The language of mental images: Characterizing hippocampal contributions to imageable word use during event construction.

Accumulating evidence suggests that the hippocampus plays a critical role in the creative and flexible use of language at the sentence or discourse level. Yet it is currently unclear whether the hippocampus also supports language use at the level of single words. A recent study by Hilverman et al. (2017) found that amnesic patients with hippocampal damage use less imageable words when describing autobiographical episodes compared to healthy controls, but this deficit was attributed to patients' deficits in episodic memory rather than impairments in linguistic functions of the hippocampus per se. Yet, in addition to affecting word use by way of its role in memory, the hippocampus could also impact language use more directly. The current study aimed to test this hypothesis by investigating the status of imageable word use in amnesia during two different types of language production tasks. In Experiment 1, participants constructed narratives about events depicted in visually presented pictures (picture narratives). In Experiment 2, participants constructed verbal narratives about remembered events from the past or simulated events in the future (past/future narratives). Across all types of narratives, patients produced words that were rated as having similar levels of imageability compared to controls. Importantly, this was the case both in patients' picture narratives, which did not require generating details from episodic memory and were matched to those of controls with respect to narrative content, and in patients' narratives about past/future events, which required generating details from memory and which were reduced in narrative content compared to those of controls. These results distinguish between the quantity and quality of individual linguistic details produced in amnesia during narrative construction, and suggest that the use of imageable linguistic representations does not depend on intact episodic memory and can be supported by regions outside the hippocampus.

Propranolol Reverses Impaired Fracture Healing Response Observed With Selective Serotonin Reuptake Inhibitor Treatment.

Selective serotonin reuptake inhibitors (SSRIs) are one of the most commonly prescribed antidepressants worldwide and recent data show significant impairment of fracture healing after treatment with the SSRI fluoxetine in mice. Here, we provide evidence that the negative effects of SSRIs can be overcome by administration of the beta-blocker propranolol at the time of fracture. First, in vitro experiments established that propranolol does not affect osteogenic differentiation. We then used a murine model of intramembranous ossification to study the potential rescue effect of propranolol on SSRI-induced impaired fracture healing. Micro-CT analysis revealed that fluoxetine treatment resulted in a smaller bony regenerate and that this decrease in bone formation can be overcome by co-treatment with propranolol. We then tested this in a clinically relevant model of endochondral ossification. Fluoxetine-treated mice with a femur fracture were treated with propranolol initiated at the time of fracture, and a battery of analyses demonstrated a reversal of the detrimental effect of fluoxetine on fracture healing in response to propranolol treatment. These experiments show for the first time to our knowledge that the negative effects of SSRIs on fracture healing can be overcome by co-treatment with a beta-blocker. © 2019 American Society for Bone and Mineral Research.