Recalled through this day but forgotten next week?-retrieval activity predicts durability of partly consolidated memories.

Even partly consolidated memories can be forgotten given sufficient time, but the brain activity associated with durability of episodic memory at different time scales remains unclear. Here, we aimed to identify brain activity associated with retrieval of partly consolidated episodic memories that continued to be remembered in the future. Forty-nine younger (20 to 38 years; 25 females) and 43 older adults (60 to 80 years, 25 females) were scanned with functional magnetic resonance imaging during associative memory retrieval 12 h post-encoding. Twelve hours is sufficient to allow short-term synaptic consolidation as well as early post-encoding replay to initiate memory consolidation. Successful memory trials were classified into durable and transient source memories based on responses from a memory test ~6 d post-encoding. Results demonstrated that successful retrieval of future durable vs. transient memories was supported by increased activity in a medial prefrontal and ventral parietal area. Individual differences in activation as well as the subjective vividness of memories during encoding were positively related to individual differences in memory performance after 6 d. The results point to a unique and novel aspect of brain activity supporting long-term memory, in that activity during retrieval of memories even after 12 h of consolidation contains information about potential for long-term durability.

Sustained upregulation of widespread hippocampal-neocortical coupling following memory encoding.

Systems consolidation of new experiences into lasting episodic memories involves hippocampal-neocortical interactions. Evidence of this process is already observed during early post-encoding rest periods, both as increased hippocampal coupling with task-relevant perceptual regions and reactivation of stimulus-specific patterns following intensive encoding tasks. We investigate the spatial and temporal characteristics of these hippocampally anchored post-encoding neocortical modulations. Eighty-nine adults participated in an experiment consisting of interleaved memory task- and resting-state periods. We observed increased post-encoding functional connectivity between hippocampus and individually localized neocortical regions responsive to stimuli encountered during memory encoding. Post-encoding modulations were manifested as a nearly system-wide upregulation in hippocampal coupling with all major functional networks. The configuration of these extensive modulations resembled hippocampal-neocortical interaction patterns estimated from active encoding operations, suggesting hippocampal post-encoding involvement exceeds perceptual aspects. Reinstatement of encoding patterns was not observed in resting-state scans collected 12 h later, nor when using other candidate seed regions. The similarity in hippocampal functional coupling between online memory encoding and offline post-encoding rest suggests reactivation in humans involves a spectrum of cognitive processes engaged during the experience of an event. There were no age effects, suggesting that upregulation of hippocampal-neocortical connectivity represents a general phenomenon seen across the adult lifespan.

Hippocampal-cortical functional connectivity during memory encoding and retrieval.

Memory encoding and retrieval are critical sub-processes of episodic memory. While the hippocampus is involved in both, less is known about its connectivity with the neocortex during memory processing in humans. This is partially due to variations in demands in common memory tasks, which inevitably recruit cognitive processes other than episodic memory. Conjunctive analysis of data from different tasks with the same core elements of encoding and retrieval can reduce the intrusion of patterns related to subsidiary perceptual and cognitive processing. Leveraging data from two large-scale functional resonance imaging studies with different episodic memory tasks (514 and 237 participants), we identified hippocampal-cortical networks active during memory tasks. Whole-brain functional connectivity maps were similar during resting state, encoding, and retrieval. Anterior and posterior hippocampus had distinct connectivity profiles, which were also stable across resting state and memory tasks. When contrasting encoding and retrieval connectivity, conjunctive encoding-related connectivity was sparse. During retrieval hippocampal connectivity was increased with areas known to be active during recollection, including medial prefrontal, inferior parietal, and parahippocampal cortices. This indicates that the stable functional connectivity of the hippocampus along its longitudinal axis is superposed by increased functional connectivity with the recollection network during retrieval, while auxiliary encoding connectivity likely reflects contextual factors.

Whole-brain connectivity during encoding: age-related differences and associations with cognitive and brain structural decline.

There is a limited understanding of age differences in functional connectivity during memory encoding. In the present study, a sample of cognitively healthy adult participants (n = 488, 18-81 years), a subsample of whom had longitudinal cognitive and brain structural data spanning on average 8 years back, underwent functional magnetic resonance imaging while performing an associative memory encoding task. We investigated (1) age-related differences in whole-brain connectivity during memory encoding; (2) whether encoding connectivity patterns overlapped with the activity signatures of specific cognitive processes, and (3) whether connectivity associated with memory encoding related to longitudinal brain structural and cognitive changes. Age was associated with lower intranetwork connectivity among cortical networks and higher internetwork connectivity between networks supporting higher level cognitive functions and unimodal and attentional areas during encoding. Task-connectivity between mediotemporal and posterior parietal regions-which overlapped with areas involved in mental imagery-was related to better memory performance only in older age. The connectivity patterns supporting memory performance in older age reflected preservation of thickness of the medial temporal cortex. The results are more in accordance with a maintenance rather than a compensation account.

