Entorhinal-Hippocampal Circuit Integrity Is Related to Mnemonic Discrimination and Amyloid-ß Pathology in Older Adults.

Mnemonic discrimination, a cognitive process that relies on hippocampal pattern separation, is one of the first memory domains to decline in aging and preclinical Alzheimer's disease. We tested whether functional connectivity (FC) within the entorhinal-hippocampal circuit, measured with high-resolution resting state fMRI, is associated with mnemonic discrimination and amyloid-ß (Aß) pathology in a sample of 64 cognitively normal human older adults (mean age, 71.3 ± 6.4 years; 67% female). FC was measured between entorhinal-hippocampal circuit nodes with known anatomical connectivity, as well as within cortical memory networks. Aß pathology was measured with 18F-florbetapir-PET, and neurodegeneration was assessed with subregional volume from structural MRI. Participants performed both object and spatial versions of a mnemonic discrimination task outside of the scanner and were classified into low-performing and high-performing groups on each task using a median split. Low object mnemonic discrimination performance was specifically associated with increased FC between anterolateral entorhinal cortex (alEC) and dentate gyrus (DG)/CA3, supporting the importance of this connection to object memory. This hyperconnectivity between alEC and DG/CA3 was related to Aß pathology and decreased entorhinal cortex volume. In contrast, spatial mnemonic discrimination was not associated with altered FC. Aß was further associated with dysfunction within hippocampal subfields, particularly with decreased FC between CA1 and subiculum as well as reduced volume in these regions. Our findings suggest that Aß may indirectly lead to memory impairment through entorhinal-hippocampal circuit dysfunction and neurodegeneration and provide a mechanism for increased vulnerability of object mnemonic discrimination.SIGNIFICANCE STATEMENT Mnemonic discrimination is a critical episodic memory process that is performed in the dentate gyrus (DG) and CA3 subfield of the hippocampus, relying on input from entorhinal cortex. Mnemonic discrimination is particularly vulnerable to decline in older adults; however, the mechanisms behind this vulnerability are still unknown. We demonstrate that object mnemonic discrimination impairment is related to hyperconnectivity between the anterolateral entorhinal cortex and DG/CA3. This hyperconnectivity was associated with amyloid-ß pathology and neurodegeneration in entorhinal cortex, suggesting aberrantly increased network activity is a pathological process. Our findings provide a mechanistic explanation of the vulnerability of object compared to spatial mnemonic discrimination in older adults and has translational implications for choice of outcome measures in clinical trials for Alzheimer's disease.

Associations between saliva and plasma cytokines in cognitively normal, older adults.

BACKGROUND: Inflammatory responses play key roles in the development and progression of many pathological conditions, including neurodegenerative diseases. Accurate quantification of inflammatory factors in saliva would be highly advantageous, given its convenience and non-invasive nature, especially in elderly populations. METHODS: In this study, we measured levels of 10 cytokines, and the pro-inflammatory factor, YKL-40, in plasma and saliva samples from a cohort of nondemented older adults (n = 71; 62% female; 70.3 ± 6.4 years) using sensitive electrochemiluminescence-based immunoassays. RESULTS: We found that the mean levels of all cytokines were higher in saliva compared to plasma and that strong sex differences were observed for both saliva and plasma cytokines in this population. Comparing each cytokine between the two biofluids, we found that levels of interferon-gamma (IFNγ), interleukin (IL)-6 and tumor necrosis factor-alpha (TNFα) in blood were significantly correlated with their respective levels in saliva. We further observed that levels of these cytokines in blood were significantly correlated with additional cytokines in saliva, including IL-1ß, IL-10, IL-8, IL12p70 and IL-13. CONCLUSIONS: These findings show that inflammatory markers in saliva are associated with those found in circulation, suggesting shared inflammatory mechanisms between these two fluids. The higher levels of cytokines measured in saliva suggest that it might represent a better peripheral fluid to gauge inflammatory processes. Finally, our findings of robust sex differences in several salivary cytokines could have important implications for their potential use as disease biomarkers in the elderly and might be related to sex differences in the prevalence of age-related conditions.

Neuropsychological and neuropathological observations of a long-studied case of memory impairment.

