BACKGROUND: Ketamine has recently attracted considerable attention for its rapid effects on patients with major depressive disorder, including treatment-resistant depression (TRD). Despite ketamine\'s promising results in treating depression, a significant number of patients do not respond to the treatment, and predicting who will benefit remains a challenge. Although its antidepressant effects are known to be linked to its action as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, the precise mechanisms that determine why some patients respond and others do not are still unclear.
OBJECTIVE: This study aims to understand the computational mechanisms underlying changes in the auditory mismatch negativity (MMN) response following treatment with intravenous ketamine. Moreover, we aim to link the computational mechanisms to their underlying neural causes and use the parameters of the neurocomputational model to make individual treatment predictions.
METHODS: This is a prospective study of 30 patients with TRD who are undergoing intravenous ketamine therapy. Prior to 3 out of 4 ketamine infusions, EEG will be recorded while patients complete the auditory MMN task. Depression, suicidality, and anxiety will be assessed throughout the study and a week after the last ketamine infusion. To translate the effects of ketamine on the MMN to computational mechanisms, we will model changes in the auditory MMN using the hierarchical Gaussian filter, a hierarchical Bayesian model. Furthermore, we will employ a conductance-based neural mass model of the electrophysiological data to link these computational mechanisms to their neural causes.
CONCLUSIONS: The findings of this study may improve understanding of the mechanisms underlying response and resistance to ketamine treatment in patients with TRD. The parameters obtained from fitting computational models to EEG recordings may facilitate single-patient treatment predictions, which could provide clinically useful prognostic information.
BACKGROUND: Clinicaltrials.gov NCT05464264. Registered June 24, 2022.

The aim of the present study was to identify cognitive alterations, as indicated by event-related potentials (ERPs), after one month of daily exposure to theta binaural beats (BBs) for 10 minutes. The recruited healthy subjects (n = 60) were equally divided into experimental and control groups. For a month, the experimental group was required to practice BBs listening daily, while the control group did not. ERPs were assessed at three separate visits over a span of one month, with a two-week interval between each visit. At each visit, ERPs were measured before and after listening. The auditory and visual ERPs significantly increased the auditory and visual P300 amplitudes consistently at each visit. BBs enhanced the auditory N200 amplitude consistently across all visits, but the visual N200 amplitude increased only at the second and third visits. Compared to the healthy controls, daily exposure to BBs for two weeks resulted in increased auditory P300 amplitude. Additionally, four weeks of BBs exposure not only increased auditory P300 amplitude but also reduced P300 latency. These preliminary findings suggest that listening to BBs at 6 Hz for 10 minutes daily may enhance certain aspects of cognitive function. However, further research is needed to confirm these effects and to understand the underlying mechanisms. Identifying the optimal duration and practice of listening to 6 Hz BBs could potentially contribute to cognitive enhancement strategies in healthy individuals.

BACKGROUND: Segments and tone are important sub-syllabic units that play large roles in lexical processing in tonal languages. However, their roles in lexical processing remain unclear, and the event-related potential (ERP) technique will benefit the exploration of the cognitive mechanism in lexical processing.
METHODS: The high temporal resolution of ERP enables the technique to interpret rapidly changing spoken language performances. The present ERP study examined the different roles of segments and tone in Mandarin Chinese lexical processing. An auditory priming experiment was designed that included five types of priming stimuli: consonant mismatch, vowel mismatch, tone mismatch, unrelated mismatch, and identity. Participants were asked to judge whether the target of the prime-target pair was a real Mandarin disyllabic word or not.
RESULTS: Behavioral results including reaction time and response accuracy and ERP results were collected. Results were different from those of previous studies that showed the dominant role of consonants in lexical access in mainly non-tonal languages like English. Our results showed that consonants and vowels play comparable roles, whereas tone plays a less important role than do consonants and vowels in lexical processing in Mandarin.
CONCLUSIONS: These results have implications for understanding the brain mechanisms in lexical processing of tonal languages.

