Event-related potentials to rare visual targets and negative symptom severity in a transdiagnostic psychiatric sample
Introduction
One of the main goals of the National Institute of Mental Health’s Research Domain Criteria (RDoC) approach is to identify causal mechanisms for particular symptoms found across different psychiatric disorders (Insel et al., 2010). Some of these, called “negative symptoms,” involve lack of pleasure (anhedonia), lack of motivation (avolition), and blunted affect (reduced expression of emotion), among others (American Psychiatric Association, 2013). Traditionally, the term “negative symptoms” has been associated with schizophrenia-spectrum disorders. However, subsets of these negative symptoms are found in diagnostic criteria or research findings pertaining to other psychiatric disorders (e.g., depression and bipolar disorder; Kaiser et al., 2011, Strauss and Cohen, 2017) and can be assessed with rating scales originally developed for patients with schizophrenia (Galynker et al., 2000). Negative symptoms are particularly resistant to current treatments, regardless of the disorder in which they appear (Correll and Schooler, 2020). Therefore, more research is needed to better understand underlying mechanisms for particular negative symptoms to inform the development of more efficacious treatments and potential prevention strategies.
One potential underlying cause of negative symptoms is impairment in higher-order cognition, which includes selective attention. In particular, it has been hypothesized that difficulties in integrating sufficient cognitive processes necessary for verbal and nonverbal communication may be linked to deficits in the emotional expressivity aspects of negative symptoms (e.g., alogia and blunted affect). Similarly, motivational deficits may be linked to deficits in higher-order cognitive functions such as selected attention and ability to modulate incoming sensory information. This can interfere with the ability to detect relevant sensory and social cues leading to difficulties in social interaction (i.e., asociality) and in initiating and persisting in activities (i.e., avolition; Pelletier-Baldelli and Holt, 2019, Strauss and Cohen, 2017).
Selective attention directs limited capacity processing resources to identify task-relevant targets from concurrent competing stimuli (Pashler, 1997). Disrupted selective attention (i.e., behavioral distractibility) is a transdiagnostic symptom found in disorders such as depression, bipolar disorder, and schizophrenia (Harvey et al., 2004, Shahaf, 2016). However, there is limited research on how selective attention performance relates to the severity of specific negative symptoms often found in these disorders. Examining how selective attention relates to negative symptoms could inform future treatments. For example, there is evidence that selective attention may be trainable (e.g., auditory in this study; Kattner and Ellermeier, 2020) and that broadly-defined attentional training may improve depression-related symptoms, but not broadly-defined negative symptoms (Prikken et al., 2019). A better understanding of how specific aspects of attention, such as selective attention, relate to specific dimensions of negative symptoms, such as anhedonia and blunted affect, may help improve understanding and aid in the creation of more targeted treatments.
Event-related potentials (ERPs), extracted from electroencephalography, have been extensively used and are well-suited for measuring individual differences in aspects of attention. ERPs can assess serial (i.e., stepwise) and parallel (i.e., simultaneous) subcomponents of attention with millisecond precision, even when a behavioral response is not present – aspects that are critical when assessing selective attention (Luck et al., 2000). While existing ERPs attention research has used either auditory or visual stimuli, the current study and literature review will focus on visual paradigms/attention. ERPs can measure unique aspects of selective visual attention, through components such as N1, N2b, P2a, and P3b (Luck et al., 2000). In general, research has suggested that earlier ERP components (e.g., N1) are associated with orienting of attention to a location in space prior to categorizing stimulus features as target-defining features (i.e., bottom-up perceptual processing), while the later components (e.g., P2a, N2b, and P3b) are indexing the evaluation of the stimulus features as members of the target-defining set (a top-down operation; Anllo-Vento and Hillyard, 1996, Hillyard and Anllo-Vento, 1998).
