317 research outputs found
Sparse representation of sounds in the unanesthetized auditory cortex
How do neuronal populations in the auditory cortex represent acoustic stimuli? Although sound-evoked neural responses in the anesthetized auditory cortex are mainly transient, recent experiments in the unanesthetized preparation have emphasized subpopulations with other response properties. To quantify the relative contributions of these different subpopulations in the awake preparation, we have estimated the representation of sounds across the neuronal population using a representative ensemble of stimuli. We used cell-attached recording with a glass electrode, a method for which single-unit isolation does not depend on neuronal activity, to quantify the fraction of neurons engaged by acoustic stimuli (tones, frequency modulated sweeps, white-noise bursts, and natural stimuli) in the primary auditory cortex of awake head-fixed rats. We find that the population response is sparse, with stimuli typically eliciting high firing rates (>20 spikes/second) in less than 5% of neurons at any instant. Some neurons had very low spontaneous firing rates (<0.01 spikes/second). At the other extreme, some neurons had driven rates in excess of 50 spikes/second. Interestingly, the overall population response was well described by a lognormal distribution, rather than the exponential distribution that is often reported. Our results represent, to our knowledge, the first quantitative evidence for sparse representations of sounds in the unanesthetized auditory cortex. Our results are compatible with a model in which most neurons are silent much of the time, and in which representations are composed of small dynamic subsets of highly active neurons
Evaluation of pressurized water cleaning systems for hardware refurbishment
Historically, refurbishment processes for RSRM motor cases and components have employed environmentally harmful materials. Specifically, vapor degreasing processes consume and emit large amounts of ozone depleting compounds. This program evaluates the use of pressurized water cleaning systems as a replacement for the vapor degreasing process. Tests have been conducted to determine if high pressure water washing, without any form of additive cleaner, is a viable candidate for replacing vapor degreasing processes. This paper discusses the findings thus far of Engineering Test Plan - 1168 (ETP-1168), 'Evaluation of Pressurized Water Cleaning Systems for Hardware Refurbishment.
Neural Decision Boundaries for Maximal Information Transmission
We consider here how to separate multidimensional signals into two
categories, such that the binary decision transmits the maximum possible
information transmitted about those signals. Our motivation comes from the
nervous system, where neurons process multidimensional signals into a binary
sequence of responses (spikes). In a small noise limit, we derive a general
equation for the decision boundary that locally relates its curvature to the
probability distribution of inputs. We show that for Gaussian inputs the
optimal boundaries are planar, but for non-Gaussian inputs the curvature is
nonzero. As an example, we consider exponentially distributed inputs, which are
known to approximate a variety of signals from natural environment.Comment: 5 pages, 3 figure
A Fokker-Planck formalism for diffusion with finite increments and absorbing boundaries
Gaussian white noise is frequently used to model fluctuations in physical
systems. In Fokker-Planck theory, this leads to a vanishing probability density
near the absorbing boundary of threshold models. Here we derive the boundary
condition for the stationary density of a first-order stochastic differential
equation for additive finite-grained Poisson noise and show that the response
properties of threshold units are qualitatively altered. Applied to the
integrate-and-fire neuron model, the response turns out to be instantaneous
rather than exhibiting low-pass characteristics, highly non-linear, and
asymmetric for excitation and inhibition. The novel mechanism is exhibited on
the network level and is a generic property of pulse-coupled systems of
threshold units.Comment: Consists of two parts: main article (3 figures) plus supplementary
text (3 extra figures
Definitions of disease burden across the spectrum of metastatic castration-sensitive prostate cancer: comparison by disease outcomes and genomics