We report neuropsychological and neuropathological findings for a patient (A.B.), who developed memory impairment after a cardiac arrest at age 39. A.B. was a clinical psychologist who, although unable to return to work, was an active participant in our neuropsychological studies for 24 y. He exhibited a moderately severe and circumscribed impairment in the formation of long-term, declarative memory (anterograde amnesia), together with temporally graded retrograde amnesia covering ∼5 y prior to the cardiac arrest. More remote memory for both facts and autobiographical events was intact. His neuropathology was extensive and involved the medial temporal lobe, the diencephalon, cerebral cortex, basal ganglia, and cerebellum. In the hippocampal formation, there was substantial cell loss in the CA1 and CA3 fields, the hilus of the dentate gyrus (with sparing of granule cells), and the entorhinal cortex. There was also cell loss in the CA2 field, but some remnants remained. The amygdala demonstrated substantial neuronal loss, particularly in its deep nuclei. In the thalamus, there was damage and atrophy of the anterior nuclear complex, the mediodorsal nucleus, and the pulvinar. There was also loss of cells in the medial and lateral mammillary nuclei in the hypothalamus. We suggest that the neuropathology resulted from two separate factors: the initial cardiac arrest (and respiratory distress) and the recurrent seizures that followed, which led to additional damage characteristic of temporal lobe epilepsy.

CaV α2δ Autoimmune Encephalitis: A Novel Antibody and its Characteristics.

OBJECTIVE: Discovery of a novel antibody would enable diagnosis and early treatment of autoimmune encephalitis. The aim was to discover a novel antibody targeting a synaptic receptor and characterize the pathogenic mechanism. METHOD: We screened for unknown antibodies in serum and cerebrospinal fluid samples from autoimmune encephalitis patients. Samples with reactivity to rat brain sections and no reactivity to conventional antibody tests underwent further processing for antibody discovery, using immunoprecipitation to primary neuronal cells, mass-spectrometry analysis, an antigen-binding assay on an antigen-overexpressing cell line, and an electrophysiological assay with cultured hippocampal neurons. RESULTS: Two patients had a novel antibody against CaV α2δ (voltage-gated calcium channel alpha-2/delta subunit). The patient samples stained neuropils of the hippocampus, basal ganglia, and cortex in rat brain sections and bound to a CaV α2δ-overexpressing cell line. Knockdown of CaV α2δ expression in cultured neurons turned off the immunoreactivity of the antibody from the patients to the neurons. The patients were associated with preceding meningitis or neuroendocrine carcinoma and responded to immunotherapy. In cultured neurons, the antibody reduced neurotransmitter release from presynaptic nerve terminals by interfering with tight coupling of calcium channels and exocytosis. INTERPRETATION: Here, we discovered a novel autoimmune encephalitis associated with anti-CaV α2δ antibody. Further analysis of the antibody in autoimmune encephalitis might promote early diagnosis and treatment. ANN NEUROL 2021;89:740-752.

Simultaneous determination of the shape and refractive index of a deformed microjet cavity from its resonances.

Measuring the boundary shape of a deformed liquid microjet is of great importance for using it as an optical resonator for various applications. However, there have been technical challenges due to transparency and uncertainty in the refractive index of the liquid. In this study, we have developed a spectroscopic technique that enables simultaneous determination of the boundary shape and the refractive index of a liquid deformed microjet. A detailed procedure of the technique based on imposition of one-to-one correspondence between experimentally observed resonances and numerically calculated ones are presented along with the measurement results including the refractive index of ethanol between a wavelength of 550 nm and 670 nm.

Reduced acoustic resonator dimensions improve focusing efficiency of bacteria and submicron particles.

In this study, we demonstrate an acoustofluidic device that enables single-file focusing of submicron particles and bacteria using a two-dimensional (2D) acoustic standing wave. The device consists of a 100 µm × 100 µm square channel that supports 2D particle focusing in the channel center at an actuation frequency of 7.39 MHz. This higher actuation frequency compared with conventional bulk acoustic systems enables radiation-force-dominant motion of submicron particles and overcomes the classical size limitation (≈2 µm) of acoustic focusing. We present acoustic radiation force-based focusing of particles with diameters less than 0.5 µm at a flow rate of 12 µL min-1, and 1.33 µm particles at flow rates up to 80 µL min-1. The device focused 0.25 µm particles by the 2D acoustic radiation force while undergoing a channel cross-section centered, single-vortex acoustic streaming. A suspension of bacteria was also investigated to evaluate the biological relevance of the device, which demonstrated the alignment of bacteria in the channel at a flow rate of up to 20 µL min-1. The developed acoustofluidic device can align submicron particles within a narrow flow stream in a highly robust manner, validating its use as a flow-through focusing chamber to perform high-throughput and accurate flow cytometry of submicron objects.

