favor more persistent solutions. Our results help clarify some seemingly contradictory experimental results on the existence of sequential vs. persistent activity based memory mechanisms in the brain.

scholarly journals Short-Term and Procedural Memory for Colours and Inferior Temporal Cortex Activity

1997 ◽  
Vol 10 (2-3) ◽  
pp. 83-92
Author(s):  
E. Castro-Sierra ◽  
E. Paredes-Díaz ◽  
J. A. Lazareff
Keyword(s):  
Short Term Memory ◽  
Temporal Cortex ◽  
Normal Subjects ◽  
Procedural Memory ◽  
Size Perception ◽  
Inferior Temporal Cortex ◽  
Short Term ◽  
Procedural Task ◽  
The Brain ◽  
Normal Controls

Two children (male, 10 years, and female, 13 years one month) with tumours of the inferior temporal (IT) cortex of the brain were studied post-surgically for their abilities to carry out a short-term memory test. This involved: differences in colour, number and shape of small plastic objects; differences in receptacles where these objects should be placed and in ways in which this placement should be done; a procedural task involving differences either in colour or in size of wooden rings employed in the task. Their performances in these tests, and those of patients with tumours of other encephalic areas, were compared with the performances of normal controls. The subjects with IT tumours spent a significantly greater amount of time than normal subjects of their age in carrying out the procedural task involving differences in colour. One of the IT subjects also spent a significantly greater amount of time in the procedural task involving size differences. Other differences in the performances of patients with encephalic tumours and the performances of normal controls were not significant. Results are discussed in relation to findings of colour and size perception and memory localized to the inferior temporal and middle temporal cortices.

scholarly journals Camelina sativa Methanolic and Ethanolic Extract Potential in Alleviating Oxidative Stress, Memory Deficits, and Affective Impairments in Stress Exposure-Based Irritable Bowel Syndrome Mouse Models

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Roxana O. Cojocariu ◽  
Ioana-Miruna Balmus ◽  
Radu Lefter ◽  
Luminita Hritcu ◽  
Daniela C. Ababei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Short Term Memory ◽  
Camelina Sativa ◽  
Stress Exposure ◽  
Short Term ◽  
Term Memory ◽  
Maze Test ◽  
Ethanolic Extracts ◽  
Irritable Bowel ◽  
The Brain

Camelina sativa is mainly used as an oilseed crop; its edible oil is being also used as a traditional home remedy for the treatment of ulcers, wounds, and eye inflammations, due to the antioxidant activities. In the present study, the chemically characterized alcoholic extracts of Camelina sativa var. Madalina defatted seeds (5 g/kg body weight p.o., suspended in CMC-Na 0.1%) were administered to stress-induced animal models of irritable bowel syndrome (based on combinations of contention stress and multifactorial stress and maternal stress) and evaluated for the behavioural (short-term memory by the Y maze test, the anxious behaviour using the elevated plus maze test, and the antidepressant effect using the forced swimming test) and brain and bowel tissue oxidative status (superoxide dismutase and glutathione peroxidase enzymes activities and malondialdehyde and total soluble protein levels) improving effects. According to the chemical characterization, the extracts were rich in sinapine, glucosinolates, and flavonol glycosides. Moreover, this study showed the beneficial effects of Camelina sativa seed methanolic and ethanolic extracts on the behaviour and brain and bowel tissues oxidative stress status of stress exposure-based IBS mouse models. Despite the slight differences in the chemical composition of the methanolic and ethanolic extracts, the results suggested that the Camelina sativa extracts could reverse the short-term memory impairments caused by stress exposure and also could decrease the intensity and frequency of the anxiety and depressive-like behaviours observed in the stress-exposed animal models of IBS. Furthermore, the Camelina sativa extracts showed a significant effect on the oxidative stress markers in the brain and bowel tissues of the studied animal model by decreasing the superoxide dismutase activity and increasing the glutathione peroxidase activity. However, the results suggested that the extracts could also increase lipid peroxidation in bowel tissues. In this way, this study provides additional evidence that the administration of Camelina sativa seed alcoholic extracts could improve cognitive performances and mood and exhibit the antioxidant capacity in both the brain and bowel tissues.

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