Middle Latency Response Research Articles

Frequency-Following Response e Potencial Evocado Auditivo de Média Latência: uma análise frente ao processamento auditivo central de jovens adultos

ABSTRACT Purpose: to compare the latency and amplitude of the Frequency-Following Response and the Auditory Middle Latency Response in typical individuals and those with altered auditory abilities, as well as to investigate the sensitivity and specificity of both assessments in relation to central auditory processing. Methods: 32 individuals of both sexes were distributed into Group 1 (without altered auditory abilities) and Group 2 (with altered auditory abilities). The groups were divided according to behavioral tests of central auditory processing. Individuals in both groups underwent auditory evoked potentials. Student’s t-test was used for analysis, considering a 5% significance. Results: in Group 2, V and A had higher latency and lower amplitude and slope. Group 2 also had lower Na and Pa amplitudes in waves A1C3 and A2C3. The Frequency-Following Response showed 93% sensitivity and specificity, while the Auditory Middle Latency Response showed 87% sensitivity and 93% specificity. Conclusion: the individuals presented with altered hearing abilities showed higher latency and lower response amplitude in the Frequency Following Response and Auditory Middle Latency Response compared to typical individuals. The Frequency- Following Response showed a better balance of sensitivity and specificity.

Auditory Middle Latency Response in Young Adult Females Perceiving Tinnitus During a Brief Period of Silence

Auditory Middle Latency Response in Young Adult Females Perceiving Tinnitus During a Brief Period of Silence

Predictive Coding and Neuronal Mismatch in the Auditory System, From Subcortical to Cortical and Beyond

Detecting unexpected stimuli in the environment is a critical function of the auditory system. Responses to unexpected “deviant” sounds are enhanced compared to responses to expected stimuli. At the human scalp, deviance detection is reflected in the mismatch negativity (MMN) and in an enhancement of the middle-latency response (MLR). Single neurons often respond more strongly to a stimulus when rare than when common, a phenomenon termed stimulus-specific adaptation (SSA). Here we compare stimulus-specific adaptation with scalp-recorded deviance-related responses. We conclude that early markers of deviance detection in the time range of the MLR could be a direct correlate of cortical SSA. Both occur at an early level of cortical activation, both are robust findings with low-probability stimuli, and both show properties of genuine deviance detection. Their causal relation with the later scalp-recorded MMN is a key question in this field.

Characteristics of the Deconvolved Transient AEP from 80Hz Steady-State Responses to Amplitude Modulation Stimulation.

This study aimed to validate the existence and investigate the characteristics of the transient responses from conventional auditory steady-state responses (ASSRs) using deconvolution methods capable of dealing with amplitude modulated (AM) stimulation. Conventional ASSRs to seven stimulus rates were recorded from 17 participants. A deconvolution method was selected and modified to accommodate the AM stimulation. The calculated responses were examined in terms of temporal features with respect to different combinations of stimulus rates. Stable transient responses consisting of early stage brainstem responses and middle latency responses were reconstructed consistently for all rate combinations, which indicates that the superposition hypothesis is applicable to the generation of approximately 80Hz ASSRs evoked by AM tones (AM-ASSRs). The new transient responses are characterized by three pairs of peak-troughs named as n0p0, n1p1, and n2p2 within 40ms. Compared with conventional ABR-MLRs, the n0p0 indicates the first neural activity where p0 might represent the main ABR components; the n1 is the counterpart of N10; the p2 is corresponding to the robust Pa at about 30ms; the p1 and n2 are absent of real counterparts. The peak-peak amplitudes show a slight decrease with increasing stimulation rate from 75 to 95Hz whereas the peak latencies change differently, which is consistent with the known rate-effect on AEPs. This is direct evidence for a transient response derived from AM-ASSRs for the first time. The characteristic components offer insight into the constitution of AM-ASSRs and may be promising in clinical applications and fundamental studies.

Auditory evoked potentials: Differences by sex, race, and menstrual cycle and correlations with common psychoacoustical tasks.

