Psychedelics in developmental stuttering to modulate brain functioning: a new therapeutic perspective?

Abstract

Developmental stuttering (DS) is a neurodevelopmental speech-motor disorder characterized by symptoms such as blocks, repetitions, and prolongations. Persistent DS often has a significant negative impact on quality of life, and interventions for it have limited efficacy. Herein, we briefly review existing research on the neurophysiological underpinnings of DS -specifically, brain metabolic and default mode/social-cognitive networks (DMN/SCN) anomalies- arguing that psychedelic compounds might be considered and investigated (e.g., in randomized clinical trials) for treatment of DS. The neural background of DS is likely to be heterogeneous, and some contribution from genetically determinants of metabolic deficiencies in the basal ganglia and speech-motor cortical regions are thought to play a role in appearance of DS symptoms, which possibly results in a cascade of events contributing to impairments in speech-motor execution. In persistent DS, the difficulties of speech are often linked to a series of associated aspects such as social anxiety and social avoidance. In this context, the SCN and DMN (also influencing a series of fronto-parietal, somato-motor, and attentional networks) may have a role in worsening dysfluencies. Interestingly, brain metabolism and SCN/DMN connectivity can be modified by psychedelics, which have been shown to improve clinical evidence of some psychiatric conditions (e.g., depression, post-traumatic stress disorder, etc.) associated with psychological constructs such as rumination and social anxiety, which also tend to be present in persistent DS. To date, while there have been no controlled trials on the effects of psychedelics in DS, anecdotal evidence suggests that these agents may have beneficial effects on stuttering and its associated characteristics. We suggest that psychedelics warrant investigation in DS.

Keywords: default mode network; developmental stuttering; neuropsychopharmacology; psychedelic compounds; social-cognitive networks.

FIGURE 1

Neural pathways involved in DS, and possible interactions with psychedelics effects. (A) A prototypical representation of the (sensorimotor) cortico-basal-thalamo-cortical circuit (CBCT), which has a role in DS neuropathology, and includes regions such as the premotor cortex, supplementary motor area, thalamus, and basal ganglia (bilaterally, in yellow on an inflated model; note that basal ganglia and thalamus are schematically superimposed only for descriptive purposes); (B) a prototypical representation of the default mode network (DMN), hypothesized to have a role in DS neuropathology as well as hypothesized to be a primary neural target of psychedelics; DMN comprises regions such as the prefrontal cortex, temporal cortex, parietal cortex, and posterior cingulate cortex (bilaterally, in yellow on an inflated model); (C) a prototypical representation of a social-cognitive network (SCN; based on Amodio and Frith, 2006; compare with Alm, 2014), which has an influence on the symptoms of DS; SCN comprises prefrontal regions, also influencing functionality of the anterior cingulate cortex and the motor cortex (e.g., supplementary motor area; all regions are shown in yellow on an inflated model); (D) a prototypical representation of the salience network (SN), which is useful for switching from DMN to TPNs, and comprises bilateral regions such as the anterior cingulate cortex and insula (in yellow on an inflated model); (E) a prototypical representation of the central executive network (CEN; as part of task-positive networks, TPNs), comprising regions such as the dorsolateral prefrontal cortex and parietal cortex (bilaterally, in yellow on an inflated model).