Subsequent Memory Effects in Cortical Pattern Similarity Differ by Semantic Class.

Although living and nonliving stimuli are known to rely on distinct brain regions during perception, it is largely unknown if their episodic memory encoding mechanisms differ as well. To investigate this issue, we asked participants to encode object pictures (e.g., a picture of a tiger) and to retrieve them later in response to their names (e.g., word "tiger"). For each of four semantic classes (living-animate, living-inanimate, nonliving-large, and nonliving-small), we examined differences in the similarity in activation patterns (neural pattern similarity [NPS]) for subsequently remembered versus forgotten items. Higher NPS for remembered items suggests an advantage of within-class item similarity, whereas lower NPS for remembered items indicates an advantage for item distinctiveness. We expect NPS within class-specific regions to be higher for remembered than for forgotten items. For example, the parahippocampal cortex has a well-known role in scene processing [Aminoff, E. M., Kveraga, K., & Bar, M. The role of the parahippocampal cortex in cognition. Trends in Cognitive Sciences, 17, 379-390, 2013], and the anterior temporal and inferior frontal gyrus have well-known roles in object processing [Clarke, A., & Tyler, L. K. Object-specific semantic coding in human perirhinal cortex. Journal of Neuroscience, 34, 4766-4775, 2014]. As such, we expect to see higher NPS for remembered items in these regions pertaining to scenes and objects, respectively. Consistent with this hypothesis, in fusiform, parahippocampal, and retrosplenial regions, higher NPS predicted memory for subclasses of nonliving objects, whereas in the left inferior frontal and left retrosplenial regions, lower NPS predicted memory for subclasses of living objects. Taken together, the results support the idea that subsequent memory depends on a balance of similarity and distinctiveness and demonstrate that the neural mechanisms of episodic encoding differ across semantic categories.

Differential Mnemonic Contributions of Cortical Representations during Encoding and Retrieval.

Several recent fMRI studies of episodic and working memory representations converge on the finding that visual information is most strongly represented in occipito-temporal cortex during the encoding phase but in parietal regions during the retrieval phase. It has been suggested that this location shift reflects a change in the content of representations, from predominantly visual during encoding to primarily semantic during retrieval. Yet, direct evidence on the nature of encoding and retrieval representations is lacking. It is also unclear how the representations mediating the encoding-retrieval shift contribute to memory performance. To investigate these two issues, in the current fMRI study, participants encoded pictures (e.g., picture of a cardinal) and later performed a word recognition test (e.g., word "cardinal"). Representational similarity analyses examined how visual (e.g., red color) and semantic representations (e.g., what cardinals eat) support successful encoding and retrieval. These analyses revealed two novel findings. First, successful memory was associated with representational changes in cortical location (from occipito-temporal at encoding to parietal at retrieval) but not with changes in representational content (visual vs. semantic). Thus, the representational encoding-retrieval shift cannot be easily attributed to a change in the nature of representations. Second, in parietal regions, stronger representations predicted encoding failure but retrieval success. This encoding-retrieval "flip" in representations mimics the one previously reported in univariate activation studies. In summary, by answering important questions regarding the content and contributions to the performance of the representations mediating the encoding-retrieval shift, our findings clarify the neural mechanisms of this intriguing phenomenon.

Hippocampal Functions Modulate Transfer-Appropriate Cortical Representations Supporting Subsequent Memory.

The hippocampus plays a central role as a coordinate system or index of information stored in neocortical loci. Nonetheless, it remains unclear how hippocampal processes integrate with cortical information to facilitate successful memory encoding. Thus, the goal of the current study was to identify specific hippocampal-cortical interactions that support object encoding. We collected fMRI data while 19 human participants (7 female and 12 male) encoded images of real-world objects and tested their memory for object concepts and image exemplars (i.e., conceptual and perceptual memory). Representational similarity analysis revealed robust representations of visual and semantic information in canonical visual (e.g., occipital cortex) and semantic (e.g., angular gyrus) regions in the cortex, but not in the hippocampus. Critically, hippocampal functions modulated the mnemonic impact of cortical representations that are most pertinent to future memory demands, or transfer-appropriate representations Subsequent perceptual memory was best predicted by the strength of visual representations in ventromedial occipital cortex in coordination with hippocampal activity and pattern information during encoding. In parallel, subsequent conceptual memory was best predicted by the strength of semantic representations in left inferior frontal gyrus and angular gyrus in coordination with either hippocampal activity or semantic representational strength during encoding. We found no evidence for transfer-incongruent hippocampal-cortical interactions supporting subsequent memory (i.e., no hippocampal interactions with cortical visual/semantic representations supported conceptual/perceptual memory). Collectively, these results suggest that diverse hippocampal functions flexibly modulate cortical representations of object properties to satisfy distinct future memory demands.Significance Statement The hippocampus is theorized to index pieces of information stored throughout the cortex to support episodic memory. Yet how hippocampal processes integrate with cortical representation of stimulus information remains unclear. Using fMRI, we examined various forms of hippocampal-cortical interactions during object encoding in relation to subsequent performance on conceptual and perceptual memory tests. Our results revealed novel hippocampal-cortical interactions that utilize semantic and visual representations in transfer-appropriate manners: conceptual memory supported by hippocampal modulation of frontoparietal semantic representations, and perceptual memory supported by hippocampal modulation of occipital visual representations. These findings provide important insights into the neural mechanisms underlying the formation of information-rich episodic memory and underscore the value of studying the flexible interplay between brain regions for complex cognition.

