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PubMed1987

Auditory neurophonic responses to amplitude-modulated tones: transfer functions and forward masking.

Two auditory neurophonic responses - one recorded from the scalp (frequency following response or FFR) and one from the auditory nerve (auditory nerve neurophonic or ANN) - were obtained following stimulation of the cat cochlea with amplitude-modulated (AM) high-frequency tones. The carrier frequencies varied between 2 and 30 kHz. The modulation frequencies varied between 400 and 3000 Hz. The AM responses were compared with pure-tone neurophonic responses. The AM response waveforms were found to have a similar spectral composition, similar rates of adaptation, and similar rates of recovery from forward masking as the comparable pure-tone responses. As with the pure-tone neurophonics, an unmodulated masking stimulus can produce prolonged depression of the probe response. The amount and duration of this depression is dependent upon the level and frequency of the masker. The frequency dependence of the depression is demonstrated by forward masked tuning curves which indicate that the AM responses arise from fiber populations which have restricted characteristic frequency distributions centered on the carrier frequency. Response amplitude as a function of stimulus level (I/O) functions, response amplitude as a function of carrier frequency (carrier transfer functions or CTF) and response amplitude as a function of modulation frequency (modulation transfer functions or MTF) were also measured. It was found that the I/O functions were saturating monotonic functions of stimulus intensity, CTFs were flat for carrier frequencies from 6 to 30 kHz, and MTFs were flat for modulation frequencies from 100 to 1500 Hz. These results are compared with similar data for single units and compound action potentials.

Acoustic Stimulation↗
PubMed1988

Modulation transfer function of efferent neurones in the guinea pig cochlea.

The dynamic properties of single olivocochlear efferent neurones in the guinea pig cochlea were examined using sinusoidally amplitude modulated (AM) pure tones. The neural discharge, when displayed as a cyclic histogram, clearly followed the rapid fluctuations in the continuous input sound. Modulation transfer functions (MTFs) were constructed and in most cases showed a peak in the modulation response (MR) at a modulation frequency (MF) of 100 Hz. At this frequency a gain of as much as 12 dB was evident relative to the 30% modulated input signal. In 24% of neurones however, a large MR was present even at low MFs. This plurality of MTFs may be the result of recorded neurones emanating from a variety of cell bodies of origin. Efferent group delays (mean of 8.2 +/- 1.0 ms) were shorter and more tightly distributed than the minimum onset latency measurements (mean of 24.2 +/- 12.5) made on the same neurones. It seems evident that a post-synaptic potential build is required from the onset of a stimulus to the first spike discharge. This may occur within a single afferent-interneurone(s)-efferent reflex arc. Among a variety of alternative explanations, the observation is consistent with the notion that the olivocochlear neurones receive facilitatory input from higher centres, which is suppressed under barbiturate anaesthesia. Continuous AM signals may allow post-synaptic build up and eliminate the dependence on this higher input and hence yield a short group delay.

Acoustic Stimulation↗
PubMed1990

Temporal modulation transfer functions for single neurons in the auditory midbrain of the leopard frog. Intensity and carrier-frequency dependence.

The sensitivity for amplitude modulation was investigated for 77 neurons from the auditory midbrain of the leopard frog. The results show that tuning to modulation frequencies occurs in about one-third of the units but is quite varied in its appearance. Two slightly differing characterizations for this tuning have been used; the overall response or rate-Modulation Transfer Function and the synchronized response or temporal-MTF (tMTF). The relation between the two characterizations is given by the vector-strength. Only one-third of the units showed a vector-strength that was significantly different from zero. Another synchronization measure, the synchronization factor which is based on the auto-coincidence function, was significantly different from zero in about 3/4 of the units. The Best Modulation Frequency (BMF) and tuning band-width were found to be independent of both stimulus intensity and carrier frequency, although the average BMF for band-pass units was slightly higher for the amphibian papilla range of carrier frequencies than for the basilar papilla range (66 Hz vs. 49 Hz). The most frequent BMF for band-pass units was around 55 Hz, this does not correspond with the dominant modulation frequency of the mating call which is around 20 Hz. The synchronization measures were negatively correlated with intensity and independent of carrier frequency. The phase response of the tMTF was used to calculate the group delay. In contrast to the latency of the units the group delay was independent of stimulus intensity.

