Toward Development of a Novel Proprioceptive Trail-Making Test: Comparing Healthy Dancers and Non-Dancers.

There is a pressing need for ecologically valid versions of traditional neuropsychological tests indexing executive function (EF), such as the Trail-Making Task (TMT), that incorporate movement and bodily awareness in healthy participants with varying abilities. We designed a proprioceptive version of the TMT (pTMT) that involved coordinated gross motor movement and proprioceptive awareness to investigate whether this measure of visual attention, task switching, and working memory positively correlated with a computerized version of the TMT (the dTMT). We aimed to establish the initial validity of our proprioceptive TMT (pTMT) by comparing performances on the dTMT and pTMT among a cohort of 36 healthy participants (18 dancers, 18 non-dancers; M age = 22, SD = 5.27; 64% female) anticipating that dancers would express higher intrinsic bodily awareness than non-dancers. Results revealed a mild to moderate but statistically significant positive correlation between dTMT and pTMT completion times [part A: r (36) = .33, p = .04; part B: r (36) = .37, p = .03] and numbers of errors [part B: r (36) = .41, p = .01] across both participant groups. These data suggest partial measurement convergence between these two TMT versions. Relative to non-dancers, dancers exhibited a higher level of performance (likely due to their better proprioceptive ability) through their faster completion times on dTMT-B [t (34) = 3.81, p = .006, d = 1.27] and pTMT-B [t (34) = 2.97, p = .005, d = .99], and their fewer errors on dTMT-B [t (34) = 2.93, p = .006, d = 1.0]. By identifying cognitive differences between these different groups of healthy individuals, our data contribute to both a theoretical understanding and the initial development of gross motor movement-based cognitive assessments, providing a path toward the further refinement of an ecologically valid full-body TMT.

Increased pupil dilation during tip-of-the-tongue states.

Tip-of-the-tongue states (TOTs) are feelings of impending word retrieval success during a current failure to retrieve a target word. Though much is known and understood about TOT states from decades of research, research on potential psychophysiological correlates of the TOT state is still in its infancy, and existing studies point toward the involvement of neural processes that are associated with enhanced attention, motivation, and information-seeking. In the present study, we demonstrate that, during instances of target retrieval failure, TOT states are associated with greater pupillary dilation (i.e., autonomic arousal) in 91% of our sample. This is the first study to demonstrate a pupillometric correlate of the TOT experience, and this finding provides an important step toward understanding emotional attributes associated with TOT states. Mean pupil dilation also increased such that instances of target identification failure that were unaccompanied by TOT states < instances in which TOTs occurred < instances of target identification success. It is possible that TOTs reflect an intermediary state between complete target retrieval failure and full target retrieval.

Trauma, posttraumatic stress disorder severity, and positive memories.

Positive memories play an important role in the aetiology and maintenance of posttraumatic stress disorder (PTSD). However, most trauma research/clinical work has focused solely on the role of traumatic memories. Thus, we examined the relationship between count of retrieved positive memories and PTSD severity, factors associated with count of retrieved positive memories (i.e., rumination, negative/positive emotion dysregulation, fear of positive emotions), and the relationship between positive memory phenomenological domains and PTSD severity. The sample included 185 trauma-exposed participants recruited through Amazon's Mechanical Turk (Mage = 35.69 years; 63.80% female). Results of linear/hierarchical regressions showed that (1) PTSD severity did not predict count of (specific) positive memories; (2) greater positive emotion dysregulation predicted fewer retrieved positive memories controlling for PTSD severity; and (3) greater PTSD severity predicted more negative valence, less vividness, less coherence, less accessibility, less clear time perspective, fewer sensory details, and greater distancing ratings of the retrieved positive memory, controlling for sleep quantity/quality. Findings add to the literature by informing PTSD theoretical perspectives; enhancing an understanding of positive memories in PTSD/trauma treatments; and highlighting potential clinical targets (e.g., positive emotion regulation), when integrating a focus on positive memories into PTSD intervention.

