Spanish versions and validation of a series of rating scales and visual analogue scales to assess the subjective effects of cannabis.

Cannabis is being legalized for medical and recreational purposes all around the world. However, the understanding of the psychological effects of cannabis is still limited, and it has been previously linked to mental disorders such as schizophrenia. Lately, new scales have been created and adapted to measure its psychological effects. The aim of this study is to create Spanish versions of some of these scales and test their psychometric characteristics. One hundred sixteen participants were recruited from Cannabis Social Clubs (CSC) in Barcelona, Spain. Participants under the effects of their own cannabis completed the Cannabis Experience Questionnaire-modified version (CEQ-mv), Addiction Research Centre Inventory-18 (ARCI-18), Psychotomimetic States Inventory (PSI) and Visual Analogue Scales (VAS). Questionnaires were completed in the CSC, providing a naturalistic setting for the study. Exploratory factor analysis and internal consistency were analyzed. PSI was reduced from a 6-factor to a 4-factor model with adequate to low reliability, ARCI-18 was reduced from a 3-factor to a 2-factor model with good reliability, and VAS were reduced from a 4-factor to a 3-factor model, also with good reliability. These questionnaires showed adequate reliability and can be used in future studies to test the subjective effects of cannabis in clinical and naturalistic settings.

The Effects of Cannabidiol and δ-9-Tetrahydrocannabinol in Social Cognition: A Naturalistic Controlled Study.

Background: Social cognition abilities such as empathy and the Theory of Mind (ToM) have been shown to be impaired in neuropsychiatric conditions such as psychotic, autistic, and bipolar disorders. The endocannabinoid system (ECS) seems to play a role in social behavior and emotional processing while it also seems to play a role in those neuropsychiatric conditions showing social cognition impairments. Main plant cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) modulate the ECS and, due to their opposite effects, have been proposed as both cause and treatment for neuropsychiatric-related disorders such as schizophrenia, anxiety, or post-traumatic stress disorder (PTSD). The aim of this study was to test the effects of THC and CBD on social cognition abilities in chronic cannabis users. Method: Eighteen members from a cannabis social club were tested for social cognition effects under the effects of different full spectrum cannabis extracts containing either THC, CBD, THC+CBD, or placebo in a naturalistic randomized double-blind crossover placebo-controlled study. Results: Results showed that participants under the effects of THC showed lower cognitive empathy when compared with the effects of CBD but not when those were compared with THC+CBD or placebo. Also, participants showed higher cognitive ToM under the effects of CBD when compared with the effects of placebo, but not when those were compared with THC or THC+CBD. However, we did not find differences on the emotional scales for empathy or ToM. Conclusions: This study provides evidence for the interaction between the effects of THC and CBD and social cognition abilities in a naturalistic environment, which can be of special interest for the clinical practice of medical cannabis on neuropsychiatric disorders. We show for the first time that CBD can improve ToM abilities in chronic cannabis users. Our results might help to understand the role of the ECS in social cognition, and their association with psychiatric and neurodevelopmental disorders such as schizophrenia or autism. Finally, we demonstrate how reliable methodologies can be implemented in naturalistic environments to collect valid ecological evidence outside classic laboratory settings.

Machine learning methods for predicting progression from mild cognitive impairment to Alzheimer's disease dementia: a systematic review.

BACKGROUND: An increase in lifespan in our society is a double-edged sword that entails a growing number of patients with neurocognitive disorders, Alzheimer's disease being the most prevalent. Advances in medical imaging and computational power enable new methods for the early detection of neurocognitive disorders with the goal of preventing or reducing cognitive decline. Computer-aided image analysis and early detection of changes in cognition is a promising approach for patients with mild cognitive impairment, sometimes a prodromal stage of Alzheimer's disease dementia. METHODS: We conducted a systematic review following PRISMA guidelines of studies where machine learning was applied to neuroimaging data in order to predict whether patients with mild cognitive impairment might develop Alzheimer's disease dementia or remain stable. After removing duplicates, we screened 452 studies and selected 116 for qualitative analysis. RESULTS: Most studies used magnetic resonance image (MRI) and positron emission tomography (PET) data but also magnetoencephalography. The datasets were mainly extracted from the Alzheimer's disease neuroimaging initiative (ADNI) database with some exceptions. Regarding the algorithms used, the most common was support vector machine with a mean accuracy of 75.4%, but convolutional neural networks achieved a higher mean accuracy of 78.5%. Studies combining MRI and PET achieved overall better classification accuracy than studies that only used one neuroimaging technique. In general, the more complex models such as those based on deep learning, combined with multimodal and multidimensional data (neuroimaging, clinical, cognitive, genetic, and behavioral) achieved the best performance. CONCLUSIONS: Although the performance of the different methods still has room for improvement, the results are promising and this methodology has a great potential as a support tool for clinicians and healthcare professionals.

