Glarin, R. K. | Search bioRxiv

bioRxiv2021

Dynamic Subcortical Modulators of Human Default Mode Network Function

The brains default mode network (DMN) enables flexible switching between internally and externally focused cognition. Precisely how this modulation occurs is not well understood, although may involve key subcortical mechanisms, including hypothesized influences from the basal forebrain (BF) and mediodorsal thalamus (MD). Here, we used ultra-high field (7T) functional magnetic resonance imaging to examine the involvement of the BF and MD across states of task-induced DMN activity modulation. Specifically, we mapped DMN activity suppression ( deactivation) when participants transitioned between rest and externally focused task performance, as well as DMN activity engagement ( activation) when task performance was internally (i.e., self) focused. Consistent with recent rodent studies, the BF showed overall activity suppression with DMN cortical regions when comparing the rest to external task conditions. Further analyses, including dynamic causal modelling, confirmed that the BF drove changes in DMN cortical activity during these rest-to-task transitions. The MD, by comparison, was specifically engaged during internally focused cognition and demonstrated a broad excitatory influence on DMN cortical activation. These results provide the first direct evidence in humans of distinct basal forebrain and thalamic circuit influences on the control of DMN function and suggest novel mechanistic avenues for ongoing translational research.

neuroscience↗

bioRxiv2021

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

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.

neuroscience↗