Hemisphere-specific effects of prefrontal theta-burst stimulation on visual recognition memory accuracy and awareness.

BACKGROUND: The prefrontal cortex has been implicated in episodic memory and the awareness of memory. Few studies have probed the nature and necessity of its role via brain stimulation. There are uncertainties regarding whether the hemisphere of stimulation predicts effects on memory and whether effects of stimulation are format-specific, with most previous studies utilizing verbal/semantic stimuli. OBJECTIVE: Our primary objective was to determine if theta-burst transcranial magnetic stimulation (TBS) to prefrontal cortex modulates visual memory accuracy, visual memory awareness, or both, and whether these effects depend on brain hemisphere. METHODS: We administered TBS to 12 individuals in either left prefrontal, right prefrontal, or a sham location on three separate days. We then administered a visual associative-memory task incorporating global-level awareness judgments and feeling-of-knowing (FOK) judgments on test trials for which retrieval failed. RESULTS: Overall memory accuracy significantly improved after right hemisphere TBS compared to sham. Simultaneously, subjects were relatively underconfident after right TBS, suggesting minimal awareness of memory accuracy improvements. The correspondence between FOKs and later recognition accuracy suggested a pattern of disruption in prospective memory monitoring accuracy after left TBS. CONCLUSIONS: Our findings provide unique evidence for improved visual memory accuracy after right prefrontal TBS. These results also suggest right prefrontal lateralization for visual memory and left-hemisphere specialization for item-level prospective memory awareness judgments. Taken together, these results provided continued support for noninvasive stimulation to prefrontal cortex as a means of potentially improving memory and causally influencing prospective memory awareness.

Memory awareness disruptions in amnestic mild cognitive impairment: comparison of multiple awareness types for verbal and visuospatial material.

Successful memory is normally accompanied by explicit awareness of retrieval and confidence in the accuracy of the retrieval product. Prior findings suggest that these features of metamemory can be dissociated from retrieval accuracy in Amnestic Mild Cognitive Impairment (aMCI). However, the literature on this question contains variable and conflicting results, likely because of differences in experimental conditions. We sought to systematically evaluate memory awareness disruptions in aMCI using multiple measures and stimulus formats within the same individuals. Memory awareness was tested with global predictions and postdictions, judgments of learning, confidence level ratings, and modified feeling-of-knowing ratings in tasks of visuospatial and verbal memory. These tests were administered to 14 individuals with aMCI and 15 healthy, age-matched controls. Memory awareness accuracy was calculated as the correspondence between subjective judgments and memory performance.Individuals with aMCI demonstrated impaired global and trial-level retrospective task awareness for visuospatial and verbal stimuli. Additionally, modified feeling-of-knowing awareness was impaired selectively for verbal stimuli. Statistical effect sizes for global awareness impairments were comparable to impairments in several objective neuropsychological memory assessments.Memory awareness (metamemory) disruptions in aMCI were most evident for a subset of subjective judgment types and task input modalities. These findings advance understanding of the nature of memory impairments in aMCI and support the utility of incorporating memory awareness testing to better characterize memory integrity in older adults.

Hippocampal functional connectivity is related to self-reported cognitive concerns in breast cancer patients undergoing adjuvant therapy.

