On the Interpretation of the Operation of Natural Selection in Class-Structured Populations.

AbstractBiological adaptation is the outcome of allele-frequency change by natural selection. At the same time, populations are usually class structured as individuals occupy different states, such as age, sex, or stage. This is known to result in the differential transmission of alleles through nonheritable fitness differences called class transmission, which also affects allele-frequency change even in the absence of selection. How does one then isolate allele-frequency change due to selection from that due to class transmission? We decompose one-generational allele-frequency change in terms of effects of selection and class transmission and show how reproductive values can be used to reach a decomposition between any two distant generations of the evolutionary process. This provides a missing relationship between multigenerational allele-frequency change and the operation of selection. It also allows a measure of fitness to be defined summarizing the effect of selection in a multigenerational evolutionary process, which connects asymptotically to invasion fitness.

Cortical Processing of Frequency Changes Reflected by the Acoustic Change Complex in Adult Cochlear Implant Users.

The purpose of this study was to examine neural substrates of frequency change detection in cochlear implant (CI) recipients using the acoustic change complex (ACC), a type of cortical auditory evoked potential elicited by acoustic changes in an ongoing stimulus. A psychoacoustic test and electroencephalographic recording were administered in 12 postlingually deafened adult CI users. The stimuli were pure tones containing different magnitudes of upward frequency changes. Results showed that the frequency change detection threshold (FCDT) was 3.79% in the CI users, with a large variability. The ACC N1' latency was significantly correlated with the FCDT and the clinically collected speech perception score. The results suggested that the ACC evoked by frequency changes can serve as a useful objective tool in assessing frequency change detection capability and predicting speech perception performance in CI users.

Identification of tumor mutations in plasma based on mutation variant frequency change (MVFC).

To overcome the dependency of strategies utilizing cell-free DNA (cfDNA) on tissue sampling, the emergence of sequencing panels for non-invasive mutation screening was promoted. However, cfDNA sequencing with panels still suffers from either inaccuracy or omission, and novel approaches for accurately screening tumor mutations solely based on plasma without gene panel restriction are urgently needed. We performed unique molecular identifier (UMI) target sequencing on plasma samples and peripheral blood mononuclear cells (PBMCs) from 85 hepatocellular carcinoma (HCC) patients receiving surgical resection, which were divided into an exploration dataset (20 patients) or an evaluation dataset (65 patients). Plasma mutations were identified in pre-operative plasma, and the mutation variant frequency change (MVFC) between post- and pre-operative plasma was then calculated. In the exploration dataset, we observed that plasma mutations with MVFC < 0.2 were enriched for tumor mutations identified in tumor tissues and had frequency changes that correlated with tumor burden; these plasma mutations were therefore defined as MVFC-identified tumor mutations. The presence of MVFC-identified tumor mutations after surgery was related to shorter relapse-free survival (RFS) in both datasets and thus indicated minimum residual disease (MRD). The combination of MVFC-identified tumor mutations and Alpha Fetoprotein (AFP) could further improve MRD detection (P < 0.0001). Identification of tumor mutations based on MVFC was also confirmed to be applicable with a different gene panel. Overall, we proposed a novel strategy for non-invasive tumor mutation screening using solely plasma that could be utilized in HCC tumor-burden monitoring and MRD detection.

Genome-wide detection of changes in allelic frequency in Landrace pigs selected for resistance to mycoplasma pneumonia of swine.

Closed-pig line breeding could change the genetic structure at a genome-wide scale because of the selection in a pig breeding population. We investigated the changes in population structure among generations at a genome-wide scale and the selected loci across the genome by comparing the observed and expected allele frequency changes in mycoplasma pneumonia of swine (MPS)-selected pigs. Eight hundred and seventy-four Landrace pigs, selected for MPS resistance without reducing average daily gain over five generations, had 37,299 single nucleotide polymorphisms (SNPs) and were used for genomic analyses. Regarding population structure, individuals in the first generation were the most widely distributed and then converged into a specific group, as they were selected over five generations. For allele frequency changes, 96 and 14 SNPs had higher allele frequency changes than the 99.9% and 99.99% thresholds of the expected changes, respectively. These SNPs were evenly spread across the genome, and a few of these selected regions overlapped with previously detected quantitative trait loci for MPS and immune-related traits. Our results indicated that the considerable changes in allele frequency were identified in many regions across the genome by closed-pig line breeding based on estimated breeding value.