Auditory brainstem responses (ABRs) and auditory middle-latency responses (AMLRs) to a click stimulus were measured in about 100 subjects. Of interest were the sex differences in those auditory evoked potentials (AEPs), the correlations between the various AEP measures, and the correlations between the AEP measures and measures of otoacoustic emissions (OAEs) and behavioral performance also measured on the same subjects. Also of interest was how the menstrual cycle affected the various AEP measures. Most ABR measures and several AMLR measures exhibited sex differences, and many of the former were substantial. The sex differences tended to be larger for latency than for amplitude of the waves, and they tended to be larger for a weak click stimulus than for a strong click. The largest sex difference was for Wave-V latency (effect size ~1.2). When subjects were dichotomized into Non-Whites and Whites, the race differences in AEPs were small within sex. However, sex and race interacted so that the sex differences often were larger for the White subjects than for the Non-White subjects, particularly for the latency measures. Contrary to the literature, no AEP measures differed markedly across the menstrual cycle. Correlations between various AEP measures, and between AEP and OAE measures, were small and showed no consistent patterns across sex or race categories. Performance on seven common psychoacoustical tasks was only weakly correlated with individual AEP measures (just as was true for the OAEs also measured on these subjects). AMLR Wave Pa unexpectedly did not show the decrease in latency and increase in amplitude typically observed for AEPs when click level was varied from 40 to 70 dB nHL (normal Hearing Level). For the majority of the measures, the variability of the distribution of scores was greater for the males than for the females.

Auditory evoked potentials as yardstick for tinnitus

<p class="abstract"><strong>Background:</strong> Aiming to evaluate the recent theoretical postulates on tinnitus underscoring the role of thalamocortical neural tracts, the present study: explores middle latency response (MLR) as a possible physiological measure of tinnitus: thus investigates the predicted exaggeration of P<sub>a</sub>-N<sub>a</sub>, N<sub>a</sub>-P<sub>b</sub> interpeak amplitudes in tinnitus patients and; explores middle latency response (MLR) as a prognostic indicator of tinnitus retraining therapy (TRT), thus evaluates possible decrease in P<sub>a</sub>-N<sub>a</sub> and N<sub>a</sub>-P<sub>b</sub> amplitude after 2 weeks exposure to tinnitus retraining therapy.</p><p class="abstract"><strong>Methods:</strong> An experimental group was constructed by randomly assigning 30 patients with mean age 38.5 years and complaining of debilitating tinnitus but with normal hearing for the study. MLR was administered on patients with normal auditory brainstem response (ABR) and otoacoustic emission (OAE) both pre- and post-tinnitus retraining therapy. </p><p class="abstract"><strong>Results:</strong> Results demonstrated no significant effect on P<sub>a</sub>, N<sub>a</sub> and N<sub>b</sub> absolute and interpeak latencies. However, significantly exaggerated P<sub>a</sub>-N<sub>a</sub> and N<sub>a</sub>-P<sub>b</sub> interpeak amplitudes between experimental and control groups as well as pre and post therapeutic groups were found.</p><p class="abstract"><strong>Conclusions:</strong> This proves that MLR may adequately reflect thalamocortical hyperactivity in cases with distressing tinnitus and demonstrable improvement post TRT warrants the use of MLR as its prognostic indicator.</p>

Noninvasive scalp recording of the middle latency responses and cortical auditory evoked potentials in the alert common marmoset

The common marmoset (Callithrix jacchus), a New World monkey, serves as a useful animal model in clinical and basic neuroscience. The present study recorded scalp auditory evoked potentials (AEP) in non-sedated common marmoset monkeys (n = 4) using a noninvasive method similar to that used in humans, and aimed to identify nonhuman primate correlates of the human AEP components. A pure tone stimulus was presented while electroencephalograms were recorded using up to 16 disk electrodes placed on the scalp and earlobes. Candidate homologues of two categories of the human AEP, namely, the middle latency responses (MLR; Na, Pa, Nb, and Pb) and the cortical auditory evoked potentials (CAEP; P1, N1, P2, N2, and the sustained potential, SP) were identified in the marmoset. These waves were labeled as CjNa, CjPa, CjNb, CjPb, CjP1, CjN1, CjP2, CjN2, and CjSP, where Cj stands for Callithrix jacchus. The last MLR component, CjPb, was identical to the first CAEP component, CjP1, similar to the relationship between Pb and P1 in humans. The peak latencies of the marmoset MLR and CAEP were generally shorter than in humans, which suggests a shorter integration time in neural processing. To our knowledge, the present study represents the first scalp recorded MLR and CAEP in the alert common marmoset. Further use of these recording methods would enable valid species comparisons of homologous brain indices between humans and animals.

