Hiroko M. Kimura

Continuous and Overlapping Expression Domains of Odorant Receptor Genes in the Olfactory Epithelium Determine the Dorsal/Ventral Positioning of Glomeruli in the Olfactory Bulb

In mammals, olfactory signals received by odorant receptors (ORs) in the olfactory epithelium (OE) are converted to a topographical map of activated glomeruli in the olfactory bulb (OB). It has been reported that the OE can be divided into four topographically distinct zones and that olfactory sensory neurons (OSNs) expressing a particular OR gene are randomly distributed within one zone. Here, we analyzed 80 different class II OR genes for their expression patterns in the OE by in situ hybridization. It was found that the expression area in the OE does not always fit into one of the four conventional zones. Expression areas are specific to each OR gene and are arranged in an overlapping and continuous manner in the OE. We also analyzed a spatial relationship between the OE and the OB for OSN projection. Our transgenic as well as DiI retrograde staining experiments demonstrated that the dorsal/ventral arrangement of glomeruli in the OB is correlated with the expression areas of corresponding ORs along the dorsomedial/ventrolateral axis in the OE. The present study indicates that the OR gene choice may be more restricted by the OSN location in the OE than what has been thought.

Towards understanding of the cortical network underlying associative memory

Declarative knowledge and experiences are represented in the association cortex and are recalled by reactivation of the neural representation. Electrophysiological experiments have revealed that associations between semantically linked visual objects are formed in neural representations in the temporal and limbic cortices. Memory traces are created by the reorganization of neural circuits. These regions are reactivated during retrieval and contribute to the contents of a memory. Two different types of retrieval signals are suggested as follows: automatic and active. One flows backward from the medial temporal lobe during the automatic retrieval process, whereas the other is conveyed as a top-down signal from the prefrontal cortex to the temporal cortex during the active retrieval process. By sending the top-down signal, the prefrontal cortex manipulates and organizes to-be-remembered information, devises strategies for retrieval and monitors the outcome. To further understand the neural mechanism of memory, the following two complementary views are needed: how the multiple cortical areas in the brain-wide network interact to orchestrate cognitive functions and how the properties of single neurons and their synaptic connections with neighbouring neurons combine to form local circuits and to exhibit the function of each cortical area. We will discuss some new methodological innovations that tackle these challenges.

Functional differentiation of memory retrieval network in macaque posterior parietal cortex.

Human fMRI studies revealed involvement of the posterior parietal cortex (PPC) during memory retrieval. However, corresponding memory-related regions in macaque PPC have not been established. In this monkey fMRI study, comparisons of cortical activity during correct recognition of previously seen items and rejection of unseen items revealed two major PPC activation sites that were differentially characterized by a serial probe recognition paradigm: area PG/PGOp in inferior parietal lobule, along with the hippocampus, was more active for initial item retrieval, while area PEa/DIP in intraparietal sulcus was for the last item. Effective connectivity analyses revealed that connectivity from hippocampus to PG/PGOp, but not to PEa/DIP, increased during initial item retrieval. The two parietal areas with differential serial probe recognition profiles were embedded in two different subnetworks of the brain-wide retrieval-related regions. These functional dissociations in the macaque PPC imply the functional correspondence of retrieval-related PPC networks in macaques and humans.

Functional Dissociation between Anterior and Posterior Temporal Cortical Regions during Retrieval of Remote Memory

Retrieval of remote memory is considered to differentially involve the anterior and posterior temporal neocortices. Previous neuropsychological studies suggest that the different posterior temporal cortical regions are involved in the retrieval of remote memory of different categories of stimuli, whereas the anterior region is involved more generally in remote memory retrieval. In the present study, using functional magnetic resonance imaging of human brains, we tested this dissociation by examining the more precise characteristics of the anterior and posterior temporal cortical regions. Two categories of stimuli, faces and scenes, were used for paired stimuli to be retrieved, and the brain activity during retrieval of paired stimuli that were learned immediately before the scanning was compared with that during retrieval of paired stimuli that were learned ∼8 weeks earlier. We found that the different posterior temporal cortical regions were activated during retrieval of different categories of remote memory in a category-specific manner, whereas the anterior temporal cortical region was activated during retrieval of remote memory in a category-general manner. Furthermore, by applying a multivariate pattern analysis to psychophysiological interactions during retrieval of remote memory relative to recent memory, we revealed the significant interaction from the category-specific posterior temporal cortical regions to the category-general anterior temporal region. These results suggest that the posterior temporal cortical regions are involved in representation and retrieval of category-specific remote memory, whereas the anterior cortical temporal region is involved in category-general retrieval process of remote memory.

