Threat Vigilance and Intrinsic Amygdala Connectivity

A well documented amygdala-dorsomedial prefrontal circuit is theorized to promote attention to threat (‘threat vigilance’). Prior research has implicated a relationship between individual differences in trait anxiety/vigilance, engagement of this circuitry, and anxiogenic features of the environment (e.g. through threat-of-shock and movie-watching). In the present study, we predicted that—for those scoring high in self-reported anxiety and a behavioral measure of threat vigilance—this circuitry is chronically engaged, even in the absence of anxiogenic stimuli. Our analyses of resting-state fMRI data (N=639) did not, however, provide evidence for such a relationship. Nevertheless, in our planned exploratory analyses, we saw a relationship between threat vigilance behavior (but not self-reported anxiety) and intrinsic amygdala-periaqueductal gray connectivity. Here, we suggest this subcortical circuitry may be chronically engaged in hypervigilant individuals, but that the amygdala-prefrontal circuitry may only be engaged in response to anxiogenic stimuli.

Functional Contribution of the Medial Prefrontal Circuitry in Major Depressive Disorder and Stress-Induced Depressive-Like Behaviors

Despite decades of research on the neurobiology of major depressive disorder (MDD), the mechanisms underlying its expression remain unknown. The medial prefrontal cortex (mPFC), a hub region involved in emotional processing and stress response elaboration, is highly impacted in MDD patients and animal models of chronic stress. Recent advances showed alterations in the morphology and activity of mPFC neurons along with profound changes in their transcriptional programs. Studies at the circuitry level highlighted the relevance of deciphering the contributions of the distinct prefrontal circuits in the elaboration of adapted and maladapted behavioral responses in the context of chronic stress. Interestingly, MDD presents a sexual dimorphism, a feature recognized in the molecular field but understudied on the circuit level. This review examines the recent literature and summarizes the contribution of the mPFC circuitry in the expression of MDD in males and females along with the morphological and functional alterations that change the activity of these neuronal circuits in human MDD and animal models of depressive-like behaviors.

Generative replay for compositional visual understanding in the prefrontal-hippocampal circuit

Understanding the visual world is a constructive process. Whilst a frontal-hippocampal circuit is known to be essential for this task, little is known about the associated neuronal computations. Visual understanding appears superficially distinct from other known functions of this circuit, such as spatial reasoning and model-based planning, but recent models suggest deeper computational similarities. Here, using fMRI, we show that representations of a simple visual scene in these brain regions are relational and compositional - key computational properties theorised to support rapid construction of hippocampal maps. Using MEG, we show that rapid sequences of representations, akin to replay in spatial navigation and planning problems, are also engaged in visual construction. Whilst these sequences have previously been proposed as mechanisms to plan possible futures or learn from the past, here they are used to understand the present. Replay sequences form constructive hypotheses about possible scene configurations. These hypotheses play out in an optimal order for relational inference, progressing from predictable to uncertain scene elements, gradually constraining possible configurations, and converging on the correct scene configuration. Together, these results suggest a computational bridge between apparently distinct functions of hippocampal-prefrontal circuitry, and a role for generative replay in constructive inference and hypothesis testing.

Neural effects of placebo analgesia in fibromyalgia patients and healthy individuals

ABSTRACTPlacebo analgesia is hypothesized to involve top-down engagement of prefrontal regions that access endogenous pain inhibiting opioid pathways. Fibromyalgia (FM) patients have neuroanatomical and neurochemical alterations in pathways relevant to placebo analgesia. Thus, it remains unclear whether placebo analgesic mechanisms would differ in FM patients compared to healthy controls (HCs). Here, using placebo-analgesia-inducing paradigms that included verbal suggestions and conditioning manipulations, we examined whether behavioral and neural placebo analgesic responses differed between 32 FM patients and 46 age- and sex-matched HCs. Participants underwent a manipulation scan, where noxious high and low heat were paired with the control and placebo cream, respectively, and a placebo experimental scan with equal noxious heat temperatures. Before the experimental scan, each participant received saline or naloxone, an opioid receptor antagonist. Across all participants, the placebo condition decreased pain intensity and unpleasantness ratings, decreased activity within the right insula and bilateral secondary somatosensory cortex, and modulated the Neurologic Pain Signature. There were no differences between HCs and FM patients in pain intensity ratings or neural responses during the placebo condition. Despite the perceptual and neural effects of the placebo manipulation, prefrontal circuitry was not activated during the expectation period and the placebo analgesia was unaltered by naloxone, suggesting placebo effects were driven more by conditioning than expectation. Together, these findings suggest that placebo analgesia can occur in both HCs and chronic pain FM patients, without the involvement of opiodergic prefrontal modulatory networks.