Assessing Trial-by-Trial Electrophysiological and Behavioral Markers of Attentional Control and Sensory Precision in Psychotic and Mood Disorders.

BACKGROUND AND HYPOTHESIS: The current study investigated the extent to which changes in attentional control contribute to performance on a visual perceptual discrimination task, on a trial-by-trial basis in a transdiagnostic clinical sample. STUDY DESIGN: Participants with schizophrenia (SZ; N = 58), bipolar disorder (N = 42), major depression disorder (N = 51), and psychiatrically healthy controls (N = 92) completed a visual perception task in which stimuli appeared briefly. The design allowed us to estimate the lapse rate and the precision of perceptual representations of the stimuli. Electroencephalograms (EEG) were recorded to examine pre-stimulus activity in the alpha band (8-13 Hz), overall and in relation to behavior performance on the task. STUDY RESULTS: We found that the attention lapse rate was elevated in the SZ group compared with all other groups. We also observed group differences in pre-stimulus alpha activity, with control participants showing the highest levels of pre-stimulus alpha when averaging across trials. However, trial-by-trial analyses showed within-participant fluctuations in pre-stimulus alpha activity significantly predicted the likelihood of making an error, in all groups. Interestingly, our analysis demonstrated that aperiodic contributions to the EEG signal (which affect power estimates across frequency bands) serve as a significant predictor of behavior as well. CONCLUSIONS: These results confirm the elevated attention lapse rate that has been observed in SZ, validate pre-stimulus EEG markers of attentional control and their use as a predictor of behavior on a trial-by-trial basis, and suggest that aperiodic contributions to the EEG signal are an important target for further research in this area, in addition to alpha-band activity.

A Transdiagnostic Study of Effort-Cost Decision-Making in Psychotic and Mood Disorders.

BACKGROUND: Research suggests that effort-cost decision-making (ECDM), the estimation of work required to obtain reward, may be a relevant framework for understanding motivational impairment in psychotic and mood pathology. Specifically, research has suggested that people with psychotic and mood pathology experience effort as more costly than controls, and thus pursue effortful goals less frequently. This study examined ECDM across psychotic and mood pathology. HYPOTHESIS: We hypothesized that patient groups would show reduced willingness to expend effort compared to controls. STUDY DESIGN: People with schizophrenia (N = 33), schizoaffective disorder (N = 28), bipolar disorder (N = 39), major depressive disorder (N = 40), and controls (N = 70) completed a physical ECDM task. Participants decided between completing a low-effort or high-effort option for small or larger rewards, respectively. Reward magnitude, reward probability, and effort magnitude varied trial-by-trial. Data were analyzed using standard and hierarchical logistic regression analyses to assess the subject-specific contribution of various factors to choice. Negative symptoms were measured with a clinician-rated interview. STUDY RESULTS: There was a significant effect of group, driven by reduced choice of high-effort options in schizophrenia. Hierarchical logistic regression revealed that reduced choice of high-effort options in schizophrenia was driven by weaker contributions of probability information. Use of reward information was inversely associated with motivational impairment in schizophrenia. Surprisingly, individuals with major depressive disorder and bipolar disorder did not differ from controls. CONCLUSIONS: Our results provide support for ECDM deficits in schizophrenia. Additionally, differences between groups in ECDM suggest a seemingly similar behavioral phenotype, reduced motivation, could arise from disparate mechanisms.

Managing EEG studies: How to prepare and what to do once data collection has begun.

In this paper, we provide guidance for the organization and implementation of EEG studies. This work was inspired by our experience conducting a large-scale, multi-site study, but many elements could be applied to any EEG project. Section 1 focuses on study activities that take place before data collection begins. Topics covered include: establishing and training study teams, considerations for task design and piloting, setting up equipment and software, development of formal protocol documents, and planning communication strategy with all study team members. Section 2 focuses on what to do once data collection has already begun. Topics covered include: (1) how to effectively monitor and maintain EEG data quality, (2) how to ensure consistent implementation of experimental protocols, and (3) how to develop rigorous preprocessing procedures that are feasible for use in a large-scale study. Links to resources are also provided, including sample protocols, sample equipment and software tracking forms, sample code, and tutorial videos (to access resources, please visit: https://osf.io/wdrj3/).