Auditory nerve (AN) function has been hypothesized to deteriorate with age and noise exposure. Here, we perform a systematic review of published studies and find that the evidence for age-related deficits in AN function is largely consistent across the literature, but there are inconsistent findings among studies of noise exposure history. Further, evidence from animal studies suggests that the greatest deficits in AN response amplitudes are found in noise-exposed aged mice, but a test of the interaction between effects of age and noise exposure on AN function has not been conducted in humans. We report a study of our own examining differences in the response amplitude of the compound action potential N1 (CAP N1) between younger and older adults with and without a self-reported history of noise exposure in a large sample of human participants (63 younger adults 18-30 years of age, 103 older adults 50-86 years of age). CAP N1 response amplitudes were smaller in older than younger adults. Noise exposure history did not appear to predict CAP N1 response amplitudes, nor did the effect of noise exposure history interact with age. We then incorporated our results into two meta-analyses of published studies of age and noise exposure history effects on AN response amplitudes in neurotypical human samples. The meta-analyses found that age effects across studies are robust (r = -0.407), but noise exposure effects are weak (r = -0.152). We conclude that noise exposure effects may be highly variable depending on sample characteristics, study design, and statistical approach, and researchers should be cautious when interpreting results. The underlying pathology of age-related and noise-induced changes in AN function are difficult to determine in living humans, creating a need for longitudinal studies of changes in AN function across the lifespan and histological examination of the AN from temporal bones collected post-mortem.

Limited auditory input, whether caused by hearing loss or by electrical stimulation through a cochlear implant (CI), can be compensated by the remaining senses. Specifically for CI users, previous studies reported not only improved visual skills, but also altered cortical processing of unisensory visual and auditory stimuli. However, in multisensory scenarios, it is still unclear how auditory deprivation (before implantation) and electrical hearing experience (after implantation) affect cortical audiovisual speech processing. Here, we present a prospective longitudinal electroencephalography (EEG) study which systematically examined the deprivation- and CI-induced alterations of cortical processing of audiovisual words by comparing event-related potentials (ERPs) in postlingually deafened CI users before and after implantation (five weeks and six months of CI use). A group of matched normal-hearing (NH) listeners served as controls. The participants performed a word-identification task with congruent and incongruent audiovisual words, focusing their attention on either the visual (lip movement) or the auditory speech signal. This allowed us to study the (top-down) attention effect on the (bottom-up) sensory cortical processing of audiovisual speech. When compared to the NH listeners, the CI candidates (before implantation) and the CI users (after implantation) exhibited enhanced lipreading abilities and an altered cortical response at the N1 latency range (90-150 ms) that was characterized by a decreased theta oscillation power (4-8 Hz) and a smaller amplitude in the auditory cortex. After implantation, however, the auditory-cortex response gradually increased and developed a stronger intra-modal connectivity. Nevertheless, task efficiency and activation in the visual cortex was significantly modulated in both groups by focusing attention on the visual as compared to the auditory speech signal, with the NH listeners additionally showing an attention-dependent decrease in beta oscillation power (13-30 Hz). In sum, these results suggest remarkable deprivation effects on audiovisual speech processing in the auditory cortex, which partially reverse after implantation. Although even experienced CI users still show distinct audiovisual speech processing compared to NH listeners, pronounced effects of (top-down) direction of attention on (bottom-up) audiovisual processing can be observed in both groups. However, NH listeners but not CI users appear to show enhanced allocation of cognitive resources in visually as compared to auditory attended audiovisual speech conditions, which supports our behavioural observations of poorer lipreading abilities and reduced visual influence on audition in NH listeners as compared to CI users.

