Data-driven profiles of attention-deficit/hyperactivity disorder using objective and ecological measures of attention, distractibility, and hyperactivity.

In the past two decades, the traditional nosology of attention-deficit/hyperactivity disorder (ADHD) has been criticized for having insufficient discriminant validity. In line with current trends, in the present study, we combined a data-driven approach with the advantages of virtual reality aiming to identify novel behavioral profiles of ADHD based on ecological and performance-based measures of inattention, impulsivity, and hyperactivity. One hundred and ten Spanish-speaking participants (6-16 years) with ADHD (medication-naïve, n = 57) and typically developing participants (n = 53) completed AULA, a continuous performance test embedded in virtual reality. We performed hybrid hierarchical k-means clustering methods over the whole sample on the normalized t-scores of AULA main indices. A five-cluster structure was the most optimal solution. We did not replicate ADHD subtypes. Instead, we identified two clusters sharing clinical scores on attention indices, susceptibility to distraction, and head motor activity, but with opposing scores on mean reaction time and commission errors; two clusters with good performance; and one cluster with average scores but increased response variability and slow RT. DSM-5 subtypes cut across cluster profiles. Our results suggest that latency of response and response inhibition could serve to distinguish among ADHD subpopulations and guide neuropsychological interventions. Motor activity, in contrast, seems to be a common feature among ADHD subgroups. This study highlights the poor feasibility of categorical systems to parse ADHD heterogeneity and the added value of data-driven approaches and VR-based assessments to obtain an accurate characterization of cognitive functioning in individuals with and without ADHD.

Transcranial direct current stimulation as a motor neurorehabilitation tool: an empirical review.

The present review collects the most relevant empirical evidence available in the literature until date regarding the effects of transcranial direct current stimulation (tDCS) on the human motor function. tDCS in a non-invasive neurostimulation technique that delivers a weak current through the brain scalp altering the cortical excitability on the target brain area. The electrical current modulates the resting membrane potential of a variety of neuronal population (as pyramidal and gabaergic neurons); raising or dropping the firing rate up or down, depending on the nature of the electrode and the applied intensity. These local changes additionally have shown long-lasting effects, evidenced by its promotion of the brain-derived neurotrophic factor. Due to its easy and safe application and its neuromodulatory effects, tDCS has attracted a big attention in the motor neurorehabilitation field among the last years. Therefore, the present manuscript updates the knowledge available about the main concept of tDCS, its practical use, safety considerations, and its underlying mechanisms of action. Moreover, we will focus on the empirical data obtained by studies regarding the application of tDCS on the motor function of healthy and clinical population, comprising motor deficiencies of a variety of pathologies as Parkinson's disease, stroke, multiple sclerosis and cerebral palsy, among others. Finally, we will discuss the main current issues and future directions of tDCS as a motor neurorehabilitation tool.

Spatial memory alterations in children with epilepsy of genetic origin or unknown cause.

Genetic generalised epilepsy or epilepsy of unknown cause can remit before adolescence. In many children, the disease does not interfere with their academic achievement. Although there are neuropsychological studies characterising the cognitive profile, there are no studies in this population focused on spatial orientation abilities. In this study, we compared children with genetic generalised epilepsy or epilepsy of unknown cause with a control group using a virtual spatial learning task. Children with epilepsy showed worse performance on the spatial orientation task, although their visuo-spatial memory, attention, and working memory were normal. These results confirm that genetic generalised epilepsy or epilepsy of unknown cause is associated with more cognitive deficits. Virtual reality technologies can complement clinical assessment.

Psychological impact of six weeks of strict home confinement in Spanish families having school-aged children with attention-deficit/hyperactivity disorder.

