Effects of transcranial direct current stimulation and transcranial random noise stimulation on working memory and task-related EEG in major depressive disorder.

OBJECTIVE: To compare effects of transcranial direct current stimulation (tDCS) and transcranial random noise stimulation with a direct-current offset (tRNS + DC-offset) on working memory (WM) performance and task-related electroencephalography (EEG) in individuals with Major Depressive Disorder (MDD). METHODS: Using a sham-controlled, parallel-groups design, 49 participants with MDD received either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left dorsolateral prefrontal cortex (DLPFC) for 20-minutes. The Sternberg WM task was completed with concurrent EEG recording before and at 5- and 25-minutes post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) was calculated for theta, upper alpha, and gamma oscillations during WM encoding and maintenance. RESULTS: tDCS significantly increased parieto-occipital upper alpha ERS/ERD during WM maintenance, observed on EEG recorded 5- and 25-minutes post-stimulation. tRNS + DC-offset did not significantly alter WM-related oscillatory activity when compared to sham stimulation. Neither tDCS nor tRNS + DC-offset improved WM performance to a significantly greater degree than sham stimulation. CONCLUSIONS: Although tDCS induced persistent effects on WM-related oscillatory activity, neither tDCS nor tRNS + DC-offset enhanced WM performance in MDD. SIGNIFICANCE: This reflects the first sham-controlled comparison of tDCS and tRNS + DC-offset in MDD. These findings directly contrast with evidence of tRNS-induced enhancements in WM in healthy individuals.

Introducing RELAX: An automated pre-processing pipeline for cleaning EEG data - Part 1: Algorithm and application to oscillations.

OBJECTIVE: Electroencephalographic (EEG) data are often contaminated with non-neural artifacts which can confound experimental results. Current artifact cleaning approaches often require costly manual input. Our aim was to provide a fully automated EEG cleaning pipeline that addresses all artifact types and improves measurement of EEG outcomes METHODS: We developed RELAX (the Reduction of Electroencephalographic Artifacts). RELAX cleans continuous data using Multi-channel Wiener filtering [MWF] and/or wavelet enhanced independent component analysis [wICA] applied to artifacts identified by ICLabel [wICA_ICLabel]). Several versions of RELAX were compared using three datasets (N = 213, 60 and 23 respectively) against six commonly used pipelines across a range of artifact cleaning metrics, including measures of remaining blink and muscle activity, and the variance explained by experimental manipulations after cleaning. RESULTS: RELAX with MWF and wICA_ICLabel showed amongst the best performance at cleaning blink and muscle artifacts while preserving neural signal. RELAX with wICA_ICLabel only may perform better at differentiating alpha oscillations between working memory conditions. CONCLUSIONS: RELAX provides automated, objective and high-performing EEG cleaning, is easy to use, and freely available on GitHub. SIGNIFICANCE: We recommend RELAX for data cleaning across EEG studies to reduce artifact confounds, improve outcome measurement and improve inter-study consistency.

RELAX part 2: A fully automated EEG data cleaning algorithm that is applicable to Event-Related-Potentials.

OBJECTIVE: Electroencephalography (EEG) is often used to examine neural activity time-locked to stimuli presentation, referred to as Event-Related Potentials (ERP). However, EEG is influenced by non-neural artifacts, which can confound ERP comparisons. Artifact cleaning reduces artifacts, but often requires time-consuming manual decisions. Most automated methods filter frequencies <1 Hz out of the data, so are not recommended for ERPs (which contain frequencies <1 Hz). Our aim was to test the RELAX (Reduction of Electroencephalographic Artifacts) pre-processing pipeline for use on ERP data. METHODS: The cleaning performance of multiple versions of RELAX were compared to four commonly used EEG cleaning pipelines across both artifact cleaning metrics and the amount of variance in ERPs explained by different conditions in a Go-Nogo task. Results RELAX with Multi-channel Wiener Filtering (MWF) and wavelet-enhanced independent component analysis applied to artifacts identified with ICLabel (wICA_ICLabel) cleaned data most effectively and produced amongst the most dependable ERP estimates. RELAX with wICA_ICLabel only or MWF_only may detect effects better for some ERPs. CONCLUSIONS: RELAX shows high artifact cleaning performance even when data is high-pass filtered at 0.25 Hz (applicable to ERP analyses). SIGNIFICANCE: RELAX is easy to implement via EEGLAB in MATLAB and freely available on GitHub. Given its performance and objectivity we recommend RELAX to improve artifact cleaning and consistency across ERP research.