Objective:To study the characteristics of Mismatch negativity（MMN） in normal hearing patients of different ages, and to compare the MMN of normal hearing subjects at different ages to explore the differences in MMN between different ages. Methods:MMN test was performed on both ears using the classic Oddball mode. A frequency of 1 000 Hz（standard stimuli） and 2 000 Hz（deviant stimuli） was used to evoked the MMN. According to different age groups: the juvenile group（7-17 years old）, the youth group（18-44 years old）, the middle-aged group（45-59 years old）, and the elderly group（60-75 years old）, with 25 cases in each group. The MMN characteristics of normal hearing subjects in different age groups were analyzed statistically and the differences between groups were compared. All subjects underwent pure tone threshold test, tympanic reactance test and ABR test before MMN test. Results:MMN waveform could be elicited from both ears of 100 subjects. Among them, the average latency of the juvenile group was（159.70±20.34） ms while the average amplitude was（4.34±2.26） μV, For the youth group, the average latency was（166.01±28.67） ms and the average amplitude was（3.70±2.28） μV. Then in the middle-aged group, the average latency was（175.16±37.24） ms, meanwhile, the average amplitude was（2.69±0.84） μV. Finally, the elderly group has an average latency of（178.03±14.37） ms and an average amplitude of（2.11±0.70） μV. Therefore, there was no statistical difference in latency and amplitude between all groups（P>0.05）, and there was no statistical difference in latency and amplitude between left and right ears among all subjects as a whole（P>0.05）. However, when the left and right ears of all groups were compared, it was found that the latency between the left and right ears of the Juvenile group had statistical significance（P<0.05）, and the amplitude difference was not statistically significant（P>0.05）, while the latency and amplitude differences between the left and right ears of other groups had no statistical significance（P>0.05）. There were also no significant differences in latency and amplitude between men and women（P>0.05）. Conclusion:There was no statistically significant difference in the latency and amplitude of mismatched negative among normal hearing subjects of different ages, and no statistically significant difference in the MMN latency and amplitude between the left and right ears of subjects and between men and women. Therefore, the study inferred that the auditory cerebral cortex of subjects aged 7-75 years old maintained a stable state for a long time after maturity, and the latency and amplitude of mismatched negative waves were relatively stable. It is not affected by age, gender and ear side, and can stably reflect the auditory cortex function of the subjects. It has broad application prospects in clinical practice, and provides a reliable detection means for future research on the changes of the auditory cerebral cortex of patients, which is worthy of our further research and clinical promotion.
目的：研究不同年龄段正常听力者失匹配负波（mismatch negativity，MMN）特点，同时对不同年龄段正常听力者MMN进行比较，探讨不同年龄段之间MMN差异。 方法：采用经典的oddball模式对受试者双耳进行MMN测试，标准刺激和偏差刺激分别为1 000 Hz和2 000 Hz的短纯音。根据不同年龄段分组：未成年组（7～17岁）、青年组（18～44岁）、中年组（45～59岁）、老年组（60～75岁），每组均25例。统计分析不同年龄段正常听力者MMN特点并比较组间差异。所有受试者在进行MMN测试前均进行纯音听阈检查、鼓室导抗检查和听性脑干反应检查。 结果：100例受试者均可正常引出MMN波形图，未成年组：平均潜伏期为（159.70±20.34） ms，平均波幅为（4.34±2.26）μV；青年组：平均潜伏期为（166.01±28.67） ms，平均波幅为（3.70±2.28）μV；中年组：平均潜伏期为（175.16±37.24） ms，平均波幅为（2.69±0.84）μV；老年组：平均潜伏期为（178.03±14.37） ms，平均波幅为（2.11±0.70）μV，各组潜伏期及波幅差异无统计学意义（P>0.05）；同时所有受试者左右耳比较时发现左右耳之间潜伏期及波幅差异无统计学意义（P>0.05），但对各个组左右耳进行比较时发现未成年组左右耳之间潜伏期差异有统计学意义（P<0.05），波幅差异无统计学意义（P>0.05），其余组左右耳之间潜伏期及波幅差异均无统计学意义（P>0.05），男女之间潜伏期及波幅差异均无统计学意义（P>0.05）。 结论：不同年龄段正常听力者间听觉失匹配负波潜伏期及波幅差异无统计学意义，受试者左右耳间、男女间MMN潜伏期及波幅无明显统计学差异，故推断7～75岁的人群听觉大脑皮层自发育成熟后长期维持在稳定的状态，其听觉失匹配负波的潜伏期及波幅比较稳定，不受年龄、性别、耳侧的影响，能够稳定地反映受试者的听觉皮层功能状态，在临床上有较广阔的应用前景，为今后研究患者的听觉大脑皮层变化提供一项可靠的检测手段，值得进一步研究并在临床上推广使用。.

Predictive processing in the brain, involving interaction between interoceptive (bodily signal) and exteroceptive (sensory) processing, is essential for understanding music as it encompasses musical temporality dynamics and affective responses. This study explores the relationship between neural correlates and subjective certainty of chord prediction, focusing on the alignment between predicted and actual chord progressions in both musically appropriate chord sequences and random chord sequences. Participants were asked to predict the final chord in sequences while their brain activity was measured using electroencephalography (EEG). We found that the stimulus preceding negativity (SPN), an EEG component associated with predictive processing of sensory stimuli, was larger for non-harmonic chord sequences than for harmonic chord progressions. Additionally, the heartbeat evoked potential (HEP), an EEG component related to interoceptive processing, was larger for random chord sequences and correlated with prediction certainty ratings. HEP also correlated with the N5 component, found while listening to the final chord. Our findings suggest that HEP more directly reflects the subjective prediction certainty than SPN. These findings offer new insights into the neural mechanisms underlying music perception and prediction, emphasizing the importance of considering auditory prediction certainty when examining the neural basis of music cognition.