Animals↗
PubMed1992

Sensitivity of neurons in cat primary auditory cortex to tones and frequency-modulated stimuli. I: Effects of variation of stimulus parameters.

In the primary auditory cortex (AI) of barbiturate-anesthetized cats multi-unit responses to tones and to frequency-modulated (FM) tonal stimuli were analyzed. Characteristic frequency (CF), sharpness of tuning, minimum threshold, and dynamic range of spike count--intensity functions were determined. Minimum threshold and dynamic range were positively correlated. The response functions to unidirectional FM sweeps of varying linear rate of change of frequency (RCF) that traversed the excitatory frequency response areas (FRAs) displayed a variety of shapes. Preferences for fast RCFs (> 1000 kHz/s) were most common. Best RCF was not correlated with measures of sharpness of tuning. Directional preference and sensitivity were quantified by a DS index which varied with RCF. About two-thirds of the multi-unit responses showed a preference for downward sweeps. Directional sensitivity was independent of CF and independent of best RCF. Measurements of latencies of phasic responses to unidirectional FM sweeps of different RCF demonstrated that the discharges of a given multi-unit over its effective RCF range were initiated at the same instantaneous frequency (effective Fi), independent of RCF. Effective Fis fell within the excitatory FRA of a given multi-unit. The relationships of effective Fis to CF show that responses were evoked only when the frequency of the signal was modulated towards CF and not when modulated away from it, and that responses were initiated before the modulation reached CF. Changes in the range and depth of modulation had only minor, if any, effects on RCF response characteristics, FM directional sensitivity, and effective Fis, as long as the beginning and ending frequencies of FM sweeps fell outside a multi-unit's FRA. Stimulus intensity also had only moderate effects on RCF response characteristics and DS. However, effective Fis were influenced in systematic fashions; with increases in intensity, effective Fis to upward and downward sweeps decreased and increased, respectively. Thus, for higher intensities FM responses were initiated at instantaneous frequencies occurring earlier in the signal. The results are compared with previous data on tone and FM sensitivity of auditory neurons in cortical and subcortical structures, and mechanisms of FM rate and directional sensitivity are discussed. The topographic representations of these neuronal properties in AI are reported in the companion report.

Acoustic Stimulation↗
PubMed1994

Temporal coding of 200% amplitude modulated signals in the ventral cochlear nucleus of cat.

The quasiperiodicity in the acoustic waveform in speech and music is a pervasive feature in our acoustic environment. The use of 200% amplitude modulated (AM) signals allows the study of rate and temporal envelope coding using three equal amplitude components, a situation that is frequently approximated in natural vocalizations. The recordings reported here were made in the ventral cochlear nucleus of the cat, a site of auditory signal feature enhancement and the origin of several ascending auditory pathways. The discharge rate vs modulation frequency relation was nearly always all-pass in shape for all unit types indicating that discharge rate is not a code for modulation frequency. Onset cells, especially onset-choppers and onset-I units, exhibited remarkable phase locking to the signal envelope, nearly to the exclusion of phase locking to the AM components. They exhibited lowpass temporal modulation transfer functions (tMTF) that occasionally had corner frequencies greater than 1 kHz. Primary-like, primary-like with notch, and onset-L units all exhibited considerable variability in their coding properties with tMTFs that varied from lowpass to bandpass in shape. The bandpass shape became more frequent with increasing stimulus levels. A common feature in cochlear nucleus units was less sensitivity to the level of the AM stimulus than is present in the auditory nerve. Phase locking to the envelope persisted over a wider range of stimulus levels than rate changes in a subset of the units studied. The tMTFs for a 100% sinusoidally modulated, spectrally-flat noise was similar in amplitude and bandwidth to those obtained for AM stimuli. The tMTF was relatively insensitive to carrier frequencies different than the unit characteristic frequency. AM synchrony vs level curves exhibited systematic shifts that equaled or exceeded dynamic rate shifts that occur with increasing levels of a noise masker. Phase locking to the envelope was robust under a wide variety of signal conditions in all unit types. The ordering of response types based on the maximum of the tMTF is onset-I = onset-chop > choppers = primarylike-with-notch = onset-L > primarylike.