The Effect of Safety Claims on Consumer Chemical Product Perceptions and the Role of Warnings.

OBJECTIVE: To assess the effect of safety claims and warnings on perceptions of consumer chemical products. BACKGROUND: Manufacturers have two contradictory objectives: to increase sales by emphasizing the positive aspects of a product and to protect consumers from hazards of the product. One of the strategies that some manufactures have devised to achieve these goals is to use anti-warnings. Safety claims placed on consumer chemical products were examined to determine if anti-warnings influenced product perceptions. METHOD: Two experiments were conducted. In Experiment 1, three consumer chemical products with manipulated safety claims were presented to 300 participants, who completed a survey to rate their perceptions of the products. In Experiment 2, the same products with the safety claims and added warnings were presented to 600 participants and were rated using the same measurements as Experiment 1. RESULTS: Safety claims on product labels decreased perceived hazards compared to no safety claims on products in both Experiments 1 and 2. In Experiment 2, added warnings raised the perceived hazards. CONCLUSION: The use of safety claims on consumer chemical products had an effect on product perceptions by decreasing hazard perceptions. The addition of strong warnings on product labels mitigated this effect. APPLICATION: This research provides empirical evidence suggesting that the use of safety claims decreased hazard perceptions of potentially hazardous consumer chemical products and can serve as a possible form of anti-warnings.

Comparative Transcriptome Analysis between Two Potato Cultivars in Tuber Induction to Reveal Associated Genes with Anthocyanin Accumulation.

Anthocyanins are generally accumulated within a few layers, including the epidermal cells of leaves and stems in plants. Solanum tuberosum cv. 'Jayoung' (hereafter, JY) is known to accumulate anthocyanin both in inner tissues and skins. We discovered that anthocyanin accumulation in the inner tissues of JY was almost diminished (more than 95% was decreased) in tuber induction condition. To investigate the transcriptomic mechanism of anthocyanin accumulation in JY flesh, which can be modulated by growth condition, we performed mRNA sequencing with white-colored flesh tissue of Solanum tuberosum cv. 'Atlantic' (hereafter, 'Daeseo', DS) grown under canonical growth conditions, a JY flesh sample grown under canonical growth conditions, and a JY flesh sample grown under tuber induction conditions. We could identify 36 common DEGs (differentially expressed genes) in JY flesh from canonical growth conditions that showed JY-specifically increased or decreased expression level. These genes were enriched with flavonoid biosynthetic process terms in GO analysis, as well as gene set enrichment analysis (GSEA) analysis. Further in silico analysis on expression levels of anthocyanin biosynthetic genes including rate-limiting genes such as StCHS and StCHI followed by RT-PCR and qRT-PCR analysis showed a strong positive correlation with the observed phenotypes. Finally, we identified StWRKY44 from 36 common DEGs as a possible regulator of anthocyanin accumulation, which was further supported by network analysis. In conclusion, we identified StWRKY44 as a putative regulator of tuber-induction-dependent anthocyanin accumulation.

Intron-retained radish (Raphanus sativus L.) RsMYB1 transcripts found in colored-taproot lines enhance anthocyanin accumulation in transgenic Arabidopsis plants.

