Garden of forking paths in ERP research - Effects of varying pre-processing and analysis steps in an N400 experiment.

This study tackles the Garden of Forking Paths, as a challenge for replicability and reproducibility of ERP studies. Here, we applied a multiverse analysis to a sample ERP N400 dataset, donated by an independent research team. We analyzed this dataset using 14 pipelines selected to showcase the full range of methodological variability found in the N400 literature using systematic review approach. The selected pipelines were compared in depth by looking into statistical test outcomes, descriptive statistics, effect size, data quality, and statistical power. In this way we provide a worked example of how analytic flexibility can impact results in research fields with high dimensionality such as ERP, when analyzed using standard null-hypothesis significance testing. Out of the methodological decisions that were varied, high-pass filter cut-off, artifact removal method, baseline duration, reference, measurement latency and locations, and amplitude measure (peak vs. mean) were all shown to affect at least some of the study outcome measures. Low-pass filtering was the only step which did not notably influence any of these measures. This study shows that even some of the seemingly minor procedural deviations can influence the conclusions of an ERP study. We demonstrate the power of multiverse analysis in both identifying the most reliable effects in a given study, and for providing insights into consequences of methodological decisions.

How to do Better N400 Studies: Reproducibility, Consistency and Adherence to Research Standards in the Existing Literature.

Given the complexity of ERP recording and processing pipeline, the resulting variability of methodological options, and the potential for these decisions to influence study outcomes, it is important to understand how ERP studies are conducted in practice and to what extent researchers are transparent about their data collection and analysis procedures. The review gives an overview of methodology reporting in a sample of 132 ERP papers, published between January 1980 - June 2018 in journals included in two large databases: Web of Science and PubMed. Because ERP methodology partly depends on the study design, we focused on a well-established component (the N400) in the most commonly assessed population (healthy neurotypical adults), in one of its most common modalities (visual images). The review provides insights into 73 properties of study design, data pre-processing, measurement, statistics, visualization of results, and references to supplemental information across studies within the same subfield. For each of the examined methodological decisions, the degree of consistency, clarity of reporting and deviations from the guidelines for best practice were examined. Overall, the results show that each study had a unique approach to ERP data recording, processing and analysis, and that at least some details were missing from all papers. In the review, we highlight the most common reporting omissions and deviations from established recommendations, as well as areas in which there was the least consistency. Additionally, we provide guidance for a priori selection of the N400 measurement window and electrode locations based on the results of previous studies.

A commentary on establishing norms for error-related brain activity during the arrow flanker task among young adults.

We suggest that a large data set for the error-related negativity (ERN) and error positivity (Pe) components of the scalp-recorded event-related brain potential (ERP) recently published as normative is not ready for such use in research and, especially, clinical application. Such efforts are challenged by an incomplete understanding of the functional significance of between-person differences in amplitudes and of nuisance factors that contribute to amplitude differences, a lack of standardization of methods, and the use of a convenience sample for the potentially normative database. To move ERPs toward standardization and useful norms, we encourage more research on the meaning of differences in ERN scores, including factors that influence between- and within-person variation, and the dissemination of protocols for data collection and processing.

ERP CORE: An open resource for human event-related potential research.

Event-related potentials (ERPs) are noninvasive measures of human brain activity that index a range of sensory, cognitive, affective, and motor processes. Despite their broad application across basic and clinical research, there is little standardization of ERP paradigms and analysis protocols across studies. To address this, we created ERP CORE (Compendium of Open Resources and Experiments), a set of optimized paradigms, experiment control scripts, data processing pipelines, and sample data (N = 40 neurotypical young adults) for seven widely used ERP components: N170, mismatch negativity (MMN), N2pc, N400, P3, lateralized readiness potential (LRP), and error-related negativity (ERN). This resource makes it possible for researchers to 1) employ standardized ERP paradigms in their research, 2) apply carefully designed analysis pipelines and use a priori selected parameters for data processing, 3) rigorously assess the quality of their data, and 4) test new analytic techniques with standardized data from a wide range of paradigms.

Inherent physiological artifacts in EEG during tDCS.

