Differential contributions of the hippocampal dentate gyrus and CA1 subfield to mnemonic discrimination.

Evidence suggests that individual hippocampal subfields are preferentially involved in various memory-related processes. Here, we demonstrated dissociations in these memory processes in two unique individuals with near-selective bilateral damage within the hippocampus, affecting the dentate gyrus (DG) in case BL and the cornu ammonis 1 (CA1) subfield in case BR. BL was impaired in discriminating highly similar objects in memory (i.e., mnemonic discrimination) but exhibited preserved overall recognition of studied objects, regardless of similarity. Conversely, BR demonstrated impaired general recognition. These results provide evidence for the DG in discrimination processes, likely related to underlying pattern separation computations, and the CA1 in retention/retrieval.

The effect of hippocampal subfield damage on rapid temporal integration through statistical learning and associative inference.

INTRODUCTION: The hippocampus (HPC) supports integration of information across time, often indexed by associative inference (AI) and statistical learning (SL) tasks. In AI, an indirect association between stimuli that never appeared together is inferred, whereas SL involves learning item relationships by extracting regularities across experiences. A recent model of hippocampal function (Schapiro et al., 2017) proposes that the HPC can support temporal integration in both paradigms through its two distinct pathways. METHODS: We tested this models' predictions in four patients with varying degrees of bilateral HPC damage and matched healthy controls, with two patients with complementary damage to either the monosynaptic or trisynaptic pathway. During AI, participants studied overlapping paired associates (AB, BC) and their memory was tested for premise pairs (AB) and for inferred pairs (AC). During SL, participants passively viewed a continuous picture sequence that contained an underlying structure of triplets that later had to be recognized. RESULTS: Binomial distributions were used to calculate above chance performance at the individual level. For AI, patients with focal HPC damage were impaired at inference but could correctly infer pairs above chance once premise pair acquisition was equated to controls; however, the patient with HPC and cortical damage showed severe impairment at recalling premise and inferred pairs, regardless of accounting for premise pair performance. For SL, none of the patients performed above chance, but notably neither did most controls. CONCLUSIONS: Associative inference of indirect relationships can be intact with HPC damage to either hippocampal pathways or the HPC more broadly, provided premise pairs can first be formed. Inference may remain intact through residual HPC tissue supporting premise pair acquisition, and/or through extra-hippocampal structures supporting inference at retrieval. Clear conclusions about hippocampal contributions to SL are precluded by low performance in controls, which we caution is not dissimilar to previous amnesic studies using the same task. This complicates interpretations of studies claiming necessity of hippocampal contributions to SL and warrants the use of a common and reliable task before conclusions can be drawn.

Scene Construction and Spatial Processing in Post-traumatic Stress Disorder.

Introduction: Post-traumatic stress disorder (PTSD) is associated with hippocampal system structural and functional impairments. Neurobiological models of PTSD posit that contextual memory for traumatic events is impaired due to hippocampal system dysfunction whilst memory of sensory details is enhanced due to amygdalar impact on sensory cortices. If hippocampal system dysfunction is a core feature of PTSD, then non-traumatic hippocampal-dependent cognitive functions such as scene construction, spatial processing, and memory should also be impaired in individuals with PTSD. Methods: Forty-six trauma survivors, half diagnosed with PTSD, performed two tasks that involved spatial processing. The first was a scene construction task which requires conjuring-up spatially coherent multimodal scenarios, completed by all participants. Twenty-six participants (PTSD: n = 13) also completed a navigation task in a virtual environment, and underwent structural T1, T2 and diffusion-tensor MRI to quantify gray and white matter integrity. We examined the relationship between spatial processing, neural integrity, and symptom severity in a multiple factor analysis. Results: Overall, patients with PTSD showed impaired performance in both tasks compared to controls. Scenes imagined by patients were less vivid, less detailed, and generated less sense of presence; importantly they had disproportionally reduced spatial coherence between details. Patients also made more errors during virtual navigation. Two components of the multiple factor analysis captured group differences. The first component explained 25% of the shared variance: participants that constructed less spatially coherent scenes also made more navigation errors and had reduced white matter integrity to long association tracts and tracts connecting the hippocampus, thalamus, and cingulate. The second component explained 20% of the variance: participants who generated fewer scene details, with less spatial coherence between them, had smaller hippocampal, parahippocampal and isthmus cingulate volumes. These participants also had increased white matter integrity to the right hippocampal cingulum bundle. Conclusion: Our results suggest that patients with PTSD are impaired at imagining even neutral spatially coherent scenes and navigating through a complex spatial environment. Patients that showed reduced spatial processing more broadly had reduced hippocampal systems volumes and abnormal white matter integrity to tracts implicated in multisensory integration.

Neurobiology of Schemas and Schema-Mediated Memory.

Schemas are superordinate knowledge structures that reflect abstracted commonalities across multiple experiences, exerting powerful influences over how events are perceived, interpreted, and remembered. Activated schema templates modulate early perceptual processing, as they get populated with specific informational instances (schema instantiation). Instantiated schemas, in turn, can enhance or distort mnemonic processing from the outset (at encoding), impact offline memory transformation and accelerate neocortical integration. Recent studies demonstrate distinctive neurobiological processes underlying schema-related learning. Interactions between the ventromedial prefrontal cortex (vmPFC), hippocampus, angular gyrus (AG), and unimodal associative cortices support context-relevant schema instantiation and schema mnemonic effects. The vmPFC and hippocampus may compete (as suggested by some models) or synchronize (as suggested by others) to optimize schema-related learning depending on the specific operationalization of schema memory. This highlights the need for more precise definitions of memory schemas.