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The four papers selected trace a coherent translational arc exploring self-other differentiation and social cognition deficits in schizophrenia. Beginning with Fuentes-Claramonte et al. (2020), neuroimaging data demonstrate that individuals with schizophrenia show reduced activation in the right temporoparietal junction (rTPJ) during other-reflection tasks, supporting the hypothesis that rTPJ dysfunction underlies impaired self-other processing. This aligns with broader theories of disrupted social cognition in schizophrenia.

The study by Lu et al. (2012) complements this by confirming the existence of a default mode network (DMN) in rats, including regions functionally analogous to the rTPJ. This provides foundational validation for rodent models in studying network-level social cognitive functions. Török et al. (2021) further this translational bridge by showing that social recognition deficits in vasopressin-deficient Brattleboro rats, a model with behavioural parallels to schizophrenia, can be ameliorated with chronic antipsychotic treatment. Finally, Brunnlieb et al. (2013) show that intranasal vasopressin modulates left TPJ activity in humans during social recognition, suggesting the TPJ is not only a site of dysfunction but also one of potential neuromodulation.

Collectively, these studies span the T0 to T2 stages of translational science. However, a gap remains between preclinical findings and clinical application. For instance, while vasopressin modulation shows promise, its therapeutic utility in schizophrenia is untested. Moreover, rodent models lack a clear TPJ homolog, requiring cautious interpretation. Still, the network-level congruence across species supports further integration of animal and human research to bridge cognitive neuroscience and psychiatric treatment.

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Brain imaging correlates of self- and other-reflection in schizophrenia

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Self- and other-reflection in schizophrenia were studied with fMRI. Patients failed to activate the right temporo-parietal junction in other-reflection. They also hyperactivated lateral prefrontal cortex for self and other-reflection. These findings…

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Ameliorating schizophrenia-like symptoms in vasopressin deficient male Brattleboro rat by chronic antipsychotic treatment - PubMed

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Due to its various function vasopressin has been associated with many psychiatric disorders, including schizophrenia. Our previous study confirmed that vasopressin-deficient (di/di) Brattleboro rat can be a good genetic model for schizophrenia. Our present aim was to confirm whether the treatment ef …

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Rat brains also have a default mode network

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The default mode network (DMN) in humans has been suggested to support a variety of cognitive functions and has been implicated in an array of neuropsychological disorders. However, its function(s) remains poorly understood. We show that rats…

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Vasopressin modulates social recognition-related activity in the left temporoparietal junction in humans

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The neuropeptide vasopressin is a key molecular mediator of social behavior in animals and humans, implicated in anxiety and autism. Social recognition, the ability to assess the familiarity of others, is essential for appropriate social…

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To examine whether individuals with schizophrenia show altered rTPJ activity during self- and other-reflection tasks compared to healthy controls.

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Figure 1: Mean Activation in Self > Facts Contrast                                             Brain regions activated during self-reflection versus semantic processing. Panels show activation in (A) healthy controls and (B) schizophrenia patients. Both groups activate the medial prefrontal cortex and precuneus; however, patients exhibit hyperactivation in the left lateral prefrontal cortex, indicating increased cognitive effort during self-reflection. 

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Background: Social cognition, particularly the ability to distinguish between self and others (i.e., theory of mind), is commonly impaired in individuals with schizophrenia.

Key Brain Region: The right temporoparietal junction (rTPJ) is a major region implicated in perspective-taking and mentalizing—processes essential for understanding others' thoughts and intentions.

Research Question: Do individuals with schizophrenia show different patterns of brain activation—especially in the rTPJ—when reflecting on themselves versus others?

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Participants: Included both schizophrenia patients and healthy controls.

Task: Participants underwent fMRI while engaging in a task requiring them to reflect on either:

Themselves,

An acquaintance, or

A public figure.

This allowed the researchers to distinguish between self-reflection and other-reflection in different social contexts.

