The neurogenesis of P1 and N1: A concurrent EEG/LFP study.

It is generally recognised that event related potentials (ERPs) of electroencephalogram (EEG) primarily reflect summed post-synaptic activity of the local pyramidal neural population(s). However, it is still not understood how the positive and negative deflections (e.g. P1, N1 etc) observed in ERP recordings are related to the underlying excitatory and inhibitory post-synaptic activity. We investigated the neurogenesis of P1 and N1 in ERPs by pharmacologically manipulating inhibitory post-synaptic activity in the somatosensory cortex of rodent, and concurrently recording EEG and local field potentials (LFPs). We found that the P1 wave in the ERP and LFP of the supragranular layers is determined solely by the excitatory post-synaptic activity of the local pyramidal neural population, as is the initial segment of the N1 wave across cortical depth. The later part of the N1 wave was modulated by inhibitory post-synaptic activity, with its peak and the pulse width increasing as inhibition was reduced. These findings suggest that the temporal delay of inhibition with respect to excitation observed in intracellular recordings is also reflected in extracellular field potentials (FPs), resulting in a temporal window during which only excitatory post-synaptic activity and leak channel activity are recorded in the ERP and evoked LFP time series. Based on these findings, we provide clarification on the interpretation of P1 and N1 in terms of the excitatory and inhibitory post-synaptic activities of the local pyramidal neural population(s).

Long-latency reductions in gamma power predict hemodynamic changes that underlie the negative BOLD signal.

Studies that use prolonged periods of sensory stimulation report associations between regional reductions in neural activity and negative blood oxygenation level-dependent (BOLD) signaling. However, the neural generators of the negative BOLD response remain to be characterized. Here, we use single-impulse electrical stimulation of the whisker pad in the anesthetized rat to identify components of the neural response that are related to "negative" hemodynamic changes in the brain. Laminar multiunit activity and local field potential recordings of neural activity were performed concurrently with two-dimensional optical imaging spectroscopy measuring hemodynamic changes. Repeated measurements over multiple stimulation trials revealed significant variations in neural responses across session and animal datasets. Within this variation, we found robust long-latency decreases (300 and 2000 ms after stimulus presentation) in gamma-band power (30-80 Hz) in the middle-superficial cortical layers in regions surrounding the activated whisker barrel cortex. This reduction in gamma frequency activity was associated with corresponding decreases in the hemodynamic responses that drive the negative BOLD signal. These findings suggest a close relationship between BOLD responses and neural events that operate over time scales that outlast the initiating sensory stimulus, and provide important insights into the neurophysiological basis of negative neuroimaging signals.

Contingent negative variation (CNV) associated with sensorimotor timing error correction.

INTRODUCTION: Detection and subsequent correction of sensorimotor timing errors are fundamental to adaptive behavior. Using scalp-recorded event-related potentials (ERPs), we sought to find ERP components that are predictive of error correction performance during rhythmic movements. METHOD: Healthy right-handed participants were asked to synchronize their finger taps to a regular tone sequence (every 600 ms), while EEG data were continuously recorded. Data from 15 participants were analyzed. Occasional irregularities were built into stimulus presentation timing: 90 ms before (advances: negative shift) or after (delays: positive shift) the expected time point. A tapping condition alternated with a listening condition in which identical stimulus sequence was presented but participants did not tap. RESULTS: Behavioral error correction was observed immediately following a shift, with a degree of over-correction with positive shifts. Our stimulus-locked ERP data analysis revealed, 1) increased auditory N1 amplitude for the positive shift condition and decreased auditory N1 modulation for the negative shift condition; and 2) a second enhanced negativity (N2) in the tapping positive condition, compared with the tapping negative condition. In response-locked epochs, we observed a CNV (contingent negative variation)-like negativity with earlier latency in the tapping negative condition compared with the tapping positive condition. This CNV-like negativity peaked at around the onset of subsequent tapping, with the earlier the peak, the better the error correction performance with the negative shifts while the later the peak, the better the error correction performance with the positive shifts. DISCUSSION: This study showed that the CNV-like negativity was associated with the error correction performance during our sensorimotor synchronization study. Auditory N1 and N2 were differentially involved in negative vs. positive error correction. However, we did not find evidence for their involvement in behavioral error correction. Overall, our study provides the basis from which further research on the role of the CNV in perceptual and motor timing can be developed.

