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Cited by 280Neuroendocrine regulation and behaviorStress Responses and CortisolNeurotransmitter Receptor Influence on Behavior

Neural mechanisms of social homeostasis

Open access
Matthews, Gillian A., Tye, Kay M.·2019·Annals of the New York Academy of Sciences
DOI 10.1111/nyas.14016PMC PMC7593988
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Abstract

Social connections are vital to survival throughout the animal kingdom and are dynamic across the life span. There are debilitating consequences of social isolation and loneliness, and social support is increasingly a primary consideration in health care, disease prevention, and recovery. Considering social connection as an “innate need,” it is hypothesized that evolutionarily conserved neural systems underlie the maintenance of social connections: alerting the individual to their absence and coordinating effector mechanisms to restore social contact. This is reminiscent of a homeostatic system designed to maintain social connection. Here, we explore the identity of neural systems regulating “social homeostasis.” We review findings from rodent studies evaluating the rapid response to social deficit (in the form of acute social isolation) and propose that parallel, overlapping circuits are engaged to adapt to the vulnerabilities of isolation and restore social connection. By considering the neural systems regulating other homeostatic needs, such as energy and fluid balance, we discuss the potential attributes of social homeostatic circuitry. We reason that uncovering the identity of these circuits/mechanisms will facilitate our understanding of how loneliness perpetuates long‐term disease states, which we speculate may result from sustained recruitment of social homeostatic circuits.

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  • Premisecitation

    Lower social integration predicts higher mortality.

    “Lower social integration (assessed by network size/participation, living arrangements, and frequency of close social contact) is predictive of elevated mortality6–9”
    Quote in the paperSubstantial claim0 of 4 sources checked
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  • Premisecitation

    Despite more opportunities for social engagement, society has seen a paradoxical rise in social isolation.

    “Yet as our outlets for social sustenance proliferate, along with the global population1, there is a paradoxical increase in social isolation within society2.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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  • Premisecitation

    Chronic social isolation in rodents has served as a developmental model of early life stress because its long-term changes resemble human neuropsychiatric disease.

    “Chronic social isolation, particularly in rodents, has been used as a developmental model of early life stress since many of the long-term maladaptive changes resemble features of human neuropsychiatric disease33.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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  • Premisecitation

    In the laboratory, mice and rats prefer social company over being alone.

    “In a laboratory setting, mice and rats prefer social company (even that of other males) over a solitary existence42,43.”
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  • Premisecitation

    Mice and rats will work to obtain social contact.

    “and will actively work to obtain social contact46,47.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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  • May combine two claims. 44
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    Premisecitation

    Perceived isolation, or loneliness, is associated with worse physical and mental health and higher mortality.

    “even just the perception of isolation (colloquially referred to as loneliness) is associated with poor physical and mental health10,11 and higher mortality rates6,8,12,13.”
    Quote in the paperSubstantial claim0 of 6 sources checked
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    • cites [6] Holt-Lunstad J, Smith TB & Layton JB Social Relationships and Mortality Risk: A Meta-analytic Review. PLoS Med 7, e1000316 (2010). PMC2910600 20668659 source

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    • cites [8] House JS, Landis KR & Umberson D. Social relationships and health. Science 241, 540– 545 (1988). 3399889 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The share of people living alone has grown, and more people report loneliness.

    “The proportion of the population who live alone has risen3 and an increasing number of people experience loneliness4,5.”
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    Premisecitation

    Wild mice and rats ancestral to laboratory strains are promiscuous and territorial but become more socially tolerant at high density and form linear dominance hierarchies.

    “The wild species of mice and rats from which laboratory strains were derived are promiscuous and territorial, but show greater social tolerance in high-density living environments and adopt linear dominance hierarchies that promote group stability41.”
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    Premisecitation

    Loneliness operates as an aversive signal that promotes adaptation to being alone and motivates reconnection.

    “This model proposes that loneliness operates as an aversive signal designed to promote adaptation to the vulnerabilities of being alone and motivate reconnection32.”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based). May combine two claims.

    Interpretationnone given

    A social homeostatic system would need to monitor social conditions, detect deviation from a set point, and activate effector systems.

    “A social homeostatic system would be required to (1) monitor social conditions; (2) detect deviation from a homeostatic “set point” in control centers; and (3) activate effector systems to elicit an appropriate response (e.g., strategies to promote social contact).”
    Quote in the paperNot a substantial claim

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    Interpretationreasoning

    Parallel, overlapping circuits mediate the response to social deficit to increase attention, motivate reconnection, and limit distress.

    “We propose that parallel, overlapping circuits mediate the response to social deficit (the output of homeostatic “effector” systems) in an effort to heighten attention to environmental stimuli, motivate social reconnection, and limit emotional distress (Fig. 2).”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Challenges to physiological homeostasis can produce motivated behaviors with strong negative drive states.