Gamma-band entrainment abnormalities in schizophrenia: Modality-specific or cortex-wide impairment?

A growing body of literature suggests that cognitive impairment in people with schizophrenia (PSZ) results from disrupted cortical excitatory/inhibitory (E-I) balance, which may be linked to gamma entrainment and can be measured noninvasively using electroencephalography (EEG). However, it is not yet known the degree to which these entrainment abnormalities covary within subjects across sensory modalities. Furthermore, the degree to which cross-modal gamma entrainment reflects variation in biological processes associated with cognitive performance remains unclear. We used EEG to measure entrainment to repetitive auditory and visual stimulation at beta (20 Hz) and gamma (30 and 40 Hz) frequencies in PSZ (n = 78) and healthy control subjects (HCS; n = 80). Three indices were measured for each frequency and modality: event-related spectral perturbation (ERSP), intertrial coherence (ITC), and phase-lag angle (PLA). Cognition and symptom severity were also assessed. We found little evidence that gamma entrainment covaried across sensory modalities. PSZ exhibited a modest correlation between modalities at 40 Hz for ERSP and ITC measures (r = 0.23-0.24); however, no other significant correlations between modalities emerged for either HCS or PSZ. Both univariate and multivariate analyses revealed that (a) the pattern of entrainment abnormalities in PSZ differed across modalities, and (b) modality rather than frequency band was the main source of variance. Finally, we observed a significant association between cognition and gamma entrainment in the auditory domain only in HCS. Gamma-band EEG entrainment does not reflect a unitary transcortical mechanism but is instead modality specific. To the extent that entrainment reflects the integrity of cortical E-I balance, the deficits observed in PSZ appear to be modality specific and not consistently associated with cognitive impairment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Is Cortical Theta-Gamma Phase-Amplitude Coupling Memory-Specific?

One of the proposed neural mechanisms involved in working memory is coupling between the theta phase and gamma amplitude. For example, evidence from intracranial recordings shows that coupling between hippocampal theta and cortical gamma oscillations increases selectively during working memory tasks. Theta-gamma phase-amplitude coupling can also be measured non-invasively through scalp EEG; however, EEG can only assess coupling within cortical areas, and it is not yet clear if this cortical-only coupling is truly memory-specific, or a more general phenomenon. We tested this directly by measuring cortical coupling during three different conditions: a working memory task, an attention task, and a passive perception condition. We find similar levels of theta-gamma coupling in all three conditions, suggesting that cortical theta-gamma phase-amplitude coupling is not a memory-specific signal, but instead reflects some other attentional or perceptual processes. Implications for understanding the brain dynamics of visual working memory are discussed.

Neural basis of the visual working memory deficit in schizophrenia: Merging evidence from fMRI and EEG.

Although people with schizophrenia (PSZ) exhibit robust and reliable deficits in working memory (WM) capacity, the neural processes that give rise to this impairment remain poorly understood. One reason for this lack of clarity is that most studies employ a single neural recording modality-each with strengths and weaknesses-with few examples of integrating results across modalities. To address this gap, we conducted a secondary analysis that combined data from an overlapping set of subjects in previously published electroencephalographic and functional magnetic resonance imaging studies that used nearly identical working memory tasks (visual change detection). The prior studies found similar patterns of results for both posterior parietal BOLD activation and suppression of the alpha frequency band within the EEG. Specifically, both signals exhibited abnormally shallow modulation as a function of the amount of information being stored in WM in PSZ. In the present study, both alpha suppression and posterior parietal BOLD activity increased as the number of items stored in WM increased. The magnitude of alpha suppression modulation was correlated with the magnitude of BOLD signal modulation in PSZ, but not in HCS. This finding suggests that the same illness-related biological processes constrain both alpha suppression and BOLD signal modulation as a function of WM storage in PSZ. The complementary strengths of these two techniques may thus combine to advance the identification of the processes underlying WM deficits in PSZ.

Absence of Excess Intra-Individual Variability in Retinal Function in People With Schizophrenia.

