It's not a lie If you believe it: Narrative analysis of autobiographical memories reveals over-confidence disposition in patients who confabulate.

Humans perceive their personal memories as fundamentally true, and although memory is prone to inaccuracies, flagrant memory errors are rare. Some patients with damage to the ventromedial prefrontal cortex (vmPFC) recall and act upon patently erroneous memories (spontaneous confabulations). Clinical observations suggest these memories carry a strong sense of confidence, a function ascribed to vmPFC in studies of memory and decision making. However, most studies of the underlying mechanisms of memory overconfidence do not directly probe personal recollections and resort instead to laboratory-based tasks and contrived rating scales. We analyzed naturalistic word use of patients with focal vmPFC damage (N = 18) and matched healthy controls (N = 23) while they recalled autobiographical memories using the Linguistic Inquiry and Word Count (LIWC) method. We found that patients with spontaneous confabulation (N = 7) tended to over-use words related to the categories of 'certainty' and of 'swearwords' compared to both non-confabulating vmPFC patients (N = 11) and control participants. Certainty related expressions among confabulating patients were at normal levels during erroneous memories and were over-expressed during accurate memories, contrary to our predictions. We found no elevation in expressions of affect (positive or negative), temporality or drive as would be predicted by some models of confabulation. Thus, erroneous memories may be associated with subjectively lower certainty, but still exceed patients' report criterion because of a global proclivity for overconfidence. This may be compounded by disinhibition reflected by elevated use of swearwords. These findings demonstrate that analysis of naturalistic expressions of memory content can illuminate global meta-mnemonic contributions to memory accuracy complementing indirect laboratory-based correlates of behavior. Memory accuracy is the result of complex interactions among multiple meta-mnemonic processes such as monitoring, report criteria, and control processes which may be shared across decision-making domains.

Impoverished details with preserved gist in remote and recent spatial memory following hippocampal and fornix lesions.

INTRODUCTION: Cognitive Map Theory predicts that the hippocampus (HPC) plays a specialized, time-invariant role in supporting allocentric spatial memory, while Standard Consolidation Theory makes the competing prediction that the HPC plays a time-limited role, with more remote memories gaining independence of HPC function. These theories, however, are largely informed by the results of laboratory-based tests that are unlikely to simulate the demands of representing real-world environments in humans. Validation of these theories is further limited by an overall focus on spatial memory of newly encountered environments and on individuals with extensive lesions to the HPC and to surrounding medial temporal lobe (MTL) regions. The current study incorporates naturalistic tests of spatial memory based on recently and remotely encountered environments navigated by individuals with lesions to the HPC/MTL or that are limited to the HPC's major output, the fornix. METHODS: Four participants with bilateral HPC/MTL and/or fornix lesions drew sketch maps of recently and remotely experienced neighbourhoods and houses. Tests of the appearance, distances, and routes between landmarks from the same real-world environments were also administered. Performance on the tasks was compared to that of control participants closely matched in terms of exposure to the same neighbourhoods and home environments as well as to actual maps. RESULTS: The performance of individuals with fornix/MTL lesions was found to be largely comparable to that of controls on objective tests of spatial memory, other than one case who was impaired on remote and recent conditions for several tasks. The nature of deficits in recent and remote spatial memory were further revealed on house floorplan drawings, which contained spatial distortions, room/structure transpositions, and omissions, and on neighbourhood sketch maps, which were intact in terms of overall layout but sparse in details such as landmarks. CONCLUSION: Lab-based tests of spatial memory of newly learned environments are unlikely to fully capture patterns of spared and impaired representations of real-world environments (e.g., peripheral features, configurations). Naturalistic tasks, including generative drawing tasks, indicate that contrary to Cognitive Map Theory, neither HPC nor MTL are critical for allocentric gross representations of large-scale environments. Conversely, the HPC appears critical for representing detailed spatial information of local naturalistic environments and environmental objects regardless of the age of the memory, contrary to Standard Consolidation Theory.

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.

Network Localization of Spontaneous Confabulation.