KEY MESSAGE: Overexpression of the naturally occurring intron-retained (IR) forms of radish RsMYB1 and RsTT8 transcripts in Arabidopsis causes a substantial increase in anthocyanin accumulation. The production of anthocyanins in plants is tightly controlled by the MYB-bHLH-WD40 (MBW) complex. In this study, analysis of four radish (Raphanus sativus L.) inbred lines with different colored taproots revealed that regulatory genes of anthocyanin biosynthesis, RsMYB1 and RsTT8, produce three transcripts, one completely spliced and two intron retention (IR1 and IR2) forms. Transcripts RsMYB1-IR1 and RsMYB1-IR2 retained the 1st (380 nt) and 2nd (149 nt) introns, respectively; RsTT8-IR1 retained the 4th intron (113 nt); RsTT8-IR2 retained both the 3rd (128 nt) and 4th introns. Levels of most IR forms were substantially low in radish samples, but the RsTT8-IR2 level was higher than RsTT8 in red skin/red flesh (RsRf) root. Since all IR forms contained a stop codon within the intron, they were predicted to encode truncated proteins with defective interaction domains, resulting in the inability to form the MBW complex in vivo. However, tobacco leaves transiently co-expressing RsMYB1-IRs and RsTT8-IRs showed substantially higher anthocyanin accumulation than those co-expressing their spliced forms. Consistently, co-expression of constructs encoding truncated proteins with spliced or IR forms of their interaction partner in tobacco leaves did not result in anthocyanin accumulation. Compared with RsMYB1, the overexpression of RsMYB1-IRs in Arabidopsis pap1 mutant increased anthocyanin accumulation by > sevenfold and upregulated the expression of Arabidopsis flavonoid biosynthesis genes including AtTT8. Our results suggest that the stable co-expression of RsMYB1-IRs in fruit trees and vegetable crops could be used to increase their anthocyanin contents.

Machine Learning Approach for Active Vaccine Safety Monitoring.

BACKGROUND: Vaccine safety surveillance is important because it is related to vaccine hesitancy, which affects vaccination rate. To increase confidence in vaccination, the active monitoring of vaccine adverse events is important. For effective active surveillance, we developed and verified a machine learning-based active surveillance system using national claim data. METHODS: We used two databases, one from the Korea Disease Control and Prevention Agency, which contains flu vaccination records for the elderly, and another from the National Health Insurance Service, which contains the claim data of vaccinated people. We developed a case-crossover design based machine learning model to predict the health outcome of interest events (anaphylaxis and agranulocytosis) using a random forest. Feature importance values were evaluated to determine candidate associations with each outcome. We investigated the relationship of the features to each event via a literature review, comparison with the Side Effect Resource, and using the Local Interpretable Model-agnostic Explanation method. RESULTS: The trained model predicted each health outcome of interest with a high accuracy (approximately 70%). We found literature supporting our results, and most of the important drug-related features were listed in the Side Effect Resource database as inducing the health outcome of interest. For anaphylaxis, flu vaccination ranked high in our feature importance analysis and had a positive association in Local Interpretable Model-Agnostic Explanation analysis. Although the feature importance of vaccination was lower for agranulocytosis, it also had a positive relationship in the Local Interpretable Model-Agnostic Explanation analysis. CONCLUSION: We developed a machine learning-based active surveillance system for detecting possible factors that can induce adverse events using health claim and vaccination databases. The results of the study demonstrated a potentially useful application of two linked national health record databases. Our model can contribute to the establishment of a system for conducting active surveillance on vaccination.

Does group cohesion foster self-directed learning for medical students? A longitudinal study.

BACKGROUND: The importance of self-directed learning (SDL) and collaborative learning has been emphasized in medical education. This study examined if there were changes in the pattern of SDL and group cohesion from the time of admission to medical school under the criterion-referenced grading system, increased group activities, and interaction of medical education curriculum. Second, it was examined whether group cohesion influences self-directed learning. METHODS: The participants were 106 medical students (71 males, 35 females) who enrolled in Yonsei University College of Medicine in Seoul, South Korea in March 2014. They were asked to complete a Korean version of the self-directed learning readiness scale (SDLRS) and group cohesion scale (GCS) at the end of each semester for three years. A repeated measures ANOVA and a correlation and regression analysis were conducted. RESULTS: All the participants completed the questionnaires. There were differences in the SDLRS scores over the three years. A significant increase was observed one year after admission followed by stable scores until the third year. There was a significant increase in GCS scores as students progressed through medical school years. Positive relationships were found between SDLRS and GCS scores, and the regression model predicted 32% variance. CONCLUSIONS: SDLRS and GCS increased as medical school years progressed. In addition, GCS is a significant factor in fostering SDLRS. Medical schools should develop various curriculum activities that enhance group cohesion among medical students, which would in turn promote SDL.

Map reading, navigating from maps, and the medial temporal lobe.