BACKGROUND: Several definitions have attempted to stratify metastatic castrate-sensitive prostate cancer (mCSPC) into low and high-volume states. However, at this time, comparison of these definitions is limited. Here we aim to compare definitions of metastatic volume in mCSPC with respect to clinical outcomes and mutational profiles. METHODS: We performed a retrospective review of patients with biochemically recurrent or mCSPC whose tumors underwent somatic targeted sequencing. 294 patients were included with median follow-up of 58.3 months. Patients were classified into low and high-volume disease per CHAARTED, STAMPEDE, and two numeric (≤3 and ≤5) definitions. Endpoints including radiographic progression-free survival (rPFS), time to development of castration resistance (tdCRPC), and overall survival (OS) were evaluated with Kaplan-Meier survival curves and log-rank test. The incidence of driver mutations between definitions were compared. RESULTS: Median OS and tdCRPC were shorter for high-volume than low-volume disease for all four definitions. In the majority of patients (84.7%) metastatic volume classification did not change across all four definitions. High volume disease was significantly associated with worse OS for all four definitions (CHAARTED: HR 2.89; p < 0.01, STAMPEDE: HR 3.82; p < 0.01, numeric ≤3: HR 4.67; p < 0.01, numeric ≤5: HR 3.76; p < 0.01) however, were similar for high (p = 0.95) and low volume (p = 0.79) disease across all four definitions. Those with discordant classification tended to have more aggressive clinical behavior and mutational profiles. Patients with low-volume disease and TP53 mutation experienced a more aggressive course with rPFS more closely mirroring high-volume disease. CONCLUSIONS: The spectrum of mCSPC was confirmed across four different metastatic definitions for clinical endpoints and genetics. All definitions were generally similar in classification of patients, outcomes, and genetic makeup. Given these findings, the simplicity of numerical definitions might be preferred, especially when integrating metastasis directed therapy. Incorporation of tumor genetics may allow further refinement of current metastatic definitions
Pain control after total knee arthroplasty: a randomized trial comparing local infiltration anesthesia and continuous femoral block
Local infiltration analgesia (LIA) is a new multimodal wound infiltration method. It
has attracted growing interest in recent years and is widely used all over the world for
treating postoperative pain after knee and hip arthroplasty. This method is based on
systematic infiltration of a mixture of ropivacaine, a long acting local anesthetic,
ketorolac, a cyclooxygenase inhibitor (NSAID), and adrenalin around all structures
subject to surgical trauma inknee and hip arthroplasty.
Two patient cohorts of 40 patients scheduled for elective total knee arthroplasty
(TKA) and 15 patients scheduled for total hip arthroplasty (THA) contributed to the
work presented in this thesis. In a randomized trial the efficacy of LIA in TKA with
regard to pain at rest and upon movement was compared to femoral block. Both
methods result in a high quality pain relief and similar morphine consumption, but
fewer patients in the LIA group reported pain of 7/10 on any occasion during the 24 h
monitoring period (paper I).
In the same patient cohort the maximal total plasma concentration of ropivacaine was
below the established toxic threshold for most patients although a few reached
potentially toxic concentrations of 1.4-1.7 mg/L. The time to maximal detected
plasma concentration was around 4-6 h after release of tourniquet in TKA (paper II).
All patients in the THA cohort were subjected to the routine LIA protocol. In these
patients both the total and unbound plasma concentration of ropivacaine was
determined. The concentration was below the established toxic threshold. As
ropivacaine binds to a-1 acid glycoprotein(AAG) we assessed the possibility that
increased AAG may decrease the unbound concentration of ropivacaine. A40 %
increase in AAG was detected during the first 24 h after surgery, however the
fraction of unbound ropivacaine remained the same. There was a trend towards
increased C max of ropivacaine with increasing age and decreasing creatinine
clearance but the statistical power was too low to draw any conclusion (paper III).
Administration of 30mg ketorolac according to the LIA protocol both in TKA and
THA resulted in a similar Cmax as previously reported after 10 mg intramuscular
ketorolac (paper II, paper IV). Neither age, nor body weight or BMI, nor creatinine
clearance, correlates to maximal ketorolac plasma concentration or total exposure to
ketorolac (AUC) (paper IV).
In conclusion, LIA provides good postoperative analgesia which is similar to femoral
block after total knee arthroplasty. The plasma concentration of ropivacaine seems to
be below toxic levels in most TKA patients. The unbound plasma concentration of
ropivcaine in THA seems to be below the toxic level.
