Magnetoencephalography reveals impaired sensory gating and change detection in older adults in the somatosensory system.

Brain electrophysiological responses can provide information about age-related decline in sensory-cognitive functions with high temporal accuracy. Studies have revealed impairments in early sensory gating and pre-attentive change detection mechanisms in older adults, but no magnetoencephalographic (MEG) studies have been undertaken into both non-attentive and attentive somatosensory functions and their relationship to ageing. Magnetoencephalography was utilized to record cortical somatosensory brain responses in young (20-28 yrs), middle-aged (46-56 yrs), and older adults (64-78 yrs) under active and passive somatosensory oddball conditions. A repeated standard stimulus was occasionally replaced by a deviant stimulus (p = .1), which was an electrical pulse on a different finger. We examined the amplitudes of M50 and M100 responses reflecting sensory gating, and later components reflecting change detection and attention shifting (M190 and M250 for the passive condition, and M200 and M350 for the active condition, respectively). Spatiotemporal cluster-based permutation tests revealed that older adults had significantly larger M100 component amplitudes than young adults for task-irrelevant stimuli in both passive and active condition. Older adults also showed a reduced M250 component and an altered M350 in response to deviant stimuli. The responses of middle-aged adults did not differ from those of younger adults, but this study should be repeated with a larger sample size. By demonstrating changes in both somatosensory gating and attentional shifting mechanisms, our findings extend previous research on the effects of ageing on pre-attentive and attentive brain functions.

Altered temporoparietal junction activity during reflected self-evaluation in sub-clinical depression.

Negative self-schema is a core symptom of depression. According to social psychological theories, two types of self-evaluations play important roles in forming the negative self-view: direct self-evaluation (that is, evaluating the self directly through one's first-person perspective introspection) and reflected self-evaluation (which requires theory of mind (ToM) ability, and is evaluating the self through reflecting on a third person's perspective). Although many previous studies have investigated the processing of the direct self-evaluation in depression, few have extended research on the reflected self-evaluation. In the current study, functional magnetic resonance imaging scans were acquired in 26 dysphoric (individuals with elevated number of depressive symptoms) and 28 control participants during both direct and reflected self-evaluation tasks. Two regions of interest were defined within bilateral temporoparietal junctions (TPJs) because their significant role in ToM. Results showed that the dysphoric participants evaluated themselves more negatively than the control participants, regardless of whose perspective they were taking. More importantly, the enhanced TPJs' activations were observed in the control group during the reflected self-evaluation task versus the direct self-evaluation task, whereas no such difference was observed in the dysphoric participants. The results are interpreted in the framework of impaired ToM ability in sub-clinical depression.  General Scientific Summary (GSS) Negative self-schema is one of the core symptoms of depression. This study suggests that the negative self-schema reflects not only in direct self-evaluation (i.e. evaluating the self via one's own introspection) but also in reflected self-evaluation (i.e. evaluating the self via others' perspective). Importantly, altered TPJ activity was found during a reflected self-evaluation task among individuals with depressive symptoms. These changes in brain function might be associated with impaired ToM ability in sub-clinical depression.

The effect of sad mood on early sensory event-related potentials to task-irrelevant faces.

It has been shown that the perceiver's mood affects the perception of emotional faces, but it is not known how mood affects preattentive brain responses to emotional facial expressions. To examine the question, we experimentally induced sad and neutral mood in healthy adults before presenting them with task-irrelevant pictures of faces while an electroencephalography was recorded. Sad, happy, and neutral faces were presented to the participants in an ignore oddball condition. Differential responses (emotional - neutral) for the P1, N170, and P2 amplitudes were extracted and compared between neutral and sad mood conditions. Emotional facial expressions modulated all the components, and an interaction effect of expression by mood was found for P1: an emotional modulation to happy faces, which was found in neutral mood condition, disappeared in sad mood condition. For N170 and P2, we found larger response amplitudes for both emotional faces, regardless of the mood. The results add to the previous behavioral findings showing that mood already affects low-level cortical feature encoding of task-irrelevant faces.

Pain modulates early sensory brain responses to task-irrelevant emotional faces.