    “Challenges to physiological homeostasis can also elicit motivated behaviors associated with strong negative “drive” states, such as overheating, thirst, and hunger, designed to appropriately adapt/direct behavior19–21.”
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  • Classified as probably not a substantial claim.

    Interpretationreasoning

    A social deficit, whether perceived or actual, is predicted to engage the social homeostatic system.

    “A deficit in social connections (whether perceived or actual) would be predicted to engage this system.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Prairie voles provide biparental care and live in extended families.

    “They show biparental care towards offspring, tend to live in extended families48,49, and are well-utilized in the study of social bonding and isolation.”
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    • Rests on an assumption: Prairie voles are socially monogamous and form an enduring, selective bond with a partner after mating.

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    Interpretationnone given

    Human loneliness may represent a state in which social homeostatic systems are activated.

    “Here, we evaluate social isolation–induced adaptations in these rodents, in light of the phenotype of human loneliness, which may also represent a state of activation of “social homeostatic systems.””
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    Premisecitation

    The term social homeostasis was previously used for stable organization in large animal groups, especially social insects.

    “This “supraorganismal” structure requires tight regulation to maintain stable hierarchical social organization when met with changes in the environment or internal composition16,17.”
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    Premisecitation

    Loneliness is theorized as an adaptive predisposition that drives maintenance of social contact and avoidance of isolation's aversive effects.

    “loneliness is theorized to represent an “adaptive predisposition” providing the motivational drive to maintain social contact and prevent the aversive consequences of isolation14,15.”
    Quote in the paperSubstantial claim0 of 2 sources checked
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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    The discrepancy in CRF findings may reflect shorter isolation duration or species differences.

    “This discrepancy may reflect the shorter duration of isolation or the different species under study.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    High self-reported loneliness in humans is associated with elevated daily cortisol output and a flatter diurnal cortisol rhythm, suggesting poor HPA regulation.

    “high self-reported loneliness in humans has been associated with elevated daily cortisol output62–66 and a flattening of diurnal cortisol rhythm65, suggesting poor regulation of the HPA axis67.”
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    Premisecitation

    Lonely people often show high anxiety and hypervigilant responses to negative social stimuli.

    “Lonely individuals often show high levels of anxiety51,52, and hypervigilant responses to negative social stimuli, suggestive of heightened recruitment of attentional and self-preservation mechanisms53.”
    Quote in the paperSubstantial claim0 of 3 sources checked
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    Premisecitation

    In adult rats, 24-hour isolation increased tyrosine hydroxylase mRNA in the LC, and an AT1 antagonist blocked this effect.

    “In adult rats, a 24-hour isolation increased tyrosine hydroxylase (TH; the rate-limiting enzyme in catecholamine synthesis) mRNA in the LC, an effect which could be blocked by an AT1 receptor antagonist81.”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Premisecitation

    The LC is the only source of noradrenergic innervation to the CNS and is involved in arousal, vigilance, and responding to environmental challenges.

    “The LC is the sole source of noradrenergic innervation to the central nervous system, best known for its role in arousal and vigilance, but more broadly thought to be recruited to combat environmental challenges84,85.”
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    Premisecitation

    Isolated adult rats show reduced exploration and increased self-grooming.

    “along with a reduction in exploratory behavior and an increase in self-grooming55–57.”
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    Premisecitation

    A 24-hour isolation in adult rats decreased CRF mRNA and protein in the PVN and reduced cortical CRF1 receptor levels.

    “a 24-hour isolation in adult rats decreased CRF mRNA and protein in the PVN75 and decreased cortical CRF1 receptor levels81.”
    Quote in the paperSubstantial claim0 of 2 sources checked
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    Premisecitation

    CRF-producing neurons are widely distributed outside the hypothalamus, including in BNST, CeA, NAc, and hippocampus, and are implicated in stress responses.

    “CRF-producing neurons are also widely distributed in extrahypothalamic regions, including the bed nucleus of the stria terminalis (BNST), central amygdala (CeA), nucleus accumbens (NAc), and hippocampus77–79, which have, likewise, been implicated in the behavioral and physiological responses to stress.”
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    Premisecitation

    Activation of DRN dopamine neurons increases social preference and can promote antinociception.

    “Considering the potential for mixed selectivity, the recent observation that activation of DRN dopamine neurons not only increases social preference118 but can promote antinociception117 could be reconciled in a number of ways.”
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    Interpretationcitation

    Social isolation may recruit this immune response to prepare an individual for the susceptibilities of being alone, including increased need for rapid inflammatory response to bacterial infections from physical injury and reduced need for protection against socially transmitted viral infections.

