The self in context: brain systems linking mental and physical health

Abstract

Increasing evidence suggests that mental health and physical health are linked by neural systems that jointly regulate somatic physiology and high-level cognition. Key systems include the ventromedial prefrontal cortex and the related default-mode network. These systems help to construct models of the 'self-in-context', compressing information across time and sensory modalities into conceptions of the underlying causes of experience. Self-in-context models endow events with personal meaning and allow predictive control over behaviour and peripheral physiology, including autonomic, neuroendocrine and immune function. They guide learning from experience and the formation of narratives about the self and one's world. Disorders of mental and physical health, especially those with high co-occurrence and convergent alterations in the functionality of the ventromedial prefrontal cortex and the default-mode network, could benefit from interventions focused on understanding and shaping mindsets and beliefs about the self, illness and treatment.

Fig. 1 |. A schematic of self-in-context models and their role in health and disease.

The ventromedial prefrontal cortex (vmPFC), together with other key regions of the default-mode network, such as the temporoparietal junction (TPJ) and posterior cingulate cortex (PCC), locates the current position of the self in a compressed low-dimensional space that captures the essential features of a situation. Locating the current state of the self on a mental or conceptual map is central to the process of ‘meaning-making’. ‘Self-in-context’ models are inference-based models of the current state that predict sensory and interoceptive input and guide behaviour and physiological regulation on the basis of predictive codes. They also shape and are shaped by beliefs, associative memory and learning. Self-in-context models are influenced by the social and environmental context of the agent, including but not limited to social norms, relationships, cultural beliefs and neighbourhood characteristics. In turn they can regulate visceral outflow via vmPFC projections to the hypothalamus and the brainstem. Self-in-context models also influence decision-making and health-relevant behaviour (for example, dietary choices and how one works and connects with others) via vmPFC connections with the basal ganglia and the mesolimbic reward circuit or frontostriatal loops. Together, the dual pathways — influences on bodily physiology and decision-making — can exert long-term effects on mental and bodily health in multiple ways, such as via their effects on inflammation and allostasis, or their interactions with other health-relevant systems, such as microbiota (for example, via dietary patterns). For instance, maladaptive thought patterns and self-in-context models may lead to a dysregulation of the autonomic nervous system, which leads to allostatic load and diminished recovery, with long-term effects on bodily organs. At the same time, self-in-context models may lead to changes in health-related behaviour such as unhealthy food choices, drug use or insufficient exercise, which also impact health in the short term and the long term.

Fig. 2 |. Anatomy and functional connectivity of the ventromedial prefrontal cortex.

a | The anatomy of the ventromedial prefrontal cortex (vmPFC) includes the ventral anterior cingulate cortex and the subgenual cingulate cortex, the gyrus rectus, the medial parts of the rostral gyrus and frontal pole, and inferior parts of the superior or medial frontal gyrus. b | Multimodal parcellation of the vmPFC and adjacent areas, based on an established whole-brain parcellation, illustrating the heterogeneity of the vmPFC in terms of anatomical features and functional co-activation patterns. c | Cortical resting-state networks. Most of the vmPFC is part of the default-mode network (DMN), especially the default A network or core DMN (here based on the parcellation by Yeo et al.), which serves as a hub between the medial temporal and dorsal subnetworks of the DMN. The most ventral part of the vmPFC (that is, the rostral gyrus and parts of the subgenual anterior cingulate cortex) is part of the limbic network. d | Brain areas associated with autonomic regulation include the vmPFC and its connections with limbic and brainstem areas (simplified overview based on REFS^,,). Red denotes ascending tracts and blue denotes descending tracts. Autonomic regulation involves connections from areas of different large-scale networks, including limbic, default-mode, salience and somatomotor areas. More details are provided in Supplementary information S1. e | Via its close connections to the hypothalamus, the vmPFC can also influence the neuroendocrine system. f | Together with the ventral striatum–nucleus accumbens (NAcc) and the ventral tegmental area (VTA), the vmPFC is part of the mesolimbic reward circuit (simplified here), which guides value-based decision-making and adaptive behaviour. 10d, dorsal part of area 10; 10pp, posterior polar part of area 10; 10r, rostral part of area 10; 10v, ventral part of area 10; 25, area 25; 9m, medial part of area 9; a24, anterior part of area 24; aMCC, anterior midcingulate cortex; Ins, insula; NAmb, nucleus ambiguus; NTS, nucleus tractus solitarius; OFC, orbitofrontal cortex; p24, posterior part of area 24; p32, pregenual area 32; PAG, periaqueductal grey; PBN, parabrachial nucleus; pOFC, posterior orbitofrontal cortex; s32, subgenual area 32; VLM, ventrolateral medulla. Part b adapted from REF., Springer Nature Limited. Part c adapted with permission from REF., American Physiological Society.

Fig. 3 |. Functional associations of ventromedial prefrontal cortex with connected brain networks.

The ventromedial prefrontal cortex (vmPFC) is closely connected to areas of the default-mode network. Together with other regions of the default-mode network, including the temporoparietal junction (TPJ), the dorsomedial prefrontal cortex (dmPFC), the hippocampus and the posterior cingulate cortex (PCC), it is involved in social cognition and self-referential thought. Both the hippocampus and the vmPFC show evidence for grid-like coding of spatial and conceptual maps, and together with other temporal and frontal areas are involved in semantic memory and conceptual processing more broadly. The most ventral part of the vmPFC is connected to the limbic network, including the orbitofrontal cortex (OFC), the ventral striatum (VS) and other subcortical areas. Together with the VS, the vmPFC is important for reward processing and decision-making. Therefore, it is amenable to interactions with the frontoparietal network, especially the dorsolateral prefrontal cortex (dlPFC) and the inferior parietal lobule (IPL), involved in executive function and self-control. Together with areas of the salience network (especially the anterior midcingulate cortex (aMCC) and the anterior insula) and subcortical regions, the vmPFC is involved in interoception and physiological regulation. Representative Neurosynth term-based meta-analytic association maps (with a threshold at false discovery rate q < 0.01, reproducible and available for download from https://neurosynth.org) illustrate the role of the vmPFC with self-referential processing, conceptual thoughts, decision-making and autonomic regulation. See Supplementary information S3 for instructions and code to recreate the visualizations of the maps seen here.