Biology subjects

Glarin, R. K.

Publications and source records attributed to Glarin, R. K..

4 recordsLinked to original sources

bioRxiv2025

Effective connectivity reveals dual-route mechanism of visual prediction precision via insula and pulvinar

The brains ability to weight predictions by their precision is a central mechanism in predictive processing, enabling optimal integration of prior expectations with incoming sensory input. Despite its theoretical significance, the neural circuitry that implements precision-weighted prediction remains unclear. Using 7-Tesla fMRI and dynamic causal modelling (DCM), this study investigated how the brain encodes the precision of predictions during a visual cueing task with high- and low-precision conditions. We focused on the key regions implicated in predictive processing: the insular cortex, the pulvinar nucleus of the thalamus, and primary visual cortex (V1). Behaviourally, participants showed significantly greater accuracy in the high-precision condition (p < .001), confirming effective task manipulation. DCM analyses revealed that high-precision predictions elicited excitatory modulation of connectivity from the insula to V1 (Pp = .95), alongside inhibitory influences from the insula to the pulvinar (Pp = .99) and from the pulvinar to V1 (Pp = .89). Furthermore, leave-one-out cross validation revealed that individual differences in behavioural sensitivity to precision were positively predicted by pulvinar-to-insula connectivity (r = .36, p = .026) and negatively predicted by the connectivity between pulvinar and V1 (pulvinar to V1: r = .35, p = .033; V1 to pulvinar: r = .37, p = .026), highlighting the behavioural relevance of these pathways. Together, these findings suggest a dual-route mechanism whereby the insula directly enhances top-down predictions in V1 while indirectly dampening bottom-up sensory input via the pulvinar. This mechanism may facilitate Bayesian integration under uncertainty and offers new hypotheses into how precision weighting may be disrupted in neuropsychiatric conditions.

neuroscience↗

bioRxiv2024

Altered basal forebrain regulation of intrinsic brain networks in depressive and anxiety disorders

Depressive and anxiety disorders are characterized by altered connectivity within and between the default mode (DMN) and salience networks. Basal forebrain subdivisions, critical for regulating network activity, remain understudied across these conditions. To address this gap, we analyzed 7-Tesla resting-state functional magnetic resonance imaging data from a transdiagnostic sample (n = 70), primarily with depressive and anxiety disorders, and healthy controls (n = 77). We used spectral dynamic causal modelling to assess effective connectivity between the medial septum/diagonal band (Ch1-3), nucleus basalis of Meynert (Ch4), ventral pallidum, and DMN and salience networks. Healthy participants showed excitatory connectivity from Ch1-3 to the DMN and from Ch4 to the anterior insula. In contrast, clinical participants exhibited greater inhibitory Ch4 to DMN connectivity and increased excitatory connectivity from Ch4 to the anterior insula. Wide-spread Ch4 connectivity dysfunction may implicate the cholinergic system as a mechanistic and therapeutic target for depressive and anxiety disorders.

neuroscience↗

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↗