Decreased haemodynamic response and decoupling of cortical gamma-band activity and tissue oxygen perfusion after striatal interleukin-1 injection.

BACKGROUND: Neurovascular coupling describes the mechanism by which the energy and oxygen demand arising from neuronal activity is met by an increase in regional blood flow, known as the haemodynamic response. Interleukin 1 (IL-1) is a pro-inflammatory cytokine and an important mediator of neuronal injury, though mechanisms through which IL-1 exerts its effects in the brain are not fully understood. In this study, we set out to investigate if increased cerebral levels of IL-1 have a negative effect on the neurovascular coupling in the cortex in response to sensory stimulation. METHODS: We used two approaches to measure the neuronal activity and haemodynamic changes in the anaesthetised rat barrel somatosensory cortex in response to mechanical whisker stimulation, before and for 6 h after intra-striatal injection of interleukin-1ß or vehicle. First, we used two-dimensional optical imaging spectroscopy (2D-OIS) to measure the size of the functional haemodynamic response, indicated by changes of oxyhaemoglobin (HbO2) and total haemoglobin (HbT) concentration. In the same animals, immunostaining of immunoglobulin G and SJC-positive extravasated neutrophils was used to confirm the pro-inflammatory effects of interleukin-1ß (IL-1ß). Second, to examine the functional coupling between neuronal activity and the haemodynamic response, we used a 'Clark-style' electrode combined with a single sharp electrode to simultaneously record local tissue oxygenation (partial pressure oxygen, pO2) in layer IV/V of the stimulated barrel cortex and multi-unit activity (MUA) together with local field potentials (LFPs), respectively. RESULTS: 2D-OIS data revealed that the size of the haemodynamic response to mechanical whisker stimulation declined over the 6 h following IL-1ß injection whereas the vehicle group remained stable, significant differences being seen after 5 h. Moreover, the size of the transient increases of neuronal LFP activity in response to whisker stimulation decreased after IL-1ß injection, significant changes compared to vehicle being seen for gamma-band activity after 1 h and beta-band activity after 3 h. The amplitude of the functional pO2 response similarly decreased after 3 h post-IL-1ß injection, whereas IL-1ß had no significant effect on the peak of whisker-stimulation-induced MUA. The stimulation-evoked increases in gamma power and pO2 correlated significantly throughout the 6 h in the vehicle group, but such a correlation was not observed in the IL-1ß-injected group. CONCLUSIONS: We conclude that intra-striatal IL-1ß decouples cortical neuronal activity from its haemodynamic response. This finding may have implications for neurological conditions where IL-1ß plays a part, especially those involving reductions in cerebral blood flow (such as stroke).

Increased peak gamma frequency in individuals with higher levels of autistic traits.

Individual differences in orientation discrimination threshold are related to both visually-induced peak gamma frequency and the presence of autistic traits. The relationship between peak gamma frequency and orientation discrimination thresholds may be due to both of these factors being mediated by levels of neural inhibition. No study has previously measured the relationship between peak gamma frequency and levels of autistic traits. Thus, this was the aim of the present study. We measured orientation discrimination thresholds and autistic traits in a neurotypical human sample (N = 33), and separately recorded electroencephalography to measure visually induced gamma activity. In line with our prediction, we found a significant relationship between peak gamma frequency and level of autistic traits. Consistent with previous work we also found significant relationships between orientation discrimination thresholds and level of autistic traits and between orientation discrimination thresholds and peak gamma frequency. Our results demonstrate that individuals with individuals with higher levels of autistic personality traits have a higher peak-gamma frequency and are better at discriminating between visual stimuli based on orientation. As both higher peak gamma frequency and lower orientation discrimination thresholds have been linked to higher levels of neural inhibition, this suggests that autistic traits co-occur with increased neural inhibition. This discovery is significant as it challenges the currently-held view that autism spectrum conditions are associated with increased neural excitation.