After the COVID-19 outbreak, early publications reported worsening symptoms and increased caregiver burden in families having children with Attention-Deficit/Hyperactivity Disorder (ADHD). In the present study, we launched an online survey to examine the psychological impact of the 41 days of strict home confinement implemented in Spain in families having children with ADHD compared to families having children with typical development (TD). We achieved a representative sample of 190 school-aged children (NADHD =100 and NTD=90) from 181 families. Respondents were mainly mothers (≈96%). We found that mother reports of hyperactive-impulsive symptoms significantly increased during home confinement regardless of ADHD diagnosis. During the lockdown, we also found that perceived stress significantly increased in mothers of ADHD and TD children, but, unexpectedly, this increase was much more noticeable for the latter group. Moreover, our study suggests that children having parents working in frontline jobs or living in families with higher household conflicts might display increased ADHD symptoms during the lockdown, irrespective of ADHD diagnosis. Our results highlight the need to provide psychological support to families most exposed to the pandemic and target household problems and mothers' well-being at intervention processes, in both ADHD and TD families.

Spatial navigation impairment in patients with refractory temporal lobe epilepsy: evidence from a new virtual reality-based task.

This study was aimed at examining spatial learning and memory in nonoperated temporal lobe epilepsy (TLE). Twenty-five patients with a refractory epileptic focus located in the temporal lobe (10 in the right hemisphere and 15 in the left hemisphere) and 25 healthy age-matched controls performed the "Boxes Room," a virtual reality version of the holeboard. They were trained in 10 trials to locate the reward boxes in a room with 16 of them available. Participants also completed a comprehensive neuropsychological evaluation. Patients performed significantly worse relative to the control group. They traveled longer distances and committed more errors than controls. No differences in performance were found within the TLE group when gender or lateralization of the epileptic focus was considered an independent variable. These findings suggest that the integrity of temporal structures in both hemispheres could be critical to spatial learning and memory and support the spatial component of the task.

Virtual reality tasks disclose spatial memory alterations in fibromyalgia.

OBJECTIVE: The objective is to assess performance on virtual reality spatial memory tasks as well as classical neuropsychological tests in patients with fibromyalgia (FM). METHODS: Fifteen FM patients and fifteen healthy age- and education-matched controls performed the virtual versions of the Morris water maze and the hole board (a virtual version called Boxes room). All participants also completed a comprehensive neuropsychological evaluation that included measures of general intelligence, attention/working memory and visuospatial memory. RESULTS: Both virtual reality tasks were demonstrated to be sensitive to spatial memory alterations. FM patients performed significantly worse than controls in the spatial navigation tasks, showing significantly more errors than their matched controls, while no significant differences were found between patients and controls regarding standard neuropsychological testing. In addition, those FM patients with longer chronicity had lower auditory memory span, visuospatial memory and general intelligence within their group. CONCLUSION: These results are the first to demonstrate that there is a spatial learning deficit in people with FM, which suggest that the hippocampal system can be disturbed in this syndrome.

A new virtual task to evaluate human place learning.

This study assesses the effectiveness of a new virtual task to evaluate human place learning. This test was based on the hole-board maze, developed for rodent research. Its design provides an easy set of levels of difficulty. Sixty-three undergraduate students (30 men and 33 women) were randomly distributed into three testing conditions; they had to find 3, 5 and 7 rewards, respectively, in a virtual room with 16 possible rewarded positions. Subjects were asked to use the minimum amount of attempts to discover all the rewards in 10 trials. In the initial trial subjects needed to visit almost all the positions to discover the rewards. However, in the last trial an important percentage of subjects did not err. Results showed that all subjects acquired the task but with different amounts of mistakes directly related to the level of difficulty of the condition. In addition, women were slower and less accurate than men. These results agree with previous results in other virtual tasks, and support the spatial component of this test.

Cognitive Vulnerability in Aging May Be Modulated by Education and Reserve in Healthy People.

