Pattern glare sensitivity distinguishes subclinical autism and schizotypy.

INTRODUCTION: Schizophrenia and autism spectrum disorder are distinct neurodevelopmental disorders sharing clinically relevant behaviours. However, early sensory responses show divergent responses. Individuals with schizophrenia typically exhibit cortical hypo-excitability whereas individuals with autism show cortical hyperexcitability. Identifying reliable neurobiological differences between the disorders can diminish misdiagnosis and optimise treatments. METHODS: The pattern glare test (PGT) is a simple measure of behavioural hyperexcitability. It measures the number of illusions seen in a static horizontal grating. We collected PGT data from non-clinical adults varying in traits of autism and schizophrenia (schizotypy). 576 undergraduate students completed an online survey consisting of the Schizotypal Personality Questionnaire - Brief Revised, the Autism Spectrum Quotient, and the PGT. RESULTS: Subclinical autism and schizotypy traits were highly positively correlated. However, only schizotypy scores were significantly predictive of reporting more pattern glare (PG) illusions. When assessing the subcomponents of the schizotypy and autism scores, positive and disorganised schizotypy traits were predictive of reporting more PG illusions. Whereas, subclinical autism factors were not predictive of PG illusions. CONCLUSIONS: High schizotypy performed the PGT in a manner consistent with behavioural hyperexcitability. The PGT distinguished subclinical autistic traits from schizotypy, suggesting potential clinical application.

Capturing postpandemic changes in research participants.

The impact of the COVID-19 pandemic on physical and mental health hardly need be reiterated. Yet, there are likely other indirect aftereffects of COVID-19 infection in addition to the direct effects. This article aims to initiate a conversation regarding difficult-to-capture outcomes of the pandemic that are relevant to researchers who test human participants. These considerations encourage collection of additional measures when assessing pre- versus postpandemic patterns of behavior.

Augmenting Virtual Reality Exposure Therapy for Social and Intergroup Anxiety With Transcranial Direct Current Stimulation.

OBJECTIVES: Exposure therapy is a cornerstone of social anxiety treatment, yet not all patients respond. Symptoms in certain social situations, including intergroup (ie, out-group) contexts, may be particularly resistant to treatment. Exposure therapy outcomes may be improved by stimulating neural areas associated with safety learning, such as the medial prefrontal cortex (mPFC). The mPFC also plays an important role in identifying others as similar to oneself. We hypothesized that targeting the mPFC during exposure therapy would reduce intergroup anxiety and social anxiety. METHODS: Participants (N = 31) with the public speaking subtype of social anxiety received active (anodal) or sham transcranial direct current stimulation (tDCS) targeting the mPFC during exposure therapy. Exposure therapy consisted of giving speeches to audiences in virtual reality. To target intergroup anxiety, half of the public speaking exposure trials were conducted with out-group audiences, defined in this study as audiences of a different ethnicity. RESULTS: Contrary to hypotheses, tDCS did not facilitate symptom reduction. Some evidence even suggested that tDCS temporarily increased in-group favoritism, although these effects dissipated at 1-month follow-up. In addition, collapsing across all participants, we found reductions across time for public speaking anxiety and intergroup anxiety. CONCLUSIONS: The data provide evidence that standard exposure therapy techniques for social anxiety can be adapted to target intergroup anxiety. Transcranial direct current stimulation targeting the mPFC may boost safety signaling, but only in contexts previously conditioned to signal safety, such as an in-group context.

The Rehabilitation Potential of Neurostimulation for Mild Traumatic Brain Injury in Animal and Human Studies.