Bupropion increases selection of high effort activity in rats tested on a progressive ratio/chow feeding choice procedure: implications for treatment of effort-related motivational symptoms.

BACKGROUND: Depression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology. METHODS: Because clinical studies have suggested that inhibition of catecholamine uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber. RESULTS: Bupropion (10.0-40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation. CONCLUSION: The ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans.

The resting-state neurovascular coupling relationship: rapid changes in spontaneous neural activity in the somatosensory cortex are associated with haemodynamic fluctuations that resemble stimulus-evoked haemodynamics.

Although promise exists for patterns of resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) brain connectivity to be used as biomarkers of early brain pathology, a full understanding of the nature of the relationship between neural activity and spontaneous fMRI BOLD fluctuations is required before such data can be correctly interpreted. To investigate this issue, we combined electrophysiological recordings of rapid changes in multi-laminar local field potentials from the somatosensory cortex of anaesthetized rats with concurrent two-dimensional optical imaging spectroscopy measurements of resting-state haemodynamics that underlie fluctuations in the BOLD fMRI signal. After neural 'events' were identified, their time points served to indicate the start of an epoch in the accompanying haemodynamic fluctuations. Multiple epochs for both neural 'events' and the accompanying haemodynamic fluctuations were averaged. We found that the averaged epochs of resting-state haemodynamic fluctuations taken after neural 'events' closely resembled the temporal profile of stimulus-evoked cortical haemodynamics. Furthermore, we were able to demonstrate that averaged epochs of resting-state haemodynamic fluctuations resembling the temporal profile of stimulus-evoked haemodynamics could also be found after peaks in neural activity filtered into specific electroencephalographic frequency bands (theta, alpha, beta, and gamma). This technique allows investigation of resting-state neurovascular coupling using methodologies that are directly comparable to that developed for investigating stimulus-evoked neurovascular responses.

Mechanisms of Cognitive Change: Training Improves the Quality But Not the Quantity of Visual Working Memory Representations.

As of yet, visual working memory (WM) training has failed to yield consistent cognitive benefits to performance in untrained tasks, despite large improvements in trained tasks. Investigating the mechanisms underlying training effects can help explain these inconsistencies. In this pre-registered, pre-test/post-test online training study, we examined how training affects the quantity and quality of representations in visual WM using continuous-reproduction tasks. N = 64 young healthy adults were randomly assigned to an experimental group or an active control group to complete four training sessions of practce in an orientation-reproduction or a visual search task, respectively. We observed that, in the trained task, only the quality, but not the quantity, of visual WM representations significantly increased in the experimental group relative to the control group. These improvements did not generalise to untrained stimuli or paradigms. Therefore, our findings suggest that training gains are not driven by enhanced capacity. Instead, gains in the quality of visual WM representations that are tied to specific stimuli and paradigms may reflect enhanced efficiency in using the existing visual WM capacity.

The three-dimensional community structure of attention-deficit hyperactivity disorder (ADHD) traits captured by the Adult ADHD Self-Report Scale: An exploratory graph analysis.

OBJECTIVE: To employ a novel analytic method-namely, exploratory graph analysis (EGA)-to subclinical attention-deficit hyperactivity disorder (ADHD) trait scores in order to reveal their dimensional structure, as well as compare EGA's performance with traditional factor-analytic techniques in doing so. METHOD: 1149 respondents from a survey panel completed the ASRS, a common ADHD scale made up of 18 distinct trait measures. EGA and factor analysis were applied to identify traits which associate with each other. RESULTS: EGA revealed 3 distinct communities, and ruled out a 2-community structure. This was in contrast to the 2-factor structure suggested by the factor analysis, and the conventional division of ADHD into two subdimensions (hyperactivity and inattention). CONCLUSION: A dimensional structure of three clusters (hyperactivity, impulsivity and inattention) may better reflect the traits underlying ADHD. EGA has benefits in terms of both analytic approach and interpretability of findings.

Investigating neural dynamics in autism spectrum conditions outside of the laboratory using mobile electroencephalography.