Reduced Hippocampal-Striatal Interactions during Formation of Durable Episodic Memories in Aging.

Encoding of durable episodic memories requires cross-talk between the hippocampus and multiple brain regions. Changes in these hippocampal interactions could contribute to age-related declines in the ability to form memories that can be retrieved after extended time intervals. Here we tested whether hippocampal-neocortical- and subcortical functional connectivity (FC) observed during encoding of durable episodic memories differed between younger and older adults. About 48 younger (20-38 years; 25 females) and 43 older (60-80 years; 25 females) adults were scanned with fMRI while performing an associative memory encoding task. Source memory was tested ~20 min and ~6 days postencoding. Associations recalled after 20 min but later forgotten were classified as transient, whereas memories retained after long delays were classified as durable. Results demonstrated that older adults showed a reduced ability to form durable memories and reduced hippocampal-caudate FC during encoding of durable memories. There was also a positive relationship between hippocampal-caudate FC and higher memory performance among the older adults. No reliable age group differences in durable memory-encoding activity or hippocampal-neocortical connectivity were observed. These results support the classic theory of striatal alterations as one cause of cognitive decline in aging and highlight that age-related changes in episodic memory extend beyond hippocampal-neocortical connections.

Continuity and Discontinuity in Human Cortical Development and Change From Embryonic Stages to Old Age.

The human cerebral cortex is highly regionalized, and this feature emerges from morphometric gradients in the cerebral vesicles during embryonic development. We tested if this principle of regionalization could be traced from the embryonic development to the human life span. Data-driven fuzzy clustering was used to identify regions of coordinated longitudinal development of cortical surface area (SA) and thickness (CT) (n = 301, 4-12 years). The principal divide for the developmental SA clusters extended from the inferior-posterior to the superior-anterior cortex, corresponding to the major embryonic morphometric anterior-posterior (AP) gradient. Embryonic factors showing a clear AP gradient were identified, and we found significant differences in gene expression of these factors between the anterior and posterior clusters. Further, each identified developmental SA and CT clusters showed distinguishable life span trajectories in a larger longitudinal dataset (4-88 years, 1633 observations), and the SA and CT clusters showed differential relationships to cognitive functions. This means that regions that developed together in childhood also changed together throughout life, demonstrating continuity in regionalization of cortical changes. The AP divide in SA development also characterized genetic patterning obtained in an adult twin sample. In conclusion, the development of cortical regionalization is a continuous process from the embryonic stage throughout life.

Examining the Subacute Effects of Mild Traumatic Brain Injury Using a Traditional and Computerized Neuropsychological Test Battery.

This study investigates subacute cognitive effects of mild traumatic brain injury (MTBI) in the Trondheim Mild TBI Study, as measured, in part, by the neuropsychological test battery of the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) program, including computerized tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and traditional paper-and-pencil tests. We investigated whether cognitive function was associated with injury severity: intracranial traumatic lesions on neuroimaging, witnessed loss of consciousness (LOC), or post-traumatic amnesia (PTA) >1 h. Further, we explored which of the tests in the CENTER-TBI battery might be associated with the largest subacute effects of MTBI (i.e., at 2 weeks post-injury). We recruited 177 patients with MTBI (16-59 years of age) from a regional trauma center and an outpatient clinic,79 trauma control participants, and 81 community control participants. The MTBI group differed from community controls only on one traditional test of processing speed (coding; p = 0.009, Cliff's delta [Δ] = 0.20). Patients with intracranial abnormalities performed worse than those without on a traditional test (phonemic verbal fluency; p = 0.043, Δ = 0.27), and patients with LOC performed differently on the Attention Switching Task from the CANTAB (p = 0.020, Δ = -0.20). Patients with PTA >1 h performed worse than those with <1 h on 10 measures, from traditional tests and the CANTAB (Δ = 0.33-0.20), likely attributable, at least in part, to pre-existing differences in intellectual functioning between groups. In general, those with MTBI had good neuropsychological outcome 2 weeks after injury and no particular CENTER-TBI computerized or traditional tests seemed to be more sensitive to subtle cognitive deficits.