Shorter Contextual Timescale Rather Than Memory Deficit in Aging.

Many aspects of cognitive ability and brain function that change as we age look like deficits on account of measurable differences in comparison to younger adult groups. One such difference occurs in auditory sensory responses that index perceptual learning. Meta-analytic findings show reliable age-related differences in auditory responses to repetitive patterns of sound and to rare violations of those patterns, variously attributed to deficits in auditory sensory memory and inhibition. Here, we determine whether proposed deficits would render older adults less prone to primacy effects, robustly observed in young adults, which present as a tendency for first learning to have a disproportionate influence over later perceptual inference. The results confirm this reduced sensitivity to primacy effects but do not support impairment in auditory sensory memory as the origin of this difference. Instead, the aging brain produces data consistent with shorter timescales of contextual reference. In conclusion, age-related differences observed previously for perceptual inference appear highly context-specific necessitating reconsideration of whether and to what function the notion of deficit should be attributed, and even whether the notion of deficit is appropriate at all.

Electrophysiological and neuropsychological assessment of cognition in spinocerebellar ataxia type 1 patients: a pilot study.

BACKGROUND: Event-related potentials (ERPs) reflect cognitive processing: negative early components (N100, N200) are involved in the sensory and perceptual processing of a stimulus, whereas late positive component P300 requires conscious attention. Both neuropsychological and affective disorders are present in patients with spinocerebellar ataxia type 1 (SCA1), but the underlying mechanisms need further clarification. MATERIALS AND METHODS: In this pilot study, we assessed cognitive processing by recording auditory ERPs in 16 consecutive SCA1 patients and 16 healthy controls (HC) matched for age and sex. Motor and nonmotor symptoms were evaluated using the Scale for the Assessment and Rating of Ataxia (SARA) and an extensive neuropsychological battery. ERPs were recorded using an oddball paradigm, and peak latency and amplitude of N100, N200, and P300 were measured in the averaged responses to target tones. RESULTS: We found in SCA1 significantly increased latencies of N200 and P300 (p=0.033, p=0.007) and decreased amplitudes of N100 and P300 (p=0.024, p=0.038) compared with HC. Furthermore, P300 latency had the highest AUC in the discrimination of SCA1 in ROC analysis. The expansion of trinucleotide repeats correlated with P300 latency (r=-0.607, p=0.048), whereas both P300 and N100 amplitudes correlated with the severity of motor symptoms (r=-0.692, p=0.003; r=-0.621; p=0.010). Significant correlations between P300 latency and the scores of Emotion Attribution Task (r=-0.633, p=0.027), as well as between N200 latency and the scores of Frontal Assessment Battery and Stroop test (r=-0.520, p=0.047; r=0.538, p=0.039), were observed. CONCLUSIONS: This research provides for the first time an extensive characterization of ERPs as useful electrophysiological markers to identify early cognitive dysfunction in SCA1.

INFLUENCE OF CONTINUOUS POSITIVE AIRWAY PRESSURE TREATMENT ON AUDITORY EVENT-RELATED POTENTIALS P300.

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by obstructions of the upper airway during sleep, resulting in repetitive breathing pauses accompanied by oxygen desaturation and arousal from sleep. OSA can be successfully treated with continuous positive airway pressure (CPAP), weight loss, positional therapy, oral appliances, hypoglossal nerve stimulation, and surgical procedures. It has been observed that untreated OSA is related to chronic disorders including hypertension, arrhythmias, congestive heart failure, coronary heart disease, diabetes mellitus, hyperlipidemia, stroke, depression, and cognitive decline. Event-related potentials (ERPs) is the procedure that has been widely used for evaluating cognitive brain functions. Using auditory event-related potentials (P300), this study aimed to examine the effect of CPAP therapy on cognitive functions in patients with moderate and severe OSA. The results of the study showed improvement in P300 latency and amplitude after 3 months of CPAP therapy, indicating a positive effect of CPAP therapy in the prevention of cognitive decline in patients with OSA.

