Figure 3.

Modulation of the mesocircuit model using apomorphine and methylphenidate. The mesocircuit system encompasses a loop involving the anterior forebrain, striatum, globus pallidus internus (GPi). Together with the thalamus, it plays a crucial role in regulating the cortical activity associated with consciousness. A compromised afferent drive to the striatum due to brain injury impairs the firing rates of the medium spiny neurons (MSNs). This deficit leads to an increased inhibitory output from the GPi to the thalamic nuclei, thereby weakening thalamocortical signalling.⁶⁶ Apomorphine acts as a dopamine receptor agonist, directly stimulating D1 and D2 receptors,³³ while methylphenidate increases dopaminergic transmission by inhibiting the reuptake of dopamine via the dopamine transporter (DAT).³⁶ The enhancement of dopamine levels and direct receptor stimulation support MSN activity, counteracting the inhibitory imbalance within the mesocircuit and ultimately promoting the restoration of forebrain dynamics. Blue arrow denotes site of pharmacological intervention, green arrows indicate excitatory neural projections and red lines represent inhibitory neural projections within the mesocircuit. The figure is an original work created using biorender.com by the first author (MHO), who has granted permission for its reuse in this context.