Biology subjects

Moffat, B. A.

Publications and source records attributed to Moffat, B. A..

5 recordsLinked to original sources

bioRxiv2025

Bivalent habenula modulation of human monoaminergic midbrain and cortical pathways

The habenula is implicated in signaling negative reward prediction errors (RPE), yet direct causal evidence demonstrating its influence on downstream human brain circuits is limited. Using ultra-high field (7T) fMRI and dynamic causal modelling across two negative RPE-inducing experimental tasks, we characterize habenula-directed connectivity with monoaminergic midbrain and cortical pathways in healthy adults. Negative feedback drove strong habenula inhibition of ventral tegmental area and dorsal raphe nucleus activity, while positive feedback had an excitatory effect. These core effects are replicated across reversal learning and perceptual decision uncertainty tasks, establishing a generalizable mechanism for behavioral adaptation. Task-specific modulatory effects emerged in pathways between the subcortical and cortical regions (ventral tegmental area[->]dorsal anterior cingulate cortex, dorsal raphe nucleus[->]medial prefrontal cortex, and dorsal anterior cingulate cortex[->]habenula), revealing context-dependent cortical elaboration of negative RPE-driven habenula signals. This provides the first evidence in humans for bivalent causal modulation of habenula function on monoaminergic midbrain and cortical pathways, demonstrating how the brain integrates negative and positive signals to guide adaptive behavior.

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↗

bioRxiv2024

High-precision neurofeedback-guided meditation training optimises real-world self-guided meditation practice for well-being

Meditation can benefit well-being and mental health, but novices often struggle to effectively recognize and disengage from mental processes during meditation due to limited awareness, potentially diminishing meditations benefits. We investigated whether personalised high-precision neurofeedback (NF) can improve disengagement from mental activity during meditation and enhance meditations outcomes. In a single-blind, controlled, longitudinal paradigm, 40 novice meditators underwent two consecutive days of meditation training with intermittent visual feedback from either their own (N=20) or a matched participants (N=20; control group) posterior cingulate cortex (PCC) activity measured using 7 Tesla functional magnetic resonance imaging. During training, the experimental group showed stronger functional decoupling of PCC from dorsolateral prefrontal cortex, indicating better control over disengagement from mental processes during meditation. This led to greater improvements in emotional well-being and mindful awareness of mental processes during a week of real-world self-guided meditation. We provide compelling evidence supporting the utility of high-precision NF-guided meditation training to optimise real-world meditation practice for well-being.

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↗