Online imaging and neuromodulation is invalid if stimulation distorts measurements beyond the point of accurate measurement. In theory, combining transcranial Direct Current Stimulation (tDCS) with electroencephalography (EEG) is compelling, as both use non-invasive electrodes and image-guided dose can be informed by the reciprocity principle. To distinguish real changes in EEG from stimulation artifacts, prior studies applied conventional signal processing techniques (e.g. high-pass filtering, ICA). Here, we address the assumptions underlying the suitability of these approaches. We distinguish physiological artifacts - defined as artifacts resulting from interactions between the stimulation induced voltage and the body and so inherent regardless of tDCS or EEG hardware performance - from methodology-related artifacts - arising from non-ideal experimental conditions or non-ideal stimulation and recording equipment performance. Critically, we identify inherent physiological artifacts which are present in all online EEG-tDCS: 1) cardiac distortion and 2) ocular motor distortion. In conjunction, non-inherent physiological artifacts which can be minimized in most experimental conditions include: 1) motion and 2) myogenic distortion. Artifact dynamics were analyzed for varying stimulation parameters (montage, polarity, current) and stimulation hardware. Together with concurrent physiological monitoring (ECG, respiration, ocular, EMG, head motion), and current flow modeling, each physiological artifact was explained by biological source-specific body impedance changes, leading to incremental changes in scalp DC voltage that are significantly larger than real neural signals. Because these artifacts modulate the DC voltage and scale with applied current, they are dose specific such that their contamination cannot be accounted for by conventional experimental controls (e.g. differing stimulation montage or current as a control). Moreover, because the EEG artifacts introduced by physiologic processes during tDCS are high dimensional (as indicated by Generalized Singular Value Decomposition- GSVD), non-stationary, and overlap highly with neurogenic frequencies, these artifacts cannot be easily removed with conventional signal processing techniques. Spatial filtering techniques (GSVD) suggest that the removal of physiological artifacts would significantly degrade signal integrity. Physiological artifacts, as defined here, would emerge only during tDCS, thus processing techniques typically applied to EEG in the absence of tDCS would not be suitable for artifact removal during tDCS. All concurrent EEG-tDCS must account for physiological artifacts that are a) present regardless of equipment used, and b) broadband and confound a broad range of experiments (e.g. oscillatory activity and event related potentials). Removal of these artifacts requires the recognition of their non-stationary, physiology-specific dynamics, and individualized nature. We present a broad taxonomy of artifacts (non/stimulation related), and suggest possible approaches and challenges to denoising online EEG-tDCS stimulation artifacts.

Electrophysiological Evidence for Impaired Control of Motor Output in Schizophrenia.

Previous research has demonstrated pervasive deficits in response-related processing in people with schizophrenia (PSZ). The present study used behavioral measures and event-related potentials (ERPs) to test the hypothesis that schizophrenia involves specific impairment in the ability to exert control over response-related processing. Twenty-two PSZ and 22 matched control participants completed a choice response task in counterbalanced testing sessions that emphasized only accuracy (the unspeeded condition) or emphasized speed and accuracy equally (the speeded condition). Control participants successfully modulated behavioral and ERP indices of response-related processing under speed pressure, as evidenced by faster and less variable reaction times (RTs) and an earlier onset and increased amplitude lateralized readiness potential (LRP). By contrast, PSZ were unable to improve RT speed or variability or to modulate the LRP under speed pressure, despite showing a decrease in accuracy. Notably, response-related deficits in PSZ emerged only in the speeded condition; behavioral and ERP measures did not differ between groups in the unspeeded condition. Together, these results indicate that impairment in the ability to exert control over response-related processing may underlie response-related deficits in schizophrenia.

Toward the neural mechanisms of reduced working memory capacity in schizophrenia.

People with schizophrenia (PSZ) demonstrate reliable reductions in working memory (WM) capacity (i.e., the number of objects that can be held in memory). The present study asked whether WM impairments in PSZ can be explained by the same neural mechanisms that underlie individual differences in WM capacity among healthy individuals. Specifically, we examined event-related potentials in PSZ and healthy matched controls during a change detection task that required the storage of multiple objects in WM. The amplitude of contralateral delay activity (CDA), which correlates with WM capacity in healthy individuals, was larger in controls than in PSZ for memory loads of 3 and 5 objects, but larger in PSZ than in controls for a memory load of 1. This same pattern was found in the subgroups of PSZ and controls with an equivalent WM capacity. Moreover, the increase in CDA amplitude was correlated with individual differences in capacity in controls, but not in PSZ. These results demonstrate that WM impairment in PSZ is not associated with the same patterns of neural activity that characterize low WM capacity in healthy individuals. We propose that WM impairment in PSZ instead reflects a specific impairment in the ability to distribute attention broadly.