Seismic Response Evaluation of High-Steep Slopes Supported by Anti-Slide Piles with Different Initial Damage Based on Shaking Table Test.

In order to study the instability development process of the slope reinforced by anti-slide piles under earthquake conditions, the dynamic response characteristics of the slope are usually taken as the main characteristics, and the model test and numerical simulation are the main research methods. In this paper, a shaking table model test is designed and completed to investigate the influence of anti-slide piles with different initial damage on the failure mode of high and steep slope under earthquake conditions. The changes in velocity, strain and natural frequency during slope vibration are tested in combination with cloud maps when sinusoidal waves of different accelerations with a peak value of 5 Hz are applied. Thus, the differences of slope failure development process and dynamic response characteristics are obtained. The experimental results show that the anti-slide pile with different initial damage has obvious influence on the slope instability process. Under the condition of good anti-slide pile quality, the failure development of the slope behind the pile is limited to soil sliding on top of the slope, slope sliding and overburden sliding; the front slope foot of pile mainly forms shear belt and local sliding. With the decrease in the initial mass of the anti-slide pile, the slope failure develops into topsoil sliding, slope sliding and deep integral sliding; analogously, the failure of the slope in front of the pile develops into a whole slip along the slip belt. The natural frequency cloud map can directly reflect the damage location of the slope, and the frequency change rate is positively correlated with the cumulative shear strain. It shows that the macro-failure characteristics of the model slope change well when the natural frequency is used as the sensitive index to measure the influence of vibration on the model slope. The threshold value of the natural frequency change rate can distinguish different development stages of the slope; 1% is the threshold value of stage II, and 1.5% is the threshold value of stage III.

Cortical potentials evoked by tone frequency changes can predict speech perception in noise.

Accurate and objective assessment of higher order auditory processing is challenging and mainly relies on evaluations that require a subjects' active participation in tests such as frequency discrimination or speech perception in noise. This study investigates the value of cortical auditory evoked potentials (CAEPs) evoked in response to auditory change stimuli, known as acoustic change complexes (ACCs), as an objective measurement of auditory performance in hearing impairment. Secondary objectives were to assess the effect of hearing loss and non-professional musical experience on the ACC, and compare the ACC to the 'conventional' CAEP evoked in response to stimulus onset. In 24 normal-hearing subjects, consisting of 12 musicians and 12 non-musicians, and 13 age-matched hearing-impaired subjects ACCs were recorded in response to 12% frequency increases at four base frequencies (0.5, 1, 2 and 4 kHz). ACC amplitudes and latencies were compared to frequency discrimination thresholds at each base frequency, and to speech perception in noise. Frequency discrimination and speech perception in noise were significantly better for larger ACC N1-P2 amplitudes and shorter N1 latencies, whereas both frequency discrimination and speech perception did not correlate with onset CAEP amplitude or latency. Multiple regression analysis for prediction of speech perception in noise revealed that the strongest model was obtained by averaging over three frequencies (1, 2 and 4 kHz) with two significant predictors: hearing loss (R2 = 0.52) and ACC latency (R2 = 0.35). Thus, explaining 87% of the variance, this model indicates that subjects with longer ACC latencies have worse speech perception in noise than subjects with comparable hearing thresholds and shorter ACC latencies. If hearing loss was removed from this model, the combination of ACC amplitude and latency over those three frequencies explained 74% of the total variance in speech perception in noise. There were no differences in frequency discrimination, speech perception, CAEP, or ACC between recreational musicians and non-musicians. We conclude that the objective ACC N1 latency is a good predictor of speech perception in noise. When confirmed in validation studies with larger numbers of subjects, it can aid clinicians in their evaluation of auditory performance and higher order processing, in particular when behavioral testing is unreliable.

Relationship Between the Ability to Detect Frequency Changes or Temporal Gaps and Speech Perception Performance in Post-lingual Cochlear Implant Users.