Study of Correlation Between EEG Electrodes for the Analysis of Cortical Responses Related to Binaural Hearing

Binaural hearing is the ability of the human auditory system to integrate information received from both ears simultaneously. Binaural hearing is fundamental in understanding speech in noisy backgrounds. Any disfunction in one or both ears could cause a disruption in the processing mechanism. Auditory evoked potentials (AEPs) are electrical potentials evoked by externally presented auditory stimuli from any part of the auditory system. A non-invasive technology, electroencephalography (EEG) is used for the monitoring of AEPs. The research aims to identify the best suited electrode positions through correlation analysis and analyse the AEP signals from the selected electrodes in order to detect binaural sensitivity of the human brain. The study evaluates the time-averaged EEG responses of normal hearing subjects to auditory stimuli. The stimuli used for the study are 500 Hz Blackman windowed pure tones, presented in either homophasic (the same phase in both ears) or antiphasic (180-degree phase difference between the two ears) conditions. The study focuses on understanding the effect of phase reversal of auditory stimuli, an under interaural time difference (ITD) cue, on the middle latency response (MLR) region of the AEPs. A correlation analysis was carried out between the eight different locations and as a result, Cz and Pz electrode positions were selected as the best suited positions for further analysis. The selected electrode signals were further processed in the time domain and frequency domain analysis. In the time domain analysis, it was found that Cz electrode for eight subjects out of nine and Pz electrode for seven subjects out of nine, had the larger area under signal curve obtained in the antiphasic condition than in the homophasic signals. Frequency domain analysis showed that the frequency bands 20 to 25Hz and 25 to 30Hz had the most energy when elicited by antiphasic stimuli than by homophasic stimuli. The findings of this study can be further utilised for the detection of binaural processing in a human brain.

Target detection in healthy 4-week old piglets from a passive two-tone auditory oddball paradigm

BackgroundPassive auditory oddball tests are effort independent assessments that evaluate auditory processing and are suitable for paediatric patient groups. Our goal was to develop a two-tone auditory oddball test protocol and use this clinical assessment in an immature large animal model. Event-related potentials captured middle latency P1, N1, and P2 responses in 4-week old (N = 16, female) piglets using a custom piglet 32- electrode array on 3 non-consecutive days. The effect of target tone frequency (250 Hz and 4000 Hz) on middle latency responses were tested in a subset of animals.ResultsResults show that infrequent target tone pulses elicit greater N1 amplitudes than frequent standard tone pulses. There was no effect of day. Electrodes covering the front of the head tend to elicit greater waveform responses. P2 amplitudes increased for higher frequency target tones (4000 Hz) than the regular 1000 Hz target tones (p < 0.05).ConclusionsTwo-tone auditory oddball tests produced consistent responses day-to-day. This clinical assessment was successful in the immature large animal model.

OCENA AUDIOLOGICZNA URAZOWEGO USZKODZENIA MÓZGU – STUDIUM PRZYPADKU

BackgroundTraumatic brain injury (TBI) is a pathology frequently causing mortality or serious sequelae. About 20% of individuals with TBI will have some degree of auditory alteration. The aim of the present study was to use behavioural and electrophysiological assessments to analyse the hearing of a patient with TBI.Case reportA young male adult who had suffered severe TBI caused by a motorcycle accident was evaluated. The patient underwent a peripheral hearing evaluation and electrophysiological assessment. Pure tone audiometry revealed profound sensorineural hearing loss in the left ear and normal hearing in the right. In the electrophysiological assessment, an ABR click test showed the presence of a response in the right ear at 80 dB HL but no response in the left ear at 90 dB HL. Evaluation of the Middle Latency Response revealed the presence of both an electrode effect (C3) and an ear effect (A1). The P300 wave showed an event-related potential within normal limits in the right ear and no responses in the left.ConclusionsThe present case study verifies the importance of assessing the peripheral and central auditory nervous system in cases of patients with a history of TBI. It reinforces the need for diagnosis and audiological monitoring of these patients.

Effects of Kainic Acid-Induced Auditory Nerve Damage on Envelope-Following Responses in the Budgerigar (Melopsittacus undulatus).