Aging is related to a deterioration of cognitive performance and to multiple alterations in the brain. Even before the beginning of a noticeable cognitive decline, the framework which holds cognitive function experiences these alterations. From a system-vulnerability point of view of cognition, the deterioration associated with age would be the collection of repercussions during a life. Brain function and structure are modified in a multidimensional way, which could concern different aspects like structural integrity, functional activity, connectivity, or glucose metabolism. From this point of view, the effects of aging could affect the most brain systems and their functional activity. In this study, we analyze the functional development of three cognitive domains in relation to aging, educational level, and cognitive reserve (CR). A total of 172 healthy subjects were divided into two age groups (young and old), and completed a battery of classic neuropsychological tests. The tests were organized and analyzed according to three cognitive domains: working memory and flexibility, visuoconstructive functions, and declarative memory. Subjects also completed a questionnaire on CR. Results showed that the performance in all cognitive domains decreased with age. In particular, tests related to working memory, flexibility, and visuoconstructive abilities were influenced by age. Nevertheless, this effect was attenuated by effects of education, mainly in visuoconstructive domain. Surprisingly, visual as well as verbal memory tests were not affected either by aging, education, or CR. Brain plasticity plays a prominent role in the aging process, but, as other studies have shown, the plasticity mechanism is quite different in healthy vs. pathological brains. Moreover, this plasticity brain mechanism could be modulated by education and CR. Specially, cognitive domains as working memory, some executive functions and the visuoconstructive abilities seem to be modulated by education. Therefore, it seems to be crucial, to propose mechanisms of maintenance of a healthy and enriched brain, since it promotes auto-regulatory mechanisms of well-aging.

Cognitive reserve, age, and their relation to attentional and executive functions.

The main objective of this research was to establish the relation between age, cognitive reserve (CR), and attentional and executive functions. One hundred and sixty healthy participants aged 20 to 65 years old completed a wide battery of frontal-lobe tasks using classical tests that assess planning and control of movement, problem solving, and inhibition of automatic response, visuomotor tracking, focused and sustained attention, shifting, spontaneity and reasoning. The total sum of the score in premorbid IQ (by means of the Weschsler Adult Intelligence Scale Vocabulary subtest), educational level, and type of profession was used as a proxy of CR. Subjects were divided into groups of low or high CR. Multiple linear and logistic analyses revealed that age is a predictor of the 20Q Test, Terman Merril's Picture task, Similarities, Digit Span (backward), Trail-Making Tests, Porteus Maze Trace, the "A" Letter Cancellation Test, and reciprocal inhibition. CR is a predictor of the Controlled Oral Word Association Test, Trail-Making Tests A and B, Digit Span (forward), and Similarities. In conclusion, a higher CR score is associated with better performance in almost all tests employed. But it has a significant contribution to performance on verbal fluency, behavioral spontaneity, reasoning, divided and complex attention, and working memory functions, which are mainly related to the dorsolateral prefrontal area.

Effect of reference frames and number of cues available on the spatial orientation of males and females in a virtual memory task.

The aim of this study was to examine the influence of the number of cues and cue location in human spatial learning. To assess their importance, subjects performed variants of a virtual task called "The Boxes Room". Participants were trained to locate, in a computer-generated environment with 16 boxes, the rewarded boxes through 8 trials. In experiment I, the number of distal cues available was zero, one, two or the standard arrangement (seven cues). In experiment II, place navigation was compared based on distal landmarks (extra-maze cues placed on the walls) and proximal landmarks (proximal cues placed between the boxes). The results of experiment I demonstrated that one cue in the room is enough to obtain a good performance in the task. Experiment II showed that groups using proximal cues were slower and less accurate than groups using distal cues. In addition, our data suggest that men are better navigators than women, as they found the rewarded boxes sooner and committed fewer errors in both studies. These results indicate that performance can change depending on the number and location of available cues.

A virtual-based task to assess place avoidance in humans.

Spatial memory can be assessed by virtual reality-based tasks, some of them similar to those previously used in rodents. In this study a virtual place avoidance task was developed based on a rodent labyrinth to evaluate human spatial memory. The task required subjects to avoid in a virtual room a prohibited zone defined solely by distal cues, while they collected rewards. The size of the to-be-avoided area was used as an independent variable as well as the gender of the participants. Subjects displayed an adequate performance after a single 5-min trial, entering the prohibited area on very few occasions. Our results showed that the size of the prohibited zone can be used to adapt task difficulty to different populations. Moreover, males were faster than females. They collected more rewards and spent less time in the prohibited area. Data collected supports the spatial component of the task and the validity of this procedure for spatial memory assessment in human beings.