scholarly journals Reinforcement regulates timing variability in thalamus

2019 ◽  
Author(s):  
Jing Wang ◽  
Eghbal Hosseini ◽  
Nicolas Meirhaeghe ◽  
Adam Akkad ◽  
Mehrdad Jazayeri
Keyword(s):  
Nervous System ◽  
Basal Ganglia ◽  
Direct Evidence ◽  
Time Intervals ◽  
Flexible Control ◽  
Timing Variability ◽  
Timing Task ◽  
The Mean ◽  
Improved Performance ◽  
Context Specific

AbstractLearning reduces variability but variability can facilitate learning. This paradoxical relationship has made it challenging to tease apart sources of variability that degrade performance from those that improve it. We tackled this question in a context-dependent timing task requiring humans and monkeys to flexibly produce different time intervals with different effectors. Subjects’ timing variability featured two novel and context-specific sources of variability: (1) slow memory-contingent fluctuations of the mean that degraded performance, and (2) fast reinforcement-dependent regulation of variance that improved performance. Signatures of these processes were evident across populations of neurons in multiple nodes of the cortico-basal ganglia circuits. However, only in a region of the thalamus involved in flexible control of timing were the slow performance-degrading fluctuations aligned to performance-optimizing regulation of variance. These findings provide direct evidence that the nervous system makes strategic use of exploratory variance to guard against other undesirable sources of variability.

scholarly journals Reinforcement regulates timing variability in thalamus

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jing Wang ◽  
Eghbal Hosseini ◽  
Nicolas Meirhaeghe ◽  
Adam Akkad ◽  
Mehrdad Jazayeri
Keyword(s):  
Frontal Cortex ◽  
Exploratory Behavior ◽  
Potential Role ◽  
Time Intervals ◽  
Putative Target ◽  
Timing Variability ◽  
Timing Task ◽  
Dorsomedial Frontal Cortex ◽  
Thalamocortical Projections ◽  
Ventrolateral Thalamus

Learning reduces variability but variability can facilitate learning. This paradoxical relationship has made it challenging to tease apart sources of variability that degrade performance from those that improve it. We tackled this question in a context-dependent timing task requiring humans and monkeys to flexibly produce different time intervals with different effectors. We identified two opposing factors contributing to timing variability: slow memory fluctuation that degrades performance and reward-dependent exploratory behavior that improves performance. Signatures of these opposing factors were evident across populations of neurons in the dorsomedial frontal cortex (DMFC), DMFC-projecting neurons in the ventrolateral thalamus, and putative target of DMFC in the caudate. However, only in the thalamus were the performance-optimizing regulation of variability aligned to the slow performance-degrading memory fluctuations. These findings reveal how variability caused by exploratory behavior might help to mitigate other undesirable sources of variability and highlight a potential role for thalamocortical projections in this process.

METABOLIC STUDIES WITH 131I-LABELED THYROXINE. II.

1963 ◽  
Vol 44 (3) ◽  
pp. 475-480 ◽  
Author(s):  
R. Grinberg
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Optic Nerve ◽  
Pituitary Gland ◽  
Time Interval ◽  
Time Intervals ◽  
Pituitary Glands ◽  
The Central Nervous System ◽  
Tentative Explanation

ABSTRACT Radiologically thyroidectomized female Swiss mice were injected intraperitoneally with 131I-labeled thyroxine (T4*), and were studied at time intervals of 30 minutes and 4, 28, 48 and 72 hours after injection, 10 mice for each time interval. The organs of the central nervous system and the pituitary glands were chromatographed, and likewise serum from the same animal. The chromatographic studies revealed a compound with the same mobility as 131I-labeled triiodothyronine in the organs of the CNS and in the pituitary gland, but this compound was not present in the serum. In most of the chromatographic studies, the peaks for I, T4 and T3 coincided with those for the standards. In several instances, however, such an exact coincidence was lacking. A tentative explanation for the presence of T3* in the pituitary gland following the injection of T4* is a deiodinating system in the pituitary gland or else the capacity of the pituitary gland to concentrate T3* formed in other organs. The presence of T3* is apparently a characteristic of most of the CNS (brain, midbrain, medulla and spinal cord); but in the case of the optic nerve, the compound is not present under the conditions of this study.