Transcranial random noise stimulation is more effective than transcranial direct current stimulation for enhancing working memory in healthy individuals: Behavioural and electrophysiological evidence.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been shown to improve working memory (WM) performance in healthy individuals, however effects tend to be modest and variable. Transcranial random noise stimulation (tRNS) can be delivered with a direct-current offset (DC-offset) to induce equal or even greater effects on cortical excitability than tDCS. To-date, no research has directly compared the effects of these techniques on WM performance or underlying neurophysiological activity. OBJECTIVE: To compare the effects of anodal tDCS, tRNS + DC-offset, or sham stimulation over the left dorsolateral prefrontal cortex (DLPFC) on WM performance and task-related EEG oscillatory activity in healthy adults. METHODS: Using a between-subjects design, 49 participants were allocated to receive either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left DLPFC. Changes in WM performance were assessed using the Sternberg WM task completed before and 5- and 25-min post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) of oscillatory activity was analysed from EEG recorded during WM encoding and maintenance. RESULTS: tRNS induced more pronounced and consistent enhancements in WM accuracy when compared to both tDCS and sham stimulation. Improvements in WM performance following tRNS were accompanied by increased theta ERS and diminished gamma ERD during WM encoding, which were significantly greater than those observed following anodal tDCS or sham stimulation. CONCLUSIONS: These findings demonstrate the potential of tRNS + DC-offset to modulate cognitive and electrophysiological measures of WM and raise the possibility that tRNS + DC-offset may be more effective and reliable than tDCS for enhancing WM performance in healthy individuals.

Individuals with depression display abnormal modulation of neural oscillatory activity during working memory encoding and maintenance.

PURPOSE: To investigate neural oscillatory activity supporting working memory (WM) processing in depressed individuals and healthy controls. METHODS: Forty-six participants with Major Depressive Disorder (MDD) and 41 healthy controls balanced on age, gender, and WM ability completed a Sternberg verbal WM task with concurrent electroencephalography recording. Oscillatory activity was calculated for upper alpha, theta, and gamma frequency bands during WM encoding and maintenance. RESULTS: WM performance did not differ between groups. When compared to healthy controls, depressed individuals displayed reduced frontal-midline theta power and increased occipital upper alpha power during WM encoding, and reductions in frontal-midline theta power and occipital gamma and upper alpha power during WM maintenance. Higher depression severity was associated with greater reductions upper alpha and gamma power during WM maintenance. CONCLUSIONS: Depressed individuals displayed prominent alterations in oscillatory activity during WM encoding and maintenance, indicating that the neural processes which support WM processing are altered in MDD even when no cognitive impairments are observed.

Differentiating responders and non-responders to rTMS treatment for depression after one week using resting EEG connectivity measures.

BACKGROUND: Non-response to repetitive transcranial magnetic stimulation (rTMS) treatment for depression is costly for both patients and clinics. Simple and cheap methods to predict response would reduce this burden. Resting EEG measures differentiate responders from non-responders, so may have utility for response prediction. METHODS: Fifty patients with treatment resistant depression and 21 controls had resting electroencephalography (EEG) recorded at baseline (BL). Patients underwent 5-8 weeks of rTMS treatment, with EEG recordings repeated at week 1 (W1). Forty-two participants had valid BL and W1 EEG data, and 12 were responders. Responders and non-responders were compared at BL and W1 in measures of theta (4-8 Hz) and alpha (8-13 Hz) power and connectivity, frontal theta cordance and alpha peak frequency. Control group comparisons were made for measures that differed between responders and non-responders. A machine learning algorithm assessed the potential to differentiate responders from non-responders using EEG measures in combination with change in depression scores from BL to W1. RESULTS: Responders showed elevated theta connectivity across BL and W1. No other EEG measures differed between groups. Responders could be distinguished from non-responders with a mean sensitivity of 0.84 (p = 0.001) and specificity of 0.89 (p = 0.002) using cross-validated machine learning classification on the combination of all EEG and mood measures. LIMITATIONS: The low response rate limited our sample size to only 12 responders. CONCLUSION: Resting theta connectivity at BL and W1 differ between responders and non-responders, and show potential for predicting response to rTMS treatment for depression.

