Imagine conscious awareness and working memory as a house, and the mediodorsal thalamus (MDT) as the driveway leading to it. When a postman carrying information arrives, they must pass through a gate that opens only for important news, preventing the house from becoming cluttered with useless paper.
In the brain, the medial prefrontal cortex (MPFC) acts as this gatekeeper. It assesses the value and self-relevance of competing thoughts and helps prioritise important information for effective decision-making.
But what happens when negative information keeps getting past the gate and entering the house, even though it may not be useful or accurate?
A core mechanism in the development and persistence of PTSD is the excessive negative appraisal of the traumatic event and its consequences. This can produce a persistent sense of threat and is associated with greater PTSD symptom severity (Brown, L.A. et al., 2019; Foa, E. B. et al., 1999).
Cognitive restructuring, a core component of cognitive behavioural therapy, helps people identify and critically examine unhelpful beliefs that contribute to psychological distress. They are encouraged to consider evidence and experiences that challenge these beliefs, enabling them to develop a more balanced perspective. The aim is to support individuals in reaching their own conclusions rather than simply providing them with alternative interpretations (Clark, 2013; Clark & Egan, 2015).
However, approximately one-third of people with PTSD still maintain their diagnosis after treatment (Bryant RA, 2019).
Agathos and colleagues (2026) investigated the brain mechanisms supporting the cognitive restructuring of negative beliefs and how alterations in these mechanisms might make such beliefs particularly resistant to change in people with PTSD.
Methods
The study used a cross-sectional design. The sample included 70 adults with PTSD and 66 trauma-exposed controls (TECs), recruited from the community in Melbourne, Australia. Diagnoses and psychiatric comorbidities were assessed using semi-structured telephone interviews.
Following cognitive restructuring training, participants underwent ultrahigh-field 7-Tesla functional magnetic resonance imaging (fMRI) while viewing 16 negative self-referential statements. They chose eight statements to challenge using cognitive restructuring strategies and silently repeated the other eight, rating their endorsement before and after the task.
General linear model (GLM) analyses identified brain regions showing greater activation when participants challenged, rather than repeated, negative cognitions. Dynamic causal modeling (DCM) was then used to estimate the strength and directionality of the influences among these pre-identified regions, based on the GLM results and prior evidence. The model included the mediodorsal thalamus (MDT) and four cortical regions: the medial prefrontal cortex (MPFC), dorsolateral prefrontal cortex (DLPFC), ventral posterior cingulate cortex (vPCC), and presupplementary motor area (preSMA). The DCM analyses included fewer participants (57 with PTSD and 59 controls), following exclusions and because a complete set of regional time series was required.
Results
On a behavioural level, before the task, participants with PTSD endorsed the negative statements more strongly (M = 4.88 ± 1.01) than TECs (M = 2.81 ± 0.96; t(134) = −12.23, P < 0.001, d = −2.10), indicating that these beliefs resonated more strongly with them. However, both groups significantly reduced their endorsement of the statements they had challenged (PTSD = t(65) = 3.72, P < 0.001, d = 0.48; TEC = t(65) = 3.22, P < 0.001, d = 0.40), with no evidence of a difference in the magnitude of this reduction between groups (t(127) = −0.03, P = 0.97, d = −0.01). This means that people with PTSD appeared just as able as controls to reduce their immediate endorsement of negative beliefs. These are immediate task ratings, however, and do not establish that beliefs change durably or that restructuring works equally well in everyday life or during therapy.
At a neural level, consistent with previous findings, cognitive restructuring involved dynamic and reciprocal interactions within a thalamocortical network centred on the mediodorsal thalamus (MDT) and involving core regions of the default mode network (DMN) and frontoparietal regulatory regions. These interactions appear to support the manipulation and updating of mental self-representations.
Previous research suggests that the MPFC acts like a gateway, helping to control which thoughts enter conscious awareness. It assigns value to competing mental representations and, through its inhibitory influence on the MDT, may filter out irrelevant information while prioritising salient information. The authors propose that, during cognitive restructuring, when information that challenges a negative belief is considered, the MPFC may reduce the self-relevant value assigned to that belief, making it less likely to re-enter conscious awareness.
The key finding was that, during cognitive restructuring, participants with PTSD showed weaker inhibitory modulation of the MDT by the MPFC than TECs (expected value of 0.20 Hz; posterior probability of 0.95). As negative information may be perceived as particularly important and relevant in PTSD, the authors suggest that weaker inhibition could allow it to remain more accessible to conscious awareness. This could make it harder for disconfirming information to update existing beliefs, leaving negative cognitions more deeply entrenched.
The strength of MPFC-to-MDT modulation did not reliably predict whether an individual had a PTSD diagnosis or not. However, within the PTSD group, it predicted the severity of negative beliefs about the world and others (r = 0.38, p = 0.006), but not beliefs about the self or self-blame. The authors therefore suggested that this association might reflect alterations in social cognition and threat appraisal associated with PTSD. However, as many participants in the sample had experienced interpersonal trauma, which may disrupt beliefs about trust and safety, it may also partly reflect the specific nature of their traumatic experiences.
Returning to our metaphor, in people with PTSD, the gatekeeper may be less able to stop postmen carrying negative messages, even when conflicting evidence suggests that they may be inaccurate. These messages may therefore keep travelling along the MDT driveway and entering the house, even when more reliable information is available.