Acoustic Stimulation↗
PubMed1995

Neuronal correlates of perceptual amplitude-modulation detection.

The goal of the present paper is to relate the coding of amplitude modulation (AM) in the auditory pathway to the behavioral detection performance. To address this issue, the detectability of AM was estimated by modelling a single neuron located in the central nucleus of the inferior colliculus (IC). The computational model is based on cochlear nucleus responses and a coincidence detection mechanism. The model replicated the main feature of the neuronal AM transfer function, namely a bandpass function. The IC-unit model was initially tuned to a 200-Hz modulation frequency. A single neurometric function for AM detection at this modulation frequency was generated using a 2-interval, 2-alternative forced-choice paradigm. On each trial of the experiments, AM was taken to be correctly detected by the model if the number of spikes in response to the modulated signal exceeded the number of spikes in an otherwise identical interval that contained an unmodulated signal. Psychometric functions for 4 human subjects were also measured under the same stimulus conditions. Comparison of the simulated neurometric and psychometric functions suggested that there was sufficient information in the rate response of an IC neuron well-tuned in the modulation-frequency domain to support behavioral detection performance.

Acoustic Stimulation↗
PubMed1994

Identification of two cysteine residues that are required for redox modulation of the NMDA subtype of glutamate receptor.

Modulation of NMDA-mediated responses by oxidizing and reducing reagents has been described in a variety of neuronal preparations. Here, we report that NMDA-gated currents of oocytes expressing heteromeric NMDA receptors are also modulated by sulfhydryl redox reagents. Each cysteine residue in the NMDAR1 (NR1) subunit and each conserved NMDAR2 (NR2) cysteine residue in a prototypical subunit (NR2B) was tested for its role in redox modulation. We have identified 2 cysteines in the NR1 subunit that are required for redox modulation of NMDA-gated currents in oocytes expressing NR1-NR2B, NR1-NR2C, or NR1-NR2D receptors. Mutation of these same 2 cysteines also eliminated potentiation by spermine and shifted the IC50 for H+ inhibition and the EC50 for NMDA. Redox modulation of heteromeric NR1-NR2A receptors appeared to be different from that of the other heteromeric receptors, indicating the presence of one or more unique redox modulatory sites on NR1-NR2A receptors.

Animals↗
PubMed1995

Serotonin modulates the voltage dependence of delayed rectifier and Shaker potassium channels in Drosophila photoreceptors.

We describe the in situ modulation of potassium channels in a semi-intact preparation of the Drosophila retina. In whole-cell recordings of photoreceptors, rapidly inactivating Shaker channels are characterized by a conspicuously negative voltage operating range; together with a delayed rectifier, these channels are specifically modulated by the putative efferent neurotransmitter serotonin. Contrary to most potassium channel modulations, serotonin induced a reversible positive shift in the voltage operating range, of +30 mV for the Shaker channels and +10-14 mV for the delayed rectifier. The maximal current amplitudes were unaffected. Modulation was not affected by the subunit-specific Shaker mutations ShE62 and T(1;Y)W32 or a null mutation of the putative modulatory subunit eag. The modulation of both channels was mimicked by intracellularly applied GTP gamma S.

Animals↗
PubMed1989

Fab fragments of monoclonal antibodies protect the human acetylcholine receptor against antigenic modulation caused by myasthenic sera.

