Frequency-specific Manner Research Articles

Modulating cerebello-thalamocortical pathways by neuronavigated cerebellar repetitive transcranial stimulation (rTMS)

Increasing evidence suggests that dysfunctions of the cortico-cerebello-thalamocortical circuit are involved in the pathophysiology of neuropsychiatric disorders. This study explores the effects of cerebellar repetitive transcranial magnetic stimulation (rTMS) on cerebello-thalamocortical pathways. Ten healthy volunteers received MRI-guided rTMS in four separate sessions (120% motor threshold, 1000 stimuli) over either the medial or the right lateral cerebellum using frequencies of 1 and 10 Hz. Motor cortex excitability was assessed before and after the intervention by paired-pulse transcranial magnetic stimulation. Depending on stimulation frequency, cerebellar rTMS differentially modified intracortical inhibition. Low frequency rTMS increased short intracortical inhibition (SICI), whereas high frequency rTMS had no significant effect on SICI. These results suggest that rTMS over the cerebellum can modulate cerebello-thalamocortical pathways in a frequency-specific manner.

Differential effects of tactile high- and low-frequency stimulation on tactile discrimination in human subjects

BackgroundLong-term potentiation (LTP) and long-term depression (LTD) play important roles in mediating activity-dependent changes in synaptic transmission and are believed to be crucial mechanisms underlying learning and cortical plasticity. In human subjects, however, the lack of adequate input stimuli for the induction of LTP and LTD makes it difficult to study directly the impact of such protocols on behavior.ResultsUsing tactile high- and low-frequency stimulation protocols in humans, we explored the potential of such protocols for the induction of perceptual changes. We delivered tactile high-frequency and low-frequency stimuli (t-HFS, t-LFS) to skin sites of approximately 50 mm2 on the tip of the index finger. As assessed by 2-point discrimination, we demonstrate that 20 minutes of t-HFS improved tactile discrimination, while t-LFS impaired performance. T-HFS-effects were stable for at least 24 hours whereas t-LFS-induced changes recovered faster. While t-HFS changes were spatially very specific with no changes on the neighboring fingers, impaired tactile performance after t-LFS was also observed on the right middle-finger. A central finding was that for both t-LFS and t-HFS perceptual changes were dependent on the size of the stimulated skin area. No changes were observed when the stimulated area was very small (< 1 mm2) indicating special requirements for spatial summation.ConclusionOur results demonstrate differential effects of such protocols in a frequency specific manner that might be related to LTP- and LTD-like changes in human subjects.

聴性定常反応聴力検査

This study describes the history, stimulus tones, detection techniques, source generators and clinical applications of auditory steady-state responses (ASSR). The most important benefit of ASSR in objective audiometry is that it can provide an accurate assessment of hearing at different audiometric frequencies in a frequency specific manner, if sinusoidally amplitude-modulated tones are used as tonal stimuli. Power spectrum analysis and phase coherence using fast Fourier transform are useful for the automatic detection of threshold because of the sinusoidal response waveform configuration. Because the detectability of ASSR changes under different arousal states, 40-Hz ASSR is suitable for waking adults and 80-Hz ASSR for sleeping children in the assessment of hearing. Regarding the sources of those responses, 40-Hz ASSR is considered the steady-state version of the middle latency response and 80-Hz ASSR is considered the steady-state version of auditory brainstem response (ABR). Bone conduction stimuli are also useful in the assessment of conductive hearing loss, though the responses are not reliable at the intensity level of 60dB or higher. The difficulty in predicting a hearing level of 500Hz or less using the 80-Hz ASSR threshold can be explained by auditory filter. Its advantage is that the thresholds at 4 different frequencies in both ears can be predicted more rapidly than ABR using the multiple simultaneous stimulation technique. In addition, the ASSR to clicks may provide a rapid screening technique. Finally, it may be helpful in assessing suprathreshold hearing to use ASSRs to sounds that sweep their intensity (sweep technique) or actual speech sounds. In this respect, ASSRs may contribute to the objective fitting of hearing aids in young children.

