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.

Progressive Neurodegeneration Across Chronic Stages of Severe Traumatic Brain Injury.

OBJECTIVE: To examine the trajectory of structural gray matter changes across 2 chronic periods of recovery in individuals who have sustained severe traumatic brain injury (TBI), adding to the growing literature indicating that neurodegenerative processes occur in the months to years postinjury. PARTICIPANTS: Patients who experienced posttraumatic amnesia of 1 hour or more, and/or scored 12 or less on the Glasgow Coma Scale at the emergency department or the scene of the accident, and/or had positive brain imaging findings were recruited while receiving inpatient care, resulting in 51 patients with severe TBI. METHODS: Secondary analyses of gray matter changes across approximately 5 months, 1 year, and 2.5 years postinjury were undertaken, using an automated segmentation protocol with improved accuracy in populations with morphological anomalies. We compared patients and matched controls on regions implicated in poorer long-term clinical outcome (accumbens, amygdala, brainstem, hippocampus, thalamus). To model brain-wide patterns of change, we then conducted an exploratory principal component analysis (PCA) on the linear slopes of all regional volumes across the 3 time points. Finally, we assessed nonlinear trends across earlier (5 months-1 year) versus later (1-2.5 years) time-windows with PCA to compare degeneration rates across time. Chronic degeneration was predicted cortically and subcortically brain-wide, and within specific regions of interest. RESULTS: (1) From 5 months to 1 year, patients showed significant degeneration in the accumbens, and marginal degeneration in the amygdala, brainstem, thalamus, and the left hippocampus when examined unilaterally, compared with controls. (2) PCA components representing subcortical and temporal regions, and regions from the basal ganglia, significantly differed from controls in the first time-window. (3) Progression occurred at the same rate across both time-windows, suggesting neither escalation nor attenuation of degeneration across time. CONCLUSION: Localized yet progressive decline emphasizes the necessity of developing interventions to offset degeneration and improve long-term functioning.

Remotely delivered environmental enrichment intervention for traumatic brain injury: Study protocol for a randomised controlled trial.

INTRODUCTION: Individuals with moderate-severe traumatic brain injury (m-sTBI) experience progressive brain and behavioural declines in the chronic stages of injury. Longitudinal studies found that a majority of patients with m-sTBI exhibit significant hippocampal atrophy from 5 to 12 months post-injury, associated with decreased cognitive environmental enrichment (EE). Encouragingly, engaging in EE has been shown to lead to neural improvements, suggesting it is a promising avenue for offsetting hippocampal neurodegeneration in m-sTBI. Allocentric spatial navigation (ie, flexible, bird's eye view approach), is a good candidate for EE in m-sTBI because it is associated with hippocampal activation and reduced ageing-related volume loss. Efficacy of EE requires intensive daily training, prohibitive within most current health delivery systems. The present protocol is a novel, remotely delivered and self-administered intervention designed to harness principles from EE and allocentric spatial navigation to offset hippocampal atrophy and potentially improve hippocampal functions such as navigation and memory for patients with m-sTBI. METHODS AND ANALYSIS: Eighty-four participants with chronic m-sTBI are being recruited from an urban rehabilitation hospital and randomised into a 16-week intervention (5 hours/week; total: 80 hours) of either targeted spatial navigation or an active control group. The spatial navigation group engages in structured exploration of different cities using Google Street View that includes daily navigation challenges. The active control group watches and answers subjective questions about educational videos. Following a brief orientation, participants remotely self-administer the intervention on their home computer. In addition to feasibility and compliance measures, clinical and experimental cognitive measures as well as MRI scan data are collected pre-intervention and post-intervention to determine behavioural and neural efficacy. ETHICS AND DISSEMINATION: Ethics approval has been obtained from ethics boards at the University Health Network and University of Toronto. Findings will be presented at academic conferences and submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: Version 3, ClinicalTrials.gov Registry (NCT04331392).

Inducing preference reversals in aesthetic choices for paintings: Introducing the contrast paradigm.