Multivariate analysis of the systemic response to auditory stimulation: An integrative approach.

NEW FINDINGS: What is the central question of this study? Auditory stimulation produces a response in different physiological systems: cardiac, peripheral blood flow, electrodermal, cortical and peripheral haemodynamic responses and auditory event-related potentials. Do all these subsystems covary when responding to auditory stimulation, suggesting a unified locus of control, or do they not covary, suggesting independent loci of control for these physiological responses? What is the main finding and its importance? Auditory sensory gating reached a fixed level of neural activity independently of the intensity of auditory stimulation. The use of multivariate techniques revealed the presence of different regulatory mechanisms for the different physiologically recorded signals. ABSTRACT: We studied the effects of an increasing amplitude of auditory stimulation on a variety of autonomic and CNS responses and their possible interdependence. The subjects were stimulated with an increasing amplitude of auditory tones while the auditory event-related potentials (ERPs), the cortical and extracerebral functional near-infrared spectroscopy (fNIRS) signal of standard and short separation channel recordings, the peripheral pulse measured by photoplethysmography, heart rate and electrodermal responses were recorded. Trials with eight tones of equal amplitude were presented. The results showed a parallel increase of activity in ERPs, fNIRS and peripheral responses with the increase in intensity of auditory stimulation. The ERPs, measured as peak-to-peak N1-P2, showed an increase in amplitude with auditory stimulation and a high attenuation from the first presentation with respect to the second to eighth presentations. Peripheral signals and standard and short channel fNIRS responses showed a decrease in amplitude in the high-intensity auditory stimulation conditions. Principal components analysis showed independent sources of variance for the recorded signals, suggesting independent control of the recorded physiological responses. The present results suggest a complex response associated to the increase of auditory stimulation with a fixed amplitude for ERPs, and a decrease in the peripheral and cortical haemodynamic response, possibly mediated by activation of the sympathetic nervous system, constituting a defensive reflex to excessive auditory stimulation.

Evaluation of multi-feature auditory deviance detection in Parkinson's disease: a mismatch negativity study.

Behavioral studies on auditory deviance detection in patients with Parkinson's disease (PD) have reported contradictory results. The primary aim of this study was to investigate auditory deviance detection of multiple auditory features in patients with PD by means of objective and reliable electroencephalographic (EEG) measurements. Twelve patients with early-stage PD and twelve age- and gender-matched healthy controls (HCs) were included in this study. Patients with PD participated without their regular dopaminergic medication. All subjects underwent an audiometric screening and performed a passive multi-feature mismatch negativity (MMN) paradigm. Repeated-measures analysis of variance (ANOVA) demonstrated no significant differences between patients with PD and HCs regarding MMN mean amplitude and latency for frequency, duration and gap deviants. Nevertheless, a trend towards increased MMN mean amplitude and latency was found in response to intensity deviants in patients with PD compared to HCs. Increased intensity MMN amplitude may indicate that more neural resources are allocated to the processing of intensity deviances in patients with PD compared to HCs. The interpretation of this intensity-specific MMN alteration is further discussed in the context of a compensatory mechanism for auditory intensity processing and involuntary attention switching in PD.

Neurophysiological investigation of auditory intensity dependence in patients with Parkinson's disease.

