A novel approach to modulating response inhibition: Multi-channel beta transcranial alternating current stimulation.

BACKGROUND: Deficits in response inhibition are associated with numerous psychiatric disorders. Previous studies have revealed the crucial role of the right inferior frontal gyrus (rIFG), pre-supplementary motor area (preSMA), and beta activity in these brain regions in response inhibition. Multi-channel transcranial alternating current stimulation (tACS) has garnered significant attention for its ability to modulate neural oscillations in brain networks. In this study, we employed multi-channel tACS targeting rIFG-preSMA network to investigate its impact on response inhibition in healthy adults. METHODS: In Experiment 1, 70 healthy participants were randomly assigned to receive 20 Hz in-phase, anti-phase, or sham stimulation over rIFG-preSMA network. Response inhibition was assessed using the stop-signal task during and after stimulation, and impulsiveness was measured via the Barratt Impulsiveness Scale. Additionally, 25 participants received stimulation at the left supraorbital area to account for potential effects of the "return" electrode. Experiment 2, consisting of 25 participants, was conducted to validate the primary findings of Experiment 1, including both in-phase and sham stimulation conditions, based on prior estimations derived from the results of Experiment 1. RESULTS: In Experiment 1, we found that in-phase stimulation significantly improved response inhibition compared with sham stimulation, whereas anti-phase stimulation did not. These findings were consistently replicated in Experiment 2. We also conducted an exploratory analysis of the multi-channel tACS impact, revealing that its effects primarily emerged during the post-stimulation phase. Furthermore, individuals with higher baseline attentional impulsiveness showed greater improvements in the in-phase stimulation group. CONCLUSIONS: These results demonstrate that in-phase beta-tACS over rIFG-preSMA network can effectively improve response inhibition in healthy adults and provides a new potential treatment for patients with deficits in response inhibition.

Dual-site beta tACS over rIFG and M1 enhances response inhibition: A parallel multiple control and replication study.

Response inhibition is a core component of cognitive control. Past electrophysiology and neuroimaging studies have identified beta oscillations and inhibitory control cortical regions correlated with response inhibition, including the right inferior frontal gyrus (rIFG) and primary motor cortex (M1). Hence, increasing beta activity in multiple brain regions is a potential way to enhance response inhibition. Here, a novel dual-site transcranial alternating current stimulation (tACS) method was used to modulate beta activity over the rIFG-M1 network in a sample of 115 (excluding 2 participants) with multiple control groups and a replicated experimental design. In Experiment 1, 70 healthy participants were randomly assigned to three dual-site beta-tACS groups, including in-phase, anti-phase or sham stimulation. During and after stimulation, participants were required to complete the stop-signal task, and electroencephalography (EEG) was collected before and after stimulation. The Barratt Impulsiveness Scale was completed before the experiment to evaluate participants' impulsiveness. In addition, we conducted an active control experiment with a sample size of 20 to exclude the potential effects of the dual-site tACS "return" electrode. To validate the behavioural findings of Experiment 1, 25 healthy participants took part in Experiment 2 and were randomized into two groups, including in-phase and sham stimulation groups. We found that compared to the sham group, in-phase but not anti-phase beta-tACS significantly improved both response inhibition performance and beta synchronization of the inhibitory control network in Experiment 1. Furthermore, the increased beta synchronization was correlated with enhanced response inhibition. In an independent sample of Experiment 2, the enhanced response inhibition performance observed in the in-phase group was replicated. After combining the data from the above two experiments, the time dynamics analysis revealed that the in-phase beta-tACS effect occurred in the post-stimulation period but not the stimulation period. The state-dependence analysis showed that individuals with poorer baseline response inhibition or higher attentional impulsiveness had greater improvement in response inhibition for the in-phase group. These findings strongly support that response inhibition in healthy adults can be improved by in-phase dual-site beta-tACS of the rIFG-M1 network, and provide a new potential treatment targets of synchronized cortical network activity for patients with clinically deficient response inhibition.

Resting-state electroencephalography theta predicts neurofeedback treatment 4-month follow-up response in nicotine addiction.

