On the lasting impact of mild traumatic brain injury on working memory: Behavioural and electrophysiological evidence.

Despite increasing recognition of the significance of mild traumatic brain injury (mTBI), the long-term cognitive consequences of the injury remain unclear. More sensitive measures that can detect subtle cognitive changes and consideration of individual variability are needed to properly characterise cognitive outcomes following mTBI. Here, we used complex behavioural tasks, individual differences approaches, and electrophysiology to investigate the long-term cognitive effects of a history of mTBI. In Experiment 1, participants with self-reported mTBI history (n=82) showed poorer verbal working memory performance on the operation span task compared to control participants (n=88), but there were no group differences in visual working memory, multitasking, cognitive flexibility, attentional control, visuospatial ability, or information processing speed. Individual differences analyses revealed that time since injury and presence of memory loss predicted visual working memory capacity and visuospatial ability, respectively, in those with mTBI history. In Experiment 2, participants with mTBI history (n=20) again demonstrated poorer verbal working memory on the operation span task compared to control participants (n=38), but no group differences were revealed on a visuospatial complex span task or simpler visual working memory measures. We also explored the electrophysiological indices of visual working memory using EEG during a change detection task. No differences were observed in early sensory event-related potentials (P1, N1) or the later negative slow wave associated with visual working memory capacity. Together, these findings suggest that mTBI history may be associated with a lasting, isolated disruption in the subsystem underlying verbal working memory storage. The results emphasize the importance of sensitive cognitive measures and accounting for individual variability in injury characteristics when assessing mTBI outcomes.

EEG might be better left alone, but ERPs must be attended to: Optimizing the late positive potential preprocessing pipeline.

The late positive potential (LPP) is an ERP component commonly used to study emotional processes and has been proposed as a neuroaffective biomarker for research and clinical uses. These applications, however, require standardized procedures for elicitation and ERP data processing. We evaluated the impact of different EEG preprocessing steps on the LPP's data quality and statistical power. Using a diverse sample of 158 adults, we implemented a multiverse analytical approach to compare preprocessing pipelines that progressively incorporated more steps: artifact detection and rejection, bad channel interpolation, and bad segment deletion. We assessed each pipeline's effectiveness by computing the standardized measurement error (SME) and conducting simulated experiments to estimate statistical power in detecting significant LPP differences between emotional and neutral images. Our findings highlighted that artifact rejection is crucial for enhancing data quality and statistical power. Voltage thresholds to reject trials contaminated by artifacts significantly affected SME and statistical power. Once artifact detection was optimized, further steps provided minor improvements in data quality and statistical power. Importantly, different preprocessing pipelines yielded similar outcomes. These results underscore the robustness of the LPP's affective modulation to preprocessing choices and the critical role of effective artifact management. By refining and standardizing preprocessing procedures, the LPP can become a reliable neuroaffective biomarker, supporting personalized clinical interventions for affective disorders.

Lower frequency range of auditory input facilitates stream segregation in older adults.

The current study investigated the effect of lower frequency input on stream segregation acuity in older, normal hearing adults. Using event-related brain potentials (ERPs) and perceptual performance measures, we previously showed that stream segregation abilities were less proficient in older compared to younger adults. However, in that study we used frequency ranges greater than 1500 Hz. In the current study, we lowered the target frequency range below 1500 Hz and found similar stream segregation abilities in younger and older adults. These results indicate that the perception of complex auditory scenes is influenced by the spectral content of the auditory input and suggest that lower frequency ranges of input in older adults may facilitate listening ability in complex auditory environments. These results also have implications for the advancement of prosthetic devices.

Habituation of Central and Electrodermal Responses to an Auditory Two-Stimulus Oddball Paradigm.