There is currently a paucity of neuroscientific data recorded from more severely affected individuals with autism spectrum conditions (ASC). Enabling data collection to take place in a more familiar environment, that is, at home, may increase access to research participation in this group. Here, we present a new accessible method of studying brain activity of autistic individuals outside the laboratory in their home environment, using mobile electroencephalography (EEG) technology. The primary aim of the present study was to test the feasibility of acquiring good quality EEG data from autistic children at home, assessed via a set of objective data quality metrics, and to develop a list of practical guidelines on how to successfully conduct an EEG experiment in such a naturalistic setting based directly upon participants' views. To demonstrate the utility of this method, we evaluated the EEG signal quality recorded from 69 children with ASC at home using a gel-based Eego Sports mobile EEG system. Five key indicators of data quality were assessed. Our results demonstrate that it is possible to record high quality EEG signal from children with ASC at home, generating data that could address a number of research questions. A user experience survey identified areas of good practice, which researchers should take into consideration when designing mobile EEG studies aiming to acquire data from children with ASC at a home environment.

Negative blood oxygen level dependence in the rat: a model for investigating the role of suppression in neurovascular coupling.

Modern neuroimaging techniques rely on neurovascular coupling to show regions of increased brain activation. However, little is known of the neurovascular coupling relationships that exist for inhibitory signals. To address this issue directly we developed a preparation to investigate the signal sources of one of these proposed inhibitory neurovascular signals, the negative blood oxygen level-dependent (BOLD) response (NBR), in rat somatosensory cortex. We found a reliable NBR measured in rat somatosensory cortex in response to unilateral electrical whisker stimulation, which was located in deeper cortical layers relative to the positive BOLD response. Separate optical measurements (two-dimensional optical imaging spectroscopy and laser Doppler flowmetry) revealed that the NBR was a result of decreased blood volume and flow and increased levels of deoxyhemoglobin. Neural activity in the NBR region, measured by multichannel electrodes, varied considerably as a function of cortical depth. There was a decrease in neuronal activity in deep cortical laminae. After cessation of whisker stimulation there was a large increase in neural activity above baseline. Both the decrease in neuronal activity and increase above baseline after stimulation cessation correlated well with the simultaneous measurement of blood flow suggesting that the NBR is related to decreases in neural activity in deep cortical layers. Interestingly, the magnitude of the neural decrease was largest in regions showing stimulus-evoked positive BOLD responses. Since a similar type of neural suppression in surround regions was associated with a negative BOLD signal, the increased levels of suppression in positive BOLD regions could importantly moderate the size of the observed BOLD response.

Spontaneous neural activity relates to psychiatric traits in 16p11.2 CNV carriers: An analysis of EEG spectral power and multiscale entropy.

Copy number variations (CNV) at the 16p11.2 chromosomal region are rare high-risk CNVs associated with various clinical features and psychiatric disorders including intellectual disability, developmental delays, and autism spectrum disorder. No study to date has investigated whether spontaneous neural activity is altered for 16p11.2 CNV carriers and whether this relates to psychiatric traits. The aim of this study is to examine the impact of 16p11.2 deletions (del) and duplications (dup) on spontaneous neural activity and its relationship to psychiatric problems. EEG was previously collected as part of the Simons Searchlight initiative. Using spectral power (delta, theta, alpha, and beta frequency bands), complexity index (CI), and multiscale entropy analysis techniques, we analyzed frontal resting-state EEG data collected from 22 16p11.2 del carriers, 14 dup carriers, and 13 controls. We then examined associations between neural activity and psychiatric traits, measured with the Child Behavior Checklist. Results indicated that EEG entropy was higher for del and dup compared to controls, respectively, at all timescales. CI was also higher for del and dup compared to controls. Theta power of 16p11.2 dup carriers was higher than controls. A strong association was found between entropy at higher timescales and anxiety problems. In addition, a strong correlation was found between theta power and pervasive developmental problems. Atypical spontaneous neural activity is implicated in 16p11.2 CNVs. With higher entropy or theta power, psychiatric traits increase in severity. Our findings provide evidence of the link between genotype, neural activity, and phenotypes in 16p11.2 CNVs.

