Dimensional perspective in ADHD neurodevelopment as a foundation for translational interventionsThe role of executive and arousal attentional processes

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is commonly conceptualized as a neurodevelopmental condition characterized by age-inappropriate and impairing levels of inattention and/or hyperactivity–impulsivity. After decades of prolific basic research into the causes and mechanisms underlying the disorder, these findings have failed to translate into interventions with a substantial impact on core ADHD symptoms. To move past this situation, a shift from the medical to the biopsychosocial model of the disorder is crucial. Based on empirical evidence, the biopsychosocial model adopts a dimensional perspective of ADHD as well as other more complex yet less restrictive assumptions than the medical one, holding considerable hope for translational progress. As part of the dimensional perspective, a fundamental step is the integration between theories aimed at explaining the general neurocognitive functioning and those that account for its variation as a function of ADHD symptom severity. Indeed, the potential alterations in ADHD should be nested within well-established neurocognitive models. In this dissertation, we focused on attention—understood as a general modulatory system of cognition—as a central axis for characterizing two key and dissociable mechanisms in both typical cognitive functioning and ADHD theories: executive and arousal processes. Each of these two domains constitutes an independent mechanism in models of the general functioning of attentional networks (M. I. Posner & Petersen, 1990) and vigilance (Luna et al., 2018). Furthermore, the main theories of ADHD are distinguished between those based on executive dysfunction (Barkley, 1997) and those focused on arousal dysregulation (Sergeant, 2000, 2005). Crucial for the recent debate on the nature of lateonset ADHD, Halperin and Schulz’s (2006) neurodevelopmental model proposes a dissociation between arousal and executive mechanisms when accounting for the early onset of ADHD versus its later development. Based on this dimensional perspective of ADHD within the broader biopsychosocial framework, the aim of the present dissertation was to deepen our understanding of the executive and arousal attentional alterations underlying ADHD symptoms across development, ultimately considering implications for translational interventions. The achievement of this general objective was carried out in five studies grouped into three chapters plus an overarching conceptual analysis that discusses the translational contributions of our findings. First, we sought to establish a neurocognitive behavioural task capable of (a) feasibly collecting large samples from different contexts, (b) measuring relevant indices of attentional functioning with sufficient reliability, and (c) differentiating between executive and arousal measures. To do so, we conducted an instrumental study focused on the Attentional Networks Test for Interaction and Vigilance—Executive and Arousal Components (ANTI-Vea; Luna et al., 2018). Based on the theoretical models of attention mentioned above, this task assesses the functioning of the three attentional networks (alerting, orienting, and executive control) and two vigilance components (executive and arousal). In this study, we developed a free and online resource to easily run, collect, and analyze large volumes of data from the ANTI-Vea, both in typical lab conditions and online in remote settings: the ANTI-Vea-UGR platform. Consistent with open science principles, the task versions are open source, anonymized ANTI-Vea online participant data is stored on a freely accessible public server, and task analyses can be performed using a custom Shiny app or with its associated R code. In addition, we undertook a narrative review of the more than a dozen studies, encompassing over a thousand participants in total, that have employed ANTI-Vea. We concluded that the reliability of most ANTI-Vea indices was acceptable when the task was used in large samples. Crucially, executive and arousal processes were empirically dissociated using the ANTI-Vea, both through experimental manipulations and within the association pattern of some attention-related constructs. Second, we conducted an empirical series of three associative studies, all following a very similar procedure: A community sample of university students perform the ANTIVea and complete self-reports on the severity of their ADHD symptoms in childhood (retrospectively assessed) and adulthood. The first of these studies (N = 113), of a more exploratory nature, found a neurodevelopmental dissociation consistent with Halperin and Schulz’s (2006) neurodevelopmental model. Concretely, arousal indices (i.e., alerting network and arousal vigilance) correlated with ADHD symptoms in childhood, whereas the decrement in executive vigilance was linked to higher symptoms in adulthood. The second study (N = 292) was a preregistered close replication of the previous one with a greater focus on transparently testing the hypothesized neurodevelopmental dissociation between executive and arousal vigilance in relation to ADHD symptoms. Unexpectedly, neither preregistered nor multiverse analyses supported the predictions of the neurodevelopmental model. The third study (N = 492) combined the samples from the two previous studies with a third sample in which participants performed the ANTI-Vea task multiple times to shed light on the neurocognitive characterization of late-onset ADHD. This final pattern of results did not support a neurodevelopmental dissociation either. On the contrary, both executive and arousal alterations were associated with ADHD symptoms in childhood, adulthood, and late onset (i.e., symptoms in adulthood after controlling for those in childhood). Third, we presented the protocol of a systematic review and meta-analysis of the effects of nonpharmacological interventions for ADHD on indices of autonomic arousal. Arousal dysregulation in ADHD, often in the form of hypo-arousal, is a potential target and mediator in interventions aimed at improving ADHD symptoms. Arousal measures of the autonomic nervous system include cardiac, electrodermal, and pupil activity, among others. The twofold aim of this study was (a) to examine whether current nonpharmacological interventions for ADHD, translational or not, can enhance the regulation of arousal mechanisms; and (b) to identify promising arousal-based translational interventions for ADHD. Preliminary results have identified 12 studies. However, due to the low statistical power and high heterogeneity across study designs and intervention types, drawing robust conclusions on the current state of the art in this area was challenging. Finally, we attempted to integrate our findings with the previous literature to derive proposals that may contribute to the future of translational interventions for ADHD in two key issues: 1. Neurocognitive nature of late-onset ADHD. Evidence mostly suggests that lateonset ADHD is not distinct from conventional ADHD at the neurocognitive level. This implies that translational interventions for ADHD should target the same underlying alterations across different stages of development, regardless of the age of disorder onset. Furthermore, this supports the idea that both child- and adult-onset ADHD can be conceptualized as mere variants of the same disorder. Whether this single disorder is neurodevelopmental or not is an open question that depends on the role (moderating vs. causal) of late-onset ADHD precursors. 2. Mechanisms of translational interventions. As we have shown, both executive and arousal alterations may underlie ADHD symptoms. However, interventions for ADHD have typically been designed to train executive domains (e.g., computerbased cognitive training), while targeting arousal regulation is generally neglected. This contrasts to current models of cognitive training, which propose that the transfer of gains is largely due to mechanisms of cognitive efficiency, which are not primarily executive. Therefore, arousal-based translational interventions for ADHD, such as effort training through learned industriousness or trigeminal nerve stimulation, are postulated as promising therapeutic options. Overall, although the therapeutic progress derived from ADHD basic research is limited, we believe that the translational logic of targeting neurocognitive processes thought to mediate ADHD pathophysiology to improve core symptoms and related impairment still has viability. While the contributions of this thesis are tentative and somewhat constrained by the design of studies, our adoption of the biopsychosocial/dimensional model and the open science framework is, in our view, essential to building a more sound and translatable ADHD science. Beyond translational interventions, promoting inclusive environments of acceptance and appreciation towards the diverse ways of thinking and behaving of people with ADHD is fundamental to the development of their personal growth, strengths, and empowerment in our society.