Auditory Event-related Potentials Research Articles

Low-Level Auditory Processing Correlates With Language Abilities: An ERP Study Investigating Sequence Learning and Auditory Processing in School-Aged Children

Abstract Auditory processing and procedural learning deficits have been associated with language learning difficulties. We investigated the relationship of these skills and school-age language abilities in children with and without a history of late talking using auditory event related potentials (ERPs). Late talking (i.e., slow early language development) increases the risk of persistent language difficulties, but its causes remain unknown. Participants in this study were children with varying language abilities (n = 60). Half of the participants (n = 30) had a history of late talking. We measured procedural learning by manipulating the predictability of sine tone stimuli in a passive auditory ERP paradigm. Auditory processing was tested by examining how the presence of noise (increasing perceptual demands) affected the ERPs. Contrary to our hypotheses on auditory processing and language development, the effect of noise on ERPs did not correlate with school-age language abilities in children with or without a history of late talking. Our paradigm failed to reveal interpretable effects of predictability leaving us unable to assess the effects of procedural learning. However, better language abilities were related to weaker responses in a 75–175 ms time window, and stronger responses in a 150–250 ms time window. We suggest that the weak early responses in children with better language ability reflect efficient processing of low-level auditory information, allowing deeper processing of later, high-level auditory information. We assume that these differences reflect variation in brain maturation between individuals with varying language abilities.

EEG dynamic source imaging using a regularized optimization with spatio-temporal constraints.

One of the most important needs in neuroimaging is brain dynamic source imaging with high spatial and temporal resolution. EEG source imaging estimates the underlying sources from EEG recordings, which provides enhanced spatial resolution with intrinsically high temporal resolution. To ensure identifiability in the underdetermined source reconstruction problem, constraints on EEG sources are essential. This paper introduces a novel method for estimating source activities based on spatio-temporal constraints and a dynamic source imaging algorithm. The method enhances time resolution by incorporating temporal evolution of neural activity into a regularization function. Additionally, two spatial regularization constraints based on and norms are applied in the transformed domain to address both focal and spread neural activities, achieved through spatial gradient and Laplacian transform. Performance evaluation, conducted quantitatively using synthetic datasets, discusses the influence of parameters such as source extent, number of sources, correlation level, and SNR level on temporal and spatial metrics. Results demonstrate that the proposed method provides superior spatial and temporal reconstructions compared to state-of-the-art inverse solutions including STRAPS, sLORETA, SBL, dSPM, and MxNE. This improvement is attributed to the simultaneous integration of transformed spatial and temporal constraints. When applied to a real auditory ERP dataset, our algorithm accurately reconstructs brain source time series and locations, effectively identifying the origins of auditory evoked potentials. In conclusion, our proposed method with spatio-temporal constraints outperforms the state-of-the-art algorithms in estimating source distribution and time courses.

Pre-attentive and Attentive Auditory Event-related Potentials in Children With Attention-Deficit Hyperactivity Disorder and Autism.

Abnormalities in auditory processing are believed to play a major role in autism and attention-deficit hyperactivity disorder (ADHD). Both conditions often co-occur in children, causing difficulties in deciding the most promising intervention. Event-related potentials (ERPs) have been investigated and are showing promise to act as potential biomarkers for both conditions. This study investigated mismatch negativity (MMN) using a passive listening task and P3b in an active auditory go/no-go discrimination task. Recordings were available from 103 children (24 females): 35 with ADHD, 27 autistic, 15 autistic children with co-occurring ADHD, and 26 neurotypical (NT) children. The age range considered was between 4 and 17 years, but varied between groups. The results revealed increases in the MMN and P3b amplitudes with age. Older children with ADHD exhibited smaller P3b amplitudes, while younger autistic children showed reduced MMN amplitudes in response to phoneme changes compared to their NT counterparts. Notably, children diagnosed with autism and ADHD did not follow this pattern; instead, they exhibited more similarities to NT children. The reduced amplitudes of phonetically elicited MMN in children with autism and reduced P3b in children with ADHD suggest that the two respective ERPs can act as potential biomarkers for each condition. However, optimisation and standardisation of the testing protocol, as well as longitudinal studies are required in order to translate these findings into clinical practice.

