The Impact of Frequency Scale on the Response Sensitivity and Reliability of Cortical Neurons to 1/f? Input Signals.
ABSTRACT: What type of principle features intrinsic inside of the fluctuated input signals could drive neurons with the maximal excitations is one of the crucial neural coding issues. In this article, we examined both experimentally and theoretically the cortical neuronal responsivity (including firing rate and spike timing reliability) to input signals with different intrinsic correlational statistics (e.g., white-type noise, showed 1/f0 power spectrum, pink noise 1/f, and brown noises 1/f2) and different frequency ranges. Our results revealed that the response sensitivity and reliability of cortical neurons is much higher in response to 1/f noise stimuli with long-term correlations than 1/f0 with short-term correlations for a broad frequency range, and also higher than 1/f2 for all frequency ranges. In addition, we found that neuronal sensitivity diverges to opposite directions for 1/f noise comparing with 1/f0 white noise as a function of cutoff frequency of input signal. As the cutoff frequency is progressively increased from 50 to 1,000 Hz, the neuronal responsiveness increased gradually for 1/f noise, while decreased exponentially for white noise. Computational simulations of a general cortical model revealed that, neuronal sensitivity and reliability to input signal statistics was majorly dominated by fast sodium inactivation, potassium activation, and membrane time constants.
Project description:We investigated the nutritional effects on carcass traits, gene expression and DNA methylation in a three generation Large White pig feeding experiment. A group of experimental (E) F0 boars were fed a standard diet supplemented with high amounts of methylating micronutrients whereas a control group (C) of F0 boars received a standard diet. These differentially fed F0 boars sired F1 boars which then sired 60 F2 pigs. Carcass traits were compared between 36 F2 descendants of E F0 boars and 24 F2 descendants of C F0 boars. The two F2 offspring groups differed with respect to backfat percentage (P?=?0.03) and tended to differ with respect to adipose tissue (P?=?0.09), fat thickness at the 10(th) rib (P?=?0.08) and at the croup (P?=?0.09) as well as percentages of shoulder (P?=?0.07). Offspring from the experimental F0 boars had a higher percentage of shoulder and were leaner compared to the control group. Gene expression profiles showed significant twofold differences in mRNA level between 8 C F2 offspring and 8 E F2 offspring for 79, 64 and 53 genes for muscle, liver and kidney RNA, respectively. We found that in liver and muscle respective pathways of lipid metabolism and metabolic pathway were over-represented for the differentially expressed genes between these groups. A DNA methylation analysis in promoters of differentially expressed genes indicated a significant difference in DNA methylation at the IYD gene. If these responses on carcass traits, gene expression and DNA methylation withstand verification and can indeed be attributed to transgenerational epigenetic inheritance, it would open up pioneering application in pork production and would have implications for human health.
Project description:Cortical neurons are often classified by current-frequency relationship. Such a static description is inadequate to interpret neuronal responses to time-varying stimuli. Theoretical studies suggested that single-cell dynamical response properties are necessary to interpret ensemble responses to fast input transients. Further, it was shown that input-noise linearizes and boosts the response bandwidth, and that the interplay between the barrage of noisy synaptic currents and the spike-initiation mechanisms determine the dynamical properties of the firing rate. To test these model predictions, we estimated the linear response properties of layer 5 pyramidal cells by injecting a superposition of a small-amplitude sinusoidal wave and a background noise. We characterized the evoked firing probability across many stimulation trials and a range of oscillation frequencies (1-1000 Hz), quantifying response amplitude and phase-shift while changing noise statistics. We found that neurons track unexpectedly fast transients, as their response amplitude has no attenuation up to 200 Hz. This cut-off frequency is higher than the limits set by passive membrane properties (approximately 50 Hz) and average firing rate (approximately 20 Hz) and is not affected by the rate of change of the input. Finally, above 200 Hz, the response amplitude decays as a power-law with an exponent that is independent of voltage fluctuations induced by the background noise.
