Mapping access to meaning in adolescents with autism: Atypical lateralization and spatiotemporal patterns as a function of language ability.

Individuals with autism spectrum disorders (ASD) vary in their language abilities, associated with atypical patterns of brain activity. However, few studies have examined the spatiotemporal profiles of lexico-semantic processing in ASD, particularly as a function of language heterogeneity. Thirty-nine high-functioning adolescents with ASD and 21 typically developing (TD) peers took part in a lexical decision task that combined semantic access with demands on cognitive control. Spatiotemporal characteristics of the processing stages were examined with a multimodal anatomically-constrained magnetoencephalography (aMEG) approach, which integrates MEG with structural MRI. Additional EEG data were acquired from a limited montage simultaneously with MEG. TD adolescents showed the canonical left-dominant activity in frontotemporal regions during both early (N250m) and late (N400m) stages of lexical access and semantic integration. In contrast, the ASD participants showed bilateral engagement of the frontotemporal language network, indicative of compensatory recruitment of the right hemisphere. The left temporal N400m was prominent in both groups, confirming preserved attempts to access meaning. In contrast, the left prefrontal N400m was reduced in ASD participants, consistent with impaired semantic/contextual integration and inhibitory control. To further investigate the impact of language proficiency, the ASD sample was stratified into high- and low-performing (H-ASD and L-ASD) subgroups based on their task accuracy. The H-ASD subgroup performed on par with the TD group and showed greater activity in the right prefrontal and bilateral temporal cortices relative to the L-ASD subgroup, suggesting compensatory engagement. The L-ASD subgroup additionally showed reduced and delayed left prefrontal N400m, consistent with more profound semantic and executive impairments in this subgroup. These distinct spatiotemporal activity profiles reveal the neural underpinnings of the ASD-specific access to meaning and provide insight into the phenotypic heterogeneity of language in ASD, which may be a result of different neurodevelopmental trajectories and adoption of compensatory strategies.

MEG Theta during Lexico-Semantic and Executive Processing Is Altered in High-Functioning Adolescents with Autism.

Neuroimaging studies have revealed atypical activation during language and executive tasks in individuals with autism spectrum disorders (ASD). However, the spatiotemporal stages of processing associated with these dysfunctions remain poorly understood. Using an anatomically constrained magnetoencephalography approach, we examined event-related theta oscillations during a double-duty lexical decision task that combined demands on lexico-semantic processing and executive functions. Relative to typically developing peers, high-functioning adolescents with ASD had lower performance accuracy on trials engaging selective semantic retrieval and cognitive control. They showed an early overall theta increase in the left fusiform cortex followed by greater activity in the left-lateralized temporal (starting at ~250 ms) and frontal cortical areas (after ~450 ms) known to contribute to language processing. During response preparation and execution, the ASD group exhibited elevated theta in the anterior cingulate cortex, indicative of greater engagement of cognitive control. Simultaneously increased activity in the ipsilateral motor cortex may reflect a less lateralized and suboptimally organized motor circuitry. Spanning early sensory-specific and late response selection stages, the higher event-related theta responsivity in ASD may indicate compensatory recruitment to offset inefficient lexico-semantic retrieval under cognitively demanding conditions. Together, these findings provide further support for atypical language and executive functions in high-functioning ASD.

Compensatory neuroadaptation to binge drinking: Human evidence for allostasis.

Animal studies have established that acute alcohol increases neural inhibition and that frequent intoxication episodes elicit neuroadaptive changes in the excitatory/inhibitory neurotransmission balance. To compensate for the depressant effects of alcohol, neural hyperexcitability develops in alcohol use disorder and is manifested through withdrawal symptoms. It is unclear, however, whether neuroadaptive changes can be observed in young, emerging adults at lower levels of consumption in the absence of withdrawal symptoms. Here, we used an anatomically constrained magnetoencephalography method to assess cortical excitability in two independent sets of experiments. We measured early visual activity (1) in social drinkers during alcohol intoxication versus placebo conditions and (2) in parallel cohorts of sober binge drinkers (BDs) and light drinkers (LDs). Acute alcohol intoxication attenuated early sensory activity in the visual cortex in social drinkers, confirming its inhibitory effects on neurotransmission. In contrast, sober BDs showed greater neural responsivity compared with a matched group of LDs. A positive correlation between alcohol consumption and neural activity in BDs is indicative of cortical hyperexcitability associated with hazardous drinking. Furthermore, neural responsivity was positively correlated with alcohol intake in social drinkers whose drinking did not reach binge levels. This study provides novel evidence of compensatory imbalance reflected in the downregulation of inhibitory and upregulation of excitatory signaling associated with binge drinking in young, emerging adults. By contrasting acute effects and a history of BD, these results support the mechanistic model of allostasis. Direct neural measures are sensitive to synaptic currents and could serve as biomarkers of neuroadaptation.