Sex differences during development in cortical temporal processing and event related potentials in wild-type and fragile X syndrome model mice

BackgroundAutism spectrum disorder (ASD) is currently diagnosed in approximately 1 in 44 children in the United States, based on a wide array of symptoms, including sensory dysfunction and abnormal language development. Boys are diagnosed ~ 3.8 times more frequently than girls. Auditory temporal processing is crucial for speech recognition and language development. Abnormal development of temporal processing may account for ASD language impairments. Sex differences in the development of temporal processing may underlie the differences in language outcomes in male and female children with ASD. To understand mechanisms of potential sex differences in temporal processing requires a preclinical model. However, there are no studies that have addressed sex differences in temporal processing across development in any animal model of ASD.MethodsTo fill this major gap, we compared the development of auditory temporal processing in male and female wildtype (WT) and Fmr1 knock-out (KO) mice, a model of Fragile X Syndrome (FXS), a leading genetic cause of ASD-associated behaviors. Using epidural screw electrodes, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (ASSR) paradigm at young (postnatal (p)21 and p30) and adult (p60) ages from both auditory and frontal cortices of awake, freely moving mice.ResultsThe results show that ERP amplitudes were enhanced in both sexes of Fmr1 KO mice across development compared to WT counterparts, with greater enhancement in adult female than adult male KO mice. Gap-ASSR deficits were seen in the frontal, but not auditory, cortex in early development (p21) in female KO mice. Unlike male KO mice, female KO mice show WT-like temporal processing at p30. There were no temporal processing deficits in the adult mice of both sexes.ConclusionsThese results show a sex difference in the developmental trajectories of temporal processing and hypersensitive responses in Fmr1 KO mice. Male KO mice show slower maturation of temporal processing than females. Female KO mice show stronger hypersensitive responses than males later in development. The differences in maturation rates of temporal processing and hypersensitive responses during various critical periods of development may lead to sex differences in language function, arousal and anxiety in FXS.

Auditory Event-related Potentials for Word Stimuli in Kannada Language Among Native Kannada Speakers with Dementia

Background: The P300 is a positive auditory event-related potential appearing around 300 msec post-oddball stimulus onset. Tone and monosyllabic stimuli have been widely used in P300 research, providing valuable insights into auditory perception, phoneme discrimination, language processing, and other cognitive processes. Bi-syllabic minimal pairs may be more challenging for some individuals because they require processing and discrimination of more complex phonemic structures. The aim of the study was to elicit and analyze the auditory event-related potentials for bi-syllabic word stimuli in the Kannada language among individuals with dementia. Method: The prospective study was conducted at the Department of Speech Pathology and Audiology. Ten native Kannada language speakers (five male; and five female) diagnosed with dementia, aged 55–70 years, were the participants. The naturally produced and recorded CVCV (Consonant vowel consonant vowel) tokens (/ko:ti/ and /ko:thi/ pair; /a: me/ and /a:ne pair) in Kannada were used in the auditory oddball paradigm. Results: The waveforms with positive peak for word (PPW) with clear morphology were used to obtain the latency and amplitude. Mean and Standard deviation (SD) value for the latency of the PPW was 545 ± 38 msec and the amplitude value of PPW was 2.5 ± 1.5 µV. Conclusion: The present study showed that when lengthier speech stimulus duration was used, the latency value of auditory event-related potential was higher. The study also showed that PPW is a reliable peak that could be used in the clinical population.

Automated ABR and MMN extraction using a customized headband for hearing screening

ObjectiveStimuli-elicited EEG responses, known as Event-Related Potentials (ERPs), reflect the health status of underlying electrophysiological processes and are frequently used for scanning sensory pathways. Current ERP extraction systems are expensive, complex, and bulky. This study aims to overcome these limitations by developing and validating a bimodal auditory ERP extractor headband. MethodsAn affordable, portable bimodal auditory ERP extractor was developed and validated for ABR (Auditory Brainstem Response) and MMN (Mismatch Negativity) response interpretation. Auditory stimuli were created using Presentation software. Adaptive filtering-based extraction was performed in EEGLAB (MATLAB) to derive the neural inferences. Extracted responses from n = 5 young adults were validated against CE-certified acquisition systems used in clinical practice. ResultsValidation results showed the grand average responses of ABR and MMN for n = 5 subjects matched. Furthermore, with and without stimuli ERP analysis showed significant differences for identified features (p = 0.00794 for ABR wave-V amplitudes, p = 1.22 * 10−5, and p = 2.62 * 10−5 for MMN peak latencies and area under the curves), ensuring that the response was due to the presented auditory stimuli. ConclusionThe results confirm the competency of the developed system to obtain MMN and ABR from young adults. A clear contrast between latency-amplitude scatter plots further ensures the competency of a developed system to acquire ABR and MMN. SignificanceThe novelty of the study is an easy-to-operate, affordable ERP extractor with adaptive filtering, wearable design, and configurable stimuli. This system can be a potential solution for large-scale hearing screening, providing detailed neural insights, including averaged responses and inter-trial variabilities.