There is accumulating evidence for auditory dysfunctions in patients with Parkinson's disease (PD). Moreover, a possible relationship has been suggested between altered auditory intensity processing and the hypophonic speech characteristics in PD. Nonetheless, further insight into the neurophysiological correlates of auditory intensity processing in patients with PD is needed primarily. In the present study, high-density EEG recordings were used to investigate intensity dependence of auditory evoked potentials (IDAEPs) in 14 patients with PD and 14 age- and gender-matched healthy control participants (HCs). Patients with PD were evaluated in both the on- and off-medication states. HCs were also evaluated twice. Significantly increased IDAEP of the N1/P2 was demonstrated in patients with PD evaluated in the on-medication state compared to HCs. Distinctive results were found for the N1 and P2 component. Regarding the N1 component, no differences in latency or amplitude were shown between patients with PD and HCs regardless of the medication state. In contrast, increased P2 amplitude was demonstrated in patients with PD evaluated in the on-medication state compared to the off-medication state and HCs. In addition to a dopaminergic deficiency, deficits in serotonergic neurotransmission in PD were shown based on increased IDAEP. Due to specific alterations of the N1-P2 complex, the current results suggest deficiencies in early-attentive inhibitory processing of auditory input in PD. This interpretation is consistent with the involvement of the basal ganglia and the role of dopaminergic and serotonergic neurotransmission in auditory gating.

The P300 auditory event-related potential as a method to assess the benefit of contralateral hearing aid use in bimodal listeners: a proof-of-concept.

Objective: Bimodal listeners vary in the amount of benefit they receive from wearing the contralateral hearing aid. This may partially depend on the listener's auditory processing capacities. The current study explores whether the P300 event-related potential can provide insight into the mechanisms underlying the benefits of wearing a contralateral hearing aid.Design: P300s were recorded using an oddball paradigm with 500 and 250 Hz tone-bursts as standard and deviant stimuli, respectively. Subjects counted the number of deviants - a measure of performance. N2b latencies, P300 latencies, N2b-P300 amplitudes, and performance were assessed during CI-only and bimodal listening.Study sample: Five bimodal listeners.Results: P300s were present in four subjects. Amplitudes were larger during bimodal listening (bimodal: 22.3 ± 4.83 µV, CI-only: 13.1 ± 3.86 µV). Both N2b and P300 latencies were shorter during bimodal (N2b: 265 ± 20.0 ms, P300: 551 ± 129.4 ms) than CI-only listening (N2b: 326 ± 42.2 ms, P300: 402 ± 38.4 ms). While performance often reached ceiling level, the difference between the standard and deviant was generally more salient during bimodal listening.Conclusions: This study provides a proof-of-concept, suggesting that P300s may provide insight into benefits that are not always measurable with behavioural tasks.

Plasticity in auditory categorization is supported by differential engagement of the auditory-linguistic network.

To construct our perceptual world, the brain categorizes variable sensory cues into behaviorally-relevant groupings. Categorical representations are apparent within a distributed fronto-temporo-parietal brain network but how this neural circuitry is shaped by experience remains undefined. Here, we asked whether speech and music categories might be formed within different auditory-linguistic brain regions depending on listeners' auditory expertise. We recorded EEG in highly skilled (musicians) vs. less experienced (nonmusicians) perceivers as they rapidly categorized speech and musical sounds. Musicians showed perceptual enhancements across domains, yet source EEG data revealed a double dissociation in the neurobiological mechanisms supporting categorization between groups. Whereas musicians coded categories in primary auditory cortex (PAC), nonmusicians recruited non-auditory regions (e.g., inferior frontal gyrus, IFG) to generate category-level information. Functional connectivity confirmed nonmusicians' increased left IFG involvement reflects stronger routing of signal from PAC directed to IFG, presumably because sensory coding is insufficient to construct categories in less experienced listeners. Our findings establish auditory experience modulates specific engagement and inter-regional communication in the auditory-linguistic network supporting categorical perception. Whereas early canonical PAC representations are sufficient to generate categories in highly trained ears, less experienced perceivers broadcast information downstream to higher-order linguistic brain areas (IFG) to construct abstract sound labels.

Attentional modulation and domain-specificity underlying the neural organization of auditory categorical perception.

