Effectiveness of Interactive Remote Rehabilitation After Total Knee Arthroplasty: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Recent advancements in neuroscience have significantly advanced our understanding of the complex roles played by the medial prefrontal cortex (mPFC) pathways to the basolateral amygdala (BLA) and nucleus accumbens (NAc). These pathways are pivotal in emotional and motivational processing, mediating behaviors that involve assessing conflicts between reward and aversion, thus enabling the brain to adaptively respond to diverse environmental stimuli (; ). Both the mPFC→BLA and mPFC→NAc pathways play key roles in shaping emotional responses and guiding decisions when animals face potential rewards or threats (). These circuits adjust behavior when reward seeking must be suppressed in the presence of aversive cues, thereby maintaining a balance between risk and reward in emotionally charged contexts. The prelimbic (PL) subdivision of the mPFC sends excitatory projections to the BLA, a pathway causally linked to fear and anxiety: optogenetic activation of PL→BLA maintains fear memories and induces anxiety-like behaviors (; ). In contrast, the mPFC→NAc pathway is implicated in exploration, reward-seeking, and motivational drive, with optogenetic activation of PL→NAc projections biasing exploratory behavior and social approach (). The mPFC-BLA circuit also integrates reward-aversion conflicts. showed that infralimbic (IL) projections to the BLA are required to suppress reward-seeking when paired with shock punishment, an effect likely mediated through BLA influence on the NAc shell (). Inactivation of PL, BLA, or NAc shell disrupts avoidance (; ). PL projections to BLA and NAc have opposing effects on avoidance: PL-BLA activation facilitates avoidance, while PL-NAc activation inhibits it (). During avoidance retrieval, PL neurons projecting to BLA are activated, while avoidance extinction activates both PL-NAc and IL-NAc projections (). Finally, reported that activation of mPFC→NAc lateral shell neurons engaged by aversive stimuli can suppress reward seeking, underscoring the role of this pathway in weighing competing motivational demands.