    “Social isolation may recruit this response to appropriately prepare an individual for the susceptibilities of being alone, which might include an increased need for a rapid inflammatory response to combat bacterial infections sustained through physical injury, but the reduced need for protection against socially transmitted viral infections15,176.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [15] Eisenberger NI & Cole SW Social neuroscience and health: neurophysiological mechanisms linking social ties with physical health. Nat. Neurosci. 15, 669– 674 (2012). 22504347 source

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  • May combine two claims.

    Interpretationreasoning

    DRN dopamine neurons may limit the vulnerabilities of being alone by increasing social motivation, promoting vigilance and arousal, and enhancing responsivity to aversive stimuli.

    “Taken together, these findings illustrate the existence of multiple mechanisms through which DRN dopamine neurons may limit the vulnerabilities of being alone: increasing social motivation, promoting vigilance/arousal, and enhancing responsivity to aversive stimuli.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Activation of BLA input to the ventral hippocampus or mPFC induces robust anxiety-like behavior in exploratory assays and suppresses social investigation in the resident-intruder assay.

    “Furthermore, activation of BLA input to the ventral hippocampus or mPFC not only induces robust anxiety-like behavior in exploratory assays but also suppress social investigation in the resident–intruder assay184–186.”
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    • cites [185] Felix-Ortiz AC BLA to vHPC inputs modulate anxiety-related behaviors. Neuron 79, 658– 664 (2013). 23972595 PMC4205569

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    Premisecitation

    DRN dopamine neurons are responsive to other salient stimuli including palatable food and unexpected foot shock, and show greater activity during wakefulness compared with sleep.

    “However, these neurons are also responsive to other salient stimuli, including palatable food and unexpected foot shock, and show greater activity during wakefulness compared with sleep, suggesting an arousal-promoting function112,115,188.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [112] Cho JR Dorsal Raphe Dopamine Neurons Modulate Arousal and Promote Wakefulness by Salient Stimuli. Neuron 94, 1205–1219.e8 (2017). 28602690 source

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    • cites [115] Groessl F. Dorsal tegmental dopamine neurons gate associative learning of fear. Nat. Neurosci. 21, 952– 962 (2018). 29950668 PMC6166775

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    Premisecitation

    Social and physical pain are processed by overlapping neural circuitry.

    “In accordance with this notion, an emerging hypothesis posits that social and physical pain are processed by overlapping neural circuitry189.”
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    Premisecitation

    Perturbations in social behavior are often, but not always, co-expressed with anxiety-related behaviors, and there is significant overlap in underlying neural correlates.

    “Perturbations in social behavior are often, but not always, co-expressed with anxiety-related behaviors, and there is significant overlap in underlying neural correlates, which suggests a tight relationship between these two forms of behavioral expression58,187.”
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    Premisecitation

    DRN dopamine neurons are active in response to social stimuli, and this activity is heightened following acute isolation.

    “Monitoring fluorescent calcium activity in vivo revealed that these neurons are active in response to social stimuli, and this activity is heightened following acute isolation118.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [118] Matthews GA Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation. Cell 164, 617– 631 (2016). 26871628 PMC4752823

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    Premisecitation

    Human imaging studies show that social disconnection engages brain regions including the dorsal anterior cingulate cortex and anterior insula cortex, which also process the affective component of physical pain.

    “This is supported by human imaging studies revealing that social disconnection engages brain regions including the dorsal anterior cingulate cortex and anterior insula cortex190, which also process the affective component of physical pain191.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [190] Eisenberger NI, Lieberman MD & Williams KD Does Rejection Hurt? An fMRI Study of Social Exclusion. Science 302, 290– 292 (2003). 14551436 source

      Not checked in the free run.

    • cites [191] Price DD Psychological and Neural Mechanisms of the Affective Dimension of Pain. Science 288, 1769– 1772 (2000). 10846154 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Hypernatremia suppresses stress-related circuitry while promoting social reward-related oxytocin pathways, which inhibits stress and anxiety behavior and facilitates social interaction.

    “Given that ATII signaling can drive HPA axis activity, these data suggest that hypernatremia concomitantly suppresses activity within stress-related circuitry, while promoting activity in social reward-related oxytocin pathways, thereby inhibiting stress/anxiety-related behavior and facilitating social interaction.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [170] Krause EG Hydration state controls stress responsiveness and social behavior. J. Neurosci. Off. J. Soc. Neurosci. 31, 5470– 5476 (2011). PMC3086063 21471383

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Certain nodes in a social homeostatic network display mixed selectivity, similar to neurons underlying other complex cognitive processes.

    “This scenario would predict that certain nodes in a social homeostatic network display “mixed selectivity,” similar to neurons underlying other complex cognitive processes181.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [181] Rigotti M. The importance of mixed selectivity in complex cognitive tasks. Nature 497, 585– 590 (2013). 23685452 PMC4412347

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Immune system changes can predict subsequent loneliness, suggesting a reciprocal relationship between immune changes and loneliness.