The use of ketorolac in LIA may not be safer than other routes of administration, and
similar restrictions should be applied in patients at risk of developing side effects
Heart rate variability in non-apneic snorers and controls before and after continuous positive airway pressure
BACKGROUND: We hypothesized that sympathetic nervous system activity (SNSA) is increased and parasympathetic nervous system activity (PNSA) is decreased during non-rapid eye movement (NREM) sleep in non-apneic, otherwise healthy, snoring individuals compared to control. Moreover, we hypothesized that these alterations in snoring individuals would be more evident during non-snoring than snoring when compared to control. METHODS: To test these hypotheses, heart rate variability was used to measure PNSA and SNSA in 11 normotensive non-apneic snorers and 12 control subjects before and 7-days after adapting to nasal continuous positive airway pressure (nCPAP). RESULTS: Our results showed that SNSA was increased and PNSA was decreased in non-apneic snorers during NREM compared to control. However, these changes were only evident during the study in which snoring was eliminated with nCPAP. Conversely, during periods of snoring SNSA and PNSA were similar to measures obtained from the control group. Additionally, within the control group, SNSA and PNSA did not vary before and after nCPAP application. CONCLUSION: Our findings suggest that long-lasting alterations in autonomic function may exist in snoring subjects that are otherwise healthy. Moreover, we speculate that because of competing inputs (i.e. inhibitory versus excitatory inputs) to the autonomic nervous system during snoring, the full impact of snoring on autonomic function is most evident during non-snoring periods
Noise Suppression and Surplus Synchrony by Coincidence Detection
The functional significance of correlations between action potentials of
neurons is still a matter of vivid debates. In particular it is presently
unclear how much synchrony is caused by afferent synchronized events and how
much is intrinsic due to the connectivity structure of cortex. The available
analytical approaches based on the diffusion approximation do not allow to
model spike synchrony, preventing a thorough analysis. Here we theoretically
investigate to what extent common synaptic afferents and synchronized inputs
each contribute to closely time-locked spiking activity of pairs of neurons. We
employ direct simulation and extend earlier analytical methods based on the
diffusion approximation to pulse-coupling, allowing us to introduce precisely
timed correlations in the spiking activity of the synaptic afferents. We
investigate the transmission of correlated synaptic input currents by pairs of
integrate-and-fire model neurons, so that the same input covariance can be
realized by common inputs or by spiking synchrony. We identify two distinct
regimes: In the limit of low correlation linear perturbation theory accurately
determines the correlation transmission coefficient, which is typically smaller
than unity, but increases sensitively even for weakly synchronous inputs. In
the limit of high afferent correlation, in the presence of synchrony a
qualitatively new picture arises. As the non-linear neuronal response becomes
dominant, the output correlation becomes higher than the total correlation in
the input. This transmission coefficient larger unity is a direct consequence
of non-linear neural processing in the presence of noise, elucidating how
synchrony-coded signals benefit from these generic properties present in
cortical networks
A Neurocomputational Model of Stimulus-Specific Adaptation to Oddball and Markov Sequences
Stimulus-specific adaptation (SSA) occurs when the spike rate of a neuron decreases with repetitions of the same stimulus, but recovers when a different stimulus is presented. It has been suggested that SSA in single auditory neurons may provide information to change detection mechanisms evident at other scales (e.g., mismatch negativity in the event related potential), and participate in the control of attention and the formation of auditory streams. This article presents a spiking-neuron model that accounts for SSA in terms of the convergence of depressing synapses that convey feature-specific inputs. The model is anatomically plausible, comprising just a few homogeneously connected populations, and does not require organised feature maps. The model is calibrated to match the SSA measured in the cortex of the awake rat, as reported in one study. The effect of frequency separation, deviant probability, repetition rate and duration upon SSA are investigated. With the same parameter set, the model generates responses consistent with a wide range of published data obtained in other auditory regions using other stimulus configurations, such as block, sequential and random stimuli. A new stimulus paradigm is introduced, which generalises the oddball concept to Markov chains, allowing the experimenter to vary the tone probabilities and the rate of switching independently. The model predicts greater SSA for higher rates of switching. Finally, the issue of whether rarity or novelty elicits SSA is addressed by comparing the responses of the model to deviants in the context of a sequence of a single standard or many standards. The results support the view that synaptic adaptation alone can explain almost all aspects of SSA reported to date, including its purported novelty component, and that non-trivial networks of depressing synapses can intensify this novelty response
- …