Opposite Roles for Cannabidiol and δ-9-Tetrahydrocannabinol in Psychotomimetic Effects of Cannabis Extracts: A Naturalistic Controlled Study.

BACKGROUND: Although δ-9-tetrahydrocannabinol (THC), the main cannabinoid from the cannabis plant, is responsible for the psychotomimetic effects of cannabis, cannabidiol (CBD), the second most abundant cannabinoid in the cannabis plant, does not show any psychotomimetic effect. Cannabidiol has even been proposed to be antipsychotic and to counteract some of the psychotomimetic effects of THC. The aim of this study was to test the potential antipsychotomimetic effects of CBD. METHOD: Eighteen members from a cannabis social club were tested for subjective and psychotomimetic effects under the effects of different full-spectrum cannabis extracts containing either THC, CBD, THC + CBD, or placebo in a naturalistic, randomized, double-blind, crossover, placebo-controlled study. RESULTS: Results showed that participants under the effects of THC + CBD showed lower psychotomimetic scores in subjective scales when compared with THC alone. Subjective scores were lower under the effects of CBD and placebo when compared with THC + CBD. Cannabidiol and placebo did not show any psychotomimetic effect. CONCLUSIONS: This study provides evidence for both the psychotomimetic effects of THC and the antipsychotomimetic effects of CBD when it is coadministered with THC in real-world situations, which can be very relevant for the clinical practice of medical cannabis. Ultimately, this study substantiates the link between the endocannabinoid system and psychotic-like symptoms and has important implications for the understanding of schizophrenia and the therapeutic potential of CBD as an antipsychotic. Lastly, we demonstrate how reliable methodologies can be implemented in real situations to collect valid ecological evidence outside classic laboratory settings.

Cognitive Enhancement via Neuromodulation and Video Games: Synergistic Effects?

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique able to modulate cortical excitability. This modulation may influence areas and networks responsible for specific cognitive processes, and the repetition of the induced temporary changes can produce long-lasting effects. TMS effectiveness may be enhanced when used in conjunction with cognitive training focused on specific cognitive functions. Playing video games can be an optimal cognitive training since it involves different cognitive components and high levels of engagement and motivation. The goal of this study is to assess the synergistic effects of TMS and video game training to enhance cognition, specifically, working memory and executive functions. We conducted a randomized 2 × 3 repeated measures (stimulation × time) study, randomly assigning 27 healthy volunteers to an active intermittent theta-burst stimulation or a sham stimulation group. Participants were assessed using a comprehensive neuropsychological battery before, immediately after, and 15 days after finishing the video game+TMS training. The training consisted of 10 sessions where participants played a 3D platform video game for 1.5 h. After each gaming session, TMS was applied over the right dorsolateral prefrontal cortex (DLPFC). All participants improved their video gaming performance, but we did not find a synergistic effect of stimulation and video game training. Neither had we found cognitive improvements related to the stimulation. We explored possible confounding variables such as age, gender, and early video gaming experience through linear regression. The early video gaming experience was related to improvements in working memory and inhibitory control. This result, although exploratory, highlights the influence of individual variables and previous experiences on brain plasticity.

Evolución de las alteraciones cognitivas tras un traumatismo craneoencefálico: ¿hay mejoría tras controlar el efecto de la práctica? / Evolution of cognitive impairment after a traumatic brain injury: is there any improvement after controlling the practice effect?

Introducción: La importancia de conocer el patrón de evolución de los déficits cognitivos en los primeros meses tras un traumatismo craneoencefálico (TCE) ha fomentado el desarrollo de numerosos estudios longitudinales. Sin embargo, los resultados de la mayoría de ellos deberían tomarse con cautela debido a la falta de un control adecuado del efecto de la práctica, que puede llevar a sobreestimar la recuperación genuina de los procesos cognitivos. Objetivo: Describir los cambios cognitivos entre las fases aguda y subaguda del TCE controlando el efecto de la práctica. Pacientes y métodos: Veintidós pacientes realizaron dos evaluaciones neuropsicológicas tras el TCE (inmediata y tras seis meses) mediante los siguientes tests: Trail Making Test (A, B, B/A y B-A), test de Stroop (P, C, PC e interferencia), clave de números, búsqueda de símbolos, dígitos directos e inversos, fluidez verbal y memoria inmediata. Para controlar el efecto de la práctica se realizó una transformación de las puntuaciones aplicando el procedimiento propuesto por Calamia et al. Resultados: Antes de controlar el efecto de la práctica, se evidenció una mejoría en las puntuaciones de todos los tests (p > 0,001). Sin embargo, tras él, la mejoría permaneció sólo en el Trail Making Test-B, B/A y B-A, la clave de números, la búsqueda de símbolos, el test de Stroop PC y los dígitos inversos. Conclusiones: La falta de control del efecto de la práctica en estudios longitudinales puede generar interpretaciones erróneas sobre el perfil de evolución de los déficits cognitivos. El patrón de recuperación tras un TCE varía en función del proceso cognitivo