Vaping Exacerbates Coronavirus-Related Pulmonary Infection in a Murine Model.

Though the current preponderance of evidence indicates the toxicity associated with the smoking of tobacco products through conventional means, less is known about the role of "vaping" in respiratory disease. "Vaping" is described as the use of electronic cigarettes (E-Cigarettes or E-Cigs), which has only more recently been available to the public (∼10 years) but has quickly emerged as a popular means of tobacco consumption worldwide. The World Health Organization (WHO) declared the SARS-CoV-2 outbreak as a global pandemic in March 2020. SARS-CoV-2 can easily be transmitted between people in close proximity through direct contact or respiratory droplets to develop coronavirus infectious disease 2019 (COVID-19). Symptoms of COVID-19 range from a mild flu-like illness with high fever to severe respiratory distress syndrome and death. The risk factors for increased disease severity remain unclear. Herein, we utilize a murine-tropic coronavirus (beta coronavirus) MHV-A59 along with a mouse model and measures of pathology (lung weight/dry ratios and histopathology) and inflammation (ELISAs and cytokine array panels) to examine whether vaping may exacerbate the pulmonary disease severity of coronavirus disease. While vaping alone did result in some noted pathology, mice exposed with intranasal vaped e-liquid suffered more severe mortality due to pulmonary inflammation than controls when exposed to coronavirus infection. Our data suggest a role for vaping in increased coronavirus pulmonary disease in a mouse model. Furthermore, our data indicate that disease exacerbation may involve calcium (Ca2+) dysregulation, identifying a potential therapeutic intervention.

Transcranial direct current stimulation for auditory verbal hallucinations: a systematic review of clinical trials.

Transcranial direct current stimulation (tDCS) has been reportedly beneficial for different neurodegenerative disorders. tDCS has been reported as a potential adjunctive or alternative treatment for auditory verbal hallucination (AVH). This study aims to review the effects of tDCS on AVH in patients with schizophrenia through combining the evidence from randomized clinical trials (RCTs). The databases of PsycINFO (2000-2019), PubMed (2000-2019), EMBASE (2000-2019), CINAHL (2000-2019), Web of Science (2000-2019), and Scopus (2000-2019) were systematically searched. The clinical trials with RCT design were selected for final analysis. A total of nine RCTs were eligible and included in the review. Nine RCTs were included in the final analysis. Among them, six RCTs reported a significant reduction of AVH after repeated sessions of tDCS, whereas three RCTs did not show any advantage of active tDCS over sham tDCS. The current studies showed an overall decrease of approximately 28% of AVH after active tDCS and 10% after sham tDCS. The tDCS protocols targeting the sensorimotor frontal-parietal network showed greater treatment effects compared with the protocols targeting other regions. In this regard, cathodal tDCS over the left temporoparietal area showed inhibitory effects on AVHs. The most effective tDCS protocol on AVHs was twice-daily sessions (2 mA, 20-minute duration) over 5 consecutive days (10 sessions) with the anode over the left dorsolateral prefrontal cortex and the cathode over the left temporal area. Some patient-specific and disease-specific factors such as young age, nonsmoking status, and higher frequencies of AVHs seemed to be the predictors of treatment response. Taken together, the results of tDCS as an alternative treatment option for AVH show controversy among current literatures, since not all studies were positive. However, the studies targeting the same site of the brain showed that the tDCS could be a promising treatment option to reduce AVH. Further RCTs, with larger sample sizes, should be conducted to reach a conclusion on the efficacy of tDCS for AVH and to develop an effective therapeutic protocol for clinical setting.

Acute vaping exacerbates microbial pneumonia due to calcium (Ca2+) dysregulation.

