Biology subjects

Felmingham, K.

Publications and source records attributed to Felmingham, K..

4 recordsLinked to original sources

bioRxiv2026

Predictability and controllability shape aversive learning and stress responses through independent computational mechanisms

BACKGROUND: An individual's adaptation to threatening environments under uncertainty is reflected in stress responses. Predictability (the ability to anticipate events) and controllability (the ability to control outcomes) are central to how one adapts, yet their joint influence on aversive learning remains unclear. METHODS: Thirty healthy adults completed a probabilistic aversive learning task in which cue-outcome contingencies varied across levels of predictability and controllability, i.e. whether shock intensity depended on prediction accuracy. Prediction accuracy, reaction time, subjective stress ratings, and skin conductance responses were recorded throughout. Trial-wise learning dynamics were estimated using the Volatile Kalman Filter. RESULTS: Prediction accuracy reduced as environments became less predictable and negatively associated with higher learning rates across predictability levels, with the strongest relationship observed in highly predictable blocks. Skin conductance responses showed that moderately predictable environments elicited responses like those in highly predictable environments when accurate predictions reduced shock intensity, but resembled responses in unpredictable environments when shock intensity was uncontrollable. Model comparison revealed a double dissociation between subjective stress ratings and skin conductance responses. Subjective ratings were best explained by model-derived volatility when prediction accuracy determined shock intensity and by belief uncertainty when it was independent of prediction accuracy, whereas skin conductance responses showed the reverse pattern. Reaction times were best explained by belief uncertainty when predictions influenced shock intensity. Higher anxiety was associated with elevated learning rates in highly and moderately predictable blocks when predictions did not control shock intensity.

neuroscience↗

bioRxiv2026

Mapping the neural circuitry of cognitive restructuring in depressive and anxiety disorders

BackgroundCognitive restructuring, the process of identifying and challenging negative thoughts, is a key technique for treating depressive and anxiety disorders. Although neuroimaging studies have characterised the brain systems supporting cognitive restructuring in healthy individuals, it remains unclear how these systems are altered in depression and anxiety, or whether each disorder is associated with distinct neural dysfunction. MethodsSeventy-three clinical participants with depressive or anxiety disorders and 70 healthy controls completed a cognitive restructuring paradigm during 7 Tesla functional magnetic resonance imaging (fMRI). The task required participants to either repeat a series of negative statements or challenge them using Socratic questioning. Group-level fMRI analyses examined the effects of depressive and anxiety symptom severity on brain activation, while dynamic causal modelling characterized the directional neural influences between implicated regions. ResultsDuring challenging compared to repeating statements, greater depressive symptoms were associated with reduced dorsolateral prefrontal cortex (dlPFC) activation. Conversely, greater anxiety symptoms were associated with greater dlPFC activation. Effective connectivity results revealed that depressive symptoms were associated with greater inhibition from the ventrolateral prefrontal cortex (vlPFC) to the ventromedial prefrontal cortex, whereas anxiety symptoms were associated with greater excitation from the dlPFC to amygdala and greater inhibition from the vlPFC to amygdala. ConclusionsWhile clinical participants modified negative beliefs as effectively as healthy controls, depressive and anxiety symptoms were associated with dissociable neural signatures during restructuring. This suggests that cognitive behavioral therapy may engage partially distinct mechanisms depending on symptom profile, a possibility that warrants longitudinal investigation of treatment response.

neuroscience↗

bioRxiv2023

A Brain Model of Disturbed Self-Appraisal in Social Anxiety Disorder

The brains default mode network has a central role in the processing of information concerning oneself. Dysfunction in this self-referential processing represents a key component of multiple mental health conditions, including social anxiety disorder (SAD). This case-control study aimed to clarify alterations to network dynamics present during self-appraisal in SAD participants. A total of 38 adolescents and young adults with SAD and 72 healthy control participants underwent a self-referential processing fMRI task. The task involved two primary conditions of interest: direct self-appraisal (thinking about oneself) and reflected self-appraisal (thinking about how others might think about oneself). Dynamic causal modelling and parametric empirical Bayes were then used to explore differences in the effective connectivity of the default mode network between groups. We observed connectivity differences between SAD and healthy control participants in the reflected self-appraisal but not the direct self-appraisal condition. Specifically, SAD participants exhibited greater excitatory connectivity from the posterior cingulate cortex (PCC) to medial prefrontal cortex (MPFC) and greater inhibitory connectivity from the inferior parietal lobule (IPL) to MPFC. In contrast, in the absence of task modulation, SAD participants exhibited reduced intrinsic connectivity, with reduced excitatory connectivity from the PCC to MPFC and reduced inhibitory connectivity from the IPL to MPFC. As such, participants with SAD showed changes to afferent connections to the MPFC which occurred during both reflected self-appraisal as well as intrinsically. The presence of connectivity differences in reflected and not direct self-appraisal is consistent with the characteristic fear of negative social evaluation that is experienced by people with SAD.

neuroscience↗

bioRxiv2021

Cortico-striatal activity characterizes human safety learning via Pavlovian conditioned inhibition

Safety learning generates associative links between neutral stimuli and the absence of threat, promoting the inhibition of fear and security-seeking behaviours. Precisely how safety learning is mediated at the level of underlying brain systems, particularly in humans, remains unclear. Here, we integrated a novel Pavlovian conditioned inhibition task with ultra-high field (UHF) fMRI to examine the neural basis of inhibitory safety learning in 49 healthy participants. In our task, participants were conditioned to two safety signals: a conditioned inhibitor that predicted threat-omission when paired with a known threat signal (A+/AX-), and a standard safety signal that generally predicted threat-omission (BC-). Both safety signals evoked equivalent autonomic and subjective learning responses but diverged strongly in terms of underlying brain activation. The conditioned inhibitor was characterized by more prominent activation of the dorsal striatum, anterior insular and dorsolateral prefrontal cortex compared to the standard safety signal, whereas the latter evoked greater activation of the ventromedial prefrontal cortex, posterior cingulate and hippocampus, among other regions. Further analyses of the conditioned inhibitor indicated that its initial learning was characterized by consistent engagement of dorsal striatal, midbrain, thalamic, premotor, and prefrontal subregions. These findings suggest that safety learning via conditioned inhibition involves a distributed cortico-striatal circuitry, separable from broader cortical regions involved with processing standard safety signals (e.g., CS-). This cortico-striatal system could represent a novel neural substrate of safety learning, underlying the initial generation of stimulus-safety associations, distinct from wider cortical correlates of safety processing, which facilitate the behavioral outcomes of learning. Significance statementIdentifying safety is critical for maintaining adaptive levels of anxiety, but the neural mechanisms of human safety learning remain unclear. Using ultra-high field fMRI, we compared learning-related brain activity for a conditioned inhibitor, which actively predicted threat-omission, and a standard safety signal (CS-), which was passively unpaired with threat. The inhibitor engaged an extended circuitry primarily featuring the dorsal striatum, along with thalamic, midbrain, and premotor/prefrontal cortex regions. The CS-exclusively involved cortical safety-related regions observed in basic safety conditioning, such as the vmPFC. These findings extend current models to include learning-specific mechanisms for encoding stimulus-safety associations, which might be distinguished from expression-related cortical mechanisms. These insights may suggest novel avenues for targeting dysfunctional safety learning in psychopathology.

neuroscience↗