scholarly journals GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii330-iii331
Author(s):  
Hirokazu Takami ◽  
Koichi Ichimura ◽  
Kohei Fukuoka ◽  
Akitake Mukasa ◽  
Nobuhito Saito ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Basal Ganglia ◽  
Pineal Gland ◽  
Germ Cell ◽  
Prognostic Significance ◽  
Germ Cell Tumors ◽  
Molecular Data ◽  
Molecular Heterogeneity ◽  
Intracranial Germ Cell Tumor

Abstract BACKGROUND We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. METHODS Data from the Intracranial Germ Cell Tumor Genome Analysis Consortium were reviewed. A total of 190 cases were classified as primary GCTs based on central pathological reviews. RESULTS All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker-positive and 6.1% of non-germinomatous GCTs were marker-negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better PFS than those at atypical sites (p=0.03). A molecular-clinical association study revealed frequent MAPK pathway mutations in males (51.4 vs 14.3 %, p=0.007), and PI3K/mTOR pathway mutations in basal ganglia cases (p=0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. CONCLUSIONS These in-depth findings of this study regarding the clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

scholarly journals Comparison of Bite Force in Patients After Treatment of Mandibular Fractures With 3-Dimensional Locking Miniplate and Standard Miniplates

2019 ◽  
Vol 1 (1) ◽  
pp. 7-10
Author(s):  
Gaurav Singh ◽  
Madan Mishra ◽  
Amit Gaur ◽  
Dhritiman Pathak
Keyword(s):  
Treatment Strategies ◽  
Bite Force ◽  
Mandibular Fractures ◽  
Time Intervals ◽  
Experimental Conditions ◽  
3 Dimensional ◽  
The Mean ◽  
Group 2 ◽  
Drilling Conditions ◽  
Group 1

Background: Fractures of the mandible can be studied and described in anatomic terms, functional considerations, treatment strategies, and outcome measures. The performance of any fixation system depends on multiple factors including plate adaptation, screw placement, bone quality, drilling conditions, and postoperative patient compliance. Bite force assesses masticatory muscle function under clinical and experimental conditions. Method: 30 patients with isolated, noncomminuted mandibular fractures were randomly divided into two equal groups. Group 1 patients were treated using 3-dimensional locking miniplates and group 2 patients were treated with standard miniplates. The bite forces were recorded at definite time intervals: preoperatively, and second week, sixth week, third month, and sixth month postoperatively. Result: At 6 weeks postoperative, 3 month postoperative, and 6 month postoperative, the mean bite force was found to be significantly higher among group 1 patients as compared to those in group 2 in all the sites. While at 2 week postoperative, the mean bite force was found to be significantly higher in Group 2 as compared to Group 1 at incisor region. Conclusion: The overall results of the present study show better performance in bite force for the 3-dimensional locking miniplate when compared with standard miniplates.

Annual hazard rates of recurrence for breast cancer after primary therapy.

1996 ◽  
Vol 14 (10) ◽  
pp. 2738-2746 ◽  
Author(s):  
T Saphner ◽  
D C Tormey ◽  
R Gray
Keyword(s):  
Breast Cancer ◽  
Eastern Cooperative Oncology Group ◽  
Entire Group ◽  
Hazard Rates ◽  
Primary Therapy ◽  
Time Intervals ◽  
Differentiating Agents ◽  
The Mean ◽  
Lower Hazard

PURPOSE To determine if the long-term increase of recurrence for breast cancer is stable or slowly decreasing, or if it ever reaches zero; and to determine the effect of prognostic factors on the hazard of recurrence. METHODS All patients entered onto the seven completed and unblinded Eastern Cooperative Oncology Group (ECOG) coordinated studies of postoperative adjuvant therapy for breast cancer were analyzed in terms of annual hazard of recurrence of breast cancer. RESULTS For the entire group, the peak hazard of recurrence occurred in the interval of 1 to 2 years. The hazard decreased consistently in the interval of 2 to 5 years. Beyond 5 years, the hazard of recurrence decreased very, very slowly through year 12. The average hazard of recurrence between years 5 and 12 for the entire population was 4.3% per year. The pattern of a peak hazard of recurrence during the first 5 years with a slowly decreasing hazard of recurrence beyond 5 years was also observed to varying degrees in most subsets. Higher risk subsets such as patients with more than three nodes positive had a higher hazard of recurrence at all time intervals, while lower risk subsets such as patients with negative nodes had a lower hazard of recurrence in all time periods. CONCLUSION Patients 5 years postsurgery for breast cancer appear to have a very slowly decreasing hazard of recurrence. The mean hazard of recurrence between years 5 to 12 postsurgery is 4.3% per year. This group of patients may be well suited for trials evaluating cytostatic drugs or differentiating agents.

