50 research outputs found
Validation of a brief telephone battery for neurocognitive assessment of patients with pulmonary arterial hypertension
BACKGROUND: The effects of pulmonary arterial hypertension on brain function are not understood, despite patients' frequent complaints of cognitive difficulties. Using clinical instruments normally administered during standard in-person assessment of neurocognitive function in adults, we assembled a battery of tests designed for administration over the telephone. The purpose was to improve patient participation, facilitate repeated test administration, and reduce the cost of research on the neuropsychological consequences of acute and chronic cardiorespiratory diseases. We undertook this study to validate telephone administration of the tests. METHODS: 23 adults with pulmonary arterial hypertension underwent neurocognitive assessment using both standard in-person and telephone test administration, and the results of the two methods compared using interclass correlations. RESULTS: For most of the tests in the battery, scores from the telephone assessment correlated strongly with those obtained by in-person administration of the same tests. Interclass correlations between 0.5 and 0.8 were observed for tests that assessed attention, memory, concentration/working memory, reasoning, and language/crystallized intelligence (p ≤ 0.05 for each). Interclass correlations for the Hayling Sentence Completion test of executive function approached significance (p = 0.09). All telephone tests were completed within one hour. CONCLUSION: Administration of this neurocognitive test battery by telephone should facilitate assessment of neuropsychological deficits among patients with pulmonary arterial hypertension living across broad geographical areas, and may be useful for monitoring changes in neurocognitive function in response to PAH-specific therapy or disease progression
Long-Term Activity-Dependent Plasticity of Action Potential Propagation Delay and Amplitude in Cortical Networks
Background: The precise temporal control of neuronal action potentials is essential for regulating many brain functions. From the viewpoint of a neuron, the specific timings of afferent input from the action potentials of its synaptic partners determines whether or not and when that neuron will fire its own action potential. Tuning such input would provide a powerful mechanism to adjust neuron function and in turn, that of the brain. However, axonal plasticity of action potential timing is counter to conventional notions of stable propagation and to the dominant theories of activity-dependent plasticity focusing on synaptic efficacies. Methodology/Principal Findings: Here we show the occurrence of activity-dependent plasticity of action potentia
Intra-household agreement of urinary elemental concentrations in Tanzania and Kenya: potential surrogates in case–control studies
Element deficiencies and excesses play important roles in non-communicable disease aetiology. When investigating their roles in epidemiologic studies without prospective designs, reverse-causality limits the utility of transient biomarkers in cases. This study aimed to investigate whether surrogate participants may provide viable proxies by assessing concentration correlations within households. We obtained spot urine samples from 245 Tanzanian and Kenyan adults (including 101 household pairs) to investigate intra-household correlations of urinary elements (As, Ba, Ca, Cd, Co, Cs, Cu, Fe, Li, Mn, Mo, Ni, Pb, Rb, S, Se, Sr, Tl, V and Zn) and concentrations (also available for: Bi, Ce, Sb, Sn and U) relative to external population-levels and health-based values. Moderate-strong correlations were observed for As (r = 0.65), Cs (r = 0.67), Li (r = 0.56), Mo (r = 0.57), Se (r = 0.68) and Tl (r = 0.67). Remaining correlations were <0.41. Median Se concentrations in Tanzania (29 µg/L) and Kenya (24 µg/L) were low relative to 5738 Canadians (59 µg/L). Exceedances (of reference 95th percentiles) were observed for: Co, Mn, Mo, Ni and U. Compared to health-based values, exceedances were present for As, Co, Mo and Se but deficiencies were also present for Mo and Se. For well correlated elements, household members in East African settings provide feasible surrogate cases to investigate element deficiencies/excesses in relation to non-communicable diseases
Molecular Constraints on Synaptic Tagging and Maintenance of Long-Term Potentiation: A Predictive Model
Protein synthesis-dependent, late long-term potentiation (LTP) and depression
(LTD) at glutamatergic hippocampal synapses are well characterized examples of
long-term synaptic plasticity. Persistent increased activity of the enzyme
protein kinase M (PKM) is thought essential for maintaining LTP. Additional
spatial and temporal features that govern LTP and LTD induction are embodied in
the synaptic tagging and capture (STC) and cross capture hypotheses. Only
synapses that have been "tagged" by an stimulus sufficient for LTP and learning
can "capture" PKM. A model was developed to simulate the dynamics of key
molecules required for LTP and LTD. The model concisely represents
relationships between tagging, capture, LTD, and LTP maintenance. The model
successfully simulated LTP maintained by persistent synaptic PKM, STC, LTD, and
cross capture, and makes testable predictions concerning the dynamics of PKM.
