Auditory aversive generalization learning prompts threat-specific changes in alpha-band activity.

Pairing a neutral stimulus with aversive outcomes prompts neurophysiological and autonomic changes in response to the conditioned stimulus (CS+), compared to cues that signal safety (CS-). One of these changes-selective amplitude reduction of parietal alpha-band oscillations-has been reliably linked to processing of visual CS+. It is, however, unclear to what extent auditory conditioned cues prompt similar changes, how these changes evolve as learning progresses, and how alpha reduction in the auditory domain generalizes to similar stimuli. To address these questions, 55 participants listened to three sine wave tones, with either the highest or lowest pitch (CS+) being associated with a noxious white noise burst. A threat-specific (CS+) reduction in occipital-parietal alpha-band power was observed similar to changes expected for visual stimuli. No evidence for aversive generalization to the tone most similar to the CS+ was observed in terms of alpha-band power changes, aversiveness ratings, or pupil dilation. By-trial analyses found that selective alpha-band changes continued to increase as aversive conditioning continued, beyond when participants reported awareness of the contingencies. The results support a theoretical model in which selective alpha power represents a cross-modal index of continuous aversive learning, accompanied by sustained sensory discrimination of conditioned threat from safety cues.

The role of pain and socioenvironmental factors on posttraumatic stress disorder symptoms in traumatically injured adults: A 1-year prospective study.

Approximately 20% of individuals who experience a traumatic injury will subsequently develop posttraumatic stress disorder (PTSD). Physical pain following traumatic injury has received increasing attention as both a distinct, functionally debilitating disorder and a comorbid symptom related to PTSD. Studies have demonstrated that both clinician-assessed injury severity and patient pain ratings can be important predictors of nonremitting PTSD; however, few have examined pain and PTSD alongside socioenvironmental factors. We postulated that both area- and individual-level socioeconomic circumstances and lifetime trauma history would be uniquely associated with PTSD symptoms and interact with the pain-PTSD association. To test these effects, pain and PTSD symptoms were assessed at four visits across a 1-year period in a sample of 219 traumatically injured participants recruited from a Level 1 trauma center. We used a hierarchal linear modeling approach to evaluate whether (a) patient-reported pain ratings were a better predictor of PTSD than clinician-assessed injury severity scores and (b) socioenvironmental factors, specifically neighborhood socioeconomic disadvantage, individual income, and lifetime trauma history, influenced the pain-PTSD association. Results demonstrated associations between patient-reported pain ratings, but not clinician-assessed injury severity scores, and PTSD symptoms, R2( fvm ) = .65. There was a significant interaction between neighborhood socioeconomic disadvantage and pain such that higher disadvantage decreased the strength of the pain-PTSD association but only among White participants, R2( fvm ) = .69. Future directions include testing this question in a larger, more diverse sample of trauma survivors (e.g., geographically diverse) and examining factors that may alleviate both pain and PTSD symptoms.

Plasma p-tau181 associated with structural changes in mild cognitive impairment.

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with dementia and is a serious concern for the health of individuals and government health care systems worldwide. Gray matter atrophy and white matter damage are major contributors to cognitive deficits in AD patients, as demonstrated by magnetic resonance imaging (MRI). Many of these brain changes associated with AD begin to occur about 15 years before the onset of initial clinical symptoms. Therefore, it is critical to find biomarkers reflective of these brain changes associated with AD to identify this disease and monitor its prognosis and development. The increased plasma level of hyperphosphorylated tau 181 (p-tau181) has been recently considered a novel biomarker for the diagnosis of AD, preclinical AD, and mild cognitive impairment (MCI). In the current study, we examined the association of cerebrospinal fluid (CSF) and plasma levels of p-tau181 with structural brain changes in cortical thickness, cortical volume, surface area, and subcortical volume in MCI patients. In this cross-sectional study, we included the information of 461 MCI patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The results of voxel-wise partial correlation analyses showed a significant negative correlation between the increased levels of plasma p-tau181, CSF total tau, and CSF p-tau181 with structural changes in widespread brain regions. These results provide evidence for the use of plasma p-tau181 as a diagnostic marker for structural changes in the brain associated with the early stages of AD and neurodegeneration.