Abnormal organization of inhibitory control functional networks in future binge drinkers.

BACKGROUND AND AIMS: Adolescent Binge drinking has become an increasing health and social concern, which cause several detrimental consequences for brain integrity. However, research on neurophysiological traits of vulnerability for binge drinking predisposition is limited at this time. In this work, we conducted a two-year longitudinal study with magnetoencephalography (MEG) over a cohort of initially alcohol-naive adolescents with the purpose of characterize inhibitory cortical networks' anomalies prior to alcohol consumption onset in those youths who will transit into binge drinkers years later. METHODS: Sixty-seven participant's inhibitory functional networks, and dysexecutive/impulsivity traits were measured by means of inhibitory task (go/no-go) and questionnaires battery. After a follow-up period of two years, we evaluated their alcohol consumption habits, sub-dividing them in two groups according to their alcohol intake patterns: future binge drinkers (fBD): n = 22; future Light/non-drinkers (fLD): n = 17. We evaluated whole-brain and seed-based functional connectivity profiles, as well as its correlation with impulsive and dysexecutive behaviours, searching for early abnormalities before consumption onset. RESULTS: For the first time, abnormalities in MEG functional networks and higher dysexecutive and impulsivity profiles were detected in alcohol-naïve adolescents who two years later became binge drinkers. Concretely, fBD exhibit a distinctive pattern of beta band hyperconnectivity among crucial regions of inhibitory control networks, positively correlated with behavioral traits and future alcohol intake rate. CONCLUSIONS: These findings strongly support the idea of early neurobiological vulnerabilities for substances consumption initiation, with inhibitory functional networks' abnormalities as a relevant neurophysiological marker of subjects at risk- we hypothesize this profile is due to neurodevelopmental and neurobiological differences involving cognitive control networks and neurotransmission pathways.

Young alcohol binge drinkers have elevated blood endotoxin, peripheral inflammation and low cortisol levels: neuropsychological correlations in women.

Alcohol binge drinking is a pattern of heavy alcohol consumption that is increasingly practiced by adolescents and young adults. Evidence indicates that alcohol binges induce peripheral inflammation and an exacerbated neuroimmune response that may participate in alcohol-induced cognitive/behavioral dysfunctions. Here, we recruited 20-year-old male and female university students who were identified as binge drinkers for at least 2 years. Compared with controls, young alcohol binge drinkers had elevated levels of blood endotoxin and upregulated markers of the toll-like receptor 4/NF-κB inflammatory pathway in peripheral blood mononuclear cells, together with pro-inflammatory cytokine/chemokine release, oxidative stress and lipid peroxidation. These changes positively correlate with the estimated blood alcohol levels achieved during alcohol binge intoxication and negatively correlate with the time elapsed from the last alcohol consumption. The immune/inflammatory changes were more prominent in female drinkers, who showed elevated levels of alcohol danger-associated molecules, such as high mobility group box 1, indicating that there are sex-related differences in the peripheral inflammatory response to alcohol. In contrast, cortisol levels were decreased in alcohol binge drinkers. Finally, higher levels of inflammatory markers, mainly monocyte chemoattractant protein-1, as well as LPS, high mobility group box 1, toll-like receptor 4, IL-6 and ciclooxygenase-2, correlated with worse scores on episodic memory and executive functioning tasks in female binge drinkers but not in male binge drinkers. These results emphasize possible risky consequences of alcohol use in binge episodes during young adulthood and call attention to sex-related differences in the alcohol-induced immune/inflammatory and neurocognitive responses.

Increased plasma oleoylethanolamide and palmitoleoylethanolamide levels correlate with inflammatory changes in alcohol binge drinkers: the case of HMGB1 in women.