Nearly three out of four survivors experience Cancer-Related Cognitive Impairment (CRCI) for months or years following treatment. Both clinical and animal studies point to the hippocampus as a likely brain region affected in CRCI, however no previous study has investigated the functional connectivity of the hippocampus in CRCI. We compared hippocampal connectivity in cancer survivors and healthy controls and tested the relationship between functional connectivity differences and measures of objective and subjective cognition. Exploratory analysis of inflammatory markers was conducted in a small subset of participants as well. FMRI data were acquired during a memory task from 16 breast cancer survivors and 17 controls. The NIH Toolbox was used to assess cognitive performance and Neuro-QoL was used to measure self-reported cognitive concerns. Whole-brain group-level comparisons identified clusters with different connectivity to the hippocampus in survivors versus controls during task. Average connectivity was extracted from clusters of significant difference between the groups and correlated with cognitive performance and subjective report. Survivors performed worse on a test of episodic memory and reported greater cognitive concern than controls. Exploratory analysis found higher IL6 in cancer survivors compared to controls. Cancer survivors demonstrated higher connectivity of hippocampus with left cuneus, left lingual, left precuneus, and right middle prefrontal gyrus compared with controls. In survivors, higher task-related hippocampal-cortical connectivity was related to worse subjective measures of cognitive concern. Of the four significant clusters, higher connectivity of the precuneus with hippocampus was significantly associated with worse cognitive concern in survivors. The observed greater hippocampal-cortical connectivity in survivors compared to controls is the first reported fMRI biomarker of subjective concern, and may represent a compensatory response to cancer and its treatments. This compensation could explain, in part, the subjective feelings of cognitive impairment that were reported by survivors.

Subtle hippocampal deformities in breast cancer survivors with reduced episodic memory and self-reported cognitive concerns.

Cancer survivors have lingering cognitive problems, however the anatomical basis for these problems has yet to be fully elucidated. Clinical studies as well as animal models of chemotherapy have pinpointed cell and volume loss to the hippocampus, however, few studies have performed shape analysis of the hippocampus on cancer survivors. This study used high-dimensional deformation mapping analysis to test whether localized hippocampal deformation differs in breast cancer survivors who received adjuvant chemotherapy coupled with hormone blockade therapy, and if deformation was related to subjective self-reported concerns and cognitive performance. 3 T MRI images were acquired from 16 pre-menopausal breast cancer survivors and 18 healthy controls without a history of cancer. Breast cancer survivors had undergone chemotherapy within the eighteen months prior to the study, and were receiving estrogen-blockade therapy at the time of the study. Automated high-dimensional deformation mapping was used to compare localized hippocampal deformation differences between groups. Self-reported subjective concerns were assessed using Neuro-QOL Cognitive Function assessment, whereas cognitive performance was evaluated using the NIH Toolbox Cognition Battery. Relative to healthy controls, cancer survivors showed significantly more inward hippocampal deformation, worse self-reported cognitive functioning, and inferior episodic memory test score. This study is the first of its kind to examine the relationship between hippocampal deformity and cognitive impairment in cancer survivors.

Reduced prefrontal activation during working and long-term memory tasks and impaired patient-reported cognition among cancer survivors postchemotherapy compared with healthy controls.

BACKGROUND: Patients who receive adjuvant chemotherapy have reported cognitive impairments that may last for years after the completion of treatment. Working memory-related and long-term memory-related changes in this population are not well understood. The objective of this study was to demonstrate that cancer-related cognitive impairments are associated with the under recruitment of brain regions involved in working and recognition memory compared with controls. METHODS: Oncology patients (n = 15) who were receiving adjuvant chemotherapy and had evidence of cognitive impairment according to neuropsychological testing and self-report and a group of age-matched, education group-matched, cognitively normal control participants (n = 14) underwent functional magnetic resonance imaging. During functional magnetic resonance imaging, participants performed a nonverbal n-back working memory task and a visual recognition task. RESULTS: On the working memory task, when 1-back and 2-back data were averaged and contrasted with 0-back data, significantly reduced activation was observed in the right dorsolateral prefrontal cortex for oncology patients versus controls. On the recognition task, oncology patients displayed decreased activity of the left-middle hippocampus compared with controls. Neuroimaging results were not associated with patient-reported cognition. CONCLUSIONS: Decreased recruitment of brain regions associated with the encoding of working memory and recognition memory was observed in the oncology patients compared with the control group. These results suggest that there is a reduction in neural functioning postchemotherapy and corroborate patient-reported cognitive difficulties after cancer treatment, although a direct association was not observed. Cancer 2016;122:258-268. © 2015 American Cancer Society.