As electronic cigarette (E-cig) use, also known as "vaping", has rapidly increased in popularity, data regarding potential pathologic effects are recently emerging. Recent associations between vaping and lung pathology have led to an increased need to scrutinize E-cigs for adverse health impacts. Our previous work (and others) has associated vaping with Ca2+-dependent cytotoxicity in cultured human airway epithelial cells. Herein, we develop a vaped e-liquid pulmonary exposure mouse model to evaluate vaping effects in vivo. Using this model, we demonstrate lung pathology through the use of preclinical measures, that is, the lung wet: dry ratio and lung histology/H&E staining. Further, we demonstrate that acute vaping increases macrophage chemotaxis, which was ascertained using flow cytometry-based techniques, and inflammatory cytokine production, via Luminex analysis, through a Ca2+-dependent mechanism. This increase in macrophage activation appears to exacerbate pulmonary pathology resulting from microbial infection. Importantly, modulating Ca2+ signaling may present a therapeutic direction for treatment against vaping-associated pulmonary inflammation.

The efficacy of interactive group psychoeducation for children with leukaemia: A randomised controlled trial.

OBJECTIVE: To evaluate an interactive group psychoeducation programme for children treated for leukaemia. METHODS: A longitudinal randomised controlled study across four UK hospitals with an immediate (N = 26) and delay control group (N = 32). The intervention covered the pathophysiology of leukaemia, its treatment, side effects and the importance of positive health behaviours. Primary outcomes were parent-reported child health related quality of life (HRQoL) and behavioural difficulties. Secondary outcomes were child-reported HRQoL, cancer-specific HRQoL, child confidence, caregiver burden, and treatment anxiety. Measures were completed pre- and immediately post-intervention, and at 13 and 26-weeks follow-up. Change over time was analysed using multilevel modelling. Acceptability questionnaires rated the intervention on benefits, recommendations, and barriers to participation. RESULTS: The intervention significantly improved parent-reported child HRQoL but did not have a significant effect on other outcomes. Acceptability of the intervention was high. CONCLUSIONS: This study provides initial evidence that interactive group psychoeducation is acceptable to families and improves HRQoL in children with leukaemia. Difficulties with recruitment removed power to detect effect sizes that are plausible for psychoeducational interventions. PRACTISE IMPLICATIONS: Further studies to explore the potential of psychoeducation to improve outcomes for children with leukaemia and an examination of barriers to participation within this population are warranted.

JUUL e-liquid exposure elicits cytoplasmic Ca2+ responses and leads to cytotoxicity in cultured airway epithelial cells.

RATIONALE: The popularity of new and emerging tobacco products such as E-cigarettes (E-cigs) is rapidly expanding worldwide. However, uncertainties surrounding the potential health consequences due to the use of such products exist and warrant further study. METHODS: Cultured A549 and Calu-3 airway epithelia were exposed to three out of the eight types of JUUL brand e-liquids ("Mint", "Virginia Tobacco" and "Menthol", all containing 3% nicotine at 1% and 3% (vol/vol) dilutions) and assessed for viability using a resazurin-based assay. Intracellular Ca2+ levels were measured using fluorescent indicators and pro-inflammatory cytokine levels were monitored by quantitative PCR (qPCR). Cultures were also analyzed by flow cytometry to evaluate apoptotic markers and cell viability. RESULTS: Exposing the airway epithelial cells to the flavored JUUL e-liquids led to significant cytotoxicity, with the "Mint" flavor being the overall most cytotoxic. The "Mint" flavored e-liquid also led to significant elevations in intracellular Ca2+ and upregulation of the pro-inflammatory cytokine IL-6 and early apoptotic marker Annexin V. CONCLUSIONS: JUUL e-liquid challenge resulted in a loss of airway epithelial cell viability, induced pro-inflammatory responses and eventually caused apoptosis.

A dynamic model of neurovascular coupling: implications for blood vessel dilation and constriction.