    “Immune system changes can also predict subsequent loneliness, suggesting a reciprocal relationship between these two phenomena64.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [64] Cole SW Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation. Proc. Natl. Acad. Sci. 112, 15142– 15147 (2015). 26598672 PMC4679065 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    AgRP neurons in the arcuate nucleus are essential for maintaining energy balance, and their activity rapidly drives feeding in hunger.

    “Specifically, the agouti-related protein (AgRP) neurons in the arcuate nucleus of the hypothalamus are essential in the maintenance of energy balance, and their activity rapidly drives feeding behavior in a state of hunger173.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [173] Krashes MJ Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J. Clin. Invest. 121, 1424– 1428 (2011). 21364278 PMC3069789 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Humans with high self-reported loneliness show enhanced proinflammatory activity but reduced antiviral response.

    “This immune response also appears to be recruited in a state of perceived isolation—humans with high self-reported loneliness show enhanced proinflammatory activity but reduced antiviral response66,177–179.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [66] Pressman SD Loneliness, social network size, and immune response to influenza vaccination in college freshmen. Health Psychol. Off. J. Div. Health Psychol. Am. Psychol. Assoc. 24, 297– 306 (2005). 15898866 source

      Not checked in the free run.

    • cites [177] Cole SW Social regulation of gene expression in human leukocytes. Genome Biol. 8, R189 (2007). PMC2375027 17854483 source

      Not checked in the free run.

    • cites [178] Creswell JD Mindfulness-Based Stress Reduction training reduces loneliness and pro-inflammatory gene expression in older adults: a small randomized controlled trial. Brain. Behav. Immun. 26, 1095– 1101 (2012). 22820409 PMC3635809 source

      Not checked in the free run.

    • cites [179] Glaser R, Kiecolt-Glaser JK, Speicher CE & Holliday JE Stress, loneliness, and changes in herpesvirus latency. J. Behav. Med. 8, 249– 260 (1985). 3003360

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Acute hypernatremia in rats is associated with increased plasma oxytocin and increased c-Fos expression in magnocellular PVN oxytocin neurons.

    “Intriguingly, acute hypernatremia in rats is also associated with increased plasma oxytocin, increased c-Fos expression in magnocellular PVN oxytocin neurons, and suppression of ATII production170.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [170] Krause EG Hydration state controls stress responsiveness and social behavior. J. Neurosci. Off. J. Soc. Neurosci. 31, 5470– 5476 (2011). PMC3086063 21471383

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Optogenetic activation of DRN dopamine neurons promoted social preference and real-time place avoidance, whereas inhibition reduced isolation-induced social preference.

    “Optogenetic activation of these neurons promoted social preference and real-time place avoidance, whereas inhibition reduced isolation-induced social preference.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [118] Matthews GA Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation. Cell 164, 617– 631 (2016). 26871628 PMC4752823

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Emotions constitute an internal state encoded by specific neural circuits that can give rise to externally observable behaviors.

    “However, it has been reasoned that emotions constitute an internal state, encoded by specific neural circuits, which can give rise to externally observable behaviors150.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [150] Anderson DJ & Adolphs R. A Framework for Studying Emotions Across Phylogeny. Cell 157, 187– 200 (2014). 24679535 PMC4098837

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Specialized circuits within discrete hypothalamic nuclei underlie parental behavior, aggression, male intruder-specific behavior, opposite-sex approach, and mating.

    “Indeed, specialized circuits, within discrete hypothalamic nuclei, underlie the expression of parental behavior211, aggression212, male intruder-specific behavior213, opposite sex approach,214 and mating212.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [211] Wu Z, Autry AE, Bergan JF, Watabe-Uchida M. & Dulac CG Galanin neurons in the medial preoptic area govern parental behavior. Nature 509, 325– 330 (2014). 24828191 PMC4105201

      Not checked in the free run.

    • cites [212] Lin D. Functional identification of an aggression locus in the mouse hypothalamus. Nature 470, 221– 226 (2011). 21307935 PMC3075820 source

      Not checked in the free run.

    • cites [213] Soden ME Genetic Isolation of Hypothalamic Neurons that Regulate Context-Specific Male Social Behavior. Cell Rep. 16, 304– 313 (2016). 27346361 PMC4945459

      Not checked in the free run.

    • cites [214] McHenry JA Hormonal gain control of a medial preoptic area social reward circuit. Nat. Neurosci. 20, 449– 458 (2017). 28135243 PMC5735833

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Social hierarchies exist in multiple species including fish, birds, rodents, and primates.

    “Grouped living can lead to the establishment of social hierarchies in multiple species including fish, birds, rodents, and primates201–204.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [201] Grosenick L, Clement TS & Fernald RD Fish can infer social rank by observation alone. Nature 445, 429– 432 (2007). 17251980

      Not checked in the free run.

