Trial-by-Trial Hippocampal Encoding Activation Predicts the Fidelity of Cortical Reinstatement During Subsequent Retrieval.

According to current models of episodic memory, the hippocampus binds together the neural representation of an experience during encoding such that it can be reinstated in cortex during subsequent retrieval. However, direct evidence linking hippocampal engagement during encoding with subsequent cortical reinstatement during retrieval is lacking. In this study, we aim to directly test the relationship between hippocampal activation during encoding and cortical reinstatement during retrieval. During a scanned encoding session, human participants studied Noun-Sound and Noun-Picture pairs. One day later, during a scanned retrieval session, participants retrieved the sounds and pictures when given the nouns as cues. First, we found that trial-by-trial hippocampal encoding activation was related to trial-by-trial reactivation during retrieval as measured by the univariate BOLD response in several modality-specific cortical regions. Second, using multivariate measures, we found a correlation between encoding-retrieval pattern similarity computed for each trial and hippocampal encoding activation on the corresponding encoding event, suggesting that the magnitude of hippocampal activation during an experience is related to the fidelity of subsequent reinstatement of cortical activity patterns during retrieval. Consistent with current theories of episodic memory, our findings demonstrate a critical link between initial hippocampal activation during an experience and subsequent cortical reinstatement.

The neural correlates of competition during memory retrieval are modulated by attention to the cues.

As people learn more facts about a concept, those facts become more difficult to remember. This is called the fan effect, where fan refers to the number of facts known about a concept. Increasing fan has been shown to decrease accuracy and increase response time and left ventrolateral prefrontal cortex (VLPFC) activity during retrieval. In this study, participants learned 36 arbitrary person-location pairings and made recognition decisions while we recorded brain activity using fMRI. We separately manipulated the fan of each person and location, as well as the training procedure with which each pair was studied. In the person focus condition, participants studied pairs with a picture of the person's face and used the person as a retrieval cue during training. In the location focus condition, participants studied pairs with a picture of the location and used the location as a retrieval cue during training. We found that the fan of the focused cue had a greater effect on response time, accuracy, and left VLPFC activity during retrieval than the fan of the unfocused cue. We also found that the parahippocampal place area (PPA) was more active during the recognition of pairs studied in the location focus condition, but not when the fan of the location was high. Overall, we found opposite effects of fan on VLPFC and PPA that were modulated by cue focus.

The ghosts of brain states past: remembering reactivates the brain regions engaged during encoding.

There is growing evidence that the brain regions involved in encoding an episode are partially reactivated when that episode is later remembered. That is, the process of remembering an episode involves literally returning to the brain state that was present during that episode. This article reviews studies of episodic and associative memory that provide support for the assertion that encoding regions are reactivated during subsequent retrieval. In the first section, studies are reviewed in which neutral stimuli were associated with different modalities of sensory stimuli or different valences of emotional stimuli. When the neutral stimuli were later used as retrieval cues, relevant sensory and emotion processing regions were reactivated. In the second section, studies are reviewed in which participants used different strategies for encoding stimuli. When the stimuli were later retrieved, regions associated with the different encoding strategies were reactivated. Together, these studies demonstrate not only that the encoding experience determines which regions are activated during subsequent retrieval but also that the same regions are activated during encoding and retrieval. In the final section, relevant questions are posed and discussed regarding the reactivation of encoding regions during retrieval.

Early neural signatures of visual short-term memory.

Visual short-term memory (VSTM) relies on a distributed network including sensory-related, posterior regions of the brain and frontal areas associated with attention and cognitive control. To characterize the fine temporal details of processing within this network, we recorded event-related potentials (ERPs) while human subjects performed a recognition-memory task. The task's difficulty was graded by varying the perceptual similarity between the items held in memory and the probe used to access memory. The evaluation of VSTM's contents against a test stimulus produced clear similarity-dependent differences in ERPs as early as 156 ms after probe onset. Posterior recording sites were the first to reflect the difficulty of the analysis, preceding their frontal counterparts by about 50 ms. Our results suggest an initial feed-forward interaction underlying stimulus-memory comparisons, consistent with the idea that visual areas contribute to temporary storage of visual information for use in ongoing tasks. This study provides a first look into early neural activity underlying the processing of visual information in short-term memory.

Characterizing the ERP Old-New effect in a short-term memory task.

The early and late components of the event-related potential (ERP) Old-New effect are well characterized with respect to long-term memory, and have been associated with processes of familiarity and recollection, respectively. Now, using a short-term memory paradigm with verbal and nonverbal stimuli, we explored the way that these two components respond to variation in recency and stimulus type. We found that the amplitude of the early component (or frontal N400, FN400) showed Old-New effects only for verbal stimuli and increased with recency. In contrast, the later component (or late positive component, LPC) showed Old-New effects across a range of stimulus types and did not scale with recency. These results are consistent with the way that these same ERP components have been characterized in long-term memory, supporting the idea that some of the same processes underlie long- and short-term item recognition.