BACKGROUND: Pain can have a significant impact on an individual's life, as it has both cognitive and affective consequences. However, our understanding of how pain affects social cognition is limited. Previous studies have shown that pain, as an alarm stimulus, can disrupt cognitive processing when focal attention is required, but whether pain also affects task-irrelevant perceptual processing remains unclear. METHODS: We examined the effect of laboratory-induced pain on event-related potentials (ERPs) to neutral, sad and happy faces before, during and after a cold pressor pain. ERPs reflecting different stages of visual processing (P1, N170 and P2) were analysed. RESULTS: Pain decreased the P1 amplitude for happy faces and increased the N170 amplitude for happy and sad faces compared to the pre-pain phase. The effect of pain on N170 was also observed in the post-pain phase. The P2 component was not affected by pain. CONCLUSIONS: Our results suggest that pain alters both featural (P1) and structural face-sensitive (N170) visual encoding of emotional faces, even when the faces are irrelevant to the task. While the effect of pain on initial feature encoding seemed to be disruptive and specific to happy faces, later processing stages showed long-lasting and increased activity for both sad and happy emotional faces. SIGNIFICANCE: The observed alterations in face perception due to pain may have consequences for real-life interactions, as fast and automatic encoding of facial emotions is important for social interactions.

Alterations in working memory maintenance of fearful face distractors in depressed participants: An ERP study.

Task-irrelevant threatening faces (e.g., fearful) are difficult to filter from visual working memory (VWM), but the difficulty in filtering non-threatening negative faces (e.g., sad) is not known. Depressive symptoms could also potentially affect the ability to filter different emotional faces. We tested the filtering of task-irrelevant sad and fearful faces by depressed and control participants performing a color-change detection task. The VWM storage of distractors was indicated by contralateral delay activity, a specific event-related potential index for the number of objects stored in VWM during the maintenance phase. The control group did not store sad face distractors, but they automatically stored fearful face distractors, suggesting that threatening faces are specifically difficult to filter from VWM in non-depressed individuals. By contrast, depressed participants showed no additional consumption of VWM resources for either the distractor condition or the non-distractor condition, possibly suggesting that neither fearful nor sad face distractors were maintained in VWM. Our control group results confirm previous findings of a threat-related filtering difficulty in the normal population while also suggesting that task-irrelevant non-threatening negative faces do not automatically load into VWM. The novel finding of the lack of negative distractors within VWM storage in participants with depressive symptoms may reflect a decreased overall responsiveness to negative facial stimuli. Future studies should investigate the mechanisms underlying distractor filtering in depressed populations.

Impact of observational and direct learning on fear conditioning generalization in humans.

Humans gain knowledge about threats not only from their own experiences but also from observing others' behavior. A neutral stimulus is associated with a threat stimulus for several times and the neutral stimulus will evoke fear responses, which is known as fear conditioning. When encountering a new event that is similar to one previously associated with a threat, one may feel afraid and produce fear responses. This is called fear generalization. Previous studies have mostly focused on fear conditioning and generalization based on direct learning, but few have explored how observational fear learning affects fear conditioning and generalization. To the best of our knowledge, no previous study has focused on the neural correlations of fear conditioning and generalization based on observational learning. In the present study, 58 participants performed a differential conditioning paradigm in which they learned the associations between neutral cues (i.e., geometric figures) and threat stimuli (i.e., electric shock). The learning occurred on their own (i.e., direct learning) and by observing other participant's responses (i.e., observational learning); the study used a within-subjects design. After each learning condition, a fear generalization paradigm was conducted by each participant independently while their behavioral responses (i.e., expectation of a shock) and electroencephalography (EEG) recordings or responses were recorded. The shock expectancy ratings showed that observational learning, compared to direct learning, reduced the differentiation between the conditioned threatening stimuli and safety stimuli and the increased shock expectancy to the generalization stimuli. The EEG indicated that in fear learning, threatening conditioned stimuli in observational and direct learning increased early discrimination (P1) and late motivated attention (late positive potential [LPP]), compared with safety conditioned stimuli. In fear generalization, early discrimination, late motivated attention, and orienting attention (alpha-event-related desynchronization [alpha-ERD]) to generalization stimuli were reduced in the observational learning condition. These findings suggest that compared to direct learning, observational learning reduces differential fear learning and increases the generalization of fear, and this might be associated with reduced discrimination and attentional function related to generalization stimuli.