Sensorineural hearing loss is a prevalent problem that adversely impacts quality of life by compromising interpersonal communication. While hair cell damage is readily detectable with the clinical audiogram, this traditional diagnostic tool appears inadequate to detect lost afferent connections between inner hair cells and auditory nerve (AN) fibers, known as cochlear synaptopathy. The envelope-following response (EFR) is a scalp-recorded response to amplitude modulation, a critical acoustic feature of speech. Because EFRs can have greater amplitude than wave I of the auditory brainstem response (ABR; i.e., the AN-generated component) in humans, the EFR may provide a more sensitive way to detect cochlear synaptopathy. We explored the effects of kainate- (kainic acid) induced excitotoxic AN injury on EFRs and ABRs in the budgerigar (Melopsittacus undulatus), a parakeet species used in studies of complex sound discrimination. Kainate reduced ABR wave I by 65-75% across animals while leaving otoacoustic emissions unaffected or mildly enhanced, consistent with substantial and selective AN synaptic loss. Compared to wave I loss, EFRs showed similar or greater percent reduction following kainate for amplitude-modulation frequencies from 380 to 940Hz and slightly less reduction from 80 to 120Hz. In contrast, forebrain-generated middle latency responses showed no consistent change post-kainate, potentially due to elevated "central gain" in the time period following AN damage. EFR reduction in all modulation frequency ranges was highly correlated with wave I reduction, though within-animal effect sizes were greater for higher modulation frequencies. These results suggest that even low-frequency EFRs generated primarily by central auditory nuclei might provide a useful noninvasive tool for detecting synaptic injury clinically.

Latency-dependent filtering and compact representation of the complete auditory pathway response.

Auditory evoked potentials (AEPs) include the auditory brainstem response (ABR), middle latency response (MLR), and cortical auditory evoked potentials (CAEPs), each one covering a specific latency range and frequency band. For this reason, ABR, MLR, and CAEP are usually recorded separately using different protocols. This article proposes a procedure providing a latency-dependent filtering and down-sampling of the AEP responses. This way, each AEP component is appropriately filtered, according to its latency, and the complete auditory pathway response is conveniently represented (with the minimum number of samples, i.e., without unnecessary redundancies). The compact representation of the complete response facilitates a comprehensive analysis of the evoked potentials (keeping the natural continuity related to the neural activity transmission along the auditory pathway), which provides a new perspective in the design and analysis of AEP experiments. Additionally, the proposed compact representation reduces the storage or transmission requirements when large databases are manipulated for clinical or research purposes. The analysis of the AEP responses shows that a compact representation with 40 samples/decade (around 120 samples) is enough for accurately representing the response of the complete auditory pathway and provides appropriate latency-dependent filtering. MatLab/Octave code implementing the proposed procedure is included in the supplementary materials.

Evidence of central involvement in essential tremor: a detailed study of auditory pathway physiology.

Essential tremor (ET) is a common tremor disorder that is likely neurodegenerative. The pathophysiology of ET involves the cerebellum and its connections in the brainstem and thalamus. Hearing dysfunction has been shown to be a non-motor finding in ET patients. A limited number of studies have suggested that cochlear pathology is the cause, but studies have not evaluated the integrity of the primary auditory pathway in ET. The main aim of this study is to investigate the integrity of the auditory pathway via auditory brainstem response (ABR) and auditory middle latency response (AMLR), thereby allowing us to evaluate the auditory pathway from the 8th cranial nerve to the cerebral cortex. Sixteen ET patients and sixteen age- and gender-matched controls (64 ears) were evaluated. In the ABR study, we detected prolongation of wave V peak latencies (ms) in ET (p = 0.02). In the AMLR study, P0 (p = 0.03), Pa (p = 0.008), Na (p = 0.03), and Nb (p = 0.01) waves differed between the two groups. Eleven ET patients and four control subjects had abnormal electrophysiological findings (ABR or AMLR or both) (68.8% vs. 25%, p = 0.01). Tremor duration was greater in ET patients with abnormal electrophysiological findings (p = 0.01). Finally, we observed prolongation of latencies after the ABR III wave, indicating that abnormalities exist within the superior olivary complex. For the first time, our research provides evidence that ET-related pathology is present at the subcortical and cortical levels of the auditory pathway.

Evoked Potentials Reveal Noise Exposure-Related Central Auditory Changes Despite Normal Audiograms.