People with schizophrenia exhibit increased intra-individual variability in both behavioral and neural signatures of cognition. Examination of intra-individual variability may uncover a unique functionally relevant aspect of impairment that is not captured by typical between-group comparisons of mean or median values. We and others have observed that retinal activity measured using electroretinography (ERG) is significantly reduced in people with schizophrenia; however, it is currently unclear whether greater intra-individual variability in the retinal response can also be observed. To investigate this, we examined intra-individual variability from 25 individuals with schizophrenia and 24 healthy controls under two fERG conditions: (1) a light-adapted condition in which schizophrenia patients demonstrated reduced amplitudes; and (2) a dark-adapted condition in which the groups did not differ in amplitudes. Intraclass correlation coefficients (ICC) were generated to measure intra-individual variability for each subject, reflecting the consistency of activation values (in µv) across all sampling points (at a 2 kHz sampling rate) within all trials within a condition. Contrary to our predictions, results indicated that the schizophrenia and healthy control groups did not differ in intra-individual variability in fERG responses in either the light- or dark-adapted conditions. This finding remained consistent when variability was calculated as the standard deviation (SD) and coefficient of variation (CV) of maximum positive and negative microvolt values within the a- and b-wave time windows. This suggests that although elevated variability in schizophrenia may be observed at perceptual and cognitive levels of processing, it is not present in the earliest stages of sensory processing in vision.

FRONTAL ALPHA ASYMMETRY IN YOUTH AT CLINICAL HIGH-RISK FOR PSYCHOSIS.

PURPOSE OF THE REVIEW: Negative symptoms are highly predictive of whether individuals at clinical high-risk (CHR) develop a psychotic disorder. However, little is known about pathophysiological mechanisms underlying negative symptoms during this period. The current study examined neurophysiological mechanisms underlying negative symptoms in CHR individuals using electroencephalography frontal alpha asymmetry power, a biomarker of approach and avoidance motivation. RECENT FINDINGS: People with schizophrenia display abnormal patterns of frontal alpha asymmetry indicative of reduced approach motivation. However, It is unknown whether similar abnormalities occur in CHR youth that predict negative symptoms. SUMMARY: Results indicated that CHR and healthy controls did not differ in frontal alpha asymmetry scores. However, in CHR youth, frontal alpha asymmetry was inversely correlated with the motivation and pleasure dimension of negative symptoms, which was accounted for by mood symptoms. Findings suggest that depression contributes to reduced approach motivation in CHR youth that manifests clinically as negative symptoms.

Alpha-band desynchronization reflects memory-specific processes during visual change detection.

Recent work investigating physiological mechanisms of working memory (WM) has revealed that modulation of alpha and beta frequency bands within the EEG plays a key role in WM storage. However, the nature of that role is unclear. In the present study, we examined event-related desynchronization of alpha and beta (α/ß-ERD) elicited by visual tasks with and without a memory component to measure the impact of a WM demand on this electrophysiological marker. We recorded EEG from 60 healthy participants while they completed three variants on a typical change detection task: one in which participants passively viewed the sample array, passive (WM-); one in which participants viewed and attended the sample array in search of a target color but did not memorize the colors, active (WM-); and one in which participants encoded, attended to, and memorized the sample array, active (WM+). Replicating previous findings, we found that active (WM+) elicited robust α/ß-ERD in frontal and posterior electrode clusters and that α-ERD was significantly associated with WM capacity. By contrast, α/ß-ERD was significantly smaller in the passive (WM-) and active (WM-) tasks, which did not consistently differ from one another. Furthermore, no such relationship was observed between WM capacity and desynchronization in the passive (WM-) or active (WM-) tasks. Taken together, these results suggest that α-ERD during memory formation reflects a memory-specific process such as consolidation or maintenance, rather than serving a generalized role in perceptual gating or engagement of attention.

Time and frequency dependent changes in resting state EEG functional connectivity following lipopolysaccharide challenge in rats.

