Assistant Professor, Department of Psychology
Ph.D. University of Texas at Austin
M.A. Charles University in Prague
Research Interests: Cognitive-Neuroscience, Memory
Overview: Memory allows us to use past experiences to navigate novel situations and inform future decisions. Because every event is unique, we need to use memory flexibly, drawing upon multiple relevant experiences to anticipate future judgments. Brain and Memory Lab studies how memories are formed and how they are linked to each other to create internal representations of the world that can guide our behavior. We investigate how different memory systems are implemented in the brain, how they represent information, and how they interact. In the quest for discovery, we rely on computer-based experiments, cognitive models of behavior, and advanced functional MRI methods.
My research focuses on how we build complex knowledge representations—such as schemas, cognitive maps or concepts—from simple learning experiences. Stacking memories as building blocks, we form knowledge that transcend direct experience, allowing us to use the memory for the past to guide behavior in the future. I am especially interested how the hippocampus—a brain structure critical for memory for individual events in our lives—interacts with the prefrontal cortex and other memory systems to support the flexible use of experience. My primary research tools include computer-based experiments, formal models of behavior, and advanced functional MRI methods.
Abstract Representation of Prospective Reward in the Hippocampus.
J Neurosci. 2018 Nov 21;38(47):10093-10101
Authors: Zeithamova D, Gelman BD, Frank L, Preston AR
Motivation enhances memory by increasing hippocampal engagement during encoding. However, whether such increased hippocampal activation reflects encoding of the value of highly rewarding events per se is less understood. Here, using a monetary incentive encoding task with a novel manipulation, we tested in humans whether the hippocampus represents abstract reward value, independent of perceptual content. During functional MRI scanning, men and women studied object pairs, each preceded by a monetary reward cue indicating the amount of money they would receive if they successfully remembered the object pair at test. Reward cues varied on both the level of reward (penny, dime, and dollar) and visual form (picture or word) across trials to dissociate hippocampal responses to reward value from those reflecting the perceptual properties of the cues. Behaviorally, participants remembered pairs associated with the high reward (dollar) more often than pairs associated with lower rewards. Neural pattern-similarity analysis revealed that hippocampal and parahippocampal cortex activation patterns discriminated between cues of different value regardless of their visual form, and that hippocampal discrimination of value was most pronounced in participants who showed the greatest behavioral sensitivity to reward. Strikingly, hippocampal patterns were most distinct for reward cues that differed in value but had similar visual appearance, consistent with theoretical proposals of hippocampal-pattern differentiation of competing representations. Our data illustrate how contextual representations within the hippocampus go beyond space and time to include information about the motivational salience of events, with hippocampal reward coding tracking the motivational impact on later memory.SIGNIFICANCE STATEMENT Motivation, such as the promise of future rewards, enhances hippocampal engagement during encoding and promotes successful retention of events associated with valuable rewards. However, whether the hippocampus explicitly encodes reward value, dissociable from sensory information, is unclear. Here, we show that the hippocampus forms abstract representation of valuable rewards, encoding conceptual rather than perceptual information about the motivational context of individual events. Reward representation within the hippocampus is associated with preferential retention of high-value events in memory. Furthermore, we show that hippocampal-pattern differentiation serves to emphasize differences between visually similar events with distinct motivational salience. Collectively, these findings indicate that hippocampal contextual representations enable individuals to distinguish the motivational value of events, leading to prioritized encoding of significant memories.
PMID: 30282732 [PubMed - in process]
Ventromedial Prefrontal Cortex Is Necessary for Normal Associative Inference and Memory Integration.