Brain vital signs as a quantitative measure of cognition: Methodological implementation in a care home environment

IntroductionManaging cognitive function in care homes is a significant challenge. Individuals in care have a variety of scores across standard clinical assessments, such as the Mini-Mental Status Exam (MMSE), and many of them have scores that fall within the range associated with dementia. A recent methodological advance, brain vital sign monitoring through auditory event-related potentials, provides an objective and sensitive physiological measurement to track abnormalities, differences, or changes in cognitive function. Taking advantage of point-of-care accessibility, the current study evaluated the methodological feasibility, the assessment of whether a particular research method can be successfully implemented, of quantitatively measuring cognition of care home residents using brain vital signs. Secondarily, the current study examined the relationship between brain vital signs, specifically the cognitive processing associated N400 component, and MMSE scores in care home residents. Materials and methodsBrain vital signs used the established N100 (auditory sensation), P300 (basic attention), and N400 (cognitive processing) event-related potential (ERP) components. A total of 52 residents were enrolled, with all participants evaluated using the MMSE. Participants were assigned into homogeneous groups based on their MMSE scores, and were categorized into low (n = 14), medium (n = 17), and high (n = 13) MMSE groups. Both brain vital sign measures and underlying ERP waveforms were examined. Statistical analyses used partial least squares correlation (PLS) analyses in which both MMSE and age were included as factors, as well as jackknife approaches, to test for significant brain vital sign changes. ResultsThe current study successfully measured and analyzed standardized, quantifiable brain vital signs in a care home setting. ERP waveform data showed specific N400 changes between MMSE groups as a function of MMSE score. PLS analyses confirmed significant MMSE-related and age-related differences in the N400 amplitude (p < 0.05, corrected). Similarly, the jackknife approach emphasized the N400 latency difference between the low and high MMSE groups. Discussion and conclusionIt was possible to acquire brain vital signs measures in care home residents. Additionally, the current study evaluated brain vital signs relative to MMSE in this group. The comparison revealed significant decreasing in N400 response amplitude (cognitive processing) as a function of both MMSE score and age, as well as a slowing of N400 latency. The findings indicate that objective neurophysiological measures of impairment are detectable in care home residents across the span of MMSE scores. Direct comparison to MMSE- and age-related variables represents a critical initial step ahead of future studies that will investigate relative improvements in sensitivity, validity, reliability and related advantages of brain vital sign monitoring.

Visual modulation of auditory evoked potentials in the cat

Visual modulation of the auditory system is not only a neural substrate for multisensory processing, but also serves as a backup input underlying cross-modal plasticity in deaf individuals. Event-related potential (ERP) studies in humans have provided evidence of a multiple-stage audiovisual interactions, ranging from tens to hundreds of milliseconds after the presentation of stimuli. However, it is still unknown if the temporal course of visual modulation in the auditory ERPs can be characterized in animal models. EEG signals were recorded in sedated cats from subdermal needle electrodes. The auditory stimuli (clicks) and visual stimuli (flashes) were timed by two independent Poison processes and were presented either simultaneously or alone. The visual-only ERPs were subtracted from audiovisual ERPs before being compared to the auditory-only ERPs. N1 amplitude showed a trend of transiting from suppression-to-facilitation with a disruption at ~ 100-ms flash-to-click delay. We concluded that visual modulation as a function of SOA with extended range is more complex than previously characterized with short SOAs and its periodic pattern can be interpreted with “phase resetting” hypothesis.