The maintenance of LTP, and consequently of at least some forms of long-term
memory, is predicted to require continual positive feedback in which PKM
enhances its own synthesis only at potentiated synapses. This feedback
underlies bistability in the activity of PKM. Second, cross capture requires
the induction of LTD to induce dendritic PKM synthesis, although this may
require tagging of a nearby synapse for LTP. The model also simulates the
effects of PKM inhibition, and makes additional predictions for the dynamics of
CaM kinases. Experiments testing the above predictions would significantly
advance the understanding of memory maintenance.Comment: v3. Minor text edits to reflect published versio
Phenomenological models of synaptic plasticity based on spike timing
Synaptic plasticity is considered to be the biological substrate of learning and memory. In this document we review phenomenological models of short-term and long-term synaptic plasticity, in particular spike-timing dependent plasticity (STDP). The aim of the document is to provide a framework for classifying and evaluating different models of plasticity. We focus on phenomenological synaptic models that are compatible with integrate-and-fire type neuron models where each neuron is described by a small number of variables. This implies that synaptic update rules for short-term or long-term plasticity can only depend on spike timing and, potentially, on membrane potential, as well as on the value of the synaptic weight, or on low-pass filtered (temporally averaged) versions of the above variables. We examine the ability of the models to account for experimental data and to fulfill expectations derived from theoretical considerations. We further discuss their relations to teacher-based rules (supervised learning) and reward-based rules (reinforcement learning). All models discussed in this paper are suitable for large-scale network simulations
Calcium control of triphasic hippocampal STDP
Bush D, Jin Y. Calcium control of triphasic hippocampal STDP. Journal of Computational Neuroscience. 2012;33(3):495-514.Synaptic plasticity is believed to represent the neural correlate of mammalian learning and memory function. It has been demonstrated that changes in synaptic conductance can be induced by approximately synchronous pairings of pre- and post- synaptic action potentials delivered at low frequencies. It has also been established that NMDAr-dependent calcium influx into dendritic spines represents a critical signal for plasticity induction, and can account for this spike-timing dependent plasticity (STDP) as well as experimental data obtained using other stimulation protocols. However, subsequent empirical studies have delineated a more complex relationship between spike-timing, firing rate, stimulus duration and post-synaptic bursting in dictating changes in the conductance of hippocampal excitatory synapses. Here, we present a detailed biophysical model of single dendritic spines on a CA1 pyramidal neuron, describe the NMDAr-dependent calcium influx generated by different stimulation protocols, and construct a parsimonious model of calcium driven kinase and phosphatase dynamics that dictate the probability of stochastic transitions between binary synaptic weight states in a Markov model. We subsequently demonstrate that this approach can account for a range of empirical observations regarding the dynamics of synaptic plasticity induced by different stimulation protocols, under regimes of pharmacological blockade and metaplasticity. Finally, we highlight the strengths and weaknesses of this parsimonious, unified computational synaptic plasticity model, discuss differences between the properties of cortical and hippocampal plasticity highlighted by the experimental literature, and the manner in which further empirical and theoretical research might elucidate the cellular basis of mammalian learning and memory function
A Brief Period of Epileptiform Activity Strengthens Excitatory Synapses in the Rat Hippocampus in Vitro
A comparison of Tau and 14-3-3 protein in the diagnosis of Creitzfeldt-Jakob disease
OBJECTIVE:
To compare the respective efficiency of CSF tau (quantitative) and CSF 14-3-3 protein (qualitative) in the diagnosis of prion disease.
METHODS:
We made measurements on 420 live subjects, who subsequently underwent a postmortem neuropathology examination, including protein chemistry, immunohistochemistry, and histology. We performed tau by ELISA. We detected 14-3-3 protein by Western blot. Both assays were optimized for maximum efficiency (accuracy).
RESULTS:
We found tau and 14-3-3 proteins to be closely correlated, but tau had a significantly better ability to predict disease status than 14-3-3 protein. Also, tau distinguished disease status at least as well as when both assays' results are combined in a variety of ways. Importantly, the area under the receiver operating characteristic curve for tau (0.82) was significantly larger than that for 14-3-3 protein (0.68) (p < 0.001). Diagnostic test statistics are provided for the study subjects with 58.3% prevalence, and for a more typical, nonselected, 7.5% prevalence as received by our center.
CONCLUSION:\ud
In this study, tau is superior to 14-3-3 protein as a marker in the diagnosis of Creutzfeldt-Jakob disease, and is as efficient singly compared to a variety of combinations with 14-3-3 protein. This is the first study of this magnitude to examine prion disease diagnostic tests in a carefully characterized patient population with detailed statistical evaluation