The N1 is a posterior negative deflection in response to visual stimuli and occurs 100–200 ms post-stimulus over posterior recording sites. The N1 is enhanced to attended stimuli and the allocation of processing capacity to sensory input (Smit et al., 2007). The N2b (also called “selection negativity”) is a bilateral posterior negative voltage deflection that occurs 180–300 ms post-stimulus and is enhanced in response to both target stimuli and infrequent non-target stimuli (Potts and Tucker, 2001). The P2a is a frontal positive voltage deflection that occurs 180–300 ms post-stimulus which is enhanced to task-relevant stimuli (Potts, 2004). In contrast to the N2b, the P2a is associated with task-relevant targets but not stimulus frequency (Potts and Tucker, 2001). The N2b and the P2a are often associated, reflecting, as postulated by Potts and Tucker (2001), the presence of a frontal/posterior interaction, in which posterior areas (i.e., N2b) attend to unexpected stimuli, while frontal areas (i.e., P2a) perform higher-order selective attention to a defined target. The P3b, a subcomponent of P300, is a centroparietal positive voltage deflection that peaks 300–500 ms post-stimulus and is larger to infrequent and/or salient targets (Johnson, 1988). The P3b is thought to reflect “top-down” deployment of selective attention to task-relevant stimuli (Chennu and Bekinschtein, 2012, Debener et al., 2002) and subsequent entry into conscious awareness and working memory (Kok, 2001).
The current study assesses ERPs recorded during a target detection task to test the hypothesis that the severity of particular negative symptoms have a stronger association with deficits in top-down versus bottom-up mechanisms of selective attention, across a transdiagnostic sample that includes a subset of disorders in which negative symptoms are common: major depressive disorder-recurrent (MDD), bipolar disorder I (BD-I), schizophrenia-spectrum disorders (SCZ), along with nonpsychiatric controls (NC). Several studies have shown a reduced P3b amplitude in individuals with SCZ, in both prodromal and acute phases of the illness (Hamilton et al., 2019, Jeon and Polich, 2003, Hamilton et al., 2019, Lee et al., 2010, Oribe et al., 2013, Shahaf, 2016). One study found that the P3b amplitude was reduced in participants in the prodromal phase who later converted to psychosis, compared to those who did not convert, suggesting that the P3b could be a vulnerability marker for psychosis (Hamilton et al., 2019). However, some longitudinal studies found an increase in P3b amplitude associated with clinical improvement over time, suggesting that visual P3b amplitude may also be a clinical state marker in schizophrenia (Mathalon et al., 2000, Park et al., 2010, Pfefferbaum et al., 1989). Other research has found that patients with SCZ, compared to NC, have a reduced amplitude in the N1, N2b, and/or P2a components during visuospatial attentional tasks (Bruder et al., 1998a, Bruder et al., 1998b, Dias et al., 2011, Ford et al., 1994, Potts et al., 2002, Wood et al., 2006).
In individuals with bipolar disorder (BD), a reduction in the P3b amplitude has been proposed as a trait marker for the disorder (see Wada et al., 2019). A few studies reported that while both SCZ and BD groups showed a reduced P3b amplitude compared to NC, the SCZ and BD samples did not statistically differ from each other (Bestelmeyer, 2012, Bestelmeyer et al., 2009). One study found that within a BD sample, a lower P3b amplitude during a visual oddball task was present in participants in the euthymic and depressive phases compared to those in the manic phase (Di Giorgio Silva et al., 2016). This finding suggests that selective attention impairment related to the P3b may be at least partially normalize during manic phases of the illness in individuals with BD. Finally, Maekawa et al. (2013) conducted a study comparing BD and NC samples during a visual oddball task and found no difference between groups in N1 and P2a amplitudes, but found a lower P3b amplitude in the BD group.
Findings for the visual P3b amplitude differences have been sparse and inconsistent for MDD samples (Bruder et al., 2012, Diner et al., 1985). Some studies suggested that the mixed findings in depression may be due to variations in the patients’ clinical presentation, suggesting that P3b amplitude reduction may be more prominent in individuals with depression who experience psychotic symptoms or suicidal ideation (Karaaslan et al., 2003). Therefore, for MDD, a reduced P3b amplitude may be secondary to a transient state-related decrease in general cognitive functioning and/or level of arousal that are common during acute depressive episodes.