High-density ear-EEG for understanding ear-centered EEG

Background. Mobile ear-EEG provides the opportunity to record EEG unobtrusively in everyday life. However, in real-life, the EEG data quickly becomes difficult to interpret, as the neural signal is contaminated by other, non-neural signal contributions. Due to the small number of electrodes in ear-EEG devices, the interpretation of the EEG becomes even more difficult. For meaningful and reliable ear-EEG, it is crucial that the brain signals we wish to record in real life are well-understood and that we make optimal use of the available electrodes. Their placement should be guided by prior knowledge about the characteristics of the signal of interest. Objective. We want to understand the signal we record with ear-EEG and make recommendations on how to optimally place a limited number of electrodes. Approach. We built a high-density ear-EEG with 31 channels spaced densely around one ear. We used it to record four auditory event-related potentials (ERPs): the mismatch negativity, the P300, the N100 and the N400. With this data, we gain an understanding of how different stages of auditory processing are reflected in ear-EEG. We investigate the electrode configurations that carry the most information and use a mass univariate ERP analysis to identify the optimal channel configuration. We additionally use a multivariate approach to investigate the added value of multi-channel recordings. Main results. We find significant condition differences for all ERPs. The different ERPs vary considerably in their spatial extent and different electrode positions are necessary to optimally capture each component. In the multivariate analysis, we find that the investigation of the ERPs benefits strongly from multi-channel ear-EEG. Significance. Our work emphasizes the importance of a strong theoretical and practical background when building and using ear-EEG. We provide recommendations on finding the optimal electrode positions. These results will guide future research employing ear-EEG in real-life scenarios.

Sensory Attenuation Deficit and Auditory Hallucinations in Schizophrenia: A Causal Mechanism or a Risk Factor? Evidence From Meta-Analyses on the N1 Event-Related Potential Component

BackgroundSensory attenuation (SA), the dampened perception of self-generated sensory information, is typically associated with reduced event-related potential signals, such as for the N1 component of auditory event-related potentials. SA, together with efficient monitoring of intentions and actions, should facilitate the distinction between self-generated and externally generated sensory events, thereby optimizing interaction with the world. According to many, SA is deficient in schizophrenia. The question arises whether altered SA reflects a sufficient mechanism to explain positive symptoms such as auditory hallucinations. A systematic association of reduced auditory SA in hallucinating patients would support this hypothesis. MethodsWe conducted a series of meta-analyses on 15 studies on auditory SA in which the N1 component of event-related potential–electroencephalogram signals was measured during talking (self-generated sensory signals condition) or when listening to prerecorded vocalizations (externally generated sensory signals condition). ResultsWe found that individuals with schizophrenia did show some auditory SA because their N1 signal was significantly attenuated in talking conditions compared with listening conditions. However, the magnitude of such attenuation was reduced in individuals with schizophrenia compared to healthy control participants. This phenomenon generalizes independently from the stage of the disease, the severity of positive symptoms, and whether patients have auditory hallucinations or not. ConclusionsThese findings suggest that reduced SA cannot be a sufficient mechanism for explaining positive symptoms such as auditory hallucinations in schizophrenia. Because reduced SA was also present in participants at risk of schizophrenia, reduced SA may represent a risk factor for the disorder. We discuss the implications of these results for clinical-cognitive models of schizophrenia.

Global Field Time-Frequency Representation-Based Discriminative Similarity Analysis of Passive Auditory ERPs for Diagnosis of Disorders of Consciousness.

Behavioural diagnosis of patients with disorders of consciousness (DOC) is challenging and prone to inaccuracies. Consequently, there have been increased efforts to develop bedside assessment based on EEG and event-related potentials (ERPs) that are more sensitive to the neural factors supporting conscious awareness. However, individual detection of residual consciousness using these techniques is less established. Here, we hypothesize that the cross-state similarity (defined as the similarity between healthy and impaired conscious states) of passive brain responses to auditory stimuli can index the level of awareness in individual DOC patients. To this end, we introduce the global field time-frequency representation-based discriminative similarity analysis (GFTFR-DSA). This method quantifies the average cross-state similarity index between an individual patient and our constructed healthy templates using the GFTFR as an EEG feature. We demonstrate that the proposed GFTFR feature exhibits superior within-group consistency in 34 healthy controls over traditional EEG features such as temporal waveforms. Second, we observed the GFTFR-based similarity index was significantly higher in patients with a minimally conscious state (MCS, 40 patients) than those with unresponsive wakefulness syndrome (UWS, 54 patients), supporting our hypothesis. Finally, applying a linear support vector machine classifier for individual MCS/UWS classification, the model achieved a balanced accuracy and F1 score of 0.77. Overall, our findings indicate that combining discriminative and interpretable markers, along with automatic machine learning algorithms, is effective for the differential diagnosis in patients with DOC. Importantly, this approach can, in principle, be transferred into any ERP of interest to better inform DOC diagnoses.

