Morgan D. Barense’s research while affiliated with University of Toronto and other places

INTRODUCTION Women with early bilateral salpingo‐oophorectomy (BSO) have greater Alzheimer's disease (AD) risk than women with spontaneous menopause (SM), but the pathway toward this risk is understudied. Considering associative memory deficits may reflect early signs of AD, we studied how BSO affected brain activity underlying associative memory. METHODS Early midlife women with BSO (with and without 17β‐estradiol therapy [ET]) and age‐matched controls (AMCs) with intact ovaries completed a face–name associative memory task during functional magnetic resonance imaging. Hippocampal activity along the anteroposterior axis during associative encoding and retrieval was compared among three groups (BSO [n = 28], BSO+ET [n = 35], AMCs [n = 40]). RESULTS Both BSO groups (with and without ET) showed lower posterior hippocampal activation during encoding compared to the AMC group. However, this difference in activation was not significantly correlated with associative memory task performance. DISCUSSION Early 17β‐estradiol loss may influence posterior hippocampal activity during associative encoding, possibly presaging late‐life AD. Highlights After ovarian removal, changes in hippocampal function may affect dementia risk. Midlife ovarian removal is associated with less activation in the posterior hippocampus. Estradiol therapy may ameliorate alterations in brain function during learning.

Purpose of Review Sleep is important for memory consolidation in laboratory-based stimuli, but less is known about how sleep impacts autobiographical memory. In our paper, we review the following: (i) the methods used to study autobiographical memory, (ii) the literature on sleep and autobiographical memory, and (iii) the role that dreaming may play in autobiographical memory consolidation. Recent Findings Reduced sleep durations, sleep deprivation, and sleep apnea were associated with reduced autobiographical memory specificity. Sleep disruptions also affected the emotional quality of these memories, such that participants recalled more negative memories and memories that were either less emotional or more negative. Sleep, relative to wake, and percent of slow-wave sleep were associated with more detail for autobiographical memories from 12–24 h prior. Finally, improved sleep quality proximal to encoding predicted improved memory accuracy at delays of around one month. Summary There is evidence that sleep is important in maintaining our ability to retrieve specific and positive autobiographical memories. In addition, there is preliminary evidence that slow-wave sleep and sleep quality are associated with greater detail and accuracy for recent autobiographical memories.

Tau pathology accumulates in the perirhinal cortex (PRC) of the medial temporal lobe (MTL) during the earliest stages of the Alzheimer's disease (AD), appearing decades before clinical diagnosis. Here, we leveraged perceptual discrimination tasks that target PRC function to detect subtle cognitive impairment even in nominally healthy older adults. Older adults who did not have a clinical diagnosis or subjective memory complaints were categorized into “at‐risk” (score <26; n = 15) and “healthy” (score ≥26; n = 23) groups based on their performance on the Montreal Cognitive Assessment. The task included two conditions known to recruit the PRC: faces and complex objects (greebles). A scene condition, known to recruit the hippocampus, and a size control condition that does not rely on the MTL were also included. Individuals in the at‐risk group were less accurate than those in the healthy group for discriminating greebles. Performance on either the face or size control condition did not predict group status above and beyond that of the greeble condition. Visual discrimination tasks that are sensitive to PRC function may detect early cognitive decline associated with AD.

We have previously shown that analyses of autocorrelation of BOLD signal applied to single voxels in healthy controls can identify gradients of temporal dynamics throughout the hippocampal long-axis that are related to behavior. A question that remains is how changes in functional and structural integrity in the brain affect single voxel autocorrelation. In this study we investigate how hippocampal autocorrelation is affected by structural and functional hippocampal dysfunction by investigating a population of patients with unilateral temporal lobe epilepsy (TLE). Many patients with TLE have mesial temporal sclerosis (MTS), characterized by scarring and neuronal loss particularly in the anterior hippocampus. Here we compared patients with left and right TLE, some with and without MTS, to healthy controls. We applied our single voxel autocorrelation method and data-driven clustering approach to segment the hippocampus based on the autocorrelation. We found that patients with left TLE had slower signal dynamics (i.e., higher autocorrelation) compared to controls, particularly in the anterior-medial portion of the hippocampus. This was true for both the epileptogenic and non-epileptogenic hemispheres. We also evaluated the extent of cluster preservation (i.e., spatial overlap with controls) of patient autocorrelation clusters and the relationship to verbal and visuospatial memory. We found that patients with greater cluster preservation in the anterior-medial hippocampus had better memory performance. Surprisingly, we did not find any effect of MTS on single voxel autocorrelation, despite the structural changes associated with the condition. These results suggest that single voxel autocorrelation may be related to functional, rather than structural, integrity.