Research has shown that inflammatory processes affect brain function and behavior through several neuroimmune pathways. However, high order brain functions affected by inflammation largely remain to be defined. Resting state functional connectivity of synchronized oscillatory activity is a valid approach to understand network processing and high order brain function under different experimental conditions. In the present study multi-electrode EEG recording in awake, freely moving rats was used to study resting state connectivity after administration of lipopolysaccharides (LPS). Male Wistar rats were implanted with 10 cortical surface electrodes and administered with LPS (2 mg/kg) and monitored for symptoms of sickness at 3, 6 and 24 h. Resting state connectivity and power were computed at baseline, 6 and 24 h. Three prominent connectivity bands were identified using a method resistant to spurious correlation: alpha (5-15 Hz), beta-gamma (20-80 Hz), and high frequency oscillation (150-200 Hz). The most prominent connectivity band, alpha, was strongly reduced 6 h after LPS administration, and returned to baseline at 24 h. Beta-gamma connectivity was also reduced at 6 h and remained reduced at 24 h. Interestingly, high frequency oscillation connectivity remained unchanged at 6 h and was impaired 24 h after LPS challenge. Expected elevations in delta and theta power were observed at 6 h after LPS administration, when behavioral symptoms of sickness were maximal. Notably, gamma and high frequency power were reduced 6 h after LPS and returned to baseline by 24 h, when the effects on connectivity were more evident. Finally, increases in cross-frequency coupling elicited by LPS were detected at 6 h for theta-gamma and at 24 h for theta-high frequency oscillations. These studies show that LPS challenge profoundly affects EEG connectivity across all identified bands in a time-dependent manner indicating that inflammatory processes disrupt both bottom-up and top-down communication across the cortex during the peak and resolution of inflammation.

No association between symptom severity and MMN impairment in schizophrenia: A meta-analytic approach.

The mismatch negativity (MMN) is an event-related potential that is consistently attenuated in people with schizophrenia. Within the predictive coding model of psychosis, MMN impairment is thought to reflect the same prediction failures that are also thought to underlie the development and crystallization of delusions and hallucinations. However, the true relationship between symptom severity and MMN impairment across studies has not yet been established. The present meta-analysis used meta-regressions to examine the relationship between MMN impairment (quantified as Hedges' g) and PANSS positive and negative symptom totals across 62 and 68 samples, respectively. Furthermore, we examined the relationship between MMN impairment and group differences in educational achievement (n = 47 samples), cognitive ability (n = 36 samples), and age (n = 86 samples). Overall, we found no significant associations between MMN impairment and symptom severity (p's > 0.50); however, we did observe a trend-level association between MMN impairment and lower education (p = 0.07) and a significant association with older age (p < 0.01) in the schizophrenia patient group. Taken together, these results challenge a simple predictive coding model of psychosis, and suggest that MMN impairment may be more closely associated with premorbid functioning than with the expression of psychotic symptoms.

Impaired suppression of delay-period alpha and beta is associated with impaired working memory in schizophrenia.

BACKGROUND: Although people with schizophrenia (PSZ) frequently exhibit reduced working memory capacity relative to healthy comparison subjects (HCS), the mechanisms that underlie this impairment are not yet known. The present study aimed to assess one putative mechanism: impaired suppression of alpha and beta frequency bands during the delay period of a visual working memory task. METHODS: The electroencephalogram (EEG) was recorded from 30 PSZ and 31 HCS while they completed a change detection task in which they were required to remember a briefly presented array of colored squares over an 1800-ms delay interval. RESULTS: Overall, we found that PSZ had significantly reduced alpha and beta-band suppression during the delay interval compared to HCS, and that these significant differences emerged early (100-200 ms after the onset of the memory array). Furthermore, the magnitude of suppression was significantly associated with task performance across both groups. Finally, the magnitude of suppression in alpha and beta frequency bands was significantly associated with a range of cognitive measures among HCS, but not PSZ. CONCLUSIONS: These results implicate impaired alpha/beta suppression during the consolidation period of working memory tasks as a promising neural mechanism that constrains capacity in PSZ.

Cognitive manipulation of brain electric microstates.