The human cell line TE671 produces large amounts of muscle nicotinic acetylcholine receptor (AChR). TE671 cells were used to determine the specificity of antibodies which can increase the internalization rate of AChR (antigenic modulation) and to test procedures for protecting AChR against this mechanism. The half-life of AChR both in the absence and the presence of anti-AChR antibodies was very similar to that of AChR on human muscle cell cultures. The relative contribution of different anti-AChR antibody fractions to the total antigenic modulation capacity of human myasthenic sera was investigated by competition experiments between Fab fragments of anti-AChR monoclonal antibodies (MoAbs) and intact antibodies (MoAb or myasthenic sera). Fab fragments, which do not induce antigenic modulation, were allowed to shield the corresponding regions of the AChR. Intact antibodies were subsequently added. It was found that protection of the main immunogenic region (MIR), but not of a region on the beta-subunit, essentially blocked the modulatory effect of the intact anti-MIR MoAbs, and approximately 80% of that of myasthenic sera. These data suggest that anti-MIR antibodies are mainly responsible for the loss of human AChR via antigenic modulation. Furthermore the observation that Fab fragments of anti-MIR MoAbs can efficiently protect AChR against antigenic modulation may have therapeutic implications.

Animals↗
PubMed1991

CD3 expression, modulation and signalling in T-cell subpopulations from MRL/Mp-lpr/lpr mice.

The expanded T-cell population of MRL/Mp-lpr2lpr mice is abnormal from a variety of standpoints. We have already shown that T-cell receptor expression and modulation are aberrant in the predominant CD4- CD8 (DN) T cell population. To investigate these abnormalities further, we examined CD3 expression and modulation in subpopulations of +/+ and lpr T cells and measured mitogen-induced Ca++ mobilization in DN lpr T cells. We found that expression and modulation of CD3 in CD4hi and CD8hi lpr single positive (SP) T cells are similar to that in +/+ T cells. We have, however, identified additional lpr cell subsets that are CD4lo or CD8lo. Their expression and modulation of CD3 are intermediate, between that of SP and DN lpr T cells. These subpopulations may thus represent a transitional stage between the SP and DN populations. The rapid modulation of CD3 in the DN population does not appear to be merely related to the lack of expression of CD4 or CD8, and may in fact cause (rather than result from) low CD3 expression. In addition, we observed impairment of CA++ mobilization in DN lpr T cells in response to concanavalin A or anti-CD3 antibody. These findings further define the abnormalities of T cells from lpr mice.

Animals↗
PubMed1996

One dimensional chemical shift modulated correlation spectroscopy of single-crystals.

A simple 1D modulation method is presented for determining the spatial correlation of chemical shifts in two different single-crystal orientations. This proposed chemical shift modulated correlation (CSMC) spectroscopy utilizes a Jeener pulse sequence to give 1D spectra containing peaks that are amplitude modulated by the chemical shifts associated with the single-crystal's evolution orientation. Conversely, the spectral frequencies in these 1D CSMC spectra designate the shifts in the crystal's orientation during the detection period. By observing the amplitude modulation of these spectral frequencies, the spatial correlation between the two chemical environments can be established for a specific nucleus from a single 1D spectrum. The CSMC procedure finishes by acquiring a normal 1D static spectrum for the crystal oriented in the evolution direction, thereby providing very accurate evolution frequencies approximated by the amplitude modulation in the CSMC spectra. The CSMC method improves the time efficiency over both the traditional goniometer method and the 2D chemical shift-chemical shift correlation method, and therefore is beneficial for the study of samples with longer T1 values.

Algorithms↗
PubMed2006

Involvement of the medial prefrontal cortex in central cardiovascular modulation in the rat.

The medial prefrontal cortex (MPFC) and specifically its ventral portion (vMPFC) have been reported to modulate autonomic responses. On the cardiovascular system, this modulation is characterized by an influence on arterial blood pressure, regional blood flow as well as cardiac sympathetic and parasympathetic responses. The vMPFC also modulates baroreflex activity. Several neurotransmitters are present in the vMPFC. Among them L-glutamate, acetylcholine and noradrenaline are involved with cardiovascular modulation. In the present review, we describe evidences on the mechanisms involved in the vMPFC-related cardiovascular modulation.