Categorical perception (CP) is highly evident in audition when listeners' perception of speech sounds abruptly shifts identity despite equidistant changes in stimulus acoustics. While CP is an inherent property of speech perception, how (if) it is expressed in other auditory modalities (e.g., music) is less clear. Moreover, prior neuroimaging studies have been equivocal on whether attentional engagement is necessary for the brain to categorically organize sound. To address these questions, we recorded neuroelectric brain responses [event-related potentials (ERPs)] from listeners as they rapidly categorized sounds along a speech and music continuum (active task) or during passive listening. Behaviorally, listeners' achieved sharper psychometric functions and faster identification for speech than musical stimuli, which was perceived in a continuous mode. Behavioral results coincided with stronger ERP differentiation between prototypical and ambiguous tokens (i.e., categorical processing) for speech but not for music. Neural correlates of CP were only observed when listeners actively attended to the auditory signal. These findings were corroborated by brain-behavior associations; changes in neural activity predicted more successful CP (psychometric slopes) for active but not passively evoked ERPs. Our results demonstrate auditory categorization is influenced by attention (active > passive) and is stronger for more familiar/overlearned stimulus domains (speech > music). In contrast to previous studies examining highly trained listeners (i.e., musicians), we infer that (i) CP skills are largely domain-specific and do not generalize to stimuli for which a listener has no immediate experience and (ii) categorical neural processing requires active engagement with the auditory stimulus.

Reduced temporal processing in older, normal-hearing listeners evident from electrophysiological responses to shifts in interaural time difference.

Previous electrophysiological studies of interaural time difference (ITD) processing have demonstrated that ITDs are represented by a nontopographic population rate code. Rather than narrow tuning to ITDs, neural channels have broad tuning to ITDs in either the left or right auditory hemifield, and the relative activity between the channels determines the perceived lateralization of the sound. With advancing age, spatial perception weakens and poor temporal processing contributes to declining spatial acuity. At present, it is unclear whether age-related temporal processing deficits are due to poor inhibitory controls in the auditory system or degraded neural synchrony at the periphery. Cortical processing of spatial cues based on a hemifield code are susceptible to potential age-related physiological changes. We consider two distinct predictions of age-related changes to ITD sensitivity: declines in inhibitory mechanisms would lead to increased excitation and medial shifts to rate-azimuth functions, whereas a general reduction in neural synchrony would lead to reduced excitation and shallower slopes in the rate-azimuth function. The current study tested these possibilities by measuring an evoked response to ITD shifts in a narrow-band noise. Results were more in line with the latter outcome, both from measured latencies and amplitudes of the global field potentials and source-localized waveforms in the left and right auditory cortices. The measured responses for older listeners also tended to have reduced asymmetric distribution of activity in response to ITD shifts, which is consistent with other sensory and cognitive processing models of aging.

Effects of language experience and stimulus context on the neural organization and categorical perception of speech.

Categorical perception (CP) represents a fundamental process in converting continuous speech acoustics into invariant percepts. Using scalp-recorded event-related brain potentials (ERPs), we investigated how tone-language experience and stimulus context influence the CP for lexical tones-pitch patterns used by a majority of the world's languages to signal word meaning. Stimuli were vowel pairs overlaid with a high-level tone (T1) followed by a pitch continuum spanning between dipping (T3) and rising (T2) contours of the Mandarin tonal space. To vary context, T1 either preceded or followed the critical T2/T3 continuum. Behaviorally, native Chinese showed stronger CP as evident by their steeper, more dichotomous psychometric functions and faster identification of linguistic pitch patterns than native English-speaking controls. Stimulus context produced shifts in both groups' categorical boundary but was more exaggerated in native listeners. Analysis of source activity extracted from primary auditory cortex revealed overall stronger neural encoding of tone in Chinese compared to English, indicating experience-dependent plasticity in cortical pitch processing. More critically, "neurometric" functions derived from multidimensional scaling and clustering of source ERPs established: (i) early auditory cortical activity could accurately predict listeners' psychometric speech identification and contextual shifts in the perceptual boundary; (ii) neurometric profiles were organized more categorically in native speakers. Our data show that tone-language experience refines early auditory cortical brain representations so as to supply more faithful templates to neural mechanisms subserving lexical pitch categorization. We infer that contextual influence on the CP for tones is determined by language experience and the frequency of pitch patterns as they occur in listeners' native lexicon.