OBJECTIVE: Spontaneous confabulation is a symptom in which false memories are conveyed by the patient as true. The purpose of the study was to identify the neuroanatomical substrate of this complex symptom and evaluate the relationship to related symptoms, such as delusions and amnesia. METHODS: Twenty-five lesion locations associated with spontaneous confabulation were identified in a systematic literature search. The network of brain regions functionally connected to each lesion location was identified with a large connectome database (N=1,000) and compared with networks derived from lesions associated with nonspecific (i.e., variable) symptoms (N=135), delusions (N=32), or amnesia (N=53). RESULTS: Lesions associated with spontaneous confabulation occurred in multiple brain locations, but they were all part of a single functionally connected brain network. Specifically, 100% of lesions were connected to the mammillary bodies (familywise error rate [FWE]-corrected p<0.05). This connectivity was specific for lesions associated with confabulation compared with lesions associated with nonspecific symptoms or delusions (FWE-corrected p<0.05). Lesions associated with confabulation were more connected to the orbitofrontal cortex than those associated with amnesia (FWE-corrected p<0.05). CONCLUSIONS: Spontaneous confabulation maps to a common functionally connected brain network that partially overlaps, but is distinct from, networks associated with delusions or amnesia. These findings lend new insight into the neuroanatomical bases of spontaneous confabulation.

Persistent post-COVID headache is associated with suppression of scale-free functional brain dynamics in non-hospitalized individuals.

INTRODUCTION: Post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) is a growing concern, with headache being a particularly debilitating symptom with high prevalence. The long-term effects of COVID-19 and post-COVID headache on brain function remain poorly understood, particularly among non-hospitalized individuals. This study focused on the power-law scaling behavior of functional brain dynamics, indexed by the Hurst exponent (H). This measure is suppressed during physiological and psychological distress and was thus hypothesized to be reduced in individuals with post-COVID syndrome, with greatest reductions among those with persistent headache. METHODS: Resting-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data were collected for 57 individuals who had COVID-19 (32 with no headache, 14 with ongoing headache, 11 recovered) and 17 controls who had cold and flu-like symptoms but  tested negative for COVID-19. Individuals were assessed an average of 4-5 months after COVID testing, in a cross-sectional, observational study design. RESULTS: No significant differences in H values were found between non-headache COVID-19 and control groups., while those with ongoing headache had significantly reduced H values, and those who had recovered from headache had elevated H values, relative to non-headache groups. Effects were greatest in temporal, sensorimotor, and insular brain regions. Reduced H in these regions was also associated with decreased BOLD activity and local functional connectivity. CONCLUSIONS: These findings provide new insights into the neurophysiological mechanisms that underlie persistent post-COVID headache, with reduced BOLD scaling as a potential biomarker that is specific to this debilitating condition.

Feasibility of diffusion-tensor and correlated diffusion imaging for studying white-matter microstructural abnormalities: Application in COVID-19.

There has been growing attention on the effect of COVID-19 on white-matter microstructure, especially among those that self-isolated after being infected. There is also immense scientific interest and potential clinical utility to evaluate the sensitivity of single-shell diffusion magnetic resonance imaging (MRI) methods for detecting such effects. In this work, the performances of three single-shell-compatible diffusion MRI modeling methods are compared for detecting the effect of COVID-19, including diffusion-tensor imaging, diffusion-tensor decomposition of orthogonal moments and correlated diffusion imaging. Imaging was performed on self-isolated patients at the study initiation and 3-month follow-up, along with age- and sex-matched controls. We demonstrate through simulations and experimental data that correlated diffusion imaging is associated with far greater sensitivity, being the only one of the three single-shell methods to demonstrate COVID-19-related brain effects. Results suggest less restricted diffusion in the frontal lobe in COVID-19 patients, but also more restricted diffusion in the cerebellar white matter, in agreement with several existing studies highlighting the vulnerability of the cerebellum to COVID-19 infection. These results, taken together with the simulation results, suggest that a significant proportion of COVID-19 related white-matter microstructural pathology manifests as a change in tissue diffusivity. Interestingly, different b-values also confer different sensitivities to the effects. No significant difference was observed in patients at the 3-month follow-up, likely due to the limited size of the follow-up cohort. To summarize, correlated diffusion imaging is shown to be a viable single-shell diffusion analysis approach that allows us to uncover opposing patterns of diffusion changes in the frontal and cerebellar regions of COVID-19 patients, suggesting the two regions react differently to viral infection.