Neurostimulation carries high therapeutic potential, accompanied by an excellent safety profile. In this review, we argue that an arena in which these tools could provide breakthrough benefits is traumatic brain injury (TBI). TBI is a major health problem worldwide, with the majority of cases identified as mild TBI (mTBI). MTBI is of concern because it is a modifiable risk factor for dementia. A major challenge in studying mTBI is its inherent heterogeneity across a large feature space (e.g., etiology, age of injury, sex, treatment, initial health status, etc.). Parallel lines of research in human and rodent mTBI can be collated to take advantage of the full suite of neuroscience tools, from neuroimaging (electroencephalography: EEG; functional magnetic resonance imaging: fMRI; diffusion tensor imaging: DTI) to biochemical assays. Despite these attractive components and the need for effective treatments, there are at least two major challenges to implementation. First, there is insufficient understanding of how neurostimulation alters neural mechanisms. Second, there is insufficient understanding of how mTBI alters neural function. The goal of this review is to assemble interrelated but disparate areas of research to identify important gaps in knowledge impeding the implementation of neurostimulation.

Working memory and sensory memory in subclinical high schizotypy: An avenue for understanding schizophrenia?

The search for robust, reliable biomarkers of schizophrenia remains a high priority in psychiatry. Biomarkers are valuable because they can reveal the underlying mechanisms of symptoms and monitor treatment progress and may predict future risk of developing schizophrenia. Despite the existence of various promising biomarkers that relate to symptoms across the schizophrenia spectrum, and despite published recommendations encouraging multivariate metrics, they are rarely investigated simultaneously within the same individuals. In those with schizophrenia, the magnitude of purported biomarkers is complicated by comorbid diagnoses, medications and other treatments. Here, we argue three points. First, we reiterate the importance of assessing multiple biomarkers simultaneously. Second, we argue that investigating biomarkers in those with schizophrenia-related traits (schizotypy) in the general population can accelerate progress in understanding the mechanisms of schizophrenia. We focus on biomarkers of sensory and working memory in schizophrenia and their smaller effects in individuals with nonclinical schizotypy. Third, we note irregularities across research domains leading to the current situation in which there is a preponderance of data on auditory sensory memory and visual working memory, but markedly less in visual (iconic) memory and auditory working memory, particularly when focusing on schizotypy where data are either scarce or inconsistent. Together, this review highlights opportunities for researchers without access to clinical populations to address gaps in knowledge. We conclude by highlighting the theory that early sensory memory deficits contribute negatively to working memory and vice versa. This presents a mechanistic perspective where biomarkers may interact with one another and impact schizophrenia-related symptoms.

Gender Differences in Adolescents' Affective Symptoms and Behavioral Disorders After Mild Traumatic Brain Injury.

OBJECTIVE: Mild traumatic brain injuries (mTBI) are considered self-limiting and full recovery is expected. Recent studies identify deficits persisting years after mTBI. Large-scale prospective data permit testing the hypothesis that mTBI increases incidence of affective and behavioral symptoms after new, past , or new and past mTBI. SETTING: The study involved secondary analyses of survey responses from the Adolescent Brain Cognitive Development (ABCD) Study. PARTICIPANTS: Adolescents in the ABCD Study ( n = 11 869; Wave 1, aged 9-10 years; Wave 2, aged 11-12 years) whose parents reported a new ( n = 157), past ( n = 1318), or new and past ( n = 50) mTBI on the Ohio State University Traumatic Brain Injury Identification Method short form were compared with controls who had no history of mTBI ( n = 9,667). DESIGN: Multivariable binary logistic regression models examined associations between a new, past, or new and past mTBI and current affective (aggression, depression, anxiety) and behavioral (somatic, thought, social, attention, attention deficit hyperactivity disorder, conduct) disorders while controlling for demographic factors and baseline symptoms. MAIN MEASURES: The primary measure was parental reports of psychiatric and behavioral symptoms on the Child Behavior Checklist. RESULTS: Girls exhibited no significant effects after a new mTBI, although a past mTBI increased anxiety (adjusted odds ratios [aOR] = 1.83, 95% confidence interval [CI: 1.15-2.90]) and attention (1.89 [1.09-3.28]) problems. Girls with new and past mTBIs reported elevated anxiety (17.90 [4.67-68.7]), aggression (7.37 [1.49-36.3]), social (9.07 [2.47-33.30]), thought (7.58 [2.24-25.60]), and conduct (6.39 [1.25-32.50]) disorders. In boys, new mTBI increased aggression (aOR = 3.83, 95% CI [1.42-10.30]), whereas past mTBI heightened anxiety (1.91 [1.42-2.95]), but new and past mTBIs had no significant effects. CONCLUSION: Adolescents are at greater risk of affective and behavioral symptoms after an mTBI. These effects differ as a function of gender and time of injury. Extended screening for mTBI history and monitoring of affective and behavioral disorders after mTBI in adolescents are warranted.