Acetylcholine↗
PubMed2006

Integrated-optic biosensor by electro-optically modulated surface plasmon resonance.

We present a new integrated-optic surface plasmon resonance (SPR) biosensor based on electro-optical modulation. The SPR characteristics for the analyte concentration detection can be electro-optically modulated by applying the voltage on the electrodes of the biosensor fabricated on lithium niobate, which is an excellent electro-optic material. Two measurement methods, electro-optically modulated SPR spectral measurement and electro-optically modulated SPR intensity measurement, are demonstrated and their measurands are the SPR wavelength and the output optical intensity, respectively. Human serum albumin is coated on the gold film surface of the proposed biosensor to detect the concentration of beta-blocker, which is a remedy for heart disease. As the applied voltage increases such that the effective index of guided mode rises, the SPR wavelength shifts toward the long wavelength side and the output optical intensity at the wavelength of 632.8 nm diminishes. The linear regression slope of the relation between the measurand and the applied voltage is dependent on the analyte concentration and can be used to determine the concentration variation. Experimental results measured by the electro-optically modulated SPR methods are compared with those measured by the conventional spectral and intensity methods, and the effects of waveguide width on the biosensor performance are discussed.

Electrodes↗
PubMed2004

alpha2-Adrenergic receptor-mediated modulation of calcium current in neocortical pyramidal neurons.

Noradrenergic projections to the cortex modulate a variety of cortical activities and calcium channels are one likely target for such modulation. We used the whole-cell patch-clamp technique to study noradrenergic modulation of barium currents in acutely dissociated pyramidal neurons from rat sensorimotor cortex. Extracellular application of specific agonists and antagonists revealed that norepinephrine (NE) reduced Ca2+ current. A major component of this modulation was due to activation of alpha2 receptors. Activation of alpha2-adrenergic receptors resulted in a fast, voltage-dependent pathway involving Gi/Go G-proteins. This pathway targeted N- and P-type calcium channels The alpha2 modulation was partially reversed by repeated action potential waveforms (APWs). N- and P-type channels have been implicated in synaptic transmission and activation of afterhyperpolarizations in these cells. Our findings suggest that NE can regulate these cellular processes by mechanisms sensitive to spike activity.

Action Potentials↗
PubMed2004

Load- and cadence-dependent modulation of somatosensory evoked potentials and Soleus H-reflexes during active leg pedaling in humans.

Modulation of transmission in group I muscle afferent pathways to the somatosensory cortex and those to the alpha-motoneuron were investigated during active leg pedaling. Cerebral somatosensory evoked potentials (SEPs) and Soleus (Sol) H-reflexes following posterior tibial nerve stimulation were recorded at four different pedaling phases. The subjects were asked to perform pedaling at three different cadences (30, 45 and 60 rpm with 0.5 kp, cadence task; C-task) and with three different workloads (at 45 rpm with 0.0, 0.5 and 1.0 kp, load task; L-task). In both C- and L-tasks, Sol H-reflexes were modulated in a phase-dependent manner, showing an increase in the power phase and a decrease in the recovery phase. In contrast, the early SEP (P30-N40) components were modulated in a phase-dependent manner when the cadence and load were low. When focusing on the power phases, significant cadence- and load-dependent modulations of the P30-N40 were found, and inversely graded with the cadence and load. The H-reflex was found to be significantly decreased at the highest cadence, i.e., cadence-dependent modulation. In contrast, the H-reflex during the L-task was found to be proportional to the load. The correlation analysis between the size of H-reflex and the amount of background (BG) electromyographic (EMG) activity demonstrated that the H-reflex in the power phase did not depend on the BG EMG in either C- or L-task. These findings suggested that transmission of muscle afferents along the ascending pathways to the cerebral cortex and the spinal cord is independently controlled in accordance with the biomechanical constraints of active pedaling.

