Biology subjects

Ceko, M.

Publications and source records attributed to Ceko, M..

3 recordsLinked to original sources

bioRxiv2021

Do we really understand the role of the prefrontal cortex in placebo analgesia?

Several reviews have strongly implicated prefrontal cortical engagement in expectation-based placebo analgesia. We recently found a robust placebo analgesic response and associated decreases in pain-related cortical activations, without observable prefrontal engagement. We hypothesized our substantial conditioning and weak verbal instructions diminished expectation-related prefrontal activation. To test this, we examined the same subjects during a conditioning procedure, in which expectancy of pain relief was high. In two conditioning sessions, noxious heat was applied to a leg region treated with an "analgesic" cream and another treated with a "moisturizing" cream. In reality, both creams were inert, but the temperature applied to the moisturizing-cream area was 2{degrees}C higher than that applied to the analgesic-cream area. Functional MRI was acquired during the second conditioning session. Pain ratings were lower for the low heat than the high heat, with corresponding reduced activations in pain-related regions. Similar to previous studies with strong expectation for pain relief, we observed more prefrontal activations during the "analgesic" than the control condition. Nevertheless, contrary to the idea of active prefrontal engagement, the relative activation was based on differences in negative BOLD signals. A literature review revealed that only a few studies conclusively showed active engagement of prefrontal cortex, i.e. increased positive BOLD signal during high expectation compared to a control, with variable timing and spatial-specificity. We suggest that this variability is due to the heterogeneous influence of cognitive, emotional and motivational factors. Future studies should attempt to unravel the multiple contributions to placebo responsiveness in the prefrontal cortex.

neuroscience↗

bioRxiv2021

Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape from innate and conditioned threats. The hypothalamic dorsal premammillary nucleus (PMd) may control escape, as it is activated by escape-inducing threats and projects to the region most implicated in flight, the dorsolateral periaqueductal gray (dlPAG). We show that in mice cholecystokinin (cck)-expressing PMd cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Lastly, human fMRI data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd as a central node of the escape network.

neuroscience↗

bioRxiv2020

Neural effects of placebo analgesia in fibromyalgia patients and healthy individuals

Placebo 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.

neuroscience↗