The orienting reaction (OR) towards a new stimulus is subject to habituation, i.e., progressively attenuates with stimulus repetition. The skin conductance responses (SCRs) are known to represent a reliable measure of OR at the peripheral level. Yet, it is still a matter of debate which of the P3 subcomponents is the most likely to represent the central counterpart of the OR. The aim of the present work was to study habituation, recovery, and dishabituation phenomena intrinsic to a two-stimulus auditory oddball paradigm, one of the most-used paradigms both in research and clinic, by simultaneously recording SCRs and P3 in twenty healthy volunteers. Our findings show that the target stimulus was capable of triggering a more marked OR, as indexed by both SCRs and P3, compared to the standard stimulus, that could be due to its affective saliency and relevance for task completion; the application of temporal principal components analysis (PCA) to the P3 complex allowed us to identify several subcomponents including both early and late P3a (eP3a; lP3a), P3b, novelty P3 (nP3), and both a positive and a negative Slow Wave (+SW; -SW). Particularly, lP3a and P3b subcomponents showed a similar behavior to that observed for SCRs , suggesting them as central counterparts of OR. Finally, the P3 evoked by the first standard stimulus after the target showed a significant dishabituation phenomenon which could represent a sign of the local stimulus change. However, it did not reach a sufficient level to trigger an SCR/OR since it did not represent a salient event in the context of the task.

Processing of emotional connotations in Chinese monomorphic and compound words reflected by the early posterior negativity.

Writing stands as one of humanity's most profound inventions, facilitating the efficient sharing and transmission of vast amounts of information. Similar to images and facial expressions, visual (written) words possess the ability to evoke emotional connotations. Understanding how the brain perceives these emotional nuances encoded in highly symbolic visual words is a key focus of the emerging field of "affective neurolinguistics." At the core of this inquiry lies the examination of the early posterior negativity (EPN), an event-related potentials (ERPs) component peaking around 300 ms after stimulus onset in the occipitotemporal scalp region. EPN has consistently emerged in response to emotional stimuli, encompassing pictures, faces, and visual words. However, prior research has notably lacked observation of EPN in response to Chinese emotional words, raising questions about potential differences in emotional processing between Chinese and other languages. Given the logographic nature of the Chinese writing system and the prevalence of compound words in the Chinese lexicon, this study aims to explore whether the emotional processing of Chinese monomorphic and compound words elicits an EPN response. Two experiments were conducted: Experiment 1 utilized one-character words (monomorphic words), while Experiment 2 employed two-character words (compound words). Participants were assigned a go/no-go task, instructed to respond to unknown words (word recognition task) or blue stimuli (color decision task). Data analysis using a data-driven mass univariate approach revealed significant ERP differences between emotional and neutral words. Notably, the time course, scalp topography, and cortical generators of the difference ERP presented a characteristic EPN response in both experiments. These findings strongly support the notion that the processing of emotional connotations in both Chinese monomorphic and compound words is reflected by the EPN, paving the way for future research using EPN as an emotion-related ERP component for investigating emotional processing of Chinese words.

Functional benefits of continuous vs. categorical listening strategies on the neural encoding and perception of noise-degraded speech.

Acoustic information in speech changes continuously, yet listeners form discrete perceptual categories to ease the demands of perception. Being a more continuous/gradient as opposed to a more discrete/categorical listener may be further advantageous for understanding speech in noise by increasing perceptual flexibility and resolving ambiguity. The degree to which a listener's responses to a continuum of speech sounds are categorical versus continuous can be quantified using visual analog scaling (VAS) during speech labeling tasks. Here, we recorded event-related brain potentials (ERPs) to vowels along an acoustic-phonetic continuum (/u/ to /a/) while listeners categorized phonemes in both clean and noise conditions. Behavior was assessed using standard two alternative forced choice (2AFC) and VAS paradigms to evaluate categorization under task structures that promote discrete vs. continuous hearing, respectively. Behaviorally, identification curves were steeper under 2AFC vs. VAS categorization but were relatively immune to noise, suggesting robust access to abstract, phonetic categories even under signal degradation. Behavioral slopes were correlated with listeners' QuickSIN scores; shallower slopes corresponded with better speech in noise performance, suggesting a perceptual advantage to noise degraded speech comprehension conferred by a more gradient listening strategy. At the neural level, P2 amplitudes and latencies of the ERPs were modulated by task and noise; VAS responses were larger and showed greater noise-related latency delays than 2AFC responses. More gradient responders had smaller shifts in ERP latency with noise, suggesting their neural encoding of speech was more resilient to noise degradation. Interestingly, source-resolved ERPs showed that more gradient listening was also correlated with stronger neural responses in left superior temporal gyrus. Our results demonstrate that listening strategy modulates the categorical organization of speech and behavioral success, with more continuous/gradient listening being advantageous to sentential speech in noise perception.