Purpose Complaints of auditory perceptual deficits, such as tinnitus and difficulty understanding speech in background noise, among individuals with clinically normal audiograms present a perplexing problem for audiologists. One potential explanation for these "hidden" auditory deficits is loss of the synaptic connections between the inner hair cells and their afferent auditory nerve fiber targets, a condition that has been termed cochlear synaptopathy. In animal models, cochlear synaptopathy can occur due to aging or exposure to noise or ototoxic drugs and is associated with reduced auditory brainstem response (ABR) wave I amplitudes. Decreased ABR wave I amplitudes have been demonstrated among young military Veterans and non-Veterans with a history of firearm use, suggesting that humans may also experience noise-induced synaptopathy. However, the downstream consequences of synaptopathy are unclear. Method To investigate how noise-induced reductions in wave I amplitude impact the central auditory system, the ABR, the middle latency response (MLR), and the late latency response (LLR) were measured in 65 young Veterans and non-Veterans with normal audiograms. Results In response to a click stimulus, the MLR was weaker for Veterans compared to non-Veterans, but the LLR was not reduced. In addition, low ABR wave I amplitudes were associated with a reduced MLR, but with an increased LLR. Notably, Veterans reporting tinnitus showed the largest mean LLRs. Conclusions These findings indicate that decreased peripheral auditory input leads to compensatory gain in the central auditory system, even among individuals with normal audiograms, and may impact auditory perception. This pattern of reduced MLR, but not LLR, was observed among Veterans even after statistical adjustment for sex and distortion product otoacoustic emission differences, suggesting that synaptic loss plays a role in the observed central gain. Supplemental Material https://doi.org/10.23641/asha.11977854.

Signal processing method for data with simultaneous recording of auditory brainstem response, middle latency response, and slow vertex response

Signal processing method for data with simultaneous recording of auditory brainstem response, middle latency response, and slow vertex response

Vestibular Migraine Patients Show Lack of Habituation in Auditory Middle Latency Responses to Repetitive Stimuli: Comparison With Meniere's Disease Patients

Objectives: To compare habituation in auditory middle latency response (AMLR) to repetitive stimuli of vestibular migraine (VM) patients with Meniere's disease (MD) patients and healthy controls (HC) and to assess usefulness of AMLR for diagnosis of VM.Subjects: Thirteen unilateral definite MD patients (2 men, 11 women, mean age 50.6), 13 definite VM patients (3 men, 10 women, mean age 45.5), and 8 HC subjects (2 men, 6 women, mean age 37.1) were enrolled.Methods: The electrodes were placed on the vertex and the spinal process of the fifth cervical vertebra. Binaural click stimulation (0.1 ms, 70 dBnHL) was presented. A total of 800 responses were averaged. Averaged responses were divided into four sets (S1 to S4) according to the temporal order. No, Po, Na, and Pa were identified, and amplitudes and latencies were measured.Results: Concerning latencies, HC subjects showed a tendency of shorter latencies. However, there was no clear effect of repetitive stimulation. Concerning No-Po amplitudes, no significant differences were observed. Raw amplitudes of Na-Pa showed statistically significant differences in S1 and S2 among the groups (p < 0.01 one-way ANOVA). Differences were shown in MD vs. VM and HC vs. VM in S1 (smaller in VM) (p < 0.01 Bonferroni's test) and in MD vs. VM in S2 (smaller in VM) (p < 0.01 Bonferroni test). Relative amplitudes of Na-Pa to S1 showed statistically significant differences in S4 (p < 0.01 one-way ANOVA). Differences were shown in MD vs. VM and HC vs. VM (larger in VM) (p < 0.01 Bonferroni's test). Differences of Na-Pa amplitudes in S2 to S4 from Na-Pa amplitude in S1 were significant in S4 of VM patients (Dunnett's test).Conclusions: VM patients showed lack of habituation (potentiation) of Na-Pa amplitude in AMLR to repetitive stimuli while MD patients and HC subjects showed habituation. Observation of lack of habituation has high diagnostic accuracy for differential diagnosis of VM from MD.

