The Etiologic, Theory-Based, Ontogenetic Hierarchical Framework of Alcohol Use Disorder: A Translational Systematic Review of Reviews

Modern nosologies (e.g., ICD-11, DSM-5) for alcohol use disorder (AUD) and dependence prioritize reliability and clinical presentation over etiology, resulting in a diagnosis that is not always strongly grounded in basic theory and research. Within these nosologies, DSM-5 AUD is treated as a discrete, largely categorical, but graded, phenomenon, which results in additional challenges (e.g., significant phenotypic heterogeneity). Efforts to increase the compatibility between AUD diagnosis and modern conceptualizations of alcohol dependence, which describe it as dimensional and partially overlapping with other psychopathology (e.g., other substance use disorders) will inspire a stronger scientific framework and strengthen AUD’s validity. We conducted a systematic review of 144 reviews to integrate addiction constructs and theories into a comprehensive framework with the aim of identifying fundamental mechanisms implicated in AUD. The product of this effort was the Etiologic, Theory-Based, Ontogenetic Hierarchical Framework (ETOH Framework) of AUD mechanisms, which outlines superdomains of cognitive control, reward, as well as negative valence and emotionality, each of which subsume narrower, hierarchically-organized components. We also outline opponent processes and self-awareness as key moderators of AUD mechanisms. In contrast with other frameworks, we recommend an increased conceptual role for negative valence and compulsion in AUD. The ETOH framework serves as a critical step towards conceptualizations of AUD as dimensional and heterogeneous. It has the potential to improve AUD assessment and aid in the development of evidence-based diagnostic measures that focus on key mechanisms in AUD, consequently facilitating treatment matching.

An opponent process for alcohol addiction based on changes in endocrine gland mass

SummaryConsuming addictive drugs is often initially pleasurable, but escalating drug intake eventually recruits physiological “anti-reward” systems called opponent processes that cause tolerance and withdrawal symptoms. Opponent processes are fundamental for the addiction process, but their physiological basis is not fully characterized. Here, we propose an opponent processes mechanism centered on the endocrine stress-response, the HPA axis. We focus on alcohol addiction, where the HPA axis is activated and secretes β-endorphin, causing euphoria and analgesia. Using a mathematical model, we show that slow changes in HPA glands act as an opponent process for β-endorphin secretion. The model explains hormone dynamics in alcohol addiction, and experiments on alcohol preference in rodents. The opponent process is based on fold-change detection (FCD) where β-endorphin responses are relative rather than absolute; FCD confers vulnerability to addiction but has adaptive roles for learning. Our model suggests gland-mass changes as potential targets for intervention in addiction.

Opponent processes in visual memories: a model of attraction and repulsion in navigating insects’ mushroom bodies

Solitary foraging insects display stunning navigational behaviours in visually complex natural environments. Current literature assumes that these insects are mostly driven by attractive visual memories, which are learnt when the insect’s gaze is precisely oriented toward the goal direction, typically along its familiar route or towards its nest. That way, an insect could return home by simply moving in the direction that appears most familiar. Here we show using virtual reconstructions of natural environments that this principle suffers from fundamental drawbacks, notably, a given view of the world does not provide information about whether the agent should turn or not to reach its goal. We propose a simple model where the agent continuously compares its current view with both goal and anti-goal visual memories, which are treated as attractive and repulsive respectively. We show that this strategy effectively results in an opponent process, albeit not at the perceptual level – such as those proposed for colour vision or polarisation detection – but at the level of environmental space. This opponent process results in a signal that strongly correlates with the angular error of the current body orientation so that a single view of the world now suffices to indicate whether the agent should turn or not. By incorporating this principle into a simple agent navigating in reconstructed natural environments, we show that it overcomes the usual shortcomings and produces a step-increase in navigation effectiveness and robustness. Our findings provide a functional explanation to recent behavioural observations in ants and why and how so-called aversive and appetitive memories must be combined. We propose a likely neural implementation based on the insect mushroom bodies’ circuitry that produces behavioural and neural predictions contrasting with previous models.Author summaryInsects such as ants and bees are excellent navigators, able to learn long foraging routes and return to their nest in complex natural habitats. To achieve this, it is believed that individuals memorise views – the visual scene as they perceive it – only when their body is precisely oriented towards the goal. As a result, the insect can return to its goal by simply being attracted in the direction that represents the highest visual familiarity. Here we use a computational approach to show that this strategy suffers from a major weakness: a single view of the world does not suffice to tell whether the agent should turn or not to reach its goal. However, a surprisingly robust solution to this problem arises if we simply assume that these insects memorise not only goal-oriented views but also anti-goal-oriented views that they then treat as repulsive. This idea clarifies several observed behaviours that were difficult to explain with previous models. Overall, this research helps us to understand how insects combine memories in specific brain areas and can navigate so efficiently despite their tiny brain.

Excitatory second-order conditioning using a backward first-order conditioned stimulus: A challenge for prediction error reduction

Prével and colleagues reported excitatory learning with a backward conditioned stimulus (CS) in a conditioned reinforcement preparation. Their results add to existing evidence of backward CSs sometimes being excitatory and were viewed as challenging the view that learning is driven by prediction error reduction, which assumes that only predictive (i.e., forward) relationships are learned. The results instead were consistent with the assumptions of both Miller’s Temporal Coding Hypothesis and Wagner’s Sometimes Opponent Processes (SOP) model. The present experiment extended the conditioned reinforcement preparation developed by Prével et al. to a backward second-order conditioning preparation, with the aim of discriminating between these two accounts. We tested whether a second-order CS can serve as an effective conditioned reinforcer, even when the first-order CS with which it was paired is a backward CS that elicits no responding. Evidence of conditioned reinforcement was found, despite no conditioned response (CR) being elicited by the first-order backward CS. The evidence of second-order conditioning in the absence of excitatory conditioning to the first-order CS is interpreted as a challenge to SOP. In contrast, the present results are consistent with the Temporal Coding Hypothesis and constitute a conceptual replication in humans of previous reports of excitatory second-order conditioning in rodents with a backward CS. The proposal is made that learning is driven by “discrepancy” with prior experience as opposed to “ prediction error.”

The development and present status of the SOP model of associative learning

The Sometimes Opponent Processes (SOP) model in its original form was especially calculated to address how expected unconditioned stimulus (US) and conditioned stimulus (CS) are rendered less effective than their novel counterparts in Pavlovian conditioning. Its several elaborations embracing the essential notion have extended the scope of the model to integrate a much greater number of phenomena of Pavlovian conditioning. Here, we trace the development of the model and add further thoughts about its extension and refinement.