People with high schizotypy experience more illusions in the Pattern Glare Test: Consistent with the hyperexcitability hypothesis.

Individuals diagnosed with schizophrenia spectrum disorders (SSD) exhibit a constellation of sensory and perceptual impairments, including hyporeactivity to external input. However, individuals with SSD also report subjective experiences of sensory flooding, suggesting sensory hyperexcitability. To identify the extent to which behavioural indices of hyperexcitability are related to non-psychotic symptoms of schizophrenia, we tested a non-clinical population measured for schizophrenia-like traits (schizotypy), and a behavioural measure of sensory hyperexcitability, specifically the number of illusions seen in the Pattern Glare Test. Two samples totaling 913 individuals completed an online version of the Schizotypal Personality Questionnaire - Brief Revised (SPQ-BR) and the Pattern Glare Test. Individuals with higher schizotypy traits reported more illusions in the Pattern Glare Test. Additionally, one of the three SPQ-BR factors, the disorganized factor, significantly predicted the number of illusions reported. These data illustrate the potential for research in non-clinical samples to inform clinically relevant research.

Can brain stimulation enhance cognition in clinical populations? A critical review.

Many psychiatric and neurological conditions are associated with cognitive impairment for which there are very limited treatment options. Brain stimulation methodologies show promise as novel therapeutics and have cognitive effects. Electroconvulsive therapy (ECT), known more for its related transient adverse cognitive effects, can produce significant cognitive improvement in the weeks following acute treatment. Transcranial magnetic stimulation (TMS) is increasingly used as a treatment for major depression and has acute cognitive effects. Emerging research from controlled studies suggests that repeated TMS treatments may additionally have cognitive benefit. ECT and TMS treatment cause neurotrophic changes, although whether these are associated with cognitive effects remains unclear. Transcranial electrical stimulation methods including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) are in development as novel treatments for multiple psychiatric conditions. These treatments may also produce cognitive enhancement particularly when stimulation occurs concurrently with a cognitive task. This review summarizes the current clinical evidence for these brain stimulation treatments as therapeutics for enhancing cognition. Acute, or short-lasting, effects as well as longer-term effects from repeated treatments are reviewed, together with potential putative neural mechanisms. Areas of future research are highlighted to assist with optimization of these approaches for enhancing cognition.

Caught in the ACTS: Defining Abstract Cognitive Task Sequences as an Independent Process.

Cognitive neuroscience currently conflates the study of serial responses (e.g., delay match to sample/nonsample, n-back) with the study of sequential operations. In this essay, our goal is to define and disentangle the latter, termed abstract cognitive task sequences (ACTS). Existing literatures address tasks requiring serial events, including procedural learning of implicit motor responses, statistical learning of predictive relationships, and judgments of attributes. These findings do not describe the behavior and underlying mechanism required to succeed at remembering to evaluate color, then shape; or to multiply, then add. A new literature is needed to characterize these sorts of second-order cognitive demands of studying a sequence of operations. Our second goal is to characterize gaps in knowledge related to ACTS that merit further investigation. In the following sections, we define more precisely what we mean by ACTS and suggest research questions that further investigation would be positioned to address.

Individual predictors and electrophysiological signatures of working memory enhancement in aging.

