Diminished baseline autonomic outflow in semantic dementia relates to left-lateralized insula atrophy.

In semantic dementia (SD), asymmetric degeneration of the anterior temporal lobes is associated with loss of semantic knowledge and alterations in socioemotional behavior. There are two clinical variants of SD: semantic variant primary progressive aphasia (svPPA), which is characterized by predominant atrophy in the anterior temporal lobe and insula in the left hemisphere, and semantic behavioral variant frontotemporal dementia (sbvFTD), which is characterized by predominant atrophy in those structures in the right hemisphere. Previous studies of behavioral variant frontotemporal dementia, an associated clinical syndrome that targets the frontal lobes and anterior insula, have found impairments in baseline autonomic nervous system activity that correlate with left-lateralized frontotemporal atrophy patterns and disruptions in socioemotional functioning. Here, we evaluated whether there are similar impairments in resting autonomic nervous system activity in SD that also reflect left-lateralized atrophy and relate to diminished affiliative behavior. A total of 82 participants including 33 people with SD (20 svPPA and 13 sbvFTD) and 49 healthy older controls completed a laboratory-based assessment of respiratory sinus arrhythmia (RSA; a parasympathetic measure) and skin conductance level (SCL; a sympathetic measure) during a two-minute resting baseline period. Participants also underwent structural magnetic resonance imaging, and informants rated their current affiliative behavior on the Interpersonal Adjective Scale. Results indicated that baseline RSA and SCL were lower in SD than in healthy controls, with significant impairments present in both svPPA and sbvFTD. Voxel-based morphometry analyses revealed left-greater-than-right atrophy related to diminished parasympathetic and sympathetic outflow in SD. While left-lateralized atrophy in the mid-to-posterior insula correlated with lower RSA, left-lateralized atrophy in the ventral anterior insula correlated with lower SCL. In SD, lower baseline RSA, but not lower SCL, was associated with lower gregariousness/extraversion. Neither autonomic measure related to warmth/agreeableness, however. Through the assessment of baseline autonomic nervous system physiology, the present study contributes to expanding conceptualizations of the biological basis of socioemotional alterations in svPPA and sbvFTD.

Medial Temporal Lobe Tau Aggregation Relates to Divergent Cognitive and Emotional Empathy Abilities in Alzheimer's Disease.

BACKGROUND: In Alzheimer's disease (AD), the gradual accumulation of amyloid-ß (Aß) and tau proteins may underlie alterations in empathy. OBJECTIVE: To assess whether tau aggregation in the medial temporal lobes related to differences in cognitive empathy (the ability to take others' perspectives) and emotional empathy (the ability to experience others' feelings) in AD. METHODS: Older adults (n = 105) completed molecular Aß positron emission tomography (PET) scans. Sixty-eight of the participants (35 women) were Aß positive and symptomatic with diagnoses of mild cognitive impairment, dementia of the Alzheimer's type, logopenic variant primary progressive aphasia, or posterior cortical atrophy. The remaining 37 (22 women) were asymptomatic Aß negative healthy older controls. Using the Interpersonal Reactivity Index, we compared current levels of informant-rated cognitive empathy (Perspective-Taking subscale) and emotional empathy (Empathic Concern subscale) in the Aß positive and negative participants. The Aß positive participants also underwent molecular tau-PET scans, which were used to investigate whether regional tau burden in the bilateral medial temporal lobes related to empathy. RESULTS: Aß positive participants had lower perspective-taking and higher empathic concern than Aß negative healthy controls. Medial temporal tau aggregation in the Aß positive participants had divergent associations with cognitive and emotional empathy. Whereas greater tau burden in the amygdala predicted lower perspective-taking, greater tau burden in the entorhinal cortex predicted greater empathic concern. Tau burden in the parahippocampal cortex did not predict either form of empathy. CONCLUSIONS: Across AD clinical syndromes, medial temporal lobe tau aggregation is associated with lower perspective-taking yet higher empathic concern.