We administered map-reading tasks in which participants navigated an array of marks on the floor by following paths on hand-held maps that made up to nine turns. The burden on memory was minimal because the map was always available. Nevertheless, because the map was held in a fixed position in relation to the body, spatial computations were continually needed to transform map coordinates into geographical coordinates as participants followed the maps. Patients with lesions limited to the hippocampus (n = 5) performed similar to controls at all path lengths (experiment 1). They were also intact at executing single moves to an adjacent location, even when trials began by facing in a direction that put the map coordinates and geographical coordinates into conflict (experiment 2). By contrast, one patient with large medial temporal lobe (MTL) lesions performed poorly overall in experiment 1 and poorly in experiment 2 when trials began by facing in the direction that placed the map coordinates and geographical coordinates in maximal conflict. Directly after testing, all patients were impaired at remembering factual details about the task. The findings suggest that the hippocampus is not needed to carry out the spatial computations needed for map reading and navigating from maps. The impairment in map reading associated with large MTL lesions may depend on damage in or near the parahippocampal cortex.

Memory, scene construction, and the human hippocampus.

We evaluated two different perspectives about the function of the human hippocampus--one that emphasizes the importance of memory and another that emphasizes the importance of spatial processing and scene construction. We gave tests of boundary extension, scene construction, and memory to patients with lesions limited to the hippocampus or large lesions of the medial temporal lobe. The patients were intact on all of the spatial tasks and impaired on all of the memory tasks. We discuss earlier studies that associated performance on these spatial tasks to hippocampal function. Our results demonstrate the importance of medial temporal lobe structures for memory and raise doubts about the idea that these structures have a prominent role in spatial cognition.

Effect of Pet Insects on the Psychological Health of Community-Dwelling Elderly People: A Single-Blinded, Randomized, Controlled Trial.

BACKGROUND: There is evidence that animal-assisted therapy has positive effects on mental health, especially in elderly people. Caring for insects is easy, relatively inexpensive, and does not require much space. OBJECTIVE: The aim of this 8-week randomized, controlled, single-blinded study was to investigate the effect of pet insects on the psychological health of community-dwelling elderly people. METHODS: Elderly subjects (≥65 years old) attending a community center in Daegu, Korea, were enrolled in the study between April and May 2014 and randomized at a 1:1 ratio to receive insect therapy and health advice or only health advice. The insect group received 5 crickets in a cage with sufficient fodder and a detailed instruction manual. At baseline and at 8 weeks, all subjects underwent psychometric tests via a direct interview [Beck Anxiety Inventory, Geriatric Depression Scale (GDS-15), Mini-Mental State Examination (MMSE), 36-Item Short Form Health Survey, Insomnia Severity Index, Fatigue Severity Scale, and Brief Encounter Psychosocial Instrument] and laboratory analyses of inflammatory and oxidative stress markers (erythrocyte sedimentation rate, high-sensitivity C-reactive protein, biological antioxidant potential, and derivatives of reactive oxygen metabolites). RESULTS: The insect-caring (n = 46) and control (n = 48) groups did not differ in baseline characteristics. The insect-caring group had significantly lower GDS-15 scores at week 8 (3.20 vs. 4.90, p = 0.004) and, after adjustment for baseline values, a significantly greater change in GDS-15 scores relative to baseline (-1.12 vs. 0.20, p = 0.011). They also had a significantly greater change in MMSE scores relative to baseline (1.13 vs. 0.31, p = 0.045). The two groups did not differ in terms of other psychometric and laboratory tests. No serious risks or adverse events were reported. CONCLUSION: Caring for insects, which is cost-effective and safe, was associated with a small to medium positive effect on depression and cognitive function in community-dwelling elderly people.

Contrasting effects on path integration after hippocampal damage in humans and rats.

The hippocampus and other medial temporal lobe structures have been linked to both memory and spatial cognition, but it has been unclear how these ideas are connected. We carried out parallel studies of path integration in patients with medial temporal lobe lesions and rats with hippocampal lesions. Subjects entered a circular arena without vision, searched for a target, and then attempted to return to the start location. Patients performed accurately, and as well as controls, so long as the outward path was relatively direct and the target was found within 20 s. In sharp contrast, rats with hippocampal lesions were impaired, even when the outward path was shorter than 1 m, involved no turns, and the target was found within 3 s. We suggest that patients succeeded because performance could be supported by working memory and that patients and rats differ after hippocampal lesions in their ability to construct a coherent working memory of spatial environments.

Direct printing of reduced graphene oxide on planar or highly curved surfaces with high resolutions using electrohydrodynamics.