Cortical iron mediates age-related decline in fluid cognition.

Brain iron dyshomeostasis disrupts various critical cellular functions, and age-related iron accumulation may contribute to deficient neurotransmission and cell death. While recent studies have linked excessive brain iron to cognitive function in the context of neurodegenerative disease, little is known regarding the role of brain iron accumulation in cognitive aging in healthy adults. Further, previous studies have focused primarily on deep gray matter regions, where the level of iron deposition is highest. However, recent evidence suggests that cortical iron may also contribute to cognitive deficit and neurodegenerative disease. Here, we used quantitative susceptibility mapping (QSM) to measure brain iron in 67 healthy participants 18-78 years of age. Speed-dependent (fluid) cognition was assessed from a battery of 12 psychometric and computer-based tests. From voxelwise QSM analyses, we found that QSM susceptibility values were negatively associated with fluid cognition in the right inferior temporal gyrus, bilateral putamen, posterior cingulate gyrus, motor, and premotor cortices. Mediation analysis indicated that susceptibility in the right inferior temporal gyrus was a significant mediator of the relation between age and fluid cognition, and similar effects were evident for the left inferior temporal gyrus at a lower statistical threshold. Additionally, age and right inferior temporal gyrus susceptibility interacted to predict fluid cognition, such that brain iron was negatively associated with a cognitive decline for adults over 45 years of age. These findings suggest that iron may have a mediating role in cognitive decline and may be an early biomarker of neurodegenerative disease.

Influence of structural and functional brain connectivity on age-related differences in fluid cognition.

We used graph theoretical measures to investigate the hypothesis that structural brain connectivity constrains the influence of functional connectivity on the relation between age and fluid cognition. Across 143 healthy, community-dwelling adults 19-79 years of age, we estimated structural network properties from diffusion-weighted imaging and functional network properties from resting-state functional magnetic resonance imaging. We confirmed previous reports of age-related decline in the strength and efficiency of structural networks, as well as in the connectivity strength within and between structural network modules. Functional networks, in contrast, exhibited age-related decline only in system segregation, a measure of the distinctiveness among network modules. Aging was associated with decline in a composite measure of fluid cognition, particularly tests of executive function. Functional system segregation was a significant mediator of age-related decline in executive function. Structural network properties did not directly influence the age-related decline in functional system segregation. The raw correlational data underlying the graph theoretical measures indicated that structural connectivity exerts a limited constraint on age-related decline in functional connectivity.

The role of conflict, feedback, and action comprehension in monitoring of action errors: Evidence for internal and external routes.

The mechanisms and brain regions underlying error monitoring in complex action are poorly understood, yet errors and impaired error correction in these tasks are hallmarks of apraxia, a common disorder associated with left hemisphere stroke. Accounts of monitoring of language posit an internal route by which production planning or competition between candidate representations provide predictive signals that monitoring is required to prevent error, and an external route in which output is monitored using the comprehension system. Abnormal reliance on the external route has been associated with damage to brain regions critical for sensory-motor transformation and a pattern of gradual error 'clean-up' called conduite d'approche (CD). Action pantomime data from 67 participants with left hemisphere stroke were consistent with versions of internal route theories positing that competition signals monitoring requirements. Support Vector Regression Lesion Symptom Mapping (SVR-LSM) showed that lesions in the inferior parietal, posterior temporal, and arcuate fasciculus/superior longitudinal fasciculus predicted action conduite d'approche, overlapping the regions previously observed in the language domain. A second experiment with 12 patients who produced substantial action CD assessed whether factors impacting the internal route (action production ability, competition) versus external route (vision of produced actions, action comprehension) influenced correction attempts. In these 'high CD' patients, vision of produced actions and integrity of gesture comprehension interacted to determine successful error correction, supporting external route theories. Viewed together, these and other data suggest that skilled actions are monitored both by an internal route in which conflict aids in detection and correction of errors during production planning, and an external route that detects mismatches between produced actions and stored knowledge of action appearance. The parallels between language and action monitoring mechanisms and neuroanatomical networks pave the way for further exploration of common and distinct processes across these domains.