Increasing empathic concern relates to salience network hyperconnectivity in cognitively healthy older adults with elevated amyloid-ß burden.

Enhanced emotional empathy, the ability to share others' affective experiences, can be a feature of Alzheimer's disease (AD), but whether emotional empathy increases in the preclinical phase of the disease is unknown. We measured emotional empathy over time (range = 0 - 7.3 years, mean = 2.4 years) in 86 older adults during a period in which they were cognitively healthy, functionally normal, and free of dementia symptoms. For each participant, we computed longitudinal trajectories for empathic concern (i.e., an other-oriented form of emotional empathy that promotes prosocial actions) and emotional contagion (i.e., a self-focused form of emotional empathy often accompanied by feelings of distress) from informant ratings of participants' empathy on the Interpersonal Reactivity Index. Amyloid-ß (Aß) positron emission tomography (PET) scans were used to classify participants as either Aß positive (Aß+, n = 23) or negative (Aß-, n = 63) based on Aß-PET cortical binding. Participants also underwent structural and task-free functional magnetic resonance imaging approximately two years on average after their last empathy assessment, at which time most participants remained cognitively healthy. Results indicated that empathic concern, but not emotional contagion, increased more over time in Aß+ participants than in Aß- participants despite no initial group difference at the first measurement. Higher connectivity between certain salience network node-pairs (i.e., pregenual anterior cingulate cortex and periaqueductal gray) predicted longitudinal increases in empathic concern in the Aß+ group but not in the Aß- group. The Aß+ participants also had higher overall salience network connectivity than Aß- participants despite no differences in gray matter volume. These results suggest gains in empathic concern may be a very early feature of AD pathophysiology that relates to hyperconnectivity in the salience network, a system that supports emotion generation and interoception. A better understanding of emotional empathy trajectories in the early stages of AD pathophysiology will broaden the lens on preclinical AD changes and help clinicians to identify older adults who should be screened for AD biomarkers.

Dynamic autonomic nervous system states arise during emotions and manifest in basal physiology.

The outflow of the autonomic nervous system (ANS) is continuous and dynamic, but its functional organization is not well understood. Whether ANS patterns accompany emotions, or arise in basal physiology, remain unsettled questions in the field. Here, we searched for brief ANS patterns amidst continuous, multichannel physiological recordings in 45 healthy older adults. Participants completed an emotional reactivity task in which they viewed video clips that elicited a target emotion (awe, sadness, amusement, disgust, or nurturant love); each video clip was preceded by a pre-trial baseline period and followed by a post-trial recovery period. Participants also sat quietly for a separate 2-min resting period to assess basal physiology. Using principal components analysis and unsupervised clustering algorithms to reduce the second-by-second physiological data during the emotional reactivity task, we uncovered five ANS states. Each ANS state was characterized by a unique constellation of patterned physiological changes that differentiated among the trials of the emotional reactivity task. These ANS states emerged and dissipated over time, with each instance lasting several seconds on average. ANS states with similar structures were also detectable in the resting period but were intermittent and of smaller magnitude. Our results offer new insights into the functional organization of the ANS. By assembling short-lived, patterned changes, the ANS is equipped to generate a wide range of physiological states that accompany emotions and that contribute to the architecture of basal physiology.

Big smile, small self: Awe walks promote prosocial positive emotions in older adults.