scholarly journals Association Between Osteoarticular Scores and Acute Phase Reactant Levels in Rheumatoid Arthritis

2009 ◽  
Vol 28 (2) ◽  
pp. 116-121 ◽  
Author(s):  
Irena Kafeđiska ◽  
Dejan Spasovski ◽  
Todor Gruev ◽  
Mane Grličkov ◽  
Kočo Cakalaroski ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Acute Phase ◽  
Acute Phase Reactant ◽  
Control Group ◽  
Time Intervals ◽  
Acute Phase Reactants ◽  
Mean Values ◽  
Cell Counts ◽  
Phase Reactant ◽  
The Mean

Association Between Osteoarticular Scores and Acute Phase Reactant Levels in Rheumatoid Arthritis The aim of this prospective control study was a quantitative evaluation of the activity of rheumatoid arthritis (RA) in certain time intervals, using articular indexes (set of 28 sensitive and 28 swollen joints), laboratory parameters (Hb, Hct, Er, Le and Plt) and acute phase reactants (ESR, RF, CRP); to determine which of the acute phase reactants is the most useful biochemical marker for the evaluation of disease activity in RA; to quantify the therapeutical and laboratory differences in certain time intervals in the group with and without immunomodulatory therapy with Methotrexate. Sixty patients with RA were included, 27 of who were treated with non-steroid antiinflammatory drugs (NSAIDs) and Methotrexate (MTX). The control group consisted of 33 patients treated only with NSAIDs because of irregular controls. In the first group of patients the disease activity was estimated at four time intervals, and in the control group of patients at three time intervals following the scores of the articular indexes, blood cell counts, ESR and CRP in every patient. In the first group of patients decreased activity of RA was found upon every following control with a consecutive decrease in mean values of the scores of articular indexes with statistically significant differences at the four time intervals. Considering laboratory parameters, there were statistically significant differences in the mean values of Hb, Er, Plt, ESR, (p=0.0462, p=0.0076, p= 0.0058, p= 0.0003). Mean values of CRP did not show statistically significant differences, but the number of patients who were CRP negative increased (there were great standard deviations). In the group of patients treated only with NSAIDs, there were statistically significant differences in the mean values of the scores of articular indexes with an increse at every following control (in favour of progression of the disease). There were no statistically significant differences considering blood cell counts, ESR and CRP (in favour of permanently active disease). In conclusion, CRP is the most useful marker for the prospective follow-up of patients with RA.

scholarly journals POS0424 DETERMINING CIRCULATING ENDOTHELIAL CELLS USING CELLSEARCH SYSTEM IN SYSTEMIC SCLEROSIS PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 441.1-441
Author(s):  
F. Pignataro ◽  
L. Zorzino ◽  
W. Maglione ◽  
A. Minniti ◽  
G. Clericuzio ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Systemic Sclerosis ◽  
Peripheral Blood ◽  
Direct Evidence ◽  
Endothelial Damage ◽  
Circulating Endothelial Cells ◽  
Cellsearch System ◽  
The Mean ◽  
Standardized Method ◽  
Active Disease