Functional organization for musical consonance and tonal pitch hierarchy in human auditory cortex.

Pitch relationships in music are characterized by their degree of consonance, a hierarchical perceptual quality that distinguishes how pleasant musical chords/intervals sound to the ear. The origins of consonance have been debated since the ancient Greeks. To elucidate the neurobiological mechanisms underlying these musical fundamentals, we recorded neuroelectric brain activity while participants listened passively to various chromatic musical intervals (simultaneously sounding pitches) varying in their perceptual pleasantness (i.e., consonance/dissonance). Dichotic presentation eliminated acoustic and peripheral contributions that often confound explanations of consonance. We found that neural representations for pitch in early human auditory cortex code perceptual features of musical consonance and follow a hierarchical organization according to music-theoretic principles. These neural correlates emerge pre-attentively within ~ 150 ms after the onset of pitch, are segregated topographically in superior temporal gyrus with a rightward hemispheric bias, and closely mirror listeners' behavioral valence preferences for the chromatic tone combinations inherent to music. A perceptual-based organization implies that parallel to the phonetic code for speech, elements of music are mapped within early cerebral structures according to higher-order, perceptual principles and the rules of Western harmony rather than simple acoustic attributes.

Coordinated plasticity in brainstem and auditory cortex contributes to enhanced categorical speech perception in musicians.

Musicianship is associated with neuroplastic changes in brainstem and cortical structures, as well as improved acuity for behaviorally relevant sounds including speech. However, further advance in the field depends on characterizing how neuroplastic changes in brainstem and cortical speech processing relate to one another and to speech-listening behaviors. Here, we show that subcortical and cortical neural plasticity interact to yield the linguistic advantages observed with musicianship. We compared brainstem and cortical neuroelectric responses elicited by a series of vowels that differed along a categorical speech continuum in amateur musicians and non-musicians. Musicians obtained steeper identification functions and classified speech sounds more rapidly than non-musicians. Behavioral advantages coincided with more robust and temporally coherent brainstem phase-locking to salient speech cues (voice pitch and formant information) coupled with increased amplitude in cortical-evoked responses, implying an overall enhancement in the nervous system's responsiveness to speech. Musicians' subcortical and cortical neural enhancements (but not behavioral measures) were correlated with their years of formal music training. Associations between multi-level neural responses were also stronger in musically trained listeners, and were better predictors of speech perception than in non-musicians. Results suggest that musicianship modulates speech representations at multiple tiers of the auditory pathway, and strengthens the correspondence of processing between subcortical and cortical areas to allow neural activity to carry more behaviorally relevant information. We infer that musicians have a refined hierarchy of internalized representations for auditory objects at both pre-attentive and attentive levels that supplies more faithful phonemic templates to decision mechanisms governing linguistic operations.

Unraveling the role of Slc10a4 in auditory processing and sensory motor gating: Implications for neuropsychiatric disorders?