    • cites [202] Morgan D. Predictors of social status in cynomolgus monkeys (Macaca fascicularis) after group formation. Am. J. Primatol. 52, 115– 131 (2000). 11078026

      Not checked in the free run.

    • cites [203] Schjelderup-Ebbe T. Beiträge zur Sozialpsychologie des Haushuhns. [Observation on the social psychology of domestic fowls.]. Z. Für Psychol. Physiol. Sinnesorgane Abt 1 Z. Für Psychol. 88, 225– 252 (1922).

      Not checked in the free run.

    • cites [204] Uhrich J. The social hierarchy in albino mice. J. Comp. Psychol. 25, 373– 413 (1938).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Differences between subordinates and dominants exist in CRF expression in BNST, CeA, MeA, and mPOA; mitochondrial function and dopamine signaling in NAc; and glutamatergic synaptic strength in mPFC.

    “These findings include differences between subordinates and dominants in CRF expression in the BNST, CeA, MeA, and mPOA206, mitochondrial function and dopamine signaling in the NAc207,208, and glutamatergic synaptic strength in the mPFC209.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [206] So N, Franks B, Lim S. & Curley JP A Social Network Approach Reveals Associations between Mouse Social Dominance and Brain Gene Expression. PLOS ONE 10, e0134509 (2015). PMC4520683 26226265

      Not checked in the free run.

    • cites [207] Hollis F. Mitochondrial function in the brain links anxiety with social subordination. Proc. Natl. Acad. Sci. 112, 15486– 15491 (2015). 26621716 PMC4687564

      Not checked in the free run.

    • cites [208] Jupp B. Social dominance in rats: Effects on cocaine self-administration, novelty reactivity and dopamine receptor binding and content in the striatum. Psychopharmacology (Berl.) 233, 579– 589 (2016). 26554388 PMC4726718

      Not checked in the free run.

    • cites [209] Wang F. Bidirectional Control of Social Hierarchy by Synaptic Efficacy in Medial Prefrontal Cortex. Science 334, 693– 697 (2011). 21960531

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Acute isolation reduces pain perception.

    “This dual role of DRN dopamine neurons also points towards a potential mechanism through which acute isolation reduces pain perception157,158.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [157] Naranjo JR & Fuentes JA Association between hypoalgesia and hypertension in rats after short-term isolation. Neuropharmacology 24, 167– 171 (1985). 3990918

      Not checked in the free run.

    • cites [158] Konecka AM & Sroczynska I. Stressors and pain sensitivity in CFW mice. Role of opioid peptides. Arch. Int. Physiol. Biochim. 98, 245– 252 (1990). 1708992

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Social rank bestows variability in subjective social experience without removing support structure for safety, warmth, and other nonsocial benefits of a group.

    “Although subordination in animal societies is not always directly related to low social connectedness or unmet social needs, social rank bestows variability in subjective social experience without removing support structure for safety, warmth and other nonsocial benefits of a group.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Homeostatic feelings can be adaptive and introduce flexibility, but also pass an element of control to the individual, taking regulation beyond purely automatic mechanisms.

    “While this process can be adaptive and introduces greater flexibility into homeostatic regulation, it also passes an element of control to the individual, taking homeostatic regulation beyond purely automatic mechanisms200.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [200] Damasio A. & Damasio H. Exploring the concept of homeostasis and considering its implications for economics. J. Econ. Behav. Organ. 126, 125– 129 (2016).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Loneliness, independent of social network size, is associated with increased blood pressure, higher rates of diabetes, hypertension, arthritis, emphysema, Alzheimer's disease, and poor health habits from lack of self-control.

    “Consistent with this, loneliness—independent of social network size—is associated with higher mortality13,193 increased blood pressure11,194, higher rate of diabetes, hypertension, arthritis, emphysema195, and Alzheimer’s disease196, along with poor health habits stemming from a lack of self-control197,198.”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [11] Hawkley LC, Masi CM, Berry JD & Cacioppo JT Loneliness is a unique predictor of age-related differences in systolic blood pressure. Psychol. Aging 21, 152– 164 (2006). 16594800 source

      Not checked in the free run.

    • cites [194] Hawkley LC, Thisted RA, Masi CM & Cacioppo JT Loneliness predicts increased blood pressure: 5-year cross-lagged analyses in middle-aged and older adults. Psychol. Aging 25, 132– 141 (2010). 20230134 PMC2841310 source

      Not checked in the free run.

    • cites [195] Tomaka J, Thompson S. & Palacios R. The relation of social isolation, loneliness, and social support to disease outcomes among the elderly. J. Aging Health 18, 359– 384 (2006). 16648391

      Not checked in the free run.

    • cites [196] Wilson RS Loneliness and risk of Alzheimer disease. Arch. Gen. Psychiatry 64, 234– 240 (2007). 17283291 source

      Not checked in the free run.