Previous studies, using modulation stimuli, on the relative effects of frequency resolution and time resolution on CI users' speech perception failed to reach a consistent conclusion. In this study, frequency change detection and temporal gap detection were used to investigate the frequency resolution and time resolution of CI users, respectively. Psychophysical and neurophysiological methods were used to simultaneously investigate the effects of frequency and time resolution on speech perception in post-lingual cochlear implant (CI) users. We investigated the effects of psychophysical results [frequency change detection threshold (FCDT), gap detection threshold (GDT)], and acoustic change complex (ACC) responses (evoked threshold, latency, or amplitude of ACC induced by frequency change or temporal gap) on speech perception [recognition rate of monosyllabic words, disyllabic words, sentences in quiet, and sentence recognition threshold (SRT) in noise]. Thirty-one adult post-lingual CI users of Mandarin Chinese were enrolled in the study. The stimuli used to induce ACCs to frequency changes were 800-ms pure tones (fundamental frequency was 1,000 Hz); the frequency change occurred at the midpoint of the tones, with six percentages of frequency changes (0, 2, 5, 10, 20, and 50%). Temporal silences with different durations (0, 5, 10, 20, 50, and 100 ms) were inserted in the middle of the 800-ms white noise to induce ACCs evoked by temporal gaps. The FCDT and GDT were obtained by two 2-alternative forced-choice procedures. The results showed no significant correlation between the CI hearing threshold and speech perception in the study participants. In the multiple regression analysis of the influence of simultaneous psychophysical measures and ACC responses on speech perception, GDT significantly predicted every speech perception index, and the ACC amplitude evoked by the temporal gap significantly predicted the recognition of disyllabic words in quiet and SRT in noise. We conclude that when the ability to detect frequency changes and the temporal gap is considered simultaneously, the ability to detect frequency changes may have no significant effect on speech perception, but the ability to detect temporal gaps could significantly predict speech perception.

Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals.

Background & Aims: Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. Methods: SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results: The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. Conclusions: Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized. Lay summary: Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses.

Cortical processing of location and frequency changes of sounds in normal hearing listeners.

Sounds we hear in our daily life contain changes in the acoustic features (e.g., frequency, intensity, and duration or "what" information) and/or changes in location ("where" information). The purpose of this study was to examine the cortical auditory evoked potentials (CAEPs) to the change within a stimulus, the acoustic change complex (ACC), in frequency (F) and location (L) of the sound in normal hearing listeners. Fifteen right-handed young normal hearing listeners participated in the electroencephalographic (EEG) recordings. The acoustic stimuli were pure tones (base frequency at 250 Hz) of 1 s, with a perceivable change either in location (L, 180°), frequency (F, 5% and 50%), or both location and frequency (L+F) in the middle of the tone. Additionally, the 250 Hz tone of 1 sec without any change was used as a reference. The participants were asked to listen passively to the stimuli and not to move their heads during the testing. Compared to the reference tone, by which only the onset-CAEP was elicited, the tones containing changes (L, F, or L+F) elicited both onset-CAEP and the ACC. The waveform analysis of ACCs from the vertex electrode (electrode Cz) showed that, larger sound changes evoked larger peak amplitudes [e.g., (L+50%F)- > L-change; (L+50%F)- > 5%F-change] and shorter the peak latencies ([(L+5%F)- < 5%F-change; 50%F- < 5%F-change; (L+50%F)- < 5%F-change] . The current density patterns for the ACC N1' peak displayed some differences between L-change vs. F-change, supporting different cortical processing for "where" and "what" information of the sound; regardless of the nature of the sound change, larger changes evoked a stronger activation than smaller changes [e.g., L- > 5%F-change; (L+5%F)- > 5%F-change; 50%F- > 5%F-change] in frontal lobe regions including the cingulate gyrus, medial frontal gyrus (MFG), superior frontal gyrus (SFG), the limbic lobe cingulate gyrus, and the parietal lobe postcentral gyrus. The results suggested that sound change-detection involves memory-based acoustic comparison (the neural encoding for the sound change vs. neural encoding for the pre-change stimulus stored in memory) and involuntary attention switch.

The Acoustic Change Complex in Response to Frequency Changes and Its Correlation to Cochlear Implant Speech Outcomes.