BACKGROUND: Psychiatric disorders, such as schizophrenia, are complex and challenging to study, partly due to the lack of suitable animal models. However, the absence of the Slc10a4 gene, which codes for a monoaminergic and cholinergic associated vesicular transporter protein, in knockout mice (Slc10a4-/-), leads to the accumulation of extracellular dopamine. A major challenge for studying schizophrenia is the lack of suitable animal models that accurately represent the disorder. We sought to overcome this challenge by using Slc10a4-/- mice as a potential model, considering their altered dopamine levels. This makes them a potential animal model for schizophrenia, a disorder known to be associated with altered dopamine signaling in the brain. METHODS: The locomotion, auditory sensory filtering and prepulse inhibition (PPI) of Slc10a4-/- mice were quantified and compared to wildtype (WT) littermates. Intrahippocampal electrodes were used to record auditory event-related potentials (aERPs) for quantifying sensory filtering in response to paired-clicks. The channel above aERPs phase reversal was chosen for reliably comparing results between animals, and aERPs amplitude and latency of click responses were quantified. WT and Slc10a4-/- mice were also administered subanesthetic doses of ketamine to provoke psychomimetic behavior. RESULTS: Baseline locomotion during auditory stimulation was similar between Slc10a4-/- mice and WT littermates. In WT animals, normal auditory processing was observed after i.p saline injections, and it was maintained under the influence of 5 mg/kg ketamine, but disrupted by 20 mg/kg ketamine. On the other hand, Slc10a4-/- mice did not show significant differences between N40 S1 and S2 amplitude responses in saline or low dose ketamine treatment. Auditory gating was considered preserved since the second N40 peak was consistently suppressed, but with increased latency. The P80 component showed higher amplitude, with shorter S2 latency under saline and 5 mg/kg ketamine treatment in Slc10a4-/- mice, which was not observed in WT littermates. Prepulse inhibition was also decreased in Slc10a4-/- mice when the longer interstimulus interval of 100 ms was applied, compared to WT littermates. CONCLUSION: The Slc10a4-/- mice responses indicate that cholinergic and monoaminergic systems participate in the PPI magnitude, in the temporal coding (response latency) of the auditory sensory gating component N40, and in the amplitude of aERPs P80 component. These results suggest that Slc10a4-/- mice can be considered as potential models for neuropsychiatric conditions.

Order effects in task-free learning: Tuning to information-carrying sound features.

Event-related potentials (ERPs) acquired during task-free passive listening can be used to study how sensitivity to common pattern repetitions and rare deviations changes over time. These changes are purported to represent the formation and accumulation of precision in internal models that anticipate future states based on probabilistic and/or statistical learning. This study features an unexpected finding; a strong order-dependence in the speed with which deviant responses are elicited that anchors to first learning. Participants heard four repetitions of a sequence in which an equal number of short (30 msec) and long (60 msec) pure tones were arranged into four blocks in which one was common (the standard, p = .875) and the other rare (the deviant, p = .125) with probabilities alternating across blocks. Some participants always heard the sequences commencing with the 30 msec deviant block, and others always with the 60 msec deviant block first. A deviance-detection component known as mismatch negativity (MMN) was extracted from responses and the point in time at which MMN reached maximum amplitude was used as the dependent variable. The results show that if participants heard sequences commencing with the 60 msec deviant block first, the MMN to the 60 msec and 30 msec deviant peaked at an equivalent latency. However, if participants heard sequences commencing with the 30 msec deviant first, the MMN peaked earlier to the 60 msec deviant. Furthermore, while the 30 msec MMN latency did not differ as a function of sequence composition, the 60 msec MMN latency did and was earlier when the sequences began with a 30 msec deviant first. By examining MMN latency effects as a function of age and hearing level it was apparent that the differentiation in 30 msec and 60 msec MMN latency expands with older age and raised hearing threshold due to prolongation of the time taken for the 30 msec MMN to peak. The observations are discussed with reference to how the initial sound composition may tune the auditory system to be more sensitive to different cues (i.e., offset responses vs perceived loudness). The order-effect demonstrates a remarkably powerful anchoring to first learning that might reflect initial tuning to the most valuable discriminating feature within a given listening environment, an effect that defies explanation based on statistical information alone.

Alterations of auditory sensory gating in mice with noise-induced tinnitus treated with nicotine and cannabis extract.