Reductions in gain from pre-masker stimulation at the signal frequency

Normal hearing individuals can detect a short duration signal at a lower signal-to-masker ratio when the signal is delayed from masker onset compared to near it. This is often referred to as the temporal effect. This effect is interesting because it may be related to changes in cochlear gain. It has been proposed that gain is high at masker onset and decreases, in a frequency specific manner, through the course of the masker. If this hypothesis was true, it is expected that frequency selectivity also decreases through the course of the masker. Using a forward masking paradigm, the current study examines the hypothesis that frequency selectivity decreases with pre-masker stimulation at the signal frequency. Growth of masking (GOM) functions and psychophysical tuning curves (PTC) were measured for the signal using a short masker preceded by a long duration precursor set at the signal frequency or well below the signal frequency. Preliminary results reveal a relatively broader PTC and a steeper GOM function when the precursor was at the signal frequency and are consistent with the hypothesis that preceding stimulation at the signal frequency reduces gain. [Work supported by the Hazelton Fund.]

Efferent‐mediated control of basilar membrane motion

Medial olivocochlear efferent (MOCE) neurones innervate the outer hair cells (OHCs) of the mammalian cochlea, and convey signals that are capable of controlling the sensitivity of the peripheral auditory system in a frequency-specific manner. Recent methodological developments have allowed the effects of the MOCE system to be observed in vivo at the level of the basilar membrane (BM). These observations have confirmed earlier theories that at least some of the MOCE's effects are mediated via the cochlea's mechanics, with the OHCs acting as the mechanical effectors. However, the new observations have also provided some unexpected twists: apparently, the MOCEs can enhance the BM's responses to some sounds while inhibiting its responses to others, and they can alter the BM's response to a single sound using at least two separate mechanisms. Such observations put new constraints on the way in which the cochlea's mechanics, and the OHCs in particular, are thought to operate.

Transcranial fluorescence imaging of auditory cortical plasticity regulated by acoustic environments in mice

Functional brain imaging using endogenous fluorescence of mitochondrial flavoprotein is useful for investigating mouse cortical activities via the intact skull, which is thin and sufficiently transparent in mice. We applied this method to investigate auditory cortical plasticity regulated by acoustic environments. Normal mice of the C57BL/6 strain, reared in various acoustic environments for at least 4 weeks after birth, were anaesthetized with urethane (1.7 g/kg, i.p.). Auditory cortical images of endogenous green fluorescence in blue light were recorded by a cooled CCD camera via the intact skull. Cortical responses elicited by tonal stimuli (5, 10 and 20 kHz) exhibited mirror-symmetrical tonotopic maps in the primary auditory cortex (AI) and anterior auditory field (AAF). Depression of auditory cortical responses regarding response duration was observed in sound-deprived mice compared with naïve mice reared in a normal acoustic environment. When mice were exposed to an environmental tonal stimulus at 10 kHz for more than 4 weeks after birth, the cortical responses were potentiated in a frequency-specific manner in respect to peak amplitude of the responses in AI, but not for the size of the responsive areas. Changes in AAF were less clear than those in AI. To determine the modified synapses by acoustic environments, neural responses in cortical slices were investigated with endogenous fluorescence imaging. The vertical thickness of responsive areas after supragranular electrical stimulation was significantly reduced in the slices obtained from sound-deprived mice. These results suggest that acoustic environments regulate the development of vertical intracortical circuits in the mouse auditory cortex.

Adaptive Plasticity in the Auditory Thalamus of Juvenile Barn Owls

Little is known about the capacity of the thalamus for experience-dependent plasticity. Here, we demonstrate adaptive changes in the tuning of auditory thalamic neurons to a major category of sound localization cue, interaural time differences (ITDs), in juvenile barn owls that experience chronic abnormal hearing. Abnormal hearing was caused by a passive acoustic filtering device implanted in one ear that altered the timing and level of sound differently at different frequencies. Experience with this device resulted in adaptive, frequency-dependent shifts in the tuning of thalamic neurons to ITD that mimicked the acoustic effects of the device. Abnormal hearing did not alter ITD tuning in the central nucleus of the inferior colliculus, the primary source of input to the auditory thalamus. Therefore, the thalamus is the earliest stage in the forebrain pathway in which this plasticity is expressed. A visual manipulation, chronic prismatic displacement of the visual field, which causes adaptive changes in ITD tuning at higher levels in the forebrain, had no effect on thalamic ITD tuning. The results demonstrate that, during the juvenile period, auditory experience shapes neuronal response properties in the thalamus in a frequency-specific manner and suggest that this thalamic plasticity is driven by self-organizational forces and not by visual instruction.