Aging into later life is often accompanied by social disconnection, anxiety, and sadness. Negative emotions are self-focused states with detrimental effects on aging and longevity. Awe-a positive emotion elicited when in the presence of vast things not immediately understood-reduces self-focus, promotes social connection, and fosters prosocial actions by encouraging a "small self." We investigated the emotional benefits of a novel "awe walk" intervention in healthy older adults. Sixty participants took weekly 15-min outdoor walks for 8 weeks; participants were randomly assigned to an awe walk group, which oriented them to experience awe during their walks, or to a control walk group. Participants took photographs of themselves during each walk and rated their emotional experience. Each day, they reported on their daily emotional experience outside of the walk context. Participants also completed pre- and postintervention measures of anxiety, depression, and life satisfaction. Compared with participants who took control walks, those who took awe walks experienced greater awe during their walks and exhibited an increasingly "small self" in their photographs over time. They reported greater joy and prosocial positive emotions during their walks and displayed increasing smile intensity over the study. Outside of the walk context, participants who took awe walks reported greater increases in daily prosocial positive emotions and greater decreases in daily distress over time. Postintervention anxiety, depression, and life satisfaction did not change from baseline in either group. These results suggest cultivating awe enhances positive emotions that foster social connection and diminishes negative emotions that hasten decline. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Anodal Transcranial Direct Current Stimulation to the Left Rostrolateral Prefrontal Cortex Selectively Improves Source Memory Retrieval.

Functional neuroimaging studies have consistently implicated the left rostrolateral prefrontal cortex (RLPFC) as playing a crucial role in the cognitive operations supporting episodic memory and analogical reasoning. However, the degree to which the left RLPFC causally contributes to these processes remains underspecified. We aimed to assess whether targeted anodal stimulation-thought to boost cortical excitability-of the left RLPFC with transcranial direct current stimulation (tDCS) would lead to augmentation of episodic memory retrieval and analogical reasoning task performance in comparison to cathodal stimulation or sham stimulation. Seventy-two healthy adult participants were evenly divided into three experimental groups. All participants performed a memory encoding task on Day 1, and then on Day 2, they performed continuously alternating tasks of episodic memory retrieval, analogical reasoning, and visuospatial perception across two consecutive 30-min experimental sessions. All groups received sham stimulation for the first experimental session, but the groups differed in the stimulation delivered to the left RLPFC during the second session (either sham, 1.5 mA anodal tDCS, or 1.5 mA cathodal tDCS). The experimental group that received anodal tDCS to the left RLPFC during the second session demonstrated significantly improved episodic memory source retrieval performance, relative to both their first session performance and relative to performance changes observed in the other two experimental groups. Performance on the analogical reasoning and visuospatial perception tasks did not exhibit reliable changes as a result of tDCS. As such, our results demonstrate that anodal tDCS to the left RLPFC leads to a selective and robust improvement in episodic source memory retrieval.

Differential Medial Temporal Lobe and Parietal Cortical Contributions to Real-world Autobiographical Episodic and Autobiographical Semantic Memory.

Autobiographical remembering can depend on two forms of memory: episodic (event) memory and autobiographical semantic memory (remembering personally relevant semantic knowledge, independent of recalling a specific experience). There is debate about the degree to which the neural signals that support episodic recollection relate to or build upon autobiographical semantic remembering. Pooling data from two fMRI studies of memory for real-world personal events, we investigated whether medial temporal lobe (MTL) and parietal subregions contribute to autobiographical episodic and semantic remembering. During scanning, participants made memory judgments about photograph sequences depicting past events from their life or from others' lives, and indicated whether memory was based on episodic or semantic knowledge. Results revealed several distinct functional patterns: activity in most MTL subregions was selectively associated with autobiographical episodic memory; the hippocampal tail, superior parietal lobule, and intraparietal sulcus were similarly engaged when memory was based on retrieval of an autobiographical episode or autobiographical semantic knowledge; and angular gyrus demonstrated a graded pattern, with activity declining from autobiographical recollection to autobiographical semantic remembering to correct rejections of novel events. Collectively, our data offer insights into MTL and parietal cortex functional organization, and elucidate circuitry that supports different forms of real-world autobiographical memory.

Multi-voxel pattern classification differentiates personally experienced event memories from secondhand event knowledge.