Maximizing signal-to-noise ratio and statistical power in ERP measurement: Single sites versus multi-site average clusters.

One important decision in every event-related potential (ERP) experiment is which electrode site(s) to use in quantifying the ERP component of interest. A common approach is to measure the ERP from a single electrode site, typically the site where the ERP component is largest. Alternatively, two or more electrode sites in a given spatial region are averaged together, and the ERP is measured from the resulting multi-site cluster. The goal of the present study was to systematically compare these two measurement approaches across a range of outcome measures and ERP components to determine whether measuring from a single electrode site or an average of multiple sites yields consistently better results. We examined seven common ERP components from the open-source ERP CORE dataset that span a range of neurocognitive processes: N170, mismatch negativity (MMN), N2pc, N400, P3, lateralized readiness potential (LRP), and error-related negativity (ERN). For each component, we compared ERP amplitude, noise level, signal-to-noise ratio, and effect size at two single electrode sites and four multi-site clusters. We also used a Monte Carlo approach to simulate within-participant and between-groups experiments with known effect magnitudes to compare statistical power at single sites and multi-site clusters. Overall, measuring from a multi-site cluster produced results that were as good as or better than measuring from a single electrode site across analyses and components, indicating that the cluster-based measurement approach may be beneficial in quantifying ERPs from a range of neurocognitive domains.

Clinical high risk for psychosis syndrome is associated with reduced neural responding to unpleasant images.

Deficits in emotion processing are core features of psychotic disorders. Electrophysiology research in schizophrenia suggests deficits in sustained engagement with emotional content (indexed by the late positive potential [LPP]) may contribute to emotion processing impairments. Despite similar behavioral emotion processing dysfunction in those at clinical high risk (CHR) for psychosis, limited research has examined neural mechanisms of impaired emotion processing in the high-risk period, where research can inform risk models. To examine mechanisms of emotion processing deficits in those at CHR for psychosis, the present study used a passive viewing task to elicit the LPP in response to emotionally engaging and neutral stimuli in 28 CHR and 32 control participants (60% female). Relative to controls, CHR participants showed reduced LPP amplitude when viewing unpleasant images (d = 0.75, p = .005) but similar LPP amplitude in response to both neutral (d = 0.35, p = .19) and pleasant images (d = 0.31, p = .24). This pattern suggests that individuals at CHR for psychosis exhibit a deficit in sustained engagement with unpleasant stimuli. Clinical and trait questionnaires were administered to examine potential exploratory explanations for group differences in LPP amplitude. Consistent with evidence suggesting LPP amplitude reflects engagement of approach/avoidance motivational systems, greater LPP amplitude was associated with greater trait-level behavioral avoidance in control participants (r = .42, p = .032) but not CHR participants (r = -.21, p = .40). Together, the present research is consistent with LPP studies in psychosis and implicates reduced sustained engagement with emotional content in the high-risk period. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neural mechanisms of motor dysfunction in individuals at clinical high-risk for psychosis: Evidence for impairments in motor activation.

Motor abnormalities are a core feature of psychotic disorders observed from the premorbid period through chronic illness, suggesting motor dysfunction may reflect the pathophysiology of psychosis. Electrophysiology research in schizophrenia suggests impaired motor activation and preparation may underlie these motor abnormalities. Despite behavioral studies suggesting similar motor dysfunction in those at clinical high-risk (CHR) for psychosis, there have been no studies examining neural mechanisms of motor dysfunction in the CHR period, where research can inform pathophysiological and risk models. The present study used the lateralized readiness potential (LRP), an event-related potential index of motor activation and preparation, to examine mechanisms of motor dysfunction in 42 CHR and 41 control participants (N = 83, 56% female). Response competition was manipulated to determine whether deficits are secondary to cognitive control impairments or reflect primary motor deficits. Behaviorally, CHR participants exhibited overall slower responses than controls. Further, relative to controls, CHR participants showed reduced activation of correct but not incorrect responses, reflected in blunted LRP amplitude under weak response competition and no difference in amplitude associated with the incorrect response under strong response competition. This pattern of results suggests individuals at CHR for psychosis exhibit primary motor deficits in activating and preparing behavioral responses and are contrary to a deficit in cognitive control. Further, blunted LRP amplitude was associated with worsening of negative symptoms at 12-month follow-up. Together, these findings are consistent with LRP studies in psychosis and implicate motor activation deficits as potential mechanisms of motor dysfunction in the high-risk period. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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.

