A thalamo-centric neural signature for restructuring negative self-beliefs

Abstract

Negative self-beliefs are a core feature of psychopathology. Despite this, we have a limited understanding of the brain mechanisms by which negative self-beliefs are cognitively restructured. Using a novel paradigm, we had participants use Socratic questioning techniques to restructure self-beliefs during ultra-high resolution 7-Tesla functional magnetic resonance imaging (UHF fMRI) scanning. Cognitive restructuring elicited prominent activation in a fronto-striato-thalamic circuit, including the mediodorsal thalamus (MD), a group of deep subcortical nuclei believed to synchronize and integrate prefrontal cortex activity, but which has seldom been directly examined with fMRI due to its small size. Increased activity was also identified in the medial prefrontal cortex (MPFC), a region consistently activated by internally focused mental processing, as well as in lateral prefrontal regions associated with regulating emotional reactivity. Using Dynamic Causal Modelling (DCM), evidence was found to support the MD as having a strong excitatory effect on the activity of regions within the broader network mediating cognitive restructuring. Moreover, the degree to which participants modulated MPFC-to-MD effective connectivity during cognitive restructuring predicted their individual tendency to engage in repetitive negative thinking. Our findings represent a major shift from a cortico-centric framework of cognition and provide important mechanistic insights into how the MD facilitates key processes in cognitive interventions for common psychiatric disorders. In addition to relaying integrative information across basal ganglia and the cortex, we propose a multifaceted role for the MD whose broad excitatory pathways act to increase synchrony between cortical regions to sustain complex mental representations, including the self.

Dynamic Subcortical Modulators of Human Default Mode Network Function

“…This result is consistent with past studies, including our own, that have reported significant MD involvement in tasks probing aspects of self-referential cognition (Araujo et al 2015;Davey et al 2016). Recently, in Steward et al (2021), we examined the MD's specific modulatory influence on distributed prefrontal regions, addressing the hypothesis that it has a key orchestrating influence on the activity of task-relevant higher cortical circuits (Parnaudeau et al 2018;Pergola et al 2018;Halassa and Sherman 2019;Wolff and Vann 2019). We used a task that evoked aspects of self-referential cognition and regulatory control and found the MD to have a robust excitatory influence on multiple PFC subregions, whilst receiving distinct reciprocal modulation from the MPFC.…”

“…Both divisions were implicated as DMN hubs in the Alves et al (2019) study, whereas in a related study by Greene et al (2020), the MD was mapped more distinctly as a 'cognitive integration zone', linking the DMN to other large-scale cortical networks. Recent work by our group has complemented these findings by mapping a broad excitatory influence of the MD on multiple prefrontal regions, including the MPFC, during a cognitive self-regulation task (Steward et al 2021). Its results argue for a distinct coordinating role of the MD during higher cognition, whereby its task-evoked activity helps to sustain the engagement of cortical function.…”

“…The basal forebrain (BF) and mediodorsal thalamus (MD) have been identified as key subcortical structures of the DMN, with evidence pointing towards their unique contributions to dynamic network functioning (Nair et al 2018;Alves et al 2019;Buckner and DiNicola 2019;Steward et al 2021). In this study, we used task-based UHF fMRI to confirm their involvement across states of DMN activity suppression and engagement, and tested neural systems models of their modulatory influence on DMN cortical regions.…”

“…Our current results broadly replicate these findings, with the MD again having a robust excitatory influence on DMN cortical regions, while receiving more moderate reciprocal input from the cortex. In Steward et al (2021), we argued that these broad excitatory influences likely serve to increase the synchrony of cortical regions to help sustain and update complex mental representations (i.e., self representations) that emerge over time. This idea is well supported by animal studies of MD-cortical circuit connectivity (e.g., Schmitt et al 2017), and gains some further support here, where we observed MD recruitment to be more sustained than DMN cortical regions over the course of the self condition epoch (Figure 4).…”

“…Physiological noise was modelled at the first level using the PhysIO Toolbox (Kasper et al 2017). This toolbox applies noise correction to fMRI sequences using physiological recordings and has been found to improve blood-oxygen level dependent (BOLD) signal sensitivity and temporal signal-to-noise ratio (tSNR) at 7T (Reynaud et al 2017; see also Steward et al 2021). The Retrospective Image-based Correction function (RETROICOR; Glover et al 2000) was applied to model the periodic effects of heartbeat and breathing on BOLD signals, using acquired cardiac/respiratory phase information.…”