Effects of post-acute COVID-19 syndrome on the functional brain networks of non-hospitalized individuals.

Introduction: The long-term impact of COVID-19 on brain function remains poorly understood, despite growing concern surrounding post-acute COVID-19 syndrome (PACS). The goal of this cross-sectional, observational study was to determine whether there are significant alterations in resting brain function among non-hospitalized individuals with PACS, compared to symptomatic individuals with non-COVID infection. Methods: Data were collected for 51 individuals who tested positive for COVID-19 (mean age 41±12 yrs., 34 female) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19 (mean age 41±14 yrs., 9 female), with both groups assessed an average of 4-5 months after COVID testing. None of the participants had prior neurologic, psychiatric, or cardiovascular illness. Resting brain function was assessed via functional magnetic resonance imaging (fMRI), and self-reported symptoms were recorded. Results: Individuals with COVID-19 had lower temporal and subcortical functional connectivity relative to controls. A greater number of ongoing post-COVID symptoms was also associated with altered functional connectivity between temporal, parietal, occipital and subcortical regions. Discussion: These results provide preliminary evidence that patterns of functional connectivity distinguish PACS from non-COVID infection and correlate with the severity of clinical outcome, providing novel insights into this highly prevalent disorder.

MRI Assessment of Cerebral Blood Flow in Nonhospitalized Adults Who Self-Isolated Due to COVID-19.

BACKGROUND: Neurological symptoms associated with coronavirus disease 2019 (COVID-19), such as fatigue and smell/taste changes, persist beyond infection. However, little is known of brain physiology in the post-COVID-19 timeframe. PURPOSE: To determine whether adults who experienced flu-like symptoms due to COVID-19 would exhibit cerebral blood flow (CBF) alterations in the weeks/months beyond infection, relative to controls who experienced flu-like symptoms but tested negative for COVID-19. STUDY TYPE: Prospective observational. POPULATION: A total of 39 adults who previously self-isolated at home due to COVID-19 (41.9 ± 12.6 years of age, 59% female, 116.5 ± 62.2 days since positive diagnosis) and 11 controls who experienced flu-like symptoms but had a negative COVID-19 diagnosis (41.5 ± 13.4 years of age, 55% female, 112.1 ± 59.5 since negative diagnosis). FIELD STRENGTH AND SEQUENCES: A 3.0 T; T1-weighted magnetization-prepared rapid gradient and echo-planar turbo gradient-spin echo arterial spin labeling sequences. ASSESSMENT: Arterial spin labeling was used to estimate CBF. A self-reported questionnaire assessed symptoms, including ongoing fatigue. CBF was compared between COVID-19 and control groups and between those with (n = 11) and without self-reported ongoing fatigue (n = 28) within the COVID-19 group. STATISTICAL TESTS: Between-group and within-group comparisons of CBF were performed in a voxel-wise manner, controlling for age and sex, at a family-wise error rate of 0.05. RESULTS: Relative to controls, the COVID-19 group exhibited significantly decreased CBF in subcortical regions including the thalamus, orbitofrontal cortex, and basal ganglia (maximum cluster size = 6012 voxels and maximum t-statistic = 5.21). Within the COVID-19 group, significant CBF differences in occipital and parietal regions were observed between those with and without self-reported on-going fatigue. DATA CONCLUSION: These cross-sectional data revealed regional CBF decreases in the COVID-19 group, suggesting the relevance of brain physiology in the post-COVID-19 timeframe. This research may help elucidate the heterogeneous symptoms of the post-COVID-19 condition. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

Has the concept of systems consolidation outlived its usefulness? Identification and evaluation of premises underlying systems consolidation.