Excitatory action of an immature glycinergic/GABAergic sound localization pathway

Most mammals determine the azimuthal direction of incoming sound using auditory cues arising from differences in interaural sound intensity. The first station in the ascending auditory pathway, which processes interaural intensity differences, is the lateral superior olive (LSO), a binaural nucleus in the auditory brainstem. LSO neurons encode interaural intensity differences by integrating excitatory input from the ipsilateral cochlea and inhibitory input from the contralateral cochlea. Both inputs converge on single neurons in a highly organized, frequency-specific manner. The correct development of the precise arrangement of these inputs and their physiological properties depends on neuronal activity. Previous studies have shown that inhibitory, glycinergic/GABAergic inputs to the LSO are transiently depolarizing, and it has been hypothesized that this depolarizing action enables developing inhibitory inputs to act as excitatory inputs. In support of this hypothesis, we recently demonstrated that depolarizing glycinergic/GABAergic inputs can increase the intracellular calcium concentration in immature LSO neurons and elicit action potentials. These results provide support for the notion that the influence of glycinergic/GABAergic synaptic activity on development of the LSO involves calcium-dependent signaling mechanisms.

Frequency specificity of cochlear damage in acute electrical injury: a longitudinal distortion product otoacoustic emission study.

To understand cochlear dysfunction and the recovery pattern of the cochlea after acute electrical injury. The cochlea is believed to be more vulnerable to direct current than to alternating current. However, the damage-and frequency-specific recovery characteristics of the cochlea have not been well described. Baseline distortion product otoacoustic emission measurements were taken via transtympanic electrodes from 19 guinea pigs. A 20-Hz alternating current and a positive direct current, both at a 1,000-microA intensity, were applied to 9 and 10 animals, respectively. The measurements were repeated immediately after the application of current and after 10 days. Comparisons were made for both groups individually in signal-to-noise ratios obtained before and immediately after, immediately and 10 days after, and before and 10 days after the application of electrical current. Alternating and direct currents caused a significant depression in signal-to-noise ratio immediately after the application. However, 10 days later, the mean signal-to-noise ratio in the animals subjected to alternating current came significantly close to the baseline value, particularly between the frequencies of 2,211 and 3,717 Hz. By contrast, the mean signal-to-noise ratio in the animals subjected to direct current remained significantly depressed throughout all frequencies except for 2,211 Hz. Baseline distortion product otoacoustic emission measurements enabled cochlear function to be monitored in a frequency-specific manner after electrical injury. The functional damages were quantitatively close to each other for both types of currents at a given intensity. Nevertheless, recovery was more apparent in the animals exposed to alternating current than in those exposed to direct current. Recovery was also better in the midfrequency region than in higher frequencies. It is hypothesized that the reason for the difference in recovery in both groups was the net charge left by direct current.

Synaptic plasticity in morphologically identified CA1 stratum radiatum interneurons and giant projection cells.

Long-term potentiation (LTP) of synaptic efficacy was examined in interneurons and giant cells in the stratum radiatum region of the hippocampal CA1 subfield. Cells were visually selected using differential interference contrast (DIC) optics and filled with biocytin while being recorded using whole-cell patch-clamp techniques. Electrophysiological criteria, including spike height, width, and degree of spike adaptation shown to sustained depolarization, proved inadequate for differentiating interneurons from giant cells. We found that cells in the stratum radiatum, however, could be reliably differentiated using DIC optics or following intracellular staining. The response of the two cell types to tetanic stimulation further dissociated them. Long-term potentiation, dependent on the activation of NMDAr (N-methyl-D-aspartate receptors), could reliably be induced in interneurons with stimuli administered at 200 Hz, but not 100 Hz. Giant cells, in contrast, exhibited NMDA receptor-dependent LTP in response to 100-Hz stimuli, but not the 200-Hz stimuli. LTP induction in interneurons also appeared temperature-dependent, being much more robust at 34 degrees C than at room temperature. The LTP in both cell types required postsynaptic calcium influx, and was not due to the passive propagation of LTP induction in neighboring pyramidal cells. These results suggest that different cell types within the hippocampal formation may preferentially alter synaptic connectivity in a frequency-specific manner.