The Latency of Auditory Event-Related Potential P300 Prolonged in School-Age Students with Unilateral Hearing Loss in a Mandarin Learning Environment.

Our study investigated the differences in speech performance and neurophysiological response in groups of school-age children with unilateral hearing loss (UHL) who were otherwise typically developing (TD). We recruited a total of 16 primary school-age children for our study (UHL = 9/TD = 7), who were screened by doctors at Shin Kong Wu-Ho-Su Memorial Hospital. We used the Peabody Picture Vocabulary Test-Revised (PPVT-R) to test word comprehension, and the PPVT-R percentile rank (PR) value was proportional to the auditory memory score (by The Children's Oral Comprehension Test) in both groups. Later, we assessed the latency and amplitude of auditory ERP P300 and found that the latency of auditory ERP P300 in the UHL group was prolonged compared with that in the TD group. Although students with UHL have typical hearing in one ear, based on our results, long-term UHL might be the cause of atypical organization of brain areas responsible for auditory processing or even visual perceptions attributed to speech delay and learning difficulties.

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

BackgroundPsychiatric 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. MethodsThe 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. ResultsBaseline 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. ConclusionThe 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.

Regional brain activity of resting-state fMRI and auditory oddball ERP with multimodal approach in individuals with internet gaming disorder.

Resting-state brain activity may be associated with the ability to perform tasks; however, a multimodal approach involving resting-state functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) has not been widely used to investigate addictive disorders. We explored resting-state fMRI and auditory oddball ERP values from 26 with internet gaming disorder (IGD) patients and 27 age- and intelligence quotient-matched healthy controls (HCs). To assess the characteristics of resting-state fMRI, we calculated regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional amplitude of low-frequency fluctuation (fALFF); we also calculated the P3 component of the ERPs. Compared with HCs, the individuals with IGD exhibited significant decreases in ReHo and fALFF values in the left inferior occipital gyrus, increased ReHo and ALFF values in the right precuneus, increased ALFF in the left superior frontal gyrus, and lower P3 amplitudes in the midline centro-parietal area during the auditory ERP task. Furthermore, the regional activity of resting-state fMRI in the right inferior temporal gyrus and the occipital regions were positively correlated with the P3 amplitudes in IGD patients, whereas ReHo values of the left hippocampus and the right amygdala were negatively correlated with P3. Our results suggest that IGD patients have difficulty interacting effectively with cognitive function and sensory processing, although its interpretations need some cautions. The findings in this study will broaden the overall understanding of the neurobiological mechanisms that underlie IGD pathophysiology.

Distinct brain dynamics and networks for processing short and long auditory time intervals

Psychophysical studies suggest that time intervals above and below 1.2 s are processed differently in the human brain. However, the neural underpinnings of this dissociation remain unclear. Here, we investigate whether distinct or common brain networks and dynamics support the passive perception of short (below 1.2 s) and long (above 1.2 s) empty time intervals. Twenty participants underwent an EEG recording during an auditory oddball paradigm with .8- and 1.6-s standard time intervals and deviant intervals either shorter (early) or longer (delayed) than the standard interval. We computed the auditory ERPs for each condition at the sensor and source levels. We then performed whole brain cluster-based permutation statistics for the CNV, N1 and P2, components, testing deviants against standards. A CNV was found only for above 1.2 s intervals (delayed deviants), with generators in temporo-parietal, SMA, and motor regions. Deviance detection of above 1.2 s intervals occurred during the N1 period over fronto-central sensors for delayed deviants only, with generators in parietal and motor regions. Deviance detection of below 1.2 s intervals occurred during the P2 period over fronto-central sensors for delayed deviants only, with generators in primary auditory cortex, SMA, IFG, cingulate and parietal cortex. We then identified deviance related changes in directed connectivity using bivariate Granger causality to highlight the networks dynamics associated with interval processing above and below 1.2. These results suggest that distinct brain dynamics and networks support the perception of time intervals above and below 1.2 s.