A primary goal of translational neuroscience is to identify the neural mechanisms of age-related cognitive decline and develop protocols to maximally improve cognition. Here, we demonstrate how interventions that apply noninvasive neurostimulation to older adults improve working memory (WM). We found that one session of sham-controlled transcranial direct current stimulation (tDCS) selectively improved WM in older adults with more education, extending earlier work and underscoring the importance of identifying individual predictors of tDCS responsivity. Improvements in WM were associated with two distinct electrophysiological signatures. First, a broad enhancement of theta network synchrony tracked improvements in behavioral accuracy, with tDCS effects moderated by education level. Further analysis revealed that accuracy dynamics reflected an anterior-posterior network distribution regardless of cathode placement. Second, specific enhancements of theta-gamma phase-amplitude coupling (PAC) reflecting tDCS current flow tracked improvements in reaction time (RT). RT dynamics further explained inter-individual variability in WM improvement independent of education. These findings illuminate theta network synchrony and theta-gamma PAC as distinct but complementary mechanisms supporting WM in aging. Both mechanisms are amenable to intervention, the effectiveness of which can be predicted by individual demographic factors.

Addressing the Gender Gap in Research: Insights from a Women in Neuroscience Conference.

There has been growing interest in quantifying the proportion of women participating in scientific conferences, publications, and committees. Numbers reveal persistent disparities, but offer few cures to the root causes of the gender gaps in research. Toward remediation, we outline five lessons learned through organizing two conferences for Women in Neuroscience (WiN). These recommendations build on participants' comments, and aim to better support women in their scientific paths and help provide equal opportunity.

Impaired visual working memory and reduced connectivity in undergraduates with a history of mild traumatic brain injury.

Mild traumatic brain injury (mTBI), or concussion, accounts for 85% of all TBIs. Yet survivors anticipate full cognitive recovery within several months of injury, if not sooner, dependent upon the specific outcome/measure. Recovery is variable and deficits in executive function, e.g., working memory (WM) can persist years post-mTBI. We tested whether cognitive deficits persist in otherwise healthy undergraduates, as a conservative indicator for mTBI survivors at large. We collected WM performance (change detection, n-back tasks) using various stimuli (shapes, locations, letters; aurally presented numbers and letters), and wide-ranging cognitive assessments (e.g., RBANS). We replicated the observation of a general visual WM deficit, with preserved auditory WM. Surprisingly, visual WM deficits were equivalent in participants with a history of mTBI (mean 4.3 years post-injury) and in undergraduates with recent sports-related mTBI (mean 17 days post-injury). In seeking the underlying mechanism of these behavioral deficits, we collected resting state fMRI (rsfMRI) and EEG (rsEEG). RsfMRI revealed significantly reduced connectivity within WM-relevant networks (default mode, central executive, dorsal attention, salience), whereas rsEEG identified no differences (modularity, global efficiency, local efficiency). In summary, otherwise healthy current undergraduates with a history of mTBI present behavioral deficits with evidence of persistent disconnection long after full recovery is expected.

Predicting Working Memory Training Benefits From Transcranial Direct Current Stimulation Using Resting-State fMRI.

The effects of transcranial direct current stimulation (tDCS) on working memory (WM) performance are promising but variable and contested. In particular, designs involving one session of tDCS are prone to variable outcomes with notable effects of individual differences. Some participants benefit, whereas others are impaired by the same tDCS protocol. In contrast, protocols including multiple sessions of tDCS more consistently report WM improvement across participants. The objective of the current project was to test whether differences in resting-state connectivity between stimulation site and two WM-relevant networks [default mode network (DMN) and central executive network (CEN)] could account for initial and longitudinal responses to tDCS. Healthy young adults completed 5 days of visual WM training during sham or anodal right frontal tDCS. The behavioral data showed that only the active tDCS group significantly improved over the visual WM training period. There were no significant correlations between initial response to tDCS and resting-state activity. DMN activity in the anterior cingulate cortex significantly correlated with WM training slope. These data underscore the importance of sampling in studies applying tDCS; homogeneity (e.g., of gender, special population, and WM capacity) may produce more consistent data in a single experiment with limited power, whereas heterogeneity is important in determining the mechanism(s) and potential for tDCS-linked protocols. This issue is a limitation in tDCS findings that continues to hamper its optimization and translational value.

No tDCS augmented working memory training benefit in undergraduates rewarded with course credit.