Neurovascular coupling in response to stimulation of the rat barrel cortex was investigated using concurrent multichannel electrophysiology and laser Doppler flowmetry. The data were used to build a linear dynamic model relating neural activity to blood flow. Local field potential time series were subject to current source density analysis, and the time series of a layer IV sink of the barrel cortex was used as the input to the model. The model output was the time series of the changes in regional cerebral blood flow (CBF). We show that this model can provide excellent fit of the CBF responses for stimulus durations of up to 16 s. The structure of the model consisted of two coupled components representing vascular dilation and constriction. The complex temporal characteristics of the CBF time series were reproduced by the relatively simple balance of these two components. We show that the impulse response obtained under the 16-s duration stimulation condition generalised to provide a good prediction to the data from the shorter duration stimulation conditions. Furthermore, by optimising three out of the total of nine model parameters, the variability in the data can be well accounted for over a wide range of stimulus conditions. By establishing linearity, classic system analysis methods can be used to generate and explore a range of equivalent model structures (e.g., feed-forward or feedback) to guide the experimental investigation of the control of vascular dilation and constriction following stimulation.

Binocular rivalry dynamics associated with high levels of self-reported autistic traits suggest an imbalance of cortical excitation and inhibition.

An imbalance in cortical excitation and inhibition (E/I) may underlie both social and non-social symptoms of autism spectrum conditions (ASC). Recent work suggests that an E/I imbalance may underlie some of the sensory differences that are characteristic of ASCs such as anomalous perception. Binocular rivalry dynamics are thought to reflect the balance of E/I in the brain and could serve as a behavioural biomarker for ASC. Previous studies of clinical ASC populations have found a slower rate of binocular rivalry transitions; increased duration of the mixed percept and reduced perceptual suppression. There are some mixed reports of altered rivalry dynamics in the neurotypical population with high self-reported levels of autistic traits. Therefore, we used simple grating stimuli to measure binocular rivalry dynamics in a sample of seventy-nine adults aged 18-55 years. We additionally measured the level of autistic traits with the AQ-10 and used CAPS as a measure of anomalous perception. Bayesian correlations showed that those with higher AQ scores had a slower rate of perceptual switching and a longer mixed percept duration. Significant regression models with CAPS and AQ score revealed that AQ score was a significant predictor of switch rate and mixed percept duration, whereas CAPS was not. We also report that CAPS significantly predicted perceptual suppression, whereas AQ score did not. Overall, our findings suggest that in a non-clinical population, autistic traits are a predictor of binocular rivalry dynamics and the cortical E/I imbalance thought to underlie symptoms of ASC may extend to the broader phenotype.

Atypical neural variability in carriers of 16p11.2 copy number variants.

Copy number variations (CNVs) at the 16p11.2 chromosomal region are associated with myriad clinical features including intellectual disability and autism spectrum disorder. The aim of this study is to determine whether 16p11.2 deletion (DEL) and duplication (DUP) carriers demonstrate a distinct and reciprocal pattern of electroencephalography (EEG) activity as represented by neural variability measures. EEG data were previously collected as part of the Simons Variation in Individuals Project. Variability measures, as estimated by single-trial ERP and spectral power analyses in the alpha and beta frequency bands, in addition to signal-to-noise ratios (SNRs), were analyzed in DEL (n = 20), DUP (n = 8), and typical (n = 11) groups. We also analyzed mean visual evoked potentials and spectral power (alpha and beta power) to facilitate comparisons with other studies of associated disorders and CNVs. From measures of single-trial variability, we found higher intraparticipant variability in P1 amplitude and timecourse amplitude in DEL compared to controls. Compared to DUP, DEL showed higher variability in absolute alpha and absolute beta power but lower variability in P1 latency. SNRs did not differ between the groups. From measures of amplitude, latency, and spectral power, DUP showed lower relative alpha power compared to controls. Although it is yet unclear whether 16p11.2 CNV dosage impacts neural activity in an opposing manner, findings suggest that 16p11.2 DEL impacts the level of variability of neural responses. Higher neural variability may play a role in a range of cognitive processes in 16p11.2 CNV carriers. Autism Res 2019, 12: 1322-1333. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The study analyzed the consistency of patterns of brain waves and rhythms in those affected with a loss or gain of DNA material in the 16p11.2 region. Compared with typical individuals, 16p11.2 deletion carriers showed greater inconsistency in the way the brain responds to the same visual event. This high inconsistency in brain activity may play a role in some core symptoms in 16p11.2 copy number variation carriers.