Alcohol binge drinking is a heavy pattern of alcohol consumption increasingly used by young people. In a previous study, we reported that young drinkers with a 2-year history of binge alcohol consumption had an overactivation of the innate immune system and peripheral inflammation when compared with controls. In the present study, we measured several biolipids that are fatty acid derivatives belonging to the acylethanolamide or 2-acylglycerol families in the plasma of the same subjects (n = 42; 20 men and 22 women). We found that during abstinence, alcohol binge drinkers had elevated plasma levels of oleoylethanolamide, palmitoleoylethanolamide, arachidonoylethanolamide, dihomo-γ-linolenoyl ethanolamide and linoleoyl ethanolamide, which positively correlated with changes in the mRNA expression of key inflammatory markers in peripheral blood mononuclear cells, such as toll-like receptors (TLR4), pro-inflammatory cytokines/chemokines interleukin-1 beta, interleukin-6 and monocyte chemoattractant protein-1, and cyclooxygenase-2. Additionally, plasma oleoylethanolamide positively correlated with plasma levels of high mobility group box-1, which is a danger-associated molecular pattern and an endogenous TLR4 agonist, specifically in female alcohol binge drinkers. No changes were observed in 2-acylglycerols in alcohol binge drinkers, although sex-related differences in these bioactive lipids as well as in palmitoleoylethanolamide and docosatetraenoylethanolamide levels were detected. These results extend the previous clinical findings observed in patients diagnosed with long-term alcohol use disorder to young users and suggest a prominent role for these lipids in the response to acute alcohol exposure.

The Brain of Binge Drinkers at Rest: Alterations in Theta and Beta Oscillations in First-Year College Students with a Binge Drinking Pattern.

Background: Previous studies have reported anomalous resting brain activity in the electroencephalogram (EEG) of alcoholics, often reflected as increased power in the beta and theta frequency bands. The effects of binge drinking, the most common pattern of excessive alcohol consumption during adolescence and youth, on brain activity at rest is still poorly known. In this study, we sought to assess the pattern of resting-state EEG oscillations in college-aged binge drinkers (BDs). Methods: Resting-state brain activity during eyes-open and eyes-closed conditions was recorded from 60 channels in 80 first-year undergraduate students (40 controls and 40 BDs). Cortical sources activity of EEG rhythms was estimated using exact Low-Resolution Electromagnetic Tomography (eLORETA) analysis. Results: EEG-source localization analysis revealed that BDs showed, in comparison with controls, significantly higher intracranial current density in the beta frequency band over the right temporal lobe (parahippocampal and fusiform gyri) during eyes-open resting state as well as higher intracranial current density in the theta band over the bilateral occipital cortex (cuneus and lingual gyrus) during eyes-closed resting condition. Conclusions: These findings are in line with previous results observing increased beta and/or theta power following chronic or heavy alcohol drinking in alcohol-dependent subjects and BDs. Increased tonic beta and theta oscillations are suggestive of an augmented cortical excitability and of potential difficulties in the information processing capacity in young BDs. Furthermore, enhanced EEG power in these frequency bands may respond to a neuromaturational delay as a result of excessive alcohol consumption during this critical brain developmental period.

Binge drinking affects brain oscillations linked to motor inhibition and execution.

INTRODUCTION: Neurofunctional studies have shown that binge drinking patterns of alcohol consumption during adolescence and youth are associated with anomalies in brain functioning. Recent evidence suggests that event-related oscillations may be an appropriate index of neurofunctional damage associated with alcoholism. However, there is no study to date that has evaluated the effects of binge drinking on oscillatory brain responses related to task performance. The purpose of the present study was to examine brain oscillations linked to motor inhibition and execution in young binge drinkers (BDs) compared with age-matched controls. METHODS: Electroencephalographic activity was recorded from 64 electrodes while 72 university students (36 controls and 36 BDs) performed a visual Go/NoGo task. Event-related oscillations along with the Go-P3 and NoGo-P3 event-related potential components were analysed. RESULTS: While no significant differences between groups were observed regarding event-related potentials, event-related oscillation analysis showed that BDs displayed a lower oscillatory response than controls in delta and theta frequency ranges during Go and NoGo conditions. CONCLUSIONS: Findings are congruent with event-related oscillation studies showing reduced delta and/or theta oscillations in alcoholics during Go/NoGo tasks. Thus, BDs appear to show disruptions in neural oscillations linked to motor inhibition and execution similar to those observed in alcohol-dependent subjects. Finally, these results are the first to evidence that oscillatory brain activity may be a sensitive indicator of underlying brain anomalies in young BDs, which could complement standard event-related potential measures.