One of the biggest challenges that face cochlear implant (CI) users is the highly variable hearing outcomes of implantation across patients. Since speech perception requires the detection of various dynamic changes in acoustic features (e.g., frequency, intensity, timing) in speech sounds, it is critical to examine the ability to detect the within-stimulus acoustic changes in CI users. The primary objective of this study was to examine the auditory event-related potential (ERP) evoked by the within-stimulus frequency changes (F-changes), one type of the acoustic change complex (ACC), in adult CI users, and its correlation to speech outcomes. Twenty-one adult CI users (29 individual CI ears) were tested with psychoacoustic frequency change detection tasks, speech tests including the Consonant-Nucleus-Consonant (CNC) word recognition, Arizona Biomedical Sentence Recognition in quiet and noise (AzBio-Q and AzBio-N), and the Digit-in-Noise (DIN) tests, and electroencephalographic (EEG) recordings. The stimuli for the psychoacoustic tests and EEG recordings were pure tones at three different base frequencies (0.25, 1, and 4 kHz) that contained a F-change at the midpoint of the tone. Results showed that the frequency change detection threshold (FCDT), ACC N1' latency, and P2' latency did not differ across frequencies (p > 0.05). ACC N1'-P2 amplitude was significantly larger for 0.25 kHz than for other base frequencies (p < 0.05). The mean N1' latency across three base frequencies was negatively correlated with CNC word recognition (r = -0.40, p < 0.05) and CNC phoneme (r = -0.40, p < 0.05), and positively correlated with mean FCDT (r = 0.46, p < 0.05). The P2' latency was positively correlated with DIN (r = 0.47, p < 0.05) and mean FCDT (r = 0.47, p < 0.05). There was no statistically significant correlation between N1'-P2' amplitude and speech outcomes (all ps > 0.05). Results of this study indicated that variability in CI speech outcomes assessed with the CNC, AzBio-Q, and DIN tests can be partially explained (approximately 16-21%) by the variability of cortical sensory encoding of F-changes reflected by the ACC.

Flowering time regulation model revisited by pooled sequencing of mass selection populations.

Maize is one of the most broadly cultivated crops throughout the world, and flowering time is a major adaptive trait for its diffusion. The biggest challenge in understanding maize flowering genetic architecture is that the trait is confounded with population structure. To eliminate the effect, we revisited the flower time genetic network by using a tropical maize population Pop32, which was under mass selection for adaptation to early flowering time in China for six generations from tropical to temperate regions. The days to anthesis (DTA) of the initial (Pop32C0), intermedia (Pop32C3), and final population (Pop32C5) was 90.77, 84.63, and 79.72 days on average, respectively. To examine the genetic mechanism and identify the genetic loci underlying this rapid change in flowering time of Pop32, we bulked 30 individuals from C0, C3, and C5 to conduct the whole genome sequencing. And we finally identified 4,973,810 high-quality single nucleotide polymorphisms (SNPs) and 6,517 genes with allele frequency significantly changed during the artificial improvement process. We speculate that these genes might participate in the adaptive improvement process and control flowering time. To identify the candidate genes for flowering time from the gene set with allele frequency changed, we carried out weighted gene co-expression network analysis (WGCNA), and identified four co-expression modules that highly associated with the flowering time development, as well as constructed the co-expression network of key flowering time genes. Gene Ontology (GO) enrichment analysis revealed that the GO terms photosynthesis/light reaction, carbohydrate binding, auxin mediated signaling pathway, response to temperature stimulus that are closely connected with flowering time. Furthermore, targeted GWAS revealed the genes are significantly connected with the flowering time. qRT-PCR of four candidate genes GRMZM2G019879, GRMZM2G055905, GRMZM2G058158, and GRMZM2G171365 showed that their expression level is similar to the flowering time genes, which playing a key role in maize flowering time transition. This study revealed that the changes of flowering time in mass selection process may be strongly associated with the variations of allele frequency changes, and we identified some important candidate genes for flowering time, which will provide a new insight for the rapid improvement of maize important agronomic traits and promote the gene cloning of maize flowering time.

Cortical potentials evoked by tone frequency changes compared to frequency discrimination and speech perception: Thresholds in normal-hearing and hearing-impaired subjects.

