Autobiographical memory (AM) provides the opportunity to study interactions among brain areas that support the search for a specific episodic memory (construction), and the later experience of mentally reliving it (elaboration). While the hippocampus supports both construction and elaboration, it is unclear how hippocampal-neocortical connectivity differs between these stages, and how this connectivity involves the anterior and posterior segments of the hippocampus, as these have been considered to support the retrieval of general concepts and recollection processes, respectively. We acquired fMRI data in 18 healthy participants during an AM retrieval task in which participants were asked to access a specific AM (construction) and then to recollect it by recovering as many episodic details as possible (elaboration). Using multivariate analytic techniques, we examined changes in functional and effective connectivity of hippocampal-neocortical interactions during these phases of AM retrieval. We found that the left anterior hippocampus interacted with frontal areas during construction and bilateral posterior hippocampi with visual perceptual areas during elaboration, indicating key roles for both hippocampi in coordinating transient neocortical networks at both AM stages. Our findings demonstrate the importance of direct interrogation of hippocampal-neocortical interactions to better illuminate the neural dynamics underlying complex cognitive tasks such as AM retrieval.

HighlightsThe vmPFC and hippocampus are closely connected brain regions whose functions are still debated.Here we directly compared the cognitive changes in humans with either bilateral hippocampal or bilateral vmPFC damage.Hippocampal and vmPFC damage both affect classic ‘hippocampal’ tasks such as autobiographical memory recall.Hippocampal and vmPFC damage have opposite effects on classic ‘vmPFC’ tasks such as moral decision making.We propose a hierarchical network model where vmPFC initiates mental imagery including hippocampal scene construction.

SUMMARYPurpose: The clinical relevance of resting state functional connectivity in neurologic disorders, including mesial temporal lobe epilepsy (mTLE), remains unclear. This study investigated how connectivity in the default mode network changes with unilateral damage to one of its nodes, the hippocampus (HC), and how such connectivity can be exploited clinically to characterize memory deficits and indicate postsurgical memory change. Methods: Functional magnetic resonance imaging (fMRI) resting state scans and neuropsychological memory assessments (Warrington Recognition Tests for Words and Faces) were performed on 19 healthy controls, 20 patients with right mTLE, and 18 patients with left mTLE. In addition, postsurgical fMRI resting state and memory change (postsurgical memory performance-presurgical memory performance) data were available for half of these patients. Key Findings: Patients with mTLE showed reduced connectivity from the posterior cingulate cortex (PCC) to the epileptogenic HC and increased PCC connectivity to the contralateral HC. Stronger PCC connectivity to the epileptogenic HC was associated with better presurgical memory and with greater postsurgical memory decline. Stronger PCC connectivity to the contralateral HC was associated with less postsurgical memory decline. Following surgery, PCC connectivity to the remaining HC increased from presurgical values and showed enhanced correlation with postsurgical memory function. It is notable that this index was superior to others (hippocampal volume, preoperative memory scores) in explaining variance in memory change following surgery. Significance: Our results demonstrate the striking clinical significance of the brain's intrinsic connectivity in evaluating cognitive capacity and indicating the potential of postsurgical cognitive morbidity in patients with mTLE.