Recognition during recall failure: Semantic feature matching as a mechanism for recognition of semantic cues when recall fails.

Research suggests that a feature-matching process underlies cue familiarity-detection when cued recall with graphemic cues fails. When a test cue (e.g., potchbork) overlaps in graphemic features with multiple unrecalled studied items (e.g., patchwork, pitchfork, pocketbook, pullcork), higher cue familiarity ratings are given during recall failure of all of the targets than when the cue overlaps in graphemic features with only one studied target and that target fails to be recalled (e.g., patchwork). The present study used semantic feature production norms (McRae et al., Behavior Research Methods, Instruments, & Computers, 37, 547-559, 2005) to examine whether the same holds true when the cues are semantic in nature (e.g., jaguar is used to cue cheetah). Indeed, test cues (e.g., cedar) that overlapped in semantic features (e.g., a_tree, has_bark, etc.) with four unretrieved studied items (e.g., birch, oak, pine, willow) received higher cue familiarity ratings during recall failure than test cues that overlapped in semantic features with only two (also unretrieved) studied items (e.g., birch, oak), which in turn received higher familiarity ratings during recall failure than cues that did not overlap in semantic features with any studied items. These findings suggest that the feature-matching theory of recognition during recall failure can accommodate recognition of semantic cues during recall failure, providing a potential mechanism for conceptually-based forms of cue recognition during target retrieval failure. They also provide converging evidence for the existence of the semantic features envisaged in feature-based models of semantic knowledge representation and for those more concretely specified by the production norms of McRae et al. (Behavior Research Methods, Instruments, & Computers, 37, 547-559, 2005).

Associative Recognition Memory Awareness Improved by Theta-Burst Stimulation of Frontopolar Cortex.

Neuroimaging and lesion studies have implicated specific prefrontal cortex locations in subjective memory awareness. Based on this evidence, a rostrocaudal organization has been proposed whereby increasingly anterior prefrontal regions are increasingly involved in memory awareness. We used theta-burst transcranial magnetic stimulation (TBS) to temporarily modulate dorsolateral versus frontopolar prefrontal cortex to test for distinct causal roles in memory awareness. In three sessions, participants received TBS bilaterally to frontopolar cortex, dorsolateral prefrontal cortex, or a control location prior to performing an associative-recognition task involving judgments of memory awareness. Objective memory performance (i.e., accuracy) did not differ based on stimulation location. In contrast, frontopolar stimulation significantly influenced several measures of memory awareness. During study, judgments of learning were more accurate such that lower ratings were given to items that were subsequently forgotten selectively following frontopolar TBS. Confidence ratings during test were also higher for correct trials following frontopolar TBS. Finally, trial-by-trial correspondence between overt performance and subjective awareness during study demonstrated a linear increase across control, dorsolateral, and frontopolar TBS locations, supporting a rostrocaudal hierarchy of prefrontal contributions to memory awareness. These findings indicate that frontopolar cortex contributes causally to memory awareness, which was improved selectively by anatomically targeted TBS.

Hippocampal contribution to implicit configuration memory expressed via eye movements during scene exploration.

Although hippocampus unequivocally supports explicit/declarative memory, fewer findings have demonstrated its role in implicit expressions of memory. We tested for hippocampal contributions to an implicit expression of configural/relational memory for complex scenes using eye-movement tracking during functional magnetic resonance imaging (fMRI) scanning. Participants studied scenes and were later tested using scenes that resembled study scenes in their overall feature configuration but comprised different elements. These configurally similar scenes were used to limit explicit memory, and were intermixed with new scenes that did not resemble studied scenes. Scene configuration memory was expressed through eye movements reflecting exploration overlap (EO), which is the viewing of the same scene locations at both study and test. EO reliably discriminated similar study-test scene pairs from study-new scene pairs, was reliably greater for similarity-based recognition hits than for misses, and correlated with hippocampal fMRI activity. In contrast, subjects could not reliably discriminate similar from new scenes by overt judgments, although ratings of familiarity were slightly higher for similar than new scenes. Hippocampal fMRI correlates of this weak explicit memory were distinct from EO-related activity. These findings collectively suggest that EO was an implicit expression of scene configuration memory associated with hippocampal activity. Visual exploration can therefore reflect implicit hippocampal-related memory processing that can be observed in eye-movement behavior during naturalistic scene viewing.