    • cites [197] Baumeister RF, Nathan C, Ciarocco NJ & Twenge JM Social Exclusion Impairs Self-Regulation. J. Pers. Soc. Psychol. 88, 589– 604 (2005). 15796662

      Not checked in the free run.

    • cites [198] DeWall CN, Baumeister RF & Vohs KD Satiated with Belongingness? Effects of Acceptance, Rejection, and Task Framing on Self-Regulatory Performance. J. Pers. Soc. Psychol. 95, 1367– 1382 (2008). 19025289 PMC2597411

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Winning-induced plasticity in the tube test was localized to a mediodorsal thalamic projection to the dorsomedial PFC, and phasic optogenetic stimulation of the dmPFC or the MDT-dmPFC projection immediately induced winning against a previously dominant cagemate.

    “Most recently, “winning”-induced plasticity in the tube test was localized to a mediodorsal thalamic (MDT) projection to the dorsomedial PFC (dmPFC), as phasic optogenetic stimulation of the dmPFC, or the MDT–dmPFC projection, immediately induced winning against a previously dominant cagemate210.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [210] Zhou T. History of winning remodels thalamo-PFC circuit to reinforce social dominance. Science 357, 162– 168 (2017). 28706064

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Homeostatic feelings act as informative regulatory interfaces, providing means for an animal to sense its physiological state and guaranteeing attention to relevant stimuli.

    “Homeostatic feelings act as “informative regulatory interfaces”—providing means for an animal to sense its physiological state and guaranteeing attention to relevant stimuli200.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [200] Damasio A. & Damasio H. Exploring the concept of homeostasis and considering its implications for economics. J. Econ. Behav. Organ. 126, 125– 129 (2016).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    AgRP activity is rapidly suppressed on sensory detection of food, suggesting that ongoing AgRP activity is dispensable for food consumption.

    “However, AgRP activity is rapidly suppressed on sensory detection of food227,228,230, which, surprisingly, suggests that ongoing AgRP activity is dispensable for food consumption.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [227] Betley JN Neurons for hunger and thirst transmit a negative-valence teaching signal. Nature 521, 180– 185 (2015). 25915020 PMC4567040 source

      Not checked in the free run.

    • cites [228] Mandelblat-Cerf Y. Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales. eLife (2015). doi: 10.7554/eLife.07122 PMC4498165 26159614 source

      Not checked in the free run.

    • cites [230] Chen Y, Lin Y-C, Kuo T-W & Knight ZA Sensory Detection of Food Rapidly Modulates Arcuate Feeding Circuits. Cell 160, 829– 841 (2015). 25703096 PMC4373539 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    AgRP and NOS1 neurons show heightened activity during hunger and thirst, their activity elicits an aversive state, and they are essential for driving feeding and drinking behaviors.

    “A potentially similar function has been described for arcuate nucleus AgRP neurons and nitric oxide synthase 1 (NOS1) neurons in the subfornical organ (SFO). These neurons show heightened activity during hunger (AgRP) and thirst (NOS1), their activity elicits an aversive state (place avoidance), and they are essential for driving feeding and drinking behaviors, respectively21,227.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [21] Zimmerman CA Thirst neurons anticipate the homeostatic consequences of eating and drinking. Nature 537, 680– 684 (2016). 27487211 PMC5161740 source

      Not checked in the free run.

    • cites [227] Betley JN Neurons for hunger and thirst transmit a negative-valence teaching signal. Nature 521, 180– 185 (2015). 25915020 PMC4567040 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mice performed operant responses to stimulate AgRP neurons in the presence, but not the absence, of food, suggesting that AgRP activity can be positively reinforcing.

    “Furthermore, mice performed operant responses to stimulate AgRP neurons in the presence, but not the absence of food, suggesting that AgRP activity can be positively reinforcing231.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [231] Chen Y, Lin Y-C, Zimmerman CA, Essner RA & Knight ZA Hunger neurons drive feeding through a sustained, positive reinforcement signal. eLife (2016). doi: 10.7554/eLife.18640 PMC5016090 27554486

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    AgRP neurons are activated in energy deficit, and their optical stimulation promotes food consumption but also elicits real-time place avoidance in the absence of food.

    “AgRP neurons are activated in a state of energy deficit228, and their optical stimulation can voraciously promote food consumption, but also elicits real-time place avoidance (indicative of an aversive state) in the absence of food173,227,229.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [228] Mandelblat-Cerf Y. Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales. eLife (2015). doi: 10.7554/eLife.07122 PMC4498165 26159614 source

      Not checked in the free run.

    • cites [173] Krashes MJ Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J. Clin. Invest. 121, 1424– 1428 (2011). 21364278 PMC3069789 source

      Not checked in the free run.

    • cites [227] Betley JN Neurons for hunger and thirst transmit a negative-valence teaching signal. Nature 521, 180– 185 (2015). 25915020 PMC4567040 source

      Not checked in the free run.

