Dataset Information

Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events.

ABSTRACT: We remember our lives as sequences of events, but it is unclear how these memories are controlled during retrieval. In rats, the medial prefrontal cortex (mPFC) is positioned to influence sequence memory through extensive top-down inputs to regions heavily interconnected with the hippocampus, notably the nucleus reuniens of the thalamus (RE) and perirhinal cortex (PER). Here, we used an hM4Di synaptic-silencing approach to test our hypothesis that specific mPFC?RE and mPFC?PER projections regulate sequence memory retrieval. First, we found non-overlapping populations of mPFC cells project to RE and PER. Second, suppressing mPFC activity impaired sequence memory. Third, inhibiting mPFC?RE and mPFC?PER pathways effectively abolished sequence memory. Finally, a sequential lag analysis showed that the mPFC?RE pathway contributes to a working memory retrieval strategy, whereas the mPFC?PER pathway supports a temporal context memory retrieval strategy. These findings demonstrate that mPFC?RE and mPFC?PER pathways serve as top-down mechanisms that control distinct sequence memory retrieval strategies.

SUBMITTER: Jayachandran M

PROVIDER: S-EPMC6662648 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events.

Jayachandran Maanasa M Linley Stephanie B SB Schlecht Maximilian M Mahler Stephen V SV Vertes Robert P RP Allen Timothy A TA

Cell reports 20190701 3

We remember our lives as sequences of events, but it is unclear how these memories are controlled during retrieval. In rats, the medial prefrontal cortex (mPFC) is positioned to influence sequence memory through extensive top-down inputs to regions heavily interconnected with the hippocampus, notably the nucleus reuniens of the thalamus (RE) and perirhinal cortex (PER). Here, we used an hM4Di synaptic-silencing approach to test our hypothesis that specific mPFC→RE and mPFC→PER projections regula ...[more]

PMID: 31315044

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Project description:BackgroundPosttraumatic stress disorder (PTSD) has been found to be associated with emotion under-modulation from the prefrontal cortex and a breakdown of the top-down control of cognition and emotion. Novel adjunct therapies such as neurofeedback (NFB) have been shown to normalize aberrant neural circuits that underlie PTSD psychopathology at rest. However, little evidence exists for NFB-linked neural improvements under emotionally relevant cognitive load. The current study sought to address this gap by examining the effects of alpha-down NFB in the context of an emotional n-back task.MethodsWe conducted a 20-week double-blind randomized, sham-controlled trial of alpha-down NFB and collected neuroimaging data before and after the NFB protocol. Participants performed an emotional 1-back and 2-back working memory task, with interleaved trauma-neutral and trauma-relevant cues in the fMRI scanner. Data from 35 participants with a primary diagnosis of PTSD were analyzed in this study (n = 18 in the experimental group undergoing alpha-down NFB, n = 17 in the sham-control group).ResultsFirstly, within-group analyses showed clinically significant reductions in PTSD symptom severity scores at the post-intervention timepoint and 3-month follow-up for the experimental group, and not for the sham-control group. The neuroimaging analyses revealed that alpha-down NFB enhanced engagement of top-down cognitive and emotional control centers, such as the dorsolateral prefrontal cortex (dlPFC), and improved integration of the anterior and posterior parts of the default mode network (DMN). Finally, our results also indicate that increased alpha-down NFB performance correlated with increased activity in brain regions involved in top-down control and bodily consciousness/embodied processing of self (TPJ and posterior insula).ConclusionThis is the first study to provide mechanistic insights into how NFB may normalize dysfunctional brain activity and connectivity in PTSD under cognitive load with simultaneous symptom provocation, adding to a growing body of evidence supporting the therapeutic neuromodulatory effects of NFB. This preliminary study highlights the benefits of alpha-down NFB training as an adjunctive therapy for PTSD and warrants further investigation into its therapeutic effects on cognitive and emotion control in those with PTSD.

Dataset Information

Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events.

Publications

Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events.

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