The 'temporality' hypothesis of confabulation posits that confabulations are true memories displaced in time, while the 'strategic retrieval' hypothesis suggests a general retrieval failure of which temporal confusion is a common symptom. Four confabulating patients with rupture of an anterior communicating artery (ACoA) aneurysm, eight non-confabulating ACoA controls and 16 normal controls participated in three experiments designed to test the two hypotheses. In Experiment 1, participants were tested on two continuous recognition tasks, one requiring temporal context distinctions, previously shown to be sensitive to confabulation and another that only requires content distinctions. Both manipulations were sensitive to confabulation, but not specific to it. Temporal context and content confusions (TCCs and CCs) can be explained as failures to make fine-grained distinctions within memory. In Experiment 2, free recall of semantic narratives that require strategic retrieval but are independent of temporal context was used to induce confabulations associated with remote memory, acquired before the onset of amnesia. Confabulators produced significantly more errors. Thus, when retrieval demands are equated, confabulations can be induced in the absence of temporal confusions. Only confabulators conflated semantic content from different remote semantic narratives and introduced idiosyncratic content, suggesting that qualitatively different mechanisms are responsible for distortions due to normal memory failure and for confabulation. Lesion analyses revealed that damage to ventromedial prefrontal cortex is sufficient for temporal context errors to occur, but additional orbitofrontal damage is crucial for spontaneous confabulation. In Experiment 3, we tested whether failure in memory monitoring is crucial for confabulation. Recognition of details from semantic and autobiographical narratives was used to minimize the initiation and search components of strategic retrieval. Only confabulators made more false alarms on both tasks, endorsed even highly implausible lures related to autobiographical events and were indiscriminately confident about their choices. These findings support a strategic retrieval account of confabulation of which monitoring is a critical component. Post-retrieval monitoring has at least two components: one is early, rapid and pre-conscious and the other is conscious and elaborate. Failure of at least the former is necessary and sufficient for confabulation. Other deficits, including TCC and CC, may be required for spontaneous confabulations to arise. The confluence of different sub-components of strategic retrieval would determine the content of confabulation and exacerbate its occurrence.

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Background: A recent randomized phase II trial evaluated stereotactic ablative radiotherapy (SABR) in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with a significant improvement in progression-free survival and a trend to an overall survival benefit, supporting progression to phase III randomized trials. Methods: Two hundred and ninety-seven patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care [SOC] palliative-intent treatments), and the SABR arm (consisting of SOC treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (prostate, breast, or renal vs. all others), and disease-free interval (defined as time from diagnosis of primary tumor until first detection of the metastases being treated on this trial; divided as ≤2 vs. > 2 years). The primary endpoint is overall survival, and secondary endpoints include progression-free survival, cost effectiveness, time to development of new metastatic lesions, quality of life (QoL), and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival. Discussion: This study will provide an assessment of the impact of SABR on survival, QoL, and cost effectiveness to determine if long-term survival can be achieved for selected patients with 1-3 oligometastatic lesions.

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