Responders to rTMS for depression show increased fronto-midline theta and theta connectivity compared to non-responders.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, but only some individuals respond. Predicting response could reduce patient and clinical burden. Neural activity related to working memory (WM) has been related to mood improvements, so may represent a biomarker for response prediction. PRIMARY HYPOTHESES: We expected higher theta and alpha activity in responders compared to non-responders to rTMS. METHODS: Fifty patients with treatment resistant depression and twenty controls performed a WM task while electroencephalography (EEG) was recorded. Patients underwent 5-8 weeks of rTMS treatment, repeating the EEG at week 1 (W1). Of the 39 participants with valid WM-related EEG data from baseline and W1, 10 were responders. Comparisons between responders and non-responders were made at baseline and W1 for measures of theta (4-8 Hz), upper alpha (10-12.5 Hz), and gamma (30-45 Hz) power, connectivity, and theta-gamma coupling. The control group's measures were compared to the depression group's baseline measures separately. RESULTS: Responders showed higher levels of WM-related fronto-midline theta power and theta connectivity compared to non-responders at baseline and W1. Responder's fronto-midline theta power and connectivity was similar to controls. Responders also showed an increase in gamma connectivity from baseline to W1, with a concurrent improvement in mood and WM reaction times. An unbiased combination of all measures provided mean sensitivity of 0.90 at predicting responders and specificity of 0.92 in a predictive machine learning algorithm. CONCLUSION: Baseline and W1 fronto-midline theta power and theta connectivity show good potential for predicting response to rTMS treatment for depression.

A rare exception to Haldane's rule: Are X chromosomes key to hybrid incompatibilities?

The prevalence of Haldane's rule suggests that sex chromosomes commonly have a key role in reproductive barriers and speciation. However, the majority of research on Haldane's rule has been conducted in species with conventional sex determination systems (XY and ZW) and exceptions to the rule have been understudied. Here we test the role of X-linked incompatibilities in a rare exception to Haldane's rule for female sterility in field cricket sister species (Teleogryllus oceanicus and T. commodus). Both have an XO sex determination system. Using three generations of crosses, we introgressed X chromosomes from each species onto different, mixed genomic backgrounds to test predictions about the fertility and viability of each cross type. We predicted that females with two different species X chromosomes would suffer reduced fertility and viability compared with females with two parental X chromosomes. However, we found no strong support for such X-linked incompatibilities. Our results preclude X-X incompatibilities and instead support an interchromosomal epistatic basis to hybrid female sterility. We discuss the broader implications of these findings, principally whether deviations from Haldane's rule might be more prevalent in species without dimorphic sex chromosomes.

Rapid evolution and gene expression: a rapidly evolving Mendelian trait that silences field crickets has widespread effects on mRNA and protein expression.

A major advance in modern evolutionary biology is the ability to start linking phenotypic evolution in the wild with genomic changes that underlie that evolution. We capitalized on a rapidly evolving Hawaiian population of crickets (Teleogryllus oceanicus) to test hypotheses about the genomic consequences of a recent Mendelian mutation of large effect which disrupts the development of sound-producing structures on male forewings. The resulting silent phenotype, flatwing, persists because of natural selection imposed by an acoustically orienting parasitoid, but it interferes with mate attraction. We examined gene expression differences in developing wing buds of wild-type and flatwing male crickets using RNA-seq and quantitative proteomics. Most differentially expressed (DE) transcripts were down-regulated in flatwing males (625 up vs. 1716 down), whereas up- and down-regulated proteins were equally represented (30 up and 34 down). Differences between morphs were clearly not restricted to a single pathway, and we recovered annotations associated with a broad array of functions that would not be predicted a priori. Using a candidate gene detection test based on homology, we identified 30% of putative Drosophila wing development genes in the cricket transcriptome, but only 10% were DE. In addition to wing-related annotations, endocrine pathways and several biological processes such as reproduction, immunity and locomotion were DE in the mutant crickets at both biological levels. Our results illuminate the breadth of genetic pathways that are potentially affected in the early stages of adaptation.

Neural evidence that conscious awareness of errors is reduced in depression following a traumatic brain injury.

Impaired error awareness is related to poorer outcome following traumatic brain injury (TBI). Error awareness deficits are also found in major depressive disorder (MDD), but have not been examined in the MDD that follows a TBI (TBI-MDD). This study assessed neural activity related to error awareness in TBI-MDD. Four groups completed a response inhibition task while EEG was recorded- healthy controls (N = 15), MDD-only (N = 15), TBI-only (N = 16), and TBI-MDD (N = 12). Error related EEG activity was compared using powerful randomisation statistics that included all electrodes and time points. Participants with TBI-MDD displayed less frontally distributed neural activity, suggesting reduced contribution from frontal generating sources. Neural activity during this time window is thought to reflect conscious awareness of errors. The TBI-only and MDD-only groups did not differ from controls, and early error processing was unaffected, suggesting early error detection is intact.

Socially flexible female choice and premating isolation in field crickets (Teleogryllus spp.).