Frequency discrimination ability varies within the normal hearing population, partially explained by factors such as musical training and age, and it deteriorates with hearing loss. Frequency discrimination, while essential for several auditory tasks, is not routinely measured in clinical setting. This study investigates cortical auditory evoked potentials in response to frequency changes, known as acoustic change complexes (ACCs), and explores their value as a clinically applicable objective measurement of frequency discrimination. In 12 normal-hearing and 13 age-matched hearing-impaired subjects, ACC thresholds were recorded at 4 base frequencies (0.5, 1, 2, 4 kHz) and compared to psychophysically assessed frequency discrimination thresholds. ACC thresholds had a moderate to strong correlation to psychophysical frequency discrimination thresholds. In addition, ACC thresholds increased with hearing loss and higher ACC thresholds were associated with poorer speech perception in noise. The ACC threshold in response to a frequency change therefore holds promise as an objective clinical measurement in hearing impairment, indicative of frequency discrimination ability and related to speech perception. However, recordings as conducted in the current study are relatively time consuming. The current clinical application would be most relevant in cases where behavioral testing is unreliable.

Over-projected Pacific warming and extreme El Niño frequency due to CMIP5 common biases.

Extreme El Niño events severely disrupt the global climate, causing pronounced socio-economic losses. A prevailing view is that extreme El Niño events, defined by total precipitation or convection in the Niño3 area, will increase 2-fold in the future. However, this projected change was drawn without removing the potential impacts of Coupled Model Intercomparison Project phase 5 (CMIP5) models' common biases. Here, we find that the models' systematic biases in simulating tropical climate change over the past century can reduce the reliability of the projected change in the Pacific sea surface temperature (SST) and its related extreme El Niño frequency. The projected Pacific SST change, after removing the impacts of 13 common biases, displays a 'La Niña-like' rather than 'El Niño-like' change. Consequently, the extreme El Niño frequency, which is highly linked to the zonal distribution of the Pacific SST change, would remain mostly unchanged under CMIP5 warming scenarios. This finding increases confidence in coping with climate risks associated with global warming.

Polygenic Selection within a Single Generation Leads to Subtle Divergence among Ecological NichesINc.

Selection on standing genetic variation may be effective enough to allow for adaptation to distinct niche environments within a single generation. Minor allele frequency changes at multiple, redundant loci of small effect can produce remarkable phenotypic shifts. Yet, demonstrating rapid adaptation via polygenic selection in the wild remains challenging. Here we harness natural replicate populations that experience similar selection pressures and harbor high within-, yet negligible among-population genetic variation. Such populations can be found among the teleost Fundulus heteroclitus that inhabits marine estuaries characterized by high environmental heterogeneity. We identify 10,861 single nucleotide polymorphisms in F. heteroclitus that belong to a single, panmictic population yet reside in environmentally distinct niches (one coastal basin and three replicate tidal ponds). By sampling at two time points within a single generation, we quantify both allele frequency change within as well as spatial divergence among niche subpopulations. We observe few individually significant allele frequency changes yet find that the "number" of moderate changes exceeds the neutral expectation by 10-100%. We find allele frequency changes to be significantly concordant in both direction and magnitude among all niche subpopulations, suggestive of parallel selection. In addition, within-generation allele frequency changes generate subtle but significant divergence among niches, indicative of local adaptation. Although we cannot distinguish between selection and genotype-dependent migration as drivers of within-generation allele frequency changes, the trait/s determining fitness and/or migration likelihood appear to be polygenic. In heterogeneous environments, polygenic selection and polygenic, genotype-dependent migration offer conceivable mechanisms for within-generation, local adaptation to distinct niches.

A Preliminary Study of the Effects of Attentive Music Listening on Cochlear Implant Users' Speech Perception, Quality of Life, and Behavioral and Objective Measures of Frequency Change Detection.