Encoding specificity instead of online integration of real-world spatial regularities for objects in working memory.

Most objects show high degrees of spatial regularity (e.g. beach umbrellas appear above, not under, beach chairs). The spatial regularities of real-world objects benefit visual working memory (VWM), but the mechanisms behind this spatial regularity effect remain unclear. The "encoding specificity" hypothesis suggests that spatial regularity will enhance the visual encoding process but will not facilitate the integration of information online during VWM maintenance. The "perception-alike" hypothesis suggests that spatial regularity will function in both visual encoding and online integration during VWM maintenance. We investigated whether VWM integrates sequentially presented real-world objects by focusing on the existence of the spatial regularity effect. Throughout five experiments, we manipulated the presentation (simultaneous vs. sequential) and regularity (with vs. without regularity) of memory arrays among pairs of real-world objects. The spatial regularity of memory objects presented simultaneously, but not sequentially, improved VWM performance. We also examined whether memory load, verbal suppression and masking, and memory array duration hindered the spatial regularity effect in sequential presentation. We found a stable absence of the spatial regularity effect, suggesting that the participants were unable to integrate real-world objects based on spatial regularities online. Our results support the encoding specificity hypothesis, wherein the spatial regularity of real-world objects can enhance the efficiency of VWM encoding, but VWM cannot exploit spatial regularity to help organize sampled sequential information into meaningful integrations.

Auditory event-related potentials in separating patients with depressive disorders and non-depressed controls: A narrative review.

This narrative review brings together the findings regarding the differences in the auditory event-related potentials (ERPs) between patients with depressive disorder and non-depressed control subjects. These studies' results can inform us of the possible alterations in sensory-cognitive processing in depressive disorders and the potential of using these ERPs in clinical applications. Auditory P3, mismatch negativity (MMN) and loudness dependence of auditory evoked potentials (LDAEP) were the subjects of the investigation. A search in PubMed yielded 84 studies. The findings of the reviewed studies were not highly consistent, but some patterns could be identified. For auditory P3b, the common findings were attenuated amplitude and prolonged latency among depressed patients. Regarding auditory MMN, especially the amplitude of duration deviance MMN was commonly attenuated, and the amplitude of frequency deviance MMN was increased in depressed patients. In LDAEP studies, generally, no differences between depressed patients and non-depressed controls were reported, although some group differences concerning specific depression subtypes were found. This review posits that future research should investigate whether certain stimulus conditions are particularly efficient at separating depressed and non-depressed participant groups. Future studies should contrast responses in different subpopulations of depressed patients, as well as different clinical groups (e.g., depressive disorder and anxiety disorder patients), to investigate the specificity of the auditory ERP alterations for depressive disorders.

Decreased intersubject synchrony in dynamic valence ratings of sad movie contents in dysphoric individuals.

Emotional reactions to movies are typically similar between people. However, depressive symptoms decrease synchrony in brain responses. Less is known about the effect of depressive symptoms on intersubject synchrony in conscious stimulus-related processing. In this study, we presented amusing, sad and fearful movie clips to dysphoric individuals (those with elevated depressive symptoms) and control participants to dynamically rate the clips' valences (positive vs. negative). We analysed both the valence ratings' mean values and intersubject correlation (ISC). We used electrodermal activity (EDA) to complement the measurement in a separate session. There were no group differences in either the EDA or mean valence rating values for each movie type. As expected, the valence ratings' ISC was lower in the dysphoric than the control group, specifically for the sad movie clips. In addition, there was a negative relationship between the valence ratings' ISC and depressive symptoms for sad movie clips in the full sample. The results are discussed in the context of the negative attentional bias in depression. The findings extend previous brain activity results of ISC by showing that depressive symptoms also increase variance in conscious ratings of valence of stimuli in a mood-congruent manner.

Magnetoencephalography Responses to Unpredictable and Predictable Rare Somatosensory Stimuli in Healthy Adult Humans.