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Figure 3: Mean Activation in Other > Facts Contrast                                         Brain regions activated during other-reflection versus semantic processing. Panels depict activation in (A) healthy controls and (B) schizophrenia patients. Healthy controls show increased activation in the right temporoparietal junction (rTPJ) during other-reflection, whereas schizophrenia patients exhibit a lack of rTPJ activation, indicating impairments in distinguishing self from others. 

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Controls: Healthy participants showed increased activation in the rTPJ during other-reflection, consistent with prior literature.

Schizophrenia Patients: Showed abnormal activation patterns, with reduced differentiation between self- and other-reflection in key areas like the rTPJ, medial prefrontal cortex, and posterior cingulate.

Notably, the rTPJ did not respond selectively to other-related reflection in patients, suggesting a breakdown in normal social processing.

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Figure 2: Group Differences in Self vs. Facts Contrast.                                    Differences in brain activation between healthy controls and schizophrenia patients during self-reflection versus semantic processing. The plot displays mean parameter estimates for the left dorsolateral prefrontal cortex (DLPFC). Schizophrenia patients show significantly greater activation in the left DLPFC, suggesting compensatory mechanisms or increased cognitive demand during self-reflection.           

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Individuals with schizophrenia showed reduced differentiation in brain activity between reflecting on themselves and others, particularly in the right temporoparietal junction (rTPJ).

In healthy controls, the rTPJ was selectively activated during other-reflection, consistent with its known role in theory of mind and perspective-taking.

The lack of rTPJ specificity in patients suggests a neural basis for social cognitive impairments commonly seen in schizophrenia, such as difficulty distinguishing self from others, paranoia, and delusional thinking.

Other affected regions included the medial prefrontal cortex and posterior cingulate cortex, indicating potential default mode network (DMN) dysfunction—pointing to broader network-level disruptions rather than isolated regional issues.

These findings emphasize that social cognition deficits in schizophrenia are not merely behavioural but tied to specific brain abnormalities.

Limitations of the study include a small sample size, possible effects of medication, and the complexity of capturing self-/other-reflection in a controlled task.

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To evaluate whether chronic antipsychotic treatment (haloperidol, clozapine, or aripiprazole) can reverse schizophrenia-like symptoms—specifically social recognition deficits and impaired sensorimotor gating—in vasopressin-deficient Brattleboro rats.

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Background: The Brattleboro rat, genetically deficient in vasopressin, exhibits behaviours analogous to schizophrenia symptoms, such as social memory impairment and sensorimotor gating deficits.​

Prior research suggests that vasopressin plays a role in social behaviour modulation.​

Research Question: Can chronic antipsychotic treatment ameliorate schizophrenia-like symptoms in vasopressin-deficient Brattleboro rats?

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Subjects: Male vasopressin-deficient Brattleboro rats and control Long-Evans rats.​

Procedure:

Rats were administered chronic treatments with antipsychotics: haloperidol, clozapine, and aripiprazole.​

Behavioural assessments included tests for social recognition and prepulse inhibition (PPI) of the startle reflex to evaluate sensorimotor gating.​

Analysis: Comparisons were made between treated and untreated groups to assess the efficacy of antipsychotic interventions on schizophrenia-like behaviours.

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Social Recognition:

Untreated Brattleboro rats displayed significant deficits in social recognition compared to controls.​

Chronic treatment with all three antipsychotics successfully normalized social recognition abilities in Brattleboro rats.​

Sensorimotor Gating (PPI):

Brattleboro rats exhibited reduced PPI, indicating impaired sensorimotor gating.​

Antipsychotic treatments restored PPI levels to those comparable with control rats.​

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Antipsychotic treatment (haloperidol, clozapine, aripiprazole) improved both social recognition and sensorimotor gating (PPI) deficits in vasopressin-deficient Brattleboro rats.

Improvement suggests that these behaviours are responsive to dopamine-modulating treatments, supporting their validity as schizophrenia-like symptoms.