Project description:<h4>Background & aims</h4>Identification of disease severity remains a challenge in the management of non-alcoholic steatohepatitis (NASH). Cytokeratin-18 (CK18), is a recently developed non-invasive biomarker for NASH. We aimed to assess the performance of CK18 in disease severity prediction among Taiwanese NASH patients.<h4>Methods</h4>A total of 76 biopsy-proven NASH patients (54 males, age = 41.0 ± 13.5 years) were consecutively recruited. The optimal cutoff values of CK18 for each stage of fibrosis were correlated with their histopathological manifestations.<h4>Results</h4>There were 23 (30.3%) patients of Metavir fibrosis stage 0 (F0), 32 (42.1%) patients of F1, 14 (18.4%) patients of F2, and 7 (9.2%) patients of F3-4, respectively. The CK18 levels among those patients of F0, F1, F2, F3-4 were 86.7 ± 75.6 U/L, 122.4 ± 123.8 U/L, 160.7 ± 120.4 U/L, and 507.3 ± 343 U/L, respectively (trend for P<0.001). The adjusted optimal cutoff value for F2 prediction was 312.5 U/L, yielding the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the accuracy of 96.4%, 28.6%, 77.9%, 75%, and 77.6%, respectively (P = 0.009). For the prediction of advanced fibrosis (F3-4), the adjusted optimal cutoff value was 374.5 U/L, yielding the sensitivity, specificity, PPV, NPV, and the accuracy of 97.1%, 54.1%, 95.7%, 66.7%, and 77.6%, respectively (P = 0.003). Among those patients without hyperuricemia, the PPV, NPV, and accuracy of CK18 reached 100%, 95.8%, and 96%, respectively (P<0.001).<h4>Conclusions</h4>CK18 combined with uric acid measurement is a promising non-invasive biomarker for prediction of disease severity in NASH patients.<h4>Trial registration</h4>ClinicalTrials.gov NCT01068444.
Project description:Cochlear implant (CI) users have been shown to benefit from residual low-frequency hearing, specifically in pitch related tasks. It remains unclear whether this benefit is dependent on fundamental frequency (F0) or other acoustic cues. Three experiments were conducted to determine the role of F0, as well as its frequency modulated (FM) and amplitude modulated (AM) components, in speech recognition with a competing voice. In simulated CI listeners, the signal-to-noise ratio was varied to estimate the 50% correct response. Simulation results showed that the F0 cue contributes to a significant proportion of the benefit seen with combined acoustic and electric hearing, and additionally that this benefit is due to the FM rather than the AM component. In actual CI users, sentence recognition scores were collected with either the full F0 cue containing both the FM and AM components or the 500-Hz low-pass speech cue containing the F0 and additional harmonics. The F0 cue provided a benefit similar to the low-pass cue for speech in noise, but not in quiet. Poorer CI users benefited more from the F0 cue than better users. These findings suggest that F0 is critical to improving speech perception in noise in combined acoustic and electric hearing.
Project description:We investigated the nutritional effects on gene expression in a three generation Large White pig feeding experiment. A group of experimental (E) F0 boars were fed a standard diet supplemented with high amounts of methylating micronutrients whereas a control (C) group of F0 boars received a standard diet. These differentially fed F0 boars sired F1 boars which then sired 60 F2 pigs. Gene expression profiles showed significant twofold differences in mRNA level between 8 C F2 offspring and 8 E F2 offspring for 79, 64 and 53 probes for muscle, liver and kidney RNA, respectively. We found that in liver and muscle respective pathways of lipid metabolism and metabolic pathway were over-represented for the differentially expressed genes. Gene expression in three tissue types of F2 offspring from differentially fed F0 boars were measured. F0 boars received either a standard diet or a standard diet supplemented with methylating micronutrients. These boars produced the F1 males that received exclusively the standard diet. The F2 generation was then produced with these F1 boars. Gene expression was measured in liver, skeletal muscle and kidney of 8 F2 pigs derived from F0 boars that received the standard diet and of 8 F2 pigs derived from those F0 boars that received the standard diet supplemented with methylating micronutrients.
Project description:A fundamental property of brain function is that the spiking activity of cortical neurons is variable and that some of this variability is correlated between neurons. Correlated activity not due to the stimulus arises from shared input but the neuronal circuit mechanisms that result in these noise correlations are not fully understood. Here we tested in the visual system if correlated variability in mid-level area V4 of visual cortex is altered following extensive lesions of primary visual cortex (V1). To this end we recorded longitudinally the neuronal correlations in area V4 of two behaving macaque monkeys before and after a V1 lesion while the monkeys fixated a grey screen. We found that the correlations of neuronal activity survived the lesions in both monkeys. In one monkey, the correlation of multi-unit spiking signals was strongly increased in the first week post-lesion, while in the second monkey, correlated activity was slightly increased, but not greater than some week-by-week fluctuations observed. The typical drop-off of inter-neuronal correlations with cortical distance was preserved after the lesion. Therefore, as V4 noise correlations remain without feedforward input from V1, these results suggest instead that local and/or feedback input seem to be necessary for correlated activity.