CD1 hearing-impaired mice. II: Group latencies and optimal f 2/f 1 ratios of distortion product otoacoustic emissions, and scanning electron microscopy

In our companion paper (Le Calvez et al., 1998), the levels of distortion product otoacoustic emissions (DPOAE) were collected in the ears of CD1 mice with progressive degeneration of cochlear outer hair cells (OHC). Their comparison to standard functional measurements such as auditory-evoked brainstem responses (ABR) showed that CD1 ears could be classified as normal or impaired in a frequency-specific manner using DPOAE levels. The present work reports how DPOAE phases and levels of young CD1 mice were affected by varying the frequency ratio of eliciting stimuli at frequencies f 1 and f 2. Normally hearing CBA/J mice served as controls. The rate of phase change of DPOAE when f 1 was varied and f 2 was fixed allowed the group delay of DPOAE to be derived. The changes of DPOAE levels during this procedure disclosed bandpass characteristics that several reports (Fahey and Allen, 1986; Brown and Gaskill, 1990) assumed to be the reflection of important features of cochlear micromechanics, possibly in relation to the coupling of OHCs to the tectorial membrane. Group delays became significantly shorter when ABR thresholds exceeded 40 dB elevation. The bandpass filter characteristics strikingly depended on auditory function so that the optimal ratio f 2/f 1 progressively shifted from 1.24 to 1.50 or more when hearing loss increased. A difference was also noted between CD1 ears whose ABR thresholds were not yet increased and control CBA/J (optimal ratio 1.20). Scanning electron microscopy disclosed a variety of often minor OHC lesions that were only roughly correlated with cochlear function. However, the presence of abnormalities in the reticular lamina associated with early changes of DPOAE fine structure as a function of f 2/f 1 supported the hypothesis of some involvement of micromechanical features in the bandpass filter characteristics of DPOAE. The sensitivity of their measurement in pathological situations is potentially interesting.

Head-related transfer functions of the barn owl: measurement and neural responses

Sounds arriving at the eardrum are filtered by the external ear and associated structures in a frequency and direction specific manner. When convolved with the appropriate filters and presented to human listeners through headphones, broadband noises can be precisely localized to the corresponding position outside of the head (reviewed in Blauert, 1997). Such a `virtual auditory space' can be a potentially powerful tool for neurophysiological and behavioral work in other species as well. We are developing a virtual auditory space for the barn owl, Tyto alba, a highly successful auditory predator that has become a well-established model for hearing research. We recorded catalogues of head-related transfer functions (HRTFs) from the frontal hemisphere of 12 barn owls and compared virtual and free sound fields acoustically and by their evoked neuronal responses. The inner ca. 1 cm of the ear canal was found to contribute little to the directionality of the HRTFs. HRTFs were recorded by inserting probetube microphones to within about 1 or 2 mm of the eardrum. We recorded HRTFs at frequencies between 2 and 11 kHz, which includes the frequencies most useful to the owl for sound localization (3–9 kHz; Konishi, 1973). Spectra of virtual sounds were within ±1 dB of amplitude and ±10° of phase of the spectra of free field sounds measured near to the eardrum. The spatial pattern of responses obtained from neurons in the inferior colliculus were almost indistinguishable in response to virtual and to free field stimulation.

Dynamics of the human EEG during prolonged wakefulness: evidence for frequency-specific circadian and homeostatic influences

The electroencephalogram (EEG) of nine healthy individuals was recorded at half-hourly intervals during ~40 h of sustained wakefulness in a constant routine protocol. EEG power density in the 0.75–9.0 Hz range exhibited a global increasing trend, and a local trough in the evening, centered ~6 h prior to the temperature minimum. The former could be attributed to a wake-dependent influence, and the latter to a circadian influence. Power density in the 9.25–12.0 Hz band showed a circadian modulation, the trough coinciding with the minimum of the endogenous rhythm of body temperature, whereas a wake-dependent influence was not evident. Power density in the 12.25–25.0 Hz range exhibited a wake-dependent increase, whereas a circadian modulation was absent. It is concluded that the circadian pacemaker and the wake-dependent (i.e. homeostatic) process affect the waking EEG in a frequency-specific manner.