Background: The high rate of long-term relapse is a major cause of smoking cessation failure. Recently, neurofeedback training has been widely used in the treatment of nicotine addiction; however, approximately 30% of subjects fail to benefit from this intervention. Our previous randomised clinical trial (RCT) examined cognition-guided neurofeedback and demonstrated a significant decrease in daily cigarette consumption at the 4-month follow-up. However, significant individual differences were observed in the 4-month follow-up effects of decreased cigarette consumption. Therefore, it is critical to identify who will benefit from pre-neurofeedback. Aims: We examined whether the resting-state electroencephalography (EEG) characteristics from pre-neurofeedback predicted the 4-month follow-up effects and explored the possible mechanisms. Methods: This was a double-blind RCT. A total of 60 participants with nicotine dependence were randomly assigned to either the real-feedback or yoked-feedback group. They underwent 6 min closed-eye resting EEG recordings both before and after two neurofeedback sessions. A follow-up assessment was conducted after 4 months. Results: The frontal resting-state theta power spectral density (PSD) was significantly altered in the real-feedback group after two neurofeedback visits. Higher theta PSD in the real-feedback group before neurofeedback was the only predictor of decreased cigarette consumption at the 4-month follow-up. Further reliability analysis revealed a significant positive correlation between theta PSD pre-neurofeedback and post-neurofeedback. A leave-one-out cross-validated linear regression of the theta PSD pre-neurofeedback demonstrated a significant correlation between the predicted and observed reductions in cigarette consumption at the 4-month follow-up. Finally, source analysis revealed that the brain mechanisms of the theta PSD predictor were located in the orbital frontal cortex. Conclusions: Our study demonstrated changes in the resting-state theta PSD following neurofeedback training. Moreover, the resting-state theta PSD may serve as a prognostic marker of neurofeedback effects. A higher resting-state theta PSD predicts a better long-term response to neurofeedback treatment, which may facilitate the selection of individualised interventions. Trial registration number: ChiCTR-IPR-17011710.

Morphological and transcriptomic analysis of attenuated and virulent strains of Phytophthora infestans.

Phytophthora infestans is a hemibiotroph Oomycete that primarily infects tomato. In this study, the growth status and pathogenicity of attenuated and virulent strains of Phytophthora infestans were determined. Furthermore, RNA-seq technology was used to explore the differences in gene transcription levels between attenuated and virulent strains. Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the differentially expressed genes (DEGs) obtained by sequencing, and the significant DEGs related to the growth and pathogenicity of the strains were screened from the significantly enriched pathways. The results revealed that compared with the virulent strain, the growth of the attenuated strain was inhibited, the structure of hyphae was destroyed, and the disease index was decreased. The differences in the growth status and disease index of the attenuated strain were related to changes in several metabolic pathways, and the DEGs in the metabolic pathways indicated alterations in the attenuated strain growth and pathogenicity. There were 2,651 DEGs in the attenuated strain, of which 1,086 were upregulated and 1,565 were downregulated. The inhibited growth of the attenuated strain was associated with accumulation of excessive glucose, decomposition of serine/glycine, and reduction of tryptophan synthesis. The reduced pathogenicity of the strain was associated with degradation of the cell wall and reduced formation of melanin and α-keto butyric acid. These results could offer insights into the mechanisms of attenuation of Phytophthora infestans.

Berberine Inhibits Human Melanoma A375.S2 Cell Migration and Invasion via Affecting the FAK, uPA, and NF-κB Signaling Pathways and Inhibits PLX4032 Resistant A375.S2 Cell Migration In Vitro.

Many studies have demonstrated that berberine inhibited the cell migration and invasion in human cancer cell lines. However, the exact molecular mechanism of berberine inhibiting the cell migration and invasion of human melanoma A375.S2 and A375.S2/PLX (PLX4032 induced resistant A375.S2) skin cancer cells remains unknown. In this study, we investigated the anti-metastasis mechanisms of berberine in human melanoma cancer A375.S2 cells and A375.S2/PLX resistant cells in vitro. Berberine at low concentrations (0, 1, 1.5 and 2 µM) induced cell morphological changes and reduced the viable cell number and inhibited the mobility, migration, and invasion of A375.S2 cells that were assayed by wound healing and transwell filter. The gelatin zymography assay showed that berberine slightly inhibited MMP-9 activity in A375.S2 cells. Results from western blotting indicated that berberine inhibited the expression of MMP-1, MMP-13, E-cadherin, N-cadherin, RhoA, ROCK1, SOS-1, GRB2, Ras, p-ERK1/2, p-c-Jun, p-FAK, p-AKT, NF-κB, and uPA after 24 h of treatment, but increased the PKC and PI3K in A375.S2 cells. PLX4032 is an inhibitor of the BRAFV600E mutation and used for the treatment of cancer cells harboring activated BRAF mutations. Berberine decrease cell number and inhibited the cell mobility in the resistant A375.S2 (A375.S2/PLX, PLX4032 generated resistant A375.S2 cells). Based on these observations, we suggest that the potential of berberine as an anti-metastatic agent in melanoma that deserves to be investigated in more detail, including in vivo studies in future.