J Neurosci. 2018 Apr 11;38(15):3767-3775
Authors: Spalding KN, Schlichting ML, Zeithamova D, Preston AR, Tranel D, Duff MC, Warren DE
The ability to flexibly combine existing knowledge in response to novel circumstances is highly adaptive. However, the neural correlates of flexible associative inference are not well characterized. Laboratory tests of associative inference have measured memory for overlapping pairs of studied items (e.g., AB, BC) and for nonstudied pairs with common associates (i.e., AC). Findings from functional neuroimaging and neuropsychology suggest the ventromedial prefrontal cortex (vmPFC) may be necessary for associative inference. Here, we used a neuropsychological approach to test the necessity of vmPFC for successful memory-guided associative inference in humans using an overlapping pairs associative memory task. We predicted that individuals with focal vmPFC damage (n = 5; 3F, 2M) would show impaired inferential memory but intact non-inferential memory. Performance was compared with normal comparison participants (n = 10; 6F, 4M). Participants studied pairs of visually presented objects including overlapping pairs (AB, BC) and nonoverlapping pairs (XY). Participants later completed a three-alternative forced-choice recognition task for studied pairs (AB, BC, XY) and inference pairs (AC). As predicted, the vmPFC group had intact memory for studied pairs but significantly impaired memory for inferential pairs. These results are consistent with the perspective that the vmPFC is necessary for memory-guided associative inference, indicating that the vmPFC is critical for adaptive abilities that require application of existing knowledge to novel circumstances. Additionally, vmPFC damage was associated with unexpectedly reduced memory for AB pairs post-inference, which could potentially reflect retroactive interference. Together, these results reinforce an emerging understanding of a role for the vmPFC in brain networks supporting associative memory processes.SIGNIFICANCE STATEMENT We live in a constantly changing environment, so the ability to adapt our knowledge to support understanding of new circumstances is essential. One important adaptive ability is associative inference which allows us to extract shared features from distinct experiences and relate them. For example, if we see a woman holding a baby, and later see a man holding the same baby, then we might infer that the two adults are a couple. Despite the importance of associative inference, the brain systems necessary for this ability are not known. Here, we report that damage to human ventromedial prefrontal cortex (vmPFC) disproportionately impairs associative inference. Our findings show the necessity of the vmPFC for normal associative inference and memory integration.
PMID: 29555854 [PubMed - in process]
Decreased Prefrontal Activation during Matrix Reasoning in Predementia Progranulin Mutation Carriers.
J Alzheimers Dis. 2018;62(2):583-589
Authors: Alexander C, Zeithamova D, Hsiung GR, Mackenzie IR, Jacova C
We tested the potential of task-based functional neuroimaging as a biomarker of emerging prefrontal brain changes in progranulin (GRN) mutations carriers. Five GRN mutation carriers free of frontotemporal dementia (FTD) and 11 non-carriers from families with FTD-GRN underwent functional MRI while solving matrix-reasoning problems. Mutation carriers displayed slower responses for more difficult problems and lower lateral prefrontal activation across all problems. Overall task-evoked posterior ventrolateral prefrontal activation predicted mutation status with 100% sensitivity and 91% specificity. Volumetric differences did not account for activation differences. Prefrontal activation may have utility as a biomarker in GRN mutation.
PMID: 29480174 [PubMed - indexed for MEDLINE]
Choosing to regulate: does choice enhance craving regulation?
Soc Cogn Affect Neurosci. 2018 03 01;13(3):300-309
Authors: Cosme D, Mobasser A, Zeithamova D, Berkman ET, Pfeifer JH
Goal-directed behavior and lifelong well-being often depend on the ability to control appetitive motivations, such as cravings. Cognitive reappraisal is an effective way to modulate emotional states, including cravings, but is often studied under explicit instruction to regulate. Despite the strong prediction from Self-Determination Theory that choice should enhance task engagement and regulation success, little is known empirically about whether and how regulation is different when participants choose (vs are told) to exert control. To investigate how choice affects neural activity and regulation success, participants reappraised their responses to images of personally-craved foods while undergoing functional neuroimaging. Participants were either instructed to view or reappraise ('no-choice') or chose freely to view or reappraise ('yes-choice'). Choice increased activity in the frontoparietal control network. We expected this activity would be associated with increased task engagement, resulting in better regulation success. However, contrary to this prediction, choice slightly reduced regulation success. Follow-up multivariate functional neuroimaging analyses indicated that choice likely disrupted allocation of limited cognitive resources during reappraisal. While unexpected, these results highlight the importance of studying upstream processes such as regulation choice, as they may affect the ability to regulate cravings and other emotional states.