BACKGROUND: The goal of working memory (WM) training is to expand capacity of this executive function. Transcranial direct current stimulation (tDCS) paired with WM training is more consistent than either alone. We have reported that tDCS targeting frontal and/or parietal regions enhanced theta phase locking, reduced alpha power, and strengthened theta-gamma phase amplitude coupling. OBJECTIVE: To determine whether tDCS to frontal or parietal sites optimized WM training gains we pre-registered a tDCS-WM training study. METHODS: 80 undergraduates were randomly assigned to one of four anodal tDCS montages: frontal (F4), parietal (P4), alternating (P4-F4), and sham (P4 or F4). Participants completed 5-training sessions over one week and returned for follow-up testing after 30 days of no-contact. RESULTS: No group showed significant improvement in trained or transfer task performance at the end of training nor at follow-up. CONCLUSIONS: This null finding marks a failure to replicate in undergraduates training benefits observed in graduate students. We argue that motivation is essential to elicit improved performance in training protocols.

Frontoparietal theta-gamma interactions track working memory enhancement with training and tDCS.

Despite considerable interest in enhancing, preserving, and rehabilitating working memory (WM), efforts to elicit sustained behavioral improvements have been met with limited success. Here, we paired WM training with transcranial direct current stimulation (tDCS) to the frontoparietal network over four days. Active tDCS enhanced WM performance by modulating interactions between frontoparietal theta oscillations and gamma activity, as measured by pre- and post-training high-density electroencephalography (EEG). Increased phase-amplitude coupling (PAC) between the prefrontal stimulation site and temporo-parietal gamma activity explained behavioral improvements, and was most effective when gamma occurred near the prefrontal theta peak. These results demonstrate for the first time that tDCS-linked WM training elicits lasting changes in behavior by optimizing the oscillatory substrates of prefrontal control.

Replacing tDCS with theta tACS provides selective, but not general WM benefits.

Working memory (WM) can be improved after repeated training sessions paired with noninvasive neurostimulation techniques. Previously, we reported that WM training paired with tDCS succeeded behaviorally by enhancing anterior-posterior theta phase coherence and reducing alpha power. Here, in two experiments we tested several theta and alpha frequencies and two transcranial alternating current stimulation (tACS) montages in an effort to shortcut WM training while preserving behavioral gains. In Experiment 1, in separate sessions participants received online tACS at two frequencies derived from the previous study with the respective goal of improving and impairing WM performance. We selected the mean group peak value theta (7 Hz) to benefit WM and alpha (11 Hz) to impair WM. Stimulation (tACS) over right frontoparietal sites (F4-P4) during 3-back WM tasks (object, spatial) produced no behavioral consequences. In Experiment 2 we stimulated at a slower theta frequency (4.5 Hz), which was also significant in our prior study, and tested whether frontoparietal or bifrontal montages would be more effective at improving WM. This experiment revealed selectively improved object WM after right frontoparietal tACS alone. In summary, one session of tACS failed to produce the magnitude or breadth of WM gains observed after 4-10 tDCS-WM training sessions. In short, despite looking for loopholes we found little tACS savings.

Visual working memory deficits in undergraduates with a history of mild traumatic brain injury.

We investigated whether a history of mild traumatic brain injury (mTBI), or concussion, has any effect on visual working memory (WM) performance. In most cases, cognitive performance is thought to return to premorbid levels soon after injury, without further medical intervention. We tested this assumption in undergraduates, among whom a history of mTBI is prevalent. Notably, participants with a history of mTBI performed worse than their colleagues with no such history. Experiment 1 was based on a change detection paradigm in which we manipulated visual WM set size from one to three items, which revealed a significant deficit at set size 3. In Experiment 2 we investigated whether feedback could rescue WM performance in the mTBI group, and found that it failed. In Experiment 3 we manipulated WM maintenance duration (set size 3, 500-1,500 ms) to investigate a maintenance-related deficit. Across all durations, the mTBI group was impaired. In Experiment 4 we tested whether retrieval demands contributed to WM deficits and showed a consistent deficit across recognition and recall probes. In short, even years after an mTBI, undergraduates perform differently on visual WM tasks than their peers with no such history. Given the prevalence of mTBI, these data may benefit other researchers who see high variability in their data. Clearly, further studies will be needed to determine the breadth of the cognitive deficits in those with a history of mTBI and to identify relevant factors that contribute to positive cognitive outcomes.