INTRODUCTION: Most cochlear implant (CI) users have difficulty in listening tasks that rely strongly on perception of frequency changes (e.g., speech perception in noise, musical melody perception, etc.). Some previous studies using behavioral or subjective assessments have shown that short-term music training can benefit CI users' perception of music and speech. Electroencephalographic (EEG) recordings may reveal the neural basis for music training benefits in CI users. OBJECTIVE: To examine the effects of short-term music training on CI hearing outcomes using a comprehensive test battery of subjective evaluation, behavioral tests, and EEG measures. DESIGN: Twelve adult CI users were recruited for a home-based music training program that focused on attentive listening to music genres and materials that have an emphasis on melody. The participants used a music streaming program (i.e., Pandora) downloaded onto personal electronic devices for training. The participants attentively listened to music through a direct audio cable or through Bluetooth streaming. The training schedule was 40 min/session/day, 5 days/week, for either 4 or 8 weeks. The pre-training and post-training tests included: hearing thresholds, Speech, Spatial and Qualities of Hearing Scale (SSQ12) questionnaire, psychoacoustic tests of frequency change detection threshold (FCDT), speech recognition tests (CNC words, AzBio sentences, and QuickSIN), and EEG responses to tones that contained different magnitudes of frequency changes. RESULTS: All participants except one finished the 4- or 8-week training, resulting in a dropout rate of 8.33%. Eleven participants performed all tests except for two who did not participate in EEG tests. Results showed a significant improvement in the FCDTs as well as performance on CNC and QuickSIN after training (p < 0.05), but no significant improvement in SSQ scores (p > 0.05). Results of the EEG tests showed larger post-training cortical auditory evoked potentials (CAEPs) in seven of the nine participants, suggesting a better cortical processing of both stimulus onset and within-stimulus frequency changes. CONCLUSION: These preliminary data suggest that extensive, focused music listening can improve frequency perception and speech perception in CI users. Further studies that include a larger sample size and control groups are warranted to determine the efficacy of short-term music training in CI users.

The Effect of Side of Implantation on the Cortical Processing of Frequency Changes in Adult Cochlear Implant Users.

Cochlear implants (CI) are widely used in children and adults to restore hearing function. However, CI outcomes are vary widely. The affected factors have not been well understood. It is well known that the right and left hemispheres play different roles in auditory perception in adult normal hearing listeners. It is unknown how the implantation side may affect the outcomes of CIs. In this study, the effect of the implantation side on how the brain processes frequency changes within a sound was examined in 12 right-handed adult CI users. The outcomes of CIs were assessed with behaviorally measured frequency change detection threshold (FCDT), which has been reported to significantly affect CI speech performance. The brain activation and regions were also examined using acoustic change complex (ACC, a type of cortical potential evoked by acoustic changes within a stimulus), on which the waveform analysis and the standardized low-resolution brain electromagnetic tomography (sLORETA) were performed. CI users showed activation in the temporal lobe and non-temporal areas, such as the frontal lobe. Right-ear CIs could more efficiently activate the contralateral hemisphere compared to left-ear CIs. For right-ear CIs, the increased activation in the contralateral temporal lobe together with the decreased activation in the contralateral frontal lobe was correlated with good performance of frequency change detection (lower FCDTs). Such a trend was not found in left-ear CIs. These results suggest that the implantation side may significantly affect neuroplasticity patterns in adults.

Long-Term Musical Training Alters Auditory Cortical Activity to the Frequency Change.

Objective: The ability to detect frequency variation is a fundamental skill necessary for speech perception. It is known that musical expertise is associated with a range of auditory perceptual skills, including discriminating frequency change, which suggests the neural encoding of spectral features can be enhanced by musical training. In this study, we measured auditory cortical responses to frequency change in musicians to examine the relationships between N1/P2 responses and behavioral performance/musical training. Methods: Behavioral and electrophysiological data were obtained from professional musicians and age-matched non-musician participants. Behavioral data included frequency discrimination detection thresholds for no threshold-equalizing noise (TEN), +5, 0, and -5 signal-to-noise ratio settings. Auditory-evoked responses were measured using a 64-channel electroencephalogram (EEG) system in response to frequency changes in ongoing pure tones consisting of 250 and 4,000 Hz, and the magnitudes of frequency change were 10%, 25% or 50% from the base frequencies. N1 and P2 amplitudes and latencies as well as dipole source activation in the left and right hemispheres were measured for each condition. Results: Compared to the non-musician group, behavioral thresholds in the musician group were lower for frequency discrimination in quiet conditions only. The scalp-recorded N1 amplitudes were modulated as a function of frequency change. P2 amplitudes in the musician group were larger than in the non-musician group. Dipole source analysis showed that P2 dipole activity to frequency changes was lateralized to the right hemisphere, with greater activity in the musician group regardless of the hemisphere side. Additionally, N1 amplitudes to frequency changes were positively related to behavioral thresholds for frequency discrimination while enhanced P2 amplitudes were associated with a longer duration of musical training. Conclusions: Our results demonstrate that auditory cortical potentials evoked by frequency change are related to behavioral thresholds for frequency discrimination in musicians. Larger P2 amplitudes in musicians compared to non-musicians reflects musical training-induced neural plasticity.