A rational account of memory predicts left prefrontal activation during controlled retrieval.

What is the role of the left prefrontal cortex in the controlled retrieval of learned information? We present a theory of declarative retrieval that posits that the amount of control exerted by this region during retrieval is inversely proportional to 1) the frequency and recency of previous experiences with the retrieved memory and 2) the associative strength between the current context and the retrieved memory. This theory is rational in the sense that it claims that declarative retrieval is highly sensitive to the statistical regularities in the environment. We demonstrate how our theory produces precise predictions of response time and neural activity during recall and test these predictions in an experiment that manipulates the frequency of previous experiences and the associative strength to the retrieval cues. Our findings suggest that the control process performed by the left prefrontal cortex directly reflects the demands of the environment on memory.

The roles of prefrontal and posterior parietal cortex in algebra problem solving: a case of using cognitive modeling to inform neuroimaging data.

In naturalistic algebra problem solving, the cognitive processes of representation and retrieval are typically confounded, in that transformations of the equations typically require retrieval of mathematical facts. Previous work using cognitive modeling has associated activity in the prefrontal cortex with the retrieval demands of algebra problems and activity in the posterior parietal cortex with the transformational demands of algebra problems, but these regions tend to behave similarly in response to task manipulations (Anderson, J.R., Qin, Y., Sohn, M.-H., Stenger, V.A., Carter, C.S., 2003. An information-processing model of the BOLD response in symbol manipulation tasks. Psychon. Bull. Rev. 10, 241-261; Qin, Y., Carter, C.S., Silk, E.M., Stenger, A., Fissell, K., Goode, A., Anderson, J.R., 2004. The change of brain activation patterns as children learn algebra equation solving. Proc. Natl. Acad. Sci. 101, 5686-5691). With this study we attempt to isolate activity in these two regions by using a multi-step algebra task in which transformation (parietal) is manipulated in the first step and retrieval (prefrontal) is manipulated in the second step. Counter to our initial predictions, both brain regions were differentially active during both steps. We designed two cognitive models, one encompassing our initial assumptions and one in which both processes were engaged during both steps. The first model provided a poor fit to the behavioral and neural data, while the second model fit both well. This simultaneously emphasizes the strong relationship between retrieval and representation in mathematical reasoning and demonstrates that cognitive modeling can serve as a useful tool for understanding task manipulations in neuroimaging experiments.

Quantitative regional cerebral blood flow MRI of animal model of attention-deficit/hyperactivity disorder.

The spontaneously hypertensive rat (SHR) has been widely used as an animal model for attention-deficit/hyperactivity disorder (AD/HD), a developmental disorder that affects 3-5% of school-age children. Quantitative high-resolution (180 x 180 x 1500 microm) perfusion magnetic resonance imaging was performed to evaluate regional CBF in AD/HD rats (SHR, n=7) and control Wistar Kyoto rats (WKY, n=9) in the frontal cortex, motor cortex, sensory cortex, corpus callosum, hippocampus, thalamus, globus pallidus, caudoputamen and whole brain. The accuracy of repeated cerebral blood flow (CBF) measurements within animals in these brain regions ranged from 3% to 10% (7 repeated measures) and across animals ranged from 15% to 18% (n=7 rats), respectively, indicating highly accurate and reproducible CBF measurements. Regional CBF of the SHR were statistically different from those of the WKY rats in all structures analyzed (P<0.05) except for the caudate putamen (P=0.09) and the globus pallidus (P=0.12). Whole brain CBF of the SHR (1.5+/-0.2 ml/g/min, mean+/-S.D.) was approximately 25% higher than that of the WKY rats (1.2+/-0.2 ml/g/min), likely due to the hypertensive nature of the AD/HD rat model. Following normalization to eliminate global CBF differences, CBF in the medial prefrontal cortex, a structure thought to be the equivalent of the human dorsolateral prefrontal cortex and widely implicated in AD/HD, was found to be higher in SHR compared to WKY rats (P<0.05). The only other structure that was found to be statistically different after normalization is the corpus callosum (P<0.05). Since resting cerebral blood flow is intricately coupled to resting neural activity, these results suggest that there was abnormal resting neural activity in the medial prefrontal cortex and the corpus callosum between the control and AD/HD animals, consistent with the hyperactivity, impulsivity, inattention, and other AD/HD-like behaviors in this animal model.