Systems consolidation has mostly been treated as a neural construct defined by the time-dependent change in memory representation from the hippocampus (HPC) to other structures, primarily the neocortex. Here, we identify and evaluate the explicit and implicit premises that underlie traditional or standard models and theories of systems consolidation based on evidence from research on humans and other animals. We use the principle that changes in neural representation over time and experience are accompanied by corresponding changes in psychological representations, and vice versa, to argue that each of the premises underlying traditional or standard models and theories of systems consolidation is found wanting. One solution is to modify or abandon the premises or theories and models. This is reflected in moderated models of systems consolidation that emphasize the early role of the HPC in training neocortical memories until they stabilize. The fault, however, may lie in the very concept of systems consolidation and its defining feature. We propose that the concept be replaced by one of memory systems reorganization, which does not carry the theoretical baggage of systems consolidation and is flexible enough to capture the dynamic nature of memory from inception to very long-term retention and retrieval at a psychological and neural level. The term "memory system reorganization" implies that memory traces are not fixed, even after they are presumably consolidated. Memories can continue to change as a result of experience and interactions among memory systems across the lifetime. As will become clear, hippocampal training of neocortical memories is only one type of such interaction, and not always the most important one, even at inception. We end by suggesting some principles of memory reorganization that can help guide research on dynamic memory processes that capture corresponding changes in memory at the psychological and neural levels.

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.

The structure of prior knowledge enhances memory in experts by reducing interference.

The influence of prior knowledge on memory is ubiquitous, making the specific mechanisms of this relationship difficult to disentangle. Here, we show that expert knowledge produces a fundamental shift in the way that interitem similarity (i.e., the perceived resemblance between items in a set) biases episodic recognition. Within a group of expert birdwatchers and matched controls, we characterized the psychological similarity space for a set of well-known local species and a set of less familiar, nonlocal species. In experts, interitem similarity was influenced most strongly by taxonomic features, whereas in controls, similarity judgments reflected bird color. In controls, perceived episodic oldness during a recognition memory task increased along with measures of global similarity between items, consistent with classic models of episodic recognition. Surprisingly, for experts, high global similarity did not drive oldness signals. Instead, for local birds memory tracked the availability of species-level name knowledge, whereas for nonlocal birds, it was mediated by the organization of generalized conceptual space. These findings demonstrate that episodic memory in experts can benefit from detailed subcategory knowledge, or, lacking that, from the overall relational structure of concepts. Expertise reshapes psychological similarity space, helping to resolve mnemonic separation challenges arising from high interitem overlap. Thus, even in the absence of knowledge about item-specific details or labels, the presence of generalized knowledge appears to support episodic recognition in domains of expertise by altering the typical relationship between psychological similarity and memory.

Early Auditory Event Related Potentials Distinguish Higher-Order From First-Order Aversive Conditioning.

Stimuli in reality rarely co-occur with primary reward or punishment to allow direct associative learning of value. Instead, value is thought to be inferred through complex higher-order associations. Rodent research has demonstrated that the formation and maintenance of first-order and higher-order associations are supported by distinct neural substrates. In this study, we explored whether this pattern of findings held true for humans. Participants underwent first-order and subsequent higher-order conditioning using an aversive burst of white noise or neutral tone as the unconditioned stimuli. Four distinct tones, initially neutral, served as first-order and higher-order conditioned stimuli. Autonomic and neural responses were indexed by pupillometry and evoked response potentials (ERPs) respectively. Conditioned aversive values of first-order and higher-order stimuli led to increased autonomic responses, as indexed by pupil dilation. Distinct temporo-spatial auditory evoked response potentials were elicited by first-order and high-order conditioned stimuli. Conditioned first-order responses peaked around 260 ms and source estimation suggested a primary medial prefrontal and amygdala source. Conversely, conditioned higher-order responses peaked around 120 ms with an estimated source in the medial temporal lobe. Interestingly, pupillometry responses to first-order conditioned stimuli were diminished after higher order training, possibly signifying concomitant incidental extinction, while responses to higher-order stimuli remained. This suggests that once formed, higher order associations are at least partially independent of first order conditioned representations. This experiment demonstrates that first-order and higher-order conditioned associations have distinct neural signatures, and like rodents, the medial temporal lobe may be specifically involved with higher-order conditioning.