Introduction: The importance of knowing the pattern of evolution of cognitive deficits in the first months after a traumatic brain injury (TBI) has encouraged the development of numerous longitudinal studies. However, the results of most of them should be taken with caution due to the lack of adequate control of practice effects that can lead to overestimating the genuine recovery of cognitive processes. Aim. To describe the cognitive changes between the acute and subacute phases of the TBI controlling the effect of the practice. Patients and methods: Twenty-two patients were assessed in two different time points after TBI (immediately and after six months) using the following tests: Trail Making Test (A, B, B/A, B-A), Stroop Test (W, C, CW, interference), Digit Symbol-Coding, Symbol Search, Digits Forward and Backward, Verbal Fluency and Short-term Memory. To control for the practice effects, a transformation of the scores was performed applying the procedure proposed by Calamia et al. Results: Before controlling the practice effects, the scores of all tests improved (p > 0.001). However, afterward, the improvement remained only in the Trail Making Test-B, B/A and B-A, Digit Symbol-Coding, Symbol Search, Stroop CW and Digits Backward. Conclusions: The lack of control of practice effects in longitudinal studies can generate misleading interpretations about the evolution of cognitive deficits. The pattern of recovery after a TBI varies depending on the cognitive process

Prefronto-cerebellar neuromodulation affects appetite in obesity.

Human neuroimaging studies have consistently reported changes in cerebellar function and integrity in association with obesity. To date, however, the nature of this link has not been studied directly. Emerging evidence suggests a role for the cerebellum in higher cognitive functions through reciprocal connections with the prefrontal cortex. The purpose of this exploratory study was to examine appetite changes associated with noninvasive prefronto-cerebellar neuromodulation in obesity. Totally, 12 subjects with class I obesity (mean body mass index 32.9 kg/m2) underwent a randomized, single-blinded, sham-controlled, crossover study, during which they received transcranial direct current stimulation ((tDCS); active/sham) aimed at simultaneously enhancing the activity of the prefrontal cortex and decreasing the activity of the cerebellum. Changes in appetite (state and food-cue-triggered) and performance in a food-modified working memory task were evaluated. We found that active tDCS caused an increase in hunger and desire to eat following food-cue exposure. In line with these data, subjects also tended to make more errors during the working memory task. No changes in basic motor performance occurred. This study represents the first demonstration that prefronto-cerebellar neuromodulation can influence appetite in individuals with obesity. While preliminary, our findings support a potential role for prefronto-cerebellar pathways in the behavioral manifestations of obesity.

Transcranial magnetic stimulation intervention in Alzheimer's disease: a research proposal for a randomized controlled trial.

OBJECTIVE: Alzheimer's disease is a major health problem in our society. To date, pharmacological treatments have obtained poor results and there is a growing interest in finding non-pharmacological interventions for this disease. Transcranial magnetic stimulation (TMS) is a non-invasive technique that is able to induce changes in brain activity and long-term modifications in impaired neural networks, becoming a promising clinical intervention. Our goal is to study the benefit of individualized TMS targeting based on the patient's functional connectivity (personalized targeting), and short duration TMS protocol, instead of current non-individualized and longer session approaches. A double blind randomized controlled trial will be conducted to assess the effects of TMS treatment immediately, 1 month, 3 months and 6 months after the end of the intervention. Fifty-four patients with a diagnosis of Alzheimer's disease will be randomly allocated into experimental (active TMS), sham control, or conventional intervention control group. We will quantify changes in cognitive, functional, and emotional deficits in Alzheimer patients, as well as the functional connectivity changes induced by the TMS treatment. RESULTS: We expect to demonstrate that personalized TMS intervention has a measurable positive impact in cognition, emotion, daily living activities and brain connectivity, thus representing a potential treatment for Alzheimer's disease. Trial registration The trial has been prospectively registered at ClinicalTrials.gov, identifier NCT03121066. Date of registration: 04/19/2017.

Impact of Prefrontal Theta Burst Stimulation on Clinical Neuropsychological Tasks.