Adult↗
PubMed2005

Unraveling the attentional functions of cortical cholinergic inputs: interactions between signal-driven and cognitive modulation of signal detection.

Neurophysiological studies demonstrated that increases in cholinergic transmission in sensory areas enhance the cortical processing of thalamic inputs. Cholinergic activity also suppresses the retrieval of internal associations, thereby further promoting sensory input processing. Behavioral studies documented the role of cortical cholinergic inputs in attentional functions and capacities by demonstrating, for example, that the integrity of the cortical cholinergic input system is necessary for attentional performance, and that the activity of cortical cholinergic inputs is selectively enhanced during attentional performance. This review aims at integrating the neurophysiological and behavioral evidence on the functions of cortical cholinergic inputs and hypothesizes that the cortical cholinergic input system generally acts to optimize the processing of signals in attention-demanding contexts. Such signals 'recruit', via activation of basal forebrain corticopetal cholinergic projections, the cortical attention systems and thereby amplify the processing of attention-demanding signals (termed 'signal-driven cholinergic modulation of detection'). The activity of corticopetal cholinergic projections is also modulated by direct prefrontal projections to the basal forebrain and, indirectly, to cholinergic terminals elsewhere in the cortex; thus, cortical cholinergic inputs are also involved in the mediation of top-down effects, such as the knowledge-based augmentation of detection (see Footnote 1) of signals and the filtering of irrelevant information (termed 'cognitive cholinergic modulation of detection'). Thus, depending on the quality of signals and task characteristics, cortical cholinergic activity reflects the combined effects of signal-driven and cognitive modulation of detection. This hypothesis begins to explain signal intensity or duration-dependent performance in attention tasks, the distinct effects of cortex-wide versus prefrontal cholinergic deafferentation on attention performance, and it generates specific predictions concerning cortical acetylcholine (ACh) release in attention task-performing animals. Finally, the consequences of abnormalities in the regulation of cortical cholinergic inputs for the manifestation of the symptoms of major neuropsychiatric disorders are conceptualized in terms of dysregulation in the signal-driven and cognitive cholinergic modulation of detection processes.

Acetylcholine↗
PubMed2003

Comprehensive two-dimensional gas chromatography using liquid nitrogen modulation: set-up and applications.

An improved modulation system for comprehensive two-dimensional gas chromatography (GC x GC) is presented. It is based on two-jet modulation with liquid nitrogen as cryogen. A valve system was designed to include subsequent re-heating of cooled capillary segments after modulation. It is demonstrated that even volatile components, such as propane or butane, are easily modulated with this system. Thus, the temperature range for GC x GC operation compared to diaphragm valve or liquid CO2 modulation is extended. The system allows highly efficient analysis of volatile and non-volatile components. Applications include separations of alkenes and gasoline samples. Also sulfur-containing hydrocarbon samples were compared via GC x GC and differences among samples of different producers were observed. Finally, headspace GC x GC investigations of volatiles found in polymer latex-coated papers round out the increasing portfolio of valuable applications.

Chromatography, Gas↗
PubMed2004

Qualification of an electro-deionization module via experimental design and ion-chromatographic studies.

To meet the needs of the laboratory-water market, a modified electro-deionization (EDI) module has been developed to produce Type 2 purified water. An EDI module consists of desalting and concentrating fluidic compartments that are both filled with anion and cation ion-exchange resins; an anode and a cathode electrode are at opposite ends. In the design in this research, the anode electrode is segmented into three parts and individual dc amperages are applied to each segment; the cathode electrode is a single common electrode. Critical to the performance and longevity of this type of EDI module are: (1) the optimization of the applied dc amperages and (2) the ionic mass balance (i.e., the concentrations of specific and total ions of the RO feedwater to the module compared to the concentrations in the water exiting the module via the desalting and concentrating compartments). To determine a suitable current for each electrode pair, a full-factorial experimental design was developed and employed. For the application of this combination of amperages, the critical parameter of specific-ion mass balance was determined using ion-chromatographic measurements.

Calibration↗