Background:Endothelial damage and fibroproliferative vasculopathy of small vessels are pathological hallmarks of Systemic Sclerosis (SSc). Detection and analysis of circulating endothelial cells (CECs) detached from affected blood vessels may be an informative tool to study vascular dysfunction and could be considered a novel biomarker of scleroderma vasculopathy. Our group first showed the presence of CECs in SSc by fluorescence-activated cell sorting (FACS), demonstrating that a raised counts of active CECs may represent direct evidence of active vascular disease in SSc. Despite these interesting data, issues related to difficulties in CEC counting through FACS analysis, due their very low concentration in peripheral blood, prevented further investigations in this field. Recently, a specific kit for the detection of CECs has been developed through the CellSearch System (CS), a semi-automated device for the standardized analysis of rare cells, such as CECs, in peripheral blood.Objectives:To assess the counts of CECs determined by the CS in SSc patients and to evaluate their clinical implication and potential as vascular biomarker in SSc.Methods:10mL of blood samples were collected from 29 subjects (19 SSc patients and 10 healthy donors - HDs) and stored in tubes containing a specific preservative, to allow the analysis of 4mL of blood within 72 hours, according to manufacturer instructions. Out of 19 SSc patients, 18 were female, 10 had the limited form and 9 the diffuse cutaneous variant of SSc. CS uses a proprietary kit containing a ferrofluid-based reagent, that target CD146 to magnetically capture CECs, and the immunofluorescent reagents to stain the CECs, defined as CD146+, CD105-PE+, DAPI+ and CD45-APC-. Clinical, laboratoristic and demographic data were also collected.Results:The mean number of CECs in patients with SSc was significantly higher in comparison to HDs (554/4mL vs. 53.5/4 mL, p=0.0042). When analyzed according to disease subset, both lcSSc and dcSSc showed significantly increased levels of CECs in comparison with HDs (p=0.003 and p=0.005, respectively). No statistical difference was observed in the mean number of CECs in patients with lcSSc compared to those with dcSSc. Regarding vascular involvement, the CECs counts strictly correlated with the presence of digital ulcers (DUs) (p=0.0001) showing a median of 863cells/4mL for the SSc patients with DUs versus a median of 276.2/4mL for the SSc patients without DUs. No statistical correlation was found between CECs and serological autoantibody pattern, skin parameters, or joint and muscle involvement. Patients with active disease, according to the EUSTAR Activity Index, showed a higher CECs value than those with inactive disease (p=0.0012).Conclusion:The amount of CECs detectable in peripheral blood has been recently proposed as a marker of endothelial damage in different vascular diseases, including SSc. However, currently no standardized method is available to determine CEC counts, which makes reported data on CECs reliable and suitable. The CS system is a commercially available semi-automated system that enables standardized determination of CECs. Thus, we examined clinical utility of CECs count by this system in SSc patients. Our results confirm that baseline CEC counts, evaluated by a new standardized method, may represent direct evidence of endothelial damage in SSc and could be a promising tool for monitoring active disease and evaluating therapeutic responses to vascular and immunosuppressive treatments.References:[1]Del Papa N, Pignataro F. Front Immunol. 2018 Jun 18;9:1383[2]De Simone C et al. J Eur Acad Dermatol Venereol. 2014 May;28(5):590-6[3]Del Papa N et al. Arthritis Rheum. 2004 Apr;50(4):1296-304Disclosure of Interests:Francesca Pignataro: None declared, Laura Zorzino: None declared, Wanda Maglione: None declared, Antonina Minniti: None declared, Giulia Clericuzio: None declared, Marco Picozzi: None declared, Cecilia Simonelli Employee of: Menarini Silicon Biosystems, Francesco Picardo Employee of: Menarini Silicon Biosystems, Roberto Caporali: None declared, Nicoletta Del Papa: None declared

The Effects of Intra-Cerebral Neuropeptide Y Infusion into the Ventral Hippocampus on Anxiety-Like Behaviour in the Elevated Plus-Maze

2018 ◽  
Author(s):  
Geoffrey Harrison
Keyword(s):  
Nervous System ◽  
Neuropeptide Y ◽  
Primary Structure ◽  
Direct Evidence ◽  
Elevated Plus Maze ◽  
Ventral Hippocampus ◽  
Ventral Aspect ◽  
Plus Maze ◽  
Evolutionarily Conserved ◽  
Defensive Behaviours

Neuropeptide Y (NPY) is one of the most prominent and evolutionarily conserved peptides in the mammalian nervous system. The hippocampus, which contains high densities of NPY producing cells and receptors, is considered a primary structure in the neuroanatomical circuitry of anxiety. Although once considered a homogenous structure, the ventral aspect of the hippocampus is now considered to play a more explicit role in anxiety regulation. To date there is no direct evidence implicating ventral hippocampal NPY in anxiety modulation. By contrasting the defensive behaviours of rats (N=24) in the elevated plus-maze (EPM) model of animal anxiety following intra-cerebral infusions of either experimental NPY (n=12), or saline (n=12), I expect that NPY infusions into the ventral hippocampus will cause marked reductions in anxiety-like behaviour. Specifically, NPY infusions at that site will increase the proportion of entries into, and time spent in, the open arm sections of the EPM, as well as decrease secondary defensive behaviours such as stretch-attend and flatback postures, head-dipping, and sniffing, while in protected portions (walled arms) of the EPM.