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.

Brain structure and function in people recovering from COVID-19 after hospital discharge or self-isolation: a longitudinal observational study protocol.

BACKGROUND: The detailed extent of neuroinvasion or deleterious brain changes resulting from COVID-19 and their time courses remain to be determined in relation to "long-haul" COVID-19 symptoms. Our objective is to determine whether there are alterations in functional brain imaging measures among people with COVID-19 after hospital discharge or self-isolation. METHODS: This paper describes a protocol for NeuroCOVID-19, a longitudinal observational study of adults aged 20-75 years at Sunnybrook Health Sciences Centre in Toronto, Ontario, that began in April 2020. We aim to recruit 240 adults, 60 per group: people who contracted COVID-19 and were admitted to hospital (group 1), people who contracted COVID-19 and self-isolated (group 2), people who experienced influenza-like symptoms at acute presentation but tested negative for COVID-19 and self-isolated (group 3, control) and healthy people (group 4, control). Participants are excluded based on premorbid neurologic or severe psychiatric illness, unstable cardiovascular disease, and magnetic resonance imaging (MRI) contraindications. Initial and 3-month follow-up assessments include multiparametric brain MRI and electroencephalography. Sensation and cognition are assessed alongside neuropsychiatric assessments and symptom self-reports. We will test the data from the initial and follow-up assessments for group differences based on 3 outcome measures: MRI cerebral blood flow, MRI resting state fractional amplitude of low-frequency fluctuation and electroencephalography spectral power. INTERPRETATION: If neurophysiologic alterations are detected in the COVID-19 groups in our NeuroCOVID-19 study, this information could inform future research regarding interventions for long-haul COVID-19. The study results will be disseminated to scientists, clinicians and COVID-19 survivors, as well as the public and private sectors to provide context on how brain measures relate to lingering symptoms.

The Role of the Ventromedial Prefrontal Cortex and Basal Forebrain in Relational Memory and Inference.

The ventromedial prefrontal cortex (vmPFC) is involved in diverse cognitive operations, from inhibitory control to processing of semantic schemas. When accompanied by damage to the basal forebrain, vmPFC lesions can also impair relational memory, the ability to form and recall relations among items. Impairments in establishing direct relations among items (e.g., A is related to B, B is related to C) can also hinder the transitive processing of indirect relationships (e.g., inferring that A and C are related through direct relations that each contain B). Past work has found that transitive inference improves when the direct relations are organized within an existing knowledge structure, or schema. This type of semantic support is most effective for individuals whose relational memory deficits are mild (e.g., healthy age-related decline) rather than pronounced (e.g., hippocampal amnesia, amnestic mild cognitive impairment). Given that vmPFC damage can produce both relational memory and schema processing deficits, such damage may pose a particular challenge in establishing the type of relational structure required for transitive inference, even when supported by preexisting knowledge. To examine this idea, we tested individuals with lesions to the mPFC on multiple conditions that varied in pre-experimental semantic support and explored the extent to which they could identify both previously studied (direct) and novel transitive (indirect) relations. Most of the mPFC cases showed marked transitive inference deficits and even showed impaired knowledge of preexisting, direct, semantic relations, consistent with disruptions to schema-related processes. However, one case with more dorsal mPFC damage showed preserved ability to identify direct relations and make novel inferences, particularly when pre-experimental knowledge could be used to support performance. These results suggest that damage to the mPFC and basal forebrain can impede establishment of ad hoc relational schemas upon which transitive inference is based, but that appealing to prior knowledge may still be useful for those neurological cases that have some degree of preserved relational memory.

Differential Influence of Ventromedial Prefrontal Cortex Lesions on Neural Representations of Schema and Semantic Category Knowledge.