Neurophysiological and Autonomic Dynamics of Threat Processing During Sustained Social Fear Generalization.

Survival in dynamic environments requires that organisms learn to predict danger from situational cues. One key facet of threat prediction is generalization from a predictive cue to similar cues, ensuring that a cue-outcome contingency is applied beyond the original learning environment. Generalization has been observed in laboratory studies of aversive conditioning: behavioral and physiological processes generalize responses from a stimulus paired with threat (the CS+) to unpaired stimuli, with response magnitudes varying with CS+ similarity. In contrast, work focusing on sensory responses in visual cortex has found a sharpening pattern, in which responses to stimuli closely resembling the CS+ are maximally suppressed, potentially reflecting lateral inhibitory interactions with the CS+ representation. Originally demonstrated with simple visual cues, changes in visuocortical tuning have also been observed in threat generalization learning across facial identities. It is unclear to what extent these visuocortical changes represent transient or sustained effects and if generalization learning requires prior conditioning to the CS+. The present study addressed these questions using EEG and pupillometry in an aversive generalization paradigm involving hundreds of trials using a gradient of facial identities. Visuocortical ssVEP sharpening occurred after dozens of trials of generalization learning without prior differential conditioning, but diminished as learning continued. By contrast, generalization of alpha power suppression, pupil dilation, and self-reported valence and arousal was seen throughout the experiment. Findings are consistent with threat processing models emphasizing the role of changing visucocortical and attentional dynamics when forming, curating, and shaping fear memories as observers continue learning about stimulus-outcome contingencies.

Plasma neurofilament light chain associated with impaired regional cerebral blood flow in healthy individuals.

Background: Recent findings suggest that the plasma axonal structural protein, neurofilament light (NFL) chain, may serve as a potential blood biomarker for early signs of neurodegenerative diseases, such as Alzheimer's disease (AD). Given the need for early detection of neurodegenerative disorders, the current study investigated the associations between regional cerebral blood flow (rCBF) in brain regions associated with neurodegenerative disorders and memory function with plasma NFL in AD, mild cognitive impairment (MCI), and healthy controls (HCs). Methods: We recruited 29 AD, 76 MCI, and 39 HCs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database in the current cross-sectional study. We used Pearson's correlation models adjusted for the effect of age, sex, and APOE genotype to investigate the association between plasma NFL and rCBF. Results: We found non-significant differences in age (F(2, 141) = 1.304; P = 0.275) and years of education (F(2, 141) = 0.013; P = 0.987). Additionally, we found significant differences between groups in terms of MMSE scores (F(2, 141) = 100.953; P < 0.001). Despite the observation of significantly reduced rCBF in AD and MCI groups versus HCs, we did not detect significant differences in plasma NFL between these groups. We found significant negative associations between plasma NFL and rCBF in various AD-related regions, these findings were only observed after analyses in all participants, and were observed in HCs alone and no significant associations were observed in the AD or MCI groups. Conclusion: These outcomes add to our current understanding surrounding the use of rCBF and plasma NFL biomarkers as tools for early detection and diagnosis of neurodegenerative diseases. A conclusion might be that the association between NFL and impaired rCBF exists before the clinical symptoms appear. Further longitudinal studies with a large sample size should be performed to examine the correlation between plasma NFL and rCBF in order to understand these complex relationships.

The Relationship Between Self-Reported Misophonia Symptoms and Auditory Aversive Generalization Leaning: A Preliminary Report.

