Age-related differences in transient gamma band activity during working memory maintenance through adolescence.

Adolescence is a stage of development characterized by neurodevelopmental specialization of cognitive processes. In particular, working memory continues to improve through adolescence, with increases in response accuracy and decreases in response latency continuing well into the twenties. Human electroencephalogram (EEG) studies indicate that gamma oscillations (35-65 Hz) during the working memory delay period support the maintenance of mnemonic information guiding subsequent goal-driven behavior, which decrease in power with development. Importantly, recent electrophysiological studies have shown that gamma events, more so than sustained activity, may underlie working memory maintenance during the delay period. However, developmental differences in gamma events during working memory have not been studied. Here, we used EEG in conjunction with a novel spectral event processing approach to investigate age-related differences in transient gamma band activity during a memory guided saccade (MGS) task in 164 10- to 30-year-olds. Total gamma power was found to significantly decrease through adolescence, replicating prior findings. Results from the spectral event pipeline showed age-related decreases in the mean power of gamma events and trial-by-trial power variability across both the delay period and fixation epochs of the MGS task. In addition, we found that while event number decreased with age during the fixation period, the developmental decrease during the delay period was more dramatic, resulting in an increase in event spiking from fixation to delay in adolescence but not adulthood. While average power of the transient gamma events was found to mediate age-related differences in total gamma power in the fixation and delay periods, the number of gamma events was related to total power in only the delay period, suggesting that the power of gamma events may underlie the sustained gamma activity seen in EEG literature while the number of events may directly support age-related improvements in working memory maintenance. Our findings provide compelling new evidence for mechanistic changes in neural processing characterized by refinements in neural function as behavior becomes optimized in adulthood.

At the Heart of Neurological Dimensionality: Cross-Nosological and Multimodal Cardiac Interoceptive Deficits.

OBJECTIVE: Neurological nosology, based on categorical systems, has largely ignored dimensional aspects of neurocognitive impairments. Transdiagnostic dimensional approaches of interoception (the sensing of visceral signals) may improve the descriptions of cross-pathological symptoms at behavioral, electrophysiological, and anatomical levels. Alterations of cardiac interoception (encompassing multidimensional variables such as accuracy, learning, sensibility, and awareness) and its neural correlates (electrophysiological markers, imaging-based anatomical and functional connectivity) have been proposed as critical across disparate neurological disorders. However, no study has examined the specific impact of neural (relative to autonomic) disturbances of cardiac interoception or their differential manifestations across neurological conditions. METHODS: Here, we used a computational approach to classify and evaluate which markers of cardiac interoception (behavioral, metacognitive, electrophysiological, volumetric, or functional) offer the best discrimination between neurological conditions and cardiac (hypertensive) disease (model 1), and among neurological conditions (Alzheimer's disease, frontotemporal dementia, multiple sclerosis, and brain stroke; model 2). In total, the study comprised 52 neurological patients (mean [standard deviation] age = 55.1 [17.3] years; 37 women), 25 cardiac patients (age = 66.2 [9.1] years; 13 women), and 72 healthy controls (age = 52.65 [17.1] years; 50 women). RESULTS: Cardiac interoceptive outcomes successfully classified between neurological and cardiac conditions (model 1: >80% accuracy) but not among neurological conditions (model 2: 53% accuracy). Behavioral cardiac interoceptive alterations, although present in all conditions, were powerful in differentiating between neurological and cardiac diseases. However, among neurological conditions, cardiac interoceptive deficits presented more undifferentiated and unspecific disturbances across dimensions. CONCLUSIONS: Our result suggests a diffuse pattern of interoceptive alterations across neurological conditions, highlighting their potential role as dimensional, transdiagnostic markers.

Early onset consumption of coca paste associated with executive-attention vulnerability markers linked to caudate-frontal structural and functional abnormalities.

Coca paste is the most popular form of smoked cocaine (SC) in Latin America and also the most widespread among adolescents in vulnerable sectors of society, thus representing a significant public health concern. Despite evidence suggesting that abnormal executive-attention function is predictive of addiction to stimulant drugs, no study to date has compared clinically relevant neuropsychological (NPS) and physiological variables between individuals with histories of smoked cocaine dependence (SCD) and insufflated cocaine hydrochloride dependence (ICD). In this study we evaluated 25 SCD and 22 ICD subjects matched by poly-consumption profiles, and 25 healthy controls (CTR) matched by age, gender, education, and socioeconomic status. An exhaustive NPS battery was used to assess cognitive domains (attention, executive functions, fluid intelligence, memory, language and social cognition). We complemented this assessment with structural (MRI) and functional (fMRI) neuroimaging data. We found that executive function and attention impairments could be explained by the administration route of cocaine, with strongest impairments for the SCD group. SCD also presented reduced grey matter density relative to ICD and CTR in the bilateral caudate, a key area for executive and attentional function. Functional connectivity between left caudate and inferior frontal regions mediated the association between brain structure and behavioral performance. Our results highlight the relevance of assessing the route of administration of stimulants, both in clinical and research settings.