Studies of autobiographical memory retrieval often use photographs to probe participants' memories for past events. Recent neuroimaging work has shown that viewing photographs depicting events from one's own life evokes a characteristic pattern of brain activity across a network of frontal, parietal, and medial temporal lobe regions that can be readily distinguished from brain activity associated with viewing photographs from someone else's life (Rissman, Chow, Reggente, and Wagner, 2016). However, it is unclear whether the neural signatures associated with remembering a personally experienced event are distinct from those associated with recognizing previously encountered photographs of an event. The present experiment used a novel functional magnetic resonance imaging (fMRI) paradigm to investigate putative differences in brain activity patterns associated with these distinct expressions of memory retrieval. Eighteen participants wore necklace-mounted digital cameras to capture events from their everyday lives over the course of three weeks. One week later, participants underwent fMRI scanning, where on each trial they viewed a sequence of photographs depicting either an event from their own life or from another participant's life and judged their memory for this event. Importantly, half of the trials featured photographic sequences that had been shown to participants during a laboratory session administered the previous day. Multi-voxel pattern analyses assessed the sensitivity of two brain networks of interest-as identified by a meta-analysis of prior autobiographical and laboratory-based memory retrieval studies-to the original source of the photographs (own life or other's life) and their experiential history as stimuli (previewed or non-previewed). The classification analyses revealed a striking dissociation: activity patterns within the autobiographical memory network were significantly more diagnostic than those within the laboratory-based network as to whether photographs depicted one's own personal experience (regardless of whether they had been previously seen), whereas activity patterns within the laboratory-based memory network were significantly more diagnostic than those within the autobiographical memory network as to whether photographs had been previewed (regardless of whether they were from the participant's own life). These results, also apparent in whole-brain searchlight classifications, provide evidence for dissociable patterns of activation across two putative memory networks as a function of whether real-world photographs trigger the retrieval of firsthand experiences or secondhand event knowledge.

Neurocognitive mechanisms of real-world autobiographical memory retrieval: insights from studies using wearable camera technology.

In recent years, investigation into the cognitive and neural mechanisms of autobiographical memory has been aided by the use of experimental paradigms incorporating wearable camera technology. By effortlessly capturing first-person images of one's life events, these cameras provide a rich set of naturalistic stimuli that can later be used to trigger the recall of specific episodes. Here, we chronicle the development and progression of such studies in behavioral and neuroimaging examinations of both clinical and nonclinical adult populations. Experiments examining the effects of periodic review of first-person images of life events have documented enhancements of autobiographical memory retrieval. Such benefits are most pronounced in patients with memory impairments, but there is mounting evidence that cognitively healthy individuals may benefit as well. Findings from functional magnetic resonance imaging experiments using wearable camera stimuli as retrieval probes have produced results that, although largely consistent with the broader episodic memory literature, have significantly extended prior findings concerning the underlying mnemonic processes and the neural representation of autobiographical information. Taken together, wearable camera technology provides a unique opportunity for studies of autobiographical memory to more closely approximate real-world conditions, thus offering enhanced ecological validity and opening up new avenues for experimental work.

Cognitive control, attention, and the other race effect in memory.

People are better at remembering faces from their own race than other races-a phenomenon with significant societal implications. This Other Race Effect (ORE) in memory could arise from different attentional allocation to, and cognitive control over, same- and other-race faces during encoding. Deeper or more differentiated processing of same-race faces could yield more robust representations of same- vs. other-race faces that could support better recognition memory. Conversely, to the extent that other-race faces may be characterized by lower perceptual expertise, attention and cognitive control may be more important for successful encoding of robust, distinct representations of these stimuli. We tested a mechanistic model in which successful encoding of same- and other-race faces, indexed by subsequent memory performance, is differentially predicted by (a) engagement of frontoparietal networks subserving top-down attention and cognitive control, and (b) interactions between frontoparietal networks and fusiform cortex face processing. European American (EA) and African American (AA) participants underwent fMRI while intentionally encoding EA and AA faces, and ~24 hrs later performed an "old/new" recognition memory task. Univariate analyses revealed greater engagement of frontoparietal top-down attention and cognitive control networks during encoding for same- vs. other-race faces, stemming particularly from a failure to engage the cognitive control network during processing of other-race faces that were subsequently forgotten. Psychophysiological interaction (PPI) analyses further revealed that OREs were characterized by greater functional interaction between medial intraparietal sulcus, a component of the top-down attention network, and fusiform cortex during same- than other-race face encoding. Together, these results suggest that group-based face memory biases at least partially stem from differential allocation of cognitive control and top-down attention during encoding, such that same-race memory benefits from elevated top-down attentional engagement with face processing regions; conversely, reduced recruitment of cognitive control circuitry appears more predictive of memory failure when encoding out-group faces.