Understanding what leads people to reverse their choices is important in many domains. We introduce a contrast paradigm for studying reversals in choices-here between pairs of abstract paintings-implemented in both within-subject (Experiment 1; N = 320) and between-subject (Experiment 2; N = 384) designs. On each trial, participants chose between a pair of paintings. A critical pair of average-beauty paintings was presented before and after either a reversal or control block. In the reversal block, we made efforts to bias preference away from the chosen average-beauty painting (by pairing it with more-beautiful paintings) and toward the non-chosen average-beauty painting (by pairing it with less-beautiful paintings). Meta-analysis revealed more reversals after reversal blocks than after control blocks, though only when the biasing manipulations succeeded. A second meta-analysis revealed that reversals were generally more likely for participants who later misidentified their initial choice, demonstrating that memory for initial choices influences later choices. Thus, the contrast paradigm has utility both for inducing choice reversals and identifying their causes.

Are there age differences in attention to emotional images following a sad mood induction? Evidence from a free-viewing eye-tracking paradigm.

Two experiments examined age differences in the effect of a sad mood induction (MI) on attention to emotional images. Younger and older adults viewed sets of four images while their eye gaze was tracked throughout an 8-s presentation. Images were viewed before and after a sad MI to assess the effect of a sad mood on attention to positive and negative scenes. Younger and older adults exhibited positively biased attention after the sad MI, significantly increasing their attention to positive images, with no evidence of an age difference in either experiment. A test of participants' recognition memory for the images indicated that the sad MI reduced memory accuracy for sad images for younger and older adults. The results suggest that heightened attention to positive images following a sad MI reflects an affect regulation strategy related to mood repair. The implications for theories of the positivity effect are discussed.

Psychological traits predict impaired awareness of deficits independently of neuropsychological factors in chronic traumatic brain injury.

OBJECTIVES: To dissociate injury-related factors from psychological contributions to impaired awareness of deficits following traumatic brain injury (TBI); impaired awareness is theorized to partly reflect psychological factors (e.g., denial), but empirical evidence for this theory is scarce. DESIGN: We examined how different factors predict awareness in patients undergoing rehabilitation (N = 43). Factors included (1) neurological (injury severity), (2) neuropsychological loss, (3) psychological (denial, projection, identification), and (4) personality (narcissism). METHODS/MAIN MEASURES: The Patient Competency Rating Scale, comparing patient with clinician reports on different functional domains; the Thematic Apperception Test, an injury-independent measure of the propensity to mobilize specific defence mechanisms; and the Narcissism Personality Inventory. RESULTS: Impaired awareness was not predicted by injury-related and neuropsychological scores but was significantly predicted by use of primitive defence mechanisms (denial and projection). Patients who underestimate their abilities also demonstrated high denial levels, but contrary to underestimators, this was positively related to depression and negatively to awareness. CONCLUSIONS: Primitive defence mechanism use significantly contributes to impaired awareness independent of injury-related factors, particularly in domains associated with self-identity. Well-validated tests of defence mechanism mobilization are needed to support clinical interpretation of and intervention with impaired awareness. More research is needed to understand the psychology of hypersensitivity to deficits. PRACTITIONER POINTS: This study provides an empirical demonstration of dissociable contributions of neurological and psychological factors to awareness of deficits in TBI. Trait proclivity to mobilize defence mechanisms in response to anxiety-provoking situations can be measured, and strongly predicts impaired awareness. Importantly, measures of psychological reactions were independent of responses to the neurological deficits themselves, discriminating between psychological and neurological contributions to impaired awareness. The importance of identifying psychological reactions to impaired awareness and hindering rehabilitation success is highlighted, and vital for clinicians to consider during the rehabilitation process. Psychological reactions to TBI can be identified using well-validated, quantitative measures of the use of psychological defences (e.g., Cramer's Thematic Apperception Test scoring system), and the authors suggest this is a critical step to properly characterize and manage awareness in patients during treatment. Although only TBI patients were examined, the results may inform impaired awareness that occur as a result of other disorders and illnesses. The patients in this study were in the chronic stages of the injury, and therefore, the results may not generalize to patients in more acute stages.