Theta oscillatory dynamics of inhibitory control,error processing,and post-error adjustments: Neural underpinnings and alcohol-induced dysregulation in social drinkers

Background

Alcohol intoxication impairs inhibitory control, resulting in disinhibited, impulsive behavior. The anterior cingulate cortex (ACC) plays an essential role in a range of executive functions and is sensitive to the effects of alcohol, which contributes to the top-down cognitive dysregulation. This study used a multimodal approach to examine the acute effects of alcohol on the neural underpinnings of inhibitory control, inhibition failures, and neurobehavioral optimization as reflected in trial-to-trial dynamics of post-error adjustments.

Methods

Adult social drinkers served as their own controls by participating in the Go/NoGo task during acute alcohol and placebo conditions in a multi-session, counterbalanced design. Distributed source modeling of the magnetoencephalographic signal was combined with structural magnetic resonance imaging to characterize the spatio-temporal dynamics of inhibitory control in the time-frequency domain.

Results

Successful response inhibition (NoGo) elicited right-lateralized event-related theta power (4 to 7 Hz). Errors elicited a short-latency increase in theta power in the dorsal (dACC), followed by activity in the rostral (rACC), which may underlie an affective “oh, no!” orienting response to errors. Error-related theta in the dACC was associated with subsequent activity of the motor areas on the first post-error trial, suggesting the occurrence of post-error output adjustments. Importantly, a gradual increase of the dACC theta across post-error trials closely tracked improvements in accuracy under placebo, which may reflect cognitive control engagement to optimize response accuracy. In contrast, alcohol increased NoGo commission errors, dysregulated theta during correct NoGo withholding, and abolished the post-error theta enhancement of cognitive control.

Conclusions

Confirming the sensitivity of frontal theta to inhibitory control and error monitoring, the results support functional and temporal dissociation along the dorso-rostral axis of the ACC and the deleterious effects of alcohol on the frontal circuitry subserving top-down regulation. Over time, alcohol-induced disinhibition may give rise to compulsive drinking and contribute to alcohol misuse.     

Orexin A Suppresses the Expression of Exosomal PD-L1 in Colon Cancer and Promotes T Cell Activity by Inhibiting JAK2/STAT3 Signaling Pathway

Digestive Diseases and Sciences - Colon cancer, ranked third in cancer related mortality, is the most common malignant cancer of digestive tract. Though immune checkpoint inhibitors show promising...     

Genetic diversity of VP3 of goose parvovirus isolated from Southeastern China during 2012–2013

Although vaccine and passive immunotherapy were widely used to prevent goose parvovirus (GPV) infection in goose industry, GPV still poses a big problem in Southeastern China. In this study, 23 GPV isolates were isolated from goslings suspected with GPV infection in Southeastern China during 2012–2013, and the genetic diversity of VP3 of GPV was analyzed. Phylogenetic tree revealed that these isolates could be clustered into two groups, and 11 of 23 could be further clustered into a new subgroup. Moreover, eight novel mutations and seventeen conserved amino acids were found in these 23 isolates in comparison with isolates previously deposited in GenBank. These isolates and findings not only provide insights into the etiology and molecular characteristics of GPV endemic in Southeastern China, but also enrich the GPV genetic information for better controlling the disease.     

VPS35 and DNAJC13 disease-causing variants in essential tremor

Exome-sequencing analyses have identified vacuolar protein sorting 35 homolog (VPS35) and DnaJ (Hsp40) homolog, subfamily C, member 13 (DNAJC13) harboring disease-causing variants for Parkinson disease (PD). Owing to the suggested clinical, pathological and genetic overlap between PD and essential tremor (ET) we assessed the presence of two VPS35 and DNAJC13 disease-causing variants in ET patients. TaqMan probes were used to genotype VPS35 c.1858G>A (p.(D620N)) (rs188286943) and DNAJC13 c.2564A>G (p.(N855S)) (rs387907571) in 571 ET patients of European descent, and microsatellite markers were used to define the disease haplotype in variant carriers. Genotyping of DNAJC13 identified two ET patients harboring the c.2564A>G (p.(N855S)) variant previously identified in PD patients. Both patients appear to share the disease haplotype previously reported. ET patients with the VPS35 c.1858G>A (p.(D620N)) variants were not observed. Although a genetic link between PD and ET has been suggested, DNAJC13 c.2564A>G (p.(N855S)) represents the first disease-causing variant identified in both, and suggests the regulation of clathrin dynamics and endosomal trafficking in the pathophysiology of a subset of ET patients.     