Individual differences reveal limited mixed-category effects during a visual working memory task.

Using stimuli from different categories may expand the capacity limits of working memory (WM) by spreading item representations across distinct neural populations. We explored this mixed-category benefit by correlating individuals' behavioral performance with fMRI measures of category information during uniform- and mixed-category trials. Behaviorally, we found weak evidence for a mixed-category benefit at the group-level, although there was a high degree of individual variability. To test whether distinct neural patterns elicited superior performance in some individuals, we correlated a multivariate measure of neural category information with multiple behavioral metrics. This revealed a widespread positive relationship, intuitive for hit rate and working memory capacity, but counterintuitive for false alarm rate. Overall, these data suggest that mixed-category effects may support working memory performance, but unexpectedly, not all participants show this benefit. Only some people may be able to take advantage of representing mixed-category information in a differentiable way.

Cognitive Effects of Transcranial Direct Current Stimulation in Healthy and Clinical Populations: An Overview.

Transcranial direct current stimulation (tDCS) is a neuromodulatory approach that is affordable, safe, and well tolerated. This review article summarizes the research and clinically relevant findings from meta-analyses and studies investigating the cognitive effects of tDCS in healthy and clinical populations. We recapitulate findings from recent studies where cognitive performance paired with tDCS was compared with performance under placebo (sham stimulation) in single sessions and longitudinal designs where cognitive effects were evaluated following repeated sessions. In summary, the tDCS literature currently indicates that the effects of tDCS on cognitive measures are less robust and less predictable compared with the more consistent effects on motor outcomes. There is also a notable difference in the consistency of single-session and longitudinal designs. In single-session tDCS designs, there are small effects amid high variability confounded by individual differences and potential sham stimulation effects. In contrast, longitudinal studies provide more consistent benefits in healthy and clinical populations, particularly when tDCS is paired with a concurrent task. Yet, these studies are few in number, thereby impeding design optimization. While there is good evidence that tDCS can modulate cognitive functioning and potentially produce longer-term benefits, a major challenge to widespread translation of tDCS is the absence of a complete mechanistic account for observed effects. Significant future work is needed to identify a priori responders from nonresponders for every cognitive task and tDCS protocol.

Frontoparietal tDCS Benefits Visual Working Memory in Older Adults With Low Working Memory Capacity.

Working memory (WM) permits maintenance of information over brief delays and is an essential executive function. Unfortunately, WM is subject to age-related decline. Some evidence supports the use of transcranial direct current stimulation (tDCS) to improve visual WM. A gap in knowledge is an understanding of the mechanism characterizing these tDCS linked effects. To address this gap, we compared the effects of two tDCS montages designed on visual working memory (VWM) performance. The bifrontal montage was designed to stimulate the heightened bilateral frontal activity observed in aging adults. The unilateral frontoparietal montage was designed to stimulate activation patterns observed in young adults. Participants completed three sessions (bilateral frontal, right frontoparietal, sham) of anodal tDCS (20 min, 2 mA). During stimulation, participants performed a visual long-term memory (LTM) control task and a visual WM task. There was no effect of tDCS on the LTM task. Participants receiving right unilateral tDCS showed a WM benefit. This pattern was most robust in older adults with low WM capacity. To address the concern that the key difference between the two tDCS montages could be tDCS over the posterior parietal cortex (PPC), we included new analyses from a previous study applying tDCS targeting the PPC paired with a recognition VWM task. No significant main effects were found. A subsequent experiment in young adults found no significant effect of either tDCS montage on either task. These data indicate that tDCS montage, age and WM capacity should be considered when designing tDCS protocols. We interpret these findings as suggestive that protocols designed to restore more youthful patterns of brain activity are superior to those that compensate for age-related changes.