Prior functional magnetic resonance imaging (fMRI) studies indicate that a core network of brain regions, including the hippocampus, is jointly recruited during episodic memory, episodic simulation, and divergent creative thinking. Because fMRI data are correlational, it is unknown whether activity increases in the hippocampus, and the core network more broadly, play a causal role in episodic simulation and divergent thinking. Here we employed fMRI-guided transcranial magnetic stimulation (TMS) to assess whether temporary disruption of hippocampal brain networks impairs both episodic simulation and divergent thinking. For each of two TMS sessions, continuous θ-burst stimulation (cTBS) was applied to either a control site (vertex) or to a left angular gyrus target region. The target region was identified on the basis of a participant-specific resting-state functional connectivity analysis with a hippocampal seed region previously associated with memory, simulation, and divergent thinking. Following cTBS, participants underwent fMRI and performed a simulation, divergent thinking, and nonepisodic control task. cTBS to the target region reduced the number of episodic details produced for the simulation task and reduced idea production on divergent thinking. Performance in the control task did not statistically differ as a function of cTBS site. fMRI analyses revealed a selective and simultaneous reduction in hippocampal activity during episodic simulation and divergent thinking following cTBS to the angular gyrus versus vertex but not during the nonepisodic control task. Our findings provide evidence that hippocampal-targeted TMS can specifically modulate episodic simulation and divergent thinking, and suggest that the hippocampus is critical for these cognitive functions.

Human retrosplenial complex (RSC), located in medial parietal cortex, has been implicated in numerous cognitive functions, including scene perception, spatial navigation, and autobiographical memory retrieval. Recently, a posterior-anterior distinction within RSC was proposed, such that posterior aspects process scene-related visual information (constituting a medial place area [MPA]), whereas anterior aspects process information that is vividly retrieved from memory, thereby supporting remembering and potentially navigation. Here, we tested this proposed distinction in a single group of participants (both male and female) using fMRI with both perceptual and mnemonic tasks. After completing a resting-state scan, participants performed a task that required constructing scenes from memory and completed a scene selectivity localizer task. We tested directly perceptual and mnemonic responses in MPA and an anterior, connectivity-defined region (CON), which showed strong functional connectivity with anterior parahippocampal place area. A double dissociation was observed, such that CON was more strongly activated during scene construction than was MPA, whereas MPA was more perceptually responsive than CON. Further, peak responses from the scene construction task were anterior to perceptual peaks in all but 1 participant and hemisphere. Finally, through analyses of the posterior-anterior response profiles, we identify the fundus of the parieto-occipital sulcus as a potential location for the crossover from perceptual to mnemonic representations and highlight a potential left-hemisphere advantage for mnemonic representations. Collectively, our results support a distinction between posterior and anterior aspects of the RSC, suggesting that more specific functional-anatomic terms should be used in its place in future work.

The necessity of the human hippocampus for remote autobiographical recall remains fiercely debated. The standard model of consolidation predicts a time-limited role for the hippocampus, but the competing multiple trace/trace transformation theories posit indefinite involvement. Lesion evidence remains inconclusive, and the inferences one can draw from functional MRI (fMRI) have been limited by reliance on covert (silent) recall, which obscures dynamic, moment-to-moment content of retrieved memories. Here, we capitalized on advances in fMRI denoising to employ overtly spoken recall. Forty participants retrieved recent and remote memories, describing each for approximately 2 min. Details associated with each memory were identified and modeled in the fMRI time-series data using a variant of the Autobiographical Interview procedure, and activity associated with the recall of recent and remote memories was then compared. Posterior hippocampal regions exhibited temporally graded activity patterns (recent events > remote events), as did several regions of frontal and parietal cortex. Consistent with predictions of the standard model, recall-related hippocampal activity differed from a non-autobiographical control task only for recent, and not remote, events. Task-based connectivity between posterior hippocampal regions and others associated with mental scene construction also exhibited a temporal gradient, with greater connectivity accompanying the recall of recent events. These findings support predictions of the standard model of consolidation and demonstrate the potential benefits of overt recall in neuroimaging experiments.

Humans can vividly recall and re-experience events from their past, and these are commonly referred to as episodic or autobiographical memories. fMRI experiments reliably associate autobiographical event recall with activity in a network of “default” or “core” brain regions. However, as prior studies have relied on covert (silent) recall procedures, current understanding may be hampered by methodological limitations that obscure dynamic effects supporting moment-to-moment content retrieval. Here, fMRI participants (N= 40) overtly (verbally) recalled memories for ∼2 min periods. The content of spoken descriptions was categorized using a variant of the Autobiographical Interview (AI) procedure (Levine et al., 2002) and temporally re-aligned with BOLD data so activity accompanying the recall of different details could be measured. Replicating prior work, sustained effects associated with autobiographical recall periods (which are insensitive to the moment-to-moment content of retrieval) fell primarily within canonical default network regions. Spoken descriptions were rich in episodic details, frequently focusing on physical entities, their ongoing activities, and their appearances. Critically, neural activity associated with recalling specific details (e.g., those related to people or places) was transient, broadly distributed, and grounded in category-selective cortex (e.g., regions related to social cognition or scene processing). Thus, although a single network may generally support the process of vivid event reconstruction, the structures required to provide detail-related information shift in a predictable manner that respects domain-level representations across the cortex.SIGNIFICANCE STATEMENTHumans can vividly recall memories of autobiographical episodes, a process thought to involve the reconstruction of numerous distinct event details. Yet how the brain represents a complex episode as it unfolds over time remains unclear and appears inconsistent across experimental traditions. One hurdle is the use of covert (silent) in-scanner recall to study autobiographical memory, which prevents experimenter knowledge of what information is being retrieved, and when, throughout the remembering process. In this experiment, participants overtly described autobiographical memories while undergoing fMRI. Activity associated with the recall and description of specific details was transient, broadly distributed, and grounded in category-selective cortex. Thus, it appears that as events unfold mentally, structures are dynamically reactivated to support vivid recollection.