Theta burst stimulation (TBS) protocols hold high promise in neuropsychological rehabilitation. Nevertheless, their ability to either decrease (continuous, cTBS) or increase (intermittent, iTBS) cortical excitability in areas other than the primary motor cortex, and their consistency modulating human behaviors with clinically relevant tasks remain to be fully established. The behavioral effects of TBS over the dorsolateral prefrontal cortex (dlPFC) are particularly interesting given its involvement in working memory (WM) and executive functions (EF), often impaired following frontal brain damage. We aimed to explore the ability of cTBS and iTBS to modulate WM and EF in healthy individuals, assessed with clinical neuropsychological tests (Digits Backward, 3-back task, Stroop Test, and Tower of Hanoi). To this end, 36 participants were assessed using the four tests 1 week prior to stimulation and immediately following a single session of either cTBS, iTBS, or sham TBS, delivered to the left dlPFC. No significant differences were found across stimulation conditions in any of the clinical tasks. Nonetheless, in some of them, active stimulation induced significant pre/post performance modulations, which were not found for the sham condition. More specifically, sham stimulation yielded improvements in the 3-back task and the Color, Color-Word, and Interference Score of the Stroop Test, an effect likely caused by task practice. Both, iTBS and cTBS, produced improvements in Digits Backward and impairments in 3-back task accuracy. Moreover, iTBS increased Interference Score in the Stroop Test in spite of the improved word reading and impaired color naming, whereas cTBS decreased the time required to complete the Tower of Hanoi. Differing from TBS outcomes reported for cortico-spinal measures on the primary motor cortex, our analyses did not reveal any of the expected performance differences across stimulation protocols. However, if one considers independently pre/post differences for each individual outcome measure and task, either one or both of the active protocols appeared to modulate WM and EF. We critically discuss the value, potential explanations, and some plausible interpretations for this set of subtle impacts of left dlPFC TBS in humans.

Neural Basis of Video Gaming: A Systematic Review.

Background: Video gaming is an increasingly popular activity in contemporary society, especially among young people, and video games are increasing in popularity not only as a research tool but also as a field of study. Many studies have focused on the neural and behavioral effects of video games, providing a great deal of video game derived brain correlates in recent decades. There is a great amount of information, obtained through a myriad of methods, providing neural correlates of video games. Objectives: We aim to understand the relationship between the use of video games and their neural correlates, taking into account the whole variety of cognitive factors that they encompass. Methods: A systematic review was conducted using standardized search operators that included the presence of video games and neuro-imaging techniques or references to structural or functional brain changes. Separate categories were made for studies featuring Internet Gaming Disorder and studies focused on the violent content of video games. Results: A total of 116 articles were considered for the final selection. One hundred provided functional data and 22 measured structural brain changes. One-third of the studies covered video game addiction, and 14% focused on video game related violence. Conclusions: Despite the innate heterogeneity of the field of study, it has been possible to establish a series of links between the neural and cognitive aspects, particularly regarding attention, cognitive control, visuospatial skills, cognitive workload, and reward processing. However, many aspects could be improved. The lack of standardization in the different aspects of video game related research, such as the participants' characteristics, the features of each video game genre and the diverse study goals could contribute to discrepancies in many related studies.

Clinical Spanish norms of the Stroop Test for traumatic brain injury and schizophrenia

The Stroop Color-Word Test is a useful tool to evaluate executive attention and speed of processing. Recent studies have provided norms for different populations of healthy individuals to avoid misinterpretation of scores due to demographic and cultural differences. In addition, clinical norms may improve the assessment of cognitive dysfunction severity and its clinical course. Spanish normative data are provided for 158 closed traumatic brain injury (TBI) and 149 first-episode schizophrenia spectrum disorder (SCH) patients. A group of 285 Spanish healthy individuals (HC) was also considered for comparison purposes. Differences between groups were found in all Stroop scores with HC outperforming both clinical groups (p < .002 in all cases; d > .3 in all cases). TBI patients scored lower than SCH patients in wordreading (p < .001 and d = .6), and color-naming conditions (p < .001 and d = .4), but not in the color-word condition (p = .34 and d = .03). However, SCH patients exhibited a higher interference effect as compared to TBI (p < .002 and d = .5). Three sets of norms stratified by age and education (HC), and by education (TBI and SCH) are presented for clinical use (AU)

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Clinical Spanish norms of the Stroop test for traumatic brain injury and schizophrenia.

The Stroop Color-Word Test is a useful tool to evaluate executive attention and speed of processing. Recent studies have provided norms for different populations of healthy individuals to avoid misinterpretation of scores due to demographic and cultural differences. In addition, clinical norms may improve the assessment of cognitive dysfunction severity and its clinical course. Spanish normative data are provided for 158 closed traumatic brain injury (TBI) and 149 first-episode schizophrenia spectrum disorder (SCH) patients. A group of 285 Spanish healthy individuals (HC) was also considered for comparison purposes. Differences between groups were found in all Stroop scores with HC outperforming both clinical groups (p .3 in all cases). TBI patients scored lower than SCH patients in word-reading (p < .001 and d = .6), and color-naming conditions (p < .001 and d = .4), but not in the color-word condition (p = .34 and d = .03). However, SCH patients exhibited a higher interference effect as compared to TBI (p < .002 and d = .5). Three sets of norms stratified by age and education (HC), and by education (TBI and SCH) are presented for clinical use.