A smaller number of studies have examined relationships between attention-related ERP amplitude and severity of specific psychiatric symptoms. In particular, most of these studies have been conducted in relation to the P3b and negative symptoms severity in patients with SCZ. For example, a study by Hamilton et al. (2019) on prodromal SCZ found a negative correlation between target P3b amplitude and severity of negative symptoms. This study theorized that negative symptom–related motivational impairments may specifically affect top-down allocation of attention to task-relevant stimuli. Similar results were found in a longitudinal study on a SCZ sample (Mathalon et al., 2000) which showed that the visual P3b amplitude was smaller during periods of time in which negative symptoms were more severe. Pfefferbaum et al. (1989) found that negative symptoms were negatively correlated with visual P3b amplitude in a medication-free SCZ sample. Finally, Lee et al. (2010) found that negative symptom scores were negatively associated with P3b amplitude in both first-episode and prodromal schizophrenia groups. The authors suggested that the P3b amplitude may reflect underlying primary pathological mechanisms that contribute to both negative symptoms and neurobiological changes.
The main goal of the current study is to examine ERP component amplitudes from a visual infrequent target detection task to assess whether severity of negative symptoms is specifically related to decreased top-down versus bottom-up mechanisms of selective attention, using a broad transdiagnostic sample (i.e., schizophrenia-spectrum disorders, bipolar disorders, unipolar depression, and NC). We hypothesized that greater averaged negative symptom severity across the entire sample, including NC, will be related to reduced ERP component amplitudes thought to reflect top-down attention (i.e., P2a, N2b, and P3b), but not bottom-up attention (i.e., N1). Based on limited existing literature, analyses involving individual negative symptom severity (i.e., anhedonia, avolition, and blunted affect) and their relationships with attention ERP component amplitudes will be exploratory.
Section snippets
Participants
We recruited participants using advertisements placed in local psychiatric facilities, the Craigslist website, and newspapers. Some advertisements mentioned recruitment of individuals with a diagnosis of either schizophrenia, schizoaffective disorder, or bipolar disorder, while other advertisements targeting nonpsychiatric controls did not mention any diagnosis. The inclusion criteria for the psychiatric group included meeting diagnostic criteria for a broad range of schizophrenia-spectrum
Results
See Table 1 for demographic and clinical characteristics by diagnostic class (for main correlations see Supplementary Table S1).
Discussion
The focus of the current study was to examine ERP components of late (i.e., N2b, P2a, and P3b) and early (i.e., N1) attention to assess whether severity of negative symptoms is specifically related to decreased top-down versus bottom-up mechanisms of selective attention, using a broad transdiagnostic sample. Consistent with our hypotheses, we found that individuals with an increased Positive and Negative Syndrome Scale – Negative Symptom Factor (PANSS – NSF) score severity showed a reduced mean
CRediT authorship contribution statement
All authors contributed to writing and editing the final manuscript. GCS wrote the initial draft of the document and conducted the statistical analyses, GFP assisted with measurement and interpretation of each ERP, JS assisted with all eye tracking analyses and methodology, C.C.C and C.C.S conducted the clinical interviews and clinician rating scales, and JSB generated the idea and methods used in study and assisted with ERP and statistical analyses.
Acknowledgments
The authors would like to thank the following research assistants for help with various aspects of this study: Julian Montaquila, Benjamin Trachik, Dana Braden, Stanley Desire, Carina Viegas, Travis Hatfield, Nicholas Joseph, Luke Van de Krol, Adam Benzekri, Cierra Godwin, Alyssa Finner, Soraya Allen, Maya Rose, Breanna Davis, Thomas Giallella, and Samuel Narajo Rincon, and Dr. Corey Bohil.