Prior knowledge, such as schemas or semantic categories, influences our interpretation of stimulus information. For this to transpire, prior knowledge must first be reinstated and then instantiated by being applied to incoming stimuli. Previous neuropsychological models implicate the ventromedial prefrontal cortex (vmPFC) in mediating these functions for schemas and the anterior/lateral temporal lobes and related structures for categories. vmPFC, however, may also affect processing of semantic category information. Here, the putative differential role of the vmPFC in the reinstatement and instantiation of schemas and semantic categories was examined by probing network-level oscillatory dynamics. Patients with vmPFC damage (n = 11) and healthy controls (n = 13) were instructed to classify words according to a given schema or category, while electroencephalography was recorded. As reinstatement is a preparatory process, we focused on oscillations occurring 500 msec prior to stimulus presentation. As instantiation occurs at stimulus presentation, we focused on oscillations occurring between stimulus presentation and 1000 msec poststimulus. We found that reinstatement was associated with prestimulus, theta and alpha desynchrony between vmPFC and the posterior parietal cortex for schemas, and between lateral temporal lobe and inferotemporal cortex for categories. Damage to the vmPFC influenced both schemas and categories, but patients with damage to the subcallosal vmPFC showed schema-specific deficits. Instantiation showed similar oscillatory patterns in the poststimulus time frame, but in the alpha and beta frequency bands. Taken together, these findings highlight distinct but partially overlapping neural mechanisms implicated in schema- and category-mediated processing.

No consolidation without representation: Correspondence between neural and psychological representations in recent and remote memory.

Memory systems consolidation is often conceived as the linear, time-dependent, neurobiological shift of memory from hippocampal-cortical to cortico-cortical dependency. We argue that contrary to this unidirectional view of memory reorganization, information about events may be retained in multiple forms (e.g., event-specific sensory-near episodic memory, event-specific gist information, event-general schematic information, or abstract semantic memory). These representations can all form at the time of the event and may continue to coexist for long durations. Their relative strength, composition, and dominance of expression change with time and experience, with task demands, and through their dynamic interaction with one another. These different psychological mnemonic representations depend on distinct functional and structural neurobiological substrates such that there is a neural-psychological representation correspondence (NPRC) among them. We discuss how the dynamics of psychological memory representations are reflected in multiple levels of neurobiological markers and their interactions. By this view, there are only variations of synaptic consolidation and memory dynamics without assuming a distinct systems consolidation process.

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).

Precuneus stimulation alters the neural dynamics of autobiographical memory retrieval.

Autobiographical memory (AM) unfolds over time, but little is known about the dynamics of its retrieval. Space-based models of memory implicate the hippocampus, retrosplenial cortex, and precuneus in early memory computations. Here we used transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) to investigate the causal role of the precuneus in the dynamics of AM retrieval. During early memory search and construction, precuneus stimulation compared to vertex stimulation led to delayed evoked neural activity within 1000 â€‹ms after cue presentation. During later memory elaboration, stimulation led to decreased sustained positivity. We further identified a parietal late positive component during memory elaboration, the amplitude of which was associated with spatial perspective during recollection. This association was disrupted following precuneus stimulation, suggesting that this region plays an important role in the neural representation of spatial perspective during AM. These findings demonstrate a causal role for the precuneus in early AM retrieval, during memory search before a specific memory is accessed, and in spatial context reinstatement during the initial stages of memory elaboration and re-experiencing. By utilizing the high temporal resolution of MEG and the causality of TMS, this study helps clarify the neural correlates of early naturalistic memory retrieval.

Rapid Cortical Plasticity Supports Long-Term Memory Formation.

The standard systems consolidation account posits that recently formed memories are initially dependent on the hippocampus and only gradually become instantiated in neocortical networks over a period of weeks to years. However, recent animal and human research has identified rapid formation of cortical engrams at the time of learning that can support hippocampal-independent memories within hours or days. Conditions that promote rapid cortical learning include relatedness to prior knowledge, activation of knowledge in the service of action selection or active discovery, and repeated retrieval. Here, we propose that cortical hubs can support rapid learning through synchronous activation of sensorimotor representational cortices. Candidate neurobiological mechanisms include unmasking of latent synaptic connections and rapid synaptic remodeling driven by disinhibitory processes.