Adaptation of primate vestibuloocular reflex to altered peripheral vestibular inputs. II Spatiotemporal properties of the adapted slow-phase eye velocity.

1. The ability of the vestibuloocular reflex (VOR) to undergo adaptive modification after selective changes in the peripheral vestibular system was investigated in rhesus monkeys by recording three-dimensional eye movements before and after inactivation of selective semicircular canals. In the preceding paper we showed that the horizontal VOR gain evoked by passive yaw oscillations after lateral semicircular canal inactivation recovers gradually over time in a frequency-specific manner. Here we present the spatial tuning of the adapted slow-phase eye velocity and describe its spatiotemporal properties as a function of time after canal inactivation. 2. The spatial organization of the VOR was investigated during oscillations at different head positions in the pitch, roll, and yaw planes, as well as in the right anterior/left posterior and left anterior/right posterior canal planes. Acutely after bilateral inactivation of the lateral semicircular canals, a small horizontal response could still be elicited that peaked during rotations in pitched head positions that would maximally stimulate vertical semicircular canals. In addition, the phase of horizontal slow-phase velocity abruptly reversed through 180 degrees at positions close to upright, similarly to torsional slow-phase velocity. These spatial response properties suggest that the small, residual horizontal response components that are present acutely after plugging of both lateral canals originate from vertical semicircular canal signals. 3. As the horizontal response amplitude increased over time, consistent changes were also observed in the spatiotemporal tuning of horizontal slow-phase velocity. 1) The spatiotemporal response properties of horizontal slow-phase velocity acquired noncosine tuning characteristics, primarily in the pitch plane, in the right anterior/left posterior and left anterior/right posterior canal planes. Accordingly, horizontal response amplitude was nonzero during rotation in any head position in these planes and response phase varied significantly as a function of head orientation. 2) The peak horizontal response amplitude shifted spatially over time, such that 5-10 mo after plugging it was maximal during rotations at head positions close to upright. 4. In parallel to these unique spatiotemporal response properties characterizing the adapted horizontal VOR, torsional slow-phase velocity also exhibited small spatiotemporal changes after lateral canal inactivation that tended to precede in time the changes associated with the horizontal response components. In contrast, vertical slow-phase velocity in the plugged animals was unaltered and continued to be characterized by cosine-tuned spatial properties in three dimensions. 5. Recovery of the horizontal response gain during yaw oscillations in upright position, as well as the unique, noncosine spatiotemporal characteristics of the adapted horizontal VOR, were also observed in an animal with all but one vertical semicircular canals inactivated. There was, however, no sign of VOR gain recovery up to 2 mo after all semicircular canals were inactivated. These results suggest that the observed recovery of horizontal VOR is at least partly due to signals originating from the remaining intact vertical canal(s). Even in the presence of a single intact vertical canal, the improvement in horizontal gaze stability is at least partly restored through spatiotemporal changes in the processing of vestibuloocular signals that improve the gain and spatial tuning of horizontal VOR at the expense of temporal response properties.

Frequency-specific identification of hearing loss using transient-evoked otoacoustic emissions to clicks and tones

Transient-evoked otoacoustic emissions (TEOAE) to clicks and to 500- and 2000-Hz brief tones were measured in 72 normal-hearing and hearing-impaired subjects (86 ears) The TEOAE's reproducibility parameter was used for the analyses. The purpose of the investigation was to determine which stimuli best predicted the presence of sensorineural hearing loss in a frequency-specific manner at 500, 1000, 2000, and 4000 Hz. Analyses of the TEOAEs filtered into frequency-specific bands showed that separation of normal and impaired ears at 1000, 2000 and 4000 Hz was best achieved by TEOAEs evoked by clicks. Identification of hearing loss at 500 Hz was best obtained using 500-Hz tone-evoked TEOAEs filtered using a band centered at 500 Hz. Octave- and half-octave-wide bands identified hearing loss equally well. An analysis sweep time of 20 ms provided slightly better results compared to 30 ms, except for 500 Hz, where the 30-ms sweep time slightly improved the identification of hearing loss. Increases in the audiometric criterion did not yield better test performance once hearing loss exceeded 20 dB HL. The findings from this study suggest that the combination of bandpass-filtered TEOAEs to clicks and TEOAEs to 500-Hz tones identifies with reasonable accuracy ears with sensorineural hearing loss at 500, 1000, 2000, and 4000 Hz.