Task-specific relationships between error-related ERPs and behavior: Flanker, Stroop, and Go/Nogo tasks.

Performance monitoring has been widely studied during different forced-choice response tasks. Participants typically show longer response times (RTs) and increased accuracy following errors, but there are inconsistencies regarding the connection between error-related event-related brain potentials (ERPs) and behavior, such as RT and accuracy. The specific task in any given study could contribute to these inconsistencies, as different tasks may require distinct cognitive processes that impact ERP-behavior relationships. The present study sought to determine whether task moderates ERP-behavior relationships and whether these relationships are robustly observed when tasks and stimuli are treated as random effects. ERPs and behavioral indices (RTs and accuracy) recorded during flanker, Stroop, and Go/Nogo tasks from 180 people demonstrated a task-specific effect on ERP-behavior relationships, such that larger previous-trial error-related negativity (ERN) predicted longer RTs and greater likelihood of a correct response on subsequent trials during flanker and Stroop tasks but not during Go/Nogo task. Additionally, larger previous-trial error positivity (Pe) predicted faster RTs and smaller variances of RTs on subsequent trials for Stroop and Go/Nogo tasks but not for flanker task. When tasks and stimuli were treated as random effects, ERP-behavior relationships were not observed. These findings support the need to consider the task used for recording performance monitoring measures when interpreting results across studies.

Subjective cognitive decline in healthy older adults is associated with altered processing of negative versus positive feedback in a probabilistic learning task.

Older adults who worry about their own cognitive capabilities declining, but who do not show evidence of actual cognitive decline in neuropsychological tests, are at an increased risk of being diagnosed with dementia at a later time. Since neural markers may be more sensitive to early stages of cognitive decline, in the present study we examined whether event-related potential responses of feedback processing, elicited in a probabilistic learning task, differ between healthy older adults recruited from the community, who either did (subjective cognitive decline/SCD-group) or did not report (No-SCD group) worry about their own cognition declining beyond the normal age-related development. In the absence of group differences in learning from emotionally charged feedback in the probabilistic learning task, the amplitude of the feedback-related negativity (FRN) varied with feedback valence differently in the two groups: In the No-SCD group, the FRN was larger for positive than negative feedback, while in the SCD group, FRN amplitude did not differ between positive and negative feedback. The P3b was enhanced for negative feedback in both groups, and group differences in P3b amplitude were not significant. Altered sensitivity in neural processing of negative versus positive feedback may be a marker of SCD.

Automatic processing of unattended mean emotion: Evidence from visual mismatch responses.

The mean emotion from multiple facial expressions can be extracted rapidly and precisely. However, it remains debated whether mean emotion processing is automatic which can occur under no attention. To address this question, we used a passive oddball paradigm and recorded event-related brain potentials when participants discriminated the changes in the central fixation while a set of four faces was presented in the periphery. The face set consisted of one happy and three angry expressions (mean negative) or one angry and three happy expressions (mean positive), and the mean negative and mean positive face sets were shown with a probability of 20% (deviant) and 80% (standard) respectively in the sequence, or the vice versa. The cluster-based permutation analyses showed that the visual mismatch negativity started early at around 92 ms and was also observed in later time windows when the mean emotion was negative, while a mismatch positivity was observed at around 168-266 ms when the mean emotion was positive. The results suggest that there might be different mechanisms underlying the processing of mean negative and mean positive emotions. More importantly, the brain can detect the changes in the mean emotion automatically, and ensemble coding for multiple facial expressions can occur in an automatic fashion without attention.

The influence of spatial and temporal attention on visual awareness-a behavioral and ERP study.

Whether attention is a prerequisite of perceptual awareness or an independent and dissociable process remains a matter of debate. Importantly, understanding the relation between attention and awareness is probably not possible without taking into account the fact that both are heterogeneous and multifaceted mechanisms. Therefore, the present study tested the impact on visual awareness of two attentional mechanisms proposed by the Posner model: temporal alerting and spatio-temporal orienting. Specifically, we evaluated the effects of attention on the perceptual level, by measuring objective and subjective awareness of a threshold-level stimulus; and on the neural level, by investigating how attention affects two postulated event-related potential correlates of awareness. We found that alerting and orienting mechanisms additively facilitate perceptual consciousness, with activation of the latter resulting in the most vivid awareness. Furthermore, we found that late positivity is unlikely to constitute a neural correlate of consciousness as its amplitude was modulated by both attentional mechanisms, but early visual awareness negativity was independent of the alerting and orienting mechanisms. In conclusion, our study reveals a nuanced relationship between attention and awareness; moreover, by investigating the effect of the alerting mechanism, this study provides insights into the role of temporal attention in perceptual consciousness.