OBJECTIVE: Increasing perceptual load alters behavioral outcomes in post-stroke fatigue (PSF). While the effect of perceptual load on top-down attentional processing is known, here we investigate if increasing perceptual load modulates bottom-up attentional processing in a fatigue dependent manner.
METHODS: In this cross-sectional observational study, in 29 first-time stroke survivors with no clinical depression, an auditory oddball task consisting of target, standard, and novel tones was performed in conditions of low and high perceptual load. Electroencephalography was used to measure auditory evoked potentials. Perceived effort was rated using the visual analog scale at regular intervals during the experiment. Fatigue was measured using the fatigue severity scale. The effect of fatigue and perceptual load on behavior (response time, accuracy, and effort rating) and auditory evoked potentials (amplitude and latency) was examined using mixed model ananlysis of variances (ANOVA).
RESULTS: Response time was prolonged with greater perceptual load and fatigue. There was no effect of load or fatigue on accuracy. Greater effort was reported with higher perceptual load both in high and low fatigue. p300a amplitude of auditory evoked potentials (AEP) for novel stimuli was attenuated in high fatigue with increasing load when compared to low fatigue. Latency of p300a was longer in low fatigue with increasing load when compared to high fatigue. There were no effects on p300b components, with smaller N100 in high load conditions.
CONCLUSIONS: High fatigue specific modulation of p300a component of AEP with increasing load is indicative of distractor driven alteration in orienting response, suggestive of compromise in bottom-up selective attention in PSF.

Auditory sensory processing is assumed to occur in a hierarchical structure including the primary auditory cortex (A1), superior temporal gyrus, and frontal areas. These areas are postulated to generate predictions for incoming stimuli, creating an internal model of the surrounding environment. Previous studies on mismatch negativity have indicated the involvement of the superior temporal gyrus in this processing, whereas reports have been mixed regarding the contribution of the frontal cortex. We designed a novel auditory paradigm, the \"cascade roving\" paradigm, which incorporated complex structures (cascade sequences) into a roving paradigm. We analyzed electrocorticography data from six patients with refractory epilepsy who passively listened to this novel auditory paradigm and detected responses to deviants mainly in the superior temporal gyrus and inferior frontal gyrus. Notably, the inferior frontal gyrus exhibited broader distribution and sustained duration of deviant-elicited responses, seemingly differing in spatio-temporal characteristics from the prediction error responses observed in the superior temporal gyrus, compared with conventional oddball paradigms performed on the same participants. Moreover, we observed that the deviant responses were enhanced through stimulus repetition in the high-gamma range mainly in the superior temporal gyrus. These features of the novel paradigm may aid in our understanding of auditory predictive coding.

We interrogated auditory sensory memory capabilities in individuals with CLN3 disease (juvenile neuronal ceroid lipofuscinosis), specifically for the feature of \"duration\" processing. Given decrements in auditory processing abilities associated with later-stage CLN3 disease, we hypothesized that the duration-evoked mismatch negativity (MMN) of the event related potential (ERP) would be a marker of progressively atypical cortical processing in this population, with potential applicability as a brain-based biomarker in clinical trials.
We employed three stimulation rates (fast: 450 ms, medium: 900 ms, slow: 1800 ms), allowing for assessment of the sustainability of the auditory sensory memory trace. The robustness of MMN directly relates to the rate at which the regularly occurring stimulus stream is presented. As presentation rate slows, robustness of the sensory memory trace diminishes. By manipulating presentation rate, the strength of the sensory memory trace is parametrically varied, providing greater sensitivity to detect auditory cortical dysfunction. A secondary hypothesis was that duration-evoked MMN abnormalities in CLN3 disease would be more severe at slower presentation rates, resulting from greater demand on the sensory memory system.
Data from individuals with CLN3 disease (N = 21; range 6-28 years of age) showed robust MMN responses (i.e., intact auditory sensory memory processes) at the medium stimulation rate. However, at the fastest rate, MMN was significantly reduced, and at the slowest rate, MMN was not detectable in CLN3 disease relative to neurotypical controls (N = 41; ages 6-26 years).
Results reveal emerging insufficiencies in this critical auditory perceptual system in individuals with CLN3 disease.