Misophonia is characterized by excessive aversive reactions to specific "trigger" sounds. Although this disorder is increasingly recognized in the literature, its etiological mechanisms and maintaining factors are currently unclear. Several etiological models propose a role of Pavlovian conditioning, an associative learning process heavily researched in similar fear and anxiety-related disorders. In addition, generalization of learned associations has been noted as a potential causal or contributory factor. Building upon this framework, we hypothesized that Misophonia symptoms arise as a consequence of overgeneralized associative learning, in which aversive responses to a noxious event also occur in response to similar events. Alternatively, heightened discrimination between conditioned threat and safety cues may be present in participants high in Misophonia symptoms, as predicted by associative learning models of Misophonia. This preliminary report (n = 34) examines auditory generalization learning using self-reported behavioral (i.e., valence and arousal ratings) and EEG alpha power reduction. Participants listened to three sine tones differing in pitch, with one pitch (i.e., CS+) paired with an aversive loud white noise blast, prompting aversive Pavlovian generalization learning. We assessed the extent to which overgeneralization versus heightened discrimination learning is associated with self-reported Misophonia symptoms, by comparing aversive responses to the CS+ and other tones similar in pitch. Behaviorally, all participants learned the contingencies between CS+ and noxious noise, with individuals endorsing elevated Misophonia showing heightened aversive sensitivity to all stimuli, regardless of conditioning and independent of hyperacusis status. Across participants, parieto-occipital EEG alpha-band power reduction was most pronounced in response to the CS+ tone, and this difference was greater in those with self-reported Misophonia symptoms. The current preliminary findings do not support the notion that overgeneralization is a feature of self-reported emotional experience in Misophonia, but that heightened sensitivity and discrimination learning may be present at the neural level.

Recommendations and publication guidelines for studies using frequency domain and time-frequency domain analyses of neural time series.

Since its beginnings in the early 20th century, the psychophysiological study of human brain function has included research into the spectral properties of electrical and magnetic brain signals. Now, dramatic advances in digital signal processing, biophysics, and computer science have enabled increasingly sophisticated methodology for neural time series analysis. Innovations in hardware and recording techniques have further expanded the range of tools available to researchers interested in measuring, quantifying, modeling, and altering the spectral properties of neural time series. These tools are increasingly used in the field, by a growing number of researchers who vary in their training, background, and research interests. Implementation and reporting standards also vary greatly in the published literature, causing challenges for authors, readers, reviewers, and editors alike. The present report addresses this issue by providing recommendations for the use of these methods, with a focus on foundational aspects of frequency domain and time-frequency analyses. It also provides publication guidelines, which aim to (1) foster replication and scientific rigor, (2) assist new researchers who wish to enter the field of brain oscillations, and (3) facilitate communication among authors, reviewers, and editors.

Neutral and threatening distracter word stimuli are unnecessarily stored in working memory but do not differ in their degree of working memory storage.

Evidence suggests that threatening stimuli induce attentional biases compared to neutral stimuli, leading to subsequent storage in working memory. The current study examined how threatening versus neutral word distracters influence attention, and how this affects the unnecessary storage of these task-irrelevant stimuli in working memory. We measured the N2pc and contralateral delay activity (CDA), two event-related potentials (ERPs) that index attentional selection and the number of items maintained in WM, respectively, as participants completed a lateralized change detection task using word stimuli. Our results replicated work demonstrating a CDA effect for word stimuli, and found that distracter words are unnecessarily stored in working memory. However, we observed non-significant differences in attentional bias and working memory storage between distracter word conditions, and individual variation in anxiety was not associated with these processes. Bayes Factor analyses supported these null effects, suggesting that differences between neutral and threatening distracter words are unlikely.

Working Memory Performance for Differentially Conditioned Stimuli.

