N,N-dimethyltryptamine (DMT) is the simplest psychedelic tryptamine and is produced naturally by many plant and animal species, including humans. While classical psychedelics, such as lysergic acid diethylamide, or psilocybin, are gaining interest because of their therapeutic potential, DMT has yet to be fully investigated. However, preliminary clinical evidence suggests that DMT and/or ayahuasca, a DMT-containing psychoactive beverage, both possess antidepressive, anxiolytic, and antiaddictive properties. In addition, the subjective effects of DMT are particularly potent. Both subjective and therapeutic cues can be largely explained via the neuromodulatory properties of DMT. In addition, DMT interacts with several neurochemical systems, including the glutamatergic, monoaminergic, and cholinergic systems. Consequently, large-scale brain dynamics can suffer acute and dramatic shifts in several networks, including visual and auditive networks, and the default-mode network. More broadly, top-down cognitive processes (predictive and contextual processing) can become restricted while bottom-up and stimuli-related processing is enhanced. Furthermore, the acute effects of DMT can crystallize to some extent by virtue of its plastogenic effects which are mediated by sigma 1 receptor, brain-derived neurotrophic factor, tropomyosin receptor kinase B, and serotonin receptor 2A. DMT-induced plasticity has been related mental well-being and therapeutic benefits. Here, I provide an updated review of the neuromodulatory effects of DMT and the mechanisms that underlie these effects. I consider the molecular targets that influence neurochemical systems, changes in large-scale cortical function and structure, and DMT-dependent neuroplasticity. Finally, I highlight the therapeutic relevance and/or risks associated with the neuromodulatory mechanisms of DMT.

Neurological damage after stroke and spinal cord injury often results in walking impairments. The theory of interlimb neural coupling implies that synchronized arm swing should be included during gait training to improve rehabilitation outcomes. We previously developed an automatic rotational orthosis for walking with arm swing (aROWAS), which produced coordinated interlimb movement when running in passive mode. The current case-series study had three aims: to develop impedance control algorithms for generating flexible movement in the aROWAS system, to validate its technical feasibility, and to investigate interlimb muscle activity when using it. A force-free controller was developed to compensate for gravity and friction, and an impedance controller was developed to produce a flexible movement pattern. Experiments were performed on three able-bodied volunteers to evaluate the feasibility of the flexible aROWAS system and muscle activity in their upper and lower limbs was recorded. In force-free mode, the leg rig was static but easily moved by small external forces, and the subjects reported very little resistance when attempting to walk synchronously in the aROWAS system. In impedance mode, the leg rig performed the pre-defined gait pattern, but the joint trajectories were adaptable to external forces. All participants produced earlier hip extension and greater knee flexion during active walking than during passive walking. Furthermore, the arm and lower limb muscles simultaneously produced higher electromyography activity. The control algorithms enabled the aROWAS system to produce walking-like coordinated joint performance in the upper and lower limbs, and also allowed for some degree of adjustment in response to voluntary input from the users. Stronger interlimb muscle activity was produced when participants walked actively in the system. This aROWAS system has the technical potential to serve as an effective tool for investigating interlimb neural coupling and as a novel testbed for walking rehabilitation with synchronized arm swing.