Funding
This work was supported by the National Institute of Mental Health (1R15MH097222-01A1; PI: J.S. Bedwell) and matching funds from University of Central Florida College of Sciences and Office of Research and Commercialization.
Conflict of interest statement
The authors have declared that no competing interests exist.
References (64)
- et al.
Transdiagnostic psychiatric symptoms related to visual evoked potential abnormalities
Psychiatry Res
(2015) - et al.
The P1 visual-evoked potential, red light, and transdiagnostic psychiatric symptoms
Brain Res
(2018) The visual P3a in schizophrenia and bipolar disorder: effects of target and distractor stimuli on the P300
Psychiatry Res
(2012)- et al.
The P300 as a possible endophenotype for schizophrenia and bipolar disorder: Evidence from twin and patient studies
Psychiatry Res
(2009) - et al.
Psychiatric symptom versus neurocognitive correlates of diminished expressivity in schizophrenia and mood disorders
Schizophr Res
(2013) - et al.
Speech deficits in serious mental illness: a cognitive resource issue?
Schizophr Res
(2014) - et al.
Auditory novelty oddball allows reliable distinction of top-down and bottom-up processes of attention
Int J Psychophysiol
(2002) - et al.
Electrical mapping in bipolar disorder patients during the oddball paradigm
J Psychiatr Res
(2016) - et al.
P300 in major depressive disorder
Psychiatry Res
(1985) - et al.
ERPs in schizophrenia: effects of antipsychotic medication
Biol Psychiatry
(1994)
Anhedonia in schizophrenia: distinctions between anticipatory and consummatory pleasure
Schizophr Res
The assessment of interpersonal pleasure: introduction of the anticipatory and consuumatory interpersonal pleasure scale (ACIPS) and preliminary findings
Psychiatry Res
Negative symptoms and the early course of schizophrenia
Psychiatry Res
P300 changes in major depressive disorders with and without psychotic features
J Affect Disord
Reduced visual P300 amplitudes in individuals at ultra-high risk for psychosis and first-episode schizophrenia
Neurosci Lett
Event-related potential studies of attention
Trends Cogn Sci
Trait and state aspects of P300 amplitude reduction in schizophrenia: a retrospective longitudinal study
Biol Psychiatry
Early and late stages of visual processing in individuals in prodromal state and first episode schizophrenia: an ERP study
Schizophr Res
Auditory and visual P300 reflecting cognitive improvement in patients with schizophrenia with quetiapine: a pilot study
Prog Neuro-Psychopharmacol Biol Psychiatry
An ERP index of task relevance evaluation of visual stimuli
Brain Cogn
Frontal evaluation and posterior representation in target detection
Brain Res Cogn Brain Res
The efficacy of computerized cognitive drill and practice training for patients with a schizophrenia-spectrum disorder: a meta-analysis
Schizophr Res
Heritability of anterior and posterior visual N1
Int J Psychophysiol
The P300 event-related potential in bipolar disorder: A systematic review and meta-analysis
J Affect Disord
Event-related potentials to auditory and visual selective attention in schizophrenia
Int J Psychophysiol
Selective attention to the color and direction of moving stimuli: Electrophysiological correlates of hierarchical feature selection
Percept Psychophys
Childhood Cat Bites Relate to Increased Adulthood Severity of Schizotypy, Psychotic-Like Experiences, and Social Anhedonia in a Transdiagnostic Psychiatric Sample
Psychopathology
Neurocognition, social cognition, perceived social discomfort, and vocational outcomes in schizophrenia
Schizophr Bull
The time course of visuospatial processing deficits in schizophrenia: an event-related brain potential study
J Abnorm Psychol
Brain ERPs of depressed patients to complex tones in an oddball task: relation of reduced P3 asymmetry to physical anhedonia
Psychophysiology
Cited by (3)
Dysfunction of visual novelty detection in physical but not social anhedonia in a non-clinical sample
2023, International Journal of Clinical and Health PsychologyObjective Detection of Tinnitus Based on Electrophysiology
2022, Brain Sciences