RESUMO
In a series of conceptually related episodes, meaning arises from the link between these events rather than from each event individually. How does the brain keep track of conceptually related sequences of events (i.e., conceptual trajectories)? In a particular kind of conceptual trajectory-a social relationship-meaning arises from a specific sequence of interactions. To test whether such abstract sequences are neurally tracked, we had participants complete a naturalistic narrative-based social interaction game, during functional magnetic resonance imaging. We modeled the simulated relationships as trajectories through an abstract affiliation and power space. In two independent samples, we found evidence of individual social relationships being tracked with unique sequences of hippocampal states. The neural states corresponded to the accumulated trial-to-trial affiliation and power relations between the participant and each character, such that each relationship's history was captured by its own neural trajectory. Each relationship had its own sequence of states, and all relationships were embedded within the same manifold. As such, we show that the hippocampus represents social relationships with ordered sequences of low-dimensional neural patterns. The number of distinct clusters of states on this manifold is also related to social function, as measured by the size of real-world social networks. These results suggest that our evolving relationships with others are represented in trajectory-like neural patterns.
RESUMO
BACKGROUND: Drug addiction is a complex brain disorder that is characterized by craving, withdrawal, and relapse, which can be perpetuated by social stress. Stemming from an acute life event, chronic stress, or trauma in a social context, social stress has a major role in the initiation and trajectory of substance use. Preclinical literature shows that early life stress exposure and social isolation facilitate and enhance drug self-administration. Epidemiological evidence links childhood adversity to increased risk for drug use and demonstrates that cumulative stress experiences are predictive of substance use severity in a dose-dependent manner. Stress and drug use induce overlapping brain alterations leading to downregulation or deficits in brain reward circuitry, thereby resulting in greater sensitization to the rewarding properties of drugs. Though stress in the context of addiction has been studied at the neural level, a gap in our understanding of the neural underpinnings of social stress in humans remains. METHODS: We conducted a systematic review of in vivo structural and functional neuroimaging studies to evaluate the neural processes associated with social stress in individuals with substance use disorder. Results were considered in relation to participants' history of social stress and with regard to the effects of social stress induced during the neuroimaging paradigm. RESULTS: An exhaustive search yielded 21 studies that matched inclusion criteria. Social stress induces broad structural and functional neural effects in individuals with substance use disorder throughout their lifespan and across drug classes. A few patterns emerged across studies: (1) many of the brain regions altered in individuals who were exposed to chronic social stress and during acute stress induction have been implicated in addiction networks (including the prefrontal cortex, insula, hippocampus, and amygdala); (2) individuals with childhood maltreatment and substance use history had decreased gray matter or activation in regions of executive functioning (including the medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex), the hippocampal complex, and the supplementary motor area; and (3) during stress-induction paradigms, activation in the anterior cingulate cortex, caudate, and amygdala was most commonly observed. CONCLUSIONS/IMPLICATIONS: A distinct overlap is shown between social stress-related circuitry and addiction circuitry, particularly in brain regions implicated in drug-seeking, craving, and relapse. Given the few studies that have thoroughly investigated social stress, the evidence accumulated to date needs to be replicated and extended, particularly using research designs and methods that disentangle the effects of substance use from social stress. Future clinical studies can leverage this information to evaluate the impact of exposure to trauma or adverse life events within substance use research. Expanding knowledge in this emerging field could help clarify neural mechanisms underlying addiction risk and progression to guide causal-experimental inquiry and novel prevention and treatment strategies.