Differences in drug effectiveness:

Aripiprazole showed strong therapeutic effects with minimal social side effects.

Some treatments improved PPI but not social behaviours as robustly, indicating distinct neural pathways.

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Chronic antipsychotic treatment reversed core schizophrenia-like symptoms in a vasopressin-deficient rat model.

Implications: Demonstrates that chronic antipsychotic therapy can improve behaviours relevant to human symptoms.

Suggests that aripiprazole may be uniquely well-suited for preserving social motivation while treating schizophrenia, making it a strong candidate for further research.

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To determine if rats have a default mode network (DMN) similar to humans, supporting their use as models for studying DMN functions and their implications in various neuropsychological disorders.

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Background:

The Default Mode Network (DMN) is a set of interconnected brain regions active during rest and implicated in self-referential thinking and social cognition.​

In humans, the DMN includes areas such as the medial prefrontal cortex, posterior cingulate cortex, and the right temporoparietal junction (rTPJ).​

Research Question: Do rats possess a DMN similar to that of humans and nonhuman primates, suggesting evolutionary conservation of this network?

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Subjects: Adult rats were used for the study.​

Procedure: Resting-state functional MRI (rs-fMRI) was conducted under light anesthesia to detect synchronous low-frequency fluctuations indicative of functional connectivity.​

Analysis: Independent component analysis (ICA) was employed to identify networks exhibiting DMN-like activity.

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Figure 1: This figure presents the spatial map of the rat default mode network (DMN) identified through independent component analysis (ICA) of resting-state functional MRI data. It highlights brain regions that are functionally connected, analogous to the human DMN. It demonstrates the existence of a DMN in rats, providing a foundation for comparative studies with humans.   

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Identification of Rat DMN: A network was identified in rats showing functional connectivity patterns analogous to the human DMN, including regions homologous to the medial prefrontal cortex and posterior cingulate cortex.​

Functional Connectivity: The identified rat DMN exhibited synchronous activity during rest, similar to observations in humans.

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Evolutionary Conservation: The presence of a DMN in rats suggests that this network is evolutionarily conserved across mammalian species.​

Link to Schizophrenia and rTPJ: Given that the human DMN encompasses the rTPJ, the identification of a similar network in rats provides a foundation for translational studies.

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Rats possess a DMN with functional connectivity patterns similar to those in humans, indicating evolutionary conservation.​

This finding supports the use of rat models to investigate DMN-related functions and dysfunctions, particularly concerning regions like the rTPJ involved in social cognition.

Implications: Rats can serve as viable models for studying DMN functionality and its role in neuropsychiatric disorders, including schizophrenia.​

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To investigate whether intranasal vasopressin alters neural activity in the left temporoparietal junction (TPJ) during social recognition tasks in humans.

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Background: The neuropeptide vasopressin has been implicated in enhancing social recognition in both animals and humans.​

Research Question: Does vasopressin administration modulate neural activity in the TPJ during social recognition tasks in humans?

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Subjects: Healthy male participants.​

Procedure:

A double-blind, placebo-controlled design was used where participants received intranasal vasopressin or placebo.​

Participants performed a face-matching task involving familiar and unfamiliar faces while undergoing functional magnetic resonance imaging (fMRI) to assess brain activity.​

Analysis: Brain activation patterns were compared between the vasopressin and placebo conditions, focusing on the TPJ region.

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TPJ Activation:

Under placebo, the left TPJ showed increased activation in response to unfamiliar faces compared to familiar ones.​

Vasopressin administration attenuated this differential activation, leading to comparable TPJ responses to both familiar and unfamiliar faces.

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Vasopressin's modulation of TPJ activity suggests its role in altering neural processing related to social recognition.​

This finding aligns with vasopressin's known effects on social behavior and supports its potential therapeutic application in conditions characterized by social cognitive deficits.

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Intranasal vasopressin alters activity in the left temporoparietal junction (TPJ) during social recognition tasks, reducing the neural distinction between familiar and unfamiliar faces.

