Abstract
BACKGROUND: The mechanisms underlying generalized forms of dissociative ('psychogenic') amnesia are poorly understood. One theory suggests that memory retrieval is inhibited via prefrontal control. Findings from cognitive neuroscience offer a candidate mechanism for this proposed retrieval inhibition. By applying predictions based on these experimental findings, we examined the putative role of retrieval suppression in dissociative amnesia. METHODS: We analyzed fMRI data from two previously reported cases of dissociative amnesia. Patients had been shown reminders from forgotten and remembered time periods (colleagues and school friends). We examined the neuroanatomical overlap between regions engaged in the unrecognized compared to the recognized condition, and the regions engaged during retrieval suppression in laboratory-based tasks. Effective connectivity analyses were performed to test the hypothesized modulatory relationship between the right anterior dorsolateral prefrontal cortex (raDLPFC) and the hippocampus. Both patients were scanned again following treatment, and analyses were repeated. RESULTS: We observed substantial functional alignment between the inhibitory regions engaged during laboratory-based retrieval suppression tasks, and those engaged when patients failed to recognize their current colleagues. This included significant activation in the raDLPFC and right ventrolateral prefrontal cortex, and a corresponding deactivation across autobiographical memory regions (hippocampus, medial PFC). Dynamic causal modeling confirmed the hypothesized modulatory relationship between the raDLPFC and the hippocampus. This pattern was no longer evident following memory recovery in the first patient, but persisted in the second patient who remained amnesic. CONCLUSIONS: Findings are consistent with an inhibitory mechanism driving down activity across core memory regions to prevent the recognition of personally relevant stimuli.