Conclusions
This study provides evidence that altered communication within the thalamocortical network may be involved in cognitive restructuring in PTSD. In particular, the weaker inhibitory influence of the MPFC on the MDT may reduce the brain’s ability to filter negative information, potentially helping to explain why negative beliefs remain so persistent in PTSD.
These findings highlight a possible neural target for future brain-based interventions. However, the study does not establish that altered MPFC–MDT connectivity causes persistent negative beliefs or that targeting this pathway would improve treatment outcomes. Longitudinal and intervention studies are needed to determine its clinical relevance.
Strengths and limitations
A key strength was the comparison of participants with PTSD with trauma-exposed controls, rather than people without a history of trauma. This helped distinguish differences associated with PTSD from those related to trauma exposure itself. Combining ultrahigh-field 7-T fMRI with dynamic causal modelling (DCM) allowed the researchers to identify brain activation during cognitive restructuring and estimate the strength and direction of influence between selected regions. They also examined the potential effects of sex and psychiatric medication and found no strong evidence that either influenced modulatory connectivity. The authors declared no competing interests, and the study was primarily supported by public research funding.
There are several important limitations to consider:
- The sample was predominantly female, particularly in the PTSD group (92.86%, compared with 75.76% in the TEC group), limiting how confidently the findings can be generalised to men.
- Moreover, 92.86% of participants with PTSD had a comorbid mood or anxiety disorder, and 72.46% were taking psychiatric medication.
- Although no strong evidence was found that sex or medication use affected modulatory connectivity, the possible influence of psychiatric comorbidities was not investigated.
- All participants were recruited from the community in Melbourne, through online advertising, which may limit the generalisability of the findings to other populations and cultural contexts.
- A high proportion of participants had also experienced interpersonal or abuse-related trauma, so it is uncertain whether the findings extend to people with different traumatic experiences.
- The cross-sectional design cannot establish whether MPFC–MDT alterations preceded trauma exposure, creating a risk factor for PTSD, or developed following trauma or the onset of the disorder. Longitudinal research involving people at high risk of trauma exposure could help clarify this relationship.
- Although the task statements reflected DSM-5 descriptions of post-traumatic cognitions, they were not linked to participants’ own traumatic experiences and did not capture the full range of altered thinking associated with PTSD. In addition, pre- and post-task self-ratings may not reliably mirror people’s ability to challenge negative beliefs in everyday life.
- Finally, dynamic causal modelling (DCM) examined a predefined and limited network. Other relevant brain regions may therefore have been excluded.
Implications for practice
The findings may help researchers understand which brain processes are altered during cognitive restructuring in PTSD and how treatments might eventually be improved. Future studies should examine whether modulation of MPFC-to-MDT connectivity during cognitive restructuring can predict an individual’s response to therapy and whether it changes following successful treatment. If these findings are replicated, they could eventually support more individualised interventions and help identify people who may benefit from additional treatment components, such as strategies designed to strengthen emotional regulation skills.
These findings should be replicated in more representative samples with a more balanced sex distribution. Future research should also examine the possible effects of psychiatric comorbidities and different types of traumas.
The authors highlight the MPFC–MDT pathway as a potential target for pharmacological and neuromodulatory interventions in people whose negative beliefs do not respond to psychotherapy. They discuss ketamine, which may influence the default mode network through the MPFC, as well as interventions targeting the MPFC, such as transcranial magnetic stimulation and neurofeedback. Although these possibilities are interesting, they remain speculative: this study did not test any of these treatments or demonstrate that changing this pathway would improve clinical outcomes. Future studies should examine whether these interventions modify MPFC–MDT connectivity and whether such changes lead to meaningful improvements.
Finally, these findings could be relevant to other conditions in which negative cognitions are a core symptom and cognitive restructuring is also used, such as anxiety and depressive disorders. Future research should investigate whether comparable alterations in thalamocortical connectivity affect cognitive restructuring across these conditions.
Statement of interests
Laura has no competing interests to declare, and acknowledges the use of generative AI tools solely for language and grammar revision.
Editor
The blog was edited by Dr Dafni Katsampa.
Links
Primary paper
James Agathos, Ben Harrison, Kim Felmingham, Christopher Davey, Richard Bryant, Mayuresh Korgaonkar, Po-Han Kung, Sevil Ince, Bradford Moffat, Rebecca Glarin & Trevor Steward (2026) Cognitive restructuring and thalamocortical circuit alterations in post-traumatic stress disorder. Nature Mental Health, 4, 594–604.
Other references
Brown LA, Belli GM, Asnaani A et al (2019) A review of the role of negative cognitions about oneself, others, and the world in the treatment of PTSD. Cognitive Therapy and Research 43, 143-173.
Foa EB, Ehlers A, Clark DM et al (1999) The Posttraumatic Cognitions Inventory (PTCI): Development and validation. Psychological Assessment 11(3), 303-314.
Clark DA (2013) Cognitive restructuring. In: Hofmann SG (ed.) The Wiley Handbook of Cognitive Behavioral Therapy. Wiley.
Clark GI, Egan SJ (2015) The Socratic method in cognitive behavioural therapy: A narrative review. Cognitive Therapy and Research 39, 863-879.
Bryant RA (2019) Post-traumatic stress disorder: A state-of-the-art review of evidence and challenges. World Psychiatry 18, 259-269.