Relationship among subjective responses, flavor, and chemical composition across more than 800 commercial cannabis varieties.

BACKGROUND: Widespread commercialization of cannabis has led to the introduction of brand names based on users' subjective experience of psychological effects and flavors, but this process has occurred in the absence of agreed standards. The objective of this work was to leverage information extracted from large databases to evaluate the consistency and validity of these subjective reports, and to determine their correlation with the reported cultivars and with estimates of their chemical composition (delta-9-THC, CBD, terpenes). METHODS: We analyzed a large publicly available dataset extracted from Leafly.com where users freely reported their experiences with cannabis cultivars, including different subjective effects and flavour associations. This analysis was complemented with information on the chemical composition of a subset of the cultivars extracted from Psilabs.org . The structure of this dataset was investigated using network analysis applied to the pairwise similarities between reported subjective effects and/or chemical compositions. Random forest classifiers were used to evaluate whether reports of flavours and subjective effects could identify the labelled species cultivar. We applied Natural Language Processing (NLP) tools to free narratives written by the users to validate the subjective effect and flavour tags. Finally, we explored the relationship between terpenoid content, cannabinoid composition and subjective reports in a subset of the cultivars. RESULTS: Machine learning classifiers distinguished between species tags given by "Cannabis sativa" and "Cannabis indica" based on the reported flavours: = 0.828 ± 0.002 (p < 0.001); and effects: = 0.9965 ± 0.0002 (p < 0.001). A significant relationship between terpene and cannabinoid content was suggested by positive correlations between subjective effect and flavour tags (p < 0.05, False-Discovery-rate (FDR)-corrected); these correlations clustered the reported effects into three groups that represented unpleasant, stimulant and soothing effects. The use of predefined tags was validated by applying latent semantic analysis tools to unstructured written reviews, also providing breed-specific topics consistent with their purported subjective effects. Terpene profiles matched the perceptual characterizations made by the users, particularly for the terpene-flavours graph (Q = 0.324). CONCLUSIONS: Our work represents the first data-driven synthesis of self-reported and chemical information in a large number of cannabis cultivars. Since terpene content is robustly inherited and less influenced by environmental factors, flavour perception could represent a reliable marker to indirectly characterize the psychoactive effects of cannabis. Our novel methodology helps meet demands for reliable cultivar characterization in the context of an ever-growing market for medicinal and recreational cannabis.

Multimodal neurocognitive markers of interoceptive tuning in smoked cocaine.

Contemporary neurocognitive models of drug addiction have associated this condition with changes in interoception -namely, the sensing and processing of body signals that fulfill homeostatic functions relevant for the onset and maintenance of addictive behavior. However, most previous evidence is inconsistent, behaviorally unspecific, and virtually null in terms of direct electrophysiological and multimodal markers. To circumvent these limitations, we conducted the first assessment of the relation between cardiac interoception and smoked cocaine dependence (SCD) in a sample of (a) 25 participants who fulfilled criteria for dependence on such a drug, (b) 22 participants addicted to insufflated clorhidrate cocaine (only for behavioral assessment), and (c) 25 healthy controls matched by age, gender, education, and socioeconomic status. We use a validated heartbeat-detection (HBD) task and measured modulations of the heart-evoked potential (HEP) during interoceptive accuracy and interoceptive learning conditions. We complemented this behavioral and electrophysiological data with offline structural (MRI) and functional connectivity (fMRI) analysis of the main interoceptive hubs. HBD and HEP results convergently showed that SCD subjects presented ongoing psychophysiological measures of enhanced interoceptive accuracy. This pattern was associated with a structural and functional tuning of interoceptive networks (reduced volume and specialized network segregation). Taken together, our findings provide the first evidence of an association between cardiac interoception and smoked cocaine, partially supporting models that propose hyper-interoception as a key aspect of addiction. More generally, our study shows that multimodal assessments of interoception could substantially inform the clinical and neurocognitive characterization of psychophysiological and neurocognitive adaptations triggered by addiction.