Differential temporo-parietal cortical networks that support relational and item-based recency judgments

There is a growing interest in the parietal cortical role for episodic memory retrieval. Previous functional magnetic resonance imaging (fMRI) studies of recency judgments, judgments of the relative temporal order of two studied items, have highlighted the involvement of the lateral prefrontal and medial temporal regions. However, the parietal cortical contribution to recency judgments has rarely been highlighted. To examine the parietal involvement, in this study, we conducted a re-analysis to increase the statistical power using three data sets (N=73) from our previous fMRI studies of recency judgments. Recency judgments can be achieved by at least two mechanisms, relational and item-based ones. It has been revealed that the left hippocampus/parahippocampal region is related to relational recency judgments, and that the right anterior temporal region is related to item-based recency judgments. We examined whether the parietal cortex is involved in these two types of recency judgments. Significant brain activity related to relational recency judgments was observed in the left ventral parietal region and, as reported previously, the left parahippocampal region. On the other hand, significant brain activity related to item-based recency judgments was observed in the left dorsal parietal region and, as reported previously, the right anterior temporal region. Furthermore, correlation analyses of resting-state BOLD signals detected significant correlations between the ventral parietal region and the parahippocampal region, as well as between the dorsal parietal region and anterior temporal region. These results suggest that the two temporo-parietal networks differentially contribute to relational and item-based recency judgments.

Dissociable Memory Traces within the Macaque Medial Temporal Lobe Predict Subsequent Recognition Performance

Functional magnetic resonance imaging (fMRI) studies have revealed that activity in the medial temporal lobe (MTL) predicts subsequent memory performance in humans. Because of limited knowledge on cytoarchitecture and axonal projections of the human MTL, precise localization and characterization of the areas that can predict subsequent memory performance are benefited by the use of nonhuman primates in which integrated approach of the MRI- and cytoarchiture-based boundary delineation is available. However, neural correlates of this subsequent memory effect have not yet been identified in monkeys. Here, we used fMRI to examine activity in the MTL during memory encoding of events that monkeys later remembered or forgot. Application of both multivoxel pattern analysis and conventional univariate analysis to high-resolution fMRI data allowed us to identify memory traces within the caudal entorhinal cortex (cERC) and perirhinal cortex (PRC), as well as within the hippocampus proper. Furthermore, activity in the cERC and the hippocampus, which are directly connected, was responsible for encoding the initial items of sequentially presented pictures, which may reflect recollection-like recognition, whereas activity in the PRC was not. These results suggest that two qualitatively distinct encoding processes work in the monkey MTL and that recollection-based memory is formed by the interplay of the hippocampus with the cERC, a focal cortical area anatomically closer to the hippocampus and hierarchically higher than previously believed. These findings will advance the understanding of common memory system between humans and monkeys and accelerate fine electrophysiological characterization of these dissociable memory traces in the monkey MTL.

Role for presupplementary motor area in inhibition of cognitive set interference

Proactive interference (PI), which is formed through repetition of certain behavior and lasts for a while, needs to be inhibited in order for subsequent behavior to prevail over the antecedent one. Although the inhibitory mechanisms in the pFC have been reported that are recruited long after one behavior is updated to another, very little is known about the inhibitory mechanisms that are recruited immediately after the update. The WCST was modified in the present fMRI study such that inhibition of PI could be examined both immediately after and long after update of behavior. Use of “dual-match” stimuli allowed us to compare two types of trials where inhibition of PI was and was not required (control and release trials, respectively). Significant activation was observed in the left pre-SMA during control versus release trials. The pre-SMA activation was selective to PI inhibition required immediately after update of behavior, which exhibited marked contrast to the left anterior prefrontal activation selective to PI inhibition required long after the update. These results reveal dissociable inhibitory mechanisms in these two regions that are recruited in the different temporal contexts of the inhibitory demands imposed during performance of the task.

Dissociable Temporo-Parietal Memory Networks Revealed by Functional Connectivity during Episodic Retrieval

Episodic memory retrieval most often recruits multiple separate processes that are thought to involve different temporal regions. Previous studies suggest dissociable regions in the left lateral parietal cortex that are associated with the retrieval processes. Moreover, studies using resting-state functional connectivity (RSFC) have provided evidence for the temporo-parietal memory networks that may support the retrieval processes. In this functional MRI study, we tested functional significance of the memory networks by examining functional connectivity of brain activity during episodic retrieval in the temporal and parietal regions of the memory networks. Recency judgments, judgments of the temporal order of past events, can be achieved by at least two retrieval processes, relational and item-based. Neuroimaging results revealed several temporal and parietal activations associated with relational/item-based recency judgments. Significant RSFC was observed between one parahippocampal region and one left lateral parietal region associated with relational recency judgments, and between four lateral temporal regions and another left lateral parietal region associated with item-based recency judgments. Functional connectivity during task was found to be significant between the parahippocampal region and the parietal region in the RSFC network associated with relational recency judgments. However, out of the four tempo-parietal RSFC networks associated with item-based recency judgments, only one of them (between the left posterior lateral temporal region and the left lateral parietal region) showed significant functional connectivity during task. These results highlight the contrasting roles of the parahippocampal and the lateral temporal regions in recency judgments, and suggest that only a part of the tempo-parietal RSFC networks are recruited to support particular retrieval processes.