    • cites [229] Aponte Y, Atasoy D. & Sternson SM AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat. Neurosci. 14, 351– 355 (2011). 21209617 PMC3049940

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Decentralized processing of different social needs may occur in separable nodes.

    “If we conceptualize these as discrete “effector systems,” then this raises the possibility that decentralized processing of different social “needs” may occur in separable nodes215.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [215] Swan M. Blockchain Thinking: The Brain as a Decentralized Autonomous Corporation [Commentary]. IEEE Technol. Soc. Mag. 34, 41– 52 (2015).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    More lonely humans show greater activation of the ventral striatum in response to familiar social cues but reduced activation in response to unfamiliar social cues.

    “In support of this concept, functional magnetic resonance imaging in humans has revealed that more lonely individuals show greater activation of the ventral striatum in response to familiar social cues223, but contrastingly reduced activation in response to unfamiliar social cues224.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [223] Inagaki TK Yearning for connection? Loneliness is associated with increased ventral striatum activity to close others. Soc. Cogn. Affect. Neurosci. nsv076 (2015). doi: 10.1093/scan/nsv076 PMC4927031 26084531

      Not checked in the free run.

    • cites [224] Cacioppo JT, Norris CJ, Decety J, Monteleone G. & Nusbaum H. In the eye of the beholder: individual differences in perceived social isolation predict regional brain activation to social stimuli. J. Cogn. Neurosci. 21, 83– 92 (2009). 18476760 PMC2810252 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted). May combine two claims.

    Premisecitation

    An alternative hypothesis proposes that AgRP activity provides a sustained positive valence signal, potentiates the incentive value of food, and supports transition from foraging to feeding via persistent changes in downstream circuitry.

    “Therefore, an alternative hypothesis proposes that AgRP activity provides a sustained positive valence signal, that potentiates the incentive value of food, and supports transition from foraging to feeding behavior via persistent changes in downstream circuitry231.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [231] Chen Y, Lin Y-C, Zimmerman CA, Essner RA & Knight ZA Hunger neurons drive feeding through a sustained, positive reinforcement signal. eLife (2016). doi: 10.7554/eLife.18640 PMC5016090 27554486

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Neural systems mediating homeostatic and hedonic feeding are intertwined and highly overlapping with reward circuitry.

    “However, while mechanistic differences exist, the neural systems mediating homeostatic and hedonic feeding are proposed to be intertwined, and highly overlapping with reward circuitry217,218.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [217] Rossi MA & Stuber GD Overlapping Brain Circuits for Homeostatic and Hedonic Feeding. Cell Metab. 27, 42– 56 (2018). 29107504 PMC5762260

      Not checked in the free run.

    • cites [218] Castro DC, Cole SL & Berridge KC Lateral hypothalamus, nucleus accumbens, and ventral pallidum roles in eating and hunger: interactions between homeostatic and reward circuitry. Front. Syst. Neurosci. 9, (2015). PMC4466441 26124708

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Motivated behaviors regulating food intake are distinguished as homeostatic or hedonic.

    “Motivated behaviors regulating food intake are often distinguished as homeostatic (essential for maintaining energy balance and survival) or hedonic (driven by sensory perception or pleasure in the absence of a need state)217.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [217] Rossi MA & Stuber GD Overlapping Brain Circuits for Homeostatic and Hedonic Feeding. Cell Metab. 27, 42– 56 (2018). 29107504 PMC5762260

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Immediate suppression of neural activity on social contact may be inappropriate for DRN dopamine neurons, and activity may persist until a stable relationship has been achieved.

    “However, an important consideration for social behavior is that (unlike food detection) initial social contact does not necessarily guarantee a rewarding social experience. Therefore immediate suppression of neural activity on social contact may be inappropriate for DRN dopamine neurons, and activity may persist until a stable relationship has been achieved.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Initial social contact does not necessarily guarantee a rewarding social experience.
56 of 56

  • The authors state this as an assumption.

    Social connection is an innate need.

    “Considering social connection as an “innate need,””

  • The paper relies on this without support.

    Social connections are vital for survival across the animal kingdom and change over the lifespan.

    “Social connections are vital to survival throughout the animal kingdom and are dynamic across the lifespan.”

  • The paper relies on this without support.

    Across the animal kingdom, social isolation can threaten survival because isolated individuals lack protection, foraging help, offspring care support, play, and mating opportunities.

    “Across the animal kingdom, social isolation can threaten survival—individuals lack protection from predators, assistance foraging, support raising offspring, opportunities for social play, and mating prospects.”

  • The paper relies on this without support.

    For many social species, social interactions are inherently rewarding and this is a major driver of social contact.

    “For many social species, the inherently rewarding nature of social interactions is a major driving force for social contact.”

  • The paper relies on this without support.