Project description:An important aspect of speech perception is the ability to group or select formants using cues in the acoustic source characteristics--for example, fundamental frequency (F0) differences between formants promote their segregation. This study explored the role of more radical differences in source characteristics. Three-formant (F1+F2+F3) synthetic speech analogues were derived from natural sentences. In Experiment 1, F1+F3 were generated by passing a harmonic glottal source (F0 = 140 Hz) through second-order resonators (H1+H3); in Experiment 2, F1+F3 were tonal (sine-wave) analogues (T1+T3). F2 could take either form (H2 or T2). In some conditions, the target formants were presented alone, either monaurally or dichotically (left ear = F1+F3; right ear = F2). In others, they were accompanied by a competitor for F2 (F1+F2C+F3; F2), which listeners must reject to optimize recognition. Competitors (H2C or T2C) were created using the time-reversed frequency and amplitude contours of F2. Dichotic presentation of F2 and F2C ensured that the impact of the competitor arose primarily through informational masking. In the absence of F2C, the effect of a source mismatch between F1+F3 and F2 was relatively modest. When F2C was present, intelligibility was lowest when F2 was tonal and F2C was harmonic, irrespective of which type matched F1+F3. This finding suggests that source type and context, rather than similarity, govern the phonetic contribution of a formant. It is proposed that wideband harmonic analogues are more effective informational maskers than narrowband tonal analogues, and so become dominant in across-frequency integration of phonetic information when placed in competition.
Project description:The purpose of this study was to investigate whether paternal high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa to alter metabolism in the F1 and F2 generation offspring White adipose tissue mRNA expression profiling of F2-female offspring from F0-founders fed either a chow or a chronic HFD challenged. Adult females were challenged or not a high-fat diet for 12 weeks. White adipose tissue was dissected at an endpoint experiment. Rats were subjected to 4 hours fasting prior to anesthesia with pentobarbital and tissue collection. Overall design: F2-females Sprague-Dawley rats from F0 founders fed or not a high-fat diet were also subjeted to high-fat consumption for 12 weeks. At terminal experiment, gonadal white adipose from 6 to 7 animals per group was collected, prepared and subjeted to the array analysis.
Project description:Speech intelligibility was measured for sentences presented in spectrally matched steady noise, single-talker interference, or speech-modulated noise. The stimuli were unfiltered or were low-pass (LP) (1200 Hz cutoff) or high-pass (HP) (1500 Hz cutoff) filtered. The cutoff frequencies were selected to produce equal performance in both LP and HP conditions in steady noise and to limit access to the temporal fine structure of resolved harmonics in the HP conditions. Masking release, or the improvement in performance between the steady noise and single-talker interference, was substantial with no filtering. Under LP and HP filtering, masking release was roughly equal but was much less than in unfiltered conditions. When the average F0 of the interferer was shifted lower than that of the target, similar increases in masking release were observed under LP and HP filtering. Similar LP and HP results were also obtained for the speech-modulated-noise masker. The findings are not consistent with the idea that pitch conveyed by the temporal fine structure of low-order harmonics plays a crucial role in masking release. Instead, any reduction in speech redundancy, or manipulation that increases the target-to-masker ratio necessary for intelligibility to beyond around 0 dB, may result in reduced masking release.
Project description:The variable responses of sensory neurons tend to be weakly correlated (spike-count correlation, rsc). This is widely thought to reflect noise in shared afferents, in which case rsc can limit the reliability of sensory coding. However, it could also be due to feedback from higher-order brain regions. Currently, the relative contributions of these sources are unknown. We addressed this by recording from populations of V1 neurons in macaques performing different discrimination tasks involving the same visual input. We found that the structure of rsc (the way rsc varied with neuronal stimulus preference) changed systematically with task instruction. Therefore, even at the earliest stage in the cortical visual hierarchy, rsc structure during task performance primarily reflects feedback dynamics. Consequently, previous proposals for how rsc constrains sensory processing need not apply. Furthermore, we show that correlations between the activity of single neurons and choice depend on feedback engaged by the task.