Linear filtering precedes nonlinear processing in early vision

Background: Nonlinearities play a significant role in early visual processing. They are central to the perception of spatial contrast variations, multiplicative transparencies and texture boundaries. This article concerns the stage of processing at which nonlinearities first become significant.Results Subjects were adapted to a high contrast sinusoidal grating followed by a brief presentation of a contrast modulated test (plaid) pattern. Thresholds for the detection of the contrast modulation (the beat) were measured. Results show that threshold elevation is greatest when the orientation and spatial frequency of the adapting grating are close to the principal Fourier frequency (the carrier) of the test pattern. Adaptation to sinewave-gratings near the frequency of the contrast modulation has relatively little effect. The data also show that the processing of contrast is frequency selective, with a peak tuning frequency near 0.4 cycles per degree.Conclusion The data are consistent with a model in which the contrast beats are processed in a frequency-specific manner, after an initial stage of frequency-specific and orientation-specific linear filtering.

変調周波数迫随反応

The ultimate goal of objective audiometry is to draw an audiogram in a frequency specific manner with no response from the subject. Auditory evoked brainstem response (ABR) is now most commonly used for objective audiometry. However, the frequency specificity of ABR elicited with tone pips is not enough to predict accurate hearing on a frequency-specific basis across the audiometric range. Amplitude-modulation following response (AMFR), which is an auditory steady-state response elicited with sinusoidally amplitude-modulated tone, is expected to be an ideal tool for objective audiometry, because of the frequency specificity of the stimulus tone.When detected by phase coherence, the threshold pattern of 40-Hz AMFR, which is elicited with tone amplitude modulated at 40 Hz, resembles very closely the corresponding audiogram patterns in all types of hearing impairment in adults while awake. However, 40-Hz AMFR is not sufficiently reliable for determining the hearing threshold in young children during sleep.On the other hand, 80-Hz AMFR is clearly detected in young children during sleep with the use of phase coherence. The threshold pattern of 80-Hz AMFR also resembles closely the corresponding audiogram pattern. An 80-Hz AMFR thus appears to be potentially useful for objective audiometry in young children during sleep.In this paper, our present knowledge about objective audiometry and AMFR is reviewed, and techniques for detecting AMFR and sources of AMFR are discussed.

Cochlear‐nucleus branches of thick (medial) olivocochlear fibers in the mouse: A cochaleotopic projection

Olivocochlear neurons have somata in the superior olivary complex and provide an efferent innervation to the cochlea. One subgroup of olivocochlear neurons, medial olivocochlear neurons, sends fibers to innervate the cochlear outer hair cells. En route to the cochlea, medial olivocochlear fibers give off branches to the ventral cochlear nucleus, the first auditory center of the brain. This study examines the cochlear-nucleus branches of medial olivocochlear fibers, comparing those from fibers that innervate the cochlear base with those from fibers that innervate the cochlear apex. Basal fibers give off dorsal branches to the granule cell lamina and ventral branches to the auditory nerve root. Apical fibers give off few dorsal branches but many ventral branches that terminate rostrally to the nerve root. This cochleotopic mapping of medial olivocochlear branches corresponds in a general way to that of afferent fibers. Unlike afferent fibers, however, the branches terminate primarily along the edges of the cochlear nucleus. In the mouse, the particular edges of termination are (1) the medial border of the ventral cochlear nucleus where it meets the underlying vestibular nerve root, and (2) the border between the ventral cochlear nucleus and the granule cell lamina. Neurons and dendrites of these border regions may thus integrate efferent and afferent information in a frequency-specific manner.

Evaluating nerve function of the inner ear

The N1 potential of the cochlear nerve has long been used to evaluate cochlear function. It has not been clear what population of nerve fibers contributes to this potential. Several lines of evidence suggest that N1 potentials evoked by tone pulses activate a very limited population of nerve fibers and thus are frequency specific. (1) The latencies correspond to cochlear travel time and neural delays. (2) Fatiguing tones produce frequency specific depressions of N1. (3) Tones mask these N1 potentials in a frequency specific manner. The effects of rise-time and tone-pulse duration on these observations will also be discussed.