Transdiagnostic neuromodulation of impulsivity: current status and future trajectories

Abstract

Impulsivity, increasingly perceived as a transdiagnostic characteristic, significantly influences diverse psychiatric conditions and emanates beyond the boundaries defined by traditional classification systems. Transdiagnostic research has shed light on the complex clinical manifestations of impulsivity, and the underpinning neural circuitry. The pressing challenge now is to translate this enhanced understanding into precise and potent interventions tailored to these different aspects of impulsivity. Recent advancements in neuromodulation, specifically targeting brain circuits, have provided encouraging evidence for improvements in clinical symptoms, and neural circuitry across various psychiatric conditions, signposting a transformative phase in crafting interventions that tackle impulsivity from a transdiagnostic perspective. However, the field continues to ascertain a universally embraced framework that effectively amalgamates these discoveries into a unified clinical methodology. The Research Domain Criteria (RDoC) delivers a neuroscientifically informed framework that aims to reconcile the neurobiological underpinnings with clinical symptoms, thereby facilitating targeted neuromodulation strategies. In this context, we propose a pioneering RDoC-compliant framework that strategically targets the neural circuits implicated in clinical impulsivity symptoms, applicable across diagnostic categories. Furthermore, we introduce a set of meticulously selected tools for each stage within this framework, thus reinforcing its applicability and aiding future investigative pursuits in this area.

Fig. 1. Transdiagnostic dimensionality of psychological impulsivity for crafting transdiagnostic assessment strategies.

This structure integrating both trait and state impulsivity insights and partitioning cognitive choices from motor actions, merits preliminary endorsement as a foundational dimension-based assessment orientation, especially directed towards further exploration of each dimension’s neurotraits.

Fig. 2. A future practical “TNMI” framework: a transdiagnostic neuromodulation framework for targeting impulsivity to address impulsivity in mental disorders.

The figure provides examples, including addiction, attention-deficit/hyperactivity disorder (ADHD), and eating disorders (ED), to illustrate the performance of impulsivity, the structure of impulsivity, and the identification of brain circuits. The framework aims to advance precision medicine in the neuromodulation for mental disorders by recognising the multidimensional nature of impulsivity. This includes impulsive choice, impulsive action, and impulsive traits and their neural correlates. The framework incorporates findings from brain circuit research and uses techniques such as magnetic resonance imaging (MRI) and electroencephalography (EEG) to study impulsive brain circuits. The diagram illustrates transcranial magnetic stimulation (TMS) as a neuromodulation technique, with potential applications in modulating impulsive brain circuits. Please note that the figure has been adapted from the ref. [24], with permission from Annual Reviews, Inc. (License ID: 1446321-2).

Fig. 3. Impulsive brain circuits and targeted neuromodulation.

The prefrontal cortex (PFC) and basal ganglia are outlined as the basic neurological circuits underlying impulsivity. Within the PFC, specific regions have been identified for their critical role in impulsivity. These regions include the infralimbic cortex, the orbitofrontal cortex (OFC), and the anterior cingulate cortex (ACC). At the same time, the nucleus accumbens (NAc), located in the basal ganglia, makes a significant contribution to impulsivity by acting as a central hub. A number of neuromodulation techniques can be used to modulate neural activity in specific regions associated with impulsivity. Magnetic electroconvulsive therapy (MECT), magnetic convulsive therapy (MCT), deep transcranial magnetic stimulation (dTMS), and high-intensity transcranial alternating current stimulation (Hi-tACS) can target the whole brain. Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES) can target superficial cortical regions such as the prefrontal cortex and orbitofrontal cortex (OFC). Temporal interference (TI), focused ultrasound (FUS), and deep brain stimulation (DBS) can be used to modulate deep nuclei such as the anterior cingulate cortex (ACC) and nucleus accumbens (NAc) in the basal ganglia. These different neuromodulation techniques offer potential therapeutic interventions for impulsivity by selectively modulating neural activity in specific regions associated with impulsive behaviour. Please note that subfigures (a-b) are reprinted with permission from ref. [139] (corresponding to original Fig. 3). Copyright 2017 by the American Association for the Advancement of Science (AAAS). Permission conveyed through Copyright Clearance Center (License ID: 1446338-1). The human architecture of the NAc was obtained from the Brainnetome Atlas [140].