Temporal summation of second pain is affected by cognitive load.

This work attempted to clarify the interaction of cognition and pain sensitization during a paradigm of Temporal Summation of Second Pain (TSSP). We analyzed pain ratings and electroencephalographic (EEG) activity obtained from 21 healthy participants during the presentation of four experimental conditions that differed in the manipulation of attention to painful stimuli or working memory load (Attention to hand & TSSP; 0-back & TSSP (low cognitive load); 2-back & TSSP (high cognitive load); 2-back (without pain)). We found that the TSSP was reduced when the attention was diverted and the cognitive load increased, and this reduction was accompanied by higher midfrontal theta activity and lower posterior alpha and central beta activity. Although it is well established that TSSP is a phenomenon that occurs at the spinal level, here we show that it is also affected by supraspinal attentional mechanisms. Delivery of painful repeated stimuli did not affect the performance of the 2-back task but was associated with smaller amplitudes of attentional event-related potentials (ERPs) after standard stimuli (not the target). The study of brain activity during TSSP allowed to clarify the role of top-down attentional modulation in pain sensitization processes. Results contribute to a better understanding of cognitive dysfunction in pain conditions and reinforce the use of therapeutic strategies based on distracting attention away from pain.

Electrophysiological Correlates of Amplified Emotion-Related Cognitive Processing Evoked by Self-Administered Disgust Images.

In the processing of emotions, the brain prepares and reacts in distinctive manners depending upon the negative or positive nuance of the emotion elicitors. Previous investigations showed that negative elicitors generally evoke more intense neural activities than positive and neutral ones, as reflected in the augmented amplitude of all sub-components of the event-related potentials (ERP) late posterior positivity (LPP) complex, while less is known about the emotion of disgust. The present study aimed to examine whether the LPP complex during the processing of disgust stimuli showed greater amplitude than other emotion elicitors with negative or positive valences, thus confirming it as a neural marker of disgust-related negativity bias at earlier or later stages. Thus, in the present study, we leveraged the ERP technique during the execution of an affective self-administered visual stimuli task to disentangle the neural contributions associated with images of positive, negative, disgust, or neutral emotions. Crucially, we showed that handling with disgust elicitors prompted the greatest neural activity and the highest delay during self-administration. Overall, we demonstrated progressive neural activities associated with the unpleasantness of the emotion elicitors and peculiar processing for disgust compared with all other emotions.

How Socially Avoidant Emerging Adults Process Social Feedback during Human-to-Human Interaction after Social Rejection: An Event-Related Potential Study.

Social avoidance refers to active non-participation in social activities, which is detrimental to healthy interpersonal interaction for emerging adults. Social rejection is a kind of negative social evaluation from others making people feel social pain. However, how socially avoidant emerging adults process social feedback information after experiencing social rejection has received less attention. The current study aimed to explore the differences in social interaction feedback processing after social rejection between a socially avoidant group (n = 16) and a comparison group (n = 16) in a human-to-human interaction context. Computer game tasks with two types of interaction (cooperation and competition) were used to record the event-related potentials when receiving social interaction feedback in two conditions (social rejection and control condition). The results showed that (1) the socially avoidant group had lower reward positivity amplitudes than the comparison group when receiving social feedback; (2) the socially avoidant group presented larger P300 amplitudes in the social rejection condition than in the control condition, but the comparison group did not; and (3) social rejection evoked more negative N1 amplitudes in the socially avoidant and comparison groups. The findings suggest that socially avoidant emerging adults may have flaws in reward sensitivity during interpersonal interaction, and they might also exert more attentional and emotional resources to social feedback after social rejection.

Probing Beat Perception with Event-Related Potentials (ERPs) in Human Adults, Newborns, and Nonhuman Primates.