Recoiling from Threat: Anxiety is Related to Heightened Suppression of Threat, Not Increased Attention to Threat.

Increased attention to threat is considered a core feature of anxiety. However, there are multiple mechanisms of attention and multiple types of threat, and the relationships among attention, threat, and anxiety are poorly understood. The present study used event-related potentials (ERPs) to separately isolate attentional selection (N2pc) and suppression (PD) of pictorial threats (photos of weapons, snakes, etc.) and conditioned threats (colored shapes paired with electric shock). In a sample of 48 young adults, both threat types were initially selected for increased attention (an N2pc), but only conditioned threats elicited subsequent suppression (a PD) and a reaction time (RT) bias. Levels of trait anxiety were unrelated to N2pc amplitude, but increased anxiety was associated with larger PDs (i.e., greater suppression) and reduced RT bias to conditioned threats. These results suggest that anxious individuals do not pay more attention to threats, but rather engage more attentional suppression to overcome threats.

The Relationship Between Depression Symptoms and Adolescent Neural Response During Reward Anticipation and Outcome Depends on Developmental Timing: Evidence From a Longitudinal Study.

BACKGROUND: Blunted neural reward responsiveness (RR) is observed in youth depression. However, it is unclear whether symptoms of depression experienced early in development relate to adolescent RR beyond current symptoms and, further, whether such relationships with RR differ during two key components of reward processing: anticipation and outcome. METHODS: Within a prospective longitudinal study oversampled for early depression, children and caregivers completed semiannual diagnostic assessments beginning in preschool. In later adolescence, mean age = 16.49 years (SD = 0.94), youths' (N = 100) neurophysiological responses to cues signaling likely win and loss and these outcomes were assessed. Longitudinally assessed dimensional depression and externalizing symptoms (often comorbid with depression as well as associated with RR) experienced at different developmental periods (preschool [age 3-5.11 years], school age [6-9.11 years], early adolescence [10-14.11 years], current) were used as simultaneous predictors of event-related potentials indexing anticipatory cue processing (cue-P3) and outcome processing (reward positivity/feedback negativity and feedback-P3). RESULTS: Blunted motivated attention to cues signaling likely win (cue-P3) was specifically predicted by early-adolescent depression symptoms. Blunted initial response to win (reward positivity) and loss (feedback negativity) outcomes was specifically predicted by preschool depression symptoms. Blunted motivational salience of win and loss outcomes (feedback-P3) was predicted by cumulative depression, not specific to any developmental stage. CONCLUSIONS: Although blunted anticipation and outcome RR is a common finding in depression, specific deficits related to motivated attention to cues and initial outcome processing may map onto the developmental course of these symptoms.

Corrigendum: Peer Victimization and Dysfunctional Reward Processing: ERP and Behavioral Responses to Social and Monetary Rewards.

[This corrects the article DOI: 10.3389/fnbeh.2019.00120.].

Neural Indicators of Anhedonia: Predictors and Mechanisms of Treatment Change in a Randomized Clinical Trial in Early Childhood Depression.

BACKGROUND: Early childhood depression is associated with anhedonia and reduced event-related potential (ERP) responses to rewarding or pleasant stimuli. Whether these neural measures are indicators of target engagement or treatment outcome is not yet known. METHODS: We measured ERP responses to win and loss feedback in a guessing task and to pleasant versus neutral pictures in young (4.0-6.9 years of age) depressed children before and after randomization to either 18 weeks of Parent-Child Interaction Therapy-Emotion Development (PCIT-ED) or waitlist. RESULTS: Analyses included reward positivity (RewP) data from 118 children randomly assigned to PCIT-ED (n = 60) or waitlist (n = 58) at baseline and late positive potential (LPP) data from 99 children (44 assigned to PCIT-ED vs. 55 assigned to waitlist) at baseline. Children undergoing PCIT-ED showed a greater reduction in anhedonia (F1,103 = 10.32, p = .002, partial η2 = .09). RewP reward responses increased more (F1,86 = 5.98, p = .02, partial η2 = .07) for PCIT-ED, but a greater change in RewP was not significantly associated with a greater reduction in major depressive disorder symptoms (r = -.12, p > .4). Baseline RewP did not predict treatment change. LPPs to positive pictures did not change across treatment, but greater baseline LPPs to positive pictures predicted a higher likelihood of remission from major depressive disorder in children undergoing PCIT-ED (B = 0.14; SE = 0.07; odds ratio = 1.15; p = .03). CONCLUSIONS: The ERP reward response improved in young children with depression during a treatment designed to enhance emotion development, providing evidence of target engagement of the neural systems associated with reward. Further, greater baseline LPP responses to positive pictures was associated with a greater likelihood of depression remission, suggesting that this ERP measure can predict which children are most likely to respond to treatment.