    Prairie voles are socially monogamous and form an enduring, selective bond with a partner after mating.

    “Alternatively, prairie voles are socially monogamous and form an enduring, selective bond with their partner following mating.”

  • The paper relies on this without support.

    Oxytocin neurons project both to the posterior pituitary and to distinct brain targets where they modulate neuronal activity.

    “Oxytocin neurons project not only to the posterior pituitary where they release oxytocin into the bloodstream but also to distinct targets within the brain for direct modulation of neuronal activity.”

  • The paper relies on this without support.

    A social homeostatic system has a control center with a set point for social contact.

    “Specifically, a change in environmental conditions and/or need state (e.g., hunger and thirst) may require a shift in the “set point” for social contact in the control center (Figs. 1b and 3).”

  • The paper relies on this without support.

    Initial social contact does not necessarily guarantee a rewarding social experience.

    “However, an important consideration for social behavior is that (unlike food detection) initial social contact does not necessarily guarantee a rewarding social experience.”
8 of 8

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • There is a long history of animal research documenting causal effects of social deprivation, including complete isolation, on brain and behavioural development during animal adolescence.

    “In contrast, there is a long history of animal research documenting the causal effects of social deprivation, including complete isolation, on brain and behavioural development during animal adolescence.31”

    From The effects of social deprivation on adolescent development and mental health (2020) · cites this paper as [31]

  • Rodent research shows social isolation causes substantial changes in brain and behaviour, especially if isolation occurs during development.

    “This rodent research has shown that social isolation causes substantial changes in brain and behaviour,31 especially if isolation occurs during development.33, 34”

    From The effects of social deprivation on adolescent development and mental health (2020) · cites this paper as [31]

  • The research provides empirical support in human participants for the 'social homeostasis' hypothesis developed based on animal models.

    “Thus, our research provides empirical support in human participants for the ‘social homeostasis’ hypothesis developed based on animal models43.”

    From Acute social isolation evokes midbrain craving responses similar to hunger (2020) · cites this paper as [43]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Seven-day isolation exceeds the review's definition of acute

    Minor

    The review defines acute isolation as lasting under one week, but later includes mice isolated for seven days in its discussion of acute isolation. Seven days is a full week, not under one week.

1 of 1

Cites

Flagged first, then by citations

1 of the 235 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. United Nations, 2017, United Nations, Department of Economic and Social Affairs, Population Division (2017), Household Size & Composition
  2. Schjelderup‐Ebbe T., 1922, Beiträge zur Sozialpsychologie des Haushuhns. [Observation on the social psychology of domestic fowls.], Z. Für Psychol. Physiol. Sinnesorgane Abt 1 Z. Für Psychol., 88, 225

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Related

Authors
Matthews, G. A., & Tye, K. M.
Affiliations
  • Massachusetts Institute of Technology (US)
  • Salk Institute for Biological Studies (US)
Corresponding author
Tye, Kay M.
ORCID
Venue
Annals of the New York Academy of Sciences
Publisher
Wiley
Published
2019-03-15
Volume
1457
Issue
1
Pages
5-25
ISSN
  • 0077-8923 (ISSN-L)
  • 1749-6632
DOI
10.1111/nyas.14016
PMC
PMC7593988
OpenAlex
W2921413914
Semantic Scholar
1aa34904db72326943bf8ffd37dcb0b8e4fa1237
Cited by
273
References
235
Citations by year
2026: 32 · 2025: 45 · 2024: 40 · 2023: 72 · 2022: 29 · 2021: 33 · 2020: 17 · 2019: 5
FWCI
3.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Annals of the New York Academy of Sciences (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Esther A. and Joseph Klingenstein Fund
  • Alfred P. Sloan Foundation
  • New York Stem Cell Foundation
  • Charles A. King Trust (Postdoctoral Research Fellowship)
  • National Institute on Aging (RF1‐AG047661‐01)
  • JPB Foundation
  • McKnight Foundation
  • National Institute of Mental Health (R01‐MH102441‐01, R01‐MH115920)
  • National Institute on Alcohol Abuse and Alcoholism (R01‐AA023305‐01)
  • NIH Office of the Director (New Innovator)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DP2‐DK‐102256‐01)
  • National Center for Complementary and Integrative Health (Pioneer Award DP1‐AT009925)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
social homeostasis, social isolation, loneliness, social connectedness, neural circuits, homeostatic regulation, social support, energy homeostasis, fluid balance, rodent models, disease susceptibility
MeSH terms
Adaptation, Psychological, Animals, Behavior, Animal, Arvicolinae, Glucocorticoids, Homeostasis, Humans, Hypothalamo-Hypophyseal System, Hypothalamus, Loneliness, Models, Neurological, Motivation, Oxytocin, Pituitary-Adrenal System, Receptors, Opioid, Social Behavior, Social Isolation, Social Support, Mice, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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