Effect of Music Training on Auditory Brainstem and Middle Latency Responses

Purpose: The auditory system has potentials to reorganize its structure and function in response to environmental changes such as training, experience, learning, injury, and disease. This is called neuroplasticity. A typical example of neuroplasticity is the music training, which demands cognitive and neural challenges resulting in enhanced auditory perception. This study investigated the effect of music training on auditory evoked responses, particularly auditory brainstem and middle latency responses. Methods: Forty college students consisting of twenty students with music training (musicians) and twenty students without music training (non-musicians) participated in the study. All participants have normal ranges in terms of pure tone audiometry, speech audiometry, and tympanometry. Auditory brainstem response (ABR) and auditory middle latency response (AMLR) from both ears were tested. Absolute latencies and amplitudes of waves in ABR and AMLR were obtained and analyzed.Results: The absolute latencies of wave I and V significantly differed between musicians and non-musicians. They were shorter for musicians than for non-musicians. Significant differences were found in the interpeak latencies of wave III-V and I-V between musicians and non-musicians. They were also shorter in musicians than for non-musicians. In addition, there were only significant differences in the latency of Na in AMLR between musicians and non-musicians. It was shorter for a musician than for non-musician.Conclusion: ABR was more sensitive to the efficacy of the music training.

Do tone duration changes that elicit the mismatch negativity also affect the preceding middle latency responses?

The human brain can automatically detect sound changes. Previous studies have reported that rare sounds presented within a sequence of repetitive sounds elicit the mismatch negativity (MMN) in the absence of attention in the latency range of 100-250ms. On the other hand, a previous study discovered that occasional changes in sound location enhance the middle latency response (MLR) elicited in the latency range of 10-50ms. Several studies have reported an increase in the amplitude of the MLR within the frame of oddball paradigms such as frequency and location changes. However, few studies have been conducted on paradigms employing a duration change. The purpose of the present study was to examine whether the peak amplitudes of the MLR components are enhanced by a change in duration. Twenty healthy Japanese men (age: 23.9±2.9years) participated in the present study. We used an oddball paradigm that contained standard stimuli with a duration of 10ms and deviant stimuli with a duration of 5ms. The peak amplitudes of the MLR for the deviant stimuli were then compared with those for the standard stimuli. No changes were observed in the peak amplitude of the MLR resulting from a duration change, whereas a definite MMN was elicited. The amplitude of the MLR was increased within the frame of oddball paradigms such as frequency and location changes. By contrast, the amplitude of the MLR was not changed within the duration change oddball paradigm that elicited the MMN.

Design of a miniature evoked potential testing system for animal assessment of hearing

A specially built apparatus has been designed to allow novel methodologies for simultaneous measurement of early, middle and late evoked potentials. Evoked potentials can be measured in active, unsedated, unrestrained rats. Typically, early evoked potentials are measured with animals that are anesthetized. Middle and late evoked potentials must be measured in awake animals. Chronically implanted electrodes provide the bioelectric potentials. To accomplish this active measurement, data are transferred wirelessly from a portable unit attached to the rat, to a computer via wireless Bluetooth. The system is controlled with a Raspberry Pi. Included are a differential input amplifier, A/D converter and low and high pass filters. The miniature system also includes a means to provide a wide range of auditory stimuli typically driving a small insert earphone. All programs and auditory stimuli are stored on micro SD cards. The pack stays in place and is not removable by the animal. This system is ideally suited for measurements of backward masking middle latency responses as a marker for Auditory Processing Disorders (APD). The pack is light and easily attachable.A specially built apparatus has been designed to allow novel methodologies for simultaneous measurement of early, middle and late evoked potentials. Evoked potentials can be measured in active, unsedated, unrestrained rats. Typically, early evoked potentials are measured with animals that are anesthetized. Middle and late evoked potentials must be measured in awake animals. Chronically implanted electrodes provide the bioelectric potentials. To accomplish this active measurement, data are transferred wirelessly from a portable unit attached to the rat, to a computer via wireless Bluetooth. The system is controlled with a Raspberry Pi. Included are a differential input amplifier, A/D converter and low and high pass filters. The miniature system also includes a means to provide a wide range of auditory stimuli typically driving a small insert earphone. All programs and auditory stimuli are stored on micro SD cards. The pack stays in place and is not removable by the animal. This system is ideally suited for...

Development of a point of care system for automated coma prognosis: a prospective cohort study protocol

IntroductionComa is a deep state of unconsciousness that can be caused by a variety of clinical conditions. Traditional tests for coma outcome prediction are based mainly on a set of...