Mismatch brain responses to unpredicted rare stimuli are suggested to be a neural indicator of prediction error, but this has rarely been studied in the somatosensory modality. Here, we investigated how the brain responds to unpredictable and predictable rare events. Magnetoencephalography responses were measured in adults frequently presented with somatosensory stimuli (FRE) that were occasionally replaced by two consecutively presented rare stimuli [unpredictable rare stimulus (UR) and predictable rare stimulus (PR); p = 0.1 for each]. The FRE and PR were electrical stimulations administered to either the little finger or the forefinger in a counterbalanced manner between the two conditions. The UR was a simultaneous electrical stimulation to both the forefinger and the little finger (for a smaller subgroup, the UR and FRE were counterbalanced for the stimulus properties). The grand-averaged responses were characterized by two main components: one at 30-100 ms (M55) and the other at 130-230 ms (M150) latency. Source-level analysis was conducted for the primary somatosensory cortex (SI) and the secondary somatosensory cortex (SII). The M55 responses were larger for the UR and PR than for the FRE in both the SI and the SII areas and were larger for the UR than for the PR. For M150, both investigated areas showed increased activity for the UR and the PR compared to the FRE. Interestingly, although the UR was larger in stimulus energy (stimulation of two fingers at the same time) and had a larger prediction error potential than the PR, the M150 responses to these two rare stimuli did not differ in source strength in either the SI or the SII area. The results suggest that M55, but not M150, can possibly be associated with prediction error signals. These findings highlight the need for disentangling prediction error and rareness-related effects in future studies investigating prediction error signals.

Attentional bias towards interpersonal aggression in depression - an eye movement study.

Depressed individuals exhibit an attentional bias towards mood-congruent stimuli, yet evidence for biased processing of threat-related information in human interaction remains scarce. Here, we tested whether an attentional bias towards interpersonally aggressive pictures over interpersonally neutral pictures could be observed to a greater extent in depressed participants than in control participants. Eye movements were recorded while the participants freely viewed visually matched interpersonally aggressive and neutral pictures, which were presented in pairs. Across the groups, participants spent more time looking at neutral pictures than at aggressive pictures, probably reflecting avoidance behavior. When the participants could anticipate the stimulus valence, depressed participants - but not controls - showed an early attentional bias towards interpersonally aggressive pictures, as indexed by their longer first fixation durations on aggressive pictures than on neutral pictures. Our results thus preliminarily suggest both an early attentional bias towards interpersonal aggression, which is present, in depressed participants, also when aggression contents are anticipated, and a later attentional avoidance of aggression. The early depression-related bias in information processing may have maladaptive effects on the way depressed individuals perceive and function in social interaction and can, therefore, maintain depressed mood.

Individual differences in working memory capacity are unrelated to the magnitudes of retrocue benefits.

Previous studies have associated visual working memory (VWM) capacity with the use of internal attention. Retrocues, which direct internal attention to a particular object or feature dimension, can improve VWM performance (i.e., retrocue benefit, RCB). However, so far, no study has investigated the relationship between VWM capacity and the magnitudes of RCBs obtained from object-based and dimension-based retrocues. The present study explored individual differences in the magnitudes of object- and dimension-based RCBs and their relationships with VWM capacity. Participants completed a VWM capacity measurement, an object-based cue task, and a dimension-based cue task. We confirmed that both object- and dimension-based retrocues could improve VWM performance. We also found a significant positive correlation between the magnitudes of object- and dimension-based RCB indexes, suggesting a partly overlapping mechanism between the use of object- and dimension-based retrocues. However, our results provided no evidence for a correlation between VWM capacity and the magnitudes of the object- or dimension-based RCBs. Although inadequate attention control is usually assumed to be associated with VWM capacity, the results suggest that the internal attention mechanism for using retrocues in VWM retention is independent of VWM capacity.

Neural generators of the frequency-following response elicited to stimuli of low and high frequency: A magnetoencephalographic (MEG) study.