The aim of this chapter is to give an overview of how the perception of rhythmic temporal regularity such as a regular beat in music can be studied in human adults, human newborns, and nonhuman primates using event-related brain potentials (ERPs). First, we discuss different aspects of temporal structure in general, and musical rhythm in particular, and we discuss the possible mechanisms underlying the perception of regularity (e.g., a beat) in rhythm. Additionally, we highlight the importance of dissociating beat perception from the perception of other types of structure in rhythm, such as predictable sequences of temporal intervals, ordinal structure, and rhythmic grouping. In the second section of the chapter, we start with a discussion of auditory ERPs elicited by infrequent and frequent sounds: ERP responses to regularity violations, such as mismatch negativity (MMN), N2b, and P3, as well as early sensory responses to sounds, such as P1 and N1, have been shown to be instrumental in probing beat perception. Subsequently, we discuss how beat perception can be probed by comparing ERP responses to sounds in regular and irregular sequences, and by comparing ERP responses to sounds in different metrical positions in a rhythm, such as on and off the beat or on strong and weak beats. Finally, we will discuss previous research that has used the aforementioned ERPs and paradigms to study beat perception in human adults, human newborns, and nonhuman primates. In doing so, we consider the possible pitfalls and prospects of the technique, as well as future perspectives.

Influence of flavor information on visual search: Attentional capture by and suppression of flavor-associated colors.

Numerous studies have demonstrated the impact of flavor cues on visual search, yet the underlying mechanisms remain elusive. In this experiment, we used event-related potentials (ERPs) to examine whether, and if so, how flavor information could lead to attentional capture by, and suppression of, flavor-associated colors. The participants were asked to taste certain flavored beverages and subsequently complete a shape-based visual search task, while their neural activities were simultaneously recorded. The behavioral results revealed that the participants made slower responses when a distractor in the flavor-associated color (DFAC) was present, suggesting an attentional bias toward the flavor-associated color. The ERP results revealed that the N2pc was detected if the target and the DFAC were shown in the same visual field (e.g. both target and DFCA on the right side of the screen), when the pairings between flavor cues and target colors were incongruent. However, the N2pc was not observed if the target and the DFAC were shown in the opposite visual fields (e.g. target on the right and DFCA on the left side of the screen) for the incongruent color-flavor pairings. Moreover, the distractor positivity (Pd) was observed if the target and the DFAC were shown in the opposite visual field for the congruent color-flavor pairings. These results suggest that both attentional capture and suppression are involved in the influence of flavor information on visual search. Collectively, these findings provide initial electrophysiological evidence on the mechanisms of the crossmodal influence of flavor cues on visual search.

Neural signatures of imaginary motivational states: desire for music, movement and social play.

The literature has demonstrated the potential for detecting accurate electrical signals that correspond to the will or intention to move, as well as decoding the thoughts of individuals who imagine houses, faces or objects. This investigation examines the presence of precise neural markers of imagined motivational states through the combining of electrophysiological and neuroimaging methods. 20 participants were instructed to vividly imagine the desire to move, listen to music or engage in social activities. Their EEG was recorded from 128 scalp sites and analysed using individual standardized Low-Resolution Brain Electromagnetic Tomographies (LORETAs) in the N400 time window (400-600 ms). The activation of 1056 voxels was examined in relation to the 3 motivational states. The most active dipoles were grouped in eight regions of interest (ROI), including Occipital, Temporal, Fusiform, Premotor, Frontal, OBF/IF, Parietal, and Limbic areas. The statistical analysis revealed that all motivational imaginary states engaged the right hemisphere more than the left hemisphere. Distinct markers were identified for the three motivational states. Specifically, the right temporal area was more relevant for "Social Play", the orbitofrontal/inferior frontal cortex for listening to music, and the left premotor cortex for the "Movement" desire. This outcome is encouraging in terms of the potential use of neural indicators in the realm of brain-computer interface, for interpreting the thoughts and desires of individuals with locked-in syndrome.

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

Introduction: Managing 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 methods: Brain 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. Results: The 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 conclusion: It 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.

Analysis of modulations of mental fatigue on intra-individual variability from single-trial event related potentials.