Targeted enhancement of cortical-hippocampal brain networks and associative memory.

The influential notion that the hippocampus supports associative memory by interacting with functionally distinct and distributed brain regions has not been directly tested in humans. We therefore used targeted noninvasive electromagnetic stimulation to modulate human cortical-hippocampal networks and tested effects of this manipulation on memory. Multiple-session stimulation increased functional connectivity among distributed cortical-hippocampal network regions and concomitantly improved associative memory performance. These alterations involved localized long-term plasticity because increases were highly selective to the targeted brain regions, and enhancements of connectivity and associative memory persisted for ~24 hours after stimulation. Targeted cortical-hippocampal networks can thus be enhanced noninvasively, demonstrating their role in associative memory.

Connections between mechanisms for anosognosia and implicit memory.

Mograbi and Morris review work highlighting an interesting phenomenon whereby individuals are explicitly anosognosic for their deficits despite intact expression of implicit awareness. Parallels exist between this phenomenon and recent cognitive neuroscience findings demonstrating intact memory test performance despite unawareness of performance. We discuss these parallels with regard to the proposed CAM model. Given that it is possible to investigate the neurological underpinnings of explicit and implicit processing in memory tasks, methods from cognitive neuroscience may offer substantial insight into implicit awareness in anosognosia in various forms of dementia as well as in addition to advancing theoretical understanding of anosognosia broadly.

Intuitively detecting what is hidden within a visual mask: familiar-novel discrimination and threat detection for unidentified stimuli.

Recognition without identification is the finding that, among recognition test items that go unidentified (as when a word is unidentified from a fragment), participants can discriminate those that were studied from those that were unstudied. In the present study, we extended this phenomenon to the more life-like situation of discriminating known from novel stimuli. Pictures of famous and nonfamous faces (Exp. 1), famous and nonfamous scenes (Exp. 2), and threatening and nonthreatening images (Exp. 3) were filtered in order to impede identification. As in list-learning recognition-without-identification paradigms, participants attempted to identify each image (e.g., whose face it was, what scene it was, or what was in the picture) and rated how familiar the image seemed on a scale of 0 (very unfamiliar) to 10 (very familiar). Among the unidentified stimuli, higher familiarity ratings were given to famous than to nonfamous faces (Exp. 1) and scenes (Exp. 2), and to threatening than to nonthreatening living/animate (but not to nonliving/nonanimate) images (Exp. 3). These findings suggest that even when a stimulus is too occluded to allow for conscious identification, enough information can be processed to allow a sense of familiarity or novelty with it, which appears also to be related to the sense of whether or not a living creature is a threat. That the sense of familiarity for unidentified stimuli may be related to threat detection for living or animate things suggests that it may be an adaptive aspect of human memory.

Recall versus familiarity when recall fails for words and scenes: the differential roles of the hippocampus, perirhinal cortex, and category-specific cortical regions.