Our brains grant us the amazing ability to remember and relive the events from the past—however, memory for these events tend to worsen as people get older. Our memories serve several important functions, helping us to guide our future actions, connect with others, and understand ourselves. As a result, memory loss can greatly impact the lives of both those who lose their memory and their loved ones. Fortunately, there are things that people can do to help support memory as we age! For example, by combining smartphone technology and findings from decades of memory research, scientists can develop new and exciting tools to improve memory. In this paper, we will describe some of our work creating and testing a smartphone application that helps older adults better remember the unique moments from their lives.

Research has documented changes in autobiographical memory and episodic future thinking in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, cognitive decline occurs gradually and recent findings suggest that subtle alterations in autobiographical memory may be evident early in the trajectory towards dementia, before AD-related symptoms emerge or a clinical diagnosis has been given. The current study used the Autobiographical Interview to examine the episodic and semantic content of autobiographical past and future events generated by healthy older adults (N=20) and older adults “at risk” of cognitive decline (as defined by their score on the Montreal Cognitive Assessment) but who do not meet criteria for formal diagnosis of MCI (N=18). The Autobiographical Interview was conducted by telephone during the COVID-19 pandemic across six monthly sessions; in each session, participants described two past and two future autobiographical events. Transcripts were scored by classifying each detail as internal (episodic) or external (non-episodic, including semantic) to the main event. Although the at-risk group exhibited a differential reduction for internal details comprising both past and future events, they did not show the expected overproduction of external details that is evident in MCI, possibly because their episodic and executive abilities were not sufficiently compromised. Multilevel modelling demonstrated that on trials lower in episodic content, semantic content was significantly increased in both groups. Although suggestive of a compensatory mechanism, the finding that the magnitude of this relationship did not differ across groups indicates it may reflect an age-related semanticization of autobiographical events that is not affected by cognitive decline. This study contributes to our knowledge of the trajectory of cognitive decline as it pertains to the ability to recollect the personal past and imagine the personal future.

In March 2020, C.T., a kind, bright, and friendly young woman underwent surgery for a midline tumor involving her septum pellucidum and extending down into her fornices bilaterally. Following tumor diagnosis and surgery, C.T. experienced significant memory deficits: C.T.'s family reported that she could remember things throughout the day, but when she woke up in the morning or following a nap, she would expect to be in the hospital, forgetting all the information that she had learned before sleep. The current study aimed to empirically validate C.T.'s pattern of memory loss and explore its neurological underpinnings. On two successive days, C.T. and age-matched controls watched an episode of a TV show and took a nap or stayed awake before completing a memory test. Although C.T. performed numerically worse than controls in both conditions, sleep profoundly exacerbated her memory impairment, such that she could not recall any details following a nap. This effect was replicated in a second testing session. High-resolution MRI scans showed evidence of the trans-callosal surgical approach's impact on the mid-anterior corpus callosum, indicated that C.T. had perturbed white matter particularly in the right fornix column, and demonstrated that C.T.'s hippocampal volumes did not differ from controls. These findings suggest that the fornix is important for processing episodic memories during sleep. As a key output pathway of the hippocampus, the fornix may ensure that specific memories are replayed during sleep, maintain the balance of sleep stages, or allow for the retrieval of memories following sleep.

The ability to flexibly categorize object concepts is essential to semantic cognition because the features that make two objects similar in one context may be irrelevant and even constitute interference in another. Thus, adaptive behavior in complex and dynamic environments requires the resolution of feature-based interference. In the current case study, we placed visual and functional semantic features in opposition across object concepts in two categorization tasks. Successful performance required the resolution of functional interference in a visual categorization task and the resolution of visual interference in a functional categorization task. In Experiment 1, we found that patient D. A., an individual with bilateral temporal lobe lesions, was unable to categorize object concepts in a context-dependent manner. His impairment was characterized by an increased tendency to incorrectly group objects that were similar on the task-irrelevant dimension, revealing an inability to resolve cross-modal semantic interference. In Experiment 2, D. A.'s categorization accuracy was comparable to controls when lures were removed, indicating that his impairment is unique to contexts that involve cross-modal interference. In Experiment 3, he again performed as well as controls when categorizing simple concepts, suggesting that his impairment is specific to categorization of complex object concepts. These results advance our understanding of the anterior temporal lobe as a system that represents object concepts in a manner that enables flexible semantic cognition. Specifically, they reveal a dissociation between semantic representations that contribute to the resolution of cross-modal interference and those that contribute to the resolution of interference within a given modality.