Electrohydrodynamic inkjet printing of reduced graphene oxide (RGO) is de-monstrated to form complex geometric devices with high resolution (line width ≈ 5 mm). Both planar and highly curved surfaces (radius of curvature ≈ 60 mm) can be used as substrates. Demonstrations of counterfeit coin recognition using RGO patterns and all-printed RGO transistors suggest substantial promise for applications in security and electronics.

Stretchable and transparent electrodes using hybrid structures of graphene-metal nanotrough networks with high performances and ultimate uniformity.

Transparent electrodes that can maintain their electrical and optical properties stably against large mechanical deformations are essential in numerous applications of flexible and wearable electronics. In this paper, we report a comprehensive analysis of the electrical, optical, and mechanical properties of hybrid nanostructures based on graphene and metal nanotrough networks as stretchable and transparent electrodes. Compared to the single material of graphene or the nanotrough, the formation of this hybrid can improve the uniformity of sheet resistance significantly, that is, a very low sheet resistance (1 Ω/sq) with a standard deviation of less than ±0.1 Ω/sq, high transparency (91% in the visible light regime), and superb stretchability (80% in tensile strain). The successful demonstration of skin-attachable, flexible, and transparent arrays of oxide semiconductor transistors fabricated using hybrid electrodes suggests substantial promise for the next generation of electronic devices.

Effects of PMMA and Cross-Linked Dextran Filler for Soft Tissue Augmentation in Rats.

This study was conducted for evaluation of the ability to maintain efficacy and biocompatibility of cross-linked dextran in hydroxypropyl methylcellulose (DiHM) and cross-linked dextran mixed with PMMA in hydroxypropyl methylcellulose (PDiHM), compared with hyaluronic acid (HA) filler. Saline and HA solution was administered in the negative and positive control groups, and DiHM and PDiHM were administered in the test groups (n = 10 in each group). The site of cranial subcutaneous injection was the mid-point of the interpupillary line, and the site of intraoral submucosal injection was the ridge crest 2 mm below the cervical line of the mandibular left incisor. Before and immediately after filler injection, intraoral photos and lateral cephalometric radiographs were taken for analysis and comparison of the effect of the filler on the injection sites. The filler injected areas were converted into sequential size changes (%) of the baseline. Histomorphologic examination was performed after 12 weeks. The smallest value in the filler injected area was observed during the experimental period in the normal saline group (p < 0.001), which was almost absorbed at 4 weeks (7.19% ± 12.72%). The HA group exhibited a steady decrease in sequential size and showed a lower value than the DiHM and PDiHM groups (saline < HA < DHiM, PDHiM, p < 0.001). DiHM and PDiHM tended to increase for the first 4 weeks and later decreased until 12 weeks. In this study on DiHM and PDiHM, there was no histological abnormality in cranial skin and oral mucosa. DiHM and PDiHM filler materials with injection system provide an excellent alternative surgical method for use in oral and craniofacial fields.

High-performance, transparent, and stretchable electrodes using graphene-metal nanowire hybrid structures.

Transparent electrodes that can remain electrically conductive and stable under large mechanical deformations are highly desirable for applications in flexible and wearable electronics. This paper describes a comprehensive study of the electrical, optical, and mechanical properties of hybrid nanostructures based on two-dimensional graphene and networks of one-dimensional metal nanowires, and their use as transparent and stretchable electrodes. Low sheet resistance (33 Ω/sq) with high transmittance (94% in visible range), robust stability against electric breakdown and oxidation, and superb flexibility (27% in bending strain) and stretchability (100% in tensile strain) are observed, and these multiple functionalities of the hybrid structures suggest a future promise for next generation electronics. The use of hybrid electrodes to fabricate oxide semiconductor transistors and single-pixel displays integrated on wearable soft contact lenses with in vivo tests are demonstrated.

Sparing of spatial mental imagery in patients with hippocampal lesions.

In four experiments, we explored the capacity for spatial mental imagery in patients with hippocampal lesions, using tasks that minimized the role of learning and memory. On all four tasks, patients with hippocampal lesions performed as well as controls. Nonetheless, in separate tests, the patients were impaired at remembering the materials that had been used to assess mental imagery. The findings suggest that the hippocampus is not needed for constructing many forms of spatial imagery but is needed for the formation of long-term memory. In future studies of the neural organization of spatial mental imagery, it will be important to separate the contribution of spatial processing from the contribution of learning and memory.