Comparison of Event‐Related Potential Markers in Amyloid Positive vs. Amyloid Negative Patients with Mild Cognitive Impairment (MCI) and Dementia in a general neurological clinic

AbstractBackgroundWe used an automated Event Related Potentials (ERP) technique to compare ERP responses in amyloid positive and negative group of 75 patients with Mild Cognitive Impairment (MCI) and Dementia in a general neurological outpatient clinic. Over the years, research labs have repeatedly reported abnormal ERP markers in patients with MCI and dementia. Recent advances in technology have made ERP testing safe, easy to use and low cost, thus rendering it suitable for clinical use. Indeed, ERPs have become more routinely used in clinical assessment of neurological patients with cognitive changes. The possibility that ERP could help identify amyloid status in MCI and dementia patients adds to the potential clinical utility of these biomarkers.MethodPatients with a history of cognitive complains underwent an auditory oddball ERP paradigm in conjunction with routine neurological evaluation and imaging studies. Standard neuropsychological testing were available in most cases. Amyloid PET imaging was done as part of the IDEAS (Imaging Dementia ‐Evidence for Amyloid Scanning) study and provided the readings for amyloid load.ERP responses were analyzed in the context of beta amyloid readings, and in relation to the patients’ degree of cognitive deficits.ResultFinal data analysis will be presented at the time of the conferenceConclusionThe possibility that ERP could help identify amyloid status in MCI and dementia patients adds to the potential clinical utility of these biomarkers. possibility that ERP could help identify amyloid status in MCI and dementia patients adds to the potential clinical utility of these biomarkers.

Comparison of Event‐Related Potential Markers in Amyloid Positive vs. Amyloid Negative Patients with Mild Cognitive Impairment (MCI) and Dementia in a general neurological clinic

AbstractBackgroundWe used an automated Event Related Potentials (ERP) technique to compare ERP responses in amyloid positive and negative group of 75 patients with Mild Cognitive Impairment (MCI) and Dementia in a general neurological outpatient clinic. Over the years, research labs have repeatedly reported abnormal ERP markers in patients with MCI and dementia. Recent advances in technology have made ERP testing safe, easy to use and low cost, thus rendering it suitable for clinical use. Indeed, ERPs have become more routinely used in clinical assessment of neurological patients with cognitive changes. The possibility that ERP could help identify amyloid status in MCI and dementia patients adds to the potential clinical utility of these biomarkers.MethodPatients with a history of cognitive complains underwent an auditory oddball ERP paradigm in conjunction with routine neurological evaluation and imaging studies. Standard neuropsychological testing were available in most cases. Amyloid PET imaging was done as part of the IDEAS (Imaging Dementia ‐Evidence for Amyloid Scanning) study and provided the readings for amyloid load. ERP responses were analyzed in the context of beta amyloid readings, and in relation to the patients’ degree of cognitive deficits.ResultFinal data analysis will be presented at the time of the conferenceConclusionThe possibility that ERP could help identify amyloid status in MCI and dementia patients adds to the potential clinical utility of these biomarkers. possibility that ERP could help identify amyloid status in MCI and dementia patients adds to the potential clinical utility of these biomarkers.

The relationship between Event‐Related Potentials and MRI cortical atrophy in a memory disorders clinic