Gastrointestinal transit time (GITT) in normal Chinese and patients

Two kinds of radiopaque pellets were ingested as markers to determine GITT in 60 normal subjects, 7 patients with ulcerative colitis (UC), 10 patients with idiopathic constipation (IC) and 8 patients with other diseases. The food contained 10-20g dietary fiber per day. Besides, GITT was determined in 14 normal subjects whose dietary content was 40-50g or 10g MO YU and 10-20g dietary fiber per day. Results are expressed in hours as 50% transit time (mean +/- s) and the values or normal subjects are as the follows: total GITT 25.0 +/- 7.3h, mouth iteum TT 9.0 +/- 3.3h, colonic TT 15.9 +/- 7.5h. There was no difference in age or sex groups. However, in high dietary fiber or MO YU group, GITT shortened significantly. Abnormal GITT was shown in patients with UC, IC, other gut and systemic diseases. In conclusion, the method employed in the present study is simple, safe and useful in the clinical study of gastrointestinal motility; and may provide important information to elucidate the pathophysiology of the diseases related to disorders in motility of the digestive tract.     

Bronchial Hyperresponsiveness in Farmers: Relation to Respiratory Symptoms, Lung Function, and Atopy

There is only limited information on the factors associated with nonspecific bronchial hyperresponsiveness (BHR) in farmers. Our purpose was to examine the relationship between BHR and respiratory symptoms, atopy, and abnormalities of lung function in a sample of French farmers. Farmers scheduled for a preventive medicine check-up in northeastern France were examined. Occupational exposure, respiratory symptoms, and work-related symptoms were assessed by questionnaire, sensitization to 34 common and agricultural allergens by skin prick tests, and BHR by the single-dose (1,200 μg) acetylcholine (ACh) challenge test. Data were obtained from 741 farmers (95% of those invited). Seventy-seven subjects (10.3%) had BHR defined as a fall in forced expiratory volume in 1 s (FEV₁) ≥ 10% after the inhalation of ACh or, for those with a poor lung function, an increase in FEV₁ > 10% and > 200 ml after the inhalation of 200 μg of salbutamol. The proportion of asthmalike symptoms, especially wheeze during work, positive skin tests to acarian (storage mites) and cereal dust allergens, and low levels of lung function was significantly greater among reactors than among nonreactors. Stepwise logistic regression analysis showed a significant and independent association between BHR and wheezing during work (OR = 4.99; 95% CI = 2.29–10.89; p= 0.0001) and baseline FEV₁ (OR = 1.49; 95% CI = 1.05–2.20; p= 0.026). In conclusion, hyperreactive farmers had significantly more asthmalike symptoms, positive skin tests, and abnormal lung function than normoreactive farmers. Work-related wheeze and low baseline FEV₁ were significantly and independently associated with BHR. Accepted for publication: 26 January 1999     

The validity of hair analysis for detecting cocaine and heroin use among addicts.

Radioimmunoassay of hair (RIAH) was compared with two criterion measures, confidential EMIT urinalysis and self-reporting of cocaine/heroin use, for a purposive sample of 134 persons in methadone treatment. Positive or negative RIAH was "confirmed" by urinalysis and/or self-report in 87 and 84% of the cases for cocaine and heroin (morphine), respectively. Corroborative evidence indicated that "excess" RIAH positives were attributable to the narrow window of detection for urinalysis (2 days), failure to admit drug use even to researchers, and/or inadvertent ingestion of small amounts of drug. A global self-report of cocaine use intensity was related to amount in the hair.     

Association of distal chromosome 2q with IDDM in Japanese subjects

Summary An insulin-dependent diabetes mellitus (IDDM)-susceptibility gene (IDDM13) has recently been mapped to a region of distal chromosome 2q, which is syntenic to the region of mouse chromosome 1 containing a murine susceptibility gene for IDDM, Idd5. To determine the contribution of this region to IDDM disease susceptibility further and to narrow the region for positional cloning of susceptibility genes, we have studied the association of distal chromosome 2q with IDDM in the genetically distinct Japanese population. A 137 mobility unit (mu) allele at D2S137 locus was significantly associated with IDDM (odds ratio 1.92, p = 0.0016). Other markers, D2S301 and D2S143, located in the same region were not associated with IDDM, indicating that IDDM13 is in linkage disequilibrium with D2S137, but not with D2S301 or D2S143. The association of D2S137 with IDDM was observed in patients lacking one of two high risk HLA alleles, DQB1 ^* 0303 and DQB1 ^* 0401, but not in patients with either of these alleles. The frequency of high risk HLA alleles was significantly lower in patients with the susceptible allele at D2S137, suggesting that IDDM13 contributes to IDDM susceptibility in subjects without high risk genotypes at IDDM1. Demonstration of allelic association of D2S137 with IDDM localizes IDDM13 in the close vicinity (< 2 centiMorgans) of D2S137, greatly facilitating fine structure mapping and positional cloning of IDDM13. [Diabetologia (1998) 41: 228–232] Received: 27 March 1997 and in revised form: 3 October 1997