Implications: Points to vasopressin-based interventions as potential therapeutic strategies for improving social cognition in clinical populations.

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Main takeaway: The rTPJ is a promising neural target for future translational research aimed at improving social functioning in schizophrenia—via pharmacological, neuromodulatory, or behavioural interventions.

Implication: Disrupted rTPJ activity suggests it could be modulated to improve social cognition in schizophrenia. It also reinforces that social deficits in schizophrenia have a neurological basis, not just a behavioural one. Furthermore, it points to potential interventions targeting broader default mode network (DMN) disruptions.

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The right temporoparietal junction (rTPJ) is a critical brain region involved in self–other differentiation, perspective-taking, and broader social cognition—all of which are impaired in schizophrenia. The four studies in this translational pathway collectively build a case for the rTPJ as a key neural target in both understanding and treating social deficits in schizophrenia.

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The rTPJ is heavily implicated in self-other differentiation and theory of mind—the ability to infer other people’s thoughts and intentions. In individuals with schizophrenia, this process is disrupted. Neuroimaging data show that while healthy individuals exhibit rTPJ activation during other-reflection, individuals with schizophrenia fail to show this selectivity, suggesting a breakdown in distinguishing their own thoughts and perspectives from those of others. This dysfunction may underlie key symptoms like paranoia, delusions of reference, and impaired social reasoning.

Meanwhile, the lTPJ, although not always the primary focus in schizophrenia literature, has emerged as a region sensitive to social recognition and familiarity judgments. In a study administering intranasal vasopressin, healthy participants showed modulated lTPJ activity, where the neural distinction between familiar and unfamiliar individuals was reduced. This suggests that the lTPJ is not only involved in processing social identity and recognition but also responsive to neurochemical modulation, offering a potential therapeutic target for social processing deficits.

The rTPJ appears crucial for distinguishing perspectives, understanding agency, and reflecting on others' intentions.

The lTPJ is more engaged in recognition, social salience, and contextual familiarity and can be pharmacologically modulated.

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While most direct human studies, such as Brunnlieb et al. (2013), report vasopressin’s modulatory effects in the left TPJ (lTPJ) during social recognition tasks, the rTPJ remains highly relevant due to its critical role in self-other differentiation, perspective-taking, and theory of mind — functions frequently disrupted in schizophrenia.

Although there is no current empirical study showing vasopressin directly modulating rTPJ activity, we can infer a potential link based on overlapping domains:

rTPJ dysfunction has been consistently linked to impairments in distinguishing self from other in schizophrenia (as shown in Fuentes-Claramonte et al., 2020).

Vasopressin, as a neuromodulator, has shown the capacity to alter TPJ activity (specifically lTPJ) and influence social recognition — a behaviour that relies on intact self-other processing.

In this way, vasopressin’s impact on TPJ function may not be strictly lateralized. Given the functional connectivity between left and right TPJ regions and their joint role in social cognition, it is plausible that modulating one side (e.g., lTPJ) may influence or compensate for activity in the other (e.g., rTPJ).

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What drew me to this topic was a deep interest in how we understand ourselves in relation to others, especially in the context of schizophrenia, where that boundary can blur in such profound ways. I had some foundational knowledge about the default mode network and the role of the temporoparietal junction in social cognition, but I hadn’t considered how these systems could be studied across both humans and animal models. I assumed the gap between basic neuroscience and psychiatric application was linear and straightforward.

Through this project, I learned how complex and multi-layered translational science really is. I saw how animal research, human imaging, and pharmacological interventions each offer a different piece of the puzzle and how critical it is to bridge them carefully. Understanding that even rats have a default mode network changed how I think about the universality of brain networks and made me more appreciative of how much we share across species.

As a neuroscientist, I now better grasp the value and limitations of modelling human cognition. As a human, I’m more aware of how fragile our sense of self can be, and how much empathy and scientific nuance are needed when studying disorders like schizophrenia.