Frequency change detection and speech perception in cochlear implant users.

Dynamic frequency changes in sound provide critical cues for speech perception. Most previous studies examining frequency discrimination in cochlear implant (CI) users have employed behavioral tasks in which target and reference tones (differing in frequency) are presented statically in separate time intervals. Participants are required to identify the target frequency by comparing stimuli across these time intervals. However, perceiving dynamic frequency changes in speech requires detection of within-interval frequency change. This study explored the relationship between detection of within-interval frequency changes and speech perception performance of CI users. Frequency change detection thresholds (FCDTs) were measured in 20 adult CI users using a 3-alternative forced-choice (3AFC) procedure. Stimuli were 1-sec pure tones (base frequencies at 0.25, 1, 4 kHz) with frequency changes occurring 0.5 s after the tone onset. Speech tests were 1) Consonant-Nucleus-Consonant (CNC) monosyllabic word recognition, 2) Arizona Biomedical Sentence Recognition (AzBio) in Quiet, 3) AzBio in Noise (AzBio-N, +10 dB signal-to-noise/SNR ratio), and 4) Digits-in-noise (DIN). Participants' subjective satisfaction with the CI was obtained. Results showed that correlations between FCDTs and speech perception were all statistically significant. The satisfaction level of CI use was not related to FCDTs, after controlling for major demographic factors. DIN speech reception thresholds were significantly correlated to AzBio-N scores. The current findings suggest that the ability to detect within-interval frequency changes may play an important role in speech perception performance of CI users. FCDT and DIN can serve as simple and rapid tests that require no or minimal linguistic background for the prediction of CI speech outcomes.

Tone-Evoked Acoustic Change Complex (ACC) Recorded in a Sedated Animal Model.

The acoustic change complex (ACC) is a scalp-recorded cortical evoked potential complex generated in response to changes (e.g., frequency, amplitude) in an auditory stimulus. The ACC has been well studied in humans, but to our knowledge, no animal model has been evaluated. In particular, it was not known whether the ACC could be recorded under the conditions of sedation that likely would be necessary for recordings from animals. For that reason, we tested the feasibility of recording ACC from sedated cats in response to changes of frequency and amplitude of pure-tone stimuli. Cats were sedated with ketamine and acepromazine, and subdermal needle electrodes were used to record electroencephalographic (EEG) activity. Tones were presented from a small loudspeaker located near the right ear. Continuous tones alternated at 500-ms intervals between two frequencies or two levels. Neurometric functions were created by recording neural response amplitudes while systematically varying the magnitude of steps in frequency centered in octave frequency around 2, 4, 8, and 16 kHz, all at 75 dB SPL, or in decibel level around 75 dB SPL tested at 4 and 8 kHz. The ACC could be recorded readily under this ketamine/azepromazine sedation. In contrast, ACC could not be recorded reliably under any level of isoflurane anesthesia that was tested. The minimum frequency (expressed as Weber fractions (df/f)) or level steps (expressed in dB) needed to elicit ACC fell in the range of previous thresholds reported in animal psychophysical tests of discrimination. The success in recording ACC in sedated animals suggests that the ACC will be a useful tool for evaluation of other aspects of auditory acuity in normal hearing and, presumably, in electrical cochlear stimulation, especially for novel stimulation modes that are not yet feasible in humans.

Effects of Exogenous Auditory Attention on Temporal and Spectral Resolution.

Previous research in the visual domain suggests that exogenous attention in form of peripheral cueing increases spatial but lowers temporal resolution. It is unclear whether this effect transfers to other sensory modalities. Here, we tested the effects of exogenous attention on temporal and spectral resolution in the auditory domain. Eighteen young, normal-hearing adults were tested in both gap and frequency change detection tasks with exogenous cuing. Benefits of valid cuing were only present in the gap detection task while costs of invalid cuing were observed in both tasks. Our results suggest that exogenous attention in the auditory system improves temporal resolution without compromising spectral resolution.