This fMRI study examined recall and familiarity for words and scenes using the novel recognition without cued recall (RWCR) paradigm. Subjects performed a cued recall task in which half of the test cues resembled studied items (and thus were familiar) and half did not. Subjects also judged the familiarity of the cue itself. RWCR is the finding that, among cues for which recall fails, subjects generally rate cues that resemble studied items as more familiar than cues that do not. For words, left and right hippocampal activity increased when recall succeeded relative to when it failed. When recall failed, right hippocampal activity was decreased for familiar relative to unfamiliar cues. In contrast, right Prc activity increased for familiar cues for which recall failed relative to both familiar cues for which recall succeeded and to unfamiliar cues. For scenes, left hippocampal activity increased when recall succeeded relative to when it failed but did not differentiate familiar from unfamiliar cues when recall failed. In contrast, right Prc activity increased for familiar relative to unfamiliar cues when recall failed. Category-specific cortical regions showed effects unique to their respective stimulus types: The visual word form area (VWFA) showed effects for recall vs. familiarity specific to words, and the parahippocampal place area (PPA) showed effects for recall vs. familiarity specific to scenes. In both cases, these effects were such that there was increased activity occurring during recall relative to when recall failed, and decreased activity occurring for familiar relative to unfamiliar cues when recall failed.

Familiarity from the configuration of objects in 3-dimensional space and its relation to déjà vu: a virtual reality investigation.

Déjà vu is the striking sense that the present situation feels familiar, alongside the realization that it has to be new. According to the Gestalt familiarity hypothesis, déjà vu results when the configuration of elements within a scene maps onto a configuration previously seen, but the previous scene fails to come to mind. We examined this using virtual reality (VR) technology. When a new immersive VR scene resembled a previously-viewed scene in its configuration but people failed to recall the previously-viewed scene, familiarity ratings and reports of déjà vu were indeed higher than for completely novel scenes. People also exhibited the contrasting sense of newness and of familiarity that is characteristic of déjà vu. Familiarity ratings and déjà vu reports among scenes recognized as new increased with increasing feature-match of a scene to one stored in memory, suggesting that feature-matching can produce familiarity and déjà vu when recall fails.

When word identification fails: ERP correlates of recognition without identification and of word identification failure.

Recognition without identification (RWI) refers to people's ability to discriminate studied from unstudied items when the items themselves fail to be identified, as when people fail to identify words from fragments. We sought to identify the ERP correlates of word fragment RWI in an effort to better understand its underlying mechanisms; in so doing, we also examined the ERP correlates of word identification failure vs. success. We found the ERP correlate of the RWI effect to be the N300; greater negativity was shown for unidentified fragments of studied words than for unidentified fragments of unstudied words between 300-325 ms post test fragment onset. We further separated the ERPs according to whether subjects showed the behavioral RWI effect or not; the N300 effect emerged only among those subjects who showed the behavioral effect, suggesting that the N300 is related to the behavioral effect itself. With regard to the ERP correlates of word identification failure vs. success, we found very early indicators of later word identification success vs. failure (starting at 125 ms) that were independent of priming. These early effects may be preconscious markers of downstream word identification success vs. failure. We also found a later persistent negativity associated with successfully identified words that we propose to be associated with executive function and possibly the successful suppression of irrelevant words that might initially come to mind when attempting to complete a unique word fragment; word fragment identification failure may sometimes be due to a failure to suppress irrelevant or incorrect words.

Can deja vu result from similarity to a prior experience? Support for the similarity hypothesis of deja vu.

The strange feeling of having been somewhere or done something before--even though there is evidence to the contrary--is called déjà vu. Although déjà vu is beginning to receive attention among scientists (Brown, 2003, 2004), few studies have empirically investigated the phenomenon. We investigated the hypothesis that déjà vu is related to feelings of familiarity and that it can result from similarity between a novel scene and that of a scene experienced in one's past. We used a variation of the recognition-without-recall method of studying familiarity (Cleary, 2004) to examine instances in which participants failed to recall a studied scene in response to a configurally similar novel test scene. In such instances, resemblance to a previously viewed scene increased both feelings of familiarity and of déjà vu. Furthermore, in the absence of recall, resemblance of a novel scene to a previously viewed scene increased the probability of a reported déjà vu state for the novel scene, and feelings of familiarity with a novel scene were directly related to feelings of being in a déjà vu state.