Preschool-Onset Major Depressive Disorder is Characterized by Electrocortical Deficits in Processing Pleasant Emotional Pictures.

Reductions in positive affect are a salient feature of preschool-onset major depressive disorder. Yet, little is known about the psychophysiological correlates of this blunted positive affect and whether reduced physiological responding to pleasant stimuli may differentiate depressed and healthy young children. 120 four-to-seven year old children with current depression and 63 psychiatrically healthy 4-to-7 year old children completed a simple picture-viewing task of pleasant and neutral pictures while event-related potentials (ERPs) were recorded. The early-childhood version of the Kiddie Schedule for Affective Disorders and Depression was used to establish psychiatric diagnoses. A one-way ANCOVA was used to test for group differences in response to pleasant and neutral pictures. Young children with depression showed a reduced response to pleasant vs. neutral pictures (LPP), after controlling for children's age (F(1,180) = 4.15, p = 0.04, η2 = 0.02). The LPP for the children with preschool-onset depression (M = 0.99, SE = 0.65) was significantly smaller than the LPP in the healthy group of young children (M = 3.27, SE = 0.90). This difference did not vary as a function of depression or anhedonia severity within the group with depression or the healthy children. Similar to older children and adolescents with depression, young children with depression display reductions in responsivity to pleasant stimuli as indexed by the LPP. These findings extend prior findings indicating a blunted response to pleasant stimuli in preschool- onset depression. Given the greater neuroplasticity of emotional response and regulation, these findings suggest clinical attention to emotional response to pleasure is an important target in preschool-onset depression. Clinical trial registration information: A Randomized Control Trial of PCIT-ED for Preschool Depression; http://clinicaltrials.gov/;NCT02076425.

Neural Indicators of Anhedonia: Predictors and Mechanisms of Treatment Change in a Randomized Clinical Trial in Early Childhood Depression.

BACKGROUND: Early childhood depression is associated with anhedonia and reduced event-related potential (ERP) responses to rewarding or pleasant stimuli. Whether these neural measures are indicators of target engagement or treatment outcome is not yet known. METHODS: We measured ERP responses to win and loss feedback in a guessing task and to pleasant versus neutral pictures in young (4.0-6.9 years of age) depressed children before and after randomization to either 18 weeks of Parent-Child Interaction Therapy-Emotion Development (PCIT-ED) treatment or waitlist (WL) control condition. RESULTS: Analyses included reward positivity (RewP) data from 118 children randomized to PCIT-ED treatment (n = 60) or WL control condition (n = 58) at baseline and late positive potential (LPP) data from 99 children (44 PCIT-ED treatment vs. 55 WL control condition) at baseline. Children in the PCIT-ED group showed a greater reduction in anhedonia (F1,103 = 10.32, p = .002, partial η2 = .09). RewP reward responses increased more (F1,87 = 5.45, p = .02, partial η2 = .06) for PCIT-ED and a greater change in RewP was associated with a greater reduction in major depressive disorder symptoms (r = -.24, p = .05). Baseline RewP did not predict treatment change. LPPs to positive pictures did not change across treatment, but greater baseline LPPs to positive pictures predicted a higher likelihood of remission from major depressive disorder in the PCIT-ED group (B = 0.14; SE = 0.07; odds ratio = 1.15; p = .03). CONCLUSIONS: The ERP reward response improved in young children with depression during a treatment designed to enhance emotion development, providing evidence of target engagement of the neural systems associated with reward. Further, greater baseline LPP responses to positive pictures were associated with a greater reduction in depression, suggesting that this ERP measure can predict which children are most likely to respond to treatment.