BACKGROUND: Intra-individual variability (IIV), a measure of variance within an individual's performance, has been demonstrated as metrics of brain responses for neural functionality. However, how mental fatigue modulates IIV remains unclear. Consequently, the development of robust mental fatigue detection methods at the single-trial level is challenging. NEW METHODS: Based on a long-duration flanker task EEG dataset, the modulations of mental fatigue on IIV were explored in terms of response time (RT) and trial-to-trial latency variations of event-related potentials (ERPs). Specifically, latency variations were quantified using residue iteration decomposition (RIDE) to reconstruct latency-corrected ERPs. We compared reconstructed ERPs with raw ERPs by means of temporal principal component analysis (PCA). Furthermore, a single-trial classification pipeline was developed to detect the changes of mental fatigue levels. RESULTS: We found an increased IIV in the RT metric in the fatigue state compared to the alert state. The same sequence of ERPs (N1, P2, N2, P3a, P3b, and slow wave, or SW) was separated from both raw and reconstructed ERPs using PCA, whereas differences between raw and reconstructed ERPs in explained variances for separated ERPs were found owing to IIV. Particularly, a stronger N2 was detected in the fatigue than alert state after RIDE. The single-trial fatigue detection pipeline yielded an acceptable accuracy of 73.3%. COMPARISON WITH EXISTING METHODS: The IIV has been linked to aging and brain disorders, and as an extension, our finding demonstrates IIV as an efficient indicator of mental fatigue. CONCLUSIONS: This study reveals significant modulations of mental fatigue on IIV at the behavioral and neural levels and establishes a robust mental fatigue detection pipeline.

Flexible multi-step hypothesis testing of human ECoG data using cluster-based permutation tests with GLMEs.

BACKGROUND: Time series analysis is critical for understanding brain signals and their relationship to behavior and cognition. Cluster-based permutation tests (CBPT) are commonly used to analyze a variety of electrophysiological signals including EEG, MEG, ECoG, and sEEG data without a priori assumptions about specific temporal effects. However, two major limitations of CBPT include the inability to directly analyze experiments with multiple fixed effects and the inability to account for random effects (e.g. variability across subjects). Here, we propose a flexible multi-step hypothesis testing strategy using CBPT with Linear Mixed Effects Models (LMEs) and Generalized Linear Mixed Effects Models (GLMEs) that can be applied to a wide range of experimental designs and data types. METHODS: We first evaluate the statistical robustness of LMEs and GLMEs using simulated data distributions. Second, we apply a multi-step hypothesis testing strategy to analyze ERPs and broadband power signals extracted from human ECoG recordings collected during a simple image viewing experiment with image category and novelty as fixed effects. Third, we assess the statistical power differences between analyzing signals with CBPT using LMEs compared to CBPT using separate t-tests run on each fixed effect through simulations that emulate broadband power signals. Finally, we apply CBPT using GLMEs to high-gamma burst data to demonstrate the extension of the proposed method to the analysis of nonlinear data. RESULTS: First, we found that LMEs and GLMEs are robust statistical models. In simple simulations LMEs produced highly congruent results with other appropriately applied linear statistical models, but LMEs outperformed many linear statistical models in the analysis of "suboptimal" data and maintained power better than analyzing individual fixed effects with separate t-tests. GLMEs also performed similarly to other nonlinear statistical models. Second, in real world human ECoG data, LMEs performed at least as well as separate t-tests when applied to predefined time windows or when used in conjunction with CBPT. Additionally, fixed effects time courses extracted with CBPT using LMEs from group-level models of pseudo-populations replicated latency effects found in individual category-selective channels. Third, analysis of simulated broadband power signals demonstrated that CBPT using LMEs was superior to CBPT using separate t-tests in identifying time windows with significant fixed effects especially for small effect sizes. Lastly, the analysis of high-gamma burst data using CBPT with GLMEs produced results consistent with CBPT using LMEs applied to broadband power data. CONCLUSIONS: We propose a general approach for statistical analysis of electrophysiological data using CBPT in conjunction with LMEs and GLMEs. We demonstrate that this method is robust for experiments with multiple fixed effects and applicable to the analysis of linear and nonlinear data. Our methodology maximizes the statistical power available in a dataset across multiple experimental variables while accounting for hierarchical random effects and controlling FWER across fixed effects. This approach substantially improves power leading to better reproducibility. Additionally, CBPT using LMEs and GLMEs can be used to analyze individual channels or pseudo-population data for the comparison of functional or anatomical groups of data.