PMID: 29462475 [PubMed - indexed for MEDLINE]
Abstract memory representations in the ventromedial prefrontal cortex and hippocampus support concept generalization.
J Neurosci. 2018 Feb 07;:
Authors: Bowman CR, Zeithamova D
Memory function involves both the ability to remember details of individual experiences and the ability to link information across events to create new knowledge. Prior research has identified the ventromedial prefrontal cortex (VMPFC) and the hippocampus as important for integrating across events in service of generalization in episodic memory. The degree to which these memory integration mechanisms contribute to other forms of generalization, such as concept learning, is unclear. The present study used a concept-learning task in humans (both sexes) coupled with model-based fMRI to test whether VMPFC and hippocampus contribute to concept generalization, and whether they do so by maintaining specific category exemplars or abstract category representations. Two formal categorization models were fit to individual subject data: a prototype model that posits abstract category representations and an exemplar model that posits category representations based on individual category members. Latent variables from each of these models were entered into neuroimaging analyses to determine whether VMPFC and the hippocampus track prototype or exemplar information during concept generalization. Behavioral model fits indicated that almost three quarters of the subjects relied on prototype information when making judgments about new category members. Paralleling prototype dominance in behavior, correlates of the prototype model were identified in VMPFC and the anterior hippocampus with no significant exemplar correlates. These results indicate that the VMPFC and portions of the hippocampus play a broad role in memory generalization and that they do so by representing abstract information integrated from multiple events.SIGNIFICANCE STATEMENTWhether people represent concepts as a set of individual category members or by deriving generalized concept representations abstracted across exemplars has been debated. In episodic memory, generalized memory representations have been shown to arise through integration across events supported by the ventromedial prefrontal cortex (VMPFC) and hippocampus. The current study combined formal categorization models with fMRI data analysis to show that the VMPFC and anterior hippocampus represent abstract prototype information during concept generalization, contributing novel evidence of generalized concept representations in the brain. Results indicate that VMPFC-hippocampal memory integration mechanisms contribute to knowledge generalization across multiple cognitive domains, with the degree of abstraction of memory representations varying along the long axis of the hippocampus.
PMID: 29437891 [PubMed - as supplied by publisher]
Trial timing and pattern-information analyses of fMRI data.
Neuroimage. 2017 06;153:221-231
Authors: Zeithamova D, de Araujo Sanchez MA, Adke A
Pattern-information approaches to fMRI data analysis are becoming increasingly popular but few studies to date have investigated experimental design optimization for these analyses. Here, we tested several designs that varied in the number of trials and trial timing within fixed duration scans while participants encoded images of animals and tools. Trial timing conditions with fixed onset-to-onset timing ranged from slow 12-s trials with two repetitions of each item to quick 6-s trials with four repetitions per item. We also tested a jittered version of the quick design with 4-8s trials. We assessed the effect of trial timing on three dependent measures: category-level (animals vs. tools) decoding accuracy using a multivoxel pattern analysis, item-level (e.g., cat vs. dog vs. lion) information estimates using pattern similarity analysis, and memory effects comparing pattern similarity scores across repetitions of individual items subsequently remembered vs. forgotten. For single trial estimates, category decoding was equal across all trial timing conditions while item-level information and memory effects were better detected using slow trial timing. When modeling events on an item-by-item basis across all repetitions of a given item, a larger number of quick, regularly spaced trials provided an advantage over fewer slow trials for category decoding while item-level information was comparable across conditions. Jittered and non-jittered versions of the quick trial timing did not differ significantly in any analysis. These results will help inform experimental design choices in future studies planning to employ pattern-information analyses and demonstrate that design optimization guidelines developed for univariate analyses of a few conditions are not necessarily optimal for pattern-information analyses and condition-rich designs.