Tinnitus is a phantom sound perception affecting both auditory and limbic structures. The mechanisms of tinnitus remain unclear and it is debatable whether tinnitus alters attention to sound and the ability to inhibit repetitive sounds, a phenomenon also known as auditory gating. Here we investigate if noise exposure interferes with auditory gating and whether natural extracts of cannabis or nicotine could improve auditory pre-attentional processing in noise-exposed mice. We used 22 male C57BL/6J mice divided into noise-exposed (exposed to a 9-11 kHz narrow band noise for 1 h) and sham (no sound during noise exposure) groups. Hearing thresholds were measured using auditory brainstem responses, and tinnitus-like behavior was assessed using Gap prepulse inhibition of acoustic startle. After noise exposure, mice were implanted with multi-electrodes in the dorsal hippocampus to assess auditory event-related potentials in response to paired clicks. The results showed that mice with tinnitus-like behavior displayed auditory gating of repetitive clicks, but with larger amplitudes and longer latencies of the N40 component of the aERP waveform. The combination of cannabis extract and nicotine improved the auditory gating ratio in noise-exposed mice without permanent hearing threshold shifts. Lastly, the longer latency of the N40 component appears due to an increased sensitivity to cannabis extract in noise-exposed mice compared to sham mice. The study suggests that the altered central plasticity in tinnitus is more sensitive to the combined actions on the cholinergic and the endocannabinoid systems. Overall, the findings contribute to a better understanding of pharmacological modulation of auditory sensory gating.

Auditory Event-Related Potentials in Older Adults with Subjective Memory Complaints.

BACKGROUND: Auditory event-related potentials (AERPs) have been suggested as possible biomarkers for the early diagnosis of Alzheimer's disease (AD). However, no study has investigated AERP measures in individuals with subjective memory complaints (SMCs), who have been suggested to be at a pre-clinical stage of AD. OBJECTIVE: This study investigated whether AERPs in older adults with SMC can be used to objectively identify those at high risk of developing AD. METHODS: AERPs were measured in older adults. Presence of SMC was determined using the Memory Assessment Clinics Questionnaire (MAC-Q). Hearing thresholds using pure-tone audiometry, neuropsychological data, levels of amyloid-ß burden and Apolipoprotein E (APOE)ɛ genotype were also obtained A classic two-tone discrimination (oddball) paradigm was used to elicit AERPs (i.e., P50, N100, P200, N200, and P300). RESULTS: Sixty-two individuals (14 male, mean age 71.9±5.2 years) participated in this study, of which, 43 (11 male, mean age 72.4±5.5 years) were SMC and 19 (3 male, mean age 70.8±4.3 years) were non-SMC (controls). P50 latency was weakly but significantly correlated with MAC-Q scores. In addition, P50 latencies were significantly longer in Aß+ individuals compared to Aß- individuals. CONCLUSION: Results suggest that P50 latencies may be a useful tool to identify individuals at higher risk (i.e., participants with high Aß burden) of developing measurable cognitive decline. Further longitudinal and cross-sectional studies in a larger cohort on SMC individuals are warranted to determine if AERP measures could be of significance for the detection of pre-clinical AD.

Functional Plasticity Coupled With Structural Predispositions in Auditory Cortex Shape Successful Music Category Learning.

Categorizing sounds into meaningful groups helps listeners more efficiently process the auditory scene and is a foundational skill for speech perception and language development. Yet, how auditory categories develop in the brain through learning, particularly for non-speech sounds (e.g., music), is not well understood. Here, we asked musically naïve listeners to complete a brief (∼20 min) training session where they learned to identify sounds from a musical interval continuum (minor-major 3rds). We used multichannel EEG to track behaviorally relevant neuroplastic changes in the auditory event-related potentials (ERPs) pre- to post-training. To rule out mere exposure-induced changes, neural effects were evaluated against a control group of 14 non-musicians who did not undergo training. We also compared individual categorization performance with structural volumetrics of bilateral Heschl's gyrus (HG) from MRI to evaluate neuroanatomical substrates of learning. Behavioral performance revealed steeper (i.e., more categorical) identification functions in the posttest that correlated with better training accuracy. At the neural level, improvement in learners' behavioral identification was characterized by smaller P2 amplitudes at posttest, particularly over right hemisphere. Critically, learning-related changes in the ERPs were not observed in control listeners, ruling out mere exposure effects. Learners also showed smaller and thinner HG bilaterally, indicating superior categorization was associated with structural differences in primary auditory brain regions. Collectively, our data suggest successful auditory categorical learning of music sounds is characterized by short-term functional changes (i.e., greater post-training efficiency) in sensory coding processes superimposed on preexisting structural differences in bilateral auditory cortex.