Decoding fMRI Signatures of Real-world Autobiographical Memory Retrieval.

Extant neuroimaging data implicate frontoparietal and medial-temporal lobe regions in episodic retrieval, and the specific pattern of activity within and across these regions is diagnostic of an individual's subjective mnemonic experience. For example, in laboratory-based paradigms, memories for recently encoded faces can be accurately decoded from single-trial fMRI patterns [Uncapher, M. R., Boyd-Meredith, J. T., Chow, T. E., Rissman, J., & Wagner, A. D. Goal-directed modulation of neural memory patterns: Implications for fMRI-based memory detection. Journal of Neuroscience, 35, 8531-8545, 2015; Rissman, J., Greely, H. T., & Wagner, A. D. Detecting individual memories through the neural decoding of memory states and past experience. Proceedings of the National Academy of Sciences, U.S.A., 107, 9849-9854, 2010]. Here, we investigated the neural patterns underlying memory for real-world autobiographical events, probed at 1- to 3-week retention intervals as well as whether distinct patterns are associated with different subjective memory states. For 3 weeks, participants (n = 16) wore digital cameras that captured photographs of their daily activities. One week later, they were scanned while making memory judgments about sequences of photos depicting events from their own lives or events captured by the cameras of others. Whole-brain multivoxel pattern analysis achieved near-perfect accuracy at distinguishing correctly recognized events from correctly rejected novel events, and decoding performance did not significantly vary with retention interval. Multivoxel pattern classifiers also differentiated recollection from familiarity and reliably decoded the subjective strength of recollection, of familiarity, or of novelty. Classification-based brain maps revealed dissociable neural signatures of these mnemonic states, with activity patterns in hippocampus, medial PFC, and ventral parietal cortex being particularly diagnostic of recollection. Finally, a classifier trained on previously acquired laboratory-based memory data achieved reliable decoding of autobiographical memory states. We discuss the implications for neuroscientific accounts of episodic retrieval and comment on the potential forensic use of fMRI for probing experiential knowledge.

Goal-Directed Modulation of Neural Memory Patterns: Implications for fMRI-Based Memory Detection.

Remembering a past event elicits distributed neural patterns that can be distinguished from patterns elicited when encountering novel information. These differing patterns can be decoded with relatively high diagnostic accuracy for individual memories using multivoxel pattern analysis (MVPA) of fMRI data. Brain-based memory detection--if valid and reliable--would have clear utility beyond the domain of cognitive neuroscience, in the realm of law, marketing, and beyond. However, a significant boundary condition on memory decoding validity may be the deployment of "countermeasures": strategies used to mask memory signals. Here we tested the vulnerability of fMRI-based memory detection to countermeasures, using a paradigm that bears resemblance to eyewitness identification. Participants were scanned while performing two tasks on previously studied and novel faces: (1) a standard recognition memory task; and (2) a task wherein they attempted to conceal their true memory state. Univariate analyses revealed that participants were able to strategically modulate neural responses, averaged across trials, in regions implicated in memory retrieval, including the hippocampus and angular gyrus. Moreover, regions associated with goal-directed shifts of attention and thought substitution supported memory concealment, and those associated with memory generation supported novelty concealment. Critically, whereas MVPA enabled reliable classification of memory states when participants reported memory truthfully, the ability to decode memory on individual trials was compromised, even reversing, during attempts to conceal memory. Together, these findings demonstrate that strategic goal states can be deployed to mask memory-related neural patterns and foil memory decoding technology, placing a significant boundary condition on their real-world utility.