The frequency-following response (FFR) to periodic complex sounds has gained recent interest in auditory cognitive neuroscience as it captures with great fidelity the tracking accuracy of the periodic sound features in the ascending auditory system. Seminal studies suggested the FFR as a correlate of subcortical sound encoding, yet recent studies aiming to locate its sources challenged this assumption, demonstrating that FFR receives some contribution from the auditory cortex. Based on frequency-specific phase-locking capabilities along the auditory hierarchy, we hypothesized that FFRs to higher frequencies would receive less cortical contribution than those to lower frequencies, hence supporting a major subcortical involvement for these high frequency sounds. Here, we used a magnetoencephalographic (MEG) approach to trace the neural sources of the FFR elicited in healthy adults (N = 19) to low (89 Hz) and high (333 Hz) frequency sounds. FFRs elicited to the high and low frequency sounds were clearly observable on MEG and comparable to those obtained in simultaneous electroencephalographic recordings. Distributed source modeling analyses revealed midbrain, thalamic, and cortical contributions to FFR, arranged in frequency-specific configurations. Our results showed that the main contribution to the high-frequency sound FFR originated in the inferior colliculus and the medial geniculate body of the thalamus, with no significant cortical contribution. In contrast, the low-frequency sound FFR had a major contribution located in the auditory cortices, and also received contributions originating in the midbrain and thalamic structures. These findings support the multiple generator hypothesis of the FFR and are relevant for our understanding of the neural encoding of sounds along the auditory hierarchy, suggesting a hierarchical organization of periodicity encoding.

Brain responses of dysphoric and control participants during a self-esteem implicit association test.

Previous studies have reported lowered implicit self-esteem at the behavioral level among depressed individuals. However, brain responses related to the lowered implicit self-esteem have not been investigated in people with depression. Here, event-related potentials were measured in 28 dysphoric participants (individuals with elevated amounts of depressive symptoms) and 30 control participants during performance of an implicit association task (IAT) suggested to reflect implicit self-esteem. Despite equivalent behavioral performance, differences in brain responses were observed between the dysphoric and the control groups in late positive component (LPC) within 400-1,000 ms poststimulus latency. For the dysphoric group, self-negativity mapping stimuli (me with negative word pairing and not-me with positive word pairing) induced significantly larger LPC amplitude as compared to self-positivity mapping stimuli (me with positive pairing and not-me with negative pairing), whereas the control group showed the opposite pattern. These results suggest a more efficient categorization toward implicit self-is-negative association, possibly reflecting lower implicit self-esteem among the dysphoric participants, in comparison to the controls. These results demonstrate the need for further investigation into the functional significance of LPC modulation during IAT and determination of whether LPC can be used as a neural marker of depressive-related implicit self-esteem.

Deviance detection in sound frequency in simple and complex sounds in urethane-anesthetized rats.

Mismatch negativity (MMN), which is an electrophysiological response demonstrated in humans and animals, reflects memory-based deviance detection in a series of sounds. However, only a few studies on rodents have used control conditions that were sufficient in eliminating confounding factors that could also explain differential responses to deviant sounds. Furthermore, it is unclear if change detection occurs similarly for sinusoidal and complex sounds. In this study, we investigated frequency change detection in urethane-anesthetized rats by recording local-field potentials from the dura above the auditory cortex. We studied change detection in sinusoidal and complex sounds in a series of experiments, controlling for sound frequency, probability, and pattern in a series of sounds. For sinusoidal sounds, the MMN controlled for frequency, adaptation, and pattern, was elicited at approximately 200 ms onset latency. For complex sounds, the MMN controlled for frequency and adaptation, was elicited at 60 ms onset latency. Sound frequency affected the differential responses. MMN amplitude was larger for the sinusoidal sounds than for the complex sounds. These findings indicate the importance of controlling for sound frequency and stimulus probabilities, which have not been fully controlled for in most previous animal and human studies. Future studies should confirm the preference for sinusoidal sounds over complex sounds in rats.

Electrical brain activity and facial electromyography responses to irony in dysphoric and non-dysphoric participants.