Social influences on mate choice are predicted to influence evolutionary divergence of closely related taxa, because of the key role mate choice plays in reproductive isolation. However, it is unclear whether females choosing between heterospecific and conspecific male signals use previously experienced social information in the same manner or to the same extent that they do when discriminating among conspecific mates only. We tested this using two field cricket sister species (Teleogryllus oceanicus and Teleogryllus commodus), in which considerable information is known about the role of male calling song in premating isolation, in addition to the influence of acoustic experience on the development of reproductive traits. We manipulated the acoustic experience of replicate populations of both species and found, unexpectedly, that experience of male calling song during rearing did not change how accurate females were in choosing a conspecific over a heterospecific male song during playback trials. However, females with acoustic experience were considerably less responsive to male song compared with naïve females. Our results suggest that variation in the acoustic environment affects mate choice in both species, but that it may have a limited impact on premating isolation. The fact that social flexibility during interspecific mate discrimination does not appear to operate identically to that which occurs during conspecific mate discrimination highlights the importance of considering the context in which animals exercise socially flexible mating behaviours. We suggest an explanation for why social flexibility might be context dependent and discuss the consequences of such flexibility for the evolution of reproductive isolation.

Does signalling mitigate the cost of agonistic interactions? A test in a cricket that has lost its song.

Prevailing models of animal communication assume that signalling during aggressive conflict mitigates the costs of fighting. We tested this assumption by staging dyadic encounters between male field crickets, Teleogryllus oceanicus, under three conditions: (i) both males could sing aggressive songs, (ii) neither male could sing, and (iii) one male could sing but the other could not. We conducted experiments on males from a Hawaiian population from Kauai that has recently evolved signal loss, and males from a Hawaiian population from the Big Island that has not. Among both populations, interactions between two silent males were characterized by higher levels of aggression than interactions involving one or two singing males. Because the level of aggression is strongly related to the cost of fighting, these data demonstrate that signalling mitigates the cost of fighting. In mixed trials, we found no statistically significant differences between the behaviour of calling and non-calling males in either population. We conclude that there is no evidence that the Kauai population exhibits special adaptations to alleviate the costs of signal loss. Finally, we found that males were much more likely to signal after their opponent's retreat than after their own retreat. Aggressive song therefore meets the definition of a 'victory display'.

Beyond the point of no return? A comparison of genetic diversity in captive and wild populations of two nearly extinct species of Goodeid fish reveals that one is inbred in the wild.

The relative importance of genetic and non-genetic factors in extinction liability has been extensively debated. Here, we examine the levels of genetic variability at 13 (seven informative) loci in wild and captive populations of two endangered species of Mexican Goodeid fish, Ameca splendens and Zoogoneticus tequila. Allelic diversity was higher in the wild populations, and F(IS) lower. Values of theta (=4Nemu) were estimated using a coalescent approach. These implied that the effective population size of all captive populations of A. splendens were smaller than that of the wild population; qualitatively similar results were obtained using an analytical method based on within-population gene identity disequilibrium. However, the wild population of Z. tequila did not show a significantly greater estimate of theta. We used the Beaumont approach to infer population declines, and found that both species showed clear evidence of a decline in effective population size, although this was stronger and probably occurred over a longer period of time in Z. tequila than in A. splendens. The decline in Z. tequila probably occurred before captive populations were established. We discuss implications for the conservation of critically endangered populations.

Are solitary and gregarious Mormon crickets (Anabrus simplex, Orthoptera, Tettigoniidae) genetically distinct?

Phase polyphenisms are usually thought to reflect plastic responses of species, independent of genetic differences; however, phase differences could correlate with genetic differentiation for various reasons. Mormon crickets appear to occur in two phases that differ in morphology and behaviour. Solitary individuals are cryptic and sedentary whereas gregarious individuals form bands, migrate, and are aposematically coloured. These traits have been thought to be phenotypically plastic and induced by environmental conditions. However, there has been no previous investigation of the extent of genetic differences between solitary and gregarious populations of this widespread North American species. We sequenced two mitochondrial genes, COII and COIII, in samples of Mormon crickets from gregarious populations west of the continental divide and solitary mountain populations primarily east of the divide. Sequencing revealed two genetically distinct clades that broadly correspond with the solitary eastern populations and the mainly gregarious western populations. We used coalescent modelling to test the hypothesis that the species consists of two deep genetic clades, as opposed to a series of equally distinct populations. Results allowed us to reject the null hypothesis that a radiation independent of phase produced these clades, and molecular clock estimates indicate the time of divergence to be approximately 2 million years ago. This work establishes that the solitary populations found in the mountains on the eastern slope are part of a clade that is genetically distinct from the western populations, which are primarily gregarious, and the implications of this apparent correlation between phase and genetic differentiation are discussed.