AbstractBackgroundThere is a need for accessible and affordable ways to assess biomarkers of Alzheimer’s disease (AD). Event‐related potentials (ERPs) are associated with disease severity of AD (Fruehwirt et al., 2019) and are a candidate biomarker for AD (Olichney et al., 2022). There is, however, little understanding of how ERP components relate to neurodegeneration of specific brain structures in AD.MethodWe investigated the correlation between electrophysiology, as measured by ERPs and brain structure using quantitative structural MRI measurements using FreeSurfer. A dataset containing older veteran memory disorders patients (N = 25) from VA Boston Healthcare System was analyzed. Participants completed an MRI and an auditory oddball task ERP paradigm.ResultAn exploratory analysis was performed using a Pearson correlation coefficient to evaluate the relationship between ERPs and the thickness and volume of different cortical areas. There was a negative relationship between P300 target amplitude and inferior temporal volume (p &lt; .05), as well as P300 target latency and thickness of the superior temporal (p &lt; .05) and transverse temporal regions (p &lt; .01). P200 standard amplitude had a positive correlation with thickness in the middle temporal (p &lt; .01), and superior temporal regions (p ≤ .05), and P200 target latency had a negative correlation with thickness of the superior temporal region (p &lt; .05). N200 target amplitude had a negative correlation with the superior parietal volume (right hemisphere = p ≤ .05, left hemisphere = p ≤ .01), left inferior temporal volume (p ≤ .05), and the middle temporal volume (left = p ≤ .05, right = p ≤ .01). N200 target latency was negatively correlated with right superior parietal volume (p ≤ .05).ConclusionA correlation was found between ERP measures P200, N200 and P300 with cortical thickness and volume of areas that are commonly impacted by AD pathology, further substantiating use of ERPs as possible AD biomarkers. We conclude that ERPs provide insights as to structural changes of brain structures affected by AD pathology. ERPs could help inform areas of brain atrophy and related patterns of cognitive impairment.

Alzheimer’s Disease genetic risk factor APoE 4 impact auditory processing in young adults

AbstractBackgroundRecent studies have suggested that prodromal stages of Alzheimer’s Disease (AD) are accompanied with central auditory system dysfunction, which may be used as early indicators of disease onset and progression. In AD patients of 60 years old and more and in APOE4 carriers, atypical patterns of oscillatory entrainment to repetitive sound transients have been reported and suggested as potential neuromarkers of AD. Whether such alterations of auditory functions relate to genetic risk factor of AD (APOE4) at an early age (&lt;30) is unknown.MethodWe used EEG recordings to measure auditory responses to repetitive sounds (1 second click trains presented at various frequencies (10‐250Hz) in 32 young neurotypical participants). To test whether auditory responsivity is affected by AD risk factor, we compared auditory brain responses from 17 APOE3 (age mean = 21.6, sd = 1.8) and 17 APOE4 carriers (age mean = 23.6, sd = 4.9).ResultComparing the magnitude of auditory event related potentials (ERP) we observed that APOE4 carriers exhibit slightly attenuated P2 and P3 ERP responses as well as delayed N1 and P2 ERP responses compared to APOE3 carriers. Focusing on Auditory Steady State Response (ASSR) power across frequencies (10‐90Hz), we observed that APOE3 carriers exhibit reliably larger neural entrainment than APOE4 carriers (Cohens’ d = 0.8, ‘large’ effect size). This difference was sustained across the peristimulus time course and did vary across stimulus frequencies.ConclusionOverall, these results suggest that central auditory differences can be detected very early in at‐risk populations. Studying these signals could help identify early AD pathology and provide an entry point for therapeutic interventions against neurodegeneration.

Is auditory processing measured by the N100 an endophenotype for psychosis? A family study and a meta-analysis.

The N100, an early auditory event-related potential, has been found to be altered in patients with psychosis. However, it is unclear if the N100 is a psychosis endophenotype that is also altered in the relatives of patients. We conducted a family study using the auditory oddball paradigm to compare the N100 amplitude and latency across 243 patients with psychosis, 86 unaffected relatives, and 194 controls. We then conducted a systematic review and a random-effects meta-analysis pooling our results and 14 previously published family studies. We compared data from a total of 999 patients, 1192 relatives, and 1253 controls in order to investigate the evidence and degree of N100 differences. In our family study, patients showed reduced N100 amplitudes and prolonged N100 latencies compared to controls, but no significant differences were found between unaffected relatives and controls. The meta-analysis revealed a significant reduction of the N100 amplitude and delay of the N100 latency in both patients with psychosis (standardized mean difference [s.m.d.] = -0.48 for N100 amplitude and s.m.d. = 0.43 for N100 latency) and their relatives (s.m.d. = - 0.19 for N100 amplitude and s.m.d. = 0.33 for N100 latency). However, only the N100 latency changes in relatives remained significant when excluding studies with affected relatives. N100 changes, especially prolonged N100 latencies, are present in both patients with psychosis and their relatives, making the N100 a promising endophenotype for psychosis. Such changes in the N100 may reflect changes in early auditory processing underlying the etiology of psychosis.