We studied irony comprehension and emotional reactions to irony in dysphoric and control participants. Electroencephalography (EEG) and facial electromyography (EMG) were measured when spoken conversations were presented with pictures that provided either congruent (non-ironic) or incongruent (ironic) contexts. In a separate session, participants evaluated the congruency and valence of the stimuli. While both groups rated ironic stimuli funnier than non-ironic stimuli, the control group rated all the stimuli funnier than the dysphoric group. N400-like activity, P600, and EMG activity indicating smiling were larger after the ironic stimuli than the non-ironic stimuli for both groups. Further, in the dysphoric group the irony modulation was evident in the electrode cluster over the right hemisphere, while no such difference in lateralization was observed in the control group. The results suggest a depression-related alteration in the P600 response associated to irony comprehension, but no alterations were found in emotional reactivity specifically related to irony.

Discovering dynamic task-modulated functional networks with specific spectral modes using MEG.

Efficient neuronal communication between brain regions through oscillatory synchronization at certain frequencies is necessary for cognition. Such synchronized networks are transient and dynamic, established on the timescale of milliseconds in order to support ongoing cognitive operations. However, few studies characterizing dynamic electrophysiological brain networks have simultaneously accounted for temporal non-stationarity, spectral structure, and spatial properties. Here, we propose an analysis framework for characterizing the large-scale phase-coupling network dynamics during task performance using magnetoencephalography (MEG). We exploit the high spatiotemporal resolution of MEG to measure time-frequency dynamics of connectivity between parcellated brain regions, yielding data in tensor format. We then use a tensor component analysis (TCA)-based procedure to identify the spatio-temporal-spectral modes of covariation among separate regions in the human brain. We validate our pipeline using MEG data recorded during a hand movement task, extracting a transient motor network with beta-dominant spectral mode, which is significantly modulated by the movement task. Next, we apply the proposed pipeline to explore brain networks that support cognitive operations during a working memory task. The derived results demonstrate the temporal formation and dissolution of multiple phase-coupled networks with specific spectral modes, which are associated with face recognition, vision, and movement. The proposed pipeline can characterize the spectro-temporal dynamics of functional connectivity in the brain on the subsecond timescale, commensurate with that of cognitive performance.

Event-Related Potentials to Changes in Sound Intensity Demonstrate Alterations in Brain Function Related to Depression and Aging.

Measures of the brain's automatic electrophysiological responses to sounds represent a potential tool for identifying age- and depression-related neural markers. However, these markers have rarely been studied related to aging and depression within one study. Here, we investigated auditory event-related potentials (ERPs) in the brain that may show different alterations related to aging and depression. We used an oddball condition employing changes in sound intensity to investigate: (i) sound intensity dependence; (ii) sensory gating; and (iii) change detection, all within a single paradigm. The ERPs of younger (18-40 years) and older (62-80 years) depressed female participants and age-matched non-depressed participants were measured. Intensity dependence was examined as the difference between N1 responses to repeated high- and low-intensity sounds, sensory gating as N1 responses to rare and repeated sounds, and change detection as indexed by the mismatch negativity (MMN). We found that intensity dependence was greater in older participants than younger ones, indicating effects related to aging but not to depression. For sensory gating, we found depression- and age-related alterations as increased N1 responses. No group differences were found for MMN. Although a sensory gating deficit was expected in older adults, this study is the first to demonstrate age-related overexcitability in sound intensity dependency. The results indicate that automatic brain responses to sound intensity changes are suitable for studying age- and depression-related neural markers but may not be sensitive enough to differentiate the effects of aging and depression.

Event-related potentials to task-irrelevant sad faces as a state marker of depression.

Negative bias in face processing has been demonstrated in depression, but there are no longitudinal investigations of negative bias in symptom reduction. We recorded event-related potentials (P1 and N170) to task-irrelevant facial expressions in depressed participants who were later provided with a psychological intervention and in never depressed control participants. Follow-up measurements were conducted for the depressed group two and 39 months later. Negative bias was found specifically in the depression group, and was demonstrated as enlarged P1 amplitude to sad faces, which normalized in the follow-up measurements when the participants had fewer symptoms. Because the P1 amplitude recorded at the baseline did not differ between the depression group that recovered and the group that did not recover after the intervention, this brain response did not show potential as a biomarker for treatment response. It could have potential, however, to serve as a state-marker of depression.