Peer Victimization and Dysfunctional Reward Processing: ERP and Behavioral Responses to Social and Monetary Rewards.

Peer victimization (or bullying) is a known risk factor for depression, especially among youth. However, the mechanisms connecting victimization experience to depression symptoms remains unknown. As depression is known to be associated with neural blunting to monetary rewards, aberrant responsiveness to social rewards may be a key deficit connecting socially stressful experiences with later depression. We, therefore, sought to determine whether adolescents' experiences with social stress would be related to their current response to social rewards over less socially relevant monetary rewards. Neural responses to monetary and social rewards were measured using event-related potentials (ERPs) to peer acceptance and rejection feedback (Island Getaway task) and to monetary reward and loss feedback (Doors task) in a sample of 56 late adolescents/emerging young adults followed longitudinally since preschool. In the Island Getaway task, participants voted whether to "keep" or "kick out" each co-player, providing an index of prosocial behavior, and then received feedback about how each player voted for the participant. Analyses tested whether early and recent peer victimization was related to response to rewards (peer acceptance or monetary gains), residualized for response to losses (peer rejection or monetary losses) using the reward positivity (RewP) component. Findings indicated that both experiencing greater early and greater recent peer victimization were significantly associated with participants casting fewer votes to keep other adolescents ("Keep" votes) and that greater early peer victimization was associated with reduced neural response to peer acceptance. Early and recent peer victimization were significantly more associated with neural response to social than monetary rewards. Together, these findings suggest that socially injurious experiences such as peer victimization, especially those occurring early in childhood, relate to two distinct but important findings: that early victimization is associated with later reduced response to peer acceptance, and is associated with later tendency to reject peers. Findings also suggest that there is evidence of specificity to reward processing of different types; thus, future research should expand studies of reward processing beyond monetary rewards to account for the possibility that individual differences may be related to other, more relevant, reward types.

How many trials does it take to get a significant ERP effect? It depends.

In designing an ERP study, researchers must choose how many trials to include, balancing the desire to maximize statistical power and the need to minimize the length of the recording session. Recent studies have attempted to quantify the minimum number of trials needed to obtain reliable measures for a variety of ERP components. However, these studies have largely ignored other variables that affect statistical power in ERP studies, including sample size and effect magnitude. The goal of the present study was to determine whether and how the number of trials, number of participants, and effect magnitude interact to influence statistical power, thus providing a better guide for selecting an appropriate number of trials. We used a Monte Carlo approach to measure the probability of obtaining a statistically significant result when testing for (a) the presence of an ERP effect, (b) within-participant condition differences in an ERP effect, and (c) between-participants group differences in an ERP effect. Each of these issues was examined in the context of the error-related negativity and the lateralized readiness potential. We found that doubling the number of trials recommended by previous studies led to more than a doubling of statistical power under many conditions. Thus, when determining the number of trials that should be included in a given study, researchers must consider the sample size, the anticipated effect magnitude, and the noise level, rather than relying solely on general recommendations about the number of trials needed to obtain a "stable" ERP waveform.

Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop.

BACKGROUND: Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities. OBJECTIVE: This report seeks to promote the science, technology and effective clinical applications of these modalities, identify research challenges, and suggest approaches for addressing these needs in order to achieve rigorous, reproducible findings that can advance clinical treatment. METHODS: The National Institute of Mental Health (NIMH) convened a workshop in September 2016 that brought together experts in basic and human neuroscience, electrical stimulation biophysics and devices, and clinical trial methods to examine the physiological mechanisms underlying tDCS/tACS, technologies and technical strategies for optimizing stimulation protocols, and the state of the science with respect to therapeutic applications and trial designs. RESULTS: Advances in understanding mechanisms, methodological and technological improvements (e.g., electronics, computational models to facilitate proper dosing), and improved clinical trial designs are poised to advance rigorous, reproducible therapeutic applications of these techniques. A number of challenges were identified and meeting participants made recommendations made to address them. CONCLUSIONS: These recommendations align with requirements in NIMH funding opportunity announcements to, among other needs, define dosimetry, demonstrate dose/response relationships, implement rigorous blinded trial designs, employ computational modeling, and demonstrate target engagement when testing stimulation-based interventions for the treatment of mental disorders.