EEG studies of wakeful rest have shown that there are brief periods in which global electrical brain activity on the scalp remains semi-stable (so-called microstates). Topographical analyses of this activity have revealed that much of the variance is explained by four distinct microstates that occur in a repetitive sequence. A recent fMRI study showed that these four microstates correlated with four known functional systems, each of which is activated by specific cognitive functions and sensory inputs. The present study used high density EEG to examine the degree to which spatial and temporal properties of microstates may be altered by manipulating cognitive task (a serial subtraction task vs. wakeful rest) and the availability of visual information (eyes open vs. eyes closed conditions). The hypothesis was that parameters of microstate D would be altered during the serial subtraction task because it is correlated with regions that are part of the dorsal attention functional system. It was also expected that the sequence of microstates would preferentially transition from all other microstates to microstate D during the task as compared to rest. Finally, it was hypothesized that the eyes open condition would significantly increase one or more microstate parameters associated with microstate B, which is associated with the visual system. Topographical analyses indicated that the duration, coverage, and occurrence of microstate D were significantly higher during the cognitive task compared to wakeful rest; in addition, microstate C, which is associated with regions that are part of the default mode and cognitive control systems, was very sensitive to the task manipulation, showing significantly decreased duration, coverage, and occurrence during the task condition compared to rest. Moreover, microstate B was altered by manipulations of visual input, with increased occurrence and coverage in the eyes open condition. In addition, during the eyes open condition microstates A and D had significantly shorter durations, while C had increased occurrence. Microstate D had decreased coverage in the eyes open condition. Finally, at least 15 microstates (identified via k-means clustering) were required to explain a similar amount of variance of EEG activity as previously published values. These results support important aspects of our hypotheses and demonstrate that cognitive manipulation of microstates is possible, but the relationships between microstates and their corresponding functional systems are complex. Moreover, there may be more than four primary microstates.

A Meta-Analysis of Mismatch Negativity in Schizophrenia: From Clinical Risk to Disease Specificity and Progression.

BACKGROUND: The observation that mismatch negativity (MMN) is consistently impaired in schizophrenia has generated considerable interest in the use of this biomarker as an index of disease risk and progression. Despite such enthusiasm, a number of issues remain unresolved regarding the nature of MMN impairment. The present study expands upon an earlier meta-analysis of MMN impairment in schizophrenia by examining impairment across a range of clinical presentations, as well as across experimental parameters. METHODS: One hundred one samples of schizophrenia patients were included in the present study, including first-episode (n = 13), chronic (n = 13), and mixed-stage (n = 75) samples. Additionally, MMN was examined in three related conditions: bipolar disorder (n = 9), unaffected first-degree relatives (n = 8), and clinical high risk (n = 16). RESULTS: We found that MMN impairment 1) likely reflects a vulnerability to disease progression in clinical high-risk populations rather than a genetic risk for the condition; 2) is largely unrelated to duration of illness after the first few years of illness, indicating that impairment is not progressive throughout the life span; 3) is present in bipolar disorder, albeit to a lesser degree than in schizophrenia; and 4) is not modulated by experimental parameters such as magnitude of change between standard and deviant tones or frequency of deviant tones but may be modulated by attentional demands. CONCLUSIONS: Such findings lay the foundation for a better understanding of the nature of MMN impairment in schizophrenia, as well as its potential as a clinically useful biomarker.

Impaired working memory capacity is not caused by failures of selective attention in schizophrenia.

The cognitive impairments associated with schizophrenia have long been known to involve deficits in working memory (WM) capacity. To date, however, the causes of WM capacity deficits remain unknown. The present study examined selective attention impairments as a putative contributor to observed capacity deficits in this population. To test this hypothesis, we used an experimental paradigm that assesses the role of selective attention in WM encoding and has been shown to involve the prefrontal cortex and the basal ganglia. In experiment 1, participants were required to remember the locations of 3 or 5 target items (red circles). In another condition, 3-target items were accompanied by 2 distractor items (yellow circles), which participants were instructed to ignore. People with schizophrenia (PSZ) exhibited significant impairment in memory for the locations of target items, consistent with reduced WM capacity, but PSZ and healthy control subjects did not differ in their ability to filter the distractors. This pattern was replicated in experiment 2 for distractors that were more salient. Taken together, these results demonstrate that reduced WM capacity in PSZ is not attributable to a failure of filtering irrelevant distractors.

To the beat of your own drum: cortical regularization of non-integer ratio rhythms toward metrical patterns.