PMID: 28411155 [PubMed - indexed for MEDLINE]
Temporal Proximity Promotes Integration of Overlapping Events.
J Cogn Neurosci. 2017 Aug;29(8):1311-1323
Authors: Zeithamova D, Preston AR
Events with overlapping elements can be encoded as two separate representations or linked into an integrated representation, yet we know little about the conditions that promote one form of representation over the other. Here, we tested the hypothesis that the proximity of overlapping events would increase the probability of integration. Participants first established memories for house-object and face-object pairs; half of the pairs were learned 24 hr before an fMRI session, and the other half 30 min before the session. During scanning, participants encoded object-object pairs that overlapped with the initial pairs acquired on the same or prior day. Participants were also scanned as they made inference judgments about the relationships among overlapping pairs learned on the same or different day. Participants were more accurate and faster when inferring relationships among memories learned on the same day relative to those acquired across days, suggesting that temporal proximity promotes integration. Evidence for reactivation of existing memories-as measured by a visual content classifier-was equivalent during encoding of overlapping pairs from the two temporal conditions. In contrast, evidence for integration-as measured by a mnemonic strategy classifier from an independent study [Richter, F. R., Chanales, A. J. H., & Kuhl, B. A. Predicting the integration of overlapping memories by decoding mnemonic processing states during learning. Neuroimage, 124, 323-335, 2016]-was greater for same-day overlapping events, paralleling the behavioral results. During inference itself, activation patterns further differentiated when participants were making inferences about events acquired on the same day versus across days. These findings indicate that temporal proximity of events promotes integration and further influences the neural mechanisms engaged during inference.
PMID: 28253077 [PubMed - indexed for MEDLINE]
Repetition suppression in the medial temporal lobe and midbrain is altered by event overlap.
Hippocampus. 2016 11;26(11):1464-1477
Authors: Zeithamova D, Manthuruthil C, Preston AR
Repeated encounters with the same event typically lead to decreased activation in the medial temporal lobe (MTL) and dopaminergic midbrain, a phenomenon known as repetition suppression. In contrast, encountering an event that overlaps with prior experience leads to increased response in the same regions. Such increased responding is thought to reflect an associative novelty signal that promotes memory updating to resolve differences between current events and stored memories. Here, we married these ideas to test whether event overlap significantly modulates MTL and midbrain responses-even when events are repeated and expected-to promote memory updating through integration. While undergoing high-resolution functional MRI, participants were repeatedly presented with objects pairs, some of which overlapped with other, intervening pairs and some of which contained elements unique from other pairs. MTL and midbrain regions showed widespread repetition suppression for nonoverlapping pairs containing unique elements; however, the degree of repetition suppression was altered for overlapping pairs. Entorhinal cortex, perirhinal cortex (PRc), midbrain, and PRc-midbrain connectivity showed repetition-related increases across overlapping pairs. Notably, increased PRc activation for overlapping pairs tracked individual differences in the ability to reason about the relationships among pairs-our behavioral measure of memory integration. Within the hippocampus, activation increases across overlapping pairs were unique to CA1 , consistent with its hypothesized comparator function. These findings demonstrate that event overlap engages MTL and midbrain functions traditionally implicated in novelty processing, even when overlapping events themselves are repeated. Our findings further suggest that the MTL-midbrain response to event overlap may promote integration of new content into existing memories, leading to the formation of relational memory networks that span experiences. Moreover, the results inform theories about the division of labor within MTL, demonstrating that the role of PRc in episodic encoding extends beyond familiarity processing and item-level recognition. © 2016 Wiley Periodicals, Inc.
PMID: 27479864 [PubMed - indexed for MEDLINE]