Primary Leptomeningeal Gliomatosis in Children and Adults: A Morphological and Molecular Comparative Study With Literature Review

Neurosurgery ◽  
2015 ◽  
Vol 78 (3) ◽  
pp. 343-352 ◽  
Author(s):  
Arnault Tauziede-Espariat ◽  
Andre Maues de Paula ◽  
Melanie Pages ◽  
Annie Laquerriere ◽  
Emilie Caietta ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Clinical Symptoms ◽  
Malignant Gliomas ◽  
Leptomeningeal Gliomatosis ◽  
Molecular Features ◽  
The Central Nervous System ◽  
The Mean

Abstract BACKGROUND: Primary leptomeningeal gliomatosis (PLG) is a poorly recognized tumor of the central nervous system. OBJECTIVE: To describe the histopathological, immunohistochemical, and molecular features of PLG. METHODS: Results of our multicentric retrospective study of 6 PLG cases (3 pediatric and 3 adult) were compared with literature data. RESULTS: The mean age was 54.7 years for adults and 8.7 years for children, with 3 males and 3 females. Clinical symptoms were nonspecific. Cerebrospinal fluid analyses showed a high protein level often associated with pleocytosis but without neoplastic cells. On neuroimaging, diffuse leptomeningeal enhancement and hydrocephalus were observed, except in 1 case. PLG was mostly misinterpreted as infectious or tumoral meningitis. The first biopsy was negative in 50% of cases. Histopathologically, PLG cases corresponded to 1 oligodendroglioma without 1p19q codeletion and 5 astrocytomas without expression of p53. No immunostaining for IDH1R132H and no mutations of IDH1/2 and H3F3A genes were found. Overall survival was highly variable (2-82 months) but seems to be increased in children treated with chemotherapy. CONCLUSION: This study shows the difficulties of PLG diagnosis. The challenge is to achieve an early biopsy to establish a diagnosis and to begin a treatment, but the prognosis remains poor. PLG seems to have a different molecular and immunohistochemical pattern compared with intraparenchymal malignant gliomas.

scholarly journals Effect of Injection Pressure of Infiltration Anesthesia to the Jawbone

2016 ◽  
Vol 63 (3) ◽  
pp. 131-138 ◽  
Author(s):  
Kenji Yoshida ◽  
Eri Tanaka ◽  
Hiroyoshi Kawaai ◽  
Shinya Yamazaki
Keyword(s):  
Local Anesthetic ◽  
White Male ◽  
Injection Pressure ◽  
Time Interval ◽  
Time Intervals ◽  
Lidocaine Concentration ◽  
The Mean ◽  
High Concentrations ◽  
Infiltration Anesthesia ◽  
Local Anesthetic Infiltration

To obtain effective infiltration anesthesia in the jawbone, high concentrations of local anesthetic are needed. However, to reduce pain experienced by patients during local anesthetic administration, low-pressure injection is recommended for subperiosteal infiltration anesthesia. Currently, there are no studies regarding the effect of injection pressure on infiltration anesthesia, and a standard injection pressure has not been clearly determined. Hence, the effect of injection pressure of subperiosteal infiltration anesthesia on local anesthetic infiltration to the jawbone was considered by directly measuring lidocaine concentration in the jawbone. Japanese white male rabbits were used as test animals. After inducing general anesthesia with oxygen and sevoflurane, cannulation to the femoral artery was performed and arterial pressure was continuously recorded. Subperiosteal infiltration anesthesia was performed by injecting 0.5 mL of 2% lidocaine containing 1/80,000 adrenaline, and injection pressure was monitored by a pressure transducer for 40 seconds. After specified time intervals (10, 20, 30, 40, 50, and 60 minutes), jawbone and blood samples were collected, and the concentration of lidocaine at each time interval was measured. The mean injection pressure was divided into 4 groups (100 ± 50 mm Hg, 200 ± 50 mm Hg, 300 ± 50 mm Hg, and 400 ± 50 mm Hg), and comparison statistical analysis between these 4 groups was performed. No significant change in blood pressure during infiltration anesthesia was observed in any of the 4 groups. Lidocaine concentration in the blood and jawbone were highest 10 minutes after the infiltration anesthesia in all 4 groups and decreased thereafter. Lidocaine concentration in the jawbone increased as injection pressure increased, while serum lidocaine concentration was significantly lower. This suggests that when injection pressure of subperiosteal infiltration anesthesia is low, infiltration of local anesthetic to the jawbone may be reduced, while transfer to oral mucosa and blood may be increased.

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