Humans perceive a wide range of temporal patterns, including those rhythms that occur in music, speech, and movement; however, there are constraints on the rhythmic patterns that we can represent. Past research has shown that sequences in which sounds occur regularly at non-metrical locations in a repeating beat period (non-integer ratio subdivisions of the beat, e.g. sounds at 430ms in a 1000ms beat) are represented less accurately than sequences with metrical relationships, where events occur at even subdivisions of the beat (integer ratios, e.g. sounds at 500ms in a 1000ms beat). Why do non-integer ratio rhythms present cognitive challenges? An emerging theory is that non-integer ratio sequences are represented incorrectly, "regularized" in the direction of the nearest metrical pattern, and the present study sought evidence of such perceptual regularization toward integer ratio relationships. Participants listened to metrical and non-metrical rhythmic auditory sequences during electroencephalogram recording, and sounds were pseudorandomly omitted from the stimulus sequence. Cortical responses to these omissions (omission elicited potentials; OEPs) were used to estimate the timing of expectations for omitted sounds in integer ratio and non-integer ratio locations. OEP amplitude and onset latency measures indicated that expectations for non-integer ratio sequences are distorted toward the nearest metrical location in the rhythmic period. These top-down effects demonstrate metrical regularization in a purely perceptual context, and provide support for dynamical accounts of rhythm perception.

Synchronization dynamics and evidence for a repertoire of network states in resting EEG.

Intrinsically driven neural activity generated at rest exhibits complex spatiotemporal dynamics characterized by patterns of synchronization across distant brain regions. Mounting evidence suggests that these patterns exhibit fluctuations and nonstationarity at multiple time scales. Resting-state electroencephalographic (EEG) recordings were examined in 12 young adults for changes in synchronization patterns on a fast time scale in the range of tens to hundreds of milliseconds. Results revealed that EEG dynamics continuously underwent rapid transitions between intermittently stable states. Numerous approximate recurrences of states were observed within single recording epochs, across different epochs separated by longer times, and between participants. For broadband (4-30 Hz) data, a majority of states could be grouped into three families, suggesting the existence of a limited repertoire of core states that is continually revisited and shared across participants. Our results document the existence of fast synchronization dynamics iterating amongst a small set of core networks in the resting brain, complementing earlier findings of nonstationary dynamics in electromagnetic recordings and transient EEG microstates.

Self-esteem and insight as predictors of symptom change in schizophrenia: a longitudinal study.

Though it is known that symptom profiles in schizophrenia change throughout the course of the illness, it is not yet clear which psychological antecedents predict these changes. The purpose of the present study was to explore "level of insight into mental illness" and "self-esteem" as predictors of positive symptom change in schizophrenia patients. Fifty-seven schizophrenia patients completed assessments of self-esteem, insight into mental illness, positive symptoms and paranoia once every four weeks for a total of eight individual testing sessions. Hierarchical linear regression analysis revealed that changes in self-esteem predicted future changes in paranoia as well as positive symptoms more broadly; decreases in self-esteem at any given time point were associated with an increase in persecutory beliefs and other positive symptoms at the following assessment. On the other hand, decreases in insight were not significantly associated with paranoia or positive symptoms, either as a stable trait of the mental illness or as a predictor of change over time. Taken together, these results suggest that change in self-esteem, but not insight, has a significant and unique association with positive symptoms of schizophrenia, and may be a valuable target for future treatment.

Phenomenological dimensions of sensory gating.

Contemporary sensory gating definitions are generally tied to the perceptual and attentional phenomenology described by McGhie and Chapman, including abnormalities in the quality of sensory input, heightened awareness of background noises, and poor selective attention reported by individuals with schizophrenia. Despite these explicit phenomenological origins, little is known about the experiential phenomena underlying contemporary operationalizations of the sensory gating construct, such as whether the construct is restricted to experiences associated with the modulation of sensory percepts includes selective attention and distractibility or even whether the construct is accessible via self-report. Because clarification of these issues has important implications for the development and testing of psychological theories and the study of psychopathology, a series of studies was conducted to (a) empirically identify the major dimensions of sensory gating-like perceptual and attentional phenomenology in healthy young adults and (b) develop a psychometrically sound self-report rating scale to capture these dimensions, the Sensory Gating Inventory (SGI). Factor analyses of Likert items measuring a broad range of sensory gating-like subjective experiences revealed 1 primary factor that encompassed anomalies of perceptual modulation (eg, perceptions of heightened stimulus sensitivity and sensory inundation) and 3 other factors measuring disturbances in the processes of focal and radial attention as well as exacerbation of sensory gating-like anomalies by fatigue and stress. Psychometrically, the SGI demonstrated strong reliability and validity. An empirically based conceptual demarcation of the sensory gating construct is offered, and directions for future research are described.