The Auditory P50 Gating in Mild Cognitive Impairment: A Case-Control Study.

Objective: Auditory P50 gating changed might be a neurophysiological biomarker of the diagnosis of Mild Cognitive Impairment (MCI). We aimed to determine the impact of MCI in auditory P50 gating. Methods: All recruited participants completed structured questionnaires and finished auditory P50 gating measure. Results: A total of 20 MCI patients and 17 controls had been recruited. MCI patients had a significant higher reduction of P50 gating at Fz site, when compared to controls (1.21 ± .68 vs .66 ± .37, P = .00). Zero point five was the best cut off point to distinguish MCI and control of auditory P50 gating S2/S1 at Fz site. The P50 average amplitude at Pz site in MCI patients was significantly higher than controls (2.62 ± 1.20 vs 1.70 ± .74, P = .01). Conclusion: MCI patients might have impaired the ability of inhibiting the repeated stimulus.

Greater tau pathology is associated with altered predictive coding.

Altered predictive coding may underlie the reduced auditory mismatch negativity amplitude observed in patients with dementia. We hypothesized that accumulating dementia-associated pathologies, including amyloid and tau, lead to disturbed predictions of our sensory environment. This would manifest as increased reliance on 'observed' sensory information with an associated increase in feedforward, and decrease in feedback, signalling. To test this hypothesis, we studied a cross-sectional cohort of participants who underwent PET imaging and high-density EEG during an oddball paradigm, and used dynamic casual modelling and Bayesian statistics to make inferences about the neuronal architectures (generators) and mechanisms (effective connectivity) underlying the observed auditory-evoked responses. Amyloid-ß imaging with [C-11] Pittsburgh Compound-B PET was qualitatively rated using established criteria. Tau-positive PET scans, with [F-18]MK-6240, were defined by an MK-6240 standardized uptake value ratio positivity threshold at 2 standard deviations above the mean of the Amyloid(-) group in the entorhinal cortex (entorhinal MK-6240 standardized uptake value ratio > 1.27). The cross-sectional cohort included a total of 56 participants [9 and 13 participants in the Tau(+) and Amyloid(+) subgroups, respectively: age interquartile range of (73.50-75.34) and (70.5-75.34) years, 56 and 69% females, respectively; 46 and 43 participants in the Tau(-) and Amyloid(-) subgroups, respectively: age interquartile range of (62.72-72.5) and (62.64-72.48) years, 67 and 65% females, respectively]. Mismatch negativity amplitudes were significantly smaller in Tau+ subgroup than Tau- subgroup (cluster statistics corrected for multiple comparisons: P = 0.028). Dynamic causal modelling showed that tau pathology was associated with increased feedforward connectivity and decreased feedback connectivity, with increased excitability of superior temporal gyrus but not inferior frontal regions. This effect on superior temporal gyrus was consistent with the distribution of tau disease on PET in these participants, indicating that the observed differences in mismatch negativity reflect pathological changes evolving in preclinical dementia. Exclusion of participants with diagnosed mild cognitive impairment or dementia did not affect the results. These observational data provide proof of concept that abnormalities in predictive coding may be detected in the preclinical phase of Alzheimer's disease. This framework also provides a construct to understand how progressive impairments lead to loss of orientation to the sensory world in dementia. Based on our modelling results, plus animal models indicating that Alzheimer's disease pathologies produce hyperexcitability of higher cortical regions through local disinhibition, mismatch negativity might be a useful monitor to deploy as strategies that target interneuron dysfunction are developed.