Anthony J. Ryals

Targeted enhancement of cortical-hippocampal brain networks and associative memory

Brain stimulation to improve human memory The hippocampus is a crucial brain area for certain types of memory. Working with humans, Wang et al. found that a specific type of non-invasive brain stimulation improved memory tests and enhanced information flow between the hippocampus and a number of other brain regions. This increased connectivity was highly specific for the individual target areas selected for each participant. Science, this issue p. 1054 Noninvasive stimulation of the brain can improve memories for episodes by boosting the connectivity between cortical regions. 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.

Can Déjà Vu Result from Similarity to a Prior Experience? Support for the Similarity Hypothesis of Déjà 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.

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.

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.

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

Recognition without identification (RWI) refers to peoples 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.

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

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.

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.

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.

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.