Previous work suggests that threat-related stimuli are stored to a greater degree in working memory compared to neutral stimuli. However, most of this research has focused on stimuli with physically salient threat attributes (e.g., angry faces), failing to account for how a "neutral" stimulus that has acquired threat-related associations through differential aversive conditioning influences working memory. The current study examined how differentially conditioned safe (i.e., CS-) and threat (i.e., CS+) stimuli are stored in working memory relative to a novel, non-associated (i.e., N) stimuli. Participants (n = 69) completed a differential fear conditioning task followed by a change detection task consisting of three conditions (CS+, CS-, N) across two loads (small, large). Results revealed individuals successfully learned to distinguishing CS+ from CS- conditions during the differential aversive conditioning task. Our working memory outcomes indicated successful load manipulation effects, but no statistically significant differences in accuracy, response time (RT), or Pashler's K measures of working memory capacity between CS+, CS-, or N conditions. However, we observed significantly reduced RT difference scores for the CS+ compared to CS- condition, indicating greater RT differences between the CS+ and N condition vs. the CS- and N condition. These findings suggest that differentially conditioned stimuli have little impact on behavioral outcomes of working memory compared to novel stimuli that had not been associated with previous safe of aversive outcomes, at least in healthy populations.

State anxiety reduces working memory capacity but does not impact filtering cost for neutral distracters.

Current theories propose that anxiety adversely impacts working memory (WM) by restricting WM capacity and interfering with efficient filtering of task-irrelevant information. The current study investigated the effect of shock-induced state anxiety on WM capacity and the ability to filter task-irrelevant neutral stimuli. We measured the contralateral delay activity (CDA), an event-related potential that indexes the number of items maintained in WM, while participants completed a lateralized change detection task. The task included low and high WM loads, as well as a low load plus distracter condition. This design was used to assess WM capacity for low and high loads and investigate an individual's ability to filter neutral task-irrelevant stimuli. Participants completed the task under two conditions, threat of shock and safe. We observed a reduced CDA in the threat compared to the safe condition that was specific for high memory load. However, we did not find any differences in CDA filtering cost between threat and safe conditions. In addition, we did not find any differences in behavioral performance between the threat and safe conditions. These findings suggest that being in an anxious state reduces the neural representation for large amounts of information in WM, but have little effect on the filtering of neutral distracters.

Reward-related distracters and working memory filtering.

Reward-related stimuli capture attention, even when they are task irrelevant. A consequence of attentional prioritization of reward-related stimuli is that they may also have preferential access to working memory like other forms of emotional information. However, whether reward-related distracters leak into working memory remains unknown. Here, using a well-validated change detection task of visual working memory capacity and filtering, we conducted two studies to directly assess the impact of reward-related distracters on working memory. In both studies, the distracters consisted of colored bars or circles that were previously associated with monetary reward. In Experiment 1, results indicated that previously rewarded distracters did not impact behavioral measures of working memory filtering efficiency compared to neutral distracters. In Experiment 2, using ERPs, we measured the contralateral delay activity (CDA), a psychophysiological index of the number of items retained in working memory, to further assess filtering efficiency. We observed that the CDA for high reward distracters was similar to low reward and neutral distracters. However, in early trials, behavioral measures revealed that previously rewarded stimuli negatively impacted working memory capacity, an effect not observed with neutral distracters. This effect, though, was not found for the CDA in early trials. In summary, our findings across two studies suggest that attentional capture by task-irrelevant reward may have minimal impact on visual working memory-findings that have important implications for delineating the boundaries of reward-cognition interactions.

Alpha band frequency differences between low-trait and high-trait anxious individuals.

Trait anxiety has been shown to cause significant impairments on attentional tasks. Current research has identified alpha band frequency differences between low-trait and high-trait anxious individuals. Here, we further investigated the underlying alpha band frequency differences between low-trait and high-trait anxious individuals during their resting state and the completion of an inhibition executive functioning task. Using human participants and quantitative electroencephalographic recordings, we measured alpha band frequency in individuals both high and low in trait anxiety during their resting state, and while they completed an Eriksen Flanker Task. Results indicated that high-trait anxious individuals exhibit a desynchronization in alpha band frequency from a resting state to when they complete the Eriksen Flanker Task. This suggests that high-trait anxious individuals maintain fewer attentional resources at rest and must martial resources for task performance as compared with low-trait anxious individuals, who appear to maintain stable cognitive resources between rest and task performance. These findings add to the cognitive neuroscience literature surrounding the role of alpha band frequency in low-trait and high-trait anxious individuals.